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5. Evidence of Gene-Environment Interactions between Common Breast Cancer Susceptibility Loci and Established Environmental Risk Factors

Author

Nickels, S, Truong, T, Hein, R, Stevens, K, Buck, K, Behrens, S, Eilber, U, Schmidt, M, Häberle, L, Vrieling, A, Gaudet, M, Figueroa, J, Schoof, N, Spurdle, AB, Rudolph, A, Fasching, PA, Hopper, JL, Makalic, E, Schmidt, DF, Southey, MC, Beckmann, MW, Ekici, AB, Fletcher, O, Gibson, L, dos Santos Silva, I, Peto, J, Humphreys, MK, Wang, J, Cordina-Duverger, E, Menegaux, F, Nordestgaard, BG, Bojesen, SE, Lanng, C, Anton-Culver, H, Ziogas, A, Bernstein, L, Clarke, CA, Brenner, H, Müller, H, Arndt, V, Stegmaier, C, Brauch, H, Brüning, T, Harth, V, Mannermaa, A, Kataja, V, Kosma, VM, Hartikainen, JM, Lambrechts, D, Smeets, D, Neven, P, Paridaens, R, Flesch-Janys, D, Obi, N, Wang-Gohrke, S, Couch, FJ, Olson, JE, Vachon, CM, Giles, GG, Severi, G, Baglietto, L, Offit, K, John, EM, Miron, A, Andrulis, IL, Knight, JA, Glendon, G, Mulligan, AM, Chanock, SJ, Lissowska, J, Liu, J, Cox, A, Cramp, H, Connley, D, Balasubramanian, S, Dunning, AM, Shah, M, Trentham-Dietz, A, Newcomb, P, Titus, L, Egan, K, Cahoon, EK, and Rajaraman, P

Abstract

Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity) in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood ratio tests to assess gene-environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (Pinteraction= 2.4×10-6) and between CASP8-rs17468277 and alcohol consumption (Pinteraction= 3.1×10-4). Overall, the per-allele odds ratio (95% confidence interval) for LSP1-rs3817198 was 1.08 (1.01-1.16) in nulliparous women and ranged from 1.03 (0.96-1.10) in parous women with one birth to 1.26 (1.16-1.37) in women with at least four births. For CASP8-rs17468277, the per-allele OR was 0.91 (0.85-0.98) in those with an alcohol intake of

Published
2013

7. Comparison of 6q25 breast cancer hits from Asian and European genome wide association studies in the Breast Cancer Association consortium (BCAC)

Author

Ashworth, Alan, Hein, R, Maranian, M, Hopper, JL, Kapuscinski, MK, Southey, MC, Park, DJ, Schmidt, MK, Broeks, A, Hogervorst, FBL, and Bueno-de-Mesquit, HB

Abstract

The 6q25.1 locus was first identified via a genome-wide association study (GWAS) in Chinese women and marked by single nucleotide polymorphism (SNP) rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association

Published
2012

8. Evaluation of variation in the phosphoinositide-3-kinase catalytic subunit alpha oncogene and breast cancer risk

Author

Stevens, KN, Garcia-Closas, M, Fredericksen, Z, Kosel, M, Pankratz, VS, Hopper, JL, Dite, GS, Apicella, C, Southey, MC, Schmidt, MK, Broeks, A, Van ‘t Veer, LJ, Tollenaar, RAEM, Fasching, PA, Beckmann, MW, Hein, A, Ekici, AB, Johnson, N, Peto, J, dos Santos Silva, I, Gibson, L, Sawyer, E, Tomlinson, I, Kerin, MJ, Chanock, S, Lissowska, J, Hunter, DJ, Hoover, RN, Thomas, GD, Milne, RL, Pérez, JI Arias, González-Neira, A, Benítez, J, Burwinkel, B, Meindl, A, Schmutzler, RK, Bartrar, CR, Hamann, U, Ko, YD, Brüning, T, Chang-Claude, J, Hein, R, Wang-Gohrke, S, Dörk, T, Schürmann, P, Bremer, M, Hillemanns, P, Bogdanova, N, Zalutsky, JV, Rogov, YI, Antonenkova, N, Lindblom, A, Margolin, S, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, J, Chenevix-Trench, G, Chen, X, Peterlongo, P, Bonanni, B, Bernard, L, Manoukian, S, Wang, X, Cerhan, J, Vachon, CM, Olson, J, Giles, GG, Baglietto, L, McLean, CA, Severi, G, John, EM, Miron, A, Winqvist, R, Pylkäs, K, Jukkola-Vuorinen, A, Grip, M, Andrulis, I, Knight, JA, Glendon, G, Mulligan, AM, Cox, A, Brock, IW, Elliott, G, Cross, SS, Pharoah, PP, Dunning, AM, Pooley, KA, Humphreys, MK, Wang, J, Kang, D, Yoo, K-Y, Noh, D-Y, Sangrajrang, S, Gabrieau, V, Brennan, P, McKay, J, Anton-Culver, H, Ziogas, A, and Couch, FJ

