Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus

BACKGROUND: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. RESULTS: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. CONCLUSION: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk

Risk Consumption: Children and Online Gaming. The Problem of “Responsible Gambling”

Online gambling is a popular activity among adolescents. However, there has been a notable increase in the number of young people who suffer or are on the verge of pathological gambling. We review the impact of online gambling on young people and discuss the desiderability of the concept of “gambling responsibly” in order to alert of their risks and effectively prevent access to minors. The main factors associated with pathological gambling are the age of start, the family environment, the infl uence of advertising, the consumption of stimulants, and the attitudes of the peer group. Both the government and the gaming industry itself should consider these factors and develop comprehensive plans that ensure a safe and controlled model game. In this context, advertising must take into account criteria of consumer protection knowing that even if they are not allowed, children can easily have access to online gambling. All agents involved, including public and social agents, must provide mechanisms for prevention and awareness of a problem that arouses little social consciousness and excessive carelessness.

Choreographies of Irish Modernity

Although movement is often viewed as forming the ‘kinetic basis’ of the modern age, the analysis of movement practices such as dance is often neglected in theories of modernity. Dance theorists such as André Lepecki (2006) and Randy Martin (1998) have argued for an awareness of how the kinaesthetic politics of modernity perform a colonization of space and bodies in their constant drive toward movement and mobility. This chapter examines how an analysis of two dance works by Irish artists, one from the early twentieth century and one from the early twenty-first century, can contribute to these discussions of modernity and dance, and how the works might illuminate connections between dance and politics in Ireland in their alternative approaches to these modernist kinaesthetic politics. Taking a brief, contextualizing look at an early dance play by William Butler Yeats, the chapter then focuses on what echoes, or afterlives, can be found from this early modernist work in a piece by contemporary dance theatre choreographer Fearghus Ó’Conchúir. In both works we see the ability of dance to create an alternative space within the pervading discourses (or movements) of a sociopolitical and cultural landscape that allows the spectator – through a visceral connection with a dancer – to experience a different perspective on the ‘idea of a nation’.

A Microbial Link to Weathering of Postglacial Rocks and Sediments, Mount Viso Area, Western Alps, Demonstrated through Analysis of a Soil/Paleosol Bio/Chronosequence

Understanding the mechanism associated with rates of weathering and evolution of rocks→sediment→soil→paleosol in alpine environments raises questions related to the impact of microbial mediation versus various diverse abiotic chemical/physical processes, even including the overall effect of cosmic impact/airburst during the early stage of weathering in Late Glacial (LG) deposits. This study is of a chronosequence of soils/paleosols, with an age range that spans the post–Little Ice Age (post-LIA; <150 yr), the Little Ice Age (LIA; AD 1500–1850), the middle Neoglacial (∼3 ka)–Younger Dryas (YD; <12.8 ka), and the LG (<15 ka). The goal is to elicit trends in weathering, soil morphogenesis, and related eubacterial population changes over the past 13–15 k.yr. The older LG/YD paleosols in the sequence represent soil morphogenesis that started during the closing stage of Pleistocene glaciation. These are compared with undated soils of midto late Neoglacial age, the youngest of LIA and post-LIA age. All profiles formed in a uniform parentmaterial ofmetabasalt composition and in moraine, rockfall, protalus, and alluvial fan deposits. Elsewhere in Europe,North America, and Asia, the cosmic impact/airburst event at 12.8 ka often produced a distinctive, carbon-rich “black mat” layer that shows evidence of high-temperature melting. At this alpine site, older profiles of similar LG age contain scorched and melted surface sediments that are otherwise similar in composition to the youngest/thinnest profiles developing in the catchment today. Moreover, microbial analysis of the sediments offers new insight into the genesis of these sediments: the C and Cu (u = unweathered) horizons in LG profiles present at 12.8 ka (now Ah/Bw) show bacterial population structures that differ markedly from recent alluvial/protalus sample bacterial populations. We propose here that these differences are, in part, a direct consequence of the age/cosmic impact/weathering processes that have occurred in the chronosequence. Of the several questions that emerge from these sequences, perhaps the most important involve the interaction of biotic-mineral factors, which need to be understood if we are to generally fully appreciate the role played by microbes in rock weathering.

