Discovery of an archetypal protein transport system in bacterial outer membranes

Bacteria have mechanisms to export proteins for diverse purposes, including colonization of hosts and pathogenesis. A small number of archetypal bacterial secretion machines have been found in several groups of bacteria and mediate a fundamentally distinct secretion process. Perhaps erroneously, proteins called 'autotransporters' have long been thought to be one of these protein secretion systems. Mounting evidence suggests that autotransporters might be substrates to be secreted, not an autonomous transporter system. We have discovered a new translocation and assembly module (TAM) that promotes efficient secretion of autotransporters in proteobacteria. Functional analysis of the TAM in Citrobacter rodentium, Salmonella enterica and Escherichia coli showed that it consists of an Omp85-family protein, TamA, in the outer membrane and TamB in the inner membrane of diverse bacterial species. The discovery of the TAM provides a new target for the development of therapies to inhibit colonization by bacterial pathogens.

What women want : qualitative analysis of consumer evaluations of maternity care in Queensland, Australia

Background Maternity care reform plans have been proposed at state and national levels in Australia, but the extent to which these respond to maternity care consumers’ expressed needs is unclear. This study examines open-text survey comments to identify women’s unmet needs and priorities for maternity care. It is then considered whether these needs and priorities are addressed in current reform plans. Methods Women who had a live single or multiple birth in Queensland, Australia, in 2010 (n 3,635) were invited to complete a retrospective self-report survey. In addition to questions about clinical and interpersonal maternity care experiences from pregnancy to postpartum, women were asked an open-ended question “Is there anything else you’d like to tell us about having your baby?” This paper describes a detailed thematic analysis of open-ended responses from a random selection of 150 women (10% of 1,510 who responded to the question). Results Four broad themes emerged relevant to improving women’s experiences of maternity care: quality of care (interpersonal and technical); access to choices and involvement in decision-making; unmet information needs; and dissatisfaction with the care environment. Some of these topics are reflected in current reform goals, while others provide evidence of the need for further reforms. Conclusions The findings reinforce the importance of some existing maternity reform objectives, and describe how these might best be met. Findings affirm the importance of information provision to enable informed choices; a goal of Queensland and national reform agendas. Improvement opportunities not currently specified in reform agendas were also identified, including the quality of interpersonal relationships between women and staff, particular unmet information needs (e.g., breastfeeding), and concerns regarding the care environment (e.g., crowding and long waiting times).

An SEM, EDS and vibrational spectroscopic study of the silicate mineral meliphanite (Ca,Na)2Be[(Si,Al)2O6(F,OH)]

The mineral meliphanite (Ca,Na)2Be[(Si,Al)2O6(F,OH)] is a crystalline sodium calcium beryllium silicate which has the potential to be used as piezoelectric material and for other ferroelectric applications. The mineral has been characterized by a combination of scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS) and vibrational spectroscopy. EDS analysis shows a material with high concentrations of Si and Ca and low amounts of Na, Al and F. Beryllium was not detected. Raman bands at 1016 and 1050 cm−1 are assigned to the SiO and AlOH stretching vibrations of three dimensional siloxane units. The infrared spectrum of meliphanite is very broad in comparison with the Raman spectrum. Raman bands at 472 and 510 cm−1 are assigned to OSiO bending modes. Raman spectroscopy identifies bands in the OH stretching region. Raman spectroscopy with complimentary infrared spectroscopy enables the characterization of the silicate mineral meliphanite.

