Deakin University

BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. METHODS: We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors-the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). FINDINGS: Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6-58·8) of global deaths and 41·2% (39·8-42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. INTERPRETATION: Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. FUNDING: Bill & Melinda Gates Foundation.

BACKGROUND: The burden of cardiovascular diseases (CVDs) remains unclear in many regions of the world. OBJECTIVES: The GBD (Global Burden of Disease) 2015 study integrated data on disease incidence, prevalence, and mortality to produce consistent, up-to-date estimates for cardiovascular burden. METHODS: CVD mortality was estimated from vital registration and verbal autopsy data. CVD prevalence was estimated using modeling software and data from health surveys, prospective cohorts, health system administrative data, and registries. Years lived with disability (YLD) were estimated by multiplying prevalence by disability weights. Years of life lost (YLL) were estimated by multiplying age-specific CVD deaths by a reference life expectancy. A sociodemographic index (SDI) was created for each location based on income per capita, educational attainment, and fertility. RESULTS: In 2015, there were an estimated 422.7 million cases of CVD (95% uncertainty interval: 415.53 to 427.87 million cases) and 17.92 million CVD deaths (95% uncertainty interval: 17.59 to 18.28 million CVD deaths). Declines in the age-standardized CVD death rate occurred between 1990 and 2015 in all high-income and some middle-income countries. Ischemic heart disease was the leading cause of CVD health lost globally, as well as in each world region, followed by stroke. As SDI increased beyond 0.25, the highest CVD mortality shifted from women to men. CVD mortality decreased sharply for both sexes in countries with an SDI >0.75. CONCLUSIONS: CVDs remain a major cause of health loss for all regions of the world. Sociodemographic change over the past 25 years has been associated with dramatic declines in CVD in regions with very high SDI, but only a gradual decrease or no change in most regions. Future updates of the GBD study can be used to guide policymakers who are focused on reducing the overall burden of noncommunicable disease and achieving specific global health targets for CVD.

OBJECTIVE: To update and expand the 2013 Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the ICU. DESIGN: Thirty-two international experts, four methodologists, and four critical illness survivors met virtually at least monthly. All section groups gathered face-to-face at annual Society of Critical Care Medicine congresses; virtual connections included those unable to attend. A formal conflict of interest policy was developed a priori and enforced throughout the process. Teleconferences and electronic discussions among subgroups and whole panel were part of the guidelines' development. A general content review was completed face-to-face by all panel members in January 2017. METHODS: Content experts, methodologists, and ICU survivors were represented in each of the five sections of the guidelines: Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption). Each section created Population, Intervention, Comparison, and Outcome, and nonactionable, descriptive questions based on perceived clinical relevance. The guideline group then voted their ranking, and patients prioritized their importance. For each Population, Intervention, Comparison, and Outcome question, sections searched the best available evidence, determined its quality, and formulated recommendations as "strong," "conditional," or "good" practice statements based on Grading of Recommendations Assessment, Development and Evaluation principles. In addition, evidence gaps and clinical caveats were explicitly identified. RESULTS: The Pain, Agitation/Sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) panel issued 37 recommendations (three strong and 34 conditional), two good practice statements, and 32 ungraded, nonactionable statements. Three questions from the patient-centered prioritized question list remained without recommendation. CONCLUSIONS: We found substantial agreement among a large, interdisciplinary cohort of international experts regarding evidence supporting recommendations, and the remaining literature gaps in the assessment, prevention, and treatment of Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) in critically ill adults. Highlighting this evidence and the research needs will improve Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) management and provide the foundation for improved outcomes and science in this vulnerable population.

Large carnivores face serious threats and are experiencing massive declines in their populations and geographic ranges around the world. We highlight how these threats have affected the conservation status and ecological functioning of the 31 largest mammalian carnivores on Earth. Consistent with theory, empirical studies increasingly show that large carnivores have substantial effects on the structure and function of diverse ecosystems. Significant cascading trophic interactions, mediated by their prey or sympatric mesopredators, arise when some of these carnivores are extirpated from or repatriated to ecosystems. Unexpected effects of trophic cascades on various taxa and processes include changes to bird, mammal, invertebrate, and herpetofauna abundance or richness; subsidies to scavengers; altered disease dynamics; carbon sequestration; modified stream morphology; and crop damage. Promoting tolerance and coexistence with large carnivores is a crucial societal challenge that will ultimately determine the fate of Earth's largest carnivores and all that depends upon them, including humans.

