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51. Variation in NF-κB signaling pathways and survival in invasive epithelial ovarian cancer

Author

Block, MS, Charbonneau, B, Vierkant, RA, Fogarty, Z, Bamlet, WR, Pharoah, PDP, Chenevix-Trench, G, Rossing, MA, Cramer, D, Pearce, CL, Schildkraut, J, Menon, U, Kjaer, SK, Levine, DA, Gronwald, J, Culver, HA, Whittemore, AS, Karlan, BY, Lambrechts, D, Wentzensen, N, Kupryjanczyk, J, Chang-Claude, J, Bandera, EV, Hogdall, E, Heitz, F, Kaye, SB, Fasching, PA, Campbell, I, Goodman, MT, Pejovic, T, Bean, YT, Hays, LE, Lurie, G, Eccles, D, Hein, A, Beckmann, MW, Ekici, AB, Paul, J, Brown, R, Flanagan, JM, Harter, P, Du Bois, A, Schwaab, I, Hogdall, CK, Lundvall, L, Olson, SH, Orlow, I, Paddock, LE, Rudolph, A, Eilber, U, Dansonka-Mieszkowska, A, Rzepecka, IK, Ziolkowska-Seta, I, Brinton, LA, Yang, H, Garcia-Closas, M, Despierre, E, Lambrechts, S, Vergote, I, Walsh, CS, Lester, J, Sieh, W, McGuire, V, Rothstein, JH, Ziogas, A, Lubinski, J, Cybulski, C, Menkiszak, J, Jensen, A, Gayther, SA, Ramus, SJ, Gentry-Maharaj, A, Berchuck, A, Wu, AH, Pike, MC, Van Den Berg, D, Terry, KL, Vitonis, AF, Ramirez, SM, Rider, DN, Knutson, KL, and Sellers, TA

Subjects
endocrine system diseases, female genital diseases and pregnancy complications
Abstract

Survival in epithelial ovarian cancer (EOC) is influenced by the host immune response, yet the key genetic determinants of inflammation and immunity that affect prognosis are not known. The nuclear factor-kB (NF-kB) transcription factor family plays an important role in many immune and inflammatory responses, including the response to cancer. We studied common inherited variation in 210 genes in the NF-kB family in 10,084 patients with invasive EOC (5,248 high-grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous) from the Ovarian Cancer Association Consortium. Associations between genotype and overall survival were assessed using Cox regression for all patients and by major histology, adjusting for known prognostic factors and correcting for multiple testing (threshold for statistical significance, P < 2.5 × 10-5). Results were statistically significant when assessed for patients of a single histology. Key associations were with caspase recruitment domain family, member 11 (CARD11) rs41324349 in patients with mucinous EOC [HR, 1.82; 95% confidence interval (CI), 1.41-2.35; P = 4.13 × 10-6] and tumor necrosis factor receptor superfamily, member 13B (TNFRSF13B) rs7501462 in patients with endometrioid EOC (HR, 0.68; 95% CI, 0.56-0.82; P = 2.33 × 10-5). Other associations of note included TNF receptor-associated factor 2 (TRAF2) rs17250239 in patients with high-grade serous EOC (HR, 0.84; 95% CI, 0.77-0.92; P = 6.49 ± 10-5) and phospholipase C, gamma 1 (PLCG1) rs11696662 in patients with clear cell EOC (HR, 0.43; 95% CI, 0.26-0.73; P = 4.56 × 10-4). These associations highlight the potential importance of genes associated with host inflammation and immunity in modulating clinical outcomes in distinct EOC histologies. © 2014 American Association for Cancer Research.

Published
2014
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54. Neurophysiologic, phenomenological, cultural, social and spiritual correlates of empathy experiences: integral psychological and person centered perspectives

Author

Edwards, S, Cramer, D, Kelaiditis, D, Edwards, D, Naidoo, N, Davidson, D, Thwala, J, Mbele, B, Siyaya, V, Singh, A, Tshabalala, P, Govender, S, and Nzima, D

Subjects
Neurophysiologic, phenomenological, cultural, social, spiritual, correlates, empathy experiences, integral psychology, person centered psychotherapy
Abstract

The main objective of this research was to explore neurophysiologic, phenomenological, cultural and social correlates of recipients’ experiences of empathy within the context of Wilber’s Integral approach and Person Centered theory and practice. Thirteen psychologists participated as co-researchers in a triangulated, within subjects’ post-test experimental design in which empathy data were compared with data from control conditions of factual information processing and rest. A consistent pattern emerged from data gathered. Empathy experiences were associated with an unexpected, statistically significant increase in alpha activity, with some associated increasing trends in theta and beta activity. Expected findings were significant decreases in delta activity accompanied by decreasing trends in gamma wave activity, muscle tension, heart and respiration rate. Individual experiences generally reflected an affective, interpersonal, cultural, social and spiritual state of normal waking consciousness. Participant consensus was that the neurophysiologic and other correlates corresponded truthfully with typical empathic moments, insights and/or peak experiences, which are associated with effective therapeutic change in traditional and contemporary healing contexts.Key words: Neurophysiologic, phenomenological, cultural, social, spiritual, correlates, empathy experiences, integral psychology, person centered psychotherapy

Published
2012

55. Ovarian cancer and smoking: individual participant meta-analysis including 28 114 women with ovarian cancer from 51 epidemiological studies

