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New school transitions can be challenging for students on the autism spectrum. No published, evidence-based interventions exist to support families and teachers of students transitioning to elementary and secondary school during this critical period. Using Community Partnered Participatory Research, we developed Building Better Bridges (BBB), a caregiver coaching intervention that includes training on effective school communication, educational rights, advocacy, and child preparation strategies. We compared BBB (n = 83) to a module/resources-only comparison (n = 87) in a four-site randomized controlled trial in racially and ethnically diverse, under-resourced communities. In our intent-to-treat analysis, caregivers and teachers in BBB rated students' transitions to the new classroom as more positive, relative to the comparison group. Results suggest this low-cost intervention can improve the transition process for families and students at high risk of poor transitions.

Abstract Background Quantitative disease resistance (QR) is a complex, dynamic trait that is most reliably quantified in field-grown crops. Traditional disease assessments offer limited potential to disentangle the contributions of different components to overall QR at critical crop developmental stages. Yet, a better functional understanding of QR could greatly support a more targeted, knowledge-based selection for QR and improve predictions of seasonal epidemics. Image-based approaches together with advanced image processing methodologies recently emerged as valuable tools to standardize relevant disease assessments, increase measurement throughput, and describe diseases along multiple dimensions. Results We present a simple, affordable, and easy-to-operate imaging set-up and imaging procedure for in-field acquisition of wheat leaf image sequences. The development of Septoria tritici blotch and leaf rusts was monitored over time via robust methods for symptom detection and segmentation, spatial alignment of images, symptom tracking, and leaf- and symptom characterization. The average accuracy of the spatial alignment of images in a time series was approximately 5 pixels (~ 0.15 mm). Leaf-level symptom counts as well as individual symptom property measurements revealed stable patterns over time that were generally in excellent agreement with visual impressions. This provided strong evidence for the robustness of the methodology to variability typically inherent in field data. Contrasting patterns in the number of lesions resulting from separate infection events and lesion expansion dynamics were observed across wheat genotypes. The number of separate infection events and average lesion size contributed to different degrees to overall disease intensity, possibly indicating distinct and complementary mechanisms of QR. Conclusions The proposed methodology enables rapid, non-destructive, and reproducible measurement of several key epidemiological parameters under field conditions. Such data can support decomposition and functional understanding of QR as well as the parameterization, fine-tuning, and validation of epidemiological models. Details of pathogenesis can translate into specific symptom phenotypes resolvable using time series of high-resolution RGB images, which may improve biological understanding of plant-pathogen interactions as well as interactions in disease complexes.

Abstract Background Cardiac arrhythmia has been reported as a significant complication of thoracic radiotherapy. Both bradyarrhythmias and tachyarrhythmias have been reported, highlighting the arrhythmia-modulating potential of radiation in certain oncologic therapies. This study aimed to analyse the arrhythmic burden in patients with cardiac implantable electrical devices (CIEDs) undergoing thoracic irradiation, examining both immediate effects of radiotherapy and long-term sequelae post-therapy. Methods and results A retrospective cohort study was conducted involving patients with CIEDs who received thoracic radiotherapy between January 2012 and December 2022. Two distinct analyses were performed involving (1) daily CIED follow-ups during radiotherapy and (2) long-term arrhythmic outcomes post-therapy. For long-term outcomes, Patients were matched in a 1:2 ratio with non-irradiated controls based on age, sex, cardiovascular risk factors, cardiac disease, and beta-blocker use. Statistical analyses included negative binomial regression and propensity score matching. A total of 186 patients underwent daily CIED monitoring during radiotherapy, with 79 receiving thoracic irradiation. Thoracic irradiation was negatively associated with atrial arrhythmia (OR 0.11 [0.02;0.70, 95% CI], adjusted p = 0.0498) and there was a tendency towards less ventricular events (OR 0.14 [0.02;1.41, 95% CI], adjusted p = 0.3572) during radiotherapy in a univariate regression analysis. This association was not significant in the multivariate (OR 0.44 [0.10;1.80, 95%-CI], p = 0.16) model including a history of atrial fibrillation, diabetes and beta-blocker use. Coronary artery disease was associated with an increase in atrial and ventricular arrhythmia. For the long-term analysis, 122 patients were followed up after thoracic (N = 33) and non-thoracic radiation (N = 89) and compared to 244 matched controls drawn from approximately 10.000 CIED-patients. There was no significant increase in arrhythmic events compared to controls over a median follow-up of 6.6 months. A previous history of ventricular or atrial arrhythmic events was the strongest predictor for events during the follow-up. Conclusion Thoracic radiotherapy can be safely administered in patients with CIEDs. However, patients with a history of arrhythmia are more prone to arrhythmic events during and after radiation. These findings highlight the need for personalized arrhythmia management strategies and further research to understand the mechanisms underlying the antiarrhythmic effects of thoracic radiation. Graphical Abstract