Promotion of good mental health, prevention, and early intervention before/at the onset of mental disorders improve outcomes. However, the range and peak ages at onset for mental disorders are not fully established. To provide robust, global epidemiological estimates of age at onset for mental disorders, we conducted a PRISMA/MOOSE-compliant systematic review with meta-analysis of birth cohort/cross-sectional/cohort studies, representative of the general population, reporting age at onset for any ICD/DSM-mental disorders, identified in PubMed/Web of Science (up to 16/05/2020) (PROSPERO:CRD42019143015). Co-primary outcomes were the proportion of individuals with onset of mental disorders before age 14, 18, 25, and peak age at onset, for any mental disorder and across International Classification of Diseases 11 diagnostic blocks. Median age at onset of specific disorders was additionally investigated. Across 192 studies (n = 708,561) included, the proportion of individuals with onset of any mental disorders before the ages of 14, 18, 25 were 34.6%, 48.4%, 62.5%, and peak age was 14.5 years (k = 14, median = 18, interquartile range (IQR) = 11-34). For diagnostic blocks, the proportion of individuals with onset of disorder before the age of 14, 18, 25 and peak age were as follows: neurodevelopmental disorders: 61.5%, 83.2%, 95.8%, 5.5 years (k = 21, median=12, IQR = 7-16), anxiety/fear-related disorders: 38.1%, 51.8%, 73.3%, 5.5 years (k = 73, median = 17, IQR = 9-25), obsessive-compulsive/related disorders: 24.6%, 45.1%, 64.0%, 14.5 years (k = 20, median = 19, IQR = 14-29), feeding/eating disorders/problems: 15.8%, 48.1%, 82.4%, 15.5 years (k = 11, median = 18, IQR = 15-23), conditions specifically associated with stress disorders: 16.9%, 27.6%, 43.1%, 15.5 years (k = 16, median = 30, IQR = 17-48), substance use disorders/addictive behaviours: 2.9%, 15.2%, 48.8%, 19.5 years (k = 58, median = 25, IQR = 20-41), schizophrenia-spectrum disorders/primary psychotic states: 3%, 12.3%, 47.8%, 20.5 years (k = 36, median = 25, IQR = 20-34), personality disorders/related traits: 1.9%, 9.6%, 47.7%, 20.5 years (k = 6, median = 25, IQR = 20-33), and mood disorders: 2.5%, 11.5%, 34.5%, 20.5 years (k = 79, median = 31, IQR = 21-46). No significant difference emerged by sex, or definition of age of onset. Median age at onset for specific mental disorders mapped on a time continuum, from phobias/separation anxiety/autism spectrum disorder/attention deficit hyperactivity disorder/social anxiety (8-13 years) to anorexia nervosa/bulimia nervosa/obsessive-compulsive/binge eating/cannabis use disorders (17-22 years), followed by schizophrenia, personality, panic and alcohol use disorders (25-27 years), and finally post-traumatic/depressive/generalized anxiety/bipolar/acute and transient psychotic disorders (30-35 years), with overlap among groups and no significant clustering. These results inform the timing of good mental health promotion/preventive/early intervention, updating the current mental health system structured around a child/adult service schism at age 18.

