Seventy samples of foamed plastic collected from a high-energy, sandy beach in SW England have been characterised by FTIR and XRF. Most samples were polyurethane (PU; n=39) or polystyrene (PS; n=27) ...that were associated with variable concentrations of Br-Cl, Fe and Zn, indicative of the presence of halogenated flame retardants, iron oxides and Zn-based additives, respectively. Many samples of rigid PU contained Pb, historically used as a catalyst, at concentrations of up to 16,000μgg−1. A physiological extraction test that simulates the conditions in the gizzard of plastic-ingesting seabirds was applied to selected samples and results revealed that while Br and Zn were not measurably bioaccessible, Pb mobilisation progressed logarithmically over a period of time with maximum accessibilities after 220h of ~10% of total metal. Foamed PU is a source of bioaccessible Pb in the marine environment that has not previously been documented.
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•Foamed plastics have been collected from a beach in SW England.•Most samples were polystyrene- (PS-) or polyurethane- (PU-) based.•Elevated Br and Cl in some samples is attributed to the presence of flame retardants.•Pb in PU at concentrations up to 1.6% is attributed to use of the metal as a catalyst.•Pb is progressively mobilised from PU in a simulated avian digestive fluid.
The gene has been proposed as an attractive unit of analysis for association studies, but a simple yet valid, powerful, and sufficiently fast method of evaluating the statistical significance of all ...genes in large, genome-wide datasets has been lacking. Here we propose the use of an extended Simes test that integrates functional information and association evidence to combine the p values of the single nucleotide polymorphisms within a gene to obtain an overall p value for the association of the entire gene. Our computer simulations demonstrate that this test is more powerful than the SNP-based test, offers effective control of the type 1 error rate regardless of gene size and linkage-disequilibrium pattern among markers, and does not need permutation or simulation to evaluate empirical significance. Its statistical power in simulated data is at least comparable, and often superior, to that of several alternative gene-based tests. When applied to real genome-wide association study (GWAS) datasets on Crohn disease, the test detected more significant genes than SNP-based tests and alternative gene-based tests. The proposed test, implemented in an open-source package, has the potential to identify additional novel disease-susceptibility genes for complex diseases from large GWAS datasets.
Exome sequencing strategy is promising for finding novel mutations of human monogenic disorders. However, pinpointing the casual mutation in a small number of samples is still a big challenge. Here, ...we propose a three-level filtration and prioritization framework to identify the casual mutation(s) in exome sequencing studies. This efficient and comprehensive framework successfully narrowed down whole exome variants to very small numbers of candidate variants in the proof-of-concept examples. The proposed framework, implemented in a user-friendly software package, named KGGSeq (http://statgenpro.psychiatry.hku.hk/kggseq), will play a very useful role in exome sequencing-based discovery of human Mendelian disease genes.
Rural medical workforce shortage contributes to health disadvantage experienced by rural communities worldwide. This study aimed to determine the regional results of an Australian Government ...sponsored national program to enhance the Australian rural medical workforce by recruiting rural background students and establishing rural clinical schools (RCS). In particular, we wished to determine predictors of graduates' longer-term rural practice and whether the predictors differ between general practitioners (GPs) and specialists.
A cross-sectional cohort study, conducted in 2012, of 729 medical graduates of The University of Queensland 2002-2011. The outcome of interest was primary place of graduates' practice categorised as rural for at least 50% of time since graduation ('Longer-term Rural Practice', LTRP) among GPs and medical specialists. The main exposures were rural background (RB) or metropolitan background (MB), and attendance at a metropolitan clinical school (MCS) or the Rural Clinical School for one year (RCS-1) or two years (RCS-2).
Independent predictors of LTRP (odds ratio 95% confidence interval) were RB (2.10 1.37-3.20), RCS-1 (2.85 1.77-4.58), RCS-2 (5.38 3.15-9.20), GP (3.40 2.13-5.43), and bonded scholarship (2.11 1.19-3.76). Compared to being single, having a metropolitan background partner was a negative predictor (0.34 0.21-0.57). The effects of RB and RCS were additive-compared to MB and MCS (Reference group): RB and RCS-1 (6.583.32-13.04), RB and RCS-2 (10.364.89-21.93). Although specialists were less likely than GPs to be in LTRP, the pattern of the effects of rural exposures was similar, although some significant differences in the effects of the duration of RCS attendance, bonded scholarships and partner's background were apparent.
