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Abstract Background The rapid and often uncontrolled rural–urban migration in Sub-Saharan Africa is transforming urban landscapes expected to provide shelter for more than 50% of Africa’s population by 2030. Consequently, the burden of malaria is increasingly affecting the urban population, while socio-economic inequalities within the urban settings are intensified. Few studies, relying mostly on moderate to high resolution datasets and standard predictive variables such as building and vegetation density, have tackled the topic of modeling intra-urban malaria at the city extent. In this research, we investigate the contribution of very-high-resolution satellite-derived land-use, land-cover and population information for modeling the spatial distribution of urban malaria prevalence across large spatial extents. As case studies, we apply our methods to two Sub-Saharan African cities, Kampala and Dar es Salaam. Methods Openly accessible land-cover, land-use, population and OpenStreetMap data were employed to spatially model Plasmodium falciparum parasite rate standardized to the age group 2–10 years (PfPR2–10) in the two cities through the use of a Random Forest (RF) regressor. The RF models integrated physical and socio-economic information to predict PfPR2–10 across the urban landscape. Intra-urban population distribution maps were used to adjust the estimates according to the underlying population. Results The results suggest that the spatial distribution of PfPR2–10 in both cities is diverse and highly variable across the urban fabric. Dense informal settlements exhibit a positive relationship with PfPR2–10 and hotspots of malaria prevalence were found near suitable vector breeding sites such as wetlands, marshes and riparian vegetation. In both cities, there is a clear separation of higher risk in informal settlements and lower risk in the more affluent neighborhoods. Additionally, areas associated with urban agriculture exhibit higher malaria prevalence values. Conclusions The outcome of this research highlights that populations living in informal settlements show higher malaria prevalence compared to those in planned residential neighborhoods. This is due to (i) increased human exposure to vectors, (ii) increased vector density and (iii) a reduced capacity to cope with malaria burden. Since informal settlements are rapidly expanding every year and often house large parts of the urban population, this emphasizes the need for systematic and consistent malaria surveys in such areas. Finally, this study demonstrates the importance of remote sensing as an epidemiological tool for mapping urban malaria variations at large spatial extents, and for promoting evidence-based policy making and control efforts.

Resumo Objetivo: Avaliar e comparar a taxa de sucesso da intubação monocanalicular ou bicanalicular em pacientes com obstrução congênita do ducto lacrimonasal (OCDLN), levando-se em consideração a taxa de sucesso, a dificuldade do procedimento e o custo dos tubos. Métodos: Foram analisados retrospectivamente 54 prontuários, totalizando 58 vias lacrimais com diagnóstico de OCDLN, que realizaram intubação das vias lacrimais monocanalicular ou bicanalicular com tubos de silicone. Anamnese, exame oftalmológico geral, testes específicos, como o Teste do Desaparecimento do Corante (TDC) e Teste de Observação de Fluoresceína na Orofaringe (TOFO), e, caso necessário, exames complementares como a dacriocistografia, foram utilizados para diagnóstico e inclusão na pesquisa. Foram tratados com intubação os pacientes sem resposta adequada ao tratamento prévio, ou seja, que permaneceram com sintomas de secreção e epífora contínua após a realização de massagem de Crigler e sondagem. Resultados: A intubação monocanalicular foi realizada em 27 vias lacrimais e a intubação bicanalicular, em 31 vias lacrimais. A taxa de sucesso foi alta em ambos os métodos, com melhora em 26 (96,3%) vias lacrimais com sonda monocanalicular e em 30 (96,8%), com sonda bicanalicular (p=0,718). As duas técnicas apresentaram 100% de sucesso nos pacientes com até 2 anos e acima de 4 anos de idade (p=1). A taxa de sucesso entre os 2 e 4 anos de idade foi de 91,5% para as monocanaliculares e 87,5% para as bicanaliculares, (p=0,652). Conclusão: o presente estudo não mostrou diferença significativa no sucesso da intubação quando utilizando sondas mono ou bicanaliculares. A intubação monocanalicular mostrou-se de mais fácil execução, ao passo que o tubo bicanalicular possui menor custo.

CRISPR/Cas9 genome editing has been used extensively in a wide variety of plant species. Creation of loss-of-function alleles, promoter variants and mutant collections are a few of the many uses of genome editing. In a typical workflow for sexually reproducing species, plants are generated that contain an integrated CRISPR/Cas9 transgene. After editing of the gene of interest, T-DNA null segregants can be identified in the next generation that contain only the desired edit. However, maintained presence of the CRISPR/Cas9 transgene and continued editing in the subsequent generations offer a range of applications for model plants and crops. In this review, we define transgenerational gene editing (TGE) as the continued editing of CRISPR/Cas9 after a genetic cross. We discuss the concept of TGE, summarize the current main applications, and highlight special cases to illustrate the importance of TGE for plant genome editing research and breeding.