BACKGROUND: Many causes of vision impairment can be prevented or treated. With an ageing global population, the demands for eye health services are increasing. We estimated the prevalence and relative contribution of avoidable causes of blindness and vision impairment globally from 1990 to 2020. We aimed to compare the results with the World Health Assembly Global Action Plan (WHA GAP) target of a 25% global reduction from 2010 to 2019 in avoidable vision impairment, defined as cataract and undercorrected refractive error. METHODS: We did a systematic review and meta-analysis of population-based surveys of eye disease from January, 1980, to October, 2018. We fitted hierarchical models to estimate prevalence (with 95% uncertainty intervals [UIs]) of moderate and severe vision impairment (MSVI; presenting visual acuity from <6/18 to 3/60) and blindness (<3/60 or less than 10° visual field around central fixation) by cause, age, region, and year. Because of data sparsity at younger ages, our analysis focused on adults aged 50 years and older. FINDINGS: Global crude prevalence of avoidable vision impairment and blindness in adults aged 50 years and older did not change between 2010 and 2019 (percentage change -0·2% [95% UI -1·5 to 1·0]; 2019 prevalence 9·58 cases per 1000 people [95% IU 8·51 to 10·8], 2010 prevalence 96·0 cases per 1000 people [86·0 to 107·0]). Age-standardised prevalence of avoidable blindness decreased by -15·4% [-16·8 to -14·3], while avoidable MSVI showed no change (0·5% [-0·8 to 1·6]). However, the number of cases increased for both avoidable blindness (10·8% [8·9 to 12·4]) and MSVI (31·5% [30·0 to 33·1]). The leading global causes of blindness in those aged 50 years and older in 2020 were cataract (15·2 million cases [9% IU 12·7-18·0]), followed by glaucoma (3·6 million cases [2·8-4·4]), undercorrected refractive error (2·3 million cases [1·8-2·8]), age-related macular degeneration (1·8 million cases [1·3-2·4]), and diabetic retinopathy (0·86 million cases [0·59-1·23]). Leading causes of MSVI were undercorrected refractive error (86·1 million cases [74·2-101·0]) and cataract (78·8 million cases [67·2-91·4]). INTERPRETATION: Results suggest eye care services contributed to the observed reduction of age-standardised rates of avoidable blindness but not of MSVI, and that the target in an ageing global population was not reached. FUNDING: Brien Holden Vision Institute, Fondation Théa, The Fred Hollows Foundation, Bill & Melinda Gates Foundation, Lions Clubs International Foundation, Sightsavers International, and University of Heidelberg.

<h3>Importance</h3> Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data. <h3>Objective</h3> To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning. <h3>Evidence Review</h3> We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence. <h3>Findings</h3> In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572 000 deaths and 15.2 million DALYs), and stomach cancer (542 000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819 000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601 000 deaths and 17.4 million DALYs), TBL cancer (596 000 deaths and 12.6 million DALYs), and colorectal cancer (414 000 deaths and 8.3 million DALYs). <h3>Conclusions and Relevance</h3> The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Despite a growing body of epidemiological evidence in recent years documenting the health impacts of racism, the cumulative evidence base has yet to be synthesized in a comprehensive meta-analysis focused specifically on racism as a determinant of health. This meta-analysis reviewed the literature focusing on the relationship between reported racism and mental and physical health outcomes. Data from 293 studies reported in 333 articles published between 1983 and 2013, and conducted predominately in the U.S., were analysed using random effects models and mean weighted effect sizes. Racism was associated with poorer mental health (negative mental health: r = -.23, 95% CI [-.24,-.21], k = 227; positive mental health: r = -.13, 95% CI [-.16,-.10], k = 113), including depression, anxiety, psychological stress and various other outcomes. Racism was also associated with poorer general health (r = -.13 (95% CI [-.18,-.09], k = 30), and poorer physical health (r = -.09, 95% CI [-.12,-.06], k = 50). Moderation effects were found for some outcomes with regard to study and exposure characteristics. Effect sizes of racism on mental health were stronger in cross-sectional compared with longitudinal data and in non-representative samples compared with representative samples. Age, sex, birthplace and education level did not moderate the effects of racism on health. Ethnicity significantly moderated the effect of racism on negative mental health and physical health: the association between racism and negative mental health was significantly stronger for Asian American and Latino(a) American participants compared with African American participants, and the association between racism and physical health was significantly stronger for Latino(a) American participants compared with African American participants. Protocol PROSPERO registration number: CRD42013005464.

