Environmental, personal, and genetic determinants of response to vitamin D supplementation in older adults

CONTEXT AND OBJECTIVE: Suboptimal vitamin D status can be corrected by vitamin D supplementation, but individual responses to supplementation vary. We aimed to examine genetic and nongenetic determinants of change in serum 25-hydroxyvitamin D (25(OH)D) after supplementation. DESIGN AND PARTICIPANTS: We used data from a pilot randomized controlled trial in which 644 adults aged 60 to 84 years were randomly assigned to monthly doses of placebo, 30 000 IU, or 60 000 IU vitamin D3 for 12 months. Baseline characteristics were obtained from a self-administered questionnaire. Eighty-eight single-nucleotide polymorphisms (SNPs) in 41 candidate genes were genotyped using Sequenom MassArray technology. Serum 25(OH)D levels before and after the intervention were measured using the Diasorin Liaison platform immunoassay. We used linear regression models to examine associations between genetic and nongenetic factors and change in serum 25(OH)D levels. RESULTS: Supplement dose and baseline 25(OH)D level explained 24% of the variability in response to supplementation. Body mass index, self-reported health status, and ambient UV radiation made a small additional contribution. SNPs in CYP2R1, IRF4, MC1R, CYP27B1, VDR, TYRP1, MCM6, and HERC2 were associated with change in 25(OH)D level, although only CYP2R1 was significant after adjustment for multiple testing. Models including SNPs explained a similar proportion of variability in response to supplementation as models that included personal and environmental factors. CONCLUSION: Stepwise regression analyses suggest that genetic variability may be associated with response to supplementation, perhaps suggesting that some people might need higher doses to reach optimal 25(OH)D levels or that there is variability in the physiologically normal level of 25(OH)D.

Insurance and transport law : controlling insurance contract terms : Section 54 of the Insurance Contracts Act – compliance, recovery and accountability

Commonwealth legislation covering insurance contracts contains numerous provisions designed to control the operation and effect of terms in life and general insurance contracts. For example, the Life Insurance Act 1995 (Cth) contains provisions regulating the consequences attendant upon incorrect statements in proposals [1] and non-payment of premiums, [2] provides that an insurer may only exclude liability in the case of suicide if it has made express provision for such contingency in its policy, [3] and severely restricts the efficacy of conditions as to war risks. [4] The Insurance Contracts Act 1984 (Cth) is even more intrusive and has a major impact upon contractual provisions in the general insurance field. It is beyond the scope of this note to explore all of these provisions in any detail but examples of controls and constraints imposed upon the operation and effect of contractual provisions include the following. A party is precluded from relying upon a provision in a contract of insurance if such reliance would amount to a failure to act with the utmost good faith. [5] Similarly, a policy provision which requires differences or disputes arising out of the insurance to be submitted to arbitration is void, [6] unless the insurance is a genuine cover for excess of loss over and above another specified insurance. [7] Similarly clause such as conciliation clauses, [8] average clauses, [9] and unusual terms [10] are given qualified operation. [11] However the provision in the Insurance Contracts Act that has the greatest impact upon, and application to, a wide range of insurance clauses and claims is s 54. This section has already generated a significant volume of case law and is the focus of this note. In particular this note examines two recent cases. The first, Johnson v Triple C Furniture and Electrical Pty Ltd [2012] 2 Qd R 337, (hereafter the Triple C case), is a decision of the Queensland Court of Appeal; and the second, Matthew Maxwell v Highway Hauliers Pty Ltd [2013] WASCA 115, (hereafter the Highway Hauliers case), is a decision of the Court of Appeal in Western Australia. This latter decision is on appeal to the High Court of Australia. The note considers too the decision of the New South Wales Court of Appeal in Prepaid Services Pty Ltd v Atradius Credit Insurance NV [2013] NSWCA 252 (hereafter the Prepaid Services case).These cases serve to highlight the complex nature of s 54 and its application, as well as the difficulty in achieving a balance between an insurer and an insured's reasonable expectations.

