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Sample records for cancer pooled analysis

  1. Fulvestrant and male breast cancer: a pooled analysis.

    PubMed

    Zagouri, Flora; Sergentanis, Theodoros N; Chrysikos, Dimosthenis; Dimopoulos, Meletios-Athanasios; Psaltopoulou, Theodora

    2015-01-01

    Male breast cancer is an uncommon malignancy; little is known regarding hormonal manipulations for tamoxifen-resistant male breast cancer patients. This is the first pooled analysis of the literature to synthesize all available data and to evaluate the efficacy and safety of fulvestrant in male breast cancer. This study was performed in accordance with the PRISMA guidelines. All studies that examined the efficacy of fulvestrant in male breast cancer, regardless of sample size, were considered eligible. The search strategy retrieved 31 articles; of these, five articles were eligible (23 patients) for this pooled analysis. The mean age of the study sample was 63.1 years. Adjuvant hormonal treatment was administered in 87.5 % of cases. Fulvestrant was given as first or second line in 40 % of patients, while as third line or beyond in 60 % of patients. 79.0 % of patients at fulvestrant administration had visceral metastases. Regarding best response, in 26.1 % PR was achieved, in 47.8 % of cases SD was recorded, whereas in 26.1 % of patients PD was noted. The median PFS was equal to 5 months. No grade 3 and 4 adverse events were recorded; of note, hot flashes were reported in 18.2 % of male breast cancer patients. Fulvestrant may potentially play a promising role in the optimal therapeutic strategy for male patients with breast cancer diagnosis. However, further clinical and pharmacokinetic investigations are more than warranted before fulvestrant use becomes a common practice in male breast cancer patients.

  2. Intrauterine devices and endometrial cancer risk: a pooled analysis of the Epidemiology of Endometrial Cancer Consortium

    PubMed Central

    Felix, Ashley S.; Gaudet, Mia M.; La Vecchia, Carlo; Nagle, Christina M.; Ou Shu, Xiao; Weiderpass, Elisabete; Olov Adami, Hans; Beresford, Shirley; Bernstein, Leslie; Chen, Chu; Cook, Linda S.; De Vivo, Immaculata; Doherty, Jennifer A.; Friedenreich, Christine M.; Gapstur, Susan M.; Hill, Dierdre; Horn-Ross, Pamela L.; Lacey, James V.; Levi, Fabio; Liang, Xiaolin; Lu, Lingeng; Magliocco, Anthony; McCann, Susan E.; Negri, Eva; Olson, Sara H.; Palmer, Julie R.; Patel, Alpa V.; Petruzella, Stacey; Prescott, Jennifer; Risch, Harvey A.; Rosenberg, Lynn; Sherman, Mark E.; Spurdle, Amanda B.; Webb, Penelope M.; Wise, Lauren A.; Xiang, Yong-Bing; Xu, Wanghong; Yang, Hannah P.; Yu, Herbert; Zeleniuch-Jacquotte, Anne; Brinton, Louise A.

    2014-01-01

    Intrauterine devices (IUDs), long-acting and reversible contraceptives, induce a number of immunological and biochemical changes in the uterine environment that could affect endometrial cancer (EC) risk. We addressed this relationship through a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We combined individual-level data from 4 cohort and 14 case-control studies, in total 8,801 EC cases and 15,357 controls. Using multivariable logistic regression, we estimated pooled odds ratios (pooled-ORs) and 95% confidence intervals (CIs) for EC risk associated with ever use, type of device, ages at first and last use, duration of use, and time since last use, stratified by study and adjusted for confounders. Ever use of IUDs was inversely related to EC risk (pooled-OR=0.81, 95% CI=0.74–0.90). Compared with never use, reduced risk of EC was observed for inert IUDs (pooled-OR=0.69, 95% CI=0.58–0.82), older age at first use (≥35 years pooled-OR=0.53, 95% CI=0.43–0.67), older age at last use (≥45 years pooled-OR=0.60, 95% CI=0.50–0.72), longer duration of use (≥10 years pooled-OR=0.61, 95% CI=0.52–0.71), and recent use (within 1 year of study entry pooled-OR=0.39, 95% CI=0.30–0.49). Future studies are needed to assess the respective roles of detection biases and biologic effects related to foreign body responses in the endometrium, heavier bleeding (and increased clearance of carcinogenic cells), and localized hormonal changes. PMID:25242594

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

    PubMed

    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

    2006-03-13

    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 > or =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.

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

    PubMed

    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

    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.

  5. HPV type distribution in invasive cervical cancers in Italy: pooled analysis of three large studies

    PubMed Central

    2012-01-01

    Objective The aim of this study is to describe the prevalence of HPV types in invasive cervical cancers in Italy from 1996 to 2008. Methods A pooled analysis of the three largest case series typed to date was performed. HPV typing was performed on paraffin-embedded slices. Molecular analyses were performed in four laboratories. Multivariate analyses were performed to test the associations between calendar time, age, and geographical area and the proportion of types 16/18. Results Out of 574 cancers, 24 (4.2%) were HPV negative. HPV 16 and 18 were responsible for 74.4% (378/508) and 80.3% (49/61) of the squamous cancers and adenocarcinomas, respectively. Other frequent types were 31 (9.5%), 45 (6.4%), and 58 (3.3%) for squamous cancers and 45 (13.3%), 31, 35, and 58 (5.0%) for adenocarcinomas. The proportion of HPV 16 and/or 18 decreased with age (p-value for trend <0.03), while it increased in cancers diagnosed in more recent years (p-value for trend < 0.005). Conclusions The impact of HPV 16/18 vaccine on cervical cancer will be greater for early onset cancers. In vaccinated women, screening could be started at an older age without reducing protection. PMID:23110797

  6. Cigarette smoking, N-acetyltransferase 2 genotypes, and breast cancer risk: pooled analysis and meta-analysis.

    PubMed

    Ambrosone, Christine B; Kropp, Silke; Yang, Jun; Yao, Song; Shields, Peter G; Chang-Claude, Jenny

    2008-01-01

    Approximately 10 years ago, it was noted that smoking increased risk of breast cancer among women with N-acetyltransferase 2 (NAT2) slow acetylation genotypes. This report was followed by a number of studies to address this question. We pooled data from 10 existing studies and also conducted a meta-analysis of 13 studies published from 1996 to October 2006 that were conducted among women, were published in English, and had adequate information on smoking and NAT2 genotyping. Raw data were requested from authors. Unconditional logistic regression was done for pooled analysis, and random effect models was done for meta-analysis. Study heterogeneity was assessed, and sensitivity tests were done when subgroups were excluded from the analysis. In the pooled analysis, there was a significant interaction between smoking, NAT2 genotype, and risk of breast cancer [pack-years (continuous variable, P(interaction) = 0.03)], with higher pack-years significantly associated with an increased risk of breast cancer among women with NAT2 slow genotypes (pooled analysis relative risk, 1.49; 95% confidence interval, 1.08-2.04). These findings were supported by the meta-analysis including all studies; pack-years were significantly associated with risk among slow acetylators in a dose-dependent fashion (meta-analysis relative risk, 1.44; 95% confidence interval, 1.23-1.68 for > or =20 pack-years versus never smokers), but not among rapid acetylators. Similar relationships were noted for smoking status (ever, never) and duration of smoking. Our results show that cigarette smoking is associated with an increase in breast cancer risk among women with NAT2 slow acetylation genotypes. Because slow NAT2 genotypes are present in 50% to 60% of Caucasian populations, smoking is likely to play an important role in breast cancer etiology.

  7. Anthropometric Factors and Thyroid Cancer Risk by Histological Subtype: Pooled Analysis of 22 Prospective Studies

    PubMed Central

    McCullough, Marjorie L.; Franceschi, Silvia; Rinaldi, Sabina; Wolk, Alicja; Neta, Gila; Olov Adami, Hans; Anderson, Kristin; Andreotti, Gabriella; Beane Freeman, Laura E.; Bernstein, Leslie; Buring, Julie E.; Clavel-Chapelon, Francoise; De Roo, Lisa A.; Gao, Yu-Tang; Gaziano, J. Michael; Giles, Graham G.; Håkansson, Niclas; Horn-Ross, Pamela L.; Kirsh, Vicki A.; Linet, Martha S.; MacInnis, Robert J.; Orsini, Nicola; Park, Yikyung; Patel, Alpa V.; Purdue, Mark P.; Riboli, Elio; Robien, Kimberly; Rohan, Thomas; Sandler, Dale P.; Schairer, Catherine; Schneider, Arthur B.; Sesso, Howard D.; Shu, Xiao-Ou; Singh, Pramil N.; van den Brandt, Piet A.; Ward, Elizabeth; Weiderpass, Elisabete; White, Emily; Xiang, Yong-Bing; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Hartge, Patricia; Berrington de González, Amy

    2016-01-01

    Background: Greater height and body mass index (BMI) have been associated with an increased risk of thyroid cancer, particularly papillary carcinoma, the most common and least aggressive subtype. Few studies have evaluated these associations in relation to other, more aggressive histologic types or thyroid cancer-specific mortality. Methods: This large pooled analysis of 22 prospective studies (833,176 men and 1,260,871 women) investigated thyroid cancer incidence associated with greater height, BMI at baseline and young adulthood, and adulthood BMI gain (difference between young-adult and baseline BMI), overall and separately by sex and histological subtype using multivariable Cox proportional hazards regression models. Associations with thyroid cancer mortality were investigated in a subset of cohorts (578,922 men and 774,373 women) that contributed cause of death information. Results: During follow-up, 2996 incident thyroid cancers and 104 thyroid cancer deaths were identified. All anthropometric factors were positively associated with thyroid cancer incidence: hazard ratios (HR) [confidence intervals (CIs)] for height (per 5 cm) = 1.07 [1.04–1.10], BMI (per 5 kg/m2) = 1.06 [1.02–1.10], waist circumference (per 5 cm) = 1.03 [1.01–1.05], young-adult BMI (per 5 kg/m2) = 1.13 [1.02–1.25], and adulthood BMI gain (per 5 kg/m2) = 1.07 [1.00–1.15]. Associations for baseline BMI and waist circumference were attenuated after mutual adjustment. Baseline BMI was more strongly associated with risk in men compared with women (p = 0.04). Positive associations were observed for papillary, follicular, and anaplastic, but not medullary, thyroid carcinomas. Similar, but stronger, associations were observed for thyroid cancer mortality. Conclusion: The results suggest that greater height and excess adiposity throughout adulthood are associated with higher incidence of most major types of thyroid cancer, including the least common but

  8. Carotenoids, retinol, tocopherols, and prostate cancer risk: pooled analysis of 15 studies123

    PubMed Central

    Key, Timothy J; Appleby, Paul N; Travis, Ruth C; Albanes, Demetrius; Alberg, Anthony J; Barricarte, Aurelio; Black, Amanda; Boeing, Heiner; Bueno-de-Mesquita, H Bas; Chan, June M; Chen, Chu; Cook, Michael B; Donovan, Jenny L; Galan, Pilar; Gilbert, Rebecca; Giles, Graham G; Giovannucci, Edward; Goodman, Gary E; Goodman, Phyllis J; Gunter, Marc J; Hamdy, Freddie C; Heliövaara, Markku; Helzlsouer, Kathy J; Henderson, Brian E; Hercberg, Serge; Hoffman-Bolton, Judy; Hoover, Robert N; Johansson, Mattias; Khaw, Kay-Tee; King, Irena B; Knekt, Paul; Kolonel, Laurence N; Le Marchand, Loic; Männistö, Satu; Martin, Richard M; Meyer, Haakon E; Mondul, Alison M; Moy, Kristin A; Neal, David E; Neuhouser, Marian L; Palli, Domenico; Platz, Elizabeth A; Pouchieu, Camille; Rissanen, Harri; Schenk, Jeannette M; Severi, Gianluca; Stampfer, Meir J; Tjønneland, Anne; Touvier, Mathilde; Trichopoulou, Antonia; Weinstein, Stephanie J; Ziegler, Regina G; Zhou, Cindy Ke; Allen, Naomi E

    2015-01-01

    Background: Individual studies have suggested that circulating carotenoids, retinol, or tocopherols may be associated with prostate cancer risk, but the studies have not been large enough to provide precise estimates of associations, particularly by stage and grade of disease. Objective: The objective of this study was to conduct a pooled analysis of the associations of the concentrations of 7 carotenoids, retinol, α-tocopherol, and γ-tocopherol with risk of prostate cancer and to describe whether any associations differ by stage or grade of the disease or other factors. Design: Principal investigators of prospective studies provided individual participant data for prostate cancer cases and controls. Risk by study-specific fifths of each biomarker was estimated by using multivariable-adjusted conditional logistic regression in matched case-control sets. Results: Data were available for up to 11,239 cases (including 1654 advanced stage and 1741 aggressive) and 18,541 controls from 15 studies. Lycopene was not associated with overall risk of prostate cancer, but there was statistically significant heterogeneity by stage of disease, and the OR for aggressive disease for the highest compared with the lowest fifth of lycopene was 0.65 (95% CI: 0.46, 0.91; P-trend = 0.032). No other carotenoid was significantly associated with overall risk of prostate cancer or with risk of advanced-stage or aggressive disease. For retinol, the OR for the highest compared with the lowest fifth was 1.13 (95% CI: 1.04, 1.22; P-trend = 0.015). For α-tocopherol, the OR for the highest compared with the lowest fifth was 0.86 (95% CI: 0.78, 0.94; P-trend < 0.001), with significant heterogeneity by stage of disease; the OR for aggressive prostate cancer was 0.74 (95% CI: 0.59, 0.92; P-trend = 0.001). γ-Tocopherol was not associated with risk. Conclusions: Overall prostate cancer risk was positively associated with retinol and inversely associated with α-tocopherol, and risk of aggressive

  9. Lung cancer risk among bricklayers in a pooled analysis of case–control studies

    PubMed Central

    Consonni, Dario; Matteis, Sara De; Pesatori, Angela C; Bertazzi, Pier Alberto; Olsson, Ann C; Kromhout, Hans; Peters, Susan; Vermeulen, Roel CH; Pesch, Beate; Brüning, Thomas; Kendzia, Benjamin; Behrens, Thomas; Stücker, Isabelle; Guida, Florence; Wichmann, Heinz-Erich; Brüske, Irene; Landi, Maria Teresa; Caporaso, Neil E; Gustavsson, Per; Plato, Nils; Tse, Lap Ah; Yu, Ignatius Tak-sun; Jöckel, Karl-Heinz; Ahrens, Wolfgang; Pohlabeln, Hermann; Merletti, Franco; Richiardi, Lorenzo; Simonato, Lorenzo; Forastiere, Francesco; Siemiatycki, Jack; Parent, Marie-Élise; Tardón, Adonina; Boffetta, Paolo; Zaridze, David; Chen, Ying; Field, John K; 't Mannetje, Andrea; Pearce, Neil; McLaughlin, John; Demers, Paul; Lissowska, Jolanta; Szeszenia-Dabrowska, Neonila; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Rudnai, Peter; Fabiánová, Eleonóra; Stanescu Dumitru, Rodica; Bueno-de-Mesquita, H B(as); Schüz, Joachim; Straif, Kurt

    2015-01-01

    Bricklayers may be exposed to several lung carcinogens, including crystalline silica and asbestos. Previous studies that analyzed lung cancer risk among these workers had several study design limitations. We examined lung cancer risk among bricklayers within SYNERGY, a large international pooled analysis of case–control studies on lung cancer and the joint effects of occupational carcinogens. For men ever employed as bricklayers we estimated odds ratios (OR) and 95% confidence intervals (CI) adjusted for study center, age, lifetime smoking history and employment in occupations with exposures to known or suspected lung carcinogens. Among 15,608 cases and 18,531 controls, there were 695 cases and 469 controls who had ever worked as bricklayers (OR: 1.47; 95% CI: 1.28–1.68). In studies using population controls the OR was 1.55 (95% CI: 1.32–1.81, 540/349 cases/controls), while it was 1.24 (95% CI: 0.93–1.64, 155/120 cases/controls) in hospital-based studies. There was a clear positive trend with length of employment (p < 0.001). The relative risk was higher for squamous (OR: 1.68, 95% CI: 1.42–1.98, 309 cases) and small cell carcinomas (OR: 1.78, 95% CI: 1.44–2.20, 140 cases), than for adenocarcinoma (OR: 1.17, 95% CI: 0.95–1.43, 150 cases) (p-homogeneity: 0.0007). ORs were still elevated after additional adjustment for education and in analyses using blue collar workers as referents. This study provided robust evidence of increased lung cancer risk in bricklayers. Although non-causal explanations cannot be completely ruled out, the association is plausible in view of the potential for exposure to several carcinogens, notably crystalline silica and to a lesser extent asbestos. What's new? In their work, bricklayers can be exposed to various airborne carcinogens, including crystalline silica and asbestos. Previous studies of cancer risk have not accounted for full employment history or smoking status, and failed to establish a firm relationship between

  10. Lung cancer risk among bricklayers in a pooled analysis of case-control studies.

    PubMed

    Consonni, Dario; De Matteis, Sara; Pesatori, Angela C; Bertazzi, Pier Alberto; Olsson, Ann C; Kromhout, Hans; Peters, Susan; Vermeulen, Roel C H; Pesch, Beate; Brüning, Thomas; Kendzia, Benjamin; Behrens, Thomas; Stücker, Isabelle; Guida, Florence; Wichmann, Heinz-Erich; Brüske, Irene; Landi, Maria Teresa; Caporaso, Neil E; Gustavsson, Per; Plato, Nils; Tse, Lap Ah; Yu, Ignatius Tak-Sun; Jöckel, Karl-Heinz; Ahrens, Wolfgang; Pohlabeln, Hermann; Merletti, Franco; Richiardi, Lorenzo; Simonato, Lorenzo; Forastiere, Francesco; Siemiatycki, Jack; Parent, Marie-Élise; Tardón, Adonina; Boffetta, Paolo; Zaridze, David; Chen, Ying; Field, John K; 't Mannetje, Andrea; Pearce, Neil; McLaughlin, John; Demers, Paul; Lissowska, Jolanta; Szeszenia-Dabrowska, Neonila; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Rudnai, Peter; Fabiánová, Eleonóra; Stanescu Dumitru, Rodica; Bueno-de-Mesquita, H Bas; Schüz, Joachim; Straif, Kurt

    2015-01-15

    Bricklayers may be exposed to several lung carcinogens, including crystalline silica and asbestos. Previous studies that analyzed lung cancer risk among these workers had several study design limitations. We examined lung cancer risk among bricklayers within SYNERGY, a large international pooled analysis of case-control studies on lung cancer and the joint effects of occupational carcinogens. For men ever employed as bricklayers we estimated odds ratios (OR) and 95% confidence intervals (CI) adjusted for study center, age, lifetime smoking history and employment in occupations with exposures to known or suspected lung carcinogens. Among 15,608 cases and 18,531 controls, there were 695 cases and 469 controls who had ever worked as bricklayers (OR: 1.47; 95% CI: 1.28-1.68). In studies using population controls the OR was 1.55 (95% CI: 1.32-1.81, 540/349 cases/controls), while it was 1.24 (95% CI: 0.93-1.64, 155/120 cases/controls) in hospital-based studies. There was a clear positive trend with length of employment (p < 0.001). The relative risk was higher for squamous (OR: 1.68, 95% CI: 1.42-1.98, 309 cases) and small cell carcinomas (OR: 1.78, 95% CI: 1.44-2.20, 140 cases), than for adenocarcinoma (OR: 1.17, 95% CI: 0.95-1.43, 150 cases) (p-homogeneity: 0.0007). ORs were still elevated after additional adjustment for education and in analyses using blue collar workers as referents. This study provided robust evidence of increased lung cancer risk in bricklayers. Although non-causal explanations cannot be completely ruled out, the association is plausible in view of the potential for exposure to several carcinogens, notably crystalline silica and to a lesser extent asbestos.

  11. Fruits, vegetables and lung cancer: a pooled analysis of cohort studies.

    PubMed

    Smith-Warner, Stephanie A; Spiegelman, Donna; Yaun, Shiaw-Shyuan; Albanes, Demetrius; Beeson, W Lawrence; van den Brandt, Piet A; Feskanich, Diane; Folsom, Aaron R; Fraser, Gary E; Freudenheim, Jo L; Giovannucci, Edward; Goldbohm, R Alexandra; Graham, Saxon; Kushi, Lawrence H; Miller, Anthony B; Pietinen, Pirjo; Rohan, Thomas E; Speizer, Frank E; Willett, Walter C; Hunter, David J

    2003-12-20

    Inverse associations between fruit and vegetable consumption and lung cancer risk have been consistently reported. However, identifying the specific fruits and vegetables associated with lung cancer is difficult because the food groups and foods evaluated have varied across studies. We analyzed fruit and vegetable groups using standardized exposure and covariate definitions in 8 prospective studies. We combined study-specific relative risks (RRs) using a random effects model. In the pooled database, 3,206 incident lung cancer cases occurred among 430,281 women and men followed for up to 6-16 years across studies. Controlling for smoking habits and other lung cancer risk factors, a 16-23% reduction in lung cancer risk was observed for quintiles 2 through 5 vs. the lowest quintile of consumption for total fruits (RR = 0.77; 95% CI = 0.67-0.87 for quintile 5; p-value, test for trend < 0.001) and for total fruits and vegetables (RR = 0.79; 95% CI = 0.69-0.90; p-value, test for trend = 0.001). For the same comparison, the association was weaker for total vegetable consumption (RR = 0.88; 95% CI = 0.78-1.00; p-value, test for trend = 0.12). Associations were similar between never, past, and current smokers. These results suggest that elevated fruit and vegetable consumption is associated with a modest reduction in lung cancer risk, which is mostly attributable to fruit, not vegetable, intake. However, we cannot rule out the possibility that our results are due to residual confounding by smoking. The primary focus for reducing lung cancer incidence should continue to be smoking prevention and cessation.

  12. Circulating Leptin and Risk of Pancreatic Cancer: A Pooled Analysis From 3 Cohorts.

    PubMed

    Stolzenberg-Solomon, Rachael Z; Newton, Christina C; Silverman, Debra T; Pollak, Michael; Nogueira, Leticia M; Weinstein, Stephanie J; Albanes, Demetrius; Männistö, Satu; Jacobs, Eric J

    2015-08-01

    Adiposity is associated with pancreatic cancer; however, the underlying mechanism(s) is uncertain. Leptin is an adipokine involved in metabolic regulation, and obese individuals have higher concentrations. We conducted a pooled, nested case-control study of cohort participants from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, and the Cancer Prevention Study II Nutrition Cohort to investigate whether prediagnostic serum leptin was associated with pancreatic cancer. A total of 731 pancreatic adenocarcinoma cases that occurred between 1986 and 2010 were included (maximum follow-up, 23 years). Incidence density-selected controls (n = 909) were matched to cases by cohort, age, sex, race, and blood draw date. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. Sex-specific quintiles were based on the distribution of the controls. Overall, serum leptin was not associated with pancreatic cancer (quintile 5 vs. quintile 1: odds ratio = 1.13, 95% confidence interval: 0.75, 1.71; Ptrend = 0.38). There was a significant interaction by follow-up time (P = 0.003), such that elevated risk was apparent only during follow-up of more than 10 years after blood draw (quintile 5 vs. quintile 1: odds ratio = 2.55, 95% confidence interval: 1.23, 5.27; Ptrend = 0.004). Our results support an association between increasing leptin concentration and pancreatic cancer; however, long follow-up is necessary to observe the relationship. Subclinical disease may explain the lack of association during early follow-up.

  13. Circulating Leptin and Risk of Pancreatic Cancer: A Pooled Analysis From 3 Cohorts

    PubMed Central

    Stolzenberg-Solomon, Rachael Z.; Newton, Christina C.; Silverman, Debra T.; Pollak, Michael; Nogueira, Leticia M.; Weinstein, Stephanie J.; Albanes, Demetrius; Männistö, Satu; Jacobs, Eric J.

    2015-01-01

    Adiposity is associated with pancreatic cancer; however, the underlying mechanism(s) is uncertain. Leptin is an adipokine involved in metabolic regulation, and obese individuals have higher concentrations. We conducted a pooled, nested case-control study of cohort participants from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, and the Cancer Prevention Study II Nutrition Cohort to investigate whether prediagnostic serum leptin was associated with pancreatic cancer. A total of 731 pancreatic adenocarcinoma cases that occurred between 1986 and 2010 were included (maximum follow-up, 23 years). Incidence density–selected controls (n = 909) were matched to cases by cohort, age, sex, race, and blood draw date. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. Sex-specific quintiles were based on the distribution of the controls. Overall, serum leptin was not associated with pancreatic cancer (quintile 5 vs. quintile 1: odds ratio = 1.13, 95% confidence interval: 0.75, 1.71; Ptrend = 0.38). There was a significant interaction by follow-up time (P = 0.003), such that elevated risk was apparent only during follow-up of more than 10 years after blood draw (quintile 5 vs. quintile 1: odds ratio = 2.55, 95% confidence interval: 1.23, 5.27; Ptrend = 0.004). Our results support an association between increasing leptin concentration and pancreatic cancer; however, long follow-up is necessary to observe the relationship. Subclinical disease may explain the lack of association during early follow-up. PMID:26085045

  14. Asian American Women in California: A Pooled Analysis of Predictors for Breast and Cervical Cancer Screening

    PubMed Central

    Breen, Nancy; Liu, Benmei; Lee, Richard; Kagawa-Singer, Marjorie

    2015-01-01

    Objectives. We examined patterns of cervical and breast cancer screening among Asian American women in California and assessed their screening trends over time. Methods. We pooled weighted data from 5 cycles of the California Health Interview Survey (2001, 2003, 2005, 2007, 2009) to examine breast and cervical cancer screening trends and predictors among 6 Asian nationalities. We calculated descriptive statistics, bivariate associations, multivariate logistic regressions, predictive margins, and 95% confidence intervals. Results. Multivariate analyses indicated that Papanicolaou test rates did not significantly change over time (77.9% in 2001 vs 81.2% in 2007), but mammography receipt increased among Asian American women overall (75.6% in 2001 vs 81.8% in 2009). Length of time in the United States was associated with increased breast and cervical cancer screening among all nationalities. Sociodemographic and health care access factors had varied effects, with education and insurance coverage significantly predicting screening for certain groups. Overall, we observed striking variation by nationality. Conclusions. Our results underscore the need for intervention and policy efforts that are targeted to specific Asian nationalities, recent immigrants, and individuals without health care access to increase screening rates among Asian women in California. PMID:25521898

  15. Red meat intake, NAT2, and risk of colorectal cancer: A pooled analysis of 11 studies

    PubMed Central

    Ananthakrishnan, Ashwin N.; Du, Mengmeng; Berndt, Sonja I.; Brenner, Hermann; Caan, Bette J.; Casey, Graham; Chang-Claude, Jenny; Duggan, David; Fuchs, Charles S.; Gallinger, Steven; Giovannucci, Edward L.; Harrison, Tabitha A.; Hayes, Richard B.; Hoffmeister, Michael; Hopper, John L.; Hou, Lifang; Hsu, Li; Jenkins, Mark A.; Kraft, Peter; Ma, Jing; Nan, Hongmei; Newcomb, Polly A.; Ogino, Shuji; Potter, John D.; Seminara, Daniela; Slattery, Martha L.; Thornquist, Mark; White, Emily; Wu, Kana; Peters, Ulrike; Chan, Andrew T.

    2014-01-01

    Background Red meat intake has been associated with risk of colorectal cancer (CRC), potentially mediated through heterocyclic amines. The metabolic efficiency of N-acetyltransferase 2 (NAT2) required for the metabolic activation of such amines is influenced by genetic variation. The interaction between red meat intake, NAT2 genotype, and CRC has been inconsistently reported. Methods We used pooled individual-level data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Red meat intake was collected by each study. We inferred NAT2 phenotype based on polymorphism at rs1495741, highly predictive of enzyme activity. Interaction was assessed using multiplicative interaction terms in multivariate-adjusted models. Results From 11 studies, 8,290 CRC cases and 9,115 controls were included. The highest quartile of red meat intake was associated with increased risk of CRC compared to the lowest quartile (OR 1.41, 95%CI 1.29 – 1.55). However, a significant association was observed only for studies with retrospective diet data, not for studies with diet prospectively assessed before cancer diagnosis. Combining all studies, high red meat intake was similarly associated with CRC in those with a rapid/intermediate NAT2 genotype (OR 1.38, 95%CI 1.20 – 1.59) as with a slow genotype (OR 1.43, 95%CI 1.28 – 1.61) (p- interaction=0.9). Conclusion We found that high red meat intake was associated with increased risk of CRC only from retrospective case-control studies and not modified by NAT2 enzyme activity. Impact Our results suggest no interaction between NAT2 genotype and red-meat intake in mediating risk of CRC. PMID:25342387

  16. Lung Cancer Risk Among Hairdressers: A Pooled Analysis of Case-Control Studies Conducted Between 1985 and 2010

    PubMed Central

    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

    2013-01-01

    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

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

    PubMed

    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

    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.

  18. Pooled Analysis of Phosphatidylinositol 3-kinase Pathway Variants and Risk of Prostate Cancer

    PubMed Central

    Koutros, Stella; Schumacher, Fredrick R.; Hayes, Richard B.; Ma, Jing; Huang, Wen-Yi; Albanes, Demetrius; Canzian, Federico; Chanock, Stephen J.; Crawford, E. David; Diver, W. Ryan; Feigelson, Heather Spencer; Giovanucci, Edward; Haiman, Christopher A.; Henderson, Brian E.; Hunter, David J.; Kaaks, Rudolf; Kolonel, Laurence N.; Kraft, Peter; Le Marchand, Loïc; Riboli, Elio; Siddiq, Afshan; Stampfer, Mier J.; Stram, Daniel O.; Thomas, Gilles; Travis, Ruth C.; Thun, Michael J.; Yeager, Meredith; Berndt, Sonja I.

    2010-01-01

    The phosphatidylinositol 3-kinase (PI3K) pathway regulates various cellular processes, including cellular proliferation and intracellular trafficking and may impact prostate carcinogenesis. Thus, we explored the association between single nucleotide polymorphisms (SNPs) in PI3K genes and prostate cancer. Pooled data from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium were examined for associations between 89 SNPs in PI3K genes (PIK3C2B, PIK3AP1, PIK3C2A, PIK3CD, and PIK3R3) and prostate cancer risk in 8,309 cases and 9,286 controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression. SNP rs7556371 in PIK3C2B was significantly associated with prostate cancer risk (ORper allele=1.08 (95% CI: 1.03, 1.14), p-trend = 0.0017) after adjustment for multiple testing (Padj=0.024). Simultaneous adjustment of rs7556371 for nearby SNPs strengthened the association (ORper allele=1.21 (95% CI: 1.09, 1.34); p-trend =0.0003). The adjusted association was stronger for men who were diagnosed before 65 years (ORper allele= 1.47 (95% CI: 1.20, 1.79), p-trend = 0.0001) or had a family history (ORper allele= 1.57 (95% CI: 1.11, 2.23), p-trend = 0.0114), and was strongest in those with both characteristics (ORper allele= 2.31 (95% CI: 1.07, 5.07), p-interaction = 0.005). Increased risks were observed among men in the top tertile of circulating insulin like growth factor-1 (IGF-1) levels (ORper allele= 1.46 (95% CI: 1.04, 2.06), p-trend=0.075). No differences were observed with disease aggressiveness (≥8/stage T3/T4/fatal). In conclusion, we observed a significant association between PIK3C2B and prostate cancer risk, especially for familial, early onset disease, which may be attributable to IGF-dependent PI3K signaling. PMID:20197460

  19. Thyroid cancer after exposure to external radiation: A pooled analysis of seven studies

    SciTech Connect

    Ron, E.; Lubin, J.H.; Pottern, L.M.; Tucker, M.A.; Boice, J.D. Jr.; Shore, R.E.; Mabuchi, Kiyohiko; Modan, B.; Schneider, A.B.

    1995-03-01

    The thyroid gland of children is especially vulnerable to the carcinogenic action of ionizing radiation. To provide insights into various modifying influences on risk, seven major studies with organ doses to individual subjects were evaluated. Five cohort studies (atomic bomb survivors, children treated for tinea capitis, two studies of children irradiated for enlarged tonsils, and infants irradiated for an enlarged thymus gland) and two case-control studies (patients with cervical cancer and childhood cancer) were studied. The combined studies include almost 120,000 people (approximately 58,000 exposed to a wide range of doses and 61,000 nonexposed subjects), nearly 700 thyroid cancers and 3,000,000 person years of follow-up. For persons exposed to radiation before age 15 years, linearity best described the dose response, even down to 0.10 Gy. At the highest doses (>10 Gy), associated with cancer therapy, there appeared to be a decrease or leveling of risk. For childhood exposures, the pooled excess relative risk per Gy (ERR/Gy) was 7.7 (95% CI = 2.1, 28.7) and the excess absolute risk per 10{sup 4} PY Gy (EAR/10{sup 4} PY Gy) was 4.4 (95% CI = 1.9, 10.1). The attributable risk percent (AR%) at 1 Gy was 88%. However, these summary estimates were affected strongly by age at exposure even within this limited age range. The ERR was greater (P = 0.07) for females than males, but the findings from the individual studies were not consistent. The EAR was higher among women, reflecting their higher rate of naturally occurring thyroid cancer. The distribution of ERR over time followed neither a simple multiplicative nor an additive pattern in relation to background occurrence. Only two cases were seen within 5 years of exposure. The ERR began to decline about 30 years after exposure but was still elevated at 40 years. Risk also decreased significantly with increasing age at exposure, with little risk apparent after age 20 years. 56 refs., 5 figs., 8 tabs.

  20. Allergies and risk of pancreatic cancer: a pooled analysis from the Pancreatic Cancer Case-Control Consortium.

    PubMed

    Olson, Sara H; Hsu, Meier; Satagopan, Jaya M; Maisonneuve, Patrick; Silverman, Debra T; Lucenteforte, Ersilia; Anderson, Kristin E; Borgida, Ayelet; Bracci, Paige M; Bueno-de-Mesquita, H Bas; Cotterchio, Michelle; Dai, Qi; Duell, Eric J; Fontham, Elizabeth H; Gallinger, Steven; Holly, Elizabeth A; Ji, Bu-Tian; Kurtz, Robert C; La Vecchia, Carlo; Lowenfels, Albert B; Luckett, Brian; Ludwig, Emmy; Petersen, Gloria M; Polesel, Jerry; Seminara, Daniela; Strayer, Lori; Talamini, Renato

    2013-09-01

    In order to quantify the risk of pancreatic cancer associated with history of any allergy and specific allergies, to investigate differences in the association with risk according to age, gender, smoking status, or body mass index, and to study the influence of age at onset, we pooled data from 10 case-control studies. In total, there were 3,567 cases and 9,145 controls. Study-specific odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression adjusted for age, gender, smoking status, and body mass index. Between-study heterogeneity was assessed by using the Cochran Q statistic. Study-specific odds ratios were pooled by using a random-effects model. The odds ratio for any allergy was 0.79 (95% confidence interval (CI): 0.62, 1.00) with heterogeneity among studies (P < 0.001). Heterogeneity was attributable to one study; with that study excluded, the pooled odds ratio was 0.73 (95% CI: 0.64, 0.84) (Pheterogeneity = 0.23). Hay fever (odds ratio = 0.74, 95% CI: 0.56, 0.96) and allergy to animals (odds ratio = 0.62, 95% CI: 0.41, 0.94) were related to lower risk, while there was no statistically significant association with other allergies or asthma. There were no major differences among subgroups defined by age, gender, smoking status, or body mass index. Older age at onset of allergies was slightly more protective than earlier age.

  1. Anthropometric Measures, Body Mass Index and Pancreatic Cancer: a Pooled Analysis from the Pancreatic Cancer Cohort Consortium (PanScan)

    PubMed Central

    Arslan, Alan A.; Helzlsouer, Kathy J.; Kooperberg, Charles; Shu, Xiao-Ou; Steplowski, Emily; Bueno-de-Mesquita, H. Bas; Fuchs, Charles S.; Gross, Myron D.; Jacobs, Eric J.; LaCroix, Andrea Z.; Petersen, Gloria M.; Stolzenberg-Solomon, Rachael Z.; Zheng, Wei; Albanes, Demetrius; Amundadottir, Laufey; Bamlet, William R.; Barricarte, Aurelio; Bingham, Sheila A.; Boeing, Heiner; Boutron-Ruault, Marie-Christine; Buring, Julie E.; Chanock, Stephen J.; Clipp, Sandra; Gaziano, J. Michael; Giovannucci, Edward L.; Hankinson, Susan E.; Hartge, Patricia; Hoover, Robert N.; Hunter, David J.; Hutchinson, Amy; Jacobs, Kevin B.; Kraft, Peter; Lynch, Shannon M.; Manjer, Jonas; Manson, JoAnn E.; McTiernan, Anne; McWilliams, Robert R.; Mendelsohn, Julie B.; Michaud, Dominique S.; Palli, Domenico; Rohan, Thomas E.; Slimani, Nadia; Thomas, Gilles; Tjønneland, Anne; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Virtamo, Jarmo; Wolpin, Brian M.; Yu, Kai; Zeleniuch-Jacquotte, Anne; Patel, Alpa V.

    2010-01-01

    Background Pooled data were analyzed from the NCI Pancreatic Cancer Cohort Consortium (PanScan) to study the association between pre-diagnostic anthropometric measures and risk of pancreatic cancer. Methods PanScan applied a nested case-control study design and included 2,170 cases and 2,209 controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression for cohort-specific quartiles of body mass index (BMI), weight, height, waist circumference, and waist-to-hip ratio (WHR), as well as conventional BMI categories: underweight (<18.5 kg/m2), normal (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), obese (30.0-34.9 kg/m2), and severely obese (≥35.0 kg/m2). Models were adjusted for potential confounders. Results Among all subjects, a positive association between increasing BMI and risk of pancreatic cancer was observed (adjusted OR for the highest vs. lowest BMI quartile = 1.33, 95% CI = 1.12-1.58, Ptrend < 0.001). Among men, the adjusted OR for pancreatic cancer for the highest vs. lowest quartile of BMI was 1.33 (95% CI = 1.04-1.69, Ptrend <0.03). Among women, the adjusted OR for pancreatic cancer for the highest quartile of BMI was 1.34 (95% CI = 1.05-1.70, Ptrend = 0.01). Increased WHR was associated with increased risk of pancreatic cancer among women (adjusted OR for the highest vs. lowest quartile = 1.87, 95% CI = 1.31-2.69, Ptrend = 0.003) but less so in men. Conclusion The findings provide strong support for a positive association between BMI and pancreatic cancer risk. In addition, centralized fat distribution may increase pancreatic cancer risk, especially in women. PMID:20458087

  2. Enzalutamide after docetaxel and abiraterone acetate treatment in prostate cancer: a pooled analysis of 10 case series.

    PubMed

    Petrelli, Fausto; Coinu, Andrea; Borgonovo, Karen; Cabiddu, Mary; Ghilardi, Mara; Lonati, Veronica; Barni, Sandro

    2015-06-01

    There are emerging data regarding the therapeutic benefit of enzalutamide (ENZ) in the treatment of patients with castration-resistant prostate cancer (CRPC) pretreated with docetaxel and abiraterone acetate. To systematically evaluate the evidence regarding the efficacy of ENZ after docetaxel and abiraterone acetate treatment in CRPC, we performed a pooled analysis of all available studies. Studies that enrolled CRPC patients treated with ENZ after docetaxel and abiraterone acetate treatment 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 (RR) and the 95% confidence interval (CI). Pooled median progression-free survival (PFS) and overall survival (OS), weighted on the number of patients of each of the selected trials, were also calculated. We tested for significant heterogeneity using the Cochran χ(2) test and the I(2) index. Ten publications were selected for inclusion in this analysis. The number of included patients was 536 (range, 23-137). Overall, the pooled RR (reduction of prostate-specific antigen by > 50%) was 22.9% (95% CI, 19.3%-27.1%). The median PFS was 3.1 months (range, 1.4-4.9 months). The median OS was 8.3 months (range, 2.85-10.6 months). In patients sensitive to abiraterone, the RR to ENZ was 35% (95% CI, 27.2%-43.7%). ENZ is moderately effective in CRPC patients who were pretreated with chemotherapy and abiraterone acetate. The greater benefit is confined in patients who responded to abiraterone acetate. Further prospective evaluations of ENZ are required and the mechanisms of resistance have to be better understood.

  3. Central adiposity, obesity during early adulthood, and pancreatic cancer mortality in a pooled analysis of cohort studies

    PubMed Central

    Genkinger, J. M.; Kitahara, C. M.; Bernstein, L.; Berrington de Gonzalez, A.; Brotzman, M.; Elena, J. W.; Giles, G. G.; Hartge, P.; Singh, P. N.; Stolzenberg-Solomon, R. Z.; Weiderpass, E.; Adami, H.-O.; Anderson, K. E.; Beane-Freeman, L. E.; Buring, J. E.; Fraser, G. E.; Fuchs, C. S.; Gapstur, S. M.; Gaziano, J. M.; Helzlsouer, K. J.; Lacey, J. V.; Linet, M. S.; Liu, J. J.; Park, Y.; Peters, U.; Purdue, M. P.; Robien, K.; Schairer, C.; Sesso, H. D.; Visvanathan, K.; White, E.; Wolk, A.; Wolpin, B. M.; Zeleniuch-Jacquotte, A.; Jacobs, E. J.

    2015-01-01

    Background Body mass index (BMI), a measure of obesity typically assessed in middle age or later, is known to be positively associated with pancreatic cancer. However, little evidence exists regarding the influence of central adiposity, a high BMI during early adulthood, and weight gain after early adulthood on pancreatic cancer risk. Design We conducted a pooled analysis of individual-level data from 20 prospective cohort studies in the National Cancer Institute BMI and Mortality Cohort Consortium to examine the association of pancreatic cancer mortality with measures of central adiposity (e.g. waist circumference; n = 647 478; 1947 pancreatic cancer deaths), BMI during early adulthood (ages 18–21 years) and BMI change between early adulthood and cohort enrollment, mostly in middle age or later (n = 1 096 492; 3223 pancreatic cancer deaths). Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. Results Higher waist-to-hip ratio (HR = 1.09, 95% CI 1.02–1.17 per 0.1 increment) and waist circumference (HR = 1.07, 95% CI 1.00–1.14 per 10 cm) were associated with increased risk of pancreatic cancer mortality, even when adjusted for BMI at baseline. BMI during early adulthood was associated with increased pancreatic cancer mortality (HR = 1.18, 95% CI 1.11–1.25 per 5 kg/m2), with increased risk observed in both overweight and obese individuals (compared with BMI of 21.0 to <23 kg/m2, HR = 1.36, 95% CI 1.20–1.55 for BMI 25.0 < 27.5 kg/m2, HR = 1.48, 95% CI 1.20–1.84 for BMI 27.5 to <30 kg/m2, HR = 1.43, 95% CI 1.11–1.85 for BMI ≥30 kg/m2). BMI gain after early adulthood, adjusted for early adult BMI, was less strongly associated with pancreatic cancer mortality (HR = 1.05, 95% CI 1.01–1.10 per 5 kg/m2). Conclusions Our results support an association between pancreatic cancer mortality and central obesity, independent of BMI, and also suggest that being overweight or obese

  4. Estrogen receptor beta rs1271572 polymorphism and invasive ovarian carcinoma risk: pooled analysis within the Ovarian Cancer Association Consortium.

    PubMed

    Lurie, Galina; Wilkens, Lynne R; Thompson, Pamela J; Shvetsov, Yurii B; Matsuno, Rayna K; Carney, Michael E; Palmieri, Rachel T; Wu, Anna H; Pike, Malcolm C; Pearce, Celeste L; Menon, Usha; Gentry-Maharaj, Aleksandra; Gayther, Simon A; Ramus, Susan J; Whittemore, Alice S; McGuire, Valerie; Sieh, Weiva; Pharoah, Paul D P; Song, Honglin; Gronwald, Jacek; Jakubowska, Anna; Cybulski, Cezary; Lubinski, Jan; Schildkraut, Joellen M; Berchuck, Andrew; Krüger Kjær, Susanne; Høgdall, Estrid; Fasching, Peter A; Beckmann, Matthias W; Ekici, Arif B; Hein, Alexander; Chenevix-Trench, Georgia; Webb, Penelope M; Beesley, Jonathan; Goodman, Marc T

    2011-01-01

    The association of ovarian carcinoma risk with the polymorphism rs1271572 in the estrogen receptor beta (ESR2) gene was examined in 4946 women with primary invasive ovarian carcinoma and 6582 controls in a pooled analysis of ten case-control studies within the Ovarian Cancer Association Consortium (OCAC). All participants were non-Hispanic white women. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression adjusted for site and age. Women with the TT genotype were at increased risk of ovarian carcinoma compared to carriers of the G allele (OR = 1.10; 95%; CI: 1.01-1.21; p = 0.04); the OR was 1.09 (CI: 0.99-1.20; p = 0.07) after excluding data from the center (Hawaii) that nominated this SNP for OCAC genotyping A stronger association of rs1271572 TT versus GT/GG with risk was observed among women aged ≤50 years versus older women (OR = 1.35; CI: 1.12-1.62; p = 0.002; p for interaction = 0.02) that remained statistically significant after excluding Hawaii data (OR = 1.34; CI: 1.11-1.61; p = 0.009). No heterogeneity of the association was observed by study, menopausal status, gravidity, parity, use of contraceptive or menopausal hormones, tumor histological type, or stage at diagnosis. This pooled analysis suggests that rs1271572 might influence the risk of ovarian cancer, in particular among younger women.

  5. Associations of Breast Cancer Risk Factors With Tumor Subtypes: A Pooled Analysis From the Breast Cancer Association Consortium Studies

    PubMed Central

    Chang-Claude, Jenny; Goode, Ellen L.; Couch, Fergus J.; Nevanlinna, Heli; Milne, Roger L.; Gaudet, Mia; Schmidt, Marjanka K.; Broeks, Annegien; Cox, Angela; Fasching, Peter A.; Hein, Rebecca; Spurdle, Amanda B.; Blows, Fiona; Driver, Kristy; Flesch-Janys, Dieter; Heinz, Judith; Sinn, Peter; Vrieling, Alina; Heikkinen, Tuomas; Aittomäki, Kristiina; Heikkilä, Päivi; Blomqvist, Carl; Lissowska, Jolanta; Peplonska, Beata; Chanock, Stephen; Figueroa, Jonine; Brinton, Louise; Hall, Per; Czene, Kamila; Humphreys, Keith; Darabi, Hatef; Liu, Jianjun; Van ‘t Veer, Laura J.; van Leeuwen, Flora E.; Andrulis, Irene L.; Glendon, Gord; Knight, Julia A.; Mulligan, Anna Marie; O’Malley, Frances P.; Weerasooriya, Nayana; John, Esther M.; Beckmann, Matthias W.; Hartmann, Arndt; Weihbrecht, Sebastian B.; Wachter, David L.; Jud, Sebastian M.; Loehberg, Christian R.; Baglietto, Laura; English, Dallas R.; Giles, Graham G.; McLean, Catriona A.; Severi, Gianluca; Lambrechts, Diether; Vandorpe, Thijs; Weltens, Caroline; Paridaens, Robert; Smeets, Ann; Neven, Patrick; Wildiers, Hans; Wang, Xianshu; Olson, Janet E.; Cafourek, Victoria; Fredericksen, Zachary; Kosel, Matthew; Vachon, Celine; Cramp, Helen E.; Connley, Daniel; Cross, Simon S.; Balasubramanian, Sabapathy P.; Reed, Malcolm W. R.; Dörk, Thilo; Bremer, Michael; Meyer, Andreas; Karstens, Johann H.; Ay, Aysun; Park-Simon, Tjoung-Won; Hillemanns, Peter; Arias Pérez, Jose Ignacio; Rodríguez, Primitiva Menéndez; Zamora, Pilar; Benítez, Javier; Ko, Yon-Dschun; Fischer, Hans-Peter; Hamann, Ute; Pesch, Beate; Brüning, Thomas; Justenhoven, Christina; Brauch, Hiltrud; Eccles, Diana M.; Tapper, William J.; Gerty, Sue M.; Sawyer, Elinor J.; Tomlinson, Ian P.; Jones, Angela; Kerin, Michael; Miller, Nicola; McInerney, Niall; Anton-Culver, Hoda; Ziogas, Argyrios; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Chen, Shou-Tung; Hsu, Giu-Cheng; Haiman, Christopher A.; Henderson, Brian E.; Le Marchand, Loic; Kolonel, Laurence N.; Lindblom, Annika; Margolin, Sara; Jakubowska, Anna; Lubiński, Jan; Huzarski, Tomasz; Byrski, Tomasz; Górski, Bohdan; Gronwald, Jacek; Hooning, Maartje J.; Hollestelle, Antoinette; van den Ouweland, Ans M. W.; Jager, Agnes; Kriege, Mieke; Tilanus-Linthorst, Madeleine M. A.; Collée, Margriet; Wang-Gohrke, Shan; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Mononen, Kari; Grip, Mervi; Hirvikoski, Pasi; Winqvist, Robert; Mannermaa, Arto; Kosma, Veli-Matti; Kauppinen, Jaana; Kataja, Vesa; Auvinen, Päivi; Soini, Ylermi; Sironen, Reijo; Bojesen, Stig E.; Dynnes Ørsted, David; Kaur-Knudsen, Diljit; Flyger, Henrik; Nordestgaard, Børge G.; Holland, Helene; Chenevix-Trench, Georgia; Manoukian, Siranoush; Barile, Monica; Radice, Paolo; Hankinson, Susan E.; Hunter, David J.; Tamimi, Rulla; Sangrajrang, Suleeporn; Brennan, Paul; McKay, James; Odefrey, Fabrice; Gaborieau, Valerie; Devilee, Peter; Huijts, P.E.A.; Tollenaar, RAEM.; Seynaeve, C.; Dite, Gillian S.; Apicella, Carmel; Hopper, John L.; Hammet, Fleur; Tsimiklis, Helen; Smith, Letitia D.; Southey, Melissa C.; Humphreys, Manjeet K.; Easton, Douglas; Pharoah, Paul; Sherman, Mark E.; Garcia-Closas, Montserrat

    2011-01-01

    Background Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors. Methods We pooled tumor marker and epidemiological risk factor data from 35 568 invasive breast cancer case patients from 34 studies participating in the Breast Cancer Association Consortium. Logistic regression models were used in case–case analyses to estimate associations between epidemiological risk factors and tumor subtypes, and case–control analyses to estimate associations between epidemiological risk factors and the risk of developing specific tumor subtypes in 12 population-based studies. All statistical tests were two-sided. Results In case–case analyses, of the epidemiological risk factors examined, early age at menarche (≤12 years) was less frequent in case patients with PR− than PR+ tumors (P = .001). Nulliparity (P = 3 × 10−6) and increasing age at first birth (P = 2 × 10−9) were less frequent in ER− than in ER+ tumors. Obesity (body mass index [BMI] ≥ 30 kg/m2) in younger women (≤50 years) was more frequent in ER−/PR− than in ER+/PR+ tumors (P = 1 × 10−7), whereas obesity in older women (>50 years) was less frequent in PR− than in PR+ tumors (P = 6 × 10−4). The triple-negative (ER−/PR−/HER2−) or core basal phenotype (CBP; triple-negative and cytokeratins [CK]5/6+ and/or epidermal growth factor receptor [EGFR]+) accounted for much of the heterogeneity in parity-related variables and BMI in younger women. Case–control analyses showed that nulliparity, increasing age at first birth, and obesity in younger women showed the expected associations with the risk of ER+ or PR+ tumors but not triple-negative (nulliparity vs parity, odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.75 to 1.19, P = .61; 5-year increase in age at first full-term birth, OR = 0.95, 95% CI = 0.86 to 1.05, P = .34; obesity in younger women, OR = 1.36, 95

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

    PubMed

    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

    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.

  7. Welding and Lung Cancer in a Pooled Analysis of Case-Control Studies

    PubMed Central

    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

    2013-01-01

    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

  8. Stomach Cancer Following Hodgkin Lymphoma, Testicular Cancer and Cervical Cancer: A Pooled Analysis of Three International Studies with a Focus on Radiation Effects.

    PubMed

    Gilbert, Ethel S; Curtis, Rochelle E; Hauptmann, Michael; Kleinerman, Ruth A; Lynch, Charles F; Stovall, Marilyn; Smith, Susan A; Weathers, Rita; Andersson, Michael; Dores, Graça M; Fraumeni, Joseph F; Fossa, Sophie D; Hall, Per; Hodgson, David C; Holowaty, Eric J; Joensuu, Heikki; Johannesen, Tom B; Langmark, Froydis; Kaijser, Magnus; Pukkala, Eero; Rajaraman, Preetha; Storm, Hans H; Vaalavirta, Leila; van den Belt-Dusebout, Alexandra W; Aleman, Berthe M; Travis, Lois B; Morton, Lindsay M; van Leeuwen, Flora E

    2017-02-01

    To further understand the risk of stomach cancer after fractionated high-dose radiotherapy, we pooled individual-level data from three recent stomach cancer case-control studies. These studies were nested in cohorts of five-year survivors of first primary Hodgkin lymphoma (HL), testicular cancer (TC) or cervical cancer (CX) from seven countries. Detailed data were abstracted from patient records and radiation doses were reconstructed to the site of the stomach cancer for cases and to the corresponding sites for matched controls. Among 327 cases and 678 controls, mean doses to the stomach were 15.3 Gy, 24.7 Gy and 1.9 Gy, respectively, for Hodgkin lymphoma, testicular cancer and cervical cancer survivors, with an overall mean dose of 10.3 Gy. Risk increased with increasing radiation dose to the stomach cancer site (P < 0.001) with no evidence of nonlinearity or of a downturn at the highest doses (≥35 Gy). The pooled excess odds ratio per Gy (EOR/Gy) was 0.091 [95% confidence interval (CI): 0.036-0.20] with estimates of 0.049 (95% CI: 0.007-0.16) for Hodgkin lymphoma, 0.27 (95% CI: 0.054-1.44) for testicular cancer and 0.096 (95% CI: -0.002-0.39) for cervical cancer (P homogeneity = 0.25). The EOR/Gy increased with time since exposure (P trend = 0.004), with an EOR/Gy of 0.38 (95% CI: 0.12-1.04) for stomach cancer occurring ≥20 years postirradiation corresponding to odds ratios of 4.8 and 10.5 at radiation doses to the stomach of 10 and 25 Gy, respectively. Of 111 stomach cancers occurring ≥20 years after radiotherapy, 63.8 (57%) could be attributed to radiotherapy. Our findings differ from those based on Japanese atomic-bomb survivors, where the overall EOR/Gy was higher and where there was no evidence of an increase with time since exposure. By pooling data from three studies, we demonstrated a clear increase in stomach cancer risk over a wide range of doses from fractionated radiotherapy with the highest risks occurring many years after exposure. These

  9. Aspirin, Nonaspirin Nonsteroidal Anti-inflammatory Drug, and Acetaminophen Use and Risk of Invasive Epithelial Ovarian Cancer: A Pooled Analysis in the Ovarian Cancer Association Consortium

    PubMed Central

    2014-01-01

    Background Regular aspirin use is associated with reduced risk of several malignancies. Epidemiologic studies analyzing aspirin, nonaspirin nonsteroidal anti-inflammatory drug (NSAID), and acetaminophen use and ovarian cancer risk have been inconclusive. Methods We analyzed pooled data from 12 population-based case–control studies of ovarian cancer, including 7776 case patients and 11843 control subjects accrued between 1992 and 2007. Odds ratios (ORs) for associations of medication use with invasive epithelial ovarian cancer were estimated in individual studies using logistic regression and combined using random effects meta-analysis. Associations between frequency, dose, and duration of analgesic use and risk of ovarian cancer were also assessed. All statistical tests were two-sided. Results Aspirin use was associated with a reduced risk of ovarian cancer (OR = 0.91; 95% confidence interval [CI] = 0.84 to 0.99). Results were similar but not statistically significant for nonaspirin NSAIDs, and there was no association with acetaminophen. In seven studies with frequency data, the reduced risk was strongest among daily aspirin users (OR = 0.80; 95% CI = 0.67 to 0.96). In three studies with dose information, the reduced risk was strongest among users of low dose (<100mg) aspirin (OR = 0.66; 95% CI = 0.53 to 0.83), whereas for nonaspirin NSAIDs, the reduced risk was strongest for high dose (≥500mg) usage (OR = 0.76; 95% CI = 0.64 to 0.91). Conclusions Aspirin use was associated with a reduced risk of ovarian cancer, especially among daily users of low-dose aspirin. These findings suggest that the same aspirin regimen proven to protect against cardiovascular events and several cancers could reduce the risk of ovarian cancer 20% to 34% depending on frequency and dose of use. PMID:24503200

  10. Radiation effects on breast cancer risk: a pooled analysis of eight cohorts.

    PubMed

    Preston, Dale L; Mattsson, Anders; Holmberg, Erik; Shore, Roy; Hildreth, Nancy G; Boice, John D

    2002-08-01

    Breast cancer incidence rates after radiation exposure in eight large cohorts are described and compared. The nature of the exposures varies appreciably, ranging from a single or a small number of high-dose-rate exposures (Japanese atomic bomb survivors, U.S. acute post-partum mastitis patients, Swedish benign breast disease patients, and U.S. infants with thymic enlargement) to highly fractionated high-dose-rate exposures (two U.S. tuberculosis cohorts) and protracted low-dose-rate exposure (two Swedish skin hemangioma cohorts). There were 1,502 breast cancers among 77,527 women (about 35,000 of whom were exposed) with 1.8 million woman-years of follow-up. The excess risk depends linearly on dose with a downturn at high doses. No simple unified summary model adequately describes the excess risks in all groups. Excess risks for the thymus, tuberculosis, and atomic bomb survivor cohorts have similar temporal patterns, depending on attained age for relative risk models and on both attained age and age at exposure for excess rate models. Excess rates were similar in these cohorts, whereas, related in part to the low breast cancer background rates for Japanese women, the excess relative risk per unit dose in the bomb survivors was four times that in the tuberculosis or thymus cohorts. Excess rates were higher for the mastitis and benign breast disease cohorts. The hemangioma cohorts showed lower excess risks suggesting ameliorating dose-rate effects for protracted low-dose-rate exposures. For comparable ages at exposure (approximately 0.5 years), the excess risk in the hemangioma cohorts was about one-seventh that in the thymus cohort, whose members received acute high-dose-rate exposures. The results support the linearity of the radiation dose response for breast cancer, highlight the importance of age and age at exposure on the risks, and suggest a similarity in risks for acute and fractionated high-dose-rate exposures with much smaller effects from low

  11. Somatic mutation spectrum of non-small cell lung cancer in African Americans: a pooled analysis

    PubMed Central

    Araujo, Luiz H.; Lammers, Philip E.; Matthews-Smith, Velmalia; Eisenberg, Rosana; Gonzalez, Adriana; Schwartz, Ann G.; Timmers, Cynthia; Shilo, Konstantin; Zhao, Weiqiang; Natarajan, Thanemozhi G.; Zhang, Jianying; Yilmaz, Ayse Selen; Liu, Tom; Coombes, Kevin; Carbone, David P.

    2015-01-01

    Introduction The mutational profile of non-small cell lung cancer (NSCLC) has become an important tool in tailoring therapy to patients, with clear differences according to the population of origin. African Americans have higher lung cancer incidence and mortality than Caucasians, yet discrepant results have been reported regarding the frequency of somatic driver mutations. We hypothesized that NSCLC has a distinct mutational profile in this group. Methods We collected NSCLC samples resected from self-reported African Americans in five sites from Tennessee, Michigan, and Ohio. Gene mutations were assessed by either SNaPshot or next generation sequencing, and ALK translocations were evaluated by fluorescence in situ hybridization. Results Two hundred sixty patients were included, mostly males (62.3%) and smokers (86.6%). Eighty-one samples (31.2%) were squamous cell carcinomas. The most frequently mutated genes were KRAS (15.4%), EGFR (5.0%), PIK3CA (0.8%), BRAF, NRAS, ERBB2, and AKT1 (0.4% each). ALK translocations were detected in 2 non-squamous tumors (1.7%), totaling 61 cases (23.5%) with driver oncogenic alterations. Among 179 non-squamous samples, 54 (30.2%) presented a driver alteration. The frequency of driver alterations altogether was lower than that reported in Caucasians, while no difference was detected in either EGFR or KRAS mutations. Overall survival was longer among patients with EGFR mutations. Conclusions We demonstrated that NSCLC from African Americans has a different pattern of somatic driver mutations than from Caucasians. The majority of driver alterations in this group are yet to be described, which will require more comprehensive panels and assessment of non-canonical alterations. PMID:26301800

  12. Multi-institutional Pooled Analysis on Adjuvant Chemoradiation in Pancreatic Cancer

    SciTech Connect

    Morganti, Alessio G.; Falconi, Massimo; Stiphout, Ruud G.P.M. van; Mattiucci, Gian-Carlo; Alfieri, Sergio; Calvo, Felipe A.; Dubois, Jean-Bernard; Fastner, Gerd; Herman, Joseph M.; Maidment, Bert W.; Miller, Robert C.; Regine, William F.; Reni, Michele; Sharma, Navesh K.; Ippolito, Edy; and others

    2014-11-15

    Purpose: To determine the impact of chemoradiation therapy (CRT) on overall survival (OS) after resection of pancreatic adenocarcinoma. Methods and Materials: A multicenter retrospective review of 955 consecutive patients who underwent complete resection with macroscopically negative margins (R0-1) for invasive carcinoma (T1-4; N0-1; M0) of the pancreas was performed. Exclusion criteria included metastatic or unresectable disease at surgery, macroscopic residual disease (R2), treatment with intraoperative radiation therapy (IORT), and a histological diagnosis of no ductal carcinoma, or postoperative death (within 60 days of surgery). In all, 623 patients received postoperative radiation therapy (RT), 575 patients received concurrent chemotherapy (CT), and 462 patients received adjuvant CT. Results: Median follow-up was 21.0 months. Median OS after adjuvant CRT was 39.9 versus 24.8 months after no adjuvant CRT (P<.001) and 27.8 months after CT alone (P<.001). Five-year OS was 41.2% versus 24.8% with and without postoperative CRT, respectively. The positive impact of CRT was confirmed by multivariate analysis (hazard ratio [HR] = 0.72; confidence interval [CI], 0.60-0.87; P=.001). Adverse prognostic factors identified by multivariate analysis included the following: R1 resection (HR = 1.17; CI = 1.07-1.28; P<.001), higher pT stage (HR = 1.23; CI = 1.11-1.37; P<.001), positive lymph nodes (HR = 1.27; CI = 1.15-1.41; P<.001), and tumor diameter >20 mm (HR = 1.14; CI = 1.05-1.23; P=.002). Multivariate analysis also showed a better prognosis in patients treated in centers with >10 pancreatic resections per year (HR = 0.87; CI = 0.78-0.97; P=.014) Conclusion: This study represents the largest comparative study on adjuvant therapy in patients after resection of carcinoma of the pancreas. Overall survival was better in patients who received adjuvant CRT.

  13. Smokeless Tobacco Use and the Risk of Head and Neck Cancer: Pooled Analysis of US Studies in the INHANCE Consortium.

    PubMed

    Wyss, Annah B; Hashibe, Mia; Lee, Yuan-Chin Amy; Chuang, Shu-Chun; Muscat, Joshua; Chen, Chu; Schwartz, Stephen M; Smith, Elaine; Zhang, Zuo-Feng; Morgenstern, Hal; Wei, Qingyi; Li, Guojun; Kelsey, Karl T; McClean, Michael; Winn, Deborah M; Schantz, Stimson; Yu, Guo-Pei; Gillison, Maura L; Zevallos, Jose P; Boffetta, Paolo; Olshan, Andrew F

    2016-10-15

    Previous studies on smokeless tobacco use and head and neck cancer (HNC) have found inconsistent and often imprecise estimates, with limited control for cigarette smoking. Using pooled data from 11 US case-control studies (1981-2006) of oral, pharyngeal, and laryngeal cancers (6,772 cases and 8,375 controls) in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium, we applied hierarchical logistic regression to estimate odds ratios and 95% confidence intervals for ever use, frequency of use, and duration of use of snuff and chewing tobacco separately for never and ever cigarette smokers. Ever use (versus never use) of snuff was strongly associated with HNC among never cigarette smokers (odds ratio (OR) = 1.71, 95% confidence interval (CI): 1.08, 2.70), particularly for oral cavity cancers (OR = 3.01, 95% CI: 1.63, 5.55). Although ever (versus never) tobacco chewing was weakly associated with HNC among never cigarette smokers (OR = 1.20, 95% CI: 0.81, 1.77), analyses restricted to cancers of the oral cavity showed a stronger association (OR = 1.81, 95% CI: 1.04, 3.17). Few or no associations between each type of smokeless tobacco and HNC were observed among ever cigarette smokers, possibly reflecting residual confounding by smoking. Smokeless tobacco use appears to be associated with HNC, especially oral cancers, with snuff being more strongly associated than chewing tobacco.

  14. Intrathecal chemotherapy as a treatment for leptomeningeal metastasis of non-small cell lung cancer: A pooled analysis.

    PubMed

    Wu, Ya-Lan; Zhou, Lin; Lu, You

    2016-08-01

    Leptomeningeal metastasis (LM) is increasingly common in patients with non-small cell lung cancer (NSCLC) due to improved treatment, and ultimately, prolonged patient survival. The current study is a pooled analysis that evaluated intrathecal chemotherapy (ITC) as a treatment for NSCLC patients with LM. The PUBMED, OVID, EBSCO and Cochrane Library databases were searched for published studies involving ITC in NSCLC patients with LM. The primary outcomes of interest included response (symptomatic, radiographic and cytological) and survival. Overall, 4 prospective studies and 5 retrospective studies were included. In total, 37 patients received ITC only, and 552 patients received multiple interventions (ITC, whole-brain radiotherapy, epidermal growth factor receptor tyrosine kinase inhibitors, systemic chemotherapy and support care). In patients with available individual information, the reevaluated cytological, clinical and radiographic rates of response to ITC were 55% (53-60%; n=49), 64% (53-79%; n=58), and 53% (n=32), respectively, and the reevaluated median survival time (from the onset of treatment, n=50) was 6.0 months (95% CI, 5.2-6.8). In patients without available individual information, the reported cytological and clinical rates of response to ITC are 14-52% and 13-50%, respectively, and the reported median survival time (from the diagnosis of LM) was 3.0-4.3 months. The clinical response rates of patients only receiving ITC varied from 71 to 79% (100% if including stable disease). The median survival time of patients who only received ITC (7.5 months) was much longer than that of patients who received multiple interventions (3.0-5.0 months). Accordingly, in NSCLC patients with LM, ITC may offer a promising response rate and survival benefits under a suitable regimen. In addition, a suitable combination strategy of multidisciplinary therapy is extremely important for these particular patients.

