Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same region.

Behagets betydelser : Döttrarnas edukation i det sena 1700-talets adelskultur

By the end of the 18th century the daughters of the nobility in the northern parts of Europe received a quite different kind of education from their brothers. Although the cultural aims of the upbringing of girls were similar to that of boys, the practice of the raising of girls was less influenced by tradition. The education of boys was one of classical humanistic and military training, but the girls were more freely educated. The unity and exclusiveness of the culture of nobility were of great importance to the continued influence of this elite. The importance of education became even greater, partly because of the unstable political situation, and partly because of the changes the Enlightenment had caused in the perception of the human essence. The delicate and ambitious hônnete homme was expected to constantly strive to a greater perfection as a Christian. On the other hand, the great weight given to aesthetics - etiquette and taste - made individual variation of the contents of education possible. Education consisted mainly in aesthetic studies; girls studied music, dancing, fine arts, epistolary skills and also the art of polite conversation. On the other hand, there was a demand for enlightenment, and one often finds personal political and social ambitions, which made competition in all skills necessary for the daughters as well. Literary sources for the education of girls are Madame LePrince de Beaumont, Madame d'Epinay, Madame de Genlis and Charles Rollin. Other, perhaps even more important sources are the letters between parents and children and papers originating from studies. Diaries and memoirs also tell us about the practice of education in day to day life. The approach of this study is semiotic. It can be stated that the code of the culture was well hidden from the outsider. This was achieved, for instance, by the adaptation of the foreign French language and culture. The core of the culture consisted of texts which only thorough examples stated the norms which were expressed as good taste. Another important feature of the culture was its tendency towards theatricalisation. The way of life was dictated by taste, and moral values were included in the aesthetic norms through the constant striving for modesty. Pleasant manners were also correct in an ethical perspective. Morality could thus also be taught through etiquette.

International Society for Applied Ethology. Special issue: a Selection of Papers from the 38th International Congress of the ISAE, Helsinki, Finland, August 2004

Welcome to the latest collection of papers selected from the International Society for Applied Ethology's (ISAE's) annual congress. The ISAE is a multi-faceted scientific society that supports applied research on animals under the influence of humankind. Every year, we aim to invite congress participants who have submitted papers, plenary talks, run workshops, or presented the memorial lecture on theoretical, review or discussion papers of topical interest to contribute to the Special Issue. These papers are peer-reviewed before being published here in Applied Animal Behaviour Science. International Society for Applied Ethology (ISAE) Special Issue 2004.

International Society for Applied Ethology. Special issue: a selection of papers from the 39th International Congress of the International Society for Applied Ethology (ISAE), Tokyo, Japan, August 2005

Welcome to the latest collection of papers selected from the International Society for Applied Ethology's (ISAE's) annual congress. The ISAE is a multi-faceted scientific society that supports applied research on animals that are managed by humans. Every year, we aim to invite congress participants who have submitted papers, plenary talks, run workshops, or presented the memorial lecture on theoretical, review or discussion papers of topical interest to contribute to the Special Issue. These papers are peer-reviewed before being published here in Applied Animal Behaviour Science. This year, we have a variety of papers to bring to your attention. The David Wood-Gush Memorial lecture, the keynote address of the congress, was given by Shigeru Watanabe on animal cognition and welfare. His paper highlights how animal's sensory capabilities relate to their welfare. On the topic of human–animal bonds, Stine Christiansen and Björn Forkman explore how animal welfare is assessed in a veterinary context, and how those assessments might be improved by ethologists. Yoshie Kakuma and co-authors report on the discussions from a workshop on the welfare of working and companion dogs in five different countries. Based on their plenary lectures, Michael Cockram discusses the factors that affect farmed animals during road transport and how these might contribute in making decisions to restrict journey times, while Clive Phillips and co-author Danica Peck examine how personality influences the behaviour and interactions between zoo-housed tigers and their keepers. We hope you enjoy these papers. Our sincere thanks go to both the authors and referees, without whom these special issues would not be possible. A selection of papers from the 39th International Congress of the International Society for Applied Ethology (ISAE), Tokyo, Japan, August 2005.

Impact of subsoil constraints on wheat yield and gross margin on fine-textured soils of the southern Victorian Mallee

The APSIM-Wheat module was used to investigate our present capacity to simulate wheat yields in a semi-arid region of eastern Australia (the Victorian Mallee), where hostile subsoils associated with salinity, sodicity, and boron toxicity are known to limit grain yield. In this study we tested whether the effects of subsoil constraints on wheat growth and production could be modelled with APSIM-Wheat by assuming that either: (a) root exploration within a particular soil layer was reduced by the presence of toxic concentrations of salts, or (b) soil water uptake from a particular soil layer was reduced by high concentration of salts through osmotic effects. After evaluating the improved predictive capacity of the model we applied it to study the interactions between subsoil constraints and seasonal conditions, and to estimate the economic effect that subsoil constraints have on wheat farming in the Victorian Mallee under different climatic scenarios. Although the soils had high levels of salinity, sodicity, and boron, the observed variability in root abundance at different soil layers was mainly related to soil salinity. We concluded that: (i) whether the effect of subsoil limitations on growth and yield of wheat in the Victorian Mallee is driven by toxic, osmotic, or both effects acting simultaneously still requires further research, (ii) at present, the performance of APSIM-Wheat in the region can be improved either by assuming increased values of lower limit for soil water extraction, or by modifying the pattern of root exploration in the soil pro. le, both as a function of soil salinity. The effect of subsoil constraints on wheat yield and gross margin can be expected to be higher during drier than wetter seasons. In this region the interaction between climate and soil properties makes rainfall information alone, of little use for risk management and farm planning when not integrated with cropping systems models.