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Prevention, Genetics, Cancer, Breast Cancer, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Breast Neoplasms, Case-Control Studies, Class I Phosphatidylinositol 3-Kinases, Female, Genetic Predisposition to Disease, Genetic Variation, Humans, Phosphatidylinositol 3-Kinases, genetic susceptibility, neoplasms, association study, GENICA Network, kConFab Investigators, Australian Ovarian Cancer Study Group, Public Health and Health Services, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundSomatic mutations in phosphoinositide-3-kinase catalytic subunit alpha (PIK3CA) are frequent in breast tumours and have been associated with oestrogen receptor (ER) expression, human epidermal growth factor receptor-2 overexpression, lymph node metastasis and poor survival. The goal of this study was to evaluate the association between inherited variation in this oncogene and risk of breast cancer.MethodsA single-nucleotide polymorphism from the PIK3CA locus that was associated with breast cancer in a study of Caucasian breast cancer cases and controls from the Mayo Clinic (MCBCS) was genotyped in 5436 cases and 5280 controls from the Cancer Genetic Markers of Susceptibility (CGEMS) study and in 30 949 cases and 29 788 controls from the Breast Cancer Association Consortium (BCAC).ResultsRs1607237 was significantly associated with a decreased risk of breast cancer in MCBCS, CGEMS and all studies of white Europeans combined (odds ratio (OR)=0.97, 95% confidence interval (CI) 0.95-0.99, P=4.6 × 10(-3)), but did not reach significance in the BCAC replication study alone (OR=0.98, 95% CI 0.96-1.01, P=0.139).ConclusionCommon germline variation in PIK3CA does not have a strong influence on the risk of breast cancer.

Published
2011

9. Assessing interactions between the associations of common genetic susceptibility variants, reproductive history and body mass index with breast cancer risk in the breast cancer association consortium: A combined case-control study

Author

Milne, RL, Gaudet, MM, Spurdle, AB, Fasching, PA, Couch, FJ, Benítez, J, Arias Pérez, JI, Zamora, MP, Malats, N, dos Santos Silva, I, Gibson, LJ, Fletcher, O, Johnson, N, Anton-Culver, H, Ziogas, A, Figueroa, J, Brinton, L, Sherman, ME, Lissowska, J, Hopper, JL, Dite, GS, Apicella, C, Southey, MC, Sigurdson, AJ, Linet, MS, Schonfeld, SJ, Freedman, DM, Mannermaa, A, Kosma, VM, Kataja, V, Auvinen, P, Andrulis, IL, Glendon, G, Knight, JA, Weerasooriya, N, Cox, A, Reed, MWR, Cross, SS, Dunning, AM, Ahmed, S, Shah, M, Brauch, H, Ko, YD, Brüning, T, Lambrechts, D, Reumers, J, Smeets, A, Wang-Gohrke, S, Hall, P, Czene, K, Liu, J, Irwanto, AK, Chenevix-Trench, G, Holland, H, Fab, KC, Giles, GG, Baglietto, L, Severi, G, Bojensen, SE, Nordestgaard, BG, Flyger, H, John, EM, West, DW, Whittemore, AS, Vachon, C, Olson, JE, Fredericksen, Z, Kosel, M, Hein, R, Vrieling, A, Flesch-Janys, D, Heinz, J, Beckmann, MW, Heusinger, K, Ekici, AB, Haeberle, L, Humphreys, MK, Morrison, J, Easton, DF, and Pharoah, PD

Abstract

Introduction: Several common breast cancer genetic susceptibility variants have recently been identified. We aimed to determine how these variants combine with a subset of other known risk factors to influence breast cancer risk in white women of European ancestry using case-control studies participating in the Breast Cancer Association Consortium.Methods: We evaluated two-way interactions between each of age at menarche, ever having had a live birth, number of live births, age at first birth and body mass index (BMI) and each of 12 single nucleotide polymorphisms (SNPs) (10q26-rs2981582 (FGFR2), 8q24-rs13281615, 11p15-rs3817198 (LSP1), 5q11-rs889312 (MAP3K1), 16q12-rs3803662 (TOX3), 2q35-rs13387042, 5p12-rs10941679 (MRPS30), 17q23-rs6504950 (COX11), 3p24-rs4973768 (SLC4A7), CASP8-rs17468277, TGFB1-rs1982073 and ESR1-rs3020314). Interactions were tested for by fitting logistic regression models including per-allele and linear trend main effects for SNPs and risk factors, respectively, and single-parameter interaction terms for linear departure from independent multiplicative effects.Results: These analyses were applied to data for up to 26,349 invasive breast cancer cases and up to 32,208 controls from 21 case-control studies. No statistical evidence of interaction was observed beyond that expected by chance. Analyses were repeated using data from 11 population-based studies, and results were very similar.Conclusions: The relative risks for breast cancer associated with the common susceptibility variants identified to date do not appear to vary across women with different reproductive histories or body mass index (BMI). The assumption of multiplicative combined effects for these established genetic and other risk factors in risk prediction models appears justified. © 2010 Milne et al.; licensee BioMed Central Ltd.