Author

Beral, V. Gaitskell, K. Hermon, C. Moser, K. Reeves, G. and Peto, R. Brinton, L. Marchbanks, P. Negri, E. Ness, R. Peeters, P. H. M. Vessey, M. Calle, E. E. Gapstur, S. M. Patel, A. V. Dal Maso, L. Talamini, R. Chetrit, A. and Hirsh-Yechezkel, G. Lubin, F. Sadetzki, S. Banks, E. and Bull, D. Callaghan, K. Crossley, B. Goodill, A. Green, J. Key, T. Sitas, F. Collins, R. Doll, R. Gonzalez, A. Lee, N. Ory, H. W. Peterson, H. B. Wingo, P. A. and Martin, N. Pardthaisong, T. Silpisornkosol, S. Theetranont, C. Boosiri, B. Chutivongse, S. Jimakorn, P. Virutamasen, P. Wongsrichanalai, C. Tjonneland, A. Titus-Ernstoff, L. and Byers, T. Rohan, T. Mosgaard, B. J. Yeates, D. and Freudenheim, J. L. Chang-Claude, J. Kaaks, R. Anderson, K. E. Folsom, A. Robien, K. Hampton, J. Newcomb, P. A. and Rossing, M. A. Thomas, D. B. Weiss, N. S. Riboli, E. and Clavel-Chapelon, F. Cramer, D. Hankinson, S. E. Tworoger, S. S. Franceschi, S. La Vecchia, C. Adami, H. O. Magnusson, C. Riman, T. Weiderpass, E. Wolk, A. Schouten, L. J. and van den Brandt, P. A. Chantarakul, N. Koetsawang, S. and Rachawat, D. Palli, D. Black, A. Freedman, D. M. Hartge, P. Hsing, A. W. Lacey, Jr., J. V. Hoover, R. N. and Schairer, C. Urban, M. Graff-Iversen, S. Selmer, R. and Bain, C. J. Green, A. C. Purdie, D. M. Siskind, V. Webb, P. M. Moysich, K. McCann, S. E. Hannaford, P. Kay, C. and Binns, C. W. Lee, A. H. Zhang, M. Nasca, P. Coogan, P. F. Palmer, J. R. Rosenberg, L. Kelsey, J. and Paffenbarger, R. Whittemore, A. Katsouyanni, K. and Trichopoulou, A. Trichopoulos, D. Tzonou, A. Dabancens, A. and Martinez, L. Molina, R. Salas, O. Goodman, M. T. and Lurie, G. Carney, M. E. Wilkens, L. R. Hartman, L. and Manjer, J. Olsson, H. Grisso, J. A. Morgan, M. Wheeler, J. E. Bunker, C. H. Edwards, R. P. Modugno, F. and Casagrande, J. Pike, M. C. Ross, R. K. Wu, A. H. Miller, A. B. Kumle, M. Gram, I. T. Lund, E. McGowan, L. and Shu, X. O. Zheng, W. Farley, T. M. M. Holck, S. Meirik, O. Risch, H. A. Collaborative Grp Epidemiological Natl Israeli Study Ovarian Canc Nurses Hlth Study

Abstract

Background Smoking has been linked to mucinous ovarian cancer, but its effects on other ovarian cancer subtypes and on overall ovarian cancer risk are unclear, and the findings from most studies with relevant data are unpublished. To assess these associations, we review the published and unpublished evidence. Methods Eligible epidemiological studies were identified by electronic searches, review articles, and discussions with colleagues. Individual participant data for 28 114 women with and 94 942 without ovarian cancer from 51 epidemiological studies were analysed centrally, yielding adjusted relative risks (RRs) of ovarian cancer in smokers compared with never smokers. Findings After exclusion of studies with hospital controls, in which smoking could have affected recruitment, overall ovarian cancer incidence was only slightly increased in current smokers compared with women who had never smoked (RR 1.06, 95% CI 1.01-1.11, p=0.01). Of 17 641 epithelial cancers with specified histology, 2314 (13%) were mucinous, 2360 (13%) endometrioid, 969 (5%) clear-cell, and 9086 (52%) serous. Smoking-related risks varied substantially across these subtypes (p(heterogeneity)

Published
2012

56. Ovarian Cancer and Body Size: Individual Participant Meta-Analysis Including 25,157 Women with Ovarian Cancer from 47 Epidemiological Studies

Author

Beral, V. Hermon, C. Peto, R. Reeves, G. Brinton, L. and Marchbanks, P. Negri, E. Ness, R. Peeters, P. H. M. and Vessey, M. Calle, E. E. Gapstur, S. M. Patel, A. V. Dal Maso, L. Talamini, R. Chetrit, A. Hirsh-Yechezkel, G. and Lubin, F. Sadetzki, S. Allen, N. Bull, D. Callaghan, K. and Crossley, B. Gaitskell, K. Goodill, A. Green, J. and Key, T. Moser, K. Collins, R. Doll, R. Gonzalez, C. A. and Lee, N. Ory, H. W. Peterson, H. B. Wingo, P. A. and Martin, N. Pardthaisong, T. Silpisornkosol, S. Theetranont, C. Boosiri, B. Chutivongse, S. Jimakorn, P. Virutamasen, P. Wongsrichanalai, C. Tjonneland, A. Titus-Ernstoff, L. and Byers, T. Rohan, T. Mosgaard, B. J. Yeates, D. and Freudenheim, J. L. Chang-Claude, J. Kaaks, R. Anderson, K. E. Folsom, A. Robien, K. Rossing, M. A. Thomas, D. B. and Weiss, N. S. Riboli, E. Clavel-Chapelon, F. Cramer, D. and Hankinson, S. E. Tworoger, S. S. Franceschi, S. La Vecchia, C. Magnusson, C. Riman, T. Weiderpass, E. Wolk, A. Schouten, L. J. van den Brandt, P. A. Chantarakul, N. and Koetsawang, S. Rachawat, D. Palli, D. Black, A. de Gonzalez, A. Berrington Freedman, D. M. Hartge, P. Hsing, A. W. Lacey, Jr., J. V. Hoover, R. N. Schairer, C. and Graff-Iversen, S. Selmer, R. Bain, C. J. Green, A. C. and Purdie, D. M. Siskind, V. Webb, P. M. McCann, S. E. and Hannaford, P. Kay, C. Binns, C. W. Lee, A. H. Zhang, M. and Ness, R. B. Nasca, P. Coogan, P. F. Palmer, J. R. and Rosenberg, L. Kelsey, J. Paffenbarger, R. Whittemore, A. and Katsouyanni, K. Trichopoulou, A. Trichopoulos, D. Tzonou, A. and Dabancens, A. Martinez, L. Molina, R. Salas, O. and Goodman, M. T. Lurie, G. Carney, M. E. Wilkens, L. R. and Hartman, L. Manjer, J. Olsson, H. Grisso, J. A. Morgan, M. Wheeler, J. E. Casagrande, J. Pike, M. C. Ross, R. K. and Wu, A. H. Miller, A. B. Kumle, M. Lund, E. McGowan, L. Shu, X. O. Zheng, W. Farley, T. M. M. Holck, S. and Meirik, O. Risch, H. A. Collaborative Grp Epidemiol Studie

Abstract

Background: Only about half the studies that have collected information on the relevance of women’s height and body mass index to their risk of developing ovarian cancer have published their results, and findings are inconsistent. Here, we bring together the worldwide evidence, published and unpublished, and describe these relationships. Methods and Findings: Individual data on 25,157 women with ovarian cancer and 81,311 women without ovarian cancer from 47 epidemiological studies were collected, checked, and analysed centrally. Adjusted relative risks of ovarian cancer were calculated, by height and by body mass index. Ovarian cancer risk increased significantly with height and with body mass index, except in studies using hospital controls. For other study designs, the relative risk of ovarian cancer per 5 cm increase in height was 1.07 (95% confidence interval [CI], 1.05-1.09; p

