A randomized, open-label two-period crossover pilot study to evaluate the relative bioavailability in the fed state of atovaquone-proguanil (Atoguanil™) versus atovaquone-proguanil hydrochloride (Malarone®) in healthy adult participants.

Atoguanil™ is a novel complex of atovaquone (ATV) and proguanil (PG) with enhanced ATV bioavailability compared to Malarone®. This pilot study assessed whether the relative bioavailability (Frel) of ATV, PG, and the primary PG metabolite cycloguanil (CG) following a single oral dose in the fed state of Atoguanil was similar to Malarone despite a 50% lower ATV dose. This open-label, single-dose, randomized 2-period, 2-treatment, balanced crossover study was conducted between 17th November 2021 and 18th March 2022. Eligible participants (aged 18-55 years) were randomized (1:1) in period 1 to Atoguanil (ATV/PG 500/348 mg) or Malarone (ATV/PG hydrochloride 1000/400 mg) administered following a high-fat, high caloric meal. After a 24-day washout period, participants crossed treatment arms. For the doses tested, Frel was assumed similar if 90%CIs were between 80 and 125% for the geometric mean ratio of the least square mean differences for each exposure parameter. In 15 evaluable participants, Frel was similar for ATV Cmax (93.6% [90%CI 83.6, 104.9]) but not AUC0-inf (77.8% [67.4, 89.8]), for PG AUC0-inf (95.6% [92.1, 99.2]) but not Cmax (82.4% [75.8, 89.5]), and for both CG Cmax (100.8% [95.0, 107.0]) and AUC0-inf (102.9% [98.4, 107.7]). Nine adverse events occurred; all were of mild severity and not considered treatment related. At the doses tested, ATV Frel was lower following Atoguanil versus Malarone based on AUC0-inf, though when adjusted for dose Frel increased by 156%. Both drugs were well tolerated with no safety concerns. ClinicalTrials.gov: NCT04866602 (April 26th, 2021).

Ecotoxicological soil risk assessment under the new soil exposure framework - an impact assessment.

For the European risk assessment (RA) for soil organisms exposed to plant protection products (PPPs) endpoints from ecotoxicological laboratory studies are compared with predicted environmental concentrations in soil (PECSOIL) at first tier. A safety margin must be met; otherwise, a higher tier RA is triggered (usually soil organism field studies). A new tiered exposure modeling guidance was published by EFSA to determine PECSOIL. This work investigates its potential impact on future soil RA. PECSOIL values for >50 active substances and metabolites were calculated and compared with the respective endpoints for soil organisms to calculate the RA failure rate. Compared to the current (FOCUS) exposure modeling, PECSOIL values for all EU regulatory zones considerably increased, e.g., resulting in active substance RA failure rates of 67%, 58% and 36% for modeling Tier-1, Tier-2 and Tier-3A, respectively. The main driving factors for elevated PECSOIL were soil bulk density, crop interception and wash-off, next to obligatory modeling and scenario adjustment factors. Spatial PECSOIL scenario selection procedures result in agronomically atypical soil characteristics (e.g., soil bulk density values in Tier-3A scenarios far below typical European agricultural areas). Consequently, exposure modeling and ecotoxicological study characteristics are inconsistent, which hinders scientifically reasonable comparison of both in the RA.

Correction: Comparison of Four Active SARS-CoV-2 Surveillance Strategies in Representative Population Sample Points: Two-Factor Factorial Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/44204.].

Intermediate-tier options in the environmental risk assessment of plant protection products for soil invertebrates-Synthesis of a workshop.

