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52. Autosomal Dominant Non-Syndromic Hearing Loss Maps to DFNA33 (13q34) and Co-Segregates with Splice Site Variants in ATP11A, A Phospholipid Flippase Gene

Author

Nicole M. Roslin, Lance P. Doucette, Sushma Singh, Ortal Barel, Curtis R. French, Jessica Squires, Terry-Lynn Young, Darren D. O’Rielly, Nelly Abdelfatah, Mordechai Shohat, Cindy Penney, Anne Griffin, Justin A. Pater, Daniel Vincent, Geoffrey Woodland, Pascale Marquis, Taylor Burt, Jim Houston, Salem Werdyani, and Susan G. Stanton

Subjects
Genetics, chemistry.chemical_compound, chemistry, Hearing loss, RNA splicing, Phospholipid, medicine, Flippase, medicine.symptom, Biology, Gene, Non syndromic
Abstract

Whole genome approaches are superior for identifying recessive genes, however discovery of dominant genes including deafness genes (DFNA) remains challenging. Herein we report a new DFNA gene, ATP11A, in a Newfoundland family with a variable form of bilateral sensorineural hearing loss (SNHL). Targeted screening of DFNA genes based on audioprofiles was unsuccessful. Genome-wide SNP genotyping linked SNHL to DFNA33 (Lod = 4.77), a locus on 13q34 previously mapped in a German family with variable SNHL in 2009. WGS identified 51 unremarkable positional variants on 13q34. Continuous clinical ascertainment identified several key recombination events and reduced the disease interval to 769 Kb, excluding all but one variant. ATP11A (NC_000013.11: g.190616G > A) is a novel point mutation predicted to be a cryptic donor splice site. RNA studies in patient-derived tissues verified in silico predictions, revealing the retention of 153bp of intron in the 3’ UTR of several ATP11A isoforms. A second, unresolved family from Israel with a similar, variable form of SNHL and a novel duplication in exon 28 of ATP11A that occurs within the splice donor sequence (intron 28). ATP11A is a type of P4-ATPase that transports (flip) phospholipids from the outer to inner leaflet of cell membranes to maintain asymmetry. Haploinsufficiency of ATP11A, the phospholipid flippase that specially transports phosphatidylserine (PS) and phosphatidylethanolamine (PE), could leave cells with PS/PE at the extracellular side vulnerable to phagocytic degradation. Given that surface PS can be pharmaceutically targeted, hearing loss due to ATP11A could potentially be treated. It is also likely that ATP11A is the gene underlying DFNA33.

Published
2021

53. A cut above: the end (and ends) of film censorship

Author

Daniel Vincent Sacco

Subjects
Power (social and political), Authorial intent, restrict, Covert, Political science, media_common.quotation_subject, Censorship, Media studies, Artistic merit, Enforcement, Discipline, media_common
Abstract

By the beginning of the twenty-first century in the West, the notion of government-appointed bodies mandated for censoring cinematic content had fallen considerably out of fashion as institutional censorship was largely curtailed. Barring widely shared concerns regarding the exposure of underage children to material deemed inappropriate, newly rebranded “classification” boards have acted to limit the extent to which they themselves can prohibit images from entering the public market, shifting their emphasis away from censorship and toward consumer edification and greater consideration of artistic merit and authorial intent. Such reform brought the policies of censorship boards in Britain, Canada, and Australia into closer alignment with the goals and processes of the Motion Picture Association of America’s ratings system. Can we then assume that cinematic censorship is effectively a thing of the past? Does the impetus to regulate and police film content continue silently to exist? Analysis of controversies surrounding particular films throughout and in the wake of this shift suggests that, while no longer practiced explicitly by governmental institutions, film censorship continues to operate through less immediately recognizable forms of cultural marginalization and restraint. Classification status drastically affects the number of platforms through which a film can be accessed and thus works, as censorship does, to restrict films from audiences. When market demands place external restraints upon film content, familiar processes of cinematic censorship can be reframed as operating within (as opposed to upon) the institutional structures and practices of cultural production. This two-part study will examine, first, the process by which certain postmillennial cinematic artworks, such as Catherine Breillat’s Fat Girl (2001) and Gaspar Noé’s Irreversible (2002), spurred reform in the policies of classification boards by highlighting the rigidity of classification criteria and, secondly, cases in which, following the shift from moral to covert censorship, artistically serious films such as Vincent Gallo’s The Brown Bunny (2003) and Abel Ferrara’s Welcome to New York (2014) have been suppressed or constrained for their challenging subject matter, most notably for their aggressive presentation of sexuality. The main objective will be determining: 1) how the shift from censorship to classification corresponded to the aesthetic strategies of a handful of boundary-pushing films; and 2) how cinematic censorship, in the absence of traditional institutional enforcement, continues to operate in the interactions between alternative networks of disciplinary power and discursive practice.

Published
2021

54. Policies in Relational Contracts

Author

Michael Powell and Daniel Vincent Barron

Subjects
0502 economics and business, 05 social sciences, Business, 050207 economics, General Economics, Econometrics and Finance, 050205 econometrics
Abstract

We consider how a firm’s policies constrain its relational contracts. A policy is a sequence of decisions made by a principal; each decision determines how agents’ efforts affect their outputs. We consider surplus-maximizing policies in a flexible dynamic moral hazard problem between a principal and several agents with unrestricted vertical transfers and no commitment. If agents cannot coordinate to punish the principal following a deviation, then the principal might optimally implement dynamically inefficient, history-dependent policies to credibly reward high-performing agents. We develop conditions under which such backward-looking policies are surplus-maximizing and illustrate how they influence promotions, hiring, and performance. (JEL D21, D82, D86, M51)

Published
2019

61. Correction: One-pot production of oxygenated monomers and selectively oxidized lignin from biomass based on plasma electrolysis

Author

Lusi A, Harish Radhakrishnan, Daniel Vincent Sahayaraj, Jean-Philippe Tessonnier, Hui Hu, and Xianglan Bai

Subjects
Environmental Chemistry, Pollution
Abstract

Correction for ‘One-pot production of oxygenated monomers and selectively oxidized lignin from biomass based on plasma electrolysis’ by Lusi A et al., Green Chem., 2021, 23, 9109–9125, DOI: 10.1039/D1GC03315H.

Published
2022

62. Teachers Influence in Curriculum Development in Kenya

Author

Daniel Vincent Nyamai and Daniel Vincent Nyamai

Abstract

Master's Thesis from the year 2020 in the subject Pedagogy - The Teacher, Educational Leadership, grade: B, University of South Wales, course: MA Education (Innovation in Learning and Teaching), language: English, abstract: This study is about the influence of teachers on curriculum development in Kenya. Previous studies have shown that teachers, as primary stakeholders of the curriculum, are the key implementers of the developed curriculum. Not much is known about their influence in the development of the national curriculum. The study investigates the current level of teacher involvement in curriculum development through analysis of case studies conducted in Kenya in regards to teacher participation in curriculum development in Kenya. Further, the study investigates how the local curriculum governing body, Kenya Institute of Curriculum Development (KICD), can ensure the full participation of teachers in curriculum development.

Published
2022

66. The Evolution of the Ozone 'Collar' in the Antarctic Lower Stratosphere during Early August 1994

Author

Mariotti, Annarita, Mechoso, Carlos R., Legras, Bernard, and Daniel, Vincent

Subjects
Climatology -- Research, Ozone layer -- Research, Evolution -- Analysis, Stratosphere -- Analysis, Earth sciences, Science and technology
Abstract

The ozone evolution in the lower stratosphere of the Southern Hemisphere during the period 5-10 August 1994 is analyzed. The analysis focuses on the ozone 'collar' (the band of maximum values in ozone mixing ratio around the Antarctic ozone 'hole' at these altitudes) and the development of 'collar filaments.' Ozone mixing ratios provided by the Microwave Limb Sounder (MLS) on board the Upper Atmosphere Research Satellite and by an ER-2 aircraft participating in the Airborne Southern Hemisphere Ozone Experiment/Measurements for Assessing the Effects of Stratospheric Aircraft campaign are compared with values at corresponding locations in high-resolution isentropic maps obtained by using the numerical scheme of 'contour advection with surgery' (CAS). The CAS reconstructed ozone maps provide a view of the way in which air masses are exported from the outskirts of the collar to form the 'tongues' of higher mixing ratios observed at lower latitudes on MLS synoptic maps. There is an overall consistency between the datasets insofar as the collar location is concerned. This location seems to be primarily defined by the local properties of the flow. Nevertheless the CAS reconstructed collar tends to become weaker than that depicted by MLS data. By means of radiative calculation estimates, it is argued that diabatic descent may be responsible for maintaining the ozone concentration approximately constant in the collar while filaments isentropically disperse collarlike mixing ratios from this region toward lower latitudes.

Published
2000

68. Ultrasound With E-Stimulation Diagnostic Nerve Blocks for Targeted Muscle Selection in Spasticity

Author

Daniel Vincent, Mahdis Hashemi, and Paul Winston

Subjects
medicine.medical_specialty, business.industry, Rehabilitation, Ultrasound, Nerve Block, Physical Therapy, Sports Therapy and Rehabilitation, Stimulation, Physical medicine and rehabilitation, Muscle Spasticity, Humans, Medicine, Spasticity, medicine.symptom, business, Musculoskeletal System, Selection (genetic algorithm), Ultrasonography
Published
2021

69. Attaining efficiency with imperfect public monitoring and one-sided Markov adverse selection

Author

Daniel Vincent Barron

Subjects
TheoryofComputation_MISCELLANEOUS, Computer Science::Computer Science and Game Theory, Markov chain, 05 social sciences, Stochastic game, Adverse selection, TheoryofComputation_GENERAL, Markov process, Bayesian game, symbols.namesake, 0502 economics and business, Economics, Repeated game, symbols, 050207 economics, Folk theorem, General Economics, Econometrics and Finance, Private information retrieval, Mathematical economics, 050205 econometrics
Abstract

I prove an efficiency result for repeated games with imperfect public monitoring in which one player's utility is privately known and evolves according to a Markov process. Under certain assumptions, patient players can attain approximately efficient payoffs in equilibrium. The public signal must satisfy a “pairwise full rank” condition that is somewhat stronger than the monitoring condition required in the Folk Theorem proved by Fudenberg, Levine, and Maskin (1994). Under stronger assumptions, the efficiency result partially extends to settings in which one player has private information that determines every player's payoff. The proof is partially constructive and uses an intuitive technique to mitigate the impact of private information on continuation payoffs.

