Suchergebnisse

We assess and compare computer science skills among final-year computer science undergraduates (seniors) in four major economic and political powers that produce approximately half of the science, technology, engineering, and mathematics graduates in the world. We find that seniors in the United States substantially outperform seniors in China, India, and Russia by 0.76–0.88 SDs and score comparably with seniors in elite institutions in these countries. Seniors in elite institutions in the United States further outperform seniors in elite institutions in China, India, and Russia by ∼0.85 SDs. The skills advantage of the United States is not because it has a large proportion of high-scoring international students. Finally, males score consistently but only moderately higher (0.16–0.41 SDs) than females within all four countries.

BACKGROUND: Between-country variation in health care resource use and its impact on outcomes in acute care settings have been challenging to disentangle from illness severity by using administrative data. METHODS: We conducted a preplanned analysis employing patient-level emergency department (ED) data from children enrolled in 2 previously conducted clinical trials. Participants aged 3 to <48 months with <72 hours of gastroenteritis were recruited in pediatric EDs in the United States (N = 10 sites; 588 participants) and Canada (N = 6 sites; 827 participants). The primary outcome was an unscheduled health care provider visit within 7 days; the secondary outcomes were intravenous fluid administration and hospitalization at or within 7 days of the index visit. RESULTS: In adjusted analysis, unscheduled revisits within 7 days did not differ (adjusted odds ratio [aOR]: 0.72; 95% confidence interval (CI): 0.50 to 1.02). At the index ED visit, although participants in Canada were assessed as being more dehydrated, intravenous fluids were administered more frequently in the United States (aOR: 4.6; 95% CI: 2.9 to 7.1). Intravenous fluid administration rates did not differ after enrollment (aOR: 1.4; 95% CI: 0.7 to 2.8; US cohort with Canadian as referent). Overall, intravenous rehydration was higher in the United States (aOR: 3.8; 95% CI: 2.5 to 5.7). Although hospitalization rates during the 7 days after enrollment (aOR: 1.1; 95% CI: 0.4 to 2.6) did not differ, hospitalization at the index visit was more common in the United States (3.9% vs 2.3%; aOR: 3.2; 95% CI: 1.6 to 6.8). CONCLUSIONS: Among children with gastroenteritis and similar disease severity, revisit rates were similar in our 2 study cohorts, despite lower rates of intravenous rehydration and hospitalization in Canadian-based EDs.

The genus Solanum comprises three food crops (potato, tomato, and eggplant), which are consumed on daily basis worldwide and also producers of notorious anti-nutritional steroidal glycoalkaloids (SGAs). Hydroxylated SGAs (i.e. leptinines) serve as precursors for leptines that act as defenses against Colorado Potato Beetle (Leptinotarsa decemlineata Say), an important pest of potato worldwide. However, SGA hydroxylating enzymes remain unknown. Here, we discover that 2-OXOGLUTARATE-DEPENDENT-DIOXYGENASE (2-ODD) enzymes catalyze SGA-hydroxylation across various Solanum species. In contrast to cultivated potato, Solanum chacoense, a widespread wild potato species, has evolved a 2-ODD enzyme leading to the formation of leptinines. Furthermore, we find a related 2-ODD in tomato that catalyzes the hydroxylation of the bitter α-tomatine to hydroxytomatine, the first committed step in the chemical shift towards downstream ripening-associated non-bitter SGAs (e.g. esculeoside A). This 2-ODD enzyme prevents bitterness in ripe tomato fruit consumed today which otherwise would remain unpleasant in taste and more toxic. ; The work was supported by the Israel Science Foundation (ISF Grant No. 1805/15) and European Research Council (ERC; SAMIT-FP7) personal grants to A.A. The research in the A.A. laboratory was supported by the European Union Seventh Framework Program FP7/2007–2013 under grant agreement no. 613692–TriForC. P.D.C. thanks Becas Chile Program (CONICYT, Chile) for PhD financial support. D.Z. was funded by the European Union's H2020 Research and Innovation Program grant # 677379 (G2P-SOL).

