Facilitators and Barriers to Uptake of an Extended Seasonal Malaria Chemoprevention Programme in Ghana: A Qualitative Study of Caregivers and Community Health Workers.

BACKGROUND: Seasonal Malaria Chemoprevention (SMC) is currently recommended for children under five in areas where malaria transmission is highly seasonal. We explored children's caregivers' and community health workers' (CHWs) responses to an extended 5-month SMC programme. METHODS: Thirteen in-depth interviews and eight focus group discussions explored optimal and suboptimal 'uptake' of SMC to examine facilitators and barriers to caregivers' uptake. RESULTS: There did not appear to be major differences between caregivers of children with optimal and sub-optimal SMC uptake in terms of their knowledge of malaria, their perceptions of the effect of SMC on a child's health, nor their understanding of chemoprevention. Caregivers experienced difficulty in prioritising SMC for well children, perceiving medication being for treatment rather than prevention. Prior to the study, caregivers had become accustomed to rapid diagnostic testing (RDT) for malaria, and therefore blood testing for malaria during the baseline survey at the start of the SMC programme may have positively influenced uptake. Facilitators of uptake included caregivers' trust in and respect for administrators of SMC (including CHWs), access to medication and supportive (family) networks. Barriers to uptake related to poor communication of timings of community gatherings, travel distances, absence during SMC home deliveries, and limited demand for SMC due to lack of previous experience. Future delivery of SMC by trained CHWs would be acceptable to caregivers. CONCLUSION: A combination of caregivers' physical access to SMC medication, the drug regimen, trust in the medical profession and perceived norms around malaria prevention all likely influenced caregivers' level of uptake. SMC programmes need to consider: 1) developing supportive, accessible and flexible modes of drug administration including home delivery and village community kiosks; 2) improving demand for preventive medication including the harnessing of learnt trust; and 3) developing community-based networks for users to support optimal uptake of SMC

Landlords' accounts of retrofit:A relational approach in the private rented sector in England

Climate change commitments and the current global energy and living cost crises require investment into energy efficiency in buildings. With one of the oldest housing stocks in Europe, the energy intensity of buildings in the United Kingdom remains high compared to other countries. The adoption of energy retrofit measures can support tackling several social, economic, and environmental objectives. Scarce uptake of these is particularly evident within the private rented sector, which presents additional hurdles compared to social and owner-occupied housing. We adopt an innovative theoretical and methodology approach at the intersection of new economic sociology and energy demand reduction literature to analyse the social relations of energy retrofitting in Brighton and Hove through interviews with landlords and experts in the field. A high percentage of private rented sector housing in poorly insulated and historical buildings, makes retrofitting in this area particularly challenging. Several strategies and policies have been implemented to decarbonise homes; yet have failed in framing the problem surrounding the adoption of retrofitting measures largely in economic terms. By contrast, our case study shows evidence of the ‘relational’ nature of a retrofitting decision-making process shaped by landlords' identities and networks of relations among and within retrofit actors; this could support tailoring more efficient policies. Place-related assets, institutional landscape, climate and built environment specificities are also critical. We are recommending more efficient strategies at the central level that allow for place specific policies; these should account for local features and relational approaches to overcome challenges to retrofit within the sector

Cost-effectiveness of district-wide seasonal malaria chemoprevention when implemented through routine malaria control programme in Kita, Mali using fixed point distribution