Published
2010

11. Implantation robot-assistée du sphincter artificiel urinaire AMS-800 chez la femme : une série multicentrique internationale de 182 patientes

Author

Peyronnet, B., primary, Cornu, J., additional, Belas, O., additional, Capon, G., additional, Biardeau, X., additional, Lecoanet, P., additional, Castro-Sader, L., additional, Borojeni, S., additional, Hein, R., additional, Hascoet, J., additional, Thibault, F., additional, Dubois, F., additional, Cardot, V., additional, Vidart, A., additional, Descazeaud, A., additional, Fournier, G., additional, and Van der aa, F., additional

Published
2022
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13. ACE inhibitors in SSc patients display a risk factor for scleroderma renal crisis—a EUSTAR analysis

Author

Bütikofer L, Varisco PA, Distler O, Kowal-Bielecka O, Allanore Y, Riemekasten G, Villiger PM, Adler S, Avouac J, Walker UA, Guiducci S, Airò P, Hachulla E, Valentini G, Carreira PE, Cozzi F, Gurman AB, Braun-Moscovici Y, Damjanov N, Ananieva LP, Scorza R, Jimenez S, Busquets J, Li M, Müller-Ladner U, Maurer B, Tyndall A, Lapadula G, Iannone F, Becvar R, Sierakowsky S, Bielecka OK, Cutolo M, Sulli A, Cuomo G, Vettori S, Rednic S, Nicoara I, Vlachoyiannopoulos P, Montecucco C, Caporali R, Novak S, Czirják L, Varju C, Chizzolini C, Kucharz EJ, Kotulska A, Kopec-Medrek M, Widuchowska M, Rozman B, Mallia C, Coleiro B, Gabrielli A, Farge D, Hij A, Hesselstrand R, Scheja A, Wollheim F, Martinovic D, Govoni M, Monaco AL, Hunzelmann N, Pellerito R, Bambara LM, Caramaschi P, Black C, Denton C, Henes J, Santamaria VO, Heitmann S, Krasowska D, Seidel M, Oleszowsky M, Burkhardt H, Himsel A, Salvador MJ, Stamenkovic B, Stankovic A, Tikly M, Starovoytova MN, Engelhart M, Strauss G, Nielsen H, Damgaard K, Szücs G, Mendoza AZ, de la Puente Buijdos C, Sifuentes Giraldo WA, Midtvedt Ø, Garen T, Launay D, Valesini G, Riccieri V, Ionescu RM, Opris D, Groseanu L, Wigley FM, Mihai CM, Cornateanu RS, Ionitescu R, Gherghe AM, Gorga M, Dobrota R, Bojinca M, Schett G, Distler JHW, Meroni P, Zeni S, Mouthon L, De Keyser F, Smith V, Cantatore FP, Corrado A, Ullman S, Iversen L, Pozzi MR, Eyerich K, Hein R, Knott E, Szechinski J, Wiland P, Szmyrka-Kaczmarek M, Sokolik R, Morgiel E, Krummel-Lorenz B, Saar P, Aringer M, Günther C, Anic B, Baresic M, Mayer M, Radominski SC, de Souza Müller C, Azevedo VF, Agachi S, Groppa L, Chiaburu L, Russu E, Zenone T, Stebbings S, Highton J, Stamp L, Chapman P, Baron M, O'Donnell J, Solanki K, Doube A, Veale D, O'Rourke M, Loyo E, Rosato E, Pisarri S, Tanaseanu