A Lancet Commission for COVID-19 task force is shaping recommendations to achieve vaccine and therapeutics access, justice, and equity. This includes ensuring safety and effectiveness harmonized through robust systems of global pharmacovigilance and surveillance. Global production requires expanding support for development, manufacture, testing, and distribution of vaccines and therapeutics to low- and middle-income countries (LMICs). Global intellectual property rules must not stand in the way of research, production, technology transfer, or equitable access to essential health tools, and in context of pandemics to achieve increased manufacturing without discouraging innovation. Global governance around product quality requires channelling widely distributed vaccines through WHO prequalification (PQ)/emergency use listing (EUL) mechanisms and greater use of national regulatory authorities. A World Health Assembly (WHA) resolution would facilitate improvements and consistency in quality control and assurances. Global health systems require implementing steps to strengthen national systems for controlling COVID-19 and for influenza vaccinations for adults including pregnant and lactating women. A collaborative research network should strive to establish open access databases for bioinformatic analyses, together with programs directed at human capacity utilization and strengthening. Combating anti-science recognizes the urgency for countermeasures to address a global-wide disinformation movement dominating the internet and infiltrating parliaments and local governments.

A Lancet Commission for COVID-19 task force is shaping recommendations to achieve vaccine and therapeutics access, justice, and equity. This includes ensuring safety and effectiveness harmonized through robust systems of global pharmacovigilance and surveillance. Global production requires expanding support for development, manufacture, testing, and distribution of vaccines and therapeutics to low- and middle-income countries (LMICs). Global intellectual property rules must not stand in the way of research, production, technology transfer, or equitable access to essential health tools, and in context of pandemics to achieve increased manufacturing without discouraging innovation. Global governance around product quality requires channelling widely distributed vaccines through WHO prequalification (PQ)/emergency use listing (EUL) mechanisms and greater use of national regulatory authorities. A World Health Assembly (WHA) resolution would facilitate improvements and consistency in quality control and assurances. Global health systems require implementing steps to strengthen national systems for controlling COVID-19 and for influenza vaccinations for adults including pregnant and lactating women. A collaborative research network should strive to establish open access databases for bioinformatic analyses, together with programs directed at human capacity utilization and strengthening. Combating anti-science recognizes the urgency for countermeasures to address a global-wide disinformation movement dominating the internet and infiltrating parliaments and local governments.

A Lancet Commission for COVID-19 task force is shaping recommendations to achieve vaccine and therapeutics access, justice, and equity. This includes ensuring safety and effectiveness harmonized through robust systems of global pharmacovigilance and surveillance. Global production requires expanding support for development, manufacture, testing, and distribution of vaccines and therapeutics to low- and middle-income countries (LMICs). Global intellectual property rules must not stand in the way of research, production, technology transfer, or equitable access to essential health tools, and in context of pandemics to achieve increased manufacturing without discouraging innovation. Global governance around product quality requires channelling widely distributed vaccines through WHO prequalification (PQ)/emergency use listing (EUL) mechanisms and greater use of national regulatory authorities. A World Health Assembly (WHA) resolution would facilitate improvements and consistency in quality control and assurances. Global health systems require implementing steps to strengthen national systems for controlling COVID-19 and for influenza vaccinations for adults including pregnant and lactating women. A collaborative research network should strive to establish open access databases for bioinformatic analyses, together with programs directed at human capacity utilization and strengthening. Combating anti-science recognizes the urgency for countermeasures to address a global-wide disinformation movement dominating the internet and infiltrating parliaments and local governments. ; https://doi.org/10.1016/j.eclinm.2021.101053

Over the past decade, a range of sensor technologies became available on the market, enabling a revolutionary shift in air pollution monitoring and assessment. With their cost of up to three orders of magnitude lower than standard/reference instruments, many avenues for applications have opened up. In particular, broader participation in air quality discussion and utilisation of information on air pollution by communities has become possible. However, many questions have been also asked about the actual benefits of these technologies. To address this issue, we conducted a comprehensive literature search including both the scientific and grey literature. We focused upon two questions: (1) Are these technologies fit for the various purposes envisaged? and (2) How far have these technologies and their applications progressed to provide answers and solutions? Regarding the former, we concluded that there is no clear answer to the question, due to a lack of: sensor/monitor manufacturers' quantitative specifications of performance, consensus regarding recommended end-use and associated minimal performance targets of these technologies, and the ability of the prospective users to formulate the requirements for their applications, or conditions of the intended use. Numerous studies have assessed and reported sensor/monitor performance under a range of specific conditions, and in many cases the performance was concluded to be satisfactory, e.g. (Castell et al. 2017, Han et al. 2017, Sousan et al. 2017). The specific use cases for sensors/monitors included outdoor in a stationary mode, outdoor in a mobile mode, indoor environments and personal monitoring. Under certain conditions of application, project goals, and monitoring environments, some sensors/monitors were fit for a specific purpose. Based on analysis of 17 large projects, which reached applied outcome stage, and typically conducted by consortia of organizations, we observed that a sizable fraction of them (~ 30%) were commercial and/or crowd-funded. This fact by itself signals a paradigm change in air quality monitoring, which previously had been primarily implemented by government organizations. An additional paradigm-shift indicator is the growing use of machine learning or other advanced data processing approaches to improve sensor/monitor agreement with reference monitors. There is still some way to go in enhancing application of the technologies for source apportionment, which is of particular necessity and urgency in developing countries. Also, there has been somewhat less progress in wide-scale monitoring of personal exposures. However, it can be argued that with a significant future expansion of monitoring networks, including indoor environments, there may be less need for wearable or portable sensors/monitors to assess personal exposure. Traditional personal monitoring would still be valuable where spatial variability of pollutants of interest is at a finer resolution than the monitoring network can resolve.

