Reducing Plasmodium falciparum malaria transmission in Africa: a model-based evaluation of intervention strategies.

BACKGROUND: Over the past decade malaria intervention coverage has been scaled up across Africa. However, it remains unclear what overall reduction in transmission is achievable using currently available tools. METHODS AND FINDINGS: We developed an individual-based simulation model for Plasmodium falciparum transmission in an African context incorporating the three major vector species (Anopheles gambiae s.s., An. arabiensis, and An. funestus) with parameters obtained by fitting to parasite prevalence data from 34 transmission settings across Africa. We incorporated the effect of the switch to artemisinin-combination therapy (ACT) and increasing coverage of long-lasting insecticide treated nets (LLINs) from the year 2000 onwards. We then explored the impact on transmission of continued roll-out of LLINs, additional rounds of indoor residual spraying (IRS), mass screening and treatment (MSAT), and a future RTS,S/AS01 vaccine in six representative settings with varying transmission intensity (as summarized by the annual entomological inoculation rate, EIR: 1 setting with low, 3 with moderate, and 2 with high EIRs), vector-species combinations, and patterns of seasonality. In all settings we considered a realistic target of 80% coverage of interventions. In the low-transmission setting (EIR approximately 3 ibppy [infectious bites per person per year]), LLINs have the potential to reduce malaria transmission to low levels (90%) or novel tools and/or substantial social improvements will be required, although considerable reductions in prevalence can be achieved with existing tools and realistic coverage levels. CONCLUSIONS: Interventions using current tools can result in major reductions in P. falciparum malaria transmission and the associated disease burden in Africa. Reduction to the 1% parasite prevalence threshold is possible in low- to moderate-transmission settings when vectors are primarily endophilic (indoor-resting), provided a comprehensive and sustained intervention program is achieved through roll-out of interventions. In high-transmission settings and those in which vectors are mainly exophilic (outdoor-resting), additional new tools that target exophagic (outdoor-biting), exophilic, and partly zoophagic mosquitoes will be required

Enhanced Mechanistic Understanding Through the Detection of Radical Intermediates in Organic Reactions

Two applications of a radical trap based on a homolytic substitution reaction (SH2') are presented for the trapping of short-lived radical intermediates in organic reactions. The first example is a photochemical cyanomethylation catalyzed by a Ru complex. Two intermediate radicals in the radical chain propagation have been trapped and detected using mass spectrometry (MS), along with the starting materials, products and catalyst degradation fragments. Although qualitative, these results helped to elucidate the reaction mechanism. In the second example, the trapping method was applied to study the radical initiation catalyzed by a triethylboronoxygen mixture. In this case, the concentration of trapped radicals was sufficiently high to enable their detection by nuclear magnetic resonance (NMR). Quantitative measurements made it possible to characterize the radical flux in the system under different reaction conditions (including variations of solvent, temperature and concentration) where modelling was complicated by chain reactions and heterogeneous mass transfer

Critical analysis of environmental water quality in South Africa Historic and current trends

South Africa is widely recognised as having an admirable water law, and as being a leader in granting a right to water, in terms of quality and quantity, to the environment. However, the water quality of South Afri-can water resources is deteriorating (eg CSIR 2010, DWA 2011a), alt-hough good water quality management structures, strategies, ap-proaches, programmes, instruments, and tools have been developed and implemented nationally. The research reported on here provides a review of changes in water quality management structures, pro-grammes and approaches over the past two decades, and highlights areas where these need updating, completion or revision. As a com-parative illustration of changes in water quality with time, changes in 11 water quality parameters in two river systems (the Crocodile River in Mpumalanga, which is moderately impacted, and the Olifants River, in Mpumalanga and Limpopo, which is severely impacted) are presented

Case Study For Linking Water Quality License Conditions With Resource Quality Objectives For The Leeutaaiboschspruit Industrial Complex Situated Within The Vaal Barrage Catchment Volume 1

In South Africa, the resource-directed measures (RDM) and the source-directed con-trols (SDC) are the two complementary strategies designed to ensure that water resources are used and protected. The RDM are directed at water resources to en-sure their protection, and include the Water Resource Classification System (WRCS), the classification of every significant water resource, the determination of the re-serve and the setting of resource quality objectives (RQOs). On the other hand, the SDC are measures imposed to restrict and control the use of water resources, not only in terms of ensuring water resource protection, but also in terms of ensuring that water resources are equitably allocated and are used efficiently. Water use li-cencing (WUL) is an example of an SDC instrument

Gravity waves in the winter stratosphere over the Southern Ocean: high-resolution satellite observations and 3-D spectral analysis.

