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Abstract Background Patient safety has become a priority issue in health policy strategies in Germany in the last several years, and is especially important in the era of climate change. This study aimed to assess public perceptions about the patient safety impact of climate change and the demographic and socioeconomic factors influencing patient perception in Germany. Methods A cross-sectional study was conducted in Germany in 2023, using data from the TK Monitor of Patient Safety. The TK Monitor of Patient Safety is a national survey of the population on the state of safety in medical care. Self-reported data were collected from 1,000 randomly selected adults living in Germany. Demographic and socioeconomic variables were regressed on climate change perception using an ordinal logistic regression approach. Results Our results revealed that half of respondents are concerned about climate change affecting their health and 40% of the respondents would like to have climate-sensitive health counseling by their general practitioner. The results showed that demographic variables, such as gender and age, and socioeconomic variables, such as education level and income, are important factors influencing the perception of climate change-related patient safety risks. However, no association was found between urban/rural residence and patient perception. Conclusions Our study highlights patient safety as a public health concern in the era of climate change. The German public appears to view climate change as harmful to patient safety. Our findings also show that it is necessary to carry out diagnoses focused on demographic and socioeconomic factors to determine which aspects should be strengthened through programs aimed at reducing patient safety risks associated with climate change.

Lignocellulosic biorefineries (LBRs) are platforms for the production of a variety of bio-based products such as biofuels, biomaterials, biochemicals, food, and feed using lignocellulosic biomass (LB) as feedstock. LBRs are still rare worldwide. Their commercialization depends on challenges associated with the entire feedstock supply chain, efficiency, sustainability, and scale-up of pretreatment methods, as well as isolation and purification of value-added products. Each step within LBRs requires the development of new technologies or the improvement of existing ones, considering all three sustainability dimensions, environmental, social, and economic. Machine learning (ML) methods are widely used in various industrial fields, including biotechnology. The merging of biotechnology and ML has driven scientific progress and opened new opportunities for the development of LBRs as well. In this review, ML methods and their efficiency, used in biotechnology (metabolic engineering, bioprocess development, and environmental engineering), are presented, followed by their application in various phases of LB valorization.

Uncertainty quantification (UQ) is a well-established category of methods to estimate the effect of parameter variations on a quantity of interest based on a solid mathematical foundation. In the wind energy field most UQ studies focus on the sensitivity of turbine loads. This article presents a framework, wrapped around a modern Python UQ library, to analyze the impact of uncertain turbine properties on aeroelastic stability. The UQ methodology applies a polynomial chaos expansion surrogate model. A comparison is made between different wind turbine simulation tools on the engineering model level (alaska/Wind, Bladed, HAWC2/HAWCStab2, and Simpack). Two case studies are used to demonstrate the effectiveness of the method to analyze the sensitivity of the aeroelastic damping of an unstable turbine mode to variations of structural blade cross-section parameters. The code-to-code comparison shows good agreement between the simulation tools for the reference model, but also significant differences in the sensitivities.

Mesoscale modeling can be used to analyze key parameters for wind turbine load assessment in a large variety of tropical cyclones. However, the modeled wind structure of tropical cyclones is known to be sensitive to the boundary layer scheme. We analyze modeled wind speed, shear, and wind veer across a wind turbine rotor plane in the eyewall and outer cyclone. We further assess the sensitivity of wind speed, shear, and veer to the boundary layer parametrization. Three model realizations of Typhoon Megi are analyzed over the open ocean using three frequently used boundary layer schemes in the Weather Research and Forecasting (WRF) model. All three typhoon simulations reasonably reproduce the cyclone track and structure. The boundary layer parametrization causes up to 15 % differences in median wind speed at hub height between the simulations. The simulated wind speed variability also depends on the boundary layer scheme. The modeled median wind shear is smaller than or equal to 0.11 used in the current IEC (International Electrotechnical Commission) standard regardless of the boundary layer scheme for the eyewall and outer cyclone region. However, up to 43.6 % of the simulated wind profiles in the eyewall region exceed 0.11. While the surface inflow angle is sensitive to the boundary layer scheme, wind veer in the lowest 400 m of the atmospheric boundary layer is less affected by the boundary layer scheme. Simulated median wind veer reaches values up to 1.7×10-2° m−1 (1.2×10-2° m−1) in the eyewall region (outer cyclone region) and is relatively small compared to moderate-wind-speed regimes. On average, simulated wind speed shear and wind veer are highest in the eyewall region. Yet strong spatial organization of wind shear and veer along the rainbands may increase wind turbine loads due to rapid changes in the wind profile at the turbine location.