ABSTRACT Human parainfluenza virus type 3 (HPIV-3) is a significant cause of lower respiratory tract infections, with the most severe disease in young infants, immunocompromised individuals, and the elderly. HPIV-3 infections are currently untreatable with licensed therapeutics, and prophylactic and therapeutic options are needed for patients at risk. To complement existing human airway models of HPIV-3 infection and develop an animal model to assess novel intervention strategies, we evaluated infection and transmission of HPIV-3 in ferrets. A well-characterized human clinical isolate (CI) of HPIV-3 engineered to express enhanced green fluorescent protein (rHPIV-3 CI-1-EGFP) was passaged on primary human airway epithelial cells (HAE) or airway organoids (AO) to avoid tissue culture adaptations. rHPIV3 CI-1-EGFP infection was assessed in vitro in ferret AO and in ferrets in vivo. Undifferentiated and differentiated ferret AO cultures supported rHPIV-3 CI-1-EGFP replication, but the ferret primary airway cells from AO were less susceptible and permissive than HAE. In vivo rHPIV-3 CI-1-EGFP replicated in the upper and lower airways of ferrets and targeted respiratory epithelial cells, olfactory epithelial cells, type I pneumocytes, and type II pneumocytes. The infection efficiently induced specific antibody responses. Taken together, ferrets are naturally susceptible to HPIV-3 infection; however, limited replication was observed that led to neither overt clinical signs nor ferret-to-ferret transmission. However, in combination with ferret AO, the ferret model of HPIV-3 infection, tissue tropism, and neutralizing antibodies complements human ex vivo lung models and can be used as a platform for prevention and treatment studies for this important respiratory pathogen. IMPORTANCE HPIV-3 is an important cause of pediatric disease and significantly impacts the elderly. Increasing numbers of immunocompromised patients suffer from HPIV-3 infections, often related to problems with viral clearance. There is a need to model HPIV-3 infections in vitro and in vivo to evaluate novel prophylaxis and treatment options. Currently existing animal models lack the potential for studying animal-to-animal transmission or the effect of immunosuppressive therapy. Here, we describe the use of the ferret model in combination with authentic clinical viruses to further complement human ex vivo models, providing a platform to study approaches to prevent and treat HPIV-3 infection. Although we did not detect ferret-to-ferret transmission in our studies, these studies lay the groundwork for further refinement of the ferret model to immunocompromised ferrets, allowing for studies of severe HPIV-3-associated disease. Such models for preclinical evaluation of prophylaxis and antivirals can contribute to reducing the global health burden of HPIV-3.

Following a huge global effort, the first World Health Organization (WHO)-endorsed catalogue of 17,356 variants in the Mycobacterium tuberculosis complex along with their classification as associated with resistance (interim), not associated with resistance (interim) or uncertain significance was made public In June 2021. This marks a critical step towards the application of next generation sequencing (NGS) data for clinical care. Unfortunately, the variant format used makes it difficult to look up variants when NGS data is generated by other bioinformatics pipelines. Furthermore, the large number of variants of uncertain significance in the catalogue hamper its useability in clinical practice. We successfully converted 98.3% of variants from the WHO catalogue format to the standardized HGVS format. We also created TBProfiler version 4.4.0 to automate the calling of all variants located in the tier 1 and 2 candidate resistance genes along with their classification when listed in the WHO catalogue. Using a representative sample of 339 clinical isolates from South Africa containing 691 variants in a tier 1 or 2 gene, TBProfiler classified 105 (15%) variants as conferring resistance, 72 (10%) as not conferring resistance and 514 (74%) as unclassified, with an average of 29 unclassified variants per isolate. Using a second cohort of 56 clinical isolates from a TB outbreak in Spain containing 21 variants in the tier 1 and 2 genes, TBProfiler classified 13 (61.9%) as unclassified, 7 (33.3%) as not conferring resistance, and a single variant (4.8%) classified as conferring resistance. Continued global efforts using standardized methods for genotyping, phenotyping and bioinformatic analyses will be essential to ensure that knowledge on genomic variants translates into improved patient care.

Using transient climate forcing based on simulations from the Alfred Wegener Institute Earth System Model (AWI-ESM), we simulate the evolution of the Greenland Ice Sheet (GrIS) from the last interglacial (125 ka, kiloyear before present) to 2100 AD with the Parallel Ice Sheet Model (PISM). The impact of paleoclimate, especially Holocene climate, on the present and future evolution of the GrIS is explored. Our simulations of the past show close agreement with reconstructions with respect to the recent timing of the peaks in ice volume and the climate of Greenland. The maximum and minimum ice volume at around 18–17 ka and 6–5 ka lag the respective extremes in climate by several thousand years, implying that the ice volume response of the GrIS strongly lags climatic changes. Given that Greenland’s climate was getting colder from the Holocene Thermal Maximum (i.e., 8 ka) to the Pre-Industrial era, our simulation implies that the GrIS experienced growth from the mid-Holocene to the industrial era. Due to this background trend, the GrIS still gains mass until the second half of the 20th century, even though anthropogenic warming begins around 1850 AD. This is also in agreement with observational evidence showing mass loss of the GrIS does not begin earlier than the late 20th century. Our results highlight that the present evolution of the GrIS is not only controlled by the recent climate changes, but is also affected by paleoclimate, especially the relatively warm Holocene climate. We propose that the GrIS was not in equilibrium throughout the entire Holocene and that the slow response to Holocene climate needs to be represented in ice sheet simulations in order to predict ice mass loss, and therefore sea level rise, accurately.

