Search

This paper reports on a laboratory experiment designed specifically to test the influence of national pride on tax honesty while using a physiological marker to observe emotional responses to patriotic priming. Participants were exposed to one of three framing videos before earning income in a real effort task and were given the chance to declare their taxable income. We find that psychological priming through exposure to symbols of Australian national pride and national identity had a positive effect on the level of tax compliance among Australian but not non-Australians. In addition, non-Australians report lower tax compliance ratios in the treatment groups than in the control group which may indicate an outgroup effect. When exploring the potential of a physiological marker of national pride we observe two different types of physiological responses to the activation and effects of national pride and its impact on tax compliance among Australians. Iconic images activate the parasympathetic nervous system while sports scenes activate the sympathetic nervous system, but both types of images and responses are positively associated with tax compliance. In addition, we find that non-Australians resident in the country for more than a year report a higher level of tax compliance, and that there are some similarities in heart rate variability (HRV) responses between Australian citizens born in the country and those born overseas who have been in Australia for a longer period. Overall, the results support the proposition that identifying with an ingroup at a national level is important for tax compliance.

Promoting mental health addresses a global societal challenge. Nature connectedness, or relatedness to natural systems, is associated with increased well-being and mental health. Among urban populations, nature connectedness has been reported as lower. Nature connectedness in urban settings has been somewhat overlooked by researchers. This cross-sectional online study addressed this issue by identifying socio-demographic predictors of urban nature connectedness among 165 students, aged 20 to 40, from the Technical University of Munich. Analysis of the data from 153 female university students was conducted using ordinal regressions, (a) separately and (b) merged with their 12 male counterparts. A separate gender analysis for males could not be performed, due to sample size limitations. Although access to nature and a considerable nature dose in terms of frequency and duration of nature contact were noted, possibly achieved through the engagement in outdoor activities, urban nature connectedness was rather low. Results showed that urban nature connectedness was negatively predicted by living in a rural area and positively predicted by engagement in outdoor activities and increased hours per week spent in nature. This information can help researchers operationalize the construct of urban nature connectedness. Furthermore, it can aid the development of interventions aimed at promoting urban nature connectedness, by encouraging urban inhabitants to (repeatedly) get in contact with and spend time in provided high-quality urban nature (e.g., during outdoor activities). To draw conclusions about causality, further research is required to identify a clear cause-effect relationship between socio-demographic characteristics and urban nature connectedness. Based on a researched dose-response relationship, a(n) (inter)national recommendation for the duration of nature contact should be established to promote urban nature connectedness and, therewith, health in urban inhabitants. Future research should also investigate further potential individual influencing factors, as well as gender and within/between-country differences among urban inhabitants.

Promoting mental health addresses a global societal challenge. Nature connectedness, or relatedness to natural systems, is associated with increased well-being and mental health. Among urban populations, nature connectedness has been reported as lower. Nature connectedness in urban settings has been somewhat overlooked by researchers. This cross-sectional online study addressed this issue by identifying socio-demographic predictors of urban nature connectedness among 165 students, aged 20 to 40, from the Technical University of Munich. Analysis of the data from 153 female university students was conducted using ordinal regressions, (a) separately and (b) merged with their 12 male counterparts. A separate gender analysis for males could not be performed, due to sample size limitations. Although access to nature and a considerable nature dose in terms of frequency and duration of nature contact were noted, possibly achieved through the engagement in outdoor activities, urban nature connectedness was rather low. Results showed that urban nature connectedness was negatively predicted by living in a rural area and positively predicted by engagement in outdoor activities and increased hours per week spent in nature. This information can help researchers operationalize the construct of urban nature connectedness. Furthermore, it can aid the development of interventions aimed at promoting urban nature connectedness, by encouraging urban inhabitants to (repeatedly) get in contact with and spend time in provided high-quality urban nature (e.g., during outdoor activities). To draw conclusions about causality, further research is required to identify a clear cause-effect relationship between socio-demographic characteristics and urban nature connectedness. Based on a researched dose-response relationship, a(n) (inter)national recommendation for the duration of nature contact should be established to promote urban nature connectedness and, therewith, health in urban inhabitants. Future research should also investigate further potential individual influencing factors, as well as gender and within/between-country differences among urban inhabitants.

The aim of this study was to capture Australian frontline healthcare workers’ (HCWs) experiences with personal protective equipment (PPE) during the COVID-19 pandemic in 2020. This was a cross-sectional study using an online survey consisting of five domains: demographics; self-assessment of COVID risk; PPE access; PPE training and confidence; and anxiety. Participants were recruited from community and hospital healthcare settings in Australia, including doctors, nurses, allied health professionals, paramedics, and aged care and support staff. Data analysis was descriptive with free-text responses analysed using qualitative content analysis and multivariable analysis performed for predictors of confidence, bullying, staff furlough and anxiety. The 2258 respondents, comprised 80% women, 49% doctors and 40% nurses, based in hospital (39%) or community (57%) settings. Key findings indicated a lack of PPE training (20%), calls for fit testing, insufficient PPE (25%), reuse or extended use of PPE (47%); confusion about changing guidelines (48%) and workplace bullying over PPE (77%). An absence of in-person workplace PPE training was associated with lower confidence in using PPE (OR 0.21, 95%CI 0.12, 0.37) and a higher likelihood of workplace bullying (OR 1.43; 95% CI 1.00, 2.03) perhaps reflecting deficiencies in workplace culture. Deficiencies in PPE availability, access and training linking to workplace bullying, can have negative physical and psychological impacts on a female dominant workforce critical to business as usual operations and pandemic response.

The aim of this study was to capture Australian frontline healthcare workers' (HCWs) experiences with personal protective equipment (PPE) during the COVID-19 pandemic in 2020. This was a cross-sectional study using an online survey consisting of five domains: demographics; self-assessment of COVID risk; PPE access; PPE training and confidence; and anxiety. Participants were recruited from community and hospital healthcare settings in Australia, including doctors, nurses, allied health professionals, paramedics, and aged care and support staff. Data analysis was descriptive with free-text responses analysed using qualitative content analysis and multivariable analysis performed for predictors of confidence, bullying, staff furlough and anxiety. The 2258 respondents, comprised 80% women, 49% doctors and 40% nurses, based in hospital (39%) or community (57%) settings. Key findings indicated a lack of PPE training (20%), calls for fit testing, insufficient PPE (25%), reuse or extended use of PPE (47%); confusion about changing guidelines (48%) and workplace bullying over PPE (77%). An absence of in-person workplace PPE training was associated with lower confidence in using PPE (OR 0.21, 95%CI 0.12, 0.37) and a higher likelihood of workplace bullying (OR 1.43; 95% CI 1.00, 2.03) perhaps reflecting deficiencies in workplace culture. Deficiencies in PPE availability, access and training linking to workplace bullying, can have negative physical and psychological impacts on a female dominant workforce critical to business as usual operations and pandemic response.