  15. Exposure–Response Analyses of Asbestos and Lung Cancer Subtypes in a Pooled Analysis of Case–Control Studies

    PubMed Central

    Vermeulen, Roel; Schüz, Joachim; Kromhout, Hans; Pesch, Beate; Peters, Susan; Behrens, Thomas; Portengen, Lützen; Mirabelli, Dario; Gustavsson, Per; Kendzia, Benjamin; Almansa, Josue; Luzon, Veronique; Vlaanderen, Jelle; Stücker, Isabelle; Guida, Florence; Consonni, Dario; Caporaso, Neil; Landi, Maria Teresa; Field, John; Brüske, Irene; Wichmann, Heinz-Erich; Siemiatycki, Jack; Parent, Marie-Elise; Richiardi, Lorenzo; Merletti, Franco; Jöckel, Karl-Heinz; Ahrens, Wolfgang; Pohlabeln, Hermann; Plato, Nils; Tardón, Adonina; Zaridze, David; McLaughlin, John; Demers, Paul; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Stanescu Dumitru, Rodica; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Boffetta, Paolo; Bueno-de-Mesquita, Bas; Forastiere, Francesco; Brüning, Thomas; Straif, Kurt

    2017-01-01

    Background: Evidence is limited regarding risk and the shape of the exposure–response curve at low asbestos exposure levels. We estimated the exposure–response for occupational asbestos exposure and assessed the joint effect of asbestos exposure and smoking by sex and lung cancer subtype in general population studies. Methods: We pooled 14 case–control studies conducted in 1985–2010 in Europe and Canada, including 17,705 lung cancer cases and 21,813 controls with detailed information on tobacco habits and lifetime occupations. We developed a quantitative job-exposure-matrix to estimate job-, time period-, and region-specific exposure levels. Fiber-years (ff/ml-years) were calculated for each subject by linking the matrix with individual occupational histories. We fit unconditional logistic regression models to estimate odds ratios (ORs), 95% confidence intervals (CIs), and trends. Results: The fully adjusted OR for ever-exposure to asbestos was 1.24 (95% CI, 1.18, 1.31) in men and 1.12 (95% CI, 0.95, 1.31) in women. In men, increasing lung cancer risk was observed with increasing exposure in all smoking categories and for all three major lung cancer subtypes. In women, lung cancer risk for all subtypes was increased in current smokers (ORs ~two-fold). The joint effect of asbestos exposure and smoking did not deviate from multiplicativity among men, and was more than additive among women. Conclusions: Our results in men showed an excess risk of lung cancer and its subtypes at low cumulative exposure levels, with a steeper exposure–response slope in this exposure range than at higher, previously studied levels. (See video abstract at, http://links.lww.com/EDE/B161.) PMID:28141674

  16. The association between socioeconomic status and tumour stage at diagnosis of ovarian cancer: a pooled analysis of 18 case-control studies

    PubMed Central

    Præstegaard, Camilla; Kjaer, Susanne K.; Nielsen, Thor S.S.; Jensen, Signe M.; Webb, Penelope M.; Nagle, Christina M.; Høgdall, Estrid; Risch, Harvey A.; Rossing, Mary Anne; Doherty, Jennifer A.; Wicklund, Kristine G.; Goodman, Marc T.; Modugno, Francesmary; Moysich, Kirsten; Ness, Roberta B.; Edwards, Robert P.; Goode, Ellen L.; Winham, Stacey J.; Fridley, Brooke L.; Cramer, Daniel W.; Terry, Kathryn L.; Schildkraut, Joellen M.; Berchuck, Andrew; Bandera, Elisa V.; Paddock, Lisa; Kiemeney, Lambertus A.; Massuger, Leon F.; Wentzensen, Nicolas; Pharoah, Paul; Song, Honglin; Whittemore, Alice S.; McGuire, Valerie; Sieh, Weiva; Rothstein, Joseph; Anton-Culver, Hoda; Ziogas, Argyrios; Menon, Usha; Gayther, Simon A.; Ramus, Susan J.; Gentry-Maharaj, Aleksandra; Wu, Anna H.; Pearce, Celeste L.; Pike, Malcolm C.; Lee, Alice W.; Chang-Claude, Jenny; Jensen, Allan

    2016-01-01

    Purpose Socioeconomic status (SES) is a known predictor of survival for several cancers and it has been suggested that SES differences affecting tumour stage at diagnosis may be the most important explanatory factor for this. However, only a limited number of studies have investigated SES differences in tumour stage at diagnosis of ovarian cancer. In a pooled analysis, we investigated whether SES as represented by level of education is predictive for advanced tumour stage at diagnosis of ovarian cancer, overall and by histotype. The effect of cigarette smoking and body mass index (BMI) on the association was also evaluated. Methods From 18 case-control studies, we obtained information on 10,601 women diagnosed with epithelial ovarian cancer. Study specific odds ratios (ORs) with corresponding 95% confidence intervals (CI) were obtained from logistic regression models and combined into a pooled odds ratio (pOR) using a random effects model. Results Overall, women who completed ≤high school had an increased risk of advanced tumour stage at diagnosis compared with women who completed >high school (pOR 1.15; 95% CI 1.03–1.28). The risk estimates for the different histotypes of ovarian cancer resembled that observed for ovarian cancers combined but did not reach statistical significance. Our results were unchanged when we included BMI and cigarette smoking. Conclusion Lower level of education was associated with an increased risk of advanced tumour stage at diagnosis of ovarian cancer. The observed socioeconomic difference in stage at diagnosis of ovarian cancer calls for further studies on how to reduce this diagnostic delay. PMID:26851750

  17. Risk factors for head and neck cancer in young adults: a pooled analysis in the INHANCE consortium

    PubMed Central

    Toporcov, Tatiana Natasha; Znaor, Ariana; Zhang, Zuo-Feng; Yu, Guo-Pei; Winn, Deborah M; Wei, Qingyi; Vilensky, Marta; Vaughan, Thomas; Thomson, Peter; Talamini, Renato; Szeszenia-Dabrowska, Neonila; Sturgis, Erich M; Smith, Elaine; Shangina, Oxana; Schwartz, Stephen M; Schantz, Stimson; Rudnai, Peter; Richiardi, Lorenzo; Ramroth, Heribert; Purdue, Mark P; Olshan, Andrew F; Eluf-Neto, José; Muscat, Joshua; Moyses, Raquel Ajub; Morgenstern, Hal; Menezes, Ana; McClean, Michael; Matsuo, Keitaro; Mates, Dana; Macfarlane, Tatiana V; Lissowska, Jolanta; Levi, Fabio; Lazarus, Philip; Vecchia, Carlo La; Lagiou, Pagona; Koifman, Sergio; Kjaerheim, Kristina; Kelsey, Karl; Holcatova, Ivana; Herrero, Rolando; Healy, Claire; Hayes, Richard B; Franceschi, Silvia; Fernandez, Leticia; Fabianova, Eleonora; Daudt, Alexander W; Curioni, Otávio Alberto; Maso, Luigino Dal; Curado, Maria Paula; Conway, David I; Chen, Chu; Castellsague, Xavier; Canova, Cristina; Cadoni, Gabriella; Brennan, Paul; Boccia, Stefania; Antunes, José Leopoldo Ferreira; Ahrens, Wolfgang; Agudo, Antonio; Boffetta, Paolo; Hashibe, Mia; Lee, Yuan-Chin Amy; Filho, Victor Wünsch

    2015-01-01

    Background: Increasing incidence of head and neck cancer (HNC) in young adults has been reported. We aimed to compare the role of major risk factors and family history of cancer in HNC in young adults and older patients. Methods: We pooled data from 25 case-control studies and conducted separate analyses for adults ≤45 years old (‘young adults’, 2010 cases and 4042 controls) and >45 years old (‘older adults’, 17 700 cases and 22 704 controls). Using logistic regression with studies treated as random effects, we estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results: The young group of cases had a higher proportion of oral tongue cancer (16.0% in women; 11.0% in men) and unspecified oral cavity / oropharynx cancer (16.2%; 11.1%) and a lower proportion of larynx cancer (12.1%; 16.6%) than older adult cases. The proportions of never smokers or never drinkers among female cases were higher than among male cases in both age groups. Positive associations with HNC and duration or pack-years of smoking and drinking were similar across age groups. However, the attributable fractions (AFs) for smoking and drinking were lower in young when compared with older adults (AFs for smoking in young women, older women, young men and older men, respectively, = 19.9% (95% CI = 9.8%, 27.9%), 48.9% (46.6%, 50.8%), 46.2% (38.5%, 52.5%), 64.3% (62.2%, 66.4%); AFs for drinking = 5.3% (−11.2%, 18.0%), 20.0% (14.5%, 25.0%), 21.5% (5.0%, 34.9%) and 50.4% (46.1%, 54.3%). A family history of early-onset cancer was associated with HNC risk in the young [OR = 2.27 (95% CI = 1.26, 4.10)], but not in the older adults [OR = 1.10 (0.91, 1.31)]. The attributable fraction for family history of early-onset cancer was 23.2% (8.60% to 31.4%) in young compared with 2.20% (−2.41%, 5.80%) in older adults. Conclusions: Differences in HNC aetiology according to age group may exist. The lower AF of cigarette smoking and alcohol drinking in young

  18. EGFR-TKI therapy for patients with brain metastases from non-small-cell lung cancer: a pooled analysis of published data

    PubMed Central

    Fan, Yun; Xu, Xiaoling; Xie, Conghua

    2014-01-01

    Introduction Brain metastases are one of the leading causes of death from non-small-cell lung cancer (NSCLC). The use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) to treat brain metastases remains controversial. Thus, we performed a pooled analysis of published data to evaluate the efficacy of EGFR-TKIs in NSCLC patients with brain metastases, particularly for tumors with activating EGFR mutations. Methods Several data sources were searched, including PubMed, Web of Science, and ASCO Annual Meetings databases. The end points were intracranial overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse events. The pooled ORR, DCR, PFS, and OS with 95% confidence intervals (CIs) were calculated employing fixed- or random-effect models, depending on the heterogeneity of the included studies. Results Sixteen published studies were included in this analysis, with a total of 464 enrolled patients. The EGFR mutational status was unknown for 362 (unselected group), and 102 had activating EGFR mutations. The pooled intracranial ORR and DCR were 51.8% (95% CI: 45.8%–57.8%) and 75.7% (95% CI: 70.3%–80.5%), respectively. A higher ORR was observed in the EGFR mutation group than in the unselected group (85.0% vs 45.1%); a similar trend was observed for the DCR (94.6% vs 71.3%). The pooled median PFS and OS were 7.4 months (95% CI, 4.9–9.9) and 11.9 months (95% CI, 7.7–16.2), respectively, with longer PFS (12.3 months vs 5.9 months) and OS (16.2 months vs 10.3 months) in the EGFR mutation group than in the unselected group. Conclusion This pooled analysis strongly suggests that EGFR-TKIs are an effective treatment for NSCLC patients with brain metastases, particularly in those patients harboring EGFR mutations. Larger prospective randomized clinical trials are warranted to confirm our conclusion and identify the most appropriate treatment model. PMID:25419145

  19. Natural vitamin C intake and the risk of head and neck cancer: a pooled analysis in the International Head and Neck Cancer Epidemiology consortiuma,b

    PubMed Central

    Edefonti, Valeria; Hashibe, Mia; Parpinel, Maria; Turati, Federica; Serraino, Diego; Matsuo, Keitaro; Olshan, Andrew F.; Zevallos, Jose P.; Winn, Deborah M.; Moysich, Kirsten; Zhang, Zuo-Feng; Morgenstern, Hal; Levi, Fabio; Kelsey, Karl; McClean, Michael; Bosetti, Cristina; Galeone, Carlotta; Schantz, Stimson; Yu, Guo-Pei; Boffetta, Paolo; Lee, Yuan-Chin Amy; Chuang, Shu-Chun; La Vecchia, Carlo; Decarli, Adriano

    2014-01-01

    Evidence of associations between single nutrients and head and neck cancer (HNC) is still more limited and less consistent than that for fruit and vegetables. However, clarification of the protective mechanisms of fruit and vegetables is important to our understanding of HNC etiology. We investigated the association between vitamin C intake from natural sources and cancer of the oral cavity/pharynx and larynx using individual-level pooled data from ten case-control studies (5959 cases and 12248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. After harmonization of study-specific exposure information via the residual method, adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using unconditional multiple logistic regression models on quintile categories of ’non-alcohol energy-adjusted’ vitamin C intake. In the presence of heterogeneity of the estimated ORs among studies, we derived those estimates from generalized linear mixed models. Higher intakes of vitamin C were inversely related to oral and pharyngeal (OR=0.54, 95% CI: 0.45–0.65, for the fifth quintile category versus the first one, p for trend<0.001) and laryngeal cancers (OR=0.52, 95% CI: 0.40–0.68, p for trend=0.006), although in the presence of heterogeneity among studies for both sites. Inverse associations were consistently observed for the anatomical subsites of oral and pharyngeal cancer, and across strata of age, sex, education, body mass index, tobacco, and alcohol, for both cancer sites. The inverse association of vitamin C intake from foods with HNC may reflect a protective effect on these cancers; however, we cannot rule out other explanations. PMID:25627906

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

    PubMed Central

    Truong, Therese; Hung, Rayjean J.; Amos, Christopher I.; Wu, Xifeng; Bickeböller, 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; Nürnberg, Peter; Stoelben, Erich; Wolf, Jürgen; 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; Müller, Heiko; Brenner, Hermann; Le Marchand, Loïc; Benhamou, Simone; Bouchardy, Christine; Teare, M. Dawn; Xue, Xiaoyan; McLaughlin, John; Liu, Geoffrey; McKay, James D.; Spitz, Margaret R.

    2010-01-01

    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

  1. Family history of cancer and risk of Pancreatic Cancer: A Pooled Analysis from the Pancreatic Cancer Cohort Consortium (PanScan)

    PubMed Central

    Jacobs, Eric J.; Chanock, Stephen J.; Fuchs, Charles S.; LaCroix, Andrea; McWilliams, Robert R.; Steplowski, Emily; Stolzenberg-Solomon, Rachael Z.; Arslan, Alan A.; Bueno-de-Mesquita, H. Bas; Gross, Myron; Helzlsouer, Kathy; Petersen, Gloria; Zheng, Wei; Agalliu, Ilir; Allen, Naomi E.; Amundadottir, Laufey; Boutron-Ruault, Marie-Christine; Buring, Julie E.; Canzian, Federico; Clipp, Sandra; Dorronsoro, Miren; Gaziano, J. Michael; Giovannucci, Edward L.; Hankinson, Susan E.; Hartge, Patricia; Hoover, Robert N.; Hunter, David J.; Jacobs, Kevin B.; Jenab, Mazda; Kraft, Peter; Kooperberg, Charles; Lynch, Shannon M.; Sund, Malin; Mendelsohn, Julie B.; Mouw, Tracy; Newton, Christina C.; Overvad, Kim; Palli, Domenico; Peeters, Petra H.M.; Rajkovic, Aleksandar; Shu, Xiao-Ou; Thomas, Gilles; Tobias, Geoffrey S.; Trichopoulos, Dimitrios; Virtamo, Jarmo; Wactawski-Wende, Jean; Wolpin, Brian M.; Yu, Kai; Zeleniuch-Jacquotte, Anne

    2010-01-01

    A family history of pancreatic cancer has consistently been associated with increased risk of pancreatic cancer. However, uncertainty remains about the strength of this association. Results from previous studies suggest a family history of select cancers (i.e. ovarian, breast, and colorectal) could also be associated, although not as strongly, with increased risk of pancreatic cancer. We examined the association between a family history of five types of cancer (pancreas, prostate, ovarian, breast, and colorectal) and risk of pancreatic cancer using data from a collaborative nested case-control study conducted by the Pancreatic Cancer Cohort Consortium. Cases and controls were from cohort studies from the United States, Europe, and China, and a case-control study from the Mayo Clinic. Analyses of family history of pancreatic cancer included 1,183 cases and 1,205 controls. A family history of pancreatic cancer in a parent, sibling, or child was associated with increased risk of pancreatic cancer (multivariate-adjusted OR = 1.76, 95% CI 1.19–2.61). A family history of prostate cancer was also associated with increased risk (OR = 1.45, 95% CI 1.12–1.89). There were no statistically significant associations with a family history of ovarian cancer (OR = 0.82, 95% CI 0.52–1.31), breast cancer (OR = 1.21, 95% CI 0.97–1.51), or colorectal cancer (OR = 1.17, 95% CI 0.93–1.47). Our results confirm a moderate sized association between a family history of pancreatic cancer and risk of pancreatic cancer and also provide evidence for an association with a family history of prostate cancer worth further study. PMID:20049842

  2. Alcohol and lung cancer risk among never smokers: A pooled analysis from the international lung cancer consortium and the SYNERGY study.

    PubMed

    Fehringer, Gordon; Brenner, Darren R; Zhang, Zuo-Feng; Lee, Yuan-Chin Amy; Matsuo, Keitaro; Ito, Hidemi; Lan, Qing; Vineis, Paolo; Johansson, Mattias; Overvad, Kim; Riboli, Elio; Trichopoulou, Antonia; Sacerdote, Carlotta; Stucker, Isabelle; Boffetta, Paolo; Brennan, Paul; Christiani, David C; Hong, Yun-Chul; Landi, Maria Teresa; Morgenstern, Hal; Schwartz, Ann G; Wenzlaff, Angela S; Rennert, Gad; McLaughlin, John R; Harris, Curtis C; Olivo-Marston, Susan; Orlow, Irene; Park, Bernard J; Zauderer, Marjorie; Barros Dios, Juan M; Ruano Raviña, Alberto; Siemiatycki, Jack; Koushik, Anita; Lazarus, Philip; Fernández-Somoano, Ana; Tardon, Adonina; Le Marchand, Loic; Brenner, Hermann; Saum, Kai-Uwe; Duell, Eric J; Andrew, Angeline S; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Zaridze, David; Rudnai, Peter; Fabianova, Eleonora; Mates, Dana; Foretova, Lenka; Janout, Vladimir; Bencko, Vladimir; Holcatova, Ivana; Pesatori, Angela Cecilia; Consonni, Dario; Olsson, Ann; Straif, Kurt; Hung, Rayjean J

    2017-05-01

    It is not clear whether alcohol consumption is associated with lung cancer risk. The relationship is likely confounded by smoking, complicating the interpretation of previous studies. We examined the association of alcohol consumption and lung cancer risk in a large pooled international sample, minimizing potential confounding of tobacco consumption by restricting analyses to never smokers. Our study included 22 case-control and cohort studies with a total of 2548 never-smoking lung cancer patients and 9362 never-smoking controls from North America, Europe and Asia within the International Lung Cancer Consortium (ILCCO) and SYNERGY Consortium. Alcohol consumption was categorized into amounts consumed (grams per day) and also modelled as a continuous variable using restricted cubic splines for potential non-linearity. Analyses by histologic sub-type were included. Associations by type of alcohol consumed (wine, beer and liquor) were also investigated. Alcohol consumption was inversely associated with lung cancer risk with evidence most strongly supporting lower risk for light and moderate drinkers relative to non-drinkers (>0-4.9 g per day: OR = 0.80, 95% CI = 0.70-0.90; 5-9.9 g per day: OR = 0.82, 95% CI = 0.69-0.99; 10-19.9 g per day: OR = 0.79, 95% CI = 0.65-0.96). Inverse associations were found for consumption of wine and liquor, but not beer. The results indicate that alcohol consumption is inversely associated with lung cancer risk, particularly among subjects with low to moderate consumption levels, and among wine and liquor drinkers, but not beer drinkers. Although our results should have no relevant bias from the confounding effect of smoking we cannot preclude that confounding by other factors contributed to the observed associations. Confounding in relation to the non-drinker reference category may be of particular importance.

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

    PubMed

    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

    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.

  4. MC1R gene variants and non-melanoma skin cancer: a pooled-analysis from the M-SKIP project

    PubMed Central

    Tagliabue, E; Fargnoli, M C; Gandini, S; Maisonneuve, P; Liu, F; Kayser, M; Nijsten, T; Han, J; Kumar, R; Gruis, N A; Ferrucci, L; Branicki, W; Dwyer, T; Blizzard, L; Helsing, P; Autier, P; García-Borrón, J C; Kanetsky, P A; Landi, M T; Little, J; Newton-Bishop, J; Sera, F; Raimondi, S

    2015-01-01

    Background: The melanocortin-1-receptor (MC1R) gene regulates human pigmentation and is highly polymorphic in populations of European origins. The aims of this study were to evaluate the association between MC1R variants and the risk of non-melanoma skin cancer (NMSC), and to investigate whether risk estimates differed by phenotypic characteristics. Methods: Data on 3527 NMSC cases and 9391 controls were gathered through the M-SKIP Project, an international pooled-analysis on MC1R, skin cancer and phenotypic characteristics. We calculated summary odds ratios (SOR) with random-effect models, and performed stratified analyses. Results: Subjects carrying at least one MC1R variant had an increased risk of NMSC overall, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC): SOR (95%CI) were 1.48 (1.24–1.76), 1.39 (1.15–1.69) and 1.61 (1.35–1.91), respectively. All of the investigated variants showed positive associations with NMSC, with consistent significant results obtained for V60L, D84E, V92M, R151C, R160W, R163Q and D294H: SOR (95%CI) ranged from 1.42 (1.19–1.70) for V60L to 2.66 (1.06–6.65) for D84E variant. In stratified analysis, there was no consistent pattern of association between MC1R and NMSC by skin type, but we consistently observed higher SORs for subjects without red hair. Conclusions: Our pooled-analysis highlighted a role of MC1R variants in NMSC development and suggested an effect modification by red hair colour phenotype. PMID:26103569

  5. Comparison of anthropometric measures as predictors of cancer incidence: A pooled collaborative analysis of 11 Australian cohorts.

    PubMed

    Harding, Jessica L; Shaw, Jonathan E; Anstey, Kaarin J; Adams, Robert; Balkau, Beverley; Brennan-Olsen, Sharon L; Briffa, Tom; Davis, Timothy M E; Davis, Wendy A; Dobson, Annette; Flicker, Leon; Giles, Graham; Grant, Janet; Huxley, Rachel; Knuiman, Matthew; Luszcz, Mary; MacInnis, Robert J; Mitchell, Paul; Pasco, Julie A; Reid, Christopher; Simmons, David; Simons, Leon; Tonkin, Andrew; Woodward, Mark; Peeters, Anna; Magliano, Dianna J

    2015-10-01

    Obesity is a risk factor for cancer. However, it is not known if general adiposity, as measured by body mass index (BMI) or central adiposity [e.g., waist circumference (WC)] have stronger associations with cancer, or which anthropometric measure best predicts cancer risk. We included 79,458 men and women from the Australian and New Zealand Diabetes and Cancer Collaboration with complete data on anthropometry [BMI, WC, Hip Circumference (HC), WHR, waist to height ratio (WtHR), A Body Shape Index (ABSI)], linked to the Australian Cancer Database. Cox proportional hazards models assessed the association between each anthropometric marker, per standard deviation and the risk of overall, colorectal, post-menopausal (PM) breast, prostate and obesity-related cancers. We assessed the discriminative ability of models using Harrell's c-statistic. All anthropometric markers were associated with overall, colorectal and obesity-related cancers. BMI, WC and HC were associated with PM breast cancer and no significant associations were seen for prostate cancer. Strongest associations were observed for WC across all outcomes, excluding PM breast cancer for which HC was strongest. WC had greater discrimination compared to BMI for overall and colorectal cancer in men and women with c-statistics ranging from 0.70 to 0.71. We show all anthropometric measures are associated with the overall, colorectal, PM breast and obesity-related cancer in men and women, but not prostate cancer. WC discriminated marginally better than BMI. However, all anthropometric measures were similarly moderately predictive of cancer risk. We do not recommend one anthropometric marker over another for assessing an individuals' risk of cancer.

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

    PubMed Central

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

    2013-01-01

    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

  7. Analysis of the TRIGA Reactor Pool Water

    DTIC Science & Technology

    1993-08-01

    AD-A270 956 L11L1I~I1 11 11 :1Ji ili! August 1993 AFRRI 93-5 TECHNICAL REPORT Analysis of the TRIGA Reactor Pool Water L OCT 1 93 John Dickson Robert...COVER~ED I August 1993 Technical Report 4 TITLE AND SUBTITLE S.FNDN NUMBERS Analysis of the TRIGA Reactor Pool Water PE: NWED QAXM 6, AUTHOR(S) Dickson...AVAILABIIY STATEMENT 1 2b. DISTRIBUTION CODE Approved for public release; distribution unlimited. 13. ABSTRACT tMaxtm -um 200 words ) 14. SUBJECTTERMS 1S

  8. Pooled analysis of the accuracy of five cervical cancer screening tests assessed in eleven studies in Africa and India.

    PubMed

    Arbyn, Marc; Sankaranarayanan, Rengaswamy; Muwonge, Richard; Keita, Namory; Dolo, Amadou; Mbalawa, Charles Gombe; Nouhou, Hassan; Sakande, Boblewende; Wesley, Ramani; Somanathan, Thara; Sharma, Anjali; Shastri, Surendra; Basu, Parthasarathy

    2008-07-01

    Cervical cancer is the main cancer among women in sub-Saharan Africa, India and other parts of the developing world. Evaluation of screening performance of effective, feasible and affordable early detection and management methods is a public health priority. Five screening methods, naked eye visual inspection of the cervix uteri after application of diluted acetic acid (VIA), or Lugol's iodine (VILI) or with a magnifying device (VIAM), the Pap smear and human papillomavirus testing with the high-risk probe of the Hybrid Capture-2 assay (HC2), were evaluated in 11 studies in India and Africa. More than 58,000 women, aged 25-64 years, were tested with 2-5 screening tests and outcome verification was done on all women independent of the screen test results. The outcome was presence or absence of cervical intraepithelial neoplasia (CIN) of different degrees or invasive cervical cancer. Verification was based on colposcopy and histological interpretation of colposcopy-directed biopsies. Negative colposcopy was accepted as a truly negative outcome. VIA showed a sensitivity of 79% (95% CI 73-85%) and 83% (95% CI 77-89%), and a specificity of 85% (95% CI 81-89%) and 84% (95% CI 80-88%) for the outcomes CIN2+ or CIN3+, respectively. VILI was on average 10% more sensitive and equally specific. VIAM showed similar results as VIA. The Pap smear showed lowest sensitivity, even at the lowest cutoff of atypical squamous cells of undetermined significance (57%; 95% CI 38-76%) for CIN2+ but the specificity was rather high (93%; 95% CI 89-97%). The HC2-assay showed a sensitivity for CIN2+ of 62% (95% CI 56-68%) and a specificity of 94% (95% CI 92-95%). Substantial interstudy variation was observed in the accuracy of the visual screening methods. Accuracy of visual methods and cytology increased over time, whereas performance of HC2 was constant. Results of visual tests and colposcopy were highly correlated. This study was the largest ever done that evaluates the cross

  9. Associations between unprocessed red and processed meat, poultry, seafood and egg intake and the risk of prostate cancer: A pooled analysis of 15 prospective cohort studies.

    PubMed

    Wu, Kana; Spiegelman, Donna; Hou, Tao; Albanes, Demetrius; Allen, Naomi E; Berndt, Sonja I; van den Brandt, Piet A; Giles, Graham G; Giovannucci, Edward; Alexandra Goldbohm, R; Goodman, Gary G; Goodman, Phyllis J; Håkansson, Niclas; Inoue, Manami; Key, Timothy J; Kolonel, Laurence N; Männistö, Satu; McCullough, Marjorie L; Neuhouser, Marian L; Park, Yikyung; Platz, Elizabeth A; Schenk, Jeannette M; Sinha, Rashmi; Stampfer, Meir J; Stevens, Victoria L; Tsugane, Shoichiro; Visvanathan, Kala; Wilkens, Lynne R; Wolk, Alicja; Ziegler, Regina G; Smith-Warner, Stephanie A

    2016-05-15

    Reports relating meat intake to prostate cancer risk are inconsistent. Associations between these dietary factors and prostate cancer were examined in a consortium of 15 cohort studies. During follow-up, 52,683 incident prostate cancer cases, including 4,924 advanced cases, were identified among 842,149 men. Cox proportional hazard models were used to calculate study-specific relative risks (RR) and then pooled using random effects models. Results do not support a substantial effect of total red, unprocessed red and processed meat for all prostate cancer outcomes, except for a modest positive association for tumors identified as advanced stage at diagnosis (advanced(r)). For seafood, no substantial effect was observed for prostate cancer regardless of stage or grade. Poultry intake was inversely associated with risk of advanced and fatal cancers (pooled multivariable RR [MVRR], 95% confidence interval, comparing ≥ 45 vs. <5 g/day: advanced 0.83, 0.70-0.99; trend test p value 0.29), fatal, 0.69, 0.59-0.82, trend test p value 0.16). Participants who ate ≥ 25 versus <5 g/day of eggs (1 egg ∼ 50 g) had a significant 14% increased risk of advanced and fatal cancers (advanced 1.14, 1.01-1.28, trend test p value 0.01; fatal 1.14, 1.00-1.30, trend test p value 0.01). When associations were analyzed separately by geographical region (North America vs. other continents), positive associations between unprocessed red meat and egg intake, and inverse associations between poultry intake and advanced, advanced(r) and fatal cancers were limited to North American studies. However, differences were only statistically significant for eggs. Observed differences in associations by geographical region warrant further investigation.

  10. Associations between unprocessed red and processed meat, poultry, seafood and egg intake and the risk of prostate cancer: A pooled analysis of 15 prospective cohort studies

    PubMed Central

    Wu, Kana; Spiegelman, Donna; Hou, Tao; Albanes, Demetrius; Allen, Naomi E.; Berndt, Sonja I.; van den Brandt, Piet A.; Giles, Graham G.; Giovannucci, Edward; Goldbohm, R. Alexandra; Goodman, Gary G.; Goodman, Phyllis J.; Håkansson, Niclas; Inoue, Manami; Key, Timothy J.; Kolonel, Laurence N.; Männistö, Satu; McCullough, Marjorie L.; Neuhouser, Marian L.; Park, Yikyung; Platz, Elizabeth A.; Schenk, Jeannette M.; Sinha, Rashmi; Stampfer, Meir J.; Stevens, Victoria L.; Tsugane, Shoichiro; Visvanathan, Kala; Wilkens, Lynne R.; Wolk, Alicja; Ziegler, Regina G.; Smith-Warner, Stephanie A.

    2016-01-01

    Reports relating meat intake to prostate cancer risk are inconsistent. Associations between these dietary factors and prostate cancer were examined in a consortium of 15 cohort studies. During follow-up, 52, 683 incident prostate cancer cases, including 4,924 advanced cases, were identified among 842, 149 men. Cox proportional hazard models were used to calculate study-specific relative risks (RR) and then pooled using random effects models. Results do not support a substantial effect of total red, unprocessed red and processed meat for all prostate cancer outcomes, except for a modest positive association for tumors identified as advanced stage at diagnosis (advanced(r)). For seafood, no substantial effect was observed for prostate cancer regardless of stage or grade. Poultry intake was inversely associated with risk of advanced and fatal cancers (pooled multivariable RR [MVRR], 95% confidence interval, comparing ≥45 vs. <5 g/day: advanced 0.83, 0.70–0.99; trend test p value 0.29), fatal, 0.69, 0.59–0.82, trend test p value 0.16). Participants who ate ≥25 versus <5 g/day of eggs (1 egg ~ 50 g) had a significant 14% increased risk of advanced and fatal cancers (advanced 1.14, 1.01–1.28, trend test p value 0.01; fatal 1.14, 1.00–1.30, trend test p value 0.01). When associations were analyzed separately by geographical region (North America vs. other continents), positive associations between unprocessed red meat and egg intake, and inverse associations between poultry intake and advanced, advanced(r) and fatal cancers were limited to North American studies. However, differences were only statistically significant for eggs. Observed differences in associations by geographical region warrant further investigation. PMID:26685908

  11. Intake of vitamins A, C, and E and folate and the risk of ovarian cancer in a pooled analysis of 10 cohort studies

    PubMed Central

    Koushik, Anita; Wang, Molin; Anderson, Kristin E.; van den Brandt, Piet; Clendenen, Tess V.; Eliassen, A. Heather; Freudenheim, Jo L.; Genkinger, Jeanine M.; Håkansson, Niclas; Marshall, James R.; McCullough, Marjorie L.; Miller, Anthony B.; Robien, Kim; Rohan, Thomas E.; Schairer, Catherine; Schouten, Leo J.; Tworoger, Shelley S.; Wang, Ying; Wolk, Alicja; Zeleniuch-Jacquotte, Anne; Smith-Warner, Stephanie A.

    2016-01-01

    Purpose Vitamins A, C and E and folate have anticarcinogenic properties and thus might protect against cancer. Few known modifiable risk factors for ovarian cancer exist. We examined the associations between dietary and total (food and supplemental) vitamin intake and the risk of invasive epithelial ovarian cancer. Methods The primary data from 10 prospective cohort studies in North America and Europe were analyzed. Vitamin intakes were estimated from validated food frequency questionnaires in each study. Study-specific relative risks (RR) were estimated using the Cox proportional hazards model and then combined using a random-effects model. Results Among 501,857 women, 1,973 cases of ovarian cancer occurred during a maximum follow-up of 7-22 years across studies. Dietary and total intake of each vitamin was not significantly associated with ovarian cancer risk. The pooled multivariate RRs (95% confidence intervals (CIs)) for incremental increases in total intake of each vitamin were 1.02 (0.97-1.07) for vitamin A (increment: 1300 mcg/day), 1.01 (0.99-1.04) for vitamin C (400 mg/day), 1.02 (0.97-1.06) for vitamin E (130 mg/day) and 1.01 (0.96-1.07) for folate (250 mcg/day). Multivitamin use (vs. non-use) was not associated with ovarian cancer risk (pooled multivariate RR=1.00, 95% CI: 0.89-1.12). Associations did not vary substantially by study, or by subgroups of the population. Greater vitamin intakes were associated with modestly higher risks of endometrioid tumors (n=156 cases), but not other histological types. Conclusion These results suggest that consumption of vitamins A, C, and E and folate during adulthood does not play a major role in ovarian cancer risk. PMID:26169298

  12. Nomograms for Prediction of Outcome With or Without Adjuvant Radiation Therapy for Patients With Endometrial Cancer: A Pooled Analysis of PORTEC-1 and PORTEC-2 Trials

    SciTech Connect

    Creutzberg, Carien L.; Stiphout, Ruud G.P.M. van; Nout, Remi A.; Lutgens, Ludy C.H.W.; Jürgenliemk-Schulz, Ina M.; Jobsen, Jan J.; Smit, Vincent T.H.B.M.; Lambin, Philippe

    2015-03-01

    Background: Postoperative radiation therapy for stage I endometrial cancer improves locoregional control but is without survival benefit. To facilitate treatment decision support for individual patients, accurate statistical models to predict locoregional relapse (LRR), distant relapse (DR), overall survival (OS), and disease-free survival (DFS) are required. Methods and Materials: Clinical trial data from the randomized Post Operative Radiation Therapy for Endometrial Cancer (PORTEC-1; N=714 patients) and PORTEC-2 (N=427 patients) trials and registered group (grade 3 and deep invasion, n=99) were pooled for analysis (N=1240). For most patients (86%) pathology review data were available; otherwise original pathology data were used. Trial variables which were clinically relevant and eligible according to data constraints were age, stage, given treatment (pelvic external beam radiation therapy (EBRT), vaginal brachytherapy (VBT), or no adjuvant treatment, FIGO histological grade, depth of invasion, and lymph-vascular invasion (LVSI). Multivariate analyses were based on Cox proportional hazards regression model. Predictors were selected based on a backward elimination scheme. Model results were expressed by the c-index (0.5-1.0; random to perfect prediction). Two validation sets (n=244 and 291 patients) were used. Results: Accuracy of the developed models was good, with training accuracies between 0.71 and 0.78. The nomograms validated well for DR (0.73), DFS (0.69), and OS (0.70), but validation was only fair for LRR (0.59). Ranking of variables as to their predictive power showed that age, tumor grade, and LVSI were highly predictive for all outcomes, and given treatment for LRR and DFS. The nomograms were able to significantly distinguish low- from high-probability patients for these outcomes. Conclusions: The nomograms are internally validated and able to accurately predict long-term outcome for endometrial cancer patients with observation, pelvic EBRT, or VBT

  13. Adjuvant chemotherapy in rectal cancer: defining subgroups who may benefit after neoadjuvant chemoradiation and resection: a pooled analysis of 3,313 patients.

    PubMed

    Maas, Monique; Nelemans, Patty J; Valentini, Vincenzo; Crane, Christopher H; Capirci, Carlo; Rödel, Claus; Nash, Garrett M; Kuo, Li-Jen; Glynne-Jones, Rob; García-Aguilar, Julio; Suárez, Javier; Calvo, Felipe A; Pucciarelli, Salvatore; Biondo, Sebastiano; Theodoropoulos, George; Lambregts, Doenja M J; Beets-Tan, Regina G H; Beets, Geerard L

    2015-07-01

    Recent literature suggests that the benefit of adjuvant chemotherapy (aCT) for rectal cancer patients might depend on the response to neoadjuvant chemoradiation (CRT). Aim was to evaluate whether the effect of aCT in rectal cancer is modified by response to CRT and to identify which patients benefit from aCT after CRT, by means of a pooled analysis of individual patient data from 13 datasets. Patients were categorized into three groups: pCR (ypT0N0), ypT1-2 tumour and ypT3-4 tumour. Hazard ratios (HR) for the effect of aCT were derived from multivariable Cox regression analyses. Primary outcome measure was recurrence-free survival (RFS). One thousand seven hundred and twenty three (1723) (52%) of 3,313 included patients received aCT. Eight hundred and ninety eight (898) patients had a pCR, 966 had a ypT1-2 tumour and 1,302 had a ypT3-4 tumour. For 122 patients response, category was missing and 25 patients had ypT0N+. Median follow-up for all patients was 51 (0-219) months. HR for RFS with 95% CI for patients treated with aCT were 1.25(0.68-2.29), 0.58(0.37-0.89) and 0.83(0.66-1.10) for patients with pCR, ypT1-2 and ypT3-4 tumours, respectively. The effect of aCT in rectal cancer patients treated with CRT differs between subgroups. Patients with a pCR after CRT may not benefit from aCT, whereas patients with residual tumour had superior outcomes when aCT was administered. The test for interaction did not reach statistical significance, but the results support further investigation of a more individualized approach to administer aCT after CRT and surgery based on pathologic staging.

  14. Preoperative Radiotherapy of Advanced Rectal Cancer With Capecitabine and Oxaliplatin With or Without Cetuximab: A Pooled Analysis of Three Prospective Phase I-II Trials

    SciTech Connect

    Weiss, Christian; Arnold, Dirk; Dellas, Kathrin; Liersch, Torsten; Hipp, Matthias; Fietkau, Rainer; Sauer, Rolf; Hinke, Axel; Roedel, Claus

    2010-10-01

    Purpose: A pooled analysis of three prospective trials of preoperative radiochemotherapy (RCT) for rectal cancer by using oxaliplatin and capecitabine with or without cetuximab was performed to evaluate the impact of additional cetuximab on pathologic complete response (pCR) rates and tumor regression (TRG) grades. Methods and Materials: Of 202 patients, 172 patients met the inclusion criteria (primary tumor stage II/III, M0). All patients received concurrent RCT, and 46 patients received additional cetuximab therapy. A correlation of pretreatment clinicopathologic factors and cetuximab treatment with early pCR rates (TRG > 50%) was performed with univariate and multivariate analyses. Toxicity data were recorded for all patients. Results: Of 172 patients, 24 (14%) patients achieved a pCR, and 84 of 172 (71%) patients showed a TRG of >50% in the surgical specimen assessment after preoperative treatment. Age, gender, and T/N stages, as well as localization of the tumor, were not associated with pCR or good TRG. The pCR rate was 16% after preoperative RCT alone and 9% with concurrent cetuximab therapy (p = 0.32). A significantly reduced TRG of >50% was found after RCT with cetuximab compared to RCT alone (p = 0.0035). This was validated by a multivariate analysis with all available clinical factors (p = 0.0037). Acute toxicity and surgical complications were not increased with additional cetuximab. Conclusions: Triple therapy with RCT and cetuximab seems to be feasible, with no unexpected toxicity. Early response assessment (TRG), however, suggests subadditive interaction. A longer follow-up (and finally randomized trials) is needed to draw any firm conclusions with respect to local and distant failure rates.

  15. Estimating and explaining the effect of education and income on head and neck cancer risk: INHANCE consortium pooled analysis of 31 case-control studies from 27 countries

    PubMed Central

    Conway, David I.; Brenner, Darren R.; McMahon, Alex D.; Macpherson, Lorna M.D.; Agudo, Antonio; Ahrens, Wolfgang; Bosetti, Cristina; Brenner, Hermann; Castellsague, Xavier; Chen, Chu; Curado, Maria Paula; Curioni, Otávio A.; Maso, Luigino Dal; Daudt, Alexander W.; de Gois Filho, José F.; D'Souza, Gypsyamber; Edefonti, Valeria; Fabianova, Eleonora; Fernandez, Leticia; Franceschi, Silvia; Gillison, Maura; Hayes, Richard B.; Healy, Claire M.; Herrero, Rolando; Holcatova, Ivana; Jayaprakash, Vijayvel; Kelsey, Karl; Kjaerheim, Kristina; Koifman, Sergio; La Vecchia, Carlo; Lagiou, Pagona; Lazarus, Philip; Levi, Fabio; Lissowska, Jolanta; Luce, Daniele; Macfarlane, Tatiana V.; Mates, Dana; Matos, Elena; McClean, Michael; Menezes, Ana M; Menvielle, Gwenn; Merletti, Franco; Morgenstern, Hal; Moysich, Kirsten; Müller, Heiko; Muscat, Joshua; Olshan, Andrew F.; Purdue, Mark P.; Ramroth, Heribert; Richiardi, Lorenzo; Rudnai, Peter; Schantz, Stimson; Schwartz, Stephen M.; Shangina, Oxana; Simonato, Lorenzo; Smith, Elaine; Stucker, Isabelle; Sturgis, Erich M.; Szeszenia-Dabrowska, Neonila; Talamini, Renato; Thomson, Peter; Vaughan, Thomas L.; Wei, Qingyi; Winn, Deborah M.; Wunsch-Filho, Victor; Yu, Guo-Pei; Zhang, Zuo-Feng; Zheng, Tongzhang; Znaor, Ariana; Boffetta, Paolo; Chuang, Shu-Chun; Ghodrat, Marianoosh; Lee, Yuan-Chin Amy; Hashibe, Mia; Brennan, Paul

    2015-01-01

    Low socioeconomic status has been reported to be associated with head and neck cancer risk. However, previous studies have been too small to examine the associations by cancer subsite, age, sex, global region and calendar time and to explain the association in terms of behavioral risk factors. Individual participant data of 23,964 cases with head and neck cancer and 31,954 controls from 31 studies in 27 countries pooled with random effects models. Overall, low education was associated with an increased risk of head and neck cancer (OR = 2.50; 95% CI = 2.02 – 3.09). Overall one-third of the increased risk was not explained by differences in the distribution of cigarette smoking and alcohol behaviors; and it remained elevated among never users of tobacco and nondrinkers (OR = 1.61; 95% CI = 1.13 – 2.31). More of the estimated education effect was not explained by cigarette smoking and alcohol behaviors: in women than in men, in older than younger groups, in the oropharynx than in other sites, in South/Central America than in Europe/North America and was strongest in countries with greater income inequality. Similar findings were observed for the estimated effect of low versus high household income. The lowest levels of income and educational attainment were associated with more than 2-fold increased risk of head and neck cancer, which is not entirely explained by differences in the distributions of behavioral risk factors for these cancers and which varies across cancer sites, sexes, countries and country income inequality levels. PMID:24996155

  16. Efficacy of FOLFOXIRI plus bevacizumab in liver-limited metastatic colorectal cancer: A pooled analysis of clinical studies by Gruppo Oncologico del Nord Ovest.

    PubMed

    Cremolini, Chiara; Casagrande, Mariaelena; Loupakis, Fotios; Aprile, Giuseppe; Bergamo, Francesca; Masi, Gianluca; Moretto R, Roberto; Pietrantonio, Filippo; Marmorino, Federica; Zucchelli, Gemma; Tomasello, Gianluca; Tonini, Giuseppe; Allegrini, Giacomo; Granetto, Cristina; Ferrari, Laura; Urbani, Lucio; Cillo, Umberto; Pilati, Pierluigi; Sensi, Elisa; Pellegrinelli, Alessio; Milione, Massimo; Fontanini, Gabriella; Falcone, Alfredo

    2017-03-01

    Secondary resection is a chance of cure for a subgroup of metastatic colorectal cancer (mCRC) patients with unresectable liver-limited disease. Medical treatment has a dual goal: to induce tumour shrinkage and to prevent disease relapse. The aims of the present analysis were to assess the efficacy of FOLFOXIRI plus bevacizumab in this setting, and to investigate whether this regimen could revert the poor prognosis of high-risk patients defined by clinical and molecular factors. We performed a pooled analysis of patients with unresectable and liver-limited mCRC, treated with first-line FOLFOXIRI plus bevacizumab in three prospective clinical trials by Gruppo Oncologico del Nord Ovest. 205 (37.9%) patients with liver-limited disease were selected, out of 541 treated patients. Liver metastases were synchronous, ≥4 and bilobar in 90%, 61%, and 79% of cases, respectively. The largest diameter was >5 cm in 42% of cases, and ≥6 segments were involved in 25%. Seventy-four patients (36.1%) underwent R0 or R1 resection of metastases. R2 resections were performed in 17 cases (8.3%). Having <6 involved segments (p < 0.001) and achieving RECIST response (p = 0.019) were associated with higher chances of resection. R0/R1 resected patients had significantly longer median progression-free survival (PFS) (18.1 versus 10.7 months, HR: 0.48 [0.35-0.66], p < 0.001) and overall survival (OS) (44.3 versus 24.4 months, HR: 0.32 [0.22-0.48], p < 0.001) compared with other patients, both in the univariate and multivariate analyses (PFS p = 0.025; OS p < 0.001). The 5-year PFS and OS rate in R0 resected patients were 12% and 43%, respectively. Neither negative baseline characteristics nor high clinical risk scores or RAS/BRAF mutations were associated with poor post-resection outcomes. In conclusion, FOLFOXIRI plus bevacizumab demonstrates efficacy in the conversion setting with considerable long-term outcome results independent of clinical and molecular prognostic

  17. Body Mass Index and Risk of Second Obesity-Associated Cancers After Colorectal Cancer: A Pooled Analysis of Prospective Cohort Studies

    PubMed Central

    Gibson, Todd M.; Park, Yikyung; Robien, Kim; Shiels, Meredith S.; Black, Amanda; Sampson, Joshua N.; Purdue, Mark P.; Beane Freeman, Laura E.; Andreotti, Gabriella; Weinstein, Stephanie J.; Albanes, Demetrius; Fraumeni, Joseph F.; Curtis, Rochelle E.; Berrington de Gonzalez, Amy; Morton, Lindsay M.

    2014-01-01

    Purpose To determine whether prediagnostic body mass index (BMI) is associated with risk of second obesity-associated cancers in colorectal cancer (CRC) survivors, and whether CRC survivors have increased susceptibility to obesity-associated cancer compared with cancer-free individuals. Patients and Methods Incident first primary CRC cases (N = 11,598) were identified from five prospective cohort studies. We used Cox proportional hazards regression models to examine associations between baseline (prediagnostic) BMI and risk of second obesity-associated cancers (postmenopausal breast, kidney, pancreas, esophageal adenocarcinoma, endometrium) in CRC survivors, and compared associations to those for first obesity-associated cancers in the full cohort. Results Compared with survivors with normal prediagnostic BMI (18.5-24.9 kg/m2), those who were overweight (25-29.9 kg/m2) or obese (30+ kg/m2) had greater risk of a second obesity-associated cancer (n = 224; overweight hazard ratio [HR], 1.39; 95% CI, 1.01 to 1.92; obese HR, 1.47; 95% CI, 1.02 to 2.12; per 5-unit change in BMI HR, 1.12; 95% CI, 0.98 to 1.29). The magnitude of risk for developing a first primary obesity-associated cancer was similar (overweight HR, 1.18; 95% CI, 1.14 to 1.21; obese HR, 1.61; 95% CI, 1.56 to 1.66; per 5-unit change in BMI HR, 1.23; 95% CI, 1.21 to 1.24). Before diagnosis CRC patients were somewhat more likely than the overall cohort to be overweight (44% v 41%) or obese (25% v 21%). Conclusion CRC survivors who were overweight or obese before diagnosis had increased risk of second obesity-associated cancers compared with survivors with normal weight. The risks were similar in magnitude to those observed for first cancers in this population, suggesting increased prevalence of overweight or obesity, rather than increased susceptibility, may contribute to elevated second cancer risks in colorectal cancer survivors compared with the general population. These results support emphasis of

  18. The SDF-1 rs1801157 Polymorphism is Associated with Cancer Risk: An Update Pooled Analysis and FPRP Test of 17,876 Participants.

    PubMed

    Tong, Xiang; Ma, Yao; Deng, Huajiang; Wang, Xixi; Liu, Sitong; Yan, Zhipeng; Peng, Shifeng; Fan, Hong

    2016-06-06

    The stromal cell derived factor-1 (SDF-1) rs1801157 gene polymorphism has been implicated in susceptibility to cancer, but the results were inconclusive. The current study was to precisely investigate the association between SDF-1 rs1801157 polymorphism and cancer risk using meta-analysis and the false positive report probability (FPRP) test. All 17,876 participants were included in the study. The meta-analysis results indicated a significant association between the SDF-1 rs1801157 polymorphism and cancer risk. By subgroup analyses, the results detected that the SDF-1 rs1801157 polymorphism was associated with cancer susceptibility among Asians and Caucasians. Additionally, we also found significant associations between the SDF-1 rs1801157 polymorphism and susceptibility to different types of cancer. However, to avoid a "false positive report", we further investigated the significant associations observed in the present meta-analysis using the FPRP test. Interestingly, the results of the FPRP test indicated that only 4 gene models were truly associated with cancer risk, especially in Asians. Moreover, we confirmed that the SDF-1 rs1801157 gene polymorphism was only associated with lung and urologic cancer risk. In summary, this study suggested that the SDF-1 rs1801157 polymorphism may serve as a risk factor for cancer development among Asians, especially an increased risk of urologic and lung cancers.

  19. Insulin-like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies

    PubMed Central

    2010-01-01

    Summary Background Insulin-like growth factor 1 (IGF1) stimulates mitosis and inhibits apoptosis. Some published results have shown an association between circulating IGF1 and breast-cancer risk, but it has been unclear whether this relationship is consistent or whether it is modified by IGF binding protein 3 (IGFBP3), menopausal status, oestrogen receptor status or other factors. The relationship of IGF1 (and IGFBP3) with breast-cancer risk factors is also unclear. The Endogenous Hormones and Breast Cancer Collaborative Group was established to analyse pooled individual data from prospective studies to increase the precision of the estimated associations of endogenous hormones with breast-cancer risk. Methods Individual data on prediagnostic IGF1 and IGFBP3 concentrations were obtained from 17 prospective studies in 12 countries. The associations of IGF1 with risk factors for breast cancer in controls were examined by calculating geometric mean concentrations in categories of these factors. The odds ratios (ORs) with 95% CIs of breast cancer associated with increasing IGF1 concentrations were estimated by conditional logistic regression in 4790 cases and 9428 matched controls, with stratification by study, age at baseline, and date of baseline. All statistical tests were two-sided, and a p value of less than 0·05 was considered significant. Findings IGF1 concentrations, adjusted for age, were positively associated with height and age at first pregnancy, inversely associated with age at menarche and years since menopause, and were higher in moderately overweight women and moderate alcohol consumers than in other women. The OR for breast cancer for women in the highest versus the lowest fifth of IGF1 concentration was 1·28 (95% CI 1·14–1·44; p<0·0001). This association was not altered by adjusting for IGFBP3, and did not vary significantly by menopausal status at blood collection. The ORs for a difference in IGF1 concentration between the highest and lowest

  20. Body mass index and risk of head and neck cancer in a pooled analysis of case–control studies in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium

    PubMed Central

    Gaudet, Mia M; Olshan, Andrew F; Chuang, Shu-Chun; Berthiller, Julien; Zhang, Zuo-Feng; Lissowska, Jolanta; Zaridze, David; Winn, Deborah M; Wei, Qingyi; Talamini, Renato; Szeszenia-Dabrowska, Neolilia; Sturgis, Erich M; Schwartz, Stephen M; Rudnai, Peter; Eluf-Neto, Jose; Muscat, Joshua; Morgenstern, Hal; Menezes, Ana; Matos, Elena; Bucur, Alexandru; Levi, Fabio; Lazarus, Philip; La Vecchia, Carlo; Koifman, Sergio; Kelsey, Karl; Herrero, Rolando; Hayes, Richard B; Franceschi, Silva; Wunsch-Filho, Victor; Fernandez, Leticia; Fabianova, Eleonora; Daudt, Alexander W; Dal Maso, Luigino; Paula Curado, Maria; Chen, Chu; Castellsague, Xavier; Benhamou, Simone; Boffetta, Paolo; Brennan, Paul; Hashibe, Mia

    2010-01-01

    Background Head and neck cancer (HNC) risk is elevated among lean people and reduced among overweight or obese people in some studies; however, it is unknown whether these associations differ for certain subgroups or are influenced by residual confounding from the effects of alcohol and tobacco use or by other sources of biases. Methods We pooled data from 17 case–control studies including 12 716 cases and the 17 438 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between body mass index (BMI) at different ages and HNC risk, adjusted for age, sex, centre, race, education, tobacco smoking and alcohol consumption. Results Adjusted ORs (95% CIs) were elevated for people with BMI at reference (date of diagnosis for cases and date of selection for controls) ≤18.5 kg/m2 (2.13, 1.75–2.58) and reduced for BMI >25.0–30.0 kg/m2 (0.52, 0.44–0.60) and BMI ≥30 kg/m2 (0.43, 0.33–0.57), compared with BMI >18.5–25.0 kg/m2. These associations did not differ by age, sex, tumour site or control source. Although the increased risk among people with BMI ≤18.5 kg/m2 was not modified by tobacco smoking or alcohol drinking, the inverse association for people with BMI > 25 kg/m2 was present only in smokers and drinkers. Conclusions In our large pooled analysis, leanness was associated with increased HNC risk regardless of smoking and drinking status, although reverse causality cannot be excluded. The reduced risk among overweight or obese people may indicate body size is a modifier of the risk associated with smoking and drinking. Further clarification may be provided by analyses of prospective cohort and mechanistic studies. PMID:20123951

  1. Results of intraoperative electron beam radiotherapy containing multimodality treatment for locally unresectable T4 rectal cancer: a pooled analysis of the Mayo Clinic Rochester and Catharina Hospital Eindhoven

    PubMed Central

    Holman, Fabian A.; Haddock, Michael G.; Gunderson, Leonard L.; Kusters, Miranda; Nieuwenhuijzen, Grard A. P.; van den Berg, Hetty A.; Nelson, Heidi

    2016-01-01

    Background The aim of this study is to analyse the pooled results of intraoperative electron beam radiotherapy (IOERT) containing multimodality treatment of locally advanced T4 rectal cancer, initially unresectable for cure, from the Mayo Clinic, Rochester, USA (MCR) and Catharina Hospital, Eindhoven, The Netherlands (CHE), both major referral centers for locally advanced rectal cancer. A rectal tumor is called locally unresectable for cure if after full clinical work-up infiltration into the surrounding structures or organs has been demonstrated, which would result in positive surgical margins if resection was the initial component of treatment. This was the reason to refer these patients to the IOERT program of one of the centers. Methods In the period from 1981 to 2010, 417 patients with locally unresectable T4 rectal carcinomas at initial presentation were treated with multimodality treatment including IOERT at either one of the two centres. The preferred treatment approach was preoperative (chemo) radiation and intended radical surgery combined with IOERT. Risk factors for local recurrence (LR), cancer specific survival, disease free survival and distant metastases (DM) were assessed. Results A total of 306 patients (73%) underwent a R0 resection. LRs and metastases occurred more frequently after an R1-2 resection (P<0.001 and P<0.001 respectively). Preoperative chemoradiation (preop CRT) was associated with a higher probability of having a R0 resection. Waiting time after preoperative treatment was inversely related with the chance of developing a LR, especially after R+ resection. In 16% of all cases a LR developed. Five-year disease free survival and overall survival (OS) were 55% and 56% respectively. Conclusions An acceptable survival can be achieved in treatment of patients with initially unresectable T4 rectal cancer with combined modality therapy that includes preop CRT and IOERT. Completeness of the resection is the most important predictive and

  2. Body Mass Index Is Prognostic in Metastatic Colorectal Cancer: Pooled Analysis of Patients From First-Line Clinical Trials in the ARCAD Database

    PubMed Central

    Loupakis, Fotios; Adams, Richard A.; Seymour, Matthew T.; Heinemann, Volker; Schmoll, Hans-Joachim; Douillard, Jean-Yves; Hurwitz, Herbert; Fuchs, Charles S.; Diaz-Rubio, Eduardo; Porschen, Rainer; Tournigand, Christophe; Chibaudel, Benoist; Falcone, Alfredo; Tebbutt, Niall C.; Punt, Cornelis J.A.; Hecht, J. Randolph; Bokemeyer, Carsten; Van Cutsem, Eric; Goldberg, Richard M.; Saltz, Leonard B.; de Gramont, Aimery; Sargent, Daniel J.; Lenz, Heinz-Josef

    2016-01-01

    Purpose In recent retrospective analyses of early-stage colorectal cancer (CRC), low and high body mass index (BMI) scores were associated with worsened outcomes. Whether BMI is a prognostic or predictive factor in metastatic CRC (mCRC) is unclear. Patients and Methods Individual data from 21,149 patients enrolled onto 25 first-line mCRC trials during 1997 to 2012 were pooled. We assessed both prognostic and predictive effects of BMI on overall survival and progression-free survival, and we accounted for patient and tumor characteristics and therapy type (targeted v nontargeted). Results BMI was prognostic for overall survival (P < .001) and progression-free survival (P < .001), with an L-shaped pattern. That is, risk of progression and/or death was greatest for low BMI; risk decreased as BMI increased to approximately 28 kg/m2, and then it plateaued. Relative to obese patients, patients with a BMI of 18.5 kg/m2 had a 27% increased risk of having a PFS event (95% CI, 20% to 34%) and a 50% increased risk of death (95% CI, 43% to 56%). Low BMI was associated with poorer survival for men than women (interaction P < .001). BMI was not predictive of treatment effect. Conclusion Low BMI is associated with an increased risk of progression and death among the patients enrolled on the mCRC trials, with no increased risk for elevated BMI, in contrast to the adjuvant setting. Possible explanations include negative effects related to cancer cachexia in patients with low BMI, increased drug delivery or selection bias in patients with high BMI, and potential for an interaction between BMI and molecular signaling pathways. PMID:26503203

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

    PubMed

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

    2011-07-01

    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.

  4. Pooled Analysis of CNS Response to Alectinib in Two Studies of Pretreated Patients With ALK-Positive Non-Small-Cell Lung Cancer.

    PubMed

    Gadgeel, Shirish M; Shaw, Alice T; Govindan, Ramaswamy; Gandhi, Leena; Socinski, Mark A; Camidge, D Ross; De Petris, Luigi; Kim, Dong-Wan; Chiappori, Alberto; Moro-Sibilot, Denis L; Duruisseaux, Michael; Crino, Lucio; De Pas, Tommaso; Dansin, Eric; Tessmer, Antje; Yang, James Chih-Hsin; Han, Ji-Youn; Bordogna, Walter; Golding, Sophie; Zeaiter, Ali; Ou, Sai-Hong Ignatius

    2016-12-01

    Purpose Alectinib has shown activity in the CNS in phase I and II studies. To further evaluate this activity, we pooled efficacy and safety data from two single-arm phase II studies (NP28761 and NP28673; ClinicalTrials.gov identifiers: NCT01871805 and NCT01801111, respectively) in patients with ALK-positive non-small-cell lung cancer (NSCLC). Patients and Methods Both studies included patients with ALK-positive NSCLC who had previously received crizotinib; all patients received alectinib 600 mg twice per day. The primary end point in both studies was independent review committee (IRC)-assessed objective response rate (ORR; by Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1). Additional end points (all by IRC) included CNS ORR (CORR), CNS disease control rate (CDCR), and CNS duration of response (CDOR). Results One hundred thirty-six patients had baseline CNS metastases (60% of the overall study populations); 50 patients (37%) had measurable CNS disease at baseline. Ninety-five patients (70%) had prior CNS radiotherapy; 55 patients completed the CNS radiotherapy more than 6 months before starting alectinib. Median follow-up time was 12.4 months (range, 0.9 to 19.7 months). For patients with baseline measurable CNS disease, IRC CORR was 64.0% (95% CI, 49.2% to 77.1%), CDCR was 90.0% (95% CI, 78.2% to 96.7%), and median CDOR was 10.8 months (95% CI, 7.6 to 14.1 months). For patients with measurable and/or nonmeasurable baseline CNS disease, IRC CORR was 42.6% (95% CI, 34.2% to 51.4%), CDCR was 85.3% (95% CI, 78.2% to 90.8%), and median CDOR was 11.1 months (95% CI, 10.3 months to not evaluable). CORR was 35.8% (95% CI, 26.2% to 46.3%) for patients with prior radiotherapy (n = 95) and 58.5% (95% CI, 42.1% to 73.7%) for patients without prior radiotherapy (n = 41). As previously reported, alectinib was well tolerated, regardless of baseline CNS disease. Conclusion Alectinib showed good efficacy against CNS metastases, in addition to systemic activity

  5. Anthropometric and Hormonal Risk Factors for Male Breast Cancer: Male Breast Cancer Pooling Project Results

    PubMed Central

    Brinton, Louise A.

    2014-01-01

    Background The etiology of male breast cancer is poorly understood, partly because of its relative rarity. Although genetic factors are involved, less is known regarding the role of anthropometric and hormonally related risk factors. Methods In the Male Breast Cancer Pooling Project, a consortium of 11 case–control and 10 cohort investigations involving 2405 case patients (n = 1190 from case–control and n = 1215 from cohort studies) and 52013 control subjects, individual participant data were harmonized and pooled. Unconditional logistic regression generated study design–specific (case–control/cohort) odds ratios (ORs) and 95% confidence intervals (CIs), with exposure estimates combined using fixed effects meta-analysis. All statistical tests were two-sided. Results Risk was statistically significantly associated with weight (highest/lowest tertile: OR = 1.36; 95% CI = 1.18 to 1.57), height (OR = 1.18; 95% CI = 1.01 to 1.38), and body mass index (BMI; OR = 1.30; 95% CI = 1.12 to 1.51), with evidence that recent rather than distant BMI was the strongest predictor. Klinefelter syndrome (OR = 24.7; 95% CI = 8.94 to 68.4) and gynecomastia (OR = 9.78; 95% CI = 7.52 to 12.7) were also statistically significantly associated with risk, relations that were independent of BMI. Diabetes also emerged as an independent risk factor (OR = 1.19; 95% CI = 1.04 to 1.37). There were also suggestive relations with cryptorchidism (OR = 2.18; 95% CI = 0.96 to 4.94) and orchitis (OR = 1.43; 95% CI = 1.02 to 1.99). Although age at onset of puberty and histories of infertility were unrelated to risk, never having had children was statistically significantly related (OR = 1.29; 95% CI = 1.01 to 1.66). Among individuals diagnosed at older ages, a history of fractures was statistically significantly related (OR = 1.41; 95% CI = 1.07 to 1.86). Conclusions Consistent findings across case–control and cohort investigations, complemented by pooled analyses, indicated important roles for

  6. Swimming Pools, Hot Rods, and Qualitative Analysis.

    ERIC Educational Resources Information Center

    Clyde, Dale D.

    1988-01-01

    Describes some reactions for the identification and application of cyanuric acid. Suggests students may find this applied chemistry interesting because of the use of cyanuric acid in swimming pools and diesel engines. Lists three tests for cyanate ion and two tests for cyanuric acid. (MVL)

  7. 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

    Gondi, Vinai; Paulus, Rebecca; Bruner, Deborah W.; Meyers, Christina A.; Gore, Elizabeth M.; Wolfson, Aaron; Werner-Wasik, Maria; Sun, Alexander Y.; Choy, Hak; Movsas, Benjamin

    2013-07-15

    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.

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

    PubMed Central

    2013-01-01

    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 < 25 (reference group) in terms of recurrence (Hazard Ratio [HR] = 1.08, 95% Confidence Interval [CI] = 0.90 to 1.30), BCM (HR = 1.02, 0.81 to 1.29), and OM (HR = 0.97, 0.78 to 1.19). Patients with severe obesity (BMI ≥ 35) had a significantly increased risk of recurrence (HR = 1.26, 1.00 to 1.59, P = 0.048), BCM (HR = 1.32, 1.00 to 1.74, P = 0.050), and OM (HR = 1.35, 1.06 to 1.71, P = 0.016) compared to our reference group. The prognostic effect of severe obesity did not vary by subtype. Conclusions Severely obese patients treated with anthracyclines and taxanes present a worse prognosis regarding recurrence, BCM, and OM than patients with BMI < 25. The magnitude of the harmful effect of BMI on survival-related outcomes was similar across subtypes. PMID:24192331

  9. Circulating 25-hydroxyvitamin D and risk of esophageal and gastric cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.

    PubMed

    Abnet, Christian C; Chen, Yu; Chow, Wong-Ho; Gao, Yu-Tang; Helzlsouer, Kathy J; Le Marchand, Loïc; McCullough, Marjorie L; Shikany, James M; Virtamo, Jarmo; Weinstein, Stephanie J; Xiang, Yong-Bing; Yu, Kai; Zheng, Wei; Albanes, Demetrius; Arslan, Alan A; Campbell, David S; Campbell, Peter T; Hayes, Richard B; Horst, Ronald L; Kolonel, Laurence N; Nomura, Abraham M Y; Purdue, Mark P; Snyder, Kirk; Shu, Xiao-Ou

    2010-07-01

    Upper gastrointestinal (GI) cancers of the stomach and esophagus have high incidence and mortality worldwide, but they are uncommon in Western countries. Little information exists on the association between vitamin D and risk of upper GI cancers. This study examined the association between circulating 25-hydroxyvitamin D (25(OH)D) and upper GI cancer risk in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Concentrations of 25(OH)D were measured from 1,065 upper GI cancer cases and 1,066 age-, sex-, race-, and season-of blood draw-matched controls from 8 prospective cohort studies. In multivariate-adjusted models, circulating 25(OH)D concentration was not significantly associated with upper GI cancer risk. Subgroup analysis by race showed that among Asians, but not Caucasians, lower concentrations of 25(OH)D (<25 nmol/L) were associated with a statistically significant decreased risk of upper GI cancer (reference: 50-<75 nmol/L) (odds ratio = 0.53, 95% confidence interval: 0.31, 0.91; P trend = 0.003). Never smokers with concentrations of <25 nmol/L showed a lower risk of upper GI cancers (odds ratio = 0.55, 95% confidence interval: 0.31, 0.96). Subgroup analyses by alcohol consumption produced opposing trends. Results do not support the hypothesis that interventions aimed at increasing vitamin D status would lead to a lower risk of these highly fatal cancers.

  10. Quality of Patient-Reported Outcome (PRO) Reporting Across Cancer Randomized Controlled Trials According to the CONSORT PRO Extension: A Pooled Analysis of 557 Trials

    PubMed Central

    Efficace, Fabio; Fayers, Peter; Pusic, Andrea; Cemal, Yeliz; Yanagawa, Jane; Jacobs, Marc; la Sala, Andrea; Cafaro, Valentina; Whale, Katie; Rees, Jonathan; Blazeby, Jane

    2016-01-01

    Background The main objectives of this study were to identify the number of randomized controlled trials (RCTs) that have included a patient-reported outcome (PRO) endpoint across a wide range of cancer specialties and to evaluate completeness of PRO reporting according to the CONSORT PRO extension. Methods RCTs with a PRO endpoint, conducted across several cancer specialties and published between 2004 and 2013 were considered. Studies were evaluated based on previously defined criteria, including the CONSORT PRO extension and the Cochrane Collaboration's tool for assessing RCT Risk of Bias. Analyses were also conducted by type of PRO endpoint (primary versus secondary) and by cancer disease site. Results A total of 56,696 potentially eligible records were scrutinized and 557 RCTs with a PRO evaluation, enrolling overall 254,677 patients, were identified. PROs were most frequently used in RCTs of breast (N=123), lung (N=85) and colorectal (N=66) cancer. Overall, PROs were secondary endpoint in 421 (76%) RCTs. Four out of six CONSORT PRO items evaluated were documented in less than 50% of the RCTs. Level of reporting was higher in RCTs with PRO as a primary endpoint. Presence of a supplementary report was the only statistically significant factor associated with greater completeness of reporting for both RCTs with PRO as primary (β=0.19; P=0.001) or secondary endpoint (β=0.30; P<0.001). Conclusion Implementation of the CONSORT PRO extension is equally important across all cancer specialties. Its use can also contribute in revealing the robust PRO design of some studies, which might be obscured by poor outcome reporting. PMID:26079197

  11. Genetic variation in the immunosuppression pathway genes and breast cancer susceptibility: a pooled analysis of 42,510 cases and 40,577 controls from the Breast Cancer Association Consortium.

    PubMed

    Lei, Jieping; Rudolph, Anja; Moysich, Kirsten B; Behrens, Sabine; Goode, Ellen L; Bolla, Manjeet K; Dennis, Joe; Dunning, Alison M; Easton, Douglas F; Wang, Qin; Benitez, Javier; Hopper, John L; Southey, Melissa C; Schmidt, Marjanka K; Broeks, Annegien; Fasching, Peter A; Haeberle, Lothar; Peto, Julian; Dos-Santos-Silva, Isabel; Sawyer, Elinor J; Tomlinson, Ian; Burwinkel, Barbara; Marmé, Frederik; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E; Flyger, Henrik; Nielsen, Sune F; Nordestgaard, Børge G; González-Neira, Anna; Menéndez, Primitiva; Anton-Culver, Hoda; Neuhausen, Susan L; Brenner, Hermann; Arndt, Volker; Meindl, Alfons; Schmutzler, Rita K; Brauch, Hiltrud; Hamann, Ute; Nevanlinna, Heli; Fagerholm, Rainer; Dörk, Thilo; Bogdanova, Natalia V; Mannermaa, Arto; Hartikainen, Jaana M; Van Dijck, Laurien; Smeets, Ann; Flesch-Janys, Dieter; Eilber, Ursula; Radice, Paolo; Peterlongo, Paolo; Couch, Fergus J; Hallberg, Emily; Giles, Graham G; Milne, Roger L; Haiman, Christopher A; Schumacher, Fredrick; Simard, Jacques; Goldberg, Mark S; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Zheng, Wei; Beeghly-Fadiel, Alicia; Winqvist, Robert; Grip, Mervi; Andrulis, Irene L; Glendon, Gord; García-Closas, Montserrat; Figueroa, Jonine; Czene, Kamila; Brand, Judith S; Darabi, Hatef; Eriksson, Mikael; Hall, Per; Li, Jingmei; Cox, Angela; Cross, Simon S; Pharoah, Paul D P; Shah, Mitul; Kabisch, Maria; Torres, Diana; Jakubowska, Anna; Lubinski, Jan; Ademuyiwa, Foluso; Ambrosone, Christine B; Swerdlow, Anthony; Jones, Michael; Chang-Claude, Jenny

    2016-01-01

    Immunosuppression plays a pivotal role in assisting tumors to evade immune destruction and promoting tumor development. We hypothesized that genetic variation in the immunosuppression pathway genes may be implicated in breast cancer tumorigenesis. We included 42,510 female breast cancer cases and 40,577 controls of European ancestry from 37 studies in the Breast Cancer Association Consortium (2015) with available genotype data for 3595 single nucleotide polymorphisms (SNPs) in 133 candidate genes. Associations between genotyped SNPs and overall breast cancer risk, and secondarily according to estrogen receptor (ER) status, were assessed using multiple logistic regression models. Gene-level associations were assessed based on principal component analysis. Gene expression analyses were conducted using RNA sequencing level 3 data from The Cancer Genome Atlas for 989 breast tumor samples and 113 matched normal tissue samples. SNP rs1905339 (A>G) in the STAT3 region was associated with an increased breast cancer risk (per allele odds ratio 1.05, 95 % confidence interval 1.03-1.08; p value = 1.4 × 10(-6)). The association did not differ significantly by ER status. On the gene level, in addition to TGFBR2 and CCND1, IL5 and GM-CSF showed the strongest associations with overall breast cancer risk (p value = 1.0 × 10(-3) and 7.0 × 10(-3), respectively). Furthermore, STAT3 and IL5 but not GM-CSF were differentially expressed between breast tumor tissue and normal tissue (p value = 2.5 × 10(-3), 4.5 × 10(-4) and 0.63, respectively). Our data provide evidence that the immunosuppression pathway genes STAT3, IL5, and GM-CSF may be novel susceptibility loci for breast cancer in women of European ancestry.

  12. 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

    Kim, Sun Young; Shim, Eun Kyung; Yeo, Hyun Yang; Baek, Ji Yeon; Hong, Yong Sang; Kim, Dae Yong; Kim, Tae Won; Kim, Jee Hyun; Im, Seock-Ah; Jung, Kyung Hae; Chang, Hee Jin

    2013-01-01

    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

  13. Assessment of Long-Term Rectal Function in Patients Who Received Pelvic Radiotherapy: A Pooled North Central Cancer Treatment Group Trial Analysis, N09C1

    PubMed Central

    Brown, Lindsay C.; Atherton, Pamela J.; Neben-Wittich, Michelle A.; Wender, Donald B.; Behrens, Robert J.; Kozelsky, Timothy F.; Loprinzi, Charles L.; Haddock, Michael G.; Martenson, James A.

    2013-01-01

    Purpose Pelvic radiotherapy (PRT) is known to adversely affect bowel function (BF) and patient well-being. This study characterized long-term BF and evaluated quality of life (QOL) in patients receiving PRT. Methods Data from 252 patients were compiled from 2 North Central Cancer Treatment Group prospective studies, which included assessment of BF and QOL by the BF questionnaire (BFQ) and Uniscale QOL at baseline and 12 and 24 months after completion of radiotherapy. BFQ scores (sum of symptoms), Uniscale results, adverse-event incidence, and baseline demographic data were compared via t test, χ2, Fisher exact, Wilcoxon, and correlation methodologies. Results The total BFQ score was higher than baseline at 12 and 24 months (P<.001). More patients had 5 or more symptoms at 12 months (13%) and 24 months (10%) than at baseline (2%). Symptoms occurring in greater than 20% of patients at 12 and 24 months were clustering, stool-gas confusion, and urgency. Factors associated with worse BF were female sex, rectal or gynecologic primary tumors, prior anterior resection of the rectum, and 5-fluorouracil chemotherapy. Patients experiencing grade 2 or higher acute toxicity had worse 24-month BF (P values, <.001-.02). Uniscale QOL was not significantly different from baseline at 12 or 24 months, despite worse BFQ scores. Conclusions PRT was associated with worse long-term BF. Worse BFQ score was not associated with poorer QOL. Further research to characterize the subset of patients at risk of significant decline in BF is warranted. PMID:23748483

  14. Swimming pool immersion accidents: an analysis from the Brisbane Drowning Study

    PubMed Central

    Pearn, John H; Nixon, James

    1997-01-01

    An analysis of a consecutive series of 66 swimming pool immersion accidents is presented; 74% of these occurred in in-ground swimming pools. The estimated accident rate per pool is fives times greater for in-ground pools compared with above-ground pools, where pools are inadequately fenced. Backyard swimming pools account for 74% of pool accidents. Motel and caravan park pools account for 9% of childhood immersion accidents, but the survival rate (17%) is very low. Fifty per cent of pool accidents occur in the family's own backyard pool, and 13.6% in a neighbour's pool; in the latter the survival rate is still low at only 33%. In only one of the 66 cases was there an adequate safety fence; in 76% of cases there was no fence or barrier whatsoever. Tables of swimming pool accidents by age, season, site, and outcome are presented. PMID:9493630

  15. NSAID Use and Risk of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: The Liver Cancer Pooling Project.

    PubMed

    Petrick, Jessica L; Sahasrabuddhe, Vikrant V; Chan, Andrew T; Alavanja, Michael C; Beane-Freeman, Laura E; Buring, Julie E; Chen, Jie; Chong, Dawn Q; Freedman, Neal D; Fuchs, Charles S; Gaziano, John Michael; Giovannucci, Edward; Graubard, Barry I; Hollenbeck, Albert R; Hou, Lifang; Jacobs, Eric J; King, Lindsay Y; Koshiol, Jill; Lee, I-Min; Linet, Martha S; Palmer, Julie R; Purdue, Mark P; Rosenberg, Lynn; Schairer, Catherine; Sesso, Howard D; Sigurdson, Alice J; Wactawski-Wende, Jean; Zeleniuch-Jacquotte, Anne; Campbell, Peter T; McGlynn, Katherine A

    2015-12-01

    Chronic inflammation plays a pivotal role in the pathogenesis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), the two most common types of liver cancer. A number of prior experimental studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin and ibuprofen, may potentially protect against liver cancer. However, no observational study has examined the association between aspirin duration and dose or other over-the-counter non-aspirin NSAIDs, such as ibuprofen, and liver cancer incidence. Furthermore, the association between NSAID use and risk of ICC is unclear. As part of the Liver Cancer Pooling Project, we harmonized data on 1,084,133 individuals (HCC = 679, ICC = 225) from 10 U.S.-based prospective cohort studies. Cox proportional hazards regression models were used to evaluate multivariable-adjusted HRs and 95% confidence intervals (CI). Current aspirin use, versus nonuse, was inversely associated with HCC (HR, 0.68; 95% CI, 0.57-0.81), which persisted when restricted to individuals not using non-aspirin NSAIDs and in a 5- and 10-year lag analysis. The association between aspirin use and HCC risk was stronger for users who reported daily use, longer duration use, and lower dosage. Ibuprofen use was not associated with HCC risk. Aspirin use was associated with a reduced ICC risk in men (HR, 0.64; 95% CI, 0.42-0.98) but not women (HR, 1.34; 95% CI, 0.89-2.01; P(interaction) = 0.01). The observed inverse association between aspirin use and liver cancer in our study, together with previous data, suggests the merit of future intervention studies of aspirin and other agents that affect chronic inflammatory pathways for HCC and possibly ICC.

