Laboratory tests with Lepidoptera to assess non-target effects of Bt maize pollen: analysis of current studies and recommendations for a standardised design

Background and approach Common standards for laboratory studies of non-target organisms are recognised as prerequisite to assist the risk assessments regarding the evaluation of environmental effects of transgenic crops. Here, we provide specific recommendations significant for experimental procedures of laboratory studies to test potential adverse effects of Bt maize on larvae of non-target Lepidoptera. We searched and analysed both ecotoxicological test protocols for pesticides in the EU as well as the non-target tests with Lepidoptera applied in unpublished industry studies submitted officially by agro-companies for the GMO authorisation in Europe. Results The classical ecotoxicology protocols applied for testing pesticides could serve as general guidelines, but do not completely fit the specific and differing requirements for assessing non-target effects of transgenic crops. The analysis of the non-target studies submitted for the application of the cultivation of Bt maize in Europe revealed critical limitations, thus corroborating the urgent need for common quality criteria. Based on our evaluations, we identified several issues requiring harmonisation or standardisation of the experimental conditions and approach, e.g., the application of Bt maize pollen, synthetic toxins, the provided diet for larvae, experimental controls, magnitude and duration of exposure to Bt, relevant variables to be recorded, and sufficient statistical power. Conclusions Our recommendations should stimulate the development of precise guidance for the authorities, and support the operationalisation of the required laboratory tests for the evaluation of non-target effects of Bt maize pollen on non-target Lepidoptera, also contributing to standards of other ecotoxicity tests with Lepidoptera larvae, e.g., for pesticides.This article has been prepared as an outcome of the BfN research project “Basisdaten zur Effektbewertung verschiedener Bt-Toxine auf Schmetterlingslarven” (FKZ 3515890100)

Longitudinal changes of mental health problems in children and adolescents treated in a primary care-based health-coaching programme – results of the PrimA-QuO cohort study

BACKGROUND: In Germany, 19.1% of boys and 14.5% of girls are affected by mental health problems (MHP). Paediatricians are usually the first in line to be contacted but they often do not feel adequately trained to diagnose and treat MHP in primary care. A major statutory health insurance fund introduced a health coaching (HC) programme to strengthen primary care consultation for MHP. The HC includes a training concept for paediatricians, standardised guidelines for actions and additional payments. The aim of this study was to investigate the potential effects of the HC programme on the change of MHP in children and adolescents. METHODS: A prospective cohort study was conducted in Bavaria, Germany, in 2018 and 2019. Data were collected at 2 points 1 year apart using an online questionnaire. Parents of patients with developmental disorder of speech and language, head/abdominal pain, conduct disorder or non-organic enuresis were approached by their health insurance. Families treated according to the HC programme form the intervention group while all others serve as controls. MHP was assessed using the Strengths and Difficulties Questionnaire (SDQ) as a child self-assessment (SDQ-S)/or external assessment by parents (SDQ-P). Determinants of SDQ total score were analysed using linear mixed effects models. RESULTS: Cross-sectional (n = 1090) and longitudinal analyses (n = 599) were performed. At baseline, a total of 23.5% had an SDQ total score “at risk” (SDQ-S > 15/SDQ-P > 13). There were no significant differences between intervention and controls. After full adjustment for all potential confounders, higher SDQ scores indicating more problems were significantly associated with male sex (2.000, p < 0.001) whereas a high parental education level was significantly associated with decreased SDQ scores (-2.127, p =0.034). There was a significant improvement in the control group over time (-0.814, p = 0.001) while the SDQ scores in the intervention group remained stable (-0.012, p = 0.020). CONCLUSION: This evaluation of the HC programme could not prove a clinically relevant intervention’s effect on the MHP developmental course. Nevertheless, (HC) paediatricians have crucial potential to improve the care of MHP patients. Targeting families with less access to support measures might help reduce the burden of MHP and be a step towards continuous improvement of care. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12875-022-01780-1