Ralstonia solanacearum causes bacterial wilt disease, leading to severe crop losses. Xylem sap from R. solanacearum-infected tomato is enriched in the disaccharide trehalose. Water-stressed plants also accumulate trehalose, which increases drought tolerance via abscisic acid (ABA) signaling. Because R. solanacearum-infected plants suffer reduced water flow, we hypothesized that bacterial wilt physiologically mimics drought stress, which trehalose could mitigate. We found that R. solanacearum-infected plants differentially expressed drought-associated genes, including those involved in ABA and trehalose metabolism, and had more ABA in xylem sap. Consistent with this, treating tomato roots with ABA reduced both stomatal conductance and stem colonization by R. solanacearum. Treating roots with trehalose increased xylem sap ABA and reduced plant water use by lowering stomatal conductance and temporarily improving water use efficiency. Trehalose treatment also upregulated expression of salicylic acid (SA)-dependent tomato defense genes; increased xylem sap levels of SA and other antimicrobial compounds; and increased bacterial wilt resistance of SA-insensitive NahG tomato plants. Additionally, trehalose treatment increased xylem concentrations of jasmonic acid and related oxylipins. Finally, trehalose-treated plants were substantially more resistant to bacterial wilt disease. Together, these data show that exogenous trehalose reduced both water stress and bacterial wilt disease and triggered systemic disease resistance, possibly through a Damage Associated Molecular Pattern (DAMP) response pathway. This suite of responses revealed unexpected linkages between plant responses to biotic and abiotic stress and suggested that R. solanacearum-infected plants increase trehalose to improve water use efficiency and increase wilt disease resistance. The pathogen may degrade trehalose to counter these efforts. Together, these results suggest that treating tomatoes with exogenous trehalose could be a practical strategy for bacterial wilt management.

The COVID-19 pandemic has caused severe health and economic impacts globally. Strategies to safely reopen economies, travel and trade are a high priority. Until a reliable vaccine is available, non-pharmaceutical techniques are the only available means of disease control. In this paper, we aim to evaluate the extent to which social distancing (SD) and facemask (FM) use can mitigate the transmission of COVID-19 when restrictions are lifted. We used a microsimulation activity-based model for Sydney Greater Metropolitan Area, to evaluate the power of SD and FM in controlling the pandemic under numerous scenarios. The hypothetical scenarios are designed to picture feasible futures under different assumptions. Assuming that the isolation of infected cases and the quarantining of close contacts are in place, different numerical tests are conducted and a full factorial two-way MANOVA test is used to evaluate the effectiveness of the FM and SD control strategies. The main and interactive effects of the containment strategies are evaluated by the total number of infections, percentage of infections reduction, the time it takes to get the pandemic under control, and the intensity of active cases.

First reported in March 2014, an Ebola epidemic impacted West Africa, most notably Liberia, Guinea and Sierra Leone. We demonstrate the value of social media for automated surveillance of infectious diseases such as the West Africa Ebola epidemic. We experiment with two variations of an existing surveillance architecture: the first aggregates tweets related to different symptoms together, while the second considers tweets about each symptom separately and then aggregates the set of alerts generated by the architecture. Using a dataset of tweets posted from the affected region from 2011 to 2014, we obtain alerts in December 2013, which is three months prior to the official announcement of the epidemic. Among the two variations, the second, which produces a restricted but useful set of alerts, can potentially be applied to other infectious disease surveillance and alert systems.

BACKGROUND:Influenza continues to cause seasonal epidemics and pandemics in humans. The burden of influenza is underestimated by traditional laboratory-based surveillance, and modelled estimates are required for influenza-attributable morbidity and mortality. We aimed to estimate the influenza-attributable hospitalisation in Australia, by influenza type. METHODS:A generalised-additive regression model was used to estimate type- and age-specific influenza-attributable hospitalisation rates per 100,000 population by principal diagnosis in Australia, from 2001 through 2013. Weekly counts of laboratory-confirmed influenza notifications and by type, influenza A and B were used as covariates in the model. Main principal diagnosis categories of interest were influenza and pneumonia and respiratory admissions. A smoothing spline was used to control for unmeasured time varying factors. Results for 2009, in which the pandemic influenza A(H1N1)pdm09 virus circulated, were not included in annual averages and are reported separately. RESULTS:During the study period, the estimated annual average, all-age, annual respiratory hospitalisation rates attributable to seasonal influenza type A, B and total influenza were 45.4 (95% CI: 34.9, 55.9), 32.6 (95% CI: 22.8, 42.4), and 76.9 (95% CI: 73.6, 80.2) per 100,000 population, respectively. During 2009, the estimated total pandemic influenza-attributable, all-age, respiratory hospitalisation rate was 56.1 (95% CI: 47.4, 64.9) per 100,000. Older adults (≥85 years of age) experienced the highest influenza-attributable hospitalisation rates for both seasonal and 2009 pandemic influenza. Collinearity between influenza A and B time series in some years limited the ability of the model to resolve differences in influenza attribution between the two virus types. CONCLUSION:Both seasonal and pandemic influenza caused considerable morbidity in Australia during the years studied, particularly among older adults. The pandemic hospitalisation rate in 2009 was lower than the average overall annual rate for seasonal influenza, but young to middle aged adults experience a hospitalisation rate similar to that of severe seasonal influenza.

Confidence in the health care system implies an expectation that sufficient and appropriate treatments will be provided if needed. The COVID-19 public health crisis is a significant, global, and (mostly) simultaneous test of the behavioral implications arising from this confidence. We explore whether populations reporting low levels of confidence in the health care system exhibit a stronger behavioral reaction to the COVID-19 pandemic. We track the dynamic responses to the COVID-19 pandemic across 38 European countries and 621 regions by employing a large dataset on human mobility generated between February 15 and June 5, 2020 and a broad range of contextual factors (e.g., deaths or policy implementations). Using a time-dynamic framework we find that societies with low levels of health care confidence initially exhibit a faster response with respect to staying home. However, this reaction plateaus sooner, and after the plateau it declines with greater magnitude than does the response from societies with high health care confidence. On the other hand, regions with higher confidence in the health care system are more likely to reduce mobility once the government mandates that its citizens are not to leave home except for essential trips, compared to those with lower health care system confidence. Regions with high trust in the government but low confidence in the health care system dramatically reduce their mobility, suggesting a correlation for trust in the state with respect to behavioral responses during a crisis.

Planning for a re-emergent epidemic of smallpox requires surge capacity of space, resources and personnel within health systems. There are many uncertainties in such a scenario, including likelihood and size of an attack, speed of response and health system capacity. We used a model for smallpox transmission to determine requirements for hospital beds, contact tracing and health workers (HCWs) in Sydney, Australia, during a modelled epidemic of smallpox. Sensitivity analysis was done on attack size, speed of response and proportion of case isolation and contact tracing. We estimated 100638 clinical HCWs and 14595 public hospital beds in Sydney. Rapid response, case isolation and contact tracing are influential on epidemic size, with case isolation more influential than contact tracing. With 95% of cases isolated, outbreak control can be achieved within 100 days even with only 50% of contacts traced. However, if case isolation and contact tracing both fall to 50%, epidemic control is lost. With a smaller initial attack and a response commencing 20 days after the attack, health system impacts are modest. The requirement for hospital beds will vary from up to 4% to 100% of all available beds in best and worst case scenarios. If the response is delayed, or if the attack infects 10000 people, all available beds will be exceeded within 40 days, with corresponding surge requirements for clinical health care workers (HCWs). We estimated there are 330 public health workers in Sydney with up to 940,350 contacts to be traced. At least 3 million respirators will be needed for the first 100 days. To ensure adequate health system capacity, rapid response, high rates of case isolation, excellent contact tracing and vaccination, and protection of HCWs should be a priority. Surge capacity must be planned. Failures in any of these could cause health system failure, with inadequate beds, quarantine spaces, personnel, PPE and inability to manage other acute health conditions.