Transport and health in China : recent collaborative research relating to vehicle factors and pollution

The nature of the transport system contributes to public health outcomes in a range of ways. The clearest contribution to public health is in the area of traffic crashes, because of their direct impact on individual death and disability and their direct costs to the health system. Other papers in this conference address these issues. This paper outlines some collaborative research between the Centre for Accident Research and Road Safety - Queensland (CARRS-Q) at QUT and Chinese researchers in areas that have indirect health impacts. Heavy vehicle dynamics: The integrity of the road surface influences crash risk, with ruts, pot-holes and other forms of road damage contributing to increased crash risks. The great majority of damage to the road surface from vehicles is caused by heavy trucks and buses, rather than cars or smaller vehicles. In some cases this damage is due to deliberate overloading, but in other cases it is due to vehicle suspension characteristics that lead to occasional high loads on particular wheels. Together with a visiting researcher and his colleagues, we have used both Queensland and Chinese data to model vehicle suspension systems that reduce the level of load, and hence the level of road damage and resulting crash risk(1-5). Toll worker exposure to vehicle emissions: The increasing construction of highways in China has also involved construction of a large number of toll roads. Tollbooth workers are potentially exposed to high levels of pollutants from vehicles, however the extent of this exposure and how it relates to standards for exposure are not well known. In a study led by a visiting researcher, we conducted a study to model these levels of exposure for a tollbooth in China(6). Noise pollution: The increasing presence of high speed roads in China has contributed to an increase in noise levels. In this collaborative study we modelled noise levels associated with a freeway widening near a university campus, and measures to reduce the noise(7). Along with these areas of research, there are many other areas of transport with health implications that are worthy of exploration. Traffic, noise and pollution contribute to a difficult environment for pedestrians, especially in an ageing society where there are health benefits to increasing physical activity. By building on collaborations such as those outlined, there is potential for a contribution to improved public health by addressing transport issues such as vehicle factors and pollution, and extending the research to other areas of travel activity. 1. Chen, Y., He, J., King, M., Chen, W. and Zhang, W. (2014). Stiffness-damping matching method of an ECAS system based on LQG control. Journal of Central South University, 21:439-446. DOI: 10.1007/s1177101419579 2. Chen, Y., He, J., King, M., Feng, Z. and Chang, W. (2013). Comparison of two suspension control strategies for multi-axle heavy truck. Journal of Central South University, 20(2): 550-562. 3. Chen, Y., He, J., King, M., Chen, W. and Zhang, W. (2013). Effect of driving conditions and suspension parameters on dynamic load-sharing of longitudinal-connected air suspensions. Science China Technological Sciences, 56(3): 666-676. DOI: 10.1007/s11431-012-5091-3 4. Chen, Y., He., J., King, M., Chen, W. and Zhang, W. (2013). Model development and dynamic load-sharing analysis of longitudinal-connected air suspensions. Strojniški Vestnik - Journal of Mechanical Engineering, 59(1):14-24. 5. Chen, Y., He, J., King, M., Liu, H. and Zhang, W. (2013). Dynamic load-sharing of longitudinal-connected air suspensions of a tri-axle semi-trailer. Proceedings of Transportation Research Board Annual Conference, Washington DC, 13-17 January 2013, paper no. 13-1117. 6. He, J., Qi, Z., Hang, W., King, M., and Zhao, C. (2011). Numerical evaluation of pollutant dispersion at a toll plaza based on system dynamics and Computational Fluid Dynamics models. Transportation Research Part C, 19(2011):510-520. 7. Zhang, C., He, J., Wang, Z., Yin, R. and King, M. (2013). Assessment of traffic noise level before and after freeway widening using traffic microsimulation and a refined classic noise prediction method. Proceedings of Transportation Research Board Annual Conference, Washington DC, 13-17 January 2013, paper no. 13-2016.

The origin of cyclical high- and low-Cr basalts with continental crust trace element signatures in the Kalkarindji Large Igneous Province

The 510 million year old Kalkarindji Large Igneous Province correlates in time with the first major extinction event after the Cambrian explosion of life. Large igneous provinces correlate with all major mass extinction events in the last 500 million years. The genetic link between large igneous provinces and mass extinction remains unclear. My work is a contribution towards understanding magmatic processes involved in the generation of Large Igneous Provinces. I concentrate on the origin of variation in Cr in magmas and have developed a model in which high temperature melts intrude into and assimilate large amounts of upper continental crust.