Abstract Roadside habitat has been touted as a conservation opportunity for insect pollinators, including the declining monarch butterfly. The spectacular monarch migration is under threat from the loss of habitat and the decline of their milkweed host plants. In the northern part of their range, roadsides could potentially produce millions of monarchs annually due to high densities of milkweed; however, roadside milkweed can accumulate chemicals from roads, such as sodium from road salt. Controlled lab studies have shown mixed effects of sodium on monarch development: small increases can be beneficial as sodium is an important micronutrient in brain and muscle development, but large increases can sometimes decrease survival. It is unclear how dietary sodium affects performance in ecologically relevant conditions and the migration itself. In this experiment, we raised monarchs outdoors, in migration‐inducing conditions, on milkweed sprayed with three levels of sodium chloride. We released 2464 tagged monarchs and held an additional 246 for further lab assays. While our recovery rates to the wintering grounds were low (N = 7 individuals), individuals from all three sodium chloride treatments made it to Mexico. Butterflies reared on control milkweed and low salt concentrated sodium in their tissues, while those on high salt diets excreted sodium, suggesting high salt levels were above a physiological optimum. There were no effects of treatment on wing coloration, survival, body size, immunity, or parasite prevalence. Taken together, our results suggest that monarchs are robust to levels of sodium in milkweeds found along roadsides, which is promising with respect to the toxicity of roadside plants.

BackgroundThere are a growing number of evidence-based interventions (EBIs) for autistic individuals, but few are successfully implemented with fidelity in under-resourced communities and with families from traditionally disenfranchised groups. Implementation science offers tools to increase EBI use in communities, but most implementation strategies are designed specific to a single EBI. It is not feasible to develop a new implementation strategy each time a new EBI is introduced in the community. Therefore, to test the effectiveness and generalizability of implementation strategies we are developing and testing a multifaceted implementation strategy with three EBIs concurrently. The goal of this protocol paper is to describe the randomized field trial of an implementation strategy for use across autism EBIs, diverse settings and participants, with the goal of increasing rapid uptake of effective practices to reach our most vulnerable children.MethodsWe developed a multifaceted implementation strategy called Using Novel Implementation Tools for Evidence-based intervention Delivery (UNITED) to facilitate the implementation and sustainment of three EBIs in under-resourced settings. We will compare fidelity to, and effectiveness of, each intervention [Mind the Gap (MTG), Remaking Recess (RR), Self-Determined Learning Model of Instruction (SDLMI)] with and without UNITED in a randomized field trial. Randomization will be stratified using a minimization allocation method. We will train community practitioners using remote delivery of modules specific to the intervention, and active coaching via Zoom for at least 6 sessions and up to 12 as dictated by each EBI. Our primary outcome is fidelity to each EBI, and our secondary outcome is at the child or family level (family empowerment for MTG, child peer social engagement for RR, and adolescent self-determination for SDLMI, respectively). We will measure progress through the implementation phases using the Stages of Implementation Completion and cost-effectiveness of UNITED.DiscussionThe results of this study will provide rigorous data on the effectiveness and generalizability of one relatively light-touch implementation strategy in increasing use of autism EBIs and associated outcomes in diverse under resourced public service settings for underrepresented autistic youth.Trial registrationMind the Gap: Clinicaltrials.gov Identifier:  NCT04972825 (Date registered July 22, 2021); Remaking Recess: Clinicaltrials.gov Identifier:  NCT04972838 (Date registered July 22, 2021); Self-Determined Learning Model of Instruction: Clinicaltrials.gov Identifier:  NCT04972851 (Date registered July 22, 2021).