CM, Popescu M, Dumitrascu A, Tiglea I, Chirieac R, Ancuta C, Furst DE, Kafaja S, de la Peña Lefebvre PG, Rubio SR, Exposito MV, Sibilia J, Chatelus E, Gottenberg JE, Chifflot H, Litinsky I, Venalis A, Butrimiene I, Venalis P, Rugiene R, Karpec D, Kerzberg E, Montoya F, Cosentino V, Castellvi I., Publica, Bütikofer, L, Varisco, Pa, Distler, O, Kowal-Bielecka, O, Allanore, Y, Riemekasten, G, Villiger, Pm, Adler, S, Avouac, J, Walker, Ua, Guiducci, S, Airò, P, Hachulla, E, Valentini, G, Carreira, Pe, Cozzi, F, Gurman, Ab, Braun-Moscovici, Y, Damjanov, N, Ananieva, Lp, Scorza, R, Jimenez, S, Busquets, J, Li, M, Müller-Ladner, U, Maurer, B, Tyndall, A, Lapadula, G, Iannone, F, Becvar, R, Sierakowsky, S, Bielecka, Ok, Cutolo, M, Sulli, A, Cuomo, G, Vettori, S, Rednic, S, Nicoara, I, Vlachoyiannopoulos, P, Montecucco, C, Caporali, R, Novak, S, Czirják, L, Varju, C, Chizzolini, C, Kucharz, Ej, Kotulska, A, Kopec-Medrek, M, Widuchowska, M, Rozman, B, Mallia, C, Coleiro, B, Gabrielli, A, Farge, D, Hij, A, Hesselstrand, R, Scheja, A, Wollheim, F, Martinovic, D, Govoni, M, Monaco, Al, Hunzelmann, N, Pellerito, R, Bambara, Lm, Caramaschi, P, Black, C, Denton, C, Henes, J, Santamaria, Vo, Heitmann, S, Krasowska, D, Seidel, M, Oleszowsky, M, Burkhardt, H, Himsel, A, Salvador, Mj, Stamenkovic, B, Stankovic, A, Tikly, M, Starovoytova, Mn, Engelhart, M, Strauss, G, Nielsen, H, Damgaard, K, Szücs, G, Mendoza, Az, de la Puente Buijdos, C, Sifuentes Giraldo, Wa, Midtvedt, Ø, Garen, T, Launay, D, Valesini, G, Riccieri, V, Ionescu, Rm, Opris, D, Groseanu, L, Wigley, Fm, Mihai, Cm, Cornateanu, R, Ionitescu, R, Gherghe, Am, Gorga, M, Dobrota, R, Bojinca, M, Schett, G, Distler, Jhw, Meroni, P, Zeni, S, Mouthon, L, De Keyser, F, Smith, V, Cantatore, Fp, Corrado, A, Ullman, S, Iversen, L, Pozzi, Mr, Eyerich, K, Hein, R, Knott, E, Szechinski, J, Wiland, P, Szmyrka-Kaczmarek, M, Sokolik, R, Morgiel, E, Krummel-Lorenz, B, Saar, P, Aringer, M, Günther, C, Anic, B, Baresic, M, Mayer, M, Radominski, Sc, de Souza Müller, C, Azevedo, Vf, Agachi, S, Groppa, L, Chiaburu, L, Russu, E, Zenone, T, Stebbings, S, Highton, J, Stamp, L, Chapman, P, Baron, M, O'Donnell, J, Solanki, K, Doube, A, Veale, D, O'Rourke, M, Loyo, E, Rosato, E, Pisarri, S, Tanaseanu, Cm, Popescu, M, Dumitrascu, A, Tiglea, I, Chirieac, R, Ancuta, C, Furst, De, Kafaja, S, de la Peña Lefebvre, Pg, Rubio, Sr, Exposito, Mv, Sibilia, J, Chatelus, E, Gottenberg, Je, Chifflot, H, Litinsky, I, Venalis, A, Butrimiene, I, Venalis, P, Rugiene, R, Karpec, D, Kerzberg, E, Montoya, F, Cosentino, V, and Castellvi, I.

