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Pelvic floor muscle exercises (PFME) are recommended for treatment of urinary incontinence with less evidence available about the effect on female sexual function (FSF) and childbirth.To investigate the effect of antenatal PFME on FSF during pregnancy and the first three months following birth as a primary outcome, and on labour and birth outcomes as a secondary outcome.200 nulliparous women were randomised to control (n = 100) and intervention (n = 100) groups. The women in the intervention group (IG) undertook PFME from 20 weeks gestation until birth and had routine antenatal care, while those in the control group (CG) received routine antenatal care only. The Female Sexual Function Index (FSFI) was used to measure FSF at 36 weeks gestation and three months postnatal. Baseline characteristics and childbirth data were also collected and analysed using SPSS.There were no statistically significant differences between the two groups in terms of FSF scores during pregnancy and on childbirth outcomes. Sexual satisfaction was slightly higher in the CG [Mean ± SD, CG: 4.35 ± 1.45 vs. IG: 3.70 ± 1.50, (P = 0.03)] at three months after birth. However, 50% of women adhered to the PFME, and 40% of women did not resume sex by three months after the birth.Though some trends were observed, the results showed no effect of PFME on sexual function or labour and birth outcomes. This needs to be interpreted considering the 50% adherence to PFME. More research is recommended.

Our objective was to quantify the effects of yogurt supplementation and nutrition education over three months on the linear growth of infants at risk of stunting. We conducted a three-arm pilot randomized controlled trial: (1) nutrition education for mothers; (2) nutrition education plus a daily yogurt supplement (50 g) for the index child; and (3) usual care (control). Dyads of children aged 4–6 months and at risk of stunting [length-for-age z-score (LAZ) ≤ −1 SD and >−2 SD] and their mothers with ≤10 years of education were eligible for the study. Participants were recruited from five slum areas in Dhaka, Bangladesh. Intention-to-treat (N = 162) and complete-case analyses (N = 127) showed no between-group statistically significant differences in LAZ or weight-for-age (WAZ). However, the yogurt group showed greater change in linear growth compared to the control (LAZ: mean difference 0.20, 95% CI: −0.06, 0.47, p-value 0.13), which was also slightly greater than the education-only group. Children in the yogurt plus group were five times (95% CI: 0.80, 31.80, p-value 0.09) more likely to meet the minimum dietary diversity (MDD) score compared to the control. A 3-month follow-up of this pilot study did not demonstrate that yogurt was beneficial to linear growth. However, there were encouraging trends that merit replication of the intervention with larger samples and longer follow-ups.

Despite the proliferation of augmented reality (AR) apps, Australian primary teachers have yet to use them widely for the teaching of multimodal literacies. Conceptualising teachers’ knowledge of using digital technologies to teach multimodal literacies as a form of technological pedagogical content knowledge or TPACK(ML), this study examined teacher differences through a cluster analysis of survey responses collected from a sample of 142 Australian primary school teachers. Two distinct clusters of teachers were derived. The first cluster with lower TPACK(ML) comprised teachers with lower self-reported confidence in facilitating new cultures of learning that are participatory and technology-driven in nature. In their open-ended survey responses, these teachers shared their unfamiliarity with AR, as well as concerns about their personal technical competency and how AR could be integrated into the curriculum. The second cluster of teachers rated themselves higher in TPACK(ML) and in how they used technology to support language learning pedagogies. They were able to propose different pedagogical strategies to engage students’ multimodal literacies meaningfully with AR in their open-ended survey responses. The implications of the study’s findings were discussed, and recommendations were proposed for designing and sustaining differentiated forms of teacher professional development for teaching multimodal literacies with emergent digital technologies.

Background and objectives: Wellbeing among university students is associated with better academic outcomes and diminished harm from mental illness. This study systematically reviews and meta-analyses longitudinal studies of the antecedents and consequences of wellbeing within this population, providing an overview which establishes a ‘natural history’ of wellbeing to form a background for intervention and policy. Method: This study was a systematic review and meta-analysis of the peer-reviewed literature, based on a broad range of search terms across four journal databases in psychology, medicine and education. Studies were organised by the domain of their study variables (i.e., Self, Relationships, or Institutional Context) and variables relating to wellbeing were extracted. The incremental effect of study variables measured at baseline upon prospective wellbeing was calculated with semipartial correlation coefficients which controlled for baseline wellbeing. Meta-regressions were used to examine the effect of follow-up interval on effect sizes. Results: Sixty-two longitudinal studies of university student cohorts were identified. In 57 studies, wellbeing was an outcome variable. Meta-analyses showed that effects were moderated by measurement interval between baseline and follow-up, becoming weaker with longer intervals, and that this was not an artifact of the measurement instrument. The study factors with the strongest positive effect sizes after controlling for baseline wellbeing were authenticity, self-esteem, self-support for autonomy, emotional repair, and ability to regulate distress and despondency; relationship commitment and group memberships; self-identification with the university and time pressure. Study factors with the strongest negative effect sizes were uncertainty regarding university, materialism, a belief in social complexity, depression, and stress. In five studies, wellbeing was an antecedent, showing positive associations with educational outcomes. Conclusion: This review identified several antecedents of student wellbeing which could be targeted for interventions. These included self-relationship, emotion regulation, and interventions to decrease mental illness. Universities might also make it easier to establish and maintain groups (e.g., study cohorts, interest groups). Many variables which affect wellbeing are not amenable to study with experimental methods, but their study and use in wellbeing interventions should not be neglected. Because the antecedents of wellbeing are numerous and diverse, further research in the area should take advantage of research methods which maximise the variety of data collected and minimise respondent burden, such as passively collected and linked data.

