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Abstract Background This study explores the health status differences between migrants and native Germans, focusing on potential disparities in their workloads. Physical and mental workloads can negatively impact individual health. Since various occupations come with distinct health-related patterns, occupational selection may contribute to systematic health disparities among socio-economic groups. Given the generally poorer health of migrants, they might experience systematic workload differences overall. Methods We suggest a conceptual framework for the empirical analysis based on the theory of health as a durable good with health consumption and health investment as key parameters. We quantify the role of work tasks, job requirements and working conditions on individual health based on detailed information from the BIBB/BAuA labour force survey 2012 and 2018. Results The empirical results reveal that migrants, i.e. foreigners and German citizens with a migration background, have a higher perception of workload and related health afflictions within the same occupation. Native Germans, on the other hand, experience a higher burden by high job requirements, both physically and mentally. The findings imply heterogeneous health impacts of work for migrants and native Germans due to differences in health consumption. Conclusions The analysis shows that migrants report worse health than natives, with stronger negative effects of work-related conditions on their health, both physically and mentally. Women, in general, report poorer health conditions than men. The findings emphasize the importance of promoting human capital to reduce economic and health disparities, though caution is advised regarding affirmative actions for migrants; further research is needed to understand the underlying mechanisms and address these issues effectively.

A life cycle inventory (LCI) dataset for food waste management was developed using secondary data from scientific literature and government reports. EPA reports on food waste management were used as the basis for collecting literature to review. Unit process parameters from the reviewed literature are compiled and combined with engineering calculations to generate LCI for food management pathways. Both the literature values and engineering calculations are reviewed and documented with notes indicating any potential limitations in the dataset.The Excel-based inventory model includes pathways for anaerobic digestion, composting – windrow and aerated static pile, landfilling, and incineration. The model includes default parameter value selections, but the inventory may also be generated using user-specified parameter values. The model includes site-specific unit process models that do not have default parameter values pre-selected. Users can specify parameter values within these unit processes to generate LCI data for the food waste management pathways in line with their project scope. Site-specific unit processes include options such as biogas and landfill gas utilization and treatment of compost and digestate. This dataset and model can be used to generate LCI for evaluating food waste management in a comprehensive life cycle assessment study.

Abstract Retinal optical coherence tomography has been identified as biomarker for disease progression in relapsing-remitting multiple sclerosis (RRMS), while the dynamics of retinal atrophy in progressive MS are less clear. We investigated retinal layer thickness changes in RRMS, primary and secondary progressive MS (PPMS, SPMS), and their prognostic value for disease activity. Here, we analyzed 2651 OCT measurements of 195 RRMS, 87 SPMS, 125 PPMS patients, and 98 controls from five German MS centers after quality control. Peripapillary and macular retinal nerve fiber layer (pRNFL, mRNFL) thickness predicted future relapses in all MS and RRMS patients while mRNFL and ganglion cell-inner plexiform layer (GCIPL) thickness predicted future MRI activity in RRMS (mRNFL, GCIPL) and PPMS (GCIPL). mRNFL thickness predicted future disability progression in PPMS. However, thickness change rates were subject to considerable amounts of measurement variability. In conclusion, retinal degeneration, most pronounced of pRNFL and GCIPL, occurs in all subtypes. Using the current state of technology, longitudinal assessments of retinal thickness may not be suitable on a single patient level.

Objective:. The primary objective of this study was to develop a length of stay (LOS) prediction model. Background:. Predicting the LOS is crucial for patient care, planning, managing expectations, and optimizing hospital resources. Prolonged LOS after colorectal surgery is largely influenced by complications, and an accurate prediction model could significantly benefit patient outcomes and healthcare efficiency. Methods:. This study included patients who underwent colorectal surgery in 14 different hospitals between January 2016 and December 2020. Two distinct random forest models were developed: one solely based on preoperative variables (preoperative prediction model [PP model]) and the other incorporating both preoperative and intraoperative variables (intraoperative prediction model [IP model]). Both models underwent validation using 10-fold cross-validation. The discriminative power of the model was assessed using the area under the curve (AUC), and calibration was evaluated using a calibration curve. The 2 developed models were compared using DeLong test. Results:. A total of 2140 patients were included in the analysis. After internal validation, the PP model achieved an AUC of 0.75 (95% confidence interval [CI]: 0.73–0.77), and the IP model achieved an AUC of 0.84 (95% CI: 0.82–0.85). The difference in discrimination between the 2 models was statistically significant (DeLong test, P < 0.001). Both models exhibited good calibration. Conclusions:. Incorporating intraoperative parameters enhances the accuracy of the predictive model for LOS after colorectal surgery. Improving LOS prediction can assist in managing the increasing number of patients and optimizing the allocation of healthcare resources.

# Background Restoring maximal muscle strength of the knee extensors (KE) and knee flexors (KF) following anterior cruciate ligament (ACL) injury and ACL reconstruction is of great importance to reduce the re-injury rate after ACL reconstruction and to reduce the risk of knee osteoarthritis. Therefore, it is essential that clinicians and healthcare providers use valid and reliable measures to assess knee muscle strength to ensure a safe return to sport. # Purpose To evaluate the reliability (test-retest reliability, inter-tester reliability and test-retest agreement) and validity (concurrent validity, convergent validity and ForceFrame (FF) vs. isokinetic dynamometer (ID) agreement) of the ForceFrame (FF) dynamometer during isometric testing of the knee extensors and flexors. # Study Design Cross-sectional study # Material and Methods Twenty-seven participants with ACL injury or reconstruction were recruited for participation in this study. maximal voluntary isometric contration (MVIC) of the knee extensors and flexors was tested on two separate days. Day one included validity assessments with FF, a gold-standard ID and a handheld dynamometer (HHD). Day two included reliability assessments with FF performed by two assessors. Main outcome measures were day-to-day test-retest reliability and agreement and inter-tester reliability of FF, and concurrent validity (FF vs. an ID and a HHD). Reliability was tested as test-retest and inter-tester reliability using interclass correlation coefficient (ICC), while agreement was tested using Bland & Altman plots with limits of agreement (LOA), standard error of measurement (SEM) and smallest detectable change (SDC). Concurrent validity between FF, ID, and HHD was assessed using Pearson's correlations and mean difference was evaluated by Bland & Altman plots. # Results Twenty-seven participants (10 females, 17 males) with a median age of 25 years (range 19-60) were included in this study. There was a good day-to-day test-retest reliability for MVIC of KE (ICC=0.77, CI95:0.48-0.90) and KF (ICC=0.83, CI95:0.61-0.92) and excellent inter-tester reliability for MVIC of KE (ICC=0.97, CI95:0.94-0.98) and KF (ICC=0.93, 95CI:0.85-0.97). Standard error of measurement (SEM) was 8% and 9%, while the smallest detectable change (SDC) was 22% and 27% for KE and KF, respectively. FF showed fair concurrent validity compared to ID for KE (r=0.56), poor concurrent validity for knee flexors (KF (r=0.24) and compared to HHD a moderate correlation for KE (r=0.74) and poor correlation for KF (r=0.12). Bland & Altman plots between FF and the ID showed a mean difference of -0.51 Nm/kg for KE and -0.32Nm/kg for KF. # Conclusions FF can be used to obtain reliable and valid results to assess MVIC of the KE, but not the KF. It should be noted that absolute results produced by the FF may be considered an underestimation of actual MVIC. The test position to assess KF in FF does not appear to be optimal, and different test-positions may be considered. # Level of evidence Level 3

