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

A global-scale applicable framework of landslide dam formation susceptibility

The formation and failure of landslide dams is an important and understudied, multi-hazard topic. A framework of landslide dam formation susceptibility evaluation was designed for large-scale studies to avoid the traditional dependence on landslide volume calculations based on empirical relationships, which requires comprehensive local inventories of landslides and landslide dams. The framework combines logistic regression landslide susceptibility models and global fluvial datasets and was tested in Italy and Japan based on landslide and landslide dam inventories collected globally. The final landslide dam formation susceptibility index identifies which river reach is most prone to landslide dam formation, based on the river width and the landslide susceptibility in the adjacent delineated slope drainage areas. The logistic regression models showed good performances with area under the receiver operating characteristics curve values of 0.89 in Italy and 0.74 in Japan. The index effectively identifies the probability of landslide dam formation for specific river reaches, as demonstrated by the higher index values for river reaches with past landslide dam records. The framework is designed to be applied globally or for other large-scale study regions, especially for less studied data-scarce regions. It also provides a preliminary evaluation result for smaller catchments and has the potential to be applied at a more detailed scale with local datasets

Flutriciclamide (F-18-GE180) PET: First-in-Human PET Study of Novel Third-Generation In Vivo Marker of Human Translocator Protein

Neuroinflammation is associated with neurodegenerative disease. PET radioligands targeting the 18-kDa translocator protein (TSPO) have been used as in vivo markers of neuroinflammation, but there is an urgent need for novel probes with improved signal-to-noise ratio. Flutriciclamide (18F-GE180) is a recently developed third-generation TSPO ligand. In this first study, we evaluated the optimum scan duration and kinetic modeling strategies for 18F-GE180 PET in (older) healthy controls. Methods: Ten healthy controls, 6 TSPO high-affinity binders, and 4 mixed-affinity binders were recruited. All subjects underwent detailed neuropsychologic tests, MRI, and a 210-min 18F-GE180 dynamic PET/CT scan using metabolite-corrected arterial plasma input function. We evaluated 5 different kinetic models: irreversible and reversible 2-tissue-compartment models, a reversible 1-tissue model, and 2 models with an extra irreversible vascular compartment. The minimal scan duration was established using 210-min scan data. The feasibility of generating parametric maps was also investigated using graphical analysis. Results: 18F-GE180 concentration was higher in plasma than in whole blood during the entire scan duration. The volume of distribution (VT) was 0.17 in high-affinity binders and 0.12 in mixed-affinity binders using the kinetic model. The model that best represented brain 18F-GE180 kinetics across regions was the reversible 2-tissue-compartment model (2TCM4k), and 90 min resulted as the optimum scan length required to obtain stable estimates. Logan graphical analysis with arterial input function gave a VT highly consistent with VT in the kinetic model, which could be used for voxelwise analysis. Conclusion: We report for the first time, to our knowledge, the kinetic properties of the novel third-generation TSPO PET ligand 18F-GE180 in humans: 2TCM4k is the optimal method to quantify the brain uptake, 90 min is the optimal scan length, and the Logan approach could be used to generate parametric maps. Although these control subjects have shown relatively low VT, the methodology presented here forms the basis for quantification for future PET studies using 18F-GE180 in different pathologies

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

A critique of Paulo Freire’s perspective on human nature to inform the construction of theoretical underpinnings for research

From Crossref via Jisc Publications RouterHistory: epub 2020-04-20, issued 2020-04-20Article version: VoRKate Sanders - ORCID 0000-0003-3516-7030 https://orcid.org/0000-0003-3516-7030This article presents a critique of Paulo Freire's philosophical perspective on human nature in the context of a doctoral research study to explore “muchness” or nurses’ subjective experience of well‐being; and demonstrates how this critique has informed the refinement of the theoretical principles used to inform research methodology and methods. Engaging in philosophical groundwork is essential for research coherence and integrity. Through this groundwork, largely informed by Freire's critical pedagogy and his ideas on humanization, I recognized the need to clarify my understanding of the concepts of persons and personhood and how this related to Freire's use of the term human beings. This clarification process is essential to ensure congruence between the theoretical principles that I draw from his work and my beliefs about persons, personhood and person‐centredness. The article begins with a brief introduction to the research, followed by an overview of Freire's philosophical perspectives, and subsequently, the critique process is presented and discussed. This process involved engaging with the vast literature and debates about what it means to be a person, to make sense of the often complex and contradictory arguments. Eventually, three headings emerged that helped me to frame my evolving understanding: Our species: human beings ; The kind that we are: human nature ; and This person that I am: personhood. Through this process of exploration, I recognized that Freire's perspective on human nature (a) foregrounded cognitive rationality, which presented itself as a limitation when considering my ontological beliefs and the focus of my research, leading me to draw on the work of Mark Johnson and his ideas about embodiment to help me to further develop my theoretical principles; (b) focused on the “collective” rather than individuals, which is a shortcoming in relation to person‐centred research that acknowledges the uniqueness of participants.21pubpub

