Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture

Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10−8). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10−4, Bonferroni corrected), of which six reached P < 5 × 10−8, including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.

Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls

Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed 19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with diseaseIRGM for Crohns disease, HLA for Crohns disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetesalthough in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases. © 2010 Macmillan Publishers Limited. All rights reserved.

Genome-wide association study identifies eight loci associated with blood pressure

Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N 71,225 European ancestry, N 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10 24), CYP1A2 (P = 1 × 10 23), FGF5 (P = 1 × 10 21), SH2B3 (P = 3 × 10 18), MTHFR (P = 2 × 10 13), c10orf107 (P = 1 × 10 9), ZNF652 (P = 5 × 10 9) and PLCD3 (P = 1 × 10 8) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1–3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region4, 5, 6, 7, 8, 9, 10, 11. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods—recursive partitioning and regression...

Students' responses to the RACQ docudrama program

Young people are over-represented in road crashes and school-based education programs, including the RACQ Docudrama program, represent initiatives aimed at improving road safety among this high-risk group. The aim of the study was to apply an extended Theory of Planned Behaviour framework to understand more about the extent to which the program influenced individuals‟ intentions to speak up to a driver engaging in risky behaviours (e.g., speeding). Senior high school students (N=260) from 5 Queensland schools completed a survey in class. The study included a Control group (n = 86) who responded to the survey prior to completing the Docudrama program and an Intervention group comprising an Intervention-Immediate (n=100) and an Intervention-Delayed group (n = 74) who completed the survey after having participated in the program either on the day or up to a week later, respectively. Overall, the findings provided support for the beneficial effects of the program. Some of the study’s key findings included: (i) Intervention group participants consistently reported significantly stronger intentions to speak up than participants in the control group; (ii) among the significant predictors of intentions, a notable finding was that the more individuals anticipated feeling regretful for not having spoken up to a risky driver, the stronger their intentions were to speak up, and; (iii) the level of fear reported by students significantly decreased and was lowest at the conclusion of the program, following facilitated group discussion. The implications of the results for future research, program development and practice are discussed.

Studies on aluminum-isopropoxide doped poly(ethylene oxide), poly(vinyl alcohol), and poly(ethylene oxide)-poly(vinyl alcohol) blends

Poly( ethylene oxide), poly(vinyl alcohol): and their blend in a 40 : 60 mole ratio were doped with aluminum isopropoxide. Their structural, thermal, and electrical properties were studied. Aluminum isopropoxide acts as a Lewis acid and thus significantly influences the electrical properties of the polymers and the blend. It also acts as a scavanger for the trace quantities of water p-resent in them, thereby reducing the magnitude of proton transport. It also affects the structure of polymers that manifests in the thermal transformation and decomposition characteristics.

Managing the impacts of sugarcane farming on the Great Barrier Reef: An evaluation of the implementation of the Polluter Pays Principle

This report provides an evaluation of the implementation of the Polluter Pays Principle (PPP) – a principle of international environmental law – in the context of pollution from sugarcane farming affecting Australia’s Great Barrier Reef (GBR). The research was part of an experiment to test methods for evaluating the effectiveness of environmental laws. Overall, we found that whilst the PPP is reflected to a limited extent in Australian law (more so in Queensland law, than at the national level), the behaviour one might expect in terms of implementing the principle was largely inadequate. Evidence of a longer term, explicit commitment to the PPP was particularly weak.

In the red shadow of the Earth

A technique is described for calculating the brightness of the atmosphere of the Earth that shines into the Earth’s umbra during a total lunar eclipse making the Moon red. This ‘Rim of Fire’ is due to refracted un scattered light from all the sunrises and sunsets rimming the Earth. In this article, a photograph of the totally eclipsed Moon was compared with the Full Moon and the difference in brightness calculated taking into account the exposure time and ISO setting. The results show that the Full Moon is over 14 000 times brighter than the totally eclipsed Moon. The relative brightness of the eclipsed Moon can be used to estimate that the luminance of Rim of Fire is over 12 trillion watts. The experiment described in this paper would be suitable as a high school or university exercise.

The atmospheric extinction of light

An experiment is described that enables students to understand the properties of atmospheric extinction due to Rayleigh scattering. The experiment requires the use of red, green and blue lasers attached to a traveling microscope or similar device. The laser beams are passed through an artificial atmosphere, made from milky water, at varying depths, before impinging on either a light meter or a photodiode integral to a Picotech Dr. DAQ ADC. A plot of measured spectral intensity verses depth reveals the contribution Rayleigh scattering has to the extinction coefficient. For the experiment with the light meter, the extinction coefficient for red, green and blue light in the milky sample of water were 0.27, 0.36 and 0.47 cm-1 respectively and 0.032, 0.037 and 0.092 cm-1 for the Picotech Dr. DAQ ADC.

Volatile compounds from the flowers of spathiphyllum Cannaefolium

Headspace analysis and solvent extraction of the pollenbearing flower spike of Spathiphyllum cannaefolium have been conducted by GC-MS, to determine the basis of the flower spike’s attractancy to certain fruit-fly species. The major components were benzyl acetate, methyleugenol, methylchavicol, p-methoxybenzyl acetate and fatty acids. Benzyl acetate is known to be attractive to D. cueurbitae, D. dorsalis and C. capitata (representing the three different ‘male-lure categories’) and methyleugenol (one of these male-lures) attracts D. cacuminatus, D. dorsalis and D. occipitalis. Thus the odoriferous flowerspike exhibits wide ranging attractancy and hence Spathiphyllum cannaefolium may have some application as a fruit-fly control measure for small orchards where ‘methyleugenol-attracted’ species (e.g. D. cacuminatus, D. dorsalis, D. occipitalis) are the dominant pests.

