Incorporating hydrology into climate suitability models changes projections of malaria transmission in Africa

Continental-scale models of malaria climate suitability typically couple well-established temperature-response models with basic estimates of vector habitat availability using rainfall as a proxy. Here we show that across continental Africa, the estimated geographic range of climatic suitability for malaria transmission is more sensitive to the precipitation threshold than the thermal response curve applied. To address this problem we use downscaled daily climate predictions from seven GCMs to run a continental-scale hydrological model for a process-based representation of mosquito breeding habitat availability. A more complex pattern of malaria suitability emerges as water is routed through drainage networks and river corridors serve as year-round transmission foci. The estimated hydro-climatically suitable area for stable malaria transmission is smaller than previous models suggest and shows only a very small increase in state-of-the-art future climate scenarios. However, bigger geographical shifts are observed than with most rainfall threshold models and the pattern of that shift is very different when using a hydrological model to estimate surface water availability for vector breeding

Urban correction of global DEMs using building density for Nairobi, Kenya

Urban flood models that use Digital Elevation Models (DEMs) to simulate extent and depth of flood inundation rely on the accuracy of DEMs for predicting flood events. Despite recent advances in developing vegetation corrected DEMs, the effect of building height and density errors in global DEMs in urban areas are still poorly understood, and their correction remains a challenge. In this research we developed a methodology for building error correction that can be applied to any other case study, where building density data and a local reference DEM data are available. This methodology was applied to Nairobi, Kenya using six global DEMs (SRTM, MERIT, ALOS, NASADEM, TanDEM-X 12 m, and TanDEM-X 90 m DEM). Our results show building error at highest building density varying between 1.25 m and 5.07 m for the DEMs used, with the MERIT DEM showing the smallest vertical height error from the reference DEM. The six DEMs were corrected by deriving a linear relationship between building density and DEM error. Our findings show that the removal of building density error resulted in the improvement of the vertical height accuracy of the global DEMs of up to 45% for MERIT and 40% for ALOS. This methodology was also applied to the Central Business District (CBD) area of Nairobi, characterized by taller buildings and high building density. The error parameters in the CBD area resulted to be between 15 to 45% higher than those of the Nairobi city wide area for the six global DEMs, thus providing further insights into the contribution of building heights to errors in global DEMs. Building height data is still unavailable on a global scale and our results show that global DEMs can be usefully corrected for building density errors in urban areas, even where specific building height data are not available

Early access schemes for innovative health technologies: the views of international stakeholders

This is the final version. Available on open access from Cambridge University Press via the DOI in this recordOBJECTIVES: Early access schemes (EASs) are approaches used by payers to balance and facilitate earlier patient access to innovative health technologies while evidence generation is ongoing. Schemes require investment from payers and are associated with significant risk since not all technologies will be routinely reimbursed. The purpose of this study was to gain the perspectives of policy experts about the key challenges for EASs and potential solutions for their optimal design and implementation. METHODS: Two virtual workshops were convened including (i) UK-based policy experts (England, Wales, and Scotland) and (ii) representatives from multiple healthcare systems (England, France, Sweden, Canada, Poland, and Norway). Participants were encouraged to share their experiences with EASs in their healthcare system and highlight key challenges for policy makers. Discussions were transcribed and analyzed using framework analysis. RESULTS: Participants agreed that EASs have value when targeted toward innovative technologies with the potential for significant clinical benefit in an area of high unmet need. Participants discussed potential solutions to the challenges faced by payers implementing EASs, including defining eligibility criteria, supporting evidence generation, and approaches to reimbursement. CONCLUSIONS: Participants agreed that EASs are one possible solution for their healthcare systems and have the potential to deliver significant clinical value to patients. However, widespread adoption of EASs is limited due to concerns about the risks for patients and healthcare budgets, further solutions are needed to deliver EASs for targeted therapies.NHS Englan

An evaluation of managed access agreements in England based on stakeholder experience