Mixed-methods evaluation of a structured primary care programme for children and adolescents with mental health problems (PrimA-QuO): a study protocol

INTRODUCTION More than 17% of German children and adolescents have clinically relevant mental health problems (MHP). Typically, general paediatricians are often the first contact for children with MHP, and referrals to specialised care tend to be the standard approach. A statutory health insurance fund developed a programme for children with MHP (Health Coaching (HC)) aiming to offer targeted but low-threshold services. However, little is known about whether HC has the potential for optimising patient care. The aim of the PrimA-QuO study is to examine the effectiveness and the acceptance, barriers and facilitators of all stakeholders of this structured primary care programme for children affected by the most frequently encountered MHP in paediatric practice. METHODS AND ANALYSIS In this mixed-methods approach, children (n=800; aged 0-17 years) with MHP meeting all inclusion criteria will be identified in the health insurance database according to International Classification of Diseases, 10th Revision diagnoses between 2018 and 2019. The qualitative component uses a series of semistructured interviews with programme developers, paediatricians trained in HC, adolescents with MHP treated according to the programme guidelines and their parents. In addition, a prospective, pragmatic, parallel-group cohort study will be conducted using an online questionnaire to examine the effects of HC on health-related quality of life of affected children and their families as well as on change in MHP. Children treated according to the HC guidelines form the intervention group, whereas all others serve as controls. Primary data from the cohort study are linked to children's health insurance claims data to calculate the costs of care as proxies for healthcare utilisation. The hypothesis is that HC is an effective and efficient primary care programme with the potential to improve patients' and their families' health outcomes. ETHICS AND DISSEMINATION The study was approved by the Ethical Committee of Ludwig-Maximilians-Universität München. Grant number 01VSF16032 (funded by the German Innovationsfonds)

Prognostic Factors for Mortality in Acute Mesenteric Ischemia.

Postoperative mortality in patients undergoing surgical and/or interventional treatment for acute mesenteric ischemia (AMI) has remained an unsolved problem in recent decades. Here, we investigated clinical predictors of postoperative mortality in a large European cohort of patients undergoing treatment for AMI. In total, 179 patients who underwent surgical and/or interventional treatment for AMI between 2009 and 2021 at our institution were included in this analysis. Associations between postoperative mortality and various clinical variables were assessed using univariate and multivariable binary logistic regression analysis. Most of the patients were diagnosed with arterial ischemia (AI; n = 104), while venous ischemia (VI; n = 21) and non-occlusive mesenteric ischemia (NOMI; n = 54) were present in a subset of patients. Overall inhouse mortality was 55.9% (100/179). Multivariable analyses identified leukocytes (HR = 1.08; p = 0.008), lactate (HR = 1.25; p = 0.01), bilirubin (HR = 2.05; p = 0.045), creatinine (HR = 1.48; p = 0.039), etiology (AI, VI or NOMI; p = 0.038) and portomesenteric vein gas (PMVG; HR = 23.02; p = 0.012) as independent predictors of postoperative mortality. In a subanalysis excluding patients with fatal prognosis at the first surgical exploration (n = 24), leukocytes (HR = 1.09; p = 0.004), lactate (HR = 1.27; p = 0.003), etiology (AI, VI or NOMI; p = 0.006), PMVG (HR = 17.02; p = 0.018) and intraoperative FFP transfusion (HR = 4.4; p = 0.025) were determined as independent predictors of postoperative mortality. Further, the risk of fatal outcome changed disproportionally with increased preoperative lactate values. The clinical outcome of patients with AMI was determined using a combination of pre- and intraoperative clinical and radiological characteristics. Serum lactate appears to be of major clinical importance as the risk of fatal outcome increases significantly with higher lactate values

99mTc-besilesomab (Scintimun®) in peripheral osteomyelitis: comparison with 99mTc-labelled white blood cells