Common values in assessing health outcomes from disease and injury: Disability weights measurement study for the Global Burden of Disease Study 2010

BACKGROUND Measurement of the global burden of disease with disability-adjusted life-years (DALYs) requires disability weights that quantify health losses for all non-fatal consequences of disease and injury. There has been extensive debate about a range of conceptual and methodological issues concerning the definition and measurement of these weights. Our primary objective was a comprehensive re-estimation of disability weights for the Global Burden of Disease Study 2010 through a large-scale empirical investigation in which judgments about health losses associated with many causes of disease and injury were elicited from the general public in diverse communities through a new, standardised approach. METHODS We surveyed respondents in two ways: household surveys of adults aged 18 years or older (face-to-face interviews in Bangladesh, Indonesia, Peru, and Tanzania; telephone interviews in the USA) between Oct 28, 2009, and June 23, 2010; and an open-access web-based survey between July 26, 2010, and May 16, 2011. The surveys used paired comparison questions, in which respondents considered two hypothetical individuals with different, randomly selected health states and indicated which person they regarded as healthier. The web survey added questions about population health equivalence, which compared the overall health benefits of different life-saving or disease-prevention programmes. We analysed paired comparison responses with probit regression analysis on all 220 unique states in the study. We used results from the population health equivalence responses to anchor the results from the paired comparisons on the disability weight scale from 0 (implying no loss of health) to 1 (implying a health loss equivalent to death). Additionally, we compared new disability weights with those used in WHO's most recent update of the Global Burden of Disease Study for 2004. FINDINGS 13,902 individuals participated in household surveys and 16,328 in the web survey. Analysis of paired comparison responses indicated a high degree of consistency across surveys: correlations between individual survey results and results from analysis of the pooled dataset were 0·9 or higher in all surveys except in Bangladesh (r=0·75). Most of the 220 disability weights were located on the mild end of the severity scale, with 58 (26%) having weights below 0·05. Five (11%) states had weights below 0·01, such as mild anaemia, mild hearing or vision loss, and secondary infertility. The health states with the highest disability weights were acute schizophrenia (0·76) and severe multiple sclerosis (0·71). We identified a broad pattern of agreement between the old and new weights (r=0·70), particularly in the moderate-to-severe range. However, in the mild range below 0·2, many states had significantly lower weights in our study than previously. INTERPRETATION This study represents the most extensive empirical effort as yet to measure disability weights. By contrast with the popular hypothesis that disability assessments vary widely across samples with different cultural environments, we have reported strong evidence of highly consistent results.

Identification of common variants associated with human hippocampal and intracranial volumes

Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temporal lobe epilepsy. Whereas many brain imaging phenotypes are highly heritable, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 × 10 -16) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 × 10 -12). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 × 10 -7).

Teaching engineering tribology: Elements of assessment design for different learning styles

This study involves teaching engineering students concepts in lubrication engineering that are heavily dependent on mathematics. Excellent learning outcomes have been observed when assessment tasks are devised for a diversity of learning styles. Providing different pathways to knowledge reduces the probability that a single barrier halts progress towards the ultimate learning objective. The interdisciplinary nature of tribology can be used advantageously to tie together multiple elements of engineering to solve real physical problems—an approach that seems to benefit a majority of engineering students. To put this into practice, various assessment items were devised on the study of hydrodynamics, culminating in a project to provide a summative evaluation of the students’ learning achievement. A survey was also conducted to assess other aspects of students’ learning experiences under the headings: ‘perception of learning’ and ‘overall satisfaction’. High degrees of achievement and satisfaction were observed. An attempt has been made to identify the elements contributing to success so that they may be applied to other challenging concepts in engineering education.

Genome-wide association analysis identifies 13 new risk loci for schizophrenia

Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-Analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.

Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity

To gain further insight into the genetic architecture of psoriasis, we conducted a meta-analysis of 3 genome-wide association studies (GWAS) and 2 independent data sets genotyped on the Immunochip, including 10,588 cases and 22,806 controls. We identified 15 new susceptibility loci, increasing to 36 the number associated with psoriasis in European individuals. We also identified, using conditional analyses, five independent signals within previously known loci. The newly identified loci shared with other autoimmune diseases include candidate genes with roles in regulating T-cell function (such as RUNX3, TAGAP and STAT3). Notably, they included candidate genes whose products are involved in innate host defense, including interferon-mediated antiviral responses (DDX58), macrophage activation (ZC3H12C) and nuclear factor (NF)-κB signaling (CARD14 and CARM1). These results portend a better understanding of shared and distinctive genetic determinants of immune-mediated inflammatory disorders and emphasize the importance of the skin in innate and acquired host defense. © 2012 Nature America, Inc. All rights reserved.

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.

Thermal conductivity of a new carbon nanotube analog: The diamond nanothread

Based on the non-equilibrium molecular dynamics simulations, we have studied the thermal conductivities of a novel ultra-thin one-dimensional carbon nanomaterial - diamond nanothread (DNT). Unlike single-wall carbon nanotube (CNT), the existence of the Stone-Wales transformations in DNT endows it with richer thermal transport characteristics. There is a transition from wave-dominated to particle-dominated transport region, which depends on the length of poly-benzene rings. However, independent of the transport region, strong length dependence in thermal conductivity is observed in DNTs with different lengths of poly-benzene ring. The distinctive SW characteristic in DNT provides more degrees of freedom to tune the thermal conductivity not found in the homogeneous structure of CNT. Therefore, DNT is an ideal platform to investigate various thermal transport mechanisms at the nanoscale. Its high tunability raises the potential to design DNTs for different applications, such as thermal connection and temperature management.

