Estimated health benefits, costs, and cost-effectiveness of eliminating industrial transfatty acids in Australia: A modelling study

Background: trans-fatty acids (TFAs) are a well-known risk factor of ischemic heart disease (IHD). In Australia, the highest TFA intake is concentrated to the most socioeconomically disadvantaged groups. Elimination of industrial TFA (iTFA) from the Australian food supply could result in reduced IHD mortality and morbidity while improving health equity. However, such legislation could lead to additional costs for both government and food industry. Thus, we assessed the potential cost-effectiveness, health gains, and effects on health equality of an iTFA ban from the Australian food supply. Methods and findings: Markov cohort models were used to estimate the impact on IHD burden and health equity, as well as the cost-effectiveness of a national ban of iTFA in Australia. Intake of TFA was assessed using the 2011–2012 Australian National Nutrition and Physical Activity Survey. The IHD burden attributable to TFA was calculated by comparing the current level of TFA intake to a counterfactual setting where consumption was lowered to a theoretical minimum distribution with a mean of 0.5% energy per day (corresponding to TFA intake only from nonindustrial sources, e.g., dairy foods). Policy costs, avoided IHD events and deaths, health-adjusted life years (HALYs) gained, and changes in IHD-related healthcare costs saved were estimated over 10 years and lifetime of the adult Australian population. Cost-effectiveness was assessed by calculation of incremental cost-effectiveness ratios (ICERs) using net policy cost and HALYs gained. Health benefits and healthcare cost changes were also assessed in subgroups based on socioeconomic status, defined by Socio-Economic Indexes for Areas (SEIFA) quintile, and remoteness. Compared to a base case of no ban and current TFA intakes, elimination of iTFA was estimated to prevent 2,294 (95% uncertainty interval [UI]: 1,765; 2,851) IHD deaths and 9,931 (95% UI: 8,429; 11,532) IHD events over the first 10 years. The greatest health benefits were accrued to the most socioeconomically disadvantaged quintiles and among Australians living outside of major cities. The intervention was estimated to be cost saving (net cost <0 AUD) or cost-effective (i.e., ICER < AUD 169,361/HALY) regardless of the time horizon, with ICERs of 1,073 (95% UI: dominant; 3,503) and 1,956 (95% UI: 1,010; 2,750) AUD/HALY over 10 years and lifetime, respectively. Findings were robust across several sensitivity analyses. Key limitations of the study include the lack of recent data of TFA intake and the small sample sizes used to estimate intakes in subgroups. As with all simulation models, our study does not prove that a ban of iTFA will prevent IHD, rather, it provides the best quantitative estimates and corresponding uncertainty of a potential effect in the absence of stronger direct evidence. Conclusions: Our model estimates that a ban of iTFAs could avert substantial numbers of IHD events and deaths in Australia and would likely be a highly cost-effective strategy to reduce social–economic and urban–rural inequalities in health. These findings suggest that elimination of iTFA can cost-effectively improve health and health equality even in countries with low iTFA intake

Can we use local climate zones for predicting malaria prevalence across sub-Saharan African cities?

Malaria burden is increasing in sub-Saharan cities because of rapid and uncontrolled urbanization. Yet very few studies have studied the interactions between urban environments and malaria. Additionally, no standardized urban land-use/land-cover has been defined for urban malaria studies. Here, we demonstrate the potential of local climate zones (LCZs) for modeling malaria prevalence rate (PfPR2-10) and studying malaria prevalence in urban settings across nine sub-Saharan African cities. Using a random forest classification algorithm over a set of 365 malaria surveys we: (i) identify a suitable set of covariates derived from open-source earth observations; and (ii) depict the best buffer size at which to aggregate them for modeling PfPR2-10. Our results demonstrate that geographical models can learn from LCZ over a set of cities and be transferred over a city of choice that has few or no malaria surveys. In particular, we find that urban areas systematically have lower PfPR2-10 (5%-30%) than rural areas (15%-40%). The PfPR2-10 urban-to-rural gradient is dependent on the climatic environment in which the city is located. Further, LCZs show that more open urban environments located close to wetlands have higher PfPR2-10. Informal settlements - represented by the LCZ 7 (lightweight lowrise) - have higher malaria prevalence than other densely built-up residential areas with a mean prevalence of 11.11%. Overall, we suggest the applicability of LCZs for more exploratory modeling in urban malaria studies. © 2020 The Author(s). Published by IOP Publishing Ltd.info:eu-repo/semantics/publishe

Economic costs of chronic disease through lost productive life years (PLYs) among Australians aged 45–64 years from 2015 to 2030:Results from a microsimulation model

Objectives: To project the number of older workers with lost productive life years (PLYs) due to chronic disease and resultant lost income; and lost taxes and increased welfare payments from 2015 to 2030. Design, setting and participants: Using a microsimulation model, Health&WealthMOD2030, the costs of chronic disease in Australians aged 45–64 were projected to 2030. The model integrates household survey data from the Australian Bureau of Statistics Surveys of Disability, Ageing and Carers (SDACs) 2003 and 2009, output from long-standing microsimulation models (STINMOD (Static Incomes Model) and APPSIM (Australian Population and Policy Simulation Model)) used by various government departments, population and labour force growth data from Treasury, and disease trends data from the Australian Burden of Disease and Injury Study (2003). Respondents aged 45–64 years in the SDACs 2003 and 2009 formed the base population. Main outcome measures: Lost PLYs due to chronic disease; resultant lost income, lost taxes and increased welfare payments in 2015, 2020, 2025 and 2030. Results: We projected 380 000 (6.4%) people aged 45–64 years with lost PLYs in 2015, increasing to 462 000 (6.5%) in 2030—a 22% increase in absolute numbers. Those with lost PLYs experience the largest reduction in income than any other group in each year compared to those employed full time without a chronic disease, and this income gap widens over time. The total economic loss due to lost PLYs consisted of lost income modelled at $A12.6 billion in 2015, increasing to$A20.5 billion in 2030—a 62.7% increase. Additional costs to the government consisted of increased welfare payments at $A6.2 billion in 2015, increasing to$A7.3 billion in 2030—a 17.7% increase; and a loss of $A3.1 billion in taxes in 2015, increasing to$A4.7 billion in 2030—a growth of 51.6%. Conclusions: There is a need for greater investment in effective preventive health interventions which improve workers’ health and work capacity.Full Tex

