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Maija Huttunen-Lenz,1 Sylvia Hansen,1 Pia Christensen,2 Thomas Meinert Larsen,2 Finn Sandø-Pedersen,2 Mathijs Drummen,3 Tanja C Adam,3 Ian A Macdonald,4,5 Moira A Taylor,5 J Alfredo Martinez,6–8 Santiago Navas-Carretero,6–8 Svetoslav Handjiev,9 Sally D Poppitt,10 Marta P Silvestre,10 Mikael Fogelholm,11 Kirsi H Pietiläinen,12,13 Jennie Brand-Miller,14 Agnes AM Berendsen,15 Anne Raben,2 Wolfgang Schlicht1 1Department of Exercise and Health Sciences, University of Stuttgart, Stuttgart, Germany; 2Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark; 3Department of Nutrition and Movement Sciences, Maastricht University, Maastricht, the Netherlands; 4MRC/ARUK Centre for Musculoskeletal Ageing Research, National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, School of Life Sciences, University of Nottingham, Nottingham, UK; 5School of Life Sciences, University of Nottingham Medical School, Nottingham, UK; 6Center for Nutrition Research at the University of Navarra, Pamplona, Spain; 7Madrid Institute of Advanced Studies (IMDEA Food), Madrid, Spain; 8Biomedical Research Centre Network in Physiopathology of Obesity and Nutrition (CIBERobn), Carlos III Institute, Madrid, Spain; 9Department of Pharmacology and Toxicology, Medical University – Sofia, Sofia, Bulgaria; 10Human Nutrition Unit, School of Biological Sciences, University of Auckland, Auckland, New Zealand; 11Department of Food and Nutrition, University of Helsinki, Helsinki, Finland; 12Obesity Research Unit, Research Program Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland; 13Abdominal Center, Endocrinology, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland; 14Charles Perkins Centre and School of Life and Environmental Biosciences, University of Sydney, Camperdown, NSW, Australia; 15Division of Human Nutrition & Health, Wageningen University & Research, Wageningen, the Netherlands Purpose: Onset of type 2 diabetes (T2D) is often gradual and preceded by impaired glucose homeostasis. Lifestyle interventions including weight loss and physical activity may reduce the risk of developing T2D, but adherence to a lifestyle change is challenging. As part of an international T2D prevention trial (PREVIEW), a behavior change intervention supported participants in achieving a healthier diet and physically active lifestyle. Here, our aim was to explore the influence of this behavioral program (PREMIT) on social-cognitive variables during an 8-week weight loss phase. Methods: PREVIEW consisted of an initial weight loss, Phase I, followed by a weight-­maintenance, Phase II, for those achieving the 8-week weight loss target of ≥ 8% from initial bodyweight. Overweight and obese (BMI ≥25 kg/m2) individuals aged 25 to 70 years with confirmed pre-diabetes were enrolled. Uni- and multivariate statistical methods were deployed to explore differences in intentions, self-efficacy, and outcome expectancies between those who achieved the target weight loss (“achievers”) and those who did not (“non-achievers”). Results: At the beginning of Phase I, no significant differences in intentions, self-efficacy and outcome expectancies between “achievers” (1,857) and “non-achievers” (163) were found. “Non-achievers” tended to be younger, live with child/ren, and attended the PREMIT sessions less frequently. At the end of Phase I, “achievers” reported higher intentions (healthy eating χ2(1)=2.57; P