The European environmental risk assessment (ERA) of plant protection products follows a tiered approach. The approach for soil invertebrates currently consists of two steps, starting with a Tier 1 assessment based on reproduction toxicity tests with earthworms, springtails, and predatory mites. In case an unacceptable risk is identified at Tier 1, field studies can be conducted as a higher-tier option. For soil invertebrates, intermediate tiers are not implemented. Hence, there is limited possibility to include additional information for the ERA to address specific concerns when the Tier 1 fails, as an alternative to, for example, a field study. Calibrated intermediate-tier approaches could help to address risks for soil invertebrates with less time and resources but also with sufficient certainty. A multistakeholder workshop was held on 2-4 March 2022 to discuss potential intermediate-tier options, focusing on four possible areas: (1) natural soil testing, (2) single-species tests (other than standard species), (3) assessing recovery in laboratory tests, and (4) the use of assembled soil multispecies test systems. The participants acknowledged a large potential in the intermediate-tier options but concluded that some issues need to be clarified before routine application of these approaches in the ERA is possible, that is, sensitivity, reproducibility, reliability, and standardization of potential new test systems. The definition of suitable assessment factors needed to calibrate the approaches to the protection goals was acknowledged. The aims of the workshop were to foster scientific exchange and a data-driven dialog, to discuss how the different approaches could be used in the risk assessment, and to identify research priorities for future work to address uncertainties and strengthen the tiered approach in the ERA for soil invertebrates. This article outlines the background, proposed methods, technical challenges, difficulties and opportunities in the ERA, and conclusions of the workshop. Integr Environ Assess Manag 2024;20:780-793. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Polymer Hydrogel Sheets with Perpendicular Cross-Linking Gradient: Non-Monotonic Actuation and Ion-Specific Effects on the Actuation Kinetics.

Non-monotonous actuation, that is, different kinds of motion in response to a single stimulus, is observed in some natural materials but difficult to implement in synthetic systems. Herein, polymer hydrogel sheets made from polyacrylamide (PAAm) or poly(dimethylacrylamide) (PDMAA) with a cross-linking gradient along the sheet thickness are reported. These are obtained by thermally initiated free radical polymerization using a specially designed Teflon mold with a glass lid. The resulting PAAm hydrogels undergo non-monotonous actuation (rolling into a tube and re-opening) when exposed to aqueous media as a single external stimulus. Their actuation kinetics is tuned with anions that have specific ion effects in their interaction with the surrounding solvent and the polymer itself: structure-breaking chloride enhances the hydration of the polymer backbone, structure-making sulfate decreases it, and is thus slowing down the actuation kinetics of the PAAm hydrogels. The PDMAA gel rolls up instantaneously in aqueous NaCl and only re-opens after 24 h. PDMAA actuation in aqueous Na2 SO4 is only moderate as the gel did not swell in that solvent. Bilayer hydrogels made from PAAm and PDMAA (without gradient) show monotonic actuation, closing in NaCl solution and re-opening in Na2 SO4 .

Drivers and pressures behind insect decline in Central and Western Europe based on long-term monitoring data.

Insect declines have been discussed intensively among experts, policymakers, and the public. Albeit, decreasing trends have been reported for a long time for various regions in Europe and North America, but the controversial discussion over the role of specific drivers and pressures still remains. A reason for these uncertainties lies within the complex networks of inter-dependent biotic and abiotic factors as well as anthropogenic activities that influence habitats, communities, populations, and individual organisms. Many recent publications aim to identify both the extent of the observed declines and potential drivers. With this literature analysis, we provide an overview of the drivers and pressures and their inter-relationships, which were concluded in the scientific literature, using some of the best-studied insect groups as examples. We conducted a detailed literature evaluation of publications on Carabidae (Coleoptera) and Lepidoptera trends with data for at least 6 years in countries of Central and Western Europe, with a focus on agricultural landscapes. From the 82 publications identified as relevant, we extracted all reported trends and classified the respective factors described according to the DPSIR model. Further, we analysed the level of scientific verification (presumed vs correlated vs examined) within these papers for these cited stressors. The extracted trends for both species groups underline the reported overall declining trend. Whether negative or positive trends were reported in the papers, our semi-quantitative analysis shows that changes in insect populations are primarily anthropogenically driven by agriculture, climate change, nature conservation activities, urbanisation, and other anthropogenic activities. Most of the identified pressures were found to act on habitat level, only a fraction attributed to direct effects to the insects. While our analysis gives an overview of existing research concerning abundance and biodiversity trends of carabids and lepidopterans, it also shows gaps in scientific data in this area, in particular in monitoring the pressures along with the monitoring of abundance trends. The scientific basis for assessing biodiversity changes in the landscape is essential to help all stakeholders involved to shape, e.g. agriculture and other human activities, in a more sustainable way, balancing human needs such as food production with conservation of nature.