Creating good lives through computer games

In this chapter we aim to explore how videogames can lead to improvements in wellbeing. Following Keyes (2007) and Huppert and So (2012) we view wellbeing as a multidimensional concept with both hedonic and eudaimonic aspects. In this chapter we take a broad approach in terms of exploring the impact of videogames on the psychological, social, and physical components of wellbeing. We explore how videogames have been shown to have an impact in each of these domains. Although there is a great deal of evidence for the actual and potential positive impacts of videogames, there are many unanswered questions regarding the situations in which there is likely to be an impact of videogame play on wellbeing, as well as the aspects of wellbeing that are likely to be impacted by videogame play. We conclude the chapter by outlining the key questions for future research. Our focus in this chapter is on the positive influences of videogames. We do not explore research on contexts in which negative impacts are possible or subgroups for which videogames could cause harm. However, these questions are obviously important and we see balanced engagement with age-appropriate videogames as a key prerequisite for any of the wellbeing benefits discussed below.

Interactive relationships among multiple dimensions of professional commitment: Implications for stress outcomes in lawyers

The purpose of this study was to examine the main and interactive effects of four dimensions of professional commitment on strain (i.e., depression, anxiety, perceived health status, and job dissatisfaction) for a sample of 176 law professionals. The study utilized a two-wave design in which professional commitment and strain were measured at Time 1 and strain was measured again at Time 2 (T2), 2 months later. A significant two-way interaction indicated that high affective commitment was related to less T2 job dissatisfaction only for lawyers with low accumulated costs. A significant four-way interaction indicated that high affective professional commitment was only related to fewer symptoms of T2 anxiety for lawyers with high normative professional commitment and both low limited alternatives and accumulated costs. A similar pattern of results emerged in regard to T2 perceived health status. The theoretical and practical implications of these results for career counselors are discussed.

Do-Rank: DCG optimization for learning-to-rank in tag-based item recommendation systems

Discounted Cumulative Gain (DCG) is a well-known ranking evaluation measure for models built with multiple relevance graded data. By handling tagging data used in recommendation systems as an ordinal relevance set of {negative,null,positive}, we propose to build a DCG based recommendation model. We present an efficient and novel learning-to-rank method by optimizing DCG for a recommendation model using the tagging data interpretation scheme. Evaluating the proposed method on real-world datasets, we demonstrate that the method is scalable and outperforms the benchmarking methods by generating a quality top-N item recommendation list.

Using an extended theory of planned behavior to predict a change in the type of blood product donated

Background Demand for essential plasma-derived products is increasing. Purpose This prospective study aims to identify predictors of voluntary non-remunerated whole blood (WB) donors becoming plasmapheresis donors. Methods Surveys were sent to WB donors who had recently (recent n = 1,957) and not recently donated (distant n = 1,012). Theory of Planned Behavior (TPB) constructs (attitude, subjective norm, self-efficacy) were extended with moral norm, anticipatory regret, and donor identity. Intentions and objective plasmapheresis donation for 527 recent and 166 distant participants were assessed. Results Multi-group analysis revealed that the model was a good fit. Moral norm and self-efficacy were positively associated while role identity (suppressed by moral norm) was negatively associated with plasmapheresis intentions. Conclusions The extended TPB was useful in identifying factors that facilitate conversion from WB to plasmapheresis donation. A superordinate donor identity may be synonymous with WB donation and, for donors with a strong moral norm for plasmapheresis, may inhibit conversion.