Attitudes and beliefs about menstruation can place restrictions on menstruating women and girls, limiting their ability to fully participate in community life, education and employment. This paper presents evidence on menstruation-related beliefs contributing to restrictive practices in Papua New Guinea (PNG), Solomon Islands (SI) and Fiji. Focus group discussions and interviews were undertaken with 307 adolescent girls, women and men in a rural and urban site in each country. Data were analysed using an inductive thematic approach. Participants described a range of attitudes and beliefs that restrict the behaviour of menstruating women and girls. Themes include the belief that menstrual blood is 'dirty'; that when menstruating, girls and women can bring 'bad luck' to men; secrecy and shame associated with menstruation; and beliefs about the impact of certain behaviours on menstruation and health. Restrictive practices were more frequently reported in PNG and SI than Fiji, and more common in rural compared with urban sites. Some restrictions, such as avoidance of household chores, were perceived as desirable or driven by women themselves. However participants identified other restrictions, such as not being able to attend church or hygienically wash menstrual hygiene materials, as unwanted, in some cases impacting on participation in school, work and community life. Education initiatives guided by women and girls, implemented by local stakeholders and grounded in a sound understanding of specific contexts are needed to address discriminatory attitudes and beliefs that contribute to unwanted restrictions, and to support enabling attitudes and beliefs regarding menstruation.

Rhinovirus infection is associated with the majority of asthma exacerbations. The role of fractalkine in anti-viral (type 1) and pathogenic (type 2) responses to rhinovirus infection in allergic asthma is unknown. To determine whether (1) fractalkine is produced in airway cells and in peripheral blood leucocytes, (2) rhinovirus infection increases production of fractalkine and (3) levels of fractalkine differ in asthmatic compared to non-asthmatic subjects. Fractalkine protein and mRNA levels were measured in bronchoalveolar lavage (BAL) cells and peripheral blood mononuclear cells (PBMCs) from non-asthmatic controls (n = 15) and mild allergic asthmatic (n = 15) subjects. Protein levels of fractalkine were also measured in macrophages polarised ex vivo to give M1 (type 1) and M2 (type 2) macrophages and in BAL fluid obtained from mild (n = 11) and moderate (n = 14) allergic asthmatic and non-asthmatic control (n = 10) subjects pre and post in vivo rhinovirus infection. BAL cells produced significantly greater levels of fractalkine than PBMCs. Rhinovirus infection increased production of fractalkine by BAL cells from non-asthmatic controls (P

Lawsonia intracellularis is an obligate intracellular bacterial pathogen that causes proliferative enteropathy (PE) in pigs. L. intracellularis infection causes extensive intestinal crypt cell proliferation and inhibits secretory and absorptive cell differentiation. However, the affected host upstream cellular pathways leading to PE are still unknown. β-catenin/Wnt signalling is essential in maintaining intestinal stem cell (ISC) proliferation and self-renewal capacity, while Notch signalling governs differentiation of secretory and absorptive lineage specification. Therefore, in this report we used immunofluorescence (IF) and quantitative reverse transcriptase PCR (RTqPCR) to examine β-catenin/Wnt and Notch-1 signalling levels in uninfected and L. intracellularis infected pig ileums at 3, 7, 14, 21 and 28 days post challenge (dpc). We found that while the significant increase in Ki67+ nuclei in crypts at the peak of L. intracellularis infection suggested enhanced cell proliferation, the expression of c-MYC and ASCL2, promoters of cell growth and ISC proliferation respectively, was down-regulated. Peak infection also coincided with enhanced cytosolic and membrane-associated β-catenin staining and induction of AXIN2 and SOX9 transcripts, both encoding negative regulators of β-catenin/Wnt signalling and suggesting a potential alteration to β-catenin/Wnt signalling levels, with differential regulation of the expression of its target genes. We found that induction of HES1 and OLFM4 and the down-regulation of ATOH1 transcript levels was consistent with the increased Notch-1 signalling in crypts at the peak of infection. Interestingly, the significant down-regulation of ATOH1 transcript levels coincided with the depletion of MUC2 expression at 14 dpc, consistent with the role of ATOH1 in promoting goblet cell maturation. The lack of significant change to LGR5 transcript levels at the peak of infection suggested that the crypt hyperplasia was not due to the expansion of ISC population. Overall, simultaneous induction of Notch-1 signalling and the attenuation of β-catenin/Wnt pathway appear to be associated with the inhibition of goblet cell maturation and enhanced crypt cell proliferation at the peak of L. intracellularis infection. Moreover, the apparent differential regulation of apoptosis between crypt and lumen cells together with the strong induction of Notch-1 signalling and the enhanced SOX9 expression along crypts 14 dpc suggest an expansion of actively dividing transit amplifying and/or absorptive progenitor cells and provide a potential basis for understanding the development and maintenance of PE.

BACKGROUND:Zoonotic avian influenza poses a major risk to China, and other parts of the world. H5N1 has remained endemic in China and globally for nearly two decades, and in 2013, a novel zoonotic influenza A subtype H7N9 emerged in China. This study aimed to improve upon our current understanding of the spreading mechanisms of H7N9 and H5N1 by generating spatial risk profiles for each of the two virus subtypes across mainland China. METHODS AND FINDINGS:In this study, we (i) developed a refined data set of H5N1 and H7N9 locations with consideration of animal/animal environment case data, as well as spatial accuracy and precision; (ii) used this data set along with environmental variables to build species distribution models (SDMs) for each virus subtype in high resolution spatial units of 1km2 cells using Maxent; (iii) developed a risk modelling framework which integrated the results from the SDMs with human and chicken population variables, which was done to quantify the risk of zoonotic transmission; and (iv) identified areas at high risk of H5N1 and H7N9 transmission. We produced high performing SDMs (6 of 8 models with AUC > 0.9) for both H5N1 and H7N9. In all our SDMs, H7N9 consistently showed higher AUC results compared to H5N1, suggesting H7N9 suitability could be better explained by environmental variables. For both subtypes, high risk areas were primarily located in south-eastern China, with H5N1 distributions found to be more diffuse and extending more inland compared to H7N9. CONCLUSIONS:We provide projections of our risk models to public health policy makers so that specific high risk areas can be targeted for control measures. We recommend comparing H5N1 and H7N9 prevalence rates and survivability in the natural environment to better understand the role of animal and environmental transmission in human infections.

[This corrects the article DOI: 10.1371/journal.pone.0174980.].

Women with a history of excisional treatment (conization) for cervical intra-epithelial neoplasia (CIN) are at increased risk of preterm birth, perinatal morbidity and mortality in subsequent pregnancy. We aimed to develop a screening model to effectively differentiate pregnancies post-conization into low- and high-risk for preterm birth, and to evaluate the impact of suture material on the efficacy of ultrasound indicated cervical cerclage. We analysed longitudinal cervical length (CL) data from 725 pregnant women post-conization attending preterm surveillance clinics at three London university Hospitals over a ten year period (2004-2014). Rates of preterm birth 37weeks. Our triage model enables timely discharge of low risk women, eliminating 36% of unnecessary follow-up CL scans. We demonstrate that preterm birth in women post-conization may be reduced by targeted cervical cerclage. Cerclage efficacy is however suture material-dependant: monofilament is preferable to braided suture. The introduction of triage prediction models has the potential to reduce the number of unnecessary CL scan for women at low risk of preterm birth.