  16. NSAID use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project

    PubMed Central

    Petrick, Jessica L.; Sahasrabuddhe, Vikrant V.; Chan, Andrew T.; Alavanja, Michael C.; Beane-Freeman, Laura E.; Buring, Julie E.; Chen, Jie; Chong, Dawn Q.; Freedman, Neal D.; Fuchs, Charles S.; Gaziano, John Michael; Giovannucci, Edward; Graubard, Barry I.; Hollenbeck, Albert R.; Hou, Lifang; Jacobs, Eric J.; King, Lindsay Y.; Koshiol, Jill; Lee, I-Min; Linet, Martha S.; Palmer, Julie R.; Purdue, Mark P.; Rosenberg, Lynn; Schairer, Catherine; Sesso, Howard D.; Sigurdson, Alice J.; Wactawski-Wende, Jean; Zeleniuch-Jacquotte, Anne; Campbell, Peter T.; McGlynn, Katherine A.

    2015-01-01

    Chronic inflammation plays a pivotal role in the pathogenesis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), the two most common types of liver cancer. A number of prior experimental studies have suggested that non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin and ibuprofen, may potentially protect against liver cancer. However, no observational study has examined the association between aspirin duration and dose or other over-the-counter non-aspirin NSAIDs, such as ibuprofen, and liver cancer incidence. Furthermore, the association between NSAID use and risk of ICC is unclear. As part of the Liver Cancer Pooling Project, we harmonized data on 1,084,133 individuals (HCC=679, ICC=225) from ten US-based prospective cohort studies. Cox proportional hazards regression models were used to evaluate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Current aspirin use, versus nonuse, was inversely associated with HCC (HR=0.68, 95% CI=0.57-0.81), which persisted when restricted to individuals not using non-aspirin NSAIDs and in a 5 and 10-year lag analysis. The association between aspirin use and HCC risk was stronger for users who reported daily use, longer duration use, and lower dosage. Ibuprofen use was not associated with HCC risk. Aspirin use was associated with a reduced ICC risk in men (HR=0.64, 95% CI=0.42-0.98) but not women (HR=1.34, 95% CI=0.89-2.01, pinteraction=0.01). The observed inverse association between aspirin use and liver cancer in our study, together with previous data, suggest the merit of future intervention studies of aspirin and other agents that affect chronic inflammatory pathways for HCC and possibly ICC. PMID:26391917

  17. Reciprocal regulation of autophagy and dNTP pools in human cancer cells

    PubMed Central

    Chen, Wei; Zhang, Lisheng; Zhang, Keqiang; Zhou, Bingsen; Kuo, Mei-Ling; Hu, Shuya; Chen, Linling; Tang, Michelle; Chen, Yun-Ru; Yang, Lixin; Ann, David K; Yen, Yun

    2014-01-01

    Ribonucleotide reductase (RNR) plays a critical role in catalyzing the biosynthesis and maintaining the intracellular concentration of 4 deoxyribonucleoside triphosphates (dNTPs). Unbalanced or deficient dNTP pools cause serious genotoxic consequences. Autophagy is the process by which cytoplasmic constituents are degraded in lysosomes to maintain cellular homeostasis and bioenergetics. However, the role of autophagy in regulating dNTP pools is not well understood. Herein, we reported that starvation- or rapamycin-induced autophagy was accompanied by a decrease in RNR activity and dNTP pools in human cancer cells. Furthermore, downregulation of the small subunit of RNR (RRM2) by siRNA or treatment with the RNR inhibitor hydroxyurea substantially induced autophagy. Conversely, cancer cells with abundant endogenous intracellular dNTPs or treated with dNTP precursors were less responsive to autophagy induction by rapamycin, suggesting that autophagy and dNTP pool levels are regulated through a negative feedback loop. Lastly, treatment with si-RRM2 caused an increase in MAP1LC3B, ATG5, BECN1, and ATG12 transcript abundance in xenografted Tu212 tumors in vivo. Together, our results revealed a previously unrecognized reciprocal regulation between dNTP pools and autophagy in cancer cells. PMID:24905824

  18. MMAPPR: Mutation Mapping Analysis Pipeline for Pooled RNA-seq

    PubMed Central

    Hill, Jonathon T.; Demarest, Bradley L.; Bisgrove, Brent W.; Gorsi, Bushra; Su, Yi-Chu; Yost, H. Joseph

    2013-01-01

    Forward genetic screens in model organisms are vital for identifying novel genes essential for developmental or disease processes. One drawback of these screens is the labor-intensive and sometimes inconclusive process of mapping the causative mutation. To leverage high-throughput techniques to improve this mapping process, we have developed a Mutation Mapping Analysis Pipeline for Pooled RNA-seq (MMAPPR) that works without parental strain information or requiring a preexisting SNP map of the organism, and adapts to differential recombination frequencies across the genome. MMAPPR accommodates the considerable amount of noise in RNA-seq data sets, calculates allelic frequency by Euclidean distance followed by Loess regression analysis, identifies the region where the mutation lies, and generates a list of putative coding region mutations in the linked genomic segment. MMAPPR can exploit RNA-seq data sets from isolated tissues or whole organisms that are used for gene expression and transcriptome analysis in novel mutants. We tested MMAPPR on two known mutant lines in zebrafish, nkx2.5 and tbx1, and used it to map two novel ENU-induced cardiovascular mutants, with mutations found in the ctr9 and cds2 genes. MMAPPR can be directly applied to other model organisms, such as Drosophila and Caenorhabditis elegans, that are amenable to both forward genetic screens and pooled RNA-seq experiments. Thus, MMAPPR is a rapid, cost-efficient, and highly automated pipeline, available to perform mutant mapping in any organism with a well-assembled genome. PMID:23299975

  19. Meat intake and cause-specific mortality: a pooled analysis of Asian prospective cohort studies123

    PubMed Central

    Lee, Jung Eun; McLerran, Dale F; Rolland, Betsy; Chen, Yu; Grant, Eric J; Vedanthan, Rajesh; Inoue, Manami; Tsugane, Shoichiro; Gao, Yu-Tang; Tsuji, Ichiro; Kakizaki, Masako; Ahsan, Habibul; Ahn, Yoon-Ok; Pan, Wen-Harn; Ozasa, Kotaro; Yoo, Keun-Young; Sasazuki, Shizuka; Yang, Gong; Watanabe, Takashi; Sugawara, Yumi; Parvez, Faruque; Kim, Dong-Hyun; Chuang, Shao-Yuan; Ohishi, Waka; Park, Sue K; Feng, Ziding; Thornquist, Mark; Boffetta, Paolo; Zheng, Wei; Kang, Daehee; Potter, John; Sinha, Rashmi

    2013-01-01

    Background: Total or red meat intake has been shown to be associated with a higher risk of mortality in Western populations, but little is known of the risks in Asian populations. Objective: We examined temporal trends in meat consumption and associations between meat intake and all-cause and cause-specific mortality in Asia. Design: We used ecological data from the United Nations to compare country-specific meat consumption. Separately, 8 Asian prospective cohort studies in Bangladesh, China, Japan, Korea, and Taiwan consisting of 112,310 men and 184,411 women were followed for 6.6 to 15.6 y with 24,283 all-cause, 9558 cancer, and 6373 cardiovascular disease (CVD) deaths. We estimated the study-specific HRs and 95% CIs by using a Cox regression model and pooled them by using a random-effects model. Results: Red meat consumption was substantially lower in the Asian countries than in the United States. Fish and seafood consumption was higher in Japan and Korea than in the United States. Our pooled analysis found no association between intake of total meat (red meat, poultry, and fish/seafood) and risks of all-cause, CVD, or cancer mortality among men and women; HRs (95% CIs) for all-cause mortality from a comparison of the highest with the lowest quartile were 1.02 (0.91, 1.15) in men and 0.93 (0.86, 1.01) in women. Conclusions: Ecological data indicate an increase in meat intake in Asian countries; however, our pooled analysis did not provide evidence of a higher risk of mortality for total meat intake and provided evidence of an inverse association with red meat, poultry, and fish/seafood. Red meat intake was inversely associated with CVD mortality in men and with cancer mortality in women in Asian countries. PMID:23902788

  20. Comparison of the EORTC criteria and PERCIST in solid tumors: a pooled analysis and review

    PubMed Central

    Kim, Jung Han

    2016-01-01

    Two sets of response criteria using PET are currently available to monitor metabolic changes in solid tumors: the criteria developed by the European Organization for Research and Treatment of Cancer (EORTC criteria) and the PET Response Criteria in Solid Tumors (PERCIST). We conducted this pooled study to investigate the strength of agreement between the EORTC criteria and PERCIST in the assessment of tumor response. We surveyed MEDLINE, EMBASE and PUBMED for articles with terms of the EORTC criteria and PERCIST between 2009 and January 2016. We searched for all the references of relevant articles and reviews using the ‘related articles’ feature in the PUBMED. There were six articles with the data on the comparison of the EORTC criteria and PERCIST. A total of 348 patients were collected; 190 (54.6%) with breast cancer, 81 with colorectal cancer, 45 with lung cancer, 14 with basal cell carcinoma in the skin, 12 with stomach cancer, and 6 with head and neck cancer. The agreement of tumor response between the EORTC criteria and PERCIST was excellent (k = 0.946). Of 348 patients, only 12 (3.4%) showed disagreement between the two criteria in the assessment of tumor response. The shift of tumor response between the EORTC criteria and PERCIST occurred mostly in patients with PMR and SMD. The estimated overall response rates were not significantly different between the two criteria (72.7% by EORTC vs. 73.6% by PERCIST). In conclusion, this pooled analysis demonstrates that the EORTC criteria and PERCIST showed almost perfect agreement in the assessment of tumor response. PMID:27517621

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

    PubMed Central

    2013-01-01

    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

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

    USGS Publications Warehouse

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

    2005-01-01

    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.

  3. Pooled analysis of clinical outcome for EGFR TKI-treated patients with EGFR mutation-positive NSCLC.

    PubMed

    Paz-Ares, Luis; Soulières, Denis; Moecks, Joachim; Bara, Ilze; Mok, Tony; Klughammer, Barbara

    2014-08-01

    Patients with non-small-cell lung cancer (NSCLC) appear to gain particular benefit from treatment with epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKI) if their disease tests positive for EGFR activating mutations. Recently, several large, controlled, phase III studies have been published in NSCLC patients with EGFR mutation-positive tumours. Given the increased patient dataset now available, a comprehensive literature search for EGFR TKIs or chemotherapy in EGFR mutation-positive NSCLC was undertaken to update the results of a previously published pooled analysis. Pooling eligible progression-free survival (PFS) data from 27 erlotinib studies (n = 731), 54 gefitinib studies (n = 1802) and 20 chemotherapy studies (n = 984) provided median PFS values for each treatment. The pooled median PFS was: 12.4 months (95% accuracy intervals [AI] 11.6-13.4) for erlotinib-treated patients; 9.4 months (95% AI 9.0-9.8) for gefitinib-treated patients; and 5.6 months (95% AI 5.3-6.0) for chemotherapy. Both erlotinib and gefitinib resulted in significantly longer PFS than chemotherapy (permutation testing; P = 0.000 and P = 0.000, respectively). Data on more recent TKIs (afatinib, dacomitinib and icotinib) were insufficient at this time-point to carry out a pooled PFS analysis on these compounds. The results of this updated pooled analysis suggest a substantial clear PFS benefit of treating patients with EGFR mutation-positive NSCLC with erlotinib or gefitinib compared with chemotherapy.

  4. Identifying sexual orientation health disparities in adolescents: analysis of pooled data from the Youth Risk Behavior Survey, 2005 and 2007.

    PubMed

    Mustanski, Brian; Van Wagenen, Aimee; Birkett, Michelle; Eyster, Sandra; Corliss, Heather L

    2014-02-01

    We studied sexual orientation disparities in health outcomes among US adolescents by pooling multiple Youth Risk Behavior Survey (YRBS) data sets from 2005 and 2007 for 14 jurisdictions. Here we describe the methodology for pooling and analyzing these data sets. Sexual orientation-related items assessed sexual orientation identity, gender of sexual contacts, sexual attractions, and harassment regarding sexual orientation. Wording of items varied across jurisdictions, so we created parallel variables and composite sexual minority variables. We used a variety of statistical approaches to address issues with the analysis of pooled data and to meet the aims of individual articles, which focused on a range of health outcomes and behaviors related to cancer, substance use, sexual health, mental health, violence, and injury.

  5. Greater Adherence to Cancer Prevention Guidelines Is Associated with Higher Circulating Concentrations of Vitamin D Metabolites in a Cross-Sectional Analysis of Pooled Participants from 2 Chemoprevention Trials.

    PubMed

    Kohler, Lindsay N; Hibler, Elizabeth A; Harris, Robin B; Oren, Eyal; Roe, Denise J; Jurutka, Peter W; Jacobs, Elizabeth T

    2017-03-01

    Background: Several lifestyle factors targeted by the American Cancer Society (ACS) Nutrition and Physical Activity Cancer Prevention Guidelines are also associated with circulating concentrations of vitamin D metabolites. This suggests that greater adherence to the ACS guidelines may be related to better vitamin D status.Objective: We examined the relation between adherence to the ACS guidelines and circulating concentrations of 2 vitamin D metabolites, 25-hydroxycholecalciferol [25(OH)D] and 1α,25-dihydroxyvitamin D [1,25(OH)2D].Methods: We conducted cross-sectional analyses of pooled participants from the Wheat Bran Fiber (n = 503) and Ursodeoxycholic Acid (n = 854) trials. A cumulative adherence score was constructed with the use of baseline data on body size, diet, physical activity, and alcohol consumption. Continuous vitamin D metabolite concentrations and clinically relevant categories were evaluated with the use of multiple linear and logistic regression models, respectively.Results: The most adherent participants were more likely to be older, white, and nonsmokers than were the least adherent. A statistically significant association was observed between guideline adherence and concentrations of circulating 25(OH)D (means ± SEs-high adherence: 32.0 ± 0.8 ng/mL; low adherence: 26.4 ± 0.7 ng/mL; P-trend < 0.001). For 1,25(OH)2D concentrations, high adherence was again significantly related to greater metabolite concentrations, with mean ± SE concentrations of 36.3 ± 1.3 pg/mL and 31.9 ± 1.0 pg/mL for high- and low-adherers, respectively (P-trend = 0.008). Furthermore, the odds of attaining a sufficient 25(OH)D status were 4.37 times higher for those most adherent than for those least adherent (95% CI: 2.47, 7.71 times).Conclusion: These findings demonstrate that greater adherence to the ACS guidelines is associated with higher circulating concentrations of both of 25(OH)D and 1,25(OH)2D.

  6. Post-diagnosis Cruciferous Vegetable Consumption and Breast Cancer Outcomes: a Report from the After Breast Cancer Pooling Project

    PubMed Central

    Nechuta, Sarah; Caan, Bette J.; Chen, Wendy Y.; Kwan, Marilyn L.; Lu, Wei; Cai, Hui; Poole, Elizabeth M.; Flatt, Shirley W.; Zheng, Wei; Pierce, John P.; Shu, Xiao Ou

    2013-01-01

    Cruciferous vegetables are a major source of glucosinolate-derived bioactive compounds such as isothiocyanates, which have been shown in animal and in vitro studies to inhibit cancer growth and progression. Few studies have investigated cruciferous vegetable intake after diagnosis and breast cancer outcomes. Using data from the After Breast Cancer Pooling Project, which includes prospective data from US and Chinese breast cancer survivors, we evaluated the association of cruciferous vegetables with breast cancer outcomes. Analyses included 11,390 women diagnosed with stage I–III invasive breast cancer (1990–2006) from four cohorts. Cruciferous vegetable intake (g/day) was assessed using food frequency questionnaires (mean of 22 months post-diagnosis). Study heterogeneity was evaluated by the Q statistic; hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using delayed-entry Cox regression models stratified by study. After a median follow-up of 9.0 years, 1,725 deaths and 1,421 recurrences were documented. In pooled analyses using study-specific quartiles, cruciferous vegetable intake was not associated with breast cancer outcomes, adjusting for known clinical prognostic factors and selected lifestyle factors. HRs (95%CIs) by increasing quartiles (reference=lowest quartile) were 1.08 (0.93–1.25), 1.01 (0.87–1.18), and 1.10 (0.95–1.28) for recurrence (Ptrend=0.34) and 1.01 (0.88–1.15), 0.97 (0.84–1.11), and 0.99 (0.86–1.13) for total mortality (Ptrend=0.84). No associations were observed for subgroups defined by ER status, stage, or tamoxifen therapy. Cruciferous vegetable intake at approximately two years after diagnosis was not associated with recurrence or mortality. Our results do not support an association between post-diagnosis cruciferous vegetable intake and breast cancer outcomes. PMID:23765086

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

    PubMed Central

    Hemminki, E.; McPherson, K.

    1997-01-01

    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. PMID:9251544

  8. PD-L1 expression as predictive biomarker in patients with NSCLC: a pooled analysis

    PubMed Central

    Natoli, Clara; Rizzo, Sergio; Galvano, Antonio; Listì, Angela; Cicero, Giuseppe; Rolfo, Christian; Santini, Daniele; Russo, Antonio

    2016-01-01

    Background Clinical trials of immune checkpoints modulators, including both programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) inhibitors, have recently shown promising activity and tolerable toxicity in pre-treated NSCLC patients. However the predictive role of PD-L1 expression is still controversial. This pooled analysis aims to clarify the association of clinical objective responses to anti PD-1/PD-L1 monoclonal antibodies (MoAbs) and tumor PD-L1 expression in pre-treated NSCLC patients. Methods Data from published studies, that evaluated efficacy and safety of PD-1/PD-L1 inhibitors in pre-treated NSCLC patients, stratified by tumor PD-L1 expression status (immunohistochemistry, cut-off point 1%), were collected by searching in PubMed, Cochrane Library, American Society of Clinical Oncology, European Society of Medical Oncology and World Conference of Lung Cancer, meeting proceedings. Pooled Odds ratio (OR) and 95% confidence intervals (95% CIs) were calculated for the Overall Response Rate (ORR) (as evaluated by Response Evaluation Criteria in Solid Tumors, version 1.1), according to PD-L1 expression status. Results A total of seven studies, with 914 patients, were eligible. Pooled analysis showed that patients with PD-L1 positive tumors (PD-L1 tumor cell staining ≥1%), had a significantly higher ORR, compared to patients with PD-L1 negative tumors (OR: 2.44; 95% CIs: 1.61-3.68). Conclusions PD-L1 tumor over-expression seems to be associated with higher clinical activity of anti PD-1/PD-L1 MoAbs, in pre-treated NSCLC patients, suggesting a potential role of PD-L1 expression, IHC cut-off point 1%, as predictive biomarker for the selection of patients to treat with immune-checkpoint inhibitors. PMID:26918451

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

    PubMed Central

    2012-01-01

    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. PMID:22862891

  10. Gait Speed Predicts Incident Disability: A Pooled Analysis

    PubMed Central

    Patel, Kushang V.; Rosano, Caterina; Rubin, Susan M.; Satterfield, Suzanne; Harris, Tamara; Ensrud, Kristine; Orwoll, Eric; Lee, Christine G.; Chandler, Julie M.; Newman, Anne B.; Cauley, Jane A.; Guralnik, Jack M.; Ferrucci, Luigi; Studenski, Stephanie A.

    2016-01-01

    Background. Functional independence with aging is an important goal for individuals and society. Simple prognostic indicators can inform health promotion and care planning, but evidence is limited by heterogeneity in measures of function. Methods. We performed a pooled analysis of data from seven studies of 27,220 community-dwelling older adults aged 65 or older with baseline gait speed, followed for disability and mortality. Outcomes were incident inability or dependence on another person in bathing or dressing; and difficulty walking ¼ – ½ mile or climbing 10 steps within 3 years. Results. Participants with faster baseline gait had lower rates of incident disability. In subgroups (defined by 0.2 m/s-wide intervals from <0.4 to ≥1.4 m/s) with increasingly greater gait speed, 3-year rates of bathing or dressing dependence trended from 10% to 1% in men, and from 15% to 1% in women, while mobility difficulty trended from 47% to 4% in men and 40% to 6% in women. The age-adjusted relative risk ratio per 0.1 m/s greater speed for bathing or dressing dependence in men was 0.68 (0.57–0.81) and in women: 0.74 (0.66–0.82); for mobility difficulty, men: 0.75 (0.68–0.82), women: 0.73 (0.67–0.80). Results were similar for combined disability and mortality. Effects were largely consistent across subgroups based on age, gender, race, body mass index, prior hospitalization, and selected chronic conditions. In the presence of multiple other risk factors for disability, gait speed significantly increased the area under the receiver operator characteristic curve. Conclusion. In older adults, gait speed predicts 3 year incidence of bathing or dressing dependence, mobility difficulty, and a composite outcome of disability and mortality. PMID:26297942

  11. Sequence analysis of pooled bacterial samples enables identification of strain variation in group A streptococcus

    PubMed Central

    Weldatsadik, Rigbe G.; Wang, Jingwen; Puhakainen, Kai; Jiao, Hong; Jalava, Jari; Räisänen, Kati; Datta, Neeta; Skoog, Tiina; Vuopio, Jaana; Jokiranta, T. Sakari; Kere, Juha

    2017-01-01

    Knowledge of the genomic variation among different strains of a pathogenic microbial species can help in selecting optimal candidates for diagnostic assays and vaccine development. Pooled sequencing (Pool-seq) is a cost effective approach for population level genetic studies that require large numbers of samples such as various strains of a microbe. To test the use of Pool-seq in identifying variation, we pooled DNA of 100 Streptococcus pyogenes strains of different emm types in two pools, each containing 50 strains. We used four variant calling tools (Freebayes, UnifiedGenotyper, SNVer, and SAMtools) and one emm1 strain, SF370, as a reference genome. In total 63719 SNPs and 164 INDELs were identified in the two pools concordantly by at least two of the tools. Majority of the variants (93.4%) from six individually sequenced strains used in the pools could be identified from the two pools and 72.3% and 97.4% of the variants in the pools could be mined from the analysis of the 44 complete Str. pyogenes genomes and 3407 sequence runs deposited in the European Nucleotide Archive respectively. We conclude that DNA sequencing of pooled samples of large numbers of bacterial strains is a robust, rapid and cost-efficient way to discover sequence variation. PMID:28361960

  12. 76 FR 72923 - Pool Corporation; Analysis To Aid Public Comment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-28

    ... From the Federal Register Online via the Government Publishing Office FEDERAL TRADE COMMISSION... received on or before December 22, 2011. ADDRESSES: Interested parties may file a comment online or on... section below. Write ``PoolCorp, File No. 101 0115'' on your comment, and file your comment online...

  13. Meta- and pooled analyses of the cytochrome P-450 1B1 Val432Leu polymorphism and breast cancer: a HuGE-GSEC review.

    PubMed

    Paracchini, Valentina; Raimondi, Sara; Gram, Inger T; Kang, Daehee; Kocabas, Neslihan A; Kristensen, Vessela N; Li, Donghui; Parl, Fritz F; Rylander-Rudqvist, Tove; Soucek, Pavel; Zheng, Wei; Wedren, Sara; Taioli, Emanuela

    2007-01-15

    The association between the cytochrome P-450 1B1 (CYP1B1) Val432Leu polymorphism and breast cancer was assessed through a meta-analysis of all published case-control studies and a pooled analysis of both published and unpublished case-control studies from the Genetic Susceptibility to Environmental Carcinogens (GSEC) database ( www.upci.upmc.edu/research/ccps/ccontrol/g_intro.html ). GSEC is a collaborative project that gathers information on studies of metabolic gene polymorphisms and cancer. Thirteen articles were included in the meta-analysis (14,331 subjects; 7,514 cases, 6,817 controls); nine data sets were included in the pooled analysis (6,842 subjects; 3,391 cases, 3,451 controls). A summary meta- or pooled estimate of the association between the CYP1B1 Val432Leu polymorphism and breast cancer could not be calculated because of statistically significant heterogeneity in the point estimates among studies. No association between the CYP1B1 Val432Leu polymorphism and breast cancer was observed in Asians (for Val/Val and Val/Leu combined, odds ratio (OR) = 1.0, 95% confidence interval (CI): 0.8, 1.2). An inverse association was observed in populations of mixed/African origin (OR = 0.8, 95% CI: 0.7, 0.9). The pooled analysis suggested a possible association in Caucasians (for Val/Val and Val/Leu combined, OR = 1.5, 95% CI: 1.1, 2.1), with effect modification across age categories. The observed effect of age on the association in Caucasians indicates that further studies are needed on the role of CYP1B1 Val432Leu in estrogen metabolism according to age, ethnicity, and menopausal status.

  14. Myelodysplastic Syndrome and Benzene Exposure Among Petroleum Workers: An International Pooled Analysis

    PubMed Central

    2012-01-01

    Background Benzene at high concentrations is known to cause acute myeloid leukemia (AML), but its relationship with other lymphohematopoietic (LH) cancers remains uncertain, particularly at low concentrations. In this pooled analysis, we examined the risk of five LH cancers relative to lower levels of benzene exposure in petroleum workers. Methods We updated three nested case–control studies from Australia, Canada, and the United Kingdom with new incident LH cancers among petroleum distribution workers through December 31, 2006, and pooled 370 potential case subjects and 1587 matched LH cancer-free control subjects. Quantitative benzene exposure in parts per million (ppm) was blindly reconstructed using historical monitoring data, and exposure certainty was scored as high, medium, or low. Two hematopathologists assigned diagnoses and scored the certainty of diagnosis as high, medium, or low. Dose–response relationships were examined for five LH cancers, including the three most common leukemia cell-types (AML, chronic myeloid leukemia [CML], and chronic lymphoid leukemia [CLL]) and two myeloid tumors (myelodysplastic syndrome [MDS] and myeloproliferative disease [MPD]). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression, controlling for age, sex, and time period. Results Cumulative benzene exposure showed a monotonic dose–response relationship with MDS (highest vs lowest tertile, >2.93 vs ≤0.348 ppm-years, OR = 4.33, 95% CI = 1.31 to 14.3). For peak benezene exposures (>3 ppm), the risk of MDS was increased in high and medium certainty diagnoses (peak exposure vs no peak exposure, OR = 6.32, 95% CI = 1.32 to 30.2) and in workers having the highest exposure certainty (peak exposure vs no peak exposure, OR = 5.74, 95% CI = 1.05 to 31.2). There was little evidence of dose–response relationships for AML, CLL, CML, or MPD. Conclusions Relatively low-level exposure to benzene experienced by petroleum

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

    PubMed

    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

    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.

  16. Analysis of the Pentagon’s Press Pool Tests

    DTIC Science & Technology

    1987-04-14

    the beginning of the Associated Press in 1849. Member organizations of a pool also have rules to abide by. As Victor Rosewater said: The original...parties to the arrangement. IVictor Rosewater , History of Cooperative News-Gathering in the United States (New York: D. Appleton and Company, 1930...Company, Inc., 1984. Reston, James. The Artillery of the Press. New York: harper & Row, 1967. Rosewater , Victor. History of Cooperative News

  17. Microbiological analysis in three diverse natural geothermal bathing pools in Iceland.

    PubMed

    Thorolfsdottir, Berglind Osk Th; Marteinsson, Viggo Thor

    2013-03-14

    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.

  18. Microbiological Analysis in Three Diverse Natural Geothermal Bathing Pools in Iceland

    PubMed Central

    Thorolfsdottir, Berglind Osk Th.; Marteinsson, Viggo Thor

    2013-01-01

    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. PMID:23493033

  19. MTHFR 677C>T Polymorphism and the Risk of Breast Cancer: Evidence from an Original Study and Pooled Data for 28031 Cases and 31880 Controls

    PubMed Central

    Sekhar, Deepa; Francis, Amirtharaj; Gupta, Nishi; Konwar, Rituraj; Kumar, Sandeep; Kumar, Surender; Thangaraj, Kumarasamy; Rajender, Singh

    2015-01-01

    Background Methylenetetrahydrofolate reductase (MTHFR) acts at an important metabolic point in the regulation of cellular methylation reaction. It assists in the conversion of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. The latter aids in remethylation of homocysteine to de novo methionine that is required for DNA synthesis. The objective of this study was to examine the effect of MTHFR 677 C>T polymorphism on the risk of breast cancer in the Indian sub-continent. Methods and Results We genotyped 677 C>T locus in 1096 individuals that were classified into cases (N=588) and controls (N=508). Genotype data were analyzed using chi-square test. No significant difference was observed in the distribution of genotypes between cases and controls in north Indian (P = 0.932), south Indian (P = 0.865), and pooled data (P = 0.680). To develop a consensus regarding the impact of 677C>T polymorphism on breast cancer risk, we also conducted a meta-analysis on 28031 cases and 31880 controls that were pooled from sixty one studies. The overall summary estimate upon meta-analysis suggested no significant correlation between the 677C>T substitution and breast cancer in the dominant model (Fixed effect model: OR = 0.97, P=0.072, Random effects model: OR = 0.96, P = 0.084) or the recessive model (Fixed effect model: OR = 1.05, P = 0.089; Random effects model: OR= 1.08, P= 0.067). Conclusion 677 C>T substitution does not affect breast cancer risk in the Indo-European and Dravidian populations of India. Analysis on pooled data further ruled out association between the 677 C>T polymorphism and breast cancer. Therefore, 677 C>T substitution does not appear to influence the risk of breast cancer. PMID:25803740

  20. Effectiveness of flexible sigmoidoscopy screening in men and women and different age groups: pooled analysis of randomised trials

    PubMed Central

    Holme, Øyvind; Schoen, Robert E; Senore, Carlo; Segnan, Nereo; Hoff, Geir; Løberg, Magnus; Bretthauer, Michael; Adami, Hans-Olov; Kalager, Mette

    2017-01-01

    Objective To compare the effectiveness of flexible sigmoidoscopy in screening for colorectal cancer by patient sex and age. Design Pooled analysis of randomised trials (the US Prostate, Lung, Colorectal and Ovarian cancer screening trial (PLCO), the Italian Screening for Colon and Rectum trial (SCORE), and the Norwegian Colorectal Cancer Prevention trial (NORCCAP)). Data sources Aggregated data were pooled from each randomised trial on incidence of colorectal cancer and mortality stratified by sex, age at screening, and colon subsite (distal v proximal). Eligibility criteria for selecting studies Invited individuals aged 55-74 (PLCO), 55-64 (SCORE), and 50-64 (NORCCAP). Individuals were randomised to receive flexible sigmoidoscopy screening once only (SCORE and NORCCAP) or twice (PLCO), or receive usual care (no intervention). Results 287 928 individuals were included in the pooled analysis; 115 139 randomised to screening and 172 789 to usual care. Compliance rates were 58%, 63%, and 87% in SCORE, NORCCAP, and PLCO, respectively. Median follow-up was 10.5 to 12.1 years. Screening reduced the incidence of colorectal cancer in men (relative risk 0.76; 95% confidence interval 0.70 to 0.83) and women (0.83; 0.75 to 0.92). No difference in the effect of screening was seen between men younger than 60 and those older than 60. Screening reduced the incidence of colorectal cancer in women younger than 60 (relative risk 0.71; 95% confidence interval 0.59 to 0.84), but not significantly in those aged 60 or older (0.90; 0.80 to 1.02). Colorectal cancer mortality was significantly reduced in both younger and older men, and in women younger than 60. Screening reduced colorectal cancer incidence to a similar extent in the distal colon in men and women, but there was no effect of screening in the proximal colon in older women with a significant interaction between sex and age group (P=0.04). Conclusion Flexible sigmoidoscopy is an effective tool for colorectal cancer

  1. Pooled analysis of clinical outcome for EGFR TKI-treated patients with EGFR mutation-positive NSCLC

    PubMed Central

    Paz-Ares, Luis; Soulières, Denis; Moecks, Joachim; Bara, Ilze; Mok, Tony; Klughammer, Barbara

    2014-01-01

    Patients with non-small-cell lung cancer (NSCLC) appear to gain particular benefit from treatment with epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKI) if their disease tests positive for EGFR activating mutations. Recently, several large, controlled, phase III studies have been published in NSCLC patients with EGFR mutation-positive tumours. Given the increased patient dataset now available, a comprehensive literature search for EGFR TKIs or chemotherapy in EGFR mutation-positive NSCLC was undertaken to update the results of a previously published pooled analysis. Pooling eligible progression-free survival (PFS) data from 27 erlotinib studies (n = 731), 54 gefitinib studies (n = 1802) and 20 chemotherapy studies (n = 984) provided median PFS values for each treatment. The pooled median PFS was: 12.4 months (95% accuracy intervals [AI] 11.6–13.4) for erlotinib-treated patients; 9.4 months (95% AI 9.0–9.8) for gefitinib-treated patients; and 5.6 months (95% AI 5.3–6.0) for chemotherapy. Both erlotinib and gefitinib resulted in significantly longer PFS than chemotherapy (permutation testing; P = 0.000 and P = 0.000, respectively). Data on more recent TKIs (afatinib, dacomitinib and icotinib) were insufficient at this time-point to carry out a pooled PFS analysis on these compounds. The results of this updated pooled analysis suggest a substantial clear PFS benefit of treating patients with EGFR mutation-positive NSCLC with erlotinib or gefitinib compared with chemotherapy. PMID:25100284

  2. Pooled Analysis of the Prognostic and Predictive Effects of KRAS Mutation Status and KRAS Mutation Subtype in Early-Stage Resected Non–Small-Cell Lung Cancer in Four Trials of Adjuvant Chemotherapy

    PubMed Central

    Shepherd, Frances A.; Domerg, Caroline; Hainaut, Pierre; Jänne, Pasi A.; Pignon, Jean-Pierre; Graziano, Stephen; Douillard, Jean-Yves; Brambilla, Elizabeth; Le Chevalier, Thierry; Seymour, Lesley; Bourredjem, Abderrahmane; Teuff, Gwénaël Le; Pirker, Robert; Filipits, Martin; Rosell, Rafael; Kratzke, Robert; Bandarchi, Bizhan; Ma, Xiaoli; Capelletti, Marzia; Soria, Jean-Charles; Tsao, Ming-Sound

    2013-01-01

    Purpose We undertook this analysis of KRAS mutation in four trials of adjuvant chemotherapy (ACT) versus observation (OBS) to clarify the prognostic/predictive roles of KRAS in non–small-cell lung cancer (NSCLC). Methods KRAS mutation was determined in blinded fashion. Exploratory analyses were performed to characterize relationships between mutation status and subtype and survival outcomes using a multivariable Cox model. Results Among 1,543 patients (763 OBS, 780 ACT), 300 had KRAS mutations (codon 12, n = 275; codon 13, n = 24; codon 14, n = 1). In OBS patients, there was no prognostic difference for overall survival for codon-12 (mutation v wild type [WT] hazard ratio [HR] = 1.04; 95% CI, 0.77 to 1.40) or codon-13 (HR = 1.01; 95% CI, 0.47 to 2.17) mutations. No significant benefit from ACT was observed for WT-KRAS (ACT v OBS HR = 0.89; 95% CI, 0.76 to 1.04; P = .15) or codon-12 mutations (HR = 0.95; 95% CI, 0.67 to 1.35; P = .77); with codon-13 mutations, ACT was deleterious (HR = 5.78; 95% CI, 2.06 to 16.2; P < .001; interaction P = .002). There was no prognostic effect for specific codon-12 amino acid substitution. The effect of ACT was variable among patients with codon-12 mutations: G12A or G12R (HR = 0.66; P = .48), G12C or G12V (HR = 0.94; P = .77) and G12D or G12S (HR = 1.39; P = .48; comparison of four HRs, including WT, interaction P = .76). OBS patients with KRAS-mutated tumors were more likely to develop second primary cancers (HR = 2.76, 95% CI, 1.34 to 5.70; P = .005) but not ACT patients (HR = 0.66; 95% CI, 0.25 to 1.75; P = .40; interaction, P = .02). Conclusion KRAS mutation status is not significantly prognostic. The potential interaction in patients with codon-13 mutations requires validation. At this time, KRAS status cannot be recommended to select patients with NSCLC for ACT. PMID:23630215

  3. Distinct cholesterogenic and lipidogenic gene expression patterns in ovarian cancer - a new pool of biomarkers

    PubMed Central

    Pampalakis, Georgios; Politi, Angeliki-Louiza; Papanastasiou, Anastasios; Sotiropoulou, Georgia

    2015-01-01

    Cancer cells display different metabolic requirements compared to nonmalignant cells imposed by their need for rapid proliferation. Alterations in cellular metabolic pathways of lipid and cholesterol synthesis have been linked to tumorigenesis and cancer progression but have not been exploited in clinical diagnosis. Here, the expression of genes related to cholesterol/lipid metabolism was measured with semiquantitative and real-time RT-PCR in RNA isolated from normal, benign and cancer ovarian tissues. We found that both SREBF2 and its target gene DHCR7 are downregulated in ovarian cancer tissues. On the contrary, SREBF1c and its target SCD1 were upregulated. The steroidogenesis regulator PDE8B was found downregulated. Oncomine analysis supported these findings, and further revealed that in ovarian cancers, the SREBF1-regulated lipidogenic pathway is activated while the SREBF2-regulated cholesterogenic pathway is repressed based on expression profiles of HMGCR and DHCR7. In conclusion, we show that ovarian cancer cells display distinct lipidogenic and cholesterogenic gene expression profiles with potential applications in the development of new biomarkers and/or treatment of ovarian cancer. Reduced cholesterol and enhanced lipid synthesis and SCD1 expression may provide an explanation for the previously reported increased membrane fluidity of ovarian cancer cells, a finding that merits further investigation. PMID:26807200

  4. Alcohol consumption and risk of melanoma among women: pooled analysis of eight case-control studies.

    PubMed

    Miura, Kyoko; Zens, Michael S; Peart, Tessa; Holly, Elizabeth A; Berwick, Marianne; Gallagher, Richard P; Mack, Thomas M; Elwood, J Mark; Karagas, Margaret R; Green, Adèle C

    2015-11-01

    While alcohol consumption is known to increase the risk of several types of cancer, evidence regarding the association between alcohol and melanoma is inconclusive. This pooled analysis was conducted to examine total alcohol consumption (grams per day), and type of alcohol consumed (beer, wine, beer and wine combined, and liquor) in relation to melanoma among women using original data from eight completed case-control studies (1886 cases and 2113 controls), with adjustment for the potential confounding effects of sun exposure-related factors. We found a positive association with ever consuming alcohol [adjusted pooled odds ratio (pOR) 1.3, 95 % confidence interval (CI) 1.1-1.5]. Specifically the pORs were 1.4 (95 % CI 1.1-1.8) for wine, 1.1 (95 % CI 0.9-1.5) for beer and 1.2 (95 % CI 1.0-1.4) for liquor. However, the pOR for the highest fourth of consumption compared with never consumption was 1.0 (95 % CI 0.7-1.3) without evidence of a trend with increasing amount of total alcohol, or separately with amount of beer, wine or liquor consumed. Stratifying by anatomic site of lesion, number of nevi, age group, or histologic subtype did not alter these results. Although the results showed a weak positive association between ever consuming alcohol and melanoma occurrence, our findings do not provide strong support for the hypothesis that alcohol consumption plays a role in the development of melanoma in women.

  5. Identification of novel cancer therapeutic targets using a designed and pooled shRNA library screen

    PubMed Central

    Oliver, David; Ji, Hao; Liu, Piaomu; Gasparian, Alexander; Gardiner, Ellen; Lee, Samuel; Zenteno, Adrian; Perinskaya, Lillian O.; Chen, Mengqian; Buckhaults, Phillip; Broude, Eugenia; Wyatt, Michael D.; Valafar, Homayoun; Peña, Edsel; Shtutman, Michael

    2017-01-01

    Targeted cancer therapeutics aim to exploit tumor-specific, genetic vulnerabilities specifically affecting neoplastic cells without similarly affecting normal cells. Here we performed sequencing-based screening of an shRNA library on a panel of cancer cells of different origins as well as normal cells. The shRNA library was designed to target a subset of genes previously identified using a whole genome screening approach. This focused shRNA library was infected into cells followed by analysis of enrichment and depletion of the shRNAs over the course of cell proliferation. We developed a bootstrap likelihood ratio test for the interpretation of the effects of multiple shRNAs over multiple cell line passages. Our analysis identified 44 genes whose depletion preferentially inhibited the growth of cancer cells. Among these genes ribosomal protein RPL35A, putative RNA helicase DDX24, and coatomer complex I (COPI) subunit ARCN1 most significantly inhibited growth of multiple cancer cell lines without affecting normal cell growth and survival. Further investigation revealed that the growth inhibition caused by DDX24 depletion is independent of p53 status underlining its value as a drug target. Overall, our study establishes a new approach for the analysis of proliferation-based shRNA selection strategies and identifies new targets for the development of cancer therapeutics. PMID:28223711

  6. Identification of novel cancer therapeutic targets using a designed and pooled shRNA library screen.

    PubMed

    Oliver, David; Ji, Hao; Liu, Piaomu; Gasparian, Alexander; Gardiner, Ellen; Lee, Samuel; Zenteno, Adrian; Perinskaya, Lillian O; Chen, Mengqian; Buckhaults, Phillip; Broude, Eugenia; Wyatt, Michael D; Valafar, Homayoun; Peña, Edsel; Shtutman, Michael

    2017-02-22

    Targeted cancer therapeutics aim to exploit tumor-specific, genetic vulnerabilities specifically affecting neoplastic cells without similarly affecting normal cells. Here we performed sequencing-based screening of an shRNA library on a panel of cancer cells of different origins as well as normal cells. The shRNA library was designed to target a subset of genes previously identified using a whole genome screening approach. This focused shRNA library was infected into cells followed by analysis of enrichment and depletion of the shRNAs over the course of cell proliferation. We developed a bootstrap likelihood ratio test for the interpretation of the effects of multiple shRNAs over multiple cell line passages. Our analysis identified 44 genes whose depletion preferentially inhibited the growth of cancer cells. Among these genes ribosomal protein RPL35A, putative RNA helicase DDX24, and coatomer complex I (COPI) subunit ARCN1 most significantly inhibited growth of multiple cancer cell lines without affecting normal cell growth and survival. Further investigation revealed that the growth inhibition caused by DDX24 depletion is independent of p53 status underlining its value as a drug target. Overall, our study establishes a new approach for the analysis of proliferation-based shRNA selection strategies and identifies new targets for the development of cancer therapeutics.

  7. Imported malaria in pregnant women: a retrospective pooled analysis

    PubMed Central

    Käser, Annina K.; Arguin, Paul M.; Chiodini, Peter L.; Smith, Valerie; Delmont, Jean; Jiménez, Beatriz C.; Färnert, Anna; Kimura, Mikio; Ramharter, Michael; Grobusch, Martin P.; Schlagenhauf, Patricia

    2015-01-01

    Summary Background Data on imported malaria in pregnant women are scarce. Method A retrospective, descriptive study of pooled data on imported malaria in pregnancy was done, using data from 1977 to 2014 from 8 different collaborators in Europe, the United States and Japan. Most cases were from the period 1991–2014. National malaria reference centresas well as specialists on this topic were asked to search their archives for cases of imported malaria in pregnancy. A total of 632 cases were collated, providing information on Plasmodium species, region of acquisition, nationality, country of residence, reason for travel, age, gestational age, prophylactic measures and treatment used, as well as on complications and outcomes in mother and child. Results Datasets from some sources were incomplete. The predominant Plasmodium species was P. falciparum in 72% of cases. Among the 543 cases where information on the use of chemoprophylaxis was known, 471 (74.5%) did not use chemoprophylaxis or used incorrect or incomplete chemoprophylaxis. The main reason for travelling was “visiting friends and relatives” VFR (48.6%) and overall, most cases of malaria were imported from West Africa (85.9%). Severe anaemia was the most frequent complication in the mother. Data on offspring outcome was limited, but spontaneous abortion was a frequently reported foetal outcome (n = 14). A total of 50 different variants of malaria treatment regimens were reported. Conclusion Imported cases of malaria in pregnancy are mainly P. falciparum acquired in sub-Saharan Africa. Malaria prevention and treatment in pregnant travellers is a challenge for travel medicine due to few data on medication safety and maternal and foetal outcomes. International, collaborative efforts are needed to capture standardized data on imported malaria cases in pregnant women. PMID:26227740

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

    SciTech Connect

    Hongbin Zhang; Haihua Zhao; Cliff Davis

    2008-06-01

    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

  9. Comprehensive analysis of correlation coefficients estimated from pooling heterogeneous microarray data

    PubMed Central

    2013-01-01

    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. PMID:23822712

  10. Vitamin D Pooling Project

    Cancer.gov

    The Vitamin D Pooling Project of Rarer Cancers brought together investigators from 10 cohorts to conduct a large prospective epidemiologic study of the association between vitamin D status and seven rarer cancers.

  11. Pooled analyses of eribulin in metastatic breast cancer patients with at least one prior chemotherapy

    PubMed Central

    Pivot, X.; Marmé, F.; Koenigsberg, R.; Guo, M.; Berrak, E.; Wolfer, A.

    2016-01-01

    Background Based on data from two multicenter, phase III clinical trials (Studies 301 and 305), eribulin (a microtubule dynamics inhibitor) is indicated in the European Union (EU) for patients with locally advanced or metastatic breast cancer (MBC) after ≥1 prior chemotherapy for advanced disease, including an anthracycline and a taxane in either the adjuvant or metastatic setting. Data from Studies 305 and 301 were pooled to investigate the efficacy of eribulin in various subgroups of patients who matched the EU label, including those with human epidermal growth factor receptor 2 (HER2)-negative and triple-negative disease. Patients and methods In Study 305 (NCT00388726), patients were randomized 2:1 to eribulin mesylate 1.4 mg/m2 (equivalent to eribulin 1.23 mg/m2 [expressed as free base]) intravenously on days 1 and 8 every 21 days] or treatment of physician's choice after 2–5 prior chemotherapies (≥2 for advanced disease), including an anthracycline and a taxane (in early/advanced setting). In Study 301 (NCT00337103), patients were randomized 1:1 to eribulin (as above) or capecitabine (1.25 g/m2 orally twice daily on days 1–14 every 21 days) following ≤3 prior chemotherapies (≤2 for advanced disease), including an anthracycline and a taxane. Efficacy end points were investigated in the intent-to-treat population and subgroups, pooled as discussed above. Results Overall, 1644 patients were included (eribulin: 946; control: 698); baseline characteristics were well matched. Overall survival was significantly longer with eribulin versus control (P < 0.01), as were progression-free survival and clinical benefit rate (both P < 0.05). Significant survival benefits with eribulin versus control were observed in a wide range of patient subgroups, including HER2-negative or triple-negative disease (all P < 0.05). Conclusion Our findings underline the survival benefit achieved by eribulin used according to EU label in the overall MBC population and in various

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

    SciTech Connect

    Lee, Percy; Eppinga, Wietse; Lagerwaard, Frank; Cloughesy, Timothy; Slotman, Benjamin; Nghiemphu, Phioanh L.; Wang, Pin-Chieh; Kupelian, Patrick; Agazaryan, Nzhde; Demarco, John; Selch, Michael T.; Steinberg, Michael; Kang, Jung Julie

    2013-07-15

    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.

  13. Pooled Genome-Wide Analysis to Identify Novel Risk Loci for Pediatric Allergic Asthma

    PubMed Central

    Ricci, Giampaolo; Astolfi, Annalisa; Remondini, Daniel; Cipriani, Francesca; Formica, Serena; Dondi, Arianna; Pession, Andrea

    2011-01-01

    Background Genome-wide association studies of pooled DNA samples were shown to be a valuable tool to identify candidate SNPs associated to a phenotype. No such study was up to now applied to childhood allergic asthma, even if the very high complexity of asthma genetics is an appropriate field to explore the potential of pooled GWAS approach. Methodology/Principal Findings We performed a pooled GWAS and individual genotyping in 269 children with allergic respiratory diseases comparing allergic children with and without asthma. We used a modular approach to identify the most significant loci associated with asthma by combining silhouette statistics and physical distance method with cluster-adapted thresholding. We found 97% concordance between pooled GWAS and individual genotyping, with 36 out of 37 top-scoring SNPs significant at individual genotyping level. The most significant SNP is located inside the coding sequence of C5, an already identified asthma susceptibility gene, while the other loci regulate functions that are relevant to bronchial physiopathology, as immune- or inflammation-mediated mechanisms and airway smooth muscle contraction. Integration with gene expression data showed that almost half of the putative susceptibility genes are differentially expressed in experimental asthma mouse models. Conclusion/Significance Combined silhouette statistics and cluster-adapted physical distance threshold analysis of pooled GWAS data is an efficient method to identify candidate SNP associated to asthma development in an allergic pediatric population. PMID:21359210

  14. Pooled Sample-Based GWAS: A Cost-Effective Alternative for Identifying Colorectal and Prostate Cancer Risk Variants in the Polish Population

    PubMed Central

    Gaj, Pawel; Maryan, Natalia; Hennig, Ewa E.; Ledwon, Joanna K.; Paziewska, Agnieszka; Majewska, Aneta; Karczmarski, Jakub; Nesteruk, Monika; Wolski, Jan; Antoniewicz, Artur A.; Przytulski, Krzysztof; Rutkowski, Andrzej; Teumer, Alexander; Homuth, Georg; Starzyńska, Teresa; Regula, Jaroslaw; Ostrowski, Jerzy

    2012-01-01

    Background Prostate cancer (PCa) and colorectal cancer (CRC) are the most commonly diagnosed cancers and cancer-related causes of death in Poland. To date, numerous single nucleotide polymorphisms (SNPs) associated with susceptibility to both cancer types have been identified, but their effect on disease risk may differ among populations. Methods To identify new SNPs associated with PCa and CRC in the Polish population, a genome-wide association study (GWAS) was performed using DNA sample pools on Affymetrix Genome-Wide Human SNP 6.0 arrays. A total of 135 PCa patients and 270 healthy men (PCa sub-study) and 525 patients with adenoma (AD), 630 patients with CRC and 690 controls (AD/CRC sub-study) were included in the analysis. Allele frequency distributions were compared with t-tests and χ2-tests. Only those significantly associated SNPs with a proxy SNP (p<0.001; distance of 100 kb; r2>0.7) were selected. GWAS marker selection was conducted using PLINK. The study was replicated using extended cohorts of patients and controls. The association with previously reported PCa and CRC susceptibility variants was also examined. Individual patients were genotyped using TaqMan SNP Genotyping Assays. Results The GWAS selected six and 24 new candidate SNPs associated with PCa and CRC susceptibility, respectively. In the replication study, 17 of these associations were confirmed as significant in additive model of inheritance. Seven of them remained significant after correction for multiple hypothesis testing. Additionally, 17 previously reported risk variants have been identified, five of which remained significant after correction. Conclusion Pooled-DNA GWAS enabled the identification of new susceptibility loci for CRC in the Polish population. Previously reported CRC and PCa predisposition variants were also identified, validating the global nature of their associations. Further independent replication studies are required to confirm significance of the newly uncovered

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

    PubMed Central

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

    2010-01-01

    There are a number of significant challenges encountered when studying development over an extended period of time including subject attrition, changing measurement structures across group and developmental period, and the need to invest substantial time and money. Integrative data analysis is an emerging set of methodologies that overcomes many of the challenges of single sample designs through the pooling of data drawn from multiple existing developmental studies. This approach is characterized by a host of advantages, but this also introduces several new complexities that must be addressed prior to broad adoption by developmental researchers. In this paper we focus on methods for fitting measurement models and creating scale scores using data drawn from multiple longitudinal studies. We present findings from the analysis of repeated measures of internalizing symptomatology that were pooled from three existing developmental studies. We describe and demonstrate each step in the analysis and we conclude with a discussion of potential limitations and directions for future research. PMID:18331129

  16. Exposure to UV radiation and risk of Hodgkin lymphoma: a pooled analysis

    PubMed Central

    Glaser, Sally L.; Schupp, Clayton W.; Ekström Smedby, Karin; de Sanjosé, Silvia; Kane, Eleanor; Melbye, Mads; Forétova, Lenka; Maynadié, Marc; Staines, Anthony; Becker, Nikolaus; Nieters, Alexandra; Brennan, Paul; Boffetta, Paolo; Cocco, Pierluigi; Glimelius, Ingrid; Clavel, Jacqueline; Hjalgrim, Henrik; Chang, Ellen T.

    2013-01-01

    Ultraviolet radiation (UVR) exposure has been inversely associated with Hodgkin lymphoma (HL) risk, but only inconsistently, only in a few studies, and without attention to HL heterogeneity. We conducted a pooled analysis of HL risk focusing on type and timing of UVR exposure and on disease subtypes by age, histology, and tumor-cell Epstein-Barr virus (EBV) status. Four case-control studies contributed 1320 HL cases and 6381 controls. We estimated lifetime, adulthood, and childhood UVR exposure and history of sunburn and sunlamp use. We used 2-stage estimation with mixed-effects models and weighted pooled effect estimates by inverse marginal variances. We observed statistically significant inverse associations with HL risk for UVR exposures during childhood and adulthood, sunburn history, and sunlamp use, but we found no significant dose-response relationships. Risks were significant only for EBV-positive HL (pooled odds ratio, 0.56; 95% confidence interval, 0.35 to 0.91 for the highest overall UVR exposure category), with a significant linear trend for overall exposure (P = .03). Pooled relative risk estimates were not heterogeneous across studies. Increased UVR exposure may protect against HL, particularly EBV-positive HL. Plausible mechanisms involving UVR induction of regulatory T cells or the cellular DNA damage response suggest opportunities for new prevention targets. PMID:24016459

  17. The science of pooling

    SciTech Connect

    Gilbert, E.

    1995-10-01

    The pooling of data from radon studies is described. Pooling refers to the analysis of original data from several studies, not meta-analysis in which summary measures from published data are analyzed. A main objective for pooling is to reduce uncertainty and to obtain more precise estimates of risk than would be available from any single study.

  18. Genetic linkage analysis using pooled DNA and infrared detection of tailed STRP primer patterns

    NASA Astrophysics Data System (ADS)

    Oetting, William S.; Wildenberg, Scott C.; King, Richard A.

    1996-04-01

    The mapping of a disease locus to a specific chromosomal region is an important step in the eventual isolation and analysis of a disease causing gene. Conventional mapping methods analyze large multiplex families and/or smaller nuclear families to find linkage between the disease and a chromosome marker that maps to a known chromosomal region. This analysis is time consuming and tedious, typically requiring the determination of 30,000 genotypes or more. For appropriate populations, we have instead utilized pooled DNA samples for gene mapping which greatly reduces the amount of time necessary for an initial chromosomal screen. This technique assumes a common founder for the disease locus of interest and searches for a region of a chromosome shared between affected individuals. Our analysis involves the PCR amplification of short tandem repeat polymorphisms (STRP) to detect these shared regions. In order to reduce the cost of genotyping, we have designed unlabeled tailed PCR primers which, when combined with a labeled universal primer, provides for an alternative to synthesizing custom labeled primers. The STRP pattern is visualized with an infrared fluorescence based automated DNA sequencer and the patterns quantitated by densitometric analysis of the allele pattern. Differences in the distribution of alleles between pools of affected and unaffected individuals, including a reduction in the number of alleles in the affected pool, indicate the sharing of a region of a chromosome. We have found this method effective for markers 10 - 15 cM away from the disease locus for a recessive genetic disease.

  19. Profiling ribonucleotide and deoxyribonucleotide pools perturbed by gemcitabine in human non-small cell lung cancer cells

    PubMed Central

    Guo, Jian-Ru; Chen, Qian-Qian; Lam, Christopher Wai Kei; Wang, Cai-Yun; Wong, Vincent Kam Wai; Chang, Zee-Fen; Zhang, Wei

    2016-01-01

    In this study, we investigated the dosage effect of gemcitabine, an inhibitor of ribonucleotide reductase (RR), on cellular levels of ribonucleotides and deoxyribonucleotides using high performance liquid chromatography-electrospray ionization tandem mass spectrometric method. As anticipated, after 4-h incubation of non-small cell lung cancer (A549) cells with gemcitabine at 0.5 and 2 μM, there were consistent reductions in levels of deoxyribonucleoside diphosphates (dNDP) and their corresponding deoxyribonucleoside triphosphates (dNTP). However, after 24-h exposure to 0.5 μM gemcitabine, the amounts of dNTP were increased by about 3 fold, whereas cells after 24-h 2 μM gemcitabine treatment exhibited deoxycytidine diphosphate (dCDP), deoxyadenosine diphosphate (dADP) and deoxyguanosine diphosphate (dGDP) levels less than 50% of control values, with deoxycytidine triphosphate (dCTP) and deoxyguanosine triphosphate (dGTP) returning to the control level. Using cell cycle analysis, we found that 24-h incubation at 0.5 μM gemcitabine resulted in a significant increase in S phase arrest, while 2 μM treatment increased G0/G1 population. Our data demonstrated the correlation between the level of RR and the increased levels of dNTPs in the group of 0.5 μM treatment for 24-h with a markedly reduced level of dFdCTP. Accordingly, we proposed that the dosage of dFdC could determine the arrested phase of cell cycle, in turn affecting the recovery of dNTPs pools. PMID:27845436

  20. Swimming Pools.

    ERIC Educational Resources Information Center

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

    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)…

  1. Autophagy provides metabolic substrates to maintain energy charge and nucleotide pools in Ras-driven lung cancer cells

    PubMed Central

    Guo, Jessie Yanxiang; Teng, Xin; Laddha, Saurabh V.; Ma, Sirui; Van Nostrand, Stephen C.; Yang, Yang; Khor, Sinan; Chan, Chang S.; Rabinowitz, Joshua D.; White, Eileen

    2016-01-01

    Autophagy degrades and is thought to recycle proteins, other macromolecules, and organelles. In genetically engineered mouse models (GEMMs) for Kras-driven lung cancer, autophagy prevents the accumulation of defective mitochondria and promotes malignancy. Autophagy-deficient tumor-derived cell lines are respiration-impaired and starvation-sensitive. However, to what extent their sensitivity to starvation arises from defective mitochondria or an impaired supply of metabolic substrates remains unclear. Here, we sequenced the mitochondrial genomes of wild-type or autophagy-deficient (Atg7−/−) Kras-driven lung tumors. Although Atg7 deletion resulted in increased mitochondrial mutations, there were too few nonsynonymous mutations to cause generalized mitochondrial dysfunction. In contrast, pulse-chase studies with isotope-labeled nutrients revealed impaired mitochondrial substrate supply during starvation of the autophagy-deficient cells. This was associated with increased reactive oxygen species (ROS), lower energy charge, and a dramatic drop in total nucleotide pools. While starvation survival of the autophagy-deficient cells was not rescued by the general antioxidant N-acetyl-cysteine, it was fully rescued by glutamine or glutamate (both amino acids that feed the TCA cycle and nucleotide synthesis) or nucleosides. Thus, maintenance of nucleotide pools is a critical challenge for starving Kras-driven tumor cells. By providing bioenergetic and biosynthetic substrates, autophagy supports nucleotide pools and thereby starvation survival. PMID:27516533

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

    SciTech Connect

    Haihua Zhao; Per F. Peterson

    2007-10-01

    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

  3. [(18)F](2S,4R)4-Fluoroglutamine PET Detects Glutamine Pool Size Changes in Triple-Negative Breast Cancer in Response to Glutaminase Inhibition.

    PubMed

    Zhou, Rong; Pantel, Austin R; Li, Shihong; Lieberman, Brian P; Ploessl, Karl; Choi, Hoon; Blankemeyer, Eric; Lee, Hsiaoju; Kung, Hank F; Mach, Robert H; Mankoff, David A

    2017-03-15

    Glutaminolysis is a metabolic pathway adapted by many aggressive cancers, including triple-negative breast cancers (TNBC), to utilize glutamine for survival and growth. In this study, we examined the utility of [(18)F](2S,4R)4-fluoroglutamine ([(18)F]4F-Gln) PET to measure tumor cellular glutamine pool size, whose change might reveal the pharmacodynamic (PD) effect of drugs targeting this cancer-specific metabolic pathway. High glutaminase (GLS) activity in TNBC tumors resulted in low cellular glutamine pool size assayed via high-resolution (1)H magnetic resonance spectroscopy (MRS). GLS inhibition significantly increased glutamine pool size in TNBC tumors. MCF-7 tumors, with inherently low GLS activity compared with TNBC, displayed a larger baseline glutamine pool size that did not change as much in response to GLS inhibition. The tumor-to-blood-activity ratios (T/B) obtained from [(18)F]4F-Gln PET images matched the distinct glutamine pool sizes of both tumor models at baseline. After a short course of GLS inhibitor treatment, the T/B values increased significantly in TNBC, but did not change in MCF-7 tumors. Across both tumor types and after GLS inhibitor or vehicle treatment, we observed a strong positive correlation between T/B values and tumor glutamine pool size measured using MRS (r(2) = 0.71). In conclusion, [(18)F]4F-Gln PET tracked cellular glutamine pool size in breast cancers with differential GLS activity and detected increases in cellular glutamine pool size induced by GLS inhibitors. This study accomplished the first necessary step toward validating [(18)F]4F-Gln PET as a PD marker for GLS-targeting drugs. Cancer Res; 77(6); 1476-84. ©2017 AACR.

  4. A meta-analysis of experimental warming effects on terrestrial nitrogen pools and dynamics.

    PubMed

    Bai, Edith; Li, Shanlong; Xu, Wenhua; Li, Wei; Dai, Weiwei; Jiang, Ping

    2013-07-01

    Global warming may have profound effects on terrestrial ecosystems. However, a comprehensive evaluation of the effects of warming on ecosystem nitrogen (N) pools and dynamics is not available. Here, we compiled data of 528 observations from 51 papers and carried out a meta-analysis of experimental warming effects on 13 variables related to terrestrial N pools and dynamics. We found that, on average, net N mineralization and net nitrification rate were increased by 52.2 and 32.2%, respectively, under experimental warming treatment. N pools were also increased by warming, although the magnitude of this increase was less than that of N fluxes. Soil microbial N and N immobilization were not changed by warming, probably because microbes are limited by carbon sources. Grassland and shrubland/heathland were less responsive to warming than forest, probably because the reduction of soil moisture by warming offset the temperature effect in these areas. Soil heating cable and all-day treatment appeared to be the most effective method on N cycling among all treatment methods. Results of this meta-analysis are useful for better understanding the response of N cycling to global warming and the underlying mechanism of warming effects on plants and ecosystem functions.

  5. Analysis of small sample size studies using nonparametric bootstrap test with pooled resampling method.

    PubMed

    Dwivedi, Alok Kumar; Mallawaarachchi, Indika; Alvarado, Luis A

    2017-03-09

    Experimental studies in biomedical research frequently pose analytical problems related to small sample size. In such studies, there are conflicting findings regarding the choice of parametric and nonparametric analysis, especially with non-normal data. In such instances, some methodologists questioned the validity of parametric tests and suggested nonparametric tests. In contrast, other methodologists found nonparametric tests to be too conservative and less powerful and thus preferred using parametric tests. Some researchers have recommended using a bootstrap test; however, this method also has small sample size limitation. We used a pooled method in nonparametric bootstrap test that may overcome the problem related with small samples in hypothesis testing. The present study compared nonparametric bootstrap test with pooled resampling method corresponding to parametric, nonparametric, and permutation tests through extensive simulations under various conditions and using real data examples. The nonparametric pooled bootstrap t-test provided equal or greater power for comparing two means as compared with unpaired t-test, Welch t-test, Wilcoxon rank sum test, and permutation test while maintaining type I error probability for any conditions except for Cauchy and extreme variable lognormal distributions. In such cases, we suggest using an exact Wilcoxon rank sum test. Nonparametric bootstrap paired t-test also provided better performance than other alternatives. Nonparametric bootstrap test provided benefit over exact Kruskal-Wallis test. We suggest using nonparametric bootstrap test with pooled resampling method for comparing paired or unpaired means and for validating the one way analysis of variance test results for non-normal data in small sample size studies. Copyright © 2017 John Wiley & Sons, Ltd.

  6. Selenium Exposure and Cancer Risk: an Updated Meta-analysis and Meta-regression

    PubMed Central

    Cai, Xianlei; Wang, Chen; Yu, Wanqi; Fan, Wenjie; Wang, Shan; Shen, Ning; Wu, Pengcheng; Li, Xiuyang; Wang, Fudi

    2016-01-01

    The objective of this study was to investigate the associations between selenium exposure and cancer risk. We identified 69 studies and applied meta-analysis, meta-regression and dose-response analysis to obtain available evidence. The results indicated that high selenium exposure had a protective effect on cancer risk (pooled OR = 0.78; 95%CI: 0.73–0.83). The results of linear and nonlinear dose-response analysis indicated that high serum/plasma selenium and toenail selenium had the efficacy on cancer prevention. However, we did not find a protective efficacy of selenium supplement. High selenium exposure may have different effects on specific types of cancer. It decreased the risk of breast cancer, lung cancer, esophageal cancer, gastric cancer, and prostate cancer, but it was not associated with colorectal cancer, bladder cancer, and skin cancer. PMID:26786590

  7. Selenium Exposure and Cancer Risk: an Updated Meta-analysis and Meta-regression.

    PubMed

    Cai, Xianlei; Wang, Chen; Yu, Wanqi; Fan, Wenjie; Wang, Shan; Shen, Ning; Wu, Pengcheng; Li, Xiuyang; Wang, Fudi

    2016-01-20

    The objective of this study was to investigate the associations between selenium exposure and cancer risk. We identified 69 studies and applied meta-analysis, meta-regression and dose-response analysis to obtain available evidence. The results indicated that high selenium exposure had a protective effect on cancer risk (pooled OR = 0.78; 95%CI: 0.73-0.83). The results of linear and nonlinear dose-response analysis indicated that high serum/plasma selenium and toenail selenium had the efficacy on cancer prevention. However, we did not find a protective efficacy of selenium supplement. High selenium exposure may have different effects on specific types of cancer. It decreased the risk of breast cancer, lung cancer, esophageal cancer, gastric cancer, and prostate cancer, but it was not associated with colorectal cancer, bladder cancer, and skin cancer.

  8. Rapid and multiplexed transcript analysis of microbial cultures using capillary electophoresis-detectable oligonucleotide probe pools.

    PubMed

    Rautio, Jari J; Kataja, Kari; Satokari, Reetta; Penttilä, Merja; Söderlund, Hans; Saloheimo, Markku

    2006-06-01

    A rapid assay for multiplex transcript analysis based on solution hybridization with pools of oligonucleotide probes was developed. In this assay called TRAC (transcript analysis with aid of affinity capture) the mRNAs to be studied are hybridized with gene-specific detection probe pools and biotinylated oligo(dT) and captured on streptavidin-coated magnetic particles. Unbound sample material and nonspecifically bound detection probes are removed and the target-specific probes are eluted and detected by capillary electrophoresis. Simultaneous treatment of 96 samples was automated using a magnetic bead particle processor. The assay enabled detection of in vitro transcribed RNA at the level of 30 amol (20 pg) and over a 300-fold linear range. Besides extracted RNA, crude cell lysates were directly used as samples. The assay was used for transcriptional analysis of selected mRNAs in the filamentous fungus Trichoderma reesei in two experimental conditions. TRAC analysis was highly reproducible, providing expression results that were consistent with conventional Northern blot analysis. The whole procedure starting from sample collecting can be carried out in 2 h, making this assay suitable for high-throughput analysis of a limited set of mRNAs e.g. in gene expression monitoring of production organism in microbial bioprocesses.

  9. Pooled analysis of genome-wide association studies of cervical intraepithelial neoplasia 3 (CIN3) identifies a new susceptibility locus

    PubMed Central

    Chen, Dan; Enroth, Stefan; Liu, Han; Sun, Yang; Wang, Huibo; Yu, Min; Deng, Lian; Xu, Shuhua; Gyllensten, Ulf

    2016-01-01

    Recent genome-wide association studies (GWASs) in subjects of European descent have identified associations between cervical cancer risk and three independent loci as well as multiple classical human leukocyte antigen (HLA) alleles at 6p21.3. To search for novel loci associated with development of cervical cancer, we performed a pooled analysis of data from two GWASs by imputing over 10 million genetic variants and 424 classical HLA alleles, for 1,553 intraepithelial neoplasia 3 (CIN3), 81 cervical cancer and 4,442 controls from the Swedish population. Notable findings were validated in an independent study of 961 patients (827 with CIN3 and 123 with cervical cancer) and 1,725 controls. Our data provided increased support for previously identified loci at 6p21.3 (rs9271898, P = 1.2 × 10−24; rs2516448, 1.1 × 10−15; and rs3130196, 2.3 × 10−9, respectively) and also confirmed associations with reported classical HLA alleles including HLA-B*07:02, -B*15:01, -DRB1*13:01, -DRB1*15:01, -DQA1*01:03, -DQB1*06:03 and -DQB1*06:02. In addition, we identified and subsequently replicated an independent signal at rs73730372 at 6p21.3 (odds ratio = 0.60, 95% confidence interval = 0.54–0.67, P = 3.0 × 10−19), which was found to be an expression quantitative trait locus (eQTL) of both HLA-DQA1 and HLA-DQB1. This is one of the strongest common genetic protective variants identified so far for CIN3. We also found HLA-C*07:02 to be associated with risk of CIN3. The present study provides new insights into pathogenesis of CIN3. PMID:27285765

  10. Sample distillation/graphitization system for carbon pool analysis by accelerator mass spectrometry (AMS)

    NASA Astrophysics Data System (ADS)

    Pohlman, J. W.; Knies, D. L.; Grabowski, K. S.; DeTurck, T. M.; Treacy, D. J.; Coffin, R. B.

