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Quantitative assessments of adverse effects of plant protection products on honey bee brood (Apis mellifera L.) may be carried out according to the methods given by the OECD Guidance Document No. 75 (2007). In recent years a number of studies displayed a strong variability in brood termination rates, a key endpoint. Due to these variances no definite conclusions regarding potential brood effects were possible, and the studies needed to be repeated. Due to this, attempts to improve the methodology were initiated by the Working Group ‘Honey bee brood' of the German AG Bienenschutz. In 2011, honey bee brood studies adapted to these identified possible improvements resulted in better results compared to historical data. Based on the analysed results, the working group recommends to improve the method by using bigger colonies with more brood, using 4 instead of 3 replicates for better interpretation of data, starting the study early in the season, avoiding major modifications of the colonies shortly before application and using larger tunnels with effective crop areas preferably > 80 m². To carry out quicker brood cell assessments to reduce stress for the colonies, it is recommended to use digital brood assessment, which allows marking a higher number of cells (e.g. 200 to 400 cells).

The effect of different contents of fullerene on the properties of polyurethane resins (PUs), including rheology and thermal properties, was investigated. Polyurethane resins were prepared through polyaddition reactions using different isocyanate monomers such as isophorone diisocyanate (IPDI), methylene diphenyl diisocyanate (MDI), hexamethylene diisocyanate (HDI), and different polyols, such as poly(oxytetramethylene) glycol (PTMG), the triol trade name FA-703, and polypropylene glycols (PPG), at an NCO/OH ratio 0.94 and a temperature of 100 °C. IR spectroscopy was used to control the polymerization of PUs through the shifting of NCO peaks. The results showed that the rheology and thermal properties of the prepared PU resins depend on the type of isocyanates and fullerene used. Based on the type of isocyanates, the PU resin prepared by MDI has the highest viscosity and thermal stability compared to the other isocyanates investigated. On the other hand, the PU resins prepared by IPDI mixed with fullerene had the highest viscosity and thermal stability. However, the initial decomposition temperature (T onset) of the PUs decreased with the addition of fullerene without affecting the maximum decomposition temperature (PDTmax) of the PU resin.

In the present work, a theoretical study of atomic ordering in the A3BCx alloy is carried out. The mutual influence of the ordering and solubility of impurity C in the A3B alloy is studied. The dependences of solubility on the composition of the alloy, temperature, degree of long-range order are found and studied. In addition, the criteria for the manifestation of extremity in the concentration and temperature dependences of solubility are obtained. The atomic ordering is studied using the average-energies’ method; the features of the C impurity solubility in the A3B alloy are elucidated using the configuration method. Experiments confirming the results of the theory are currently unknown to authors. However, the available experimental data on determining the temperatures of martensitic transformation (Tm) and superconducting transition (Tc) for the Nb3SnHx alloy allow us to hope and assert a possible agreement between the data of theory and experiment.

The concept of 'social-ecological systems', which explores the relationships between society and the environment, was at the center of this study. The study aims to describe Israeli environmental-education master students' level of understanding of the social-ecological systems concept. We used a designated rubric score to analyze drawings and explanations and to identify the levels of understanding asking: How can the analysis of drawings and explanations, using Attentive Teaching as an educational approach, enable the identification of conceptual changes in understanding the social-ecological systems concept? The 270 drawings and explanations of 49 participants were analyzed, and they indicated a general increase in the level of understanding of the social-ecological systems concept. Attentive Teaching, as an educational approach, was found to lead to conceptual change. Drawings and explanations, as an assessment methodology may lead to better understanding of the social-ecological systems concept and may encourage action in relation to the environmental crisis.

OBJECTIVE: To investigate claims patterns for metamizole and other non-opioid analgesics in Switzerland. To characterise users of these non-opioid analgesics regarding sex, age, comedications and canton of residence. METHODS: We conducted a retrospective descriptive study using administrative claims data of outpatient prescribed non-opioid analgesics of the Swiss health insurance company Helsana between January 2014 and December 2019. First, we evaluated the number of claims and defined daily doses per year of metamizole, ibuprofen, diclofenac and paracetamol in adults aged 18 years or over. Second, we characterised new users of these non-opioid analgesics in terms of sex, age, claimed comedications and canton of residence. RESULTS: From 2014 to 2019, among the investigated non-opioid analgesics, metamizole showed the highest increase in claims (+9545 claims, +50%) and defined daily doses (+86,869 defined daily doses, +84%) per 100,000 adults. Metamizole users had the highest median age (62 years [IQR: 44–77]) compared to ibuprofen (47 years [IQR: 33–62]), diclofenac (57 years [IQR: 43–71]) and paracetamol (58 years [IQR: 39–75]) users. Metamizole users also more frequently claimed proton pump inhibitors, anticoagulants, platelet aggregation inhibitors and antihypertensive drugs than users of other non-opioid analgesics. While metamizole was most frequently claimed in German-speaking regions of Switzerland, ibuprofen and paracetamol were most frequently claimed in the French-speaking regions and diclofenac in German- and Italian-speaking regions. CONCLUSION: In Switzerland, metamizole was increasingly claimed between 2014 and 2019. Metamizole was most frequently claimed by older adults and patients with comedications suggestive of underlying conditions, which can be worsened or caused by use of nonsteroidal anti-inflammatory drugs. The lack of studies regarding the effectiveness and safety of metamizole in this population warrants further investigation.