Strengthening national public health institutes: a systematic review on institution building in the public sector.

Introduction: Strong and efficient institutions are vital to the development of well-functioning governments and strong societies. The term "institution building" encompasses the creation, support, development, and strengthening of organizations and institutions. Still, there is little aggregated evidence on "institution building" considering a wider system-thinking approach, best practices, or development cooperation specifically in the field of public health. In 2007, the International Association of National Public Health Institutes (IANPHI) created a guiding Framework that countries may use for developing National Public Health Institutes (NPHIs). This Framework is currently being revised. Methods: In this context, we conducted a systematic review to facilitate this revision with recent evidence on institution building and its potential contribution to NPHI. We followed the PRISMA guidelines for systematic reviews, searching for relevant publications in seven scientific databases (Pubmed, VHL/LILACS, EconLit, Google Scholar, Web of Science, World Affairs Online, ECONBIZ) and four libraries (World Bank; European Health for All database of the World Health Organization European Region, WHO; Organization for Economic Cooperation and Development, OECD; and the African Union Common Repository). The search was carried out in October 2021. We used the "framework analysis" tool for systematically processing documents according to key themes. Results: As a result, we identified 3,015 records, of which we included 62 documents in the final review. This systematic review fills a major gap of aggregated information on institution building in the field of public health and National Public Health Institutes. It is to our knowledge the first systematic review of this kind. The overriding result is the identification and definition of six domains of institution building in the health sector: "governance," "knowledge and innovation," "inter-institutional cooperation," "monitoring and control," "participation," and "sustainability and context-specific adaptability." Discussion: Our results show that the described domains are highly relevant to the public health sector, and that managers and the scientific community recognize their importance. Still, they are often not applied consistently when creating or developing NPHIs. We conclude that organizations engaged in institution building of NPHIs, including IANPHI, may greatly benefit from state-of-the-art research on institution building as presented in this study.

Comparison of Four Active SARS-CoV-2 Surveillance Strategies in Representative Population Sample Points: Two-Factor Factorial Randomized Controlled Trial.

BACKGROUND: The COVID-19 pandemic is characterized by rapid increases in infection burden owing to the emergence of new variants with higher transmissibility and immune escape. To date, monitoring the COVID-19 pandemic has mainly relied on passive surveillance, yielding biased epidemiological measures owing to the disproportionate number of undetected asymptomatic cases. Active surveillance could provide accurate estimates of the true prevalence to forecast the evolution of the pandemic, enabling evidence-based decision-making. OBJECTIVE: This study compared 4 different approaches of active SARS-CoV-2 surveillance focusing on feasibility and epidemiological outcomes. METHODS: A 2-factor factorial randomized controlled trial was conducted in 2020 in a German district with 700,000 inhabitants. The epidemiological outcome comprised SARS-CoV-2 prevalence and its precision. The 4 study arms combined 2 factors: individuals versus households and direct testing versus testing conditioned on symptom prescreening. Individuals aged ≥7 years were eligible. Altogether, 27,908 addresses from 51 municipalities were randomly allocated to the arms and 15 consecutive recruitment weekdays. Data collection and logistics were highly digitized, and a website in 5 languages enabled low-barrier registration and tracking of results. Gargle sample collection kits were sent by post. Participants collected a gargle sample at home and mailed it to the laboratory. Samples were analyzed with reverse transcription loop-mediated isothermal amplification (RT-LAMP); positive and weak results were confirmed with real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Recruitment was conducted between November 18 and December 11, 2020. The response rates in the 4 arms varied between 34.31% (2340/6821) and 41.17% (2043/4962). The prescreening classified 16.61% (1207/7266) of the patients as COVID-19 symptomatic. Altogether, 4232 persons without prescreening and 7623 participating in the prescreening provided 5351 gargle samples, of which 5319 (99.4%) could be analyzed. This yielded 17 confirmed SARS-CoV-2 infections and a combined prevalence of 0.36% (95% CI 0.14%-0.59%) in the arms without prescreening and 0.05% (95% CI 0.00%-0.108%) in the arms with prescreening (initial contacts only). Specifically, we found a prevalence of 0.31% (95% CI 0.06%-0.58%) for individuals and 0.35% (95% CI 0.09%-0.61%) for households, and lower estimates with prescreening (0.07%, 95% CI 0.0%-0.15% for individuals and 0.02%, 95% CI 0.0%-0.06% for households). Asymptomatic infections occurred in 27% (3/11) of the positive cases with symptom data. The 2 arms without prescreening performed the best regarding effectiveness and accuracy. CONCLUSIONS: This study showed that postal mailing of gargle sample kits and returning home-based self-collected liquid gargle samples followed by high-sensitivity RT-LAMP analysis is a feasible way to conduct active SARS-CoV-2 population surveillance without burdening routine diagnostic testing. Efforts to improve participation rates and integration into the public health system may increase the potential to monitor the course of the pandemic. TRIAL REGISTRATION: Deutsches Register Klinischer Studien (DRKS) DRKS00023271; https://tinyurl.com/3xenz68a. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-021-05619-5.