Understanding how to source agricultural raw materials sustainably is challenging in today's globalized food system given the variety of issues to be considered and the multitude of suggested indicators for representing these issues. Furthermore, stakeholders in the global food system both impact these issues and are themselves vulnerable to these issues, an important duality that is often implied but not explicitly described. The attention given to these issues and conceptual frameworks varies greatly--depending largely on the stakeholder perspective--as does the set of indicators developed to measure them. To better structure these complex relationships and assess any gaps, we collate a comprehensive list of sustainability issues and a database of sustainability indicators to represent them. To assure a breadth of inclusion, the issues are pulled from the following three perspectives: major global sustainability assessments, sustainability communications from global food companies, and conceptual frameworks of sustainable livelihoods from academic publications. These terms are integrated across perspectives using a common vocabulary, classified by their relevance to impacts and vulnerabilities, and categorized into groups by economic, environmental, physical, human, social, and political characteristics. These issues are then associated with over 2,000 sustainability indicators gathered from existing sources. A gap analysis is then performed to determine if particular issues and issue groups are over or underrepresented. This process results in 44 "integrated" issues--24 impact issues and 36 vulnerability issues--that are composed of 318 "component" issues. The gap analysis shows that although every integrated issue is mentioned at least 40% of the time across perspectives, no issue is mentioned more than 70% of the time. A few issues infrequently mentioned across perspectives also have relatively few indicators available to fully represent them. Issues in the impact framework generally have fewer gaps than those in the vulnerability framework.

Abstract
The rapid adoption of glyphosate-resistant crops at the end of the 20th century caused a simplification of weed management that relied heavily on glyphosate for weed control. However, the effectiveness of glyphosate has diminished. A greater understanding of trends related to glyphosate use will shed new light on weed adaptation to a product that transformed global agriculture. Objectives were to (1) quantify the change in weed control efficacy from postemergence (POST) glyphosate use on troublesome weeds in corn and soybean and (2) determine the extent to which glyphosate preceded by a preemergence (PRE) improved the efficacy and consistency of weed control compared to glyphosate alone. Herbicide evaluation trials from 24 institutions across the United States of America and Canada from 1996 to 2021 were compiled into a single database. Two subsets were created; one with glyphosate applied POST, and the other with a PRE herbicide followed by glyphosate applied POST. Within each subset, mean and variance of control ratings for seven problem weed species were regressed over time for nine US states and one Canadian province. Mean control with POST glyphosate alone decreased over time while variability in control increased. Glyphosate preceded by a labeled PRE herbicide showed little change in mean control or variability in control over time. These results illustrate the rapid adaptation of agronomically important weed species to the paradigm-shifting product glyphosate. Including more diversity in weed management systems is essential to slowing weed adaptation and prolonging the usefulness of existing and future technologies.

Nature-based solutions (NBS) for hydro-meteorological risks (HMRs) reduction and management are becoming increasingly popular, but challenges such as the lack ofwell-recognised standardmethodologies to evaluate their performance and upscale their implementation remain.We systematically evaluate the current state-of-the art on the models and tools that are utilised for the optimum allocation, design and efficiency evaluation of NBS for five HMRs (flooding, droughts, heatwaves, landslides, and storm surges and coastal erosion). We found that methods to assess the complex issue of NBS efficiency and cost-benefits analysis are still in the development stage and they have only been implemented through the methodologies developed for other purposes such as fluid dynamics models in micro and catchment scale contexts. Of the reviewed numerical models and tools MIKE-SHE, SWMM(for floods), ParFlow-TREES, ACRU, SIMGRO (for droughts), WRF, ENVI-met (for heatwaves), FUNWAVE-TVD, BROOK90 (for landslides), TELEMAC and ADCIRC (for storm surges) are more flexible to evaluate the performance and effectiveness of specific NBS such as wetlands, ponds, trees, parks, grass, green roof/walls, tree roots, vegetations, coral reefs, mangroves, sea grasses, oyster reefs, sea salt marshes, sandy beaches and dunes.We conclude that themodels and tools that are capable of assessing the multiple benefits, particularly the performance and cost-effectiveness of NBS for HMR reduction and management are not readily available. Thus, our synthesis of modelling methods can facilitate their selection that can maximise opportunities and refute the current political hesitation of NBS deployment compared with grey solutions for HMR management but also for the provision of a wide range of social and economic co-benefits. However, there is still a need for bespoke modelling tools that can holistically assess the various components of NBS from an HMR reduction andmanagement perspective. Such tools can facilitate impact assessmentmodelling under different ...

