Global, regional, and national age–sex specifi c all-cause and cause-specifi c mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background Up-to-date evidence on levels and trends for age-sex-specific all-cause and cause-specific mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specific all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specific causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65·3 years (UI 65·0–65·6) in 1990, to 71·5 years (UI 71·0–71·9) in 2013, while the number of deaths increased from 47·5 million (UI 46·8–48·2) to 54·9 million (UI 53·6–56·3) over the same interval. Global progress masked variation by age and sex: for children, average absolute differences between countries decreased but relative differences increased. For women aged 25–39 years and older than 75 years and for men aged 20–49 years and 65 years and older, both absolute and relative differences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10·7%, from 4·3 million deaths in 1990 to 4·8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specific mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.

Spectrophotometric analysis of phenols, which involves a hemin-graphene hybrid nanoparticles with peroxidase-like activity

Phenols are well known noxious compounds, which are often found in various water sources. A novel analytical method has been researched and developed based on the properties of hemin–graphene hybrid nanosheets (H–GNs). These nanosheets were synthesized using a wet-chemical method, and they have peroxidase-like activity. Also, in the presence of H2O2, the nanosheets are efficient catalysts for the oxidation of the substrate, 4-aminoantipine (4-AP), and the phenols. The products of such an oxidation reaction are the colored quinone-imines (benzodiazepines). Importantly, these products enabled the differentiation of the three common phenols – pyrocatechol, resorcin and hydroquinone, with the use of a novel, spectroscopic method, which was developed for the simultaneous determination of the above three analytes. This spectroscopic method produced linear calibrations for the pyrocatechol (0.4–4.0 mg L−1), resorcin (0.2–2.0 mg L−1) and hydroquinone (0.8–8.0 mg L−1) analytes. In addition, kinetic and spectral data, obtained from the formation of the colored benzodiazepines, were used to establish multi-variate calibrations for the prediction of the three phenol analytes found in various kinds of water; partial least squares (PLS), principal component regression (PCR) and artificial neural network (ANN) models were used and the PLS model performed best.

Kallikrein 4 (hK4) and prostate-specific antigen (PSA) are associated with the loss of E-cadherin and an epithelial-mesenchymal transition (EMT)-like effect in prostate cancer cells

Prostate-specific antigen (PSA) and the related kallikrein family of serine proteases are current or emerging biomarkers for prostate cancer detection and progression. Kallikrein 4 (KLK4/hK4) is of particular interest, as KLK4 mRNA has been shown to be elevated in prostate cancer. In this study, we now show that the comparative expression of hK4 protein in prostate cancer tissues, compared with benign glands, is greater than that of PSA and kallikrein 2 (KLK2/hK2), suggesting that hK4 may play an important functional role in prostate cancer progression in addition to its biomarker potential. To examine the roles that hK4, as well as PSA and hK2, play in processes associated with progression, these kallikreins were separately transfected into the PC-3 prostate cancer cell line, and the consequence of their stable transfection was investigated. PC-3 cells expressing hK4 had a decreased growth rate, but no changes in cell proliferation were observed in the cells expressing PSA or hK2. hK4 and PSA, but not hK2, induced a 2.4-fold and 1.7-fold respective increase, in cellular migration, but not invasion, through Matrigel, a synthetic extracellular matrix. We hypothesised that this increase in motility displayed by the hK4 and PSA-expressing PC-3 cells may be related to the observed change in structure in these cells from a typical rounded epithelial-like cell to a spindle-shaped, more mesenchymal-like cell, with compromised adhesion to the culture surface. Thus, the expression of E-cadherin and vimentin, both associated with an epithelial-mesenchymal transition (EMT), was investigated. E-cadherin protein was lost and mRNA levels were significantly decreased in PC-3 cells expressing hK4 and PSA (10-fold and 7-fold respectively), suggesting transcriptional repression of E-cadherin, while the expression of vimentin was increased in these cells. The loss of E-cadherin and associated increase in vimentin are indicative of EMT and provides compelling evidence that hK4, in particular, and PSA have a functional role in the progression of prostate cancer through their promotion of tumour cell migration.

Elucidating the host-pathogen interactions between in vitro human cells and enterovirus 71 in Hand, Foot and Mouth Disease (HFMD)

This study has provided further understanding of the pathogenesis of EV71, one of the major etiological agents associated with significant mortality in Hand, Foot and Mouth disease. Elucidating the host-pathogen interaction and the mechanism that the virus uses to bypass host defence systems to establish infection will aid in the development of potential antiviral therapeutics against EV71.

