Aging, Transition, and Estimating the Global Burden of Disease

The World Health Organization's Global Burden of Disease (GBD) reports are an important tool for global health policy makers, however the accuracy of estimates for countries undergoing an epidemiologic transition is unclear. We attempted to validate the life table model used to generate estimates for all-cause mortality in developing countries.Data were obtained for males and females from the Human Mortality Database for all countries with available data every ten years from 1900 to 2000. These provided inputs for the GBD life table model and served as comparison observed data. Above age sixty model estimates of survival for both sexes differed substantially from those observed. Prior to the year 1960 for males and 1930 for females, estimated survival tended to be greater than observed; following 1960 for both males and females estimated survival tended to be less than observed. Viewing observed and estimated survival separately, observed survival past sixty increased over the years considered. For males, the increase was from a mean (sd) probability of 0.22 (0.06) to 0.46 (0.1). For females, the increase was from 0.26 (0.06) to 0.65 (0.08). By contrast, estimated survival past sixty decreased over the same period. Among males, estimated survival probability declined from 0.54 (0.2) to 0.09 (0.06). Among females, the decline was from 0.36 (0.12) to 0.15 (0.08).These results show that the GBD mortality model did not accurately estimate survival at older ages as developed countries transitioned in the twentieth century and may be similarly flawed in developing countries now undergoing transition. Estimates of the size of older-age populations and their attributable disease burden should be reconsidered

Economic outcomes of percutaneous coronary intervention with drug-eluting stents versus bypass surgery for patients with left main or three-vessel coronary artery disease: One-year results from the SYNTAX trial

Objectives: To evaluate the cost-effectiveness of alternative approaches to revascularization for patients with three-vessel or left main coronary artery disease (CAD). Background: Previous studies have demonstrated that, despite higher initial costs, long-term costs with bypass surgery (CABG) in multivessel CAD are similar to those for percutaneous coronary intervention (PCI). The impact of drug-eluting stents (DES) on these results is unknown. Methods: The SYNTAX trial randomized 1,800 patients with left main or three-vessel CAD to either CABG (n = 897) or PCI using paclitaxel-eluting stents (n = 903). Resource utilization data were collected prospectively for all patients, and cumulative 1-year costs were assessed from the perspective of the U.S. healthcare system. Results: Total costs for the initial hospitalization were $5,693/patient higher with CABG, whereas follow-up costs were$2,282/patient higher with PCI due mainly to more frequent revascularization procedures and higher outpatient medication costs. Total 1-year costs were thus $3,590/patient higher with CABG, while quality-adjusted life expectancy was slightly higher with PCI. Although PCI was an economically dominant strategy for the overall population, cost-effectiveness varied considerably according to angiographic complexity. For patients with high angiographic complexity (SYNTAX score > 32), total 1-year costs were similar for CABG and PCI, and the incremental cost-effectiveness ratio for CABG was$43,486 per quality-adjusted life-year gained. Conclusions: Among patients with three-vessel or left main CAD, PCI is an economically attractive strategy over the first year for patients with low and moderate angiographic complexity, while CABG is favored among patients with high angiographic complexity

Dendritic cells induce antigen-specific regulatory T cells that prevent graft versus host disease and persist in mice

Regulatory T cells generated by allostimulation with dendritic cells, transforming growth factor β, and retinoic acid stably express Foxp3 and can suppress even ongoing GVHD in mice

A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.Comment: 41 page

Australian vegetated coastal ecosystems as global hotspots for climate change mitigation

Policies aiming to preserve vegetated coastal ecosystems (VCE; tidal marshes, mangroves and seagrasses) to mitigate greenhouse gas emissions require national assessments of blue carbon resources. Here, we present organic carbon (C) storage in VCE across Australian climate regions and estimate potential annual CO2 emission benefits of VCE conservation and restoration. Australia contributes 5–11% of the C stored in VCE globally (70–185 Tg C in aboveground biomass, and 1,055–1,540 Tg C in the upper 1 m of soils). Potential CO2 emissions from current VCE losses are estimated at 2.1–3.1 Tg CO2-e yr-1, increasing annual CO2 emissions from land use change in Australia by 12–21%. This assessment, the most comprehensive for any nation to-date, demonstrates the potential of conservation and restoration of VCE to underpin national policy development for reducing greenhouse gas emissions

Australian vegetated coastal ecosystems as global hotspots for climate change mitigation