Analysing industry needs to fine tune IPM project activities

As a first step to better targeting the activities of a project for improving management of western flower thrips, Frankliniella occidentialis, (WFT) in field grown vegetable crops, we surveyed growers, consultants and other agribusiness personnel in two regions of Queensland. Using face-to-face interviews, we collected data on key pests and measures used to manage them, the importance of WFT and associated viral diseases, sources of pest management information and additional skills and knowledge needed by growers and industry. Responses were similar in the two regions. While capsicum growers in one northern Queensland district had suffered serious losses from WFT damage in 2002, in general the pest was not seen as a major problem. In cucurbit crops, the silverleaf whitefly (Bemisia tabaci biotype B) was considered the most difficult insect pest to manage. Pest control tactics were largely based on pesticides although many respondents mentioned non-chemical methods such as good farm hygiene practices, control of weed hosts and regular crop monitoring, particularly when prompted. Respondents wanted to know more about pest identification, biology and damage, spray application and the best use of insecticides. Natural enemies were mentioned infrequently. Keeping up to date with available pesticide options, availability of new chemicals and options for a district-wide approach to managing pests emerged as key issues. Growers identified agricultural distributors, consultants, Queensland Department of Primary Industries staff, other growers and their own experience as important sources of information. Field days, workshops and seminars did not rank highly. Busy vegetable growers wanted these activities to be short and relevant, and preferred to be contacted by post and facsimile rather than email. In response to these results, we are focusing on three core, interrelated project extension strategies: (i) short workshops, seminars and farm walks to provide opportunities for discussion, training and information sharing with growers and their agribusiness advisors; (ii) communication via newsletters and information leaflets; (iii) support for commercialisation of services.

Grazing management influences the dynamics of populations of Stylosanthes hippocampoides (Oxley fine stem stylo)

This paper describes a study to identify those factors which control the persistence of the Subtropical legume Stylosanthes hippocampoides, formerly S. guianensis cv. Oxley (fine stem stylo). The dynamics of S. hippocampoides populations was recorded in permanent quadrats at 2 stocking rates in a grazing study conducted between 1987 and 1992 in south-eastern Queensland. Density of mature plants fluctuated between 10 and 60 plants/m(2) during the 5 years with the major contributing factors being variations in seedling recruitment and survival, which, in turn, reflected the size of the soil seed bank and seasonal rainfall. Plant density was consistently higher at the lower stocking rate of 1 beast/1.5 ha compared with 1 beast/1 ha; however, the effect of stocking rate was minor compared with fluctuation due to seasonal variation in rainfall. The maximum life span of the original plants exceeded 5 years, while the survival of seedling cohorts was strongly impacted by seasonal rainfall. Total exclosure from grazing during summer increased the size of the soil seed bank although a precise time period during summer was not identified, while grazing at the lower stocking pressure produced the same outcome. It was concluded that the large seasonal variation that occurs in S. hippocampoides density is driven by large seasonal variation in seedling recruitment, which, in turn, is influenced by the size of the soil seed bank.

Preparation of CaTiO3 fine powders by the hydrothermal method

Fine powders consisting of 0.1–0.5 μm size crystallites of CaTiO3 are prepared at 150–200°C by the hydrothermal method starting from hydrated titania gel and reactive calcium oxide suspended as an aqueous slurry in an autoclave. The resulting high-purity CaTiO3 is characterised by TEM, X-ray powder diffraction, chemical analyses and sintering characteristics. The hydrothermally prepared CaTiO3 powders are sinterable to high-density ceramics below 1400°C. The dc conductivity behaviour of the chemically reduced ceramics is presented.

Hydrothermal preparation of Ba(Ti,Zr)O3 fine powders

Fine powders consisting of aggregated submicron crystallites of Ba(Ti,Zr)O3 in the complete range of Ti/Zr ratios are prepared at 85–130°C by hydrothermal method, starting from TiO2 + ZrO2 · xH2O mixed gel and Ba(OH)2 solution. The products obtained below 110°C incorporate considerable amounts of H2O and OH− within the lattice. As-prepared BaTiO3 is cubic and converts to tetragonal phase after the heat treatment at 1200°C, accompanied by the loss of residual hydroxyl ions. TEM investgations of the growth features show a transformation of the gel to the crystallite. Ba2+ ions entering the gel produce chemical changes within the gel, followed by dehydration, resulting in a cubic perovskite phase irrespective of Ti/Zr. The sintering properties of these powders to fine-grained, high density ceramics and their dielectric properties are presented.