Subjects
INVOLVEMENT, Male, Hypertension, Renal, ACE inhibitors, lcsh:Diseases of the musculoskeletal system, Scleroderma Renal Crisis, MULTICENTER, Angiotensin-Converting Enzyme Inhibitors, Scleroderma, Scleroderma renal crisis, 0302 clinical medicine, Risk Factors, Medicine and Health Sciences, Medicine, 030212 general & internal medicine, Prospective Studies, 610 Medicine & health, Renal, Antihypertensive drugs, Outcome, antihypertensive drugs, arterial hypertension, outcome, scleroderma renal crisis, Incidence (epidemiology), Incidence, Hazard ratio, Acute Kidney Injury, Middle Aged, Europe, Treatment Outcome, Population Surveillance, Cohort, Hypertension, Female, 360 Social problems & social services, Proto-oncogene tyrosine-protein kinase Src, Research Article, Arterial hypertension, medicine.medical_specialty, 03 medical and health sciences, ENDOTHELIN-1, Internal medicine, Humans, Risk factor, Aged, 030203 arthritis & rheumatology, Scleroderma, Systemic, business.industry, SYSTEMIC-SCLEROSIS, Systemic, medicine.disease, Concomitant, lcsh:RC925-935, business
Abstract

Objectives To investigate the effect of ACE inhibitors (ACEi) on the incidence of scleroderma renal crisis (SRC) when given prior to SRC in the prospectively collected cohort from the European Scleroderma Trial and Research Group (EUSTAR). Methods SSc patients without prior SRC and at least one follow-up visit were included and analyzed regarding SRC, arterial hypertension, and medication focusing on antihypertensive medication and glucocorticoids (GC). Results Out of 14,524 patients in the database, we identified 7648 patients with at least one follow-up. In 27,450 person-years (py), 102 patients developed SRC representing an incidence of 3.72 (3.06–4.51) per 1000 py. In a multivariable time-to-event analysis adjusted for age, sex, disease severity, and onset, 88 of 6521 patients developed SRC. The use of ACEi displayed an increased risk for the development of SRC with a hazard ratio (HR) of 2.55 (95% confidence interval (CI) 1.65–3.95). Adjusting for arterial hypertension resulted in a HR of 2.04 (95%CI 1.29–3.24). There was no evidence for an interaction of ACEi and arterial hypertension (HR 0.83, 95%CI 0.32–2.13, p = 0.69). Calcium channel blockers (CCB), angiotensin receptor blockers (ARB), endothelin receptor antagonists, and GC—mostly in daily dosages below 15 mg of prednisolone—did not influence the hazard for SRC. Conclusions ACEi in SSc patients with concomitant arterial hypertension display an independent risk factor for the development of SRC but are still first choice in SRC treatment. ARBs might be a safe alternative, yet the overall safety of alternative antihypertensive drugs in SSc patients needs to be further studied.

Published
2020

16. Factors associated with health-related quality of life among community-dwelling older adults: the APPCARE study

Author

Esmée L. S. Bally, Sophie A. Korenhof, Lizhen Ye, Amy van Grieken, Siok Swan Tan, Francesco Mattace-Raso, Elena Procaccini, Tamara Alhambra-Borrás, and Hein Raat

Subjects
Medicine, Science
Abstract

Abstract This study aimed to identify the factors associated with health-related quality of life (HRQOL) among community-dwelling older adults. Physical and mental HRQOL were measured by the 12-item Short Form Health Survey (SF-12) at baseline and follow-up. Linear regression models were used to evaluate associations between socio-demographic, health, and lifestyle factors and HRQOL. The sample included 661 participants (mean age = 77.4 years). Frailty was negatively associated with physical HRQOL (B = − 5.56; P

Published
2024
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17. A lifestyle screening tool for young children in the community: needs and wishes of parents and youth healthcare professionals

Author

Anne Krijger, Lieke Schiphof-Godart, Caren Lanting, Liset Elstgeest, Hein Raat, and Koen Joosten

Subjects
Lifestyle, Toddlers, Youth healthcare, Prevention, Focus groups, Public aspects of medicine, RA1-1270
Abstract

Abstract Background Youth healthcare has an important role in promoting a healthy lifestyle in young children in order to prevent lifestyle-related health problems. To aid youth healthcare in this task, a new lifestyle screening tool will be developed. The aim of this study was to explore how youth healthcare professionals (YHCP) could best support parents in improving their children’s lifestyle using a new lifestyle screening tool for young children. Methods We conducted four and seven focus groups among parents (N = 25) and YHCP (N = 25), respectively. Two main topics were addressed: the experiences with current practice of youth healthcare regarding lifestyle in young children, and the requirements for the lifestyle screening tool to be developed. The focus groups were recorded, transcribed verbatim and analysed using an inductive approach. Results Both parents and YHCP indicated that young children’s lifestyles are often discussed during youth healthcare appointments. While parents felt that this discussion could be more in-depth, YHCP mainly needed clues to continue the discussion. According to parents and YHCP, a new lifestyle screening tool for young children should be easy to use, take little time and provide courses of action. Moreover, it should be attractive to complete and align with the family concerned. Conclusions According to parents and YHCP, a new lifestyle screening tool for young children could be useful to discuss specific lifestyle topics in more detail and to provide targeted advice.

Published
2024
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18. Whole-ocean network design and implementation pathway for Arctic marine conservation

Author

Timothy D. James, Martin Sommerkorn, Boris Solovyev, Nikita Platonov, John Morrison, Natalia Chernova, Maria V. Gavrilo, Martine Giangioppi, Irina Onufrenya, John C. Roff, Olga V. Shpak, Hein Rune Skjoldal, Vasily Spiridonov, Jeff A. Ardron, Stanislav Egorovich Belikov, Bodil A. Bluhm, Tom Christensen, Jørgen S. Christiansen, Olga A. Filatova, Mette Frost, Adrian Gerhartz-Abraham, Kasper Lambert Johansen, Oleg V. Karamushko, Erin Keenan, Anatoly A. Kochnev, Melanie L. Lancaster, Evgeniya Melikhova, Will Merritt, Anders Mosbech, Maria N. Pisareva, Peter Rask Møller, Maria Solovyeva, Grigori Tertitski, and Irina S. Trukhanova

Subjects
Oceanography, GC1-1581, Environmental sciences, GE1-350
Abstract

Abstract Forestalling the decline of global biodiversity requires urgent and transformative action at all levels of government and society, particularly in the Arctic Ocean and adjacent seas where rapid changes are already underway. Amid growing scientific support and mounting pressure, the majority of nations have committed to the most ambitious conservation targets yet. However, without an approach that inclusively and equitably reconciles conservation and sustainable ocean use, these targets will likely go unmet. Here, we present ArcNet: a network design framework to help achieve ocean-scale, area-based marine conservation in the Arctic. The framework is centred around a suite of web-based tools and a ~ 5.9 million km2 network of 83 priority areas for conservation designed through expert-driven systematic conservation planning using conservation targets for over 800 features representing Arctic biodiversity. The ArcNet framework is intended to help adapt to new and emerging information, foster collaboration, and identify tailored conservation measures within a global context at different levels of planning and implementation.