Background Seasonal malaria chemoprevention (SMC) is a strategy for malaria control recommended by the World Health Organization (WHO) since 2012 for Sahelian countries. The Mali National Malaria Control Programme adopted a plan for pilot implementation and nationwide scale-up by 2016. Given that SMC is a relatively new approach, there is an urgent need to assess the costs and cost effectiveness of SMC when implemented through the routine health system to inform decisions on resource allocation. Methods Cost data were collected from pilot implementation of SMC in Kita district, which targeted 77,497 children aged 3–59 months. Starting in August 2014, SMC was delivered by fixed point distribution in villages with the first dose observed each month. Treatment consisted of sulfadoxine-pyrimethamine and amodiaquine once a month for four consecutive months, or rounds. Economic and financial costs were collected from the provider perspective using an ingredients approach. Effectiveness estimates were based upon a published mathematical transmission model calibrated to local epidemiology, rainfall patterns and scale-up of interventions. Incremental cost effectiveness ratios were calculated for the cost per malaria episode averted, cost per disability adjusted life years (DALYs) averted, and cost per death averted. Results The total economic cost of the intervention in the district of Kita was US $357,494. Drug costs and personnel costs accounted for 34$0.73 and US $0.86, respectively; total annual financial and economic costs per child receiving SMC were US$2.92 and US $3.43, respectively. Accounting for coverage, the economic cost per child fully adherent (receiving all four rounds) was US$6.38 and US $4.69, if weighted highly adherent, (receiving 3 or 4 rounds of SMC). When costs were combined with modelled effects, the economic cost per malaria episode averted in children was US$4.26 (uncertainty bound 2.83–7.17), US $144 (135–153) per DALY averted and US$ 14,503 (13,604–15,402) per death averted. Conclusions When implemented at fixed point distribution through the routine health system in Mali, SMC was highly cost-effective. As in previous SMC implementation studies, financial incentives were a large cost component

Waratah Seed-1: Australia\u27s First Commercial Ride Share Satellite

In this paper, we report on a 6U CubeSat named Waratah Seed-1, designed by the ARC Training Centre for CubeSats, UAVs, and their Applications (CUAVA) and partners under the Waratah Seed project. Waratah Seed is a pilot Space Qualification Mission initiated under the NSW Government\u27s Space Industry Development Strategy with partial funding from Investment NSW. The goal of the mission is to allow NSW and Australian space industry groups to test their technology in space by flying on a 6U ride-share CubeSat. This project is the first of its kind in Australia, allowing space-tech start-ups and other groups to access a satellite spaceflight to test payloads at an inexpensive rate and in a more accessible way. The mission will help overcome one of the key barriers to gaining space flight heritage and should help accelerate the development of the Australian space ecosystem. The design of the WS-1 Satellite bus is based on its predecessor, the 3U CUAVA-1 CubeSat, and its sister 6U spacecraft CUAVA-2. The main payloads are a GPS reflectometry payload from UNSW and partners and a thermal management payload from UTS in collaboration with Mawson Rovers and Spiral Blue. Furthermore, there will be one edge computing payload from Spiral Blue, two solar cell test payloads, one each by Euroka Power and Extraterrestrial Power, a material test payload by Dandelions, a tactile, force, and torque sensor test payload by Sperospace and Contactile, an electropermanent magnetotorquer from DenebSpace and a space debris and plasma environment instrument from CUAVA and the University of Sydney. The satellite is scheduled for launch in July 2024 via SpaceX\u27s Transporter 11

Author Correction: Implementation, coverage and equity of large-scale door-to-door delivery of Seasonal Malaria Chemoprevention (SMC) to children under 10 in Senegal.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper

Common variation in the miR-659 binding-site of GRN is a major risk factor for TDP43-positive frontotemporal dementia

Loss-of-function mutations in progranulin (GRN) cause ubiquitin- and TAR DNA-binding protein 43 (TDP-43)-positive frontotemporal dementia (FTLD-U), a progressive neurodegenerative disease affecting ∼10% of early-onset dementia patients. Here we expand the role of GRN in FTLD-U and demonstrate that a common genetic variant (rs5848), located in the 3′-untranslated region (UTR) of GRN in a binding-site for miR-659, is a major susceptibility factor for FTLD-U. In a series of pathologically confirmed FTLD-U patients without GRN mutations, we show that carriers homozygous for the T-allele of rs5848 have a 3.2-fold increased risk to develop FTLD-U compared with homozygous C-allele carriers (95% CI: 1.50–6.73). We further demonstrate that miR-659 can regulate GRN expression in vitro, with miR-659 binding more efficiently to the high risk T-allele of rs5848 resulting in augmented translational inhibition of GRN. A significant reduction in GRN protein was observed in homozygous T-allele carriers in vivo, through biochemical and immunohistochemical methods, mimicking the effect of heterozygous loss-of-function GRN mutations. In support of these findings, the neuropathology of homozygous rs5848 T-allele carriers frequently resembled the pathological FTLD-U subtype of GRN mutation carriers. We suggest that the expression of GRN is regulated by miRNAs and that common genetic variability in a miRNA binding-site can significantly increase the risk for FTLD-U. Translational regulation by miRNAs may represent a common mechanism underlying complex neurodegenerative disorders