Published
2017

70. A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer

Author

Harald Surowy, Rulla M. Tamimi, Javier Benitez, Wing-Yee Lo, Celine M. Vachon, Nadege Presneau, John J. Spinelli, Ann Smeets, Hoda Anton-Culver, Veli-Matti Kosma, Christopher A. Haiman, Martha J. Shrubsole, Ross L. Prentice, Diana Eccles, Ursula Eilber, Loic Le Marchand, Katri Pylkäs, Jirong Long, Michael P. Lux, Sara Margolin, Hedy S. Rennert, Tom Maishman, Mary B. Daly, Rita K. Schmutzler, Julian Peto, Sune F. Nielsen, Eric Hahnen, Niclas Håkansson, Børge G. Nordestgaard, Mitul Shah, Matthias W. Beckmann, Anthony J. Swerdlow, Barbara Burwinkel, Rudolf Kaaks, Usha Menon, William J. Tapper, Argyrios Ziogas, Peter Hillemanns, Fares Al-Ejeh, Roger L. Milne, Wolfgang Janni, Pascal Guénel, Mikael Eriksson, Clarice R. Weinberg, Kyriaki Michailidou, Jonathan Beesley, Marike Gabrielson, J. Esteban Castelao, Margriet Collée, Janet E. Olson, Gad Rennert, Per Broberg, Rob A. E. M. Tollenaar, David Cox, Paolo Peterlongo, Helian Feng, Brian D. Carter, Nichola Johnson, Emmanouil Saloustros, Dijana Plaseska-Karanfilska, Kimberly F. Doheny, Paul L. Auer, Hans Wildiers, Jacques Simard, Michael Untch, Per Hall, Martine Dumont, Julie M. Cunningham, Thilo Dörk, Mary Beth Terry, Jenny Chang-Claude, Lang Wu, Irene L. Andrulis, Xiaohong R. Yang, Caroline Baynes, Isabel dos-Santos-Silva, Douglas F. Easton, Wei Shi, Emily Hallberg, Camilla Wendt, Hiltrud Brauch, Diana Torres, Olufunmilayo I. Olopade, David Van Den Berg, Georgia Chenevix-Trench, Alfons Meindl, Stig E. Bojesen, Jonine D. Figueroa, Dale P. Sandler, Vessela N. Kristensen, Christine L. Clarke, Wei Zheng, Manuela Gago-Dominguez, E Rozali, Henrik Flyger, Sheila Seal, Guanmengqian Huang, Marjanka K. Schmidt, Håkan Olsson, Christopher G. Scott, Kamila Czene, Laura Fachal, Rodney J. Scott, Jennifer Stone, Sara Y. Brucker, Qin Wang, David J. Hunter, Maya Ghoussaini, Christoph Engel, Keith Humphreys, Susan M. Gapstur, Daniel C. Tessier, Paolo Radice, John L. Hopper, Audrey Y. Jung, Lucy Xia, Atocha Romero, Chenjie Zeng, Peter A. Fasching, Jan Lubinski, Anna González-Neira, Nazneen Rahman, Robert N. Hoover, Thérèse Truong, Fergus J. Couch, Anna Marie Mulligan, Robert J. MacInnis, Ute Hamann, Hanne Meijers-Heijboer, Brigitte Rack, Simon S. Cross, Federico Canzian, J.-P. Meyer, Sara Lindström, Natalia Bogdanova, Trinidad Caldés, Olivia Fletcher, Peter Kraft, Elinor J. Sawyer, Alexander Gusev, Louise A. Brinton, Diether Lambrechts, Bingshan Li, Kristan J. Aronson, Jane Romm, Anja Rudolph, Peter Devilee, Qiuyin Cai, Arto Mannermaa, Elad Ziv, Alice S. Whittemore, Abigail Thomas, Hermann Brenner, Montserrat Garcia-Closas, Patrick Neven, Kristine Jones, Miriam Dwek, Sibylle Loibl, Heli Nevanlinna, Jolanta Lissowska, Susan L. Neuhausen, Elza Khusnutdinova, Marina Bermisheva, Alicja Wolk, Lin Fritschi, Xingyi Guo, Angela Cox, Michael Jones, Xiaoqing Chen, Esther M. John, Richard Barfield, Volker Arndt, Patricia Harrington, Quinten Waisfisz, Daniel Vincent, Antoinette Hollestelle, Dimitrios Mavroudis, JoAnn E. Manson, Joe Dennis, Walter C. Willett, Stacey L. Edwards, Melissa C. Southey, Andreas Schneeweiss, Jack A. Taylor, Robert Winqvist, Mia M. Gaudet, David E. Goldgar, Anna Jakubowska, Paul D.P. Pharoah, Kathrin Thöne, Dieter Flesch-Janys, Mark S. Goldberg, Craig Luccarini, Sten Cornelissen, Jingmei Li, Michael J. Kerin, Myrto Barrdahl, Xiao-Ou Shu, Alison M. Dunning, Manjeet K. Bolla, Carl Blomqvist, Graham G. Giles, Hans Christiansen, A. Heather Eliassen, Valerie Rhenius, Alexander Hein, Belynda Hicks, Ivana Maleva Kostovska, Tongguang Cheng, Yingchang Lu, CCA - Cancer biology and immunology, Amsterdam Neuroscience - Complex Trait Genetics, Human genetics, Amsterdam Reproduction & Development (AR&D), Clinical Genetics, Medical Oncology, Guo, Xingyi [0000-0001-5269-1294], Al-Ejeh, Fares [0000-0002-1553-0077], Li, Bingshan [0000-0003-2129-168X], Gusev, Alexander [0000-0002-7980-4620], Andrulis, Irene L [0000-0002-4226-6435], Arndt, Volker [0000-0001-9320-8684], Brauch, Hiltrud [0000-0001-7531-2736], Collée, Margriet [0000-0002-9272-9346], Cox, Angela [0000-0002-5138-1099], Cunningham, Julie M [0000-0002-8159-3025], Fachal, Laura [0000-0002-7256-9752], Fletcher, Olivia [0000-0001-9387-7116], Hein, Alexander [0000-0003-2601-3398], Hicks, Belynda [0000-0001-8014-4888], Hollestelle, Antoinette [0000-0003-1166-1966], Jakubowska, Anna [0000-0002-5650-0501], Khusnutdinova, Elza [0000-0003-2987-3334], Li, Jingmei [0000-0001-8587-7511], Menon, Usha [0000-0003-3708-1732], Nevanlinna, Heli [0000-0002-0916-2976], Nordestgaard, Børge G [0000-0002-1954-7220], Pylkäs, Katri [0000-0002-2449-0521], Rennert, Gad [0000-0002-8512-068X], Romero, Atocha [0000-0002-1634-7397], Saloustros, Emmanouil [0000-0002-0485-0120], Scott, Christopher G [0000-0003-1340-0647], Shrubsole, Martha J [0000-0002-5591-7575], Wolk, Alicja [0000-0001-7387-6845], Ziogas, Argyrios [0000-0003-4529-3727], Pharoah, Paul DP [0000-0001-8494-732X], Milne, Roger L [0000-0001-5764-7268], Easton, Douglas F [0000-0003-2444-3247], Zheng, Wei [0000-0003-1226-070X], Apollo - University of Cambridge Repository, Human Genetics, and ARD - Amsterdam Reproduction and Development

Subjects
0301 basic medicine, Risk, medicine.medical_specialty, Gene Expression, Genome-wide association study, Breast Neoplasms, Biology, Genome-wide association studies, Polymorphism, Single Nucleotide, Article, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, SDG 3 - Good Health and Well-being, Genetic model, Genetics, medicine, Humans, Genetic Predisposition to Disease, Genetic association, medicine.disease, 3. Good health, 030104 developmental biology, 030220 oncology & carcinogenesis, Case-Control Studies, Expression quantitative trait loci, Medical genetics, Female, Gene expression, Breast Cancer Genetics, Genome-Wide Association Study
Abstract

The breast cancer risk variants identified in genome-wide association studies explain only a small fraction of the familial relative risk, and the genes responsible for these associations remain largely unknown. To identify novel risk loci and likely causal genes, we performed a transcriptome-wide association study evaluating associations of genetically predicted gene expression with breast cancer risk in 122,977 cases and 105,974 controls of European ancestry. We used data from the Genotype-Tissue Expression Project to establish genetic models to predict gene expression in breast tissue and evaluated model performance using data from The Cancer Genome Atlas. Of the 8,597 genes evaluated, significant associations were identified for 48 at a Bonferroni-corrected threshold of P −6, including 14 genes at loci not yet reported for breast cancer. We silenced 13 genes and showed an effect for 11 on cell proliferation and/or colony-forming efficiency. Our study provides new insights into breast cancer genetics and biology.

Published
2019

71. The functional ALDH2 polymorphism is associated with breast cancer risk: A pooled analysis from the Breast Cancer Association Consortium

Author

Anna González-Neira, Qin Wang, Daniel C. Tessier, John J. Spinelli, Valerie Gaborieau, Keitaro Matsuo, Paul D.P. Pharoah, Catherine S. Healey, Motoki Iwasaki, Don M. Conroy, Shoichiro Tsugane, Artitaya Lophatananon, Ji Yeob Choi, Mikael Hartman, Alison M. Dunning, Chiu-Chen Tseng, Nur Aishah Taib, Roger L. Milne, Sue K. Park, Anna H. Wu, Kenneth Muir, Kyriaki Michailidou, Tomotaka Ugai, Kristan J. Aronson, Douglas F. Easton, Soo Hwang Teo, Sung-Won Kim, Chen-Yang Shen, Suleeporn Sangrajrang, Ava Kwong, Tsun Chan, Daniel Vincent, Esther M. John, Manjeet K. Bolla, Joe Dennis, Pei Ei Wu, Wei Zheng, Ching Wan Chan, Hidemi Ito, Xiao-Ou Shu, Daehee Kang, Dennis, Joe [0000-0003-4591-1214], Dunning, Alison [0000-0001-6651-7166], Easton, Douglas [0000-0003-2444-3247], Pharoah, Paul [0000-0001-8494-732X], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Oncology, Adult, medicine.medical_specialty, lcsh:QH426-470, Alcohol Drinking, Estrogen receptor, aldehyde dehydrogenase‐2, Single-nucleotide polymorphism, Breast Neoplasms, 030105 genetics & heredity, Polymorphism, Single Nucleotide, aldehyde dehydrogenase-2, Alcohol Drinking/epidemiology, 03 medical and health sciences, Breast cancer, breast cancer, Asian People, single nucleotide polymorphism, Internal medicine, Epidemiology, Genotype, Genetics, medicine, Humans, Asian Continental Ancestry Group/genetics, Gene–environment interaction, Aldehyde Dehydrogenase, Mitochondrial/genetics, Molecular Biology, Genetics (clinical), ALDH2, Aged, business.industry, Breast Neoplasms/epidemiology, Aldehyde Dehydrogenase, Mitochondrial, Odds ratio, Original Articles, Middle Aged, medicine.disease, 3. Good health, lcsh:Genetics, 030104 developmental biology, Original Article, Female, Gene-Environment Interaction, business, acetaldehyde
Abstract

BACKGROUND: Epidemiological studies consistently indicate that alcohol consumption is an independent risk factor for female breast cancer (BC). Although the aldehyde dehydrogenase 2 (ALDH2) polymorphism (rs671: Glu>Lys) has a strong effect on acetaldehyde metabolism, the association of rs671 with BC risk and its interaction with alcohol intake have not been fully elucidated. We conducted a pooled analysis of 14 case-control studies, with individual data on Asian ancestry women participating in the Breast Cancer Association Consortium.METHODS: We included 12,595 invasive BC cases and 12,884 controls for the analysis of rs671 and BC risk, and 2,849 invasive BC cases and 3,680 controls for the analysis of the gene-environment interaction between rs671 and alcohol intake for BC risk. The pooled odds ratios (OR) with 95% confidence intervals (CI) associated with rs671 and its interaction with alcohol intake for BC risk were estimated using logistic regression models.RESULTS: The Lys/Lys genotype of rs671 was associated with increased BC risk (OR = 1.16, 95% CI 1.03-1.30, p = 0.014). According to tumor characteristics, the Lys/Lys genotype was associated with estrogen receptor (ER)-positive BC (OR = 1.19, 95% CI 1.05-1.36, p = 0.008), progesterone receptor (PR)-positive BC (OR = 1.19, 95% CI 1.03-1.36, p = 0.015), and human epidermal growth factor receptor 2 (HER2)-negative BC (OR = 1.25, 95% CI 1.05-1.48, p = 0.012). No evidence of a gene-environment interaction was observed between rs671 and alcohol intake (p = 0.537).CONCLUSION: This study suggests that the Lys/Lys genotype confers susceptibility to BC risk among women of Asian ancestry, particularly for ER-positive, PR-positive, and HER2-negative tumor types.