    2000-10-01

    A facility at the Naval Research Laboratory (NRL), Washington, DC, has been developed to extract, trap, cryogenically distill and graphitize carbon from a suite of organic and inorganic carbon pools for analysis by accelerator mass spectrometry (AMS). The system was developed to investigate carbon pools associated with the formation and stability of methane hydrates. However, since the carbon compounds found in hydrate fields are ubiquitous in aquatic ecosystems, this apparatus is applicable to a number of oceanographic and environmental sample types. Targeted pools are dissolved methane, dissolved organic carbon (DOC), dissolved inorganic carbon (DIC), solid organic matrices (e.g., seston, tissue and sediments), biomarkers and short chained (C 1-C 5) hydrocarbons from methane hydrates. In most instances, the extraction, distillation and graphitization events are continuous within the system, thus, minimizing the possibility of fractionation or contamination during sample processing. A variety of methods are employed to extract carbon compounds and convert them to CO 2 for graphitization. Dissolved methane and DIC from the same sample are sparged and cryogenically separated before the methane is oxidized in a high temperature oxygen stream. DOC is oxidized to CO 2 by 1200 W ultraviolet photo-oxidation lamp, and solids oxidized in sealed, evacuated tubes. Hydrocarbons liberated from the disassociation of gas hydrates are cryogenically separated with a cryogenic temperature control unit, and biomarkers separated and concentrated by preparative capillary gas chromatography (PCGC). With this system, up to 20 samples, standards or blanks can be processed per day.

  11. Cryptococcal meningitis in systemic lupus erythematosus patients: pooled analysis and systematic review.

    PubMed

    Fang, Wenjie; Chen, Min; Liu, Jia; Hagen, Ferry; Ms, Abdullah; Al-Hatmi; Zhang, Peilian; Guo, Yun; Boekhout, Teun; Deng, Danqi; Xu, Jianping; Pan, Weihua; Liao, Wanqing

    2016-09-07

    Cryptococcal meningitis is an important fungal infection among systemic lupus erythematosus patients. We conducted a pooled analysis and systematic review to describe the epidemiological and clinical profile of cryptococcal meningitis in systemic lupus erythematosus patients. From two hospitals in China and nine literature databases, cases and prevalence data were collected for pooled analysis and meta-analysis, respectively. Categorical variables of cases were compared using a χ(2)-test on the statistical program of SAS. A multiple regression analysis was performed to ascertain independent predictors significantly correlated with prognosis. Meta-analysis was conducted by the statistical program of R. The prevalence of cryptococcal meningitis in systemic lupus erythematosus patients was 0.5%. Patients were predominantly females and adults. A prednisone equivalent of more than 30 mg/day before infection was associated with higher mortality (odds ratio (OR)=9.69 (1.54, 60.73)). In all, 36.8-38.9% patients showed low lupus activity when they developed the crytococcal infection. Moreover, 38.2% of the patients were misdiagnosed. The estimated case-fatality rate was 23.6%. Our results suggest that more emphasis should be placed to further understand lupus-related cryptococcal meningitis and to develop better prophylaxis and management strategies to combat this condition.

  12. Cryptococcal meningitis in systemic lupus erythematosus patients: pooled analysis and systematic review

    PubMed Central

    Fang, Wenjie; Chen, Min; Liu, Jia; Hagen, Ferry; MS, Abdullah; Al-Hatmi; Zhang, Peilian; Guo, Yun; Boekhout, Teun; Deng, Danqi; Xu, Jianping; Pan, Weihua; Liao, Wanqing

    2016-01-01

    Cryptococcal meningitis is an important fungal infection among systemic lupus erythematosus patients. We conducted a pooled analysis and systematic review to describe the epidemiological and clinical profile of cryptococcal meningitis in systemic lupus erythematosus patients. From two hospitals in China and nine literature databases, cases and prevalence data were collected for pooled analysis and meta-analysis, respectively. Categorical variables of cases were compared using a χ2-test on the statistical program of SAS. A multiple regression analysis was performed to ascertain independent predictors significantly correlated with prognosis. Meta-analysis was conducted by the statistical program of R. The prevalence of cryptococcal meningitis in systemic lupus erythematosus patients was 0.5%. Patients were predominantly females and adults. A prednisone equivalent of more than 30 mg/day before infection was associated with higher mortality (odds ratio (OR)=9.69 (1.54, 60.73)). In all, 36.8–38.9% patients showed low lupus activity when they developed the crytococcal infection. Moreover, 38.2% of the patients were misdiagnosed. The estimated case-fatality rate was 23.6%. Our results suggest that more emphasis should be placed to further understand lupus-related cryptococcal meningitis and to develop better prophylaxis and management strategies to combat this condition. PMID:27599471

  13. A pooled analysis of body mass index and mortality among African Americans.

    PubMed

    Cohen, Sarah S; Park, Yikyung; Signorello, Lisa B; Patel, Alpa V; Boggs, Deborah A; Kolonel, Laurence N; Kitahara, Cari M; Knutsen, Synnove F; Gillanders, Elizabeth; Monroe, Kristine R; Berrington de Gonzalez, Amy; Bethea, Traci N; Black, Amanda; Fraser, Gary; Gapstur, Susan; Hartge, Patricia; Matthews, Charles E; Park, Song-Yi; Purdue, Mark P; Singh, Pramil; Harvey, Chinonye; Blot, William J; Palmer, Julie R

    2014-01-01

    Pooled analyses among whites and East Asians have demonstrated positive associations between all-cause mortality and body mass index (BMI), but studies of African Americans have yielded less consistent results. We examined the association between BMI and all-cause mortality in a sample of African Americans pooled from seven prospective cohort studies: NIH-AARP, 1995-2009; Adventist Health Study 2, 2002-2008; Black Women's Health Study, 1995-2009; Cancer Prevention Study II, 1982-2008; Multiethnic Cohort Study, 1993-2007; Prostate, Lung, Colorectal and Ovarian Screening Trial, 1993-2009; Southern Community Cohort Study, 2002-2009. 239,526 African Americans (including 100,175 never smokers without baseline heart disease, stroke, or cancer), age 30-104 (mean 52) and 71% female, were followed up to 26.5 years (mean 11.7). Hazard ratios (HR) and 95% confidence intervals (CI) for mortality were derived from multivariate Cox proportional hazards models. Among healthy, never smokers (11,386 deaths), HRs (CI) for BMI 25-27.4, 27.5-29.9, 30-34.9, 35-39.9, 40-49.9, and 50-60 kg/m(2) were 1.02 (0.92-1.12), 1.06 (0.95-1.18), 1.32 (1.18-1.47), 1.54 (1.29-1.83), 1.93 (1.46-2.56), and 1.93 (0.80-4.69), respectively among men and 1.06 (0.99-1.15), 1.15 (1.06-1.25), 1.24 (1.15-1.34), 1.58 (1.43-1.74), 1.80 (1.60-2.02), and 2.31 (1.74-3.07) respectively among women (reference category 22.5-24.9). HRs were highest among those with the highest educational attainment, longest follow-up, and for cardiovascular disease mortality. Obesity was associated with a higher risk of mortality in African Americans, similar to that observed in pooled analyses of whites and East Asians. This study provides compelling evidence to support public health efforts to prevent excess weight gain and obesity in African Americans.

  14. Automated vessel segmentation using cross-correlation and pooled covariance matrix analysis.

    PubMed

    Du, Jiang; Karimi, Afshin; Wu, Yijing; Korosec, Frank R; Grist, Thomas M; Mistretta, Charles A

    2011-04-01

    Time-resolved contrast-enhanced magnetic resonance angiography (CE-MRA) provides contrast dynamics in the vasculature and allows vessel segmentation based on temporal correlation analysis. Here we present an automated vessel segmentation algorithm including automated generation of regions of interest (ROIs), cross-correlation and pooled sample covariance matrix analysis. The dynamic images are divided into multiple equal-sized regions. In each region, ROIs for artery, vein and background are generated using an iterative thresholding algorithm based on the contrast arrival time map and contrast enhancement map. Region-specific multi-feature cross-correlation analysis and pooled covariance matrix analysis are performed to calculate the Mahalanobis distances (MDs), which are used to automatically separate arteries from veins. This segmentation algorithm is applied to a dual-phase dynamic imaging acquisition scheme where low-resolution time-resolved images are acquired during the dynamic phase followed by high-frequency data acquisition at the steady-state phase. The segmented low-resolution arterial and venous images are then combined with the high-frequency data in k-space and inverse Fourier transformed to form the final segmented arterial and venous images. Results from volunteer and patient studies demonstrate the advantages of this automated vessel segmentation and dual phase data acquisition technique.

  15. 3-Bromopyruvate induces rapid human prostate cancer cell death by affecting cell energy metabolism, GSH pool and the glyoxalase system.

    PubMed

    Valenti, Daniela; Vacca, Rosa A; de Bari, Lidia

    2015-12-01

    3-bromopyruvate (3-BP) is an anti-tumour drug effective on hepatocellular carcinoma and other tumour cell types, which affects both glycolytic and mitochondrial targets, depleting cellular ATP pool. Here we tested 3-BP on human prostate cancer cells showing, differently from other tumour types, efficient ATP production and functional mitochondrial metabolism. We found that 3-BP rapidly induced cultured androgen-insensitive (PC-3) and androgen-responsive (LNCaP) prostate cancer cell death at low concentrations (IC(50) values of 50 and 70 μM, respectively) with a multimodal mechanism of action. In particular, 3-BP-treated PC-3 cells showed a selective, strong reduction of glyceraldeide 3-phosphate dehydrogenase activity, due to the direct interaction of the drug with the enzyme. Moreover, 3-BP strongly impaired both glutamate/malate- and succinate-dependent mitochondrial respiration, membrane potential generation and ATP synthesis, concomitant with the inhibition of respiratory chain complex I, II and ATP synthase activities. The drastic reduction of cellular ATP levels and depletion of GSH pool, associated with significant increase in cell oxidative stress, were found after 3-BP treatment of PC-3 cells. Interestingly, the activity of both glyoxalase I and II, devoted to the elimination of the cytotoxic methylglyoxal, was strongly inhibited by 3-BP. Both N-acetylcysteine and aminoguanidine, GSH precursor and methylglyoxal scavenger, respectively, prevented 3-BP-induced PC-3 cell death, showing that impaired cell antioxidant and detoxifying capacities are crucial events leading to cell death. The provided information on the multi-target cytotoxic action of 3-BP, finally leading to PC-3 cell necrosis, might be useful for future development of 3-BP as a therapeutic option for prostate cancer treatment.

  16. Coffee consumption and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma by sex: The Liver Cancer Pooling Project

    PubMed Central

    Petrick, Jessica L.; Freedman, Neal D.; Graubard, Barry I.; Sahasrabuddhe, Vikrant V.; Lai, Gabriel Y.; Alavanja, Michael C.; Beane-Freeman, Laura E.; Boggs, Deborah A.; Buring, Julie E.; Chan, Andrew T.; Chong, Dawn Q.; Fuchs, Charles S.; Gapstur, Susan M.; Gaziano, John Michael; Giovannucci, Edward L.; Hollenbeck, Albert R.; King, Lindsay Y.; Koshiol, Jill; Lee, I-Min; Linet, Martha S.; Palmer, Julie R.; Poynter, Jenny N.; Purdue, Mark P.; Robien, Kim; Schairer, Catherine; Sesso, Howard D.; Sigurdson, Alice J.; Zeleniuch-Jacquotte, Anne; Wactawski-Wende, Jean; Campbell, Peter T.; McGlynn, Katherine A.

    2015-01-01

    Background Coffee consumption has been reported to be inversely associated with hepatocellular carcinoma (HCC), the most common type of liver cancer. Caffeine has chemopreventive properties, but whether caffeine is responsible for the coffee-HCC association is not well studied. In addition, few studies have examined the relationship by sex, and no studies have examined whether there is an association between coffee and intrahepatic cholangiocarcinoma (ICC), the second most common type of liver cancer. Methods In the Liver Cancer Pooling Project, a consortium of U.S.-based cohort studies, data from 1,212,893 individuals (HCC n=860, ICC n=260) in nine cohorts were pooled. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression. Results Higher coffee consumption was associated with lower risk of HCC (HR>3 cups/day vs. non-drinker, 0.73; 95% CI, 0.53-0.99; ptrend cups/day=<0.0001). More notable reduced risk was seen among women than men (pinteraction=0.07). Women who consumed more than three cups of coffee per day were at a 54% lower risk of HCC (HR, 0.46; 95% CI, 0.26-0.81), whereas men had more modest reduced risk of HCC (HR, 0.93; 95% CI, 0.63-1.37). The associations were stronger for caffeinated coffee (HR>3 cups/day vs. non-drinker, 0.71, 95% CI, 0.50-1.01) than decaffeinated coffee (HR, 0.92; 95% CI, 0.55-1.54). There was no relationship between coffee consumption and ICC. Conclusions These findings suggest that, in a U.S. population, coffee consumption is associated with reduced risk of HCC. Impact Further research into specific coffee compounds and mechanisms that may account for these associations is needed. PMID:26126626

  17. p53 deficiency induces cancer stem cell pool expansion in a mouse model of triple-negative breast tumors.

    PubMed

    Chiche, A; Moumen, M; Romagnoli, M; Petit, V; Lasla, H; Jézéquel, P; de la Grange, P; Jonkers, J; Deugnier, M-A; Glukhova, M A; Faraldo, M M

    2016-10-24

    Triple-negative breast cancer is a heterogeneous disease characterized by the expression of basal cell markers, no estrogen or progesterone receptor expression and a lack of HER2 overexpression. Triple-negative tumors often display activated Wnt/β-catenin signaling and most have impaired p53 function. We studied the interplay between p53 loss and Wnt/β-catenin signaling in stem cell function and tumorigenesis, by deleting p53 from the mammary epithelium of K5ΔNβcat mice displaying a constitutive activation of Wnt/β-catenin signaling in basal cells. K5ΔNβcat transgenic mice present amplification of the basal stem cell pool and develop triple-negative mammary carcinomas. The loss of p53 in K5ΔNβcat mice led to an early expansion of mammary stem/progenitor cells and accelerated the formation of triple-negative tumors. In particular, p53-deficient tumors expressed high levels of integrins and extracellular matrix components and were enriched in cancer stem cells. They also overexpressed the tyrosine kinase receptor Met, a feature characteristic of human triple-negative breast tumors. The inhibition of Met kinase activity impaired tumorsphere formation, demonstrating the requirement of Met signaling for cancer stem cell growth in this model. Human basal-like breast cancers with predicted mutated p53 status had higher levels of MET expression than tumors with wild-type p53. These results connect p53 loss and β-catenin activation to stem cell regulation and tumorigenesis in triple-negative cancer and highlight the role of Met signaling in maintaining cancer stem cell properties, revealing new cues for targeted therapies.Oncogene advance online publication, 24 October 2016; doi:10.1038/onc.2016.396.

  18. Bulky DNA adducts in white blood cells: a pooled analysis of 3600 subjects

    PubMed Central

    Ricceri, Fulvio; Godschalk, Roger; Peluso, Marco; Phillips, David H.; Agudo, Antonio; Georgiadis, Panos; Loft, Steffen; Tjonneland, Anne; Raaschou-Nielsen, Ole; Palli, Domenico; Perera, Frederica; Vermeulen, Roel; Taioli, Emanuela; Sram, Radim J.; Munnia, Armelle; Rosa, Fabio; Allione, Alessandra; Matullo, Giuseppe; Vineis, Paolo

    2013-01-01

    Background Bulky DNA adducts are markers of exposure to genotoxic aromatic compounds, which reflect an individual’s ability to metabolically activate carcinogens and to repair DNA damage. Polycyclic aromatic hydrocarbons (PAH) represent a major class of carcinogens that are capable of forming such adducts. Factors that have been reported to be related to DNA adduct levels include smoking, diet, body mass index (BMI), genetic polymorphisms, the season of collection of biologic material, and air pollutants. Methods We pooled eleven studies (3,600 subjects) in which bulky DNA adducts were measured in human white blood cells with similar 32P-postlabelling techniques and for which a similar set of variables was available, including individual data on age, gender, ethnicity, batch, smoking habits, BMI, season of blood collection and a limited set of gene variants. Results Lowest DNA adduct levels were observed in the spring (median 0.50 adducts per 108 nucleotides), followed by summer (0.64), autumn (0.70) and winter (0.85) (p=0.006). The same pattern emerged in multivariate analysis, but only among never smokers (p=0.02). Adduct levels were significantly lower (p=0.001) in Northern Europe (the Netherlands, Denmark) (mean 0.60, median 0.40) than in Southern Europe (Italy, Spain, France, Greece) (mean 0.79, median 0.60). Conclusions In this large pooled analysis, we have found only weak associations between bulky DNA adducts and exposure variables. Seasonality (with higher adducts levels in winter) and air pollution may partly explain some of the inter-area differences (North vs South Europe), but most inter-area and inter-individual variation in adduct levels still remain unexplained. Impact Our study describes the largest pooled analysis of bulky DNA adducts so far, showing that inter-individual variation is still largely unexplained, though seasonality appears to play a role. PMID:20921335

  19. Pooled analysis of recent studies on magnetic fields and childhood leukaemia

    PubMed Central

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

    2010-01-01

    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 μT, 0.2–0.3 μT and ⩾0.3 μT, compared with <0.1 μT, 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. PMID:20877339

  20. Peroral endoscopic myotomy for the treatment of esophageal achalasia: systematic review and pooled analysis.

    PubMed

    Patel, K; Abbassi-Ghadi, N; Markar, S; Kumar, S; Jethwa, P; Zaninotto, G

    2016-10-01

    Peroral endoscopic myotomy (POEM) is a novel approach to performing esophageal myotomy for the treatment of achalasia. This review aims to assess subjective and objective metrics of achalasia treatment efficacy, perioperative adverse events and the incidence of postoperative gastroesophageal reflux disease in patients treated with POEM. Secondary aims include a pooled analysis comparison of the clinical outcomes and procedural safety of POEM versus laparoscopic Heller's myotomy (LHM). A systematic review of the literature, up to and including January 15, 2015, was conducted for studies reporting POEM outcomes. Studies comparing POEM to LHM were also included for the purpose of pooled analysis. Outcomes from 1122 POEM patients, from 22 studies, are reported in this systematic review. Minor operative adverse events included capno/pneumo-peritoneum (30.6%), capno/pneumo-thorax (11.0%) and subcutaneous emphysema (31.6%). Major operative adverse events included mediastinal leak (0.3%), postoperative bleeding (1.1%) and a single mortality (0.09%). There was an improvement in lower esophageal sphincter pressure and timed barium esophagram column height of 66% and 80% post-POEM, respectively. Symptom improvement was demonstrated with a pre- and post-POEM Eckardt score ± standard deviation of 6.8 ± 1.0 and 1.2 ± 0.6, respectively. Pre- and post-POEM endoscopy showed esophagitis in 0% and 19% of patients, respectively. The median (interquartile range) points scored for study quality was 15 (14-16) out of total of 32. Pooled analysis of three comparative studies between LHM and POEM showed similar results for adverse events, perforation rate, operative time and a nonsignificant trend toward a reduced length of hospital stay in the POEM group. In conclusion, POEM is a safe and effective treatment for achalasia, showing significant improvements in objective metrics and achalasia-related symptoms. Randomized comparative studies of LHM and POEM are required to determine the

  1. Pirfenidone for idiopathic pulmonary fibrosis: analysis of pooled data from three multinational phase 3 trials.

    PubMed

    Noble, Paul W; Albera, Carlo; Bradford, Williamson Z; Costabel, Ulrich; du Bois, Roland M; Fagan, Elizabeth A; Fishman, Robert S; Glaspole, Ian; Glassberg, Marilyn K; Lancaster, Lisa; Lederer, David J; Leff, Jonathan A; Nathan, Steven D; Pereira, Carlos A; Swigris, Jeffrey J; Valeyre, Dominique; King, Talmadge E

    2016-01-01

    Pirfenidone is an antifibrotic agent that has been evaluated in three multinational phase 3 trials in patients with idiopathic pulmonary fibrosis (IPF). We analysed pooled data from the multinational trials to obtain the most precise estimates of the magnitude of treatment effect on measures of disease progression.All patients randomised to pirfenidone 2403 mg·day(-1) or placebo in the CAPACITY or ASCEND studies were included in the analysis. Pooled analyses of outcomes at 1 year were based on the pre-specified end-points and analytic methods described in the ASCEND study protocol.A total of 1247 patients were included in the analysis. At 1 year, pirfenidone reduced the proportion of patients with a ≥10% decline in per cent predicted forced vital capacity or death by 43.8% (95% CI 29.3-55.4%) and increased the proportion of patients with no decline by 59.3% (95% CI 29.0-96.8%). A treatment benefit was also observed for progression-free survival, 6-min walk distance and dyspnoea. Gastrointestinal and skin-related adverse events were more common in the pirfenidone group, but rarely led to discontinuation.Analysis of data from three phase 3 trials demonstrated that treatment with pirfenidone for 1 year resulted in clinically meaningful reductions in disease progression in patients with IPF.

  2. Psychological distress in relation to site specific cancer mortality: pooling of unpublished data from 16 prospective cohort studies

    PubMed Central

    Russ, Tom C; Stamatakis, Emmanuel; Kivimäki, Mika

    2017-01-01

    Objective To examine the role of psychological distress (anxiety and depression) as a potential predictor of site specific cancer mortality. Design Pooling of individual participant data from 16 prospective cohort studies initiated 1994-2008. Setting Nationally representative samples drawn from the health survey for England (13 studies) and the Scottish health survey (three studies). Participants 163 363 men and women aged 16 or older at study induction, who were initially free of a cancer diagnosis, provided self reported psychological distress scores (based on the general health questionnaire, GHQ-12) and consented to health record linkage. Main outcome measure Vital status records used to ascertain death from 16 site specific malignancies; the three Scottish studies also had information on cancer registration (incidence). Results The studies collectively contributed an average of 9.5 years of mortality surveillance during which there were 16 267 deaths (4353 from cancer). After adjustment for age, sex, education, socioeconomic status, body mass index (BMI), and smoking and alcohol intake, and with reverse causality (by left censoring) and missing data (by imputation) taken into account, relative to people in the least distressed group (GHQ-12 score 0-6), death rates in the most distressed group (score 7-12) were consistently raised for cancer of all sites combined (multivariable adjusted hazard ratio 1.32, 95% confidence interval 1.18 to 1.48) and cancers not related to smoking (1.45, 1.23 to 1.71), as well as carcinoma of the colorectum (1.84, 1.21 to 2.78), prostate (2.42, 1.29 to 4.54), pancreas (2.76, 1.47 to 5.19), oesophagus (2.59, 1.34 to 5.00), and for leukaemia (3.86, 1.42 to 10.5). Stepwise associations across the full range of distress scores were observed for colorectal and prostate cancer. Conclusion This study contributes to the growing evidence that psychological distress might have some predictive capacity for selected cancer

  3. Exciting Pools

    ERIC Educational Resources Information Center

    Wright, Bradford L.

    1975-01-01

    Advocates the creation of swimming pool oscillations as part of a general investigation of mechanical oscillations. Presents the equations, procedure for deriving the slosh modes, and methods of period estimation for exciting swimming pool oscillations. (GS)

  4. Probabilistic risk analysis of HCDA scenarios in a pool-type breeder reactor

    SciTech Connect

    Page, R.J.; Mueller, C.J.; Rothman, A.B.; Chasanov, M.; Sevy, R.; Marchaterre, J.F.; Froehle, P.J.; Pedersen, D.R.; Farhadieh, R.

    1985-01-01

    One potential design for the future generation of nuclear reactors is that of the breeder reactor. As with present-day reactors there is the necessity for demonstrating that such a reactor will be operable with very small risk to the public. As a result, a probabilistic risk analysis (PRA) will be a valuable tool in the design of future nuclear plants. This paper presents a risk analysis performed to evaluate hypothetical core disruptive accidents (HCDAs) in a large, pool-type LMFBR, and how it was used to evaluate the reduction in risk brought about by the addition of various safety-related design options. It was shown that the base design met the NRC risk guidelines with some margin, and that a design option featuring emergency cooling of the reactor vessel greatly reduced the risk.

  5. PWR core and spent fuel pool analysis using scale and nestle

    SciTech Connect

    Murphy, J. E.; Maldonado, G. I.; St Clair, R.; Orr, D.

    2012-07-01

    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)

  6. BAC-pool sequencing and analysis confirms growth-associated QTLs in the Asian seabass genome

    PubMed Central

    Shen, Xueyan; Ngoh, Si Yan; Thevasagayam, Natascha May; Prakki, Sai Rama Sridatta; Bhandare, Pranjali; Tan, Andy Wee Kiat; Tan, Gui Quan; Singh, Siddharth; Phua, Norman Chun Han; Vij, Shubha; Orbán, László

    2016-01-01

    The Asian seabass is an important marine food fish that has been cultured for several decades in Asia Pacific. However, the lack of a high quality reference genome has hampered efforts to improve its selective breeding. A 3D BAC pool set generated in this study was screened using 22 SSR markers located on linkage group 2 which contains a growth-related QTL region. Seventy-two clones corresponding to 22 FPC contigs were sequenced by Illumina MiSeq technology. We co-assembled the MiSeq-derived scaffolds from each FPC contig with error-corrected PacBio reads, resulting in 187 sequences covering 9.7 Mb. Eleven genes annotated within this region were found to be potentially associated with growth and their tissue-specific expression was investigated. Correlation analysis demonstrated that SNPs in ctsb, skp1 and ppp2ca can be potentially used as markers for selecting fast-growing fingerlings. Conserved syntenies between seabass LG2 and five other teleosts were identified. This study i) provided a 10 Mb targeted genome assembly; ii) demonstrated NGS of BAC pools as a potential approach for mining candidates underlying QTLs of this species; iii) detected eleven genes potentially responsible for growth in the QTL region; and iv) identified useful SNP markers for selective breeding programs of Asian seabass. PMID:27821852

  7. Quality and rigor of the concept mapping methodology: a pooled study analysis.

    PubMed

    Rosas, Scott R; Kane, Mary

    2012-05-01

    The use of concept mapping in research and evaluation has expanded dramatically over the past 20 years. Researchers in academic, organizational, and community-based settings have applied concept mapping successfully without the benefit of systematic analyses across studies to identify the features of a methodologically sound study. Quantitative characteristics and estimates of quality and rigor that may guide for future studies are lacking. To address this gap, we conducted a pooled analysis of 69 concept mapping studies to describe characteristics across study phases, generate specific indicators of validity and reliability, and examine the relationship between select study characteristics and quality indicators. Individual study characteristics and estimates were pooled and quantitatively summarized, describing the distribution, variation and parameters for each. In addition, variation in the concept mapping data collection in relation to characteristics and estimates was examined. Overall, results suggest concept mapping yields strong internal representational validity and very strong sorting and rating reliability estimates. Validity and reliability were consistently high despite variation in participation and task completion percentages across data collection modes. The implications of these findings as a practical reference to assess the quality and rigor for future concept mapping studies are discussed.

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

    SciTech Connect

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

    1993-01-01

    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.

  9. Diclofenac topical solution compared with oral diclofenac: a pooled safety analysis

    PubMed Central

    Roth, Sanford H; Fuller, Philip

    2011-01-01

    Background Topical nonsteroidal anti-inflammatory drug (NSAID) formulations, which produce less systemic exposure compared with oral formulations, are an option for the management of osteoarthritis (OA). However, the overall safety and efficacy of these agents compared with oral or systemic therapy remains controversial. Methods Two 12-week, double-blind, double-dummy, randomized, controlled, multicenter studies compared the safety and efficacy profiles of diclofenac topical solution (TDiclo) with oral diclofenac (ODiclo). Each study independently showed that TDiclo had similar efficacy to ODiclo. To compare the safety profiles of TDiclo and ODiclo, a pooled safety analysis was performed for 927 total patients who had radiologically confirmed symptomatic OA of the knee. This pooled analysis included patients treated with TDiclo, containing 45.5% dimethyl sulfoxide (DMSO), and those treated with ODiclo. Safety assessments included monitoring of adverse events (AEs), recording of vital signs, dermatologic evaluation of the study knee, and clinical laboratory evaluation. Results AEs occurred in 312 (67.1%) patients using TDiclo versus 298 (64.5%) of those taking ODiclo. The most common AE with TDiclo was dry skin at the application site (24.1% vs 1.9% with ODiclo; P < 0.0001). Fewer gastrointestinal (25.4% vs 39.0%; P < 0.0001) and cardiovascular (1.5% vs 3.5%; P = 0.055) AEs occurred with TDiclo compared with ODiclo. ODiclo was associated with significantly greater increases in liver enzymes and creatinine, and greater decreases in creatinine clearance and hemoglobin (P < 0.001 for all). Conclusions These findings suggest that TDiclo represents a useful alternative to oral NSAID therapy in the management of OA, with a more favorable safety profile. PMID:21811391

  10. Arteriovenous malformations of the corpus callosum: Pooled analysis and systematic review of literature

    PubMed Central

    Pabaney, Aqueel H.; Ali, Rushna; Kole, Maximillian; Malik, Ghaus M.

    2016-01-01

    Background: Arteriovenous malformations (AVMs) of the corpus callosum (CC) are rare entities. We performed a systematic review of the available literature to better define the natural history, patient characteristics, and treatment options for these lesions. Methods: A MEDLINE, Google Scholar, and The Cochrane Library search were performed for studies published through June 2015. Data from all eligible studies were used to examine epidemiology, natural history, clinical features, treatment strategies, and outcomes of patients with CC-AVMs. A systematic review and pooled analysis of the literature were performed. Results: Our search yielded 37 reports and 230 patients. Mean age at presentation was 26.8 years (±13.12 years). AVMs were most commonly located in the splenium (43%), followed by the body (31%), and then the genu (23%) of the CC. A Spetzler-Martin grade of III was the most common (37%). One hundred eighty-seven (81.3%) patients presented with hemorrhage, 91 (40%) underwent microsurgical excision, and 87 (38%) underwent endovascular embolization. Radiosurgery was performed on 57 (25%) patients. Complete obliteration of the AVM was achieved in 102 (48.1%) patients and approximately twice as often when microsurgery was performed alone or in combination with other treatment modalities (94% vs. 49%; P < 0.001). Mean modified Rankin Scale (mRS) at presentation was 1.54 and mean mRS at last follow-up was 1.31. This difference was not statistically significant (P = 0.35). Conclusion: We present an analysis of the pooled data in the form of a systematic review focusing on management of CC-AVMs. This review aims to provide a valuable tool to aid in decision making when dealing with this particular subtype of AVM. PMID:27127713

  11. ORIGAMI Automator Primer. Automated ORIGEN Source Terms and Spent Fuel Storage Pool Analysis

    SciTech Connect

    Wieselquist, William A.; Thompson, Adam B.; Bowman, Stephen M.; Peterson, Joshua L.

    2016-04-01

    Source terms and spent nuclear fuel (SNF) storage pool decay heat load analyses for operating nuclear power plants require a large number of Oak Ridge Isotope Generation and Depletion (ORIGEN) calculations. SNF source term calculations also require a significant amount of bookkeeping to track quantities such as core and assembly operating histories, spent fuel pool (SFP) residence times, heavy metal masses, and enrichments. The ORIGEN Assembly Isotopics (ORIGAMI) module in the SCALE code system provides a simple scheme for entering these data. However, given the large scope of the analysis, extensive scripting is necessary to convert formats and process data to create thousands of ORIGAMI input files (one per assembly) and to process the results into formats readily usable by follow-on analysis tools. This primer describes a project within the SCALE Fulcrum graphical user interface (GUI) called ORIGAMI Automator that was developed to automate the scripting and bookkeeping in large-scale source term analyses. The ORIGAMI Automator enables the analyst to (1) easily create, view, and edit the reactor site and assembly information, (2) automatically create and run ORIGAMI inputs, and (3) analyze the results from ORIGAMI. ORIGAMI Automator uses the standard ORIGEN binary concentrations files produced by ORIGAMI, with concentrations available at all time points in each assembly’s life. The GUI plots results such as mass, concentration, activity, and decay heat using a powerful new ORIGEN Post-Processing Utility for SCALE (OPUS) GUI component. This document includes a description and user guide for the GUI, a step-by-step tutorial for a simplified scenario, and appendices that document the file structures used.

  12. Statistical model specification and power: recommendations on the use of test-qualified pooling in analysis of experimental data.

    PubMed

    Colegrave, Nick; Ruxton, Graeme D

    2017-03-29

    A common approach to the analysis of experimental data across much of the biological sciences is test-qualified pooling. Here non-significant terms are dropped from a statistical model, effectively pooling the variation associated with each removed term with the error term used to test hypotheses (or estimate effect sizes). This pooling is only carried out if statistical testing on the basis of applying that data to a previous more complicated model provides motivation for this model simplification; hence the pooling is test-qualified. In pooling, the researcher increases the degrees of freedom of the error term with the aim of increasing statistical power to test their hypotheses of interest. Despite this approach being widely adopted and explicitly recommended by some of the most widely cited statistical textbooks aimed at biologists, here we argue that (except in highly specialized circumstances that we can identify) the hoped-for improvement in statistical power will be small or non-existent, and there is likely to be much reduced reliability of the statistical procedures through deviation of type I error rates from nominal levels. We thus call for greatly reduced use of test-qualified pooling across experimental biology, more careful justification of any use that continues, and a different philosophy for initial selection of statistical models in the light of this change in procedure.

  13. An Analysis of Pool Surface Deformation Due to a Plunging Liquid Jet

    DTIC Science & Technology

    1993-10-31

    pool surface depression by the plunging liquid jet (which leads to the entrainment of air ) was completed...technique. INTRODUCTION The entrainment of non-condensible gases by a plunging liquid jet impacting a liquid pool is important for some practical...the surface is such that the surface tension is not large enough to keep the pool surface from getting near the plunging liquid jet and thus air

  14. Predictors of Local Recurrence Following Accelerated Partial Breast Irradiation: A Pooled Analysis

    SciTech Connect

    Shah, Chirag; Wilkinson, John Ben; Lyden, Maureen; Beitsch, Peter; Vicini, Frank A.

    2012-04-01

    Purpose: To analyze a pooled set of nearly 2,000 patients treated on the American Society of Breast Surgeons (ASBS) Mammosite Registry Trial and at William Beaumont Hospital (WBH) to identify factors associated with local recurrence following accelerated partial breast irradiation (APBI). Methods and Materials: A total of 1,961 women underwent partial breast irradiation between April 1993 and November 2010 as part of the ASBS Registry Trial or at WBH. Rates of ipsilateral breast tumor recurrence (IBTR), regional recurrence (RR), distant metastases (DM), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS) were analyzed for each group and for the pooled cohort. Clinical, pathologic, and treatment-related variables were analyzed including age, tumor stage/size, estrogen receptor status, surgical margins, and lymph node status to determine their association with IBTR. Results: The two groups weres similar, but WBH patients were more frequently node positive, had positive margins, and were less likely to be within the American Society for Radiation Oncology-unsuitable group. At 5 years, the rates of IBTR, RR, DM, DFS, CSS, and OS for the pooled group of patients were 2.9%, 0.5%, 2.4%, 89.1%, 98.5%, and 91.8%, respectively. The 5-year rate of true recurrence/marginal miss was 0.8%. Univariate analysis of IBTR found that negative estrogen receptor status (odds ratio [OR], 2.83, 95% confidence interval 1.55-5.13, p = 0.0007) was the only factor significantly associated with IBTR, while a trend was seen for age less than 50 (OR 1.80, 95% confidence interval 0.90-3.58, p = 0.10). Conclusions: Excellent 5-year outcomes were seen following APBI in over 1,900 patients. Estrogen receptor negativity was the only factor associated with IBTR, while a trend for age less than 50 was noted. Significant differences in factors associated with IBTR were noted between cohorts, suggesting that factors driving IBTR may be predicated based on the risk

  15. Interaction analysis of the new pooled cohort equations for 10-year atherosclerotic cardiovascular disease risk estimation: a simulation analysis

    PubMed Central

    Schiros, Chun G; Denney, Thomas S; Gupta, Himanshu

    2015-01-01

    Objectives To evaluate the individual and interacting impacts of the continuous variables (age, total cholesterol (total-C), high-density lipoprotein cholesterol (HDL-C) and systolic blood pressure(BP)) on 10-year atherosclerotic cardiovascular disease (ASCVD) risk and better understand the pattern of predicted 10-year risk with change of each variable using recently published new pooled cohort equations. Design Simulation analysis was performed across the whole range of the boundary limits suggested for the continuous variables for groupings based on race and gender in the pooled cohort 10-year risk equations. Setting Computer-based simulation analysis. Participants Data were generated by simulation using prespecified variable ranges. Intervention Data simulation and visual display of the hazard analysis. Main outcome measures Interactions of age with other variables were analysed using multidimensional visualisation and hazard analysis. Results In African–American females, due to the interaction of age with HDL-C, treated BP and untreated BP, increasing age may not always increase 10-year risk. Furthermore, in the same cohort, increasing HDL-C level may result in higher 10-year risk for older individuals. For Caucasian females, due to square of Ln (age) term in the equation, the age-risk curve does not monotonically increase with age. The vertex is within the given age range of 40–79 years for a certain range of total-C and HDL-C, indicating that age may not always result in increased predicted 10-year risk. Conclusions The new pooled cohort equations are sophisticated as they take into account the interactions of the continuous variables in predicting 10-year risk. We find situations where the estimated 10-year risk does not follow the general secular trends. The impact of such interesting patterns may be substantial and therefore further exploration is needed as it has direct implications in clinical management for primary prevention. PMID:25941176

  16. Efficacy of otilonium bromide in irritable bowel syndrome: a pooled analysis

    PubMed Central

    Clavé, Pere; Tack, Jan

    2017-01-01

    Background: Otilonium bromide (OB) is a spasmolytic agent acting as an L-type calcium channel antagonist in intestinal and colonic smooth muscle cells (SMCs). We analyzed three independent clinical trials with homogeneous design on patients with irritable bowel syndrome (IBS). After 2 weeks receiving placebo, patients were randomized to receive OB (3 × 40 mg daily) or placebo for 15 weeks. We aimed to perform a pooled analysis of the data from these homogeneous clinical trials to evaluate the efficacy of OB treatment on symptoms and global response of patients. Methods: A total of 883 patients with IBS (69.8% women, mean age 46.2 years, 43.8% mixed type) were included, 442 treated with OB and 441 with placebo. The efficacy results from the three studies at weeks 5, 10 and 15 were pooled in an intention-to-treat (ITT) strategy, analyzed with a logistic regression model and described by forest plots. Results: Despite a placebo effect in all efficacy variables, a significant therapeutic effect of OB was observed at weeks 10 and 15 with reference to: (a) intensity and frequency of abdominal pain; (b) rate of responders as evaluated by patients (71.8% at week 10 and 77.2% at week 15); (c) severity of bloating; (d) rate of responders as evaluated by physicians (55% at week 10 and 63.9% at week 15). No significant OB effect was observed in stool frequency and consistency. Conclusions: OB is more effective than placebo in IBS treatment. Therapeutic benefits are significant after 10 weeks and are maximal after 15 weeks of treatment. PMID:28246548

  17. Community analysis of plant biomass-degrading microorganisms from Obsidian Pool, Yellowstone National Park

    SciTech Connect

    Vishnivetskaya, Tatiana A.; Hamilton-Brehm, Scott D.; Podar, Mircea; Mosher, Jennifer J.; Palumbo, Anthony V.; Phelps, Tommy J.; Keller, Martin; Elkins, James G.

    2014-10-16

    The conversion of lignocellulosic biomass into biofuels can potentially be improved by employing robust microorganisms and enzymes that efficiently deconstruct plant polysaccharides at elevated temperatures. Many of the geothermal features of Yellowstone National Park (YNP) are surrounded by vegetation providing a source of allochthonic material to support heterotrophic microbial communities adapted to utilize plant biomass as a primary carbon and energy source. In this paper, a well-known hot spring environment, Obsidian Pool (OBP), was examined for potential biomass-active microorganisms using cultivation-independent and enrichment techniques. Analysis of 33,684 archaeal and 43,784 bacterial quality-filtered 16S rRNA gene pyrosequences revealed that archaeal diversity in the main pool was higher than bacterial; however, in the vegetated area, overall bacterial diversity was significantly higher. Of notable interest was a flooded depression adjacent to OBP supporting a stand of Juncus tweedyi, a heat-tolerant rush commonly found growing near geothermal features in YNP. The microbial community from heated sediments surrounding the plants was enriched in members of the Firmicutes including potentially (hemi)cellulolytic bacteria from the genera Clostridium, Anaerobacter, Caloramator, Caldicellulosiruptor, and Thermoanaerobacter. Enrichment cultures containing model and real biomass substrates were established at a wide range of temperatures (55–85 °C). Microbial activity was observed up to 80 °C on all substrates including Avicel, xylan, switchgrass, and Populus sp. Finally, independent of substrate, Caloramator was enriched at lower (<65 °C) temperatures while highly active cellulolytic bacteria Caldicellulosiruptor were dominant at high (>65 °C) temperatures.

  18. Community analysis of plant biomass-degrading microorganisms from Obsidian Pool, Yellowstone National Park.

    PubMed

    Vishnivetskaya, Tatiana A; Hamilton-Brehm, Scott D; Podar, Mircea; Mosher, Jennifer J; Palumbo, Anthony V; Phelps, Tommy J; Keller, Martin; Elkins, James G

    2015-02-01

    The conversion of lignocellulosic biomass into biofuels can potentially be improved by employing robust microorganisms and enzymes that efficiently deconstruct plant polysaccharides at elevated temperatures. Many of the geothermal features of Yellowstone National Park (YNP) are surrounded by vegetation providing a source of allochthonic material to support heterotrophic microbial communities adapted to utilize plant biomass as a primary carbon and energy source. In this study, a well-known hot spring environment, Obsidian Pool (OBP), was examined for potential biomass-active microorganisms using cultivation-independent and enrichment techniques. Analysis of 33,684 archaeal and 43,784 bacterial quality-filtered 16S rRNA gene pyrosequences revealed that archaeal diversity in the main pool was higher than bacterial; however, in the vegetated area, overall bacterial diversity was significantly higher. Of notable interest was a flooded depression adjacent to OBP supporting a stand of Juncus tweedyi, a heat-tolerant rush commonly found growing near geothermal features in YNP. The microbial community from heated sediments surrounding the plants was enriched in members of the Firmicutes including potentially (hemi)cellulolytic bacteria from the genera Clostridium, Anaerobacter, Caloramator, Caldicellulosiruptor, and Thermoanaerobacter. Enrichment cultures containing model and real biomass substrates were established at a wide range of temperatures (55-85 °C). Microbial activity was observed up to 80 °C on all substrates including Avicel, xylan, switchgrass, and Populus sp. Independent of substrate, Caloramator was enriched at lower (<65 °C) temperatures while highly active cellulolytic bacteria Caldicellulosiruptor were dominant at high (>65 °C) temperatures.

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

    NASA Astrophysics Data System (ADS)

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

    2014-06-01

    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.

  20. Community analysis of plant biomass-degrading microorganisms from Obsidian Pool, Yellowstone National Park

    DOE PAGES

    Vishnivetskaya, Tatiana A.; Hamilton-Brehm, Scott D.; Podar, Mircea; ...

    2014-10-16

    The conversion of lignocellulosic biomass into biofuels can potentially be improved by employing robust microorganisms and enzymes that efficiently deconstruct plant polysaccharides at elevated temperatures. Many of the geothermal features of Yellowstone National Park (YNP) are surrounded by vegetation providing a source of allochthonic material to support heterotrophic microbial communities adapted to utilize plant biomass as a primary carbon and energy source. In this paper, a well-known hot spring environment, Obsidian Pool (OBP), was examined for potential biomass-active microorganisms using cultivation-independent and enrichment techniques. Analysis of 33,684 archaeal and 43,784 bacterial quality-filtered 16S rRNA gene pyrosequences revealed that archaeal diversitymore » in the main pool was higher than bacterial; however, in the vegetated area, overall bacterial diversity was significantly higher. Of notable interest was a flooded depression adjacent to OBP supporting a stand of Juncus tweedyi, a heat-tolerant rush commonly found growing near geothermal features in YNP. The microbial community from heated sediments surrounding the plants was enriched in members of the Firmicutes including potentially (hemi)cellulolytic bacteria from the genera Clostridium, Anaerobacter, Caloramator, Caldicellulosiruptor, and Thermoanaerobacter. Enrichment cultures containing model and real biomass substrates were established at a wide range of temperatures (55–85 °C). Microbial activity was observed up to 80 °C on all substrates including Avicel, xylan, switchgrass, and Populus sp. Finally, independent of substrate, Caloramator was enriched at lower (<65 °C) temperatures while highly active cellulolytic bacteria Caldicellulosiruptor were dominant at high (>65 °C) temperatures.« less

  1. Pool Purification

    NASA Technical Reports Server (NTRS)

    1988-01-01

    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.

  2. Tiotropium HandiHaler® and Respimat® in COPD: a pooled safety analysis

    PubMed Central

    Halpin, David MG; Dahl, Ronald; Hallmann, Christoph; Mueller, Achim; Tashkin, Donald

    2015-01-01

    Introduction Tiotropium is prescribed for the treatment of chronic obstructive pulmonary disease (COPD) and delivered via HandiHaler® (18 μg once daily) or Respimat® Soft Mist™ inhaler (5 μg once daily). The recent TIOtropium Safety and Performance In Respimat® (TIOSPIR™) study demonstrated that both exhibit similar safety profiles. This analysis provides an updated comprehensive safety evaluation of tiotropium® using data from placebo-controlled HandiHaler® and Respimat® trials. Methods Pooled analysis of adverse event (AE) data from tiotropium HandiHaler® 18 μg and Respimat® 5 μg randomized, double-blind, parallel-group, placebo-controlled, clinical trials in patients with COPD (treatment duration ≥4 weeks). Incidence rates, rate ratios (RRs), and 95% confidence intervals (CIs) were determined for HandiHaler® and Respimat® trials, both together and separately. Results In the 28 HandiHaler® and 7 Respimat® trials included in this analysis, 11,626 patients were treated with placebo and 12,929 with tiotropium, totaling 14,909 (12,469 with HandiHaler®; 2,440 with Respimat®) patient-years of tiotropium exposure. Mean age was 65 years, and mean prebronchodilator forced expiratory volume in 1 second (FEV1) was 1.16 L (41% predicted). The risk (RR [95% CI]) of AEs (0.90 [0.87, 0.93]) and of serious AEs (SAEs) (0.94 [0.89, 0.99]) was significantly lower in the tiotropium than in the placebo group (HandiHaler® and Respimat® pooled results), and there was a numerically lower risk of fatal AEs (FAEs) (0.90 [0.79, 1.01]). The risk of cardiac AEs (0.93 [0.85, 1.02]) was numerically lower in the tiotropium group. Incidences of typical anticholinergic AEs, but not SAEs, were higher with tiotropium. Analyzed separately by inhaler, the risks of AE and SAE in the tiotropium groups remained lower than in placebo and similarly for FAEs. Conclusion This analysis indicates that tiotropium is associated with lower rates of AEs, SAEs, and similar rates of FAEs

  3. Pharmacogenomics of platinum-based chemotherapy response in NSCLC: a genotyping study and a pooled analysis

    PubMed Central

    Chen, Juan; Wang, Zhan; Zou, Ting; Cui, Jiajia; Yin, Jiye; Zheng, Wei; Jiang, Wuzhong; Zhou, Honghao; Liu, Zhaoqian

    2016-01-01

    Published data showed inconsistent results about associations of extensively studied polymorphisms with platinum-based chemotherapy response. Our study aimed to provide reliable conclusions of these associations by detecting genotypes of the SNPs in a larger sample size and summarizing a comprehensive pooled analysis. 13 SNPs in 8 genes were genotyped in 1024 NSCLC patients by SequenomMassARRAY. 39 published studies and our study were included in meta-analysis. Patients with GA or GG genotypes of XRCC1 G1196 had better response than AA genotype carriers (Genotyping study: OR = 0.72, 95%CI: 0.53-0.96, P = 0.028; Meta-analysis: OR = 0.74, 95%CI: 0.62-0.89, P = 0.001). Patients carrying CT or TT genotypes of XRCC1 C580T could be more sensitive to platinum-based chemotherapy compared to patients with CC genotype (OR = 0.54, 95%CI: 0.37-0.80, P = 0.002). CC genotype of XRCC3 C18067T carriers showed more resistance to platinum-based chemotherapy when compared to those with CT or TT genotypes (OR = 0.69, 95%CI: 0.52-0.91, P = 0.009). Our study indicated that XRCC1 G1196A/C580T and XRCC3 C18067T should be paid attention for personalized platinum-based chemotherapy in NSCLC patients. PMID:27248474

  4. Genome-wide Association Study of Subtype-Specific Epithelial Ovarian Cancer Risk Alleles Using Pooled DNA

    PubMed Central

    Earp, Madalene A.; Kelemen, Linda E.; Magliocco, Anthony M.; Swenerton, Kenneth D.; Chenevix–Trench, Georgia; Lu, Yi; Hein, Alexander; Ekici, Arif B.; Beckmann, Matthias W.; Fasching, Peter A.; Lambrechts, Diether; Despierre, Evelyn; Vergote, Ignace; Lambrechts, Sandrina; Doherty, Jennifer A.; Rossing, Mary Anne; Chang-Claude, Jenny; Rudolph, Anja; Friel, Grace; Moysich, Kirsten B.; Odunsi, Kunle; Sucheston-Campbell, Lara; Lurie, Galina; Goodman, Marc T.; Carney, Michael E.; Thompson, Pamela J.; Runnebaum, Ingo B.; Dürst, Matthias; Hillemanns, Peter; Dörk, Thilo; Antonenkova, Natalia; Bogdanova, Natalia; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M.; Butzow, Ralf; Bunker, Clareann H.; Modugno, Francesmary; Edwards, Robert P.; Ness, Roberta B.; du Bois, Andreas; Heitz, Florian; Schwaab, Ira; Harter, Philipp; Karlan, Beth Y.; Walsh, Christine; Lester, Jenny; Jensen, Allan; Kjær, Susanne K.; Høgdall, Claus K.; Høgdall, Estrid; Lundvall, Lene; Sellers, Thomas A.; Fridley, Brooke L.; Goode, Ellen L.; Cunningham, Julie M.; Vierkant, Robert A.; Giles, Graham G.; Baglietto, Laura; Severi, Gianluca; Southey, Melissa C.; Liang, Dong; Wu, Xifeng; Lu, Karen; Hildebrandt, Michelle A.T.; Levine, Douglas A.; Bisogna, Maria; Schildkraut, Joellen M.; Iversen, Edwin S.; Weber, Rachel Palmieri; Berchuck, Andrew; Cramer, Daniel W.; Terry, Kathryn L.; Poole, Elizabeth M.; Tworoger, Shelley S.; Bandera, Elisa V.; Chandran, Urmila; Orlow, Irene; Olson, Sara H.; Wik, Elisabeth; Salvesen, Helga B.; Bjorge, Line; Halle, Mari K.; van Altena, Anne M.; Aben, Katja K.H.; Kiemeney, Lambertus A.; Massuger, Leon F.A.G.; Pejovic, Tanja; Bean, Yukie T.; Cybulski, Cezary; Gronwald, Jacek; Lubinski, Jan; Wentzensen, Nicolas; Brinton, Louise A.; Lissowska, Jolanta; Garcia–Closas, Montserrat; Dicks, Ed; Dennis, Joe; Easton, Douglas F.; Song, Honglin; Tyrer, Jonathan P.; Pharoah, Paul D. P.; Eccles, Diana; Campbell, Ian G.; Whittemore, Alice S.; McGuire, Valerie; Sieh, Weiva; Rothstein, Joseph H.; Flanagan, James M.; Paul, James; Brown, Robert; Phelan, Catherine M.; Risch, Harvey A.; McLaughlin, John R.; Narod, Steven A.; Ziogas, Argyrios; Anton-Culver, Hoda; Gentry-Maharaj, Aleksandra; Menon, Usha; Gayther, Simon A.; Ramus, Susan J.; Wu, Anna H.; Pearce, Celeste L.; Pike, Malcolm C.; Dansonka-Mieszkowska, Agnieszka; Rzepecka, Iwona K; Szafron, Lukasz M; Kupryjanczyk, Jolanta; Cook, Linda S.; Le, Nhu D.; Brooks–Wilson, Angela

    2014-01-01

    Epithelial ovarian cancer (EOC) is a heterogeneous cancer with both genetic and environmental risk factors. Variants influencing the risk of developing the less-common EOC subtypes have not been fully investigated. We performed a genome-wide association study (GWAS) of EOC according to subtype by pooling genomic DNA from 545 cases and 398 controls of European descent, and testing for allelic associations. We evaluated for replication 188 variants from the GWAS (56 variants for mucinous, 55 for endometrioid and clear cell, 53 for low malignant potential (LMP) serous, and 24 for invasive serous EOC), selected using pre-defined criteria. Genotypes from 13,188 cases and 23,164 controls of European descent were used to perform unconditional logistic regression under the log-additive genetic model; odds ratios (OR) and 95% confidence intervals are reported. Nine variants tagging 6 loci were associated with subtype-specific EOC risk at P<0.05, and had an OR that agreed in direction of effect with the GWAS results. Several of these variants are in or near genes with a biological rationale for conferring EOC risk, including ZFP36L1 and RAD51B for mucinous EOC (rs17106154, OR=1.17, P=0.029, n=1,483 cases), GRB10 for endometrioid and clear cell EOC (rs2190503, P=0.014, n=2,903 cases), and C22orf26/BPIL2 for LMP serous EOC (rs9609538, OR=0.86, P=0.0043, n=892 cases). In analyses that included the 75 GWAS samples, the association between rs9609538 (OR=0.84, P=0.0007) and LMP serous EOC risk remained statistically significant at P<0.0012 adjusted for multiple testing. Replication in additional samples will be important to verify these results for the less-common EOC subtypes. PMID:24190013

  5. Comparison of the RECIST 1.0 and RECIST 1.1 in patients treated with targeted agents: a pooled analysis and review

    PubMed Central

    Kim, Jung Han

    2016-01-01

    Patients treated with targeted agents were not included in the data warehouse when the RECIST 1.1 was revised in 2009. We conducted this pooled analysis to investigate the impact of the RECIST 1.1 on the assessment of tumor response in cancer patients treated with targeted agents. We surveyed MEDLINE, EMBASE and PubMed for articles with terms of the RECIST 1.0 or RECIST 1.1. We searched for all the references of relevant articles and reviews using the ‘related articles’ feature in the PubMed. There were six articles in the literature comparing the clinical impacts of the RECIST 1.0 and RECIST 1.1 in patients treated with targeted agents for advanced or metastatic cancer. A total of 322 patients were recruited from the six trials; 217 with non-small cell lung cancer, 23 with thyroid cancer, 20 with gastrointestinal stromal tumor, and 62 with renal cell carcinoma. Because of new lymph node criteria, eight patients (2.5%) had no target lesions when adopting the RECIST 1.1. The number of target lesions by the RECIST 1.1 was significantly lower than that by the RECIST 1.0 (P < 0.001). However, the RECIST 1.1 showed high concordance with the RECIST 1.0 in the assessment of best tumor responses (k = 0.908). Seventeen patients (5.6%) showed discrepancy in the best tumor response between the RECIST 1.0 and RECIST 1.1. This pooled study demonstrates that the RECIST 1.1 shows the highly concordant response assessment with the RECIST 1.0 in patients treated with targeted agents. PMID:26885610

  6. External beam radiotherapy for palliation of painful bone metastases: pooled data bioeffect dose response analysis of dose fractionation

    NASA Astrophysics Data System (ADS)

    Naveen, T.; Supe, Sanjay S.; Ganesh, K. M.; Samuel, Jacob

    2009-01-01

    Bone metastases develop in up to 70% of newly diagnosed cancer patients and result in immobility, anxiety, and depression, severely diminishing the patients quality of life. Radiotherapy is a frequently used modality for bone metastasis and has been shown to be effective in reducing metastatic bone pain and in some instances, causing tumor shrinkage or growth inhibition. There is controversy surrounding the optimal fractionation schedule and total dose of external beam radiotherapy, despite many randomized trials and overviews addressing the issue. This study was undertaken to apply BED to clinical fractionation data of radiotherapeutic management of bone metastases in order to arrive at optimum BED values for acceptable level of response rate. A computerised literature search was conducted to identify all prospective clinical studies that addressed the issue of fractionation for the treatment of bone metastasis. The results of these studies were pooled together to form the database for the analysis. A total of 4111 number of patients received radiation dose ranging from 4 to 40.5 Gy in 1 to 15 fractions with dose per fraction ranging from 2 to 10 Gy. Single fraction treatments were delivered in 2013 patients and the dose varied from 4 to 10 Gy. Multifraction treatments were delivered in 2098 patients and the dose varied from 15 to 40.5 Gy. The biological effective dose (BED) was evaluated for each fractionation schedule using the linear quadratic model and an α/β value of 10 Gy. Response rate increased significantly beyond a BED value of 14.4 Gy (p < 0.01). Based on our analysis and indications from the literature about higher retreatment and fracture rate of single fraction treatments, minimum BED value of 14.4 Gy is recommended.

  7. β-Blockers Reduce Breast Cancer Recurrence and Breast Cancer Death: A Meta-Analysis.

    PubMed

    Childers, W Kurtis; Hollenbeak, Christopher S; Cheriyath, Pramil

    2015-12-01

    The normal physiologic stress mechanism, mediated by the sympathetic nervous system, causes a release of the neurotransmitters epinephrine and norepinephrine. Preclinical data have demonstrated an effect on tumor progression and metastasis via the sympathetic nervous system mediated primarily through the β-adrenergic receptor (β-AR) pathway. In vitro data have shown an increase in tumor growth, migration, tumor angiogenesis, and metastatic spread in breast cancer through activation of the β-AR. Retrospective cohort studies on the clinical outcomes of β-blockers in breast cancer outcomes showed no clear consensus. The purpose of this study was to perform a systematic review and meta-analysis of the effect of β-blockers on breast cancer outcomes. A systematic review was performed using the Cochrane library and PubMed. Publications between the dates of January 2010 and December 2013 were identified. Available hazard ratios (HRs) were extracted for breast cancer recurrence, breast cancer death, and all-cause mortality and pooled using a random effects meta-analysis. A total of 7 studies contained results for at least 1 of the outcomes of breast cancer recurrence, breast cancer death, or all-cause mortality in breast cancer patients receiving β-blockers. In the 5 studies that contained results for breast cancer recurrence, there was no statistically significant risk reduction (HR, 0.67; 95% confidence interval [CI], 0.39-1.13). Breast cancer death results were contained in 4 studies, which also suggested a significant reduction in risk (HR, 0.50; 95% CI, 0.32-0.80). Among the 4 studies that reported all-cause mortality, there was no significant effect of β-blockers on risk (HR, 1.02; 95% CI, 0.75-1.37). Results of this systematic review and meta-analysis suggest that the use of β-blockers significantly reduced risk of breast cancer death among women with breast cancer.

  8. 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 ...

  9. 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...

  10. Semi-Professional Rugby League Players have Higher Concussion Risk than Professional or Amateur Participants: A Pooled Analysis.

    PubMed

    King, Doug; Hume, Patria; Gissane, Conor; Clark, Trevor

    2017-02-01

    A combined estimate of injuries within a specific sport through pooled analysis provides more precise evidence and meaningful information about the sport, whilst controlling for between-study variation due to individual sub-cohort characteristics. The objective of this analysis was to review all published rugby league studies reporting injuries from match and training participation and report the pooled data estimates for rugby league concussion injury epidemiology. A systematic literature analysis of concussion in rugby league was performed on published studies from January 1990 to October 2015. Data were extracted and pooled from 25 studies that reported the number and incidence of concussions in rugby league match and training activities. Amateur rugby league players had the highest incidence of concussive injuries in match activities (19.1 per 1000 match hours) while semi-professional players had the highest incidence of concussive injuries in training activities (3.1 per 1000 training hours). This pooled analysis showed that, during match participation activities, amateur rugby league participants had a higher reported concussion injury rate than professional and semi-professional participants. Semi-professional participants had nearly a threefold greater concussion injury risk than amateur rugby league participants during match participation. They also had nearly a 600-fold greater concussion injury risk than professional rugby league participants during training participation.

  11. Pooled Analysis of Six Pharmacologic and Nonpharmacologic Interventions for Vasomotor Symptoms

    PubMed Central

    Guthrie, Katherine A.; LaCroix, Andrea Z.; Ensrud, Kristine E.; Joffe, Hadine; Newton, Katherine M.; Reed, Susan D.; Caan, Bette; Carpenter, Janet S.; Cohen, Lee S.; Freeman, Ellen W.; Larson, Joseph C.; Manson, JoAnn E.; Rexrode, Kathy; Skaar, Todd C.; Sternfeld, Barbara; Anderson, Garnet L.

    2015-01-01

    Objective To describe the effects of six interventions for menopausal vasomotor symptoms relative to control in a pooled analysis, facilitating translation of the results for clinicians and symptomatic women. The MsFLASH (Menopause Strategies: Finding Lasting Answers for Symptoms and Health) network tested these interventions in three randomized clinical trials (RCTs). Methods An analysis of pooled individual-level data from three RCTs is presented. Participants were 899 peri- and postmenopausal women with at least 14 bothersome vasomotor symptoms/week. Interventions included escitalopram 10–20 mg/day, non-aerobic yoga, aerobic exercise, 1.8 g/day omega-3 fatty acid supplementation, low-dose oral 17-beta-estradiol 0.5-mg/day, and low-dose venlafaxine XR 75-mg/day. The main outcome measures were changes from baseline in mean daily vasomotor symptoms frequency and bother during 8–12 weeks of treatment. Linear regression models estimated differences in outcomes between each intervention and corresponding control group, adjusted for baseline characteristics. Models included trial-specific intercepts, effects of the baseline outcome measure, and time. Results The 8-week reduction in vasomotor symptoms frequency from baseline relative to placebo was similar for escitalopram at −1.4/day (95% CI: −2.7 to −0.2), low-dose estradiol at −2.4 (95% CI: −3.4 to −1.3), and venlafaxine at −1.8 (95% CI: −2.8 to −0.8); vasomotor symptoms bother reduction was minimal and did not vary across these three pharmacologic interventions (means −0.2 to −0.3 relative to placebo). No effects on vasomotor symptoms frequency or bother were seen with aerobic exercise, yoga or omega-3 supplements. Conclusions These analyses suggest that escitalopram, low-dose estradiol, and venlafaxine provide comparable, modest reductions in vasomotor symptoms frequency and bother among women with moderate hot flushes. Clinical Trial Registration ClinicalTrials.gov, www

  12. Essential Indicators Identifying Chronic Inorganic Mercury Intoxication: Pooled Analysis across Multiple Cross-Sectional Studies

    PubMed Central

    Doering, Stefan

    2016-01-01

    Background The continuous exposure to inorganic mercury vapour in artisanal small-scale gold mining (ASGM) areas leads to chronic health problems. It is therefore essential to have a quick, but reliable risk assessing tool to diagnose chronic inorganic mercury intoxication. This study re-evaluates the state-of-the-art toolkit to diagnose chronic inorganic mercury intoxication by analysing data from multiple pooled cross-sectional studies. The primary research question aims to reduce the currently used set of indicators without affecting essentially the capability to diagnose chronic inorganic mercury intoxication. In addition, a sensitivity analysis is performed on established biomonitoring exposure limits for mercury in blood, hair, urine and urine adjusted by creatinine, where the biomonitoring exposure limits are compared to thresholds most associated with chronic inorganic mercury intoxication in artisanal small-scale gold mining. Methods Health data from miners and community members in Indonesia, Tanzania and Zimbabwe were obtained as part of the Global Mercury Project and pooled into one dataset together with their biomarkers mercury in urine, blood and hair. The individual prognostic impact of the indicators on the diagnosis of mercury intoxication is quantified using logistic regression models. The selection is performed by a stepwise forward/backward selection. Different models are compared based on the Bayesian information criterion (BIC) and Cohen`s kappa is used to evaluate the level of agreement between the diagnosis of mercury intoxication based on the currently used set of indicators and the result based on our reduced set of indicators. The sensitivity analysis of biomarker exposure limits of mercury is based on a sequence of chi square tests. Results The variable selection in logistic regression reduced the number of medical indicators from thirteen to ten in addition to the biomarkers. The estimated level of agreement using ten of thirteen medical

  13. A pooled analysis of the efficacy of monepantel, an amino-acetonitrile derivative against gastrointestinal nematodes of sheep.

    PubMed

    Hosking, Barry C; Kaminsky, Ronald; Sager, Heinz; Rolfe, Peter F; Seewald, Wolfgang

    2010-01-01

    Monepantel is the first compound from the amino-acetonitrile derivative class of anthelmintics to be developed for the control of gastrointestinal nematodes of sheep. An analysis of pooled data from a series of controlled studies is reported providing a single point of efficacy (+/- 95% confidence interval) for each gastrointestinal nematode tested at the fourth larval and/or adult stages. For most nematode species, the pooled efficacy was greater than 99%, and for the remaining few species, efficacy was greater than 90%. These data are well supported by field studies conducted across five countries, where the pooled efficacy (on the basis of fecal worm egg count reduction) was in most cases, greater than 99% (depending on the calculation used). Monepantel is highly effective when administered to sheep at 2.5 mg/kg, and its introduction as a new anthelmintic for sheep is timely, given the problems with anthelmintic resistance that the world's sheep farmers are now experiencing.

  14. Research on Optimization of Pooling System and Its Application in Drug Supply Chain Based on Big Data Analysis.

    PubMed

    Wu, DengFeng; Mao, Hongyi

    2017-01-01

    Reform of drug procurement is being extensively implemented and expanded in China, especially in today's big data environment. However, the pattern of supply mode innovation lags behind procurement improvement. Problems in financial strain and supply break frequently occur, which affect the stability of drug supply. Drug Pooling System is proposed and applied in a few pilot cities to resolve these problems. From the perspective of supply chain, this study analyzes the process of setting important parameters and sets out the tasks of involved parties in a pooling system according to the issues identified in the pilot run. The approach is based on big data analysis and simulation using system dynamic theory and modeling of Vensim software to optimize system performance. This study proposes a theoretical framework to resolve problems and attempts to provide a valuable reference for future application of pooling systems.

  15. Research on Optimization of Pooling System and Its Application in Drug Supply Chain Based on Big Data Analysis

    PubMed Central

    2017-01-01

    Reform of drug procurement is being extensively implemented and expanded in China, especially in today's big data environment. However, the pattern of supply mode innovation lags behind procurement improvement. Problems in financial strain and supply break frequently occur, which affect the stability of drug supply. Drug Pooling System is proposed and applied in a few pilot cities to resolve these problems. From the perspective of supply chain, this study analyzes the process of setting important parameters and sets out the tasks of involved parties in a pooling system according to the issues identified in the pilot run. The approach is based on big data analysis and simulation using system dynamic theory and modeling of Vensim software to optimize system performance. This study proposes a theoretical framework to resolve problems and attempts to provide a valuable reference for future application of pooling systems. PMID:28293258

  16. Biogenic and non-biogenic Si pools in terrestrial ecosystems: results from a novel analysis method

    NASA Astrophysics Data System (ADS)

    Barao, Lucia; Vandevenne, Floor; Clymans, Wim; Meire, Patrick; Frings, Patrick; Conley, Daniel; Struyf, Eric

    2015-04-01

    Silicon (Si) is a chemical element frequently associated with highly abundant silicate minerals in the Earth crust. Over millions of years, the interaction of such minerals with the atmosphere and hydrosphere produces a myriad of processed compounds, and the mineral weathering consumes CO2 during the process. The weathering of minerals also triggers the export of dissolved Si (DSi) to coastal waters and the ocean. Here, DSi is deposited in diatom frustules, in an amorphous biogenic form (BSi). Diatoms account for 50% of the primary production and are crucial for the export of carbon into the deep sea. In recent years, it was acknowledged that terrestrial systems filter the Si transition from the terrestrial mineral to the marine and coastal biological pool, by the incorporation of DSi into plants. In this process, DSi is taken up by roots together with other nutrients and precipitates in plant cells in amorphous structures named phytoliths. After dead, plant tissues become mixed in the top soil, where BSi is available for dissolution and will control the DSi availability in short time scales. Additionally, Si originated from soil forming processes can also significantly interfere with the global cycle. The Si cycle in terrestrial ecosystems is a key factor to coastal ecology, plant ecology, biogeochemistry and agro-sciences, but the high variability of different biogenic and non-biogenic Si pools remains as an obstacle to obtain accurate measurements. The traditional methods, developed to isolate diatoms in ocean sediments, only account for simple mineral corrections. In this dissertation we have adapted a novel continuous analysis method (during alkaline extraction) that uses Si-Al ratios and reactivity to differ biogenic from non-biogenic fractions. The method was originally used in marine sediments, but we have developed it to be applicable in a wide range of terrestrial, aquatic and coastal ecosystems. We first focused on soils under strong human impact in

  17. AlncRNA HULC as an effective biomarker for surveillance of the outcome of cancer: A meta-analysis

    PubMed Central

    Liu, Yi; Peng, Ji; Cao, Yong; Su, Zhan; Wang, Tieqiang; Cheng, Jinquan; Hu, Dongsheng

    2017-01-01

    Purpose High expression of highly upregulated in iver cancer (HULC) has been found associated with increased metastasis and poor prognosis with cancer. This meta-analysis aimed to determine the pooled effect of HULC on metastasis and prognosis of cancers. Method The studies were accessed using multiple databases. RevMan5.3 and STATA14.0 were used to estimate pooled effects, the heterogeneity among studies, and publication bias for the association of HULC and overall survival (OS). Results A total of 9 studies of 966 cancer patients were included. Risk of lymph node metastasis was increased with high versus low HULC expression (pooled odds ratio [OR] = 4.83, 95% confidence interval [CI] 1.59–14.63) as was distant metastasis (pooled OR = 5.44, 95% CI 2.33–12.74). Furthermore, OS time was shortened with high HULC expression (pooled hazard ratio [HR] = 1.48, 95% CI 1.03–2.12), especially in Chinese patients (pooled HR = 2.04, 95% CI 1.55–2.68), and risk of recurrence was increased (pooled OR = 6.68, 95% CI 2.77–16.13). Conclusion HULC might be a potential biomarker for therapy and prognosis surveillance in cancers. PMID:28146578

  18. Disease Risk Analysis and Post-Release Health Surveillance for a Reintroduction Programme: the Pool Frog Pelophylax lessonae.

    PubMed

    Sainsbury, A W; Yu-Mei, R; Ågren, E; Vaughan-Higgins, R J; Mcgill, I S; Molenaar, F; Peniche, G; Foster, J

    2016-07-08

    There are risks from disease in undertaking wild animal reintroduction programmes. Methods of disease risk analysis have been advocated to assess and mitigate these risks, and post-release health and disease surveillance can be used to assess the effectiveness of the disease risk analysis, but results for a reintroduction programme have not to date been recorded. We carried out a disease risk analysis for the reintroduction of pool frogs (Pelophylax lessonae) to England, using information gained from the literature and from diagnostic testing of Swedish pool frogs and native amphibians. Ranavirus and Batrachochytrium dendrobatidis were considered high-risk disease threats for pool frogs at the destination site. Quarantine was used to manage risks from disease due to these two agents at the reintroduction site: the quarantine barrier surrounded the reintroduced pool frogs. Post-release health surveillance was carried out through regular health examinations of amphibians in the field at the reintroduction site and collection and examination of dead amphibians. No significant health or disease problems were detected, but the detection rate of dead amphibians was very low. Methods to detect a higher proportion of dead reintroduced animals and closely related species are required to better assess the effects of reintroduction on health and disease.

  19. A Probabilistic Analysis of Sparse Coded Feature Pooling and Its Application for Image Retrieval

    PubMed Central

    Zhang, Yunchao; Chen, Jing; Huang, Xiujie; Wang, Yongtian

    2015-01-01

    Feature coding and pooling as a key component of image retrieval have been widely studied over the past several years. Recently sparse coding with max-pooling is regarded as the state-of-the-art for image classification. However there is no comprehensive study concerning the application of sparse coding for image retrieval. In this paper, we first analyze the effects of different sampling strategies for image retrieval, then we discuss feature pooling strategies on image retrieval performance with a probabilistic explanation in the context of sparse coding framework, and propose a modified sum pooling procedure which can improve the retrieval accuracy significantly. Further we apply sparse coding method to aggregate multiple types of features for large-scale image retrieval. Extensive experiments on commonly-used evaluation datasets demonstrate that our final compact image representation improves the retrieval accuracy significantly. PMID:26132080

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

    PubMed Central

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

    2012-01-01

    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. PMID:22249086

  1. Defining the Role of the MHC in Autoimmunity: A Review and Pooled Analysis

    PubMed Central

    Fernando, Michelle M. A.; Stevens, Christine R.; Walsh, Emily C.; De Jager, Philip L.; Goyette, Philippe; Plenge, Robert M.; Vyse, Timothy J.; Rioux, John D.