Objectives:It is unknown whether there are sex-related profiles of cardiometabolic health that contribute differently to age-related changes in brain health during midlife. We studied how latent classes of middle-aged individuals clustering by age, sex, menopause and cardiometabolic health were associated with brain structure and cognitive performance.Methods:Health, brain and abdominal magnetic resonance imaging (MRI) data from the UK Biobank cohort (men and women >40 years in the United Kingdom) were used. We applied latent class analysis to identify groups of individuals based on age, sex, menopausal status and cardiometabolic health. We examined associations of class membership with brain volumes (total brain [TBV], grey matter [GMV], white matter [WMV], hippocampal [HV], white matter hyperintensities [WMHV]) and cognitive performance.Results:Data were available for 36,420 individuals (mean age 64.9 years, 48.5% women). Eight latent classes differing in age, sex and cardiometabolic risk were identified. Class 1 (reference class) included individuals with the lowest probability of older age and cardiometabolic risk, and they had the most positive associations with cognitive function and brain volumes. In those aged >60, but not in those aged 50-60 years, the negative associations of age with TBV, GMV and WMV were greater in the class comprising healthier older women than classes comprising older men of varying cardiometabolic and vascular health. There were no age-class interactions for cognitive test performance.Conclusions:Latent class analysis detected groups of middle-aged individuals clustering by cardiometabolic health. The relationship of age with brain volumes varies by sex, menopausal status and cardiometabolic health profile.

An Italian ryegrass cultivar (Lolium multiflorum Lam. cv. Bb2067), selected and bred for increased leaf magnesium (Mg) concentration in the 1970s, reduced the incidence of hypomagnesaemia in sheep under experimental grazings. Here, we report evidence from archival experiments showing that cv. Bb2067 had consistently greater Mg concentrations at multiple sites. We also aimed to quantify variation in leaf Mg concentration among modern perennial ryegrass (Lolium perenne L.), hybrid ryegrass (Lolium perenne × multiflorum), and tall fescue (Festuca arundinacea Shreb.) cultivars. Data are reported from unpublished 1980s field-plot experiments for cv. Bb2067 and contemporaneous reference cultivars, sown at two UK locations in 1983 and 1984, and from 397 cultivars of modern forage grass in 13 UK-based breeding experiments sampled in spring 2013. Across sites, years and cuts, cv. Bb2067 had a consistently greater leaf Mg concentration and lower potassium (K) concentration and forage tetany index (FTI) than reference cultivars in the 1980s experiments. Seasonal variation in leaf Mg and K concentrations and FTI were observed in the 1980s experiments, with K concentrations being generally greatest and Mg concentrations smallest in spring. Among modern forage grasses, there was large variation in leaf Mg concentration (up to 6.3-fold) and FTI (up to 2.1-fold), both within and between species, which varied independently of yield. Among a subset of hybrid ryegrass cultivars, there is evidence that the high Mg trait is already present in some modern breeding lines, albeit previously unreported. The variation in leaf Mg concentration and FTI among old and new cultivars shows there is considerable potential to breed forages with improved mineral quality to improve livestock health, potentially without compromising yield or other nutritional traits.

The human innate immunity factor apolipoprotein L-I (APOL1) protects against infection by several protozoan parasites, including Trypanosoma brucei brucei. Endocytosis and acidification of high-density lipoprotein–associated APOL1 in trypanosome endosomes leads to eventual lysis of the parasite due to increased plasma membrane cation permeability, followed by colloid-osmotic swelling. It was previously shown that recombinant APOL1 inserts into planar lipid bilayers at acidic pH to form pH-gated nonselective cation channels that are opened upon pH neutralization. This corresponds to the pH changes encountered during endocytic recycling, suggesting APOL1 forms a cytotoxic cation channel in the parasite plasma membrane. Currently, the mechanism and domains required for channel formation have yet to be elucidated, although a predicted helix-loop-helix (H-L-H) was suggested to form pores by virtue of its similarity to bacterial pore-forming colicins. Here, we compare recombinant human and baboon APOL1 orthologs, along with interspecies chimeras and individual amino acid substitutions, to identify regions required for channel formation and pH gating in planar lipid bilayers. We found that whereas neutralization of glutamates within the H-L-H may be important for pH-dependent channel formation, there was no evidence of H-L-H involvement in either pH gating or ion selectivity. In contrast, we found two residues in the C-terminal domain, tyrosine 351 and glutamate 355, that influence pH gating properties, as well as a single residue, aspartate 348, that determines both cation selectivity and pH gating. These data point to the predicted transmembrane region closest to the APOL1 C terminus as the pore-lining segment of this novel channel-forming protein.