Abstract Aims Oncological patients suspected at risk for cardiotoxicity are recommended to undergo intensified cardiological surveillance. We investigated the value of cardiac biomarkers and patient‐related risk factors [age, cardiovascular risk factors (CVRFs), and cardiac function] for the prediction of all‐cause mortality (ACM) and the development of cardiotoxicity. Methods and results Between January 2016 and December 2020, patients with oncological diseases admitted to the Cardio‐Oncology Unit at the Heidelberg University Hospital were included. They were evaluated by medical history, physical examination, 12‐lead electrocardiogram, 2D echocardiography, and cardiac biomarkers [high‐sensitivity cardiac troponin T (hs‐cTnT) and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP)]. The primary endpoint was defined as ACM and the secondary endpoint was defined as cardiotoxicity, as defined by the European Society of Cardiology. Of the 1971 patients enrolled, the primary endpoint was reached by 490 patients (25.7%) with a median of 363.5 [interquartile range (IQR) 121.8, 522.5] days after presentation. Hs‐cTnT of ≥ 7 ng/L [odds ratio (OR) 1.82, P

Abstract Switzerland’s livestock production causes high environmental costs and depends strongly on feed imports. While plant-based protein demand increases, the local grain legume production is negligible ( ~ 9000 hectares). Here, we investigated the potential of sustainable legume protein production based on an expert survey followed by a quantitative analysis based on yield, soil, terrain and climate data. Pea, soybean and faba bean showed high potential for Swiss agriculture given adaptions in policy, pricing and breeding. The potential grain legume production area was 107,734 hectares on suitable arable land (Scenario I). Switzerland’s self-sufficiency could be increased by cutting imports and maximizing legume production on 181,479 hectares (Scenario II) in expense of grassland and fodder maize. This would replace approximately 41% of animal protein consumption with plant-based protein, preserving 32% of milk and 24% of meat protein. In conclusion, domestic legume production could be substantially increased while improving human and environmental health.

Canopy temperature (CT) is often interpreted as representing leaf activity traits such as photosynthetic rates, gas exchange rates, or stomatal conductance. This interpretation is based on the observation that leaf activity traits correlate with transpiration which affects leaf temperature. Accordingly, CT measurements may provide a basis for high throughput assessments of the productivity of wheat canopies during early grain filling, which would allow distinguishing functional from dysfunctional stay-green. However, whereas the usefulness of CT as a fast surrogate measure of sustained vigor under soil drying is well established, its potential to quantify leaf activity traits under high-yielding conditions is less clear. To better understand sensitivity limits of CT measurements under high yielding conditions, we generated within-genotype variability in stay-green functionality by means of differential short-term pre-anthesis canopy shading that modified the sink:source balance. We quantified the effects of these modifications on stay-green properties through a combination of gold standard physiological measurements of leaf activity and newly developed methods for organ-level senescence monitoring based on timeseries of high-resolution imagery and deep-learning-based semantic image segmentation. In parallel, we monitored CT by means of a pole-mounted thermal camera that delivered continuous, ultra-high temporal resolution CT data. Our results show that differences in stay-green functionality translate into measurable differences in CT in the absence of major confounding factors. Differences amounted to approximately 0.8°C and 1.5°C for a very high-yielding source-limited genotype, and a medium-yielding sink-limited genotype, respectively. The gradual nature of the effects of shading on CT during the stay-green phase underscore the importance of a high measurement frequency and a time-integrated analysis of CT, whilst modest effect sizes confirm the importance of restricting screenings to a limited range of morphological and phenological diversity.

Abstract The efficacy of pembrolizumab monotherapy versus chemotherapy increased with increasing programmed death ligand 1 (PD‐L1) expression, as quantified by combined positive score (CPS; PD‐L1 expression on both tumour cells and immune cells) in patients with previously treated metastatic triple‐negative breast cancer (mTNBC) in the phase 3 KEYNOTE‐119 study. This exploratory analysis was conducted to determine whether the expression of PD‐L1 on tumour cells contributes to the predictive value of PD‐L1 CPS in mTNBC. PD‐L1 expression in tumour samples was assessed using PD‐L1 IHC 22C3 pharmDx and quantified using both CPS and tumour proportion score (TPS; PD‐L1 expression on tumour cells alone). Calculated immune cell density (CID) was defined as CPS minus TPS. The ability of each scoring method (CPS, TPS, and CID) to predict clinical outcomes with pembrolizumab was evaluated. With pembrolizumab, the area under the receiver operating characteristic curve was 0.69 (95% CI = 0.58–0.80) for CPS, 0.55 (95% CI = 0.46–0.64) for TPS, and 0.67 (95% CI = 0.56–0.77) for CID. After correction for cutoff prevalence, CPS performed as well as, if not better than, CID with respect to predicting objective response rate, progression‐free survival, and overall survival. Data from this exploratory analysis suggest that, although PD‐L1 expression on immune cells alone is predictive of response to programmed death 1 blockade in mTNBC, adding tumour PD‐L1 expression assessment (i.e. CPS, which combines immune cell and tumour cell PD‐L1 expression) may improve prediction. PD‐L1 CPS thus remains an effective and broadly applicable uniform scoring system for enriching response to programmed death 1 blockade with pembrolizumab in mTNBC as well as other tumour types.