Published
2012

57. An epidemiologic risk prediction model for ovarian cancer in Europe : the EPIC study

Author

Li, K., Huesing, A., Fortner, R. T., Tjonneland, A., Hansen, L., Dossus, L., Chang-Claude, J., Bergmann, M., Steffen, A., Bamia, C., Trichopoulos, D., Trichopoulou, A., Palli, D., Mattiello, A., Agnoli, C., Tumino, R., Onland-Moret, N. C., Peeters, P. H., Bueno-de-Mesquita, H. B(as), Gram, I. T., Weiderpass, E., Sanchez-Cantalejo, E., Chirlaque, M-D, Duell, E. J., Ardanaz, E., Idahl, Annika, Lundin, E., Khaw, K-T, Travis, R. C., Merritt, M. A., Gunter, M. J., Riboli, E., Ferrari, P., Terry, K., Cramer, D., Kaaks, R., Li, K., Huesing, A., Fortner, R. T., Tjonneland, A., Hansen, L., Dossus, L., Chang-Claude, J., Bergmann, M., Steffen, A., Bamia, C., Trichopoulos, D., Trichopoulou, A., Palli, D., Mattiello, A., Agnoli, C., Tumino, R., Onland-Moret, N. C., Peeters, P. H., Bueno-de-Mesquita, H. B(as), Gram, I. T., Weiderpass, E., Sanchez-Cantalejo, E., Chirlaque, M-D, Duell, E. J., Ardanaz, E., Idahl, Annika, Lundin, E., Khaw, K-T, Travis, R. C., Merritt, M. A., Gunter, M. J., Riboli, E., Ferrari, P., Terry, K., Cramer, D., and Kaaks, R.

Abstract

Background: Ovarian cancer has a high case-fatality ratio, largely due to late diagnosis. Epidemiologic risk prediction models could help identify women at increased risk who may benefit from targeted prevention measures, such as screening or chemopreventive agents. Methods: We built an ovarian cancer risk prediction model with epidemiologic risk factors from 202 206 women in the European Prospective Investigation into Cancer and Nutrition study. Results: Older age at menopause, longer duration of hormone replacement therapy, and higher body mass index were included as increasing ovarian cancer risk, whereas unilateral ovariectomy, longer duration of oral contraceptive use, and higher number of full-term pregnancies were decreasing risk. The discriminatory power (overall concordance index) of this model, as examined with five-fold cross-validation, was 0.64 (95% confidence interval (CI): 0.57, 0.70). The ratio of the expected to observed number of ovarian cancer cases occurring in the first 5 years of follow-up was 0.90 (293 out of 324, 95% CI: 0.81-1.01), in general there was no evidence for miscalibration. Conclusion: Our ovarian cancer risk model containing only epidemiological data showed modest discriminatory power for a Western European population. Future studies should consider adding informative biomarkers to possibly improve the predictive ability of the model.

Published
2015
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58. Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk

Author

Kar, S.P., Tyrer, J.P., Li, Q., Lawrenson, K., Aben, K.K.H., Anton-Culver, H., Antonenkova, N., Chenevix-Trench, G., Baker, H., Bandera, E.V., Bean, Y.T., Beckmann, M.W., Berchuck, A., Bisogna, M., Bjorge, L., Bogdanova, N., Brinton, L., Brooks-Wilson, A., Butzow, R., Campbell, I., Carty, K., Chang-Claude, J., Chen, Y.A., Chen, Z., Cook, L.S., Cramer, D., Cunningham, J.M., Cybulski, C., Dansonka-Mieszkowska, A., Dennis, J., Dicks, E., Doherty, J.A., Dork, T., Bois, A. du, Durst, M., Eccles, D., Easton, D.F., Edwards, R.P., Ekici, A.B., Fasching, P.A., Fridley, B.L., Gao, Y.T., Gentry-Maharaj, A., Giles, G.G., Glasspool, R., Goode, E.L., Goodman, M.T., Grownwald, J., Harrington, P., Harter, P., Hein, A., Heitz, F., Hildebrandt, M.A.T., Hillemanns, P., Hogdall, E., Hogdall, C.K., Hosono, S., Iversen, E.S., Jakubowska, A., Paul, J., Jensen, A., Ji, B.T., Karlan, B.Y., Kjaer, S.K., Kelemen, L.E., Kellar, M., Kelley, J., Kiemeney, L.A.L.M., Krakstad, C., Kupryjanczyk, J., Lambrechts, D., Lambrechts, S., Le, N.D., Lee, A.W., Lele, S., Leminen, A., Lester, J., Levine, D.A., Liang, D., Lissowska, J., Lu, K., Lubinski, J., Lundvall, L., Massuger, L.F., Matsuo, K., McGuire, V., McLaughlin, J.R., McNeish, I.A., Menon, U., Modugno, F., Moysich, K.B., Narod, S.A., Nedergaard, L., Ness, R.B., Nevanlinna, H., Odunsi, K., Olson, S.H., Orlow, I., Orsulic, S., Weber, R.P., Kar, S.P., Tyrer, J.P., Li, Q., Lawrenson, K., Aben, K.K.H., Anton-Culver, H., Antonenkova, N., Chenevix-Trench, G., Baker, H., Bandera, E.V., Bean, Y.T., Beckmann, M.W., Berchuck, A., Bisogna, M., Bjorge, L., Bogdanova, N., Brinton, L., Brooks-Wilson, A., Butzow, R., Campbell, I., Carty, K., Chang-Claude, J., Chen, Y.A., Chen, Z., Cook, L.S., Cramer, D., Cunningham, J.M., Cybulski, C., Dansonka-Mieszkowska, A., Dennis, J., Dicks, E., Doherty, J.A., Dork, T., Bois, A. du, Durst, M., Eccles, D., Easton, D.F., Edwards, R.P., Ekici, A.B., Fasching, P.A., Fridley, B.L., Gao, Y.T., Gentry-Maharaj, A., Giles, G.G., Glasspool, R., Goode, E.L., Goodman, M.T., Grownwald, J., Harrington, P., Harter, P., Hein, A., Heitz, F., Hildebrandt, M.A.T., Hillemanns, P., Hogdall, E., Hogdall, C.K., Hosono, S., Iversen, E.S., Jakubowska, A., Paul, J., Jensen, A., Ji, B.T., Karlan, B.Y., Kjaer, S.K., Kelemen, L.E., Kellar, M., Kelley, J., Kiemeney, L.A.L.M., Krakstad, C., Kupryjanczyk, J., Lambrechts, D., Lambrechts, S., Le, N.D., Lee, A.W., Lele, S., Leminen, A., Lester, J., Levine, D.A., Liang, D., Lissowska, J., Lu, K., Lubinski, J., Lundvall, L., Massuger, L.F., Matsuo, K., McGuire, V., McLaughlin, J.R., McNeish, I.A., Menon, U., Modugno, F., Moysich, K.B., Narod, S.A., Nedergaard, L., Ness, R.B., Nevanlinna, H., Odunsi, K., Olson, S.H., Orlow, I., Orsulic, S., and Weber, R.P.

