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The magnitude and distribution of physical and societal impacts from long-lived greenhouse gases are insensitive to the emission source location; the same is not true for major coemitted short-lived pollutants such as aerosols. Here, we combine novel global climate model simulations with established response functions to show that a given aerosol emission from different regions produces divergent air quality and climate changes and associated human system impacts, both locally and globally. The marginal global damages to infant mortality, crop productivity, and economic growth from aerosol emissions and their climate effects differ by more than an order of magnitude depending on source region, with certain regions creating global external climate changes and impacts much larger than those felt locally. The complex distributions of aerosol-driven societal impacts emerge from geographically distinct and region-specific aerosol-climate interactions, estimation of which is enabled by the full Earth System Modeling Framework used here.

BackgroundApproaches that allow easy access to pre-exposure prophylaxis (PrEP), such as over-the-counter provision at pharmacies, could facilitate risk-informed PrEP use and lead to lower HIV incidence, but their cost-effectiveness is unknown. We aimed to evaluate conditions under which risk-informed PrEP use is cost-effective.MethodsWe applied a mathematical model of HIV transmission to simulate 3000 setting-scenarios reflecting a range of epidemiological characteristics of communities in sub-Saharan Africa. The prevalence of HIV viral load greater than 1000 copies per mL among all adults (HIV positive and negative) varied from 1·1% to 7·4% (90% range). We hypothesised that if PrEP was made easily available without restriction and with education regarding its use, women and men would use PrEP, with sufficient daily adherence, during so-called seasons of risk (ie, periods in which individuals are at risk of acquiring infection). We refer to this as risk-informed PrEP. For each setting-scenario, we considered the situation in mid-2021 and performed a pairwise comparison of the outcomes of two policies: immediate PrEP scale-up and then continuation for 50 years, and no PrEP. We estimated the relationship between epidemic and programme characteristics and cost-effectiveness of PrEP availability to all during seasons of risk. For our base-case analysis, we assumed a 3-monthly PrEP cost of US$29 (drug $11, HIV test $4, and $14 for additional costs necessary to facilitate education and access), a cost-effectiveness threshold of $500 per disability-adjusted life-year (DALY) averted, an annual discount rate of 3%, and a time horizon of 50 years. In sensitivity analyses, we considered a cost-effectiveness threshold of $100 per DALY averted, a discount rate of 7% per annum, the use of PrEP outside of seasons of risk, and reduced uptake of risk-informed PrEP.FindingsIn the context of PrEP scale-up such that 66% (90% range across setting-scenarios 46-81) of HIV-negative people with at least one non-primary condomless sex partner take PrEP in any given period, resulting in 2·6% (0·9-6·0) of all HIV negative adults taking PrEP at any given time, risk-informed PrEP was predicted to reduce HIV incidence by 49% (23-78) over 50 years compared with no PrEP. PrEP was cost-effective in 71% of all setting-scenarios, and cost-effective in 76% of setting-scenarios with prevalence of HIV viral load greater than 1000 copies per mL among all adults higher than 2%. In sensitivity analyses with a $100 per DALY averted cost-effectiveness threshold, a 7% per year discount rate, or with PrEP use that was less well risk-informed than in our base case, PrEP was less likely to be cost-effective, but generally remained cost-effective if the prevalence of HIV viral load greater than 1000 copies per mL among all adults was higher than 3%. In sensitivity analyses based on additional setting-scenarios in which risk-informed PrEP was less extensively used, the HIV incidence reduction was smaller, but the cost-effectiveness of risk-informed PrEP was undiminished.InterpretationUnder the assumption that making PrEP easily accessible for all adults in sub-Saharan Africa in the context of community education leads to risk-informed use, PrEP is likely to be cost-effective in settings with prevalence of HIV viral load greater than 1000 copies per mL among all adults higher than 2%, suggesting the need for implementation of such approaches, with ongoing evaluation.FundingUS Agency for International Development, US President's Emergency Plan for AIDS Relief, and Bill & Melinda Gates Foundation.

Poor air quality is thought to be an important mortality risk factor globally1-3, but there is little direct evidence from the developing world on how mortality risk varies with changing exposure to ambient particulate matter. Current global estimates apply exposure-response relationships that have been derived mostly from wealthy, mid-latitude countries to spatial population data4, and these estimates remain unvalidated across large portions of the globe. Here we combine household survey-based information on the location and timing of nearly 1 million births across sub-Saharan Africa with satellite-based estimates5 of exposure to ambient respirable particulate matter with an aerodynamic diameter less than 2.5 μm (PM2.5) to estimate the impact of air quality on mortality rates among infants in Africa. We find that a 10 μg m-3 increase in PM2.5 concentration is associated with a 9% (95% confidence interval, 4-14%) rise in infant mortality across the dataset. This effect has not declined over the last 15 years and does not diminish with higher levels of household wealth. Our estimates suggest that PM2.5 concentrations above minimum exposure levels were responsible for 22% (95% confidence interval, 9-35%) of infant deaths in our 30 study countries and led to 449,000 (95% confidence interval, 194,000-709,000) additional deaths of infants in 2015, an estimate that is more than three times higher than existing estimates that attribute death of infants to poor air quality for these countries2,6. Upward revision of disease-burden estimates in the studied countries in Africa alone would result in a doubling of current estimates of global deaths of infants that are associated with air pollution, and modest reductions in African PM2.5 exposures are predicted to have health benefits to infants that are larger than most known health interventions.