Genetic variability of Tomato spotted wilt virus in Australia and validation of real time RT-PCR for its detection in single and bulked leaf samples

The potential for large-scale use of a sensitive real time reverse transcription polymerase chain reaction (RT-PCR) assay was evaluated for the detection of Tomato spotted wilt virus (TSWV) in single and bulked leaf samples by comparing its sensitivity with that of DAS-ELISA. Using total RNA extracted with RNeasy® or leaf soak methods, real time RT-PCR detected TSWV in all infected samples collected from 16 horticultural crop species (including flowers, herbs and vegetables), two arable crop species, and four weed species by both assays. In samples in which DAS-ELISA had previously detected TSWV, real time RT-PCR was effective at detecting it in leaf tissues of all 22 plant species tested at a wide range of concentrations. Bulk samples required more robust and extensive extraction methods with real time RT-PCR, but it generally detected one infected sample in 1000 uninfected ones. By contrast, ELISA was less sensitive when used to test bulked samples, once detecting up to 1 infected in 800 samples with pepper but never detecting more than 1 infected in 200 samples in tomato and lettuce. It was also less reliable than real time RT-PCR when used to test samples from parts of the leaf where the virus concentration was low. The genetic variability among Australian isolates of TSWV was small. Direct sequencing of a 587 bp region of the nucleoprotein gene (S RNA) of 29 isolates from diverse crops and geographical locations yielded a maximum of only 4.3% nucleotide sequence difference. Phylogenetic analysis revealed no obvious groupings of isolates according to geographic origin or host species. TSWV isolates, that break TSWV resistance genes in tomato or pepper did not differ significantly in the N gene region studied, indicating that a different region of the virus genome is responsible for this trait.

Vilijonkka ikkunassa - Tove Janssonin muumiteosten kuva, sana ja liike

Tove Jansson (1914--2001) was a Finnish illustrator, author, artist, caricaturist and comic artist. She is best known for her Moomin Books, written in Swedish, which she illustrated herself, and published between 1945 and 1977. My study focuses on the interweaving of images and words in Jansson s picturebooks, novels and short stories situated in the fantasy world of Moomin Valley. In particular, it concentrates on Jansson s development of a special kind of aesthetics of movement and stasis, based upon both illustration and text. The conventions of picturebook art and illustration are significant to both Jansson s visual art and her writing, and she was acutely conscious of them. My analysis of Jansson s work begins by discussing her first published picturebooks and less familiar illustrations (before she began her Moomin books) and I then proceed to discuss her three Moomin picturebooks, The Book about Moomin, Mymble and Little My; Who Will Comfort Toffle?, and The Dangerous Journey. The discussion moves from images to words and from words to images: Barthes s (1982) concept of anchoring and, in particular, what he calls relaying , form a point of reading and viewing Moomin texts and illustrations in a complementary relation, in which the message s unity occurs on a higher level: that of the story, the anecdote, the diegesis . The eight illustrated Moomin novels and one collection of short stories are analysed in a similar manner, taking into account the academic discourse about picturebooks which was developed in the last decade of the 20th century and beginning of the 21st century by, among others, scholars such as Nodelman, Rhedin, Doonan, Thiele, Stephens, Lewis, Nikolajeva and Scott. In her Moomin books, Jansson uses a wide variety of narrative and illustrative styles which are complementary to each other. Each book is different and unique in its own way, but a certain development or progression of mood and representation can be seen when assessing the series as a whole. Jansson s early stories are happy and adventurous but her later Moomin novels, beginning from Moominland Midwinter, focus more on the interiority of the characters, placing them in difficult situations which approximate social reality. This orientation is also reflected in the representation of movement and space. The books which were published first include more obviously descriptive passages, exemplifying the tradition of literary pictorialism. Whereas in Jansson s later work, the space develops into something that is alive which can have an enduring effect on the characters personalities and behaviour. This study shows how the idea of an image a dynamic image -- forms a holistic foundation for Jansson s imagination and work. The idea of central perspective, or frame, for instance, provided inspiration for whole stories or in the way that she developed her characters, as in the case of the Fillyjonk, who is a complex female figure, simultaneously frantic and prim. The idea of movement is central to the narrative art of picturebooks and illustrated texts, particularly in relation to the way that action is depicted. Jansson, however, also develops a specific choreography of characters in which poses and postures signify action, feelings and relationships. Here, I use two ideas from modern dance, contraction and release (Graham), to characterise the language of movement which is evident in Jansson s words and images. In Jansson s final Moomin novels and short stories, the idea of space becomes more and more dynamic and closely linked with characterisation. My study also examines a number of Jansson s early sketches for her Moomin novels, in which movement is performed much more dramatically than in those illustrations which appeared in the last novels to be published.

A Novel Operator-Splitting Technique for One-Dimensional Laminar Premixed Flames

This paper is concerned the calculation of flame structure of one-dimensional laminar premixed flames using the technique of operator-splitting. The technique utilizes an explicit method of solution with one step Euler for chemistry and a novel probabilistic scheme for diffusion. The relationship between diffusion phenomenon and Gauss-Markoff process is exploited to obtain an unconditionally stable explicit difference scheme for diffusion. The method has been applied to (a) a model problem, (b) hydrazine decomposition, (c) a hydrogen-oxygen system with 28 reactions with constant Dρ 2 approximation, and (d) a hydrogen-oxygen system (28 reactions) with trace diffusion approximation. Certain interesting aspects of behaviour of the solution with non-unity Lewis number are brought out in the case of hydrazine flame. The results of computation in the most complex case are shown to compare very favourably with those of Warnatz, both in terms of accuracy of results as well as computational time, thus showing that explicit methods can be effective in flame computations. Also computations using the Gear-Hindmarsh for chemistry and the present approach for diffusion have been carried out and comparison of the two methods is presented.