Abstract

Contains fulltext : 153484.pdf (publisher's version ) (Closed access), BACKGROUND: Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by coexpression may also be enriched for additional EOC risk associations. METHODS: We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly coexpressed with each selected TF gene in the unified microarray dataset of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this dataset were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls). RESULTS: Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P < 0.05 and FDR < 0.05). These results were replicated (P < 0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network. CONCLUSION: We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development. IMPACT: Network analysis integrating large, context-specific datasets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization. Cancer Epidemiol Biomarkers Prev; 24(10); 1574-84. (c)2015 AACR.

Published
2015

59. An epidemiologic risk prediction model for ovarian cancer in Europe: The EPIC study

Author

Epi Kanker Team 1, JC onderzoeksprogramma Kanker, Cancer, Cardiovasculaire Epi Team 3, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Li, K., Huesing, A., Fortner, R. T., Tjonneland, A., Hansen, L., Dossus, L., Chang-Claude, J., Bergmann, M., Steffen, A., Bamia, C., Trichopoulos, D., Trichopoulou, A., Palli, D., Mattiello, A., Agnoli, C., Tumino, R., Onland-Moret, N. C., Peeters, P. H., Bueno-de-Mesquita, H. B(as), Gram, I. T., Weiderpass, E., Sanchez-Cantalejo, E., Chirlaque, M-D, Duell, E. J., Ardanaz, E., Idahl, A., Lundin, E., Khaw, K-T, Travis, R. C., Merritt, M. A., Gunter, M. J., Riboli, E., Ferrari, P., Terry, K., Cramer, D., Kaaks, R., Epi Kanker Team 1, JC onderzoeksprogramma Kanker, Cancer, Cardiovasculaire Epi Team 3, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Li, K., Huesing, A., Fortner, R. T., Tjonneland, A., Hansen, L., Dossus, L., Chang-Claude, J., Bergmann, M., Steffen, A., Bamia, C., Trichopoulos, D., Trichopoulou, A., Palli, D., Mattiello, A., Agnoli, C., Tumino, R., Onland-Moret, N. C., Peeters, P. H., Bueno-de-Mesquita, H. B(as), Gram, I. T., Weiderpass, E., Sanchez-Cantalejo, E., Chirlaque, M-D, Duell, E. J., Ardanaz, E., Idahl, A., Lundin, E., Khaw, K-T, Travis, R. C., Merritt, M. A., Gunter, M. J., Riboli, E., Ferrari, P., Terry, K., Cramer, D., and Kaaks, R.

Published
2015

60. An epidemiologic risk prediction model for ovarian cancer in Europe: the EPIC study

Author

Li, K, primary, Hüsing, A, additional, Fortner, R T, additional, Tjønneland, A, additional, Hansen, L, additional, Dossus, L, additional, Chang-Claude, J, additional, Bergmann, M, additional, Steffen, A, additional, Bamia, C, additional, Trichopoulos, D, additional, Trichopoulou, A, additional, Palli, D, additional, Mattiello, A, additional, Agnoli, C, additional, Tumino, R, additional, Onland-Moret, N C, additional, Peeters, P H, additional, Bueno-de-Mesquita, H B(as), additional, Gram, I T, additional, Weiderpass, E, additional, Sánchez-Cantalejo, E, additional, Chirlaque, M-D, additional, Duell, E J, additional, Ardanaz, E, additional, Idahl, A, additional, Lundin, E, additional, Khaw, K-T, additional, Travis, R C, additional, Merritt, M A, additional, Gunter, M J, additional, Riboli, E, additional, Ferrari, P, additional, Terry, K, additional, Cramer, D, additional, and Kaaks, R, additional

Published
2015
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61. Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23 257 women with ovarian cancer and 87 303 controls

Author

Beral, V. Doll, R. Hermon, C. Peto, R. Reeves, G. and Brinton, L. Green, A. C. Marchbanks, P. Negri, E. Ness, R. Peeters, P. Vessey, M. Calle, E. E. Rodriguez, C. and Dal Maso, L. Talamini, R. Cramer, D. Hankinson, S. E. and Tworoger, S. S. Chetrit, A. Hirsh-Yechezkel, G. Lubin, F. and Sadetzki, S. Appleby, P. Banks, E. de Gonzalez, A. Berrington Bull, D. Crossley, B. Goodil, A. Green, I. and Green, J. Key, T. Collins, R. Gonzalez, C. A. Lee, N. Ory, H. W. Peterson, H. B. Wingo, P. A. Martin, N. and Pardthaisong, T. Silpisornkosol, S. Theetranont, C. and Boosiri, B. Chutivongse, S. Jimakorn, P. Virutamasen, P. and Wongsrichanalai, C. Titus-Ernstoff, L. Mosgaard, M. J. and Yeates, D. Chang-Claude, J. Rossing, M. A. Thomas, D. and Weiss, N. Franceschi, S. La Vecchia, C. Adami, H. O. and Magnusson, C. Riman, T. Weiderpass, E. Wolk, A. Brinton, L. A. Freedman, D. M. Hartge, P. Lacey, J. M. Hoover, R. and Schouten, L. J. van den Brandt, P. A. Chantarakul, N. and Koetsawang, S. Rachawat, D. Graff-Iversen, S. Selmer, R. and Bain, C. J. Green, A. C. Purdie, D. M. Siskind, V. Webb, P. M. McCann, S. E. Hannaford, P. Kay, C. Binns, C. W. and Lee, A. H. Zhang, M. Nasca, P. Coogan, P. F. Kelsey, J. Paffenbarger, R. Whittemore, A. Katsouyanni, K. and Trichopoulou, A. Trichopoulos, D. Tzonou, A. Dabancens, A. and Martinez, L. Molina, R. Salas, O. Goodman, M. T. and Laurie, G. Carney, M. E. Wilkens, L. R. Bladstrom, A. and Olsson, H. Ness, R. B. Grisso, J. A. Morgan, M. Wheeler, J. E. Peeters, P. Casagrande, J. Pike, M. C. Ross, R. K. and Wu, A. H. Kumle, M. Lund, E. McGowan, L. Shu, X. O. and Zheng, W. Farley, T. M. M. Holck, S. Meirik, O. and Risch, H. A. Collaborative Grp Epidemiological