Abstract Background Health professionals are increasingly called upon and willing to engage in planetary health care and management. However, so far, this topic is rarely covered in medical curricula. As the need for professional communication is particularly high in this subject area, this study aimed to evaluate whether the objective structured clinical examination (OSCE) could be used as an accompanying teaching tool. Methods During the winter semester 2022/2023, 20 third- and fifth-year medical students voluntarily participated in a self-directed online course, three workshops, and a formal eight-station OSCE on planetary health care and management. Each examinee was also charged alternatingly as a shadower with the role of providing feedback. Experienced examiners rated students’ performance using a scoring system supported by tablet computers. Examiners and shadowers provided timely feedback on candidates` performance in the OSCE. Immediately after the OSCE, students were asked about their experience using a nine-point Likert-scale survey and a videotaped group interview. Quantitative analysis included the presentation of the proportional distribution of student responses to the survey and of box plots showing percentages of maximum scores for the OSCE performance. The student group interview was analyzed qualitatively. Results Depending on the sub-theme, 60% -100% of students rated the subject of planetary health as likely to be useful in their professional lives. Similar proportions (57%-100%) were in favour of integrating planetary health into required courses. Students perceived learning success from OSCE experience and feedback as higher compared to that from online courses and workshops. Even shadowers learned from observation and feedback discussions. Examiners assessed students’ OSCE performance at a median of 80% (interquartile range: 83%-77%) of the maximum score. Conclusions OSCE can be used as an accompanying teaching tool for advanced students on the topic of planetary health care and management. It supports learning outcomes, particularly in terms of communication skills to sensitise and empower dialogue partners, and to initiate adaptation steps at the level of individual patients and local communities.

As part of the Horizon 2020 InfraROB project aimed at enhancing road safety through innovative robotic solutions, a compact autonomous vehicle has been developed to repair asphalt potholes. Central to this system is a 3D printer capable of extruding a novel cold-asphalt mixture, specifically designed for patching road surfaces. The printer is mounted on a small robot that autonomously navigates to potholes, while the human operator controls the operation from a secure location outside the traffic area. The system’s development involved several key steps: designing the repair mixture, constructing the 3D printer for mixture extrusion, implementing a photogrammetric technique to accurately measure pothole geometry for printing, and integrating the extrusion system with the robotic platform. Two preliminary tests were conducted in controlled environments at Sapienza University of Rome to check the reliability of calculation of the amount of material needed to fill in the potholes. Finally, the entire procedure was tested on an Italian motorway, demonstrating the system’s functionality without encountering operational issues.

Abstract Background Data are the evidentiary basis for scientific hypotheses, analyses and publication, for policy formation and for decision-making. They are essential to the evaluation and testing of results by peer scientists both present and future. There is broad consensus in the scientific and conservation communities that data should be freely, openly available in a sustained, persistent and secure way, and thus standards for 'free' and 'open' access to data have become well developed in recent years. The question of effective access to data remains highly problematic. Discussion Specifically with respect to scientific publishing, the ability to critically evaluate a published scientific hypothesis or scientific report is contingent on the examination, analysis, evaluation - and if feasible - on the re-generation of data on which conclusions are based. It is not coincidental that in the recent 'climategate' controversies, the quality and integrity of data and their analytical treatment were central to the debate. There is recent evidence that even when scientific data are requested for evaluation they may not be available. The history of dissemination of scientific results has been marked by paradigm shifts driven by the emergence of new technologies. In recent decades, the advance of computer-based technology linked to global communications networks has created the potential for broader and more consistent dissemination of scientific information and data. Yet, in this digital era, scientists and conservationists, organizations and institutions have often been slow to make data available. Community studies suggest that the withholding of data can be attributed to a lack of awareness, to a lack of technical capacity, to concerns that data should be withheld for reasons of perceived personal or organizational self interest, or to lack of adequate mechanisms for attribution. Conclusions There is a clear need for institutionalization of a 'data publishing framework' that can address sociocultural, technical-infrastructural, policy, political and legal constraints, as well as addressing issues of sustainability and financial support. To address these aspects of a data publishing framework - a systematic, standard approach to the formal definition and public disclosure of data - in the context of biodiversity data, the Global Biodiversity Information Facility (GBIF, the single inter-governmental body most clearly mandated to undertake such an effort) convened a Data Publishing Framework Task Group. We conceive this data publishing framework as an environment conducive to ensure free and open access to world's biodiversity data. Here, we present the recommendations of that Task Group, which are intended to encourage free and open access to the worlds' biodiversity data.

