International STakeholder NETwork (ISTNET): creating a developmental neurotoxicity (DNT) testing road map for regulatory purposes.

A major problem in developmental neurotoxicity (DNT) risk assessment is the lack of toxicological hazard information for most compounds. Therefore, new approaches are being considered to provide adequate experimental data that allow regulatory decisions. This process requires a matching of regulatory needs on the one hand and the opportunities provided by new test systems and methods on the other hand. Alignment of academically and industrially driven assay development with regulatory needs in the field of DNT is a core mission of the International STakeholder NETwork (ISTNET) in DNT testing. The first meeting of ISTNET was held in Zurich on 23-24 January 2014 in order to explore the concept of adverse outcome pathway (AOP) to practical DNT testing. AOPs were considered promising tools to promote test systems development according to regulatory needs. Moreover, the AOP concept was identified as an important guiding principle to assemble predictive integrated testing strategies (ITSs) for DNT. The recommendations on a road map towards AOP-based DNT testing is considered a stepwise approach, operating initially with incomplete AOPs for compound grouping, and focussing on key events of neurodevelopment. Next steps to be considered in follow-up activities are the use of case studies to further apply the AOP concept in regulatory DNT testing, making use of AOP intersections (common key events) for economic development of screening assays, and addressing the transition from qualitative descriptions to quantitative network modelling.

Analytical Strategies for Doping Control Purposes: Needs, Challenges, and Perspectives.

The fight against doping in sports has been governed since 1999 by the World Anti-Doping Agency (WADA), an independent institution behind the implementation of the World Anti-Doping Code (Code). The intent of the Code is to protect clean athletes through the harmonization of anti-doping programs at the international level with special attention to detection, deterrence and prevention of doping.1 A new version of the Code came into force on January 1st 2015, introducing, among other improvements, longer periods of sanctioning for athletes (up to four years) and measures to strengthen the role of anti-doping investigations and intelligence. To ensure optimal harmonization, five International Standards covering different technical aspects of the Code are also currently in force: the List of Prohibited Substances and Methods (List), Testing and Investigations, Laboratories, Therapeutic Use Exemptions (TUE) and Protection of Privacy and Personal Information. Adherence to these standards is mandatory for all anti-doping stakeholders to be compliant with the Code. Among these documents, the eighth version of International Standard for Laboratories (ISL), which also came into effect on January 1st 2015, includes regulations for WADA and ISO/IEC 17025 accreditations and their application for urine and blood sample analysis by anti-doping laboratories.2 Specific requirements are also described in several Technical Documents or Guidelines in which various topics are highlighted such as the identification criteria for gas chromatography (GC) and liquid chromatography (LC) coupled to mass spectrometry (MS) techniques (IDCR), measurements and reporting of endogenous androgenic anabolic agents (EAAS) and analytical requirements for the Athlete Biological Passport (ABP).

How differential management strategies affect Ips typographus L. dispersal

Bark beetle outbreaks have a devastating effect on economically important forests worldwide, thus requiring extensive application of management control strategies. The presence of unmanaged protected areas in close proximity to managed forests can instigate concerns that bark beetle infestations may spread from unmanaged into managed stands. We studied the impact of differential management of forest stands on the dispersal dynamics of the European spruce bark beetle, Ips typographus, making use of inferential population genetics on mitochondrial and nuclear genomes. Bayesian inferences of migration rates and a most parsimonious dispersal tree show that outgoing gene flow was consistently higher from managed to unmanaged areas. Reason for that is likely the thorough removal of potential breeding material in managed forests and thus the dispersal of the base stock beetles from these areas to unmanaged areas where breeding material is available. Our study suggests that the potential threat posed by unmanaged to managed forests in regard to I. typographus infestation needs to be carefully re-considered.

Cost-minimization analysis of three decision strategies for cardiac revascularization : results of the "suspected CAD"cohort of the european cardiovascular magnetic resonance registry.