EVERSUN: A phase 2 trial of alternating sunitinib and everolimus as first-line therapy for advanced renal cell carcinoma

Background We hypothesised that alternating inhibitors of the vascular endothelial growth factor receptor (VEGFR) and mammalian target of rapamycin pathways would delay the development of resistance in advanced renal cell carcinoma (aRCC). Patients and methods A single-arm, two-stage, multicentre, phase 2 trial to determine the activity, feasibility, and safety of 12-week cycles of sunitinib 50 mg daily 4 weeks on / 2 weeks off, alternating with everolimus 10 mg daily for 5 weeks on / 1 week off, until disease progression or prohibitive toxicity in favourable or intermediate-risk aRCC. The primary end point was proportion alive and progression-free at 6 months (PFS6m). The secondary end points were feasibility, tumour response, overall survival (OS), and adverse events (AEs). The correlative objective was to assess biomarkers and correlate with clinical outcome. Results We recruited 55 eligible participants from September 2010 to August 2012. Demographics: mean age 61, 71% male, favourable risk 16%, intermediate risk 84%. Cycle 2 commenced within 14 weeks for 80% of participants; 64% received ≥22 weeks of alternating therapy; 78% received ≥22 weeks of any treatment. PFS6m was 29/55 (53%; 95% confidence interval [CI] 40% to 66%). Tumour response rate was 7/55 (13%; 95% CI 4% to 22%, all partial responses). After median follow-up of 20 months, 47 of 55 (86%) had progressed with a median progression-free survival of 8 months (95% CI 5–10), and 30 of 55 (55%) had died with a median OS of 17 months (95% CI 12–undefined). AEs were consistent with those expected for each single agent. No convincing prognostic biomarkers were identified. Conclusions The EVERSUN regimen was feasible and safe, but its activity did not meet pre-specified values to warrant further research. This supports the current approach of continuing anti-VEGF therapy until progression or prohibitive toxicity before changing treatment.

QoE modelling for VP9 and H.265 videos on mobile devices

Current mobile devices and streaming video services support high definition (HD) video, increasing expectation for more contents. HD video streaming generally requires large bandwidth, exerting pressures on existing networks. New generation of video compression codecs, such as VP9 and H.265/HEVC, are expected to be more effective for reducing bandwidth. Existing studies to measure the impact of its compression on users’ perceived quality have not been focused on mobile devices. Here we propose new Quality of Experience (QoE) models that consider both subjective and objective assessments of mobile video quality. We introduce novel predictors, such as the correlations between video resolution and size of coding unit, and achieve a high goodness-of-fit to the collected subjective assessment data (adjusted R-square >83%). The performance analysis shows that H.265 can potentially achieve 44% to 59% bit rate saving compared to H.264/AVC, slightly better than VP9 at 33% to 53%, depending on video content and resolution.

WNT16 influences bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk

We aimed to identify genetic variants associated with cortical bone thickness (CBT) and bone mineral density (BMD) by performing two separate genome-wide association study (GWAS) meta-analyses for CBT in 3 cohorts comprising 5,878 European subjects and for BMD in 5 cohorts comprising 5,672 individuals. We then assessed selected single-nucleotide polymorphisms (SNPs) for osteoporotic fracture in 2,023 cases and 3,740 controls. Association with CBT and forearm BMD was tested for ~2.5 million SNPs in each cohort separately, and results were meta-analyzed using fixed effect meta-analysis. We identified a missense SNP (Thr>Ile; rs2707466) located in the WNT16 gene (7q31), associated with CBT (effect size of -0.11 standard deviations [SD] per C allele, P = 6.2×10-9). This SNP, as well as another nonsynonymous SNP rs2908004 (Gly>Arg), also had genome-wide significant association with forearm BMD (-0.14 SD per C allele, P = 2.3×10-12, and -0.16 SD per G allele, P = 1.2×10-15, respectively). Four genome-wide significant SNPs arising from BMD meta-analysis were tested for association with forearm fracture. SNP rs7776725 in FAM3C, a gene adjacent to WNT16, was associated with a genome-wide significant increased risk of forearm fracture (OR = 1.33, P = 7.3×10-9), with genome-wide suggestive signals from the two missense variants in WNT16 (rs2908004: OR = 1.22, P = 4.9×10-6 and rs2707466: OR = 1.22, P = 7.2×10-6). We next generated a homozygous mouse with targeted disruption of Wnt16. Female Wnt16-/- mice had 27% (P<0.001) thinner cortical bones at the femur midshaft, and bone strength measures were reduced between 43%-61% (6.5×10-13<P<5.9×10-4) at both femur and tibia, compared with their wild-type littermates. Natural variation in humans and targeted disruption in mice demonstrate that WNT16 is an important determinant of CBT, BMD, bone strength, and risk of fracture. © 2012 Zheng et al.