Abstract Background A professional recognition mechanism is required to encourage expedited publishing of an adequate volume of 'fit-for-use' biodiversity data. As a component of such a recognition mechanism, we propose the development of the Data Usage Index (DUI) to demonstrate to data publishers that their efforts of creating biodiversity datasets have impact by being accessed and used by a wide spectrum of user communities. Discussion We propose and give examples of a range of 14 absolute and normalized biodiversity dataset usage indicators for the development of a DUI based on search events and dataset download instances. The DUI is proposed to include relative as well as species profile weighted comparative indicators. Conclusions We believe that in addition to the recognition to the data publisher and all players involved in the data life cycle, a DUI will also provide much needed yet novel insight into how users use primary biodiversity data. A DUI consisting of a range of usage indicators obtained from the GBIF network and other relevant access points is within reach. The usage of biodiversity datasets leads to the development of a family of indicators in line with well known citation-based measurements of recognition.

BackgroundThis preliminary retrospective cohort study investigates the potential additive prophylactic effect of erenumab, a fully human monoclonal antibody that blocks the calcitonin gene-related peptide receptor, in combination with ongoing onabotulinumtoxin A (onaBoNT-A) treatment in patients suffering from chronic migraine.MethodsThe study included 218 patients and investigated the effects of adding erenumab to the existing treatment regimen. The primary outcome was the MIDAS (Migraine Disability Assessment) score assessed 3 months after the introduction of erenumab.ResultsThe results indicated a significant improvement of the MIDAS score, suggesting a reduction in migraine-related disability following the addition of erenumab to onaBoNT-A. In the inter group comparison, dual therapy showed a significantly greater reduction of the MIDAS when compared to a switch from onaBoNT-A to erenumab monotherapy, but not compared to initiation of onaBoNT-A monotherapy. It is hypothesized that the observed additive effects are due to the independent modes of action of erenumab and onabotulinumtoxin A.ConclusionThis study suggests that the combination of erenumab with onaBoNT-A may offer an improved approach for the treatment of chronic migraine in selected patients. However, the results highlight the need for prospective, controlled studies to validate these findings and determine the optimal combination of treatments tailored to the individual patient.

The dataset contains ∼1.1 million records of total greenhouse gases directly emitted annually by economic sectors and households in the US from 2012-2020. Data are given for 16 unique greenhouse gases by 118 aggregate sectors for each state, and as totals by these aggregate sectors as well as by 540 detailed sectors at the national level. The dataset is a product of updated sector attribution models that improve upon the National Greenhouse Gas Industry Attribution Model. This paper provides documentation of the methods used to produce these datasets and proof of validation of the dataset, along with relevant supporting tables, figures, and source code.

Abstract Neurological manifestations of coronavirus disease 2019 (COVID-19) have been frequently described. In this prospective study of hospitalized COVID-19 patients without a history of neurological conditions, we aimed to analyze their prevalence and prognostic value based on established, standardized and objective methods. Patients were investigated using a multimodal electrophysiological approach, accompanied by neuropsychological and neurological examinations. Prevalence rates of central (CNS) and peripheral (PNS) nervous system affections were calculated and the relationship between neurological affections and mortality was analyzed using Firth logistic regression models. 184 patients without a history of neurological diseases could be enrolled. High rates of PNS affections were observed (66% of 138 patients receiving electrophysiological PNS examination). CNS affections were less common but still highly prevalent (33% of 139 examined patients). 63% of patients who underwent neuropsychological testing (n = 155) presented cognitive impairment. Logistic regression models revealed pathology in somatosensory evoked potentials as an independent risk factor of mortality (Odds Ratio: 6.10 [1.01–65.13], p = 0.049). We conclude that hospitalized patients with moderate to severe COVID-19 display high rates of PNS and CNS affection, which can be objectively assessed by electrophysiological examination. Electrophysiological assessment may have a prognostic value and could thus be helpful to identify patients at risk for deterioration.

Abstract Background Embolic stroke of undetermined source (ESUS) accounts for a substantial proportion of ischaemic strokes. A stroke recurrence score has been shown to predict the risk of recurrent stroke in patients with ESUS based on a combination of clinical and imaging features. This study aimed to externally validate the performance of the ESUS recurrence score using data from a randomized controlled trial. Methods The validation dataset consisted of eligible stroke patients with available magnetic resonance imaging (MRI) data enrolled in the PreDAFIS sub-study of the MonDAFIS study. The score was calculated using three variables: age (1 point per decade after 35 years), presence of white matter hyperintensities (2 points), and multiterritorial ischaemic stroke (3 points). Patients were assigned to risk groups as described in the original publication. The model was evaluated using standard discrimination and calibration methods. Results Of the 1054 patients, 241 (22.9%) were classified as ESUS. Owing to insufficient MRI quality, three patients were excluded, leaving 238 patients (median age 65.5 years [IQR 20.75], 39% female) for analysis. Of these, 30 (13%) patients experienced recurrent ischaemic stroke or transient ischemic attack (TIA) during a follow-up period of 383 patient-years, corresponding to an incidence rate of 7.8 per 100 patient-years (95% CI 5.3–11.2). Patients with an ESUS recurrence score value of ≥ 7 had a 2.46 (hazard ratio (HR), 95% CI 1.02–5.93) times higher risk of stroke recurrence than patients with a score of 0–4. The cumulative probability of stroke recurrence in the low-(0–4), intermediate-(5–6), and high-risk group (≥ 7) was 9%, 13%, and 23%, respectively (log-rank test, χ2 = 4.2, p = 0.1). Conclusions This external validation of a published scoring system supports a threshold of ≥ 7 for identifying ESUS patients at high-risk of stroke recurrence. However, further adjustments may be required to improve the model’s performance in independent cohorts. The use of risk scores may be helpful in guiding extended diagnostics and further trials on secondary prevention in patients with ESUS. Trial registration: Clinical Trials, NCT02204267. Registered 30 July 2014, https://clinicaltrials.gov/ct2/show/NCT02204267 .