The hydrochlorination of alkenes has been extensively studied in research and is commonly featured in organic chemistry textbooks as an exemplification of the Markovnikov rule. However, the application of this reaction is typically limited to specific alkenes, such as highly substituted ones, styrenes, or strained systems. Conversely, monosubstituted or 1,2-disubstituted alkenes do not readily react with HCl gas or solutions of HCl gas at practical rates. The challenges associated with hydrochlorination reactions for these "non-activated" alkenes have spurred considerable research efforts over the past 30 years, which constitute the primary focus of this review. The discussion begins with classical polar hydrochlorinations, followed by metal-promoted radical hydrochlorinations, and concludes with a brief overview of recent anti-Markovnikov hydrochlorinations.

Abstract Background Previous studies have shown that growing up with rheumatic conditions can fuel dissatisfaction and psychological distress, which in turn affects disease self-management and treatment adherence. Primary objective of this study was to estimate the prevalence of anxiety and depression symptoms in adolescents and young adults (AYA) with juvenile idiopathic arthritis (JIA) and to identify correlates of conspicuous screening results. Methods Initiated as part of the COACH multicenter observational study, outpatients aged 12 to 21 years participating in the National Pediatric Rheumatological Database (NPRD) were prospectively screened for mental health using the Patient Health Questionnaire-9 (PHQ-9) and the Generalised Anxiety Disorder Scale-7 (GAD-7). Results Data from 1,150 adolescents with JIA (mean age 15.6 ± 2.2 years; mean disease duration 7.2 ± 4.9 years, 69% female, 43% oligoarthritis, 26% polyarthritis) were analysed. Overall, 32.7% (n = 316) of AYA showed conspicuous screening results, of whom 30.4% reported clinically relevant suicidal or self-harm thoughts. About 19% of screened patients showed moderate to severe depressive or anxious symptoms. AYA with conspicuous screening results were older (15.8 vs. 15.2 years; p

BackgroundThe influence of atrial fibrillation (AF) and blood pressure (BP) on brain lesions and cognitive function is unclear. We aimed to investigate the association of BP with different types of brain lesions and cognitive decline in patients with AF.MethodsOverall, 1,213 AF patients underwent standardized brain magnetic resonance imaging at baseline and after 2 years, as well as yearly neurocognitive testing. BP was measured at baseline and categorized according to guidelines. New lesions were defined as new or enlarged brain lesions after 2 years. We defined cognitive decline using three different neurocognitive tests. Logistic and Cox regression analyses were performed to examine the associations of BP with new brain lesions and cognitive decline.ResultsThe mean age was 71 ± 8.4 years, 74% were male and mean BP was 135 ± 18/79 ± 12 mmHg. New ischemic lesions and white matter lesions were found in 5.4% and 18.4%, respectively. After multivariable adjustment, BP was not associated with the presence of new brain lesions after 2 years. There was no association between BP and cognitive decline over a median follow-up of 6 years when using the Montreal Cognitive Assessment or Digit Symbol Substitution Test. However, BP categories were inversely associated with cognitive decline using the Semantic Fluency Test, with the strongest association in patients with hypertension grade 1 [Hazard Ratio (95% Confidence Interval) 0.57(0.42 to 0.77)], compared to patients with optimal BP (p for linear trend: 0.025).ConclusionsIn a large cohort of AF patients, there was no association between BP and incidence of brain lesions after 2 years. Also, there was no consistent association between BP and cognitive decline over a follow-up of 6 years. Clinical Trial Registrationhttps://clinicaltrials.gov/study/NCT02105844, Identifier (NCT02105844).

OBJECTIVES: Due to the increasing complexity of the healthcare system, effective communication and data exchange between hospitalists (in-hospital physicians) and primary care physicians (PCPs) is both central and challenging. In Switzerland, little is known about hospitalists’ perception of their communication with PCPs. The primary objective was to assess hospitalists’ satisfaction with their communication with PCPs. Secondary objectives addressed all information about the referral process and communication with PCPs during and after the hospital encounter. Lastly, the results of a previous survey among PCPs were juxtaposed to compare their responses to similar questions. METHODS: This study surveyed hospitalists in six hospitals in the Central Switzerland region. The survey was sent via email to hospitalists from November 2021 to February 2022. The questionnaire contained 17 questions with single- and multiple-choice answers and the option of free-text entry. Exploratory multivariable logistic regression was used to analyse independent associations. RESULTS: In total, 276 of 1134 hospitalists responded (response rate 24.3%): (1) the majority of hospitalists are satisfied with the general communication (n = 162, 58.7%) as well as with referral letters (n = 145, 52.5%), (2) preferred information channels for referral letters are email (n = 212, 76.8%) and electronic portals (n = 181, 65.5%), (3) the three most important items of information in referrals are: medication list, diagnoses and reason for referral. In multivariable regression, compared to other clinicians, internists independently favoured informing PCPs of emergency admissions of their patients in a timely manner (OR 2.04; 95%CI 1.21–3.49). Comparing responses from PCPs (n = 109), the most prominent discrepancy was that 67% (n = 184) of hospitalists claimed to “always” inform after an encounter, whereas only 7% (n = 8) of PCPs agreed. CONCLUSION: Most hospitalists are satisfied with the communication with PCPs and prefer electronic communication channels. Room for improvement was found around timely transmission of patient information before and after hospital encounters.