This article describes a new database—TM‐Link—that contains 12 million trademark applications and registrations across six jurisdictions. A feature of the database is the identification of trademark equivalents (or families) within and across national trademark offices. Equivalent trademarks are two, or more, insignias for the same product applied for by the same company. Unlike patents, the incentive to file for global priority is comparatively weak since legal priority for trademarks is territorial. To identify the number of true trademark equivalents we therefore create synthetic links using a neural network‐based machine learning algorithm.

Do production capabilities of countries evolve from existing capabilities or emerge de novo? The Product Space approach developed by Hidalgo, Klinger, Barabási and Hausmann postulates that a country’s existing industrial structure largely determines its opportunities for industrial upgrading. However, this is difficult to reconcile with the export dynamism of many developing countries such as Thailand, Malaysia, Costa Rica and Vietnam that transformed from primary commodity dependence to exporters of dynamic manufactured products. In each of these cases, global production sharing facilitated industrial transition. In this article, we advance the Product Space approach to accommodate the role of global production sharing. Using a newly constructed multi-country data set of manufacturing exports that distinguishes between trade within global production networks and traditional horizontal trade, we find that that existing industrial structure has a smaller impact, but trade openness has a greater impact, on industrial upgrading within vertically integrated global industries.

Evidence suggests that Arabic-speaking refugees in Australia seek help from informal sources, including religious and community leaders, when experiencing mental health issues. Despite their significant influence, there is scarce research exploring attitudes of Arabic-speaking leaders toward mental illness. The current exploratory study explored mental illness stigma and various factors among Arabic-speaking religious and community leaders. This study uses a subset of data from an evaluation trial of mental health literacy training for Arabic-speaking religious and community leaders. Our dataset contains the pre-intervention survey responses for 52 Arabic-speaking leaders (69.2% female, mean age = 47.1, SD = 15.3) on the ability to recognise a mental disorder, beliefs about causes for developing mental illness, and two stigma measures, personal stigma, and social distance. Being female was associated with a decrease in personal stigma. An increase in age was associated with an increase in personal stigma. Correct recognition of a mental disorder was associated with decreased personal stigma, and after adjusting for age and gender, significance was retained for the I-would-not-tell-anyone subscale. Endorsing the cause “being a person of weak character” was associated with an increase in personal stigma. There is an urgent need for future research to elucidate stigma to develop effective educational initiatives for stigma reduction among Arabic-speaking leaders.

Apolipoprotein L-I (APOL1) is a channel-forming effector of innate immunity. The common human APOL1 variant G0 provides protection against infection with certain Trypanosoma and Leishmania parasite species, but it cannot protect against the trypanosomes responsible for human African trypanosomiasis. Human APOL1 variants G1 and G2 protect against human-infective trypanosomes but also confer a higher risk of developing chronic kidney disease. Trypanosome-killing activity is dependent on the ability of APOL1 to insert into membranes at acidic pH and form pH-gated cation channels. We previously mapped the channel's pore-lining region to the C-terminal domain (residues 332–398) and identified a membrane-insertion domain (MID, residues 177–228) that facilitates acidic pH-dependent membrane insertion. In this article, we further investigate structural determinants of cation channel formation by APOL1. Using a combination of site-directed mutagenesis and targeted chemical modification, our data indicate that the C-terminal heptad-repeat sequence (residues 368–395) is a bona fide leucine zipper domain (ZIP) that is required for cation channel formation as well as lysis of trypanosomes and mammalian cells. Using protein-wide cysteine-scanning mutagenesis, coupled with the substituted cysteine accessibility method, we determined that, in the open channel state, both the N-terminal domain and the C-terminal ZIP domain are exposed on the intralumenal/extracellular side of the membrane and provide evidence that each APOL1 monomer contributes four transmembrane domains to the open cation channel conformation. Based on these data, we propose an oligomeric topology model in which the open APOL1 cation channel is assembled from the coiled-coil association of C-terminal ZIP domains.

Offshoring research and development (R&D) commonly invokes concerns regarding the loss of high value jobs and a hollowing out of technological capabilities, but it can also benefit domestic firms by enabling them to tap into the global technological frontier. We study the effect of R&D offshoring on industrial productivity in the home country using industry-level data for 18 OECD countries over a 26-year period. Simultaneity between productivity and R&D offshoring is addressed by using foreign tax policy as an instrument for offshored R&D. We show that R&D offshoring contributes positively to productivity in the home country, irrespective of the host country destination.

The introduction of High Productivity Vehicles (HPVs) in Australia, through the Performance Based Standards (PBS) scheme, was predicated on new mechanical engineering standards that were mandated especially for these new vehicles. These standards improved vehicle stability, general performance and safety, especially safety. Two national surveys showed both massive safety and productivity benefits compared to conventional Australian road freight fleets. The first Australian PBS vehicles operated under permits from 1997 but the formalized Australian scheme was implemented in 2006. So arguably the introduction of HPVs under permit and now under a formal regulatory PBS framework has allowed some 20 years of research observations. However, only one major type of single rigid, high productivity truck, without a trailer, has been active in an urban environment as a pilot, over that time. This paper examines this special urban High Productivity Vehicle which could be exceptionally useful for the urban freight task in many countries should they ever adopt it.