Abstract Background Although there are many proven effective physical activity (PA) interventions for older adults, implementation in a real world setting is often limited. This study describes the systematic development of a multifaceted implementation intervention targeting the implementation of an evidence-based computer-tailored PA intervention and evaluates its use and feasibility. Methods The implementation intervention was developed following the Intervention Mapping (IM) protocol, supplemented with insights from implementation science literature. The implementation intervention targets the municipal healthcare policy advisors, as an important implementation stakeholder in Dutch healthcare system. The feasibility of the implementation intervention was studied among these stakeholders using a pretest–posttest design within 8 municipal healthcare settings. Quantitative questionnaires were used to assess task performance (i.e. achievement of performance objectives), and utilization of implementation strategies (as part of the intervention). Furthermore, changes in implementation determinants were studied by gathering quantitative data before, during and after applying the implementation intervention within a one-year period. Additionally, semi-structured interviews with stakeholders assessed their considerations regarding the feasibility of the implementation intervention. Results A multi-faceted implementation intervention was developed in which implementation strategies (e.g. funding, educational materials, meetings, building a coalition) were selected to target the most relevant identified implementation determinants. Most implementation strategies were used as intended. Execution of performance objectives for adoption and implementation was relatively high (75–100%). Maintenance objectives were executed to a lesser degree (13–63%). No positive changes in implementation determinants were found. None of the stakeholders decided to continue implementation of the PA intervention further, mainly due to the unforeseen amount of labour and the disappointing reach of end-users. Conclusion The current study highlights the importance of a thorough feasibility study in addition to the use of IM. Although feasibility results may have demonstrated that stakeholders broadly accepted the implementation intervention, implementation determinants did not change favorably, and stakeholders had no plans to continue the PA intervention. Yet, choices made during the development of the implementation intervention (i.e. the operationalization of Implementation Mapping) might not have been optimal. The current study describes important lessons learned when developing an implementation intervention, and provides recommendations for developers of future implementation interventions.

Abstract In order to minimise food waste, side streams from feed and food production are increasingly being (re-) used in food supply chains. Such reuse contributes to the desire to implement circularity in food and agricultural systems. However, the reuse of side products in circular food systems may impact food safety, for instance, contaminant residues present at low levels in biomass may accumulate when reusing streams. In order to assess potential food safety issues related to circular food systems, a framework has been developed in this study. Based on this framework, appropriate actions can be taken to prevent from human health risks. The framework consists of three steps: 1. Describing the changes in the food supply chain as a result of the circularity transition; 2. Identifying potential food safety hazards related to the change; and 3. Prioritising food safety hazards related to the circularity transition. For the prioritisation, both the presence of the hazards in final foods and the effects of the hazards on human health need to be assessed. Persistence of the hazard in the environment and potential transfer from the environment to the final food product are relevant elements to include. The framework was tested in three case studies, showing that it allows for a prioritisation between hazards. Based on the case study results, circularity not so much influences the health effects of the hazards, but rather their presence depending on the persistence and transfer of food safety hazards in a circular system.

Abstract The transition from linear production towards a circular agro-food system is an important step towards increasing Europe’s sustainability. This requires re-designing the food production systems, which inevitably comes with challenges as regards controlling the safety of our food, animals and the ecosystem. Where in current food production systems many food safety hazards are understood and well-managed, it is anticipated that with the transition towards circular food production systems, known hazards may re-emerge and new hazards will appear or accumulate, leading to new -and less understood- food safety risks. In this perspective paper, we present a simple, yet effective approach, to identify knowledge gaps with regard to food safety in the transition to a circular food system. An approach with five questions is proposed, derived from current food safety management approaches like HACCP. Applying this to two cases shows that risk assessment and management should emphasize more on the exposure to unexpected (with regards to its nature and its origin) hazards, as hazards might circulate and accumulate in the food production system. Five knowledge gaps became apparent: there’s a need for (1) risk assessment and management to focus more on unknown hazards and mixtures of hazards, (2) more data on the occurrence of hazards in by-products, (3) better understanding the fate of hazards in the circular food production system, (4) the development of models to adequately perform risk assessments for a broad range of hazards and (5) new ways of valorization of co-products in which a safe-by-design approach should be adopted.