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

Reconfiguring ruins: Beyond Ruinenlust

What explains the global proliferation of interest in ruins? Can ruins be understood beyond their common framing as products of European Romanticism? Might a transdisciplinary approach allow us to see ruins differently? These questions underpinned the Arts and Humanities Research Council–funded project Reconfiguring Ruins, which deployed approaches from history, literature, East Asian studies, and geography to reflect on how ruins from different historical contexts are understood by reference to different theoretical frameworks. In recognition of the value of learning from other models of knowledge production, the project also involved a successful collaboration with the Museum of London Archaeology and the artist-led community The NewBridge Project in Newcastle. By bringing these varied sets of knowledges to bear on the project’s excavations of specific sites in the United Kingdom, the United States, and Japan, the article argues for an understanding of ruins as thresholds, with ruin sites providing unique insights into the relationship between lived pasts, presents, and futures. It does so by developing three key themes that reflect on the process of working collaboratively across the arts, humanities, and social sciences, including professional archaeology: inter- and transdisciplinarity, the limits of cocreation, and traveling meanings and praxis. Meanings of specific ruins are constructed out of specific languages and cultural resonances and read though different disciplines, but can also be reconfigured through concepts and practices that travel beyond disciplinary, cultural, and linguistic borders. As we show here, the ruin is, and should be, a relational concept that moves beyond the romantic notion of Ruinenlust

Drug coverage in treatment of malaria and the consequences for resistance evolution - evidence from the use of sulphadoxine/pyrimethamine

BACKGROUND\ud \ud It is argued that, the efficacy of anti-malarials could be prolonged through policy-mediated reductions in drug pressure, but gathering evidence of the relationship between policy, treatment practice, drug pressure and the evolution of resistance in the field is challenging. Mathematical models indicate that drug coverage is the primary determinant of drug pressure and the driving force behind the evolution of drug resistance. These models show that where the basis of resistance is multigenic, the effects of selection can be moderated by high recombination rates, which disrupt the associations between co-selected resistance genes.\ud \ud METHODS\ud \ud To test these predictions, dhfr and dhps frequency changes were measured during 2000-2001 while SP was the second-line treatment and contrasted these with changes during 2001-2002 when SP was used for first-line therapy. Annual cross sectional community surveys carried out before, during and after the policy switch in 2001 were used to collect samples. Genetic analysis of SP resistance genes was carried out on 4,950 Plasmodium falciparum infections and the selection pressure under the two policies compared.\ud \ud RESULTS\ud \ud The influence of policy on the parasite reservoir was profound. The frequency of dhfr and dhps resistance alleles did not change significantly while SP was the recommended second-line treatment, but highly significant changes occurred during the subsequent year after the switch to first line SP. The frequency of the triple mutant dhfr (N51I,C59R,S108N) allele (conferring pyrimethamine resistance) increased by 37% - 63% and the frequency of the double A437G, K540E mutant dhps allele (conferring sulphadoxine resistance) increased 200%-300%. A strong association between these unlinked alleles also emerged, confirming that they are co-selected by SP.\ud \ud CONCLUSION\ud \ud The national policy change brought about a shift in treatment practice and the resulting increase in coverage had a substantial impact on drug pressure. The selection applied by first-line use is strong enough to overcome recombination pressure and create significant linkage disequilibrium between the unlinked genetic determinants of pyrimethamine and sulphadoxine resistance, showing that recombination is no barrier to the emergence of resistance to combination treatments when they are used as the first-line malaria therapy