Pasifika populations experience high incidence and prevalence of obesity and T2DM. However, no international review of lifestyle intervention studies amongst Pasifika communities exists. This study seeks to identify the effect and translatability of lifestyle strategies on weight amongst Pasifika populations.Lifestyle studies involving ≥90% adult Pasifika participants measuring weight change were eligible for inclusion. Database searching was carried out up to December 2021. Databases searched were MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCOhost) and ProQuest Central. Risk of bias was assessed using RoB2 (RCTs) and the National Heart, Lung and Blood Institute (NHLBI) quality assessment tool. Meta-analysis and meta-regression used a bivariate random-effects model. Strategies were coded against pre-identified components of the newly proposed Cultural and Sustainability Assessment of Intervention (CSAI) framework.Twenty-three studies (Qualitative and quantitative analysis show tailored lifestyle interventions has had an estimated small but beneficial effect on WL amongst Pasifika communities. Potential for tailored interventions design to incorporate psychosocial and behavioural considerations. The CSAI has the potential for systematically identifying cultural and sustainability components of efficacy in interventions.This review was funded under Western Sydney University's Postgraduate Research Scholarship.

The human apolipoprotein L gene family encodes the apolipoprotein L1–6 (APOL1–6) proteins, which are effectors of the innate immune response to viruses, bacteria and protozoan parasites. Due to a high degree of similarity between APOL proteins, it is often assumed that they have similar functions to APOL1, which forms cation channels in planar lipid bilayers and membranes resulting in cytolytic activity. However, the channel properties of the remaining APOL proteins have not been reported. Here, we used transient overexpression and a planar lipid bilayer system to study the function of APOL proteins. By measuring lactate dehydrogenase release, we found that APOL1, APOL3, and APOL6 were cytolytic, whereas APOL2, APOL4, and APOL5 were not. Cells expressing APOL1 or APOL3, but not APOL6, developed a distinctive swollen morphology. In planar lipid bilayers, recombinant APOL1 and APOL2 required an acidic environment for the insertion of each protein into the membrane bilayer to form an ion conductance channel. In contrast, recombinant APOL3, APOL4, and APOL5 readily inserted into bilayers to form ion conductance at neutral pH, but required a positive voltage on the side of insertion. Despite these differences in membrane insertion properties, the ion conductances formed by APOL1-4 were similarly pH-dependent and cation-selective, consistent with conservation of the pore-lining region in each protein. Thus, despite structural conservation, the APOL proteins are functionally different. We propose that these proteins interact with different membranes and under different voltage and pH conditions within a cell to effect innate immunity to different microbial pathogens.

This paper reports on the construction of a new database – called TM-Link – that contains 12 million trade mark applications and registrations across six jurisdictions – Australia, Canada, New Zealand, the United States, the United Kingdom and the European Union. A new feature of the database is the identification of trade mark equivalents (or families) within and across national trade mark offices. Equivalent trade marks are two, or more, insignias for the same product applied for by the same company. For patents, equivalents can be easily identified as they are almost universally linked through a legal priority nominated in the application, but for trade marks legal priority is territorial, so the incentive to file for global priority is comparatively weak. To identify the number of true trade mark equivalents we therefore create synthetic links using a neural network-based machine learning algorithm.

Objectives Age and female sex are risk factors for dementia, and menopause is associated with cognitive dysfunction. Previous work largely considered the effects of sex and menopause as being independent of age. We studied whether age interacts with sex or menopause in explaining imaging biomarkers of dementia during midlife. Methods In this cross-sectional study of UK Biobank participants with brain magnetic resonance imaging (MRI), we explored the interaction of age with sex or menopausal status in explaining total brain volume (TBV), gray matter volume (GMV), white matter volume (WMV), white matter hyperintensity volume (WMHV), regional cortical volume , and subcortical volume. Results Data were available for 1827 postmenopausal women, 230 pre/perimenopausal women and 2165 men (median age 63.3 years). There was a significant interaction between age and sex (P = .024) for TBV, where the inverse association age with TBV was steeper in women (β = –5.35 mL/year) than in men (β = –4.77 mL/year). Similar age–sex interactions were also observed for GMV and WMV. In women, there was a significant interaction between age and menopausal status (P = .007) where the inverse association of age with TBV was steeper in postmenopausal (β = –5.89 mL/year) than in pre/perimenopausal women (β = –1.61 mL/year). Similar age–menopause interactions were found in predicting lower GMV and higher WMHV. Differences in the direction of these age–sex and age–menopause interactions were found for regional cortical and subcortical brain volumes. Conclusion Sex and menopause both interact with age during midlife in explaining MRI biomarkers of dementia. Further work is required to understand the mechanisms driving these interactions to develop strategies for delaying dementia.