© 2019, The Author(s). Policies aiming to preserve vegetated coastal ecosystems (VCE; tidal marshes, mangroves and seagrasses) to mitigate greenhouse gas emissions require national assessments of blue carbon resources. Here, we present organic carbon (C) storage in VCE across Australian climate regions and estimate potential annual CO2 emission benefits of VCE conservation and restoration. Australia contributes 5–11% of the C stored in VCE globally (70–185 Tg C in aboveground biomass, and 1,055–1,540 Tg C in the upper 1 m of soils). Potential CO2 emissions from current VCE losses are estimated at 2.1–3.1 Tg CO2-e yr-1, increasing annual CO2 emissions from land use change in Australia by 12–21%. This assessment, the most comprehensive for any nation to-date, demonstrates the potential of conservation and restoration of VCE to underpin national policy development for reducing greenhouse gas emissions

Australian vegetated coastal ecosystems as global hotspots for climate change mitigation

Unidad de excelencia María de Maeztu MdM-2015-0552Policies aiming to preserve vegetated coastal ecosystems (VCE; tidal marshes, mangroves and seagrasses) to mitigate greenhouse gas emissions require national assessments of blue carbon resources. Here, we present organic carbon (C) storage in VCE across Australian climate regions and estimate potential annual CO emission benefits of VCE conservation and restoration. Australia contributes 5-11% of the C stored in VCE globally (70-185 Tg C in aboveground biomass, and 1,055-1,540 Tg C in the upper 1 m of soils). Potential CO emissions from current VCE losses are estimated at 2.1-3.1 Tg CO-e yr, increasing annual CO emissions from land use change in Australia by 12-21%. This assessment, the most comprehensive for any nation to-date, demonstrates the potential of conservation and restoration of VCE to underpin national policy development for reducing greenhouse gas emissions

Identification of Host Cytosolic Sensors and Bacterial Factors Regulating the Type I Interferon Response to Legionella pneumophila

Legionella pneumophila is a gram-negative bacterial pathogen that replicates in host macrophages and causes a severe pneumonia called Legionnaires' Disease. The innate immune response to L. pneumophila remains poorly understood. Here we focused on identifying host and bacterial factors involved in the production of type I interferons (IFN) in response to L. pneumophila. It was previously suggested that the delivery of L. pneumophila DNA to the host cell cytosol is the primary signal that induces the type I IFN response. However, our data are not easily reconciled with this model. We provide genetic evidence that two RNA-sensing proteins, RIG-I and MDA5, participate in the IFN response to L. pneumophila. Importantly, these sensors do not seem to be required for the IFN response to L. pneumophila DNA, whereas we found that RIG-I was required for the response to L. pneumophila RNA. Thus, we hypothesize that bacterial RNA, or perhaps an induced host RNA, is the primary stimulus inducing the IFN response to L. pneumophila. Our study also identified a secreted effector protein, SdhA, as a key suppressor of the IFN response to L. pneumophila. Although viral suppressors of cytosolic RNA-sensing pathways have been previously identified, analogous bacterial factors have not been described. Thus, our results provide new insights into the molecular mechanisms by which an intracellular bacterial pathogen activates and also represses innate immune responses

Toward a 21st-century health care system: Recommendations for health care reform

The coverage, cost, and quality problems of the U.S. health care system are evident. Sustainable health care reform must go beyond financing expanded access to care to substantially changing the organization and delivery of care. The FRESH-Thinking Project (www.fresh-thinking.org) held a series of workshops during which physicians, health policy experts, health insurance executives, business leaders, hospital administrators, economists, and others who represent diverse perspectives came together. This group agreed that the following 8 recommendations are fundamental to successful reform: 1. Replace the current fee-for-service payment system with a payment system that encourages and rewards innovation in the efficient delivery of quality care. The new payment system should invest in the development of outcome measures to guide payment. 2. Establish a securely funded, independent agency to sponsor and evaluate research on the comparative effectiveness of drugs, devices, and other medical interventions. 3. Simplify and rationalize federal and state laws and regulations to facilitate organizational innovation, support care coordination, and streamline financial and administrative functions. 4. Develop a health information technology infrastructure with national standards of interoperability to promote data exchange. 5. Create a national health database with the participation of all payers, delivery systems, and others who own health care data. Agree on methods to make de-identified information from this database on clinical interventions, patient outcomes, and costs available to researchers. 6. Identify revenue sources, including a cap on the tax exclusion of employer-based health insurance, to subsidize health care coverage with the goal of insuring all Americans. 7. Create state or regional insurance exchanges to pool risk, so that Americans without access to employer-based or other group insurance could obtain a standard benefits package through these exchanges. Employers should also be allowed to participate in these exchanges for their employees' coverage. 8. Create a health coverage board with broad stakeholder representation to determine and periodically update the affordable standard benefit package available through state or regional insurance exchanges