This is the final version. Available on open access from Cambridge University Press via the DOI in this recordOBJECTIVES: The objective of this research was to evaluate managed access policy in England, drawing upon the expertise of a range of stakeholders involved in its implementation. METHODS: Seven focus groups were conducted with payer and health technology assessment representatives, clinicians, and representatives from industry and patient/carer organizations within England. Transcripts were analyzed using framework analysis to identify stakeholders' views on the successes and challenges of managed access policy. RESULTS: Stakeholders discussed the many aims of managed access within the National Health Service in England, and how competing aims had affected decision making. While stakeholders highlighted a number of priorities within eligibility criteria for managed access agreements (MAAs), stakeholders agreed that strict eligibility criteria would be challenging to implement due to the highly variable nature of innovative technologies and their indications. Participants highlighted challenges faced with implementing MAAs, including evidence generation, supporting patients during and after the end of MAAs, and agreeing and reinforcing contractual agreements with industry. CONCLUSIONS: Managed access is one strategy that can be used by payers to resolve uncertainty for innovative technologies that present challenges for reimbursement and can also deliver earlier access to promising technologies for patients. However, participants cautioned that managed access is not a "silver bullet," and there is a need for greater clarity about the aims of managed access and how these should be prioritized in decision making. Discussions between key stakeholders involved in managed access identified challenges with implementing MAAs and these experiences should be used to inform future managed access policy.NHS Englan

An analysis of uncertainties and data collection agreements in the cancer drugs fund

Background: Managed Access Agreements (MAAs) are a commercial arrangement that provide patients earlier access to innovative health technologies while uncertainties in the evidence base are resolved through data collection. In the UK, data collection agreements (DCAs) outline the evidence that will be collected during the MAA period and are intended to resolve uncertainties in the clinical- and cost-effectiveness of a technology sufficient for the National Institute of Health and Care Excellence (NICE) committee to make a final decision on reimbursement. Objective: The aim of this study was to identify the primary uncertainties leading to a recommendation for entry to the Cancer Drugs Fund (CDF) and evaluate how the corresponding DCAs attempt to address these. Methods: A database of MAAs agreed within the CDF was compiled with coverage between July 2016 and December 2020 (the time during which evidence generation was routinely collected within the CDF up until the time of analysis). Uncertainties in the evidence base for technologies entering the CDF were analysed alongside the outcomes planned for data collection during the MAA. These data provide an overview of the key uncertainties surrounding health technologies in the CDF on entry and the types of evidence targeted by DCAs. Results: In the assessment of 39 Cancer Drugs Fund (CDF) cases, NICE committees identified a total of 108 key uncertainties in cost-effectiveness estimates. Overall survival was the most commonly identified uncertainty, followed by generalisability of the evidence to the target population. DCAs specified a range of outcomes relevant to understanding the clinical effectiveness of the technology, though fewer than half (43.6%) of the DCAs addressed all the key uncertainties identified by the NICE committee. Conclusion: The analysis indicated that data collection within the CDF is not sufficient to resolve all the uncertainties identified by the NICE committee, meaning that other approaches will be needed at re-appraisal to ensure that the NICE committee can reach a final decision on reimbursement

Protective Efficacy of Menthol Propylene Glycol Carbonate Compared to N, N-diethyl-Methylbenzamide Against Mosquito Bites in Northern Tanzania.

The reduction of malaria parasite transmission by preventing human-vector contact is critical in lowering disease transmission and its outcomes. This underscores the need for effective and long lasting arthropod/insect repellents. Despite the reduction in malaria transmission and outcomes in Tanzania, personal protection against mosquito bites is still not well investigated. This study sought to determine the efficacy of menthol propylene glycol carbonate (MR08), Ocimum suave as compared to the gold standard repellent N, N-diethyl-methylbenzamide (DEET), either as a single dose or in combination (blend), both in the laboratory and in the field against Anopheles gambiae s.l and Culex quinquefasciatus. In the laboratory evaluations, repellents were applied on one arm while the other arm of the same individual was treated with a base cream. Each arm was separately exposed in cages with unfed female mosquitoes. Repellents were evaluated either as a single dose or as a blend. Efficacy of each repellent was determined by the number of mosquitoes that landed and fed on treated arms as compared to the control or among them. In the field, evaluations were performed by human landing catches at hourly intervals from 18:00  hr to 01:00  hr. A total of 2,442 mosquitoes were collected during field evaluations, of which 2,376 (97.30%) were An. gambiae s.l while 66 (2.70%) were Cx. quinquefaciatus. MR08 and DEET had comparatively similar protective efficacy ranging from 92% to 100 for both single compound and blends. These findings indicate that MR08 has a similar protective efficacy as DEET for personal protection outside bed nets when used singly and in blends. Because of the personal protection provided by MR08, DEET and blends as topical applicants in laboratory and field situations, these findings suggest that, these repellents could be used efficiently in the community to complement existing tools. Overall, Cx. quinquefasciatus were significantly prevented from blood feeding compared to An. gambiae s.l. The incorporation of these topical repellents for protection against insect bites can be of additional value in the absence or presence of IRS and ITNs coverage. However, a combination of both the physical (bed nets) and the repellent should be used in an integrated manner for maximum protection, especially before going to bed. Additional research is needed to develop repellents with longer duration of protection

Predicting the exposure of diving grey seals to shipping noise.