Published
2019

72. Provision of comprehensive, culturally competent palliative care in the Qikiqtaaluk region of Nunavut: Health care providers' perspectives

Author

Daniel, Vincent, Jill, Rice, Jessica, Chan, and Pamela, Grassau

Subjects
Advance Care Planning, Cross-Sectional Studies, Attitude of Health Personnel, Inuit, Professional-Family Relations, Research, Palliative Care, Humans, Nunavut, Culturally Competent Care, Qualitative Research
Abstract

OBJECTIVE: To explore health care providers’ perceptions of the provision of palliative care in the Qikiqtaaluk (formerly known as Baffin) region of Nunavut. DESIGN: An exploratory, qualitative, cross-sectional design using in-depth, semistructured interviews. SETTING: Qikiqtaaluk region of Nunavut. PARTICIPANTS: Seven physicians and 6 registered nurses who worked in Iqaluit or other northern Inuit communities in the Qikiqtaaluk region of Nunavut. METHODS: Thirteen health care providers participated in in-person or telephone semistructured interviews, which were audiorecorded and transcribed verbatim. MAIN FINDINGS: Interviews with the participating health care providers in the Qikiqtaaluk region of Nunavut revealed 5 complex and interwoven themes that influence the provision of comprehensive, culturally competent palliative care services to Indigenous patients: respecting Inuit culture, end-of-life care planning, and the role of family; recognizing the importance of the northern community (sense of home); being aware of the limited health care resources; recognizing the critical role of medical interpreters; and improving the quality of palliative care programs and resources, as well as health care provider training in palliative care and Inuit end-of-life care. CONCLUSION: Health care providers in the Qikiqtaaluk region of Nunavut have identified several important themes that influence the provision of culturally sensitive and comprehensive palliative care, most notably the need to develop palliative care resources and programs. It is hoped that the results of this study can be used to help guide palliative care strategies including program development and educational initiatives for health care providers. These initiatives can help build community capacity within a currently underserviced population and improve end-of-life care services available to Nunavut patients and their families. Further studies are required to determine the perspectives of medical interpreters, as well as palliative care patients and their families.

Published
2019

77. The Allocation of Future Business: Dynamic Relational Contracts with Multiple Agents

Author

Isaiah Andrews and Daniel Vincent Barron

Subjects
Microeconomics, Economics and Econometrics, Incentive, 0502 economics and business, 05 social sciences, Principal (computer security), Optimal allocation, Economics, Relational contract, 050207 economics, Construct (philosophy), 050205 econometrics
Abstract

We consider how a firm dynamically allocates business among several suppliers to motivate them in a relational contract. The firm chooses one supplier who exerts private effort. Output is non-contractible, and each supplier observes only his own relationship with the principal. In this setting, allocation decisions constrain the transfers that can be promised to suppliers in equilibrium. Consequently, optimal allocation decisions condition on payoff-irrelevant past performance to make strong incentives credible. We construct a dynamic allocation rule that attains first-best whenever any allocation rule does. This allocation rule performs strictly better than any rule that depends only on payoff-relevant information. (JEL D21, D82, L14, L24)

Published
2016

78. Cryoneurotomy to Reduce Spasticity and Improve Range of Motion in Spastic Flexed Elbow: A Visual Vignette

Author

Paul Winston, Jonathan Rubenstein, Alexandra W Harvey, and Daniel Vincent

Subjects
Adult, Male, medicine.medical_specialty, Elbow, MEDLINE, Physical Therapy, Sports Therapy and Rehabilitation, Cryosurgery, Physical medicine and rehabilitation, Elbow Joint, medicine, Spastic, Humans, Spasticity, Range of Motion, Articular, Aged, Retrospective Studies, business.industry, Rehabilitation, Middle Aged, medicine.anatomical_structure, Vignette, Muscle Spasticity, Female, medicine.symptom, Range of motion, business
Published
2020

79. 'Split personality' and the stigma of schizophrenia

Author

Daniel Vincent Riordan

Subjects
Psychiatry and Mental health, medicine.medical_specialty, History and Philosophy of Science, Schizophrenia (object-oriented programming), media_common.quotation_subject, medicine, Personality, Stigma (botany), Psychology, Psychiatry, Applied Psychology, media_common
Published
2018

80. Publisher Correction: Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation

Author

Maya Ghoussaini, Stacey L. Edwards, Kyriaki Michailidou, Silje Nord, Richard Cowper-Sal·lari, Kinjal Desai, Siddhartha Kar, Kristine M. Hillman, Susanne Kaufmann, Dylan M. Glubb, Jonathan Beesley, Joe Dennis, Manjeet K. Bolla, Qin Wang, Ed Dicks, Qi Guo, Marjanka K. Schmidt, Mitul Shah, Robert Luben, Judith Brown, Kamila Czene, Hatef Darabi, Mikael Eriksson, Daniel Klevebring, Stig E. Bojesen, Børge G. Nordestgaard, Sune F. Nielsen, Henrik Flyger, Diether Lambrechts, Bernard Thienpont, Patrick Neven, Hans Wildiers, Annegien Broeks, Laura J. Van’t Veer, Emiel J. Th Rutgers, Fergus J. Couch, Janet E. Olson, Emily Hallberg, Celine Vachon, Jenny Chang-Claude, Anja Rudolph, Petra Seibold, Dieter Flesch-Janys, Julian Peto, Isabel dos-Santos-Silva, Lorna Gibson, Heli Nevanlinna, Taru A. Muranen, Kristiina Aittomäki, Carl Blomqvist, Per Hall, Jingmei Li, Jianjun Liu, Keith Humphreys, Daehee Kang, Ji-Yeob Choi, Sue K. Park, Dong-Young Noh, Keitaro Matsuo, Hidemi Ito, Hiroji Iwata, Yasushi Yatabe, Pascal Guénel, Thérèse Truong, Florence Menegaux, Marie Sanchez, Barbara Burwinkel, Frederik Marme, Andreas Schneeweiss, Christof Sohn, Anna H. Wu, Chiu-chen Tseng, David Van Den Berg, Daniel O. Stram, Javier Benitez, M Pilar Zamora, Jose Ignacio Arias Perez, Primitiva Menéndez, Xiao-Ou Shu, Wei Lu, Yu-Tang Gao, Qiuyin Cai, Angela Cox, Simon S. Cross, Malcolm W. R. Reed, Irene L. Andrulis, Julia A. Knight, Gord Glendon, Sandrine Tchatchou, Elinor J. Sawyer, Ian Tomlinson, Michael J. Kerin, Nicola Miller, Christopher A. Haiman, Brian E. Henderson, Fredrick Schumacher, Loic Le Marchand, Annika Lindblom, Sara Margolin, Soo Hwang Teo, Cheng Har Yip, Daphne S. C. Lee, Tien Y. Wong, Maartje J. Hooning, John W. M. Martens, J. Margriet Collée, Carolien H. M. van Deurzen, John L. Hopper, Melissa C. Southey, Helen Tsimiklis, Miroslav K. Kapuscinski, Chen-Yang Shen, Pei-Ei Wu, Jyh-Cherng Yu, Shou-Tung Chen, Grethe Grenaker Alnæs, Anne-Lise Borresen-Dale, Graham G. Giles, Roger L. Milne, Catriona McLean, Kenneth Muir, Artitaya Lophatananon, Sarah Stewart-Brown, Pornthep Siriwanarangsan, Mikael Hartman, Hui Miao, Shaik Ahmad Bin Syed Buhari, Yik Ying Teo, Peter A. Fasching, Lothar Haeberle, Arif B. Ekici, Matthias W. Beckmann, Hermann Brenner, Aida Karina Dieffenbach, Volker Arndt, Christa Stegmaier, Anthony Swerdlow, Alan Ashworth, Nick Orr, Minouk J. Schoemaker, Montserrat García-Closas, Jonine Figueroa, Stephen J. Chanock, Jolanta Lissowska, Jacques Simard, Mark S. Goldberg, France Labrèche, Martine Dumont, Robert Winqvist, Katri Pylkäs, Arja Jukkola-Vuorinen, Hiltrud Brauch, Thomas Brüning, Yon-Dschun Koto, Paolo Radice, Paolo Peterlongo, Bernardo Bonanni, Sara Volorio, Thilo Dörk, Natalia V. Bogdanova, Sonja Helbig, Arto Mannermaa, Vesa Kataja, Veli-Matti Kosma, Jaana M. Hartikainen, Peter Devilee, Robert A. E. M. Tollenaar, Caroline Seynaeve, Christi J. Van Asperen, Anna Jakubowska, Jan Lubinski, Katarzyna Jaworska-Bieniek, Katarzyna Durda, Susan Slager, Amanda E. Toland, Christine B. Ambrosone, Drakoulis Yannoukakos, Suleeporn Sangrajrang, Valerie Gaborieau, Paul Brennan, James McKay, Ute Hamann, Diana Torres, Wei Zheng, Jirong Long, Hoda Anton-Culver, Susan L. Neuhausen, Craig Luccarini, Caroline Baynes, Shahana Ahmed, Mel Maranian, Catherine S. Healey, Anna González-Neira, Guillermo Pita, M Rosario Alonso, Nuria Álvarez, Daniel Herrero, Daniel C. Tessier, Daniel Vincent, Francois Bacot, Ines de Santiago, Jason Carroll, Carlos Caldas, Melissa A. Brown, Mathieu Lupien, Vessela N. Kristensen, Paul D. P. Pharoah, Georgia Chenevix-Trench, Juliet D. French, Douglas F. Easton, and Alison M. Dunning

Subjects
Oncology, medicine.medical_specialty, Multidisciplinary, business.industry, Published Erratum, MEDLINE, General Physics and Astronomy, Locus (genetics), General Chemistry, medicine.disease, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, 030220 oncology & carcinogenesis, Internal medicine, medicine, 030212 general & internal medicine, business
Abstract

GWAS have identified a breast cancer susceptibility locus on 2q35. Here we report the fine mapping of this locus using data from 101,943 subjects from 50 case-control studies. We genotype 276 SNPs using the ‘iCOGS’ genotyping array and impute genotypes for a further 1,284 using 1000 Genomes Project data. All but two, strongly correlated SNPs (rs4442975 G/T and rs6721996 G/A) are excluded as candidate causal variants at odds against >100:1. The best functional candidate, rs4442975, is associated with oestrogen receptor positive (ER+) disease with an odds ratio (OR) in Europeans of 0.85 (95% confidence interval=0.84−0.87; P=1.7 × 10−43) per t-allele. This SNP flanks a transcriptional enhancer that physically interacts with the promoter of IGFBP5 (encoding insulin-like growth factor-binding protein 5) and displays allele-specific gene expression, FOXA1 binding and chromatin looping. Evidence suggests that the g-allele confers increased breast cancer susceptibility through relative downregulation of IGFBP5, a gene with known roles in breast cell biology., Previous studies identified an association between the 2q35 locus and breast cancer. Here, the authors show that a SNP at 2q35, rs4442975, is associated with oestrogen receptor positive disease and suggest that this effect is mediated through the downregulation of a known breast cancer gene, IGFBP5.

Published
2018

81. Relational Adaptation Under Reel Authority

Author

Kevin Murphy, Ricard Gil, Robert Gibbons, and Daniel Vincent Barron

Subjects
Microeconomics, media_common.quotation_subject, Reel, Business, Adaptation (computer science), Discretion, media_common
Abstract

We study relationships between parties who have different preferences about how to tailor decisions to changing circumstances. Our model suggests that relational contracts supported by formal contracts may achieve efficient relational adaptation. Our empirics consider revenue-sharing contracts between movie distributors and an exhibitor. The exhibitor has discretion about whether and when to show a movie, and the parties frequently renegotiate formal contracts after a movie has finished its run. We document that such ex post renegotiation is consistent with rewarding the exhibitor for making efficient adaptation decisions.

