A realist synthesis of randomised control trials involving use of community health workers for delivering child health interventions in low and middle income countries

<p>Abstract</p> <p>Background</p> <p>A key constraint to saturating coverage of interventions for reducing the burden of childhood illnesses in Low and Middle Income Countries (LMIC) is the lack of human resources. Community health workers (CHW) are potentially important actors in bridging this gap. Evidence exists on effectiveness of CHW in management of some childhood illnesses (IMCI). However, we need to know how and when this comes to be. We examine evidence from randomized control trials (RCT) on CHW interventions in IMCI in LMIC from a realist perspective with the aim to see if they can yield insight into the working of the interventions, when examined from a different perspective.</p> <p>Methods</p> <p>The realist approach involves educing the mechanisms through which an intervention produced an outcome in a particular context. 'Mechanisms' are reactions, triggered by the interaction of the intervention and a certain context, which lead to change. These are often only implicit and are actually hypothesized by the reviewer. This review is limited to unravelling these from the RCTs; it is thus a hypothesis generating exercise.</p> <p>Results</p> <p>Interventions to improve CHW performance included 'Skills based training of CHW', 'Supervision and referral support from public health services', 'Positioning of CHW in the community'. When interventions were applied in context of CHW programs embedded in local health services, with beneficiaries who valued services and had unmet needs, the interventions worked if following mechanisms were triggered: anticipation of being valued by the community; perception of improvement in social status; sense of relatedness with beneficiaries and public services; increase in self esteem; sense of self efficacy and enactive mastery of tasks; sense of credibility, legitimacy and assurance that there was a system for back-up support. Studies also showed that if context differed, even with similar interventions, negative mechanisms could be triggered, compromising CHW performance.</p> <p>Conclusion</p> <p>The aim of this review was to explore if RCTs could yield insight into the working of the interventions, when examined from a different, a realist perspective. We found that RCTs did yield some insight, but the hypotheses generated were very general and not well refined. These hypotheses need to be tested and refined in further studies.</p

Wild bonobos host geographically restricted malaria parasites including a putative new <i>Laverania</i> species

Malaria parasites, though widespread among wild chimpanzees and gorillas, have not been detected in bonobos. Here, we show that wild-living bonobos are endemically Plasmodium infected in the eastern-most part of their range. Testing 1556 faecal samples from 11 field sites, we identify high prevalence Laverania infections in the Tshuapa-Lomami-Lualaba (TL2) area, but not at other locations across the Congo. TL2 bonobos harbour P. gaboni, formerly only found in chimpanzees, as well as a potential new species, Plasmodium lomamiensis sp. nov. Rare co-infections with non-Laverania parasites were also observed. Phylogenetic relationships among Laverania species are consistent with co-divergence with their gorilla, chimpanzee and bonobo hosts, suggesting a timescale for their evolution. The absence of Plasmodium from most field sites could not be explained by parasite seasonality, nor by bonobo population structure, diet or gut microbiota. Thus, the geographic restriction of bonobo Plasmodium reflects still unidentified factors that likely influence parasite transmission

Genomes of cryptic chimpanzee Plasmodium species reveal key evolutionary events leading to human malaria

African apes harbour at least six Plasmodium species of the subgenus Laverania, one of which gave rise to human Plasmodium falciparum. Here we use a selective amplification strategy to sequence the genome of chimpanzee parasites classified as Plasmodium reichenowi and Plasmodium gaboni based on the subgenomic fragments. Genome-wide analyses show that these parasites indeed represent distinct species, with no evidence of cross-species mating. Both P. reichenowi and P. gaboni are 10-fold more diverse than P. falciparum, indicating a very recent origin of the human parasite. We also find a remarkable Laverania-specific expansion of a multigene family involved in erythrocyte remodelling, and show that a short region on chromosome 4, which encodes two essential invasion genes, was horizontally transferred into a recent P. falciparum ancestor. Our results validate the selective amplification strategy for characterizing cryptic pathogen species, and reveal evolutionary events that likely predisposed the precursor of P. falciparum to colonize humans

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Ultrafast Studies of Hot-Hole Dynamics in Au/p-GaN Heterostructures

Harvesting non-equilibrium hot carriers from photo-excited metal nanoparticles has enabled plasmon-driven photochemical transformations and tunable photodetection with resonant nanoantennas. Despite numerous studies on the ultrafast dynamics of hot electrons, to date, the temporal evolution of hot holes in metal-semiconductor heterostructures remains unknown. An improved understanding of the carrier dynamics in hot-hole-driven systems is needed to help expand the scope of hot-carrier optoelectronics beyond hot-electron-based devices. Here, using ultrafast transient absorption spectroscopy, we show that plasmon-induced hot-hole injection from gold (Au) nanoparticles into the valence band of p-type gallium nitride (p-GaN) occurs within 200 fs, placing hot-hole transfer on a similar timescale as hot-electron transfer. We further observed that the removal of hot holes from below the Au Fermi level exerts a discernible influence on the thermalization of hot electrons above it, reducing the peak electronic temperature and decreasing the electron-phonon coupling time relative to Au samples without a pathway for hot-hole collection. First principles calculations corroborate these experimental observations, suggesting that hot-hole injection modifies the relaxation dynamics of hot electrons in Au nanoparticles through ultrafast modulation of the d-band electronic structure. Taken together, these ultrafast studies substantially advance our understanding of the temporal evolution of hot holes in metal-semiconductor heterostructures and suggest new strategies for manipulating and controlling the energy distributions of hot carriers on ultrafast timescales