Deep Learning-Based Algorithm for Automatic Detection of Pulmonary Embolism in Chest CT Angiograms.

PURPOSE: Since the prompt recognition of acute pulmonary embolism (PE) and the immediate initiation of treatment can significantly reduce the risk of death, we developed a deep learning (DL)-based application aimed to automatically detect PEs on chest computed tomography angiograms (CTAs) and alert radiologists for an urgent interpretation. Convolutional neural networks (CNNs) were used to design the application. The associated algorithm used a hybrid 3D/2D UNet topology. The training phase was performed on datasets adequately distributed in terms of vendors, patient age, slice thickness, and kVp. The objective of this study was to validate the performance of the algorithm in detecting suspected PEs on CTAs. METHODS: The validation dataset included 387 anonymized real-world chest CTAs from multiple clinical sites (228 U.S. cities). The data were acquired on 41 different scanner models from five different scanner makers. The ground truth (presence or absence of PE on CTA images) was established by three independent U.S. board-certified radiologists. RESULTS: The algorithm correctly identified 170 of 186 exams positive for PE (sensitivity 91.4% [95% CI: 86.4-95.0%]) and 184 of 201 exams negative for PE (specificity 91.5% [95% CI: 86.8-95.0%]), leading to an accuracy of 91.5%. False negative cases were either chronic PEs or PEs at the limit of subsegmental arteries and close to partial volume effect artifacts. Most of the false positive findings were due to contrast agent-related fluid artifacts, pulmonary veins, and lymph nodes. CONCLUSIONS: The DL-based algorithm has a high degree of diagnostic accuracy with balanced sensitivity and specificity for the detection of PE on CTAs.

Safety, Tolerability, and Parasite Clearance Kinetics in Controlled Human Malaria Infection after Direct Venous Inoculation of Plasmodium falciparum Sporozoites: A Model for Evaluating New Blood-Stage Antimalarial Drugs.