Altered microRNA expression in frontotemporal lobar degeneration with TDP-43 pathology caused by progranulin mutations

<p>Abstract</p> <p>Background</p> <p>Frontotemporal lobar degeneration (FTLD) is a progressive neurodegenerative disorder that can be triggered through genetic or sporadic mechanisms. MicroRNAs (miRNAs) have become a major therapeutic focus as their pervasive expression and powerful regulatory roles in disease pathogenesis become increasingly apparent. Here we examine the role of miRNAs in FTLD patients with TAR DNA-binding protein 43 pathology (FTLD-TDP) caused by genetic mutations in the progranulin (<it>PGRN</it>) gene.</p> <p>Results</p> <p>Using miRNA array profiling, we identified the 20 miRNAs that showed greatest evidence (unadjusted P < 0.05) of dysregulation in frontal cortex of eight FTLD-TDP patients carrying <it>PGRN </it>mutations when compared to 32 FTLD-TDP patients with no apparent genetic abnormalities. Quantitative real-time PCR (qRT-PCR) analyses provided technical validation of the differential expression for 9 of the 20 miRNAs in frontal cortex. Additional qRT-PCR analyses showed that 5 out of 9 miRNAs (miR-922, miR-516a-3p, miR-571, miR-548b-5p, and miR-548c-5p) were also significantly dysregulated (unadjusted P < 0.05) in cerebellar tissue samples of <it>PGRN </it>mutation carriers, consistent with a systemic reduction in PGRN levels. We developed a list of gene targets for the 5 candidate miRNAs and found 18 genes dysregulated in a reported FTLD mRNA study to exhibit anti-correlated miRNA-mRNA patterns in affected cortex and cerebellar tissue. Among the targets is brain-specific angiogenesis inhibitor 3, which was recently identified as an important player in synapse biology.</p> <p>Conclusions</p> <p>Our study suggests that miRNAs may contribute to the pathogenesis of FTLD-TDP caused by <it>PGRN </it>mutations and provides new insight into potential future therapeutic options.</p

Shearwater Foraging in the Southern Ocean: The Roles of Prey Availability and Winds

Background Sooty (Puffinus griseus) and short-tailed (P. tenuirostris) shearwaters are abundant seabirds that range widely across global oceans. Understanding the foraging ecology of these species in the Southern Ocean is important for monitoring and ecosystem conservation and management. Methodology/Principal Findings Tracking data from sooty and short-tailed shearwaters from three regions of New Zealand and Australia were combined with at-sea observations of shearwaters in the Southern Ocean, physical oceanography, near-surface copepod distributions, pelagic trawl data, and synoptic near-surface winds. Shearwaters from all three regions foraged in the Polar Front zone, and showed particular overlap in the region around 140°E. Short-tailed shearwaters from South Australia also foraged in Antarctic waters south of the Polar Front. The spatial distribution of shearwater foraging effort in the Polar Front zone was matched by patterns in large-scale upwelling, primary production, and abundances of copepods and myctophid fish. Oceanic winds were found to be broad determinants of foraging distribution, and of the flight paths taken by the birds on long foraging trips to Antarctic waters. Conclusions/Significance The shearwaters displayed foraging site fidelity and overlap of foraging habitat between species and populations that may enhance their utility as indicators of Southern Ocean ecosystems. The results highlight the importance of upwellings due to interactions of the Antarctic Circumpolar Current with large-scale bottom topography, and the corresponding localised increases in the productivity of the Polar Front ecosystem