Emotion and its regulation predicts gluten-free diet adherence in adults with coeliac disease

Objective The aim of this study was to explore the mediating and moderating relationships between emotional perceptions of coeliac disease, negative emotional states, emotion regulation, emotional eating and gluten-free diet adherence. Method Adults with coeliac disease (N = 253) were recruited from state organisations of Coeliac Australia and completed an online questionnaire measuring illness perceptions, emotion regulation strategies, negative emotional states, emotional eating and gluten-free diet adherence. Results Participants' levels of depression and anxiety, but not stress or emotional eating, were associated with gluten-free diet adherence. Emotional perception of coeliac disease was also associated with gluten-free diet adherence, and this relationship was partially mediated by depression and anxiety. Furthermore, the emotion regulation strategies of cognitive reappraisal and expressive suppression moderated the relationship between emotional perceptions and depression, but not emotional perceptions and anxiety. Conclusions Interventions to improve dietary adherence for adults with coeliac disease displaying depressive symptoms should aim to increase the use of cognitive reappraisal and reduce the use of expressive suppression. Future studies should also explore mechanisms that may moderate the relationship between emotional perceptions and anxiety.

Childhood atopic dermatitis : a cross-sectional study of relationships between child and parent factors, atopic dermatitis management, and disease severity

Background: Successful management of atopic dermatitis poses a significant and ongoing challenge to parents of affected children. Despite frequent reports of child behaviour problems and parenting difficulties, there is a paucity of literature examining relationships between child behaviour and parents' confidence and competence with treatment. Objectives: To examine relationships between child, parent, and family variables, parents' self-efficacy for managing atopic dermatitis, self-reported performance of management tasks, observed competence with providing treatment, and atopic dermatitis severity. Design: Cross-sectional study design. Participants A sample of 64 parent-child dyads was recruited from the dermatology clinic of a paediatric tertiary referral hospital in Brisbane, Australia. Methods: Parents completed self-report questionnaires examining child behaviour, parents' adjustment, parenting conflict, parents' relationship satisfaction, and parents' self-efficacy and self-reported performance of key management tasks. Severity of atopic dermatitis was assessed using the Scoring Atopic Dermatitis index. A routine home treatment session was observed, and parents' competence in carrying out the child's treatment assessed. Results: Pearson's and Spearman's correlations identified significant relationships (p< .05) between parents' self-efficacy and disease severity, child behaviour difficulties, parent depression and stress, parenting conflict, and relationship satisfaction. There were also significant relationships between each of these variables and parents' self-reported performance of management tasks. More profound child behaviour difficulties were associated with more severe atopic dermatitis and greater parent stress. Using multiple linear regressions, significant proportions of variation in parents' self-efficacy and self-reported task performance were explained by child behaviour difficulties and parents' formal education. Self-efficacy emerged as a likely mediator for relationships between both child behaviour and parents' education, and self-reported task performance. Direct observation of treatment sessions revealed strong relationships between parents' treatment competence and parents' self-efficacy, outcome expectations, and self-reported task performance. Less competent task performance was also associated with greater parent-reported child behaviour difficulties, parent depression and stress, parenting conflict, and relationship dissatisfaction. Conclusion: This study revealed the importance of child behaviour to parents' confidence and practices in the context of atopic dermatitis management. Children with more severe atopic dermatitis are at risk of presenting with challenging behaviour problems and their parents struggle to manage the condition successfully.

IMU aided 3D visual odometry for car-like vehicles

We present a method for calculating odome- try in three-dimensions for car-like ground ve- hicles with an Ackerman-like steering model. In our approach we use the information from a single camera to derive the odometry in the plane and fuse it with roll and pitch informa- tion derived from an on-board IMU to extend to three-dimensions, thus providing odometric altitude as well as traditional x and y transla- tion. We have mounted the odometry module on a standard Toyota Prado SUV and present results from a car-park environment as well as from an off-road track.

Coverage algorithms for an under-actuated car-like vehicle in an uncertain environment

A coverage algorithm is an algorithm that deploys a strategy as to how to cover all points in terms of a given area using some set of sensors. In the past decades a lot of research has gone into development of coverage algorithms. Initially, the focus was coverage of structured and semi-structured indoor areas, but with time and development of better sensors and introduction of GPS, the focus has turned to outdoor coverage. Due to the unstructured nature of an outdoor environment, covering an outdoor area with all its obstacles and simultaneously performing reliable localization is a difficult task. In this paper, two path planning algorithms suitable for solving outdoor coverage tasks are introduced. The algorithms take into account the kinematic constraints of an under-actuated car-like vehicle, minimize trajectory curvatures, and dynamically avoid detected obstacles in the vicinity, all in real-time. We demonstrate the performance of the coverage algorithm in the field by achieving 95% coverage using an autonomous tractor mower without the aid of any absolute localization system or constraints on the physical boundaries of the area.

