Pubertal development and prostate cancer risk: Mendelian randomization study in a population-based cohort.

BACKGROUND: Epidemiological studies have observed a positive association between an earlier age at sexual development and prostate cancer, but markers of sexual maturation in boys are imprecise and observational estimates are likely to suffer from a degree of uncontrolled confounding. To obtain causal estimates, we examined the role of pubertal development in prostate cancer using genetic polymorphisms associated with Tanner stage in adolescent boys in a Mendelian randomization (MR) approach. METHODS: We derived a weighted genetic risk score for pubertal development, combining 13 SNPs associated with male Tanner stage. A higher score indicated a later puberty onset. We examined the association of this score with prostate cancer risk, stage and grade in the UK-based ProtecT case-control study (n = 2,927), and used the PRACTICAL consortium (n = 43,737) as a replication sample. RESULTS: In ProtecT, the puberty genetic score was inversely associated with prostate cancer grade (odds ratio (OR) of high- vs. low-grade cancer, per tertile of the score: 0.76; 95 % CI, 0.64-0.89). In an instrumental variable estimation of the causal OR, later physical development in adolescence (equivalent to a difference of one Tanner stage between pubertal boys of the same age) was associated with a 77 % (95 % CI, 43-91 %) reduced odds of high Gleason prostate cancer. In PRACTICAL, the puberty genetic score was associated with prostate cancer stage (OR of advanced vs. localized cancer, per tertile: 0.95; 95 % CI, 0.91-1.00) and prostate cancer-specific mortality (hazard ratio amongst cases, per tertile: 0.94; 95 % CI, 0.90-0.98), but not with disease grade. CONCLUSIONS: Older age at sexual maturation is causally linked to a reduced risk of later prostate cancer, especially aggressive disease.This work was supported by the World Cancer Research Fund (2011/419) and Cancer Research UK (C18281/A19169). The Integrative Epidemiology Unit (IEU) is supported by the MRC and the University of Bristol (G0600705, MC_UU_12013/19), and the Integrative Cancer Epidemiology Programme is supported by Cancer Research UK programme grant C18281/A19169. The National Institute for Health Research (NIHR) Bristol Nutrition Biomedical Research Unit is funded by the NIHR and is a partnership between University Hospitals Bristol NHS Foundation Trust and the University of Bristol. The ProtecT study is supported by the UK NIHR Health Technology Assessment (HTA) Programme (HTA 96/20/99; ISRCTN20141297). Funding for PRACTICAL and the iCOGS infrastructure came from: the European Community’s Seventh Framework Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/ A16565), the National Institutes of Health (CA128978), and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 – the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. We acknowledge support from the NIHR to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust.This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s12916-016-0602-

Re-enchantment: not all fairytales are for children

Re-enchantment is an online interactive documentary project exploring why fairy stories continue to enchant, entertain, fascinate and horrify contemporary adult audiences. The rich media environment of Re-enchantment offers an extremely immersive experience to explore fairy tales. By finding symbols on the forest paths the user is transported into seven story spaces: Bluebeard, Snow White, Beauty and the Beast, Hansel and Gretel, Cinderella, Rapunzel and Red Riding Hood. Each story in its unique way invites you to navigate the historical, social, cultural and psychological layers embedded in the traditional tales, to discover their meaning for adults today and to view the way they are being re-imagined by contemporary artists. Re-enchantment is a poetic and provocative act of creative interpretation, bringing together digital video, documentary footage, photography, animation, still images and sound. The website is hosted by ABC (Australian Broadcasting Corporation) on-line

Preliminary development of a sewerage infrastructure buffer assessment tool for engineering risk and strategic land use planning

Urban expansion continues to encroach on once isolated sewerage infrastructure. In this context,legislation and guidelines provide limited direction to the amenity allocation of appropriate buffer distances for land use planners and infrastructure providers. Topography, wind speed and direction,temperature, humidity, existing land uses and vegetation profiles are some of the factors that require investigation in analytically determining a basis for buffer separations. This paper discusses the compilation and analysis of six years of Logan sewerage odour complaint data. Graphically,relationships between the complaints, topographical features and meteorological data are presented. Application of a buffer sizing process could assist planners and infrastructure designers alike, whilst automatically providing extra green spaces. Establishing a justifiable criterion for buffer zone allocations can only assist in promoting manageable growth for healthier and more sustainable communities

Development of a methodological basis for assessing the effectiveness of value-oriented management of development of a restaurant business enterprise

Abstract: The object of research is the process of value-oriented management of the development of a restaurant business. The article argues that value-oriented management of the development of a restaurant business is aimed at achieving the goal of maximizing the key determinants of value. The parameters and elements of the configuration of the value concept (strategic assets, nomadic competencies, the consumer value frame of the restaurant service) are determined, the content and nature of which reflects the individual elements of the value-oriented management of the restaurant business. The research methodology is based on theoretical and methodological analysis of scientific literature, economic methods, and observations, comparable, measurement, analysis and matrix modeling. To develop a Y-matrix model for assessing the effectiveness of value-based development management, which represents the relationship between strategic assets, key competencies and the value frame, the expert method and the method of multivariate comparative analysis are used. The results of this research show that the elements of consumer value that are basic for the development of restaurant businesses in the modern competitive space are: the uniqueness of the restaurant concept, originality of the menu, pricing policy, service, safety standards, atmosphere, innovation and emotions. For the empirical convergence of the concept of value, a Y-matrix is built. Based on the use of the method of multivariate comparative analysis, the implementation degree of key competencies and strategic assets in the creation of structural elements of consumer value is assessed. To determine the efficiency level of value-based development management at the restaurant business, the value resonance coefficient is calculated. Based on the research results, a list of key competencies is determined, on the development of which it is necessary to focus the attention of the management of the restaurant business. The practical significance of research lies in the possibility of its use as a tool for strategic value analysis in the restaurant business. The proposed approach allows to determine the emphasis of management impact in order to maximize the value of restaurant services