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.

Antithrombin III associated with fibrinogen predicts the risk of cerebral ischemic stroke

Background and purpose: The purpose of this study is to examine the feasibility of developing plasma predictive value biomarkers of cerebral ischemic stroke before imaging evidence is acquired. Methods: Blood samples were obtained from 198 patients who attended our neurology department as emergencies - with symptoms of vertigo, numbness, limb weakness, etc. - within 4.5 h of symptom onset, and before imaging evidence was obtained and medical treatment. After the final diagnosis was made by MRI/DWI/MRA or CTA in the following 24-72 h, the above cases were divided into two groups: stroke group and non-stroke group according to the imaging results. The levels of baseline plasma antithrombin III (AT-III), thrombin-antithrombin III (TAT), fibrinogen, D-dimer and high-sensitivity C-reactive protein (hsCRP) in the two groups were assayed. Results: The level of the baseline AT-III in the stroke group was 118.07 ± 26.22%, which was lower than that of the non-stroke group (283.83 ± 38.39%). The levels of TAT, fibrinogen, hsCRP were 7.24 ± 2.28 μg/L, 5.49 ± 0.98 g/L, and 2.17 ± 1.07 mg/L, respectively, which were higher than those of the non-stroke group (2.53 ± 1.23 μg/L, 3.35 ± 0.50 g/L, 1.82 ± 0.67 mg/L). All the P-values were less than 0.001. The D-dimer level was 322.57 ± 60.34 μg/L, which was slightly higher than that of the non-stroke group (305.76 ± 49.52 μg/L), but the P-value was 0.667. The sensitivities of AT-III, TAT, fibrinogen, D-dimer and hsCRP for predicting ischemic stroke tendency were 97.37%, 96.05%, 3.29%, 7.89%, but the specificity was 93.62%, 82.61%, 100% and 100%, respectively, and all the P-values were less than 0.001. High levels of D-dimer and hsCRP were mainly seen in the few cases with severe large-vessel infarction. Conclusions: Clinical manifestations of acute focal neurological deficits were associated with plasma AT-III and fibrinogen. These tests might help the risk assessment of acute cerebral ischemic stroke and/or TIA with infarction tendency in the superacute stage before positive imaging evidence is obtained.

Study of Pinna nobilis growth from inner record: How biased are posterior adductor muscle scars estimates?

Previous studies have shown that the external growth records of the posterior adductor muscle scar (PAMS) of the bivalve Pinna nobilis are incomplete and do not produce accurate age estimations. We have developed a new methodology to study age and growth using the inner record of the PAMS, which avoids the necessity of costly in situ shell measurements or isotopic studies. Using the inner record we identified the positions of PAMS previously obscured by nacre and estimated the number of missing records in adult specimens with strong abrasion of the calcite layer in the anterior portion of the shell. The study of the PAMS and inner record of two shells that were 6 years old when collected showed that only 2 and 3 PAMS were observed, while 6 inner records could be counted, thus confirming our working methodology. Growth parameters of a P. nobilis population located in Moraira, Spain (western Mediterranean) were estimated with the new methodology and compared to those obtained using PAMS data and in situ measurements. For the comparisons, we applied different models considering the data alternatively as length-at-age (LA) and tag-recapture (TR). Among every method we tested to fit the Von Bertalanffy growth model, we observed that LA data from inner record fitted to the model using non-linear mixed effects and the estimation of missing records using the calcite width was the most appropriate. The equation obtained with this method, L = 573*(1 - e(-0.16(t-0.02))), is very similar to that calculated previously from in situ measurements for the same population.

Structure of the K6 capsular polysaccharide from Acinetobacter baumannii isolate RBH4

The structure of the capsular polysaccharide (CPS) from an Acinetobacter baumannii global clone 2 (GC2) clinical isolate RBH4 that carries the KL6 gene cluster was elucidated by means of chemical and spectroscopical methods. The repeating unit of K6 CPS is linear and contains N-acetyl-d-galactosamine (d-GalpNAc), two d-galactose (d-Galp) residues and 5,7-di-N-acetylpseudaminic acid (Pse5Ac7Ac). The synthesis of these sugars could be attributed to genes in the KL6 capsule biosynthesis gene cluster, and the formation of the linkages between the sugars were assigned to glycosyltransferases or the Wzy polymerase encoded in KL6.