    2008-01-01

    The major histocompatibility complex (MHC) is one of the most extensively studied regions in the human genome because of the association of variants at this locus with autoimmune, infectious, and inflammatory diseases. However, identification of causal variants within the MHC for the majority of these diseases has remained difficult due to the great variability and extensive linkage disequilibrium (LD) that exists among alleles throughout this locus, coupled with inadequate study design whereby only a limited subset of about 20 from a total of approximately 250 genes have been studied in small cohorts of predominantly European origin. We have performed a review and pooled analysis of the past 30 years of research on the role of the MHC in six genetically complex disease traits – multiple sclerosis (MS), type 1 diabetes (T1D), systemic lupus erythematosus (SLE), ulcerative colitis (UC), Crohn's disease (CD), and rheumatoid arthritis (RA) – in order to consolidate and evaluate the current literature regarding MHC genetics in these common autoimmune and inflammatory diseases. We corroborate established MHC disease associations and identify predisposing variants that previously have not been appreciated. Furthermore, we find a number of interesting commonalities and differences across diseases that implicate both general and disease-specific pathogenetic mechanisms in autoimmunity. PMID:18437207

  2. Assessing coal-mine safety regulation: A pooled time-series analysis

    SciTech Connect

    Chun Youngpyoung.

    1991-01-01

    This study attempts to assess the independent, relative, and conjoint effects of four types of variables on coal-mine safety: administrative (mine inspections, mine investigations, and mine safety grants); political (state party competition, gubernatorial party affiliation, and deregulation); economic (state per-capita income and unemployment rates); task-related (mine size, technology, and type of mining), and state dummy variables. Trend, Pearson correlation, and pooled time-series analyses are performed on fatal and nonfatal injury rates reported in 25 coal-producing states during the 1975-1985 time period. These are then interpreted in light of three competing theories of regulation: capture, nonmarket failure, and threshold. Analysis reveals: (1) distinctions in the total explanatory power of the model across different types of injuries, as well as across presidential administrations; (2) a consistently more powerful impact on safety of informational implementation tools (safety education grants) over command-and-control approaches (inspections and investigations) or political variables; and (3) limited, albeit conjectural, support for a threshold theory of regulation in the coal mine safety arena.

  3. Staphylococcus aureus bloodstream infection: A pooled analysis of five prospective, observational studies

    PubMed Central

    Kaasch, Achim J.; Barlow, Gavin; Edgeworth, Jonathan D.; Fowler, Vance G.; Hellmich, Martin; Hopkins, Susan; Kern, Winfried V.; Llewelyn, Martin J.; Rieg, Siegbert; Rodriguez-Baño, Jesús; Scarborough, Matthew; Seifert, Harald; Soriano, Alex; Tilley, Robert; Tőrők, M. Estée; Weiβ, Verena; Wilson, A. Peter R.; Thwaites, Guy E.

    2014-01-01

    Summary Objectives Staphylococcus aureus bacteraemia is a common, often fatal infection. Our aim was to describe how its clinical presentation varies between populations and to identify common determinants of outcome. Methods We conducted a pooled analysis on 3395 consecutive adult patients with S. aureus bacteraemia. Patients were enrolled between 2006 and 2011 in five prospective studies in 20 tertiary care centres in Germany, Spain, United Kingdom, and United States. Results The median age of participants was 64 years (interquartile range 50–75 years) and 63.8% were male. 25.4% of infections were associated with diabetes mellitus, 40.7% were nosocomial, 20.6% were caused by methicillin-resistant S. aureus (MRSA), although these proportions varied significantly across studies. Intravenous catheters were the commonest identified infective focus (27.7%); 8.3% had endocarditis. Crude 14 and 90-day mortality was 14.6% and 29.2%, respectively. Age, MRSA bacteraemia, nosocomial acquisition, endocarditis, and pneumonia were independently associated with death, but a strong association was with an unidentified infective focus (adjusted hazard ratio for 90-day mortality 2.92; 95% confidence interval 2.33 to 3.67, p < 0.0001). Conclusion The baseline demographic and clinical features of S. aureus bacteraemia vary significantly between populations. Mortality could be reduced by assiduous MRSA control and early identification of the infective focus. PMID:24247070

  4. Power analysis of QTL detection in half-sib families using selective DNA pooling.

    PubMed

    Baro JA; Carleos, C; Corral, N; López, T; Cañón, J

    2001-01-01

    Individual loci of economic importance (QTL) can be detected by comparing the inheritance of a trait and the inheritance of loci with alleles readily identifiable by laboratory methods (genetic markers). Data on allele segregation at the individual level are costly and alternatives have been proposed that make use of allele frequencies among progeny, rather than individual genotypes. Among the factors that may affect the power of the set up, the most important are those intrinsic to the QTL: the additive effect of the QTL, and its dominance, and distance between markers and QTL. Other factors are relative to the choice of animals and markers, such as the frequency of the QTL and marker alleles among dams and sires. Data collection may affect the detection power through the size of half-sib families, selection rate within families, and the technical error incurred when estimating genetic frequencies. We present results for a sensitivity analysis for QTL detection using pools of DNA from selected half-sibs. Simulations showed that conclusive detection may be achieved with families of at least 500 half-sibs if sires are chosen on the criteria that most of their marker alleles are either both missing, or one is fixed, among dams.

  5. Highly-multiplexed barcode sequencing: an efficient method for parallel analysis of pooled samples

    PubMed Central

    Smith, Andrew M.; Heisler, Lawrence E.; St.Onge, Robert P.; Farias-Hesson, Eveline; Wallace, Iain M.; Bodeau, John; Harris, Adam N.; Perry, Kathleen M.; Giaever, Guri; Pourmand, Nader; Nislow, Corey

    2010-01-01

    Next-generation sequencing has proven an extremely effective technology for molecular counting applications where the number of sequence reads provides a digital readout for RNA-seq, ChIP-seq, Tn-seq and other applications. The extremely large number of sequence reads that can be obtained per run permits the analysis of increasingly complex samples. For lower complexity samples, however, a point of diminishing returns is reached when the number of counts per sequence results in oversampling with no increase in data quality. A solution to making next-generation sequencing as efficient and affordable as possible involves assaying multiple samples in a single run. Here, we report the successful 96-plexing of complex pools of DNA barcoded yeast mutants and show that such ‘Bar-seq’ assessment of these samples is comparable with data provided by barcode microarrays, the current benchmark for this application. The cost reduction and increased throughput permitted by highly multiplexed sequencing will greatly expand the scope of chemogenomics assays and, equally importantly, the approach is suitable for other sequence counting applications that could benefit from massive parallelization. PMID:20460461

  6. Pooled analysis of tiotropium Respimat(®) pharmacokinetics in cystic fibrosis.

    PubMed

    Sharma, Ashish; Geller, David E; Moroni-Zentgraf, Petra; Kattenbeck, Sabine; Schmid, Marion; Boland, Katja; Rapp, Barbara; Konstan, Michael W; Ratjen, Felix; Elborn, J Stuart; Koker, Paul

    2014-12-01

    Tiotropium is the first bronchodilator to be studied systematically in cystic fibrosis (CF). We investigated whether any intrinsic or extrinsic factors affected pharmacokinetic (PK) parameters of inhaled tiotropium delivered by Respimat(®) in adults and children with CF. Tiotropium PK in patients with CF was compared with that of healthy volunteers and patients with chronic obstructive pulmonary disease (COPD). This pooled analysis summarizes the PK parameters of inhaled tiotropium Respimat(®) across 9 early- and late-phase trials involving 27 healthy volunteers (1 trial), 409 patients with CF (3 trials), and 281 patients with COPD (5 trials). Patients with CF aged 5 to 11, 12 to 17, and ≥ 18 years had similar tiotropium plasma concentrations (geometric mean C(0.083,ss,norm): 2.22 pg/mL/μg; not determined for patients aged <5 years). The fraction excreted unchanged in the urine was 3.4-fold lower for patients aged 0.4 to <5 years than for those aged 5 to 11 years (fe(0-4,ss): 1.19% vs 4.09%). Tiotropium PK parameters were similar between CF patients and COPD patients.

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

    PubMed Central

    Xu, Dachun; Xu, Yawei

    2014-01-01

    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

  8. Estimation of the relative sensitivity of qPCR analysis using pooled samples.

    PubMed

    Muniesa, Ana; Ferreira, Chelo; Fuertes, Héctor; Halaihel, Nabil; de Blas, Ignacio

    2014-01-01

    The high sensitivity of qPCR makes it a desirable diagnostic method in epidemiological surveillance programs. However, due to high costs, the use of pooling has been suggested. In this paper, an algorithm based on the Montecarlo method has been designed and implemented. The algorithm had been tested in many different situations, and finally it was validated with a real dataset. Moreover, based on the results obtained and depending on pooling conditions, a drastic decrease of sensitivity is observed.

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

    SciTech Connect

    Molineaux, B.; Lachal, B.; Guisan, O. )

    1994-07-01

    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.

  10. Volatile disinfection by-product analysis from chlorinated indoor swimming pools.

    PubMed

    Weaver, William A; Li, Jing; Wen, Yuli; Johnston, Jessica; Blatchley, Michael R; Blatchley, Ernest R

    2009-07-01

    Chlorination of indoor swimming pools is practiced for disinfection and oxidation of reduced compounds that are introduced to water by swimmers. However, there is growing concern associated with formation for chlorinated disinfection by-products (DBPs) in these settings. Volatile DBPs are of particular concern because they may promote respiratory ailments and other adverse health effects among swimmers and patrons of indoor pool facilities. To examine the scope of this issue, water samples were collected from 11 pools over a 6month period and analyzed for free chlorine and their volatile DBP content. Eleven volatile DBPs were identified: monochloramine (NH(2)Cl), dichloramine (NHCl(2)), trichloramine (NCl(3)), chloroform (CHCl(3)), bromoform (CHBr(3)), dichlorobromomethane (CHBrCl(2)), dibromochloromethane (CHBr(2)Cl), cyanogen chloride (CNCl), cyanogen bromide (CNBr), dichloroacetonitrile (CNCHCl(2)), and dichloromethylamine (CH(3)NCl(2)). Of these 11 DBPs, 10 were identified as regularly occurring, with CHBrCl(2) only appearing sporadically. Pool water samples were analyzed for residual chlorine compounds using the DPD colorimetric method and by membrane introduction mass spectrometry (MIMS). These two methods were chosen as complementary measures of residual chlorine, and to allow for comparisons between the methods. The DPD method was demonstrated to consistently overestimate inorganic chloramine content in swimming pools. Pairwise correlations among the measured volatile DBPs allowed identification of dichloromethylamine and dichloroacetonitrile as potential swimming pool water quality indicator compounds.

  11. Pooling analysis of genetic data: the association of leptin receptor (LEPR) polymorphisms with variables related to human adiposity.

    PubMed Central

    Heo, M; Leibel, R L; Boyer, B B; Chung, W K; Koulu, M; Karvonen, M K; Pesonen, U; Rissanen, A; Laakso, M; Uusitupa, M I; Chagnon, Y; Bouchard, C; Donohoue, P A; Burns, T L; Shuldiner, A R; Silver, K; Andersen, R E; Pedersen, O; Echwald, S; Sørensen, T I; Behn, P; Permutt, M A; Jacobs, K B; Elston, R C; Hoffman, D J; Allison, D B

    2001-01-01

    Analysis of raw pooled data from distinct studies of a single question generates a single statistical conclusion with greater power and precision than conventional metaanalysis based on within-study estimates. However, conducting analyses with pooled genetic data, in particular, is a daunting task that raises important statistical issues. In the process of analyzing data pooled from nine studies on the human leptin receptor (LEPR) gene for the association of three alleles (K109R, Q223R, and K656N) of LEPR with body mass index (BMI; kilograms divided by the square of the height in meters) and waist circumference (WC), we encountered the following methodological challenges: data on relatives, missing data, multivariate analysis, multiallele analysis at multiple loci, heterogeneity, and epistasis. We propose herein statistical methods and procedures to deal with such issues. With a total of 3263 related and unrelated subjects from diverse ethnic backgrounds such as African-American, Caucasian, Danish, Finnish, French-Canadian, and Nigerian, we tested effects of individual alleles; joint effects of alleles at multiple loci; epistatic effects among alleles at different loci; effect modification by age, sex, diabetes, and ethnicity; and pleiotropic genotype effects on BMI and WC. The statistical methodologies were applied, before and after multiple imputation of missing observations, to pooled data as well as to individual data sets for estimates from each study, the latter leading to a metaanalysis. The results from the metaanalysis and the pooling analysis showed that none of the effects were significant at the 0.05 level of significance. Heterogeneity tests showed that the variations of the nonsignificant effects are within the range of sampling variation. Although certain genotypic effects could be population specific, there was no statistically compelling evidence that any of the three LEPR alleles is associated with BMI or waist circumference in the general

  12. Leisure Time Physical Activity and Mortality: A Detailed Pooled Analysis of the Dose-Response Relationship

    PubMed Central

    Arem, Hannah; Moore, Steven C.; Patel, Alpa; Hartge, Patricia; de Gonzalez, Amy Berrington; Visvanathan, Kala; Campbell, Peter T.; Freedman, Michal; Weiderpass, Elisabete; Adami, Hans Olov; Linet, Martha S.; Lee, I-Min; Matthews, Charles E.

    2015-01-01

    Importance The 2008 Physical Activity Guidelines for Americans recommended a minimum of 75 vigorous-intensity or 150 moderate-intensity minutes per week (7.5 metabolic equivalent hours per week (MET h/wk)) of aerobic activity for “substantial” health benefit, and suggested “additional” benefits by doing more than double this amount. However, the upper limit of longevity benefit or possible harm with more physical activity is unclear. Objective To quantify the dose-response association between leisure-time physical activity and mortality, and to define the upper limit of benefit or harm associated with more physical activity. Design We pooled data from six studies in the NCI Cohort Consortium (baseline 1992–2003). We used Cox proportional hazards regression with cohort stratification to generate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI). Median follow-up time was 14.2 years. Setting Population-based prospective cohorts in the U.S. and Europe with self-reported physical activity. Participants 661,137 men and women (116,686 deaths); median age 62 (range 21–98) years. Exposure Leisure-time moderate- to vigorous-intensity physical activity Main Outcome Mortality Results Compared to those reporting no leisure-time physical activity, we observed a 20% lower mortality risk among those performing less than the recommended 7.5 MET h/wk minimum (HR=0.80, 95% CI 0.78–0.82), a 31% lower risk at 1–2 times the recommended minimum (0.69, 0.67–0.70), and a 37% lower risk at 2–3 times the minimum (0.63, 0.62–0.65). An upper threshold for mortality benefit occurred at 3–5 times the physical activity recommendation (0.61, 0.59–0.62), but compared to the recommended minimum, the additional benefit was modest (31% vs. 39%). There was no evidence of harm at 10+ times the recommended minimum (0.68, 0.59–0.78). A similar dose-response was observed for mortality due to cardiovascular disease and to cancer. Conclusions and

  13. Genome-wide association study of subtype-specific epithelial ovarian cancer risk alleles using pooled DNA.

    PubMed

    Earp, Madalene A; Kelemen, Linda E; Magliocco, Anthony M; Swenerton, Kenneth D; Chenevix-Trench, Georgia; Lu, Yi; Hein, Alexander; Ekici, Arif B; Beckmann, Matthias W; Fasching, Peter A; Lambrechts, Diether; Despierre, Evelyn; Vergote, Ignace; Lambrechts, Sandrina; Doherty, Jennifer A; Rossing, Mary Anne; Chang-Claude, Jenny; Rudolph, Anja; Friel, Grace; Moysich, Kirsten B; Odunsi, Kunle; Sucheston-Campbell, Lara; Lurie, Galina; Goodman, Marc T; Carney, Michael E; Thompson, Pamela J; Runnebaum, Ingo B; Dürst, Matthias; Hillemanns, Peter; Dörk, Thilo; Antonenkova, Natalia; Bogdanova, Natalia; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M; Butzow, Ralf; Bunker, Clareann H; Modugno, Francesmary; Edwards, Robert P; Ness, Roberta B; du Bois, Andreas; Heitz, Florian; Schwaab, Ira; Harter, Philipp; Karlan, Beth Y; Walsh, Christine; Lester, Jenny; Jensen, Allan; Kjær, Susanne K; Høgdall, Claus K; Høgdall, Estrid; Lundvall, Lene; Sellers, Thomas A; Fridley, Brooke L; Goode, Ellen L; Cunningham, Julie M; Vierkant, Robert A; Giles, Graham G; Baglietto, Laura; Severi, Gianluca; Southey, Melissa C; Liang, Dong; Wu, Xifeng; Lu, Karen; Hildebrandt, Michelle A T; Levine, Douglas A; Bisogna, Maria; Schildkraut, Joellen M; Iversen, Edwin S; Weber, Rachel Palmieri; Berchuck, Andrew; Cramer, Daniel W; Terry, Kathryn L; Poole, Elizabeth M; Tworoger, Shelley S; Bandera, Elisa V; Chandran, Urmila; Orlow, Irene; Olson, Sara H; Wik, Elisabeth; Salvesen, Helga B; Bjorge, Line; Halle, Mari K; van Altena, Anne M; Aben, Katja K H; Kiemeney, Lambertus A; Massuger, Leon F A G; Pejovic, Tanja; Bean, Yukie T; Cybulski, Cezary; Gronwald, Jacek; Lubinski, Jan; Wentzensen, Nicolas; Brinton, Louise A; Lissowska, Jolanta; Garcia-Closas, Montserrat; Dicks, Ed; Dennis, Joe; Easton, Douglas F; Song, Honglin; Tyrer, Jonathan P; Pharoah, Paul D P; Eccles, Diana; Campbell, Ian G; Whittemore, Alice S; McGuire, Valerie; Sieh, Weiva; Rothstein, Joseph H; Flanagan, James M; Paul, James; Brown, Robert; Phelan, Catherine M; Risch, Harvey A; McLaughlin, John R; Narod, Steven A; Ziogas, Argyrios; Anton-Culver, Hoda; Gentry-Maharaj, Aleksandra; Menon, Usha; Gayther, Simon A; Ramus, Susan J; Wu, Anna H; Pearce, Celeste L; Pike, Malcolm C; Dansonka-Mieszkowska, Agnieszka; Rzepecka, Iwona K; Szafron, Lukasz M; Kupryjanczyk, Jolanta; Cook, Linda S; Le, Nhu D; Brooks-Wilson, Angela

    2014-05-01

    Epithelial ovarian cancer (EOC) is a heterogeneous cancer with both genetic and environmental risk factors. Variants influencing the risk of developing the less-common EOC subtypes have not been fully investigated. We performed a genome-wide association study (GWAS) of EOC according to subtype by pooling genomic DNA from 545 cases and 398 controls of European descent, and testing for allelic associations. We evaluated for replication 188 variants from the GWAS [56 variants for mucinous, 55 for endometrioid and clear cell, 53 for low-malignant potential (LMP) serous, and 24 for invasive serous EOC], selected using pre-defined criteria. Genotypes from 13,188 cases and 23,164 controls of European descent were used to perform unconditional logistic regression under the log-additive genetic model; odds ratios (OR) and 95 % confidence intervals are reported. Nine variants tagging six loci were associated with subtype-specific EOC risk at P < 0.05, and had an OR that agreed in direction of effect with the GWAS results. Several of these variants are in or near genes with a biological rationale for conferring EOC risk, including ZFP36L1 and RAD51B for mucinous EOC (rs17106154, OR = 1.17, P = 0.029, n = 1,483 cases), GRB10 for endometrioid and clear cell EOC (rs2190503, P = 0.014, n = 2,903 cases), and C22orf26/BPIL2 for LMP serous EOC (rs9609538, OR = 0.86, P = 0.0043, n = 892 cases). In analyses that included the 75 GWAS samples, the association between rs9609538 (OR = 0.84, P = 0.0007) and LMP serous EOC risk remained statistically significant at P < 0.0012 adjusted for multiple testing. Replication in additional samples will be important to verify these results for the less-common EOC subtypes.

  14. Well-characterized open pool experiment data and analysis for model validation and development.

    SciTech Connect

    Sundberg, David W.; Brown, Alexander L.; Blanchat, Thomas K.

    2006-12-01

    Four Well-Characterized Open Pool fires were conducted by Fire Science and Technology Department. The focus of the Well-Characterized Open Pool fire series was to provide environmental information for open pool fires on a physics first principal basis. The experiments measured the burning rate of liquid fuel in an open pool and the resultant heat flux to a weapon-sized object and the surrounding environment with well-characterized boundary and initial conditions. Results presented in this report include a general description of test observation (pre- and post-test), wind measurements, fire plume topology, average fuel recession and heat release rates, and incident heat flux to the pool and to the calorimeters. As expected, results of the experiments show a strong correlation between wind conditions, fuel vaporization (mass loss) rate, and incident heat flux to the fuel and ground surface and calorimeters. Numerical fire simulations using both temporally- and spatially-dependant wind boundary conditions were performed using the Vulcan fire code. Comparisons of data to simulation predictions showed similar trends; however, simulation-predicted incident heat fluxes were lower than measured.

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

    NASA Astrophysics Data System (ADS)

    Hadad, Kamal; Ayobian, Navid

    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 γ 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 γ 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.

  16. Experimental analysis of nanofluid pool boiling heat transfer in copper bead packed porous layers

    NASA Astrophysics Data System (ADS)

    Chen, Wei; Wang, Ji

    2017-03-01

    Coupling the nanofluid as working fluid and the copper beads packed porous structure on heating surface were employed to enhance the pool boiling heat transfer by changing the fluid properties with the adjunction of nanoparticles in liquid and altering the heating surface with a bead porous layer. Due to the higher thermal conductivity, the copper beads served as an extended heating surface and the boiling nucleation sites rose, but the flow resistance increased. The CuO-water and SiO2-water nanofluids as well as the pure water were respectively employed as working fluids in the pool boiling experiments. Comparing with the base fluid of water, the higher thermal conductivity and lower surface tension occur in the nanofluids and those favor the boiling heat transfer, but the higher viscosity and density of nanofluids serve as deteriorative factors. So, the concentration region of the nanofluids should be chosen properly. The maximum relative error between the collected experimental data of the pure water on a flat surface and the theoretical prediction of pool boiling using the Rohsenow correlation was less than 12 %. The comparisons of the pool boiling heat transfer characteristics were also conducted between the pure water and the nanofluids respectively on the horizontal flat surface and on the heating surface packed with a copper bead porous layer. Besides, the boiling bubble generation, integration and departure have a great affect on the pool boiling and were recorded with a camera in the bead stacked porous structures at different heat flux.

  17. Friends and Symptom Dimensions in Patients with Psychosis: A Pooled Analysis

    PubMed Central

    Giacco, Domenico; McCabe, Rose; Kallert, Thomas; Hansson, Lars; Fiorillo, Andrea; Priebe, Stefan

    2012-01-01

    Background Having friends is associated with more favourable clinical outcomes and a higher quality of life in mental disorders. Patients with schizophrenia have fewer friends than other mentally ill patients. No large scale studies have evaluated so far what symptom dimensions of schizophrenia are associated with the lack of friendships. Methods Data from four multi-centre studies on outpatients with schizophrenia and related disorders (ICD F20-29) were included in a pooled analysis (N = 1396). We established whether patients had close friends and contact with friends by using the equivalent items on friendships of the Manchester Short Assessment of Quality of Life or of the Lancashire Quality of Life Profile. Symptoms were measured by the Brief Psychiatric Rating Scale or by the identical items included in the Positive and Negative Syndrome Scale. Results Seven hundred and sixty-nine patients (55.1%) had seen a friend in the previous week and 917 (65.7%) had someone they regarded as a close friend. Low levels of negative symptoms and hostility were significantly associated with having a close friend and contact with a friend. Overall, almost twice as many patients with absent or mild negative symptoms had met a friend in the last week, compared with those with moderate negative symptoms. Conclusions Higher levels of negative symptoms and hostility are specifically associated with the lack of friendships in patients with psychotic disorders. These findings suggest the importance of developing effective treatments for negative symptoms and hostility in order to improve the probability of patients with schizophrenia to have friends. PMID:23185552

  18. Safety Profile of Nivolumab Monotherapy: A Pooled Analysis of Patients With Advanced Melanoma.

    PubMed

    Weber, Jeffrey S; Hodi, F Stephen; Wolchok, Jedd D; Topalian, Suzanne L; Schadendorf, Dirk; Larkin, James; Sznol, Mario; Long, Georgina V; Li, Hewei; Waxman, Ian M; Jiang, Joel; Robert, Caroline

    2017-03-01

    Purpose We conducted a retrospective analysis to assess the safety profile of nivolumab monotherapy in patients with advanced melanoma and describe the management of adverse events (AEs) using established safety guidelines. Patients and Methods Safety data were pooled from four studies, including two phase III trials, with patients who received nivolumab 3 mg/kg once every 2 weeks. We evaluated rate of treatment-related AEs, time to onset and resolution of select AEs (those with potential immunologic etiology), and impact of select AEs and suppressive immune-modulating agents (IMs) on antitumor efficacy. Results Among 576 patients, 71% (95% CI, 67% to 75%) experienced any-grade treatment-related AEs (most commonly fatigue [25%], pruritus [17%], diarrhea [13%], and rash [13%]), and 10% (95% CI, 8% to 13%) experienced grade 3 to 4 treatment-related AEs. No drug-related deaths were reported. Select AEs (occurring in 49% of patients) were most frequently skin related, GI, endocrine, and hepatic; grade 3 to 4 select AEs occurred in 4% of patients. Median time to onset of select AEs ranged from 5 weeks for skin to 15 weeks for renal AEs. Approximately 24% of patients received systemic IMs to manage select AEs, which in most cases resolved. Adjusting for number of doses, objective response rate (ORR) was significantly higher in patients who experienced treatment-related select AEs of any grade compared with those who did not. ORRs were similar in patients who did and patients who did not receive systemic IMs. Conclusion Treatment-related AEs with nivolumab monotherapy were primarily low grade, and most resolved with established safety guidelines. Use of IMs did not affect ORR, although treatment-related select AEs of any grade were associated with higher ORR, but no progression-free survival benefit.

  19. Synoptic climatological analysis of persistent cold air pools over the Carpathian Basin

    NASA Astrophysics Data System (ADS)

    Szabóné André, Karolina; Bartholy, Judit; Pongrácz, Rita

    2016-04-01

    A persistent cold air pool (PCAP) is a winter-time, anticyclone-related weather event over a relatively large basin. During this time the air is colder near the surface than aloft. This inversion near the surface can last even for weeks. As the cold air cools down, relative humidity increases and fog forms. The entire life cycle of a PCAP depends on the large scale circulation pattern. PCAP usually appears when an anticyclone builds up after a cold front passed over the examined basin, and it is usually destructed by a coming strong cold front of another midlatitude cyclone. Moreover, the intensity of the anticyclone affects the intensity of the PCAP. PCAP may result in different hazards for the population: (1) Temperature inversion in the surface layers together with weak wind may lead to severe air pollution causing health problems for many people, especially, elderly and children. (2) The fog and/or smog during chilly weather conditions often results in freezing rain. Both fog and freezing rain can distract transportation and electricity supply. Unfortunately, the numerical weather prediction models have difficulties to predict PCAP formation and destruction. One of the reasons is that PCAP is not defined objectively with a simple formula, which could be easily applied to the numerical output data. However, according to some recommendations from the synoptic literature, the shallow convective potential energy (SCPE) can be used to mathematically describe PCAP. In this study, we used the ERA-Interim reanalysis datasets to examine this very specific weather event (i.e., PCAP) over the Carpathian Basin. The connection between the mean sea level pressure and some PCAP measures (e.g., SCPE, energy deficit, etc.) is evaluated. For instance, we used logistic regression to identify PCAP periods over the Carpathian Basin. Then, further statistical analysis includes the evaluation of the length and intensity of these PCAP periods.

  20. Device Closure of Patent Foramen Ovale after Stroke: Pooled Analysis of Completed Randomized Trials

    PubMed Central

    Kent, David M.; Dahabreh, Issa J.; Ruthazer, Robin; Furlan, Anthony J.; Reisman, Mark; Carroll, John D.; Saver, Jeffrey L.; Smalling, Richard W.; Jüni, Peter; Mattle, Heinrich P.; Meier, Bernhard; Thaler, David E

    2015-01-01

    Background The comparative effectiveness of percutaneous closure of patent foramen ovale (PFO) plus medical therapy versus medical therapy alone for cryptogenic stroke is uncertain. Objectives We performed the first pooled analysis of individual participant data from completed randomized trials comparing PFO closure versus medical therapy in patients with cryptogenic stroke. Methods We analyzed data on 2 devices (STARFlex and Amplatzer PFO Occluder) evaluated in 3 trials. The primary composite outcome was stroke, transient ischemic attack (TIA), or death; the secondary outcome was stroke. We used log-rank tests and (unadjusted and covariate-adjusted) Cox regression models to compare device closure versus medical therapy. Results Among 2,303 patients, closure was not significantly associated with the primary composite outcome. The difference became significant after covariate adjustment (hazard ratio [HR]: 0.68; p = 0.049). For the outcome of stroke, all comparisons were statistically significant, with unadjusted and adjusted HRs of 0.58 (p = 0.043) and 0.58 (p = 0.044), respectively. In analyses limited to the 2 occluder device trials, the effect of closure was not significant for the composite outcome, but was for the stroke outcome (unadjusted HR: 0.39; p = 0.013. Subgroup analyses did not identify significant heterogeneity of treatment effects. Atrial fibrillation was more common among closure patients. Conclusions Among patients with PFO and cryptogenic stroke, closure reduced recurrent stroke and had a statistically significant effect on the composite of stroke, TIA, and death in adjusted but not unadjusted analyses. PMID:26916479

  1. Quantitative analysis of synaptic vesicle pool replenishment in cultured cerebellar granule neurons using FM dyes.

    PubMed

    Cheung, Giselle; Cousin, Michael A

    2011-11-11

    After neurotransmitter release in central nerve terminals, SVs are rapidly retrieved by endocytosis. Retrieved SVs are then refilled with neurotransmitter and rejoin the recycling pool, defined as SVs that are available for exocytosis(1,2). The recycling pool can generally be subdivided into two distinct pools - the readily releasable pool (RRP) and the reserve pool (RP). As their names imply, the RRP consists of SVs that are immediately available for fusion while RP SVs are released only during intense stimulation(1,2). It is important to have a reliable assay that reports the differential replenishment of these SV pools in order to understand 1) how SVs traffic after different modes of endocytosis (such as clathrin-dependent endocytosis and activity-dependent bulk endocytosis) and 2) the mechanisms controlling the mobilisation of both the RRP and RP in response to different stimuli. FM dyes are routinely employed to quantitatively report SV turnover in central nerve terminals(3-8). They have a hydrophobic hydrocarbon tail that allows reversible partitioning in the lipid bilayer, and a hydrophilic head group that blocks passage across membranes. The dyes have little fluorescence in aqueous solution, but their quantum yield increases dramatically when partitioned in membrane(9). Thus FM dyes are ideal fluorescent probes for tracking actively recycling SVs. The standard protocol for use of FM dye is as follows. First they are applied to neurons and are taken up during endocytosis (Figure 1). After non-internalised dye is washed away from the plasma membrane, recycled SVs redistribute within the recycling pool. These SVs are then depleted using unloading stimuli (Figure 1). Since FM dye labelling of SVs is quantal(10), the resulting fluorescence drop is proportional to the amount of vesicles released. Thus, the recycling and fusion of SVs generated from the previous round of endocytosis can be reliably quantified. Here, we present a protocol that has been modified to

  2. Association between dioxin and cancer incidence and mortality: a meta-analysis

    NASA Astrophysics Data System (ADS)

    Xu, Jinming; Ye, Yao; Huang, Fang; Chen, Hanwen; Wu, Han; Huang, Jian; Hu, Jian; Xia, Dajing; Wu, Yihua

    2016-11-01

    The objective of the present study was to systematically assess the association between dioxin/2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and cancer incidence and mortality. Systematic literature searches were conducted until July 2015 in Pubmed, Embase and Cochrane library to identify relevant studies. A random-effects model was applied to estimate the pooled odds ratio (OR), risk ratio (RR), standard incidence ratio (SIR) or standard mortality ratio (SMR) for cancer incidence or mortality. In addition, dose-response, meta-regression, subgroup, and publication bias analyses were conducted. Thirty-one studies involving 29,605 cancer cases and 3,478,748 participants were included. Higher external exposure level of TCDD was significantly associated with all cancer mortality (pooled SMR = 1.09, 95% CI: 1.01–1.19, p = 0.04), but not all cancer incidence (pooled RR = 1.01, 95% CI: 0.97–1.06, p = 0.49). Higher blood level of TCDD was both significantly associated with all cancer incidence (pooled RR = 1.57, 95% CI: 1.21–2.04, p = 0.001) and all cancer mortality (pooled SMR = 1.45, 95% CI: 1.25–1.69, p < 0.001). Subgroup analysis suggested that higher external exposure and blood level of TCDD were both significantly associated with the mortality caused by non-Hodgkin’s lymphoma. In conclusion, external exposure and blood level of TCDD were both significantly associated with all cancer mortality, especially for non-Hodgkin’s lymphoma.

  3. Association between dioxin and cancer incidence and mortality: a meta-analysis

    PubMed Central

    Xu, Jinming; Ye, Yao; Huang, Fang; Chen, Hanwen; Wu, Han; Huang, Jian; Hu, Jian; Xia, Dajing; Wu, Yihua

    2016-01-01

    The objective of the present study was to systematically assess the association between dioxin/2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and cancer incidence and mortality. Systematic literature searches were conducted until July 2015 in Pubmed, Embase and Cochrane library to identify relevant studies. A random-effects model was applied to estimate the pooled odds ratio (OR), risk ratio (RR), standard incidence ratio (SIR) or standard mortality ratio (SMR) for cancer incidence or mortality. In addition, dose-response, meta-regression, subgroup, and publication bias analyses were conducted. Thirty-one studies involving 29,605 cancer cases and 3,478,748 participants were included. Higher external exposure level of TCDD was significantly associated with all cancer mortality (pooled SMR = 1.09, 95% CI: 1.01–1.19, p = 0.04), but not all cancer incidence (pooled RR = 1.01, 95% CI: 0.97–1.06, p = 0.49). Higher blood level of TCDD was both significantly associated with all cancer incidence (pooled RR = 1.57, 95% CI: 1.21–2.04, p = 0.001) and all cancer mortality (pooled SMR = 1.45, 95% CI: 1.25–1.69, p < 0.001). Subgroup analysis suggested that higher external exposure and blood level of TCDD were both significantly associated with the mortality caused by non-Hodgkin’s lymphoma. In conclusion, external exposure and blood level of TCDD were both significantly associated with all cancer mortality, especially for non-Hodgkin’s lymphoma. PMID:27897234

  4. Development of a Self-Report Physical Function Instrument for Disability Assessment: Item Pool Construction and Factor Analysis

    PubMed Central

    McDonough, Christine M.; Jette, Alan M.; Ni, Pengsheng; Bogusz, Kara; Marfeo, Elizabeth E; Brandt, Diane E; Chan, Leighton; Meterko, Mark; Haley, Stephen M.; Rasch, Elizabeth K.

    2014-01-01

    Objectives To build a comprehensive item pool representing work-relevant physical functioning and to test the factor structure of the item pool. These developmental steps represent initial outcomes of a broader project to develop instruments for the assessment of function within the context of Social Security Administration (SSA) disability programs. Design Comprehensive literature review; gap analysis; item generation with expert panel input; stakeholder interviews; cognitive interviews; cross-sectional survey administration; and exploratory and confirmatory factor analyses to assess item pool structure. Setting In-person and semi-structured interviews; internet and telephone surveys. Participants A sample of 1,017 SSA claimants, and a normative sample of 999 adults from the US general population. Interventions Not Applicable. Main Outcome Measure Model fit statistics Results The final item pool consisted of 139 items. Within the claimant sample 58.7% were white; 31.8% were black; 46.6% were female; and the mean age was 49.7 years. Initial factor analyses revealed a 4-factor solution which included more items and allowed separate characterization of: 1) Changing and Maintaining Body Position, 2) Whole Body Mobility, 3) Upper Body Function and 4) Upper Extremity Fine Motor. The final 4-factor model included 91 items. Confirmatory factor analyses for the 4-factor models for the claimant and the normative samples demonstrated very good fit. Fit statistics for claimant and normative samples respectively were: Comparative Fit Index = 0.93 and 0.98; Tucker-Lewis Index = 0.92 and 0.98; Root Mean Square Error Approximation = 0.05 and 0.04. Conclusions The factor structure of the Physical Function item pool closely resembled the hypothesized content model. The four scales relevant to work activities offer promise for providing reliable information about claimant physical functioning relevant to work disability. PMID:23542402

  5. Angiotensin II and FCCP mobilizes calcium from different intracellular pools in adrenal glomerulosa cells; analysis of calcium fluxes.

    PubMed

    Balla, T; Szebeny, M; Kanyar, B; Spät, A

    1985-08-01

    The aim of the present study was to examine the effect of angiotensin II on the different pools of exchangeable Ca2+ in isolated rat adrenal glomerulosa cells. On the basis of steady state analysis of 45Ca exchange curves at least three kinetically distinct Ca2+ compartments are present in these cells. The most rapidly exchangeable compartment was regarded as Ca2+ loosely bound to the glycocalyx and the other compartments were considered to be intracellular Ca2+ pools. The effect of angiotensin II on different intracellular compartments was examined by adding the hormone at different phases of Ca2+ washout. Angiotensin increased the rate of 45Ca efflux within 1.5 min when added at the beginning of the washout. This effect, however, could not be detected when the hormone was added at the 30th min of washout, indicating that at least one hormone sensitive pool had lost most of its radioactivity by this time. In contrast to angiotensin II, the mitochondrial uncoupler FCCP mobilized almost the same quantity of 45Ca irrespective of the time of its addition during the washout. This latter finding suggests that this presumably mitochondrial Ca2+ pool has a slow rate of exchange and thus differs from the pool initially mobilized by angiotensin II. The initial Ca2+ mobilizing effect of angiotensin II was also observed in a Ca2+-free media which contained EGTA, indicating that this effect is not triggered by increased Ca2+ influx. In the present study we demonstrate in the intact glomerulosa cell that angiotensin II mobilizes Ca2+ from an intracellular Ca2+ store which appears to be distinct from the FCCP-sensitive store.

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

    SciTech Connect

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

    1994-06-01

    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 significant maintenance for the entire system life, as much as 20 to 30 years. Long-term liquid-metal boiling stability and materials compatibility with refluxing NaK-78 is not known and must be determined for the pool boiler receiver. No boiling system has been demonstrated for a significant duration with the current porous boiling enhancement surface and materials. Therefore, it is necessary to simulate the full-scale pool boiler design as much as possible, including flux levels, materials, and operating cycles. On-sun testing is impractical because of the limited test time available. A test vessel was constructed with a porous boiling enhancement surface. The boiling surface consisted of a brazed stainless steel powder with about 50% porosity. The vessel was heated with a quartz lamp array providing about go W/CM2 peak incident thermal flux. The vessel was charged with NaK-78. This allows the elimination of costly electric preheating, both on this test and on fullscale receivers. The vessel was fabricated from Haynes 230 alloy. The vessel operated at 750{degrees}C around the clock, with a 1/2-hour shutdown cycle to ambient every 8 hours. The test completed 7500 hours of lamp-on operation time, and over 1000 startups from ambient. The test was terminated when a small leak in an Inconel 600 thermowell was detected. The test design and data are presented here. Metallurgical analysis of virgin and tested materials has begun, and initial results are also presented.

  7. An analysis of pool surface deformation due to a plunging liquid jet

    NASA Astrophysics Data System (ADS)

    Bonetto, F.; Drew, D. A.; Lahey, Richard T., Jr.

    1993-10-01

    When a liquid jet impacts a pool containing the same liquid and surrounded by a still gas, a surface depression is produced. The surface shape is determined by the Weber number and the Bond number. In this work the shape of the surface is obtained as a function of the Weber number and Bond number by using a non-singular perturbation technique.

  8. A pooled analysis to define vitamin D dose requirements for fracture prevention in seniors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Meta-analyses reached conflicting results regarding vitamin D and fracture reduction. We pooled individual participant-level data from 11 double-blind RCTs of oral vitamin D supplementation (daily, weekly, 4-monthly) with or without calcium compared with placebo or calcium in seniors age 65 and olde...

  9. Characterizing sexual function in patients with generalized anxiety disorder: a pooled analysis of three vilazodone studies

    PubMed Central

    Clayton, Anita H; Durgam, Suresh; Tang, Xiongwen; Chen, Changzheng; Ruth, Adam; Gommoll, Carl

    2016-01-01

    Background Vilazodone has been shown to reduce core symptoms of generalized anxiety disorder (GAD) in three randomized, double-blind, placebo-controlled trials. Since sexual dysfunction (SD) is not well characterized in GAD, a post hoc analysis of these trials was conducted to evaluate the effects of vilazodone on sexual functioning in GAD patients. Materials and methods Data were pooled from one fixed-dose trial of vilazodone 20 and 40 mg/day (NCT01629966) and two flexible-dose studies of vilazodone 20–40 mg/day (NCT01766401, NCT01844115) in adults with GAD. Sexual functioning was assessed using the Changes in Sexual Functioning Questionnaire (CSFQ). Outcomes included mean change from baseline to end of treatment (EOT) in CSFQ total score and percentage of patients shifting from SD at baseline (CSFQ total score ≤47 for males, ≤41 for females) to normal functioning at EOT. Treatment-emergent adverse events related to sexual functioning were also analyzed. Results A total of 1,373 patients were included in the analyses. SD at baseline was more common in females (placebo, 46.4%; vilazodone, 49%) than in males (placebo, 35.1%; vilazodone, 40.9%). CSFQ total score improvement was found in both females (placebo, +1.2; vilazodone, +1.6) and males (placebo, +2.1; vilazodone, +1.0), with no statistically significant differences between treatment groups. The percentage of patients who shifted from SD at baseline to normal sexual functioning at EOT was higher in males (placebo, 40.6%; vilazodone, 35.7%) than in females (placebo, 24.9%; vilazodone, 34.9%); no statistical testing was performed. Except for erectile dysfunction and delayed ejaculation in vilazodone-treated males (2.4% and 2.1%, respectively), no treatment-emergent adverse events related to sexual functioning occurred in ≥2% of patients in either treatment group. Conclusion Approximately 35%–50% of patients in the vilazodone GAD studies had SD at baseline. Vilazodone and placebo had similar effects on

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

    PubMed Central

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

    2014-01-01

    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. PMID:25019505

  11. Three-Dimensional Ignition and Flame Propagation Above Liquid Fuel Pools: Computational Analysis

    NASA Technical Reports Server (NTRS)

    Cai, Jinsheng; Sirignano, William A.

    2001-01-01

    A three-dimensional unsteady reactive Navier-Stokes code is developed to study the ignition and flame spread above liquid fuels initially below the flashpoint temperature. Opposed air flow to the flame spread due to forced and/or natural convection is considered. Pools of finite width and length are studied in air channels of prescribed height and width. Three-dimensional effects of the flame front near the edge of the pool are captured in the computation. The formation of a recirculation zone in the gas phase similar to that found in two-dimensional calculations is also present in the three-dimensional calculations. Both uniform spread and pulsating spread modes are found in the calculated results.

  12. Liposomal amphotericin B (AmBisome) efficacy in confirmed invasive aspergillosis and other filamentous fungal infections in immunocompromised hosts: a pooled analysis.

    PubMed

    Cordonnier, C; Bresnik, M; Ebrahimi, R

    2007-05-01

    A pooled efficacy analysis applying current diagnostic standards for case selection was performed on previously published trials of liposomal amphotericin B for invasive filamentous fungal infections (IFFI). Favourable responses were observed in 51% of microbiologically confirmed cases of proven or probable IFFI. Despite the limitations inherent in a retrospective analysis of pooled studies, the response rates observed in this analysis were consistent with previous reports for antifungal therapy with amphotericin B deoxycholate or voriconazole in the treatment of invasive aspergillosis.

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

    PubMed

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

    2014-02-01

    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.

  14. Prolactin receptor attenuation induces zinc pool redistribution through ZnT2 and decreases invasion in MDA-MB-453 breast cancer cells

    SciTech Connect

    Bostanci, Zeynep; Alam, Samina; Soybel, David I.; Kelleher, Shannon L.

    2014-02-15

    Prolactin receptor (PRL-R) activation regulates cell differentiation, proliferation, cell survival and motility of breast cells. Prolactin (PRL) and PRL-R over-expression are strongly implicated in breast cancer, particularly contributing to tumor growth and invasion in the more aggressive estrogen-receptor negative (ER−) disease. PRL-R antagonists have been suggested as potential therapeutic agents; however, mechanisms through which PRL-R antagonists exert their actions are not well-understood. Zinc (Zn) is a regulatory factor for over 10% of the proteome, regulating critical cell processes such as proliferation, cell signaling, transcription, apoptosis and autophagy. PRL-R signaling regulates Zn metabolism in breast cells. Herein we determined effects of PRL-R attenuation on cellular Zn metabolism and cell function in a model of ER-, PRL-R over-expressing breast cancer cells (MDA-MB-453). PRL-R attenuation post-transcriptionally increased ZnT2 abundance and redistributed intracellular Zn pools into lysosomes and mitochondria. ZnT2-mediated lysosomal Zn sequestration was associated with reduced matrix metalloproteinase 2 (MMP-2) activity and decreased invasion. ZnT2-mediated Zn accumulation in mitochondria was associated with increased mitochondrial oxidation. Our results suggest that PRL-R antagonism in PRL-R over-expressing breast cancer cells may reduce invasion through the redistribution of intracellular Zn pools critical for cellular function. - Highlights: • PRL-R attenuation increased ZnT2 expression. • PRL-R attenuation increased lysosomal and mitochondrial Zn accumulation. • PRL-R attenuation decreased MMP-2 and invasion. • PRL-R antagonists may modulate lysosomal and mitochondrial Zn pools.

  15. Serum selenium levels and prostate cancer risk: A MOOSE-compliant meta-analysis.

    PubMed

    Cui, Zhigang; Liu, Dezhong; Liu, Chun; Liu, Gang

    2017-02-01

    Some observational studies have shown that elevated serum selenium levels are associated with reduced prostate cancer risk; however, not all published studies support these results. A literature search of PubMed, Embase, Medline, and the Cochrane Library up until September 2016 identified 17 studies suitable for further investigation. A meta-analysis was conducted on these studies to investigate the association between serum selenium levels and subsequent prostate cancer risk. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the overall OR of prostate cancer for the highest versus the lowest levels of serum selenium. We found a pooled OR (95% CI) of 0.76 (0.64, 0.91; P < 0.05). In subgroup analysis, an inverse association between serum selenium levels and prostate cancer risk was found in each of case-control studies, current and former smokers, high-grade cancer cases, advanced cancer cases, and different populations. Such correlations were not found for subgroups containing each of cohort studies, nonsmokers, low-grade cancer cases, and early stage cancer cases. In conclusion, our study suggests an inverse relationship between serum selenium levels and prostate cancer risk. However, further cohort studies and randomized control trials based on non-Western populations are required.

  16. Polymorphisms in the intercellular adhesion molecule 1 gene and cancer risk: a meta-analysis

    PubMed Central

    Tang, Weifeng; Wang, Yafeng; Chen, Yuanmei; Gu, Haiyong; Chen, Shuchen; Kang, Mingqiang

    2015-01-01

    Objectives: The correlation between intercellular adhesion molecule 1 (ICAM-1) common polymorphisms (rs5498 A>G and rs3093030 C>T) and cancer susceptibility has been explored in various ethnic groups and different cancer types; however, these investigations have yielded contradictory results. To address the relationship more precisely, we performed this meta-analysis. Design and methods: EmBase, PubMed and China National Knowledge Infrastructure (CNKI) databases were searched by two authors independently for eligible publications before April 8, 2015. Random-effects or fixed-effects model was harnessed to calculate the pooled odds ratios (ORs) and 95% confidence intervals (CIs) when appropriate. Results: The result suggested that the ICAM-1 rs5498 A>G polymorphism is not associated with cancer susceptibility in overall cancer. In a stratified analysis by ethnicity, a significant increased cancer risk was identified among Asians, but the inverse association was found among Caucasians. In a stratified analysis by cancer type, ICAM-1 rs5498 A>G polymorphism was associated with a significantly increased risk of oral cancer, but with protection from colorectal cancer and melanoma. ICAM-1 rs3093030 C>T polymorphism is not correlated with cancer susceptibility. Conclusions: In summary, this meta-analysis highlights that the ICAM-1 rs5498 A>G polymorphism probably contributes to decreased susceptibility to cancer, especially in Caucasians, in melanoma and colorectal cancer subgroup, but it may be a risk factor for oral cancer and Asians. PMID:26550112

  17. Fascin Is Critical for the Maintenance of Breast Cancer Stem Cell Pool Predominantly via the Activation of the Notch Self-Renewal Pathway.

    PubMed

    Barnawi, Rayanah; Al-Khaldi, Samiyah; Majed Sleiman, Ghida; Sarkar, Abdullah; Al-Dhfyan, Abdullah; Al-Mohanna, Falah; Ghebeh, Hazem; Al-Alwan, Monther

    2016-12-01

    An emerging dogma shows that tumors are initiated and maintained by a subpopulation of cancer cells that hijack some stem cell features and thus referred to as "cancer stem cells" (CSCs). The exact mechanism that regulates the maintenance of CSC pool remains largely unknown. Fascin is an actin-bundling protein that we have previously demonstrated to be a major regulator of breast cancer chemoresistance and metastasis, two cardinal features of CSCs. Here, we manipulated fascin expression in breast cancer cell lines and used several in vitro and in vivo approaches to examine the relationship between fascin expression and breast CSCs. Fascin knockdown significantly reduced stem cell-like phenotype (CD44(hi) /CD24(lo) and ALDH(+) ) and reversal of epithelial to mesenchymal transition. Interestingly, expression of the embryonic stem cell transcriptional factors (Oct4, Nanog, Sox2, and Klf4) was significantly reduced when fascin expression was down-regulated. Functionally, fascin-knockdown cells were less competent in forming colonies and tumorspheres, consistent with lower basal self-renewal activity and higher susceptibility to chemotherapy. Fascin effect on CSC chemoresistance and self-renewability was associated with Notch signaling. Activation of Notch induced the relevant downstream targets predominantly in the fascin-positive cells. Limiting-dilution xenotransplantation assay showed higher frequency of tumor-initiating cells in the fascin-positive group. Collectively, our data demonstrated fascin as a critical regulator of breast CSC pool at least partially via activation of the Notch self-renewal signaling pathway and modification of the expression embryonic transcriptional factors. Targeting fascin may halt CSCs and thus presents a novel therapeutic approach for effective treatment of breast cancer. Stem Cells 2016;34:2799-2813 Video Highlight: https://youtu.be/GxS4fJ_Ow-o.

  18. Underscreened Women Remain Overrepresented in the Pool of Cervical Cancer Cases in Spain: A Need to Rethink the Screening Interventions

    PubMed Central

    Ibáñez, Raquel; Alejo, María; Combalia, Neus; Tarroch, Xavier; Autonell, Josefina; Codina, Laia; Culubret, Montserrat; Bosch, Francesc Xavier; de Sanjosé, Silvia

    2015-01-01

    Objective. Audit of women with invasive cervical cancer (CC) is critical for quality control within screening activities. We analysed the screening history in the 10 years preceding the study entry in women with and without CC during 2000–2011. Methods. 323 women with CC from six pathology departments in Catalonia (Spain) and 23,782 women with negative cytology were compared. Age, previous history of cytologies, and histological type and FIGO stage were collected from the pathology registries. Logistic regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (CI95%). Results. History of cytology was registered in 26.2% of CC cases and in 78% of the control women (P < 0.0001) and its frequency decreased with increasing age. Compared to women with squamous cell carcinoma, adenocarcinoma cases were significantly more likely to have a cytology within the 3-year interval preceding cancer diagnosis (OR = 2.6 CI 95%: 1.2–5.6) and to have normal cytology results in previous screenings (OR = 2.4 CI 95%: 1.2–4.5). FIGO II–IV cases were more common among older women (older than 60 years). Conclusions. Absence of prior screening history was extremely common among CC cases compared to controls. Organized actions to reduce underscreened women and use of highly sensitive HPV-based tests could be important to reduce CC burden. PMID:26180804

  19. Body mass index, cigarette smoking, and alcohol consumption and cancers of the oral cavity, pharynx, and larynx: modeling odds ratios in pooled case-control data.

    PubMed

    Lubin, Jay H; Gaudet, Mia M; Olshan, Andrew F; Kelsey, Karl; Boffetta, Paolo; Brennan, Paul; Castellsague, Xavier; Chen, Chu; Curado, Maria Paula; Dal Maso, Luigino; Daudt, Alexander W; Fabianova, Eleonora; Fernandez, Leticia; Wünsch-Filho, Victor; Franceschi, Silvia; Herrero, Rolando; Koifman, Sergio; La Vecchia, Carlo; Lazarus, Philip; Levi, Fabio; Lissowska, Jolanta; Mates, Ioan Nicolae; Matos, Elena; McClean, Michael; Menezes, Ana; Morgenstern, Hal; Muscat, Joshua; Eluf Neto, Jose; Purdue, Mark P; Rudnai, Peter; Schwartz, Stephen M; Shangina, Oxana; Sturgis, Erich M; Szeszenia-Dabrowska, Neonilia; Talamini, Renato; Wei, Qingyi; Winn, Deborah; Zhang, Zuo-Feng; Hashibe, Mia; Hayes, Richard B

    2010-06-15

    Odds ratios for head and neck cancer increase with greater cigarette and alcohol use and lower body mass index (BMI; weight (kg)/height(2) (m(2))). Using data from the International Head and Neck Cancer Epidemiology Consortium, the authors conducted a formal analysis of BMI as a modifier of smoking- and alcohol-related effects. Analysis of never and current smokers included 6,333 cases, while analysis of never drinkers and consumers of < or =10 drinks/day included 8,452 cases. There were 8,000 or more controls, depending on the analysis. Odds ratios for all sites increased with lower BMI, greater smoking, and greater drinking. In polytomous regression, odds ratios for BMI (P = 0.65), smoking (P = 0.52), and drinking (P = 0.73) were homogeneous for oral cavity and pharyngeal cancers. Odds ratios for BMI and drinking were greater for oral cavity/pharyngeal cancer (P < 0.01), while smoking odds ratios were greater for laryngeal cancer (P < 0.01). Lower BMI enhanced smoking- and drinking-related odds ratios for oral cavity/pharyngeal cancer (P < 0.01), while BMI did not modify smoking and drinking odds ratios for laryngeal cancer. The increased odds ratios for all sites with low BMI may suggest related carcinogenic mechanisms; however, BMI modification of smoking and drinking odds ratios for cancer of the oral cavity/pharynx but not larynx cancer suggests additional factors specific to oral cavity/pharynx cancer.

  20. Use of snus and acute myocardial infarction: pooled analysis of eight prospective observational studies.

    PubMed

    Hansson, Jenny; Galanti, Maria Rosaria; Hergens, Maria-Pia; Fredlund, Peeter; Ahlbom, Anders; Alfredsson, Lars; Bellocco, Rino; Eriksson, Marie; Hallqvist, Johan; Hedblad, Bo; Jansson, Jan-Håkan; Nilsson, Peter; Pedersen, Nancy; Trolle Lagerros, Ylva; Ostergren, Per-Olof; Magnusson, Cecilia

    2012-10-01

    The use of snus (also referred to as Scandinavian or Swedish moist smokeless tobacco), which is common in Sweden and increasing elsewhere, is receiving increasing attention since considered a tobacco smoke "potential reduction exposure product". Snus delivers a high dose of nicotine with possible hemodynamic effects, but its impact on cardiovascular morbidity and mortality is uncertain. The aim of this study was to investigate whether snus use is associated with risk of and survival after acute myocardial infarction (AMI). Data from eight prospective cohort studies set in Sweden was pooled and reanalysed. The relative risk of first time AMI and 28-day case-fatality was calculated for 130,361 men who never smoked. During 2,262,333 person-years of follow-up, 3,390 incident events of AMI were identified. Current snus use was not associated with risk of AMI (pooled multivariable hazard ratio 1.04, 95 % confidence interval 0.93 to 1.17). The short-term case fatality rate appeared increased in snus users (odds ratio 1.28, 95 % confidence interval 0.99 to 1.68). This study does not support any association between use of snus and development of AMI. Hence, toxic components other than nicotine appear implicated in the pathophysiology of smoking related ischemic heart disease. Case fatality after AMI is seemingly increased among snus users, but this relationship may be due to confounding by socioeconomic or life style factors.

  1. Parity and endometrial cancer risk: a meta-analysis of epidemiological studies.

    PubMed

    Wu, Qi-Jun; Li, Yuan-Yuan; Tu, Chao; Zhu, Jingjing; Qian, Ke-Qing; Feng, Tong-Bao; Li, Changwei; Wu, Lang; Ma, Xiao-Xin

    2015-09-16

    The association between parity and endometrial cancer risk is inconsistent from observational studies. We aimed to quantitatively assess the relationship by summarizing all relevant epidemiological studies. PubMed (MEDLINE), Embase and Scopus were searched up to February 2015 for eligible case-control studies and prospective studies. Random-effects model was used to pool risk estimations. Ten prospective studies, 35 case-control studies and 1 pooled analysis of 10 cohort and 14 case-control studies including 69681 patients were identified. Pooled analysis revealed that there was a significant inverse association between parity and risk of endometrial cancer (relative risk (RR) for parous versus nulliparous: 0.69, 95% confidence interval (CI) 0.65-0.74; I(2) = 76.9%). By evaluating the number of parity, we identified that parity number of 1, 2 or 3 versus nulliparous demonstrated significant negative association (RR = 0.73, 95% CI 0.64-0.84, I(2) = 88.3%; RR = 0.62, 95% CI 0.53-0.74, I(2) = 92.1%; and RR = 0.68, 95% CI 0.65-0.70, I(2) = 20.0% respectively). The dose-response analysis suggested a nonlinear relationship between the number of parity and endometrial cancer risk. The RR decreased when the number of parity increased. This meta-analysis suggests that parity may be associated with a decreased risk of endometrial cancer. Further studies are warranted to replicate our findings.

  2. Prognostic value of Muc5AC in gastric cancer: A meta-analysis

    PubMed Central

    Zhang, Chuan-Tao; He, Ke-Cheng; Pan, Fei; Li, Yuan; Wu, Jiang

    2015-01-01

    AIM: To assess the correlation between decreased Muc5AC expression and patients’ survival and clinicopathological characteristics by conducting a meta-analysis. METHODS: Literature searches were performed in PubMed and EMBASE, and 11 studies met our criteria. Summary hazard ratios or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the effect. For the pooled analysis of the correlation between decreased Muc5AC expression and clinicopathological characteristics (tumour invasion depth, lymph node metastasis, tumour-node-metastasis stage, tumour size, venous invasion and lymphatic invasion), ORs and their variance were combined to estimate the effect. RESULTS: Eleven retrospective cohort studies comprising 2135 patients were included to assess the association between Muc5AC expression and overall survival and/or clinicopathological characteristics. Decreased Muc5AC expression was significantly correlated with poor overall survival of gastric cancer patients (pooled HR = 1.35, 95%CI: 1.08-1.7). Moreover, decreased Muc5AC expression was also significantly associated with tumour invasion depth (pooled OR = 2.12, 95%CI: 1.56-2.87) and lymph node metastasis (pooled OR = 1.56, 95%CI: 1.00-2.44) in gastric cancer. CONCLUSION: Decreased Muc5AC expression might be a poor prognostic predictor for gastric cancer. PMID:26420972

  3. [Cancer Genome Atlas Pan-cancer Analysis Project].

    PubMed

    Zhang, Kun; Wang, Hong

    2015-04-01

    Cancer can exhibit different forms depending on the site of origin, cell types, the different forms of genetic mutations which also affect cancer therapeutic effect. Although many genes have been demonstrated to change a direct result of the change in phenotype, however, many cancers lineage complex molecular mechanisms are still not fully elucidated. Therefore, The Cancer Genome Atlas (TCGA) Research Network analyzed a large human tumors, in order to find the molecular changes in DNA, RNA, protein and epigenetic level, The results contain a wealth of data provides us with an opportunity for common, personality and new ideas throughout the cancer lineages form a whole description. Pan-cancer genome program first compares the 12 kinds of cancer types. Analysis of different tumor molecular changes and their functions, will tell us how effective treatment method is applied to a similar phenotype of the tumor.

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

    SciTech Connect

    Dana, S.W.

    1980-03-01

    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.

  5. Effects of Different Analysis Strategies on Paired Associative Stimulation. A Pooled Data Analysis from Three Research Labs

    PubMed Central

    List, Jonathan; Vach, Werner; Flöel, Agnes; Klöppel, Stefan

    2016-01-01

    Paired associative stimulation (PAS) is a widely used transcranial magnetic stimulation (TMS) paradigm to non-invasively induce synaptic plasticity in the human brain in vivo. Altered PAS-induced plasticity has been demonstrated for several diseases. However, researchers are faced with a high inter- and intra-subject variability of the PAS response. Here, we pooled original data from nine PAS studies from three centers and analyzed the combined dataset of 190 healthy subjects with regard to age dependency, the role of stimulation parameters and the effect of different statistical methods. We observed no main effect of the PAS intervention over all studies (F(2;362) = 0.44; p = 0.644). The rate of subjects showing the expected increase of motor evoked potential (MEP) amplitudes was 53%. The PAS effect differed significantly between studies as shown by a significant interaction effect (F(16;362) = 1.77; p = 0.034) but post-hoc testing did not reveal significant effects after correction for multiple tests. There was a trend toward increased variability of the PAS effect in older subjects. Acquisition parameters differed across studies but without systematically influencing changes in MEP-size. The use of post/baseline quotients systematically indicated stronger PAS effects than post/baseline difference or the logarithm of the post/baseline quotient. The non-significant PAS effects across studies and a wide range of responder rates between studies indicate a high variability of this method. We were thus not able to replicate findings from a previous meta-analysis showing robust effects of PAS. No pattern emerged regarding acquisition parameters that at this point could guide future studies to reduce variability and help increase response rate. For future studies, we propose to report the responder rate and recommend the use of the logarithmized post/baseline quotient for further analyses to better address the possibility that results are driven by few extreme cases

  6. Coffee consumption and risk of endometrial cancer: findings from a large up-to-date meta-analysis.

    PubMed

    Je, Youjin; Giovannucci, Edward

    2012-10-01

    Several epidemiological studies have examined the association between coffee drinking and risk of endometrial cancer. To provide a quantitative assessment of this association, we conducted a meta-analysis of observational studies published up to October 2011 through a search of MEDLINE and EMBASE databases and the reference lists of retrieved article. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model, and generalized least square trend estimation was used to assess dose-response relationships. A total of 16 studies (10 case-control and six cohort studies) on coffee intake with 6,628 endometrial cancer cases were included in the meta-analysis. The pooled RR of endometrial cancer for the highest versus lowest categories of coffee intake was 0.71 (95% CI: 0.62-0.81; p for heterogeneity = 0.13). By study design, the pooled RRs were 0.69 (95% CI: 0.55-0.87) for case-control studies and 0.70 (95% CI: 0.61-0.80) for cohort studies. By geographic region, the inverse association was stronger for three Japanese studies (pooled RR = 0.40; 95% CI: 0.25-0.63) than five studies from USA/Canada (pooled RR = 0.69; 95% CI: 0.60-0.79) or eight studies from Europe (pooled RR = 0.79; 95% CI: 0.63-0.99). An increment of one cup per day of coffee intake conferred a pooled RR of 0.92 (95% CI: 0.90-0.95). In conclusion, our findings suggest that increased coffee intake is associated with a reduced risk of endometrial cancer, consistently observed for cohort and case-control studies. More large studies are needed to determine subgroups to obtain more benefits from coffee drinking in relation to endometrial cancer risk.

  7. Effect of dried-bonito broth on mood states: a pooled analysis of four randomized controlled human trials.

    PubMed

    Kuroda, Motonaka; Nozawa, Yoshizu

    2008-08-01

    Dried-bonito broth is commonly employed as a soup and sauce base in Japanese cuisine and is considered to be a nutritional supplement that promotes recovery from fatigue. Previous human trials have indicated that the ingestion of dried-bonito broth improves several mood states including fatigue, however, the effects in these studies have differed. The aim of this study was to clarify the effects of daily ingestion of dried-bonito broth on mood states by a pooled analysis of the randomized placebo-controlled trials. Five comparisons in four trials were selected for the pooled analysis (n = 159). The ingestion of dried-bonito broth significantly decreased the scores for fatigue (P = 0.032) and increased those for vigor (P = 0.027) compared to the placebo ingestion, suggesting that the dried-bonito broth improved fatigue felt in daily life. Furthermore, the ingestion of dried-bonito broth decreased the scores for tension-anxiety (P = 0.004) and confusion (P = 0.008) compared to the placebo ingestion. The ingestion of dried-bonito broth also significantly decreased the scores for total mood disturbance (P = 0.005). These results suggest that the ingestion of dried-bonito broth improves mood states especially fatigue, vigor, tension-anxiety and confusion.

  8. Two chemically distinct light-absorbing pools of urban organic aerosols: A comprehensive multidimensional analysis of trends.

    PubMed

    Paula, Andreia S; Matos, João T V; Duarte, Regina M B O; Duarte, Armando C

    2016-02-01

    The chemical and light-absorption dynamics of organic aerosols (OAs), a master variable in the atmosphere, have yet to be resolved. This study uses a comprehensive multidimensional analysis approach for exploiting simultaneously the compositional changes over a molecular size continuum and associated light-absorption (ultraviolet absorbance and fluorescence) properties of two chemically distinct pools of urban OAs chromophores. Up to 45% of aerosol organic carbon (OC) is soluble in water and consists of a complex mixture of fluorescent and UV-absorbing constituents, with diverse relative abundances, hydrophobic, and molecular weight (Mw) characteristics between warm and cold periods. In contrast, the refractory alkaline-soluble OC pool (up to 18%) is represented along a similar Mw and light-absorption continuum throughout the different seasons. Results suggest that these alkaline-soluble chromophores may actually originate from primary OAs sources in the urban site. This work shows that the comprehensive multidimensional analysis method is a powerful and complementary tool for the characterization of OAs fractions. The great diversity in the chemical composition and optical properties of OAs chromophores, including both water-soluble and alkaline-soluble OC, may be an important contribution to explain the contrasting photo-reactivity and atmospheric behavior of OAs.

  9. What’s old is new again: yeast mutant screens in the era of pooled segregant analysis by genome sequencing

    PubMed Central

    Curtin, Chris; Toni, Cordente

    2016-01-01

    While once de-rigueur for identification of genes involved in biological processes, screening of chemically induced mutant populations is an approach that has largely been superseded for model organisms such as Saccharomyces cerevisiae. Availability of single gene deletion/overexpression libraries and combinatorial synthetic genetic arrays provide yeast researchers more structured ways to probe genetic networks. Furthermore, in the age of inexpensive DNA sequencing, methodologies such as mapping of quantitative trait loci (QTL) by pooled segregant analysis and genome-wide association enable the identification of multiple naturally occurring allelic variants that contribute to polygenic phenotypes of interest. This is, however, contingent on the capacity to screen large numbers of individuals and existence of sufficient natural phenotypic variation within the available population. The latter cannot be guaranteed and non-selectable, industrially relevant phenotypes, such as production of volatile aroma compounds, pose severe limitations on the use of modern genetic techniques due to expensive and time-consuming downstream analyses. An interesting approach to overcome these issues can be found in Den Abt et al. 1 (this issue of Microbial Cell), where a combination of repeated rounds of chemical mutagenesis and pooled segregant analysis by whole genome sequencing was applied to identify genes involved in ethyl acetate formation, demonstrating a new path for industrial yeast strain development and bringing classical mutant screens into the 21st century

  10. Pooling and Analysis of Published in Vitro Data: A Proof of Concept Study for the Grouping of Nanoparticles

    PubMed Central

    Simkó, Myrtill; Tischler, Sonja; Mattsson, Mats-Olof

    2015-01-01

    The study aim was to test the applicability of pooling of nanomaterials-induced in vitro data for identifying the toxic capacity of specific (SiO2, TiO2, ZnO, CuO, CeO2 and carbon nanotubes, [CNT]) nanoparticles (NP) and to test the usefulness for grouping purposes. Publication selection was based on specific criteria regarding experimental conditions. Two relevant biological endpoints were selected; generation of intracellular reactive oxygen species (ROS) and viability above 90%. The correlations of the ROS ratios with the NP parameters’ size, concentration, and exposure time were analysed. The obtained data sets were then analysed with multiple regression analysis of variance (ANOVA) and the Tukey post-hoc test. The results show that this method is applicable for the selected metal oxide NP, but might need reconsideration and a larger data set for CNT. Several statistically significant correlations and results were obtained, thus validating the method. Furthermore, the relevance of the combination of ROS release with a cell viability test was shown. The data also show that it is advisable to compare ROS production of professional phagocytic with non-phagocytic cells. In conclusion, this is the first systematic analysis showing that pooling of available data into groups is a useful method for evaluation of data regarding NP induced toxicity in vitro. PMID:26540047

  11. Incidence and Mortality of Solid Cancers in People Exposed In Utero to Ionizing Radiation: Pooled Analyses of Two Cohorts from the Southern Urals, Russia

    PubMed Central

    Deltour, Isabelle; Krestinina, Lyudmila; Sokolnikov, Mikhail; Tsareva, Yulia; Tolstykh, Evgenia; Schüz, Joachim

    2016-01-01

    Background Previous studies have shown that acute external in utero exposure to ionizing radiation can increase cancer risk. It is not known whether chronic exposure at low dose rates, including due to radionuclide intake, influences the lifetime risk of solid cancers in the offspring. The objective of this study was to investigate solid cancer risk after in utero irradiation. Methods Cancer incidence and mortality over a 60-year period (from January 1950 to December 2009) were analyzed in the Urals Prenatally Exposed Cohort (UPEC). The cohort comprised in utero exposed offspring of Mayak Production Association female workers and of female residents of Techa River villages. Some of the offspring also received postnatal exposure, either due to becoming radiation workers themselves or due to continuing to live in the contaminated areas of the Techa River. The mortality analyses comprised 16,821 subjects (601,372 person-years), and the incidence analyses comprised 15,813 subjects (554,411 person-years). Poisson regression was used to quantify the relative risk as a function of the in utero soft tissue dose (with cumulative doses up to 944.9 mGy, mean dose of 14.1 mGy in the pooled cohort) and the postnatal stomach dose for solid cancer incidence and mortality. Results When a log-linear model was used, relative risk of cancer per 10 mGy of in utero dose was 0.99 (95% confidence interval (CI) = 0.96 to 1.01) based on incidence data and 0.98 (CI = 0.94 to 1.01) based on mortality data. Postnatal exposure to ionizing radiation was positively associated with the solid cancer risk in members of the UPEC, with a relative risk of 1.02 per 10mGy CI = 1.00 to 1.04). Conclusions No strong evidence was found that chronic low-dose-rate exposure of the embryo and fetus increased the risk of solid cancers in childhood or in adulthood. For both incidence and mortality, a tendency towards a decreased relative risk was noted with increasing doses to soft tissues of the fetus. Further

  12. Distinct Biochemical Pools of Golgi Phosphoprotein 3 in the Human Breast Cancer Cell Lines MCF7 and MDA-MB-231

    PubMed Central

    Luchsinger, Charlotte; Rivera-Dictter, Andrés; Arriagada, Cecilia; Acuña, Diego; Aguilar, Marcelo; Cavieres, Viviana; Burgos, Patricia V.; Ehrenfeld, Pamela; Mardones, Gonzalo A.