Screening for asymptomatic peripheral artery disease (aPAD) with the ankle-brachial index (ABI) test is hypothesized to reduce disease progression and cardiovascular (CV) events by identifying individuals who may benefit from early initiation of medical therapy. Using a Markov model, we evaluated the cost effectiveness of initiating medical therapy (e.g. statin and ACE-inhibitor) after a positive ankle-brachial index (ABI) screen in 65-year-old patients. We modeled progression to symptomatic PAD (sPAD) and CV events with and without ABI screening, evaluating differences in costs and quality-adjusted life years (QALYs). The cost of the ABI test, physician visit, new medication, CV events, and interventions for sPAD were incorporated in the model. We performed sensitivity analysis on model variables with uncertainty. Our model found an incremental cost of US $338 and an incremental QALY of 0.00380 with one-time ABI screening, resulting in an incremental cost-effectiveness ratio (ICER) of $88,758/QALY over a 35-year period. The variables with the largest effects in the ICER were aPAD disease prevalence, cost of monthly medication after a positive screen and 2-year medication adherence rates. Screening high-risk populations, such as tobacco users, where the prevalence of PAD may be 2.5 times higher, decreases the ICER to $24,092/QALY. Our analysis indicates the cost effectiveness of one-time screening for aPAD depends on prevalence, medication costs, and adherence to therapies for CV disease risk reduction. Screening in higher-risk populations under favorable assumptions about medication adherence results in the most favorable cost effectiveness, but limitations in the primary data preclude definitive assessment of cost effectiveness.

Synthetic downscaling of tropical cyclones (TCs) is critically important to estimate the long‐term hazard of rare high‐impact storm events. Existing downscaling approaches rely on statistical or statistical‐deterministic models that are capable of generating large samples of synthetic storms with characteristics similar to observed storms. However, these models do not capture the complex two‐way interactions between a storm and its environment. In addition, these approaches either necessitate a separate TC size model to simulate storm size or involve post‐processing to capture the asymmetries in the simulated surface wind. In this study, we present an innovative data‐driven approach for TC synthetic downscaling. Using a machine learning‐based high‐resolution global weather model (ML‐GWM), our approach can simulate the full life cycle of a storm with asymmetric surface wind that accounts for the two‐way interactions between the storm and its environment. This approach consists of multiple components: a data‐driven model for generating synthetic TC seeds, a blending method that seamlessly integrates storm seeds into the surrounding while maintaining the seed structure, and a model based on a recurrent neural network to correct for biases in storm intensity. Compared to observations and synthetic storms simulated using existing statistical‐deterministic and statistical downscaling approaches, our method shows the ability to effectively capture many aspects of TC statistics, including track density, landfall frequency, landfall intensity, and outermost wind extent. Leveraging the computational efficiency of ML‐GWM, our approach shows substantial potential for TC regional hazard and risk assessment. Plain Language Summary: Tropical cyclones (TCs) cause significant destruction each year. It is crucial to accurately assess the risks they present, but this is challenging due to a scarcity of historical data. A commonly used approach involves creating a large number of synthetic TCs that share key characteristics with real storms. However, traditional synthetic TC generation approaches do not capture the complex interactions between storms and their larger‐scale environment. Furthermore, these approaches do not adequately represent the asymmetric structure of TCs. Recently, advances in machine learning‐based global weather model (ML‐GWM) have provided highly accurate and efficient high‐resolution global weather forecasts that surpass conventional numerical weather forecasting. Here, we introduce a novel synthetic TC generation approach, which we call the synthetic TC‐GENerative Model (or "TC‐GEN"), leveraging the state‐of‐the‐art ML‐GWM. We show that TC‐GEN can generate a large number of synthetic storms that allow the interaction between the storm and its environment. We evaluate the performance of TC‐GEN in various aspects, including several landfall characteristics, which are of the most importance for local TC risk analysis. Our study also serves as a compelling example of the transformative impact of machine learning and data science in revolutionizing climate studies during the era of artificial intelligence. Key Points: We introduce a novel approach to tropical cyclone (TC) downscaling using a machine learning based global weather model, named "TC‐GEN"We generate and integrate synthetic TC seeds into the surrounding environment using a data‐driven approachTC‐GEN establishes a framework that opens the possibility of modeling the two‐way interactions between storms and the environment [ABSTRACT FROM AUTHOR]