Background For the majority of patients with atrial fibrillation (AF), disease management has improved in recent years. However, there are still populations underrepresented or excluded in current registries and randomized controlled trials. HERA‐FIB (Heidelberg Registry of Atrial Fibrillation) was planned to assess real‐world evidence for the prevalence, demographic characteristics and management of patients with the diagnosis of AF presenting consecutively to a chest pain unit. Methods and Results HERA‐FIB is a retrospective, observational, single‐center study on patients with a diagnosis of AF presenting to a chest pain unit from June 2009 until March 2020. This article describes the structure, governance, outcome assessment, quality and data collection processes of the registry. Additionally, characteristics of populations of special interest are described. The study consecutively enrolled 10 222 patients presenting with AF to the chest pain unit of the University Hospital of Heidelberg. Clinical parameters and patient characteristics were assessed retrospectively. Outcome parameters included rates for all‐cause death, stroke, myocardial infarction and major bleedings. We were able to investigate patient cohorts of special interest such as advanced chronic kidney disease, octogenarians, and those with acute coronary syndrome who are often underrepresented in current studies and randomized controlled trials. Conclusions HERA‐FIB is one of the largest real‐world single‐center retrospective registries on patients with AF, which captures the era of transition from vitamin K antagonists to non–vitamin K oral anticoagulation regimens in clinical practice and offers the possibility to investigate patient populations usually underrepresented or excluded in current available randomized controlled trials and registries. Registration URL: https://www.clinicaltrials.gov; unique identifier: NCT05995561.

Objective: The intrauterine environment during pregnancy is a critical factor in the development of obesity, diabetes, and cardiovascular disease in offspring. Maternal exercise prevents the detrimental effects of a maternal high fat diet on the metabolic health in adult offspring, but the effects of maternal exercise on offspring cardiovascular health have not been thoroughly investigated. Methods: To determine the effects of maternal exercise on offspring cardiovascular health, female mice were fed a chow (C; 21% kcal from fat) or high-fat (H; 60% kcal from fat) diet and further subdivided into sedentary (CS, HS) or wheel exercised (CW, HW) prior to pregnancy and throughout gestation. Offspring were maintained in a sedentary state and chow-fed throughout 52 weeks of age and subjected to serial echocardiography and cardiomyocyte isolation for functional and mechanistic studies. Results: High-fat fed sedentary dams (HS) produced female offspring with reduced ejection fraction (EF) compared to offspring from chow-fed dams (CS), but EF was preserved in offspring from high-fat fed exercised dams (HW) throughout 52 weeks of age. Cardiomyocytes from HW female offspring had increased kinetics, calcium cycling, and respiration compared to CS and HS offspring. HS offspring had increased oxidation of the RyR2 in cardiomyocytes coupled with increased baseline sarcomere length, resulting in RyR2 overactivity, which was negated in female HW offspring. Conclusions: These data suggest a role for maternal exercise to protect against the detrimental effects of a maternal high-fat diet on female offspring cardiac health. Maternal exercise improved female offspring cardiomyocyte contraction, calcium cycling, respiration, RyR2 oxidation, and RyR2 activity. These data present an important, translatable role for maternal exercise to preserve cardiac health of female offspring and provide insight on mechanisms to prevent the transmission of cardiovascular diseases to subsequent generations.