Herpes zoster (HZ) is a common condition that increases in incidence with older age but vaccines are available to prevent the disease. However, there are limited data estimating the health system burden attributable to herpes zoster by age.In this study, we quantified excess healthcare resource usage associated with HZ during the acute/sub-acute period of disease (21days before to 90 days after onset) in 5952 cases and an equal number of controls matched on age, sex, and prior healthcare resource usage. Estimates were adjusted for potential confounders in multivariable regression models. Using population-based estimates of HZ incidence, we calculated the age-specific excess number of health service usage events attributable to HZ in the population.Per HZ case, there was an average of 0.06 (95% CI 0.04-0.08) excess hospitalisations, 1.61 (95% CI 1.51-1.69) excess general practitioner visits, 1.96 (95% CI 1.86-2.15) excess prescriptions filled and 0.11 (95% CI 0.09-0.13) excess emergency department visits. The average number of healthcare resource use events, and the estimated excess per 100,000 population increased with increasing age but were similar for men and women, except for higher rates of hospitalisation in men. The excess annual HZ associated burden of hospitalisations was highest in adults ≥80 years (N = 2244, 95%CI 1719-2767); GP visits was highest in those 60-69 years (N = 50567, 95%CI 39958-61105), prescriptions and ED visits were highest in 70-79 years (N = 50524, 95%CI 40634-60471 and N = 2891, 95%CI 2319-3449 respectively).This study provides important data to establish the healthcare utilisation associated with HZ against which detailed cost-effectiveness analyses of HZ immunisation in older adults can be conducted.

Background and objectivesAnti-hypertensive treatment with the angiotensin II receptor antagonist olmesartan is a rare cause of severe Sprue-like enteropathy. To substantiate the hypothesis that olmesartan interferes with gut immune homeostasis, clinical, histopathological and immune features were compared in olmesartan-induced-enteropathy (OIE) and in autoimmune enteropathy (AIE).MethodsMedical files of seven patients with OIE and 4 patients with AIE enrolled during the same period were retrospectively reviewed. Intestinal biopsies were collected for central histopathological review, T cell Receptor clonality and flow cytometric analysis of isolated intestinal lymphocytes.ResultsAmong seven olmesartan-treated patients who developed villous atrophy refractory to a gluten free diet, three had extra-intestinal autoimmune diseases, two had antibodies reacting with the 75 kilodalton antigen characteristic of AIE and one had serum anti-goblet cell antibodies. Small intestinal lesions and signs of intestinal lymphocyte activation were thus reminiscent of the four cases of AIE diagnosed during the same period. Before olmesartan discontinuation, remission was induced in all patients (7/7) by immunosuppressive drugs. After interruption of both olmesartan and immunosuppressive drugs in six patients, remission was maintained in 4 but anti-TNF-α therapy was needed in two.ConclusionThis case-series shows that olmesartan can induce intestinal damage mimicking AIE. OIE usually resolved after olmesartan interruption but immunosuppressive drugs may be necessary to achieve remission. Our data sustain the hypothesis that olmesartan interferes with intestinal immuno regulation in predisposed individuals.

BackgroundIncreasing trends in incidence of herpes zoster (HZ) have been reported in Australia and internationally. This may reflect the impact of childhood VZV vaccination programs introduced universally in Australia in late 2005. The objective of this study was to evaluate changes in incidence of HZ and PHN in Australia over time, and associated healthcare resource utilisation.MethodsAustralian data on general practice (GP) encounters for HZ, specific antiviral prescribing data from the pharmaceutical benefits scheme, emergency department presentations from the states of NSW and Victoria and national hospitalisation data for HZ were analysed for time trends using regression models. Two time periods (2000-2006 and 2006-2013) were compared which correspond broadly with the pre- and post- universal VZV vaccination period.ResultsAll data sources showed increasing rates of HZ with age and over time. The GP database showed a significant annual increase in encounters for HZ of 2.5 per 100,000 between 1998 and 2013, and the rates of prescriptions for HZ increased by 4.2% per year between 2002 and 2012. In the 60+ population HZ incidence was estimated to increase from 11.9 to 15.4 per 1,000 persons using GP data or from 12.8 to 14.2 per 1,000 persons using prescription data (pDiscussionThe burden of HZ in Australia is substantial, and continues to increase over time. This increase is seen both pre- and post-universal VZV vaccination in 2005, and is most prominent in the older population. The substantial burden of HZ, along with ageing of the Australian population and the importance of healthy ageing, warrants consideration of HZ vaccination for the elderly.

The heritability of Major Depressive Disorder (MDD) has been estimated at 37% based largely on twin studies that rely on contested assumptions. More recently, the heritability of MDD has been estimated on large populations from registries such as the Swedish, Finnish, and Chinese cohorts. Family-based designs utilise a number of different relationships and provide an alternative means of estimating heritability. Generation Scotland: Scottish Family Health Study (GS:SFHS) is a large (n = 20,198), family-based population study designed to identify the genetic determinants of common diseases, including Major Depressive Disorder. Two thousand seven hundred and six individuals were SCID diagnosed with MDD, 13.5% of the cohort, from which we inferred a population prevalence of 12.2% (95% credible interval: 11.4% to 13.1%). Increased risk of MDD was associated with being female, unemployed due to a disability, current smokers, former drinkers, and living in areas of greater social deprivation. The heritability of MDD in GS:SFHS was between 28% and 44%, estimated from a pedigree model. The genetic correlation of MDD between sexes, age of onset, and illness course were examined and showed strong genetic correlations. The genetic correlation between males and females with MDD was 0.75 (0.43 to 0.99); between earlier (≤ age 40) and later (> age 40) onset was 0.85 (0.66 to 0.98); and between single and recurrent episodic illness course was 0.87 (0.72 to 0.98). We found that the heritability of recurrent MDD illness course was significantly greater than the heritability of single MDD illness course. The study confirms a moderate genetic contribution to depression, with a small contribution of the common family environment (variance proportion = 0.07, CI: 0.01 to 0.15), and supports the relationship of MDD with previously identified risk factors. This study did not find robust support for genetic differences in MDD due to sex, age of onset, or illness course. However, we found an intriguing difference in heritability between recurrent and single MDD illness course. These findings establish GS:SFHS as a valuable cohort for the genetic investigation of MDD.