We review and analyse the factors affecting the solubility of interstitial atoms (H) in the metal alloys. The electronic structure and atomic ordering of the AB-type alloys, as well as methods of calculation of the solubility for ordering cubic alloys with octahedral interstitial pores are considered. We study the parameters of interstitial atoms, which make it possible to predict a decrease or increase in solubility, when the main role belongs to the ordering of the system. The parameters of the static distribution of atoms are determined. The relative solubility is represented as a function of the long-range order parameter (η), and the influence of bulk effects on this parameter is considered. The following systems are studied: Fe–Ni, Au–Cu, Pd–Au, Fe–Cr, Ti–Al, Cu–Zn, Ag–Zn, Fe–Al, Au–Ag, Fe–V, Pd–Pt, Ni–Mn, Ni–Fe, Cu–Au, Cu–Pd, Pd–Nb, Pd–Ag, as well as three-component alloys. As shown, through introducing impurities into the alloy, we can change significantly its physical-mechanical, electrical, magnetic, and other properties.

The review article describes modern fillers of metal and polymer matrices, their properties and applications. We discuss the main parameters of fillers, their advantages and disadvantages, the results of investigations and experiments, which may be useful for scientists and engineers working in the fields of chemistry and materials science and developing new promising materials. Different materials used as the fillers for metal and polymer matrices are reviewed. To create composites of the new generation with improved properties, nanostructured materials such as graphene, fullerenes, nanotubes, nanopowders of metals and their alloys are used. Carbon fillers can be the strongest graphitizer, which is important for ferrous metallurgy. Nanofillers have the ultradispersed dimensions and high specific-surface values, which allows for changing significantly the physicochemical and functional characteristics of the matrix. As noted in the article, the use of fillers allows controlling the structural composition of the melt and helps to form additional crystallization centres. This, in turn, can affect significantly the properties of the material, such as mechanical strength, heat resistance, etc.

ABSTRACTEffective processes for synthesizing antibody-drug conjugates (ADCs) require: 1) site-specific incorporation of the payload to avoid interference with binding to the target epitope, 2) optimal drug/antibody ratio to achieve sufficient potency while avoiding aggregation or solubility problems, and 3) a homogeneous product to facilitate approval by regulatory agencies. In conventional ADCs, the drug molecules are chemically attached randomly to antibody surface residues (typically Lys or Cys), which can interfere with epitope binding and targeting, and lead to overall product heterogeneity, long-term colloidal instability and unfavorable pharmacokinetics. Here, we present a more controlled process for generating ADCs where drug is specifically conjugated to only Fab N-linked glycans in a narrow ratio range through functionalized sialic acids. Using a bacterial sialytransferase, we incorporated N-azidoacetylneuraminic acid (Neu5NAz) into the Fab glycan of cetuximab. Since only about 20% of human IgG1 have a Fab glycan, we extended the application of this approach by using molecular modeling to introduce N-glycosylation sites in the Fab constant region of other therapeutic monoclonal antibodies. We used trastuzumab as a model for the incorporation of Neu5NAz in the novel Fab glycans that we designed. ADCs were generated by clicking the incorporated Neu5NAz with monomethyl auristatin E (MMAE) attached to a self-immolative linker terminated with dibenzocyclooctyne (DBCO). Through this process, we obtained cetuximab-MMAE and trastuzumab-MMAE with drug/antibody ratios in the range of 1.3 to 2.5. We confirmed that these ADCs still bind their targets efficiently and are as potent in cytotoxicity assays as control ADCs obtained by standard conjugation protocols. The site-directed conjugation to Fab glycans has the additional benefit of avoiding potential interference with effector functions that depend on Fc glycan structure.