The Context-integrity of the global carbon regime: The relevance and impact of the World Trade Organization

In the study of the integrity of the global carbon regime there are a number of institutions that must be considered for their impacts on this system. In particular, the subject matter of this chapter is concerned with the main international institution for trade, the World Trade Organization (the WTO). Otherwise stated, this chapter is concerned with how the institutional integrity of the global carbon regime aligns with the values and policy objectives of the WTO. This is done with a view to consider whether the global carbon regime aligns with these values and objectives in a way demonstrative of context-integrity. This alignment is not a single-sided undertaking and, therefore, it is essential that the underlying values of the WTO themselves align with the global carbon regime. I suggest this is particularly crucial given the importance of the objectives of the climate change regime, and the scientific predictions of the current climate projections.

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Concentrations of phthalates and DINCH metabolites in pooled urine from Queensland, Australia

Dialkyl phthalate esters (phthalates) are ubiquitous chemicals used extensively as plasticizers, solvents and adhesives in a range of industrial and consumer products. 1,2-Cyclohexane dicarboxylic acid, diisononyl ester (DINCH) is a phthalate alternative introduced due to a more favourable toxicological profile, but exposure is largely uncharacterised. The aim of this study was to provide the first assessment of exposure to phthalates and DINCH in the general Australian population. De-identified urine specimens stratified by age and sex were obtained from a community-based pathology laboratory and pooled (n = 24 pools of 100). Concentrations of free and total species were measured using online solid phase extraction isotope dilution high performance liquid chromatography tandem mass spectrometry. Concentrations ranged from 2.4 to 71.9 ng/mL for metabolites of di(2-ethylhexyl)phthalate, and from < 0.5 to 775 ng/mL for all other metabolites. Our data suggest that phthalate metabolites concentrations in Australia were at least two times higher than in the United States and Germany; and may be related to legislative differences among countries. DINCH metabolite concentrations were comparatively low and consistent with the limited data available. Ongoing biomonitoring among the general Australian population may help assess temporal trends in exposure and assess the effectiveness of actions aimed at reducing exposures.

LMS acceptance: The instructor role

Learning management systems (LMS) have become the norm in recent years in higher education to further engage students and lecturers. The e-learning tools within LMS provide knowledge sharing and community building opportunities that can support both critical thinking and higher order learning skills through conversation and collaboration. However, the mere existence of tools does not guarantee users’ adoption and acceptance. Several effective arrangements are required to engage users. This paper focuses on different aspects of lecturers’ attitude that impact user engagement with LMS tools reporting on findings from 74 interviews with students and lecturers from different disciplines within a major Australian university. Results indicate that lecturers’ teaching style and habits, active participation in online activities as well as designing appropriate tasks and assessment procedure are important determinants of lecturers’ attitude in engaging students with LMS tools.

Promoting and maintaining physical activity in the transition to retirement: A systematic review of interventions for adults around retirement age

It has been argued that transition points in life, such as the approach towards, and early years of retirement present key opportunities for interventions to improve the health of the population. Research has also highlighted inequalities in health status in the retired population and in response to interventions which should be addressed. We aimed to conduct a systematic review to synthesise international evidence on the types and effectiveness of interventions to increase physical activity among people around the time of retirement. A systematic review of literature was carried out between February 2014 and April 2015. Searches were not limited by language or location, but were restricted by date to studies published from 1990 onwards. Methods for identification of relevant studies included electronic database searching, reference list checking, and citation searching. Systematic search of the literature identified 104 papers which described study populations as being older adults. However, we found only one paper which specifically referred to their participants as being around the time of retirement. The intervention approaches for older adults encompassed: training of health care professionals; counselling and advice giving; group sessions; individual training sessions; in-home exercise programmes; in-home computer-delivered programmes; in-home telephone support; in-home diet and exercise programmes; and community-wide initiatives. The majority of papers reported some intervention effect, with evidence of positive outcomes for all types of programmes. A wide range of different measures were used to evaluate effectiveness, many were self-reported and few studies included evaluation of sedentary time. While the retirement transition is considered a significant point of life change, little research has been conducted to assess whether physical activity interventions at this time may be effective in promoting or maintaining activity, or reducing health inequalities. We were unable to find any evidence that the transition to retirement period was, or was not a significant point for intervention. Studies in older adults more generally indicated that a range of interventions might be effective for people around retirement age.