Published
2018

82. Cryoneurotomy as a novel adjunct to botulinum toxin treatment for the spastic elbow: A case study

Author

Daniel Vincent, Rajiv Reebye, Patricia Mills, Paul Winston, and Carl Ganzert

Subjects
030506 rehabilitation, medicine.medical_specialty, business.industry, Elbow, Toxicology, Botulinum toxin, Adjunct, Surgery, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Spastic, Medicine, 0305 other medical science, business, 030217 neurology & neurosurgery, medicine.drug
Published
2018

83. Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer

Author

Vesa Kataja, Aida Karina Dieffenbach, Chia-Ni Hsiung, Catherine S. Healey, Gie Hooi Tan, Soo Hwang Teo, Domenico Palli, Frederik Marme, Katri Pylkäs, Roger L. Milne, Jaana M. Hartikainen, Gord Glendon, Susan L. Slager, Chen-Yang Shen, Fredrick R. Schumacher, Daniel F. Schmidt, Suleeporn Sangrajrang, Kee Seng Chia, Lorna Gibson, Pascal Guénel, Alice S. Whittemore, Jenny Chang-Claude, Yu Tang Gao, Hidemi Ito, Simon S. Cross, Sofia Khan, Marie Sanchez, Daniel Vincent, Daniel Herrero, Nicola Miller, Antoinette Hollestelle, Caroline M. Seynaeve, Christopher A. Haiman, Hermann Brenner, Kay-Tee Khaw, Loris Bernard, Habibul Ahsan, Melissa C. Southey, David Van Den Berg, Martha J. Shrubsole, Daniel O. Stram, William Blot, Mel Maranian, Robert Winqvist, Keitaro Matsuo, John W. M. Martens, Heli Nevanlinna, Mia M. Gaudet, Anna Jakubowska, Christine D. Berg, Paul D.P. Pharoah, Jacques Simard, Manjeet K. Bolla, Dieter Flesch-Janys, Mark S. Goldberg, Paul Brennan, Ching Wan Chan, Sune F. Nielsen, Sara Lindström, Mitul Shah, Matthias W. Beckmann, Craig Luccarini, Jonathan Beesley, Kyriaki Michailidou, Paolo Peterlongo, Marc J. Gunter, Anna González-Neira, Ji Yeob Choi, Per Hall, Sarah Stewart-Brown, Keith Humphreys, Hui Cai, Kathleen E. Malone, Elinor J. Sawyer, Louise A. Brinton, Marjanka K. Schmidt, Xiao-Ou Shu, Barbara Perkins, Lotte Maxild Mortensen, Chiu-Chen Tseng, Hanne Meijers-Heijboer, Minouk J. Schoemaker, Keun-Young Yoo, Julia A. Knight, Alan Ashworth, Stig E. Bojesen, Kamila Czene, Artitaya Lophatananon, Graham G. Giles, S. Ahmed, Kazuo Tajima, Douglas F. Easton, Maria Kabisch, Arja Jukkola-Vuorinen, Wei Lu, Peter A. Fasching, Irene L. Andrulis, Clare Turnbull, Caroline Baynes, Christine B. Ambrosone, Jan Lubinski, Muriel A. Adank, A. Meindl, Taru A. Muranen, Siranoush Manoukian, Susan M. Gapstur, Natalia Bogdanova, Alexander Hein, Annika Lindblom, Nazneen Rahman, Annegien Broeks, Lothar Haeberle, Federico Canzian, G Pita, Ming-Feng Hou, Hiroji Iwata, Drakoulis Yannoukakos, Diana Torres, Vessela N. Kristensen, Peter Devilee, Qiuyin Cai, Christi J Asperen, John L. Hopper, Diether Lambrechts, Michael Lush, Hans Wildiers, Joe Dennis, Sandra L. Halverson, Carl Blomqvist, Erik Van Limbergen, Malin Sund, Daehee Kang, Grethe I. Grenaker Alnæs, Marilie D. Gammon, Ursula Eilber, Ian Tomlinson, Thérèse Truong, Amanda E. Toland, Anna Marie Mulligan, Kirsimari Aaltonen, Olivia Fletcher, Jonine D. Figueroa, Angela Cox, Pei Ei Wu, Maartje J. Hooning, Catriona McLean, Georgia Chenevix-Trench, Pornthep Siriwanarangsan, Malcolm W.R. Reed, Emily Hallberg, Sara Margolin, Volker Arndt, Montserrat Garcia-Closas, Francois Bacot, Rita K. Schmutzler, Julian Peto, David J. Hunter, Thomas Brüning, Katarzyna Jaworska, Christof Sohn, Børge G. Nordestgaard, Enes Makalic, Hatef Darabi, Barbara Burwinkel, Petra P.H. Peeters, J. Margriet Collée, Rongxi Yang, Robert N. Hoover, Eiliv Lund, Fergus J. Couch, Ute Hamann, Jirong Long, Wei Zheng, Sabine Behrens, Giske Ursin, Muhammad G. Kibriya, Claire Mulot, Laure Dossus, Helen Tsimiklis, Tomasz Huzarski, Peter Kraft, Anja Rudolph, Arto Mannermaa, Alison M. Dunning, Lisa B. Signorello, Valerie Gaborieau, Kenneth Muir, Anthony J. Swerdlow, Javier Benitez, Judith S. Brand, Sander Canisius, Hoda Anton-Culver, Veli-Matti Kosma, Thilo Dörk, Sten Cornelissen, Christa Stegmaier, Cheng Har Yip, Brian E. Henderson, Harald Surowy, Jingmei Li, Nur Aishah Taib, W. Ryan Diver, Carmel Apicella, Janet E. Olson, Kristiina Aittomäki, Celine M. Vachon, Regina M. Santella, Dimitrios Trichopoulos, Jianjun Liu, Nick Orr, Martine Dumont, Christian Sutter, Sue K. Park, Mikael Hartman, Susan L. Neuhausen, Hui Miao, M. Pilar Zamora, Anna H. Wu, Rob B. van der Luijt, Isabel dos-Santos-Silva, Graham Casey, Henrik Flyger, M. Rosario Alonso, Nuria Álvarez, Michael J. Kerin, Loic Le Marchand, Jose Ignacio Arias Perez, Mikael Eriksson, Esther M. John, Quinten Waisfisz, Qin Wang, Daniel C. Tessier, Paolo Radice, Robert A.E.M. Tollenaar, James McKay, Silje Nord, Hiltrud Brauch, José María Huerta, Stephen J. Chanock, Mervi Grip, Patrick Neven, Senno Verhoef, Clinical Genetics, Obstetrics & Gynecology, Medical Oncology, Cardiothoracic Surgery, Dennis, Joe [0000-0003-4591-1214], Wang, Jean [0000-0002-9139-0627], Khaw, Kay-Tee [0000-0002-8802-2903], Pharoah, Paul [0000-0001-8494-732X], Dunning, Alison [0000-0001-6651-7166], Easton, Douglas [0000-0003-2444-3247], Apollo - University of Cambridge Repository, Human genetics, and CCA - Oncogenesis

Subjects
Breast Neoplasms, Single-nucleotide polymorphism, Genome-wide association study, Biology, Research Support, Polymorphism, Single Nucleotide, N.I.H, Cohort Studies, brca1, Breast cancer, Research Support, N.I.H., Extramural, Meta-Analysis as Topic, SDG 3 - Good Health and Well-being, common variants, Journal Article, estrogen, chek2-asterisk-1100delc, Genetics, medicine, Humans, Genetic Predisposition to Disease, 1000 Genomes Project, Non-U.S. Gov't, genotype imputation, risk, Genetic association, Research Support, Non-U.S. Gov't, Chromatin binding, Extramural, Cancer, Microarray Analysis, confer susceptibility, medicine.disease, 3. Good health, ovarian-cancer, Genetic Loci, Case-Control Studies, alleles, Female, Imputation (genetics), Genome-Wide Association Study, metaanalysis
Abstract

Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1. ispartof: Nature Genetics vol:47 issue:4 pages:373-80 ispartof: location:United States status: published