Serfling-type periodic regression models have been widely used to identify and analyse epidemic of influenza. In these approaches, the baseline is traditionally determined using cleaned historical non-epidemic data. However, we found that the previous exclusion of epidemic seasons was empirical, since year-year variations in the seasonal pattern of activity had been ignored. Therefore, excluding fixed 'epidemic' months did not seem reasonable. We made some adjustments in the rule of epidemic-period removal to avoid potentially subjective definition of the start and end of epidemic periods. We fitted the baseline iteratively. Firstly, we established a Serfling regression model based on the actual observations without any removals. After that, instead of manually excluding a predefined 'epidemic' period (the traditional method), we excluded observations which exceeded a calculated boundary. We then established Serfling regression once more using the cleaned data and excluded observations which exceeded a calculated boundary. We repeated this process until the R2 value stopped to increase. In addition, the definitions of the onset of influenza epidemic were heterogeneous, which might make it impossible to accurately evaluate the performance of alternative approaches. We then used this modified model to detect the peak timing of influenza instead of the onset of epidemic and compared this model with traditional Serfling models using observed weekly case counts of influenza-like illness (ILIs), in terms of sensitivity, specificity and lead time. A better performance was observed. In summary, we provide an adjusted Serfling model which may have improved performance over traditional models in early warning at arrival of peak timing of influenza.

Marine sponge-associated actinomycetes are considered as promising sources for the discovery of novel biologically active compounds. In the present study, a total of 64 actinomycetes were isolated from 12 different marine sponge species that had been collected offshore the islands of Milos and Crete, Greece, eastern Mediterranean. The isolates were affiliated to 23 genera representing 8 different suborders based on nearly full length 16S rRNA gene sequencing. Four putatively novel species belonging to genera Geodermatophilus, Microlunatus, Rhodococcus and Actinomycetospora were identified based on a 16S rRNA gene sequence similarity of < 98.5% to currently described strains. Eight actinomycete isolates showed bioactivities against Trypanosma brucei brucei TC221 with half maximal inhibitory concentration (IC50) values

BackgroundOfficial statistics under-estimate influenza deaths. Time series methods allow the estimation of influenza-attributable mortality. The methods often model background, non-influenza mortality using a cyclic, harmonic regression model based on the Serfling approach. This approach assumes that the seasonal pattern of non-influenza mortality is the same each year, which may not always be accurate.AimTo estimate Australian seasonal and pandemic influenza-attributable mortality from 2003 to 2009, and to assess a more flexible influenza mortality estimation approach.MethodsWe used a semi-parametric generalized additive model (GAM) to replace the conventional seasonal harmonic terms with a smoothing spline of time ('spline model') to estimate influenza-attributable respiratory, respiratory and circulatory, and all-cause mortality in persons aged ResultsCompared with the harmonic model, the spline model improved model fit by up to 20%. In ConclusionsThe spline model achieved a better model fit. The study provides additional evidence that seasonal influenza, particularly A/H3N2, remains an important cause of mortality in Australia and that the epidemic of pandemic influenza A (H1N1)pdm09 virus in 2009 did not result in mortality greater than seasonal A/H3N2 influenza mortality, even in younger age groups.

Neuropilins and semaphorins are known as modulators of axon guidance, angiogenesis, and organogenesis in the developing nervous system, but have been recently evidenced as also playing a role in the immune system. Here we describe the expression and role of semaphorin 3F (SEMA3F) and its receptor neuropilin-2 (NRP2) in human T cell precursors. NRP2 and SEMA3F are expressed in the human thymus, in both lymphoid and non-lymphoid compartments. SEMA3F have a repulsive effect on thymocyte migration and inhibited CXCL12- and sphingosine-1-phosphate (S1P)-induced thymocyte migration by inhibiting cytoskeleton reorganization prior to stimuli. Moreover, NRP2 and SEMA3F are expressed in human T-cell acute lymphoblastic leukemia/lymphoma primary cells. In these tumor cells, SEMA3F also blocks their migration induced by CXCL12 and S1P. Our data show that SEMA3F and NRP2 are further regulators of human thymocyte migration in physiological and pathological conditions.

BackgroundHistorically, counting influenza recorded in administrative health outcome databases has been considered insufficient to estimate influenza attributable morbidity and mortality in populations. We used database record linkage to evaluate whether modern databases have similar limitations.MethodsPerson-level records were linked across databases of laboratory notified influenza, emergency department (ED) presentations, hospital admissions and death registrations, from the population (∼6.9 million) of New South Wales (NSW), Australia, 2005 to 2008.ResultsThere were 2568 virologically diagnosed influenza infections notified. Among those, 25% of 40 who died, 49% of 1451 with a hospital admission and 7% of 1742 with an ED presentation had influenza recorded on the respective database record. Compared with persons aged ≥65 years and residents of regional and remote areas, respectively, children and residents of major cities were more likely to have influenza coded on their admission record. Compared with older persons and admitted patients, respectively, working age persons and non-admitted persons were more likely to have influenza coded on their ED record. On both ED and admission records, persons with influenza type A infection were more likely than those with type B infection to have influenza coded. Among death registrations, hospital admissions and ED presentations with influenza recorded as a cause of illness, 15%, 28% and 1.4%, respectively, also had laboratory notified influenza. Time trends in counts of influenza recorded on the ED, admission and death databases reflected the trend in counts of virologically diagnosed influenza.ConclusionsA minority of the death, hospital admission and ED records for persons with a virologically diagnosed influenza infection identified influenza as a cause of illness. Few database records with influenza recorded as a cause had laboratory confirmation. The databases have limited value for estimating incidence of influenza outcomes, but can be used for monitoring variation in incidence over time.

BackgroundElderly people do not mount strong immune responses to vaccines. We compared 23-valent capsular polysaccharide (23vPPV) alone versus 7-valent conjugate (PCV7) vaccine followed by 23vPPV 6 months later in hospitalized elderly.MethodsParticipants were randomized to receive 23vPPV or PCV7-23vPPV. Antibodies against serotypes 3, 4, 6A, 6B, 9V, 14, 18C, 19A, 19F, 23F were measured by enzyme-linked immunosorbent (ELISA) and opsonophagocytic (OPA) assays at baseline, 6 months and 12 months.ResultsOf 312 recruited, between 40% and 72% of subjects had undetectable OPA titres at baseline. After one dose, PCV7 recipients had significantly higher responses to serotypes 9V (both assays) and 23F (OPA only), and 23vPPV recipients had significantly higher responses to serotype 3 (ELISA), 19F and 19A (OPA only). In subjects with undetectable OPA titres at baseline, a proportionately greater rise in OPA titre (PConclusionWe did not show overwhelming benefit of one vaccine over the other. Low baseline immunity does not preclude a robust immune response, reiterating the importance of vaccinating the frail elderly. A schedule of PCV7-23vPPV prevents waning of antibody, suggesting that both vaccines could be useful in the elderly. Follow up studies are needed to determine persistence of immunity.Trial registrationThe Australian Clinical Trials Registry ACTRN12607000387426.