Abstract Refractory out-of-hospital cardiac arrest (OHCA) has a very poor prognosis, with survival rates at around 10%. Extracorporeal membrane oxygenation (ECMO) for patients in refractory arrest, known as ECPR, aims to provide perfusion to the patient whilst the underlying cause of arrest can be addressed. ECPR use has increased substantially, with varying survival rates to hospital discharge. The best outcomes for ECPR occur when the time from cardiac arrest to implementation of ECPR is minimised. To reduce this time, systems must be in place to identify the correct patient, expedite transfer to hospital, facilitate rapid cannulation and ECMO circuit flows. We describe the process of activation of ECPR, patient selection, and the steps that emergency department clinicians can utilise to facilitate timely cannulation to ensure the best outcomes for patients in refractory cardiac arrest. With these processes in place our survival to hospital discharge for OHCA patients is 35%, with most patients having a good neurological function.

Abstract The present opinion deals with the re‐evaluation of shellac (E 904) when used as a food additive and with the new application on the extension of use of shellac (E 904) in dietary foods for special medical purposes. The Panel derived an acceptable daily intake (ADI) of 4 mg/kg body weight (bw) per day for wax‐free shellac (E 904) produced by physical decolouring, based on a NOAEL of 400 mg/kg bw per day and applying an uncertainty factor of 100. The Panel concluded that the ADI of 4 mg/kg bw per day should be considered temporary for wax‐free shellac (E 904) produced by chemical bleaching, while new data are generated on the identity and levels of the organochlorine impurities in E 904. This ADI is not applicable for wax‐containing shellac as a food additive. For several age groups, the ADI was exceeded at the 95th percentile in the non‐brand‐loyal exposure assessment scenario and maximum level exposure assessment scenario. Considering the low exceedance and the fact that both the exposure estimation and the toxicological evaluation of shellac were conservative, the panel concluded that the calculated exceedance of the ADI does not indicate a safety concern. The Panel recommended to the European Commission separating specifications for E 904 depending on the manufacturing process, chemical bleaching and physical decolouring, because they result in different impurities; revising the definition of the food additive to include a description of each manufacturing process; deleting information on wax‐containing shellac from the EU specifications; revising the acid value for wax‐free shellac produced by chemical bleaching; lowering the maximum limit for lead; to consider introducing limits for other toxic elements potentially present in shellac; including a maximum limit for chloroform and total inorganic chloride in the EU specification for shellac produced by chemical bleaching.

Abstract Background To determine the effectiveness of applying the Sydney Triage to Admission Risk Tool (START) in conjunction with senior early assessment in different Emergency Departments (EDs). Methods This multicentre implementation study, conducted in two metropolitan EDs, used a convenience sample of ED patients. Patients who were admitted, after presenting to both EDs, and were assessed using the existing senior ED clinician assessment, were included in the study. Patients in the intervention group were assessed with the assistance of START, while patients in the control group were assessed without the assistance of START. Outcomes measured were ED length of stay and proportion of patients correctly identified as an in-patient admission by START. Results A total of 773 patients were evaluated using the START tool at triage across both sites (Intervention group n = 355 and control group n = 418 patients). The proportion of patients meeting the 4-hour length of stay thresholds was similar between the intervention and control groups (30.1% vs. 28.2%; p = 0.62). The intervention group was associated with a reduced ED length of stay when compared to the control group (351 min, interquartile range (IQR) 221.0–565.0 min versus 383 min, IQR 229.25–580.0 min; p = 0.85). When stratified into admitted and discharged patients, similar results were seen. Conclusion In this extension of the START model of care implementation study in two metropolitan EDs, START, when used in conjunction with senior early assessment was associated with some reduced ED length of stay.