Abstract Ocrelizumab is a B cell-depleting drug widely used in relapsing–remitting multiple sclerosis (RRMS) and primary-progressive MS. In RRMS, it is becoming increasingly apparent that accumulation of disability not only manifests as relapse-associated worsening (RAW) but also as progression independent of relapse activity (PIRA) throughout the disease course. This study’s objective was to investigate the role of PIRA in RRMS patients treated with ocrelizumab. We performed a single-center, retrospective, cross-sectional study of clinical data acquired at a German tertiary multiple sclerosis referral center from 2018 to 2022. All patients with RRMS treated with ocrelizumab for at least six months and complete datasets were analyzed. Confirmed disability accumulation (CDA) was defined as a ≥ 12-week confirmed increase from the previous expanded disability status scale (EDSS) score of ≥ 1.0 if the previous EDSS was ≤ 5.5 or a ≥ 0.5-point increase if the previous EDSS was > 5.5. PIRA was defined as CDA without relapse since the last EDSS measurement and at least for the preceding 12 weeks. RAW was defined as CDA in an interval of EDSS measurements with ≥ 1 relapses. Cox proportional hazard models were used to analyze the probability of developing PIRA depending on various factors, including disease duration, previous disease-modifying treatments (DMTs), and optical coherence tomography-assessed retinal degeneration parameters. 97 patients were included in the analysis. Mean follow-up time was 29 months (range 6 to 51 months). 23.5% developed CDA under ocrelizumab therapy (n = 23). Of those, the majority developed PIRA (87.0% of CDA, n = 20) rather than RAW (13.0% of CDA, n = 3). An exploratory investigation using Cox proportional hazards ratios revealed two possible factors associated with an increased probability of developing PIRA: a shorter disease duration prior to ocrelizumab (p = 0.02) and a lower number of previous DMTs prior to ocrelizumab (p = 0.04). Our data show that in ocrelizumab-treated RRMS patients, the main driver of disability accumulation is PIRA rather than RAW. Furthermore, these real-world data show remarkable consistency with data from phase 3 randomized controlled trials of ocrelizumab in RRMS, which may increase confidence in translating results from tightly controlled RCTs into the real-world clinical setting.

This study deals with synthetic biomaterials that are biocompatible and mechanically stable to serve as a potential bone graft for improved mandibular reconstruction. To fabricate novel hybrid scaffolds containing beta-tricalcium phosphate (β-TCP) and zirconia (ZrO2), 3D printing was combined with Freeze Foaming to achieve a certain porosity, mimicking cancellous bone. The aim was to characterize the differentiation capacity of human pre-osteoblasts on the hybrid scaffolds. Although a good biocompatibility was demonstrated for the tested components of the hybrid scaffold, pure β-TCP foams showed the best results regarding osteogenic differentiation and pro-inflammatory processes. To enhance the osteoinductive properties of the β-TCP foam, the structures were also biofunctionalized with bone morphogenic protein 2 (BMP–2) and its effect was analyzed either on single cell cultures of pre-osteoblasts or pre-osteoblasts directly co-cultured with human peripheral blood mononuclear cells (PBMCs). The latter served to analyze the induction of bone remodelling processes. The immobilization of BMP-2 on scaffolds and its biological accessibility could be demonstrated, however, the biofunctionalization did not result in an enhanced differentiation capacity and bone remodeling processes of either pre-osteoblasts or directly co-cultured pre-osteoblasts and PBMCs.

The soil water retention curve (SWRC) is a key soil property required for predicting basic hydrological processes. The SWRC is often obtained in the laboratory with non-harmonized methods. Moreover, procedures associated with each method are not standardized. This can induce a lack of reproducibility between laboratories using different methods and procedures or using the same methods with different procedures. The goal of this study was to estimate the inter- and intralaboratory variability of the measurement of the wet part (from 10 to 300 hPa) of the SWRC. An interlaboratory comparison was carried out between 14 laboratories, using artificially constructed, porous reference samples that were transferred between laboratories according to a statistical design. The retention measurements were modelled by a series of linear mixed models using a Bayesian approach. This allowed the detection of sample-to-sample variability, interlaboratory variability, intralaboratory variability and the effects of sample changes between measurements. The greatest portion of the differences in the measurement of SWRCs was due to interlaboratory variability. The intralaboratory variability was highly variable depending on the laboratory. Some laboratories successfully reproduced the same SWRC on the same sample, while others did not. The mean intralaboratory variability over all laboratories was smaller than the mean interlaboratory variability. A possible explanation for these results is that all laboratories used slightly different methods and procedures. We believe that this result may be of great importance regarding the quality of SWRC databases built by pooling SWRCs obtained in different laboratories. The quality of pedotransfer functions or maps that might be derived is probably hampered by this inter- and intralaboratory variability. The way forward is that measurement procedures of the SWRC need to be harmonized and standardized.

Background: Due to centralization and super-specialization in medicine, hospital mergers are increasingly common. Their effect on postoperative outcomes in highly specialized surgical departments is unclear. As quality metrics often worsen after major organizational changes, preservation of quality of care during an hospital merge is of the utmost importance. Objective: To evaluate the effect of a merger of two Dutch university hospitals on quality of surgical care, volume, and timeliness of care. Methods: The upper gastro-intestinal and hepato-biliary-pancreatic sections merged on the 27th of January 2020 and the 31th of May 2021 respectively. Outcomes of all adult surgical patients were compared six months before and six months after the merger. Short-term quality metrics, volume, and timeliness of care were assessed. Results: Overall, a cohort of 631 patients were included of whom 195 were upper gastro-intestinal (97 prior to the merger, 98 after the merger) and 436 (223 prior to the merger, 213 after) hepato-biliary-pancreatic patients. There were no differences in mortality, readmission, number and severity of complications, volume, and timeliness of care six months post-merger as compared to before merger. Conclusion: This study shows that a hospital merger of two university hospitals can be performed without jeopardizing patient safety and while benefitting from centralization of highly specialized care and enhancement of medical research. Key message: This study investigated the impact of a merger of two Dutch university hospitals on quality of care, timeliness of care, and volume. It showed no deterioration in the evaluated short-term quality metrics, volume or timeliness for upper GI and HPB surgery, suggesting that a hospital merger of two university hospitals can be performed safely, while benefitting from centralization of highly specialized care and enhancement of medical research.