Published
2024
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24. Robot-assisted artificial urinary sphincter implantation in female patients: An international multicenter series of 182 patients

Author

Peyronnet, B., primary, Cornu, J-N., additional, Belas, O., additional, Capon, G., additional, Biardeau, X., additional, Lecoanet, P., additional, Castro-Sader, L., additional, Borojeni, S., additional, Hein, R., additional, Hascoet, J., additional, Thibault, F., additional, Dubois, F., additional, Cardot, V., additional, Vidart, A., additional, Descazeaud, A., additional, Fournier, G., additional, and Van Der Aa, F., additional

Published
2022
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27. Electrochemical Anion Sensing: Supramolecular Approaches

Author

Hein, R, Beer, PD, and Davis, JJ

Subjects
chemistry.chemical_classification, chemistry, 010405 organic chemistry, Supramolecular chemistry, Non-covalent interactions, Nanotechnology, General Chemistry, 010402 general chemistry, Electrochemistry, 01 natural sciences, 0104 chemical sciences
Abstract

Anions play a vital role in a broad range of environmental, technological, and physiological processes, making their detection/quantification valuable. Electroanalytical sensors offer much to the selective, sensitive, cheap, portable, and real-time analysis of anion presence where suitable combinations of selective (noncovalent) recognition and transduction can be integrated. Spurred on by significant developments in anion supramolecular chemistry, electrochemical anion sensing has received considerable attention in the past two decades. In this review, we provide a detailed overview of all electroanalytical techniques that have been used for this purpose, including voltammetric, impedimetric, capacititive, and potentiometric methods. We will confine our discussion to sensors that are based on synthetic anion receptors with a specific focus on reversible, noncovalent interactions, in particular, hydrogen- and halogen-bonding. Apart from their sensory properties, we will also discuss how electrochemical techniques can be used to study anion recognition processes (e.g., binding constant determination) and will furthermore provide a detailed outlook over future efforts and promising new avenues in this field.

Published
2020

29. Onkologie III: Grundlagen

Author

Kornfehl, J., Wilfing, A., Hermann, M., Grubeck-Loebenstein, B., Bettinger, B., Lörz, M., Knecht, R., v. Ilberg, C., Klima, A., Bettinger, R., Weber, A., Clasen, B., Kaffenberger, W., v. Beuningen, D., Herold-Mende, C., Ouhayoun, J.-P., Maier, H., Bosch, F. X., Mahran, A., Sinn, H. P., Born, I. A., Weidauer, H., Wustrow, T. P. U., Hein, R., Issing, W. J., Krieg, T., Pettig, C., Jakschies, D., Fibich, C., v. Wussow, P., Deicher, H., Lehnhardt, E., Arndt, O., Bauer, I., Brock, J., Gutmann, R., Feyh, J., Kastenbauer, E., Rolfs, F., Rausch, P. Ch., Schreiber, F., Neu, W., Feldmann, Harald, and Herberhold, Claus

Published
1993
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34. Dia-Klinik

Author

Braun-Falco, O., Landthaler, M., Ruzicka, Th., Kaudewitz, P., Bieber, K., Eckert, F., Schirren, C. G., Lübke, S., Herzer, P., Krieg, Th., Hohenleutner, U., von der Helm, D., Hein, R., Schrallhammer, K., Georgii, A., Neubert, U., Grimm, W., Korting, H. C., Trautner, B., Bergner, Th., Przybilla, B., Löscher, T., Behrendt, H., Stolz, W., Burg, G., Schulte, Ch., Linke, R., Parsch, E.-M., Konz, B., Spornraft, P., Bilek, P., Wolff, H., Merkle, T., Fröschl, M., Bieber, Th., Meurer, M., Lissner, Dr. A., Zienicke, H., Vieluf, D., Ring, J., Gollhausen, R., Soehnchen, R., Abeck, D., Lobkowicz, F., Hartinger, A., Stallmann, D., Donhauser, G., Braun-Falco, Otto, editor, and Ring, Johannes, editor

Published
1990
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36. Electrochemical anion sensing in solution and at receptive interfaces