Background Refugee populations have particularly high rates of mental health problems, including Posttraumatic Stress Disorder (PTSD) and depression. However, uptake of mental health care may be low even when severe depression and PTSD symptoms are present in individuals following resettlement. This is likely due, at least in part, to cultural influences on refugees’ knowledge and beliefs about mental health problems and their treatment. We sought to provide preliminary evidence for the effectiveness of a culturally tailored mental health promotion program for Arabic-speaking refugees. Methods A total of 33 Arabic-speaking refugees resettled in South Western Sydney were recruited and completed intervention which consisted of weekly three-hour sessions for 4 weeks delivered in Arabic. Key aspects of mental health literacy, help-seeking intentions and levels of general psychological distress were assessed, by means of a self-report survey, pre-intervention, (immediately) post-intervention and 3 months following intervention. Results Of the 33 participants that completed the intervention, 31 completed the immediate post-intervention survey and 29 completed the 3 months follow-up survey. Improvements in most aspects of mental health literacy assessed were found immediately post-intervention and at follow-up, although only changes relating to stigmatising attitudes were statistically significant. Additionally, a statistically significant decrease in participants’ levels of general psychological distress was observed immediately following the intervention, and this decrease was sustained at follow-up. Conclusion While further research employing a more rigorous study design and larger sample size will be needed, results of this initial trial suggest that a culturally tailored mental health promotion program targeting key aspects of mental health literacy can improve the mental health of Arabic-speaking refugees resettled in a Western nation.

Recently evolved alleles of Apolipoprotein L-1 (APOL1) provide increased protection against African trypanosome parasites while also significantly increasing the risk of developing kidney disease in humans. APOL1 protects against trypanosome infections by forming ion channels within the parasite, causing lysis. While the correlation to kidney disease is robust, there is little consensus concerning the underlying disease mechanism. We show in human cells that the APOL1 renal risk variants have a population of active channels at the plasma membrane, which results in an influx of both Na+and Ca2+. We propose a model wherein APOL1 channel activity is the upstream event causing cell death, and that the activate-state, plasma membrane-localized channel represents the ideal drug target to combat APOL1-mediated kidney disease.

The spread of COVID-19 is expected to put a large strain on many hospital resources, including ICU bed space, and mortuary capacity. In this report we study the possible demands on ICU and mortuary capacity in Sydney, Australia, using an adapted SEIR epidemiological model.

Interest in trypanosome lytic factors (TLFs) and apolipoprotein L1, the ion channel-forming protein component of TLFs, has increased tenfold since 2010. This is due to the association of African variants of APOL1 with kidney disease such that interest has reached circles beyond parasitology. We have extensive experience purifying and working with these proteins and protein complexes. Herein we describe our detailed purification protocols to aid the new burgeoning field by providing an opportunity for consistency in reagents used across laboratories. We emphasize that it is imperative to maintain APOL1 protein intact (~42 kDa) to analyze the active ion channel-forming component/protein.

Background There is now evolving data exploring the relationship between depression and various individual lifestyle factors such as diet, physical activity, sleep, alcohol intake, and tobacco smoking. While this data is compelling, there is a paucity of longitudinal research examining how multiple lifestyle factors relate to depressed mood, and how these relations may differ in individuals with major depressive disorder (MDD) and those without a depressive disorder, as ‘healthy controls’ (HC). Methods To this end, we assessed the relationships between 6 key lifestyle factors (measured via self-report) and depressed mood (measured via a relevant item from the Patient Health Questionnaire) in individuals with a history of or current MDD and healthy controls (HCs). Cross-sectional analyses were performed in the UK Biobank baseline sample, and longitudinal analyses were conducted in those who completed the Mental Health Follow-up. Results Cross-sectional analysis of 84,860 participants showed that in both MDD and HCs, physical activity, healthy diet, and optimal sleep duration were associated with less frequency of depressed mood (all p p p p p p p = 0.024), while a better-quality diet was indicated to be protective of depressed mood in HCs (OR = 0.92; p = 0.045) but was not associated with depressed mood in the MDD sample. In a cross-sectional (OR = 0.91; p Conclusions Our data suggest that several lifestyle factors are associated with depressed mood, and in particular, it calls into consideration habits involving increased screen time and a poor sleep and dietary pattern as being partly implicated in the germination or exacerbation of depressed mood.

Interest in trypanosome lytic factors (TLFs) and apolipoprotein L1, the ion channel-forming protein component of TLFs, has increased tenfold since 2010. This is due to the association of African variants of APOL1 with kidney disease such that interest has reached circles beyond parasitology. We have extensive experience purifying and working with these proteins and protein complexes. Herein we describe our detailed purification protocols to aid the new burgeoning field by providing an opportunity for consistency in reagents used across laboratories. We emphasize that it is imperative to maintain APOL1 protein intact (~42 kDa) to analyze the active ion channel-forming component/protein.

Multiple endocrine neoplasia type 1 (MEN 1) has marked severity variation between individuals with the same mutation. To investigate any relationship between promoter methylation and clinical features, blood and tissue samples were collected from 16 members of the Tasman 1 MEN 1 kindred carrying a common splice site mutation and 7 patients with sporadic MEN 1. Methylation at 39 CpGs in the MEN1 promoter were assessed in formalin fixed, paraffin embedded parathyroid tissue. Clinical disease severity markers included age at first parathyroid operation, parathyroid hormone level and corrected serum calcium levels. Six patients with sporadic hyperparathyroidism were used for comparison. Minimal methylation was observed in all patients across CpG sites 1-23. In contrast, hypermethylation was observed at CpG sites 24-31 in MEN 1 patients, a pattern not observed in patients with non-MEN 1 parathyroid disease. Mean methylation at sites 24-31 was significantly correlated with age at first parathyroid operation (r = 0.652, p = 0.041). A permutation test, utilising the mean correlation coefficient (r = -0.401) revealed a possible association between relative PHPT severity and methylation score for each significant CpG site (p0.103). This novel study reveals evidence supporting a possible association between altered MEN1 promoter methylation and clinical severity of disease.