Postoperative epidural fibrosis (EF) is still a major limitation to the success of spine surgery. Fibrotic adhesions in the epidural space, initiated via local trauma and inflammation, can induce difficult-to-treat pain and constitute the main cause of failed back surgery syndrome, which not uncommonly requires operative revision. Manifold agents and methods have been tested for EF relief in order to mitigate this longstanding health burden and its socioeconomic consequences. Although several promising strategies could be identified, few have thus far overcome the high translational hurdle, and there has been little change in standard clinical practice. Nonetheless, notable research progress in the field has put new exciting avenues on the horizon. In this review, we outline the etiology and pathogenesis of EF, portray its clinical and surgical presentation, and critically appraise current efforts and novel approaches toward enhanced prevention and treatment.

Abstract Background Peer support is an essential part of recovery-oriented care worldwide. Contextual factors have an impact on the implementation of peer support work. However, research has paid little attention to similarities and differences of implementation factors in settings varying by income-level and cultural values. The aim of this study is to assess the factors influencing the implementation of a peer support intervention across study sites in low-, middle- and high-income countries in line with the Consolidation Framework for Implementation Research (CFIR). Method 6 focus groups with a total of 54 key informants with relevant contextual (organisational) knowledge regarding implementation facilitators and barriers were conducted at six study sites Ulm and Hamburg (Germany), Butabika (Uganda), Dar es Salaam (Tanzania), Be’er Sheva (Israel), and Pune (India) before and 1.5 years after the start of UPSIDES peer support. Transcripts were analysed using qualitative content analysis. Results Across study sites key informants reported benefits of peer support for service users and peer support workers as implementation facilitators. At study sites with lower resources, reduced workload for mental health workers and improved access to mental health services through peer support were perceived as implementation facilitators (CFIR Domain 1: Intervention characteristics). The degree of engagement of mental health workers (CFIR Domain 3: Inner Setting/Domain 4: Individuals involved) varied across study sites and was seen either as a barrier (low engagement) or a facilitator (high engagement). Across study sites, adequate training of peer support workers (CFIR Domain 5: Implementation process) was seen as animplementation facilitator, while COVID-19 as well as low resource availability were reported as implementation barriers (CFIR Domain 2: Outer setting). Conclusions This study highlights the importance of considering contextual factors when implementing peer support, including previous experience and perceived benefits. Particular attention should be given to organisational benefits such as workload reduction and the allocation of sufficient resources as key drivers in LMICs. In HICs, the potential of organisational benefits for successful implementation should be further investigated and promoted.

Abstract Background The experience of benefit-finding and growth (BFG), defined as perceiving positive life changes resulting from adversity, is increasingly studied among youths with chronic health conditions (CCs). However, empirical evidence is scarce for explaining individual differences in BFG. The study aimed to test a model of BFG, including an interplay of personal and environmental factors and coping processes. Methods A sample of N = 498 youths (12–21 years) recruited from three German patient registries for CCs (type 1 diabetes: n = 388, juvenile idiopathic arthritis: n = 82, cystic fibrosis: n = 28) completed a questionnaire including self-reported optimism, social support from parents and peers, coping strategies, and BFG. The model was created to reflect the theoretical assumptions of the Life Crisis and Personal Growth model and current empirical evidence. Structural equation modeling was conducted to evaluate the incremental explanatory power of optimism, peer group integration, parental support, acceptance, cognitive reappraisal, and seeking social support over and above sociodemographic and disease-related characteristics. Results The model (CFI = 0.93; RMSEA = 0.04; SRMR = 0.05) explained 32% of the variance in BFG. Controlling for sociodemographic and disease-related characteristics, acceptance, cognitive reappraisal, and seeking social support were directly and positively linked to BFG. All tested coping strategies significantly mediated the association between optimism and BFG, whereas seeking social support significantly mediated the relation between peer group integration and BFG. Discussion The study stresses the prominent role of emotion-focused coping strategies and peer group integration in enhancing BFG in youths with CCs. Trial registration German Clinical Trials Register (DRKS), no. DRKS00025125. Registered on May 17, 2021.