Important topics in land–atmosphere (L–A) feedback research are water and energy balances and heterogeneities of fluxes at the land surface and in the atmospheric boundary layer (ABL). To target these questions, the Land–Atmosphere Feedback Observatory (LAFO) has been installed in southwestern Germany. The instrumentation allows comprehensive and high-resolution measurements from the bedrock to the lower free troposphere. Grouped into three components, atmosphere, soil and land surface, and vegetation, the LAFO observation strategy aims for simultaneous measurements in all three compartments. For this purpose the LAFO sensor synergy contains lidar systems to measure the atmospheric key variables of humidity, temperature and wind. At the land surface, eddy covariance stations are operated to record the energy distribution of radiation, sensible, latent and ground heat fluxes. Together with a water and temperature sensor network, the soil water content and temperature are monitored in the agricultural investigation area. As for vegetation, crop height, leaf area index and phenological growth stage values are registered. The observations in LAFO are organized into operational measurements and intensive observation periods (IOPs). Operational measurements aim for long time series datasets to investigate statistics, and we present as an example the correlation between mixing layer height and surface fluxes. The potential of IOPs is demonstrated with a 24 h case study using dynamic and thermodynamic profiles with lidar and a surface layer observation that uses the scanning differential absorption lidar to relate atmospheric humidity patterns to soil water structures. Both IOPs and long-term observations will provide new insight into exchange processes and their statistics for improving the representation of L–A feedbacks in climate and numerical weather prediction models. The lidar component in particular will support the investigation of coupling to the atmosphere.

Background Lower socioeconomic status (SES) is associated with higher mortality rates and the likelihood of receiving less evidence-based treatment after stroke. In contrast, little is known about the impact of SES on recovery after discharge from inpatient rehabilitation. The aim of this study was to investigate the influence of SES on long-term recovery after stroke.Patients and methods In a prospective, observational, multicentre study, inpatients were recruited towards the end of rehabilitation. The 12-month follow-up focussed on upper limb motor recovery, measured by the Fugl-Meyer score. A clinically relevant improvement of ≥5.25 points was considered recovery. Patient-centric measures such as the Patient-reported Outcomes Measurement Information System-Physical Health (PROMIS-10 PH) provided secondary outcomes. Information on schooling, vocational training, income and occupational status pre-stroke entered a multidimensional SES index. Multivariate logistic regression models calculating odds ratios (ORs) and corresponding confidence intervals (CIs) were applied. SES was added to an initial model including age, sex and baseline neurological deficit. Additional exploratory analyses examined the association between SES and outpatient treatment.Results One hundred and seventy-six patients were enrolled of whom 98 had SES and long-term recovery data. Model comparisons showed the SES-model superior to the initial model (Akaike information criterion (AIC): 123 vs. 120, Pseudo R2: 0.09 vs. 0.13). The likelihood of motor recovery (OR = 17.12, 95%CI = 1.31; 224.18) and PROMIS-10 PH improvement (OR = 20.76, 95%CI = 1.28; 337.11) were significantly increased with higher SES, along with more frequent use of outpatient therapy (p = .02).Conclusions Higher pre-stroke SES is associated with better long-term recovery after discharge from rehabilitation. Understanding these factors can improve outpatient long-term stroke care and lead to better recovery.KEY MESSAGEHigher pre-stroke socioeconomic status (SES) is associated with better long-term recovery after discharge from rehabilitation both in terms of motor function and self-reported health status.Higher SES is associated with significantly higher utilization of outpatient therapies.Discharge management of rehabilitation clinics should identify and address socioeconomic factors in order to detect individual needs and to improve outpatient recovery. Article registration: clinicaltrials.gov NCT04119479.

IntroductionGiven its wide availability and cost-effectiveness, multidimensional flow cytometry (mFC) became a core method in the field of immunology allowing for the analysis of a broad range of individual cells providing insights into cell subset composition, cellular behavior, and cell-to-cell interactions. Formerly, the analysis of mFC data solely relied on manual gating strategies. With the advent of novel computational approaches, (semi-)automated gating strategies and analysis tools complemented manual approaches.MethodsUsing Bayesian network analysis, we developed a mathematical model for the dependencies of different obtained mFC markers. The algorithm creates a Bayesian network that is a HC tree when including raw, ungated mFC data of a randomly selected healthy control cohort (HC). The HC tree is used to classify whether the observed marker distribution (either patients with amyotrophic lateral sclerosis (ALS) or HC) is predicted. The relative number of cells where the probability q is equal to zero is calculated reflecting the similarity in the marker distribution between a randomly chosen mFC file (ALS or HC) and the HC tree.ResultsIncluding peripheral blood mFC data from 68 ALS and 35 HC, the algorithm could correctly identify 64/68 ALS cases. Tuning of parameters revealed that the combination of 7 markers, 200 bins, and 20 patients achieved the highest AUC on a significance level of p < 0.0001. The markers CD4 and CD38 showed the highest zero probability. We successfully validated our approach by including a second, independent ALS and HC cohort (55 ALS and 30 HC). In this case, all ALS were correctly identified and side scatter and CD20 yielded the highest zero probability. Finally, both datasets were analyzed by the commercially available algorithm ‘Citrus’, which indicated superior ability of Bayesian network analysis when including raw, ungated mFC data.DiscussionBayesian network analysis might present a novel approach for classifying mFC data, which does not rely on reduction techniques, thus, allowing to retain information on the entire dataset. Future studies will have to assess the performance when discriminating clinically relevant differential diagnoses to evaluate the complementary diagnostic benefit of Bayesian network analysis to the clinical routine workup.

BACKGROUND:Retinal optical coherence tomography (OCT) is a clinical and research tool in multiple sclerosis, where it has shown significant retinal nerve fiber (RNFL) and ganglion cell (RGC) layer thinning, while postmortem studies have reported RGC loss. Although retinal pathology in experimental autoimmune encephalomyelitis (EAE) has been described, comparative OCT studies among EAE models are scarce. Furthermore, the best practices for the implementation of OCT in the EAE lab, especially with afoveate animals like rodents, remain undefined. We aimed to describe the dynamics of retinal injury in different mouse EAE models and outline the optimal experimental conditions, scan protocols, and analysis methods, comparing these to histology to confirm the pathological underpinnings. METHODS:Using spectral-domain OCT, we analyzed the test-retest and the inter-rater reliability of volume, peripapillary, and combined horizontal and vertical line scans. We then monitored the thickness of the retinal layers in different EAE models: in wild-type (WT) C57Bl/6J mice immunized with myelin oligodendrocyte glycoprotein peptide (MOG35-55) or with bovine myelin basic protein (MBP), in TCR2D2 mice immunized with MOG35-55, and in SJL/J mice immunized with myelin proteolipid lipoprotein (PLP139-151). Strain-matched control mice were sham-immunized. RGC density was counted on retinal flatmounts at the end of each experiment. RESULTS:Volume scans centered on the optic disc showed the best reliability. Retinal changes during EAE were localized in the inner retinal layers (IRLs, the combination of the RNFL and the ganglion cell plus the inner plexiform layers). In WT, MOG35-55 EAE, progressive thinning of IRL started rapidly after EAE onset, with 1/3 of total loss occurring during the initial 2 months. IRL thinning was associated with the degree of RGC loss and the severity of EAE. Sham-immunized SJL/J mice showed progressive IRL atrophy, which was accentuated in PLP-immunized mice. MOG35-55-immunized TCR2D2 mice showed severe EAE and retinal thinning. MBP immunization led to very mild disease without significant retinopathy. CONCLUSIONS:Retinal neuroaxonal damage develops quickly during EAE. Changes in retinal thickness mirror neuronal loss and clinical severity. Monitoring of the IRL thickness after immunization against MOG35-55 in C57Bl/6J mice seems the most convenient model to study retinal neurodegeneration in EAE.