Análisis de Factibilidad “Centro Ecuestre San Isidro” Sede regional UNA Camoapa (Periodo 2016-2020)

El presente proyecto C entro Ecuestre “San Isidro ” estará ubi cado en el municipio de Camoapa, departamento de Boaco, tiene como propósito fortalecer la formación y capacitación de los criadores de equinos en el municipio de Camoapa durante el periodo 2016 - 2020. El proyecto consiste en el acondicionamiento de un local para fortalecer las capacidades a través de las técnicas ecuestres en el municipio de Camoapa , tiene los componentes de mejoramiento de instalaciones, capacitación, gestión y organización . La metodología utilizada consistió en sondeo dirigido a productores y criadores a través del análi sis deductivo e inductivo de información del contexto en el sector y específicamente con información de la zona del segmento equino. Se recopil ó información de fuentes primarias y secundarias como documentos escritos e internet utilizan do técnicas como: en cuestas, observación, e instrumentos como cuestionario de preguntas abiertas y cerradas, matrices y tablas de salida. R esultados demuestran la necesidad de brindar servicios de capacitación en calzado, doma, nutrición, equitaciones, sanidad equina, genétic a y rodeos; mejoramiento de la calidad en la atención a usuarios, tecnificación y certificac ión anual de un aproximado de 144 (participantes) técnicos. Indirectamente s e espera d inamizar la actividad comercial, promover el turismo y Brindar asistencia técn ica a productores con el apoyo de la organización de asociación de criadores de equinos .El proyecto es factible por la alta demanda de servicios de capacitación requeridos e n la zona , desde el punto de vista técnico existe personal especializado en la zon a p ara el acondicionamiento de las instalacion es y el t alento necesario para la capacitación, ubicación ventajosa cercano a las zonas urbanas, se dispone de servicios básicos y organización funcional derivada de la administración de la UNA S ede R egional Ca moapa. El pr oyecto es de alta contribución social , con impactos significativos en el sector al fortalecer las capacidades humanas de los usuarios beneficiados mediante la capacitación y entrenamiento a clubes hípicos, asociación de ganaderos y aficionados en la actividad ecuestre , e l fomento de las hípicas, el turismo, las f iestas y ferias patronales en el rescate de la cultura en el manejo y aprovechamiento equino en contribuciones a la economía con generación de empleo directos e indirecto . E n lo ambienta l, el proyecto es viable, porque no tendrá impactos negativos severos ; s in embargo , se planifican realizar obr as de prevención y conservación, para la sostenibilidad ambiental del proyecto .

A Figured Worlds Perspective on Middle School Learners' Climate Literacy Development

The purpose of this study was to investigate the nature of the relationship between middle school science learners’ conditions and their developing understandings of climate change. I applied the anthropological theoretical perspective of figured worlds (Holland, Lachicotte, Skinner, & Cain, 1998) to examine learners’ views of themselves and their capacities to act in relation to climate change. My overarching research question was: How are middle school science learners’ figured worlds of climate change related to the conditions in which they are embedded? I used a descriptive single-case study design to examine the climate change ideas of eight purposefully selected 6th grade science learners. Data sources included: classroom observations, curriculum documents, interviews, focus groups, and written assessments and artifacts, including learners’ self- generated drawings. I identified six analytic lenses with which to explore the data. Insights from the application of these analytic lenses provided information about the elements of participants’ climate change stories, which I reported through the use of a storytelling heuristic. I then synthesized elements of participants’ collective climate change story, which provided an “entrance” (Kitchell, Hannan, & Kempton, 2000, p. 96) into their figured world of climate change. Aspects of learners’ conditions—such as their worlds of school, technology and media use, and family—appeared to shape their figured world of climate change. Within their figured world of climate change, learners saw themselves—individually and as members of groups—as inhabiting a variety of climate change identities, some of which were in conflict with each other. I posited that learners’ enactment of these identities – or the ways in which they expressed their climate change agency – had the potential to reshape or reinforce their conditions. Thus, learners’ figured worlds of climate change might be considered “spaces of authoring” (Holland et al., 1998, p. 45) with potential for inciting social and environmental change. The nature of such change would hinge on the extent to which these nascent climate change identities become salient for these early adolescent learners through their continued climate change learning experiences. Implications for policy, curriculum and instruction, and science education research related to climate change education are presented.