The geostatistical characterization of the subsurface is confronted with the double challenge of large uncertainties and high exploration costs. Making use of all available data sources is consequently very important. Bayesian inference is able to mitigate uncertainties in such a data-scarce context by drawing on available background information in the form of a prior distribution. To make such a prior distribution transparent and objective, it should be calibrated against a data set containing estimates of the target variable from available sites. In this study, we provide a collection of covariance and/or variogram functions of the subsurface hydraulic parameters from a large number of sites. We analyze this data set by fitting a number of widely used variogram model functions and show how they can be used to derive prior distributions of the parameters of said functions. In addition, we discuss a number of conclusions that can be drawn for our analysis and possible uses for the data set.

In the case of a single-digit picosecond bunch length, synchrotron light sources produce intense coherent radiation up to the THz range. The reduction of the bunch length by lowering the momentum compaction factor (low-α) gives rise to the microbunching instability, which is on the one hand a crucial roadblock in the x-ray range during to the resulting effective bunch lengthening, but on the other hand also an opportunity for the generation of intense THz radiation if it can be controlled appropriately. In the KIT storage ring KARA (Karlsruhe Research Accelerator), two parallel plates with periodic rectangular corrugations are planned to be installed as a proof of principle in an electron storage ring. These plates create an additional longitudinal impedance based on their geometry, which can affect the beam dynamics. The resulting impedance manipulation will be used to study and control the longitudinal electron beam dynamics and the emitted coherent synchrotron radiation. This paper presents the results of systematic studies in simulation of the impact of additional corrugated plate impedances on the longitudinal beam dynamics using the example of the KARA storage ring. If the periodicity of the wake function of the corrugated plates matches the size of the substructures in the longitudinal bunch profile, the instability threshold can be effectively manipulated. This extends intense THz radiation to different beam current regimes.

This article focuses on young people’s understanding of algorithms and their learning methods. While many younger individuals are deeply familiar with digital media, it is erroneous to assume that this familiarity is equivalent to operational or critical knowledge. Given that algorithm awareness has only recently become a topic of debate, daily life practices and knowledge processes need further study, particularly through the lens of audiences. The analysis is based on 42 interviews carried out as part of a project on young people, news, and digital citizenship in Portugal. From the analysis, we came up with five profiles that include different ways of understanding and learning about algorithms: ethereal, ambivalent, unfamiliar, negative, and positive perspectives. Preliminary findings reveal strategies youth employ to bypass the influence of algorithms, with a dominant perspective of learning through the proximity contexts: alone, with social media (TikTok and Instagram), with peers/family, and few cases mentioning school, that surprisingly, is almost absent as a learning atmosphere. Given the newness of the collective awareness of the power of algorithms, the presented scenario claims that we need for a more structural and institutional learning context and response, which could help prevent recurring scenarios akin to digital “bowling alone.”

Whole-body electromyostimulation has proven to be a highly effective alternative to conventional resistance-type exercise training. However, due to adverse effects in the past, very extensive contraindications have been put in place for the commercial, non-medical WB-EMS market. Considering recent positive innovations e.g., federal regulation, mandatory trainer education, revised guidelines, and new scientific studies on WB-EMS application, we believe that a careful revision of the very restrictive contraindications on WB-EMS is needed. This applies all the more because many cohorts with limited options for conventional exercise have so far been excluded. During a first meeting of an evidence-based consensus process, stakeholders from various backgrounds (e.g., research, education, application) set the priorities for revising the contraindications. We decided to focus on four categories of absolute contraindications: “Arteriosclerosis, arterial circulation disorders”, “Diabetes mellitus” (DM), “Tumor and cancer” (TC), “Neurologic diseases, neuronal disorders, epilepsy”. Based on scientific studies, quality criteria, safety aspects and benefit/risk assessment of the category, DM and TC were moved to the relative contraindication catalogue, while arteriosclerosis/arterial circulation disorders and neurologic diseases/neuronal disorders/epilepsy were still considered as absolute contraindications. While missing evidence suggests maintaining the status of neurologic diseases/neuronal disorders as an absolute contraindication, the risk/benefit-ratio does not support the application of WB-EMS in people with arteriosclerosis/arterial circulation diseases. Despite these very cautious modifications, countries with less restrictive structures for non-medical WB-EMS should consider our approach critically before implementing the present revisions. Considering further the largely increased amount of WB-EMS trials we advice regular updates of the present contraindication list.