Published
2015

85. Association analysis identifies 65 new breast cancer risk loci

Author

Michael Jones, Dong-Young Noh, Martha J. Shrubsole, Chen-Yang Shen, Xiaoqing Chen, Esther M. John, Patricia Harrington, Quinten Waisfisz, Sue K. Park, Miriam Dwek, Christa Stegmaier, Sibylle Loibl, Wing-Yee Lo, Suleeporn Sangrajrang, Susan L. Neuhausen, Marina Bermisheva, Alicja Wolk, Christof Sohn, Keun-Young Yoo, Arja Jukkola-Vuorinen, Kathrin Thöne, James McKay, John J. Spinelli, Brian D. Carter, Elza Khusnutdinova, Francois Bacot, Paul L. Auer, Anna H. Wu, Christopher I. Amos, Johanna I. Kiiski, Hans Wildiers, Manjeet K. Bolla, Soo Hwang Teo, Julie M. Cunningham, Zhaoming Wang, Dieter Flesch-Janys, Argyrios Ziogas, Ann Smeets, Min Hyuk Lee, Xiaohong R. Yang, Carl Blomqvist, Natalia Antonenkova, Vassilios Georgoulias, Siranoush Manoukian, Anne Lise Børresen-Dale, Montserrat Garcia-Closas, Priyanka Sharma, Michael J. Kerin, Loic Le Marchand, Yoshio Kasuga, Michael Untch, Thomas Brüning, Natalia Bogdanova, Juliet D. French, Mark E. Sherman, Diana Eccles, Don M. Conroy, Marcia Adams, Pascal Guénel, Jonine D. Figueroa, Somchai Thanasitthichai, Jonathan Beesley, Paolo Peterlongo, Angela Cox, Graham G. Giles, Hans Christiansen, Irene L. Andrulis, Caroline Baynes, V. Shane Pankratz, Kristine Jones, Wei Zheng, Motoki Iwasaki, Rita K. Schmutzler, Julian Peto, Sara Margolin, Hedy S. Rennert, Hidemi Ito, Caroline Seynaeve, Jirong Long, Rachel Lloyd, Mark S. Goldberg, Javier Benitez, Børge G. Nordestgaard, Kathleen E. Malone, A. Heather Eliassen, Valerie Rhenius, Kristan J. Aronson, Maartje J. Hooning, Ursula Eilber, Christopher A. Haiman, Ji Yeob Choi, Jaana M. Hartikainen, Ian W. Brock, Barbara Burwinkel, Brigitte Rack, Mitul Shah, Matthias W. Beckmann, Belynda Hicks, Bernardo Bonanni, Alexander Hein, Leslie Bernstein, Christine L. Clarke, Emilie Cordina-Duverger, Sabine Behrens, Hoda Anton-Culver, Angela Brooks-Wilson, Bin Zhu, Gord Glendon, Banu Arun, José A. García-Sáenz, Jose Ignacio Arias Perez, Anne Grundy, Ans M.W. van den Ouweland, Nadege Presneau, Volker Arndt, Mikael Eriksson, Simon S. Cross, Craig Luccarini, Anthony J. Swerdlow, Veli-Matti Kosma, Hui Miao, Ming-Feng Hou, Hiroji Iwata, Christi J. van Asperen, Henrik Flyger, Jennifer Stone, Qin Wang, Penny Soucy, Heli Nevanlinna, Jane Heyworth, Shoichiro Tsugane, Annika Lindblom, Curtis Olswold, Trinidad Caldés, Laura Fachal, Ed Dicks, Shirley Hui, Katja Butterbach, Alison M. Dunning, Peter Devilee, Qiuyin Cai, Antonis C. Antoniou, Diether Lambrechts, Katarzyna Kaczmarek, Katri Pylkäs, Fredrick R. Schumacher, Arif B. Ekici, Aaron D. Norman, Jolanta Lissowska, Daniel C. Tessier, N Hamel, Paolo Radice, Håkan Olsson, Vessela N. Kristensen, Ling Tong, Harald Surowy, Rulla M. Tamimi, Jonathan Tyrer, Michael P. Lux, Stacey L. Edwards, Kathryn J. Ruddy, Giske Ursin, Myrto Barrdahl, Xiao-Ou Shu, Primitiva Menéndez, Sara Y. Brucker, Elad Ziv, Kenneth Muir, Eric Hahnen, Andy C. H. Lee, Rodney J. Scott, Lothar Haeberle, Darya Prokofyeva, Isabel dos-Santos-Silva, Peter Kraft, David G. Cox, Jong Won Lee, Sunil R. Lakhani, Kelly-Anne Phillips, Douglas F. Easton, Melissa C. Southey, Jan Lubinski, Jose E. Castelao, Hanne Meijers-Heijboer, Ivana Maleva Kostovska, Siddhartha Kar, Renske Keeman, Celine M. Vachon, Diana Torres, Stephen J. Chanock, Jack A. Taylor, Emiel J. Th. Rutgers, Chuen Neng Lee, Jason Vollenweider, Gadi Rennert, Jane Romm, Amy E. McCart Reed, Kee Seng Chia, Thomas Rüdiger, Anja Rudolph, Catriona McLean, David Van Den Berg, Christopher G. Scott, Mervi Grip, Lucy Xia, Georgia Chenevix-Trench, Robert Winqvist, Mary Beth Terry, Jenny Chang-Claude, Hans-Ulrich Ulmer, Mikael Hartman, Dona N. Ho, Maria Kabisch, Christoph Engel, Claire Mulot, Grethe I. Grenaker Alnæs, Arto Mannermaa, Nazneen Rahman, Tjoung-Won Park-Simon, Atocha Romero, Lin Fritschi, Manuela Gago-Dominguez, Matthias Ruebner, Valerie Gaborieau, Keitaro Matsuo, Asha Rostamianfar, Emmanouil Saloustros, Dijana Plaseska-Karanfilska, J.-P. Meyer, Sara Lindström, Annegien Broeks, Audrey Lemaçon, Tsun Leung Chan, Tongguang Cheng, Robert J. MacInnis, Habibul Ahsan, Federico Canzian, Paul Brennan, Mia M. Gaudet, David E. Goldgar, Anna Jakubowska, Paul D.P. Pharoah, Jacek Gronwald, Sung-Won Kim, Daehee Kang, Daniel O. Stram, Nichola Johnson, Rob B. van der Luijt, Sten Cornelissen, Camilla Wendt, Dylan M. Glubb, Olufunmilayo I. Olopade, Usha Menon, David J. Hunter, Kristiina Aittomäki, Jamie Allen, Chiu-Chen Tseng, Keith Humphreys, Edmond S. K. Ma, Peter Hillemanns, Hiltrud Brauch, Chia-Ni Hsiung, Sheila Seal, Junko Ishiguro, Dale P. Sandler, Peter Schürmann, Gary D. Bader, Sarah Stewart-Brown, Flavio Lejbkowicz, Marike Gabrielson, Wolfgang Janni, Judith S. Brand, Jingmei Li, Ava Kwong, Stig E. Bojesen, Ying Zheng, Mila Pinchev, Yu Tang Gao, Susan E. Hankinson, Elinor J. Sawyer, Per Broberg, Sofia Khan, Grace Sheng, Alfons Meindl, Margriet Collée, Jyh-Cherng Yu, Ute Krüger, Louise A. Brinton, Elizabeth W. Pugh, Thilo Dörk, Hilary K. Finucane, Peter A. Fasching, Shan Wang-Gohrke, Jenna Lilyquist, Muriel A. Adank, Marjanka K. Schmidt, Susan M. Gapstur, Sune F. Nielsen, Maya Ghoussaini, Minouk J. Schoemaker, Roger L. Milne, Jacques Simard, Clarice R. Weinberg, Kyriaki Michailidou, Shivaani Mariapun, Rob A. E. M. Tollenaar, Lizet E. van der Kolk, Nicola Miller, Anna González-Neira, Ian Tomlinson, Thérèse Truong, Ross L. Prentice, Anna Marie Mulligan, Jason S. Carroll, Taiki Yamaji, Carolina Ellberg, Mingajeva Elvira, Olivia Fletcher, Arnaud Droit, Per Hall, Maria Elena Martinez, Maria Tengström, Hui Cai, Xia Jiang, Janet E. Olson, Julia A. Knight, Nick Orr, Angel Carracedo, Guanmengqian Huang, Martine Dumont, Cheng Har Yip, Tom Maishman, Mary B. Daly, Artitaya Lophatananon, Niclas Håkansson, Steven N. Hart, Nur Aishah Taib, Andreas Schneeweiss, Daniel F. Schmidt, Daniel Vincent, Antoinette Hollestelle, Dimitrios Mavroudis, JoAnn E. Manson, Joe Dennis, Walter C. Willett, Rudolf Kaaks, Karen McCue, Enes Makalic, Kimberly F. Doheny, Eunjung Lee, Robert N. Hoover, Fergus J. Couch, Ute Hamann, Alice S. Whittemore, Hermann Brenner, Lorraine Durcan, Kamila Czene, Patrick Neven, John L. Hopper, Clinical Genetics, Medical Oncology, Human Genetics, CCA - Cancer biology and immunology, Dennis, Joe [0000-0003-4591-1214], Wang, Jean [0000-0002-9139-0627], Tyrer, Jonathan [0000-0003-3724-4757], Dicks, Ed [0000-0002-0617-0401], Lee, Andrew [0000-0003-0677-0252], Allen, Jamie [0000-0002-8677-2225], Fachal Vilar, Laura [0000-0002-7256-9752], Carroll, Jason [0000-0003-3643-0080], Rhenius, Valerie [0000-0003-4215-3235], Antoniou, Antonis [0000-0001-9223-3116], Pharoah, Paul [0000-0001-8494-732X], Dunning, Alison [0000-0001-6651-7166], Easton, Douglas [0000-0003-2444-3247], Apollo - University of Cambridge Repository, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, and Amsterdam Reproduction & Development (AR&D)

Subjects
0301 basic medicine, Multifactorial Inheritance, Genome-wide association study, Regulatory Sequences, Nucleic Acid, skin and connective tissue diseases, Cancer genetics, Genetics, Multidisciplinary, medicine.diagnostic_test, 3. Good health, Europe, annotation, Medical genetics, Female, Asian Continental Ancestry Group, medicine.medical_specialty, Asia, architecture, European Continental Ancestry Group, ABCTB Investigators, Locus (genetics), Breast Neoplasms, Biology, Polymorphism, Single Nucleotide, Risk Assessment, Article, White People, NBCS Collaborators, 03 medical and health sciences, Breast cancer, Asian People, SDG 3 - Good Health and Well-being, Genetic variation, ConFab/AOCS Investigators, expression, medicine, Genetic predisposition, Journal Article, Humans, Computer Simulation, Genetic Predisposition to Disease, biological pathways, Genetic association, Genetic testing, Genetic association study, Binding Sites, interaction networks, medicine.disease, comprehensive molecular portraits, mutations, susceptibility loci, 030104 developmental biology, Genetic Loci, genome-wide association, protein, Transcription Factors, Genome-Wide Association Study
Abstract

Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P

Published
2017

88. Enterococcus, Salmonella y H₂S. Control remoto de la resistencia a antibióticos

Author

Thomas López, Daniel Vincent and González Zorn, Bruno

Subjects
Microbiología
Abstract

Enterococcus faecalis y Enterococcus faecium son dos de los principales patógenos nosocomiales a nivel mundial, ocasionando cuadros de endocarditis, infecciones urinarias y septicemias. Esto se debe, entre otras razones, a su elevada resistencia a condiciones adversas del medio y a multitud de antibióticos. Entre los mecanismos que presentan los enterococos para resistir a los antimicrobianos, el de mayor trascendencia clínica es su resistencia intrínseca a las cefalosporinas (un valioso grupo de antibióticos perteneciente a la familia de los beta-lactámicos), lo que limita las opciones terapéuticas disponibles para combatir las infecciones provocadas por estas especies. En la presente Tesis Doctoral, hemos descubierto un fenómeno capaz de anular la resistencia intrínseca de Enterococcus, volviéndole susceptible a la acción de las cefalosporinas. Esto ocurre cuando los enterococos son expuestos a la presencia del ácido sulfhídrico, abreviado como H₂S. Este gas, considerado durante siglos como un metabolito celular de desecho, está reconocido actualmente como un gasotransmisor de gran importancia, regulando diferentes procesos fisiológicos y patológicos en Eucariotas así como en Procariotas. Profundizando en nuestro trabajo, hemos encontrado que la resistencia a las cefalosporinas de Enterococcus no solo se revierte al añadir H₂S al medio, sino que el mismo resultado tiene lugar cuando el H₂S es producido y excretado por otra bacteria, incluso aunque ambas especies se sitúen físicamente separadas entre sí. Por tanto, esta Tesis presenta avances importantes en dos temas. Por un lado, el hecho de que Enterococcus sea susceptible a la combinación de las cefalosporinas con el H₂S abre la puerta al diseño de futuras alternativas terapéuticas frente a patógenos multirresistentes. Por otro lado, hasta donde sabemos es la primera vez que se describe la capacidadde una bacteria para producir, a distancia, un efecto con consecuencias letales sobre otra bacteria, resultado sorprendente, una vez más, la complejidad del mundo bacteriano.

Published
2017

89. U-505

Author

Rear-Admiral Daniel Vincent Gallery and Rear-Admiral Daniel Vincent Gallery

Abstract

Admiral Daniel V. Gallery boarded and captured a German U-Boat at sea in June, 1944—the first American officer to so capture an enemy warship since 1815!U-505 is Admiral Gallery's own story of his extraordinary feat—and also a gripping narrative of the fierce Allied war against the German U-Boat fleet.“EXCELLENT.”—Chicago Tribune“Terrific…the first-hand story of Uncle Sam's U-Boat killers.”—Chicago Daily News“Brimming with thrills.”—Philadelphia News“An engrossing tale…Pungent, entertaining, informative.”—Navy Times“A humdinger of a sea story…a highly readable book, trimmed from stem to stern with the writer's irrepressible sense of humor.”—Chicago Sunday Times“Excellent in several ways: it provides a fine quick survey of the whole Atlantic war, it describes the operation of the German U-boat service, and, most dramatically, it tells how an American task force under Admiral Gallery achieved the unique feat of capturing a German submarine.”—Publishers'Weekly“U-505 IS ONE OF THE WAR'S MOST EXCITING MEMOIRS.”—Chicago News“One of the best non-fiction books about World War II.”—Raleigh News & Observer“A first-rate adventure tale…suspense and excitement told with a seaman's salty zest…excellent reading.”—Chicago Sunday Tribune“A masterful job that merits the attention of every lover of sea stories.”—Pittsburgh Press

Published
2016

91. Acid, silver, and solvent-free gold-catalyzed hydrophenoxylation of internal alkynes

Author

Kevin J. Garcia, Marcia E. Richard, Robert A. Stockland, Daniel Vincent Fraccica, Peter M. Findeis, Victoria L. Resh, Rosa M. Ciccarelli, Erica J. Miller, Aakash Shah, and Erin C. Holahan

Subjects
silver-free, 010402 general chemistry, solvent-free, 01 natural sciences, Full Research Paper, Catalysis, lcsh:QD241-441, Silver salts, chemistry.chemical_compound, lcsh:Organic chemistry, Organic chemistry, Phenols, hydrophenoxylation, lcsh:Science, acid-free, Solvent free, catalysis, 010405 organic chemistry, organic chemicals, Single component, Organic Chemistry, single component, gold, gold catalysis, 0104 chemical sciences, Chemistry, chemistry, lcsh:Q, Carbene
Abstract

A range of arylgold compounds have been synthesized and investigated as single-component catalysts for the hydrophenoxylation of unactivated internal alkynes. Both carbene and phosphine-ligated compounds were screened as part of this work, and the most efficient catalysts contained either JohnPhos or IPr/SIPr. Phenols bearing either electron-withdrawing or electron-donating groups were efficiently added using these catalysts. No silver salts, acids, or solvents were needed for the catalysis, and either microwave or conventional heating afforded moderate to excellent yields of the vinyl ethers.