There is high spatial overlap between grey seals and shipping traffic, and the functional hearing range of grey seals indicates sensitivity to underwater noise emitted by ships. However, there is still very little data regarding the exposure of grey seals to shipping noise, constraining effective policy decisions. Particularly, there are few predictions that consider the at-sea movement of seals. Consequently, this study aimed to predict the exposure of adult grey seals and pups to shipping noise along a three-dimensional movement track, and assess the influence of shipping characteristics on sound exposure levels. Using ship location data, a ship source model, and the acoustic propagation model, RAMSurf, this study estimated weighted 24-h sound exposure levels (10-1000 Hz) (SELw). Median predicted 24-h SELw was 128 and 142 dB re 1 μPa2s for the pups and adults, respectively. The predicted exposure of seals to shipping noise did not exceed best evidence thresholds for temporary threshold shift. Exposure was mediated by the number of ships, ship source level, the distance between seals and ships, and the at-sea behaviour of the seals. The results can inform regulatory planning related to anthropogenic pressures on seal populations

Kinetic analysis of the translocator protein positron emission tomography ligand [F-18]GE-180 in the human brain

Purpose: PET can image neuroinflammation by targeting the translocator protein (TSPO), which is upregulated in activated microglia. The high nonspecific binding of the first-generation TSPO radioligand [11C]PK-11195 limits accurate quantification. [18F]GE-180, a novel TSPO ligand, displays superior binding to [11C]PK-11195 in vitro. Our objectives were to: (1) evaluate tracer characteristics of [18F]GE-180 in the brains of healthy human subjects; and (2) investigate whether the TSPO Ala147Thr polymorphism influences outcome measures. // Methods: Ten volunteers (five high-affinity binders, HABs, and five mixed-affinity binders, MABs) underwent a dynamic PET scan with arterial sampling after injection of [18F]GE-180. Kinetic modelling of time–activity curves with one-tissue and two-tissue compartment models and Logan graphical analysis was applied to the data. The primary outcome measure was the total volume of distribution (V T) across various regions of interest (ROIs). Secondary outcome measures were the standardized uptake values (SUV), the distribution volume and SUV ratios estimated using a pseudoreference region. // Results: The two-tissue compartment model was the best model. The average regional delivery rate constant (K 1) was 0.01 mL cm−3 min−1 indicating low extraction across the blood–brain barrier (1 %). The estimated median V T across all ROIs was also low, ranging from 0.16 mL cm−3 in the striatum to 0.38 mL cm−3 in the thalamus. There were no significant differences in V T between HABs and MABs across all ROIs. // Conclusion: A reversible two-tissue compartment model fitted the data well and determined that the tracer has a low first-pass extraction (approximately 1 %) and low V T estimates in healthy individuals. There was no observable dependency on the rs6971 polymorphism as compared to other second-generation TSPO PET tracers. Investigation of [18F]GE-180 in populations with neuroinflammatory disease is needed to determine its suitability for quantitative assessment of TSPO expression

Distributive justice with and without culture

Academic treatments of distributive justice normally adopt a static approach centred on resource allocation among a set of individual agents. The resulting models, expressed in mathematical language, make no allowance for culture, as they never engage with the society’s way of life or the moulding of individuals within society. This paper compares the static approach to distributive justice with a cultural one, arguing that a case for redistribution should rest upon its cultural effects in assisting well-being and social cohesion. Unless we recognise culture, we can have little understanding of why inequalities matter, where they come from, and how they might be reduced. Redistribution may be motivated by universal value judgements taken from external sources, but it also entails internal cultural changes that refashion social relations through cumulative causation. In practical terms, it has to penetrate beyond reallocating resource endowments to bring revised attitudes in a society less tolerant of unequal outcomes. Egalitarian reforms will flourish only if they generate and reflect an egalitarian culture