Among both specialists and GPs, rural background and rural clinical school attendance are independent, duration-dependent, and additive, predictors of longer-term rural practice. Metropolitan-based medical schools can enhance both specialist and GP rural medical workforce by enrolling rural background medical students and providing them with long-term rural undergraduate clinical training. Policy settings to achieve optimum rural workforce outcomes may differ between specialists and GPs.
Women are more likely to leave science, technology, engineering, and mathematics compared to men, in part because they lack similar role models such as peers, teaching assistants, and instructors. We ...examined the effect of a brief, scalable online intervention that consisted of a letter from a female role model who normalized concerns about belonging, presented time spent on academics as an investment, and exemplified overcoming challenges on academic performance and persistence. The intervention was implemented in introductory psychology (Study 1, N = 258) and chemistry (Study 2, N = 68) courses. Relative to the control group, the intervention group had higher grades and lower failing and withdrawal rates.
The extended Simes’ test (known as GATES) and scaled chi-square test were proposed to combine a set of dependent genome-wide association signals at multiple single-nucleotide polymorphisms (SNPs) for ...assessing the overall significance of association at the gene or pathway levels. The two tests use different strategies to combine association p values and can outperform each other when the number of and linkage disequilibrium between SNPs vary. In this paper, we introduce a hybrid set-based test (HYST) combining the two tests for genome-wide association studies (GWASs). We describe how HYST can be used to evaluate statistical significance for association at the protein-protein interaction (PPI) level in order to increase power for detecting disease-susceptibility genes of moderate effect size. Computer simulations demonstrated that HYST had a reasonable type 1 error rate and was generally more powerful than its parents and other alternative tests to detect a PPI pair where both genes are associated with the disease of interest. We applied the method to three complex disease GWAS data sets in the public domain; the method detected a number of highly connected significant PPI pairs involving multiple confirmed disease-susceptibility genes not found in the SNP- and gene-based association analyses. These results indicate that HYST can be effectively used to examine a collection of predefined SNP sets based on prior biological knowledge for revealing additional disease-predisposing genes of modest effects in GWASs.
Exome sequencing is becoming a standard tool for mapping Mendelian disease-causing (or pathogenic) non-synonymous single nucleotide variants (nsSNVs). Minor allele frequency (MAF) filtering approach ...and functional prediction methods are commonly used to identify candidate pathogenic mutations in these studies. Combining multiple functional prediction methods may increase accuracy in prediction. Here, we propose to use a logit model to combine multiple prediction methods and compute an unbiased probability of a rare variant being pathogenic. Also, for the first time we assess the predictive power of seven prediction methods (including SIFT, PolyPhen2, CONDEL, and logit) in predicting pathogenic nsSNVs from other rare variants, which reflects the situation after MAF filtering is done in exome-sequencing studies. We found that a logit model combining all or some original prediction methods outperforms other methods examined, but is unable to discriminate between autosomal dominant and autosomal recessive disease mutations. Finally, based on the predictions of the logit model, we estimate that an individual has around 5% of rare nsSNVs that are pathogenic and carries ~22 pathogenic derived alleles at least, which if made homozygous by consanguineous marriages may lead to recessive diseases.
Increased left atrial (LA) size and reduced global contractility are related to adverse cardiac events. The potential incremental value of assessing regional LA contractility is unknown. To assess ...the feasibility of measuring this variable angle, independent 2-dimensional speckle-tracking strain echocardiography (2D-SpTr) was used to measure regional LA strain (epsilon) and strain rate (SR) in normal individuals of various ages.
From standard apical views, 2D-SpTr was used on 84 normal subjects to measure longitudinal velocity, epsilon, and SR in 13 LA segmental regions. The values obtained from the different atrial regions were compared with each other and corresponding LA volumes before and after LA contraction.
Regional LA epsilon and SR could be measured in 77 of 84 normal subjects (94%). A consistent pattern of differences in LA regional function was noted with the annular regions, and particularly the inferior wall having a larger average peak velocity and epsilon and SR values in comparison with the mid and superior LA segments. Peak epsilon and SR during LA contraction had only a modest correlation with LA volumes.
The angle-independent technique of 2D-SpTr tracking can analyze regional LA epsilon and SR in 94% of normal subjects. Regional differences in LA contractility are consistently present. The annular regions, and especially the inferior wall have the highest values for LA epsilon and SR. The significance of these findings and their possible use in identifying disease states will require further study.