Introduction Approximately 30% of somatic hospital inpatients experience psychosocial distress, contributing to increased (re-)hospitalisation rates, treatment resistance, morbidity, and direct and indirect costs. However, such distress often remains unrecognised and unaddressed. We established ‘SomPsyNet’, a ‘stepped and collaborative care model’ (SCCM) for somatic hospital inpatients, aiming at alleviating this issue through early identification of distress and provision of appropriate care, providing problem-focused pathways and strengthening collaborative care. We report the protocol of the ‘SomPsyNet’ study, aiming to evaluate implementation and impact of the SCCM on distressed patients’ health-related quality of life. Secondary objectives include assessing efficacy of the screening procedures, influence of SCCM on other health outcomes and associated costs.Methods and analysis Our stepped wedge cluster randomised trial conducted at three tertiary hospitals comprises three conditions: treatment as usual (TAU) without screening for distress (phase 0), TAU with screening but without consequences (phase I, main comparator) and TAU with screening and psychosomatic-psychiatric consultations for those distressed (phase II). The time-of-transition between phases I and II was randomised. Sample size target is N=2200–2500 participants, with 6 month follow-up for distressed (anticipated n=640–700) and a subsample of non-distressed (anticipated n=200) patients. Primary outcome is mental health-related quality of life (SF-36 ‘Mental Health Component Summary score’); secondary outcomes include psychosocial distress, anxiety, depressive and somatic symptoms, symptom burden and distress, resilience, social support and qualitative of life, assessed by internationally accepted instruments, with good psychometric properties. Further, health claims data will be used to assess SCCM’s impact on direct and indirect costs.Ethics and dissemination SomPsyNet adheres to the Helsinki Declaration and is approved by the ‘Ethikkommission Nordwest- und Zentralschweiz’ (2019–01724). Findings will be published in peer-reviewed journals and communicated to participants, healthcare professionals and the public.Trial registration number Swiss National Clinical Trials Portal; ClinicalTrials.gov (NCT04269005, updated 19.09.2023).

During the August 21, 2017, solar eclipse, high school students measured secondary cosmic ray flux using QuarkNet detectors. These students conducted experiments examining cosmic ray flux, shower, speed of muons, and muon lifetime using QuarkNet cosmic ray muon detectors (CRMDs). These detectors measure muon flux of momenta greater than ~2 GeV, a threshold imposed by deflection due to Earth's magnetic field. This study utilized CRMDs, which are readily available for students, to investigate any deviation in secondary cosmic ray flux resulting from a solar eclipse. Other groups have conducted experiments regarding cosmic rays during eclipses: Kandemir et al. reported on low-energy muons (under 1 GeV) during the eclipse of August 11, 1999; Nayak et al. and Bhaskar et al. studied air showers for gamma ray point sources; and Nishina et al. studied muon flux during a 1936 eclipse. Cosmic rays are charged particles created in exploding stars and active galaxies and travel through interplanetary space at relativistic velocities. The flux is largely unchanged between day and night, when Earth blocks the Sun, and the presence of the Sun and Moon has little effect. A total eclipse provides a dramatic opportunity to search for that fraction of cosmic rays created by the Sun that are intercepted by the Moon. We hypothesized that muon flux will change during a total solar eclipse; however, we designed the experiment to search for signals at various angular scales near the direction of the Sun and to set upper limits on production from the Sun if no signal was observed.

Abstract Background Cancer cachexia is associated with reduced body weight, appetite and quality of life (QOL) with no approved treatments. Growth hormone secretagogues like macimorelin have potential to mitigate these effects. Methods This pilot study assessed the safety and efficacy of macimorelin for 1 week. Efficacy was defined a priori as 1‐week change in body weight (≥0.8 kg), plasma insulin‐like growth factor (IGF)‐1 (≥50 ng/mL) or QOL (≥15%). Secondary outcomes included food intake, appetite, functional performance, energy expenditure and safety laboratory parameters. Patients with cancer cachexia were randomized to 0.5 or 1.0 mg/kg macimorelin or placebo; outcomes were assessed non‐parametrically. Results Participants receiving at least one of either macimorelin dose were combined (N = 10; 100% male; median age = 65.50 ± 2.12) and compared with placebo (N = 5; 80% male; median age = 68.00 ± 6.19). Efficacy criteria achieved: body weight (macimorelin N = 2; placebo N = 0; P = 0.92); IGF‐1 (macimorelin N = 0; placebo N = 0); QOL by Anderson Symptom Assessment Scale (macimorelin N = 4; placebo N = 1; P = 1.00) or Functional Assessment of Chronic Illness Therapy‐Fatigue (FACIT‐F; macimorelin N = 3; placebo N = 0; P = 0.50). No related serious or non‐serious adverse events were reported. In macimorelin recipients, change in FACIT‐F was directly associated with change in body weight (r = 0.92, P = 0.001), IGF‐1 (r = 0.80, P = 0.01), and caloric intake (r = 0.83, P = 0.005), and inversely associated with change in energy expenditure (r = −0.67, P = 0.05). Conclusions Daily oral macimorelin for 1 week was safe and numerically improved body weight and QOL in patients with cancer cachexia compared with placebo. Longer term administration should be evaluated for mitigation of cancer‐induced reductions in body weight, appetite and QOL in larger studies.