Designing turbulence promoters with optimal geometry and using them for ultrafiltration systems has been a key challenge in mitigating membrane fouling. In this study, six different turbulence promoters were created using three-dimensional printing technology and applied in dead-end ultrafiltration. Three-dimensional-printed (3DP) turbulence promoter configurations were integrated into a classical batch ultrafiltration cell. The effects of these configurations and the stirring speeds on the permeate filtration flux, organic rejections, and membrane resistances were investigated. The fouling control efficiency of the 3DP promoters was evaluated using two polyethersulfone membranes in a stirred ultrafiltration cell with model dairy wastewater. The Hermia and resistance-in-series models were studied to further investigate the membrane fouling mechanism. Of the Hermia models, the cake layer model best described the fouling in this membrane filtration system. It can be concluded that the 3DP turbulence promoters, combined with intense mechanical stirring, show great promise in terms of permeate flux enhancement and membrane fouling mitigation. Using a well-designed 3DP turbulence promoter improves the hydrodynamic flow conditions on the surface of the stirred membrane separation cells based on computational fluid dynamics modeling. Therefore, the factors effecting the fabrication of 3DP turbulence promoters are important, and further research should be devoted to revealing them.

Severe aortic valve stenosis is the most frequent valve pathology in the western world and approximately 50% of these patients have concomitant coronary artery disease (CAD). Revascularization of proximal obstructive CAD in patients undergoing surgical aortic valve replacement (SAVR) is common practice considered appropriate. However, the management of patients with CAD undergoing transcatheter aortic valve implantation (TAVI) is more controversial. Nevertheless, performing percutaneous coronary intervention (PCI) of significant (>70%) proximal coronary lesions is a widely adopted strategy, but robust supporting scientific evidence is missing. Some studies suggest that complex CAD with incomplete revascularization negatively impacts outcomes post-TAVI. As increasingly younger patients are undergoing TAVI, optimizing the long-term outcomes will become more important. Although PCI in TAVI patients is safe, no benefit on outcomes has been demonstrated, possibly due to an inadequate selection of prognostically important lesions for revascularization. A possible solution might be the use of coronary physiological indices, but these have their own limitations and more data is needed to support widespread adoption. In this review we provide an overview of current evidence on the outcomes after aortic valve replacement (AVR) and the evidence regarding revascularization in this population.

Excess sodium intake raises blood pressure which increases the risk of chronic kidney disease (CKD). We aimed to estimate the impact of reduced sodium intake on future CKD burden in Australia. A multi-cohort proportional multistate lifetable model was developed to estimate the potential impact on CKD burden and health expenditure if the Australian Suggested Dietary Target (SDT) and the National Preventive Health Strategy 2021–2030 (NPHS) sodium target were achieved. Outcomes were projected to 2030 and over the lifetime of adults alive in 2019. Achieving the SDT and NPHS targets could lower population mean systolic blood pressure by 2.1 mmHg and 1.7 mmHg, respectively. Compared to normal routines, attaining the SDT and NPHS target by 2030 could prevent 59,220 (95% UI, 53,140–65,500) and 49,890 (44,377–55,569) incident CKD events, respectively, while postponing 568 (479–652) and 511 (426–590) CKD deaths, respectively. Over the lifetime, this generated 199,488 health-adjusted life years (HALYs) and AUD 644 million in CKD healthcare savings for the SDT and 170,425 HALYs and AUD 514 million for the NPHS. CKD due to hypertension and CKD due to other/unspecified causes were the principal contributors to the HALY gains. Lowering sodium consumption in Australia could deliver substantial CKD health and economic benefits.

Locating a cryptographic operation in a side-channel trace, i.e. finding out where it is in the time domain, without having a template, can be a tedious task even for unprotected implementations. The sheer amount of data can be overwhelming. In a simple call to OpenSSL for AES-128 ECB encryption of a single data block, only 0.00028% of the trace relate to the actual AES-128 encryption. The rest is overhead. We introduce the (to our best knowledge) first method to locate a cryptographic operation in a side-channel trace in a largely automated fashion. The method exploits meta information about the cryptographic operation and requires an estimate of its implementation’s execution time. The method lends itself to parallelization and our implementation in a tool greatly benefits from GPU acceleration. The tool can be used offline for trace segmentation and for generating a template which can then be used online in real-time waveformmatching based triggering systems for trace acquisition or fault injection. We evaluate it in six scenarios involving hardware and software implementations of different cryptographic operations executed on diverse platforms. Two of these scenarios cover realistic protocol level use-cases and demonstrate the real-world applicability of our tool in scenarios where classical leakage-detection techniques would not work. The results highlight the usefulness of the tool because it reliably and efficiently automates the task and therefore frees up time of the analyst. The method does not work on traces of implementations protected by effective time randomization countermeasures, e.g. random delays and unstable clock frequency, but is not affected by masking, shuffling and similar countermeasures.