Plasmodium falciparum sporozoite (PfSPZ) direct venous inoculation (DVI) using cryopreserved, infectious PfSPZ (PfSPZ Challenge [Sanaria, Rockville, Maryland]) is an established controlled human malaria infection model. However, to evaluate new chemical entities with potential blood-stage activity, more detailed data are needed on safety, tolerability, and parasite clearance kinetics for DVI of PfSPZ Challenge with established schizonticidal antimalarial drugs. This open-label, phase Ib study enrolled 16 malaria-naïve healthy adults in two cohorts (eight per cohort). Following DVI of 3,200 PfSPZ (NF54 strain), parasitemia was assessed by quantitative polymerase chain reaction (qPCR) from day 7. The approved antimalarial artemether-lumefantrine was administered at a qPCR-defined target parasitemia of ≥ 5,000 parasites/mL of blood. The intervention was generally well tolerated, with two grade 3 adverse events of neutropenia, and no serious adverse events. All 16 participants developed parasitemia after a mean of 9.7 days (95% CI 9.1-10.4) and a mean parasitemia level of 511 parasites/mL (95% CI 369-709). The median time to reach ≥ 5,000 parasites/mL was 11.5 days (95% CI 10.4-12.4; Kaplan-Meier), at that point the geometric mean (GM) parasitemia was 15,530 parasites/mL (95% CI 10,268-23,488). Artemether-lumefantrine was initiated at a GM of 12.1 days (95% CI 11.5-12.7), and a GM parasitemia of 6,101 parasites/mL (1,587-23,450). Mean parasite clearance time was 1.3 days (95% CI 0.9-2.1) and the mean log10 parasite reduction ratio over 48 hours was 3.6 (95% CI 3.4-3.7). This study supports the safety, tolerability, and feasibility of PfSPZ Challenge by DVI for evaluating the blood-stage activity of candidate antimalarial drugs.

Mode of action of fluopyram in plant-parasitic nematodes.

Plant-parasitic nematodes (PPN) are responsible for severe yield losses in crop production. Management is challenging as effective and safe means are rare. Recently, it has been discovered that the succinate dehydrogenase (SDH) inhibitor fluopyram is highly effective against PPN while accompanying an excellent safety profile. Here we show that fluopyram is a potent inhibitor of SDH in nematodes but not in mammals, insects and earthworm, explaining the selectivity on molecular level. As a consequence of SDH inhibition, fluopyram impairs ATP generation and causes paralysis in PPN and Caenorhabditis elegans. Interestingly, efficacy differences of fluopyram amongst PPN species can be observed. Permanent exposure to micromolar to nanomolar amounts of fluopyram prevents Meloidogyne spp. and Heterodera schachtii infection and their development at the root. Preincubation of Meloidogyne incognita J2 with fluopyram followed by a recovery period effectively reduces gall formation. However, the same procedure does not inhibit H. schachtii infection and development. Sequence comparison of sites relevant for ligand binding identified amino acid differences in SDHC which likely mediate selectivity, coincidently revealing a unique amino acid difference within SDHC conserved among Heterodera spp. Docking and C. elegans mutant studies suggest that this minute difference mediates altered sensitivity of H. schachtii towards fluopyram.

Arbuscular Mycorrhizal Fungi and the Need for a Meaningful Regulatory Plant Protection Product Testing Strategy.

Arbuscular mycorrhizal fungi (AMF) perform key soil ecosystem services and, because of their symbiotic relationship with plant roots, may be exposed to the plant protection products (PPPs) applied to soils and crops. In 2017, the European Food Safety Authority (EFSA) released a scientific opinion addressing the state of the science on risk assessment of PPPs for in-soil organisms, recommending the inclusion of AMF ecotoxicological testing in the PPP regulatory process. However, it is not clear how this can be implemented in a tiered, robust, and ecologically relevant manner. Through a critical review of current literature, we examine the recommendations made within the EFSA report and the methodologies available to integrate AMF into the PPP risk assessment and provide perspective and commentary on their agronomic and ecological relevance. We conclude that considerable research questions remain to be addressed prior to the inclusion of AMF into the in-soil organism risk assessment, many of which stem from the unique challenges associated with including an obligate symbiont within the PPP risk assessment. Finally, we highlight critical knowledge gaps and the further research required to enable development of relevant, reliable, and robust scientific tests alongside pragmatic and scientifically sound guidance to ensure that any future risk-assessment paradigm is adequately protective of the ecosystem services it aims to preserve. Environ Toxicol Chem 2022;41:1808-1823. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Trends of overweight and obesity among preschool children from 2013 to 2018: a cross-sectional study in Rhine-Neckar County and the City of Heidelberg, Germany.