Abstract

Background Oral contraceptives were introduced almost 50 years ago, and over 100 million women currently use them. Oral contraceptives can reduce the risk of ovarian cancer, but the eventual public-health effects of this reduction will depend on how long the protection lasts after use ceases. We aimed to assess these effects. Methods Individual data for 23 257 women with ovarian cancer (cases) and 87 303 without ovarian cancer (controls) from 45 epidemiological studies in 21 countries were checked and analysed centrally. The relative risk of ovarian cancer in relation to oral contraceptive use was estimated, stratifying by study, age, parity, and hysterectomy. Findings Overall 7308 (31%) cases and 32 717 (37%) controls had ever used oral contraceptives, for average durations among users of 4 . 4 and 5 . 0 years, respectively. The median year of cancer diagnosis was 1993, when cases were aged an average of 56 years. The longer that women had used oral contraceptives, the greater the reduction in ovarian cancer risk (p

Published
2008

62. Risk of ovarian cancer and the NF-kappaB pathway: genetic association with IL1A and TNFSF10

Author

Charbonneau, B., Block, M.S., Bamlet, W.R., Vierkant, R.A., Kalli, K.R., Fogarty, Z., Rider, D.N., Sellers, T.A., Tworoger, S.S., Poole, E., Risch, H.A., Salvesen, H.B., Kiemeney, B., Baglietto, L., Giles, G.G., Severi, G., Trabert, B., Wentzensen, N., Chenevix-Trench, G., Whittemore, A.S., Sieh, W., Chang-Claude, J., Bandera, E.V., Orlow, I., Terry, K., Goodman, M.T., Thompson, P.J., Cook, L.S., Rossing, M.A., Ness, R.B., Narod, S.A., Kupryjanczyk, J., Lu, K., Butzow, R., Dork, T., Pejovic, T., Campbell, I., Le, N.D., Bunker, C.H., Bogdanova, N., Runnebaum, I.B., Eccles, D., Paul, J., Wu, A.H., Gayther, S.A., Hogdall, E., Heitz, F., Kaye, S.B., Karlan, B.Y., Anton-Culver, H., Gronwald, J., Hogdall, C.K., Lambrechts, D., Fasching, P.A., Menon, U., Schildkraut, J., Pearce, C.L., Levine, D.A., Kjaer, S.K., Cramer, D., Flanagan, J.M., Phelan, C.M., Brown, R., Massuger, L.F.A.G., Song, H., Doherty, J.A., Krakstad, C., Liang, D., Odunsi, K., Berchuck, A., Jensen, A., Lubinski, J., Nevanlinna, H., Bean, Y.T., Lurie, G., Ziogas, A., Walsh, C., Despierre, E., Brinton, L., Hein, A., Rudolph, A., Dansonka-Mieszkowska, A., Olson, S.H., Harter, P., Tyrer, J., Vitonis, A.F., Brooks-Wilson, A., Aben, K.K.H., Pike, M.C., Ramus, S.J., Wik, E., Cybulski, C., Lin, J., Sucheston, L., Edwards, R., McGuire, V., Lester, J., Bois, A. du, Lundvall, L., et al., Charbonneau, B., Block, M.S., Bamlet, W.R., Vierkant, R.A., Kalli, K.R., Fogarty, Z., Rider, D.N., Sellers, T.A., Tworoger, S.S., Poole, E., Risch, H.A., Salvesen, H.B., Kiemeney, B., Baglietto, L., Giles, G.G., Severi, G., Trabert, B., Wentzensen, N., Chenevix-Trench, G., Whittemore, A.S., Sieh, W., Chang-Claude, J., Bandera, E.V., Orlow, I., Terry, K., Goodman, M.T., Thompson, P.J., Cook, L.S., Rossing, M.A., Ness, R.B., Narod, S.A., Kupryjanczyk, J., Lu, K., Butzow, R., Dork, T., Pejovic, T., Campbell, I., Le, N.D., Bunker, C.H., Bogdanova, N., Runnebaum, I.B., Eccles, D., Paul, J., Wu, A.H., Gayther, S.A., Hogdall, E., Heitz, F., Kaye, S.B., Karlan, B.Y., Anton-Culver, H., Gronwald, J., Hogdall, C.K., Lambrechts, D., Fasching, P.A., Menon, U., Schildkraut, J., Pearce, C.L., Levine, D.A., Kjaer, S.K., Cramer, D., Flanagan, J.M., Phelan, C.M., Brown, R., Massuger, L.F.A.G., Song, H., Doherty, J.A., Krakstad, C., Liang, D., Odunsi, K., Berchuck, A., Jensen, A., Lubinski, J., Nevanlinna, H., Bean, Y.T., Lurie, G., Ziogas, A., Walsh, C., Despierre, E., Brinton, L., Hein, A., Rudolph, A., Dansonka-Mieszkowska, A., Olson, S.H., Harter, P., Tyrer, J., Vitonis, A.F., Brooks-Wilson, A., Aben, K.K.H., Pike, M.C., Ramus, S.J., Wik, E., Cybulski, C., Lin, J., Sucheston, L., Edwards, R., McGuire, V., Lester, J., Bois, A. du, Lundvall, L., and et al.

Abstract

Contains fulltext : 136742.pdf (publisher's version ) (Closed access), A missense single-nucleotide polymorphism (SNP) in the immune modulatory gene IL1A has been associated with ovarian cancer risk (rs17561). Although the exact mechanism through which this SNP alters risk of ovarian cancer is not clearly understood, rs17561 has also been associated with risk of endometriosis, an epidemiologic risk factor for ovarian cancer. Interleukin-1alpha (IL1A) is both regulated by and able to activate NF-kappaB, a transcription factor family that induces transcription of many proinflammatory genes and may be an important mediator in carcinogenesis. We therefore tagged SNPs in more than 200 genes in the NF-kappaB pathway for a total of 2,282 SNPs (including rs17561) for genotype analysis of 15,604 cases of ovarian cancer in patients of European descent, including 6,179 of high-grade serous (HGS), 2,100 endometrioid, 1,591 mucinous, 1,034 clear cell, and 1,016 low-grade serous, including 23,235 control cases spanning 40 studies in the Ovarian Cancer Association Consortium. In this large population, we confirmed the association between rs17561 and clear cell ovarian cancer [OR, 0.84; 95% confidence interval (CI), 0.76-0.93; P = 0.00075], which remained intact even after excluding participants in the prior study (OR, 0.85; 95% CI, 0.75-0.95; P = 0.006). Considering a multiple-testing-corrected significance threshold of P < 2.5 x 10(-5), only one other variant, the TNFSF10 SNP rs6785617, was associated significantly with a risk of ovarian cancer (low malignant potential tumors OR, 0.85; 95% CI, 0.79-0.91; P = 0.00002). Our results extend the evidence that borderline tumors may have a distinct genetic etiology. Further investigation of how these SNPs might modify ovarian cancer associations with other inflammation-related risk factors is warranted.