Multispecies aggregations of tuna, dolphins, and seabirds are prevalent and conspicuous in the vast waters of the eastern tropical Pacific and form the basis of a commercial fishery for yellowfin tuna (Thunnus albacares) through setting on schools of dolphins, which is among the largest tuna fisheries in the world. Incidental dolphin mortality associated with the development and early years of the fishery was high; by 1993 it was estimated that eastern spinner dolphins (Stenella longirostris orientalis) had been reduced to 44% and northeastern offshore spotted dolphins (S. attenuata attenuata) to 19% of pre-fishery levels. Efforts to reduce this mortality began at the inception of the fishery and comprised a diverse array of approaches: modifications to fishing methods and fishing gear (backdown, Medina panel, high-intensity floodlights, swimmers to disentangle and release dolphins); U.S. legislation (through the U.S. Marine Mammal Protection Act, MMPA, and subsequent amendments); international agreements (including the International Dolphin Conservation Program that established dolphin mortality limits, and the legally binding multilateral Agreement on the International Dolphin Conservation Program); and economic incentives [notably through establishment of the U.S. dolphin-safe label and positive certification by the Marine Stewardship Council (MSC)]. Together, these bycatch mitigation efforts have been remarkably successful; dolphin mortality due to entanglement as recorded by fisheries observers (hereafter, entanglement mortality) has been reduced by > 99%. Despite this, the degree to which dolphin populations have recovered remains unclear. Multiple lines of evidence indicate that individual dolphins experience multiple sets in their lifetimes and although causality has not been established, research suggests that chase and encirclement might have impacts on dolphins in addition to entanglement mortality. These impacts potentially include increased fetal and/or calf mortality, separation of nursing females and their calves, decreased fecundity, increased predation, disruption of mating and other social systems, and ecological disruption. The strong management emphasis on monitoring entanglement mortality, and the infrastructure necessary to support this monitoring (in particular, 100% observer coverage on large purse-seiners) require funding to the extent that other activities, particularly continued surveys to monitor stock status and clarify the potential influence of other effects of the fishery on dolphin populations, are currently inadequately funded.

A SARS-CoV-2 vírus okozta COVID-19 pandémia az eddigi egyik legnagyobb kihívás, amivel az emberiség a XXI. században szembe kellett, hogy nézzen. Jelen tanulmányban bemutatott kutatás az új típusú koronavírus-fertőzés első magyarországi hullámának tér- és időbeli lefutását modellezi, remélve, hogy hozzájárul a vírus terjedésének feltérképezéséhez. A modellezéshez ágens alapú módszertant használtam, az ágensek a magyar lakónépesség tagjait testesítik meg. A program a futtatás során 6, fertőzés átadására alkalmas társas érintkezési módot különböztet meg A népességet koruk és gazdasági aktivitásuk alapján 8 aktivitási csoportba osztottam. Az egyes aktivitási csoportok eltérő mértékben vesznek részt a definiált társas érintkezési formákban. A fertőzésterjedés vizsgálatához 12 forgatókönyvet alakítottam ki, amelyek eltérhetnek aszerint, hogy mekkora a feltételezett alap reprodukciós ráta, a külföldi forrásból származó fertőzések az ország mely részén jelennek meg, hogy életbe lépnek-e a modellfuttatás során fertőzést korlátozó szabályok, és ha igen, a fertőzés kezdetétől számítva milyen késéssel. A korlátozásokat nem tartalmazó forgatókönyvek az elvárható exponenciális görbét rajzolják ki, 6 napos duplázódással. A kapott eredmények a munkahelyen történő fertőzések elsődleges szerepét mutatják a fertőzés továbbterjesztésében, ezt követi az iskolai, illetve a háztartáson belüli fertőzésátadás. A modellezés területi eredményeinek kiértékelése alapján a fertőzés elsősorban a nagy földrajzi távokat is áthidalni képes hierarchikus diffúzióval, másrészt az ingázási kapcsolatokon keresztül terjed a települések között. A bevezetett korlátozások elsősorban a hierarchikus diffúziós terjedést gátolták meg, és megnövelték a háztartáson belüli fertőzésátadás relatív jelentőségét. A kapott eredmények alapján a korlátozások elégségesnek bizonyultak az exponenciális növekedés megtörésére mind az alacsonyabb, mint a magasabb alap reprodukciós rátát tartalmazó forgatókönyvekben. A kapott eredményeket a hivatalos fertőzésszámokkal és a H-UNCOVER országosan reprezentatív felmérés tapasztalataival is összevetettem.

Vaccination is the most effective measure to prevent infections in the general population. Its efficiency strongly depends on the function and composition of the immune system. If the immune system lacks critical components, patients will not be fully protected despite a completed vaccination schedule. Antigen-specific serum immunoglobulin levels are broadly used correlates of protection. These are the products of terminally differentiated B cells – plasma cells. Here we reviewed the literature on how aberrancies in B-cell composition and function influence immune responses to vaccinations. In a search through five major literature databases, 6,537 unique articles published from 2000 and onwards were identified. 75 articles were included along three major research lines: extremities of life, immunodeficiency and immunosuppression. Details of the protocol can be found in the International Prospective Register of Systematic Reviews [PROSPERO (registration number CRD42021226683)]. The majority of articles investigated immune responses in adults, in which vaccinations against pneumococci and influenza were strongly represented. Lack of baseline information was the most common reason of exclusion. Irrespective of study group, three parameters measured at baseline seemed to have a predictive value in assessing vaccine efficacy: (1) distribution of B-cell subsets (mostly a reduction in memory B cells), (2) presence of exhausted/activated B cells, or B cells with an aberrant phenotype, and (3) pre-existing immunological memory. In this review we showed how pre-immunization (baseline) knowledge of circulating B cells can be used to predict vaccination efficacy. We hope that this overview will contribute to optimizing vaccination strategies, especially in immunocompromised patients.