Nature-based solutions (NBS) for hydro-meteorological risks (HMRs) reduction and management are becoming increasingly popular, but challenges such as the lack of well-recognised standard methodologies to evaluate their performance and upscale their implementation remain. We systematically evaluate the current state-of-the art on the models and tools that are utilised for the optimum allocation, design and efficiency evaluation of NBS for five HMRs (flooding, droughts, heatwaves, landslides, and storm surges and coastal erosion). We found that methods to assess the complex issue of NBS efficiency and cost-benefits analysis are still in the development stage and they have only been implemented through the methodologies developed for other purposes such as fluid dynamics models in micro and catchment scale contexts. Of the reviewed numerical models and tools MIKE-SHE, SWMM (for floods), ParFlow-TREES, ACRU, SIMGRO (for droughts), WRF, ENVI-met (for heatwaves), FUNWAVE-TVD, BROOK90 (for landslides), TELEMAC and ADCIRC (for storm surges) are more flexible to evaluate the performance and effectiveness of specific NBS such as wetlands, ponds, trees, parks, grass, green roof/walls, tree roots, vegetations, coral reefs, mangroves, sea grasses, oyster reefs, sea salt marshes, sandy beaches and dunes. We conclude that the models and tools that are capable of assessing the multiple benefits, particularly the performance and cost-effectiveness of NBS for HMR reduction and management are not readily available. Thus, our synthesis of modelling methods can facilitate their selection that can maximise opportunities and refute the current political hesitation of NBS deployment compared with grey solutions for HMR management but also for the provision of a wide range of social and economic co-benefits. However, there is still a need for bespoke modelling tools that can holistically assess the various components of NBS from an HMR reduction and management perspective. Such tools can facilitate impact assessment modelling under ...

Nature-based solutions (NBS) for hydro-meteorological risks (HMRs) reduction and management are becoming increasingly popular, but challenges such as the lack of well-recognised standard methodologies to evaluate their performance and upscale their implementation remain. We systematically evaluate the current state-of-the art on the models and tools that are utilised for the optimum allocation, design and efficiency evaluation of NBS for five HMRs (flooding, droughts, heatwaves, landslides, and storm surges and coastal erosion). We found that methods to assess the complex issue of NBS efficiency and cost-benefits analysis are still in the development stage and they have only been implemented through the methodologies developed for other purposes such as fluid dynamics models in micro and catchment scale contexts. Of the reviewed numerical models and tools MIKE-SHE, SWMM (for floods), ParFlow-TREES, ACRU, SIMGRO (for droughts), WRF, ENVI-met (for heatwaves), FUNWAVE-TVD, BROOK90 (for landslides), TELEMAC and ADCIRC (for storm surges) are more flexible to evaluate the performance and effectiveness of specific NBS such as wetlands, ponds, trees, parks, grass, green roof/walls, tree roots, vegetations, coral reefs, mangroves, sea grasses, oyster reefs, sea salt marshes, sandy beaches and dunes. We conclude that the models and tools that are capable of assessing the multiple benefits, particularly the performance and cost-effectiveness of NBS for HMR reduction and management are not readily available. Thus, our synthesis of modelling methods can facilitate their selection that can maximise opportunities and refute the current political hesitation of NBS deployment compared with grey solutions for HMR management but also for the provision of a wide range of social and economic co-benefits. However, there is still a need for bespoke modelling tools that can holistically assess the various components of NBS from an HMR reduction and management perspective. Such tools can facilitate impact assessment modelling under different NBS scenarios to build a solid evidence base for upscaling and replicating the implementation of NBS.