Activation of endosomal dynein motors by stepwise assembly of Rab7–RILP–p150Glued, ORP1L, and the receptor βlll spectrin

The small GTPase Rab7 controls late endocytic transport by the minus end–directed motor protein complex dynein–dynactin, but how it does this is unclear. Rab7-interacting lysosomal protein (RILP) and oxysterol-binding protein–related protein 1L (ORP1L) are two effectors of Rab7. We show that GTP-bound Rab7 simultaneously binds RILP and ORP1L to form a RILP–Rab7–ORP1L complex. RILP interacts directly with the C-terminal 25-kD region of the dynactin projecting arm p150Glued, which is required for dynein motor recruitment to late endocytic compartments (LEs). Still, p150Glued recruitment by Rab7–RILP does not suffice to induce dynein-driven minus-end transport of LEs. ORP1L, as well as βIII spectrin, which is the general receptor for dynactin on vesicles, are essential for dynein motor activity. Our results illustrate that the assembly of microtubule motors on endosomes involves a cascade of linked events. First, Rab7 recruits two effectors, RILP and ORP1L, to form a tripartite complex. Next, RILP directly binds to the p150Glued dynactin subunit to recruit the dynein motor. Finally, the specific dynein motor receptor Rab7–RILP is transferred by ORP1L to βIII spectrin. Dynein will initiate translocation of late endosomes to microtubule minus ends only after interacting with βIII spectrin, which requires the activities of Rab7–RILP and ORP1L

Precise evaluation of leaked information with universal2 privacy amplification in the presence of quantum attacker

We treat secret key extraction when the eavesdropper has correlated quantum states. We propose quantum privacy amplification theorems different from Renner's, which are based on quantum conditional R\'{e}nyi entropy of order 1+s. Using those theorems, we derive an exponential decreasing rate for leaked information and the asymptotic equivocation rate, which have not been derived hitherto in the quantum setting

The HLS19-COM-P, a New Instrument for Measuring Communicative Health Literacy in Interaction with Physicians: Development and Validation in Nine European Countries

Background: Sufficient communicative health literacy (COM-HL) is important for patients actively participating in dialogue with physicians, expressing their needs and desires for treatment, and asking clarifying questions. There is a lack of instruments combining communication and HL proficiency. Hence, the aim was to establish an instrument with sufficient psychometric properties for measuring COM-HL. Methods: The HLS19-COM-P instrument was developed based on a conceptual framework integrating HL with central communicative tasks. Data were collected using different data collection modes in nine countries from December 2019 to January 2021 (n = 18,674). Psychometric properties were assessed using Rasch analysis and confirmatory factor analysis. Cronbach’s alpha and Person separation index were considered for reliability. Results: The 11-item version (HLS19-COM-P-Q11) and its short version of six items (HLS19-COM-P-Q6) fit sufficiently the unidimensional partial credit Rasch model, obtained acceptable goodness-of-fit indices and high reliability. Two items tend to under-discriminate. Few items displayed differential item functioning (DIF) across person factors, and there was no consistent pattern in DIF across countries. All items had ordered response categories. Conclusions: The HLS19-COM-P instrument was well accepted in nine countries, in different data collection modes, and could be used to measure COM-HL.publishedVersio

Efficient CRISPR-mediated base editing in Agrobacterium spp.

Agrobacterium spp. are important plant pathogens that are the causative agents of crown gall or hairy root disease. Their unique infection strategy depends on the delivery of part of their DNA to plant cells. Thanks to this capacity, these phytopathogens became a powerful and indispensable tool for plant genetic engineering and agricultural biotechnology. Although Agrobacterium spp. are standard tools for plant molecular biologists, current laboratory strains have remained unchanged for decades and functional gene analysis of Agrobacterium has been hampered by time-consuming mutation strategies. Here, we developed clustered regularly inter-spaced short palindromic repeats (CRISPR)-mediated base editing to enable the efficient introduction of targeted point mutations into the genomes of both Agrobacterium tumefaciens and Agro-bacterium rhizogenes. As an example, we generated EHA105 strains with loss-of-function mutations in recA, which were fully functional for maize (Zea mays) transformation and confirmed the importance of RolB and RolC for hairy root development by A. rhizogenes K599. Our method is highly effective in 9 of 10 colonies after transformation, with edits in at least 80% of the cells. The genomes of EHA105 and K599 were resequenced, and genome-wide off-target analysis was applied to investigate the edited strains after curing of the base editor plasmid. The off-targets present were characteristic of Cas9-independent off-targeting and point to TC motifs as activity hotspots of the cytidine deaminase used. We anticipate that CRISPR-mediated base editing is the start of "engineering the engineer," leading to improved Agrobacterium strains for more efficient plant transformation and gene editing