This paper documents a practical security evaluation of the Tesla Model X keyless entry system. In contrast to other works, the keyless entry system analysed in this paper employs secure symmetric-key and public-key cryptographic primitives implemented by a Common Criteria certified Secure Element. We document the internal workings of this system, covering the key fob, the body control module and the pairing protocol. Additionally, we detail our reverse engineering techniques and document several security issues. The identified issues in the key fob firmware update mechanism and the key fob pairing protocol allow us to bypass all of the cryptographic security measures put in place. To demonstrate the practical impact of our research we develop a fully remote Proof-of-Concept attack that allows to gain access to the vehicle’s interior in a matter of minutes and pair a modified key fob, allowing to drive off. Our attack is not a relay attack, as our new key fob allows us to start the car anytime anywhere. Finally, we provide an analysis of the update performed by Tesla to mitigate our findings. Our work highlights how the increased complexity and connectivity of vehicular systems can result in a larger and easier to exploit attack surface.

Dietary salt reduction has been recommended as a cost-effective population-wide strategy to prevent cardiovascular disease. The health and economic impact of salt consumption on the future burden of stroke in Vietnam is not known.Objective: To estimate the avoidable incidence of and deaths from stroke, as well as the healthy life years and healthcare costs that could be gained from reducing salt consumption in Vietnam.Methods: This was a macrosimulation health and economic impact assessment study. Data on blood pressure, salt consumption and stroke epidemiology were obtained from the Vietnam 2015 STEPS survey and the Global Burden of Disease study. A proportional multi-cohort multistate lifetable Markov model was used to estimate the impact of achieving the Vietnam national salt targets of 8 g/day by 2025 and 7 g/day by 2030, and to the 5 g/day WHO recommendation by 2030. Probabilistic sensitivity analysis was conducted to quantify the uncertainty in our projections.Results: If the 8 g/day, 7 g/day, and 5 g/day targets were achieved, the prevalence of hypertension could reduce by 1.2% (95% uncertainty interval [UI]: 0.5 to 2.3), 2.0% (95% UI: 0.8 to 3.6), and 3.5% (95% UI: 1.5 to 6.3), respectively. This would translate, respectively, to over 80,000, 180,000, and 257,000 incident strokes and over 18,000, 55,000, and 73,000 stroke deaths averted. By 2025, over 56,554 stroke-related health-adjusted life years (HALYs) could be gained while saving over US$ 42.6 million in stroke healthcare costs. By 2030, about 206,030 HALYs (for 7 g/day target) and 262,170 HALYs (for 5 g/day target) could be gained while saving over US$ 88.1 million and US$ 122.3 million in stroke healthcare costs respectively.Conclusion: Achieving the national salt reduction targets could result in substantial population health and economic benefits. Estimated gains were larger if the WHO salt targets were attained and if changes can be sustained over the longer term. Future work should consider the equity impacts of specific salt reduction programs.

Recent years have seen a significant increase in the adoption of electric vehicles, and investments in electric vehicle charging infrastructure and rooftop photo-voltaic installations. The ability to delay electric vehicle charging provides inherent flexibility that can be used to compensate for the intermittency of photo-voltaic generation and optimize against fluctuating electricity prices. Exploiting this flexibility, however, requires smart control algorithms capable of handling uncertainties from photo-voltaic generation, electric vehicle energy demand and user’s behaviour. This paper proposes a control framework combining the advantages of reinforcement learning and rule-based control to coordinate the charging of a fleet of electric vehicles in an office building. The control objective is to maximize self-consumption of locally generated electricity and consequently, minimize the electricity cost of electric vehicle charging. The performance of the proposed framework is evaluated on a real-world data set from EnergyVille, a Belgian research institute. Simulation results show that the proposed control framework achieves a 62.5% electricity cost reduction compared to a business-as-usual or passive charging strategy. In addition, only a 5% performance gap is achieved in comparison to a theoretical near-optimal strategy that assumes perfect knowledge on the required energy and user behaviour of each electric vehicle.

The Walloon region of Belgium has launched a research project that aims at elaborating a methodology for automated, high-quality land cover mapping, based primarily on its yearly 0.25m orthophoto coverage. Whereas in urban areas an object-based (OBIA) approach has been the privileged path in the last years as it allows taking into account shape information relevant for the characterization of man-made constructions, such an approach has its limits in the rural and more natural areas due to increased difficulties for segmentation and less sharp boundaries, thus calling for a pixel-based approach. The project thus consists in developing a combination of methods, and to integrate their results through an ensemble fusion approach. As many of the more natural land cover classes have temporal profiles which cannot be detected in a one-date orthoimage, Sentinel 1 and 2 data are also included in order to take advantage of their higher spectral and temporal resolution. All methods are trained using existing regional databases. In a second step, we combine the different LC classification results by fusioning them into one high-accuracy (over 90% OA) product, using a series of different approaches ranging from rule-based to machine learning to the Dempster-Shafer method. The entire toolchain is based on free and open source software, mainly GRASS GIS and Orfeo ToolBox. Results indicate the importance of the quality of the individual classifications for the fusion results and justify the choice of combining OBIA and pixel-based approaches in order to avoid the pitfalls of each.

