Meteorological human discomfort indices or bioclimatic indices are important metrics to gauge potential risks to human health under varying environmental thermal exposures. Derived using sub-daily ...meteorological variables from a quality-controlled reanalysis data product (Global Land Data Assimilation System—GLDAS), a new high-resolution global dataset referred to as “HDI_0p25_1970_2018” is presented in this study. The dataset includes the following daily indices at 0.25° × 0.25° gridded resolution: (i) Apparent Temperature indoors (ATind); (ii) two variants of Apparent Temperature outdoors in shade (ATot); (iii) Heat Index (HI); (iv) Humidex (HDEX); (v) Wet Bulb Temperature (WBT); (vi) two variants of Wet Bulb Globe Temperature (WBGT); (vii) Thom Discomfort Index (DI); and (viii) Windchill Temperature (WCT). Spanning 49 years over the period 1970–2018, HDI_0p25_1970_2018 fills gaps in existing climate indices datasets by being the only high-resolution historical global-gridded daily time-series of multiple human discomfort indices based on different meteorological parameters, thus offering applications in wide-ranging climate zones and thermal-comfort environments.
Cooling and heating degree‐days (CDD/HDD) are important metrics used in energy studies as a proxy for determining demand and consumption patterns of residential/commercial buildings and work spaces. ...Driven by the requirements of energy impact modellers, policymakers and building design experts; a new historical high‐spatial resolution, global gridded dataset of degree‐days constructed using various base (threshold) temperatures (Tb) is presented in this study. Derived using sub‐daily temperature from a quality‐controlled reanalysis data product (Global Land Data Assimilation System—GLDAS), the dataset called ‘DegDays_0p25_1970_2018’ includes monthly and annual (i) CDD; (ii) HDD; and (iii) CDD computed using wet‐bulb temperature (CDDwb) at 0.25° × 0.25° gridded resolution, covering 49 years over the period 1970–2018. The Tb used for assembling DegDays_0p25_1970_2018 include 18, 18.3, 22, 23, 24, 25°C for CDD and CDDwb; and 10, 15, 15.5, 16, 17 and 18°C for HDD, respectively. The data of individual indices are made publicly available in the commonly used scientific Network Common Data Form 4 (NetCDF4) and Georeferenced Tagged Image File (GeoTIFF) formats. DegDays_0p25_1970_2018 fills gaps in existing energy indicators’ datasets by being the only high‐resolution historical global gridded time series based on multiple threshold temperatures, thus offering applications in wide‐ranging climate zones and thermal comfort environments. The richness of DegDays_0p25_1970_2018 lies in its flexibility by allowing users to aggregate the degree‐days not only at varying spatial scales (such as administrative levels, national boundaries, economic organizations e.g. OECD; with or without population weights), but also at varying temporal scales (such as seasons), thereby offering climatologists with a potential to examine global teleconnection patterns more discretely.
Abstract
Climate adaptation actions can be energy-intensive, but how adaptation feeds back into the energy system and the environment is absent in nearly all up-to-date energy scenarios. Here we ...quantify the impacts of adaptation actions entailing direct changes in final energy use on energy investments and costs, greenhouse gas emissions, and air pollution. We find that energy needs for adaptation increase considerably over time and with warming. The resulting addition in capacity for power generation leads to higher greenhouse gas emissions, local air pollutants, and energy system costs. In the short to medium term, much of the added capacity for power generation is fossil-fuel based. We show that mitigation pathways accounting for the adaptation-energy feedback would require a higher global carbon price, between 5% and 30% higher. Because of the benefits in terms of reduced adaptation needs, energy system costs in ambitious mitigation scenarios would be lower than previous estimates, and they would turn negative in well-below-2-degree scenarios, pointing at net gains in terms of power system costs.
Brain aging and neurodegeneration are associated with prominent microglial reactivity and activation of innate immune response pathways, commonly referred to as neuroinflammation. One such pathway, ...the type I interferon response, recognizes viral or mitochondrial DNA in the cytoplasm via activation of the recently discovered cyclic dinucleotide synthetase cGAS and the cyclic dinucleotide receptor STING. Here we show that the FDA-approved antiviral drug ganciclovir (GCV) induces a type I interferon response independent of its canonical thymidine kinase target. Inhibition of components of the STING pathway, including STING, IRF3, Tbk1, extracellular IFNβ, and the Jak-Stat pathway resulted in reduced activity of GCV and its derivatives. Importantly, functional STING was necessary for GCV to inhibit inflammation in cultured myeloid cells and in a mouse model of multiple sclerosis. Collectively, our findings uncover an unexpected new activity of GCV and identify the STING pathway as a regulator of microglial reactivity and neuroinflammation.
