Toll-like receptor 4 and CD14 polymorphisms in ankylosing spondylitis: Evidence of a weak association in finns

Objective To investigate the association of CD14 and Toll-like receptor (TLR4) with ankylosing spondylitis (AS). Methods A promoter variant in CD14 and 2 coding polymorphisms in TLR4 were investigated in UK and Finnish families with AS and in a UK case-control study. A metaanalysis of published TLR4 and CD14 studies was performed. Results In the Finnish study the CD74-260bp T variant showed an association (p = 0.006), and the common 2-marker TLR4 haplotype showed a weak association (global p = 0.03), with AS. No associations were seen in the UK based studies or in the metaanalyses. Conclusion CD14 and TLR4 showed an association with AS in the Finns only.

Engineering cellulose nanofibre suspensions to control filtration resistance and sheet permeability

This study examines and quantifies the effect of adding polyelectrolytes to cellulose nanofibre suspensions on the gel point of cellulose nanofibre suspensions, which is the lowest solids concentration at which the suspension forms a continuous network. The lower the gel point, the faster the drainage time to produce a sheet and the higher the porosity of the final sheet formed. Two new techniques were designed to measure the dynamic compressibility and the drainability of nanocellulose–polyelectrolyte suspensions. We developed a master curve which showed that the independent variable controlling the behaviour of nanocellulose suspensions and its composite is the structure of the flocculated suspension which is best quantified as the gel point. This was independent of the type of polyelectrolyte used. At an addition level of 2 mg/g of nanofibre, a reduction in gel point over 50 % was achieved using either a high molecular weight (13 MDa) linear cationic polyacrylamide (CPAM, 40 % charge), a dendrimer polyethylenimine of high molecular weight of 750,000 Da (HPEI) or even a low molecular weight of 2000 Da (LPEI). There was no significant difference in the minimum gel point achieved, despite the difference in polyelectrolyte morphology and molecular weight. In this paper, we show that the gel point controls the flow through the fibre suspension, even when comparing fibre suspensions with solids content above the gel point. A lower gel point makes it easier for water to drain through the fibre network,reducing the pressure required to achieve a given dewatering rate and reducing the filtering time required to form a wet laid sheet. We further show that the lower gel point partially controls the structure of the wet laid sheet after it is dried. Halving the gel point increased the air permeability of the dry sheet by 37, 46 and 25 %, when using CPAM, HPEI and LPEI, respectively. The resistance to liquid flow was reduced by 74 and 90 %, when using CPAM and LPEI. Analysing the paper formed shows that sheet forming process and final sheet properties can be engineered and controlled by adding polyelectrolytes to the nanofibre suspension.

Spin it to win it: A comparison of constraints-led versus traditional coaching approaches

This thesis aimed to compare the effects of constraints-led and traditional coaching approaches on young cricket spin bowlers, with a specific research focus on increasing spin rates (i.e., Revolutions per Minute). Participants were 22 spin bowlers from either an Australia state youth squad or an academy in England. Results indicate that adopting a constraints-led approach can benefit younger, inexperienced bowlers, whilst a traditional approach may assist more skilled, older bowlers. The findings are discussed with regards to how they may inform the learning design of training programs by cricket coaches.

Fine mapping of variants associated with endometriosis in the WNT4 region on chromosome 1p36

Genome-wide association studies show strong evidence of association with endometriosis for markers on chromosome 1p36 spanning the potential candidate genes WNT4, CDC42 and LINC00339. WNT4 is involved in development of the uterus, and the expression of CDC42 and LINC00339 are altered in women with endometriosis. We conducted fine mapping to examine the role of coding variants in WNT4 and CDC42 and determine the key SNPs with strongest evidence of association in this region. We identified rare coding variants in WNT4 and CDC42 present only in endometriosis cases. The frequencies were low and cannot account for the common signal associated with increased risk of endometriosis. Genotypes for five common SNPs in the region of chromosome 1p36 show stronger association signals when compared with rs7521902 reported in published genome scans. Of these, three SNPs rs12404660, rs3820282, and rs55938609 were located in DNA sequences with potential functional roles including overlap with transcription factor binding sites for FOXA1, FOXA2, ESR1, and ESR2. Functional studies will be required to identify the gene or genes implicated in endometriosis risk.