Abstract Background Most studies measure the impact of ischemic heart disease (IHD) on individuals using quality of life metrics such as disability-adjusted life-years (DALYs); however, IHD also has an enormous impact on productive life years (PLYs). The objective of this study was to project the indirect costs of IHD resulting from lost PLYs to older Australian workers (45–64 years), government, and society 2015–2030. Methods Nationally representative data from the Surveys of Disability, Ageing and Carers (2003, 2009) were used to develop the base population in the microsimulation model (Health&WealthMOD2030), which integrated data from established microsimulation models (STINMOD, APPSIM), Treasury’s population and workforce projections, and chronic conditions trends. Results We projected that 6700 people aged 45–64 were out of the labour force due to IHD in 2015, increasing to 8100 in 2030 (21 increase). National costs consisted of a loss of AU$273 (US$263) million in income for people with IHD in 2015, increasing to AU$443 ($US426) million (62% increase). For the government, extra welfare payments increased from AU$106 (US$102) million in 2015 to AU$143 (US$138) million in 2030 (35% increase); and lost income tax revenue increased from AU$74 (US$71) million in 2015 to AU$117 (US$113) million in 2030 (58% increase). A loss of AU$785 (US$755) million in GDP was projected for 2015, increasing to AU$1125 (US$1082) million in 2030. Conclusions Significant costs of IHD through lost productivity are incurred by individuals, the government, and society. The benefits of IHD interventions include not only improved health but also potentially economic benefits as workforce capacity.

Abstract Background A consensus is emerging in the literature that urban form can impact health by either facilitating or deterring physical activity (PA). However, there is a lack of evidence measuring population health and the economic benefits relating to alternative urban forms. We examined the issue of housing people within two distinct types of urban development forms: a medium-density brownfield development in an established area with existing amenities (e.g. daily living destinations, transit), and a low-density suburban greenfield development. We predicted the health and economic benefits of a brownfield development compared with a greenfield development through their influence on PA. Methods We combined a new Walkability Planning Support System (Walkability PSS) with a quantitative health impact assessment model. We used the Walkability PSS to estimate the probability of residents’ transport walking, based on their exposure to urban form in the brownfield and greenfield developments. We developed the underlying algorithms of the Walkability PSS using multi-level multivariate logistic regression analysis based on self-reported data for transport walking from the Victorian Integrated Survey of Transport and Activity 2009–10 and objectively measured urban form in the developments. We derived the difference in transport walking minutes per week based on the probability of transport walking in each of the developments and the average transport walking time per week among those who reported any transport walking. We then used the well-established method of the proportional multi-cohort multi-state life table model to translate the difference in transport walking minutes per week into health and economic benefits. Results If adult residents living in the greenfield neighbourhood were instead exposed to the urban development form observed in a brownfield neighbourhood, the incidence and mortality of physical inactivity-related chronic diseases would decrease. Over the life course of the exposed population (21,000), we estimated 1600 health-adjusted life years gained and economic benefits of A$94 million. Discussion Our findings indicate that planning policies that create walkable neighbourhoods with access to shops, services and public transport will lead to substantial health and economic benefits associated with reduced incidence of physical inactivity related diseases and premature death.

In view of the grave situation during the first two waves of SARS-CoV-2 virus (severe acute respiratory syndrome coronavirus-2), nursing homes (NHs) were prioritised for vaccination once vaccines became available in Belgium. The aim of this study was to assess the effect of the COVID-19 (Coronavirus Disease 2019) vaccination campaign on COVID-19 cases, hospital admissions, and deaths among residents living in Belgian NHs. All 1545 Belgian NHs were invited to participate in a COVID-19 surveillance program. In Belgium, before vaccination, COVID-19 morbidity and mortality rates were driven by the situation in the NHs. Shortly after the COVID-19 vaccination campaign, and later the booster campaign, the number of hospital admissions and deaths among NH residents dropped, while clear peaks could be observed among the general population. The impact of vaccination on virus circulation was less effective than expected. However, due to the high vaccination coverage, NH residents remain well protected against hospital admission and death due to COVID-19 more than one year after being vaccinated.

Objective To explore the stakeholders’ perceptions of current practices and challenges in priority setting for non-communicable disease (NCD) control in Kenya.Design A qualitative study approach conducted within a 1-day stakeholder workshop that followed a deliberative dialogue process.Setting Study was conducted within a 1-day stakeholder workshop that was held in October 2019 in Nairobi, Kenya.Participants Stakeholders who currently participate in the national level policymaking process for health in Kenya.Outcome measure Priority setting process for NCD control in Kenya.Results Donor funding was identified as a key factor that informed the priority setting process for NCD control. Misalignment between donors’ priorities and the country’s priorities for NCD control was seen as a hindrance to the process. It was identified that there was minimal utilisation of context-specific evidence from locally conducted research. Additional factors seen to inform the priority setting process included political leadership, government policies and budget allocation for NCDs, stakeholder engagement, media, people’s cultural and religious beliefs.Conclusion There is an urgent need for development aid partners to align their priorities to the specific NCD control priority areas that exist in the countries that they extend aid to. Additionally, context-specific scientific evidence on effective local interventions for NCD control is required to inform areas of priority in Kenya and other low-income and middle-income countries. Further research is needed to develop best practice guidelines and tools for the creation of national-level priority setting frameworks that are responsive to the identified factors that inform the priority setting process for NCD control.