BACKGROUND: Early childhood overweight and obesity is a growing public health concern worldwide. Few recent studies have addressed how time trends varied by sociodemographic characteristics at the regional level using large and high-quality data. This study determines how time trends vary in the prevalence of early childhood overweight and obesity by age, gender, and migration background at the regional level. METHODS: We used a Kernel-density curve to describe the BMI distribution, and evaluated the trends of overweight and obesity by age, gender, and migration background using logistic regression. RESULTS: Mean BMI and the overall prevalence of overweight and obesity increased among preschool children aged 4-6 years in the Rhine-Neckar County and the City of Heidelberg. After adjusting for age, sex, and migration background, trends of overweight significantly increased only among male children in the age 5 year group with migration background (P < 0.05), and an upward trend of obesity was observed only among male children in the age 5 year group and female children in the age 6 year group with migration background (P < 0.05). CONCLUSIONS: BMI distribution as well as general prevalence of overweight and obesity are still increasing among preschool children. Children with migration backgrounds, particularly male children in the age 5 year groups and female children in the age 6 year group should be prioritized. Health promotion strategies for children with migration backgrounds will help address this challenge.

The National Health Insurance System of Indonesia and primary care physicians' job satisfaction: a prospective qualitative study.

BACKGROUND: The implementation of the National Health Insurance System (NHIS) in Indonesia has been changing the primary care physician (PCP) work condition and their job satisfaction. OBJECTIVE: This research aimed to explore the reasons behind PCPs' satisfaction and dissatisfaction with job satisfaction's aspect under the NHIS reform. METHODS: We conducted an exploratory qualitative study within two areas in Central Java, Indonesia, using semi-structured in-depth interviews with 34 PCPs and 19 triangulation sources. We conducted both inductive and deductive analyses by the NVivo 11. RESULTS: Most PCPs felt dissatisfied with the following aspects of the NHIS: referral system, NHIS health services standard, NHIS programmes, performance evaluation and pay-for-performance, relationship with patient and workloads. PCPs felt constrained with the referral regulation and non-specialist diagnoses, which led to dissatisfaction with performance evaluation and the pay-for-performance implementation. Furthermore, an increase in workload and conflict with patients resulted from patients' misunderstanding the NHIS health service procedures. However, PCPs felt satisfied with the chronic disease management programme and patients' appreciation. CONCLUSIONS: This study presents the reasons behind PCPs' satisfaction and dissatisfaction with job satisfaction's aspect under the NHIS reform. There is a need for additional discussion among all stakeholders (Ministry of Health, Social Security Agency for Health/SSAH, primary health care and physician's professional organizations about the non-specialist diagnoses list, performance evaluation and pay-for-performance). The government and SSAH need to improve the communication and socialization of the NHIS procedures/regulations.

In 2014, Indonesia implemented a National Health Insurance System (NHIS). The reform affected the primary care physicians' (PCPs') work conditions and job satisfaction. This qualitative study explored the reasons behind PCPs' satisfaction and dissatisfaction with the job satisfactions' aspect in the NHIS. We interviewed 34 PCPs and 19 triangulation sources in Semarang City and Demak Regency (Central Java). Findings showed that most physicians felt dissatisfied with the NHIS referral system, health services standard, some NHIS programmes, performance evaluation and pay-for-performance, relationship with patients and workload. Mostly, the patients­PCPs' conflicts were due to the misunderstanding of the NHIS health service procedures. However, the PCPs also received patients' appreciation. For improving the reform implementation and PCPs' job satisfaction, the physicians' concerned, leading to dissatisfaction, must be addressed.

Investigating the role of soil mesofauna abundance and biodiversity for organic matter breakdown in arable fields.