Abstract
Alopecia areata is a chronic hair loss disorder that involves autoimmune disruption of hair follicles by CD8+ T cells. Most patients present with patchy hair loss on the scalp that improves spontaneously or with topical and intralesional steroids, topical minoxidil, or topical immunotherapy. However, recurrence of hair loss is common, and patients with extensive disease may require treatment with oral corticosteroids or oral Janus kinase (JAK) inhibitors, both of which may cause systemic toxicities with long-term use. Itaconate is an endogenous molecule synthesized in macrophages that exerts anti-inflammatory effects. To investigate the use of itaconate derivatives for treating alopecia areata, we designed a prodrug of 4-methyl itaconate (4-MI), termed SCD-153, with increased lipophilicity compared to 4-MI (CLogP 1.159 vs. 0.1442) to enhance skin and cell penetration. Topical SCD-153 formed 4-MI upon penetrating the stratum corneum in C57BL/6 mice and showed low systemic absorption. When added to human epidermal keratinocytes stimulated with polyinosinic-polycytidylic acid (poly I:C) or interferon (IFN)γ, SCD-153 significantly attenuated poly I:C-induced interleukin (IL)-6, Toll-like receptor 3, IL-1β, and IFNβ expression, as well as IFNγ-induced IL-6 expression. Topical application of SCD-153 to C57BL/6 mice in the resting (telogen) phase of the hair cycle induced significant hair growth that was statistically superior to vehicle (dimethyl sulfoxide), the less cell-permeable itaconate analogues 4-MI and dimethyl itaconate, and the JAK inhibitor tofacitinib. Our results suggest that SCD-153 is a promising topical candidate for treating alopecia areata.

Nature-based solutions (NBS) are being promoted as adaptive measures against predicted increasing hydrometeorological hazards (HMHs), such as heatwaves and floods which have already caused significant loss of life and economic damage across the globe. However, the underpinning factors such as policy framework, end-users' interests and participation for NBS design and operationalisation are yet to be established. We discuss the operationalisation and implementation processes of NBS by means of a novel concept of Open-Air Laboratories (OAL) for its wider acceptance. The design and implementation of environmentally, economically, technically and socio-culturally sustainable NBS require inter- and transdisciplinary approaches which could be achieved by fostering co-creation processes by engaging stakeholders across various sectors and levels, inspiring more effective use of skills, diverse knowledge, manpower and resources, and connecting and harmonising the adaptation aims. The OAL serves as a benchmark for NBS upscaling, replication and exploitation in policy-making process through monitoring by field measurement, evaluation by key performance indicators and building solid evidence on their short- and long-term multiple benefits in different climatic, environmental and socio-economic conditions, thereby alleviating the challenges of political resistance, financial barriers and lack of knowledge. We conclude that holistic management of HMHs by effective use of NBS can be achieved with standard compliant data for replicating and monitoring NBS in OALs, knowledge about policy silos and interaction between research communities and end-users. Further research is needed for multi-risk analysis of HMHs and inclusion of NBS into policy frameworks, adaptable at local, regional and national scales leading to modification in the prevalent guidelines related to HMHs. The findings of this work can be used for developing synergies between current policy frameworks, scientific research and practical implementation of NBS in Europe and beyond for its wider acceptance.

Nature-based solutions (NBS) are being promoted as adaptive measures against predicted increasing hydrometeorological hazards (HMHs), such as heatwaves and floods which have already caused significant loss of life and economic damage across the globe. However, the underpinning factors such as policy framework, end-users' interests and participation for NBS design and operationalisation are yet to be established. We discuss the operationalisation and implementation processes of NBS by means of a novel concept of Open-Air Laboratories (OAL) for its wider acceptance. The design and implementation of environmentally, economically, technically and socio-culturally sustainable NBS require inter- and transdisciplinary approaches which could be achieved by fostering co-creation processes by engaging stakeholders across various sectors and levels, inspiring more effective use of skills, diverse knowledge, manpower and resources, and connecting and harmonising the adaptation aims. The OAL serves as a benchmark for NBS upscaling, replication and exploitation in policy-making process through monitoring by field measurement, evaluation by key performance indicators and building solid evidence on their short- and long-term multiple benefits in different climatic, environmental and socioeconomic conditions, thereby alleviating the challenges of political resistance, financial barriers and lack of knowledge. We conclude that holistic management of HMHs by effective use of NBS can be achieved with standard-compliant data for replicating and monitoring NBS in OALs, knowledge about policy silos and interaction between research communities and end-users. Further research is needed for multi-risk analysis of HMHs and inclusion of NBS into policy frameworks, adaptable at local, regional and national scales leading to modification in the prevalent guidelines related to HMHs. The findings of this work can be used for developing synergies between current policy frameworks, scientific research and practical implementation of NBS in ...