Abstract Background Persons with spinal cord injury (SCI) living in the community often require care. The boundaries between professional home care and informal care are blurred, and it is unclear who the typical user of home care is. The objective of this study was to describe the characteristics of persons with SCI using professional home care in Switzerland, determine the frequency of home care visits, and investigate the association of sociodemographic factors, SCI-specific characteristics, secondary health conditions, and functional independence with the use of home care. Methods We used cross-sectional data from the 2017 community survey of the Swiss Spinal Cord Injury Cohort Study (SwiSCI). Out of 3,959 eligible individuals 1294 completed the questionnaire and were included in the analysis (response rate 33%). Using descriptive statistics, differences between home care users and non-users as well as the frequency of home care visits were investigated. The association between sociodemographic factors, SCI-specific characteristics, secondary health conditions, functional independence and the use of home care was analyzed using multivariable logistic regression. Multiple imputation was used to account for missing data. Results Of 1,294 participants, 280 (22%) used professional home care. The median weekly professional home care duration was 6 h (Q1 = 2, Q3 = 12). More home care was used in persons with lower functional independence (Odds ratio (OR) 0.30 per 10 unit decrease in the Spinal Cord Independence Measure, 95%-Confidence interval (CI) 0.24–0.37), fewer secondary health conditions (OR 0.96 per unit Spinal Cord Injury Secondary Conditions Scale, 95%-CI 0.94–0.99), tetraplegia (OR 2.77, 95%-CI 1.92–4.00), women (OR 2.42, 95%-CI 1.70–3.43), higher age (OR 1.22 per 10 years increase, 95%-CI 1.06–1.39), living alone (OR 2.48, 95%-CI 1.53–4.03), and those receiving support from an informal caregiver (OR 1.88, 95%-CI 1.27–2.77). Conclusions This is the first study to examine the use of professional home care from the perspective of persons with SCI in Switzerland. Lower functional independence strongly predicts increased home care use. The findings showed that professional home care complements informal care and is more likely to be used by individuals with SCI who live alone, have tetraplegia, and are female.

Abstract The potential effects of microplastic particle exposure on environmental organisms has sparked intense research activities. Various studies have been conducted, however on a limited set of mostly pristine polymer materials. In parallel to the ongoing research activities, it is discussed to include non-natural polymers into the registration process under REACH. Currently, non-natural polymers are exempted from registration, based on the general assumption of being non-hazardous due to their high molecular weight. In addition, the extensive number of polymers exceeding the registration capacities was mentioned as a reason for exemption. Hence, relevant polymers requiring a registration shall be selected according to specific criteria that help to identify those with a concern for hazardous effects. In the line of these developments we here present the results of a systematic ecotoxicity testing of 16 microplastic particles of different polymer composition, part of which are micronized polymer powders used in 3D printing (intentionally produced primary microplastic, losing particle shape by the 3D printing). All polymer materials were systematically varied and extensively characterised with regard to their properties (e.g. particle size, cross-linking, molar mass distribution, end groups, reactivity). Most of the polymers exerted toxicity in 48 h acute Daphnia magna immobilisation assay and 72 h chronic Raphidocelis subcapitata growth inhibition assay, except one PA and one HDPE material showing toxicity in D. magna, and one HDPE material showing toxicity in green algae. From these results we conclude that none of the microplastic particles studied here, independent of their polymer properties, give raise to concern for hazardous effects.

Abstract Elderly patients with AML ineligible for induction have a dismal prognosis; hence disease stabilization is a primary treatment goal. This case of a 75-year-old patient with secondary AML receiving the combination of decitabine and ATRA (within the DECIDER trial, NCT00867672) demonstrates an above-average survival. The therapy administered over 52 cycles led to complete molecular and hematological remission and resulted in 5.3 years overall survival. Clonal evolution of the leukemic clone could be demonstrated using DNA sequencing methods. According to the literature, this case constitutes the longest continued HMA exposure in an elderly AML patient ineligible for standard chemotherapy.

This virtual workshop was convened by the National Heart, Lung, and Blood Institute, in partnership with the Office of Strategic Coordination of the Office of the National Institutes of Health Director, and held September 2 to 3, 2020. The intent was to assemble a multidisciplinary group of experts in basic, translational, and clinical research in neuroscience and cardiopulmonary disorders to identify knowledge gaps, guide future research efforts, and foster multidisciplinary collaborations pertaining to autonomic neural mechanisms of cardiopulmonary regulation. The group critically evaluated the current state of knowledge of the roles that the autonomic nervous system plays in regulation of cardiopulmonary function in health and in pathophysiology of arrhythmias, heart failure, sleep and circadian dysfunction, and breathing disorders. Opportunities to leverage the Common Fund's SPARC (Stimulating Peripheral Activity to Relieve Conditions) program were characterized as related to nonpharmacologic neuromodulation and device-based therapies. Common themes discussed include knowledge gaps, research priorities, and approaches to develop novel predictive markers of autonomic dysfunction. Approaches to precisely target neural pathophysiological mechanisms to herald new therapies for arrhythmias, heart failure, sleep and circadian rhythm physiology, and breathing disorders were also detailed.