Published
2014

64. Ovarian Cancer and Body Size : Individual Participant Meta-Analysis Including 25,157 Women with Ovarian Cancer from 47 Epidemiological Studies

Author

Beral, V., Hermon, C., Peto, R., Reeves, G., Brinton, L., Marchbanks, P., Negri, E., Ness, R., Peeters, P. H. M., Vessey, M., Calle, E. E., Gapstur, S. M., Patel, A. V., Dal Maso, L., Talamini, R., Chetrit, A., Hirsh-Yechezkel, G., Lubin, F., Sadetzki, S., Allen, N., Bull, D., Callaghan, K., Crossley, B., Gaitskell, K., Goodill, A., Green, J., Key, T., Moser, K., Collins, R., Doll, R., Gonzalez, C. A., Lee, N., Ory, H. W., Peterson, H. B., Wingo, P. A., Martin, N., Pardthaisong, T., Silpisornkosol, S., Theetranont, C., Boosiri, B., Chutivongse, S., Jimakorn, P., Virutamasen, P., Wongsrichanalai, C., Tjonneland, A., Titus-Ernstoff, L., Byers, T., Rohan, T., Mosgaard, B. J., Yeates, D., Freudenheim, J. L., Chang-Claude, J., Kaaks, R., Anderson, K. E., Folsom, A., Robien, K., Rossing, M. A., Thomas, D. B., Weiss, N. S., Riboli, E., Clavel-Chapelon, F., Cramer, D., Hankinson, S. E., Tworoger, S. S., Franceschi, S., La Vecchia, C., Magnusson, C., Riman, T., Weiderpass, E., Wolk, A., Schouten, L. J., van den Brandt, P. A., Chantarakul, N., Koetsawang, S., Rachawat, D., Palli, D., Black, A., de Gonzalez, A. Berrington, Freedman, D. M., Hartge, P., Hsing, A. W., Lacey, J. V., Jr., Hoover, R. N., Schairer, C., Graff-Iversen, S., Selmer, R., Bain, C. J., Green, A. C., Purdie, D. M., Siskind, V., Webb, P. M., McCann, S. E., Hannaford, P., Kay, C., Binns, C. W., Lee, A. H., Zhang, M., Ness, R. B., Nasca, P., Coogan, P. F., Palmer, J. R., Rosenberg, L., Kelsey, J., Paffenbarger, R., Whittemore, A., Katsouyanni, K., Trichopoulou, A., Trichopoulos, D., Tzonou, A., Dabancens, A., Martinez, L., Molina, R., Salas, O., Goodman, M. T., Lurie, G., Carney, M. E., Wilkens, L. R., Hartman, L., Manjer, J., Olsson, H., Grisso, J. A., Morgan, M., Wheeler, J. E., Casagrande, J., Pike, M. C., Ross, R. K., Wu, A. H., Miller, A. B., Kumle, M., Lund, E., McGowan, L., Shu, X. O., Zheng, W., Farley, T. M. M., Holck, S., Meirik, O., Risch, H. A., Beral, V., Hermon, C., Peto, R., Reeves, G., Brinton, L., Marchbanks, P., Negri, E., Ness, R., Peeters, P. H. M., Vessey, M., Calle, E. E., Gapstur, S. M., Patel, A. V., Dal Maso, L., Talamini, R., Chetrit, A., Hirsh-Yechezkel, G., Lubin, F., Sadetzki, S., Allen, N., Bull, D., Callaghan, K., Crossley, B., Gaitskell, K., Goodill, A., Green, J., Key, T., Moser, K., Collins, R., Doll, R., Gonzalez, C. A., Lee, N., Ory, H. W., Peterson, H. B., Wingo, P. A., Martin, N., Pardthaisong, T., Silpisornkosol, S., Theetranont, C., Boosiri, B., Chutivongse, S., Jimakorn, P., Virutamasen, P., Wongsrichanalai, C., Tjonneland, A., Titus-Ernstoff, L., Byers, T., Rohan, T., Mosgaard, B. J., Yeates, D., Freudenheim, J. L., Chang-Claude, J., Kaaks, R., Anderson, K. E., Folsom, A., Robien, K., Rossing, M. A., Thomas, D. B., Weiss, N. S., Riboli, E., Clavel-Chapelon, F., Cramer, D., Hankinson, S. E., Tworoger, S. S., Franceschi, S., La Vecchia, C., Magnusson, C., Riman, T., Weiderpass, E., Wolk, A., Schouten, L. J., van den Brandt, P. A., Chantarakul, N., Koetsawang, S., Rachawat, D., Palli, D., Black, A., de Gonzalez, A. Berrington, Freedman, D. M., Hartge, P., Hsing, A. W., Lacey, J. V., Jr., Hoover, R. N., Schairer, C., Graff-Iversen, S., Selmer, R., Bain, C. J., Green, A. C., Purdie, D. M., Siskind, V., Webb, P. M., McCann, S. E., Hannaford, P., Kay, C., Binns, C. W., Lee, A. H., Zhang, M., Ness, R. B., Nasca, P., Coogan, P. F., Palmer, J. R., Rosenberg, L., Kelsey, J., Paffenbarger, R., Whittemore, A., Katsouyanni, K., Trichopoulou, A., Trichopoulos, D., Tzonou, A., Dabancens, A., Martinez, L., Molina, R., Salas, O., Goodman, M. T., Lurie, G., Carney, M. E., Wilkens, L. R., Hartman, L., Manjer, J., Olsson, H., Grisso, J. A., Morgan, M., Wheeler, J. E., Casagrande, J., Pike, M. C., Ross, R. K., Wu, A. H., Miller, A. B., Kumle, M., Lund, E., McGowan, L., Shu, X. O., Zheng, W., Farley, T. M. M., Holck, S., Meirik, O., and Risch, H. A.