Faecal incontinence in childhood : a multidisciplinary approach including biofeedback

One hundred and seven children with faecal incontinence were evaluated and managed over a 3 year period by a multidisciplinary team. After initial clinical assessment, evaluation of defaecatory mechanisms (using a balloon model) and assessment of personal-social development and self-concept were undertaken. Management was based on initial bowel evacuation, short-term laxatives, and habit training involving systematic use of positive reinforcement; 69 children received biofeedback conditioning. Idiopathic megacolon with constipation and soiling was the most common finding (98 cases). Other diagnoses included previously undiagnosed neurogenic bowel (three cases), post-surgical anal anomalies (four cases), and psychogenic encopresis (two cases). Idiopathic megacolon was characterized by decreased rectal sensation, increased threshold for external sphincter relaxation and an inability to evacuate. Faecal incontinence was associated with an undesirably low social self-concept (70% of the 40 evaluated), but was not related to a delay in development (mean general developmental quotient = 105 ± 8, for the 35 tested). Family psychopathology warranting referral for family therapy was found in 14 children (13%). The management programme yielded a short-term (3 months) cure rate of 68% and a long-term (12 months) cure rate of 90%, with 10% having continued soiling which varied from occasional to several incidents/week. No significant improvement in self-concept was observed overall, although marked improvements were observed in some children. We conclude that disordered defaecatory dynamics are a major determinant of faecal incontinence in children. Undesirably low social self-concepts but normal developmental ability accompany this condition. Management is facilitated by a multidisciplinary approach, acknowledging the role of both behavioural and physiological components of the problem. This approach is effective in eradicating soiling in the majority of cases, comparing favourably with other published data.

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.

Phosphorus nutrition and tolerance of cotton to water stress: II. Water relations, free and bound water and leaf expansion rate

In previous experiments, increased leaf-Phosphorus (P) content with increasing P supply enhanced the individual leaf expansion and water content of fresh cotton leaves in a severely drying soil. In this paper, we report on the bulk water content of leaves and its components, free and bound water, along with other measures of plant water status, in expanding cotton leaves of various ages in a drying soil with different P concentrations. The bound water in living tissue is more likely to play a major role in tolerance to abiotic stresses by maintaining the structural integrity and/or cell wall extensibility of the leaves, whilst an increased amount of free water might be able to enhance solute accumulation, leading to better osmotic adjustment and tolerance to water stress, and maintenance of the volumes of sub-cellular compartments for expansive leaf growth. There were strong correlations between leaf-P%, leaf water (total, free and bound water) and leaf expansion rate (LER) under water stress conditions in a severely drying soil. Increased soil-P enhanced the uptake of P from a drying soil, leading to increased supply of osmotically active inorganic solutes to the cells in growing leaves. This appears to have led to the accumulation of free water and more bound water, ultimately leading to increased leaf expansion rates as compared to plants in low P soil under similar water stress conditions. The greater amount of bound and free water in the high-P plants was not necessarily associated with changes in cell turgor, and appears to have maintained the cell-wall properties and extensibility under water stressed conditions in soils that are nutritionally P-deficient.

Phosphorus nutrition and tolerance of cotton to water stress I. Seed cotton yield and leaf morphology

Seed cotton yield and morphological changes in leaf growth were examined under drying soil with different phosphorus (P) concentrations in a tropical climate. Frequent soil drying is likely to induce a decrease in nutrients particularly P due to reduced diffusion and poor uptake, in addition to restrictions in available water, with strong interactive effects on plant growth and functioning. Increased soil P in field and in-ground soil core studies increased the seed cotton yield and related morphological growth parameters in a drying soil, with hot (daily maximum temperature >33°C) and dry conditions (relative humidity, 25% to 35%), particularly during peak boll formation and filling stage. The soil water content in the effective rooting zone (top 0.4 m) decreased to -1.5 MPa by day 5 of the soil drying cycle. However, the increased seed cotton yield for the high-P plants was closely related to increasing leaf area with increased P supply. Plant height, leaf fresh mass and leaf area per plant were positively related to the leaf P%, which increased with increasing P supply. Low P plants were lower in plant height, leaf area, and leaf tissue water in the drying soil. Individual leaf area and the water content of the fresh leaf (ratio of dry mass to fresh mass) were significantly dependent on leaf P%.