Global, regional, and national incidence, prevalence, and mortality of HIV, 1980–2017, and forecasts to 2030, for 195 countries and territories: a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017

Background Understanding the patterns of HIV/AIDS epidemics is crucial to tracking and monitoring the progress of prevention and control efforts in countries. We provide a comprehensive assessment of the levels and trends of HIV/AIDS incidence, prevalence, mortality, and coverage of antiretroviral therapy (ART) for 1980–2017 and forecast these estimates to 2030 for 195 countries and territories. Methods We determined a modelling strategy for each country on the basis of the availability and quality of data. For countries and territories with data from population-based seroprevalence surveys or antenatal care clinics, we estimated prevalence and incidence using an open-source version of the Estimation and Projection Package—a natural history model originally developed by the UNAIDS Reference Group on Estimates, Modelling, and Projections. For countries with cause-specific vital registration data, we corrected data for garbage coding (ie, deaths coded to an intermediate, immediate, or poorly defined cause) and HIV misclassification. We developed a process of cohort incidence bias adjustment to use information on survival and deaths recorded in vital registration to back-calculate HIV incidence. For countries without any representative data on HIV, we produced incidence estimates by pulling information from observed bias in the geographical region. We used a re-coded version of the Spectrum model (a cohort component model that uses rates of disease progression and HIV mortality on and off ART) to produce age-sex-specific incidence, prevalence, and mortality, and treatment coverage results for all countries, and forecast these measures to 2030 using Spectrum with inputs that were extended on the basis of past trends in treatment scale-up and new infections. Findings Global HIV mortality peaked in 2006 with 1·95 million deaths (95% uncertainty interval 1·87–2·04) and has since decreased to 0·95 million deaths (0·91–1·01) in 2017. New cases of HIV globally peaked in 1999 (3·16 million, 2·79–3·67) and since then have gradually decreased to 1·94 million (1·63–2·29) in 2017. These trends, along with ART scale-up, have globally resulted in increased prevalence, with 36·8 million (34·8–39·2) people living with HIV in 2017. Prevalence of HIV was highest in southern sub-Saharan Africa in 2017, and countries in the region had ART coverage ranging from 65·7% in Lesotho to 85·7% in eSwatini. Our forecasts showed that 54 countries will meet the UNAIDS target of 81% ART coverage by 2020 and 12 countries are on track to meet 90% ART coverage by 2030. Forecasted results estimate that few countries will meet the UNAIDS 2020 and 2030 mortality and incidence targets. Interpretation Despite progress in reducing HIV-related mortality over the past decade, slow decreases in incidence, combined with the current context of stagnated funding for related interventions, mean that many countries are not on track to reach the 2020 and 2030 global targets for reduction in incidence and mortality. With a growing population of people living with HIV, it will continue to be a major threat to public health for years to come. The pace of progress needs to be hastened by continuing to expand access to ART and increasing investments in proven HIV prevention initiatives that can be scaled up to have population-level impact

Short-Lived Trace Gases in the Surface Ocean and the Atmosphere

The two-way exchange of trace gases between the ocean and the atmosphere is important for both the chemistry and physics of the atmosphere and the biogeochemistry of the oceans, including the global cycling of elements. Here we review these exchanges and their importance for a range of gases whose lifetimes are generally short compared to the main greenhouse gases and which are, in most cases, more reactive than them. Gases considered include sulphur and related compounds, organohalogens, non-methane hydrocarbons, ozone, ammonia and related compounds, hydrogen and carbon monoxide. Finally, we stress the interactivity of the system, the importance of process understanding for modeling, the need for more extensive field measurements and their better seasonal coverage, the importance of inter-calibration exercises and finally the need to show the importance of air-sea exchanges for global cycling and how the field fits into the broader context of Earth System Science

The effects of ethanol, phenobarbital, and baclofen on ethanol withdrawal in the rhesus monkey

Physical dependence on ethanol was produced in four rhesus monkeys by IV ethanol administration every 8 h. Ethanol was administered on each occasion until the eyeblink reflex was lost. Evidence of physical dependence development, in the form of tremoring 8 h after an infusion, appeared on day 8 of chronic administration. Abrupt cessation of ethanol administration following 16 days of chronic administration was accompanied by moderate to severe tremoring, retching, vomiting, and one or more convulsions. Peak withdrawal occurred between 12 and 32 h after abrupt discontinuation of ethanol administration, and decreased over a period of 64–204 h. Ethanol dependence was then reinstated. Once every 3–4 days, ethanol was withheld for 16 h. Withdrawal signs were scored for the first 12 h of this period, and then a test dose of ethanol, phenobarbital, or baclofen was administered. Withdrawal or intoxication signs were scored over the next 4 h, at which time ethanol administration was resumed. Both ethanol and phenobarbital suppressed ethanol withdrawal sign in a dose-related manner, and produced dose-related intoxication. Baclofen was largely ineffective in reducing withdrawal-induced tremors, although it was capable of producing sedation of a different type than that produced by phenobarbital and ethanol.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46414/1/213_2004_Article_BF00435315.pd

A quasi-experimental test of an intervention to increase the use of thiazide-based treatment regimens for people with hypertension