Uncertainty quantification (UQ) methods play a pivotal role in reducing the impact of uncertainties during both optimization and decision making processes. They have been applied to solve a variety of real-world problems in science and engineering. Bayesian approximation and ensemble learning techniques are two widely-used types of uncertainty quantification (UQ) methods. In this regard, researchers have proposed different UQ methods and examined their performance in a variety of applications such as computer vision (e.g., self-driving cars and object detection), image processing (e.g., image restoration), medical image analysis (e.g., medical image classification and segmentation), natural language processing (e.g., text classification, social media texts and recidivism risk-scoring), bioinformatics, etc. This study reviews recent advances in UQ methods used in deep learning, investigates the application of these methods in reinforcement learning, and highlights fundamental research challenges and directions associated with UQ.

IMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden. OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019. EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs). FINDINGS: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles. CONCLUSIONS AND RELEVANCE: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.

Student feedback literacy denotes the understandings, capacities and dispositions needed to make sense of information and use it to enhance work or learning strategies. In this conceptual paper, student responses to feedback are reviewed and a number of barriers to student uptake of feedback are discussed. Four inter-related features are proposed as a framework underpinning students’ feedback literacy: appreciating feedback; making judgments; managing affect; and taking action. Two well-established learning activities, peer feedback and analysing exemplars, are discussed to illustrate how this framework can be operationalized. Some ways in which these two enabling activities can be re-focused more explicitly towards developing students’ feedback literacy are elaborated. Teachers are identified as playing important facilitating roles in promoting student feedback literacy through curriculum design, guidance and coaching. The implications and conclusion summarise recommendations for teaching and set out an agenda for further research

Ionic liquids offer a unique suite of properties that make them important candidates for a number of energy related applications. Cation–anion combinations that exhibit low volatility coupled with high electrochemical and thermal stability, as well as ionic conductivity, create the possibility of designing ideal electrolytes for batteries, super-capacitors, actuators, dye sensitised solar cells and thermo-electrochemical cells. In the field of water splitting to produce hydrogen they have been used to synthesize some of the best performing water oxidation catalysts and some members of the protic ionic liquid family co-catalyse an unusual, very high energy efficiency water oxidation process. As fuel cell electrolytes, the high proton conductivity of some of the protic ionic liquid family offers the potential of fuel cells operating in the optimum temperature region above 100 °C. Beyond electrochemical applications, the low vapour pressure of these liquids, along with their ability to offer tuneable functionality, also makes them ideal as CO2 absorbents for post-combustion CO2 capture. Similarly, the tuneable phase properties of the many members of this large family of salts are also allowing the creation of phase-change thermal energy storage materials having melting points tuned to the application. This perspective article provides an overview of these developing energy related applications of ionic liquids and offers some thoughts on the emerging challenges and opportunities.

Urbanization and climate change are together exacerbating water scarcity-where water demand exceeds availability-for the world's cities. We quantify global urban water scarcity in 2016 and 2050 under four socioeconomic and climate change scenarios, and explored potential solutions. Here we show the global urban population facing water scarcity is projected to increase from 933 million (one third of global urban population) in 2016 to 1.693-2.373 billion people (one third to nearly half of global urban population) in 2050, with India projected to be most severely affected in terms of growth in water-scarce urban population (increase of 153-422 million people). The number of large cities exposed to water scarcity is projected to increase from 193 to 193-284, including 10-20 megacities. More than two thirds of water-scarce cities can relieve water scarcity by infrastructure investment, but the potentially significant environmental trade-offs associated with large-scale water scarcity solutions must be guarded against.

Deep autoencoder has been extensively used for anomaly detection. Training on the normal data, the autoencoder is expected to produce higher reconstruction error for the abnormal inputs than the normal ones, which is adopted as a criterion for identifying anomalies. However, this assumption does not always hold in practice. It has been observed that sometimes the autoencoder "generalizes" so well that it can also reconstruct anomalies well, leading to the miss detection of anomalies. To mitigate this drawback for autoencoder based anomaly detector, we propose to augment the autoencoder with a memory module and develop an improved autoencoder called memory-augmented autoencoder, i.e. MemAE. Given an input, MemAE firstly obtains the encoding from the encoder and then uses it as a query to retrieve the most relevant memory items for reconstruction. At the training stage, the memory contents are updated and are encouraged to represent the prototypical elements of the normal data. At the test stage, the learned memory will be fixed, and the reconstruction is obtained from a few selected memory records of the normal data. The reconstruction will thus tend to be close to a normal sample. Thus the reconstructed errors on anomalies will be strengthened for anomaly detection. MemAE is free of assumptions on the data type and thus general to be applied to different tasks. Experiments on various datasets prove the excellent generalization and high effectiveness of the proposed MemAE.