Abstract

Background: Only about half the studies that have collected information on the relevance of women's height and body mass index to their risk of developing ovarian cancer have published their results, and findings are inconsistent. Here, we bring together the worldwide evidence, published and unpublished, and describe these relationships. Methods and Findings: Individual data on 25,157 women with ovarian cancer and 81,311 women without ovarian cancer from 47 epidemiological studies were collected, checked, and analysed centrally. Adjusted relative risks of ovarian cancer were calculated, by height and by body mass index. Ovarian cancer risk increased significantly with height and with body mass index, except in studies using hospital controls. For other study designs, the relative risk of ovarian cancer per 5 cm increase in height was 1.07 (95% confidence interval [CI], 1.05-1.09; p<0.001); this relationship did not vary significantly by women's age, year of birth, education, age at menarche, parity, menopausal status, smoking, alcohol consumption, having had a hysterectomy, having first degree relatives with ovarian or breast cancer, use of oral contraceptives, or use of menopausal hormone therapy. For body mass index, there was significant heterogeneity (p<0.001) in the findings between ever-users and never-users of menopausal hormone therapy, but not by the 11 other factors listed above. The relative risk for ovarian cancer per 5 kg/m(2) increase in body mass index was 1.10 (95% CI, 1.07-1.13; p<0.001) in never-users and 0.95 (95% CI, 0.92-0.99; p = 0.02) in ever-users of hormone therapy. Conclusions: Ovarian cancer is associated with height and, among never-users of hormone therapy, with body mass index. In high-income countries, both height and body mass index have been increasing in birth cohorts now developing the disease. If all other relevant factors had remained constant, then these increases in height and weight would be associated with

Published
2012
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65. Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium

Author

Pearce, C L, Near, A M, Van Den Berg, D J, Ramus, S J, Gentry-Maharaj, A, Menon, U, Gayther, S A, Anderson, A R, Edlund, C K, Wu, A H, Chen, X, Beesley, J, Webb, P M, Holt, S K, Chen, C, Doherty, J A, Rossing, M A, Whittemore, A S, McGuire, V, DiCioccio, R A, Goodman, M T, Lurie, G, Carney, M E, Wilkens, L R, Ness, R B, Moysich, K B, Edwards, R, Jennison, E, Kjær, Susanne Krüger, Hogdall, E, Hogdall, C K, Goode, E L, Sellers, T A, Vierkant, R A, Cunningham, J M, Cunningham, J C, Schildkraut, J M, Berchuck, A, Moorman, P G, Iversen, E S, Cramer, D W, Terry, K L, Vitonis, A F, Titus-Ernstoff, L, Song, H, Pharoah, P D P, Spurdle, A B, Anton-Culver, H, Ziogas, A, Brewster, W, Pearce, C L, Near, A M, Van Den Berg, D J, Ramus, S J, Gentry-Maharaj, A, Menon, U, Gayther, S A, Anderson, A R, Edlund, C K, Wu, A H, Chen, X, Beesley, J, Webb, P M, Holt, S K, Chen, C, Doherty, J A, Rossing, M A, Whittemore, A S, McGuire, V, DiCioccio, R A, Goodman, M T, Lurie, G, Carney, M E, Wilkens, L R, Ness, R B, Moysich, K B, Edwards, R, Jennison, E, Kjær, Susanne Krüger, Hogdall, E, Hogdall, C K, Goode, E L, Sellers, T A, Vierkant, R A, Cunningham, J M, Cunningham, J C, Schildkraut, J M, Berchuck, A, Moorman, P G, Iversen, E S, Cramer, D W, Terry, K L, Vitonis, A F, Titus-Ernstoff, L, Song, H, Pharoah, P D P, Spurdle, A B, Anton-Culver, H, Ziogas, A, and Brewster, W

Abstract

Udgivelsesdato: 2009-Jan-27, The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P< or =0.10 in a log-additive model: rs2740574 in CYP3A4 (P=0.011), rs1805386 in LIG4 (P=0.007), and rs3218536 in XRCC2 (P=0.095). Additional genotyping in other OCAC studies was undertaken and only the variant in CYP3A4, rs2740574, continued to show an association in the replication data among homozygous carriers: OR(homozygous(hom))=2.50 (95% CI 0.54-11.57, P=0.24) with 1406 cases and 2827 controls. Overall, in the combined data the odds ratio was 2.81 among carriers of two copies of the minor allele (95% CI 1.20-6.56, P=0.017, p(het) across studies=0.42) with 1969 cases and 3491 controls. There was no association among heterozygous carriers. CYP3A4 encodes a key enzyme in oestrogen metabolism and our finding between rs2740574 and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted.

Published
2009

67. L'identité française entre tradition et modernité. De Clovis à Renan et de Louis XVI à Sarkozy

Author

Putman Cramer, D., Kok Escalle, M.C.J. (Thesis Advisor), Putman Cramer, D., and Kok Escalle, M.C.J. (Thesis Advisor)

Abstract

L'identité française en 2008 se trouve entre ses racines traditionnelles de christianisme et d'une monarchie et les valeurs républicaines, notamment de la laïcité. Pourtant, la République « une et indivisible » se heurte à la réalité humaine en ce qui concerne la diversité culturelle, le droit à la différence, les données sociologiques et en plus dépasse la coupure fondatrice de 1789. Ce fossé entre une volonté politique et la dimension humaine se prononce encore plus face à l'Autre : les « barbares » dépourvu d´un esprit éclairé. Actuellement, il s'agit d'une crise identitaire, à cause du fossé entre les valeurs traditionnelles et contemporaines et de l´occultation et la délégitimation de l'identité nationale. Le manque de réperes culturels posent problèmes d'assimilation et d'intégration aux immigrés.

Published
2008

70. Potential Role of HE4 in Multimodal Screening for Epithelial Ovarian Cancer

Author

Urban, N., primary, Thorpe, J. D., additional, Bergan, L. A., additional, Forrest, R. M., additional, Kampani, A. V., additional, Scholler, N., additional, O'Briant, K. C., additional, Anderson, G. L., additional, Cramer, D. W., additional, Berg, C. D., additional, McIntosh, M. W., additional, Hartge, P., additional, and Drescher, C. W., additional

Published
2011
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80. Human productivity program definition

Author

Cramer, D. B

Subjects
Man/System Technology And Life Support
Abstract

The optimization of human productivity on the space station within the existing resources and operational constraints is the aim of the Human Productivity Program. The conceptual objectives of the program are as follows: (1) to identify long lead technology; (2) to identify responsibility for work elements; (3) to coordinate the development of crew facilities and activities; and (4) to lay the foundation for a cost effective approach to improving human productivity. Human productivity work elements are also described and examples are presented.

Published
1985

81. Physiological Considerations of Artificial Gravity

Author

Cramer, D. B

Subjects
Aerospace Medicine
Abstract

Weightlessness produces significant physiological changes. Whether these changes will stabilize or achieve medical significance is not clear. Artificial gravity is the physiological countermeasure, and the tether system represents an attractive approach to artificial gravity. The need for artificial gravity is examined.

Published
1985

82. Space Station and the life sciences

Author

White, R. J, Leonard, J. I, Cramer, D. B, and Bishop, W. P

Subjects
Aerospace Medicine
Abstract

Previous fundamental research in space life sciences is examined, and consideration is devoted to studies relevant to Space Station activities. Microgravity causes weight loss, hemoconcentration, and orthostatic intolerance when astronauts returns to earth. Losses in bone density, bone calcium, and muscle nitrogen have also been observed, together with cardiovascular deconditioning, fluid-electrolyte metabolism alteration, and space sickness. Experiments have been performed with plants, bacteria, fungi, protozoa, tissue cultures, invertebrate species, and with nonhuman vertebrates, showing little effect on simple cell functions. The Spacelab first flight will feature seven life science experiments and the second flight, two. Further studies will be performed on later flights. Continued life science studies to optimize human performance in space are necessary for the efficient operation of a Space Station and the assembly of large space structures, particularly in interaction with automated machinery.