Infiltration in soils is a key process that partitions precipitation at the land surface into surface runoff and water that enters the soil profile. We reviewed the basic principles of water infiltration in soils and we analyzed approaches commonly used in land surface models (LSMs) to quantify infiltration as well as its numerical implementation and sensitivity to model parameters. We reviewed methods to upscale infiltration from the point to the field, hillslope, and grid cell scales of LSMs. Despite the progress that has been made, upscaling of local-scale infiltration processes to the grid scale used in LSMs is still far from being treated rigorously. We still lack a consistent theoretical framework to predict effective fluxes and parameters that control infiltration in LSMs. Our analysis shows that there is a large variety of approaches used to estimate soil hydraulic properties. Novel, highly resolved soil information at higher resolutions than the grid scale of LSMs may help in better quantifying subgrid variability of key infiltration parameters. Currently, only a few LSMs consider the impact of soil structure on soil hydraulic properties. Finally, we identified several processes not yet considered in LSMs that are known to strongly influence infiltration. Especially, the impact of soil structure on infiltration requires further research. To tackle these challenges and integrate current knowledge on soil processes affecting infiltration processes into LSMs, we advocate a stronger exchange and scientific interaction between the soil and the land surface modeling communities.

Abstract Objective Ultrasonography (US) has become the first-line imaging modality even for physicians who are not imaging specialists. The progress has not yet been sufficiently considered in medical education. The aim was to develop a curriculum that integrates US as a compulsory part into medical education directly from the start, to build up professional competencies toward residency. Methods Development was based on Kern’s six-step approach to identify problems, specify needs, define goals, outline strategies, and propose methods. Results The proposed curriculum follows a spiral course within which students should pass through four levels of training with increasing complexity. Students will be asked to independently prepare for courses by using learning videos. On the first training level, US should be closely linked to anatomy and physiology courses. Competency-centered courses should be held in small groups. On the second level, in the third year of education, students will apply point-of-care ultrasonography concerning multiple medical disciplines. On the third level, they will select a compulsory course in a specialty of their choice, held at five consecutive dates. From then on, US will be conducted in patients. Finally, during the final year, students are expected to use US under pro-active supervision with a large degree of independence and confidence. Throughout the curriculum, the discipline of radiology combines vertically with foundational sciences and horizontally with other medical specialties. Conclusion The conceptual proposal for a longitudinal US curriculum presented here has been developed by radiologists to equip students with competencies needed for contemporary patient care.

Abstract Background In breast cancer patients, late-term upper limb sequelae, such as shoulder pain and impaired shoulder function, remain common after primary breast cancer surgery. The aim of this trial is to evaluate whether an expert assessment of shoulder impairments, followed by an individualised treatment plan, is superior to a minimal physiotherapeutic rehabilitation program in reducing shoulder symptoms, among women with late-term shoulder impairments after primary breast cancer. Methods/design The study is designed as a stratified, parallel-group, assessor-blinded, randomised, controlled trial conducted in Denmark; 130 participants with late-term shoulder impairments 3–7 years after primary surgery for breast cancer will be recruited. Participants will be randomised (allocation 1:1) to either an expert assessment of shoulder impairments followed by an individualised treatment plan or to follow a minimal physiotherapeutic rehabilitation program delivered in a pamphlet. The primary outcome will be a change in shoulder pain and function from baseline to 12 weeks after initiating the treatment, as measured by the patient-reported outcome Shoulder Pain and Disability Index (SPADI) questionnaire. Discussion There has been an insufficient focus in research and clinical practice on late-term shoulder impairment in women following surgery for breast cancer. This trial will focus on interventions towards late-term shoulder impairments and is expected to provide evidence-based knowledge to physiotherapists and women about the management of shoulder pain and impaired shoulder function. Trial registration ClinicalTrials.gov NCT05277909. Registered on 11 March 2022.

Objective To explore patient, clinician and decision-maker perceptions on a clinical trial evaluating the effectiveness of total hip arthroplasty (THA) compared with exercise to inform the trial protocol.Design This is an exploratory qualitative case study using a constructivist paradigm.Setting and participants Participants were enrolled into three key stakeholder groups: patients eligible for THA, clinicians, and decision makers. Focus group interviews were conducted in undisturbed conference rooms at two hospitals in Denmark, according to group status using semi-structured interview guides.Analysis Interviews were recorded, transcribed verbatim and thematic analysed using an inductive approach.Results We conducted 4 focus group interviews with 14 patients, 1 focus group interview with 4 clinicians (2 orthopaedic surgeons and 2 physiotherapists) and 1 focus group interview with 4 decision-makers. Two main themes were generated. ‘Treatment expectations and beliefs impact management choices’ covered three supporting codes: Treatment without surgery is unlikely to lead to recovery; Clinician authority impacts the management narrative; The ‘surgery vs exercise’ debate. ‘Factors influencing clinical trial integrity and feasibility’ highlighted three supporting codes: Who is considered eligible for surgery?; Facilitators and barriers for surgery and exercise in a clinical trial context; Improvements in hip pain and hip function are the most important outcomes.Conclusions Based on key stakeholder treatment expectations and beliefs, we implemented three main strategies to improve the methodological rigorousness of our trial protocol. First, we added an observational study investigating the generalisability to address a potential low enrolment rate. Second, we developed an enrolment procedure using generic guidance and balanced narrative conveyed by an independent clinician to facilitate communication of clinical equipoise. Third, we adopted change in hip pain and function as the primary outcome. These findings highlight the value of patient and public involvement in the development of trial protocols to reduce bias in comparative clinical trials evaluating surgical and non-surgical management.Trial registration number NCT04070027 (pre-results).