This paper develops a general service sector model of repurchase intention from the consumer theory literature. A key contribution of the structural equation model is the incorporation of customer perceptions of equity and value and customer brand preference into an integrated repurchase intention analysis. The model describes the extent to which customer repurchase intention is influenced by seven important factors – service quality, equity and value, customer satisfaction, past loyalty, expected switching cost and brand preference. The general model is applied to customers of comprehensive car insurance and personal superannuation services. The analysis finds that although perceived quality does not directly affect customer satisfaction, it does so indirectly via customer equity and value perceptions. The study also finds that past purchase loyalty is not directly related to customer satisfaction or current brand preference and that brand preference is an intervening factor between customer satisfaction and repurchase intention. The main factor influencing brand preference was perceived value with customer satisfaction and expected switching cost having less influence.

\n\t\t\t\t\tThis article provides an update for 2015 on the burden of cardiovascular disease (CVD), with a particular focus on coronary heart disease (CHD) and stroke, across the countries of Europe. Cardiovascular disease is still the most common cause of death within Europe, causing almost two times as many deaths as cancer across the continent. Although there is clear evidence, where data are available, that mortality from CHD and stroke has decreased substantially over the last 5-10 years, there are still large inequalities found between European countries, in both current rates of death and the rate at which these decreases have occurred. Similarly, rates of treatment, particularly surgical intervention, differ widely between those countries for which data are available, indicating a range of inequalities between them. This is also the first time in the series that we use the 2013 European Standard Population (ESP) to calculate age-standardized death rates (ASDRs). This new standard results in ASDRs around two times as large as the 1976 ESP for CVD conditions such as CHD but changes little the relative rankings of countries according to ASDR.\n\t\t\t\t

STUDY QUESTION: What is the recommended assessment and management of women with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise and consumer preference? SUMMARY ANSWER: International evidence-based guidelines, including 166 recommendations and practice points, addressed prioritized questions to promote consistent, evidence-based care and improve the experience and health outcomes of women with PCOS. WHAT IS KNOWN ALREADY: Previous guidelines either lacked rigorous evidence-based processes, did not engage consumer and international multidisciplinary perspectives, or were outdated. Diagnosis of PCOS remains controversial, and assessment and management are inconsistent. The needs of women with PCOS are not being adequately met and evidence practice gaps persist. STUDY DESIGN, SIZE, DURATION: International evidence-based guideline development engaged professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. Appraisal of Guidelines for Research and Evaluation (AGREE) II-compliant processes were followed, with extensive evidence synthesis. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation and ultimately recommendation strength. PARTICIPANTS/MATERIALS, SETTING, METHODS: Governance included a six continent international advisory and a project board, five guideline development groups, and consumer and translation committees. Extensive health professional and consumer engagement informed guideline scope and priorities. Engaged international society-nominated panels included pediatrics, endocrinology, gynecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, public health and other experts, alongside consumers, project management, evidence synthesis and translation experts. In total, 37 societies and organizations covering 71 countries engaged in the process. Twenty face-to-face meetings over 15 months addressed 60 prioritized clinical questions involving 40 systematic and 20 narrative reviews. Evidence-based recommendations were developed and approved via consensus voting within the five guideline panels, modified based on international feedback and peer review, with final recommendations approved across all panels. MAIN RESULTS AND THE ROLE OF CHANCE: The evidence in the assessment and management of PCOS is generally of low to moderate quality. The guideline provides 31 evidence based recommendations, 59 clinical consensus recommendations and 76 clinical practice points all related to assessment and management of PCOS. Key changes in this guideline include: (i) considerable refinement of individual diagnostic criteria with a focus on improving accuracy of diagnosis; (ii) reducing unnecessary testing; (iii) increasing focus on education, lifestyle modification, emotional wellbeing and quality of life; and (iv) emphasizing evidence based medical therapy and cheaper and safer fertility management. LIMITATIONS, REASONS FOR CAUTION: Overall evidence is generally low to moderate quality, requiring significantly greater research in this neglected, yet common condition, especially around refining specific diagnostic features in PCOS. Regional health system variation is acknowledged and a process for guideline and translation resource adaptation is provided. WIDER IMPLICATIONS OF THE FINDINGS: The international guideline for the assessment and management of PCOS provides clinicians with clear advice on best practice based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation program supports the guideline with an integrated evaluation program. STUDY FUNDING/COMPETING INTEREST(S): The guideline was primarily funded by the Australian National Health and Medical Research Council of Australia (NHMRC) supported by a partnership with ESHRE and the American Society for Reproductive Medicine. Guideline development group members did not receive payment. Travel expenses were covered by the sponsoring organizations. Disclosures of conflicts of interest were declared at the outset and updated throughout the guideline process, aligned with NHMRC guideline processes. Full details of conflicts declared across the guideline development groups are available at https://www.monash.edu/medicine/sphpm/mchri/pcos/guideline in the Register of disclosures of interest. Of named authors, Dr Costello has declared shares in Virtus Health and past sponsorship from Merck Serono for conference presentations. Prof. Laven declared grants from Ferring, Euroscreen and personal fees from Ferring, Euroscreen, Danone and Titus Healthcare. Prof. Norman has declared a minor shareholder interest in an IVF unit. The remaining authors have no conflicts of interest to declare. The guideline was peer reviewed by special interest groups across our partner and collaborating societies and consumer organizations, was independently assessed against AGREE-II criteria, and underwent methodological review. This guideline was approved by all members of the guideline development groups and was submitted for final approval by the NHMRC.