PurposeThe purpose of this study was to determine if microRNA profiling of urine and plasma at radical prostatectomy can distinguish potentially lethal from indolent prostate cancer.Materials and methodsA panel of microRNAs was profiled in the plasma of 70 patients and the urine of 33 patients collected prior to radical prostatectomy. Expression of microRNAs was correlated to the clinical endpoints at a follow-up time of 3.9 years to identify microRNAs that may predict clinical response after radical prostatectomy. A machine learning approach was applied to test the predictive ability of all microRNAs profiled in urine, plasma, and a combination of both, and global performance assessed using the area under the receiver operator characteristic curve (AUC). Validation of urinary expression of miRNAs was performed on a further independent cohort of 36 patients.ResultsThe best predictor in plasma using eight miRs yielded only moderate predictive performance (AUC = 0.62). The best predictor of high-risk disease was achieved using miR-16, miR-21 and miR-222 measured in urine (AUC = 0.75). This combination of three microRNAs in urine was a better predictor of high-risk disease than any individual microRNA. Using a different methodology we found that this set of miRNAs was unable to predict high-volume, high-grade disease.ConclusionsOur initial findings suggested that plasma and urinary profiling of microRNAs at radical prostatectomy may allow prognostication of prostate cancer behaviour. However we found that the microRNA expression signature failed to validate in an independent cohort of patients using a different platform for PCR. This highlights the need for independent validation patient cohorts and suggests that urinary microRNA signatures at radical prostatectomy may not be a robust way to predict the course of clinical disease after definitive treatment for prostate cancer.

In many communities, older men (i.e., over 25 years of age) have not come forward for Voluntary Medical Male Circumcision (VMMC) services. Reasons for low demand among this group of men are not well understood, and may vary across geographic and cultural contexts. This paper examines the facilitators and barriers to VMMC demand in Turkana County, Kenya, with a focus on older men. This is one of the regions targeted by the VMMC program in Kenya because the Turkana ethnic group does not traditionally circumcise, and the rates of HIV and STD transmission are high.Twenty focus group discussions and 69 in-depth interviews were conducted with circumcised and uncircumcised men and their partners to elicit their attitudes and perceptions toward male circumcision. The interviews were conducted in urban, peri-urban, and rural communities across Turkana. Our results show that barriers to circumcision include stigma associated with VMMC, the perception of low risk for HIV for older men and their "protection by marriage," cultural norms, and a lack of health infrastructure. Facilitators include stigma against not being circumcised (since circumcision is associated with modernity), protection against disease including HIV, and cleanliness. It was also noted that older men should adopt the practice to serve as role models to younger men.Both men and women were generally supportive of VMMC, but overcoming barriers with appropriate communication messages and high quality services will be challenging. The justification of circumcision being a biomedical procedure for protection against HIV will be the most important message for any communication strategy.

T lymphocytes (T cells) undergo metabolic reprogramming after activation to provide energy and biosynthetic materials for growth, proliferation and differentiation. Distinct T cell subsets, however, adopt metabolic programs specific to support their needs. As CD4 T cells coordinate adaptive immune responses while CD8 T cells become cytotoxic effectors, we compared activation-induced proliferation and metabolic reprogramming of these subsets. Resting CD4 and CD8 T cells were metabolically similar and used a predominantly oxidative metabolism. Following activation CD8 T cells proliferated more rapidly. Stimulation led both CD4 and CD8 T cells to sharply increase glucose metabolism and adopt aerobic glycolysis as a primary metabolic program. Activated CD4 T cells, however, remained more oxidative and had greater maximal respiratory capacity than activated CD8 T cells. CD4 T cells were also associated with greater levels of ROS and increased mitochondrial content, irrespective of the activation context. CD8 cells were better able, however, to oxidize glutamine as an alternative fuel source. The more glycolytic metabolism of activated CD8 T cells correlated with increased capacity for growth and proliferation, along with reduced sensitivity of cell growth to metabolic inhibition. These specific metabolic programs may promote greater growth and proliferation of CD8 T cells and enhance survival in diverse nutrient conditions.

BACKGROUND: In October 2004, Manam Island volcano in Papua New Guinea erupted, causing over 10 000 villagers to flee to internally displaced person (IDP) camps, including 550 from Dugulaba village. Following violence over land access in March 2010, the IDPs fled the camps, and four months later concurrent outbreaks of acute watery diarrhea and unusual neurological complaints were reported in this population. MATERIALS AND METHODS: A retrospective case-control study was conducted to identify the risk factors for peripheral neuropathy. Rectal swabs were collected from cases of acute watery diarrhea. Hair and serum metals and metalloids were analyzed by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). RESULTS: There were 17 deaths among the 550 village inhabitants during the outbreak period at a crude mortality rate 21-fold that of a humanitarian crisis. Vibrio cholerae O1 El Tor Ogawa was confirmed among the population. Access to community-level rehydration was crucial to mortality. Peripheral neuropathy was diagnosed among cases with neurological symptoms. A balanced diet was significantly protective against neuropathy. A dose-response relationship was seen between peripheral neuropathy and a decreasing number of micronutrient- rich foods in the diet. Deficiencies in copper, iron, selenium and zinc were identified among the cases of peripheral neuropathy. CONCLUSIONS: Cholera likely caused the mostly preventable excess mortality. Peripheral neuropathy was not caused by cholera, but cholera may worsen existing nutritional deficiencies. The peripheral neuropathy was likely caused by complex micronutrient deficiencies linked to non-diversified diets that potentially increased the vulnerability of this population, however a new zinc-associated neuropathy could not be ruled out. Reoccurrence can be prevented by addressing the root cause of displacement and ensuring access to arable land and timely resettlement.

Defective Rhinovirus induced interferon-β and interferon-λ production has been reported in bronchial epithelial cells from asthmatics but the mechanisms of defective interferon induction in asthma are unknown. Virus infection can induce interferon through Toll like Receptors (TLR)3, TLR7 and TLR8. The role of these TLRs in interferon induction in asthma is unclear. This objective of this study was to measure the type I and III interferon response to TLR in bronchial epithelial cells and peripheral blood cells from atopic asthmatics and non-atopic non-asthmatics. Bronchial epithelial cells and peripheral blood mononuclear cells from atopic asthmatic and non-atopic non-asthmatic subjects were stimulated with agonists to TLR3, TLR4 & TLRs7-9 and type I and III interferon and pro-inflammatory cytokine, interleukin(IL)-6 and IL-8, responses assessed. mRNA expression was analysed by qPCR. Interferon proteins were analysed by ELISA. Pro-inflammatory cytokines were induced by each TLR ligand in both cell types. Ligands to TLR3 and TLR7/8, but not other TLRs, induced interferon-β and interferon-λ in bronchial epithelial cells. The ligand to TLR7/8, but not those to other TLRs, induced only type I interferons in peripheral blood mononuclear cells. No difference was observed in TLR induced interferon or pro-inflammatory cytokine production between asthmatic and non-asthmatic subjects from either cell type. TLR3 and TLR7/8,, stimulation induced interferon in bronchial epithelial cells and peripheral blood mononuclear cells. Interferon induction to TLR agonists was not observed to be different in asthmatics and non-asthmatics.

There is believed to be a 'beauty premium' in key life outcomes: it is thought that people perceived to be more physically attractive have better educational outcomes, higher-status jobs, higher wages, and are more likely to marry. Evidence for these beliefs, however, is generally based on photographs in hypothetical experiments or studies of very specific population subgroups (such as college students). The extent to which physical attractiveness might have a lasting effect on such outcomes in 'real life' situations across the whole population is less well known. Using longitudinal data from a general population cohort of people in the West of Scotland, this paper investigated the association between physical attractiveness at age 15 and key socioeconomic outcomes approximately 20 years later. People assessed as more physically attractive at age 15 had higher socioeconomic positions at age 36- in terms of their employment status, housing tenure and income - and they were more likely to be married; even after adjusting for parental socioeconomic background, their own intelligence, health and self esteem, education and other adult socioeconomic outcomes. For education the association was significant for women but not for men. Understanding why attractiveness is strongly associated with long-term socioeconomic outcomes, after such extensive confounders have been considered, is important.