Intact soil food webs are pivotal to maintaining essential soil functions, such as carbon recycling, sequestering, and biomass production. Although the functional role of micro- (e.g., bacteria and fungi) and macrofauna (e.g., earthworms) is comparatively well established, the importance of the mesofauna community (e.g., abundance and diversity of Acari and Collembola) in maintaining soil functionality is less clear. We investigated this question in a six-month field experiment in arable soil by actively manipulating mesofauna abundance and biodiversity through the application of two legacy insecticides (lindane and methamidophos) at sufficiently high doses to reduce mesofauna abundance (well above previously registered application rates; 2.5 and 7.5 kg a.s./ha for lindane, and 0.6 and 3 kg a.s./ha for methamidophos) and measure the impact on organic matter degradation. Our results demonstrate that both insecticides had reduced Collembola and Acari abundances by up to 80% over the study's six-month duration. In addition, we observed less pronounced and more complex changes in mesofauna biodiversity over time. These included insecticide-dependent temporal fluctuations (both reduction and increase) for different estimates (indices) of local (alpha)-diversity over time and no lasting impact for most estimates after six months. Even at these exceptionally high field rates, Collembola and Acari diversity was observed to generally recover by six months. In contrast, considering organic matter breakdown, we found no evidence of a treatment-related effect. These results suggest that organic matter breakdown in arable soils is likely driven by other trophic levels (e.g., microorganisms or earthworms) with only a limited influence of the mesofauna community. We discuss these findings with regard to their implications for our current understanding of soil food web function and future European soil risk assessments. Integr Environ Assess Manag 2022;18:1423-1433. © 2021 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Effectiveness and cost-effectiveness of four different strategies for SARS-CoV-2 surveillance in the general population (CoV-Surv Study): study protocol for a two-factorial randomized controlled multi-arm trial with cluster sampling.

BACKGROUND: To achieve higher effectiveness in population-based SARS-CoV-2 surveillance and to reliably predict the course of an outbreak, screening, and monitoring of infected individuals without major symptoms (about 40% of the population) will be necessary. While current testing capacities are also used to identify such asymptomatic cases, this rather passive approach is not suitable in generating reliable population-based estimates of the prevalence of asymptomatic carriers to allow any dependable predictions on the course of the pandemic. METHODS: This trial implements a two-factorial, randomized, controlled, multi-arm, prospective, interventional, single-blinded design with cluster sampling and four study arms, each representing a different SARS-CoV-2 testing and surveillance strategy based on individuals' self-collection of saliva samples which are then sent to and analyzed by a laboratory. The targeted sample size for the trial is 10,000 saliva samples equally allocated to the four study arms (2500 participants per arm). Strategies differ with respect to tested population groups (individuals vs. all household members) and testing approach (without vs. with pre-screening survey). The trial is complemented by an economic evaluation and qualitative assessment of user experiences. Primary outcomes include costs per completely screened person, costs per positive case, positive detection rate, and precision of positive detection rate. DISCUSSION: Systems for active surveillance of the general population will gain more importance in the context of pandemics and related disease prevention efforts. The pandemic parameters derived from such active surveillance with routine population monitoring therefore not only enable a prospective assessment of the short-term course of a pandemic, but also a more targeted and thus more effective use of local and short-term countermeasures. TRIAL REGISTRATION: ClinicalTrials.gov DRKS00023271 . Registered November 30, 2020, with the German Clinical Trials Register (Deutsches Register Klinischer Studien).

The Role of Source-Sink Dynamics in the Assessment of Risk to Nontarget Arthropods from the Use of Plant Protection Products.

The concept of source-sink dynamics as a potentially important component of metapopulation dynamics was introduced in the 1980s. The objective of the present review was to review the considerable body of work that has been developed, to consider its theoretical implications as well as to understand how source-sink dynamics may manifest under field conditions in the specific case of nontarget arthropods in the agricultural environment. Our review concludes that metapopulation dynamics based on field observations are often far more complex than existing theoretical source-sink models would indicate, because they are dependent on numerous population processes and influencing factors. The difficulty in identifying and measuring these factors likely explains why empirical studies assessing source-sink dynamics are scarce. Furthermore, we highlight the importance of considering the spatial and temporal heterogeneity of agricultural landscapes when assessing the population dynamics of nontarget arthropods in the context of the risk from the use of plant protection products. A need is identified to further develop and thoroughly validate predictive population models, which can incorporate all factors relevant to a specific system. Once reliable predictive models for a number of representative nontarget arthropod species are available, they could provide a meaningful tool for refined risk evaluations (higher tier level risk assessment), addressing specific concerns identified at the initial evaluation stages (lower tier level risk assessment). Environ Toxicol Chem 2021;40:2667-2679. © 2021 ERM, FMC, Syngenta, Bayer AG, BASF SE, Corteva agriscience. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Chemoprotective Antimalarial Activity of P218 against Plasmodium falciparum: A Randomized, Placebo-Controlled Volunteer Infection Study.