    2016-01-01

    Golgi phosphoprotein 3 (GOLPH3) has been implicated in the development of carcinomas in many human tissues, and is currently considered a bona fide oncoprotein. Importantly, several tumor types show overexpression of GOLPH3, which is associated with tumor progress and poor prognosis. However, the underlying molecular mechanisms that connect GOLPH3 function with tumorigenicity are poorly understood. Experimental evidence shows that depletion of GOLPH3 abolishes transformation and proliferation of tumor cells in GOLPH3-overexpressing cell lines. Conversely, GOLPH3 overexpression drives transformation of primary cell lines and enhances mouse xenograft tumor growth in vivo. This evidence suggests that overexpression of GOLPH3 could result in distinct features of GOLPH3 in tumor cells compared to that of non-tumorigenic cells. GOLPH3 is a peripheral membrane protein mostly localized at the trans-Golgi network, and its association with Golgi membranes depends on binding to phosphatidylinositol-4-phosphate. GOLPH3 is also contained in a large cytosolic pool that rapidly exchanges with Golgi-associated pools. GOLPH3 has also been observed associated with vesicles and tubules arising from the Golgi, as well as other cellular compartments, and hence it has been implicated in several membrane trafficking events. Whether these and other features are typical to all different types of cells is unknown. Moreover, it remains undetermined how GOLPH3 acts as an oncoprotein at the Golgi. Therefore, to better understand the roles of GOLPH3 in cancer cells, we sought to compare some of its biochemical and cellular properties in the human breast cancer cell lines MCF7 and MDA-MB-231 with that of the non-tumorigenic breast human cell line MCF 10A. We found unexpected differences that support the notion that in different cancer cells, overexpression of GOLPH3 functions in diverse fashions, which may influence specific tumorigenic phenotypes. PMID:27123979

  13. Comparative genomic analysis of esophageal cancers.

    PubMed

    Caygill, Christine P J; Gatenby, Piers A C; Herceg, Zdenko; Lima, Sheila C S; Pinto, Luis F R; Watson, Anthony; Wu, Ming-Shiang

    2014-09-01

    The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on comparative genomic analysis of esophageal cancers: genomic polymorphisms, the genetic and epigenetic drivers in esophageal cancers, and the collection of data in the UK Barrett's Oesophagus Registry.

  14. Vitamin E intake and risk of amyotrophic lateral sclerosis: a pooled analysis of data from 5 prospective cohort studies.

    PubMed

    Wang, Hao; O'Reilly, Éilis J; Weisskopf, Marc G; Logroscino, Giancarlo; McCullough, Marjorie L; Schatzkin, Arthur; Kolonel, Laurence N; Ascherio, Alberto

    2011-03-15

    The authors investigated whether vitamin E intake was associated with amyotrophic lateral sclerosis (ALS) in the Nurses' Health Study (1976-2004), the Health Professionals Follow-up Study (1986-2004), the Cancer Prevention Study II Nutrition Cohort (1992-2004), the Multiethnic Cohort Study (1993-2005), and the National Institutes of Health-AARP Diet and Health Study (1995-2005). ALS deaths were identified through the National Death Index. In the Nurses' Health Study and the Health Professionals Follow-up Study, confirmed nonfatal ALS cases were also included. Cohort-specific results were estimated using Cox proportional hazards models and pooled using random-effects models. Among 1,055,546 participants, 805 developed ALS. Overall, using vitamin E supplements was not associated with ALS. However, within cohorts with information on duration of vitamin E supplement use (231 cases), ALS rates declined with increasing years of use (P-trend=0.01). Compared with nonusers, the multivariable-adjusted relative risk was 1.05 (95% confidence interval (CI): 0.60, 1.84) among users for ≤1 year (12 cases), 0.77 (95% CI: 0.33, 1.77) among users for 2-4 years (7 cases), and 0.64 (95% CI: 0.39, 1.04) among users for ≥5 years (18 cases). For dietary vitamin E intake, the multivariable-adjusted relative risk comparing the highest quartile with the lowest was 0.79 (95% CI: 0.61, 1.03); an inverse dose-response was evident in women (P-trend=0.002) but not in men (P-trend=0.71). In this large, pooled prospective study, long-term vitamin E supplement use was associated with lower ALS rates. A possible protective effect of vitamin E deserves further consideration.

  15. BAC-pool sequencing and analysis of large segments of A12 and D12 homoeologous chromosomes in upland cotton.

    PubMed

    Buyyarapu, Ramesh; Kantety, Ramesh V; Yu, John Z; Xu, Zhanyou; Kohel, Russell J; Percy, Richard G; Macmil, Simone; Wiley, Graham B; Roe, Bruce A; Sharma, Govind C

    2013-01-01

    Although new and emerging next-generation sequencing (NGS) technologies have reduced sequencing costs significantly, much work remains to implement them for de novo sequencing of complex and highly repetitive genomes such as the tetraploid genome of Upland cotton (Gossypium hirsutum L.). Herein we report the results from implementing a novel, hybrid Sanger/454-based BAC-pool sequencing strategy using minimum tiling path (MTP) BACs from Ctg-3301 and Ctg-465, two large genomic segments in A12 and D12 homoeologous chromosomes (Ctg). To enable generation of longer contig sequences in assembly, we implemented a hybrid assembly method to process ~35x data from 454 technology and 2.8-3x data from Sanger method. Hybrid assemblies offered higher sequence coverage and better sequence assemblies. Homology studies revealed the presence of retrotransposon regions like Copia and Gypsy elements in these contigs and also helped in identifying new genomic SSRs. Unigenes were anchored to the sequences in Ctg-3301 and Ctg-465 to support the physical map. Gene density, gene structure and protein sequence information derived from protein prediction programs were used to obtain the functional annotation of these genes. Comparative analysis of both contigs with Arabidopsis genome exhibited synteny and microcollinearity with a conserved gene order in both genomes. This study provides insight about use of MTP-based BAC-pool sequencing approach for sequencing complex polyploid genomes with limited constraints in generating better sequence assemblies to build reference scaffold sequences. Combining the utilities of MTP-based BAC-pool sequencing with current longer and short read NGS technologies in multiplexed format would provide a new direction to cost-effectively and precisely sequence complex plant genomes.

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

    PubMed

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

    2014-01-15

    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 three 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 five with other NSAIDs) that were performed in six 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: 1.15-1.44 and 1.25; 95% CI: 1.06-1.46, respectively). For aspirin use, we found no overall increased risk (pooled RR: 1.10; 95% CI: 0.95-1.28), except for non-US studies (five studies, pooled RR: 1.17; 95% CI: 1.04-1.33). 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.

  17. Greater weight loss among men participating in a commercial weight loss program: a pooled analysis of 2 randomized controlled trials.

    PubMed

    Barraj, Leila M; Murphy, Mary M; Heshka, Stanley; Katz, David L

    2014-02-01

    Being overweight and obese are significant health concerns for men and women, yet despite comparable needs for effective weight loss and maintenance strategies, little is known about the success of commercial weight loss programs in men. This study tests the hypothesis that men participating in a commercial weight loss program (Weight Watchers) had significantly greater weight loss than men receiving limited support from health professionals for weight loss (controls). A pooled analysis of weight loss and related physiologic parameter data from 2 randomized clinical trials was conducted. After 12 months, analysis of covariance tests showed that men in the commercial program group (n = 85) lost significantly more weight (P < .01) than men in the control group (n = 84); similar significant differences were observed for body mass index and waist circumference. These results suggest that participation in a commercial weight loss program may be a more effective means to lose weight and maintain weight loss.

  18. In utero exposure to radiation and haematological malignancies: pooled analysis of Southern Urals cohorts

    PubMed Central

    Schüz, Joachim; Deltour, Isabelle; Krestinina, Lyudmila Y; Tsareva, Yulia V; Tolstykh, Evgenia I; Sokolnikov, Mikhail E; Akleyev, Alexander V

    2017-01-01

    Background: It is scientifically uncertain whether in utero exposure to low-dose ionising radiation increases the lifetime risk of haematological malignancies. Methods: We pooled two cohorts from the Southern Urals comprising offspring of female workers of a large nuclear facility (the Mayak Production Association) and of women living in areas along the Techa River contaminated by nuclear accidents/waste from the same facility, with detailed dosimetry. Results: The combined cohort totalled 19 536 subjects with 700 504 person-years at risk over the period of incidence follow-up, and slightly more over the period of mortality follow-up, yielding 58 incident cases and 36 deaths up to age 61 years. Risk was increased in subjects who received in utero doses of ⩾80 mGy (excess relative risk (ERR): 1.27; 95% confidence interval (CI): −0.20 to 4.71), and the risk increased consistently per 100 mGy of continuous exposure in utero (ERR: 0.77; CI: 0.02 to 2.56). No association was apparent in mortality-based analyses. Results for leukaemia and lymphoma were similar. A very weak positive association was observed between incidence and postnatal exposure. Conclusions: In summary, the results suggest a positive association between in utero exposure to ionising radiation and risk of haematological malignancies, but the small number of outcomes and inconsistent incidence and mortality findings preclude firm conclusions. PMID:27855443

  19. Analysis of an open-air swimming pool solar heating system by using an experimentally validated TRNSYS model

    SciTech Connect

    Ruiz, Elisa; Martinez, Pedro J.

    2010-01-15

    In the case of private outdoor swimming pools, seldom larger than 100 m{sup 2}, conventional auxiliary heating systems are being installed less and less. Solar heating is an option to extend the swimming season. The temperature evolution of an open-air swimming pool highly depends on the wind speed directly on the water surface, which at the same time is influenced by the surroundings of the pool. In this paper, the TRNSYS model of a private open-air pool with a 50-m{sup 2} surface was validated by registering the water temperature evolution and the meteorological data at the pool site. Evaporation is the main component of energy loss in swimming pools. Six different sets of constants found in literature were considered to evaluate the evaporative heat transfer coefficient with the purpose of finding the most suitable one for the TRNSYS pool model. In order to do that, the evolution of the pool water temperature predicted by the TRNSYS pool model was compared with the experimentally registered one. The simulation with TRNSYS of the total system, including the swimming pool and the absorber circuit integrated into the existing filter circuit, provided information regarding the increase of the pool temperature for different collector areas during the swimming season. This knowledge, together with the economic costs, support the decision about the absorber field size. (author)

  20. Mediation by Peer Violence Victimization of Sexual Orientation Disparities in Cancer-Related Tobacco, Alcohol, and Sexual Risk Behaviors: Pooled Youth Risk Behavior Surveys

    PubMed Central

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

    2014-01-01

    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

  1. Circulating adiponectin levels and risk of endometrial cancer: Systematic review and meta-analysis.

    PubMed

    Li, Zhi-Jun; Yang, Xue-Ling; Yao, Yan; Han, Wei-Qing; Li, B O

    2016-06-01

    Previous epidemiological studies have presented conflicting results regarding associations between circulating adiponectin (APN) levels and the risk of endometrial cancer. Thus a meta-analysis was performed to investigate the association between these factors. Multiple electronic sources, including PubMed, SpringerLink and Google Scholar databases were searched to identify relevant studies for the present meta-analysis. All of the selected studies examined the correlation between circulating APN levels and endometrial cancer. The standardized mean difference (SMD) and 95% confidence intervals (CIs) were estimated and pooled using meta-analysis methods. Overall, 18 case-control studies met the inclusion criteria. A total of 5,692 participants and 2,337 cases of endometrial cancer were included in this meta-analysis. The SMD of the pooled analysis (95% CI) were -1.96 (-2.60, -1.31), P=0.000. When the cancer grades were compared, the APN values were not significantly different between the grades of endometrial cancer [G1 vs. G3, 1.02 (-0.68, 2.72), P>0.05; G1 vs. G2, 0.34 (-0.86, 1.54), P>0.05]. However, there was a significant association between high APN levels and postmenopausal endometrial cancer cases with an SMD (95% CI) of -2.27 (-4.36, -0.18) and P<0.05, however, no association was observed in premenopausal endometrial cancer cases with an SMD (95% CI) of -1.52 (-3.49, 0.45) and P>0.05. The low circulating APN level increases the risk of endometrial cancer, whereas the high APN level decreases this risk in postmenopausal women. Circulating APN as simple biomarkers may be a promising tool for the prevention, early diagnosis and disease monitoring of endometrial cancer.

  2. Circulating adiponectin levels and risk of endometrial cancer: Systematic review and meta-analysis

    PubMed Central

    LI, ZHI-JUN; YANG, XUE-LING; YAO, YAN; HAN, WEI-QING; LI, BO

    2016-01-01

    Previous epidemiological studies have presented conflicting results regarding associations between circulating adiponectin (APN) levels and the risk of endometrial cancer. Thus a meta-analysis was performed to investigate the association between these factors. Multiple electronic sources, including PubMed, SpringerLink and Google Scholar databases were searched to identify relevant studies for the present meta-analysis. All of the selected studies examined the correlation between circulating APN levels and endometrial cancer. The standardized mean difference (SMD) and 95% confidence intervals (CIs) were estimated and pooled using meta-analysis methods. Overall, 18 case-control studies met the inclusion criteria. A total of 5,692 participants and 2,337 cases of endometrial cancer were included in this meta-analysis. The SMD of the pooled analysis (95% CI) were −1.96 (−2.60, −1.31), P=0.000. When the cancer grades were compared, the APN values were not significantly different between the grades of endometrial cancer [G1 vs. G3, 1.02 (−0.68, 2.72), P>0.05; G1 vs. G2, 0.34 (−0.86, 1.54), P>0.05]. However, there was a significant association between high APN levels and postmenopausal endometrial cancer cases with an SMD (95% CI) of −2.27 (−4.36, −0.18) and P<0.05, however, no association was observed in premenopausal endometrial cancer cases with an SMD (95% CI) of −1.52 (−3.49, 0.45) and P>0.05. The low circulating APN level increases the risk of endometrial cancer, whereas the high APN level decreases this risk in postmenopausal women. Circulating APN as simple biomarkers may be a promising tool for the prevention, early diagnosis and disease monitoring of endometrial cancer. PMID:27284314

  3. A meta-analysis of soil salinization effects on nitrogen pools, cycles and fluxes in coastal ecosystems.

    PubMed

    Zhou, Minghua; Butterbach-Bahl, Klaus; Vereecken, Harry; Brüggemann, Nicolas

    2017-03-01

    Salinity intrusion caused by land subsidence resulting from increasing groundwater abstraction, decreasing river sediment loads and increasing sea level because of climate change has caused widespread soil salinization in coastal ecosystems. Soil salinization may greatly alter nitrogen (N) cycling in coastal ecosystems. However, a comprehensive understanding of the effects of soil salinization on ecosystem N pools, cycling processes and fluxes is not available for coastal ecosystems. Therefore, we compiled data from 551 observations from 21 peer-reviewed papers and conducted a meta-analysis of experimental soil salinization effects on 19 variables related to N pools, cycling processes and fluxes in coastal ecosystems. Our results showed that the effects of soil salinization varied across different ecosystem types and salinity levels. Soil salinization increased plant N content (18%), soil NH4(+) (12%) and soil total N (210%), although it decreased soil NO3(-) (2%) and soil microbial biomass N (74%). Increasing soil salinity stimulated soil N2 O fluxes as well as hydrological NH4(+) and NO2(-) fluxes more than threefold, although it decreased the hydrological dissolved organic nitrogen (DON) flux (59%). Soil salinization also increased the net N mineralization by 70%, although salinization effects were not observed on the net nitrification, denitrification and dissimilatory nitrate reduction to ammonium in this meta-analysis. Overall, this meta-analysis improves our understanding of the responses of ecosystem N cycling to soil salinization, identifies knowledge gaps and highlights the urgent need for studies on the effects of soil salinization on coastal agro-ecosystem and microbial N immobilization. Additional increases in knowledge are critical for designing sustainable adaptation measures to the predicted intrusion of salinity intrusion so that the productivity of coastal agro-ecosystems can be maintained or improved and the N losses and pollution of the natural

  4. MSH3 rs26279 polymorphism increases cancer risk: a meta-analysis

    PubMed Central

    Miao, Hui-Kai; Chen, Li-Ping; Cai, Dong-Ping; Kong, Wei-Ju; Xiao, Li; Lin, Jie

    2015-01-01

    Previous studies have investigated the association of mutS homolog 3 (MSH3) rs26279 G > A polymorphism with the risk of different types of cancers including colorectal cancer, breast cancer, prostate cancer, bladder cancer, thyroid cancer, ovarian cancer and oesophageal cancer. However, its association with cancer remains conflicting. We performed a comprehensive meta-analysis to derive a more precise estimation of the relationship between MSH3 rs26279 G > A polymorphism and cancer susceptibility. Systematically searching the PubMed and EMBASE databases yielded 11 publications with 12 studies of 3282 cases and 6476 controls. The strength of the association was determined by crude odds ratios (OR) and 95% confidence intervals (CI). Overall, pooled risk estimates demonstrated that MSH3 rs26279 G > A was significantly associated with an increased overall cancer risk under all the genetic models (GG vs. AA: OR = 1.27, 95% CI = 1.09-1.48, P = 0.002; AG vs. AA: OR = 1.10, 95% CI = 1.00-1.21, P = 0.045; GG vs. AG + AA: OR = 1.23, 95% CI = 1.06-1.42, P = 0.005; AG + GG vs. AA: OR = 1.13, 95% CI = 1.04-1.24, P = 0.006; G vs. A: OR = 1.13, 95% CI = 1.05-1.20, P = 0.001). The association was more evident for colorectal cancer and breast cancer. Moreover, the significant association was also observed in the following subgroups: Europeans, Asians, population-based studies, hospital-based studies, and studies comprising relatively large sample size (≥ 200). Our meta-analysis results demonstrated that MSH3 rs26279 G > A polymorphism is associated with an increased risk of overall cancer, especially for the colorectal cancer and breast cancer. PMID:26617824

  5. Cruciferous vegetables intake and the risk of colorectal cancer: a meta-analysis of observational studies

    PubMed Central

    Wu, Q. J.; Yang, Y.; Vogtmann, E.; Wang, J.; Han, L. H.; Li, H. L.; Xiang, Y. B.

    2013-01-01

    Background Epidemiological studies have reported inconsistent associations between cruciferous vegetable (CV) intake and colorectal cancer (CRC) risk. To our knowledge, a comprehensive and quantitative assessment of the association between CV intake and CRC has not been reported. Methods Relevant articles were identified by searching MEDLINE. We pooled the relative risks (RR) from individual studies using a random-effect model and carried out heterogeneity and publication bias analyses. Results Twenty-four case–control and 11 prospective studies were included in our analysis. When all studies were pooled, we yielded a significantly inverse association between CV (RR: 0.82; 95% confidence interval 0.75–0.90) intake and CRC risk. Specific analysis for cabbage and broccoli yielded similar result. When separately analyzed, case–control studies of CV intake yield similar results, and the results from the prospective studies showed borderline statistical significance. Moreover, significant inverse associations were also observed in colon cancer and its distal subsite both among prospective and case–control studies. Conclusions Findings from this meta-analysis provide evidence that high intake of CV was inversely associated with the risk of CRC and colon cancer in humans. Further analysis on other specific CV, food preparation methods, stratified results by anatomic cancer site, and subsite of colon cancer should be extended in future study. PMID:23211939

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

    PubMed Central

    2014-01-01

    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 PMID:24886180

  7. Morphology of drying blood pools

    NASA Astrophysics Data System (ADS)

    Laan, Nick; Smith, Fiona; Nicloux, Celine; Brutin, David; D-Blood project Collaboration

    2016-11-01

    Often blood pools are found on crime scenes providing information concerning the events and sequence of events that took place on the scene. However, there is a lack of knowledge concerning the drying dynamics of blood pools. This study focuses on the drying process of blood pools to determine what relevant information can be obtained for the forensic application. We recorded the drying process of blood pools with a camera and measured the weight. We found that the drying process can be separated into five different: coagulation, gelation, rim desiccation, centre desiccation, and final desiccation. Moreover, we found that the weight of the blood pool diminishes similarly and in a reproducible way for blood pools created in various conditions. In addition, we verify that the size of the blood pools is directly related to its volume and the wettability of the surface. Our study clearly shows that blood pools dry in a reproducible fashion. This preliminary work highlights the difficult task that represents blood pool analysis in forensic investigations, and how internal and external parameters influence its dynamics. We conclude that understanding the drying process dynamics would be advancement in timeline reconstitution of events. ANR funded project: D-Blood Project.

  8. Cancer risk in patients receiving renal replacement therapy: A meta-analysis of cohort studies

    PubMed Central

    Shang, Weifeng; Huang, Liu; Li, Li; Li, Xiaojuan; Zeng, Rui; Ge, Shuwang; Xu, Gang

    2016-01-01

    It has been reported that patients receiving renal replacement therapy (RRT), including dialysis and kidney transplantation, tend to have an increased risk of cancer; however, studies on the degree of this risk have remained inconclusive. The present meta-analysis was therefore performed to quantify the cancer risk in patients with RRT. Cohort studies assessing overall cancer risk in RRT patients published before May 29, 2015 were included following systematic searches with of PubMed, EMBASE and the reference lists of the studies retrieved. Random-effects meta-analyses were used to pool standardized incidence rates (SIRs) with 95% confidence intervals (CIs). Heterogeneity tests, sensitivity analyses and publication bias assessment were performed. A total of 18 studies including 22 cohort studies were eventually identified, which comprised a total of 1,528,719 patients. In comparison with the general population, the pooled SIR for patients with dialysis including non-melanoma skin cancer (NMSC), dialysis excluding NMSC, transplantation including NMSC, transplantation excluding NMSC and RRT were 1.40 (95% CI, 1.36–1.45), 1.35 (95% CI, 1.23–1.50), 3.26 (95% CI, 2.29–4.63), 2.08 (95% CI, 1.73–2.50) and 2.01 (95% CI, 1.70–2.38), respectively. The cancer risk was particularly high in subgroups of large sample size trials, female patients, younger patients (age at first dialysis, 0–34 years; age at transplantation, 0–20 years), the first year of RRT and non-Asian transplant patients. A significant association was also found between RRT and the majority of organ-specific cancers. However, neither dialysis nor transplantation was associated with breast, body of uterus, colorectal or prostate cancer. Significant heterogeneity was found regarding the association between RRT and overall cancer as well as the majority of site-specific cancer types. However, this heterogeneity had no substantial influence on the pooled SIR for overall cancer in RRT according to the

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

    PubMed Central

    2011-01-01

    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

  10. Pooled analysis of the reports of pomalidomide after failure of lenalidomide and (or) bortezomib for multiple myeloma.

    PubMed

    Sheng, Zhixin; Liu, Guangyu

    2016-06-01

    The use of pomalidomide after lenalidomide and (or) bortezomib failure in patients with multiple myeloma is not clearly clarified in clinical practice. We sought to compile the available clinical reports to better understand the effectiveness of pomalidomide after failure of lenalidomide and (or) bortezomib. We searched published reports including pomalidomide, lenalidomide and (or) bortezomib. Seven reports were identified. Pomalidomide-based regimen was pomalidomide plus low-dose dexamethasone (POM + LoDEX). Six randomized controlled trials enrolling a total of 641 patients that evaluated the treatment effects of pomalidomide after lenalidomide and (or) bortezomib failure in patients with multiple myeloma were included. Pooled results showed that the overall response rate (ORR) was 31% in the POM + LoDEX group. Analysis of heterogeneity showed very little (p = 0.997, I(2)  = 0%), suggesting that response rates of POM + LoDEX therapy were consistent across those included trials. Stable disease was achieved in 40% of 603 patients (heterogeneity: p = 0.980, I(2)  = 0%). In those >65 years, overall response was achieved in 32% of 71 patients (heterogeneity: p = 0.77, I(2)  = 0%). POM + LoDEX showed promising activity in the 95 patients with high-risk cytogenetic abnormalities: ORR was 27% (heterogeneity: p = 0.97, I(2)  = 0%). In the pooled analysis, toxicity consisted primarily of myelosuppression: Grade 3 or 4 neutropenia was seen in 53% (heterogeneity: p = 0.857, I(2)  = 0%). Pomalidomide may produce clinical benefits in patients who had shown refractory on prior lenalidomide and (or) bortezomib therapy. Moreover, elder patients and high-risk cytogenetic abnormalities were not negative predictors for pomalidomide response after lenalidomide and (or) bortezomib failure. Copyright © 2015 John Wiley & Sons, Ltd.

  11. Development and optimization of SPECT gated blood pool cluster analysis for the prediction of CRT outcome

    SciTech Connect

    Lalonde, Michel Wassenaar, Richard; Wells, R. Glenn; Birnie, David; Ruddy, Terrence D.

    2014-07-15

    Purpose: Phase analysis of single photon emission computed tomography (SPECT) radionuclide angiography (RNA) has been investigated for its potential to predict the outcome of cardiac resynchronization therapy (CRT). However, phase analysis may be limited in its potential at predicting CRT outcome as valuable information may be lost by assuming that time-activity curves (TAC) follow a simple sinusoidal shape. A new method, cluster analysis, is proposed which directly evaluates the TACs and may lead to a better understanding of dyssynchrony patterns and CRT outcome. Cluster analysis algorithms were developed and optimized to maximize their ability to predict CRT response. Methods: About 49 patients (N = 27 ischemic etiology) received a SPECT RNA scan as well as positron emission tomography (PET) perfusion and viability scans prior to undergoing CRT. A semiautomated algorithm sampled the left ventricle wall to produce 568 TACs from SPECT RNA data. The TACs were then subjected to two different cluster analysis techniques, K-means, and normal average, where several input metrics were also varied to determine the optimal settings for the prediction of CRT outcome. Each TAC was assigned to a cluster group based on the comparison criteria and global and segmental cluster size and scores were used as measures of dyssynchrony and used to predict response to CRT. A repeated random twofold cross-validation technique was used to train and validate the cluster algorithm. Receiver operating characteristic (ROC) analysis was used to calculate the area under the curve (AUC) and compare results to those obtained for SPECT RNA phase analysis and PET scar size analysis methods. Results: Using the normal average cluster analysis approach, the septal wall produced statistically significant results for predicting CRT results in the ischemic population (ROC AUC = 0.73;p < 0.05 vs. equal chance ROC AUC = 0.50) with an optimal operating point of 71% sensitivity and 60% specificity. Cluster

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

    PubMed

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

    2010-01-01

    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.

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

    PubMed

    Ródenas, J; Abarca, A; Gallardo, S

    2011-08-01

    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.

  14. Evaluation of prostate cancer antigen 3 for detecting prostate cancer: a systematic review and meta-analysis

    NASA Astrophysics Data System (ADS)

    Cui, Yong; Cao, Wenzhou; Li, Quan; Shen, Hua; Liu, Chao; Deng, Junpeng; Xu, Jiangfeng; Shao, Qiang

    2016-05-01

    Previous studies indicate that prostate cancer antigen 3 (PCA3) is highly expressed in prostatic tumors. However, its clinical value has not been characterized. The aim of this study was to investigate the clinical value of the urine PCA3 test in the diagnosis of prostate cancer by pooling the published data. Clinical trials utilizing the urine PCA3 test for diagnosing prostate cancer were retrieved from PubMed and Embase. A total of 46 clinical trials including 12,295 subjects were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (‑LR), diagnostic odds ratio (DOR) and area under the curve (AUC) were 0.65 (95% confidence interval [CI]: 0.63–0.66), 0.73 (95% CI: 0.72–0.74), 2.23 (95% CI: 1.91–2.62), 0.48 (95% CI: 0.44–0.52), 5.31 (95% CI: 4.19–6.73) and 0.75 (95% CI: 0.74–0.77), respectively. In conclusion, the urine PCA3 test has acceptable sensitivity and specificity for the diagnosis of prostate cancer and can be used as a non-invasive method for that purpose.

  15. Evaluation of prostate cancer antigen 3 for detecting prostate cancer: a systematic review and meta-analysis

    PubMed Central

    Cui, Yong; Cao, Wenzhou; Li, Quan; Shen, Hua; Liu, Chao; Deng, Junpeng; Xu, Jiangfeng; Shao, Qiang

    2016-01-01

    Previous studies indicate that prostate cancer antigen 3 (PCA3) is highly expressed in prostatic tumors. However, its clinical value has not been characterized. The aim of this study was to investigate the clinical value of the urine PCA3 test in the diagnosis of prostate cancer by pooling the published data. Clinical trials utilizing the urine PCA3 test for diagnosing prostate cancer were retrieved from PubMed and Embase. A total of 46 clinical trials including 12,295 subjects were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (−LR), diagnostic odds ratio (DOR) and area under the curve (AUC) were 0.65 (95% confidence interval [CI]: 0.63–0.66), 0.73 (95% CI: 0.72–0.74), 2.23 (95% CI: 1.91–2.62), 0.48 (95% CI: 0.44–0.52), 5.31 (95% CI: 4.19–6.73) and 0.75 (95% CI: 0.74–0.77), respectively. In conclusion, the urine PCA3 test has acceptable sensitivity and specificity for the diagnosis of prostate cancer and can be used as a non-invasive method for that purpose. PMID:27161545

  16. Parity and thyroid cancer risk: a meta-analysis of epidemiological studies.

    PubMed

    Zhu, Jingjing; Zhu, Xiao; Tu, Chao; Li, Yuan-Yuan; Qian, Ke-Qing; Jiang, Cheng; Feng, Tong-Bao; Li, Changwei; Liu, Guang Jian; Wu, Lang

    2016-04-01

    Although observational studies have assessed the relationship between parity and thyroid cancer risk, the findings are inconsistent. To quantitatively assess the association, we conducted a systematic review and meta-analysis. PubMed and Embase were searched up to January 2015. Prospective or case-control studies that evaluated the association between parity and thyroid cancer risk were included. We used the fixed-effects model to pool risk estimates. After literature search, 10 prospective studies, 12 case-control studies and 1 pooled analysis of 14 case-control studies including 8860 patients were identified. The studies had fair methodological quality. Pooled analysis suggested that there was a significant association between parity and risk of thyroid cancer (RR for parous versus nulliparous: 1.09, 95% CI 1.03-1.15; I2=33.4%). The positive association persisted in almost all strata of subgroup analyses based on study design, location, study quality, type of controls, and confounder adjustment, although in some strata statistical significance was not detected. By evaluating the number of parity, we identified that both parity number of 2 versus nulliparous and parity number of 3 versus nulliparous demonstrated significant positive associations (RR=1.11, 95% CI 1.01-1.22; I2=31.1% and RR=1.16, 95% CI 1.01-1.33; I2=19.6% respectively). The dose-response analysis suggested neither a non-linear nor linear relationship between the number of parity and thyroid cancer risk. In conclusion, this meta-analysis suggests a potential association between parity and risk of thyroid cancer in females. However, the lack of detection of a dose-response relationship suggests that further studies are needed to better understand the relationship.

  17. Extrapulmonary small cell carcinoma of lymph node: Pooled analysis of all reported cases

    PubMed Central

    Sehgal, Inderpaul Singh; Kaur, Harpreet; Dhooria, Sahajal; Bal, Amanjit; Gupta, Nalini; Behera, Digambar; Singh, Navneet

    2016-01-01

    AIM: To study clinical outcomes and management of lymph nodes extrapulmonary small cell carcinoma (LNEPSCC). METHODS: Herein, we perform a systematic search of published literature in the PubMed and EMBASE databases for studies describing LNEPSCC. For uniformity of reporting, LNEPSCC was staged as limited if it involved either single lymph node station or if surgery with curative intent had been undertaken. The disease was staged extensive if it involved two or more lymph node regions. RESULTS: The systematic literature review yielded eight descriptions (n = 14) involving cervical, submandibular and inguinal lymph nodes. Eleven (64.7%) patients had limited disease (LD) and six (35.3%) had extensive disease (ED) at presentation. Chemotherapy (n = 6, 35.3%) or surgery (n = 4, 23.5%) were the most common form of treatment given to these patients. Complete response was achieved in 12 (70.6%) of the patients. Median (interquartile range) progression free survival and overall survival was 15 (7-42) mo and 22 (12.75-42) mo respectively. Of the three illustrative cases, two patients each had ED at presentation and achieved complete remission with platinum based combination chemotherapy. CONCLUSION: LNEPSCC is a rare disease with less than 15 reported cases in world literature. Surgical resection with curative intent is feasible in those with LD while platinum based combination chemoradiation is associated with favorable outcomes in patients with ED. Prognosis of LNEPSCC is better than that of small cell lung cancer in general. PMID:27298771

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

    PubMed Central

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

    2013-01-01

    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. PMID:24345868

  19. The Cancer Genome Atlas Pan-Cancer analysis project.

    PubMed

    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

    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.

  20. Association among Dietary Flavonoids, Flavonoid Subclasses and Ovarian Cancer Risk: A Meta-Analysis

    PubMed Central

    You, Ruxu; Yang, Yu; Liao, Jing; Chen, Dongsheng; Yu, Lixiu

    2016-01-01

    Background Previous studies have indicated that intake of dietary flavonoids or flavonoid subclasses is associated with the ovarian cancer risk, but presented controversial results. Therefore, we conducted a meta-analysis to derive a more precise estimation of these associations. Methods We performed a search in PubMed, Google Scholar and ISI Web of Science from their inception to April 25, 2015 to select studies on the association among dietary flavonoids, flavonoid subclasses and ovarian cancer risk. The information was extracted by two independent authors. We assessed the heterogeneity, sensitivity, publication bias and quality of the articles. A random-effects model was used to calculate the pooled risk estimates. Results Five cohort studies and seven case-control studies were included in the final meta-analysis. We observed that intake of dietary flavonoids can decrease ovarian cancer risk, which was demonstrated by pooled RR (RR = 0.82, 95% CI = 0.68–0.98). In a subgroup analysis by flavonoid subtypes, the ovarian cancer risk was also decreased for isoflavones (RR = 0.67, 95% CI = 0.50–0.92) and flavonols (RR = 0.68, 95% CI = 0.58–0.80). While there was no compelling evidence that consumption of flavones (RR = 0.86, 95% CI = 0.71–1.03) could decrease ovarian cancer risk, which revealed part sources of heterogeneity. The sensitivity analysis indicated stable results, and no publication bias was observed based on the results of Funnel plot analysis and Egger’s test (p = 0.26). Conclusions This meta-analysis suggested that consumption of dietary flavonoids and subtypes (isoflavones, flavonols) has a protective effect against ovarian cancer with a reduced risk of ovarian cancer except for flavones consumption. Nevertheless, further investigations on a larger population covering more flavonoid subclasses are warranted. PMID:26960146

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

    SciTech Connect

    Cesare Saltini, Massimo Amicosante

    2009-12-19

    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

  2. Forecasting Fuel Consumption Requirements for the Air Force Flying Hour Program Using Pooled Time Series Analysis

    DTIC Science & Technology

    2009-04-01

    unfavorable outcome. Any given prediction of a linear regression model is the mean and has an associated standard deviation. Using Monte Carlo ...and standard deviation parameters for a Monte Carlo simulation to determine the quantitative uncertainty or risk in the models predictions is...Statistics and Data Analysis Using JMP® and JMP IN® Software." SAS Institute Inc., 2001. Schwartz, Lawrence, Isabela Castaneda , Ronald L. Straight

  3. Does Valproic Acid or Levetiracetam Improve Survival in Glioblastoma? A Pooled Analysis of Prospective Clinical Trials in Newly Diagnosed Glioblastoma

    PubMed Central

    Happold, Caroline; Gorlia, Thierry; Chinot, Olivier; Gilbert, Mark R.; Nabors, L. Burt; Wick, Wolfgang; Pugh, Stephanie L.; Hegi, Monika; Cloughesy, Timothy; Roth, Patrick; Reardon, David A.; Perry, James R.; Mehta, Minesh P.; Stupp, Roger

    2016-01-01

    Purpose Symptomatic epilepsy is a common complication of glioblastoma and requires pharmacotherapy. Several uncontrolled retrospective case series and a post hoc analysis of the registration trial for temozolomide indicated an association between valproic acid (VPA) use and improved survival outcomes in patients with newly diagnosed glioblastoma. Patients and Methods To confirm the hypothesis suggested above, a combined analysis of survival association of antiepileptic drug use at the start of chemoradiotherapy with temozolomide was performed in the pooled patient cohort (n = 1,869) of four contemporary randomized clinical trials in newly diagnosed glioblastoma: AVAGlio (Avastin in Glioblastoma; NCT00943826), CENTRIC (Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Methylated Gene Promoter Status; NCT00689221), CORE (Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Unmethylated Gene Promoter Status; NCT00813943), and Radiation Therapy Oncology Group 0825 (NCT00884741). Progression-free survival (PFS) and overall survival (OS) were compared between: (1) any VPA use and no VPA use at baseline or (2) VPA use both at start of and still after chemoradiotherapy. Results of Cox regression models stratified by trial and adjusted for baseline prognostic factors were analyzed. The same analyses were performed with levetiracetam (LEV). Results VPA use at start of chemoradiotherapy was not associated with improved PFS or OS compared with all other patients pooled (PFS: hazard ratio [HR], 0.91; 95% CI, 0.77 to 1.07; P = .241; OS: HR, 0.96; 95% CI, 0.80 to 1.15; P = .633). Furthermore, PFS and OS of patients taking VPA both at start of and still after chemoradiotherapy were not different from those without antiepileptic drug use at both time points (PFS: HR, 0.92; 95% CI, 0.74 to 1.15; P = .467; OS: HR, 1.10; 95% CI, 0.86 to 1.40; P = .440). Similarly, no

  4. Association between CHFR gene hypermethylation and gastric cancer risk: a meta-analysis

    PubMed Central

    Shi, Hua; Wang, Xiaojing; Wang, Jianbo; Pan, Jundi; Liu, Junwei; Ye, Bin

    2016-01-01

    Background The association between the hypermethylation of CHFR gene and gastric cancer risk has been investigated by a number of studies. However, the sample size of the majority of these studies was very small. To get a more a convincing conclusion, here we performed a meta-analysis of the previously published studies to assess the association between CHFR methylation and the risk of gastric cancer. Methods Eligible studies were identified by searching the MEDLINE/PubMed, Embase, and Web of Science databases before May 2016 without any language restriction. The strength of the association was estimated by odds ratio with its 95% confidence interval (CI). Results Totally 1,399 samples, including 758 gastric cancer cases and 641 controls, from 13 studies were included in the present meta-analysis. Compared with non-cancer controls, the pooled OR of CHFR methylation in gastric cancer patients was 9.08 (95% CI: 6.40–12.88, P<0.001), suggesting that the methylation of CHFR was significantly associated with increased risk of gastric cancer. Similar results were observed when subgroup analyses were performed stratified by country, ethnicity, and methylation testing methods. Conclusion Our meta-analysis showed a strong positive correlation between CHFR methylation and risk of gastric cancer, suggesting that CHFR methylation might be a promising biomarker for the diagnosis of gastric cancer. PMID:27994471

  5. MC1R variants increased the risk of sporadic cutaneous melanoma in darker-pigmented Caucasians: a pooled-analysis from the M-SKIP project.

    PubMed

    Pasquali, Elena; García-Borrón, José C; Fargnoli, Maria Concetta; Gandini, Sara; Maisonneuve, Patrick; Bagnardi, Vincenzo; Specchia, Claudia; Liu, Fan; Kayser, Manfred; Nijsten, Tamar; Nagore, Eduardo; Kumar, Rajiv; Hansson, Johan; Kanetsky, Peter A; Ghiorzo, Paola; Debniak, Tadeusz; Branicki, Wojciech; Gruis, Nelleke A; Han, Jiali; Dwyer, Terry; Blizzard, Leigh; Landi, Maria Teresa; Palmieri, Giuseppe; Ribas, Gloria; Stratigos, Alexander; Council, M Laurin; Autier, Philippe; Little, Julian; Newton-Bishop, Julia; Sera, Francesco; Raimondi, Sara

    2015-02-01

    The MC1R gene is a key regulator of skin pigmentation. We aimed to evaluate the association between MC1R variants and the risk of sporadic cutaneous melanoma (CM) within the M-SKIP project, an international pooled-analysis on MC1R, skin cancer and phenotypic characteristics. Data included 5,160 cases and 12,119 controls from 17 studies. We calculated a summary odds ratio (SOR) for the association of each of the nine most studied MC1R variants and of variants combined with CM by using random-effects models. Stratified analysis by phenotypic characteristics were also performed. Melanoma risk increased with presence of any of the main MC1R variants: the SOR for each variant ranged from 1.47 (95%CI: 1.17-1.84) for V60L to 2.74 (1.53-4.89) for D84E. Carriers of any MC1R variant had a 66% higher risk of developing melanoma compared with wild-type subjects (SOR; 95%CI: 1.66; 1.41-1.96) and the risk attributable to MC1R variants was 28%. When taking into account phenotypic characteristics, we found that MC1R-associated melanoma risk increased only for darker-pigmented Caucasians: SOR (95%CI) was 3.14 (2.06-4.80) for subjects with no freckles, no red hair and skin Type III/IV. Our study documents the important role of all the main MC1R variants in sporadic CM and suggests that they have a direct effect on melanoma risk, independently on the phenotypic characteristics of carriers. This is of particular importance for assessing preventive strategies, which may be directed to darker-pigmented Caucasians with MC1R variants as well as to lightly pigmented, fair-skinned subjects.

  6. MC1R variants increased the risk of sporadic cutaneous melanoma in darker-pigmented Caucasians: a pooled-analysis from the M-SKIP project

    PubMed Central

    Pasquali, Elena; García-Borrón, José C.; Fargnoli, Maria Concetta; Gandini, Sara; Maisonneuve, Patrick; Bagnardi, Vincenzo; Specchia, Claudia; Liu, Fan; Kayser, Manfred; Nijsten, Tamar; Nagore, Eduardo; Kumar, Rajiv; Hansson, Johan; Kanetsky, Peter A.; Ghiorzo, Paola; Debniak, Tadeusz; Branicki, Wojciech; Gruis, Nelleke A.; Han, Jiali; Dwyer, Terry; Blizzard, Leigh; Landi, Maria Teresa; Palmieri, Giuseppe; Ribas, Gloria; Stratigos, Alexander; Council, M.Laurin; Autier, Philippe; Little, Julian; Newton-Bishop, Julia; Sera, Francesco; Raimondi, Sara

    2015-01-01

    The MC1R gene is a key regulator of skin pigmentation. We aimed to evaluate the association between MC1R variants and the risk of sporadic cutaneous melanoma (CM) within the M-SKIP project, an international pooled-analysis on MC1R, skin cancer and phenotypic characteristics. Data included 5,160 cases and 12,119 controls from 17 studies. We calculated a Summary Odds Ratio (SOR) for the association of each of the nine most studied MC1R variants and of variants combined with CM by using random-effects models. Stratified analysis by phenotypic characteristics were also performed. Melanoma risk increased with presence of any of the main MC1R variants: the SOR for each variant ranged from 1.47 (95%CI: 1.17–1.84) for V60L to 2.74 (1.53–4.89) for D84E. Carriers of any MC1R variant had a 66% higher risk of developing melanoma compared to wild-type subjects (SOR; 95%CI: 1.66; 1.41–1.96), and the risk attributable to MC1R variants was 28%. When taking into account phenotypic characteristics, we found that MC1R–associated melanoma risk increased only for darker-pigmented Caucasians: SOR (95%CI) was 3.14 (2.06–4.80) for subjects with no freckles, no red hair and skin type III/IV. Our study documents the important role of all the main MC1R variants in sporadic CM and suggests that they have a direct effect on melanoma risk, independently on the phenotypic characteristics of carriers. This is of particular importance for assessing preventive strategies, which may be directed to darker-pigmented Caucasians with MC1R variants as well as to lightly-pigmented, fair-skinned subjects. PMID:24917043

  7. Identification of novel causative genes determining the complex trait of high ethanol tolerance in yeast using pooled-segregant whole-genome sequence analysis.

    PubMed

    Swinnen, Steve; Schaerlaekens, Kristien; Pais, Thiago; Claesen, Jürgen; Hubmann, Georg; Yang, Yudi; Demeke, Mekonnen; Foulquié-Moreno, María R; Goovaerts, Annelies; Souvereyns, Kris; Clement, Lieven; Dumortier, Françoise; Thevelein, Johan M

    2012-05-01

    High ethanol tolerance is an exquisite characteristic of the yeast Saccharomyces cerevisiae, which enables this microorganism to dominate in natural and industrial fermentations. Up to now, ethanol tolerance has only been analyzed in laboratory yeast strains with moderate ethanol tolerance. The genetic basis of the much higher ethanol tolerance in natural and industrial yeast strains is unknown. We have applied pooled-segregant whole-genome sequence analysis to map all quantitative trait loci (QTL) determining high ethanol tolerance. We crossed a highly ethanol-tolerant segregant of a Brazilian bioethanol production strain with a laboratory strain with moderate ethanol tolerance. Out of 5974 segregants, we pooled 136 segregants tolerant to at least 16% ethanol and 31 segregants tolerant to at least 17%. Scoring of SNPs using whole-genome sequence analysis of DNA from the two pools and parents revealed three major loci and additional minor loci. The latter were more pronounced or only present in the 17% pool compared to the 16% pool. In the locus with the strongest linkage, we identified three closely located genes affecting ethanol tolerance: MKT1, SWS2, and APJ1, with SWS2 being a negative allele located in between two positive alleles. SWS2 and APJ1 probably contained significant polymorphisms only outside the ORF, and lower expression of APJ1 may be linked to higher ethanol tolerance. This work has identified the first causative genes involved in high ethanol tolerance of yeast. It also reveals the strong potential of pooled-segregant sequence analysis using relatively small numbers of selected segregants for identifying QTL on a genome-wide scale.

  8. Occupation and Risk of Non-Hodgkin Lymphoma and Its Subtypes: A Pooled Analysis from the InterLymph Consortium

    PubMed Central

    ‘t Mannetje, Andrea; De Roos, Anneclaire J.; Boffetta, Paolo; Vermeulen, Roel; Benke, Geza; Fritschi, Lin; Brennan, Paul; Foretova, Lenka; Maynadié, Marc; Becker, Nikolaus; Nieters, Alexandra; Staines, Anthony; Campagna, Marcello; Chiu, Brian; Clavel, Jacqueline; de Sanjose, Silvia; Hartge, Patricia; Holly, Elizabeth A.; Bracci, Paige; Linet, Martha S.; Monnereau, Alain; Orsi, Laurent; Purdue, Mark P.; Rothman, Nathaniel; Lan, Qing; Kane, Eleanor; Costantini, Adele Seniori; Miligi, Lucia; Spinelli, John J.; Zheng, Tongzhang; Cocco, Pierluigi; Kricker, Anne

    2015-01-01

    Background: Various occupations have been associated with an elevated risk of non-Hodgkin lymphoma (NHL), but results have been inconsistent across studies. Objectives: We investigated occupational risk of NHL and of four common NHL subtypes with particular focus on occupations of a priori interest. Methods: We conducted a pooled analysis of 10,046 cases and 12,025 controls from 10 NHL studies participating in the InterLymph Consortium. We harmonized the occupational coding using the 1968 International Standard Classification of Occupations (ISCO-1968) and grouped occupations previously associated with NHL into 25 a priori groups. Odds ratios (ORs) adjusted for center, age, and sex were determined for NHL overall and for the following four subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and peripheral T-cell lymphoma (PTCL). Results: We confirmed previously reported positive associations between NHL and farming occupations [field crop/vegetable farm workers OR = 1.26; 95% confidence interval (CI): 1.05, 1.51; general farm workers OR = 1.19; 95% CI: 1.03, 1.37]; we also confirmed associations of NHL with specific occupations such as women’s hairdressers (OR = 1.34; 95% CI: 1.02, 1.74), charworkers/cleaners (OR = 1.17; 95% CI: 1.01, 1.36), spray-painters (OR = 2.07; 95% CI: 1.30, 3.29), electrical wiremen (OR = 1.24; 95% CI: 1.00, 1.54), and carpenters (OR = 1.42; 95% CI: 1.04, 1.93). We observed subtype-specific associations for DLBCL and CLL/SLL in women’s hairdressers and for DLBCL and PTCL in textile workers. Conclusions: Our pooled analysis of 10 international studies adds to evidence suggesting that farming, hairdressing, and textile industry–related exposures may contribute to NHL risk. Associations with women’s hairdresser and textile occupations may be specific for certain NHL subtypes. Citation: ‘t Mannetje A, De Roos AJ, Boffetta P, Vermeulen R, Benke G

  9. Hypertension and breast cancer risk: a systematic review and meta-analysis

    PubMed Central

    Han, Hedong; Guo, Wei; Shi, Wentao; Yu, Yamei; Zhang, Yunshuo; Ye, Xiaofei; He, Jia

    2017-01-01

    Observational studies examining the relationship between hypertension and breast cancer risk have reported conflicting findings. We conducted this systematic review and meta-analysis to summarize the evidence regarding the association between hypertension and risk of breast cancer. Eligible studies were identified through a comprehensive literature search of PubMed, EMBASE, and the Cochrane library until August 2016. We included observational studies that reported relative risks (RR) with corresponding 95% confidence intervals (CIs). Results from individual studies were pooled by using a random-effects model. 29 articles of 30 studies, with totally 11643 cases of breast cancer, were eligible for inclusion in the meta-analysis. We observed a statistically significant association between hypertension and increased breast cancer risk (RR: 1.15; 95% CI: 1.08, 1.22). In the subgroup analysis, we found a positive association between hypertension and breast cancer incidence among postmenopausal women (RR: 1.20; 95% CI: 1.09, 1.31). In contrast, hypertension was not associated with risk of breast cancer among premenopausal women (RR: 0.97; 95% CI: 0.84, 1.12) and Asian population (RR: 1.07; 95% CI: 0.94, 1.22).This meta-analysis collectively suggests a significantly association between hypertension and breast cancer risk, specifically for postmenopausal hypertensive women. PMID:28317900

  10. Serum Selenium Levels and Cervical Cancer: Systematic Review and Meta-Analysis.

    PubMed

    He, Du; Wang, Zaiping; Huang, Chuying; Fang, Xiping; Chen, Dian

    2017-03-02

    Several studies have investigated the relationship between serum Se concentration and cervical cancer, but the results were inconsistent. Thus, we conducted a systematic review and meta-analysis to evaluate the association between serum selenium levels and cervical cancer. Twelve studies investigating the association by univariate analysis and five studies by multivariate analysis were identified after a systematic search of PubMed, Wanfang, CNKI, and SinoMed databases. Standard mean differences (SMD) or odds ratios (OR) with the corresponding 95% confidence intervals (CI) were pooled to compare the selenium levels between different groups. In univariate analysis, serum selenium levels in cervical cancer cases were significantly lower than in controls (SMD = -4.86, 95% CI -6.03-3.69). Subgroup analysis showed consistent results. In multivariate analysis, serum selenium levels in cervical cancer cases were also significantly lower than in controls (OR = 0.55, 95% CI 0.42-0.73). After treatment, the serum selenium levels increased significantly (SMD = 2.59, 95% CI 0.50-4.69). In conclusion, high serum selenium levels were associated with cervical cancer, and selenium exposure might be a protective factor for cervical cancer.

  11. Analysis of the influenza virus gene pool of avian species from southern China.

    PubMed

    Lin, Y P; Shu, L L; Wright, S; Bean, W J; Sharp, G B; Shortridge, K F; Webster, R G

    1994-02-01

    Although Southern China has been considered the epicenter of human influenza pandemics, little is known about the genetic composition of influenza viruses in lower mammals or birds in that region. To provide information on the molecular epidemiology of these viruses, we used dot blot hybridization and phylogenetic methods to study the internal genes (PB1, PB2, PA, NP, M, and NS) of 106 avian influenza A viruses isolated from a total of 11,798 domestic ducks, chickens, and geese raised in Southern China including Hong Kong. All 636 genes examined were characteristic of avian influenza viruses; no human or swine influenza genes were detected. Thus, influenza virus reassortants do not appear to be maintained in the domesticated birds of Southeast Asia, eliminating opportunities for further gene reassortment. Phylogenetic analysis showed that the internal genes of these viruses belong to the Eurasian avian lineage, supporting geographical separation of the major avian lineages. The PB1 genes were most similar to A/Singapore/57 (H2N2) and Hong Kong (H3N2) viral genes, supporting an avian origin for the recent human H2N2 and H3N2 pandemic strains. The majority of internal genes from avian influenza viruses in Southern China belong to the Eurasian lineage and are similar to viruses that have recently been transmitted to humans, swine, and horses. This study provides evidence that the transmission of avian influenza viruses and their genes to other species is unidirectional and that the transmission of mammalian influenza virus strains to domestic poultry is probably not a factor in the generation of new pandemic strains.

  12. Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies.

    PubMed

    Studerus, Erich; Kometer, Michael; Hasler, Felix; Vollenweider, Franz X

    2011-11-01

    Psilocybin and related hallucinogenic compounds are increasingly used in human research. However, due to limited information about potential subjective side effects, the controlled medical use of these compounds has remained controversial. We therefore analysed acute, short- and long-term subjective effects of psilocybin in healthy humans by pooling raw data from eight double-blind placebo-controlled experimental studies conducted between 1999 and 2008. The analysis included 110 healthy subjects who had received 1-4 oral doses of psilocybin (45-315 µg/kg body weight). Although psilocybin dose-dependently induced profound changes in mood, perception, thought and self-experience, most subjects described the experience as pleasurable, enriching and non-threatening. Acute adverse drug reactions, characterized by strong dysphoria and/or anxiety/panic, occurred only in the two highest dose conditions in a relatively small proportion of subjects. All acute adverse drug reactions were successfully managed by providing interpersonal support and did not need psychopharmacological intervention. Follow-up questionnaires indicated no subsequent drug abuse, persisting perception disorders, prolonged psychosis or other long-term impairment of functioning in any of our subjects. The results suggest that the administration of moderate doses of psilocybin to healthy, high-functioning and well-prepared subjects in the context of a carefully monitored research environment is associated with an acceptable level of risk.

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

    PubMed Central

    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.

    2013-01-01

    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

  14. Flow injection analysis system based on amperometric thin-film transducers for free chlorine detection in swimming pool waters.

    PubMed

    Olivé-Monllau, Rosa; Orozco, Jahir; Fernández-Sánchez, César; Baeza, Mireia; Bartrolí, Jordi; Jimenez-Jorquera, Cecilia; Céspedes, Francisco

    2009-03-15

    This work reports on the performance of a user-friendly flow injection analysis (FIA) system for the monitoring of free chlorine. A methacrylate flow cell integrating a gold thin-film microelectrode, together with an on-chip gold counter electrode, both fabricated by microfabrication technology, provided robustness, low output impedance, rapid response and low cost to the proposed flow system. An external Ag/AgCl reference electrode placed downstream the chip completes the electrochemical cell. Amperometric detection of chlorine was carried out at a set potential of +350 mV, without oxygen interference. The proposed flow system responded linearly to chlorine concentrations in a range from 0.2 to 5 mgl(-1), with a sensitivity of 0.23 microAlmg(-1), the estimated limit of detection being 0.02 mgl(-1). In addition, the system response was kept stable for at least 10 days (+/-3sigma criterion), by keeping the flow system in an inert atmosphere when not in use. Fifteen samples of swimming pool waters were analyzed and no matrix effects were detected. Also, results were in good agreement with those obtained by a standard method. The excellent analytical performance of the system together with its good working stability would also enable its application for the detection of chlorine in other matrices such as tap water or chlorine stock solutions.

  15. Caesarean delivery and risk of childhood leukaemia: a pooled analysis from the Childhood Leukemia International Consortium (CLIC)

    PubMed Central

    Marcotte, Erin L; Thomopoulos, Thomas P; Infante-Rivard, Claire; Clavel, Jacqueline; Petridou, Eleni Th; Schüz, Joachim; Ezzat, Sameera; Dockerty, John D; Metayer, Catherine; Magnani, Corrado; Scheurer, Michael E; Mueller, Beth A; Mora, Ana M; Wesseling, Catharina; Skalkidou, Alkistis; Rashed, Wafaa M; Francis, Stephen S; Ajrouche, Roula; Erdmann, Friederike; Orsi, Laurent; Spector, Logan G

    2017-01-01

    Summary Background Results from case-control studies have shown an increased risk of acute lymphoblastic leukaemia (ALL) in young children born by caesarean delivery, and prelabour caesarean delivery in particular; however, an association of method of delivery with childhood leukaemia subtypes has yet to be established. We therefore did a pooled analysis of data to investigate the association between childhood leukaemia and caesarean delivery. Methods We pooled data from 13 case-control studies from the Childhood Leukemia International Consortium done in nine countries (Canada, Costa Rica, Egypt, France, Germany, Greece, Italy, New Zealand, and the USA) for births from 1970-2013. We analysed caesarean delivery overall and by indications that probably resulted in prelabour caesarean delivery or emergency caesarean delivery. We used multivariable logistic regression models, adjusted for child's birthweight, sex, age, ethnic origin, parental education, maternal age, and study, to estimate odds ratios (ORs) and 95% CIs for the risk of ALL and acute myeloid leukaemia (AML) in children aged 0-14 years at diagnosis. Findings The studies provided data for 8780 ALL cases, 1332 AML cases, and 23 459 controls, of which the birth delivery method was known for 8655 (99%) ALL cases, 1292 (97%) AML cases, and 23 351 (>99%) controls. Indications for caesarean delivery were available in four studies (there were caesarean deliveries for 1061 of 4313 ALL cases, 138 of 664 AML cases, and 1401 of 5884 controls). The OR for all indications of caesarean delivery and ALL was 1.06 (95% CI 0.99–1.13), and was significant for prelabour caesarean delivery and ALL (1.23 [1.04-1.47]; p=0.018). Emergency caesarean delivery was not associated with ALL (OR 1.02 [95% CI 0.81-1.30]). AML was not associated with caesarean delivery (all indications OR 0.99 [95% CI 0.84-1.17]; prelabour caesarean delivery 0.83 [0.54-1.26]; and emergency caesarean delivery 1.05 [0.63-1.77]). Interpretation Our

  16. Efficacy and Safety of Nivolumab Alone or in Combination With Ipilimumab in Patients With Mucosal Melanoma: A Pooled Analysis.

    PubMed

    D'Angelo, Sandra P; Larkin, James; Sosman, Jeffrey A; Lebbé, Celeste; Brady, Benjamin; Neyns, Bart; Schmidt, Henrik; Hassel, Jessica C; Hodi, F Stephen; Lorigan, Paul; Savage, Kerry J; Miller, Wilson H; Mohr, Peter; Marquez-Rodas, Ivan; Charles, Julie; Kaatz, Martin; Sznol, Mario; Weber, Jeffrey S; Shoushtari, Alexander N; Ruisi, Mary; Jiang, Joel; Wolchok, Jedd D

    2017-01-10

    Purpose Mucosal melanoma is an aggressive malignancy with a poor response to conventional therapies. The efficacy and safety of nivolumab (a programmed death-1 checkpoint inhibitor), alone or combined with ipilimumab (a cytotoxic T-lymphocyte antigen-4 checkpoint inhibitor), have not been reported in this rare melanoma subtype. Patients and Methods Data were pooled from 889 patients who received nivolumab monotherapy in clinical studies, including phase III trials; 86 (10%) had mucosal melanoma and 665 (75%) had cutaneous melanoma. Data were also pooled for patients who received nivolumab combined with ipilimumab (n = 35, mucosal melanoma; n = 326, cutaneous melanoma). Results Among patients who received nivolumab monotherapy, median progression-free survival was 3.0 months (95% CI, 2.2 to 5.4 months) and 6.2 months (95% CI, 5.1 to 7.5 months) for mucosal and cutaneous melanoma, with objective response rates of 23.3% (95% CI, 14.8% to 33.6%) and 40.9% (95% CI, 37.1% to 44.7%), respectively. Median progression-free survival in patients treated with nivolumab combined with ipilimumab was 5.9 months (95% CI, 2.8 months to not reached) and 11.7 months (95% CI, 8.9 to 16.7 months) for mucosal and cutaneous melanoma, with objective response rates of 37.1% (95% CI, 21.5% to 55.1%) and 60.4% (95% CI, 54.9% to 65.8%), respectively. For mucosal and cutaneous melanoma, respectively, the incidence of grade 3 or 4 treatment-related adverse events was 8.1% and 12.5% for nivolumab monotherapy and 40.0% and 54.9% for combination therapy. Conclusion To our knowledge, this is the largest analysis of data for anti-programmed death-1 therapy in mucosal melanoma to date. Nivolumab combined with ipilimumab seemed to have greater efficacy than either agent alone, and although the activity was lower in mucosal melanoma, the safety profile was similar between subtypes.

  17. The cargo protein MAP17 (PDZK1IP1) regulates the cancer stem cell pool activating the Notch pathway by abducting NUMB.

    PubMed

    Garcia-Heredia, Jose M; Lucena-Cacace, Antonio; Verdugo-Sivianes, Eva M; Perez, Marco; Carnero, Amancio

    2017-02-02

    Purpose Cancer stem cells (CSCs) are self-renewing tumor cells, with ability to generate the diverse differentiated tumor cell subpopulations. They differ from normal stem cells in the deregulation of the mechanisms that normally controls stem cell physiology. CSCs are the origin of metastasis and highly resistant to therapy. Therefore the understanding of the CSC origin and deregulated pathways is important for tumor control. Experimental design We have included experiments in vitro, in cell lines and tumors of different origins. We have used PDXs and public transcriptomic databases of human tumors. Results MAP17 (PDZKIP1), a small cargo protein overexpressed in tumors, interacts with NUMB through the PDZ-binding domain activating the Notch pathway, leading to an increase in stem cell factors and cancer-initiating-like cells. Identical behavior was mimicked by inhibiting NUMB. Conversely, MAP17 downregulation in a tumor cell line constitutively expressing this gene led to Notch pathway inactivation and a marked reduction of stemness. In PDX models, MAP17 levels directly correlated with tumorsphere formation capability. Finally, in human colon, breast or lung there is a strong correlation of MAP17 expression with a signature of Notch and stem cell genes. Conclusions MAP17 overexpression activates Notch pathway by sequestering NUMB. High levels of MAP17 correlated with tumorspheres formation and Notch and Stem gene transcription. Its direct modification causes direct alteration of tumorsphere number and Notch and Stem pathway transcription. This defines a new mechanism of Notch pathway activation and Stem cell pool increase that may be active in a large percentage of tumors.

  18. Choline and betaine consumption lowers cancer risk: a meta-analysis of epidemiologic studies

    PubMed Central

    Sun, Shanwen; Li, Xiao; Ren, Anjing; Du, Mulong; Du, Haina; Shu, Yongqian; Zhu, Lingjun; Wang, Wei

    2016-01-01

    A number of human and animal in vitro or in vivo studies have investigated the relationship between dietary choline and betaine and cancer risk, suggesting that choline and betaine consumption may be protective for cancer. There are also a few epidemiologic studies exploring this relationship, however, with inconsistent conclusions. The PubMed and Embase were searched, from their inception to March 2016, to identify relevant studies and we brought 11 articles into this meta-analysis eventually. The pooled relative risks (RRs) of cancer for the highest versus the lowest range were 0.82 (95% CI, 0.70 to 0.97) for choline consumption only, 0.86 (95%CI, 0.76 to 0.97) for betaine consumption only and 0.60 (95%CI, 0.40 to 0.90) for choline plus betaine consumption, respectively. Significant protective effect of dietary choline and betaine for cancer was observed when stratified by study design, location, cancer type, publication year, sex and quality score of study. An increment of 100 mg/day of choline plus betaine intake helped reduce cancer incidence by 11% (0.89, 95% CI, 0.87 to 0.92) through a dose-response analysis. To conclude, choline and betaine consumption lowers cancer incidence in this meta-analysis, but further studies are warranted to verify the results. PMID:27759060

  19. Poultry consumption and prostate cancer risk: a meta-analysis

    PubMed Central

    He, Qian; Wan, Zheng-ce; Xu, Xiao-bing; Wu, Jing

    2016-01-01

    Background. Several kinds of foods are hypothesized to be potential factors contributing to the variation of prostate cancer (PCa) incidence. But the effect of poultry on PCa is still inconsistent and no quantitative assessment has been published up to date. So we conducted this meta-analysis to clarify the association between them. Materials and Methods. We conducted a literature search of PubMed and Embase for studies examining the association between poultry consumption and PCa up to June, 2015. Pooled risk ratio (RR) and corresponding 95% confidence interval (CI) of the highest versus lowest poultry consumption categories were calculated by fixed-effect model or random-effect model. Results. A total of 27 (12 cohort and 15 case-control) studies comprising 23,703 cases and 469,986 noncases were eligible for inclusion. The summary RR of total PCa incidence was 1.03 (95% CI [0.95–1.11]) for the highest versus lowest categories of poultry intake. The heterogeneity between studies was not statistically significant (P = 0.768, I2 = 28.5%). Synthesized analysis of 11 studies on high stage PCa and 8 studies on chicken exposure also demonstrated null association. We also did not obtain significant association in the subgroup of cohort study (RR = 1.04, 95% CI [0.98–1.10]), as well as in the subgroups of population-based case-control study and hospital-based case-control study. Then the studies were divided into three geographic groups: Western countries, Asia and South America. The pooled RRs in these areas did not reveal statistically significant association between poultry and PCa. Conclusions. This meta-analysis suggests no association between poultry consumption and PCa risk. Further well-designed studies are warranted to confirm the result. PMID:26855875

  20. Collaborative Depression Treatment in Older and Younger Adults with Physical Illness: Pooled Comparative Analysis of Three Randomized Clinical Trials

    PubMed Central

    Ell, Kathleen; Aranda, María P.; Xie, Bin; Lee, Pey-Jiuan; Chou, Chih-Ping

    2010-01-01

    Objective There have been few comparisons of the effectiveness of collaborative depression care between older versus younger adults with co-morbid illness, particularly among low-income populations. Design Intent-to-treat analyses are conducted on pooled data from three randomized controlled trials that tested collaborative care aimed at improving depression, quality of life and treatment receipt. Settings Trials were conducted in oncology and primary care safety net clinics and diverse home health care programs. Participants 1,081 patients with major depressive symptoms and cancer, diabetes or other co-morbid illness. Intervention Similar intervention protocols included patient, provider, socio-cultural and organizational adaptations. Measurements The PHQ-9 depression, SF-12/20 quality-of-life, self-reported hospitalization, ER, ICU utilization, and antidepressant, psychotherapy treatment receipt are assessed at baseline, 6, 12 months. Results There are no significant differences in reducing depression symptoms (P ranged 0.18-0.58), improving quality-of-life (t=1.86, df=669, P=0.07 for physical functioning at 12 months; and P ranged 0.23-0.99 for all others) between patients ≥60 versus 18-59. Both age group intervention patients have significantly higher rates of a 50% PHQ-9 reduction (older: Wald χ2[df=1]=4.82, p=0.03; younger: Wald χ2[df=1]=6.47, p=0.02), greater reduction in major depression rates (older: Wald χ2[df=1]=7.72, p=0.01; younger: Wald χ2[df=1]=4.0, p=0.05) than enhanced-usual-care patients at 6 months, and are no significant age group differences in treatment type or intensity. Conclusion Collaborative depression care in individuals with co-morbid illness is as effective in reducing depression in older patients as younger patients, including among low-income, minority patients. Patient, provider, and organizational adaptations of depression care management models may contribute to positive outcomes. PMID:20220588

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

    PubMed

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

    2012-01-01

    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 μg/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 μg/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 μg/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.

  2. Safety and efficacy of the Pipeline embolization device for treatment of intracranial aneurysms: a pooled analysis of 3 large studies.

    PubMed

    Kallmes, David F; Brinjikji, Waleed; Cekirge, Saruhan; Fiorella, David; Hanel, Ricardo A; Jabbour, Pascal; Lopes, Demetrius; Lylyk, Pedro; McDougall, Cameron G; Siddiqui, Adnan

    2016-10-28

    OBJECTIVE The authors performed a pooled analysis of 3 studies-IntrePED (International Retrospective Study of the Pipeline Embolization Device), PUFS (Pipeline for Uncoilable or Failed Aneurysms Study), and ASPIRe (Aneurysm Study of Pipeline in an Observational Registry)-in order to assess angiographic outcomes and clinical safety of the Pipeline embolization device (PED). METHODS IntrePED was a retrospective study, while PUFS and ASPIRe were prospective studies. For each patient included in these studies, the authors collected baseline demographic data, aneurysm characteristics, and procedural details. The primary outcomes for this combined analysis were clinical outcomes, including neurological morbidity and mortality and major ipsilateral intracranial hemorrhage and ischemic stroke. The secondary outcomes were angiographic occlusion rates, which were available for ASPIRe and PUFS only. RESULTS A total of 1092 patients with 1221 aneurysms were included across the 3 studies. The mean aneurysm size was 12.0 ± 7.8 mm and the mean neck size was 6.6 ± 4.8 mm. The major ipsilateral ischemic stroke rate was 3.7% (40/1091). The major ipsilateral intracranial hemorrhage rate was 2.0% (22/1091). The major neurological morbidity rate was 5.7% (62/1091). The neurological mortality rate was 3.3% (36/1091). The combined major morbidity and neurological mortality rate was 7.1% (78/1091). The complete occlusion rates were 75.0% at 180 days (111/148) and 85.5% at 1 year (94/110). The overall aneurysm retreatment rate was 3.0% (33/1091) at a mean follow-up time of 10.2 ± 10.8 months. CONCLUSIONS Endovascular treatment of intracranial aneurysms with the PED is safe and effective. Angiographic occlusion rates progressed with follow-up. Rates of stroke, hemorrhage, morbidity and mortality, and retreatment were low, especially given the fact that the aneurysms treated were generally large and wide necked.

  3. Pooling techniques for bioassay screening

    SciTech Connect

    Sun, L.C.; Baum, J.W.; Kaplan, E; Moorthy, A.R.

    1996-03-01

    Pooling techniques commonly are used to increase the throughput of samples used for screening purposes. While the advantages of such techniques are increased analytical efficiency and cost savings, the sensitivity of measurements decreases because it is inversely proportional to the number of samples in the pools. Consequently, uncertainties in estimates of dose and risk which are based on the results of pooled samples increase as the number of samples in the pools increases in all applications. However, sensitivities may not be seriously degraded, for example, in urinalysis, if the samples in the pools are of known time duration, or if the fraction of some attribute of the grab urine samples to that in a 24-hour composite is known (e.g., mass, specific gravity, creatinine, or volume, per 24-h interval). This paper presents square and cube pooling schemes that greatly increase throughput and can considerably reduce analytical costs (on a sample basis). The benefit-cost ratios for 5{times}5 square and 5{times}5{times}5 cube pooling schemes are 2.5 and 8.3, respectively. Three-dimensional and higher arrayed pooling schemes would result in even greater economies; however, significant improvements in analytical sensitivity are required to achieve these advantages. These are various other considerations for designing a pooling scheme, where the number of dimensions and of samples in the optimum array are influenced by: (1) the minimal detectable amount (MDA) of the analytical processes, (2) the screening dose-rate requirements, (3) the maximum masses or volumes of the composite samples that can be analyzed, (4) the information already available from results of composite analysis, and (5) the ability of an analytical system to guard against both false negative and false positive results. Many of these are beyond the scope of this paper but are being evaluated.