•Ganciclovir induces type I interferon signaling and modulates microglial reactivity•Microglial reactivity is associated with upregulation of innate immune adaptor STING•Ganciclovir inhibits microglial inflammation in EAE mouse model through STING
Mathur et al. describe a non-canonical function of the antiviral drug ganciclovir in microglia. Ganciclovir induces a type I interferon response and reduces neuroinflammation in a mouse model of multiple sclerosis. The innate immune adaptor STING is required for this activity of ganciclovir.
Malaria is a parasitic disease that remains a global health burden. The ability of the parasite to rapidly develop resistance to therapeutics drives an urgent need for the delivery of new drugs. The ...Medicines for Malaria Venture have compounds known for their antimalarial activity, but not necessarily the molecular targets. In this study, we assess the ability of the "MMV 400" compounds to inhibit the activity of three metalloaminopeptidases from Plasmodium falciparum, PfA-M1, PfA-M17 and PfM18 AAP. We have developed a multiplex assay system to allow rapid primary screening of compounds against all three metalloaminopeptidases, followed by detailed analysis of promising compounds. Our results show that there were no PfM18AAP inhibitors, whereas two moderate inhibitors of the neutral aminopeptidases PfA-M1 and PfA-M17 were identified. Further investigation through structure-activity relationship studies and molecular docking suggest that these compounds are competitive inhibitors with novel binding mechanisms, acting through either non-classical zinc coordination or independently of zinc binding altogether. Although it is unlikely that inhibition of PfA-M1 and/or PfA-M17 is the primary mechanism responsible for the antiplasmodial activity reported for these compounds, their detailed characterization, as presented in this work, pave the way for their further optimization as a novel class of dual PfA-M1/PfA-M17 inhibitors utilising non-classical zinc binding groups.
Climate extreme indices (CEIs) are important metrics that not only assist in the analysis of regional and global extremes in meteorological events, but also aid climate modellers and policymakers in ...the assessment of sectoral impacts. Global high-spatial-resolution CEI datasets derived from quality-controlled historical observations, or reanalysis data products are scarce. This study introduces a new high-resolution global gridded dataset of CEIs based on sub-daily temperature and precipitation data from the Global Land Data Assimilation System (GLDAS). The dataset called “CEI_0p25_1970_2016” includes 71 annual (and in some cases monthly) CEIs at 0.25 ∘ × 0.25 ∘ gridded resolution, covering 47 years over the period 1970–2016. The data of individual indices are publicly available for download in the commonly used Network Common Data Form 4 (NetCDF4) format. Potential applications of CEI_0p25_1970_2016 presented here include the assessment of sectoral impacts (e.g., Agriculture, Health, Energy, and Hydrology), as well as the identification of hot spots (clusters) showing similar historical spatial patterns of high/low temperature and precipitation extremes. CEI_0p25_1970_2016 fills gaps in existing CEI datasets by encompassing not only more indices, but also by being the only comprehensive global gridded CEI data available at high spatial resolution.
Silver Diamine Fluoride (SDF) is a clear liquid that combines the remineralising effects of fluoride with the antibacterial effects of silver. It is a promising therapeutic agent for managing carious ...lesions in young children and those with special care needs. However, a major complication of SDF is black staining of the skin, mucosa, lips, tongue, and cheeks if improperly applied. This case report presents a complication following SDF application and its management. A 24-month-old girl presented with decayed teeth in the upper back tooth region of the jaw, and SDF application was performed on tooth no. 54 and 64. However, due to the child’s extremely negative behavior and movement during the application of SDF, staining occurred on the chin and lower lip a few hours later. Watchful observation, patient reassurance, and follow-up led to adequate patient management.
Climate change could lead to high economic burden for individuals (i.e. low income and high prices). While economic conditions are important determinants of climate change vulnerability, ...environmental epidemiological studies focus primarily on the direct impact of temperature on morbidity and mortality without accounting for climate-induced impacts on the economy. More integrated approaches are needed to provide comprehensive assessments of climate-induced direct and indirect impacts on health. This paper provides some perspectives on how epidemiological and economic impact assessments could be better integrated. We argue that accounting for the economic repercussions of climate change on people's health and, vice versa, the consequences of health effects on the economy could provide more realistic scenario projections and could be more useful for adaptation policy.
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