Published
1983

83. The first dedicated life sciences mission - Spacelab 4

Author

Cramer, D. R, Reid, D. H, and Klein, H. P

Subjects
Astronautics (General)
Abstract

The details of the payload and the experiments in Spacelab 4, the first Spacelab mission dedicated entirely to the life sciences, are discussed. The payload of Spacelab 4, carried in the bay of the Shuttle Orbiter, consists of 25 tentatively selected investigations combined into a comprehensive integrated exploration of the effects of acute weightlessness on living systems. The payload contains complementary designs in the human and animal investigations in order to validate animal models of human physiology in weightlessness. Animals used as experimental subjects will include squirrel monkeys, laboratory rats, several species of plants, and frog eggs. The main scientific objectives of the investigations include the study of the acute cephalic fluid shift, cardiovascular adaptation to weightlessness, including postflight reductions in orthostatic tolerance and exercise capacity, and changes in vestibular function, including space motion sickness, associated with weightlessness. Other scientific objective include the study of red cell mass reduction, negative nitrogen balance, altered calcium metabolism, suppressed in vitro lymphocyte reactivity, gravitropism and photropism in plants, and fertilization and early development in frog eggs.

Published
1983
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84. Antimotion-sickness efficacy of scopolamine 12 and 72 hours after transdermal administration

Author

Graybiel, A, Cramer, D. B, and Wood, C. D

Subjects
Aerospace Medicine
Abstract

The antimotion sickness remedy, transdermal therapeutic system-scopolamine, administered in this experiment was scheduled to deliver 1.0 mg of scopolamine over a period of 3 d, and this paper compares its efficacy 12 and 72 h after administration. In a double-blind study, six male college students were individually exposed to a standardized provocative test in a slow rotation room after six apparently identical treatments comprising four placebos and two medications. Efficacy was categorized as beneficial, inconsequential, or detrimental. None of the responses was detrimental. Following the first administration of the therapeutic system, there were four beneficial responses after 12 h but none was beneficial after 72 h. Following the second treatment regimen, there were four beneficial responses after 12 h and three beneficial responses after 72 h. Great individual differences were demonstrated, two subjects accounting for six beneficial responses and two accounting for only one beneficial response. The difference in efficacy after 12 and 72 h has practical and theoretical significance.

Published
1982

85. Life science research in space - The Spacelab era

Author

Farrell, R. M, Cramer, D. B, and Reid, D. H

Subjects
Life Sciences (General)
Abstract

The events leading up to Spacelab mission 4, which is to be dedicated exclusively to life sciences experimentation in 1984-85, are described. Out of 400 experiment proposals initially received and assessed, 87 candidates were chosen for definition studies to identify the resources which would be required. These proposals addressed such problems encountered in previous space flights as space motion sickness, cardiovascular deconditioning and muscle wasting, calcium loss, and red cell mass reduction. Additional experiments were selected from bioengineering, plant physiology, and cell biology. Human subjects will consist of a Mission Specialist Astronaut and up to four Payload Specialists. Equipment to be used in experimentation includes biotelemetry systems, microscopes, cameras, centrifuges and refrigerators, all of which have been designed for use in weightless conditions. The 87 candidate experiments will be further reduced to about 20.

Published
1982

86. Experimental motion sickness - Efficacy of transdermal scopolamine plus ephedrine

Author

Graybiel, A, Cramer, D. B, and Wood, C. D

Subjects
Aerospace Medicine
Abstract

A double-blind, placebo-controlled study compared the efficacy of transdermal therapeutic system-scopolamine administered alone and combined with ephedrine sulfate given orally in doses of 12.5, 25, and 50 mg. Eight normal male students were exposed to stressful accelerations in a slow-rotation room after receiving 10 apparently identical treatments comprising the four drugs and six placebos. Efficacy of the drug was defined in terms of the placebo range and categorized as beneficial, inconsequential, or detrimental. None of the effects was detrimental. Overall beneficial effects were 60% for transdermal therapeutic system-scopolamine (plus placebo) and 57% for the three transdermal therapeutic system-scopolamine plus ephedrine combinations.

Published
1981

87. Successful trnasfer of adaptation environments in navy flight training

Author

Cramer, D. B, Graybiel, A, and Oosterveld, W. J

Subjects
Man/System Technology And Life Support
Abstract

Two flight students, grounded for the reason they were highly susceptible to motion sickness, completed their training after gradually adapting 10 rpm, achieved by executing head movements during small stepwise increases in angular velocity. Subject 1 executed a total of about 77,000 head movements within a period of five months and Subject 2 executed about 108,000 head movements within a period of 42 days. The transfer of the adaptation acquired in the laboratory to most motion environments aloft was good; the notable exception involved weightless maneuvers in the case of Subject 1. Both were on flight status when contacted recently. The current motion sickness susceptibility in Subject 1 in the fall of 1975 was assessed. He reached a (mild) motion sickness endpoint, in the rotating room, at 17 rpm; the average endpoint is 7 to 8 rpm. Some practical and theoretical implications are discussed.

Published
1977

96. The influence of vision on susceptibility to acute motion sickness studied under quantifiable stimulus-response conditions

Author

Oosterveld, W. J, Graybiel, A, and Cramer, D. B

Subjects
Biosciences
Abstract

Twenty-four healthy men, 22 to 25 years of age, were exposed to stressful accelerations in a rotating room until acute mild motion sickness was elicited. Thirteen subjects in one group were exposed first with eyes open and later with eyes covered; the reverse order was used with the remaining eleven in the other group. The stressful accelerations were generated by requiring the subject to execute 120 standardized head movements at each 1-rpm increase in angular velocity until the desired endpoint was reached. When susceptibility to motion sickness with eyes open and covered is compared, 19 subjects were more susceptible with eyes open, three with eyes covered, and in the remaining two susceptibility was the same. The maximum difference in velocity between trial 1 and 2 was 7 rpm when susceptibility was greater with eyes open and 3 rpm when it was greater with eyes covered; the means, respectively, were 3.2 and 2.0 rpm. Among subjects manifesting greater susceptibility with eyes open than covered the group differences were small, indicating little or no adaptation effects. The findings are discussed mainly on the basis that vision may act also to decrease susceptibility under the stimulus conditions described.

Published
1971

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