The diagnosis of osteomyelitis is a challenge for diagnostic imaging. Nuclear medicine procedures including white blood cell imaging have been successfully used for the identification of bone infections. This multinational, phase III clinical study in 22 European centres was undertaken to compare anti-granulocyte imaging using the murine IgG antibody besilesomab (Scintimun) with (99m)Tc-labelled white blood cells in patients with peripheral osteomyelitis. A total of 119 patients with suspected osteomyelitis of the peripheral skeleton received (99m)Tc-besilesomab and (99m)Tc-hexamethylpropyleneamine oxime (HMPAO)-labelled white blood cells (WBCs) in random order 2-4 days apart. Planar images were acquired at 4 and 24 h after injection. All scintigraphic images were interpreted in an off-site blinded read by three experienced physicians specialized in nuclear medicine, followed by a fourth blinded reader for adjudication. In addition, clinical follow-up information was collected and a final diagnosis was provided by the investigators and an independent truth panel. Safety data including levels of human anti-mouse antibodies (HAMA) and vital signs were recorded. The agreement in diagnosis across all three readers between Scintimun and (99m)Tc-HMPAO-labelled WBCs was 0.83 (lower limit of the 95% confidence interval 0.8). Using the final diagnosis of the local investigator as a reference, Scintimun had higher sensitivity than (99m)Tc-HMPAO-labelled WBCs (74.8 vs 59.0%) at slightly lower specificity (71.8 vs 79.5%, respectively). All parameters related to patient safety (laboratory data, vital signs) did not provide evidence of an elevated risk associated with the use of Scintimun except for two cases of transient hypotension. HAMA were detected in 16 of 116 patients after scan (13.8%). Scintimun imaging is accurate, efficacious and safe in the diagnosis of peripheral bone infections and provides comparable information to (99m)Tc-HMPAO-labelled WBCs

A process-based model of conifer forest structure and function with special emphasis on leaf lifespan

We describe the University of Sheffield Conifer Model (USCM), a process-based approach for simulating conifer forest carbon, nitrogen, and water fluxes by up-scaling widely applicable relationships between leaf lifespan and function. The USCM is designed to predict and analyze the biogeochemistry and biophysics of conifer forests that dominated the ice-free high-latitude regions under the high pCO2 “greenhouse” world 290–50 Myr ago. It will be of use in future research investigating controls on the contrasting distribution of ancient evergreen and deciduous forests between hemispheres, and their differential feedbacks on polar climate through the exchange of energy and materials with the atmosphere. Emphasis is placed on leaf lifespan because this trait can be determined from the anatomical characteristics of fossil conifer woods and influences a range of ecosystem processes. Extensive testing of simulated net primary production and partitioning, leaf area index, evapotranspiration, nitrogen uptake, and land surface energy partitioning showed close agreement with observations from sites across a wide climatic gradient. This indicates the generic utility of our model, and adequate representation of the key processes involved in forest function using only information on leaf lifespan, climate, and soils

Nonparametric Information Geometry

The differential-geometric structure of the set of positive densities on a given measure space has raised the interest of many mathematicians after the discovery by C.R. Rao of the geometric meaning of the Fisher information. Most of the research is focused on parametric statistical models. In series of papers by author and coworkers a particular version of the nonparametric case has been discussed. It consists of a minimalistic structure modeled according the theory of exponential families: given a reference density other densities are represented by the centered log likelihood which is an element of an Orlicz space. This mappings give a system of charts of a Banach manifold. It has been observed that, while the construction is natural, the practical applicability is limited by the technical difficulty to deal with such a class of Banach spaces. It has been suggested recently to replace the exponential function with other functions with similar behavior but polynomial growth at infinity in order to obtain more tractable Banach spaces, e.g. Hilbert spaces. We give first a review of our theory with special emphasis on the specific issues of the infinite dimensional setting. In a second part we discuss two specific topics, differential equations and the metric connection. The position of this line of research with respect to other approaches is briefly discussed.Comment: Submitted for publication in the Proceedings od GSI2013 Aug 28-30 2013 Pari