Abstract We report the findings of a single‐dose, randomized, three‐period cross‐over, clinical trial in healthy Chinese individuals (n = 24) comparing the pharmacokinetics of insulin degludec/liraglutide (IDegLira) with its individual components. Furthermore, we report a population pharmacokinetic analysis of a 26‐week, phase III, treat‐to‐target, randomized trial of 720 Chinese individuals with type 2 diabetes. Participants were randomized to IDegLira, degludec or liraglutide, all once daily with metformin. The pharmacokinetic profiles of IDegLira were similar to its individual components. Dose proportionality was indicated for both IDegLira components. Although there were no relevant covariate effects on degludec exposure, liraglutide exposure was inversely correlated with bodyweight. In conclusion, for the Chinese population, the pharmacokinetics of the fixed‐ratio combination IDegLira is similar to that of its individual components.

Background: Restoring maximal muscle strength of the knee extensors (KE) and knee flexors (KF) following anterior cruciate ligament (ACL) injury and ACL reconstruction is of great importance to reduce the re-injury rate after ACL reconstruction and to reduce the risk of knee osteoarthritis. Therefore, it is essential that clinicians and healthcare providers use valid and reliable measures to assess knee muscle strength to ensure a safe return to sport. Purpose: To evaluate the reliability (test-retest reliability, inter-tester reliability and test-retest agreement) and validity (concurrent validity, convergent validity and ForceFrame (FF) vs. isokinetic dynamometer (ID) agreement) of the ForceFrame (FF) dynamometer during isometric testing of the knee extensors and flexors. Study Design: Cross-sectional study Material and Methods: Twenty-seven participants with ACL injury or reconstruction were recruited for participation in this study. maximal voluntary isometric contration (MVIC) of the knee extensors and flexors was tested on two separate days. Day one included validity assessments with FF, a gold-standard ID and a handheld dynamometer (HHD). Day two included reliability assessments with FF performed by two assessors. Main outcome measures were day-to-day test-retest reliability and agreement and inter-tester reliability of FF, and concurrent validity (FF vs. an ID and a HHD). Reliability was tested as test-retest and inter-tester reliability using interclass correlation coefficient (ICC), while agreement was tested using Bland & Altman plots with limits of agreement (LOA), standard error of measurement (SEM) and smallest detectable change (SDC). Concurrent validity between FF, ID, and HHD was assessed using Pearson's correlations and mean difference was evaluated by Bland & Altman plots. Results: Twenty-seven participants (10 females, 17 males) with a median age of 25 years (range 19-60) were included in this study. There was a good day-to-day test-retest reliability for MVIC of KE (ICC=0.77, CI95:0.48-0.90) and KF (ICC=0.83, CI95:0.61-0.92) and excellent inter-tester reliability for MVIC of KE (ICC=0.97, CI95:0.94-0.98) and KF (ICC=0.93, 95CI:0.85-0.97). Standard error of measurement (SEM) was 8% and 9%, while the smallest detectable change (SDC) was 22% and 27% for KE and KF, respectively. FF showed fair concurrent validity compared to ID for KE (r=0.56), poor concurrent validity for knee flexors (KF (r=0.24) and compared to HHD a moderate correlation for KE (r=0.74) and poor correlation for KF (r=0.12). Bland & Altman plots between FF and the ID showed a mean difference of -0.51 Nm/kg for KE and -0.32Nm/kg for KF. Conclusions: FF can be used to obtain reliable and valid results to assess MVIC of the KE, but not the KF. It should be noted that absolute results produced by the FF may be considered an underestimation of actual MVIC. The test position to assess KF in FF does not appear to be optimal, and different test-positions may be considered. Level of evidence: Level 3 [ABSTRACT FROM AUTHOR]

We present a comprehensive, high-quality dataset characterizing soil–vegetation and land surface processes from continuous measurements conducted in two climatically contrasting study regions in southwestern Germany: the warmer and drier Kraichgau region with a mean temperature of 9.7 ∘C and annual precipitation of 890 mm and the cooler and wetter Swabian Alb with mean temperature 7.5 ∘C and annual precipitation of 1042 mm. In each region, measurements were conducted over a time period of nine cropping seasons from 2009 to 2018. The backbone of the investigation was formed by six eddy-covariance (EC) stations which measured fluxes of water, energy and carbon dioxide between the land surface and the atmosphere at half-hourly resolution. This resulted in a dataset containing measurements from a total of 54 site years containing observations with a multitude of crops, as well as considerable variation in local growing-season climates. The presented multi-site, multi-year dataset is composed of crop-related data on phenological development stages, canopy height, leaf area index, vegetative and generative biomass, and their respective carbon and nitrogen content. Time series of soil temperature and soil water content were monitored with 30 min resolution at various points in the soil profile, including ground heat fluxes. Moreover, more than 1200 soil samples were taken to study changes of carbon and nitrogen contents. The dataset is available at https://doi.org/10.20387/bonares-a0qc-46jc (Weber et al., 2021). One field in each region is still fully set up as continuous observatories for state variables and fluxes in intensively managed agricultural fields.