An examination of Special Forces and their transfer of skillsets under crisis management settings in Singapore

The thesis focuses on military crisis management and strategy.

Control of the spatial homogeneity of pore surface chemistry in particulate activated carbon

We show here that a physical activation process that is diffusion-controlled yields an activated carbon whose chemistry – both elemental and functional – varies radially through the particles. For the ∼100 μm particles considered here, diffusion-controlled activation in CO2 at 800 °C saw a halving in the oxygen concentration from the particle periphery to its center. It was also observed that this activation process leads to an increase in keto and quinone groups from the particle periphery towards the center and the inverse for other carbonyls as well as ether and hydroxyl groups, suggesting the two are formed under CO2-poor and -rich environments, respectively. In contrast to these observations, use of physical activation processes where diffusion-control is absent are shown to yield carbons whose chemistry is radially invariant. This suggests that a non-diffusion limited activation processes should be used if the performance of a carbon is dependent on having a specific optimal pore surface chemical composition.

Poïétique de la création sonore au cinéma : la figure de l’artiste-poïéticien

Nous proposons, dans ce mémoire, d’explorer les possibilités pratiques et pédagogiques d’une approche autopoïétique de la création sonore au cinéma. Notre principal souci sera de saisir les modalités de l’ascèse propre aux artistes qui se livrent à une telle activité, comprise comme un « apprentissage de soi par soi » (Foucault), afin de faire celui qui peut faire l’œuvre (processus de subjectivation), et le rôle descriptif et opératoire de cet exercice - en tant qu’effort pour penser de façon critique son propre savoir-faire -, dans le faire-œuvre et l’invention de possibles dans l’écriture audio-visuelle cinématographique. Pour ce faire, d’une part, nous étudierons, à partir de témoignages autopoïétiques, le rapport réflexif de trois créateurs sonores à leur pratique et leur effort pour penser (et mettre en place) les conditions d’une pratique et d’une esthétique du son filmique comme forme d’art sonore dans un contexte audio-visuel, alors qu’ils travaillent dans un cadre normalisant : Randy Thom, Walter Murch et Franck Warner. D’autre part, nous recourrons à différentes considérations théoriques (la théorie de l’art chez Deleuze et Guattari, la « surécoute » chez Szendy, l’histoire de la poïétique à partir de Valéry, etc.) et pratiques (la recherche musicale chez Schaeffer, la relation maître-apprenti, les rapports entre automatisme et pensée dans le cinéma moderne chez Artaud et Godard, etc.), afin de contextualiser et d’analyser ces expériences de création, avec l’objectif de problématiser la figure de l’artiste-poïéticien sur un plan éthique dans le sillage de la théorie des techniques de soi chez Foucault.