Aim: Marine protected areas (MPAs) are increasingly implemented to conserve or restore coral reef biodiversity, yet evidence of their benefits for enhancing coral cover is limited and variable. Location: 30 MPAs worldwide and nearby sites (within 10 km). Taxa: Cover of key functional groups for coral (total, branching, massive and tabular), and algae (total, filamentous, foliose) and total biomass of reef fish trophic groups (excavator, scraper, browser, higher carnivore). Methods: We used a global dataset obtained using standardized survey methods at 465 sites associated with 30 MPAs in 28 ecoregions to test the effects of five key MPA attributes (>10 years old, well‐enforced, no‐take, large and isolated) on coral cover, algal cover and reef fish biomass. We also tested the direct (reducing disturbance by human activities) versus indirect pathways (increasing grazing potential through recovering populations of herbivorous fishes) by which MPAs can influence coral and algal cover. Results: Only well‐enforced, no‐take and old (>10 years) MPAs had higher total coral cover (response ratio 1.08–1.19×) than fished sites, mostly due to the increased cover of massive coral growth forms (1.34–2.06×). This effect arose through both the direct influence of protection and indirect benefits of depressed algal cover by recovering herbivorous fish biomass. Neither the direct (standardized coefficient = 0.06) nor indirect effects (standardized coefficient = 0.04) of no‐take protection on coral cover were particularly strong, likely reflecting regional differences in fishing gear, targeted species and trophic webs. Conclusions: MPAs promote the persistence of some functional groups of corals, and thus represent an important management tool, globally.

Background: Data suggest that the prediction of adult cardiovascular disease using a model comprised entirely of adult nonlaboratory-based risk factors is equivalent to an approach that additionally incorporates adult lipid measures. We assessed and compared the utility of a risk model based solely on nonlaboratory risk factors in adolescence versus a lipid model based on nonlaboratory risk factors plus lipids for predicting high-risk carotid intima-media thickness (cIMT) in adulthood. Methods: The study comprised 2893 participants 12 to 18 years of age from 4 longitudinal cohort studies from the United States (Bogalusa Heart Study and the Insulin Study), Australia (Childhood Determinants of Adult Health Study), and Finland (The Cardiovascular Risk in Young Finns Study) and followed into adulthood when cIMT was measured (mean follow-up, 23.4 years). Overweight status was defined according to the Cole classification. Hypertension was defined according to the Fourth Report on High Blood Pressure in Children and Adolescents from the National High Blood Pressure Education Program. High-risk plasma lipid levels were defined according to the National Cholesterol Education Program Expert Panel on Cholesterol Levels in Children. High cIMT was defined as a study-specific value ≥90th percentile. Age and sex were included in each model. Results: In univariate models, all risk factors except for borderline high and high triglycerides in adolescence were associated with high cIMT in adulthood. In multivariable models (relative risk [95% confidence interval]), male sex (2.7 [2.0–2.6]), prehypertension (1.4 [1.0–1.9]), hypertension (1.9 [1.3–2.9]), overweight (2.0 [1.4–2.9]), obesity (3.7 [2.0–7.0]), borderline high low-density lipoprotein cholesterol (1.6 [1.2–2.2]), high low-density lipoprotein cholesterol (1.6 [1.1–2.1]), and borderline low high-density lipoprotein cholesterol (1.4 [1.0–1.8]) remained significant predictors of high cIMT ( P P =0.02). Conclusions: Nonlaboratory-based risk factors and lipids measured in adolescence independently predicted preclinical atherosclerosis in young adulthood. The addition of lipid measurements to traditional clinic-based risk factor assessment provided a statistically significant but clinically modest improvement on adolescent prediction of high cIMT in adulthood.

Fish capture has far-reaching but inadequately assessed implications for marine food webs. At the community level, such effects are typically investigated using dynamic models that rely on partially subjective categorization of species into trophic groups and that mostly overlook the substantial contribution of ontogenetic dietary variation within fish species. Here, we estimate consumption by fish communities at 376 southern Australian sites by applying a recently developed statistical model that predicts diet for individual fish based on their body size and taxonomic identity, with predicted diets then summed to estimate total community consumption. Impacts of fishing and human population density as top-down pressures on shallow reef communities were thereby resolved at fine taxonomic scales. Fishes were estimated to consume 71% more prey biomass in southern Australian no-take marine protected areas (MPAs) relative to fished sites. Consumption of algae and sessile invertebrates was unexpectedly high in MPAs, an outcome not apparent with fish species allocated into pre-defined trophic groups. Extension of this individual size-structured modelling approach provides an opportunity to fill important knowledge gaps in understanding human impacts on marine food webs.