Hydrothermal synthesis of Ba(Ti, Sn)O3 fine powders and dielectric properties of the corresponding ceramics

Fine powders of submicron-sized crystallites of BaTiO3 were prepared at 85–130°C by the hydrothermal method, starting from TiO2.ξH2O gel and Ba(OH)2 solution. The products obtained below 110°C incorporated considerable amounts of H2O and OH− in the lattice. As-prepared BaTiO3 is cubic and converts to the tetragonal phase after heat treatment at 1200°C, accompanied by the loss of residual OH− ions. Hydrothermal reaction of SnO2.ξH2O gel with Ba(OH)2 at 150–260°C gives rise to the hydrated phase, BaSn(OH)6.3H2O, due to the amphoteric nature of SnO2.ξH2O which stabilises Sn(OH)62− anions in basic media. On heating in air or releasing the pressure in situ at 260°C, BaSn(OH)6.3H2O converts to BaSnO3 through an intermediate, BaSnO(OH)4. Solid solutions of Ba(Ti,Sn)O3 are directly formed from (TiO2 + SnO2)..ξH2O gel up to 35 mol% SnO2. At higher Sn contents, the hydrothermal products are mixtures of BaSn(OH)6.3H2O and BaTiO3, which on annealing at 1000°C result in monophasic Ba(Ti,Sn)O3. The sintering characteristics and the dielectric properties of the ceramics prepared out of these fine powders are presented. The dielectric properties of fine-grained Ba(Ti,Sn)O3 ceramics are explained on the basis of the prevailing diffuse phase transition behaviour.

A Note on the Determination of Plastic Limit of Fine-Grained Soils

Plastic limit of fine-grained soils is conventionally determined in the laboratory by the soil thread rolling method. Many adverse comments have been recorded in the geotechnical engineering literature on the method about its reproducibility and operator dependency. The presen experimental study, which is based on a well-planned and meticulously executed experimental program, critically evaluates the effect of size of the rolled soil thread on the plastic limit of fine-grained soil and the operator dependency of the results. The results have shown that if the plastic limit tests are performed by a trained operator, then consistent results can be obtained and that the effect of size of the rolled soil thread on plastic limit is negligibly small.

Low-temperature preparation of fine-particle cobaltites

A novel solid-solution precursor method for the preparation of fine-particle cobaltites at low temperatures has been described. The precursors, hydrazinium metal hydrazine carboxylate hydrates, N2H5M1/3Co2/3(N2H3COO)3 · H2O, where M = Mg, Mn, Fe, Co, Ni, and Zn, decompose in air <250°C to yield corresponding metal cobaltites, MCo2O4. Formation of cobaltites has been confirmed by thermogravimetry (TG) weight loss, IR, and X-ray diffraction. Combustion of the precursor in air yields fine-particle cobaltites with surface areas in the range of 12–115 m2g−1 and particle sizes of 1–40 μm. Low decomposition temperatures of the precursors accompanied by the evolution of large amounts of gases appear to control the particle size of the cobaltites.

A novel combustion process for the synthesis of fine particle α-alumina and related oxide materials

Synthesis of fine particle α-alumina and related oxide materials such as MgAl2O4, CaAl2O4, Y3Al5O12 (YAG), Image , β′-alumina, LaAlO3 and ruby powder (Image ) has been achieved at low temperatures (500°C) by the combustion of corresponding metal nitrate-urea mixtures. Solid combustion products have been identified by their characteristic X-ray diffraction patterns. The fine particle nature of α-alumina and related oxide materials has been investigated using SEM, TEM, particle size analysis and surface area measurements.

CYP19A1 fine-mapping and Mendelian randomization: Estradiol is causal for endometrial cancer

Candidate gene studies have reported CYP19A1 variants to be associated with endometrial cancer and with estradiol (E2) concentrations. We analyzed 2937 single nucleotide polymorphisms (SNPs) in 6608 endometrial cancer cases and 37 925 controls and report the first genome wide-significant association between endometrial cancer and a CYP19A1 SNP (rs727479 in intron 2, P=4.8x10(-11)). SNP rs727479 was also among those most strongly associated with circulating E2 concentrations in 2767 post-menopausal controls (P=7.4x10(-8)). The observed endometrial cancer odds ratio per rs727479 A-allele (1.15, CI=1.11-1.21) is compatible with that predicted by the observed effect on E2 concentrations (1.09, CI=1.03-1.21), consistent with the hypothesis that endometrial cancer risk is driven by E2. From 28 candidate-causal SNPs, 12 co-located with three putative gene-regulatory elements and their risk alleles associated with higher CYP19A1 expression in bioinformatical analyses. For both phenotypes, the associations with rs727479 were stronger among women with a higher BMI (Pinteraction=0.034 and 0.066 respectively), suggesting a biologically plausible gene-environment interaction.