Poïétique de la création sonore au cinéma : la figure de l’artiste-poïéticien

Nous proposons, dans ce mémoire, d’explorer les possibilités pratiques et pédagogiques d’une approche autopoïétique de la création sonore au cinéma. Notre principal souci sera de saisir les modalités de l’ascèse propre aux artistes qui se livrent à une telle activité, comprise comme un « apprentissage de soi par soi » (Foucault), afin de faire celui qui peut faire l’œuvre (processus de subjectivation), et le rôle descriptif et opératoire de cet exercice - en tant qu’effort pour penser de façon critique son propre savoir-faire -, dans le faire-œuvre et l’invention de possibles dans l’écriture audio-visuelle cinématographique. Pour ce faire, d’une part, nous étudierons, à partir de témoignages autopoïétiques, le rapport réflexif de trois créateurs sonores à leur pratique et leur effort pour penser (et mettre en place) les conditions d’une pratique et d’une esthétique du son filmique comme forme d’art sonore dans un contexte audio-visuel, alors qu’ils travaillent dans un cadre normalisant : Randy Thom, Walter Murch et Franck Warner. D’autre part, nous recourrons à différentes considérations théoriques (la théorie de l’art chez Deleuze et Guattari, la « surécoute » chez Szendy, l’histoire de la poïétique à partir de Valéry, etc.) et pratiques (la recherche musicale chez Schaeffer, la relation maître-apprenti, les rapports entre automatisme et pensée dans le cinéma moderne chez Artaud et Godard, etc.), afin de contextualiser et d’analyser ces expériences de création, avec l’objectif de problématiser la figure de l’artiste-poïéticien sur un plan éthique dans le sillage de la théorie des techniques de soi chez Foucault.

Numerical investigation of a trapped vortex miniature ramjet combustor

The design of a miniature ramjet combustor using gaseous methane fuel for Mach 2.5 has been conducted. The main challenges stem mainly from the insufficient space for mixing and burning, short residence time, and the flame stabilization. Impossible utilization of relatively large air-blast fuel injectors provides more difficulties for the design. The trapped vortex combustor, as a novel way of flameholding by trapping the pilot flame inside a cavity instead of exposing it to the mainstream, is selected. Three main parts are studied numerically, which include the cold flowfield characteristics, the fuel-injection schemes, and the overall combustion performance. The results show that the drag coefficient can helptodetermine the optimum cavity size for trappingastable vortex. Injecting all the fuel inthe cavity always leads to an overly fuel-rich condition, whereas injecting in front of the cavity with a momentum flux ratio q between 0.61 and 1.0 can successfully achieve stoichiometric mixing in the cavity. However, compared to nonreacting fuel mixing, the combustion performance is found to be more sensitive to the value of q. Among the cases studied, the one with a small q of about 0.61 has more intense pilot flames andshorter main combustor flames. The effectsofangled injection, upstream injection location, and the combustor length based on the found q are also investigated.

The ‘Security of Security’: making up the Australian intelligence community 1975–2015

The legal and institutional arrangements for Australian security and intelligence underwent major changes in the 1970s. Existing agencies were publicly acknowledged for the first time, new agencies were established, new powers of investigation and surveillance were introduced and an emergent ‘intelligence community’ was formed. As in Canada (and the USA), numerous ‘crises’ in Australian intelligence practices led to and informed various commissions of inquiry that made visible previously hidden intelligence institutions and associated surveillance practices. Subsequent inquiries, security and intelligence plans, national statements and reforms in Australia built upon these developments, which were indicative of a good measure of continuity in intelligence and surveillance arrangements. This chapter identifies how intelligence and security arrangements were 'problematised’ from the 1970s, and a new ‘intelligence community’ was created as an object of governing.

National security, surveillance and terror: Canada and Australia in comparative perspective

This edited collection brings together leading scholars to comparatively investigate national security, surveillance and terror in the early 21st century in two major western jurisdictions, Canada and Australia. Observing that much debate about these topics is dominated by US and UK perspectives, the volume provides penetrating analysis of national security and surveillance practices in two under-studied countries that reveals critical insights into current trends. Written by a wide range of experts in their respective fields, this book addresses a fascinating array of timely questions about the relationship among national security, privacy and terror in the two countries and beyond. Chapters include critical assessments of topics such as: National Security Intelligence Collection since 9/11, The Border as Checkpoint in an Age of Hemispheric Security and Surveillance, Unmanned Aerial Vehicles and Law Enforcement, as well as Federal Government Departments and Security Regimes. An engaging and empirically driven study, this collection will be of great interest to scholars of security and surveillance studies, policing, and comparative criminology.