Summary We identify an intronic deletion in VANGL1 that predisposes to renal injury in high risk populations through a kidney-intrinsic process. Half of all SLE patients develop nephritis, yet the predisposing mechanisms to kidney damage remain poorly understood. There is limited evidence of genetic contribution to specific organ involvement in SLE.1,2 We identify a large deletion in intron 7 of Van Gogh Like 1 (VANGL1), which associates with nephritis in SLE patients. The same deletion occurs at increased frequency in an indigenous population (Tiwi Islanders) with 10-fold higher rates of kidney disease compared with non-indigenous populations. Vangl1 hemizygosity in mice results in spontaneous IgA and IgG deposition within the glomerular mesangium in the absence of autoimmune nephritis. Serum transfer into B cell-deficient Vangl1+/− mice results in mesangial IgG deposition indicating that Ig deposits occur in a kidney-intrinsic fashion in the absence of Vangl1. These results suggest that Vangl1 acts in the kidney to prevent Ig deposits and its deficiency may trigger nephritis in individuals with SLE., Graphical abstract, Highlights • Intronic deletions in VANGL1 are associated with risks of glomerulonephritis in SLE • Vangl1+/− mice develop spontaneous deposition of immunoglobulin in glomeruli • Vangl1+/− mice do not develop glomerulonephritis despite antibody deposition • Immunoglobulin deposition in Vangl1+/− occurs in a kidney-intrinsic manner, The organ specificity risks of lupus nephritis are unclear. Jiang et al. identify a common intronic deletion in VANGL1 that increases risks of nephritis in SLE patients. Vangl1+/− mice develop spontaneous deposition of immunoglobulin in the kidney without glomerulonephritis in a kidney intrinsic manner.

Despite the prevalence of R&D tax incentives, the amount of additional investment induced by each dollar of tax revenue forgone remains contested. It is notoriously difficult to identify the impact of R&D tax incentives because all firms are potentially eligible and because benefit and investment are jointly determined. Using comprehensive, firm-level data, we apply difference-in-difference analysis around a significant policy reform in Australia in 2012. We find that firms invest an additional $1.90 for every dollar of tax revenue forgone.

In order to measure the effect of tax credits on private R&D investment, researchers confront the difficult problem of finding an exogenous measure of tax policy that exhibits sufficient variation ...

Emerging evidence suggests that the basis for variation in late-life mobility is attributable, in part, to genetic factors, which may become increasingly important with age. Our objective was to systematically assess the contribution of genetic variation to gait speed in older individuals. We conducted a meta-analysis of gait speed GWASs in 31,478 older adults from 17 cohorts of the CHARGE consortium, and validated our results in 2,588 older adults from 4 independent studies. We followed our initial discoveries with network and eQTL analysis of candidate signals in tissues. The meta-analysis resulted in a list of 536 suggestive genome wide significant SNPs in or near 69 genes. Further interrogation with Pathway Analysis placed gait speed as a polygenic complex trait in five major networks. Subsequent eQTL analysis revealed several SNPs significantly associated with the expression of PRSS16, WDSUB1 and PTPRT, which in addition to the meta-analysis and pathway suggested that genetic effects on gait speed may occur through synaptic function and neuronal development pathways. No genome-wide significant signals for gait speed were identified from this moderately large sample of older adults, suggesting that more refined physical function phenotypes will be needed to identify the genetic basis of gait speed in aging.

Introduction and objectives Epoprostenol is a synthetic prostacyclin analogue which has been used in the treatment of pulmonary arterial hypertension (PAH) for a number of years. To date, it has been the only disease targeted therapy to have demonstrated an overall survival benefit for PAH patients (Demerouti et al., 2019). The previously available formulation of epoprostenol (Flolan 10.5) was thermolabile, meaning that it had to be prepared daily by patients and kept on ice to delay degradation. Recently a new formulation (Flolan 12) with greater thermostability has meant that these restrictions are no longer needed. The objective of our study was to transition patients onto Flolan 12 and examine for any safety issues associated with this transition, as well as looking at impact of quality of life (QoL), 6-minute walk distance (6MWD) and NT-proBNP. Methods All patients in our unit receiving a stable dose of intravenous epoprostenol for at least 3 months as of November 2016 were included in the study (n=22). Over the next 12 months these patients were transitioned onto Flolan 12. We compared 6MWD, NT-proBNP and QoL measures prior to treatment transition and then at first routine clinical follow-up following transition. QoL was measured using the Emphasis-10 questionnaire. We also utilised a separate questionnaire which focused on the effect of epoprostenol use on activities of daily living. The was completed pre- and post-transition. Results No safety issues were identified following transition to Flolan 12. No significant changes in QoL, 6MWD (see figure 1) or NT-proBNP were observed across the cohort following transition. All but one of the patients preferred the new formulation of epoprostenol. The one remaining patient expressed no preference. Conclusions Analysis of QoL, 6MWD and NT-proBNP has shown no detrimental clinical effects from the transition to the new formulation. The new formulation of epoprostenol has been well received by our patients due to its convenience. Reference DEMEROUTI, E., KARYOFYLLIS, P., MANGINAS, A., ANTHI, A., KARATASAKIS, G., ATHANASSOPOULOS, G. & VOUDRIS, V. 2019. Improving Survival in Patients with Pulmonary Arterial Hypertension: Focus on Intravenous Epoprostenol. Am J Cardiovasc drugs, 19, 99–105.