Atmospheric gravity waves play a key role in the transfer of energy and momentum between layers of the Earth's atmosphere. However, nearly all Global Circulation Models (GCMs) seriously under-represent the momentum fluxes of gravity waves at latitudes near 60° S. This can result in modelled winter stratospheres that are unrealistically cold – a significant bias known as the "cold-pole problem". There is thus a need for measurements of gravity-wave fluxes near 60S to test and constrain GCMs. Such measurements are notoriously difficult, because they require 3-D observations of wave properties if the fluxes are to be estimated without using significant limiting assumptions. Here we use 3-D satellite measurements of stratospheric gravity waves from NASA's AIRS/Aqua instrument. We present the first extended application of a 3-D Stockwell transform (3DST) method to determine localised gravity-wave amplitudes, wavelengths and directions of propagation around the entire region of the Southern Ocean near 60° S during austral winter 2010. We first validate our method using a synthetic wave field and two case studies of real gravity waves over the Southern Andes and the island of South Georgia. A new technique to overcome wave amplitude attenuation problems in previous methods is also presented. We then characterise large-scale gravity-wave occurrence frequencies, directional momentum fluxes and short-timescale intermittency over the entire Southern Ocean. Our results show that highest wave-occurrence frequencies, amplitudes and momentum fluxes are observed in the stratosphere over the mountains of the Southern Andes and Antarctic Peninsula. However, we find that around 60–80 % of total zonal-mean momentum flux is located over the open Southern Ocean during June–August, where a large "belt" of increased wave-occurrence frequencies, amplitudes and fluxes is observed. Our results also suggest significant short-timescale variability of fluxes from both orographic and non-orographic sources in the region. A particularly striking result is a widespread convergence of gravity-wave momentum fluxes towards latitudes around 60° S from the north and south. We propose that this convergence, which is observed at nearly all longitudes during winter, accounts for a significant part of the under-represented flux in GCMs at these latitudes

Long‐Term Variability and Tendencies in Mesosphere and Lower Thermosphere Winds From Meteor Radar Observations Over Esrange (67.9°N, 21.1°E)

Long-term variabilities of monthly zonal (U) and meridional winds (V) in northern polar mesosphere and lower thermosphere (MLT, ∼80–100 km) are investigated using meteor radar observations during 1999–2022 over Esrange (67.9°N, 21.1°E). The summer (June-August) mean zonal winds are characterized by westward flow up to ∼88–90 km and eastward flow above this height. The summer mean meridional winds are equatorward with strong jet at ∼85–90 km and it weakens above this height. The U and V exhibit strong interannual variability that varies with altitude and month or season. The responses of U and V anomalies (from 1999 to 2003) to solar cycle (SC), Quasi Biennial Oscillation at 10 and 30 hPa, El Niño-Southern Oscillation, North Atlantic Oscillation, ozone (O3) and carbon dioxide (CO2) are analyzed using multiple linear regression. From analysis, significant regions of correlations between MLT winds and above potential drivers vary with altitude and month. The positive responses of U and V to SC (up to 15 m/s/100 sfu) indicates the strengthening of eastward winds in mid-late winter, and poleward winds in late autumn and early winter. The O3 likely intensifies the eastward and poleward winds (∼100 m/s/ppmv) in winter and early spring. The CO2 significantly influence the eastward flow in late winter and summer (above ∼90–95 km) and strengthen the meridional circulation. The significant positive trend in U peaks in summer, late autumn and early winter (∼0.6 m/s/year), the negative trend in V is more prominent in summer above ∼90–95 km

Elevated circulating amyloid concentrations in obesity and diabetes promote vascular dysfunction

Diabetes, obesity and Alzheimer’s disease (AD) are associated with vascular complications and impaired nitric oxide (NO) production. Furthermore, increased β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), APP and β-amyloid (Aβ) are linked with vascular disease development and raised BACE1 and Aβ accompany hyperglycemia and hyperlipidemia. However, the causal relationship between obesity and diabetes, raised Aβ and vascular dysfunction is unclear. We report that diet-induced obesity (DIO) in mice raised plasma and vascular Aβ42 that correlated with decreased NO bioavailability, endothelial dysfunction and raised blood pressure. Genetic or pharmacological reduction of BACE1 activity and Aβ42 prevented and reversed, respectively, these outcomes. In contrast, expression of human mutant APP in mice or Aβ42 infusion into control diet-fed mice to mimic obese levels impaired NO production, vascular relaxation and raised blood pressure. In humans, raised plasma Aβ42 correlated with diabetes and endothelial dysfunction. Mechanistically, higher Aβ42 reduced endothelial NO synthase (eNOS), cyclic GMP and protein kinase G (PKG) activity independently of diet whereas endothelin-1 was increased by diet and Aβ42. Lowering Aβ42 reversed the DIO deficit in the eNOS-cGMP-PKG pathway and decreased endothelin-1. Our findings suggest that BACE1 inhibitors may have therapeutic value in the treatment of vascular disease associated with diabetes

Variant signal peptides of vaccine antigen, FHbp, impair processing affecting surface localization and antibody-mediated killing in most meningococcal isolates

© Copyright © 2019 da Silva, Karlyshev, Oldfield, Wooldridge, Bayliss, Ryan and Griffin. Meningococcal lipoprotein, Factor H binding protein (FHbp), is the sole antigen of the Trumenba vaccine (Pfizer) and one of four antigens of the Bexsero vaccine (GSK) targeting Neisseria meningitidis serogroup B isolates. Lipidation of FHbp is assumed to occur for all isolates. We show in the majority of a collection of United Kingdom isolates (1742/1895) non-synonymous single nucleotide polymorphisms (SNPs) in the signal peptide (SP) of FHbp. A single SNP, common to all, alters a polar amino acid that abolishes processing: lipidation and SP cleavage. Whilst some of the FHbp precursor is retained in the cytoplasm due to reduced binding to SecA, remarkably some is translocated and further surface-localized by Slam. Thus we show Slam is not lipoprotein-specific. In a panel of isolates tested, the overall reduced surface localization of the precursor FHbp, compared to isolates with an intact SP, corresponded with decreased susceptibility to antibody-mediated killing. Our findings shed new light on the canonical pathway for lipoprotein processing and translocation of important relevance for lipoprotein-based vaccines in development and in particular for Trumenba