Genome-Wide Association Studies of Asthma in Population-Based Cohorts Confirm Known and Suggested Loci and Identify an Additional Association near HLA

Rationale: Asthma has substantial morbidity and mortality and a strong genetic component, but identification of genetic risk factors is limited by availability of suitable studies. Objectives: To test if population-based cohorts with self-reported physician-diagnosed asthma and genome-wide association (GWA) data could be used to validate known associations with asthma and identify novel associations. Methods: The APCAT (Analysis in Population-based Cohorts of Asthma Traits) consortium consists of 1,716 individuals with asthma and 16,888 healthy controls from six European-descent population-based cohorts. We examined associations in APCAT of thirteen variants previously reported as genome-wide significant (P<5x10-8) and three variants reported as suggestive (P<5×10-7). We also searched for novel associations in APCAT (Stage 1) and followed-up the most promising variants in 4,035 asthmatics and 11,251 healthy controls (Stage 2). Finally, we conducted the first genome-wide screen for interactions with smoking or hay fever. Main Results: We observed association in the same direction for all thirteen previously reported variants and nominally replicated ten of them. One variant that was previously suggestive, rs11071559 in RORA, now reaches genome-wide significance when combined with our data (P = 2.4×10-9). We also identified two genome-wide significant associations: rs13408661 near IL1RL1/IL18R1 (PStage1+Stage2 = 1.1x10-9), which is correlated with a variant recently shown to be associated with asthma (rs3771180), and rs9268516 in the HLA region (PStage1+Stage2 = 1.1x10-8), which appears to be independent of previously reported associations in this locus. Finally, we found no strong evidence for gene-environment interactions with smoking or hay fever status. Conclusions: Population-based cohorts with simple asthma phenotypes represent a valuable and largely untapped resource for genetic studies of asthma. © 2012 Ramasamy et al.

Ankylosing spondylitis is associated with the anthrax toxin receptor 2 gene (ANTXR2)

Objectives ANTXR2 variants have been associated with ankylosing spondylitis (AS) in two previous genome-wide association studies (GWAS) (p∼9×10-8). However, a genome-wide significant association (p<5×10-8) was not observed. We conducted a more comprehensive analysis of ANTXR2 in an independent UK sample to confirm and refine this association. Methods A replication study was carried out with 2978 cases and 8365 controls. Then, these were combined with non-overlapping samples from the two previous GWAS in a meta-analysis. Human leukocyte antigen (HLA)-B27 stratification was also performed to test for ANTXR2-HLA-B27 interaction. Results Out of nine single nucleotide polymorphisms (SNP) in the study, five SNPs were nominally associated (p<0.05) with AS in the replication dataset. In the meta-analysis, eight SNPs showed evidence of association, the strongest being with rs12504282 (OR=0.88, p=6.7×10-9). Seven of these SNPs showed evidence for association in the HLA-B27-positive subgroup, but none was associated with HLA-B27-negative AS. However, no statistically significant interaction was detected between HLA-B27 and ANTXR2 variants. Conclusions ANTXR2 variants are clearly associated with AS. The top SNPs from two previous GWAS (rs4333130 and rs4389526) and this study (rs12504282) are in strong linkage disequilibrium (r2≥0.76). All are located near a putative regulatory region. Further studies are required to clarify the role played by these ANTXR2 variants in AS.