BACKGROUND: Coronary artery disease (CAD) continues to be one of the top public health burden. Perfusion cardiovascular magnetic resonance (CMR) is generally accepted to detect CAD, while data on its cost effectiveness are scarce. Therefore, the goal of the study was to compare the costs of a CMR-guided strategy vs two invasive strategies in a large CMR registry. METHODS: In 3'647 patients with suspected CAD of the EuroCMR-registry (59 centers/18 countries) costs were calculated for diagnostic examinations (CMR, X-ray coronary angiography (CXA) with/without FFR), revascularizations, and complications during a 1-year follow-up. Patients with ischemia-positive CMR underwent an invasive CXA and revascularization at the discretion of the treating physician (=CMR + CXA-strategy). In the hypothetical invasive arm, costs were calculated for an initial CXA and a FFR in vessels with ≥50 % stenoses (=CXA + FFR-strategy) and the same proportion of revascularizations and complications were applied as in the CMR + CXA-strategy. In the CXA-only strategy, costs included those for CXA and for revascularizations of all ≥50 % stenoses. To calculate the proportion of patients with ≥50 % stenoses, the stenosis-FFR relationship from the literature was used. Costs of the three strategies were determined based on a third payer perspective in 4 healthcare systems. RESULTS: Revascularizations were performed in 6.2 %, 4.5 %, and 12.9 % of all patients, patients with atypical chest pain (n = 1'786), and typical angina (n = 582), respectively; whereas complications (=all-cause death and non-fatal infarction) occurred in 1.3 %, 1.1 %, and 1.5 %, respectively. The CMR + CXA-strategy reduced costs by 14 %, 34 %, 27 %, and 24 % in the German, UK, Swiss, and US context, respectively, when compared to the CXA + FFR-strategy; and by 59 %, 52 %, 61 % and 71 %, respectively, versus the CXA-only strategy. In patients with typical angina, cost savings by CMR + CXA vs CXA + FFR were minimal in the German (2.3 %), intermediate in the US and Swiss (11.6 % and 12.8 %, respectively), and remained substantial in the UK (18.9 %) systems. Sensitivity analyses proved the robustness of results. CONCLUSIONS: A CMR + CXA-strategy for patients with suspected CAD provides substantial cost reduction compared to a hypothetical CXA + FFR-strategy in patients with low to intermediate disease prevalence. However, in the subgroup of patients with typical angina, cost savings were only minimal to moderate.

Pre-dispersal predation effect on seed packaging strategies and seed viability.

An increased understanding of intraspecific seed packaging (i.e. seed size/number strategy) variation across different environments may improve current knowledge of the ecological forces that drive seed evolution in plants. In particular, pre-dispersal seed predation may influence seed packaging strategies, triggering a reduction of the resources allocated to undamaged seeds within the preyed fruits. Assessing plant reactions to pre-dispersal seed predation is crucial to a better understanding of predation effects, but the response of plants to arthropod attacks remains unexplored. We have assessed the effect of cone predation on the size and viability of undamaged seeds in populations of Juniperus thurifera with contrasting seed packaging strategies, namely, North African populations with single-large-seeded cones and South European populations with multi-small-seeded cones. Our results show that the incidence of predation was lower on the single-large-seeded African cones than on the multi-small-seeded European ones. Seeds from non-preyed cones were also larger and had a higher germination success than uneaten seeds from preyed cones, but only in populations with multi-seeded cones and in cones attacked by Trisetacus sp., suggesting a differential plastic response to predation. It is possible that pre-dispersal seed predation has been a strong selective pressure in European populations with high cone predation rates, being a process which maintains multi-small-seeded cones and empty seeds as a strategy to save some seeds from predation. Conversely, pre-dispersal predation might not have a strong effect in the African populations with single-large-seeded cones characterized by seed germination and filling rates higher than those in the European populations. Our results indicate that differences in pre-dispersal seed predators and predation levels may affect both selection on and intraspecific variation in seed packaging.

Stratégies de communication au service de la formation: quelques outils pratiques [Effective communication strategies to frame the trainer-trainee dialogue in the clinical setting].

Communication between trainer and trainee plays a central role in teaching and learning in the clinical environment. There are various strategies to frame the dialogue between trainee and trainer. These strategies allow trainers to be more effective in their supervision, which is important in our busy clinical environment. Communication strategies are well adapted to both in- and out-patient settings, to both under- and postgraduate contexts. This article presents three strategies that we think are particularly useful. They are meant to give feedback, to ask questions and to present a case.

Variation in treatment strategies of Swiss general practitioners for subclinical hypothyroidism in older adults.

QUESTIONS UNDER STUDY: As the best management of subclinical hypothyroidism is controversial, we aimed to assess variations in treatment strategies depending on different Swiss regions, physician and patient characteristics. METHODS: We performed a case-based survey among general practitioners (GPs) in different Swiss regions, which consisted of eight hypothetical cases presenting a female patient with subclinical hypothyroidism and nonspecific complaints differing by age, vitality status and thyroid-stimulating hormone (TSH) concentration. RESULTS: A total of 262 GPs participated in the survey. There was considerable variation in the levothyroxine starting dose chosen by GPs, ranging from 25 µg to 100 µg. Across the Swiss regions, GPs in the Bern region were significantly more inclined to treat, with a higher probability of initiating treatment (60%, p = 0.01) and higher mean starting doses (45 µg, p <0.01) compared with the French-speaking region (44%, 36 µg); the Zurich region had intermediate values (52%, 39 µg). We found no association between treatment rate and other physician characteristics. GPs were more reluctant to initiate treatment in 85-year-old than in 70-year-old women (odds ratio [OR] 0.77, 95% confidence interval [CI] 0.63-0.94), and more likely to treat women with a TSH of 15 mU/l than those with a TSH of 6mU/l (OR 8.71, 95% CI 6.21-12.20). CONCLUSIONS: There are strong variations in treatment strategies for elderly patients with subclinical hypothyroidism across different Swiss regions, including use of higher starting doses than the recommended 25 µg in the Swiss guidelines, which recommend a starting dose of 25 µg. These variations likely reflect the current uncertainty about the benefits of treatment, which arise from the current lack of evidence from adequately powered clinical trials.