Scrutinising the other : incapacity, suspicion and manipulation in a death investigation

In common law countries like England, Australia, the USA and Canada, certain deaths come to be investigated through the coronial system. These include sudden, unnatural or suspicious deaths as well as those which appear to be the result of naturally occurring disease but the precise cause is unknown. When a reportable death occurs in Australia, a number of professional groups become involved in its investigation – police, coroners, pathologists and counsellors. While research has demonstrated the importance of training and education for staff in the context of criminal investigations – with its over-representation of vulnerable and marginalised populations – this is less likely to occur in the context of death investigations, despite such investigations also involving the over-representation of vulnerable populations. This paper, part of larger funded research on the decision-making of coronial professionals in the context of cultural and religious difference, explores the ways in which cultural and religious minority groups – in this case Islam, Judaism and Indigeneity – become differently positioned during the death investigation based upon how they are perceived as ‘other’. Our research raises three issues. First, positioning as ‘the other’ is dependent on the professional training of the staff member, with police and pathologists far more likely than coroners to be suspicious or ignorant of difference. Second, specific historical and contemporary events effect the Othering of religious and cultural difference. Third, the grieving practices associated with religious and cultural difference can be collectively Othered through their perceived opposition to modernity.

Using internet search queries for infectious disease surveillance: screening diseases for suitability

Background Internet-based surveillance systems provide a novel approach to monitoring infectious diseases. Surveillance systems built on internet data are economically, logistically and epidemiologically appealing and have shown significant promise. The potential for these systems has increased with increased internet availability and shifts in health-related information seeking behaviour. This approach to monitoring infectious diseases has, however, only been applied to single or small groups of select diseases. This study aims to systematically investigate the potential for developing surveillance and early warning systems using internet search data, for a wide range of infectious diseases. Methods Official notifications for 64 infectious diseases in Australia were downloaded and correlated with frequencies for 164 internet search terms for the period 2009–13 using Spearman’s rank correlations. Time series cross correlations were performed to assess the potential for search terms to be used in construction of early warning systems. Results Notifications for 17 infectious diseases (26.6%) were found to be significantly correlated with a selected search term. The use of internet metrics as a means of surveillance has not previously been described for 12 (70.6%) of these diseases. The majority of diseases identified were vaccine-preventable, vector-borne or sexually transmissible; cross correlations, however, indicated that vector-borne and vaccine preventable diseases are best suited for development of early warning systems. Conclusions The findings of this study suggest that internet-based surveillance systems have broader applicability to monitoring infectious diseases than has previously been recognised. Furthermore, internet-based surveillance systems have a potential role in forecasting emerging infectious disease events, especially for vaccine-preventable and vector-borne diseases

If you're going to be a leader, at least act like it! Prejudice towards women who are tentative in leader roles

Role congruity theory predicts prejudice towards women who meet the agentic requirements of the leader role. In line with recent findings indicating greater acceptance of agentic behaviour from women, we find evidence for a more subtle form of prejudice towards women who fail to display agency in leader roles. Using a classic methodology, the agency of male and female leaders was manipulated using assertive or tentative speech, presented through written (Study 1, N = 167) or verbal (Study 2, N = 66) communications. Consistent with predictions, assertive women were as likeable and influential as assertive men, while being tentative in leadership reduced the likeability and influence of women, but not of men. Although approval of agentic behaviour from women in leadership reflects progress, evidence that women are quickly singled out for disapproval if they fail to show agency is important for understanding how they continue to be at a distinct disadvantage to men in leader roles.

Hand, foot and mouth disease in China: Evaluating an automated system for the detection of outbreaks

Objective To evaluate the performance of China’s infectious disease automated alert and response system in the detection of outbreaks of hand, foot and mouth (HFM) disease. Methods We estimated size, duration and delay in reporting HFM disease outbreaks from cases notified between 1 May 2008 and 30 April 2010 and between 1 May 2010 and 30 April 2012, before and after automatic alert and response included HFM disease. Sensitivity, specificity and timeliness of detection of aberrations in the incidence of HFM disease outbreaks were estimated by comparing automated detections to observations of public health staff. Findings The alert and response system recorded 106 005 aberrations in the incidence of HFM disease between 1 May 2010 and 30 April 2012 – a mean of 5.6 aberrations per 100 days in each county that reported HFM disease. The response system had a sensitivity of 92.7% and a specificity of 95.0%. The mean delay between the reporting of the first case of an outbreak and detection of that outbreak by the response system was 2.1 days. Between the first and second study periods, the mean size of an HFM disease outbreak decreased from 19.4 to 15.8 cases and the mean interval between the onset and initial reporting of such an outbreak to the public health emergency reporting system decreased from 10.0 to 9.1 days. Conclusion The automated alert and response system shows good sensitivity in the detection of HFM disease outbreaks and appears to be relatively rapid. Continued use of this system should allow more effective prevention and limitation of such outbreaks in China.