Abstract Background Potato seed tubers are colonized and inhabited by soil-borne microbes, that can affect the performance of the emerging daughter plant in the next season. In this study, we investigated the intergenerational inheritance of microbiota from seed tubers to next-season daughter plants under field condition by amplicon sequencing of bacterial and fungal microbiota associated with tubers and roots, and tracked the microbial transmission from different seed tuber compartments to sprouts. Results We observed that field of production and potato genotype significantly (P

Abstract Background Plant microbiomes play crucial roles in nutrient cycling and plant growth, and are shaped by a complex interplay between plants, microbes, and the environment. The role of bacteria as mediators of the 400-million-year-old partnership between the majority of land plants and, arbuscular mycorrhizal (AM) fungi is still poorly understood. Here, we test whether AM hyphae-associated bacteria influence the success of the AM symbiosis. Results Using partitioned microcosms containing field soil, we discovered that AM hyphae and roots selectively assemble their own microbiome from the surrounding soil. In two independent experiments, we identified several bacterial genera, including Devosia, that are consistently enriched on AM hyphae. Subsequently, we isolated 144 pure bacterial isolates from a mycorrhiza-rich sample of extraradical hyphae and isolated Devosia sp. ZB163 as root and hyphal colonizer. We show that this AM-associated bacterium synergistically acts with mycorrhiza on the plant root to strongly promote plant growth, nitrogen uptake, and mycorrhization. Conclusions Our results highlight that AM fungi do not function in isolation and that the plant-mycorrhiza symbiont can recruit beneficial bacteria that support the symbiosis. Video Abstract

A better understanding of differences in the nature of human computer interaction (HCI) relating to GIS software can help with learning spatial concepts and spatial thinking skills. This motivates our study, which aims to create a standard measure of interaction with GIS software that can be used individually or along with existing measurement instruments for spatial thinking to generalize results across studies for evaluating GIS interaction and usability. The study developed a composite taxonomy identifying types of user interactions and strategies with GIS in relation to different spatial concepts and processes of reasoning. The taxonomy was used as a framework to create tasks which users can complete with GIS software as a measure interaction with GIS. Study data were collected from 35 students enrolled in an online undergraduate course covering fundamentals of geographic information science and technology. Following three course assignments using GIS software to demonstrate a range of spatial concepts for problem solving, students completed various tasks constituting the standard measure of GIS interaction. The results indicate that the standard measure succeeds in measuring how individuals interact with GIS and strategize to complete different spatial tasks. The standard measure of GIS interaction will be useful for the development of usability guidelines for GIS and further contributes to research in the acquisition and application of spatial concepts and reasoning in learning environments.

Abstract The EFSA Panel on Food Additive and Flavourings (FAF Panel) provides a scientific opinion on the safety of soy leghemoglobin from genetically modified Komagataella phaffii as a food additive in accordance with Regulation (EC) No 1331/2008. The proposed food additive, LegH Prep, is intended to be used as a colour in meat analogue products. The yeast Komagataella phaffii strain MXY0541 has been genetically modified to produce soy leghemoglobin; the safety of the genetic modification is under assessment by the EFSA GMO Panel (EFSA‐GMO‐NL‐2019‐162). The amount of haem iron provided by soy leghemoglobin from its proposed uses in meat analogue products is comparable to that provided by similar amounts of different types of meat. The exposure to iron from the proposed food additive, both at the mean and 95th percentile exposure, will be below the ‘safe levels of intake’ established by the NDA Panel for all population groups. Considering that the components of the proposed food additive will be digested to small peptide, amino acids and haem B; the recipient (non GM) strain qualifies for qualified presumption of safety status; no genotoxicity concern has been identified and no adverse effects have been identified at the highest dose tested in the available toxicological studies, the Panel concluded that there was no need to set a numerical acceptable daily intake (ADI) and that the food additive does not raise a safety concern at the proposed use in food category 12.9 and maximum use level. The Panel concluded that the use of soy leghemoglobin from genetically modified Komagataella phaffii MXY0541 as a new food additive does not raise a safety concern at the proposed use and use level. This safety evaluation of the proposed food additive remains provisional subject to the ongoing safety assessment of the genetic modification of the production strain by the GMO Panel (EFSA‐GMO‐NL‐2019‐162).