Reduced withdrawal and failure rates of accelerated nursing students enrolled in pharmacology is associated with a supportive intervention

Background To reduce nursing shortages, accelerated nursing programs are available for domestic and international students. However, the withdrawal and failure rates from these programs may be different than for the traditional programs. The main aim of our study was to improve the retention and experience of accelerated nursing students. Methods The academic background, age, withdrawal and failure rates of the accelerated and traditional students were determined. Data from 2009 and 2010 were collected prior to intervention. In an attempt to reduce the withdrawal of accelerated students, we set up an intervention, which was available to all students. The assessment of the intervention was a pre-post-test design with non-equivalent groups (the traditional and the accelerated students). The elements of the intervention were a) a formative website activity of some basic concepts in anatomy, physiology and pharmacology, b) a workshop addressing study skills and online resources, and c) resource lectures in anatomy/physiology and microbiology. The formative website and workshop was evaluated using questionnaires. Results The accelerated nursing students were five years older than the traditional students (p < 0.0001). The withdrawal rates from a pharmacology course are higher for accelerated nursing students, than for traditional students who have undertaken first year courses in anatomy and physiology (p = 0.04 in 2010). The withdrawing students were predominantly the domestic students with non-university qualifications or equivalent experience. The failure rates were also higher for this group, compared to the traditional students (p = 0.05 in 2009 and 0.03 in 2010). In contrast, the withdrawal rates for the international and domestic graduate accelerated students were very low. After the intervention, the withdrawal and failure rates in pharmacology for domestic accelerated students with non-university qualifications were not significantly different than those of traditional students. Conclusions The accelerated international and domestic graduate nursing students have low withdrawal rates and high success rates in a pharmacology course. However, domestic students with non-university qualifications have higher withdrawal and failure rates than other nursing students and may be underprepared for university study in pharmacology in nursing programs. The introduction of an intervention was associated with reduced withdrawal and failure rates for these students in the pharmacology course.

Hospital in the Nursing Home program reduces emergency department presentations and hospital admissions from residential aged care facilities in Queensland, Australia: A quasi-experimental study

Background There has been considerable publicity regarding population ageing and hospital emergency department (ED) overcrowding. Our study aims to investigate impact of one intervention piloted in Queensland Australia, the Hospital in the Nursing Home (HiNH) program, on reducing ED and hospital attendances from residential aged care facilities (RACFs). Methods A quasi-experimental study was conducted at an intervention hospital undertaking the program and a control hospital with normal practice. Routine Queensland health information system data were extracted for analysis. Results Significant reductions in the number of ED presentations per 1000 RACF beds (rate ratio (95 % CI): 0.78 (0.67–0.92); p = 0.002), number of hospital admissions per 1000 RACF beds (0.62 (0.50–0.76); p < 0.0001), and number of hospital admissions per 100 ED presentations (0.61 (0.43–0.85); p = 0.004) were noticed in the experimental hospital after the intervention; while there were no significant differences between intervention and control hospitals before the intervention. Pre-test and post-test comparison in the intervention hospital also presented significant decreases in ED presentation rate (0.75 (0.65–0.86); p < 0.0001) and hospital admission rate per RACF bed (0.66 (0.54–0.79); p < 0.0001), and a non-significant reduction in hospital admission rate per ED presentation (0.82 (0.61–1.11); p = 0.196). Conclusions Hospital in the Nursing Home program could be effective in reducing ED presentations and hospital admissions from RACF residents. Implementation of the program across a variety of settings is preferred to fully assess the ongoing benefits for patients and any possible cost-savings.