BACKGROUND:The aetiological role of human papillomavirus (HPV) in oesophageal squamous cell carcinoma (OSCC) has been widely researched for more than three decades, with conflicting findings. In the absence of a large, adequately powered single case-control study, a meta-analysis of all available case-control studies is the most rigorous way of identifying any potential association between HPV and OSCC. We present the first global meta-analysis of case-control studies investigating the role of HPV in OSCC. METHODS:Case-control studies investigating OSCC tissue for presence of HPV DNA were identified. 21 case-control studies analyzing a total of 1223 cases and 1415 controls, met our inclusion criteria. HPV detection rates were tabulated for each study and all studies were assessed for quality. The random effects method was used to pool the odds ratios (OR). RESULTS:From all OSCC specimens included in this meta-analysis, 35% (426/1223) were positive for HPV DNA. The pooled OR for an HPV-OSCC association was 3.04 (95% CI 2.20 to 4.20). Meta-regression analysis did not find a significant association between OR and any of the quality domains. Influence analysis was non-significant for the effect of individual studies on the pooled estimate. Studies conducted in countries with low to medium OSCC incidence showed a stronger relationship (OR 4.65, 95% CI 2.47 to 8.76) than regions of high OSCC incidence (OR 2.65, 95% CI 1.80 to 3.91). CONCLUSIONS:Uncertainty around the aetiological role of HPV in OSCC is due largely to the small number and scale of appropriately designed studies. Our meta-analysis of these studies suggests that HPV increases the risk of OSCC three-fold. This study provides the strongest evidence to date of an HPV-OSCC association. The importance of these findings is that prophylactic vaccination could be of public health benefit in prevention of OSCC in countries with high OSCC incidence.

BACKGROUND: 15-deoxy-Δ 12,14- Prostaglandin J2 (15dPGJ2) inhibits Nuclear factor kappa B (NF-κB) in human myocytes and amniocytes and delays inflammation induced preterm labour in the mouse. 15dPGJ2 is a ligand for the Chemoattractant Receptor Homologous to the T helper 2 cell (CRTH2), a G protein-coupled receptor, present on a subset of T helper 2 (Th2) cells, eosinophils and basophils. It is the second receptor for Prostaglandin D2, whose activation leads to chemotaxis and the production of Th2-type interleukins. The cellular distribution of CRTH2 in non-immune cells has not been extensively researched, and its identification at the protein level has been limited by the lack of specific antibodies. In this study we explored the possibility that CRTH2 plays a role in 15dPGJ2-mediated inhibition of NF-κB and would therefore represent a novel small molecule therapeutic target for the prevention of inflammation induced preterm labour. METHODS: The effect of a small molecule CRTH2 agonist on NF-κB activity in human cultured amniocytes and myocytes was assessed by detection of p65 and phospho-p65 by immunoblot. Endogenous CRTH2 expression in amniocytes, myocytes and peripheral blood mononuclear cells (PBMCs) was examined by PCR, western analysis and flow cytometry, with amniocytes and myocytes transfected with CRTH2 acting as a positive control in flow cytometry studies. RESULTS: The CRTH2 agonist had no effect on NF-κB activity in amniocytes and myocytes. Although CRTH2 mRNA was detected in amniocytes and myocytes, CRTH2 was not detectable at the protein level, as demonstrated by western analysis and flow cytometry. 15dPGJ2 inhibited phospho-65 in PBMC'S, however the CRTH2 antagonist was not able to attenuate this effect. In conclusion, CRTH2 is not expressed on human amniocytes or myocytes and plays no role in the mechanism of 15dPGJ2-mediated inhibition of NF-κB.

BACKGROUND: Prior to the onset of human labour there is an increase in the synthesis of prostaglandins, cytokines and chemokines in the fetal membranes, particular the amnion. This is associated with activation of the transcription factor nuclear factor kappa B (NFκB). In this study we characterised the level of NFκB activity in amnion epithelial cells as a measure of amnion activation in samples collected from women undergoing caesarean section at 39 weeks gestation prior to the onset of labour. METHODOLOGY/PRINCIPAL FINDINGS: We found that a proportion of women exhibit low or moderate NFκB activity while other women exhibit high levels of NFκB activity (n = 12). This activation process does not appear to involve classical pathways of NFκB activation but rather is correlated with an increase in nuclear p65-Rel-B dimers. To identify the full range of genes upregulated in association with amnion activation, microarray analysis was performed on carefully characterised non-activated amnion (n = 3) samples and compared to activated samples (n = 3). A total of 919 genes were upregulated in response to amnion activation including numerous inflammatory genes such cyclooxygenase-2 (COX-2, 44-fold), interleukin 8 (IL-8, 6-fold), IL-1 receptor accessory protein (IL-1RAP, 4.5-fold), thrombospondin 1 (TSP-1, 3-fold) and, unexpectedly, oxytocin receptor (OTR, 24-fold). Ingenuity Pathway Analysis of the microarray data reveal the two main gene networks activated concurrently with amnion activation are i) cell death, cancer and morphology and ii) cell cycle, embryonic development and tissue development. CONCLUSIONS/SIGNIFICANCE: Our results indicate that assessment of amnion NFκB activation is critical for accurate sample classification and subsequent interpretation of data. Collectively, our data suggest amnion activation is largely an inflammatory event that occurs in the amnion epithelial layer as a prelude to the onset of labour.

The clinical, radiological and pathological similarities between sarcoidosis and tuberculosis can make disease differentiation challenging. A complicating factor is that some cases of sarcoidosis may be initiated by mycobacteria. We hypothesised that immunological profiling might provide insight into a possible relationship between the diseases or allow us to distinguish between them.We analysed bronchoalveolar lavage (BAL) fluid in sarcoidosis (n = 18), tuberculosis (n = 12) and healthy volunteers (n = 16). We further investigated serum samples in the same groups; sarcoidosis (n = 40), tuberculosis (n = 15) and healthy volunteers (n = 40). A cross-sectional analysis of multiple cytokine profiles was performed and data used to discriminate between samples.We found that BAL profiles were indistinguishable between both diseases and significantly different from healthy volunteers. In sera, tuberculosis patients had significantly lower levels of the Th2 cytokine interleukin-4 (IL-4) than those with sarcoidosis (p = 0.004). Additional serum differences allowed us to create a linear regression model for disease differentiation (within-sample accuracy 91%, cross-validation accuracy 73%).These data warrant replication in independent cohorts to further develop and validate a serum cytokine signature that may be able to distinguish sarcoidosis from tuberculosis. Systemic Th2 cytokine differences between sarcoidosis and tuberculosis may also underly different disease outcomes to similar respiratory stimuli.