Published
2013

92. Common genetic determinants of breast-cancer risk in East Asian women: a collaborative study of 23 637 breast cancer cases and 25 579 controls

Author

Joe Dennis, Sarah Stewart-Brown, Per Hall, Hui Cai, Pei Ei Wu, Soo Chin Lee, Alison M. Dunning, Kenneth Muir, Wenjin Wang, Min Hyuk Lee, Francois Bacot, Hyuna Sung, Chiu-Chen Tseng, Zefang Ren, Hidemi Ito, Artitaya Lophatananon, Ben Zhang, Wei Lu, Kexin Chen, Jong Won Lee, Daniel O. Stram, Mi Kyung Kim, Wonshik Han, Chiun-Sheng Huang, Soo Hwang Teo, Ji Yeob Choi, David Van Den Berg, Hui Miao, Xiao-Ou Shu, Jiajun Shi, Wei Zheng, Mikael Hartman, Hongbing Shen, Jirong Long, Douglas F. Easton, Qin Wang, Javier Benitez, Chun Li, Hideo Tanaka, Jyh Cherng Yu, Bu Tian Ji, Motoki Iwasaki, Daniel C. Tessier, Thomas C. Putti, Daniel Vincent, Tien Yin Wong, Ming-Feng Hou, Ui-Soon Khoo, Keitaro Matsuo, Cheng Har Yip, Hiroji Iwata, Keun-Young Yoo, Dong Young Noh, Paul D.P. Pharoah, Anna H. Wu, Sung-Won Kim, In Nee Kang, Yong-Bing Xiang, Ying Zheng, Wanqing Wen, Jong-Young Lee, Pornthep Siriwanarangsan, Chen-Yang Shen, Suleeporn Sangrajrang, Daehee Kang, Aiko Sueta, Yu Tang Gao, Qiuyin Cai, Kyriaki Michailidou, Manjeet K. Humphreys, Sue K. Park, and Christopher A. Haiman

Subjects
Adult, Oncology, China, medicine.medical_specialty, Population, Estrogen receptor, Breast Neoplasms, Single-nucleotide polymorphism, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Asian People, Internal medicine, Republic of Korea, Genetics, medicine, Humans, Genetic Predisposition to Disease, education, Molecular Biology, Genetics (clinical), Aged, 030304 developmental biology, Genetic association, 0303 health sciences, education.field_of_study, Association Studies Articles, Case-control study, Cancer, General Medicine, Middle Aged, medicine.disease, 3. Good health, Receptors, Estrogen, Case-Control Studies, 030220 oncology & carcinogenesis, Female, Genome-Wide Association Study
Abstract

In a consortium including 23 637 breast cancer patients and 25 579 controls of East Asian ancestry, we investigated 70 single-nucleotide polymorphisms (SNPs) in 67 independent breast cancer susceptibility loci recently identified by genome-wide association studies (GWASs) conducted primarily in European-ancestry populations. SNPs in 31 loci showed an association with breast cancer risk at P < 0.05 in a direction consistent with that reported previously. Twenty-one of them remained statistically significant after adjusting for multiple comparisons with the Bonferroni-corrected significance level of, published_or_final_version

Published
2013

93. The OncoArray Consortium: a network for understanding the genetic architecture of common cancers

Author

Katja Butterbach, Daniel C. Tessier, Dennis J. Hazelett, Stephen J. Chanock, Paul Brennan, Zhaoming Wang, Marc T. Goodman, Ali Amin Al Olama, Daniela Seminara, Tracy A. O'Mara, Craig Luccarini, Lesley McGuffog, David Van Den Berg, Andy C. H. Lee, James McKay, Stephen B. Gruber, Sue K. Park, Jack A. Taylor, Graham G. Giles, Michael F. Seldin, Alison M. Dunning, Zsofia Kote-Jarai, Sara Lindström, David E. Goldgar, Irene Brüske-Hohlfeld, Stig E. Bojesen, Paul D.P. Pharoah, Jonathan Marchini, Rosalind A. Eeles, Karoline Kuchenbaecker, Laura Fachal, Penny Soucy, Rayjean J. Hung, Ahsan Kamal, Marjorie J. Riggan, Xiangjun Xiao, Fergus J. Couch, Francois Bacot, Georgia Chenevix-Trench, John K. Field, Amanda B. Spurdle, Christopher A. Haiman, Julie M. Cunningham, Andrew Berchuck, Fredrick R. Schumacher, Elizabeth M. Gillanders, Simon A. Gayther, Belynda Hicks, Laura Ottini, David J. Hunter, Peter Kraft, Charlisse Caga-Anan, Jane Romm, Sylvie Laboissiere, Heike Bickeböller, Catherine M. Phelan, Jacques Simard, Graham Casey, Stephanie L. Schmit, Yafang Li, Sune F. Nielsen, Thomas A. Sellers, Hua Ling, Christopher K. Edlund, Yongyong Shi, Liesel M. FitzGerald, Stefanie A. Nelson, Rita K. Schmutzler, Gerhard A. Coetzee, Linda E. Kelemen, Kimberly F. Doheny, Elizabeth W. Pugh, Antonis C. Antoniou, Melanie Waldenberger, Judith L. Forman, Angela Risch, Ulrike Peters, Joe Dennis, David V. Conti, Daniel Vincent, Stephen Demetriades, Jinyoung Byun, Sara Benlloch, Tameka Shelford, Hongbing Shen, Douglas F. Easton, Mads Thomassen, Marcia Adams, Christopher I. Amos, Kenneth Offit, Kyriaki Michailidou, Judith Manz, Deborah J. Thompson, Dennis, Joe [0000-0003-4591-1214], Dunning, Alison [0000-0001-6651-7166], Fachal Vilar, Laura [0000-0002-7256-9752], Lee, Andrew [0000-0003-0677-0252], Thompson, Deborah [0000-0003-1465-5799], Amin Al Olama, Ali [0000-0002-7178-3431], Antoniou, Antonis [0000-0001-9223-3116], Pharoah, Paul [0000-0001-8494-732X], Easton, Douglas [0000-0003-2444-3247], and Apollo - University of Cambridge Repository

Subjects
Male, 0301 basic medicine, epistasis, genetic epidemiology, Genotype, Epidemiology, Single-nucleotide polymorphism, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, Risk Assessment, Article, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Genetic Predisposition to Disease/epidemiology, Genetic variation, Mendelian randomization, Prevalence, Humans, cancer, Genetic Predisposition to Disease, Selection, Genetic, Genotyping, Genetics, ancestry, Genetic Variation, Polymorphism, Single Nucleotide/genetics, Prognosis, Genetic architecture, 3. Good health, 030104 developmental biology, Genetic Variation/genetics, Oncology, 030220 oncology & carcinogenesis, OncoArray Consortium, genetic architecture, cancers, Genome-Wide Association Study/methods, Female, DNA microarray, Neoplasms/epidemiology, Genome-Wide Association Study, genetic susceptibility
Abstract

Background: Common cancers develop through a multistep process often including inherited susceptibility. Collaboration among multiple institutions, and funding from multiple sources, has allowed the development of an inexpensive genotyping microarray, the OncoArray. The array includes a genome-wide backbone, comprising 230,000 SNPs tagging most common genetic variants, together with dense mapping of known susceptibility regions, rare variants from sequencing experiments, pharmacogenetic markers and cancer related traits. Methods: The OncoArray can be genotyped using a novel technology developed by Illumina to facilitate efficient genotyping. The consortium developed standard approaches for selecting SNPs for study, for quality control of markers and for ancestry analysis. The array was genotyped at selected sites and with prespecified replicate samples to permit evaluation of genotyping accuracy among centers and by ethnic background. Results: The OncoArray consortium genotyped 447,705 samples. A total of 494,763 SNPs passed quality control steps with a sample success rate of 97% of the samples. Participating sites performed ancestry analysis using a common set of markers and a scoring algorithm based on principal components analysis. Conclusions: Results from these analyses will enable researchers to identify new susceptibility loci, perform fine mapping of new or known loci associated with either single or multiple cancers, assess the degree of overlap in cancer causation and pleiotropic effects of loci that have been identified for disease-specific risk, and jointly model genetic, environmental and lifestyle related exposures. Impact: Ongoing analyses will shed light on etiology and risk assessment for many types of cancer. TRICL (Transdisciplinary Research for Cancer of Lung) and International Lung Cancer Consortium (ILCCO): National Institute of Health U19 CA148127-01 (C.I. Amos, J. Byun, Y. Li, X. Xiao, J. L. Forman, A. Risch, H. Bickeböller, M. Waldenberger, I. Brüske, J. Manz, P. Brennan, R. Hung, H. Shen, Y. Shi, A. Kamal, C. I. Amos, J.K. Field), Canadian Cancer Society Research Institute (no. 020214, R. Hung). DRIVE (Discovery, Biology, and Risk of Inherited Variants in Breast Cancer): National Institute of Health U19 CA148065 (D.J. Hazelett, D. F. Easton, S. Lindström, P. Kraft, J. Dennis, A. Dunning, K. Michailidou, L. Fachal, S. Benlloch, J. Cunningham, K. Butterbach, K. Offit, R. Schmutzler, L. Ottini, D. Vincent). CORECT (ColoRectal Transdisciplinary Study): National Institute of Health U19 CA148107; R01 CA81488, P30 CA014089 (S. Gruber, U. Peters, G. Casey). ELLIPSE (ELLIPSE, Elucidating Loci in Prostate Cancer Susceptibility): This work was support by U19 CA148537(F. Schumacher, S.A. Gayther, S.L. Schmit, C.K. Edlund, D.J. Hazelett, G.A. Coetzee, C. Haiman, S. Demetriades, D. Van Den Berg). FOCI (Transdisciplinary Cancer Genetic Association and Interacting Studies): National Institutes of Health U19 CA148112- 01 (T.A. Sellers, C. Phelan), R01-CA122443(B. Hicks) ) P50-CA116201, CA192393 (F. Couch), P50-CA136393(J. Cunningham, F. Couch), OCAC - CA-149429 (C. Phelan). , P30-CA15083 (B. Hicks), Cancer Research UK (C490/A8339(A. Antoniou, P. Pharoah, A. Dunning), C490/A16561(P. Pharoah, A. Dunning), C490/A10119 (A. Dunning, P. Pharoah), C490/A10124 (A. Dunning, P. Pharoah)). ASTERISK: a Hospital Clinical Research Program (PHRC) and supported by the Regional Council of Pays de la Loire, the Groupement des Entreprises Françaises dans la Lutte contre le Cancer (GEFLUC), the Association Anne de Bretagne Génétique and the Ligue Régionale Contre le Cancer (LRCC) (F. Bacot). DACHS: German Research Council (Deutsche Downloaded from cebp.aacrjournals.org on October 31, 2016. © 2016 American Association for Cancer Research. Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Author Manuscript Published OnlineFirst on October 3, 2016; DOI: 10.1158/1055-9965.EPI-16-0106 Forschungsgemeinschaft, BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, and CH 117/1-1, C.K. Edlund), and the German Federal Ministry of Education and Research (01KH0404 and 01ER0814). Prostate Lung Colon Ovarian Screening trial: Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. The GC-HBOC (German Consortium of Hereditary Breast and Ovarian Cancer) is supported by the German Cancer Aid (grant no 110837, coordinator: R. Schmutzler, Cologne). The PERSPECTIVE (J. Simard) project was supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research (MOP-86727, L.E. Kelemen), the Ministère de l’Économie, Innovation et Exportation du Québec through Genome Québec, and thee Quebec Breast Cancer Foundation, including additional funding from the Canadian Breast Cancer Foundation and the National Cancer Institute USA through Breast Cancer Family Registry Cohort (#1UM1CA164920-01A1). European Union Framework Programme for Research and Innovation (MSCA-IF-2014-EF-656144)(L. Fachal). The Breast Cancer Research Foundation, P30 CA08748, Andrew Sabin Foundation (K. Offit). CIDR genotyping for the Oncoarray was conducted under contract 268201200008I to K.Doheny and through grant 1X01HG007491- 01 to C.I. Amos. This is the author accepted manuscript. The final version is available from American Association for Cancer Research via http://dx.doi.org/10.1158/1055-9965.EPI-16-0106