Establishing turf grass increases soil greenhouse gas emissions in peri-urban environments

Urbanization is becoming increasingly important in terms of climate change and ecosystem functionality worldwide. We are only beginning to understand how the processes of urbanization influence ecosystem dynamics and how peri-urban environments contribute to climate change. Brisbane in South East Queensland (SEQ) currently has the most extensive urban sprawl of all Australian cities. This leads to substantial land use changes in urban and peri-urban environments and the subsequent gaseous emissions from soils are to date neglected for IPCC climate change estimations. This research examines how land use change effects methane (CH4) and nitrous oxide (N2O) fluxes from peri-urban soils and consequently influences the Global Warming Potential (GWP) of rural ecosystems in agricultural use undergoing urbanization. Therefore, manual and fully automated static chamber measurements determined soil gas fluxes over a full year and an intensive sampling campaign of 80 days after land use change. Turf grass, as the major peri-urban land cover, increased the GWP by 415 kg CO2-e ha 1 over the first 80 days after conversion from a well-established pasture. This results principally from increased daily average N2O emissions of 0.5 g N2O ha-1 d-1 from the pasture to 18.3 g N2O ha-1 d-1 from the turf grass due to fertilizer application during conversion. Compared to the native dry sclerophyll eucalypt forest, turf grass establishment increases the GWP by another 30 kg CO2-e ha 1. The results presented in this study clearly indicate the substantial impact of urbanization on soil-atmosphere gas exchange in form of non-CO2 greenhouse gas emissions particularly after turf grass establishment.

Can technology provide a glimmer of hope for economic growth in the midst of chaos? A case of Zimbabwe

In this paper we examine the effect of technology on economic growth in Zimbabwe over the period 1975–2014 whilst accounting for structural breaks. We use the extended Cobb–Douglas type Solow (Q J Econ 70(1):65–94, 1956) framework and the ARDL bounds procedure to examine cointegration and short run and long run effects. Using unit root tests, we note that structural changes in Zimbabwe are generally marked by the period 1982 onwards. We find that mobile technology has a positive short-run (0.09 %) and long-run (0.08 %) impact on the output per capita. The structural changes post-1982 periods show positive impact in the short-run (0.06) and the long-run (0.09), whereas the coefficient of trend in the short-run (−0.03) and the long-run (−0.04) is negative. The Granger non-causality test shows a unidirectional causality from capital stock (investment) per capita to output per capita and a bi-directional causality between mobile cellular technology and output per capita. The plausible reasons for estimated magnitude effects and the direction of causality are explained for policy deliberation.

VisArchive: a time and relevance based visual interface for searching, browsing, and exploring project archives

Background Project archives are becoming increasingly large and complex. On construction projects in particular, the increasing amount of information and the increasing complexity of its structure make searching and exploring information in the project archive challenging and time-consuming. Methods This research investigates a query-driven approach that represents new forms of contextual information to help users understand the set of documents resulting from queries of construction project archives. Specifically, this research extends query-driven interface research by representing three types of contextual information: (1) the temporal context is represented in the form of a timeline to show when each document was created; (2) the search-relevance context shows exactly which of the entered keywords matched each document; and (3) the usage context shows which project participants have accessed or modified a file. Results We implemented and tested these ideas within a prototype query-driven interface we call VisArchive. VisArchive employs a combination of multi-scale and multi-dimensional timelines, color-coded stacked bar charts, additional supporting visual cues and filters to support searching and exploring historical project archives. The timeline-based interface integrates three interactive timelines as focus + context visualizations. Conclusions The feasibility of using these visual design principles is tested in two types of project archives: searching construction project archives of an educational building project and tracking of software defects in the Mozilla Thunderbird project. These case studies demonstrate the applicability, usefulness and generality of the design principles implemented.

Bringing nature to schools to promote children’s physical activity

Physical activity (PA) is essential for human health and wellbeing across all age, socioeconomic and ethnic groups. Engagement with the natural world is a new defining criterion for enhancing the benefits of PA particularly for children and young people. Interacting with nature benefits children’s social and emotional wellbeing, develops resilience and reduces the risk of obesity and type 2 diabetes across all population groups. Governments around the world are now recognising the importance of children spending more active time outdoors. However, children’s outdoor activities, free play and nature-related exploration are often structured and supervised by adults due to safety concerns and risks. In this context schools become more accessible and safe options for children to engage in PA outdoors with the presence of nature features. Research on school designs involving young children has revealed that children prefer nature-related features in school environments. Affordances in nature may increase children’s interest in physically active behaviours. Given that present school campuses are designed for operational efficiency and economic reasons there is a need to re-design schools responding to the positive role of nature on human health. If schools were re-designed to incorporate diverse natural features children’s PA and consequent health and wellbeing would likely improve markedly.