No evidence for genetic association with the let-7 microRNA-binding site or other common KRAS variants in risk of endometriosis

STUDY QUESTION Is there a contribution of the minor allele at the KRAS single nucleotide polymorphism (SNP) rs61764370 in the let-7 microRNA-binding site to endometriosis risk? SUMMARY ANSWER We found no evidence for association between endometriosis risk and rs61764370 or any other SNPs in KRAS. WHAT IS KNOWN ALREADY The rs61764370 SNP in the 3' untranslated region of the KRAS gene is predicted to disrupt a complementary binding site (LCS6) for the let-7 microRNA, and was recently reported to be at a high frequency (31%) in 132 women of varying ancestry with endometriosis compared with frequencies in a database of population controls (up to 7.6% depending on ancestry), suggesting a strong effect of this KRAS SNP in the aetiology of endometriosis. STUDY DESIGN, SIZE AND DURATION This was a case-control study with a total of 11 206 subjects. The study was performed between February 2012 and July 2012. PARTICIPANTS/MATERIALS, SETTINGAND METHODS We first investigated a possible association between common markers in KRAS and endometriosis risk from our genome-wide association (GWA) data in 3194 surgically confirmed endometriosis cases and 7060 controls of European ancestry. Although rs61764370 was not genotyped on the GWA arrays, five SNPs typed in the study were highly correlated with this variant. The rs61764370 and two SNPs highly correlated with rs61764370 were then genotyped in 933 endometriosis cases and 952 controls using the Sequenom MassARRAY platform. MAIN RESULTS AND THE ROLE OF CHANCE There was no evidence for an association between rs61764370 and endometriosis risk P = 0.411 and odds ratio = 1.10 (95% confidence intervals: 0.88-1.36). We also found no evidence for an association between the highly correlated SNP rs17387019 and endometriosis. Their minor allele frequencies in cases and controls were of 0.087-0.091 similar to the population frequency reported previously for this variant in controls. Analyses of endometriosis cases with revised American Fertility Society stage III/IV disease also showed no evidence for an association between these SNPs and endometriosis risk. LIMITATIONS AND REASONS FOR CAUTION The GWA and genotyped data sets were not independent since individuals and cases from some families overlap. Controls in our GWA study were not screened for endometriosis. WIDER IMPLICATIONS OF THE FINDINGS The key SNP, rs61764370, was genotyped in a subset of samples. Our results do not support the suggestion that carrying the minor allele at rs61764370 contributes to a significant number of endometriosis cases and rs61764370 is, therefore, unlikely to be a useful marker of endometriosis risk. STUDY FUNDING/COMPETING INTEREST(S) The research was funded by grants from the Australian National Health and Medical Research Council and Wellcome Trust. None of the authors has competing interests for the study.

Evaluation of polymorphisms in predicted target sites for micro RNAs differentially expressed in endometriosis

Previous microarray analyses identified 22 microRNAs (miRNAs) differentially expressed in paired ectopic and eutopic endometrium of women with and without endometriosis. To investigate further the role of these miRNAs in women with endometriosis, we conducted an association study aiming to explore the relationship between endometriosis risk and single-nucleotide polymorphisms (SNPs) in miRNA target sites for these differentially expressed miRNAs. A panel of 102 SNPs in the predicted miRNA binding sites were evaluated for an endometriosis association study and an ingenuity pathway analysis was performed. Fourteen rare variants were identified in this study. We found SNP rs14647 in the Wolf-Hirschhorn syndrome candidate gene1 (WHSC1) 3'UTR (untranslated region) was associated with endometriosis-related infertility presenting an odds ratio of 12.2 (95% confidence interval = 2.4-60.7, P = 9.03 x 10(-5)). SNP haplotype AGG in the solute carrier family 22, member 23 (SLC22A23) 3'UTR was associated with endometriosis-related infertility and more severe disease. With the individual genotyping data, ingenuity pathways analysis identified the tumour necrosis factor and cyclin-dependant kinase inhibitor as major factors in the molecular pathways. Significant associations between WHSC1 alleles and endometriosis-related infertility and SLC22A23 haplotypes and the disease severe stage were identified. These findings may help focus future research on subphenotypes of this disease. Replication studies in independent large sample sets to confirm and characterize the involvement of the gene variation in the pathogenesis of endometriosis are needed.