Background: Injury prevention is highly needed in physically active populations, such as pre-service and in-service physical education teachers (PETs). As a lack of adherence to preventive strategies is problematic in injury, it seems crucial to develop and optimize interventions that correspond to the specific needs and wishes of PETs. Aim: The purpose of the present study was fourfold. Specifically, we aimed at (1) systematically optimizing an injury prevention intervention for PETs, based on teachers' qualitative evaluation of the intervention, (2) quantitatively investigating whether the appreciation of the injury prevention intervention was higher after optimization, (3) examining whether participation in the intervention resulted in positive changes in teachers' perceived utility of, and confidence to apply the proposed preventive strategies, as well as their knowledge about these strategies, and (4) describing teachers' adherence to the proposed preventive strategies while they were engaging in the intervention. Participants: Twenty PETs (13 men, Mage = 42.1 ± 12.17 years) from nine different secondary schools in Flanders (Belgium) voluntarily participated in this study. The intervention, based on findings from the continuing professional development (CPD) literature, and the principles of the self determination theory, took place on two different training days (Training A and Training B) and consisted of seven intrinsic injury prevention strategies. Data collection and analysis: Qualitative data on teachers' appreciation of the intervention were collected by means of focus group interviews, which were used to optimize the intervention (Aim 1). Quantitative data on teachers' appreciation were collected directly after they had engaged in the intervention and were used to compare the appreciation from the initial to more optimized versions of the trainings (Aim 2). Further, by means of repeated measures ANOVAs positive evolutions in teachers' belief in the utility of, confidence to apply and knowledge about the provided strategies across time were examined (Aim 3). Finally, teachers' adherence was evaluated by relying on weekly online registrations of minutes and types of preventive strategies teachers had practised during the past week (Aim 4). Data collection and analysis: Qualitative data on teachers' appreciation of the intervention were collected by means of focus group interviews, which were used to optimize the intervention (Aim 1). Quantitative data on teachers' appreciation were collected directly after they had engaged in the intervention and were used to compare the appreciation from the initial to more optimized versions of the trainings (Aim 2). Further, by means of repeated measures ANOVAs positive evolutions in teachers' belief in the utility of, confidence to apply and knowledge about the provided strategies across time were examined (Aim 3). Finally, teachers' adherence was evaluated by relying on weekly online registrations of minutes and types of preventive strategies teachers had practised during the past week (Aim 4). Findings: Despite the relatively high initial appreciation scores (4.2 out of 5), the optimized versions of the trainings scored better on interaction, intelligibility, innovation, practical usefulness, and recommendation (Aims 1 and 2). Significant differences were found over time in terms of within-teacher changes in perceived utility of (4.05-4.73-4.48; p < 0.001), confidence to apply (3.75-3.96-4.26; p < 0.001) and knowledge about preventive strategies (2.49-3.53-3.39; p < 0.001; Aim 3). Finally, prospective registrations of teachers' adherence to the proposed strategies showed a mean time of 62.1 ± 48.6 min/week with a balanced distribution of the different strategies (Aim 4). Conclusions: The present study developed an intervention that optimally fulfils the wishes and needs of the target population, namely PETs, and can readily be implemented in PET education programmes or CPD programmes for in-service PETs. Results of this pilot study are promising because teachers displayed increases in several relevant outcomes. Various suggestions are formulated on how to increase PETs' appreciation of CPD programmes.

Measles virus (MV) is a highly contagious respiratory virus responsible for outbreaks associated with significant morbidity and mortality among children and young adults. Although safe and effective measles vaccines are available, the COVID-19 pandemic has resulted in vaccination coverage gaps that may lead to the resurgence of measles when restrictions are lifted. This puts individuals who cannot be vaccinated, such as young infants and immunocompromised individuals, at risk. Therapeutic interventions are complicated by the long incubation time of measles, resulting in a narrow treatment window. At present, the only available WHO-advised option is treatment with intravenous immunoglobulins, although this is not approved as standard of care. Antivirals against measles may contribute to intervention strategies to limit the impact of future outbreaks. Here, we review previously described antivirals and antiviral assays, evaluate the antiviral efficacy of a number of compounds to inhibit MV dissemination in vitro, and discuss potential application in specific target populations. We conclude that broadly reactive antivirals could strengthen existing intervention strategies to limit the impact of measles outbreaks.

As a special case of statistical learning, ensemble methods are well suited for the analysis of opportunistically collected data that involve many weak and sometimes specialized predictors, especially when subject-matter knowledge favors inductive approaches. In this paper, we analyze data on the incidental mortality of dolphins in the purse-seine fishery for tunas in the eastern Pacific Ocean. The goal is to identify those rare purse-seine sets for which incidental mortality would be expected but none was reported. The ensemble method random forests is used to classify sets according to whether mortality was (response = 1) or was not (response = 0) reported. To identify questionable reporting practice, we construct "residuals" as the difference between the categorical response (0, 1) and the proportion of trees in the forest that correctly classify a given set. Two uses of these residuals to identify suspicious data are illustrated. This approach shows promise as a means to identify suspect data gathered for environmental monitoring.

Background Reducing dietary sodium (salt) intake has been proposed as a population-wide strategy to reduce blood pressure and cardiovascular disease (CVD). The cost-effectiveness of such strategies has hitherto not been investigated in Cameroon.Methods A multicohort multistate life table Markov model was used to evaluate the cost-effectiveness of three population salt reduction strategies: mass media campaign, school-based salt education programme and low-sodium salt substitute. A healthcare system perspective was considered and adults alive in 2016 were simulated over the life course. Outcomes were changes in disease incidence, mortality, health-adjusted life years (HALYs), healthcare costs and incremental cost-effectiveness ratios (ICERs) over the lifetime. Probabilistic sensitivity analysis was used to quantify uncertainty.Results Over the life span of the cohort of adults alive in Cameroon in 2016, substantial numbers of new CVD events could be prevented, with over 10 000, 79 000 and 84 000 CVD deaths that could be averted from mass media, school education programme and salt substitute interventions, respectively. Population health gains over the lifetime were 46 700 HALYs, 348 800 HALYs and 368 400 HALYs for the mass media, school education programme and salt substitute interventions, respectively. ICERs showed that all interventions were dominant, with probabilities of being cost-saving of 84% for the school education programme, 89% for the mass media campaign and 99% for the low sodium salt substitute. Results were largely robust in sensitivity analysis.Conclusion All the salt reduction strategies evaluated were highly cost-effective with very high probabilities of being cost-saving. Salt reduction in Cameroon has the potential to save many lives and offers good value for money.

