Trust realisation in multi-domain collaborative environments

In the Internet-age, the geographical boundaries that have previously impinged upon inter-organisational collaborations have become decreasingly important. Of more importance for such collaborations is the notion and subsequent nature of trust - this is especially so in Grid-like environments where resources are both made available and subsequently accessed and used by remote users from a multitude of institutions with a variety of different privileges spanning across the collaborating resources. In this context, the ability to dynamically negotiate and subsequently enforce security policies driven by various levels of inter-organisational trust is essential. In this paper we present a dynamic trust negotiation (DTN) model and associated prototype implementation showing the benefits and limitations DTN incurs in supporting n-tier delegation hops needed for trust realisation in multi-domain collaborative environments

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions. Funding: Bill & Melinda Gates Foundation

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. Methods: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model—a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates—with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality—which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. Findings: The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2–100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1–290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1–211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4–48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3–37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7–9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. Interpretation: Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. Funding: Bill & Melinda Gates Foundation

Cardiovascular disease and the potential protective role of antioxidants

ArticleEpidemiological studies have shown that in the 20th century, cardiovascular disease was responsible for less than ten percent of all deaths globally. However, recent reports indicate that the trend has changed with studies showing that cardiovascular disease currently accounts for about thirty percent of all deaths in the world. It is generally accepted that smoking, high blood cholesterol levels, high triglyceride levels, elevated LDL levels, elevated blood pressure, physical inactivity, insulin resistance, obesity and type 2-diabetes are risk factors for cardiovascular disease. Unfortunately these known risk factors do not provide a full explanation for all cases of heart disease. Recent research has identified what is preferentially termed novel risk factors that may assist to identify persons or populations at risk of developing cardiovascular disease. One such novel risk factor is the presence in the body of freeand hydroxyperoxide radicals. It has been reported that free-and hydroxyperoxide radicals have the potential to damage biological compounds and structures such as proteins, membrane lipids, DNA and carbohydrates and that such damage caused by these radicals are said to be involved in the aetiology and pathogenesis of different diseases such as cardiovascular disease. The link between deficiencies of antioxidants and production of free-and hydroxyperoxide radicals has been reported. This review paper reports on cardiovascular disease, its associated risk factors and the potential protective role of antioxidants in the prevention and management of cardiovascular disease

Red palm oil: nutritional, physiological and therapeutic roles in improving human wellbeing and quality of life.

ArticleA growing interest in dietary palm oil has been observed due to the link between dietary fats and cardiovascular diseases. This review provides a comprehensive overview of current scientific information on the nutritional, physiological, and biochemical roles of red palm oil in improving the wellbeing and quality of life. Specifically, the role of red palm oil in supplementation and in diseases such as cancer and atherosclerosis is discussed. However, despite the various health benefits of red palm oil, moderate intake is recommended because excess intake may promote high cholesterol levels thus increasing the risk of cardiovascular diseases

Selenium: its potential role in male infertility

Currently, biomedical research is showing interest in the anti-oxidant activity of selenium. This could be due to compelling evidence that reported that oxidative damage to cells and cell membranes is one of the causative agents in the pathogenesis of many disease states including male infertility. Selenium is a trace element which may be found in soil, water and some foods and is considered to be an essential element which plays an active role in several metabolic pathways and is believed to perform several important roles in the human body. These roles include anti-oxidative activities at cellular level and participating in different enzyme systems. Selenium also serves as a vital component in the maintenance of muscle cell and red blood cell integrity, playing a role in the synthesis of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). It has also been reported that selenium is essential in the detoxification of toxic metals in the human system, foetal respiration and energy transfer reactions as well as in the production of sperm cells. It is thought that male infertility can be the result of a selenium deficiency as the absence of selenium in the testicular tissues induces degeneration which results in the active impairment of sperm motility as the first indication of impending infertility. This review paper investigates the role of selenium in male infertility

Possible benefits of micronutrient supplementation in the treatment and management of HIV infection and AIDS

ArticleRecently, several reports have indicated that individuals living with HIV/AIDS undergo a condition of chronic oxidative stress with a resultant decline in nutritional antioxidants and other micronutrients. It has also been reported that these micronutrient deficiencies interfere with immune functions, weaken epithelial integrity, contribute to oxidative stress and enhance HIV disease progression. Reports from observational studies have led to an increasing interest in the possible benefits of micronutrient supplementation as a cost-effective strategy for improving oxidative and nutritional status. Micronutrient supplementation may also assist in the possible prevention of vertical transmission of HIV from mother to child especially in low-income countries where antiretroviral therapy and prophylactic drugs are not readily available. However, there are conflicting reports from other observational studies as to the usefulness or benefits of micronutrient supplementation in the treatment and management of HIV/AIDS. In this review we examine possible benefits of micronutrient supplementation in the treatment and management of HIV infection and AIDS

Microbicides: a possible prevention approach to HIV transmission among African women.

ArticlePoverty, cultural belief and refusal to use condoms are some of the factors that contribute to the spread of HIV infection among African communities. There is a dire need to pursue research into the development, provision and the use of microbicides for African women. This review paper provides information and recommendations on the possible use of microbicides to prevent HIV infection among African women

Modulation of erythrocyte antioxidant enzyme levels by red palm oil supplementation in male Wistar rats.

ArticleThe depletion of antioxidants including antioxidant enzymes is known to increase the risk of complications in conditions such as cardiovascular disease, diabetes and cancer. In order to investigate such effects, a study was performed to examine the influence of red palm oil (RPO) supplementation on antioxidant enzymes in a rodent model. Male Wistar rats weighing 120-150 g were randomly divided into a control group that was fed a standard rat chow and an experimental group that received a daily dose of 2 ml of red palm oil incorporated in standard rat chow over a period of 6 weeks. Blood samples were collected from the animals at the end of the feeding period and antioxidant enzymes superoxide dismutase (SOD), glutathione reductase (GR), catalase (CAT) and reduced glutathione (GSH) (a non-enzymatic antioxidant protein) were measured spectrophotometrically. Results showed that RPO caused a significant increase in the activities of SOD, CAT and GR but showed no observable effect on GSH. Our findings suggest that RPO could minimize oxidative damage through its potential ability to increase antioxidant enzymes and it may therefore play a role in the prevention and treatment of oxidative injuries to cells. However, further studies are required to explore and support this hypothesis

Evaluation of cryptolepine and huperzine derivatives as lead compounds towards new agents for the treatment of human African Trypanosomiasis.

noThe alkaloid cryptolepine (1) and eight synthetic analogues (2-8) were assessed for in vitro activities against Trypanosoma brucei. Four of the analogues were found to be highly potent with IC50 values of less than 3 nM and three of these were assessed against T. brucei brucei infection in rats. The most effective compound was 2,7-dibromocryptolepine (7); a single oral dose of 20 mg/Kg suppressed parasitaemia and increased the mean survival time to 13.6 days compared with 8.4 days for untreated controls. In addition, four huperzine derivatives (9-12) were shown to have in vitro antitrypanosomal activities with IC50 values from 303-377 nM