Access To Justice In The ASEAN The Key Role Of UNCITRAL

UNCITRAL’s operation as a subsidiary of the UN General Assembly, tasked to unify and harmonise international trade law is a necessary and indispensable element of the UN’s mandate to maintain international peace and security. Strong legal frameworks which are compatible with those of international trading partners often accompany accelerated growth in economic capacity and stability. Over time, access to markets and resultant growth in economic and human development creates a disincentive for instability as incomes and standards of living rise. Human and economic development, facilitated by a modernised and just legal framework that is available to the broadest range of recipients goes hand in hand with the maintenance of domestic and regional peace, particularly in regions such as the ASEAN , one of the fastest growing in the world covering approximately 30% of global population and with a number of strong global economic neighbours including Japan, Korea, China (to the north), Australia (to the south) and Singapore (to the west). In an increasingly interconnected world, the ability of government, enterprise and individuals to participate in the global supply chain offers opportunities for economic growth and development. Over its almost 50 years of operations, UNCITRAL has produced a range of important texts that are designed to underpin world trade. A key implicit assumption underpinning the development of UNCITRAL texts is that the texts, once adopted can and will be applied in adopting states.

A multi-centre open-label randomised non-inferiority trial comparing watchful waiting to antibiotic treatment for acute otitis media without perforation in low-risk urban Aboriginal and Torres Strait Islander children (the WATCH trial): study protocol for a randomised controlled trial

Background Treatment guidelines recommend watchful waiting for children older than 2 years with acute otitis media (AOM) without perforation, unless they are at high risk of complications. The high prevalence of chronic suppurative otitis media (CSOM) in remote Aboriginal and Torres Strait Islander communities leads these children to be classified as high risk. Urban Aboriginal and Torres Strait Islander children are at lower risk of complications, but evidence to support the subsequent recommendation for watchful waiting in this population is lacking. Methods/Design This non-inferiority multi-centre randomised controlled trial will determine whether watchful waiting is non-inferior to immediate antibiotics for urban Aboriginal and Torres Strait Islander children with AOM without perforation. Children aged 2 − 16 years with AOM who are considered at low risk for complications will be recruited from six participating urban primary health care services across Australia. We will obtain informed consent from each participant or their guardian. The primary outcome is clinical resolution on day 7 (no pain, no fever of at least 38 °C, no bulging eardrum and no complications of AOM such as perforation or mastoiditis) as assessed by general practitioners or nurse practitioners. Participants and outcome assessors will not be blinded to treatment. With a sample size of 198 children in each arm, we have 80 % power to detect a non-inferiority margin of up to 10 % at a significance level of 5 %, assuming clinical improvement of at least 80 % in both groups. Allowing for a 20 % dropout rate, we aim to recruit 495 children. We will analyse both by intention-to-treat and per protocol. We will assess the cost- effectiveness of watchful waiting compared to immediate antibiotic prescription. We will also report on the implementation of the trial from the perspectives of parents/carers, health professionals and researchers. Discussion The trial will provide evidence for the safety and effectiveness of watchful waiting for the management of AOM in Aboriginal and Torres Strait Islander children living in urban settings who are considered to be at low risk of complications.

The psychometric properties of the Kessler Psychological Distress Scale (K6) in a general population sample of adolescents

The 6-item Kessler Psychological Distress Scale (K6; Kessler et al., 2002) is a screener for psychological distress that has robust psychometric properties among adults. Given that a significant proportion of adolescents experience mental illness, there is a need for measures that accurately and reliably screen for mental disorders in this age group. This study examined the psychometric properties of the K6 in a large general population sample of adolescents (N = 4,434; mean age = 13.5 years; 44.6% male). Factor analyses were conducted to examine the dimensionality of the K6 in adolescents and to investigate sex-based measurement invariance. This study also evaluated the K6 as a predictor of scores on the Strengths and Difficulties Questionnaire (SDQ; Goodman, 1997). The K6 demonstrated high levels of internal consistency, with the 6 items loading primarily on 1 factor. Consistent with previous research, females reported higher mean levels of psychological distress when compared with males. The identification of sex-based measurement noninvariance in the item thresholds indicated that these mean differences most likely represented reporting bias in the K6 items rather than true differences in the underlying psychological distress construct. The K6 was a fair to good predictor of abnormal scores on the SDQ, but predictive utility was relatively low among males. Future research needs to focus on refining and augmenting the K6 scale to maximize its utility in adolescents. (PsycINFO Database Record (c) 2015 APA, all rights reserved)