Staying at the top is getting tougher and more challenging due to the fast-growing and changing digital technologies and AI-based solutions. The world of technology, mass customization, and advanced manufacturing is experiencing a rapid transformation. Robots are becoming even more important as they can now be coupled with the human mind by means of brain–machine interface and advances in artificial intelligence. A strong necessity to increase productivity while not removing human workers from the manufacturing industry is imposing punishing challenges on the global economy. To counter these challenges, this article introduces the concept of Industry 5.0, where robots are intertwined with the human brain and work as collaborator instead of competitor. This article also outlines a number of key features and concerns that every manufacturer may have about Industry 5.0. In addition, it presents several developments achieved by researchers for use in Industry 5.0 applications and environments. Finally, the impact of Industry 5.0 on the manufacturing industry and overall economy is discussed from an economic and productivity point of view, where it is argued that Industry 5.0 will create more jobs than it will take away.

Environmental exposure to active pharmaceutical ingredients (APIs) can have negative effects on the health of ecosystems and humans. While numerous studies have monitored APIs in rivers, these employ different analytical methods, measure different APIs, and have ignored many of the countries of the world. This makes it difficult to quantify the scale of the problem from a global perspective. Furthermore, comparison of the existing data, generated for different studies/regions/continents, is challenging due to the vast differences between the analytical methodologies employed. Here, we present a global-scale study of API pollution in 258 of the world's rivers, representing the environmental influence of 471.4 million people across 137 geographic regions. Samples were obtained from 1,052 locations in 104 countries (representing all continents and 36 countries not previously studied for API contamination) and analyzed for 61 APIs. Highest cumulative API concentrations were observed in sub-Saharan Africa, south Asia, and South America. The most contaminated sites were in low- to middle-income countries and were associated with areas with poor wastewater and waste management infrastructure and pharmaceutical manufacturing. The most frequently detected APIs were carbamazepine, metformin, and caffeine (a compound also arising from lifestyle use), which were detected at over half of the sites monitored. Concentrations of at least one API at 25.7% of the sampling sites were greater than concentrations considered safe for aquatic organisms, or which are of concern in terms of selection for antimicrobial resistance. Therefore, pharmaceutical pollution poses a global threat to environmental and human health, as well as to delivery of the United Nations Sustainable Development Goals.