Abstract Addressing threats to biodiversity from pest species is a global challenge. One such challenge is to mitigate the impact of an overabundant Australian songbird, the noisy miner Manorina melanocephala, on woodland birds. The overabundance of noisy miners is listed as a key threatening process under federal biodiversity legislation, but current understanding of where and how noisy miner populations can be managed to yield conservation benefits is unclear. We evaluated the effectiveness of noisy miner removal across 12 treatment areas totaling 3913 ha and nine control areas totaling 1487 ha important for the critically endangered regent honeyeater Anthochaera phrygia. Removal of noisy miners significantly reduced their densities in all but one of the treatment areas. In 10 of the 12 treatment areas, noisy miner densities remained below an impact threshold of 0.65–0.83 birds ha−1 for at least 3 to more than 12 months. The percentage of suitable noisy miner habitat in the surrounding landscape was not a strong predictor of noisy miner management success. Regent honeyeaters occupied six treatment areas, nesting successfully in four. The abundance of other songbirds increased post‐miner removal in seven areas, decreased in three, and was mixed in two. Data from the control areas showed some variation in songbird numbers was independent of noisy miner management. We conclude that noisy miners can be managed in areas of high conservation value for a minimum cost of AUD $10 ha−1. Larger treatment areas may be more important than the broader landscape context in maintaining long‐term noisy miner suppression. Standardized, long‐term monitoring is crucial to identify not only the drivers of pest species recolonization but also locations where threats from pests on endangered species can be addressed effectively while minimizing animal welfare and financial costs.

Abstract Background In the time of the coronavirus disease 2019 (COVID-19) pandemic, in-person lectures had to be shifted to online learning. This study aimed to evaluate students’ and lecturers’ perception and effectiveness of a virtual inverted classroom (VIC) concept on clinical radiology in comparison to a historic control. Methods In the winter semester 2020/21, 136 fourth year medical students who completed the clinical radiology VIC during the pandemic, were included in the single centre, prospective study. Results were compared with a historic control that had finished the physical inverted classroom (PIC) in the immediately preceding year. The VIC consisted of an initial phase of self-determined preparation with learning videos and a second interactive phase of clinical case studies alternating between the virtual lecture hall and virtual buzz groups. At the end of the lecture series, students rated the lecture on a scale of 1 (most positive assessment) to 6 (most negative assessment) through an online survey platform. Additionally, they reported their impressions in free-form text. Lecturers were invited to comment on the VIC in a group interview. Main outcomes were final grades and student perception of the VIC. Results Students’ general impression of VIC was lower than that of PIC (median value of 3 [IQR 4, 2] and 1 [IQR 0, 0], p

Abstract Background Impaired motor functions after stroke are common and negatively affect patients' activities of daily living and quality of life. In particular, hand motor function is essential for daily activities, but often returns slowly and incompletely after stroke. However, few data are available on the long-term dynamics of motor recovery and self-reported health status after stroke. The Interdisciplinary Platform for Rehabilitation Research and Innovative Care of Stroke Patients (IMPROVE) project aims to address this knowledge gap by studying the clinical course of recovery after inpatient rehabilitation. Methods In this prospective observational longitudinal multicenter study, patients were included towards the end of inpatient rehabilitation after ischemic or hemorrhagic stroke. Follow-up examination was performed at three, six, and twelve months after enrollment. Motor function was assessed by the Upper Extremity Fugl-Meyer Assessment (FMA), grip and pinch strength, and the nine-hole peg test. In addition, Patient-Reported Outcomes Measurement Information System 10-Question Short Form (PROMIS-10) was included. Linear mixed effect models were fitted to analyze change over time. To study determinants of hand motor function, patients with impaired hand function at baseline were grouped into improvers and non-improvers according to hand motor function after twelve months. Results A total of 176 patients were included in the analysis. Improvement in all motor function scores and PROMIS-10 was shown up to 1 year after inpatient rehabilitation. FMA scores improved by an estimate of 5.0 (3.7–6.4) points per year. In addition, patient-reported outcome measures increased by 2.5 (1.4–3.6) and 2.4 (1.4–3.4) per year in the physical and mental domain of PROMIS-10. In the subgroup analysis non-improvers showed to be more often female (15% vs. 55%, p = 0.0155) and scored lower in the Montreal Cognitive Assessment (25 [23–27] vs. 22 [20.5–24], p = 0.0252). Conclusions Continuous improvement in motor function and self-reported health status is observed up to 1 year after inpatient stroke rehabilitation. Demographic and clinical parameters associated with these improvements need further investigation. These results may contribute to the further development of the post-inpatient phase of stroke rehabilitation. Trial registration: The trial is registered at ClinicalTrials.gov (NCT04119479).

Abstract Background Endovascular revascularization has established as the first-line therapy of femoropopliteal artery disease. Paclitaxel-coated balloon angioplasty proved to be superior to plain old balloon angioplasty (POBA) regarding prevention of restenosis and need for recurrent revascularization. Over the past years, paclitaxel was the only active drug to inhibit neointimal proliferation which could be processed to an appropriate balloon coating. The purpose of this study is to assess whether efficacy and safety of sirolimus-coated balloon angioplasty is noninferior to paclitaxel-coated balloon angioplasty. Methods This randomized controlled, single-blinded, multicentre, investigator-initiated noninferiority trial aims to enrol a total of 478 participants with symptomatic femoropopliteal artery disease of Rutherford category 2 to 4 due to de novo stenosis or restenosis. After pre-dilation, participants will be allocated in a 1:1 ratio to either sirolimus- or paclitaxel-coated balloon angioplasty. Post-dilation with the drug-coated balloon (DCB) used or standard balloon is mandatory in case ≥ 50%, and optional in case of ≥ 30% residual diameter stenosis. Bailout stenting with bare-metal nitinol stents should be conducted in case of flow-limiting dissection. Primary noninferiority endpoints are primary patency and the composite of all-cause mortality, major target limb amputation, and clinically driven target lesion revascularization at 12 months. Secondary outcomes are clinical and hemodynamic improvement, change in health-related quality of life, and safety throughout 60 months. Discussion Although concerns about long-term safety of paclitaxel-coated devices were not confirmed by recent patient-level data analyses, conflicting evidence contributed to a loss of confidence among patients and physicians. Therefore, sirolimus, known for a broader therapeutic range than paclitaxel, may serve as a welcome alternative. This will be justified if noninferiority of sirolimus-coated balloon angioplasty against the current standard of paclitaxel-coated balloon angioplasty can be demonstrated. Trial registration ClinicalTrials.gov NCT04475783 . Registered on 17 July 2020 EUDAMED No. CIV-20-11-035172, DRKS00022452

The effects of thrombolysis therapy in stroke on structural connectivity are not well understood. Here, the authors show with causal mediation analysis that the clinical benefits of thrombolysis in anterior circulation stroke are mediated via structural connectivity.