Published
2016

94. Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array

Author

Artitaya Lophatananon, W. Ryan Diver, Stig E. Bojesen, Roman Corral, Fredrick R. Schumacher, Stephen J. Chanock, Shannon K. McDonnell, Graham G. Giles, Craig C. Teerlink, Douglas F. Easton, Cezary Cybulski, Brian E. Henderson, Judith A. Clements, Ali Amin Al Olama, Francois Bacot, David P. Dearnaley, Elio Riboli, Peter Klarskov, Daniel Vincent, Rosemary A. Wilkinson, Danielle M. Karyadi, Michelle Guy, Vincent Khoo, Christopher A. Haiman, Afshan Siddiq, M. Andreas Røder, Amit Joshi, Jong Y. Park, Walther Vogel, Henrik Grönberg, Angela Cox, Rudolf Kaaks, Nora Pashayan, Timothy J. Key, C. R. J. Woodhouse, Jarmo Virtamo, Meredith Yeager, Malgorzata Tymrakiewicz, Sune F. Nielsen, Richard B. Hayes, Johanna Schleutker, Gianluca Severi, Robert Huddart, Wei Zheng, Thomas A. Sellers, Melanie Maranian, Shahana Ahmed, David E. Neal, Daniel Leongamornlert, Zsofia Kote-Jarai, Tiina Wahlfors, Loic Le Marchand, Kay-Tee Khaw, Tokhir Dadaev, Lisa A. Cannon-Albright, Janet L. Stanford, William J. Blot, Andy C. H. Lee, Freddie C. Hamdy, Siqun L. Zheng, Rosalind A. Eeles, Alison M. Dunning, Mariana C. Stern, Melissa C. Southey, Don M. Conroy, Kenneth Muir, Ahva Shahabi, Alan Horwich, Gerald L. Andriole, Antje E. Rinckleb, Srilakshmi Srinivasan, Tim Dudderidge, Joe Dennis, Radka Kaneva, Vanio Mitev, Angela Morgan, Sue A. Ingles, Adam S. Kibel, Markus Aly, Koveela Govindasami, Maya Ghoussaini, Jenny L Donovan, Manuel R. Teixeira, Emma J. Sawyer, Sara Lindström, Jiangfeng Xu, Maren Weischer, Ed Dicks, Jyotsna Batra, S Jugurnauth-Little, Hui-Yi Lin, Suzanne Kolb, Lisa B. Signorello, Dallas R. English, Antonis C. Antoniou, Federico Canzian, Anssi Auvinen, Mia M. Gaudet, Paula Paulo, Paul D.P. Pharoah, Heiko Müller, Qiuyin Cai, Børge G. Nordestgaard, Esther M. John, Sonja I. Berndt, D J Schaid, Daniele Campa, Chris Ogden, Colin Cooper, Craig Luccarini, Jan Lubinski, Elaine A. Ostrander, Ruth C. Travis, Dominika Wokołorczyk, John L. Hopper, Sofia Maia, Sara Benlloch, Chris Parker, Erika M. Kwon, Nicholas van As, Caroline Baynes, C. Slavov, Teuvo L.J. Tammela, Ethan M. Lange, Daniel C. Tessier, David J. Hunter, Dietrich Rothenbacher, Robert A. Stephenson, Liesel M. FitzGerald, Christiane Maier, Hermann Brenner, Kathleen A. Cooney, Graham A. Colditz, Felicity Lose, Edward J. Saunders, Demetrius Albanes, Stephen N. Thibodeau, Fredrik Wiklund, Amanda B. Spurdle, Jan Adolfsson, Susan M. Gapstur, Peter Kraft, Bettina F. Drake, and Alan Thompson

Subjects
Male, genetic association, genotype, Genome-wide association study, Bioinformatics, genetic risk, developed country, Prostate cancer, 0302 clinical medicine, Risk Factors, Genotype, Cooperative Behavior, breast cancer, cancer prognosis, cancer susceptibility, cell adhesion, cell cycle arrest, chromosome 14, chromosome 2, double stranded DNA break, embryo development, extracellular matrix, gene frequency, gene linkage disequilibrium, genetic predisposition, Gleason score, heterozygote, human, intron, priority journal, promoter region, prostate cancer, quality control, regulator gene, Oligonucleotide Array Sequence Analysis, 0303 health sciences, education.field_of_study, 3. Good health, 030220 oncology & carcinogenesis, Population, Single-nucleotide polymorphism, Biology, ta3111, Polymorphism, Single Nucleotide, 03 medical and health sciences, Meta-Analysis as Topic, Genetics, medicine, Humans, Genetic Predisposition to Disease, education, Genotyping, 030304 developmental biology, Case-control study, Cancer, Prostatic Neoplasms, medicine.disease, ta3122, Genetic Loci, Case-Control Studies, Genome-Wide Association Study
Abstract

Prostate cancer is the most frequently diagnosed cancer in males in developed countries. To identify common prostate cancer susceptibility alleles, we genotyped 211,155 SNPs on a custom Illumina array (iCOGS) in blood DNA from 25,074 prostate cancer cases and 24,272 controls from the international PRACTICAL Consortium. Twenty-three new prostate cancer susceptibility loci were identified at genome-wide significance (P < 5 × 10(-8)). More than 70 prostate cancer susceptibility loci, explaining ∼30% of the familial risk for this disease, have now been identified. On the basis of combined risks conferred by the new and previously known risk loci, the top 1% of the risk distribution has a 4.7-fold higher risk than the average of the population being profiled. These results will facilitate population risk stratification for clinical studies.

Published
2016

95. Variations in 5-methylcytosine and 5-hydroxymethylcytosine among human brain, blood, and saliva using oxBS and the Infinium MethylationEPIC array

Author

Jeffrey A. Gross, Francois Lefebvre, Daniel Vincent, Pierre-Eric Lutz, Guillaume Bourque, Gustavo Turecki, Francois Bacot, Department of Psychiatry [Montréal], McGill University, CHU Strasbourg, Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and McGill University = Université McGill [Montréal, Canada]

Subjects
0301 basic medicine, Saliva, oxBS, Bisulfite sequencing, Computational biology, Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, chemistry.chemical_compound, medicine, 5-hydroxymethylcytosine, 5-methylcytosine, Methods Manuscript, 5-Hydroxymethylcytosine, InfiniumEPIC, Human brain, 3. Good health, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 5-Methylcytosine, 030104 developmental biology, medicine.anatomical_structure, chemistry, Human genome, General Agricultural and Biological Sciences, Cytosine, DNA
Abstract

International audience; Investigating 5-methylcytosine (5mC) has led to many hypotheses regarding molecular mechanism underlying human diseases and disorders. Many of these studies, however, utilize bisulfite conversion alone, which cannot distinguish 5mC from its recently discovered oxidative product, 5-hydroxymethylcytosine (5hmC). Furthermore, previous array-based technologies do not have the necessary probes to adequately investigate both modifications simultaneously. In this manuscript, we used technical replicates of DNA from human brain, human blood, and human saliva, in combination with oxidative bisul-fite conversion and Illumina's Infinium MethylationEPIC array, to analyze 5mC and 5hmC at more than 650 000 and 450 000 relevant loci, respectively, in the human genome. We show the presence of loci with detectable 5mC and 5hmC to be equally distributed across chromosomes and genomic features, while also being present in genomic regions with transcriptional regulatory properties. We also describe 2528 5hmC sites common across tissue types that show a strong association with immune-related functions. Lastly, in human brain, we show that 5hmC accounts for one-third of the total signal from bisulfite-converted data. As such, not only do our results confirm the efficacy and sensitivity of pairing oxidative bisulfite conversion and the EPIC array to detect 5mC and 5hmC in all three tissue types, but they also highlight the importance of dissociating 5hmC from 5mC in future studies related to cytosine modifications.

Published
2016

96. Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs)

Author

Stacey L. Edwards, Daniel Vincent, Antoinette Hollestelle, Melissa C. Southey, Thilo Dörk, Jonine Figueroa, Robert Winqvist, Wei Zheng, Keitaro Matsuo, Fergus J. Couch, Don M. Conroy, Anna Jakubowska, Paul D.P. Pharoah, Sara Margolin, Simon S. Cross, Joe Dennis, Rebecca Mayes, Annegien Broeks, Mitul Shah, Matthias W. Beckmann, Mahdi Moradi Marjaneh, Pei-Ei Wu, Javier Benitez, Hanna Fues Wahl, Ute Hamann, Rita K. Schmutzler, Guillermo Pita, Nichola Johnson, Suleeporn Sangrajrang, James McKay, Barbara Burwinkel, Hoda Anton-Culver, Pascal Guénel, Douglas F. Easton, Veli-Matti Kosma, Hidemi Ito, Angela Cox, Georgia Chenevix-Trench, M. Rosario Alonso, Mark S. Goldberg, Hatef Darabi, Volker Arndt, Qin Wang, Manjeet K. Bolla, Nick Orr, Soo Hwang Teo, Soo-Chin Lee, Penny Soucy, Jonathan Beesley, Paolo Peterlongo, Ji Yeob Choi, Anthony J. Swerdlow, Jacques Simard, Kamila Czene, Anna González-Neira, Jenny Chang-Claude, Heli Nevanlinna, Ian Tomlinson, Thérèse Truong, Chen-Yang Shen, Harald Surowy, Henrik Flyger, Marjanka K. Schmidt, Graham G. Giles, John L. Hopper, Celine M. Vachon, Olivia Fletcher, Stig E. Bojesen, Mikael Hartman, Arnaud Droit, Per Hall, Cheng Har Yip, Maya Ghoussaini, Artitaya Lophatananon, Mieke Kriege, Anna H. Wu, Siranoush Manoukian, Kyriaki Michailidou, Christopher A. Haiman, Roger L. Milne, Xiao-Ou Shu, Daniel O. Stram, Katri Pylkäs, Sofia Khan, Irene L. Andrulis, Annika Lindblom, Emily Hallberg, Diana Torres, Anja Rudolph, Arto Mannermaa, Hermann Brenner, Vessela N. Kristensen, Daehee Kang, Caroline Seynaeve, Elinor J. Sawyer, Silje Nord, Hiltrud Brauch, Jan Lubinski, Natalia Bogdanova, Juliet D. French, Susan L. Neuhausen, Montserrat Garcia-Closas, Thomas Brüning, Loic Le Marchand, Peter A. Fasching, Diether Lambrechts, Daniel C. Tessier, Peter Devilee, Eva Galle, Alfons Meindl, Alison M. Dunning, Siddhartha Kar, Kenneth Muir, Curtis Olswold, Wang, Jean [0000-0002-9139-0627], Dennis, Joe [0000-0003-4591-1214], Easton, Douglas [0000-0003-2444-3247], Pharoah, Paul [0000-0001-8494-732X], Dunning, Alison [0000-0001-6651-7166], Apollo - University of Cambridge Repository, Department of Obstetrics and Gynecology, Clinicum, School of Medicine / Clinical Medicine, Cancer Research UK (Reino Unido), European Research Council, NIH - National Cancer Institute (NCI) (Estados Unidos), Post-cancer GWAS Initiative, Dutch Cancer Society (Holanda), Biobanking and BioMolecular resources Research Infrastructure (Países Bajos), Instituto de Salud Carlos III, Finlands Akademi (Finlandia), Ministry of Education, Culture, Sports, Science, and Technology (Japón), Japan Agency for Medical Research and Development, United States Army Medical Research and Development Command, California Breast Cancer Research Program, Stichting tegen Kanker, Deutsche Krebshilfe, National Health and Medical Research Council (Australia), Ministry of Economic Development, Innovation and Export Trade, Ministry of Higher Education (Malasia), Agency for Science, Technology and Research (Singapur), National Medical Research Council (Singapur), The Research Council of Norway, Southern and Eastern Norway Regional Health Authority, Finnish Cancer (Center of Excellence grant), Genetic Associations and Mechanisms in Oncology (GAME-ON) Initiative, Yorkshire Cancer Research, BRL (Basic Research Laboratory) program through the National Research Foundation of Korea - Ministry of Education, Science and Technology, NIH - National Cancer Institute (NCI). Specialized Programs of Research Excellence (SPOREs) (Estados Unidos), Hellenic Cooperative Oncology Group research grant, Institute of Cancer Research (Reino Unido), United States of Department of Health & Human Services, Medical Oncology, and Obstetrics & Gynecology