Abstract The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of naringenin [FL‐no: 16.132] as a new flavouring substance, in accordance with Regulation (EC) No 1331/2008. No other substances with sufficient structural similarity have been identified in existing FGEs that could be used to support a read‐across approach. The information provided on the manufacturing process, the composition and the stability of [FL‐no: 16.132] was considered sufficient. From studies carried out with naringenin, the Panel concluded that there is no concern with respect to genotoxicity. The use of naringenin as a flavouring substance at added portions exposure technique (APET) exposure levels is unlikely to pose a risk for drug interaction. For the toxicological evaluation of naringenin, the Panel requested an extended one‐generation toxicity study on naringenin, in line with the requirements of the Procedure and to investigate the consequence of a possible endocrine‐disrupting activity. The Panel considered that changes in thymus weight, litter size, post‐implantation loss and a consistent reduced pup weight in the high‐dose F2 generation could not be dismissed and selected therefore, the mid‐dose of 1320 mg/kg body weight (bw) per day for the parental males as the no observed adverse effect level (NOAEL) of the study. The exposure estimates for [FL‐no: 16.132] (31,500 and 50,000 μg/person per day for children and adults, respectively) were above the threshold of toxicological of concern (TTC) for its structural class (III). Using the NOAEL of 1320 mg/kg bw per day at step A4 of the procedure, margins of exposure (MoE) of 1590 and 630 could be calculated for adults and children, respectively. Based on the calculated MoEs, the Panel concluded that the use of naringenin as a flavouring substance does not raise a safety concern.

Abstract Guar gum (E 412) was re‐evaluated in 2017 by the former EFSA Panel on Food Additives and Nutrient sources added to Food (ANS). As a follow‐up to this assessment, the Panel on Food Additives and Flavourings (FAF) was requested to assess the safety of guar gum (E 412) for its uses as food additive in food for infants below 16 weeks of age belonging to food categories 13.1.1 (Infant formulae) and 13.1.5.1 (Dietary foods for infants for special medical purposes and special formulae for infants). In addition, the FAF Panel was requested to address the issues already identified during the re‐evaluation of the food additive when used in food for the general population. The process involved the publication of a call for data to allow the interested business operators to provide the requested information to complete the risk assessment. In the response to EFSA requests, one IBO stated that E 412 is not used in food categories 13.1.1 and 13.1.5.1, but it is present in products under food category 13.1.5.2. The Panel concluded that the submitted data are not sufficient to support the safe use of guar gum (E 412) in food for infants (below and above 16 weeks of age) and young children under FC 13.1.1, 13.1.5.1 and 13.1.5.2. Additionally, the Panel concluded that the technical data provided by the IBO support further amendments of the specifications for E 412 laid down in Commission Regulation (EU) No 231/2012.

Abstract The EFSA Panel on Food Additives and Flavourings (FAF) was requested to evaluate the safety of 2‐methyl‐1‐(2‐(5‐(p‐tolyl)‐1H‐imidazol‐2‐yl)piperidin‐1‐yl)butan‐1‐one [FL‐no: 16.134] as a new flavouring substance, in accordance with Regulation (EC) No 1331/2008. The substance has not been reported to occur naturally and is chemically synthesised. In food, it is intended to be used as a flavouring substance only in chewing gum. The chronic dietary exposure to [FL‐no: 16.134] was estimated to be 45 μg/person per day for a 60‐kg adult and 28.4 μg/person per day for a 15‐kg 3‐year‐old child. [FL‐no: 16.134] did not show genotoxicity in a bacterial reverse mutation test and an in vitro mammalian cell micronucleus assay. Based on the submitted toxicokinetic and metabolism data, it can be predicted that the flavouring substance is metabolised to innocuous products only. The Panel derived a lower confidence limit of the benchmark dose (BMDL) of 0.71 mg/kg bw per day for a 20% increase in the relative thyroid (including parathyroid) weight observed in a 90‐day toxicity study in rats. Based on this BMDL, adequate margins of exposure of 887 and 374 could be calculated for adults and children, respectively. The Panel concluded that there is no safety concern for [FL‐no: 16.134], when used as a flavouring substance at the estimated level of dietary exposure, based on the intended use and use levels as specified in Appendix B. The Panel further concluded that the combined exposure to [FL‐no: 16.134] from its use as a food flavouring substance and from its presence in toothpaste and mouthwash is also not of safety concern.