Author

Hein, R, Davis, J, and Beer, P

Subjects
Chemistry
Abstract

This thesis describes the investigation of halogen bonding and hydrogen bonding anion receptors for the electrochemical sensing of anions in solution and at receptor-modified electrodes. Chapter 1 introduces the general concepts of supramolecular host-guest chemistry and electrochemical anion sensing. A range of voltammetric, impedimetric and potentiometric anion sensors and their basic operational principles are discussed. Chapter 2 describes redox-active ferrocene- or osmium (II) bipyridyl-containing anion receptors for the voltammetric detection of anions in aqueous-organic solvent systems. This includes detailed studies and comparisons of voltammetric sensing under diffusive as well as surface-confined conditions. Chapter 3 explores the unprecedented use of non-Faradaic capacitance spectroscopy for the sensing of anions in pure water. This is demonstrated at surface-immobilised foldamer receptors enabling the selective sensing of perrhenate, thiocyanate and iodide. Chapter 4 expands on the use of the capacitive methodology developed in Chapter 3 for the enantioselective detection of anions at chiral molecular films. Chapter 5 investigates the sensing of ion-pairs via non-Faradaic capacitance spectroscopy at surface-confined heteroditopic receptors.

Published
2021

37. Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): health-related quality-of-life results from a double-blind, randomised, controlled, phase 3 trial

Author

Bottomley, A., Coens, C., Mierzynska, J., Blank, C. U., Mandalà, M., Long, G. V., Atkinson, V. G., Dalle, S., Haydon, A. M., Meshcheryakov, A., Khattak, A., Carlino, M. S., Sandhu, S., Puig, S., Ascierto, P. A., Larkin, J., Lorigan, P. C., Rutkowski, P., Schadendorf, D., Koornstra, R., Hernandez-Aya, L., Di Giacomo, A. M., van den Eertwegh, A. J. M., Grob, J. -J., Gutzmer, R., Jamal, R., van Akkooi, A. C. J., Krepler, C., Ibrahim, N., Marreaud, S., Kicinski, M., Suciu, S., Robert, C., Eggermont, A. M. M., EORTC Melanoma Group, Lesimple, T., Maio, M., Linette, G., Mortier, L., Svane, I. M., Schachter, J., Brown, M., Hersey, P., Barrow, C., Kudchadkar, R., Dutriaux, C., Song, X., Quaglino, P., Queirolo, P., Meier, F., Stroyakovskiy, D., Guillot, B., Romero, P. L. O., Bastholt, L., Garbe, C., Grange, F., Mohr, P., Algazi, A., Bechter, O., Hernberg, M., Loquai, C., Meiss, F., Chiarion Sileni, V., Bar-Sela, G., Fitzharris, B., Saiag, P., Arnault, J. -P., Simon, J. -C., Stephens, R., Baurain, J. -F., Lebbe, C., Combemale, P., Dummer, R., Hauschild, A., Parente, P., Yamazaki, N., Milhem, M., Leccia, M. -T., Geoffrois, L., Kretschmer, L., Dunwoodie, E., Walker, J., Lotem, M., Hendler, D., Mackiewicz, A., Sekulovic, L., Dzienis, M., Hospers, G. A. P., Siano, M., Hassel, J., Corrie, P., Passos, M. -J., Levin, M., Hoeller, C., Machet, L., Hallmeyer, S., Waterston, A., Descamps, V., Kiecker, F., Aarts, M., Schmidt, H., Raimundo, A., Nyakas, M., Lacour, J. -P., Berking, C., Ferrucci, P. F., Jameson, M., Kim, K., Yokota, K., Kerger, J., Aubin, F., Groenewegen, G., Kapiteijn, H., Boehncke, W. -H., Utikal, J., Casasola, R., Marshall, E., Ferraresi, V., Richtig, E., Matkovic, S., Inozume, T., Crook, T., Mcneil, C., Kiyohara, Y., Avril, M. -F., Hein, R., Terheyden, P., Nathan, P., Aoi, J., Skytta, T., Jouary, T., Takenouchi, T., Straume, O., Martins, C., Mukhametshina, G., Boehncke, Wolf-Henning, Internal medicine, CCA - Cancer Treatment and quality of life, European Organisation for Research and Treatment of Cancer [Bruxelles] (EORTC), European Cancer Organisation [Bruxelles] (ECCO), Ospedale 'Santa Maria della Misericordia' = University Hospital 'Santa Maria della Misericordia', The University of Sydney, Princess Alexandra Hospital, Brisbane, University of Queensland [Brisbane], Centre Léon Bérard [Lyon], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Edith Cowan University (ECU), Universitat de Barcelona (UB), The Christie NHS Foundation Trust [Manchester, Royaume-Uni], Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Radboud University Medical Center [Nijmegen], Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), University Hospital of Siena, Amsterdam UMC - Amsterdam University Medical Center, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hannover Medical School [Hannover] (MHH), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), Merck & Co. Inc, AP-HP. Université Paris Saclay, Institut Gustave Roussy (IGR), University Medical Center [Utrecht], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Merck Sharp & Dohme., and Guided Treatment in Optimal Selected Cancer Patients (GUTS)