Subjects
0301 basic medicine, Vesicular Transport Proteins, Genome-wide association study, 0302 clinical medicine, Breast cancer, Genetics research, Medicine and Health Sciences, HUMAN GENOME, Genetics, Multidisciplinary, Chromosome Mapping, ASSOCIATION, Tag SNP, 3. Good health, 030220 oncology & carcinogenesis, Female, EXPRESSION, SUSCEPTIBILITY LOCI, Genotype, European Continental Ancestry Group, 3122 Cancers, Quantitative Trait Loci, Locus (genetics), Single-nucleotide polymorphism, Breast Neoplasms, Biology, Polymorphism, Single Nucleotide, Article, White People, REGION, RC0254, 03 medical and health sciences, SDG 3 - Good Health and Well-being, REVEALS, medicine, SNP, Humans, Genetic Predisposition to Disease, FUNCTIONAL VARIANTS, Genetic association, RISK LOCUS, CONSORTIUM, medicine.disease, ENHANCERS, 030104 developmental biology, Risk factors, Imputation (genetics), Chromosomes, Human, Pair 17, Genome-Wide Association Study
Abstract

Genome-wide association studies have found SNPs at 17q22 to be associated with breast cancer risk. To identify potential causal variants related to breast cancer risk, we performed a high resolution fine-mapping analysis that involved genotyping 517 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of genotypes for 3,134 SNPs in more than 89,000 participants of European ancestry from the Breast Cancer Association Consortium (BCAC). We identified 28 highly correlated common variants, in a 53 Kb region spanning two introns of the STXBP4 gene, that are strong candidates for driving breast cancer risk (lead SNP rs2787486 (OR = 0.92; CI 0.90–0.94; P = 8.96 × 10−15)) and are correlated with two previously reported risk-associated variants at this locus, SNPs rs6504950 (OR = 0.94, P = 2.04 × 10−09, r2 = 0.73 with lead SNP) and rs1156287 (OR = 0.93, P = 3.41 × 10−11, r2 = 0.83 with lead SNP). Analyses indicate only one causal SNP in the region and several enhancer elements targeting STXBP4 are located within the 53 kb association signal. Expression studies in breast tumor tissues found SNP rs2787486 to be associated with increased STXBP4 expression, suggesting this may be a target gene of this locus., published version, peerReviewed

Published
2016
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97. Optimal versus satisfactory decision making: a case study of sales with a target

Author

Daniel Vincent, Christopher Sissons, and Jacek B. Krawczyk

Subjects
Operations research, Economics, Satisficing, Neologism, Information Systems, Management Information Systems
Abstract

We consider a common managerial problem where an agent strives to achieve a prescribed target. We use this problem as a vehicle for comparing and discussing two approaches to decision making: optimising and “satisficing” (where the latter is a neologism due to H. Simon, 1976 Economics Nobel Prize Winner). We compute the optimising and satisfactory strategies for the problem at hand and highlight the differences in their outcomes.

Published
2012

98. Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Author

Martine Tranchant, Fergus J. Couch, Meeri Otsukka, Sabine Behrens, Jirong Long, Nadia Obi, Kamila Czene, John L. Hopper, Heather Thorne, Robert Pilarski, Anja Rudolph, Simon S. Cross, Volker Harth, Gabrielle Colleran, Hatef Darabi, Thomas Van Brussel, Eunjung Lee, Anne Lotz, E. Krol-Warmerdam, M. Pilar Zamora, Qin Wang, Andy C. H. Lee, Annie Fung, Kara Sargus, Melissa C. Southey, Katja Butterbach, Nuria Álvarez, Francois Bacot, Jeffrey G. Meyer, Ian W. Brock, Jessica Clague De Hart, Pierre Laurent-Puig, Irene L. Andrulis, Pei Chao, Arnaud Droit, Per Hall, Daniel C. Tessier, Paolo Radice, Frederic Robidoux, Don M. Conroy, Irja Erkkilä, Daniel Vincent, Antoinette Hollestelle, Christopher A. Hilker, Alicia Beeghly-Fadiel, Muhabbet Celik, Peggy Reynolds, Caroline Baynes, Sophia S. Wang, Katri Pylkäs, Kang In Nee, Robert Winqvist, Henrik Flyger, Annette Heemskerk, Sara Margolin, Hui Cai, Julie M. Cunningham, Prat Boonyawongviroj, Bernardo Bonanni, Anthony J. Swerdlow, Dan Connley, Huiyan Ma, Valerie Gaborieau, David O. Nelson, Keitaro Matsuo, Sylvie La Boissière, Pornthep Siriwanarungsan, Hidemi Ito, Ursula Eilber, Matthias W. Beckmann, Sylvia Rabstein, Natalia Bogdanova, Anna Jakubowska, Yves Raoul, Robert A.E.M. Tollenaar, Frans B. L. Hogervorst, Hannah L Park, Pierre Kerbrat, Ying Zheng, Paul D.P. Pharoah, Wanqing Wen, Judith Heinz, Annika Lindblom, Christa Stegmaier, Manjeet K. Bolla, Loris Bernard, Anna H. Wu, Alison M. Dunning, Hermann Brenner, A. Green, Thilo Dörk, Chia-Ni Hsiung, Dennis Deapen, Michael G. Schrauder, Gilian Peuteman, S.E. Higham, Sabapathy P. Balasubramanian, Irene Feroce, Christina Justenhoven, Angela Jones, William J. Blot, Nichola Johnson, Petra Seibold, D. Bowtell, Jiajun Shi, Wei Zheng, U Hamann, Pascal Guenel, P. Webb, Soo Hwang Teo, Daniela Zaffaroni, J. Blom, Rita K. Schmutzler, Douglas F. Easton, Yani Lu, Witold Zatonski, Phuah Sze Yee, Susan L. Neuhausen, Kenneth Muir, Sofia Khan, Daehee Kang, Silke Landrith, Helena Kemiläinen, Maggie Angelakos, Rich Pinder, Javier Benitez, Til Olchers, Senno Verhoef, Fred Schumacher, Martha J. Shrubsole, Teresa Selander, Teh Yew Ching, Christof Sohn, Patrick Arveux, Dorota M. Gertig, Saila Kauppila, Mervi Grip, Florentia Fostira, Jenny Chang-Claude, Michael Stagner, Kathleen Corthouts, Ellen Van Der Schoot, H Nevanlinna, Peter Bugert, Christian Baisch, Eija Myöhänen, Sonja Wolf, Hoda Anton-Culver, Nicola Miller, Cheng Har Yip, Neonila Szeszenia-Dabrowska, Nicholas K. Hayward, Dieter Flesch-Janys, Barbara Burwinkel, J. Molenaar, Eileen Williams, Marjanka K. Schmidt, Yon Ko, Anja Nieuwlaat, Chen-Yang Shen, Veli-Matti Kosma, Ian Tomlinson, Thérèse Truong, Amanda E. Toland, Artitaya Lophatananon, Mikael Hartman, Jonathan Beesley, Bernard Peissel, Paolo Peterlongo, Ji Yeob Choi, Craig Luccarini, Rosalind A. Eeles, Niall M. McInerney, Bernard Thienpont, Xiao-Ou Shu, Léa Héguy, Maya Ghoussaini, Sander Canisius, Wing-Yee Lo, Suleeporn Sangrajrang, Nur Aishah Taib, June Yashiki, Kirsimari Aaltonen, Louise A. Brinton, Elinor J. Sawyer, Alina Vrieling, Angela Cox, Frederik Marmé, Matthias Rübner, Graham G. Giles, Sonja Oeser, Hans Christiansen, Andrew Rowan, Ed Dicks, Andeas Schneeweiß, Catriona McLean, Antonis C. Antoniou, B. Pesch, Eveline Niedermayr, Volker Arndt, Janet E. Olson, Dominiek Smeets, Jingmei Li, Georgia Chenevix-Trench, Claire Mulot, Siranoush Manoukian, Hans Fischer, Ellen Crepin, Arto Mannermaa, Ali Amin Al Olama, Helen Cramp, Ans M.W. van den Ouweland, Olivia Fletcher, Sharon A. Windebank, Peter Hillemanns, Nayana Weerasooriya, James V. Lacey, Leslie Bernstein, Romuald Le Scodan, Giulietta Scuvera, P. Parsons, Thomas C. Putti, Elaine Ryder-Mills, Sara Benlloch, Beata Peplonska, Stig E. Bojesen, Kimberley Chua, Stefan Nickels, Nick Orr, Roger L. Milne, Tuomas Heikkinen, Christopher A. Haiman, Natalia Antonenkova, Volker Hermann, Maria Kabisch, Kenneth Offit, Julia A. Knight, Angela Maniscalco, Arja Jukkola-Vuorinen, Hartwig Ziegler, Chenjie Zeng, Jacques Simard, Pamela L. Horn-Ross, Daphne S.C. Lee, Xingyi Guo, Jan Lubinski, Michael J. Kerin, Loic Le Marchand, Sune F. Nielsen, Peter Devilee, A. De Fazio, Qiuyin Cai, Annie Turgeon, Yoon Sook-Yee, Silje Nord, Petra Bos, Hiltrud Brauch, Kyriaki Michailidou, Shivaani Mariapun, Kari Mononen, Alfons Meindl, Peter B. Kang, Siddhartha Kar, Alessandra Rossi, G. Chenevix-Trench, Diether Lambrechts, Karl von Smitten, Zsofia Kote-Jarai, Emiel J. Th. Rutgers, Chiu-Chen Tseng, Peter A. Fasching, Lesley McGuffog, Annegien Broekss, Johann H. Karstens, Montserrat Garcia-Closas, Thomas Brüning, David C. Whiteman, Judi Maskiell, Clinical Genetics, Cardiothoracic Surgery, Medical Oncology, and Obstetrics & Gynecology

Subjects
Genetic Markers, Linkage disequilibrium, Epidemiology, Locus (genetics), Genome-wide association study, Breast Neoplasms, Biology, Polymorphism, Single Nucleotide, Article, Breast cancer, SDG 3 - Good Health and Well-being, Risk Factors, medicine, Humans, Genetic Predisposition to Disease, Gene, Genetics, Molecular epidemiology, Case-control study, Chromosome Mapping, medicine.disease, Logistic Models, Oncology, Genetic marker, Genetic Loci, Case-Control Studies, Female, Chromosomes, Human, Pair 4, Genome-Wide Association Study
Abstract

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk. Cancer Epidemiol Biomarkers Prev; 24(11); 1680–91. ©2015 AACR.

Published
2015

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