  4. Sirolimus effects on cancer incidence after kidney transplantation: a meta-analysis.

    PubMed

    Yanik, Elizabeth L; Siddiqui, Kulsoom; Engels, Eric A

    2015-09-01

    Sirolimus, an immunosuppressant option for kidney transplant recipients, may reduce cancer risk by interrupting the mammalian target of rapamycin pathway. However, studies of sirolimus and cancer incidence in kidney recipients have not been definitive, and have had limited ability to examine specific cancer types. The literature was systematically reviewed to identify randomized controlled trials (RCTs) and observational studies of kidney recipients that compared sirolimus users to sirolimus nonusers. Meta-analytic methods were used to obtain pooled estimates of the association between sirolimus use and incidence of total cancer and specific cancer types. Estimates were stratified by study type (RCT vs. observational) and use of cyclosporine (an immunosuppressant that affects DNA repair). Twenty RCTs and two observational studies were eligible for meta-analysis, including 39,039 kidney recipients overall. Sirolimus use was associated with lower overall cancer incidence (incidence rate ratio [IRR] = 0.71, 95% CI = 0.56-0.90), driven by a reduction in incidence of nonmelanoma skin cancer (NMSC, IRR = 0.49, 95% CI = 0.32-0.76). The protective effect of sirolimus on NMSC risk was most notable in studies comparing sirolimus against cyclosporine (IRR = 0.19, 95% CI = 0.04-0.84). After excluding NMSCs, there was no overall association between sirolimus and incidence of other cancers (IRR = 1.06, 95% CI = 0.69-1.63). However, sirolimus use had associations with lower kidney cancer incidence (IRR = 0.40, 95% CI = 0.20-0.81), and higher prostate cancer incidence (IRR = 1.85, 95% CI = 1.17-2.91). Among kidney recipients, sirolimus users have lower NMSC risk, which may be partly due to removal of cyclosporine. Sirolimus may also reduce kidney cancer risk but did not appear protective for other cancers, and it may actually increase prostate cancer risk.

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

    PubMed Central

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

    2014-01-01

    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. PMID:25006674

  6. Coffee consumption and prostate cancer risk: a meta-analysis of cohort studies.

    PubMed

    Liu, Huan; Hu, Guang-Hui; Wang, Xing-Chun; Huang, Tian-Bao; Xu, Liang; Lai, Peng; Guo, Zhui-Feng; Xu, Yun-Fei

    2015-01-01

    This meta-analysis was conducted to assess the association between coffee consumption and prostate cancer risk. Thirteen cohort studies with 34,105 cases and 539,577 participants were included in the meta-analysis. The summary relative risks (RRs) with 95% confidence intervals (CIs) for different coffee intake levels were calculated. Dose-response relationship was assessed using generalized least square trend estimation. The pooled RR for the highest vs. lowest coffee intake was 0.90 (95% CI: 0.85-0.95), with no significant heterogeneity across studies (P = 0.267; I(2) = 17.5%). The dose-response analysis showed a lower cancer risk decreased by 2.5% (RR = 0.975; 95% CI: 0.957-0.995) for every 2 cups/day increment in coffee consumption. Stratifying by geographic region, there was a statistically significant protective influence of coffee on prostate cancer risk among European populations. In subgroup analysis of prostate cancer grade, the summary RRs were 0.89 (95% CI: 0.83-0.96) for nonadvanced, 0.82 (95% CI: 0.61-1.10) for advanced and 0.76 (95% CI: 0.55-1.06) for fatal diseases. Our findings suggest that coffee consumption may be associated with a reduced risk of prostate cancer and it also has an inverse association with nonadvanced prostate cancer. Because of the limited number of studies, more prospective studies with large sample size are needed to confirm this association.

  7. Association between cholesterol intake and pancreatic cancer risk: evidence from a meta-analysis.

    PubMed

    Chen, Hongqiang; Qin, Shiyong; Wang, Minghai; Zhang, Tao; Zhang, Shuguang

    2015-02-04

    Quantification of the association between the intake of cholesterol and risk of pancreatic cancer is still conflicting. We therefore conducted a meta-analysis to summarize the evidence from epidemiological studies of cholesterol intake and the risk of pancreatic cancer. Pertinent studies were delivered by PubMed and Web of Knowledge issued through April of 2014. A random effects model was used to process the data for analysis. Sensitivity analysis and publication bias were conducted. Dose-response relationship was assessed by restricted cubic spline and variance-weighted least squares regression analysis. With 4513 pancreatic cases exemplified, 16 articles were applied in the meta-analysis. Pooled results suggest that cholesterol intake level was significantly associated with the risk of pancreatic cancer [summary relative risk (RR) = 1.371, 95%CI = 1.155-1.627, I(2) = 58.2%], especially in America [summary RR = 1.302, 95%CI = 1.090-1.556]. A linear dose-response relation was attested that the risk of pancreatic cancer rises by 8% with 100 mg/day of cholesterol intake. [summary RR = 1.08, 95% CI = 1.04-1.13]. In conclusion, our analysis suggests that a high intake of cholesterol might increase the risk of pancreatic cancer, especially in America.

  8. Worldwide Prevalence of Human Papillomavirus and Relative Risk of Prostate Cancer: A Meta-analysis

    PubMed Central

    Yang, Lin; Xie, Shuanghua; Feng, Xiaoshuang; Chen, Yuheng; Zheng, Tongzhang; Dai, Min; Ke Zhou, Cindy; Hu, Zhibin; Li, Ni; Hang, Dong

    2015-01-01

    Despite the increasing number of studies conducted recently to evaluate the association between HPV infections and the risk of prostate cancer, the results remain inconclusive. Furthermore, the prevalence and distribution of overall and individual HPV types worldwide in prostate cancer has not been reported until now. Therefore, we estimated the prevalence of HPV in prostate cancer by pooling data of 46 studies with 4919 prostate cancer cases, taking into account the heterogeneity of major related parameters, including study region, specimen type, HPV DNA source, detection method, publication calendar period and Gleason score. Moreover, we tested the association of HPV infections with prostate cancer risks by a meta-analysis of 26 tissue-based case-control studies. We found that the prevalence of HPV infection was 18.93% (95% CI = 17.84–20.05%) in prostate cancer cases, and most of which were high-risk HPV types (17.73%, 95% CI = 16.52–18.99%). The prevalence varied by region, PCR primers used, publication calendar period and Gleason score. Our study also showed a significantly increased risk of prostate cancer with the positivity of overall HPV detected in prostate tissues (OR = 1.79, 95% CI = 1.29–2.49) and revealed the geographic variation of association strength (P < 0.001). In conclusion, HPV infections may contribute to the risk of prostate cancer. PMID:26441160

  9. Worldwide Prevalence of Human Papillomavirus and Relative Risk of Prostate Cancer: A Meta-analysis.

    PubMed

    Yang, Lin; Xie, Shuanghua; Feng, Xiaoshuang; Chen, Yuheng; Zheng, Tongzhang; Dai, Min; Zhou, Cindy Ke; Hu, Zhibin; Li, Ni; Hang, Dong

    2015-10-06

    Despite the increasing number of studies conducted recently to evaluate the association between HPV infections and the risk of prostate cancer, the results remain inconclusive. Furthermore, the prevalence and distribution of overall and individual HPV types worldwide in prostate cancer has not been reported until now. Therefore, we estimated the prevalence of HPV in prostate cancer by pooling data of 46 studies with 4919 prostate cancer cases, taking into account the heterogeneity of major related parameters, including study region, specimen type, HPV DNA source, detection method, publication calendar period and Gleason score. Moreover, we tested the association of HPV infections with prostate cancer risks by a meta-analysis of 26 tissue-based case-control studies. We found that the prevalence of HPV infection was 18.93% (95% CI = 17.84-20.05%) in prostate cancer cases, and most of which were high-risk HPV types (17.73%, 95% CI = 16.52-18.99%). The prevalence varied by region, PCR primers used, publication calendar period and Gleason score. Our study also showed a significantly increased risk of prostate cancer with the positivity of overall HPV detected in prostate tissues (OR = 1.79, 95% CI = 1.29-2.49) and revealed the geographic variation of association strength (P < 0.001). In conclusion, HPV infections may contribute to the risk of prostate cancer.

  10. Bevacizumab Addition in Neoadjuvant Treatment Increases the Pathological Complete Response Rates in Patients with HER-2 Negative Breast Cancer Especially Triple Negative Breast Cancer: A Meta-Analysis

    PubMed Central

    Zhang, Jing; Zhang, Binglan; Shi, Changle; Liu, Lei

    2016-01-01

    Background Neoadjuvant therapy is administered to breast cancer patients as an induction process before surgery or radiotherapy to reduce tumor size. Human epidermal growth factor receptor-2 (HER-2) negative breast cancer lacks effective standard target therapy. Bevacizumab has a controversial role in the treatment of breast cancer and we conduct a meta-analysis to evaluate the value of adding bevacizumab in neoadjuvant regimen. Methods Potentially eligible studies were retrieved using PubMed, EMBASE and Medline. Clinical characteristics of patients and statistical data with pathological complete response (pCR) data were collected. Then a meta-analysis model was established to investigate the correlation between administration of bevacizumab in neoadjuvant therapy and pCR rates in HER-2 negative breast cancer. Results Seven eligible studies and 5408 patients were yielded. The pCR rates for “breast” or “breast plus lymph node” were similar. In subgroup analysis, we emphasized on patients with triple-negative breast cancer (TNBC). In the criterion of “lesions in breast” the pooled ORs was 1.55 [1.29, 1.86], P<0.00001 and regarding to the evaluation criterion of “lesions in breast and lymph nodes”, the pooled ORs was 1.48 [1.23, 1.78], P<0.0001, in favor of bevacizumab administration. Conclusion According to our pooled results, we finally find that bevacizumab addition as a neoadjuvant chemotherapy component, for induction use with limited cycle to improve the pCR rates and patients may avoid long-term adverse event and long-term invalid survival improvement. Especially in subgroup analysis, pCR rates could be improved significantly and physicians could consider bevacizumab with caution. As patients could avoid the adverse event caused by long-term using of bevacizumab, long-term quality of life improvement may be achieved, especially in TNBC. PMID:27579484

  11. p53 codon 72 polymorphism and breast cancer risk: A meta-analysis

    PubMed Central

    HOU, JING; JIANG, YUAN; TANG, WENRU; JIA, SHUTING

    2013-01-01

    p53 is a tumor suppressor gene and plays important roles in the etiology of breast cancer. Studies have produced conflicting results concerning the role of p53 codon 72 polymorphism (G>C) on the risk of breast cancer; therefore, a meta-analysis was performed to estimate the association between the p53 codon 72 polymorphism and breast cancer. Screening of the PubMed database was conducted to identify relevant studies. Studies containing available genotype frequencies of the p53 codon 72 polymorphism were selected and a pooled odds ratio (OR) with 95% confidence interval (CI) was used to assess the association. Sixty-one published studies, including 28,539 breast cancer patients and 32,788 controls were identified. The results suggest that variant genotypes are not associated with breast cancer risk (Pro/Pro + Arg/Pro vs. Arg/Arg: OR=1.016, 95% CI=0.931–1.11, P=0.722). The symmetric funnel plot, Egger’s test (P=0.506) and Begg’s test (P=0.921) were all suggestive of the lack of publication bias. This meta-analysis suggests that the p53 codon 72 Pro/Pro + Arg/Pro genotypes are not associated with an increased risk of breast cancer. To validate the association between the p53 codon 72 polymorphism and breast cancer, further studies with larger numbers of participants worldwide are required. PMID:23737888

  12. Effects of alteplase for acute stroke on the distribution of functional outcomes: a pooled analysis of nine trials

    PubMed Central

    Lees, Kennedy R; Emberson, Jonathan; Blackwell, Lisa; Bluhmki, Erich; Davis, Stephen M; Donnan, Geoffrey A; Grotta, James C; Kaste, Markku; von Kummer, Rüdiger; Lansberg, Maarten G; Lindley, Richard I; Lyden, Patrick; Murray, Gordon D; Sandercock, Peter AG; Toni, Danilo; Toyoda, Kazunori; Wardlaw, Joanna M; Whiteley, William N; Baigent, Colin; Hacke, Werner; Howard, George

    2016-01-01

    Background Thrombolytic therapy with intravenous alteplase within 4.5 hours of ischaemic stroke onset increases the overall likelihood of an excellent outcome (no, or non-disabling, symptoms). Any improvement in functional outcome distribution has value, and herein we provide an assessment of the effect of alteplase on the distribution of the functional level by treatment delay, age and stroke severity. Methods Pre-specified pooled analysis of 6756 patients from nine randomised trials comparing alteplase versus placebo/open control. Ordinal logistic regression models assessed treatment differences after adjustment for treatment delay, age, stroke severity, and relevant interaction term(s). Results Treatment with alteplase was beneficial for a delay in treatment extending to 4.5 hours after stroke onset, with a greater benefit with earlier treatment. Neither age nor stroke severity significantly influenced the slope of the relation between benefit and time to treatment initiation. For the observed case mix of patients treated within 4.5 h of stroke onset, (mean 3 hours and 20 minutes), the net absolute benefit of alteplase (i.e., the difference between those who would do better if given alteplase and those who would do worse) was 55 patients per 1,000 treated (95% CI 13-91; p=0.004). Conclusions Treatment with intravenous alteplase initiated within 4.5 hours of stroke onset increases the chance of achieving an improved level of function for all patients across the age spectrum including the over 80s and across all severities of stroke studied (top vs bottom fifth means: 22 vs 4); the earlier that treatment is initiated, the greater the benefit. PMID:27507856

  13. A retrospective pooled analysis assessing the effect of age on the immunogenicity of Havrix™ in healthy adults.

    PubMed

    Van Der Meeren, Olivier; Crasta, Priya; de Ridder, Marc

    2015-01-01

    Over recent decades, the global incidence of hepatitis A virus infection has been reduced by improvements in sanitation infrastructure and through immunization programs. The immunogenicity and field efficacy of the inactivated hepatitis A vaccine (Havrix™, GSK, Belgium) has been demonstrated in clinical trials, population-impact studies as well as in several outbreak settings. However, immunological data in older populations are limited, with only few studies assessing the immune response of this vaccine in adults aged ≥ 40 years. This retrospective pooled analysis of 4 2-dose primary vaccination studies compared the immunogenicity and safety of the inactivated hepatitis A vaccine in adults aged ≥ 40 years with subjects aged 20-30 years (control group; N = 80 in each group). Fifteen days after the first vaccine dose, 79.7% (95% CI: 68.8-88.2) and 92.3% (95% CI: 84.0-97.1) of subjects were seropositive in the ≥ 40 years and control groups, respectively; 97.5% (95% CI: 91.2-99.7) and 97.4% (95% CI: 91.0-99.7), respectively, were seropositive one month after the first dose. All subjects in both groups (95% CIs: 95.4-100 and 95.3-100, respectively) were seropositive one month after the second dose. Safety profiles were similar in both groups. In conclusion, the inactivated hepatitis A vaccine induced similar immune responses in adults aged ≥ 40 and 20-30 years one month after the first and second dose whereas younger subjects may demonstrate a higher seroconversion rate 15 days after the first dose.

  14. Metabolic assessment of aripiprazole as adjunctive therapy in major depressive disorder: a pooled analysis of 2 studies.

    PubMed

    Fava, Maurizio; Wisniewski, Stephen R; Thase, Michael E; Baker, Ross A; Tran, Quynh-Van; Pikalov, Andrei; Yang, Huyuan; Marcus, Ronald N; Berman, Robert M

    2009-08-01

    In 2 identical multicenter, double-blind, placebo-controlled trials, an 8-week prospective treatment phase to ensure inadequate response to standard antidepressants was followed with 6 weeks of aripiprazole (2-20 mg/d) or placebo, plus a standard antidepressant. This pooled analysis involving 737 patients across the 2 studies evaluated the metabolic effects of adjunctive aripiprazole in patients with major depressive disorder. Outcomes included mean change from end of prospective treatment phase to endpoint in body weight, waist circumference, fasting levels of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides (TG), fasting plasma glucose, and glycosylated hemoglobin (hemoglobin A1C). Logistic regression determined whether baseline variables were associated with weight gain or whether weight change was associated with clinical outcome. Statistically significant increases occurred in mean body weight (adjunctive aripiprazole, +1.73 kg, vs adjunctive placebo, +0.38 kg; P < 0.001). Significantly more subjects receiving adjunctive aripiprazole had clinically relevant (> or = 7%) weight gain versus placebo (5.2% vs 0.6%; P < 0.001). More patients treated with adjunctive aripiprazole shifted body mass index category group from normal to overweight and from overweight to obese than those treated with adjunctive placebo. Body mass index, sex, age, Montgomery-Asberg Depression Rating Scale score, fasting TG, fasting glucose, and standard antidepressants were not clinically meaningful predictors of weight gain with adjunctive aripiprazole, and change in weight had no correlation with clinical outcome. Adjunctive aripiprazole produced no significant changes versus placebo in mean waist circumference, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, TG, fasting plasma glucose, or hemoglobin A1C. Also, there was no apparent change in the incidence of National Cholesterol

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

    SciTech Connect

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

    1982-01-01

    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.

  16. DataSHIELD: resolving a conflict in contemporary bioscience—performing a pooled analysis of individual-level data without sharing the data

    PubMed Central

    Wolfson, Michael; Wallace, Susan E; Masca, Nicholas; Rowe, Geoff; Sheehan, Nuala A; Ferretti, Vincent; LaFlamme, Philippe; Tobin, Martin D; Macleod, John; Little, Julian; Fortier, Isabel; Knoppers, Bartha M; Burton, Paul R

    2010-01-01

    Background Contemporary bioscience sometimes demands vast sample sizes and there is often then no choice but to synthesize data across several studies and to undertake an appropriate pooled analysis. This same need is also faced in health-services and socio-economic research. When a pooled analysis is required, analytic efficiency and flexibility are often best served by combining the individual-level data from all sources and analysing them as a single large data set. But ethico-legal constraints, including the wording of consent forms and privacy legislation, often prohibit or discourage the sharing of individual-level data, particularly across national or other jurisdictional boundaries. This leads to a fundamental conflict in competing public goods: individual-level analysis is desirable from a scientific perspective, but is prevented by ethico-legal considerations that are entirely valid. Methods Data aggregation through anonymous summary-statistics from harmonized individual-level databases (DataSHIELD), provides a simple approach to analysing pooled data that circumvents this conflict. This is achieved via parallelized analysis and modern distributed computing and, in one key setting, takes advantage of the properties of the updating algorithm for generalized linear models (GLMs). Results The conceptual use of DataSHIELD is illustrated in two different settings. Conclusions As the study of the aetiological architecture of chronic diseases advances to encompass more complex causal pathways—e.g. to include the joint effects of genes, lifestyle and environment—sample size requirements will increase further and the analysis of pooled individual-level data will become ever more important. An aim of this conceptual article is to encourage others to address the challenges and opportunities that DataSHIELD presents, and to explore potential extensions, for example to its use when different data sources hold different data on the same individuals. PMID:20630989

  17. High lncRNA H19 expression as prognostic indicator: data mining in female cancers and polling analysis in non-female cancers

    PubMed Central

    Peng, Li; Liu, Zhao-Yang; Li, Wen-Ling; Zhang, Chao-Yang; Zhang, Ya-Qin; Pan, Xi; Chen, Jun; Li, Yue-Hui

    2017-01-01

    Upregulation of lncRNA H19 expression is associated with an unfavorable prognosis in some cancers. However, the prognostic value of H19 in female-specific cancers has remained uncharacterized. In this study, the prognostic power of high H19 expression in female cancer patients from the TCGA datasets was analyzed using Kaplan-Meier survival curves and Cox's proportional hazard modeling. In addition, in a meta-analysis of non-female cancer patients from TCGA datasets and 12 independent studies, hazard ratios (HRs) with 95% confidence interval (CI) for overall survival (OS) and disease-free survival (DFS)/relapse-free survival (RFS)/metastasis-free survival (MFS)/progression-free survival (PFS) were pooled to assess the prognostic value of high H19 expression. Kaplan-Meier analysis revealed that patients with uterine corpus cancer and higher H19 expression had a shorter OS (HR=2.710, p<0.05), while females with cervical cancer and increased H19 expression had a shorter RFS (HR=2.261, p<0.05). Multivariate Cox regression analysis showed that high H19 expression could independently predict a poorer prognosis in cervical cancer patients (HR=4.099, p<0.05). In the meta-analysis, patients with high H19 expression showed a poorer outcome in non-female cancer (p<0.05). These results suggest that high lncRNA H19 expression is predictive of an unfavorable prognosis in two female cancers (uterine corpus endometrioid cancer and cervical cancer) as well as in non-female cancer patients. PMID:27926484

  18. Soy intake and breast cancer risk: A meta-analysis of epidemiological studies

    NASA Astrophysics Data System (ADS)

    Bahrom, Suhaila; Idris, Nik Ruzni Nik

    2016-06-01

    The impact of soy intake on breast cancer risk has been investigated extensively. However, these studies reported conflicting results. The objective of this study is to perform comprehensive review and updated meta-analysis on the association between soy intake and breast cancer risk and to identify significant factors which may contribute to the inconsistencies of results of the individual studies. Based on reviews of existing meta-analysis, we identified four main factors which contributed to the inconsistencies of results of individual studies on the association of soy intake and breast cancer risk namely; region, menopausal status of the patients, soy type and study design. Accordingly, we performed an updated meta-analysis of 57 studies grouped by the identified factors. Pooled ORs of studies carried out in Asian countries suggested that soy isoflavones consumption was inversely associated with the risk of breast cancer among both pre and postmenopausal women (OR=0.63, 95% CI: 0.54-0.74 for premenopausal women; OR=0.63, 95% CI: 0.52-0.75 for postmenopausal women). However, pooled OR of studies carried out in Western countries shows that there is no statistically significant association between soy intake and breast cancer risk (OR=0.98, 95% CI: 0.93-1.03). Our study suggests that soy food intake is associated with significantly reduced risk of breast cancer for women in Asian but not in Western countries. Further epidemiological studies need to be conducted with more comprehensive information about the dietary intake and relative exposure among the women in these two different regions.

  19. Identification of Homogeneous and Heterogeneous Variables in Pooled Cohort Studies

    PubMed Central

    Cheng, Xin; Lu, Wenbin; Liu, Mengling

    2016-01-01

    Summary Pooled analyses integrate data from multiple studies and achieve a larger sample size for enhanced statistical power. When heterogeneity exists in variables’ effects on the outcome across studies, the simple pooling strategy fails to present a fair and complete picture of the effects of heterogeneous variables. Thus, it is important to investigate the homogeneous and heterogeneous structure of variables in pooled studies. In this paper, we consider the pooled cohort studies with time-to-event outcomes and propose a penalized Cox partial likelihood approach with adaptively weighted composite penalties on variables’ homogeneous and heterogeneous effects. We show that our method can characterize the variables as having heterogeneous, homogeneous, or null effects, and estimate non-zero effects. The results are readily extended to high-dimensional applications where the number of parameters is larger than the sample size. The proposed selection and estimation procedure can be implemented using the iterative shooting algorithm. We conduct extensive numerical studies to evaluate the performance of our proposed method and demonstrate it using a pooled analysis of gene expression in patients with ovarian cancer. PMID:25732747

  20. Common polymorphisms in CD44 gene and susceptibility to cancer: a systematic review and meta-analysis of 45 studies

    PubMed Central

    Fang, Tingting; Cai, Yangke; Xu, Yue; Yan, Cunye; Zhang, Li; Liang, Chaozhao

    2016-01-01

    CD44 is one of the commonly recognized stem cell markers, which plays a critical role in many cancer related cellular processes. Relationships between CD44 polymorphisms and cancer risk have been widely investigated previously, whereas results derived from these studies were inconclusive and controversial. We conducted present meta-analysis aiming to explore the association between CD44 polymorphisms and cancer risk. We calculated pooled odds ratios (ORs) corresponding with the 95% confidence intervals (CIs) to make the evaluation clear. Embase, Web of Science, PubMed and Cochrane Library databases were retrieved to identify all eligible publications. As a result, a total of 12 publications comprised 25,777 cases and 27,485 controls fulfilled the inclusion criteria. Nevertheless, the pooled analyses suggested that no significant association was uncovered between CD44 (rs10836347, rs11821102, rs13347, rs1425802, rs353639, rs713330 and rs187115) polymorphisms with overall cancer risk. Subsequently, we conducted subgroup analysis for rs13347 polymorphism based on source of control, and we identified a significantly increased cancer risk for the population-based (P-B) group restricted to a recessive model (TT vs. TC+CC: OR = 2.030, 95%CI: 1.163-3.545, PAdjust < 0.001). In conclusion, our meta-analysis demonstrates that CD44 polymorphisms may not represent risk factors for cancer. Future well-designed large-scale case-control studies are warranted to verify our findings. PMID:27738347

  1. Androgen receptor gene CAG repeat polymorphism and ovarian cancer risk: A meta-analysis.

    PubMed

    Deng, Yang; Wang, Jue; Wang, Ling; Du, Yan

    2017-02-28

    Ovarian cancer is one of the common gynecological malignancies worldwide. It is usually diagnosed at a later stage, thus missing the best opportunity for treatment. Despite the advancement of ovarian cancer treatment, the prognosis is still poor. Androgen receptor (AR) may play a role in ovarian carcinogenesis. Previous studies regarding the association between AR CAG repeat length and ovarian cancer risk reported inconsistent results. Therefore, we conducted a meta-analysis to evaluate the association between AR CAG repeat length and ovarian cancer risk following the MOOSE guidelines. PubMed, Web of Science, EBSCO and other databases were searched up to September 15(th) 2016. Case control studies with clear definition of CAG repeat length and detailed genotype information were included. Two authors independently reviewed and extracted data. Pooled analysis and subgroup analysis stratified by ethnicity were performed for different genetic models. Begg's funnel plot and Egger's test were performed for publication bias estimation. Overall, there was no association between the AR CAG repeat polymorphism and ovarian cancer risk. However, short CAG repeat polymorphism was associated with increased ovarian cancer risk in African Americans and Chinese under the dominant model, whereas a reverse association was observed in Caucasians and Italians under the other three models. Our study results should be interpreted with caution. Further well-designed epidemiological and functional studies are needed to elucidate the role of AR in ovarian carcinogenesis.

  2. Prognostic value of the neutrophil to lymphocyte ratio in lung cancer: A meta-analysis.

    PubMed

    Yin, Yongmei; Wang, Jun; Wang, Xuedong; Gu, Lan; Pei, Hao; Kuai, Shougang; Zhang, Yingying; Shang, Zhongbo

    2015-07-01

    Recently, a series of studies explored the correlation between the neutrophil to lymphocyte ratio and the prognosis of lung cancer. However, the current opinion regarding the prognostic role of the neutrophil to lymphocyte ratio in lung cancer is inconsistent. We performed a meta-analysis of published articles to investigate the prognostic value of the neutrophil to lymphocyte ratio in lung cancer. The hazard ratio (HR) and its 95% confidence interval (CI) were calculated. An elevated neutrophil to lymphocyte ratio predicted worse overall survival, with a pooled HR of 1.243 (95%CI: 1.106-1.397; P(heterogeneity)=0.001) from multivariate studies and 1.867 (95%CI: 1.487-2.344; P(heterogeneity)=0.047) from univariate studies. Subgroup analysis showed that a high neutrophil to lymphocyte ratio yielded worse overall survival in non-small cell lung cancer (NSCLC) (HR=1.192, 95%CI: 1.061-1.399; P(heterogeneity)=0.003) as well as small cell lung cancer (SCLC) (HR=1.550, 95% CI: 1.156-2.077; P(heterogeneity)=0.625) in multivariate studies. The synthesized evidence from this meta-analysis of published articles demonstrated that an elevated neutrophil to lymphocyte ratio was a predictor of poor overall survival in patients with lung cancer.

  3. Flavonoids intake and risk of prostate cancer: a meta-analysis of observational studies.

    PubMed

    Guo, K; Liang, Z; Liu, L; Li, F; Wang, H

    2016-12-01

    The aim of the study was to assess the association between total flavonoids/flavonoid subclasses intake and prostate cancer risk. Several databases were searched to select eligible studies with predefined criteria. Risk ratios (RRs) with 95% confidence intervals (CIs) were used as the effect size. Publication bias and sensitivity analysis were performed. A total of five studies including four prospective cohort studies and one case-control study were included in the meta-analysis. The pooled result demonstrated a significantly increased risk of prostate cancer with higher intake of total flavonoids (RR = 1.12, 95% CI: 1.02-1.23, P = 0.013). However, sensitivity analysis indicated that there lacked a significant association after removing the study of Wang et al. (RR = 1.17, 95% CI: 0.94-1.46). Subgroup analysis stratified by flavonoids subclasses found that higher intake of anthocyanidins and flavan-3-ols were significantly associated with increased prostate cancer risk (RR = 1.12, 95% CI: 1.03-1.21, P = 0.011; RR = 1.21, 95% CI: 1.10-1.32, P < 0.001). Sensitivity analysis also indicated that after removing Wang's study, no significant association between anthocyanidins intake and prostate cancer risk was detected (RR = 1.22, 95% CI: 0.97-1.54). In conclusion, higher intake of flavonoids may not be associated with prostate cancer risk.

  4. A meta-analysis of alcohol consumption and thyroid cancer risk

    PubMed Central

    Wang, Xiaofei; Cheng, Wenli; Li, Jingdong; Zhu, Jingqiang

    2016-01-01

    Background It is still inconclusive whether alcohol consumption affects the risk of thyroid cancer. We conducted a meta-analysis of available epidemiological data to address this issue. Results Compared with nondrinkers, the pooled relative risks (RRs) and corresponding 95% confidential intervals (CIs) of thyroid cancer were 0.80 (95% CI 0.71-0.90) for any drinkers, 0.81 (95% CI 0.70-0.93) for light and 0.71 (95% CI 0.63-0.79) for moderate drinkers. The dose–response analysis suggested that there is no evidence of a dose-risk relationship between alcohol intaking and thyroid cancer risk (P = 0.112). Methods Eligible studies were identified by searching PubMed and EMbase databases. A total of 24 studies, included 9,990 cases with thyroid cancer, were included in this meta-analysis. We defined light alcohol intake as ≤ one drink/day and moderate as >one drink/day. The summary risk estimates were calculated by the random effects model. A dose-response analysis was also conducted for modeling the dose-risk relation. Conclusion This meta-analysis confirmed an inverse association between alcohol consumption and thyroid cancer risk. Further studies are needed to better understand the potential mechanisms underlying this association. PMID:27385005

  5. Postoperative opioid sparing with injectable hydroxypropyl-β-cyclodextrin-diclofenac: pooled analysis of data from two Phase III clinical trials

    PubMed Central

    Gan, Tong J; Singla, Neil; Daniels, Stephen E; Hamilton, Douglas A; Lacouture, Peter G; Reyes, Christian RD; Carr, Daniel B

    2017-01-01

    Purpose Use of nonopioid analgesics (including nonsteroidal anti-inflammatory drugs) for postoperative pain management can reduce opioid consumption and potentially prevent opioid-related adverse events. This study examined the postoperative opioid-sparing effect of repeated-dose injectable diclofenac formulated with hydroxypropyl-β-cyclodextrin (HPβCD)-diclofenac. Patients and methods Pooled data from two double-blind, randomized, placebo- and active comparator-controlled Phase III trials were analyzed. Patients received HPβCD-diclofenac, placebo, or ketorolac by intravenous injection every 6 hours for up to 5 days following abdominal/pelvic or orthopedic surgery. Rescue opioid use was evaluated from the time of first study drug administration to up to 120 hours following the first dose in the overall study population and in subgroups defined by baseline pain severity, age, and HPβCD-diclofenac dose. Results Overall, 608 patients received ≥1 dose of study medication and were included in the analysis. While 93.2% of patients receiving placebo required opioids, the proportion of patients requiring opioids was significantly lower for patients receiving HPβCD-diclofenac (18.75, 37.5, or 50 mg) or ketorolac (P<0.005 for all comparisons). Mean cumulative opioid dose and number of doses were significantly lower among patients receiving HPβCD-diclofenac versus placebo for the 0–24 through 0–120 hour time periods (P<0.0001), as well as versus ketorolac for the 0–72 through 0–120 hour time periods (P<0.05). HPβCD-diclofenac significantly reduced opioid consumption versus placebo in subgroups based on baseline pain severity (moderate, severe) and age (<65 years, ≥65 years) from the 0–24 hour period onward. When compared to ketorolac, HPβCD-diclofenac also significantly reduced cumulative opioid consumption among patients with moderate baseline pain (0–72 through 0–120 hours) and opioid dose number among patients ≥65 years old (0–24 through 0

  6. Coffee consumption and risk of prostate cancer: a meta-analysis of prospective cohort studies.

    PubMed

    Cao, Shiyi; Liu, Ling; Yin, Xiaoxu; Wang, Yunxia; Liu, Junan; Lu, Zuxun

    2014-02-01

    Observational studies and animal evidence suggest an association between coffee consumption and the risk of prostate cancer. However, the results are inconsistent. We evaluated the association by conducting a meta-analysis of prospective cohort studies. PubMed and Embase were searched through June 2013 to identify studies that met predetermined inclusion criterion. A random-effects model was used to calculate the pooled risk estimates. Ten prospective cohort studies involving 8973 patients with prostate cancer and 206 096 participants were included in this systematic review. Compared with individuals who seldom or never drink coffee, the pooled relative risk of prostate cancer was 0.88 (95% confidence interval: 0.82-0.95) for regular coffee drinkers. Exclusion of any single study did not materially alter the combined risk estimate. Visual inspection of a funnel plot and Begg's and Egger's tests did not indicate evidence of publication bias. In summary, integrated evidence from prospective cohort studies supports the hypothesis that coffee consumption may decrease the risk of prostate cancer.

  7. Swimming pool granuloma

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/001357.htm Swimming pool granuloma To use the sharing features on this page, please enable JavaScript. A swimming pool granuloma is a long-term (chronic) skin ...

  8. Swimming Pool Safety

    MedlinePlus

    ... Prevention Listen Español Text Size Email Print Share Swimming Pool Safety Page Content ​What is the best way to keep my child safe around swimming pools? An adult should actively watch children at ...

  9. Institutional Boundaries and Common-Pool Resource Management: A Comparative Analysis of Water Management Programs in California

    ERIC Educational Resources Information Center

    Heikkila, Tanya

    2004-01-01

    Policymakers and academics often identify institutional boundaries as one of the factors that shape the capacity of jurisdictions to manage natural resources such as water, forests, and scenic lands. This article examines two key bodies of literature--common-pool resource management theory and local public economy theory--to explain how the…

  10. Targeting VEGFR-2 in Metastatic Gastric Cancer: Results From a Literature-Based Meta-Analysis.

    PubMed

    Roviello, Giandomenico; Polom, Karol; Roviello, Franco; Marrelli, Daniele; Multari, Andrea Giovanni; Paganini, Giovanni; Pacifico, Chiara; Generali, Daniele

    2017-02-06

    Angiogenesis is a key process in cancer development. We performed a meta-analysis to assess the efficacy and safety of the novel VEGFR-2 inhibitors in patients with metastatic gastric and gastroesophageal junction cancer. A literature-based meta-analysis of randomized controlled trials (RCTs) was undertaken. The primary outcome was the overall survival. The pooled analysis from RCTs on anti-VEGFR-2 inhibitors revealed a significant increase in overall survival (hazard ratio for death: 0.69, 95% confidence interval: 0.55-0.87; p = .002). This study confirms the efficacy of novel anti-VEGFR-2 inhibitors. The future studies of these agents will evaluate alone and in combination with chemotherapy the early line of treatment along with the identification of proper predictive biomarker.

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

    PubMed Central

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

    2013-01-01

    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

  12. GSTT1 polymorphism and breast cancer risk in the Chinese population: an updated meta-analysis and review

    PubMed Central

    Xiao, Zhang-Sheng; Li, Yun; Guan, Yan-Li; Li, Jia-Gen

    2015-01-01

    Background: Although a number of studies have been conducted on the association between GSTT1 polymorphism and breast cancer in China, this association remains elusive and controversial. To clarify the effects of GSTT1 polymorphism on the risk of breast cancer, an updated meta-analysis was performed in the Chinese population. Material/methods: Related studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) to up 28th January 2015. Pooled ORs and 95% CIs were used to assess the strength of the associations. Results: A total of 13 studies including 3387 breast cancer cases and 5085 controls were involved in this meta-analysis. Overall, a significant association (OR = 1.31, 95% CI: 1.02-1.67) was found between the null GSTT1 and breast cancer risk when all studies in Chinese population pooled into the meta-analysis. In subgroup analyses stratified by geographic areas and source of controls, it revealed the significant results in population-based studies (OR = 1.42, 95% CI: 1.23-1.65) and South China (OR = 1.47, 95% CI: 1.27-1.70). Conclusions: This meta-analysis showed that the null GSTT1 may be potential biomarkers for breast cancer risk in Chinese, and further studies with gene-gene and gene-environment interactions are required for definite conclusions. PMID:26221202

  13. Association between vitamin C intake and lung cancer: a dose-response meta-analysis

    PubMed Central

    Luo, Jie; Shen, Li; Zheng, Di

    2014-01-01

    Epidemiological studies evaluating the association between the intake of vitamin C and lung cancer risk have produced inconsistent results. We conducted a meta-analysis to assess the association between them. Pertinent studies were identified by a search of PubMed, Web of Knowledge and Wan Fang Med Online through December of 2013. Random-effect model was used to combine the data for analysis. Publication bias was estimated using Begg's funnel plot and Egger's regression asymmetry test. Eighteen articles reporting 21 studies involving 8938 lung cancer cases were included in this meta-analysis. Pooled results suggested that highest vitamin C intake level versus lowest level was significantly associated with the risk of lung cancer [summary relative risk (RR) = 0.829, 95%CI = 0.734–0.937, I2 = 57.8%], especially in the United States and in prospective studies. A linear dose-response relationship was found, with the risk of lung cancer decreasing by 7% for every 100 mg/day increase in the intake of vitamin C [summary RR = 0.93, 95%CI = 0.88–0.98]. No publication bias was found. Our analysis suggested that the higher intake of vitamin C might have a protective effect against lung cancer, especially in the United States, although this conclusion needs to be confirmed. PMID:25145261

  14. Dietary fat intake and ovarian cancer risk: a meta-analysis of epidemiological studies

    PubMed Central

    Qiu, Wenlong; Lu, Heng; Qi, Yana; Wang, Xiuwen

    2016-01-01

    Observational studies assessing the association of dietary fat and risk of ovarian cancer yield discrepant results. Pertinent prospective cohort studies were identified by a PubMed search from inception to December 2015. Sixteen independent case-control and nine cohort studies on dietary fat intake were included, with approximately 900,000 subjects in total. Relative risks (RRs) with 95% confidence intervals were pooled using a random effects model. Heterogeneity, sensitivity analysis and publication bias were assessed; subgroup analysis and analysis stratified by EOC histology were conducted. The reported studies showed a significant increase of ovarian cancer risk with high consumption of total-, saturated-, and trans-fats, while serous ovarian cancer was more susceptible to dietary fat consumption than other pathological subtypes. No evidence of positive association between dietary fat intake and ovarian cancer risk was provided by cohort studies. Menopausal status, hormone replacement therapy, body mass index (BMI), and pregnancy times, modified the objective associations. In conclusion, the meta-analysis findings indicate that high consumption of total, saturated and trans-fats increase ovarian cancer risk, and different histological subtypes have different susceptibility to dietary fat. PMID:27119509

  15. Meta-Analysis of Prognostic and Clinical Significance of CD44v6 in Esophageal Cancer.

    PubMed

    Hu, Bangli; Luo, Wei; Hu, Rui-Ting; Zhou, You; Qin, Shan-Yu; Jiang, Hai-Xing

    2015-08-01

    CD44v6 is a cell adhesion molecule that plays an important role in the development and progression of esophageal cancer. However, the prognostic value and clinical significance of CD44v6 in esophageal cancer remains controversial. In the present study, we aimed to clarify these relationships through a meta-analysis.We performed a comprehensive search of studies from PubMed, EMBASE, Ovid library database, Google scholar, and Chinese National Knowledge Infrastructure databases that were published before June 2015. The odds ratio (OR) and pooled hazard ratio (HR) with the 95% confidence intervals (CI) were used to estimate the effects.Twenty-one studies including 1504 patients with esophageal cancer were selected to assess the prognostic value and clinical significance of CD44v6 in these patients. The results showed that the expression of CD44v6 was higher in esophageal cancer tissue than in normal colorectal tissue (OR=9.19, 95% CI=6.30-13.42). Moreover, expression of CD44v6 was higher in patients with lymphoid nodal metastasis, compared to those without (OR=6.91, 95% CI=4.81-9.93). The pooled results showed that CD44v6 was associated with survival in patients with esophageal cancer (HR = 2.47, 95% CI = 1.56-3.92). No significant difference in CD44v6 expression was found in patients with different histological types and tumor stages (both P>0.05). Moreover, no publication bias was found among the studies (all P > 0.05).This meta-analysis demonstrates that CD44v6 is associated with the metastasis of esophageal cancer and a poor prognosis, but is not associated with the histological types and tumor stages.

  16. The therapy of amblyopia: an analysis of the results of amblyopia therapy utilizing the pooled data of published studies.

    PubMed Central

    Flynn, J T; Schiffman, J; Feuer, W; Corona, A

    1998-01-01

    CONTEXT: Although the treatment of amblyopia with occlusion has changed little over the past 3 centuries, there is little agreement about which regimes are most effective and for what reasons. OBJECTIVE: To determine the outcome of occlusion therapy in patients with anisometropic, strabismic, and strabismic-anisometropic amblyopia employing the raw data from 961 patients reported in 23 studies published between 1965 and 1994. DESIGN: Analysis of the published literature on amblyopia therapy results during the above interval, utilizing primary data obtained from the authors of these articles or tables published in the articles detailing individual patient outcomes. PARTICIPANTS: 961 amblyopic patients, participants in 23 studies, undergoing patching therapy for amblyopia from 1965 to 1994 with anisometropia, strabismus, or anisometropia-strabismus. MAIN OUTCOMES: In the pooled data set, success of occlusion therapy was defined as visual acuity of 20/40 at the end of treatment. RESULTS: Success by the 20/40 criteria was achieved in 512 of 689 (74.3%) patients. By category, 312 of 402 (77.6%) were successful in strabismic amblyopia, 44 of 75 (58.7%) in strabismic-anisometropic amblyopia, and 72 of 108 (66.7%) in anisometropic amblyopia. Success was not related to the duration of occlusion therapy, type of occlusion used, accompanying refractive error, patient's sex, or eye. Univariate analyses showed that success was related to the age at which therapy was initiated; the type of amblyopia; the depth of visual loss before treatment for the anisometropic patients and the strabismic patients, but not for the anisometropic-strabismic patients; and the difference in spherical equivalents between eyes, for the anisometropic patients. Logistic/linear regression revealed that 3 were independent predictors of a successful outcome of amblyopia therapy. CONCLUSIONS: Factors that appear most closely related to a successful outcome are age, type of amblyopia, and depth of visual

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

    PubMed Central

    2013-01-01

    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

  18. Clinical Predictors of Venetoclax Pharmacokinetics in Chronic Lymphocytic Leukemia and Non-Hodgkin's Lymphoma Patients: a Pooled Population Pharmacokinetic Analysis.

    PubMed

    Jones, Aksana K; Freise, Kevin J; Agarwal, Suresh K; Humerickhouse, Rod A; Wong, Shekman L; Salem, Ahmed Hamed

    2016-09-01

    Venetoclax (ABT-199/GDC-0199) is a selective, potent, first-in-class BCL-2 inhibitor that restores apoptosis in cancer cells and has demonstrated clinical efficacy in a variety of hematological malignancies. The objective of this analysis was to characterize the population pharmacokinetics of venetoclax and identify demographic, pathophysiologic, and treatment factors that influence its pharmacokinetics. Plasma concentration samples from 505 subjects enrolled in 8 clinical studies were analyzed using non-linear mixed-effects modeling. Venetoclax plasma concentrations were best described by a two-compartment PK model with first-order absorption and elimination. The terminal half-life in cancer subjects was estimated to be approximately 26 h. Moderate and strong CYP3A inhibitors decreased venetoclax apparent clearance by 19% and 84%, respectively, while weak CYP3A inhibitors and inducers did not affect clearance. Additionally, concomitant rituximab administration was estimated to increase venetoclax apparent clearance by 21%. Gastric acid-reducing agent co-administration had no impact on the rate or extent of venetoclax absorption. Females had 32% lower central volume of distribution when compared to males. Food increased the bioavailability by 2.99- to 4.25-fold when compared to the fasting state. Mild and moderate renal and hepatic impairment, body weight, age, race, weak CYP3A inhibitors and inducers as well as OATP1B1 transporter phenotype and P-gp, BCRP, and OATP1B1/OATP1B3 modulators had no impact on venetoclax pharmacokinetics. Venetoclax showed minimal accumulation with accumulation ratio of 1.30-1.44. In conclusion, the concomitant administration of moderate and strong CYP3A inhibitors and rituximab as well as food were the main factors impacting venetoclax pharmacokinetics, while patient characteristics had only minimal impact.

  19. Exhaled breath analysis for lung cancer

    PubMed Central

    Sutedja, Tom G.; Zimmerman, Paul V.

    2013-01-01

    Early diagnosis of lung cancer results in improved survival compared to diagnosis with more advanced disease. Early disease is not reliably indicated by symptoms. Because investigations such as bronchoscopy and needle biopsy have associated risks and substantial costs, they are not suitable for population screening. Hence new easily applicable tests, which can be used to screen individuals at risk, are required. Biomarker testing in exhaled breath samples is a simple, relatively inexpensive, non-invasive approach. Exhaled breath contains volatile and non-volatile organic compounds produced as end-products of metabolic processes and the composition of such compounds varies between healthy subjects and subjects with lung cancer. Many studies have analysed the patterns of these compounds in exhaled breath. In addition studies have also reported that the exhaled breath condensate (EBC) can reveal gene mutations or DNA abnormalities in patients with lung cancer. This review has summarised the scientific evidence demonstrating that lung cancer has distinct chemical profiles in exhaled breath and characteristic genetic changes in EBC. It is not yet possible to accurately identify individuals with lung cancer in at risk populations by any of these techniques. However, analysis of both volatile organic compounds in exhaled breath and of EBC have great potential to become clinically useful diagnostic and screening tools for early stage lung cancer detection. PMID:24163746

  20. Content analysis of cancer blog posts*

    PubMed Central

    Kim, Sujin

    2009-01-01

    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. PMID:19851489

  1. Tumor Necrosis Factor-α T-857C (rs1799724) Polymorphism and Risk of Cancers: A Meta-Analysis

    PubMed Central

    Wang, June

    2016-01-01

    Objectives. To investigate the potential association of tumor necrosis factor-α T-857C polymorphism with susceptibility to the five common malignant tumors. Materials and Methods. A comprehensive search of PubMed/Medline, Embase, and Web of Science databases was performed up to November 2015. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to assess the strength of the association. Subgroup analysis, heterogeneity analyses, and publication bias were also texted in the meta-analysis. Results. A total of twenty-two publications involving 5215 cases and 6755 controls were recruited. Overall, the meta-analysis revealed an increased risk between the TNF-α T-857C polymorphism and gastric cancer susceptibility in T versus C model, heterozygote genetic model, and dominant genetic model. An increased risk between the TNF-α T-857C polymorphism and hepatocellular cancer susceptibility in homozygote genetic model and recessive genetic model was also found. No significant association was found between the TNF-α T-857C polymorphism and colorectal cancer, cervical cancer, and prostate cancer. Conclusions. Our meta-analyses suggest that TNF-α T-857C polymorphism may be associated with increased risk of gastric cancer and hepatocellular cancer development. Therefore, the TNF-α T-857C polymorphism could be considered as one possible risk factor of gastric cancer and hepatocellular cancer according to our study. PMID:28115787

  2. Does higher screw density improve radiographic and clinical outcomes in adolescent idiopathic scoliosis? A systematic review and pooled analysis.

    PubMed

    Luo, Ming; Wang, Wengang; Shen, Mingkui; Luo, Xin; Xia, Lei

    2017-02-03

    OBJECTIVE The radiographic and clinical outcomes of low-density (LD) versus high-density (HD) screw constructs in patients with adolescent idiopathic scoliosis (AIS) treated with all-pedicle screw constructs are still controversial. A systematic review and pooled analysis were performed to compare radiographic, perioperative, and quality-of-life (QOL) outcomes and complications in patients with moderate AIS treated with LD or HD screw constructs. METHODS The MEDLINE, Embase, and Web of Science databases were searched for English-language articles addressing LD versus HD screw constructs in AIS patients treated with all-pedicle screw constructs. The division of LD and HD groups was based on relative screw density and screw techniques. This systematic analysis strictly followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, and all articles included in the analysis met the criteria specified in the guidelines. Two reviewers independently assessed the quality of the studies using the Newcastle-Ottawa Scale. Date on radiographic, perioperative, and QOL outcomes and complications were extracted from the included studies. RESULTS Twelve studies, involving a total of 827 patients (480 treated with LD constructs, 347 with HD), were analyzed-1 randomized controlled trial, 1 quasi-randomized controlled trial, and 10 retrospective studies. The patients' age at surgery, preoperative Cobb angle of the major curve, amount of thoracic kyphosis, and major curve flexibility were reasonably distributed, and no statistically significant differences were found. Regarding the outcomes at most recent follow-up, there were no significant differences in the Cobb angle of the major curve (mean difference 0.96°, 95% CI -0.06° to 1.98°, p = 0.06, I(2) = 1%), major curve correction (mean difference -0.72%, 95% CI -2.96% to 1.52%, p = 0.53, I(2) = 0%), thoracic kyphosis (mean difference -1.67°, 95% CI -4.59° to 1.25°, p = 0.26, I(2) = 79

  3. Risk of Lung Cancer in Workers Exposed to Benzidine and/or Beta-Naphthylamine: A Systematic Review and Meta-Analysis.

    PubMed

    Tomioka, Kimiko; Saeki, Keigo; Obayashi, Kenji; Kurumatani, Norio

    2016-09-05

    Benzidine (BZ) and beta-naphthylamine (BNA) have been classified as definite human carcinogens for bladder cancer by the International Agency for Research on Cancer. However, the epidemiological evidence for an association between exposure to BZ and/or BNA and lung cancer has been inconclusive. We conducted a systematic review and meta-analysis to determine the risk for lung cancer among workers exposed to BZ/BNA. A systematic literature search was conducted to identify studies that had reported occupational BZ/BNA exposure and the outcome of interest (lung cancer death and/or incidence). Meta-analyses were performed using random effects models to combine standardized mortality ratios (SMRs) or standardized incidence ratios (SIRs). We identified 23 retrospective cohort studies including 1745 cases of lung cancer; only one study reported smoking-adjusted lung cancer risk. A significantly increased lung cancer risk (pooled SMR/SIR 1.28; 95% CI, 1.14-1.43) was observed by combining all studies, with significant heterogeneity among studies (I(2) = 64.1%, P < 0.001). Effect estimates were higher for studies with direct BZ/BNA exposure (ie, dyestuff and manufacturing industries) (pooled SMR/SIR 1.58; 95% CI, 1.31-1.89), and studies that identified BZ/BNA-associated bladder cancer with SMR/SIR ≥4.7 (pooled SMR/SIR 1.68; 95% CI, 1.35-2.09). Effect estimates were similar for studies with and without concomitant occupational exposure to chromium, asbestos, arsenic, or bis(chloromethyl) ether. The cumulative meta-analysis showed that the evidence of association between occupational BZ/BNA exposure and lung cancer has been stable since 1995. Although the results of this meta-analysis have the potential for confounding by smoking and heterogeneity, our findings suggest that a finding of lung cancer following occupational BZ/BNA exposure should be considered to be a potential occupational disease.

  4. Association between Breastfeeding and Endometrial Cancer Risk: Evidence from a Systematic Review and Meta-Analysis

    PubMed Central

    Wang, Lianlian; Li, Jingxi; Shi, Zhan

    2015-01-01

    Quantification of the association between breastfeeding and risk of endometrial cancer is still conflicting. We therefore conducted a meta-analysis to assess the association between breastfeeding and endometrial cancer risk. Pertinent studies were identified by a search of PubMed and Web of Knowledge through April 2015. A random effect model was used to combine the data for analysis. Sensitivity analysis and publication bias were conducted. Dose-response relationships were assessed by restricted cubic spline and variance-weighted least squares regression analysis. Fourteen articles involving 5158 endometrial cancer cases and 706,946 participants were included in this meta-analysis. Pooled results suggested that breastfeeding significantly reduced the risk of endometrial cancer (summary relative risk (RR): 0.77, 95% CI: 0.62–0.96, I2: 63.0%), especially in North America (summary RR: 0.87, 95% CI: 0.79–0.95). A linear dose-response relationship was found, with the risk of endometrial cancer decreased by 2% for every one-month increase in the duration of breastfeeding (summary RR: 0.98, 95% CI: 0.97–0.99). Our analysis suggested that breastfeeding, particularly a longer duration of breastfeeding, was inversely associated with the risk of endometrial cancer, especially in North America, but not in Europe and Asia, probably due to the small number of cases included. Due to this limitation, further studies originating in other countries are required to assess the association between breastfeeding and endometrial cancer risk. PMID:26184301

  5. The Effect of Diabetes Mellitus on Lung Cancer Prognosis: A PRISMA-compliant Meta-analysis of Cohort Studies.

    PubMed

    Zhu, Linhai; Cao, Hongxin; Zhang, Tiehong; Shen, Hongchang; Dong, Wei; Wang, Liguang; Du, Jiajun

    2016-04-01

    Previous studies suggested that diabetes mellitus (DM) was associated with risk and mortality of cancer, but studies investigating the correlation between DM and lung cancer prognosis remain controversial. Herein, a meta-analysis was performed to derive a more precise estimate of the prognostic role of DM in lung cancer.Medline and Embase were searched for eligible articles from inception to October 25, 2015. The pooled hazard ratio (HR) with its 95% confidence interval (95% CI) was calculated to evaluate the correlation between DM and lung cancer prognosis. Subgroup meta-analysis was performed based on the histology and the treatment methods.A total of 20 cohort studies from 12 articles were included in the meta-analysis. Also, 16 studies investigated the overall survival (OS) and 4 studies investigated the progression-free survival (PFS). DM was significantly associated with the inferior OS of lung cancer with the pooled HR 1.28 (95% CI: 1.10-1.49, P = 0.001). The association was prominent in the nonsmall cell lung cancer (NSCLC) subgroup (HR 1.35, 95%CI: 1.14-1.60, P = 0.002), whereas the association was not significant in the small cell lung cancer (SCLC) subgroup (HR 1.33, 95% CI: 0.87-2.03, P = 0.18). When NSCLC patients were further stratified by treatment methods, DM had more influence on the surgically treated subgroup than the nonsurgically treated subgroup. There was no obvious evidence for publication bias by Begg's and Egger's test.The results of this meta-analysis exhibit an association of DM with inferior prognosis amongst lung cancer patients, especially the surgically treated NSCLC patients. Given the small number of studies included in this meta-analysis, the present conclusion should be consolidated with more high-quality prospective cohort studies or randomized controlled trials.

  6. Risk analysis of colorectal cancer incidence by gene expression analysis

    PubMed Central

    Shangkuan, Wei-Chuan; Lin, Hung-Che; Chang, Yu-Tien; Jian, Chen-En; Fan, Hueng-Chuen; Chen, Kang-Hua; Liu, Ya-Fang; Hsu, Huan-Ming; Chou, Hsiu-Ling; Yao, Chung-Tay

    2017-01-01

    Background Colorectal cancer (CRC) is one of the leading cancers worldwide. Several studies have performed microarray data analyses for cancer classification and prognostic analyses. Microarray assays also enable the identification of gene signatures for molecular characterization and treatment prediction. Objective Microarray gene expression data from the online Gene Expression Omnibus (GEO) database were used to to distinguish colorectal cancer from normal colon tissue samples. Methods We collected microarray data from the GEO database to establish colorectal cancer microarray gene expression datasets for a combined analysis. Using the Prediction Analysis for Microarrays (PAM) method and the GSEA MSigDB resource, we analyzed the 14,698 genes that were identified through an examination of their expression values between normal and tumor tissues. Results Ten genes (ABCG2, AQP8, SPIB, CA7, CLDN8, SCNN1B, SLC30A10, CD177, PADI2, and TGFBI) were found to be good indicators of the candidate genes that correlate with CRC. From these selected genes, an average of six significant genes were obtained using the PAM method, with an accuracy rate of 95%. The results demonstrate the potential of utilizing a model with the PAM method for data mining. After a detailed review of the published reports, the results confirmed that the screened candidate genes are good indicators for cancer risk analysis using the PAM method. Conclusions Six genes were selected with 95% accuracy to effectively classify normal and colorectal cancer tissues. We hope that these results will provide the basis for new research projects in clinical practice that aim to rapidly assess colorectal cancer risk using microarray gene expression analysis. PMID:28229027

  7. Depression and anxiety in ovarian cancer: a systematic review and meta-analysis of prevalence rates

    PubMed Central

    Watts, Sam; Prescott, Philip; Mason, Jessica; McLeod, Natalie; Lewith, George

    2015-01-01

    Objectives To systematically review the literature pertaining to the prevalence of depression and anxiety in patients with ovarian cancer as a function of treatment stage. Design Systematic review and meta-analysis. Participants 3623 patients with ovarian cancer from primary research investigations. Primary outcome measure The prevalence of depression and anxiety in patients with ovarian cancer as a function of treatment stage. Results We identified 24 full journal articles that met the inclusion criteria for entry into the meta-analysis resulting in a pooled sample size of 3623 patients. The meta-analysis of prevalence rates identified pretreatment, on-treatment and post-treatment depression prevalences of 25.34% (CI 22.79% to 28.07%), 22.99% (CI 19.85% to 26.46%) and 12.71% (CI 10.14% to 15.79%), respectively. Pretreatment, on-treatment and post-treatment anxiety prevalences were 19.12% (CI 17.11% to 21.30%), 26.23% (CI 22.30% to 30.56%) and 27.09% (CI 23.10% to 31.49%). Conclusions Our findings suggest that the prevalence of depression and anxiety in women with ovarian cancer, across the treatment spectrum, is significantly greater than in the healthy female population. With the growing emphasis on improving the management of survivorship and quality of life, we conclude that further research is warranted to ensure psychological distress in ovarian cancer is not underdiagnosed and undertreated. PMID:26621509

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

    PubMed

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

    2014-05-01

    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

  9. An updated dose–response meta-analysis of coffee consumption and liver cancer risk

    PubMed Central

    Yu, Chengbo; Cao, Qing; Chen, Ping; Yang, Shigui; Deng, Min; Wang, Yugang; Li, Lanjuan

    2016-01-01

    Prospective cohort studies of the relationship between coffee consumption and liver cancer risk have drawn different conclusions. Therefore, a dose-response meta-analysis of prospective cohort studies was performed to disentangle this causal relationship. Prospective cohort studies of the association between coffee consumption and liver cancer risk published prior to Jan 9, 2016 were identified by searching in the PubMed and EMBASE databases. Extracted data were analyzed using a random-effects model. Of the 2892 records identified using the search strategy, a total of twenty cohort studies from ten publications were included in the final meta-analysis. The pooled estimate of relative risk (RR) with 95% confidence interval (CI) for highest vs. non/occasional coffee drinkers was 0.55(0.44–0.67). No evidence of publication bias was observed (p for Egger’s test = 0.229). Sensitivity analysis indicated the results were robust. Dose-response analysis revealed a significant linear dose-response relationship between coffee consumption and liver cancer risk (p = 0.36). Subgroup analyses stratified by pre-specified variables (gender, geographic region, and adjusted factors) indicated similar results within individual subgroups. Our meta-analysis suggested that coffee consumption is inversely associated with liver cancer risk. PMID:27910873

  10. Clinicopathological characteristics and prognostic value of cancer stem cell marker CD133 in breast cancer: a meta-analysis

    PubMed Central

    Li, Zhan; Yin, Songcheng; Zhang, Lei; Liu, Weiguang; Chen, Bo; Xing, Hua

    2017-01-01

    Background The association of CD133 overexpression with clinicopathological significance and prognosis in patients with breast cancer remains controversial. We thus performed a meta-analysis to evaluate the role of CD133 expression in the development and prognosis of breast cancer. Methods The databases PubMed, Embase, and Cochrane Library (updated to August 1, 2016) were searched. Pooled odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (95% CI) were used to evaluate the impact of CD133 expression on clinicopathological features, overall survival, and disease-free survival. Results A total of 1,734 patients from 13 studies were subject to final analysis. The results showed a significant association between overexpression of CD133 and estrogen receptor status (OR 0.35, 95% CI 0.18–0.70), progesterone receptor status (OR 0.56, 95% CI 0.43–0.74), human epidermal growth factor-2 status (OR 1.81, 95% CI 1.33–2.45), lymph node metastasis (OR 1.98, 95% CI 1.34–2.92), and tumor histological grade (OR 1.79, 95% CI 1.26–2.54) in breast cancer. However, no significant correlation was found between upregulation of CD133 expression and onset age (OR 1.03, 95% CI 0.70–1.53) or tumor size (OR 1.29, 95% CI 0.80–2.09). Moreover, CD133-positive breast cancer patients had a higher risk of mortality (HR 1.91, 95% CI 1.21–3.03) and disease progression (HR 2.70, 95% CI 1.05–6.95). Conclusion This meta-analysis suggested that CD133 might be a predictor of clinical outcomes as well as prognosis and could be a potentially new gene therapy target for breast cancer patients. PMID:28243121

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

    PubMed Central

    2013-01-01

    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 < 0.001; GG vs. TG + TT: OR = 1.726, 95% CI 1.251–2.380, P = 0.001; GG + TG vs. TT: OR = 1.169, 95% CI 1.048–1.304, P = 0.005). In subgroup 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. PMID:24423195

  12. Zinc Intake and Risk of Prostate Cancer: Case-Control Study and Meta-Analysis

    PubMed Central

    Dabbous, Firas; Ali, Mohamed M.; Batai, Ken; Shah, Ebony; Kittles, Rick A.

    2016-01-01

    Zinc is an essential dietary element that has been implicated in the pathogenesis of prostate cancer, a cancer that disproportionately affects men of African descent. Studies assessing the association of zinc intake and prostate cancer have yielded inconsistent results. Furthermore, very little is known about the relationship between zinc intake and prostate cancer among African Americans. We examined the association between self-reported zinc intake and prostate cancer in a hospital-based case-control study of African Americans. We then compared our results with previous studies by performing a meta-analysis to summarize the evidence regarding the association between zinc and prostate cancer. Newly diagnosed African American men with histologically confirmed prostate cancer (n = 127) and controls (n = 81) were recruited from an urban academic urology clinic in Washington, DC. Controls had higher zinc intake, with a mean of 14 mg/day versus 11 mg/day for cases. We observed a non-significant, non-linear increase in prostate cancer when comparing tertiles of zinc intake (OR <6.5 vs 6.5–12.5mg/day 1.8, 95% CI: 0.6,5.6; OR <6.5 vs >12.5mg/day 1.3, 95% CI: 0.2,6.5). The pooled estimate from 17 studies (including 3 cohorts, 2 nested case-control, 11 case-control studies, and 1 randomized clinical trial, with a total of 111,199 participants and 11,689 cases of prostate cancer) was 1.07hi vs lo 95% CI: 0.98–1.16. Using a dose-response meta-analysis, we observed a non-linear trend in the relationship between zinc intake and prostate cancer (p for nonlinearity = 0.0022). This is the first study to examine the relationship between zinc intake in black men and risk of prostate cancer and systematically evaluate available epidemiologic evidence about the magnitude of the relationship between zinc intake and prostate cancer. Despite of the lower intake of zinc by prostate cancer patients, our meta-analysis indicated that there is no evidence for an association between zinc

  13. Statin use and breast cancer survival and risk: a systematic review and meta-analysis

    PubMed Central

    Li, Yuan-Yuan; Zhu, Jingjing; Qian, Ke-Qing; Li, Wen-Jing; Wu, Lang

    2015-01-01

    The purpose of this study is to determine the associations between statin use and breast cancer survival and risk by performing a systematic review and meta-analysis. We searched PubMed, Embase and Web of Science up to August 2015 for identifying relevant prospective or case-control studies, or randomized clinical trials. Five prospective studies involving 60,911 patients reported the association between statin use and breast cancer mortality. Eleven prospective studies, 12 case-control studies and 9 randomized clinical trials involving 83,919 patients reported the association between statin use and breast cancer risk. After pooling estimates from all available studies, there was a significantly negative association between pre-diagnosis statin use and breast cancer mortality (for overall survival (OS): hazard ratio (HR) = 0.68, 95% confidence interval (CI) 0.54–0.84; for disease specific survival (DSS): HR = 0.72, 95% CI 0.53–0.99). There was also a significant inverse association between post-diagnosis statin use and breast cancer DSS (HR = 0.65, 95% CI 0.43–0.98), although the association with breast cancer OS did not reach statistical significance (HR = 0.71, 95% CI 0.48–1.07). Additionally, there was a non-linear relationship for the duration of post-diagnosis statin use with breast cancer specific mortality. On the other hand, with regards to the relationship between statin use and breast cancer risk, no significant association was detected. Our analyses suggest that although statin use may not influence breast cancer risk, the use of statin may be associated with decrease mortality of breast cancer patients. Further large-scale studies are warranted to validate our findings. PMID:26472026

  14. The Association between Telomere Length and Cancer Prognosis: Evidence from a Meta-Analysis

    PubMed Central

    Li, Lu; Zhou, Ying; Wang, Chao; Hou, Shuxun

    2015-01-01

    Background Telomeres are essential for chromosomal integrity and stability. Shortened telomere length (TL) has been associated with risk of cancers and aging-related diseases. Several studies have explored associations between TL and cancer prognosis, but the results are conflicting. Methods Prospective studies on the relationship between TL and cancer survival were identified by a search of PubMed up to May 25, 2015. There were no restrictions on the cancer type or DNA source. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. Meta-analysis approaches were conducted to determine pooled relative risks and 95% confidence intervals. Results Thirty-three articles containing forty-five independent studies were ultimately involved in our meta-analysis, of which twenty-seven were about overall cancer survival and eighteen were about cancer progression. Short TL was associated with increased cancer mortality risk (RR = 1.30, 95%CI: 1.06–1.59) and poor cancer progression (RR = 1.44, 95%CI: 1.10–1.88), both with high levels of heterogeneity (I2 = 83.5%, P = 0.012for overall survival and I2 = 75.4%, P = 0.008 for progression). TL was an independent predictor of overall cancer survival and progression in chronic lymphocytic leukemia. Besides, short telomeres were also associated with increased colorectal cancer mortality and decreased overall survival of esophageal cancer, but not in other cancers. Cancer progression was associated with TL in Asian and America populations and short TL predicted poor cancer survival in older populations. Compared with tumor tissue cells, TL in blood lymphocyte cells was better for prediction. In addition, the associations remained significant when restricted to studies with adjustments for age, with larger sample sizes, measuring TL using southern blotting or estimating risk effects by hazard ratios. Conclusion Short TL demonstrated a significant association with poor cancer survival, suggesting the

  15. Meta-analysis of residential exposure to radon gas and lung cancer.

    PubMed Central

    Pavia, Maria; Bianco, Aida; Pileggi, Claudia; Angelillo, Italo F.

    2003-01-01

    OBJECTIVES: To investigate the relation between residential exposure to radon and lung cancer. METHODS: A literature search was performed using Medline and other sources. The quality of studies was assessed. Adjusted odds ratios with 95% confidence intervals (CI) for the risk of lung cancer among categories of levels of exposure to radon were extracted. For each study, a weighted log-linear regression analysis of the adjusted odds ratios was performed according to radon concentration. The random effect model was used to combine values from single studies. Separate meta-analyses were performed on results from studies grouped with similar characteristics or with quality scores above or equal to the median. FINDINGS: Seventeen case-control studies were included in the meta-analysis. Quality scoring for individual studies ranged from 0.45 to 0.77 (median, 0.64). Meta-analysis based on exposure at 150 Bq/m3 gave a pooled odds ratio estimate of 1.24 (95% CI, 1.11-1.38), which indicated a potential effect of residential exposure to radon on the risk of lung cancer. Pooled estimates of fitted odds ratios at several levels of randon exposure were all significantly different from unity--ranging from 1.07 at 50 Bq/m3 to 1.43 at 250 Bq/m3. No remarkable differences from the baseline analysis were found for odds ratios from sensitivity analyses of studies in which > 75% of eligible cases were recruited (1.12, 1.00-1.25) and studies that included only women (1.29, 1.04-1.60). CONCLUSION: Although no definitive conclusions may be drawn, our results suggest a dose-response relation between residential exposure to radon and the risk of lung cancer. They support the need to develop strategies to reduce human exposure to radon. PMID:14758433

  16. Association between three exonuclease 1 polymorphisms and cancer risks: a meta-analysis

    PubMed Central

    Chen, Zi-Yu; Zheng, Si-Rong; Zhong, Jie-Hui; Zhuang, Xiao-Duan; Zhou, Jue-Yu

    2016-01-01

    To date, the results of studies exploring the relation between exonuclease 1 (Exo1) polymorphisms and cancer risks have differed. In this study, we performed a meta-analysis to investigate the effect of the three most extensively studied Exo1 polymorphisms (Pro757Leu, Glu589Lys, and Glu670Gly) on cancer susceptibility. The related studies published before August 5, 2015, were collected by searching the PubMed and EMBASE databases. We found 16 publications containing studies that were eligible for our study, including 10 studies for Pro757Leu polymorphism (4,093 cases and 3,834 controls), 12 studies for Glu589Lys polymorphism (6,479 cases and 6,550 controls), and 7 studies for Glu670Gly polymorphism (3,700 cases and 3,496 controls). Pooled odds ratios and 95% confidence intervals were used to assess the strength of the associations, and all the statistical analyses were calculated using the software program STATA version 12.0. Our results revealed that the Pro757Leu polymorphism was significantly associated with a reduced cancer risk, whereas an inverse association was found for the Glu589Lys polymorphism. Furthermore, subgroup analysis of smoking status indicated that the Glu589Lys polymorphism was significantly associated with an increased cancer risk in smokers, but not in nonsmokers. However, no evidence was found for an association between the Glu670Gly polymorphism and cancer risk. In conclusion, this meta-analysis suggests that the Pro757Leu polymorphism may provide protective effects against cancer, while the Glu589Lys polymorphism may be a risk factor for cancer. Moreover, the Glu670Gly polymorphism may have no influence on cancer susceptibility. In the future, large-scaled and well-designed studies are needed to achieve a more precise and comprehensive result. PMID:26966378

  17. Aspirin Use and Lung Cancer Risk: A Possible Relationship? Evidence from an Updated Meta-Analysis

    PubMed Central

    Xu, Lei; Yu, Jing; Wu, Yan; Geng, Jiang; Yao, Xu-dong

    2015-01-01

    Background and Purpose Growing evidence has emerged and controversial results reported on possible relationship between aspirin use and lung cancer risk. We, therefore, conducted this updated and comprehensive meta-analysis to evaluate this issue, with focus on dose-risk and duration-risk relationships. Methods We searched electronic databases including PUBMED, EMBASE and Cochrane library to identify eligible studies. Relative risk (RR) and its 95% confidence interval (CI) were used for cohort studies, while odds ratio (OR) were employed for case-control studies. The random effects and fixed effects models were used for analyses. Results 18 studies were identified including 19835 lung cancer cases, which were eligible for inclusion in the present meta-analysis. Pooled data from case-control studies showed a significant inverse association between regular aspirin use and lung cancer risk. But for cohort studies, insignificant association was detected with little evidence of heterogeneity (RR: 1.05, 95%CI: 0.95 – 1.16; I2: 10.3%, p value: 0.351). In case-control studies, standard aspirin use (>325mg) was related to lower lung cancer incidence, compared with low-dose aspirin use (75–100mg). A similar trend was observed in cohort studies. Besides, when analysis was restricted to long time regular aspirin use (>5 years), insignificant results were reported in both cohort and case-control studies. Finally, regular aspirin use might result in higher reduction of non-small cell lung cancer incidence among men. Conclusions Our findings do not support the protective effect of regular aspirin use on lung cancer risk. Long time aspirin use, sex, dose and type of lung cancer might alter the effect of aspirin use on lung cancer risk. More well-designed studies are needed to further clarify these associations. PMID:25849465

  18. Alcohol drinking and the risk of colorectal cancer death: a meta-analysis.

    PubMed

    Cai, Shaofang; Li, Yingjun; Ding, Ye; Chen, Kun; Jin, Mingjuan

    2014-11-01

    A causal link between alcohol consumption and colorectal cancer (CRC) was established only recently by the International Agency for Research on Cancer. However, the quantitative association between alcohol drinking and CRC mortality is still an open question. We performed a systemic review and meta-analysis on epidemiological studies to quantify the risk for CRC mortality at different levels of alcohol consumption. A literature search was carried out in PubMed and Web of Science to identify all relevant studies published from January 1966 to June 2013. The pooled relative risk (RR) and the corresponding 95% confidence interval (CI) were estimated by categorical meta-analysis. A dose-risk relation was also analyzed. Nine cohort studies exploring the association between CRC mortality and alcohol drinking were identified. Compared with non/occasional drinkers, the pooled RR was 1.03 (95% CI, 0.93-1.15) for any, 0.97 (95% CI, 0.86-1.10) for light (≤12.5 g/day of ethanol), 1.04 (95% CI, 0.94-1.16) for moderate (12.6-49.9 g/day of ethanol), and 1.21 (1.01-1.46) for heavy drinkers (≥50 g/day of ethanol). For heavy drinkers, the pooled estimate was apparently higher for men (RR=1.28; 95% CI, 1.13-1.46) than for women (RR=0.79; 95% CI, 0.40-1.54; P(heterogeneity)=0.007). The dose-response analysis showed a J-shaped relationship between alcohol consumption and CRC mortality. The present meta-analysis provides the evidence for an association between heavy alcohol drinking (≥50 g/day of ethanol) and CRC mortality.