Backgroundtrans-fatty acids (TFAs) are a well-known risk factor of ischemic heart disease (IHD). In Australia, the highest TFA intake is concentrated to the most socioeconomically disadvantaged groups. Elimination of industrial TFA (iTFA) from the Australian food supply could result in reduced IHD mortality and morbidity while improving health equity. However, such legislation could lead to additional costs for both government and food industry. Thus, we assessed the potential cost-effectiveness, health gains, and effects on health equality of an iTFA ban from the Australian food supply.Methods and findingsMarkov cohort models were used to estimate the impact on IHD burden and health equity, as well as the cost-effectiveness of a national ban of iTFA in Australia. Intake of TFA was assessed using the 2011-2012 Australian National Nutrition and Physical Activity Survey. The IHD burden attributable to TFA was calculated by comparing the current level of TFA intake to a counterfactual setting where consumption was lowered to a theoretical minimum distribution with a mean of 0.5% energy per day (corresponding to TFA intake only from nonindustrial sources, e.g., dairy foods). Policy costs, avoided IHD events and deaths, health-adjusted life years (HALYs) gained, and changes in IHD-related healthcare costs saved were estimated over 10 years and lifetime of the adult Australian population. Cost-effectiveness was assessed by calculation of incremental cost-effectiveness ratios (ICERs) using net policy cost and HALYs gained. Health benefits and healthcare cost changes were also assessed in subgroups based on socioeconomic status, defined by Socio-Economic Indexes for Areas (SEIFA) quintile, and remoteness. Compared to a base case of no ban and current TFA intakes, elimination of iTFA was estimated to prevent 2,294 (95% uncertainty interval [UI]: 1,765; 2,851) IHD deaths and 9,931 (95% UI: 8,429; 11,532) IHD events over the first 10 years. The greatest health benefits were accrued to the most socioeconomically disadvantaged quintiles and among Australians living outside of major cities. The intervention was estimated to be cost saving (net cost ConclusionsOur model estimates that a ban of iTFAs could avert substantial numbers of IHD events and deaths in Australia and would likely be a highly cost-effective strategy to reduce social-economic and urban-rural inequalities in health. These findings suggest that elimination of iTFA can cost-effectively improve health and health equality even in countries with low iTFA intake.

This paper addressed in what ways national curriculum policy in Norway and Brazil adopted the global accountability logic of which OECD and other international organizations are proponents. It borrowed from an institutional logics perspective to explain the complexity found within the accountability logic across these two nation-states. The method used was thematic analysis of the national curriculum policy. The findings revealed that national curriculum policy is informed by the international context, but translated within national contexts. Norway elaborated the accountability logic to encompass multiple aspects of this logic that reinforced each other to create a cohesive policy. In Brazil, tensions between different social groups resulted in a curriculum policy with contradictory aspects of the accountability logic. The translations of the global accountability logic reflected the context-specific features of each country and illustrated both homogeneity and heterogeneity that still exists in different educational contexts.

Future human missions to the surface of the Moon and Mars will involve scientific exploration requiring new support tools to enable rapid and high quality science decision-making. Here, we describe the PANGAEA (Planetary ANalogue Geological and Astrobiological Exercise for Astronauts) Mineralogical Database developed by ESA (European Space Agency): a catalog of petrographic and spectroscopic information on all currently known minerals identified on the Moon, Mars, and associated with meteorites. The catalog also includes minerals found in the analog field sites used for ESA's geology and astrobiology training course PANGAEA, to broaden the database coverage. The Mineralogical Database is composed of the Summary Catalog of Planetary Analog Minerals and of the Spectral Archive and is freely available in the public repository of ESA PANGAEA. The Summary Catalog provides essential descriptive information for each mineral, including name (based on the International Mineralogical Association recommendation), chemical formula, mineral group, surface abundance on planetary bodies, geological significance in the context of planetary exploration, number of collected VNIR and Raman spectra, likelihood of detection using different spectral methods, and bibliographic references evidencing their detection in extraterrestrial or terrestrial analog environments. The Spectral Archive provides a standard library for planetary in-situ human and robotic exploration covering Visual-Near-Infrared reflective (VNIR) and Raman spectroscopy (Raman). To populate this library, we collected VNIR and Raman spectra for mineral entries in the Summary Catalog from open-access archives and analyzed them to select the ones with the best spectral features. We also supplemented this collection with our own bespoke measurements. Additionally, we compiled the chemical compositions for all the minerals based on their empirical formula, to allow identification using the measured abundances provided by LIBS and XRF analytical instruments. When integrated into an operational support system like ESA's Electronic Fieldbook (EFB) system, the Mineralogical Database can be used as a real-time and autonomous decision support tool for sampling operations on the Moon, Mars and during astronaut geological field training. It provides both robust spectral libraries to support mineral identification from instrument outputs, and relevant contextualized information on detected minerals.

[This corrects the article DOI: 10.1371/journal.pmed.1002326.].