BACKGROUND: Influenza is an important cause of morbidity and mortality for frail older people. Whilst the antiviral drug oseltamivir (a neuraminidase inhibitor) is approved for treatment and prophylaxis of influenza during outbreaks, there have been no trials comparing treatment only (T) versus treatment and prophylaxis (T&P) in Aged Care Facilities (ACFs). Our objective was to compare a policy of T versus T&P for influenza outbreaks in ACFs. METHODS AND FINDINGS: We performed a cluster randomised controlled trial in 16 ACFs, that followed a policy of either "T"-oseltamivir treatment (75 mg twice a day for 5 days)-or "T&P"-treatment and prophylaxis (75 mg once a day for 10 days) for influenza outbreaks over three years, in addition to enhanced surveillance. The primary outcome measure was the attack rate of influenza. Secondary outcomes measures were deaths, hospitalisation, pneumonia and adverse events. Laboratory testing was performed to identify the viral cause of influenza-like illness (ILI) outbreaks. The study period 30 June 2006 to 23 December 2008 included three southern hemisphere winters. During that time, influenza was confirmed as the cause of nine of the 23 ILI outbreaks that occurred amongst the 16 ACFs. The policy of T&P resulted in a significant reduction in the influenza attack rate amongst residents: 93/255 (36%) in residents in T facilities versus 91/397 (23%) in T&P facilities (p=0.002). We observed a non-significant reduction in staff: 46/216 (21%) in T facilities versus 47/350 (13%) in T&P facilities (p=0.5). There was a significant reduction in mean duration of outbreaks (T=24 days, T&P=11 days, p=0.04). Deaths, hospitalisations and pneumonia were non-significantly reduced in the T&P allocated facilities. Drug adverse events were common but tolerated. CONCLUSION: Our trial lacked power but these results provide some support for a policy of "treatment and prophylaxis" with oseltamivir in controlling influenza outbreaks in ACFs. TRIAL REGISTRATION: [corrected] Australian Clinical Trials Registry ACTRN12606000278538.

BACKGROUND: Cell culture media conditioned by human foreskin fibroblasts (HFFs) provide a complex supplement of protein and metabolic factors that support in vitro proliferation of human embryonic stem cells (hESCs). However, the conditioning process is variable with different media batches often exhibiting differing capacities to maintain hESCs in culture. While recent studies have examined the protein complement of conditioned culture media, detailed information regarding the metabolic component of this media is lacking. METHODOLOGY/PRINCIPAL FINDINGS: Using a (1)H-Nuclear Magnetic Resonance ((1)H-NMR) metabonomics approach, 32 metabolites and small compounds were identified and quantified in media conditioned by passage 11 HFFs (CMp11). A number of metabolites were secreted by HFFs with significantly higher concentration of lactate, alanine, and formate detected in CMp11 compared to non-conditioned media. In contrast, levels of tryptophan, folate and niacinamide were depleted in CMp11 indicating the utilisation of these metabolites by HFFs. Multivariate statistical analysis of the (1)H-NMR data revealed marked age-related differences in the metabolic profile of CMp11 collected from HFFs every 24 h over 72 h. Additionally, the metabolic profile of CMp11 was altered following freezing at -20°C for 2 weeks. CM derived from passage 18 HFFs (CMp18) was found to be ineffective at supporting hESCs in an undifferentiated state beyond 5 days culture. Multivariate statistical comparison of CMp11 and CMp18 metabolic profiles enabled rapid and clear discrimination between the two media with CMp18 containing lower concentrations of lactate and alanine as well as higher concentrations of glucose and glutamine. CONCLUSIONS/SIGNIFICANCE: (1)H-NMR-based metabonomics offers a rapid and accurate method of characterising hESC conditioning media and is a valuable tool for monitoring, controlling and optimising hESC culture media preparation.

It has previously been hypothesized that lower socio-economic status can accelerate biological ageing, and predispose to early onset of disease. This study investigated the association of socio-economic and lifestyle factors, as well as traditional and novel risk factors, with biological-ageing, as measured by telomere length, in a Glasgow based cohort that included individuals with extreme socio-economic differences.A total of 382 blood samples from the pSoBid study were available for telomere analysis. For each participant, data was available for socio-economic status factors, biochemical parameters and dietary intake. Statistical analyses were undertaken to investigate the association between telomere lengths and these aforementioned parameters.The rate of age-related telomere attrition was significantly associated with low relative income, housing tenure and poor diet. Notably, telomere length was positively associated with LDL and total cholesterol levels, but inversely correlated to circulating IL-6.These data suggest lower socio-economic status and poor diet are relevant to accelerated biological ageing. They also suggest potential associations between elevated circulating IL-6, a measure known to predict cardiovascular disease and diabetes with biological ageing. These observations require further study to tease out potential mechanistic links.

The Drosophila dumpy gene consists of seventy eight coding exons and encodes a huge extracellular matrix protein containing large numbers of epidermal growth factor-like (EGF) modules and a novel module called dumpy (DPY). A molecular analysis of forty five mutations in the dumpy gene of Drosophila melanogaster was carried out. Mutations in this gene affect three phenotypes: wing shape, thoracic cuticular defects, and lethality. Most of the mutations were chemically induced in a single dumpy allele and were analyzed using a nuclease that cleaves single base pair mismatches in reannealed duplexes followed by dHPLC. Additionally, several spontaneous mutations were analyzed. Virtually all of the chemically induced mutations, except for several in a single exon, either generate nonsense codons or lesions that result in downstream stop codons in the reading frame. The remaining chemically induced mutations remove splice sites in the nascent dumpy message. We propose that the vast majority of nonsense mutations that affect all three basic dumpy phenotypes are in constitutive exons, whereas nonsense mutants that remove only one or two of the basic functions are in alternatively spliced exons. Evolutionary comparisons of the dumpy gene from seven Drosophila species show strong conservation of the 5' ends of exons where mutants with partial dumpy function are found. In addition, reverse transcription PCR analyses reveal transcripts in which exons marked by nonsense mutations with partial dumpy function are absent.

We aimed to examine the association between obstetrician assessment of maternal physical health at the time of pregnancy and offspring cardiovascular disease risk.We examined this association in a birth cohort of 11,106 individuals, with 245,000 person years of follow-up. We were concerned that any associations might be explained by residual confounding, particularly by family socioeconomic position. In order to explore this we used multivariable regression models in which we adjusted for a range of indicators of socioeconomic position and we explored the specificity of the association. Specificity of association was explored by examining associations with other health related outcomes. Maternal physical health was associated with cardiovascular disease: adjusted (socioeconomic position, complications of pregnancy, birthweight and childhood growth at mean age 5) hazard ratio comparing those described as having poor or very poor health at the time of pregnancy to those with good or very good health was 1.55 (95%CI: 1.05, 2.28) for coronary heart disease, 1.91 (95%CI: 0.99, 3.67) for stroke and 1.57 (95%CI: 1.13, 2.18) for either coronary heart disease or stroke. However, this association was not specific. There were strong associations for other outcomes that are known to be related to socioeconomic position (3.61 (95%CI: 1.04, 12.55) for lung cancer and 1.28 (95%CI:1.03, 1.58) for unintentional injury), but not for breast cancer (1.10 (95%CI:0.48, 2.53)).These findings demonstrate that a simple assessment of physical health (based on the appearance of eyes, skin, hair and teeth) of mothers at the time of pregnancy is a strong indicator of the future health risk of their offspring for common conditions that are associated with poor socioeconomic position and unhealthy behaviours. They do not support a specific biological link between maternal health across her life course and future risk of cardiovascular disease in her offspring.