A technique for designing the blade systems of Francis turbine is proposed. Starting with the determination the main parameters of the turbine components, where it is compatible with the operation of a hydraulic turbine at a given head. Also, the diameter of the impeller required to generate the nominal power. Then, using the realizing of the quasi-three-dimensional approach, the shape of the blade is obtained as a first approximation for a given blade, a series of calculations of three-dimensional single-phase and twophase viscous flow is performed to determine the efficiency of the turbine at different operating modes, the cavitation properties of the turbine, respectively. The critical cavitation coefficient is determined for three operating points of hydraulic turbines. Using Multi-objective Genetic Algorithm (MOGA), the optimization of energy and cavitation properties is carried out for three operations pointes. The mathematical model is based on the Latin hypercube method. As a result of the optimization, a significant improvement in the efficiency of the hydraulic turbine has been obtained, especially at partial loads.

Posttraumatic stress disorder (PTSD) and eating disorders (ED) frequently co-occur, but the mechanisms underlying this association remain unclear. EDs are characterized by features of maladaptive eating behaviors including disinhibited eating and cognitive dietary restraint. Identifying the genetic overlap between PTSD symptoms and maladaptive eating behaviors may elucidate biological mechanisms and potential treatment targets. A community sample of 400 same-sex twins (102 monozygotic and 98 dizygotic pairs) completed the PTSD Checklist-Civilian (PCL-C) for PTSD symptoms and the Three-Factor Eating Questionnaire-Reduced (TFEQ-R18) for eating behaviors (uncontrolled eating, emotional eating, and cognitive dietary restraint). We used biometric modeling to examine the genetic and environmental relationships between PCL-C and TFEQ-R18 total and subscales scores. Heritability was estimated at 48% for PTSD symptoms and 45% for eating behavior overall. Bivariate models revealed a significant genetic correlation between PTSD symptoms and eating behavior overall (rg =.34; CI:.07,.58) and Uncontrolled Eating (rg =.53; CI:.24,.84), and a significant environmental correlation between PTSD symptoms and Emotional Eating (re =.30; CI:.12,.45). These findings suggest the influence of common etiology. Future research and clinical efforts should focus on developing integrated treatments.

One of the obstacles preventing change of teaching methods in schools is teachers’ traditional conceptualizations of ‘teaching’ as transmissive and teacher-centered. The aim of this study was to track changes in experienced teachers’ concept of ‘teaching’, following their exposure to attentive teaching. This is a dialogical method in which the learners represent their concepts in drawings and written explanations, and discuss them with their teacher and peers. Method: This was a multiple-case study. The participants were three teachers who attended an attentive teaching professional development course. They drew ‘teaching’ in the first, sixth, and the last, fifteenth, session, and provided explanations of their drawings. Findings: At the start of the course, they described teaching as a unidirectional process of transmitting knowledge. In the middle, they became more aware of the students as individuals who should be listened to. By the end of the course, teaching was portrayed as multi-directional (and enjoyable), so that all the participants, including the teacher, teach and learn from each other. Conclusions: This study shows that by studying, experiencing, and implementing attentive teaching, it is possible to change experienced teachers’ traditional beliefs without directly challenging them, and that drawings can track the changes’ trajectory.

Toscana virus is a major cause of arboviral disease in humans in the Mediterranean basin during summer. However, early virus-host cell interactions and entry mechanisms remain poorly characterized. Investigating iPSC-derived human neurons and cell lines, we found that virus binding to the cell surface was specific, and 50% of bound virions were endocytosed within 10 min. Virions entered Rab5a+ early endosomes and, subsequently, Rab7a+ and LAMP-1+ late endosomal compartments. Penetration required intact late endosomes and occurred within 30 min following internalization. Virus entry relied on vacuolar acidification, with an optimal pH for viral membrane fusion at pH 5.5. The pH threshold increased to 5.8 with longer pre-exposure of virions to the slightly acidic pH in early endosomes. Strikingly, the particles remained infectious after entering late endosomes with a pH below the fusion threshold. Overall, our study establishes Toscana virus as a late-penetrating virus and reveals an atypical use of vacuolar acidity by this virus to enter host cells.