BACKGROUND: Despite recent high-quality evidence for their cost-effectiveness, thiazides are underused for controlling hypertension. The goal of this study was to design and test a practice-based intervention aimed at increasing the use of thiazide-based antihypertensive regimens. METHODS: This quasi-experimental study was carried out in general medicine ambulatory practices of a large, academically-affiliated Veterans Affairs hospital. The intervention group consisted of the practitioners (13 staff and 215 trainees), nurses, and patients (3,502) of the teaching practice; non-randomized concurrent controls were the practitioners (31 providers) and patients (18,292) of the non-teaching practices. Design of the implementation intervention was based on Rogers' Diffusion of Innovations model. Over 10.5 months, intervention teams met weekly or biweekly and developed and disseminated informational materials among themselves and to trainees, patients, and administrators. These teams also reviewed summary electronic-medical-record data on thiazide use and blood pressure (BP) goal attainment. Outcome measures were the proportion of hypertensive patients prescribed a thiazide-based regimen, and the proportion of hypertensive patients attaining BP goals regardless of regimen. Thirty-three months of time-series data were available; statistical process control charts, change point analyses, and before-after analyses were used to estimate the intervention's effects. RESULTS: Baseline use of thiazides and rates of BP control were higher in the intervention group than controls. During the intervention, thiazide use and BP control increased in both groups, but changes occurred earlier in the intervention group, and primary change points were observed only in the intervention group. Overall, the pre-post intervention difference in proportion of patients prescribed thiazides was greater in intervention patients (0.091 vs. 0.058; p = 0.0092), as was the proportion achieving BP goals (0.092 vs. 0.044; p = 0.0005). At the end of the implementation period, 41.4% of intervention patients were prescribed thiazides vs. 30.6% of controls (p < 0.001); 51.6% of intervention patients had achieved BP goals vs. 44.3% of controls (p < 0.001). CONCLUSION: This multi-faceted intervention appears to have resulted in modest improvements in thiazide prescribing and BP control. The study also demonstrates the value of electronic medical records for implementation research, how Rogers' model can be used to design and launch an implementation strategy, and how all members of a clinical microsystem can be involved in an implementation effort

A Fluorescence Reporter Model Defines “Tip-DCs” as the Cellular Source of Interferon β in Murine Listeriosis

Production of type I interferons, consisting mainly of multiple IFNα subtypes and IFNβ, represents an essential part of the innate immune defense against invading pathogens. While in most situations, namely viral infections, this class of cytokines is indispensable for host survival they mediate a detrimental effect during infection with L. monocytogenes by rendering macrophages insensitive towards IFNγ signalling which leads to a lethal bacterial pathology in mice. Due to a lack of suitable analytic tools the precise identity of the cell population responsible for type I IFN production remains ill-defined and so far these cells have been described to be macrophages. As in general IFNβ is the first type I interferon to be produced, we took advantage of an IFNβ fluorescence reporter-knockin mouse model in which YFP is expressed from a bicistronic mRNA linked by an IRES to the endogenous ifnb mRNA to assess the IFNβ production on a single cell level in situ. Our results showed highest frequencies and absolute numbers of IFNβ+ cells in the spleen 24 h after infection with L. monocytogenes where they were located predominately in the white pulp within the foci of infection. Detailed FACS surface marker analyses, intracellular cytokine stainings and T cell proliferation assays revealed that the IFNβ+ cells were a phenotypically and functionally further specialized subpopulation of TNF and iNOS producing DCs (Tip-DCs) which are known to be essential for the early containment of L. monocytogenes infection. We proved that the IFNβ+ cells exhibited the hallmark characteristics of Tip-DCs as they produced iNOS and TNF and possessed T cell priming abilities. These results point to a yet unappreciated ambiguous role for a multi-effector, IFNβ producing subpopulation of Tip-DCs in controlling the balance between containment of L. monocytogenes infection and effects detrimental to the host driven by IFNβ

Antimetastatic Effects of Phyllanthus on Human Lung (A549) and Breast (MCF-7) Cancer Cell Lines

BACKGROUND: Current chemotherapeutic drugs kill cancer cells mainly by inducing apoptosis. However, they become ineffective once cancer cell has the ability to metastasize, hence the poor prognosis and high mortality rate. Therefore, the purpose of this study was to evaluate the antimetastatic potential of Phyllanthus (P. niruri, P. urinaria, P. watsonii, and P. amarus) on lung and breast carcinoma cells. METHODOLOGY/PRINCIPAL FINDINGS: Cytotoxicity of Phyllanthus plant extracts were first screened using the MTS reduction assay. They were shown to inhibit MCF-7 (breast carcinoma) and A549 (lung carcinoma) cells growth with IC(50) values ranging from 50-180 µg/ml and 65-470 µg/ml for methanolic and aqueous extracts respectively. In comparison, they have lower toxicity on normal cells with the cell viability percentage remaining above 50% when treated up to 1000 µg/ml for both extracts. After determining the non-toxic effective dose, several antimetastasis assays were carried out and Phyllanthus extracts were shown to effectively reduce invasion, migration, and adhesion of both MCF-7 and A549 cells in a dose-dependent manner, at concentrations ranging from 20-200 µg/ml for methanolic extracts and 50-500 µg/ml for aqueous extracts. This was followed by an evaluation of the possible modes of cell death that occurred along with the antimetastatic activity. Phyllanthus was shown to be capable of inducing apoptosis in conjunction with its antimetastastic action, with more than three fold increase of caspases-3 and -7, the presence of DNA-fragmentation and TUNEL-positive cells. The ability of Phyllanthus to exert antimetastatic activities is mostly associated to the presence of polyphenol compounds in its extracts. CONCLUSIONS/SIGNIFICANCE: The presence of polyphenol compounds in the Phyllanthus plant is critically important in the inhibition of the invasion, migration, and adhesion of cancer cells, along with the involvement of apoptosis induction. Hence, Phyllanthus could be a valuable candidate in the treatment of metastatic cancers