Subjects
Male, Skin Neoplasms, Medizin, Skin Neoplasms / drug therapy, Pembrolizumab, law.invention, Cancer development and immune defence Radboud Institute for Health Sciences [Radboudumc 2], MESH: Aged, 80 and over, 0302 clinical medicine, Melanoma / pathology, Randomized controlled trial, law, Monoclonal, 80 and over, Clinical endpoint, MESH: Double-Blind Method, 030212 general & internal medicine, Humanized, Melanoma, MESH: Aged, ddc:616, Aged, 80 and over, education.field_of_study, MESH: Middle Aged, Antibodies, Monoclonal, Humanized, Neoplasm Staging, Quality of Life, Double-Blind Method, Adult, Aged, Middle aged, Humans [MeSH], Hazard ratio, MESH: Neoplasm Staging, Middle Aged, Oncology, 030220 oncology & carcinogenesis, Female, Humans, medicine.medical_specialty, Melanoma / psychology, Skin Neoplasms / psychology, MESH: Melanoma, Antibodies, Monoclonal, Humanized / therapeutic use, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Placebo, Antibodies, Melanoma / mortality, 03 medical and health sciences, Internal medicine, medicine, Adjuvant therapy, education, Skin Neoplasms / pathology, MESH: Humans, Melanoma / drug therapy, business.industry, MESH: Skin Neoplasms, MESH: Quality of Life, MESH: Adult, Skin Neoplasms / mortality, MESH: Male, Clinical trial, MESH: Antibodies, Monoclonal, Humanized, business, MESH: Female
Abstract

Background: The European Organisation for Research and Treatment of Cancer (EORTC) 1325-MG/KEYNOTE-054 trial in patients with resected, high-risk stage III melanoma demonstrated improved recurrence-free survival with adjuvant pembrolizumab compared with placebo (hazard ratio 0·57 [98·4% CI 0·43-0·74]; pMethods: This double-blind, randomised, controlled, phase 3 trial was done at 123 academic centres and community hospitals across 23 countries. Patients aged 18 years or older with previously untreated histologically confirmed stage IIIA, IIIB, or IIIC resected cutaneous melanoma, and an Eastern Cooperative Oncology Group performance status score of 1 or 0 were eligible. Patients were randomly assigned (1:1) using a central interactive voice-response system on the basis of a minimisation technique stratified for stage and geographic region to receive intravenously 200 mg pembrolizumab or placebo. Treatment was administered every 3 weeks for 1 year, or until disease recurrence, unacceptable toxicity, or death. The primary endpoint of the trial was recurrence-free survival (reported elsewhere). HRQOL was a prespecified exploratory endpoint, with global health/quality of life (GHQ) over 2 years measured by the EORTC QLQ-C30 as the primary analysis. Analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02362594, and EudraCT, 2014-004944-37, and long-term follow-up is ongoing.Findings: Between Aug 26, 2015, and Nov 14, 2016, 1019 patients were assigned to pembrolizumab (n=514) or placebo (n=505). Median follow-up was 15·1 months (IQR 12·8-16·9) at the time of this analysis. HRQOL compliance was greater than 90% at baseline, greater than 70% during the first year, and greater than 60% thereafter for both groups. Because of low absolute compliance numbers at later follow-up, the analysis was truncated to week 84. Baseline GHQ scores were similar between groups (77·55 [SD 18·20] in the pembrolizumab group and 76·54 [17·81] in the placebo group) and remained stable over time. The difference in average GHQ score between the two groups over the 2 years was -2·2 points (95% CI -4·3 to -0·2). The difference in average score during treatment was -1·1 points (95% CI -3·2 to 0·9) and the difference in average score after treatment was -2·2 points (-4·8 to 0·4). These differences are within the 5-point clinical relevance threshold for the QLQ-C30 and are therefore clinically non-significant.Interpretation: Pembrolizumab does not result in a clinically significant decrease in HRQOL compared with placebo when given as adjuvant therapy for patients with resected, high-risk stage III melanoma. These results support the use of adjuvant pembrolizumab in this setting. placebo when given as adjuvant therapy for patients with resected, high-risk stage III melanoma. These results support the use of adjuvant pembrolizumab in this setting. placebo when given as adjuvant therapy for patients with resected, high-risk stage III melanoma. These results support the use of adjuvant pembrolizumab in this setting.

Published
2021

48. Implantation robot-assistée du sphincter artificiel urinaire AMS-800 chez la femme : une série multicentrique internationale de 125 patientes

Author

Peyronnet, B., primary, Capon, G., additional, Belas, O., additional, Biardeau, X., additional, Lecoanet, P., additional, Castro-Sader, L., additional, Allue, M., additional, Hein, R., additional, Daher, M., additional, Hascoet, J., additional, Auble, A., additional, Thibault, F., additional, Cornu, J.N., additional, Dubois, F., additional, Gamé, X., additional, Cardot, V., additional, Vidart, A., additional, Descazeaud, A., additional, Fournier, G., additional, and Van Der Aa, F., additional

Published
2020
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