P218 is a highly selective dihydrofolate reductase inhibitor with potent in vitro activity against pyrimethamine-resistant Plasmodium falciparum. This single-center, randomized, double-blind, placebo-controlled phase Ib study evaluated P218 safety, pharmacokinetics, and chemoprotective efficacy in a P. falciparum sporozoite (PfSPZ) volunteer infection study (VIS). Consecutive dose safety and tolerability were evaluated (cohort 1), with participants receiving two oral doses of P218 1,000 mg 48 hours apart (n = 6), or placebo (n = 2). P218 chemoprotective efficacy was assessed (cohorts 2 and 3) with direct venous inoculation of 3,200 aseptic, cryopreserved PfSPZ (NF54 strain) followed 2 hours later with two P218 doses of 1,000 mg (cohort 2, n = 9) or 100 mg (cohort 3, n = 9) administered 48 hours apart, or placebo (n = 6). Parasitemia was assessed from day 7 using quantitative PCR targeting the var gene acidic terminal sequence (varATS qPCR). By day 28, all participants in cohort 2 (P218 1,000 mg) and 8/9 in cohort 3 (P218 100 mg) were sterilely protected post-PfSPZ VIS, confirming P218 P. falciparum chemoprotective activity. With placebo, all six participants became parasitemic (geometric mean time to positive parasitemia 10.6 days [90% CI: 9.9-11.4]). P218 pharmacokinetics were similar in participants with or without induced infection. Adverse events of any cause occurred in 45.8% (11/24) of participants who received P218 and 50.0% (4/8) following placebo; all were mild/moderate in severity, transient, and self-limiting. There were no clinically relevant changes in laboratory parameters, vital signs, or electrocardiograms. P218 displayed excellent chemoprotective efficacy against P. falciparum with favorable safety and tolerability.

Governing heatwaves in Europe: comparing health policy and practices to better understand roles, responsibilities and collaboration.

BACKGROUND: The expectation that climate change will further exacerbate extreme weather events such as heatwaves is of primary concern to policymakers and scientists. Effective governance is fundamental to preparedness for and response to such threats. This paper explores the governance structures of European heat health action plans and provides insights into key stakeholders, roles, responsibilities and collaboration. METHODS: This was a two-phase qualitative study, in which we complemented a desk review of 15 European national heat health action plans (NHHAPs) with, after obtaining informed consent, 68 interviews in nine countries with key informants involved in the development, implementation and/or evaluation of these NHHAPs. A thematic analysis was used to analyze the NHHAPs inductively. This analysis focused on three themes: identifying key stakeholders, defining and assigning roles and collaboration among stakeholders. The iteratively created codebook was then applied to the analysis of the key informant interviews. All analyses were done using NVivo 10 qualitative analysis software. RESULTS: The majority of the NHHAPs have governance as one of their main objectives, to support the coordination of actions and collaboration among involved stakeholders. There are, however, significant differences between plan and practice. On the basis of the available data, we have little insight into the process of stakeholder identification, but we do find that most countries involve the same types of stakeholders. Roles are mainly defined and assigned in relation to the alert levels of the warning system, causing other role aspects and other roles to be vague and ambiguous. Collaboration is key to many NHHAP elements and is mainly experienced positively, though improvements and new collaborations are considered. CONCLUSIONS: Our findings show a need for a more deliberate and structured approach to governance in the context of NHHAPs. A cross-sectoral approach to the identification of key stakeholders can facilitate a broader preparedness and response to heatwaves. Roles and responsibilities of stakeholders should be defined and assigned more clearly to avoid confusion and to improve effective implementation. To this extent, we identify and describe seven key roles and potential stakeholders to which these roles are usually assigned. Finally, also collaboration among stakeholders can benefit from a cross-sectoral approach, but also formal structures can be beneficial.