Maladaptive emotion regulation strategies and stress sensitivity mediate the relation between adverse life events and attenuated positive psychotic symptoms.

INTRODUCTION: There is now solid evidence for a relation between adverse life events (ALE) and psychotic symptoms in patients with psychosis and in the general population. A recent study has shown that this relation may be partially mediated by stress sensitivity, suggesting the influence of other factors. The aim of this study was to assess the mediation effect of emotion regulation strategies and stress sensitivity in the relation between ALE and attenuated positive psychotic symptoms (APPS) in the general population. METHODS: Hundred and twelve healthy volunteers were evaluated with measures of APPS, emotion regulation strategies, ALE and stress sensitivity. RESULTS: Results demonstrated that the relation between ALE, hallucination and delusion proneness was completely mediated by maladaptive emotion regulation strategies, but not by stress sensitivity. However, in addition to maladaptive emotion regulation strategies, stress sensitivity demonstrated a mediation effect between ALE and attenuated positive psychotic positive symptoms when positive psychotic symptoms were grouped together. CONCLUSIONS: There are probably several possible trajectories leading to the formation of positive psychotic symptoms and the results of the present study reveal that one such trajectory may involve the maladaptive regulation of negative emotions alongside a certain general vulnerability after experiencing ALE.

Latent Class Analysis of Gambling Activities in a Sample of Young Swiss Men : Association with Gambling Problems, Substance Use Outcomes, Personality Traits and Coping Strategies.

The study aimed to identify different patterns of gambling activities (PGAs) and to investigate how PGAs differed in gambling problems, substance use outcomes, personality traits and coping strategies. A representative sample of 4989 young Swiss males completed a questionnaire assessing seven distinct gambling activities, gambling problems, substance use outcomes, personality traits and coping strategies. PGAs were identified using latent class analysis (LCA). Differences between PGAs in gambling and substance use outcomes, personality traits and coping strategies were tested. LCA identified six different PGAs. With regard to gambling and substance use outcomes, the three most problematic PGAs were extensive gamblers, followed by private gamblers, and electronic lottery and casino gamblers, respectively. By contrast, the three least detrimental PGAs were rare or non-gamblers, lottery only gamblers and casino gamblers. With regard to personality traits, compared with rare or non-gamblers, private and casino gamblers reported higher levels of sensation seeking. Electronic lottery and casino gamblers, private gamblers and extensive gamblers had higher levels of aggression-hostility. Extensive and casino gamblers reported higher levels of sociability, whereas casino gamblers reported lower levels of anxiety-neuroticism. Extensive gamblers used more maladaptive and less adaptive coping strategies than other groups. Results suggest that gambling is not a homogeneous activity since different types of gamblers exist according to the PGA they are engaged in. Extensive gamblers, electronic and casino gamblers and private gamblers may have the most problematic PGAs. Personality traits and coping skills may predispose individuals to PGAs associated with more or less negative outcomes.

Les strategies de coping chez les proches aidants de personnes atteintes de schizophrenie

Problématique. Les proches aidants jouent un rôle primordial de soutien auprès des personnes atteintes de schizophrénie. La symptomatologie et les perturbations du fonctionnement psychosocial des personnes atteintes de cette maladie peuvent entraîner un fardeau extrêmement élevé pour leur entourage. Les approches psycho-éducatives sont reconnues pour favoriser des stratégies de coping ayant comme impact d'atténuer la détresse des proches aidants et d'améliorer les relations interpersonnelles entre le proche aidant et la personne souffrant de schizophrénie. Buts: décrire et explorer les stratégies de coping chez les proches aidants de personnes atteintes de schizophrénie. Méthode: cette étude descriptive exploratoire a été menée auprès de 45 proches aidants, recrutés selon un échantillonnage de convenance. Ils ont rempli deux auto-questionnaires : (a) le questionnaire sociodémographique et (b) le Family Coping Questionnaire. Des statistiques descriptives de distributions et des analyses corrélationnelles bivariées ont été effectuées. Résultats: les résultats montrent que les stratégies de coping centrées sur le problème et les stratégies de coping centrées sur le maintien social sont plus utilisées que celles appartenant au coping centré sur l'émotion. Cependant, les stratégies de coping centré sur l'émotion sont encore souvent utilisées. Conclusion: malgré les limites de cette étude liées à la taille de l'échantillon, les résultats sont compatibles avec les études antérieures. Il semble important de poursuivre des recherches dans ce domaine pour mieux comprendre les associations entre les représentations de la maladie et les stratégies de coping. Il semble aussi crucial de développer, auprès des proches aidants, les interventions qui leur permettent une meilleure gestion des émotions.