Mesenchymal stromal cells transiently alter the inflammatory milieu post-transplant to delay graft-versus-host disease

Background: Multipotent mesenchymal stromal cells suppress T-cell function in vitro, a property that has underpinned their use in treating clinical steroid-refractory graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. However the potential of mesenchymal stromal cells to resolve graft-versus-host disease is confounded by a paucity of pre-clinical data delineating their immunomodulatory effects in vivo. Design and Methods: We examined the influence of timing and dose of donor-derived mesenchymal stromal cells on the kinetics of graft-versus-host disease in two murine models of graft-versus-host disease (major histocompatibility complex-mismatched: UBI-GFP/BL6 [H-2b]→BALB/c [H-2d] and the sibling transplant mimic, UBI-GFP/BL6 [H-2b]→BALB.B [H-2b]) using clinically relevant conditioning regimens. We also examined the effect of mesenchymal stromal cell infusion on bone marrow and spleen cellular composition and cytokine secretion in transplant recipients. Results: Despite T-cell suppression in vitro, mesenchymal stromal cells delayed but did not prevent graft-versus-host disease in the major histocompatibility complex-mismatched model. In the sibling transplant model, however, 30% of mesenchymal stromal cell-treated mice did not develop graft-versus-host disease. The timing of administration and dose of the mesenchymal stromal cells influenced their effectiveness in attenuating graft-versus-host disease, such that a low dose of mesenchymal stromal cells administered early was more effective than a high dose of mesenchymal stromal cells given late. Compared to control-treated mice, mesenchymal stromal cell-treated mice had significant reductions in serum and splenic interferon-γ, an important mediator of graft-versus-host disease. Conclusions: Mesenchymal stromal cells appear to delay death from graft-versus-host disease by transiently altering the inflammatory milieu and reducing levels of interferon-γ. Our data suggest that both the timing of infusion and the dose of mesenchymal stromal cells likely influence these cells’ effectiveness in attenuating graft-versus-host disease.

Reduced intensity conditioning for allogeneic hematopoietic stem cell transplant determines the kinetics of acute Graft-Versus-Host Disease

Background Preparative myeloablative conditioning regimens for allogeneic hematopoietic stem-cell transplantation (HSCT) may control malignancy and facilitate engraftment but also contribute to transplant related mortality, cytokine release, and acute graft-versus-host disease (GVHD). Reduced intensity conditioning (RIC) regimens have decreased transplant related mortality but the incidence of acute GVHD, while delayed, remains unchanged. There are currently no in vivo allogeneic models of RIC HSCT, limiting studies into the mechanism behind RIC-associated GVHD. Methods We developed two RIC HSCT models that result in delayed onset GVHD (major histocompatibility complex mismatched (UBI-GFP/BL6 [H-2b]→BALB/c [H-2d]) and major histocompatibility complex matched, minor histocompatibility mismatched (UBI-GFP/BL6 [H-2b]→BALB.B [H-2b])) enabling the effect of RIC on chimerism, dendritic cell (DC) chimerism, and GVHD to be investigated. Results In contrast with myeloablative conditioning, we observed that RIC-associated delayed-onset GVHD is characterized by low production of tumor necrosis factor-α, maintenance of host DC, phenotypic DC activation, increased T-regulatory cell numbers, and a delayed emergence of activated donor DC. Furthermore, changes to the peritransplant milieu in the recipient after RIC lead to the altered activation of DC and the induction of T-regulatory responses. Reduced intensity conditioning recipients suffer less early damage to GVHD target organs. However, as donor cells engraft, activated donor DC and rising levels of tumor necrosis factor-α are associated with a later onset of severe GVHD. Conclusions Delineating the mechanisms underlying delayed onset GVHD in RIC HSCT recipients is vital to improve the prediction of disease onset and allow more targeted interventions for acute GVHD.

Developing a therapeutic anti-dendritic cell antibody to prevent graft versus host disease

Host and donor dendritic cells (DC) stimulate alloreactive donor T lymphocytes, and initiate GVHD. We have shown that polyclonal antibody to the DC surface activation marker human CD83 (anti hCD83), which depletes activated DC, can prevent human DC and T cell induced lethal xenogeneic GVHD in SCID mice without impairing T cell mediated anti-leukaemic and anti-viral (CMV and influenza) immunity (J Exp Med 2009; 206: 387). Therefore, we made and tested a polyclonal anti mouse CD83 (RAM83) antibody in murine HSCT models and developed a human mAb against hCD83 as a potential new therapeutic immunosuppressive agent.