Abstract Background Preventing foot ulcers in people with diabetes can increase quality of life and reduce costs. Despite the availability of various interventions to prevent foot ulcers, recurrence rates remain high. We hypothesize that a multimodal treatment approach incorporating various footwear, self-management, and education interventions that matches an individual person’s needs can reduce the risk of ulcer recurrence with beneficial cost-utility. The aim of this study is to assess the effect on foot ulcer recurrence, footwear adherence, and cost-utility of an integrated personalized assistive devices approach in high-risk people with diabetes. Methods In a parallel-group multicenter randomized controlled trial, 126 adult participants with diabetes mellitus type 1 or 2, loss of protective sensation based on the presence of peripheral neuropathy, a healed plantar foot ulcer in the preceding 4 years, and possession of any type of custom-made footwear will be included. Participants will be randomly assigned to either enhanced therapy or usual care. Enhanced therapy consists of usual care and additionally a personalized treatment approach including pressure-optimized custom-made footwear, pressure-optimized custom-made footwear for indoor use, at-home daily foot temperature monitoring, and structured education, which includes motivational interviewing and personalized feedback on adherence and self-care. Participants will be followed for 12 months. Assessments include barefoot and in-shoe plantar pressure measurements; questionnaires concerning quality of life, costs, disease, and self-care knowledge; physical activity and footwear use monitoring; and clinical monitoring for foot ulcer outcomes. The study is powered for 3 primary outcomes: foot ulcer recurrence, footwear adherence, and cost-utility, the primary clinical, patient-related, and health-economic outcome respectively. Discussion This is the first study to integrate multiple interventions for ulcer prevention into a personalized state-of-the-art treatment approach and assess their combined efficacy in a randomized controlled trial in people with diabetes at high ulcer risk. Proven effectiveness, usability, and cost-utility will facilitate implementation in healthcare, improve the quality of life of high-risk people with diabetes, and reduce treatment costs. Trial registration ClinicalTrials.gov NCT05236660. Registered on 11 February 2022.

Abstract Quillaia extract (E 999) was re‐evaluated in 2019 by the EFSA Panel on Food Additives and Flavourings (FAF). EFSA derived an acceptable daily intake (ADI) of 3 mg saponins/kg bw per day for E 999. Following a European Commission call for data to submit data to fill the data gaps, the present follow‐up opinion assesses data provided by interested business operators (IBOs) to support an amendment of the EU specifications for E 999. Additionally, this opinion deals with the assessment of the proposed extension of use for E 999 in food supplements supplied in a solid and liquid form, excluding food supplements for infants and young children and, as a carrier in botanical nutrients. The Panel concluded that the proposed extension of use, if authorised, could result in an exceedance of the ADI at the maximum of the ranges of the mean for children, adolescents and the elderly, and for all populations at the 95th percentile. An additional proposed extension of use for E 999 to be used as a carrier for glazing agents on entire fresh fruits and vegetables has been received. Since no information on the proposed use levels of E 999 on a saponins content basis has been provided by this applicant, the Panel was not able to evaluate the safety of this extension of use. Considering the technical data submitted, the Panel recommended some modifications of the existing EU specifications for E 999, mainly to lower the limits for lead, mercury and arsenic and to include a maximum limit for cadmium and for calcium oxalate. The Panel also recommended that the limits would be expressed on a saponins basis. The Panel proposed to revise the definition of E 999 to better describe the composition in a qualitative way.