  19. Metabolic syndrome is associated with increased breast cancer risk: a systematic review with meta-analysis.

    PubMed

    Bhandari, Ruchi; Kelley, George A; Hartley, Tara A; Rockett, Ian R H

    2014-01-01

    Background. Although individual metabolic risk factors are reported to be associated with breast cancer risk, controversy surrounds risk of breast cancer from metabolic syndrome (MS). We report the first systematic review and meta-analysis of the association between MS and breast cancer risk in all adult females. Methods. Studies were retrieved by searching four electronic reference databases [PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, and ProQuest through June 30, 2012] and cross-referencing retrieved articles. Eligible for inclusion were longitudinal studies reporting associations between MS and breast cancer risk among females aged 18 years and older. Relative risks and 95% confidence intervals were calculated for each study and pooled using random-effects models. Publication bias was assessed quantitatively (Trim and Fill) and qualitatively (funnel plots). Heterogeneity was examined using Q and I (2) statistics. Results. Representing nine independent cohorts and 97,277 adult females, eight studies met the inclusion criteria. A modest, positive association was observed between MS and breast cancer risk (RR: 1.47, 95% CI, 1.15-1.87; z = 3.13; p = 0.002; Q = 26.28, p = 0.001; I (2) = 69.55%). No publication bias was observed. Conclusions. MS is associated with increased breast cancer risk in adult women.

  20. P53 codon 72 Arg/Pro polymorphism and lung cancer risk in Asians: an updated meta-analysis.

    PubMed

    Wang, Siyang; Lan, Xingang; Tan, Sheng; Wang, Siwen; Li, Yu

    2013-10-01

    The polymorphism of p53 codon 72, a transversion of G to C (Arg to Pro), has been demonstrated to be associated with the risk for lung cancer. However, individual studies conducted in Asians have provided conflicting and inconclusive findings. Thus, we performed a meta-analysis by pooling all currently available case-control studies to estimate the effect of p53 codon 72 Arg/Pro polymorphism on the development of lung cancer. The pooled odds ratios (ORs) with the corresponding 95 % confidence intervals (95 %CIs) were calculated to assess this effect. A total of 14 individual studies involving 7,929 cases and 5,924 controls were included into this meta-analysis according to the inclusion criteria. The overall OR for the dominant genetic model indicated that the p53 codon 72 Arg/Pro variant was positively correlated with lung cancer risk (ORArg/Pro + Pro/Pro vs. Arg/Arg = 1.14, 95 %CI 1.07-1.23, P OR < 0.001). Similar results were found in the stratified analysis of population-based studies. The histological types of lung cancer and smoking status seemed to exert no effect on the lung cancer risk. Sensitivity analysis confirmed the stability of the above findings. The updated meta-analysis suggests that the p53 codon 72 Arg/Pro polymorphism is a risk factor for lung cancer in the Asian population. However, the potential role of gene-environment interaction in lung cancer susceptibility needs further investigation in future studies with high quality.

  1. Association between the XRCC3 polymorphisms and breast cancer risk: meta-analysis based on case-control studies.

    PubMed

    He, Xiao-Feng; Wei, Wu; Su, Jiao; Yang, Zi-Xuan; Liu, Yi; Zhang, Ying; Ding, Da-Peng; Wang, Wei

    2012-05-01

    The previous published data on the association between X-ray repair cross-complementing group 3 (XRCC3) T241M, A4541G, and A17893G polymorphisms and breast cancer risk remained controversial. Hence, we performed a meta-analysis to investigate the association between breast cancer and XRCC3 T241M (21,910 cases and 23,961 controls), A4541G (9,633 cases and 10,994 controls), and A17893G polymorphisms (10,761 cases and 12,235 controls) in different inheritance models. When all the eligible studies were pooled into the meta-analysis of XRCC3 T241M polymorphism, significantly increased risk of breast cancer was observed in recessive model (odds' ratio [OR] = 1.10, 95% confidence interval [CI] = 1.04-1.16) and in additive model (OR = 1.10, 95% CI = 1.03-1.16). No significant association was found between A4541G polymorphism and breast cancer risk. When all the eligible studies were pooled into the meta-analysis of XRCC3 A17893G polymorphism, no significant association was found in any genetic model. Additionally, when one study was deleted in the sensitive analysis, the results of XRCC3 A17893G were changed in the additive model (OR = 0.90, 95% CI = 0.82-0.99) and dominant model (OR = 0.94, 95% CI = 0.89-0.99). In summary, this meta-analysis indicates that T241M polymorphism show an increased breast cancer risk and A17893G polymorphism may be associated with decreased breast cancer risk. A study with the larger sample size is needed to further evaluated gene-environment interaction on XRCC3 T241M, A4541G, and A17893G polymorphisms and breast cancer risk.

  2. Polychlorinated biphenyls and breast cancer: A congener-specific meta-analysis.

    PubMed

    Leng, Ling; Li, Jing; Luo, Xiu-mei; Kim, Jun-young; Li, Yi-meng; Guo, Xue-mei; Chen, Xi; Yang, Qiao-yun; Li, Guang; Tang, Nai-jun

    2016-03-01

    The incidence of breast cancer is related to various risk factors, especially that the environmental and lifestyle factors account for major contribution at the rate of 70% to 95% over all. However, there still remains some controversy over the epidemiological evidence regarding the effects of environmental carcinogens on the risk of breast cancer. We conducted a quantitative meta-analysis aiming at full evaluation of the effects of polychlorinated biphenyls (PCBs) on breast cancer in a congener-specific fashion. Four online literature databases were systematically searched before 1st January 2015, for studies stating correlation between PCB congeners and breast cancer. The Newcastle-Ottawa Scale was used to evaluate the quality of the studies that were included in our analysis. Sixteen studies were included in our final meta-analysis after screening based on the priori inclusion criteria. Nine PCB congeners were reported by more than two studies and they were presented in detail. The pooled Odds Ratios (ORs) showed a significant increase in the risk of breast cancer in individuals with higher plasma/fat levels of PCB 99 (OR: 1.36; 95% CI: 1.02 to 1.80), PCB 183 (OR: 1.56; 95% CI: 1.25 to 1.95) and PCB 187 (OR: 1.18; 95% CI: 1.01 to 1.39). Besides, the outcomes did not support a relationship between dioxin-like PCB congeners and the risk of breast cancer. The results of our meta-analysis imply that PCB 99, PCB 183 and PCB 187 would increase the risk of breast cancer. The mechanism of this increased risk may be by the induction of the CYP2B family in cytochrome P450 enzymes.

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

    PubMed

    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

    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.

  4. Flavonoids, Flavonoid Subclasses, and Esophageal Cancer Risk: A Meta-Analysis of Epidemiologic Studies.

    PubMed

    Cui, Lingling; Liu, Xinxin; Tian, Yalan; Xie, Chen; Li, Qianwen; Cui, Han; Sun, Changqing

    2016-06-08

    Flavonoids have been suggested to play a chemopreventive role in carcinogenesis. However, the epidemiologic studies assessing dietary intake of flavonoids and esophageal cancer risk have yielded inconsistent results. This study was designed to examine the association between flavonoids, each flavonoid subclass, and the risk of esophageal cancer with a meta-analysis approach. We searched for all relevant studies with a prospective cohort or case-control study design published from January 1990 to April 2016, using PUBMED, EMBASE, and Web of Science. Pooled odds ratios (ORs) were calculated using fixed or random-effect models. In total, seven articles including 2629 cases and 481,193 non-cases were selected for the meta-analysis. Comparing the highest-intake patients with the lowest-intake patients for total flavonoids and for each flavonoid subclass, we found that anthocyanidins (OR = 0.60, 95% CI: 0.49-0.74), flavanones (OR = 0.65, 95% CI: 0.49-0.86), and flavones (OR = 0.78, 95% CI 0.64-0.95) were inversely associated with the risk of esophageal cancer. However, total flavonoids showed marginal association with esophageal cancer risk (OR = 0.78, 95% CI: 0.59-1.04). In conclusion, our study suggested that dietary intake of total flavonoids, anthocyanidins, flavanones, and flavones might reduce the risk of esophageal cancer.

  5. Impact of XRCC2 Arg188His Polymorphism on Cancer Susceptibility: A Meta-Analysis

    PubMed Central

    Deng, Xiangbing; Wei, Mingtian; Wu, Qingbin; Yang, Tinghan; Zhou, Yanhong; Wang, Ziqiang

    2014-01-01

    Background Association between the single nucleotide polymorphism rs3218536 (known as Arg188His) located in the X-ray repair cross complementing group 2 (XRCC2) gene and cancer susceptibility has been widely investigated. However, results thus far have remained controversial. A meta-analysis was performed to identify the impact of this polymorphism on cancer susceptibility. Methods PubMed and Embase databases were searched systematically until September 7, 2013 to obtain all the records evaluating the association between the XRCC2 Arg188His polymorphism and the risk of all types of cancers. We used the odds ratio (OR) as measure of effect, and pooled the data in a Mantel-Haenszel weighed random-effects meta-analysis to provide a summary estimate of the impact of this polymorphism on breast cancer, ovarian cancer and other cancers. All the analyses were carried out in STATA 12.0. Results With 30868 cases and 38656 controls, a total of 45 case-control studies from 26 publications were eventually included in our meta-analysis. No significant association was observed between the XRCC2 Arg188His polymorphism and breast cancer susceptibility (dominant model: OR = 0.94, 95%CI = 0.86–1.04, P = 0.232). However, a significant impact of this polymorphism was detected on decreased ovarian cancer risk (dominant model: OR = 0.83, 95%CI = 0.73–0.95, P = 0.007). In addition, we found this polymorphism was associated with increased upper aerodigestive tract (UADT) cancer susceptibility (dominant model: OR = 1.51, 95%CI = 1.04–2.20, P = 0.032). Conclusion The Arg188His polymorphism might play different roles in carcinogenesis of various cancer types. Current evidence did not suggest that this polymorphism was directly associated with breast cancer susceptibility. However, this polymorphism might contribute to decreased gynecological cancer risk and increased UADT cancer risk. More preclinical and epidemiological studies were still imperative

  6. The efficacy and toxicity profile of metronomic chemotherapy for metastatic breast cancer: A meta-analysis

    PubMed Central

    Liang, Jinyan; Dai, Xiaomeng; Wan, Chao; Hong, Xiaohua; Zhang, Kai; Liu, Li

    2017-01-01

    Purpose The current meta-analysis aimed to summarize the available evidence for the efficacy and serious adverse events (AEs) associated with use of metronomic chemotherapy (MCT) in patients with metastatic breast cancer (MBC). Method Electronic databases (PubMed, EMBASE database, Web of Knowledge, and the Cochrane database) were systematically searched for articles related to the use of MCT in MBC patients. Eligible studies included clinical trials of MBC patients treated with MCT that presented sufficient data related to tumor response, progression-free survival (PFS), overall survival (OS), and grade 3/4 AEs. A meta-analysis was performed using a random effects model. Results This meta-analysis consists of 22 clinical trials with 1360 patients. The pooled objective response rate and clinical benefit rate of MCT were 34.1% (95% CI 27.4–41.5) and 55.6% (95% CI 49.2–61.9), respectively. The overall 6-month PFS, 12-month OS, and 24-month OS rates were 56.8% (95% CI 48.3–64.9), 70.3% (95% CI 62.6–76.9), and 40.0% (95% CI 30.6–50.2), respectively. The pooled incidence of grade 3/4 AEs was 29.5% (95% CI 21.1–39.5). There was no statistically significant difference observed in any endpoint between subgroups defined by concomitant anti-cancer therapies or chemotherapy regimens. After excluding one controversial study, we observed a trend showing lower toxicity rates with the use of MCT alone compared to use of MCT with other anti-cancer therapies (P = 0.070). Conclusions Metronomic chemotherapy may be effective for use in patients with metastatic breast cancer. MCT used alone is possibly equally effective and less toxic than combination therapies. Well-designed RCTs are needed to obtain more evidence. PMID:28296916

  7. Multiplex sequencing of pooled mitochondrial genomes-a crucial step toward biodiversity analysis using mito-metagenomics.

    PubMed

    Tang, Min; Tan, Meihua; Meng, Guanliang; Yang, Shenzhou; Su, Xu; Liu, Shanlin; Song, Wenhui; Li, Yiyuan; Wu, Qiong; Zhang, Aibing; Zhou, Xin

    2014-12-16

    The advent in high-throughput-sequencing (HTS) technologies has revolutionized conventional biodiversity research by enabling parallel capture of DNA sequences possessing species-level diagnosis. However, polymerase chain reaction (PCR)-based implementation is biased by the efficiency of primer binding across lineages of organisms. A PCR-free HTS approach will alleviate this artefact and significantly improve upon the multi-locus method utilizing full mitogenomes. Here we developed a novel multiplex sequencing and assembly pipeline allowing for simultaneous acquisition of full mitogenomes from pooled animals without DNA enrichment or amplification. By concatenating assemblies from three de novo assemblers, we obtained high-quality mitogenomes for all 49 pooled taxa, with 36 species >15 kb and the remaining >10 kb, including 20 complete mitogenomes and nearly all protein coding genes (99.6%). The assembly quality was carefully validated with Sanger sequences, reference genomes and conservativeness of protein coding genes across taxa. The new method was effective even for closely related taxa, e.g. three Drosophila spp., demonstrating its broad utility for biodiversity research and mito-phylogenomics. Finally, the in silico simulation showed that by recruiting multiple mito-loci, taxon detection was improved at a fixed sequencing depth. Combined, these results demonstrate the plausibility of a multi-locus mito-metagenomics approach as the next phase of the current single-locus metabarcoding method.

  8. LinguisticBelief and PoolEvidence

    SciTech Connect

    DARBY, JOHN

    2008-03-11

    LinguisticBelief allows the creation and analysis of combinations of linguistic variables with epistemic uncertainty for decision making. The model is solved using approximate reasoning to implement the belief/plausibility measure of uncertainty for combinations of variables expressed as purely linguistic fuzzy sets. PoolEvidence pools evidence for linguistic variables from many experts for input into LinguisticBelief.

  9. Prognostic Significance of VEGF-C Expression in Patients with Breast Cancer: A Meta-Analysis

    PubMed Central

    LIANG, Bin; LI, Yunhui

    2014-01-01

    Abstract Background Vascular endothelial growth factor (VEGF)-C, as a lymphangiogenic factor, plays important roles in the progression of several malignancies. However, its clinical prognostic value in breast cancer still remains controversial. We performed a meta-analysis of available studies to assess the association between VEGF-C expression and the ou-tcomes of breast cancer patients Methods We searched eligible studies in three English databases (MEDLINE, EMBASE, and Web of Science) and two Chinese databases (Wanfang and Chinese National Knowledge Infrastructure databases). Key words used in the research included ‘VEGF-C”, “breast cancer”, “immunohistochemistry”, “breast neoplasma(s)”, “breast carcinoma”, “metastasis”, and “prognosis”. Fourteen studies with a total of 1, 573 breast cancer cases were finally included into the meta-analysis. The pooled odds ratios (ORs) with the corresponding 95% confidence interval (95% CIs) for lymph node metastasis, overall survival, and disease-free survival were calculated by using fixed-effects or random-effects models. Heterogeneity and publication bias were also assessed. Results Meta-analysis of random-effects model showed VEGF-C expression was associated with lymph node metastasis in patients with breast cancer (random-effects, OR = 2.14; 95 % CI 1.21—3.77, P = 0.009). VEGF-C expression was associated with poorer overall survival (fixed-effects, OR = 2.46, 95% CI: 1.46—4.14, P < 0.001) and disease-free survival (fixed-effects, OR = 2.10, 95% CI: 1.32—3.35, P = 0.002) in patients with breast cancer. Conclusion VEGF-C expression is positively associated with lymph node metastasis in breast cancer, and VEGF-C detection in breast cancer might be an effective and feasible means to predict outcome. PMID:26060735

  10. Pyruvate kinase M2 (PKM2) expression correlates with prognosis in solid cancers: a meta-analysis

    PubMed Central

    Zhu, Xuejie; Hu, Xiaoli; Zheng, Lihong; Zhu, Xueqiong

    2017-01-01

    Pyruvate kinase M2 (PKM2) is the key enzyme in the Warburg effect and plays a central role in cancer cell metabolic reprogramming. Recently, quite a few studies have investigated the correlation between PKM2 expression and prognosis in multiple cancer patients, but results were inconsistent. We therefore performed a meta-analysis to explore the prognostic value of PKM2 expression in patients with solid cancer. Here twenty-seven individual studies from 25 publications with a total of 4796 cases were included to explore the association between PKM2 and overall survival (OS) or disease-free survival (DFS)/ progression-free survival (PFS)/ recurrent-free survival (RFS) in subjects with solid cancer. Pooled analysis showed that high levels of PKM2 was significantly associated with a poorer overall survival (HR = 1.73; 95%CI = 1.48-2.03) and DFS/ PFS/ RFS (HR = 1.90; 95%CI = 1.39-2.59) irrespective of cancer types. Different analysis models (univariate or multivariate models), sample-sizes (≤100 or >100), and methods for data collection (direct extraction or indirect extraction) had no impact on the negative prognostic effect of PKM2 over-expression. Nevertheless, stratified by cancer type, high-expression of PKM2 was associated with an unfavorable OS in breast cancer, esophageal squamous carcinoma, hepatocellular carcinoma and gallbladder cancer; whereas was not correlated with a worse OS in pancreatic cancer and gastric cancer. In conclusion, over-expression of PKM2 is associated with poor prognosis in most solid cancers and it might be a potentially useful biomarker for predicting cancer prognosis in future clinical applications. PMID:27911861

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

    SciTech Connect

    Choi, Insup.

    1989-01-01

    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.

  12. Indacaterol/glycopyrronium in symptomatic patients with COPD (GOLD B and GOLD D) versus salmeterol/fluticasone: ILLUMINATE/LANTERN pooled analysis

    PubMed Central

    Vogelmeier, Claus; Zhong, Nanshan; Humphries, Michael J; Mezzi, Karen; Fogel, Robert; Bader, Giovanni; Patalano, Francesco; Banerji, Donald

    2016-01-01

    Background Indacaterol/glycopyrronium (IND/GLY) is approved for maintenance treatment of adult patients with COPD. This post hoc analysis explored the efficacy and safety of IND/GLY versus salmeterol/fluticasone (SFC) in symptomatic (Global Initiative for Chronic Obstructive Lung Disease [GOLD] B and GOLD D) patients with moderate-to-severe COPD. Patients and methods Data from LANTERN and ILLUMINATE studies were pooled and analyzed. In both studies, symptomatic COPD patients were randomized to once-daily IND/GLY 110 μg/50 μg or twice-daily SFC 50 μg/500 μg. End points were pre-dose trough forced expiratory volume in one second (FEV1), standardized area under the curve for FEV1 from 0 to 12 hours (FEV1 AUC0–12 hours), peak FEV1, peak forced vital capacity (FVC), pre-dose trough FVC, Transition Dyspnea Index (TDI) total score, St George’s Respiratory Questionnaire total score, rescue medication use and safety. Results A total of 1,263 patients were classified as either GOLD B (n=809) or GOLD D (n=454). At week 26, IND/GLY demonstrated statistically significant improvement in all lung function parameters versus SFC in patients in both the GOLD B and GOLD D subgroups. TDI total score and rescue medication use were significantly improved with IND/GLY versus SFC in the overall population and in the GOLD B (TDI total score only) and GOLD D (rescue medication only) subgroups. IND/GLY also reduced the rate of exacerbations in the pooled population. Overall safety profile was comparable with a higher incidence of pneumonia in the SFC-treated group. Conclusion In this pooled analysis, IND/GLY demonstrated superior efficacy compared with SFC in patients in the GOLD B and GOLD D subgroups and supported its use in symptomatic COPD patients. PMID:28008244

  13. Predictors of outcome following venlafaxine extended-release treatment of DSM-IV generalized anxiety disorder: a pooled analysis of short- and long-term studies.

    PubMed

    Pollack, Mark H; Meoni, Paolo; Otto, Michael W; Simon, Naomi; Hackett, David

    2003-06-01

    This pooled analysis evaluated potential predictive abilities of baseline demographic factors, psychiatric history, and DSM-IV diagnostic criteria for short- and long-term outcome after treatment with venlafaxine extended release (XR) or placebo in patients with generalized anxiety disorder (GAD). Pooled data from 1,839 patients in five placebo-controlled studies of venlafaxine XR for GAD were analyzed by logistic regression. Odds ratios (ORs) were used to quantify pretreatment factors' abilities to predict response (50% reduction, baseline Hamilton Rating Scale for Anxiety [HAM-A] severity) and remission (total HAM-A score pooled analysis to date, pretreatment factors were associated with treatment outcome in patients with GAD receiving venlafaxine XR or placebo. The strongest trends emerged for history of substance abuse or dependence and symptoms of restlessness, sleep disturbance, and difficulty concentrating.

  14. Utility of a Genetic Risk Score to Predict Recurrent Cardiovascular Events 1 Year After an Acute Coronary Syndrome: A Pooled Analysis of the RISCA, PRAXY, and TRIUMPH Cohorts

    PubMed Central

    Labos, Christopher; Martinez, Sara C.; Leo Wang, Rui Hao; Lenzini, Petra A.; Pilote, Louise; Bogaty, Peter; Brophy, James M.; Engert, James C.; Cresci, Sharon; Thanassoulis, George

    2015-01-01

    Background Limited evidence exists regarding the utility of genetic risk scores (GRS) in predicting recurrent cardiovascular events after acute coronary syndrome (ACS). We sought to determine whether a GRS would predict early recurrent cardiovascular events within 1 year of ACS. Methods & Results Participants admitted with acute coronary syndromes from the RISCA, PRAXY, and TRIUMPH cohorts, were genotyped for 30 single nucleotide polymorphisms (SNPs) associated with coronary artery disease (CAD) or myocardial infarction (MI) in prior genome wide association studies. A 30 SNP CAD/MI GRS was constructed. The primary endpoint was defined as all-cause mortality, recurrent ACS or cardiac re-hospitalization within 1 year of ACS admission. Results across all cohorts for the 30 SNP CAD/MI GRS were pooled using a random-effects model. There were 1040 patients from the RISCA cohort, 691 patients from the PRAXY cohort, and 1772 patients from the TRIUMPH cohort included in the analysis and 389 occurrences of the primary endpoint of recurrent events at 1-year post-ACS. In unadjusted and fully adjusted analyses, a 30 SNP GRS was not significantly associated with recurrent events (HR per allele 0.97 (95%CI 0.91–1.03) for RISCA, HR 0.99 (95%CI 0.93–1.05) for PRAXY, 0.98 (95%CI 0.94–1.02) for TRIUMPH, and 0.98 (95%CI 0.95–1.01) for the pooled analysis). Addition of this GRS to the GRACE risk model did not significantly improve risk prediction. Conclusion The 30 MI SNP GRS was not associated with recurrent events 1-year post ACS in pooled analyses across cohorts and did not improve risk discrimination or reclassification indices. Our results suggest that the genetic etiology of early events post-ACS may differ from later events. PMID:26232166

  15. Increased Risk of Pancreatic Cancer Related to Gallstones and Cholecystectomy: A Systematic Review and Meta-Analysis.

    PubMed

    Fan, Yonggang; Hu, Jie; Feng, Bing; Wang, Wei; Yao, Guoliang; Zhai, Jingming; Li, Xin

    2016-04-01

    To investigate the potential roles of gallstones and cholecystectomy in pancreatic carcinogenesis, we performed the first meta-analysis of all currently published studies by pooling relative risks (RRs) with 95% confidence intervals (95% CIs). Stratified analysis by ethnicity, study design, and common adjusted factors were also conducted. Individuals with a history of gallstones and cholecystectomy were at increased risk of pancreatic cancer (RR, 1.39; 95% CI, 1.28-1.52; P < 0.001). Gallstones and cholecystectomy were also associated with an elevated risk of pancreatic cancer, respectively (for gallstones: RR, 1.70; 95% CI, 1.30-2.21; P < 0.001; for cholecystectomy: RR, 1.31; 95% CI, 1.19-1.43; P < 0.001). The positive association is observed among not only the Asian population but also whites. The pooled findings were further confirmed by sensitivity analysis and stratified analyses in case-control and cohort studies. Stratified analyses by different adjusted factors further showed that the increased risk of pancreatic cancer was independent of confounders including diabetes, obesity, smoking, and follow-up years of postcholecystectomy. A history of gallstones and cholecystectomy is a robust risk factor for pancreatic cancer. Gallstone disease or cholecystectomy alone is also an independent risk factor for pancreatic carcinogenesis.

  16. The association between prognosis of breast cancer and first-degree family history of breast or ovarian cancer: a systematic review and meta-analysis.

    PubMed

    Song, Jun-Long; Chen, Chuang; Yuan, Jing-Ping; Sun, Sheng-Rong

    2017-02-07

    Whether a positive family history of breast cancer or ovarian cancer (FHBOC) would affect the prognosis of breast cancer is still up for debate and further study. This meta-analysis was performed to clarify this issue. We reviewed two databases (PubMed and CNKI) for research articles published at any time from the inception of these databases to April 1, 2016 for articles detecting the impact of FHBOC on the prognosis of breast cancer. A meta-analysis was conducted to generated combined hazard ratios (HR) with 95% confidence intervals (CI) for overall survival (OS) and breast cancer-specific survival (BCSS). Eighteen studies were included in our qualitative analysis, with 15 studies ultimately part of the quantitative analysis. The pooled results demonstrated that a positive FHBOC was associated with better OS (0.89, 95% CI 0.83-0.95) and BCSS (0.90, 95% CI 0.82-0.99). In subgroup analyses, several subgroups (maximally adjusted studies, population based studies, high quality studies, family history of breast cancer, studies from Europe, studies from Asia, 1 affected relative, or tumor size > 2 cm), a positive first-degree FHBOC was associated with better prognosis of breast cancer. Notably, for those patients who underwent breast-conserving surgery, first-degree FHBOC was not a risk factor for OS (HR 1.08, 95% CI 0.53-2.21). Our meta-analysis demonstrated that a first-degree FHBOC was associated with better OS and BCSS in patients with breast cancer. These findings support that clinical management should not differ between women with and without FHBOC.

  17. Pesticide exposure and risk of bladder cancer: A meta-analysis

    PubMed Central

    Xie, Bo; Zhu, Yi; Wu, Jian; Li, Shiqi; Meng, Shuai; Zheng, Xiangyi; Ji, Alin; Xie, Liping

    2016-01-01

    Objective We conducted a meta-analysis to quantitatively evaluate the correlation between pesticide exposure and the risk of bladder cancer by summarizing the results of published case-control and cohort studies. Methods A systematic literature search of articles update to February 2015 was conducted via Pubmed, Web of Science, Cochrane Library, and the Chinese National Knowledge Infrastructure (CNKI) databases, and the references of the retrieved articles. Fixed- or random-effect models were used to summarize the estimates of OR with 95% CIs for the highest versus the lowest exposure of pesticide. Results The pooled OR estimates indicated that pesticide exposure was associated with an increased risk of bladder cancer (OR=1.649, 95% CI 1.223-2.223). In subgroup analysis, we detected pesticide exposure demonstrated as a significant risk factor on bladder cancer in America (OR=1.741, 95% CI 1.270-2.388). Similar results were discovered in both case-control group and cohort group (OR=2.075, 95% CI 1.183-3.638, OR=1.146, 95% CI 1.074-1.223, respectively). No evidence of publication bias was found by Begg's or Egger's test (P = 0.210, P = 0.358, respectively). Conclusion In conclusion, our meta-analysis indicated that pesticide exposure was associated with an increased risk of bladder cancer. Further researches should be conducted to confirm the findings in our study and better clarify the potential biological mechanisms. PMID:27557494

  18. Coffee Consumption and Risk of Gastric Cancer: A Large Updated Meta-Analysis of Prospective Studies

    PubMed Central

    Xie, Feiyue; Wang, Dan; Huang, Zhifang; Guo, Yajun

    2014-01-01

    The potential role of coffee consumption in the development of various types of cancer has been extensively investigated in epidemiologic studies. How coffee consumption may modulate risk of gastric cancer, however, remains a subject open for investigation. To better quantify this relation, we quantitatively summarized evidence from prospective studies. Eligible studies were identified on PubMed databases. The summary risk estimates were obtained using the random-effects model. Subgroup, sensitivity and dose-response analyses were conducted. The present meta-analysis included 12 prospective cohort studies. A pooled analysis of these studies suggested that coffee consumption (highest vs. lowest consumption) was not associated with risk of gastric cancer (RR = 1.12, 95% CI = 0.93–1.36). In the subgroup analysis, significant increased risk was detected in the U.S. studies (RR = 1.36, 95% CI = 1.06–1.74) and in the studies with <10 years of follow-up (RR = 1.24, 95% CI = 1.00–1.54), and the greatest increase in risk was observed in those studies without adjustment for smoking (RR = 1.48, 95% CI = 1.13–1.93). There was some evidence of publication bias (P for Egger’s test = 0.03). Cumulative evidence from prospective studies suggests that coffee consumption is not associated with risk of gastric cancer. The observed positive results may be confounded by smoking and need further investigation. PMID:25237829

  19. Coffee consumption and risk of gastric cancer: a large updated meta-analysis of prospective studies.

    PubMed

    Xie, Feiyue; Wang, Dan; Huang, Zhifang; Guo, Yajun

    2014-09-18

    The potential role of coffee consumption in the development of various types of cancer has been extensively investigated in epidemiologic studies. How coffee consumption may modulate risk of gastric cancer, however, remains a subject open for investigation. To better quantify this relation, we quantitatively summarized evidence from prospective studies. Eligible studies were identified on PubMed and Embase databases. The summary risk estimates were obtained using the random-effects model. Subgroup, sensitivity and dose-response analyses were conducted. The present meta-analysis included 12 prospective cohort studies. A pooled analysis of these studies suggested that coffee consumption (highest vs. lowest consumption) was not associated with risk of gastric cancer (RR = 1.12, 95% CI = 0.93-1.36). In the subgroup analysis, significant increased risk was detected in the U.S. studies (RR = 1.36, 95% CI = 1.06-1.74) and in the studies with <10 years of follow-up (RR = 1.24, 95% CI = 1.00-1.54), and the greatest increase in risk was observed in those studies without adjustment for smoking (RR = 1.48, 95% CI = 1.13-1.93). There was some evidence of publication bias (P for Egger's test = 0.03). Cumulative evidence from prospective studies suggests that coffee consumption is not associated with risk of gastric cancer. The observed positive results may be confounded by smoking and need further investigation.

  20. Effects of physical exercise during adjuvant breast cancer treatment on physical and psychosocial dimensions of cancer-related fatigue: A meta-analysis.

    PubMed

    van Vulpen, Jonna K; Peeters, Petra H M; Velthuis, Miranda J; van der Wall, Elsken; May, Anne M

    2016-03-01

    Cancer-related fatigue has a multidimensional nature and complaints typically increase during adjuvant treatment for breast cancer. Physical exercise might prevent or reduce cancer-related fatigue. So far, no meta-analysis has investigated the effects of physical exercise on different dimensions of fatigue. The aim of the present meta-analysis was to investigate the effects of physical exercise during adjuvant breast cancer treatment on physical and psychosocial dimensions of fatigue. We performed a systematic literature search in PubMed, Embase and the Cochrane Library in June 2015. Randomised controlled trials reporting the effects of physical exercise during adjuvant breast cancer treatment on different dimensions of fatigue were included. Pooled effects of 6 exercise programmes (including 784 patients) showed significant beneficial exercise effects on general fatigue (ES: -0.22, 95% CI -0.38; -0.05) and physical fatigue (ES: -0.35, 95% CI -0.49; -0.21). Effects on fatigue subscales 'reduced activity' (ES: -0.22, 95% CI -0.38; -0.05) and 'reduced motivation' (ES: -0.18, 95% CI -0.35; -0.01) were also in favour of physical exercise. No effects were found on cognitive and affective fatigue. Including only the supervised exercise programmes (n=4 studies), slightly larger pooled effect estimates were found on general fatigue (ES: -0.25, 95% CI -0.47; -0.04) and physical fatigue (-0.39, 95% CI -0.56; -0.23). In conclusion, physical exercise during adjuvant breast cancer treatment has beneficial effects on general fatigue, physical fatigue, 'reduced activity' and 'reduced motivation', but did not show effects on cognitive and affective fatigue. Largest effect sizes are found for physical fatigue, suggesting that this is the fatigue dimension most sensitive to physical exercise.

  1. GSTM1 polymorphism is related to risks of nasopharyngeal cancer and laryngeal cancer: a meta-analysis

    PubMed Central

    Zhang, Fengying; Wu, Xijiang; Niu, Jinming; Kang, Xiufeng; Cheng, Liya; Lv, Yanchun; Wu, Meimei

    2017-01-01

    Background Accumulating data have reported that GSTM1 polymorphism may be related to nasopharyngeal cancer (NPC) and laryngeal cancer (LC). This meta-analysis was performed to investigate the relationship between GSTM1 polymorphism and risks of NPC and LC. Methods Pubmed, Embase, and China National Knowledge Infrastructure (CNKI) databases were searched for potential articles. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the relationship of GSTM1 polymorphism with the risks of NPC and LC. I2>50% or P<0.05 indicates significant heterogeneity. When heterogeneity existed, the random-effects model was used to pool data, otherwise, the fixed-effects model was adopted. Publication bias was detected by Begg’s funnel plot and Egger’s regression. Quality of each study was evaluated by Newcastle-Ottawa Scale. Results Thirty-two eligible articles were included. Pooled outcome suggested the significant relationship of GSTM1 null genotype with increased risk of LC (OR =1.28, 95% CI =1.05–1.54). Compared with hospital-based (HB) population, GSTM1 null genotype was also related to increased risk of LC (OR =1.38, 95% CI =1.06–1.80). Positive relationship of GSTM1 null genotype with enhanced risk of NPC was observed (OR =1.43, 95% CI =1.26–1.63). A similar trend was also observed in the subgroup analysis by source of control (population-based [PB]: OR =1.39, 95% CI =1.18–1.63; HB: OR =1.52, 95% CI =1.22–1.89). Conclusion GSTM1 null genotype is related to increased risk of NPC and LC. PMID:28331336

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

    PubMed

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

    2014-08-01

    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.

  3. HMGB1 overexpression as a prognostic factor for survival in cancer: a meta-analysis and systematic review

    PubMed Central

    Li, Huijun; Chen, Qi; Song, Ruixiang; Zhao, Lin

    2016-01-01

    As there are millions of cancer deaths every year, it is of great value to identify applicable prognostic biomarkers. As an important alarm, the prognostic role of high mobility group box 1 (HMGB1) in cancer remains controversial. We aim to assess the association of HMGB1 expression with prognosis in cancer patients. Systematic literature searches of PubMed, Embase and Web of Science databases were performed for eligible studies of HMGB1 as prognostic factor in cancer. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the influence of HMGB1 expression on overall survival (OS) and progression-free survival (PFS) in cancer patients. 18 studies involving 11 different tumor types were included in meta-analysis. HMGB1 overexpression was significantly associated with poorer OS (HR: 1.99; 95% CI, 1.71-2.31) and PFS (HR: 2.26; 95% CI, 1.65-3.10) irrespective of cancer types including gastric cancer, colorectal cancer, hepatocellular carcinoma, pancreatic cancer, nasopharyngeal carcinoma, head and neck squamous-cell carcinoma, esophageal cancer, malignant pleural mesothelioma, bladder cancer, prostate cancer, and cervical carcinoma. Subgroup analyses indicated geographical area and size of studies did not affect the prognostic effects of HMGB1 for OS. Morever, HMGB1 overexpression had a consistent correlation with poorer OS when detected by immunohistochemistry in tissues and enzyme-linked immunosorbent assay in serum, whereas the correlation did not exist by quantitative real-time reverse-transcription polymerase chain reaction in tissues. HMGB1 overexpression is associated with poorer prognosis in patients with various types of cancer, suggesting that it is a prognostic factor and potential biomarker for survival in cancer. PMID:27391431

  4. Suicide Attempt Characteristics Among Veterans and Active-Duty Service Members Receiving Mental Health Services: A Pooled Data Analysis

    PubMed Central

    Villatte, Jennifer L.; O’Connor, Stephen S.; Leitner, Rebecca; Kerbrat, Amanda H.; Johnson, Lora L.; Gutierrez, Peter M.

    2015-01-01

    Past suicidal behaviors are among the strongest and most consistent predictors of eventual suicide and may be particularly salient in military suicide. The current study compared characteristics of suicide attempts in veterans (N = 746) and active-duty service members (N = 1,013) receiving treatment for acute suicide risk. Baseline data from six randomized controlled trials were pooled and analyzed using robust regression. Service members had greater odds of having attempted suicide relative to veterans, though there were no differences in number of attempts made. Service members also had higher rates of premilitary suicide attempts and nonsuicidal self-injury (NSSI). Veterans disproportionately attempted suicide by means of overdose. In veterans, combat deployment was associated with lower odds of lifetime suicide attempt, while history of NSSI was associated with greater attempt odds. Neither was significantly associated with lifetime suicide attempt in service members. Implications for suicide assessment and treatment are discussed. PMID:26740909

  5. Meta-analysis of the association between APC promoter methylation and colorectal cancer

    PubMed Central

    Ding, Zhenyu; Jiang, Tong; Piao, Ying; Han, Tao; Han, Yaling; Xie, Xiaodong

    2015-01-01

    Previous studies investigating the association between adenomatous polyposis coli (APC) gene promoter methylation and colorectal cancer (CRC) have yielded conflicting results. The aim of this study was to comprehensively evaluate the potential application of the detection of APC promoter methylation to the prevention and treatment of CRC. PubMed, Embase, and MEDLINE (results updated to October 2014) were searched for relevant studies. The effect size was defined as the weighted odds ratio (OR), which was calculated using either the fixed-effects or random-effects model. Prespecified subgroup and sensitivity analyses were conducted to evaluate potential heterogeneity among the included studies. Nineteen studies comprising 2,426 participants were selected for our meta-analysis. The pooled results of nine studies comprising a total of 740 subjects indicated that APC promoter methylation was significantly associated with CRC risk (pooled OR 5.53; 95% confidence interval [CI] 3.50–8.76; P<0.01). Eleven studies with a total of 1,219 patients evaluated the association between APC promoter methylation and the presence of CRC metastasis, and the pooled OR was 0.80 (95% CI 0.44–1.46; P=0.47). A meta-analysis conducted with four studies with a total of 467 patients found no significant correlation between APC promoter methylation and the presence of colorectal adenoma (pooled OR 1.85; 95% CI 0.67–5.10; P=0.23). No significant correlation between APC promoter methylation and patients’ Dukes’ stage, TNM stage, differentiation grade, age, or sex was identified. In conclusion, APC promoter methylation was found to be significantly associated with a higher risk of developing CRC. The findings indicate that APC promoter methylation may be a potential biomarker for the carcinogenesis of CRC. PMID:25632237

  6. Meta-analysis of the association between APC promoter methylation and colorectal cancer.

    PubMed

    Ding, Zhenyu; Jiang, Tong; Piao, Ying; Han, Tao; Han, Yaling; Xie, Xiaodong

    2015-01-01

    Previous studies investigating the association between adenomatous polyposis coli (APC) gene promoter methylation and colorectal cancer (CRC) have yielded conflicting results. The aim of this study was to comprehensively evaluate the potential application of the detection of APC promoter methylation to the prevention and treatment of CRC. PubMed, Embase, and MEDLINE (results updated to October 2014) were searched for relevant studies. The effect size was defined as the weighted odds ratio (OR), which was calculated using either the fixed-effects or random-effects model. Prespecified subgroup and sensitivity analyses were conducted to evaluate potential heterogeneity among the included studies. Nineteen studies comprising 2,426 participants were selected for our meta-analysis. The pooled results of nine studies comprising a total of 740 subjects indicated that APC promoter methylation was significantly associated with CRC risk (pooled OR 5.53; 95% confidence interval [CI] 3.50-8.76; P<0.01). Eleven studies with a total of 1,219 patients evaluated the association between APC promoter methylation and the presence of CRC metastasis, and the pooled OR was 0.80 (95% CI 0.44-1.46; P=0.47). A meta-analysis conducted with four studies with a total of 467 patients found no significant correlation between APC promoter methylation and the presence of colorectal adenoma (pooled OR 1.85; 95% CI 0.67-5.10; P=0.23). No significant correlation between APC promoter methylation and patients' Dukes' stage, TNM stage, differentiation grade, age, or sex was identified. In conclusion, APC promoter methylation was found to be significantly associated with a higher risk of developing CRC. The findings indicate that APC promoter methylation may be a potential biomarker for the carcinogenesis of CRC.

  7. Shotgun metagenomic analysis of metabolic diversity and microbial community structure in experimental vernal pools subjected to nitrate pulse

    PubMed Central

    2013-01-01

    Background Human activities have greatly increased nitrogen (N) levels in natural habitats through atmospheric N deposition and nutrient leaching, which can have large effects on N cycling and other ecosystem processes. Because of the significant role microorganisms play in N cycling, high inputs of nitrogenous compounds, such as nitrate (NO3-), into natural ecosystems could have cascading effects on microbial community structure and the metabolic processes that microbes perform. To investigate the multiple effects of NO3- pollution on microbial communities, we created two shotgun metagenomes from vernal pool microcosms that were either enriched with a solution of 10 mg NO3--N (+NO3-) or received distilled water as a control (−N). Results After only 20 hours of exposure to NO3-, the initial microbial community had shifted toward one containing a higher proportional abundance of stress tolerance and fermentation environmental gene tags (EGTs). Surprisingly, we found no changes to N metabolism EGTs, even though large shifts in denitrification rates were seen between the +NO3- and –N microcosms. Thus, in the absence of NO3- addition, it is plausible that the microbes used other respiratory pathways for energy. Respiratory pathways involving iron may have been particularly important in our –N microcosms, since iron acquisition EGTs were proportionally higher in the –N metagenome. Additionally, we noted a proportional increase in Acidobacteria and Alphaproteobacteria EGTs in response to NO3- addition. These community shifts in were not evident with TRFLP, suggesting that metagenomic analyses may detect fine-scale changes not possible with community profiling techniques. Conclusions Our results suggest that the vernal pool microbial communities profiled here may rely on their metabolic plasticity for growth and survival when certain resources are limiting. The creation of these metagenomes also highlights how little is known about the effects of NO3

  8. BiobankConnect: software to rapidly connect data elements for pooled analysis across biobanks using ontological and lexical indexing

    PubMed Central

    Pang, Chao; Hendriksen, Dennis; Dijkstra, Martijn; van der Velde, K Joeri; Kuiper, Joel; Hillege, Hans L; Swertz, Morris A

    2015-01-01

    Objective Pooling data across biobanks is necessary to increase statistical power, reveal more subtle associations, and synergize the value of data sources. However, searching for desired data elements among the thousands of available elements and harmonizing differences in terminology, data collection, and structure, is arduous and time consuming. Materials and methods To speed up biobank data pooling we developed BiobankConnect, a system to semi-automatically match desired data elements to available elements by: (1) annotating the desired elements with ontology terms using BioPortal; (2) automatically expanding the query for these elements with synonyms and subclass information using OntoCAT; (3) automatically searching available elements for these expanded terms using Lucene lexical matching; and (4) shortlisting relevant matches sorted by matching score. Results We evaluated BiobankConnect using human curated matches from EU-BioSHaRE, searching for 32 desired data elements in 7461 available elements from six biobanks. We found 0.75 precision at rank 1 and 0.74 recall at rank 10 compared to a manually curated set of relevant matches. In addition, best matches chosen by BioSHaRE experts ranked first in 63.0% and in the top 10 in 98.4% of cases, indicating that our system has the potential to significantly reduce manual matching work. Conclusions BiobankConnect provides an easy user interface to significantly speed up the biobank harmonization process. It may also prove useful for other forms of biomedical data integration. All the software can be downloaded as a MOLGENIS open source app from http://www.github.com/molgenis, with a demo available at http://www.biobankconnect.org. PMID:25361575

  9. Efficacy of alirocumab according to background statin type and dose: pooled analysis of 8 ODYSSEY Phase 3 clinical trials

    PubMed Central

    Catapano, Alberico L.; Lee, L. Veronica; Louie, Michael J.; Thompson, Desmond; Bergeron, Jean; Krempf, Michel

    2017-01-01

    Low-density lipoprotein cholesterol (LDL-C) reductions with the PCSK9 monoclonal antibody alirocumab may be affected by background statin dose due to increased PCSK9 levels with higher statin doses. Data from 8 Phase 3 trials conducted with background statin (n = 4629) were pooled by alirocumab dose (75 or 150 mg every 2 weeks) and control (placebo/ezetimibe), and analyzed by background statin type/dose. Overall, 58.4% received high-dose statins (atorvastatin 40–80 mg, rosuvastatin 20–40 mg, simvastatin 80 mg), 28.6% moderate-dose statins (atorvastatin 20–<40 mg, rosuvastatin 10–<20 mg, simvastatin 40–<80 mg), and 12.9% low-dose statins (atorvastatin <20 mg, rosuvastatin <10 mg, simvastatin <40 mg). Mean baseline PCSK9 levels were higher with high versus moderate and low statin doses (318.5 vs 280.6 ng/mL). Baseline LDL-C levels were similar across pools, regardless of statin intensity. No associations were observed between statin type/dose and LDL-C % change from baseline or % of patients achieving LDL-C goals at Week 24 for alirocumab versus control (interaction P-values non-significant). Incidence of adverse events was similar for alirocumab versus control, except for a higher rate of injection-site reactions with alirocumab. In summary, alirocumab provided consistent LDL-C reductions and was generally well tolerated independent of background statin type/dose. PMID:28374849

  10. 13 CFR 120.611 - Pools backing Pool Certificates.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Pools backing Pool Certificates. 120.611 Section 120.611 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Secondary Market Certificates § 120.611 Pools backing Pool Certificates. (a) Pool characteristics. As...

  11. Optical spectra analysis for breast cancer diagnostics

    NASA Astrophysics Data System (ADS)

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

    2011-11-01

    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.

  12. Analysis of variance, normal quantile-quantile correlation and effective expression support of pooled expression ratio of reference genes for defining expression stability.

    PubMed

    Priyadarshi, Himanshu; Das, Rekha; Kumar, Shivendra; Kishore, Pankaj; Kumar, Sujit

    2017-01-01

    Identification of a reference gene unaffected by the experimental conditions is obligatory for accurate measurement of gene expression through relative quantification. Most existing methods directly analyze variability in crossing point (Cp) values of reference genes and fail to account for template-independent factors that affect Cp values in their estimates. We describe the use of three simple statistical methods namely analysis of variance (ANOVA), normal quantile-quantile correlation (NQQC) and effective expression support (EES), on pooled expression ratios of reference genes in a panel to overcome this issue. The pooling of expression ratios across the genes in the panel nullify the sample specific effects uniformly affecting all genes that are falsely reflected as instability. Our methods also offer the flexibility to include sample specific PCR efficiencies in estimations, when available, for improved accuracy. Additionally, we describe a correction factor from the ANOVA method to correct the relative fold change of a target gene if no truly stable reference gene could be found in the analyzed panel. The analysis is described on a synthetic data set to simplify the explanation of the statistical treatment of data.

  13. Living near nuclear power plants and thyroid cancer risk: A systematic review and meta-analysis.

    PubMed

    Kim, Jaeyoung; Bang, Yejin; Lee, Won Jin

    2016-02-01

    There has been public concern regarding the safety of residing near nuclear power plants, and the extent of risk for thyroid cancer among adults living near nuclear power plants has not been fully explored. In the present study, a systematic review and meta-analysis of epidemiologic studies was conducted to investigate the association between living near nuclear power plants and the risk of thyroid cancer. A comprehensive literature search was performed on studies published up to March 2015 on the association between nuclear power plants and thyroid cancer risk. The summary standardized incidence ratio (SIR), standardized mortality ratio (SMR), and 95% confidence intervals (CIs) were calculated using a random-effect model of meta-analysis. Sensitivity analyses were performed by study quality. Thirteen studies were included in the meta-analysis, covering 36 nuclear power stations in 10 countries. Overall, summary estimates showed no significant increased thyroid cancer incidence or mortality among residents living near nuclear power plants (summary SIR=0.98; 95% CI 0.87-1.11, summary SMR=0.80; 95% CI 0.62-1.04). The pooled estimates did not reveal different patterns of risk by gender, exposure definition, or reference population. However, sensitivity analysis by exposure definition showed that living less than 20 km from nuclear power plants was associated with a significant increase in the risk of thyroid cancer in well-designed studies (summary OR=1.75; 95% CI 1.17-2.64). Our study does not support an association between living near nuclear power plants and risk of thyroid cancer but does support a need for well-designed future studies.

  14. Association between dietary vitamin C intake and risk of esophageal cancer: A dose-response meta-analysis.

    PubMed

    Bo, Yacong; Lu, Yan; Zhao, Yan; Zhao, Erjiang; Yuan, Ling; Lu, Weiquan; Cui, Lingling; Lu, Quanjun

    2016-04-15

    While several epidemiological studies have investigated the association between vitamin C and risk of esophageal cancer, the results remain inconsistent. In the present study, a meta-analysis was conducted to assess the impact of dietary vitamin C intake on esophageal cancer risk. Online databases were searched up to March 29, 2015, for studies on the association between dietary vitamin C intake and esophageal cancer risk. Pooled risk ratios (RRs) or odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Dose-response analyses were performed using the method of restricted cubic splines with four knots at percentiles of 5, 35, 65 and 95% of the distribution. Publication bias was estimated using Egger's tests and funnel plots. In all, 15 articles were included in this meta-analysis, including 20 studies, containing 7063 controls and 3955 cases of esophageal cancer. By comparing the highest vs. the lowest categories of vitamin C intake, we found that vitamin C was inversely associated with the risk of esophageal cancer [overall OR = 0.58, 95% CI = 0.49-0.68, I(2) = 56%]. A linear dose-response relationship was found. With an increase in dietary vitamin C intake of 50 mg/day, the risk of esophageal cancer statistically decreased by 13% (OR = 0.87, 95% CI = 0.80-0.93, p(linearity) = 0.0002). In conclusion, our analysis suggested that the higher intake of dietary vitamin C might have a protective effect against esophageal cancer.

  15. Prognostic Role of the Pretreatment C-Reactive Protein/Albumin Ratio in Solid Cancers: A Meta-Analysis

    PubMed Central

    Li, Nan; Tian, Guang-Wei; Wang, Ying; Zhang, Hui; Wang, Zi-hui; Li, Guang

    2017-01-01

    The C-reactive protein/albumin ratio (CAR) has been shown to play a significant prognostic role in several cancers. We aimed to comprehensively explore the potential role of the CAR as a prognostic indicator in solid cancers. In this meta-analysis, we collected data from 10 studies that examined the association between serum CAR and overall survival in patients with cancer. This meta-analysis included 4592 tumor patients. The eligible studies were found through the PubMed and Web of Science databases updated on 6 Oct 2016. The pooled hazard ratio (2.01, 95% CI: 1.58–2.56, p < 0.001) indicated that high CAR yielded worse survival in different cancers. Subgroup analyses showed a significant association between CAR and prognosis, regardless of the cutoff value, cutoff value selection, treatment method, country, sample size, stage and cancer type. This meta-analysis suggests that CAR may be a potential prognostic marker in solid cancers. However, further large prospective studies should be conducted to explore the critical role of CAR in survival of cancer patients. PMID:28128229

  16. XRCC3 T241M polymorphism and lung cancer risk in the Han Chinese population: a meta-analysis.

    PubMed

    Zhang, J H; Wen, Q L; Yang, C; Li, A L; Liu, Y; Li, X S

    2014-11-11

    Numerous studies have evaluated the association between the X-ray repair cross-complementing group 3 (XRCC3) T241M polymorphism and lung cancer risk; however, the actual association is controversial. We examined whether the T241M polymorphism confers a lung cancer risk in China. We searched the PubMed, Google Scholar, and China National Knowledge Infrastructure databases to identify studies that examined the association between the XRCC3 T241M polymorphism and the risk of lung cancer. We estimated the pooled odds ratio with its 95% confidence interval to assess this association. A total of 3977 patients with lung cancer and 3761 controls from 8 comparative studies were included in this meta-analysis. The meta-analysis results revealed no significant association between the XRCC3 T241M polymorphism and lung cancer risk. In the subgroup analysis, 6 studies with sample sizes over 500 found that the T241M polymorphism had no association with lung cancer. The XRCC3 T241M polymorphism may not be a risk factor for lung cancer. However, larger studies involving a stratified case-control population and biological characterization are needed to validate this finding.

  17. Secondhand smoke exposure and risk of lung cancer in Japan: a systematic review and meta-analysis of epidemiologic studies

    PubMed Central

    Hori, Megumi; Tanaka, Hirokazu; Wakai, Kenji; Sasazuki, Shizuka; Katanoda, Kota

    2016-01-01

    Objective Systematic evaluation of the association between secondhand smoke exposure and lung cancer in Japan has yet to be conducted. Here, we performed a systematic review and meta-analysis of the relationship between secondhand smoke and lung cancer in Japanese non-smokers. Methods Relevant studies were collected from the MEDLINE and Ichushi Web databases using a combination of search terms and Medical Subject Headings. Eligible studies were identified, and relative risks or odds ratios were extracted to calculate pooled risk estimates. This procedure was performed independently by at least two authors. Stratified analyses were carried out according to study design, publication year, and whether or not potential confounding variables were accounted for. The presence of publication bias was assessed via funnel plots. Results We identified four cohort studies and five case-control studies. Quantitative synthesis was conducted only for secondhand smoke exposure in the home during adulthood. Of the 12 populations included in meta-analysis, positive secondhand smoke exposure-lung cancer associations were observed in 11, whereas an inverse association was found in the remaining 1. The pooled relative risk of lung cancer associated with secondhand smoke exposure was 1.28 (95% confidence interval: 1.10–1.48). We found no evidence of publication bias, and a significant association remained even when potentially missing studies were included (pooled relative risk: 1.26; 95% confidence interval: 1.09–1.46). The results were stable across different subgroup analyses, including by study design, publication year, and when adjusting for confounding variables. Conclusions Secondhand smoke exposure in the home during adulthood results in a statistically significant increase in the risk of lung cancer. PMID:27511987

  18. A Cross-Cancer Genetic Association Analysis of the DNA repair and DNA Damage Signaling Pathways for Lung, Ovary, Prostate, Breast and Colorectal Cancer

    PubMed Central

    Scarbrough, Peter M.; Weber, Rachel Palmieri; Iversen, Edwin S.; Brhane, Yonathan; Amos, Christopher I.; Kraft, Peter; Hung, Rayjean J.; Sellers, Thomas A.; Witte, John S.; Pharoah, Paul; Henderson, Brian E.; Gruber, Stephen B.; Hunter, David J.; Garber, Judy E.; Joshi, Amit D.; McDonnell, Kevin; Easton, Doug F.; Eeles, Ros; Kote-Jarai, Zsofia; Muir, Kenneth; Doherty, Jennifer A.; Schildkraut, Joellen M.

    2015-01-01

    Background DNA damage is an established mediator of carcinogenesis, though GWAS have identified few significant loci. This cross-cancer site, pooled analysis was performed to increase the power to detect common variants of DNA repair genes associated with cancer susceptibility. Methods We conducted a cross-cancer analysis of 60,297 SNPs, at 229 DNA repair gene regions, using data from the NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) Network. Our analysis included data from 32 GWAS and 48,734 controls and 51,537 cases across five cancer sites (breast, colon, lung, ovary, and prostate). Because of the unavailability of individual data, data were analyzed at the aggregate level. Meta-analysis was performed using the Association analysis for SubSETs (ASSET) software. To test for genetic associations that might escape individual variant testing due to small effect sizes, pathway analysis of eight DNA repair pathways was performed using hierarchical modeling. Results We identified three susceptibility DNA repair genes, RAD51B (p < 5.09 × 10−6), MSH5 (p < 5.09 × 10−6) and BRCA2 (p = 5.70 × 10−6). Hierarchical modeling identified several pleiotropic associations with cancer risk in the base excision repair, nucleotide excision repair, mismatch repair, and homologous recombination pathways. Conclusions Only three susceptibility loci were identified which had all been previously reported. In contrast, hierarchical modeling identified several pleiotropic cancer risk associations in key DNA repair pathways. Impact Results suggest that many common variants in DNA repair genes are likely associated with cancer susceptibility through small effect sizes that do not meet stringent significance testing criteria. PMID:26637267

  19. Analysis of cancer patients admitted to intensive care unit

    PubMed Central

    Aksoy, Yakup; Kaydu, Ayhan; Sahin, Omer Fatih; Kacar, Cem Kivilcim

    2016-01-01

    OBJECTIVE: The present study is an analysis of cancer patients who received follow-up treatment for either cancer-related complications or treatment-associated side effects while hospitalized in the intensive care unit (ICU). METHODS: Records of cancer patients treated at Dr. Lütfi Kırdar Kartal Training and Research Hospital ICU between January 1, 2011 and December 31, 2012 were retrospectively reviewed. Demographic data and type of cancer were recorded in prepared forms and subsequently analyzed. RESULTS: Among 2240 ICU patients treated and hospitalized between January 1, 2011 and December 31, 2012, 482 cancer patients were identified and included in the study. Percentage of cancer patients in ICU was 23.9%. Male to female ratio was determined to be 1.55. First 3 most common cancers found were colorectal (19.7%), lung (15.7%), and stomach cancers (11.6%). Mortality rate of cancer patients hospitalized in ICU was 46.6%. Larynx, lung, urinary bladder, skin, rectosigmoid, hematological, and kidney cancer were more prevalent in male patients, whereas esophageal cancer was seen in more female patients than male patients. Incidence of stomach, brain, and pancreatic cancers, as well as unclassified tumors, was found to be unrelated to gender. CONCLUSION: Rectosigmoid cancer was most common type of cancer observed in our ICU. Esophageal cancer was observed in more females than males, while larynx cancer was more frequently present in males. PMID:28275754

  20. Enhancing cancer clonality analysis with integrative genomics

    PubMed Central

    2015-01-01

    Introduction It is understood that cancer is a clonal disease initiated by a single cell, and that metastasis, which is the spread of cancer from the primary site, is also initiated by a single cell. The seemingly natural capability of cancer to adapt dynamically in a Darwinian manner is a primary reason for therapeutic failures. Survival advantages may be induced by cancer therapies and also occur as a result of inherent cell and microenvironmental factors. The selected "more fit" clones outmatch their competition and then become dominant in the tumor via propagation of progeny. This clonal expansion leads to relapse, therapeutic resistance and eventually death. The goal of this study is to develop and demonstrate a more detailed clonality approach by utilizing integrative genomics. Methods Patient tumor samples were profiled by Whole Exome Sequencing (WES) and RNA-seq on an Illumina HiSeq 2500 and methylation profiling was performed on the Illumina Infinium 450K array. STAR and the Haplotype Caller were used for RNA-seq processing. Custom approaches were used for the integration of the multi-omic datasets. Results Reported are major enhancements to CloneViz, which now provides capabilities enabling a formal tumor multi-dimensional clonality analysis by integrating: i) DNA mutations, ii) RNA expressed mutations, and iii) DNA methylation data. RNA and DNA methylation integration were not previously possible, by CloneViz (previous version) or any other clonality method to date. This new approach, named iCloneViz (integrated CloneViz) employs visualization and quantitative methods, revealing an integrative genomic mutational dissection and traceability (DNA, RNA, epigenetics) thru the different layers of molecular structures. Conclusion The iCloneViz approach can be used for analysis of clonal evolution and mutational dynamics of multi-omic data sets. Revealing tumor clonal complexity in an integrative and quantitative manner facilitates improved mutational

  1. Next generation semiconductor based sequencing of bitter taste receptor genes in different pig populations and association analysis using a selective DNA pool-seq approach.

    PubMed

    Ribani, A; Bertolini, F; Schiavo, G; Scotti, E; Utzeri, V J; Dall'Olio, S; Trevisi, P; Bosi, P; Fontanesi, L

    2017-02-01

    Taste perception in animals affects feed intake and may influence production traits. In particular, bitter is sensed by receptors encoded by the family of TAS2R genes. In this research, using a DNA pool-seq approach coupled with next generation semiconductor based target resequencing, we analysed nine porcine TAS2R genes (TAS2R1, TAS2R3, TAS2R4, TAS2R7, TAS2R9, TAS2R10, TAS2R16, TAS2R38 and TAS2R39) to identify variability and, at the same time, estimate single nucleotide polymorphism (SNP) allele frequencies in several populations and testing differences in an association analysis. Equimolar DNA pools were prepared for five pig breeds (Italian Duroc, Italian Landrace, Pietrain, Meishan and Casertana) and wild boars (5-10 individuals each) and for two groups of Italian Large White pigs with extreme and divergent back fat thickness (50 + 50 pigs). About 1.8 million reads were obtained by sequencing amplicons generated from these pools. A total of 125 SNPs were identified, of which 37 were missense mutations. Three of them (p.Ile53Phe and p.Trp85Leu in TAS2R4; p.Leu37Ser in TAS2R39) could have important effects on the function of these bitter taste receptors, based on in silico predictions. Variability in wild boars seems lower than that in domestic breeds potentially as a result of selective pressure in the wild towards defensive bitter taste perception. Three SNPs in TAS2R38 and TAS2R39 were significantly associated with back fat thickness. These results may be important to understand the complexity of taste perception and their associated effects that could be useful to develop nutrigenetic approaches in pig breeding and nutrition.

  2. Pooled Analysis of the Cow's Milk-related-Symptom-Score (CoMiSS™) as a Predictor for Cow's Milk Related Symptoms

    PubMed Central

    Steenhout, Philippe; Järvi, Anette; Garreau, Anne-Sophie; Mukherjee, Rajat

    2017-01-01

    Purpose The diagnosis of cow's milk (CM) allergy is a challenge. The Cow's Milk-related-Symptom-Score (CoMiSS™) was developed to offer primary health care providers a reliable diagnostic tool for CM related symptoms. The predictive prospective value of the CoMiSS™ was evaluated in three clinical trials. Methods Pooled analyses of the three studies were conducted based on regressing the results of the month-1 challenge test on the month-1 CoMiSS™, adjusting for baseline CoMiSS™ using a logistic regression model. In addition a logistic regression model was also fitted to the month-1 challenge test result with the change in CoMiSS™ from baseline as a predictor. Results Results suggest that infants having a low CoMiSS™ (median, 5) after 1 month dietary treatment free from intact CM protein have a significant risk of having a positive challenge test (odds ratio, 0.83; 95% confidence interval, 0.75-0.93; p=0.002). Pooled data suggest that the change in CoMiSS™ from baseline to month-1 can predict CM related symptoms as a confirmed diagnosis according to the challenge test at month-1. However, in order to validate such a tool, infants without CM related symptoms would also need to be enrolled in a validation trial. A concern is that it may not be ethical to expose healthy infants to a therapeutic formula and a challenge test. Conclusion Pooled data analysis emphasizes that the CoMiSS™ has the potential to be of interest in infants suspected to have CM-related-symptoms. A prospective validation trial is needed.

  3. Identification of reference genes for circulating microRNA analysis in colorectal cancer

    PubMed Central

    Niu, Yanqin; Wu, Yike; Huang, Jinyong; Li, Qing; Kang, Kang; Qu, Junle; Li, Furong; Gou, Deming

    2016-01-01

    Quantitative real-time PCR (qPCR) is the most frequently used method for measuring expression levels of microRNAs (miRNAs), which is based on normalization to endogenous references. Although circulating miRNAs have been regarded as potential non-invasive biomarker of disease, no study has been performed so far on reference miRNAs for normalization in colorectal cancer. In this study we tried to identify optimal reference miRNAs for qPCR analysis across colorectal cancer patients and healthy individuals. 485 blood-derived miRNAs were profiled in serum sample pools of both colorectal cancer and healthy control. Seven candidate miRNAs chosen from profiling results as well as three previous reported reference miRNAs were validated using qPCR in 30 colorectal cancer patients and 30 healthy individuals, and thereafter analyzed by statistical algorithms BestKeeper, geNorm and NormFinder. Taken together, hsa-miR-93-5p, hsa-miR-25-3p and hsa-miR-106b-5p were recommended as a set of suitable reference genes. More interestingly, the three miRNAs validated from 485 miRNAs are derived from a single primary transcript, indicting the cluster may be highly conserved in colorectal cancer. However, all three miRNAs differed significantly between healthy individuals and non-small cell lung cancer or breast cancer patients and could not be used as reference genes in the two types of cancer. PMID:27759076

  4. A Platelet Acquired Storage Pool Disorder Associated with Tamoxifen Therapy

    PubMed Central

    Nayak, Lalitha; Schmaier, Alvin H.

    2012-01-01

    The antiestrogenic drug tamoxifen, used in patients with breast cancer, is associated with an increase in arterial and venous thrombotic events, the mechanism of which is not clearly understood. We report a case of a lady who presented with new bruising and prolonged bleeding following a tooth extraction 4–6 weeks after starting tamoxifen. Investigations were consistent with an acquired platelet storage pool disorder. Repeat platelet function analysis was normal, performed 3 months after discontinuation of tamoxifen. We present a previously clinically unreported effect of tamoxifen on platelet function. PMID:23326738

  5. 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

  6. Soy food consumption and lung cancer risk: a meta-analysis using a common measure across studies.

    PubMed

    Wu, Sheng Hui; Liu, Zhong

    2013-01-01

    A published meta-analysis pooled individual studies by using the study-specific odds ratio (OR) or relative risk (RR) for the highest vs. lowest category of soy or isoflavone intake from each study, but it should be problematic to make comparison between studies/populations for lung cancer risk as the quantiles are so different from different studies/populations. Therefore, we conducted a meta-analysis to explore the association between exposure of estimated daily soy protein intake in grams and lung cancer risk. We extracted ORs or RRs and 95% confidence intervals (CIs), converted them to the estimated ones for daily soy protein intake and pooled them using fixed or random effects models from 11 epidemiologic studies. Overall, the inverse association between daily grams of soy protein intake and risk of lung cancer was borderline statistically significant (OR = 0.98, 95% CI = 0.96 to 1.00); the inverse association was statistically significant in nonsmokers (OR = 0.96; 95% CI = 0.93 to 0.99) and stronger than in smokers (P for difference <0.05). No statistical significance for the associations was observed between genders, the origin of the participants, study design and types of soy intake. This study suggests a borderline reduction in risk of lung cancer with daily soy protein intake in grams, and a significant inverse association in nonsmokers.

  7. Growth hormone replacement therapy reduces risk of cancer in adult with growth hormone deficiency: A meta-analysis

    PubMed Central

    Li, Zhanzhan; Zhou, Qin; Li, Yanyan; Fu, Jun; Huang, Xinqiong; Shen, Liangfang

    2016-01-01

    The risk of growth hormone on cancer in adult with growth hormone deficiency remains unclear. We carried out a meta-analysis to evaluate the risk of cancer in adult with and without growth hormone replacement therapy. We searched PubMed, Web of Science, China National Knowledge Infrastructure, and WanFang databases up to 31 July 2016 for eligible studies. Pooled risk ratio (RR) with 95% confidence interval (CI) was calculated using fixed-or random-effects models if appropriate. The Newcastle-Ottawa Scale was used to assess the study quality. Two retrospective and seven prospective studies with a total of 11191 participants were included in the final analysis. The results from fixed-effects model showed this therapy was associated with the deceased risk of cancer in adult with growth hormone deficiency (RR=0.69, 95%CI: 0.59-0.82), with low heterogeneity within studies (I2=39.0%, P=0.108). We performed sensitivity analyses by sequentially omitting one study each time, and the pooled RRs did not materially change, indicating that our results were statistically stable. Begger's and Egger's tests suggested that there was no publication bias (Z=-0.63, P=0.520; t=0.16, P=0.874). Our study suggests that growth hormone replacement therapy could reduce risk of cancer in adult with growth hormone deficiency. PMID:27835910

  8. Clinical Outcomes of Specific Immunotherapy in Advanced Pancreatic Cancer: A Systematic Review and Meta-Analysis.

    PubMed

    Chen, Jiang; Xiao-Zhong, Guo; Qi, Xing-Shun

    2017-01-01

    Specific immunotherapies, including vaccines with autologous tumor cells and tumor antigen-specific monoclonal antibodies, are important treatments for PC patients. To evaluate the clinical outcomes of PC-specific immunotherapy, we performed a systematic review and meta-analysis of the relevant published clinical trials. The effects of specific immunotherapy were compared with those of nonspecific immunotherapy and the meta-analysis was executed with results regarding the overall survival (OS), immune responses data, and serum cancer markers data. The pooled analysis was performed by using the random-effects model. We found that significantly improved OS was noted for PC patients utilizing specific immunotherapy and an improved immune response was also observed. In conclusion, specific immunotherapy was superior in prolonging the survival time and enhancing immunological responses in PC patients.

  9. Clinical Outcomes of Specific Immunotherapy in Advanced Pancreatic Cancer: A Systematic Review and Meta-Analysis

    PubMed Central

    Qi, Xing-Shun

    2017-01-01

    Specific immunotherapies, including vaccines with autologous tumor cells and tumor antigen-specific monoclonal antibodies, are important treatments for PC patients. To evaluate the clinical outcomes of PC-specific immunotherapy, we performed a systematic review and meta-analysis of the relevant published clinical trials. The effects of specific immunotherapy were compared with those of nonspecific immunotherapy and the meta-analysis was executed with results regarding the overall survival (OS), immune responses data, and serum cancer markers data. The pooled analysis was performed by using the random-effects model. We found that significantly improved OS was noted for PC patients utilizing specific immunotherapy and an improved immune response was also observed. In conclusion, specific immunotherapy was superior in prolonging the survival time and enhancing immunological responses in PC patients. PMID:28265583

  10. BRAF-activated lncRNA predicts gastrointestinal cancer patient prognosis: a meta-analysis