Background Australia is an ethnically diverse nation with one of the largest refugee resettlement programs worldwide. Evidence suggests that although the risk of developing mental disorders in culturally linguistically diverse (CALD) adolescents may be elevated, professional help-seeking in CALD youth is low. This study sought to evaluate the face-to-face teen (tMHFA) and Youth Mental Health First Aid (YMHFA) training with a CALD focus, which aimed at improving mental health literacy (MHL) and skills in youth and adults assisting adolescents with mental health problems. Methods An uncontrolled pre-, post-, and follow-up design was used to measure improvement in MHL measures in year 10 students and adults. Results A total of 372 year 10 students from 2 high schools were trained. 308 responded to the pre-training questionnaire, 220 responded to the post-training questionnaire, and 256 completed the 3-month follow-up questionnaire. A total of 34 adults were trained, 32 responded to the pre-questionnaire and 31 responded to the post-training questionnaire and 20 completed the 3-month follow-up questionnaire. Following training, students were more likely to endorse ‘helpful’ adults as valid sources of help (p Conclusion Our findings indicated the training led to an improvement in a number of measures of MHL and helpful intentions of both the adolescents and adults evaluated. These results indicate that CALD tMHFA and YMHFA are a recommended way of upskilling those trained and thereby leading to the improvement youth mental health in areas with high proportion of ethnically diverse groups.

Trypanosomiasis is a devastating neglected tropical disease that affects millions of livestock and thousands of humans each year. Only two subspecies of Trypanosoma brucei can cause disease in humans, while immunity to most trypanosomes is mediated in primates by HDL-associated circulating complexes called trypanosome lytic factors (TLFs) 1 and 2. Both TLFs are similar in composition, though TLF2 uniquely contains non-covalently associated IgM antibodies, the role and origin of which remain unclear. Here, we show that these TLF2-IgMs interact with TLF components and trypanosome surface proteins, including variant surface glycoprotein (VSG), likely facilitating complex biogenesis and TLF uptake into parasites. We also demonstrate that TLF2-IgMs are natural antibodies that, while present at basal concentrations in healthy individuals, are elicited by trypanosome infection in both murine models and human sleeping sickness patients. These data suggest that poly- and selfreactive natural antibodies such as TLF2-IgMs may play a role in antimicrobial immunity.

Analysis of international trade at the sub-national region level is perennially hampered by the lack of granular data. We contribute a new analytic approach for understanding trade performance of sub-national regions using a newly constructed international trademark filing dataset. We show that international trademarks provide an indicator of regional export activity by analyzing US data aggregated to the industry and State level. Our new dataset shows more detailed information about exporting businesses than have previously been unavailable such as the company name, industry, market and location. It is therefore valuable for public sector export promotion programs as well as business seeking timely information about the behavior of their competitors.

Purpose To highlight the potential benefits for long-term use of silicone hydrogels daily disposable (DD) contact lenses, particularly with patients who are noncompliant, sleeping or napping while wearing their lenses, or those who have higher oxygen demands and wear this modality for decades. Methods Published data for corneal swelling with lenses and no lens wear were used to develop a nonlinear least squares model. The edema load experienced with a range of oxygen transmissibilities (Dk/t) and wear compliance (sleep and napping) was determined. A mixed-effects linear regression model was used to compare the edema load for high and average corneal swellers. Results The edema load generated demonstrates that a high Dk/t silicone hydrogel lens results in edema levels close to that with no lens wear. In comparison, hydrogels with a Dk/t of 27 (× 10−9 [cm mL{O2}][s mL mm Hg]), worn on a daily wear schedule will result in 1.5 times more edema and up to two times more if the patient is noncompliant over each decade of wear. High swellers after four decades of wear will have an edema load 10 to 17 times greater than average swellers depending on Dk/t and their degree of noncompliance with the daily wear modality. Conclusions Prescribing silicone hydrogel DD lenses, particularly with higher DK/t, may help to maintain the long-term ocular health of patients, when they wear their lenses fulltime for many decades. Translational Relevance Illustrates the importance of Dk/t for any CL wear modality where patients nap or sleep in lenses or have high oxygen needs.

Predicting diet of animals in ecological communities is necessary for a better understanding of trophic links and piecing together food webs to inform ecosystem-based management. A dietary model, Consume, was recently developed to predict detailed dietary information for fishes on the basis of fish identity and size. This model was field-tested over a continental scale, predicting community-level consumption for other temperate marine fish communities that differed in species composition and size structure. Using local stomach contents data to field-test predictions, accurate performance of the model was found across 14 locations around southern Australia. Prey type and mean prey size were predicted for fishes at new locations with high accuracy (mean percentage overlap between predicted and actual prey types = 73%; r2 between predicted and observed mean prey size = 89%) when trained with stomach contents data from subsets of sampled fishes at all locations. Model accuracy dropped, but was still respectable, when using training data only from one location (prey type accuracy = 67%; mean prey size r2 = 56%). Prey type was more accurately predicted on the basis of consumer body size than species identity, while consumer family identity and size were needed for accurate prediction of mean prey size. The most important factors were evaluated by leaving out predictors (species, genus and family identity; size of consumer; habitat, location, ecoregion and biogeographic province). Exclusion of geographical location information resulted in little loss in accuracy. Our results highlight the need for consideration of consumer body size in trophic models, rather than binning species into functional groups solely on the basis of taxonomy. Application of Consume to situations where no dietary information exists, but at least fish family identity and size structure are known, will provide a novel mechanism for testing important ecological hypotheses and assessing trophic consequences of anthropogenically-induced changes in community structure.