Background: Expanding statin use may help to alleviate the excess burden of atherosclerotic cardiovascular disease in people iving with HIV (PLHIV). Pravastatin and pitavastatin are preferred agents due to their lack of substantial interaction with antiretroviral therapy. We aimed to evaluate the cost-effectiveness of pravastatin and pitavastatin for the primary prevention of atherosclerotic cardiovascular disease among PLHIV in the United States. Methods: We developed a microsimulation model that randomly selected (with replacement) individuals from the Data-collection on Adverse Effects of Anti-HIV Drugs study with follow-up between 2013 and 2016. Our study population was PLHIV aged 40 to 75 years, stable on antiretroviral therapy and not currently using lipid-lowering therapy. Direct medical costs and quality-adjusted life-years (QALYs) were assigned in annual cycles and discounted at 3% per year. We assumed a willingness-to-pay threshold of $100,000/QALY gained. The interventions assessed were as follows: (1) treating no one with statins; (2) treating everyone with generic pravastatin 40 mg/day (drug cost $236/year) and (3) treating everyone with branded pitavastatin 4 mg/day (drug cost $2,828/year). The model simulated each individual's probability of experiencing atherosclerotic cardiovascular disease over 20 years. Results: Persons receiving pravastatin accrued 0.024 additional QALYs compared with those not receiving a statin, at an incremental cost of $1338, giving an incremental cost-effectiveness ratio of $56,000/QALY gained. Individuals receiving pitavastatin accumulated 0.013 additional QALYs compared with those using pravastatin, at an additional cost of $18,251, giving an incremental cost-effectiveness ratio of $1,444,000/QALY gained. These findings were most sensitive to the pill burden associated with daily statin administration, statin costs, statin efficacy and baseline atherosclerotic cardiovascular disease risk. In probabilistic sensitivity analysis, no statin was optimal in 5.2% of simulations, pravastatin was optimal in 94.8% of simulations and pitavastatin was never optimal. Conclusions: Pravastatin was projected to be cost-effective compared with no statin. With substantial price reduction, pitavastatin may be cost-effective compared with pravastatin. These findings bode well for the expanded use of statins among PLHIV in the United States. To gain greater confidence in our conclusions it is important to generate strong, HIV-specific estimates on the efficacy of statins and the quality-of-life burden associated with taking an additional daily pill. Keywords: HIV; cardiovascular disease; statin; cost-effectiveness; United States; antiretroviral therapy Received 4 September 2020; Accepted 23 February 2021, 1 | INTRODUCTION People living with HIV (PLHIV) have an elevated risk of atherosclerotic cardiovascular disease (ASCVD) compared to people without HIV [1]. This is only partially explained by the [...]

Introduction: People living with HIV (PLHIV) have an elevated risk of atherosclerotic cardiovascular disease (CVD) compared to their HIV-negative peers. Expanding statin use may help alleviate this burden. However, the choice of statin in the context of antiretroviral therapy is challenging. Pravastatin and pitavastatin improve cholesterol levels in PLHIV without interacting substantially with antiretroviral therapy. They are also more expensive than most statins. We evaluated the cost-effectiveness of pravastatin and pitavastatin for the primary prevention of CVD among PLHIV in Thailand who are not currently using lipidlowering therapy. Methods: We developed a discrete-state microsimulation model that randomly selected (with replacement) individuals from the TREAT Asia HIV Observational Database cohort who were aged 40 to 75 years, receiving antiretroviral therapy in Thailand, and not using lipid-lowering therapy. The model simulated each individual's probability of experiencing CVD. We evaluated: (1) treating no one with statins; (2) treating everyone with pravastatin 20mg/day (drug cost 7568 Thai Baht ($US243)/year) and (3) treating everyone with pitavastatin 2 mg/day (drug cost 8182 Baht ($US263)/year). Direct medical costs and quality-adjusted life-years (QALYs) were assigned in annual cycles over a 20-year time horizon and discounted at 3% per year. We assumed the Thai healthcare sector perspective. Results: Pravastatin was estimated to be less effective and less cost-effective than pitavastatin and was therefore dominated (extended) by pitavastatin. Patients receiving pitavastatin accumulated 0.042 additional QALYs compared with those not using a statin, at an extra cost of 96,442 Baht ($US3095), giving an incremental cost-effectiveness ratio of 2,300,000 Baht ($US73,812)/QALY gained. These findings were sensitive to statin costs and statin efficacy pill burden, and targeting of PLHIV based on CVD risk. At a willingness-to-pay threshold of 160,000 Baht ($US5135)/QALY gained, we estimated that pravastatin would become cost-effective at an annual cost of 415 Baht ($US13.30)/year and pitavastatin would become cost-effective at an annual cost of 600 Baht ($US19.30)/year. Conclusions: Neither pravastatin nor pitavastatin were projected to be cost-effective for the primary prevention of CVD among PLHIV in Thailand who are not currently using lipid-lowering therapy. We do not recommend expanding current use of these drugs among PLHIV in Thailand without substantial price reduction. Keywords: HIV; cardiovascular disease; statin; cost-effectiveness; Thailand; antiretroviral therapy, 1 | INTRODUCTION People living with HIV (PLHIV) have an elevated risk of atherosclerotic cardiovascular disease (CVD) compared to their HIV-negative peers [1]. This is only partially explained by the [...]