Summary: Background: Cognitive behavioural therapy (CBT) forms the standard psychotherapy for schizophrenia spectrum disorders (SSD). We aimed to summarize and evaluate the evidence on the effectiveness of CBT for SSD. Methods: In this umbrella review, we searched PubMed, Embase, Cochrane Database, and PsychInfo, for meta-analyses of randomised controlled trials (RCTs) of CBT in SSD published between database inception up to Aug 18, 2023. Inclusion criteria were RCTs investigating individually provided CBT in a population of patients with SSD, compared to either standard care, treatment as usually, or any other psychosocial therapies. No restrictions concerning follow-up or language were applied. We used the “assessment of multiple systematic reviews” (AMSTAR-2) appraisal checklist for the evaluation of methodological quality of meta-analysis. We extracted summary metrics from eligible studies in duplicate. The strength of evidence was classified by the sample size, p-value, excess significance bias, prediction intervals, significance of largest study, and heterogeneity. The strength of evidence was ranked according to established criteria as: convincing, highly suggestive, suggestive, weak, or not significant. Primary outcomes were general psychopathology, positive and negative symptoms. This study is registered in PROSPERO, CRD42022334671. Findings: We found 26 eligible meta-analyses, of which 16 meta-analyses provided sufficient data. Using the AMSTAR-2, we found limitations in details concerning the selection of study design, quality of the search and reporting of funding in included meta-analyses. A minority of 42.9% of the comparisons showed a significant result in favor of CBT; 57.1% were non-significant with no convincing or highly suggestive evidence. Suggestive evidence was found in favor of CBT for general psychopathology (6.2%, N = 34 RCTs, effect size (ES) = −0.33 (−0.47; −0.19), I2 = 67.93), delusions (16.7%, N = 27, ES = 0.36 (0.22; 0.51), I2 = 50.47), and hallucinations (33.3%, N = 28, ES = 0.32 (0.19; 0.46), I2 = 45.14) at the end of treatment (EoT). Weak (N = 34 RCTs, ES = −0.13 (−0.24; −0.02), I2 = 51.28), or non-significant evidence (N = 28 RCTs, ES = 0.12 (−0.03; 0.27) I2 = 64.63) was found for negative symptoms at EoT. At longer follow-up, evidence became weak or non-significant. Interpretation: Findings suggest that the effectiveness of CBT on general and positive symptoms in SSD at EoT was small to medium, while we found inconsistent evidence for a sustainable effect. CBT has no convincing impact on other relevant outcomes. Guidelines may use these results to specify their recommendations. Funding: None.

Antibiotics are widely used in intensive animal husbandry in the Netherlands and are subsequently emitted to soil via manure. To predict degradation and mobility in soil, generic sorption models have been derived. However, most of the coefficients used in generic models are based on a limited range of soils and have not been validated for agricultural soils in the Netherlands. To improve model predictions and assess to what extent differences among soils affect sorption and degradation, an experimental study has been performed. Using a recently developed experimental approach, both the degradation (DT50) and mobility (Kd) of eight selected commonly used antibiotics were determined in 29 typical Dutch agricultural soils. Median DT50 values range from 5.3 days for Sulfadiazine to 120 days for Trimethoprim but are affected by soil type. The ratio of the lowest and highest DT50 for a given antibiotic among soils can be as large as 151, for Tylosin. Measured values of the logKd also range from 0.19 for Sulfadiazine to more than 2 for Doxycycline, Flumequine, Trimethoprim, Tylosin and Enrofloxacine. The impact of soil on Kd is large, especially for more mobile antibiotics such as Sulfadoxine and Sulfadiazine. Both the range in DT50 and Kd can be predicted reasonably well using a Freundlich type regression model that accounts for the variation in soil type and sampling depth. Organic matter, iron oxides, pH and clay content appear to be the main constituents and explain between 29 % (Trimethoprim) and 77 % of the variation in DT50 and between 64 % (Lincomycin) and 87 % (Sulfadoxine and Sulfadiazine) of the variation of Kd. The effect of depth on DT50 and Kd is however limited. The information thus obtained in combination with local data on soil type can be used to more accurately predict the potential risk of relevant antibiotics in soil and transport to ground- and nearby surface waters.