Abstract Background The impact of sex hormones on right and left auricular contractile apparatus function is largely unknown. We evaluated the impact of sex hormones on left and right heart contractility at the level of myocardial filaments harvested from left and right auricles during elective coronary artery bypass surgery. Methods 150 patients (132 male; 18 female) were enrolled. Preoperative testosterone and estradiol levels were measured with Immunoassay. Calcium induced force measurements were performed with left- and right auricular myofilaments in a skinned fiber model. Correlation analysis was used for comparison of force values and levels of sex hormones and their ratio. Results Low testosterone was associated with higher top force values in right-sided myofilaments but not in left-sided myofilaments for both sexes (p = 0.000 in males, p = 0.001 in females). Low estradiol levels were associated with higher top force values in right-sided myofilaments (p 0.000) in females and only borderline significantly associated with higher top force values in males (p 0.056). In females, low estradiol levels correlated with higher top force values in left sided myofilaments (p 0.000). In males, higher Estradiol/Testosterone ratio (E/T ratio) was only associated with higher top force values from right auricular myofilaments (p 0.04) In contrast, in females higher E/T ratio was associated with lower right auricular myofilament top force values (p 0.03) and higher top force values in left-sided myofilaments (p 0.000). Conclusions This study shows that patients’ comorbidities influence left and right sided contractility and may blur results concerning influence of sex hormones if not eliminated. A sex hormone dependent influence is obvious with different effects on the left and right ventricle. The E/T ratio and its impact on myofilament top force showed divergent results between genders, and may partially explain gender differences in patients with cardiovascular disease.

Abstract Background As the first point of contact for patients with health issues, general practitioners (GPs) are frequently confronted with patients presenting with non-specific symptoms of unclear origin. This can result in delayed, prolonged or false diagnoses. To accelerate and improve the diagnosis of diseases, clinical decision support systems would appear to be an appropriate tool. The objective of the project ‘Smart physician portal for patients with unclear disease’ (SATURN) is to employ a user-centered design process based on the requirements analysis presented in this paper to develop an artificial Intelligence (AI)-based diagnosis support system that specifically addresses the needs of German GPs. Methods Requirements analysis for a GP-specific diagnosis support system was conducted in an iterative process with five GPs. First, interviews were conducted to analyze current workflows and the use of digital applications in cases of diagnostic uncertainty (as-is situation). Second, we focused on collecting and prioritizing tasks to be performed by an ideal smart physician portal (to-be situation) in a workshop. We then developed a task model with corresponding user requirements. Results Numerous GP-specific user requirements were identified concerning the tasks and subtasks: performing data entry (open system, enter patient data), reviewing results (receiving and evaluating results), discussing results (with patients and colleagues), scheduling further diagnostic procedures, referring to specialists (select, contact, make appointments), and case closure. Suggested features particularly concerned the process of screening and assessing results: e.g., the system should focus more on atypical patterns of common diseases than on rare diseases only, display probabilities of differential diagnoses, ensure sources and results are transparent, and mark diagnoses that have already been ruled out. Moreover, establishing a means of using the platform to communicate with colleagues and transferring patient data directly from electronic patient records to the system was strongly recommended. Conclusions Essential user requirements to be considered in the development and design of a diagnosis system for primary care could be derived from the analysis. They form the basis for mockup-development and system engineering.

Depression during pregnancy is detrimental for the wellbeing of the expectant mother and can exert long-term consequences on the offspring's development and mental health. In this context, both the gestational environment and the postpartum milieu may be negatively affected by the depressive pathology. It is, however, challenging to assess whether the contributions of prenatal and postnatal depression exposure are distinct, interactive, or cumulative, as it is unclear whether antenatal effects are due to direct effects on fetal development or because antenatal symptoms continue postnatally. Preclinical models have sought to answer this question by implementing stressors that induce a depressive-like state in the dams during pregnancy and studying the effects on the offspring. The aim of our present study was to disentangle the contribution of direct stress in utero from possible changes in maternal behavior in a novel model of preconceptional stress based on social isolation rearing (SIR). Using a cross-fostering paradigm in this model, we show that while SIR leads to subtle changes in maternal behavior, the behavioral changes observed in the offspring are driven by a complex interaction between sex, and prenatal and postnatal maternal factors. Indeed, male offspring are more sensitive to the prenatal environment, as demonstrated by behavioral and transcriptional changes driven by their birth mother, while females are likely affected by more complex interactions between the pre and the postpartum milieu, as suggested by the important impact of their surrogate foster mother. Taken together, our findings suggest that male and female offspring have different time-windows and behavioral domains of susceptibility to maternal preconceptional stress, and thus underscore the importance of including both sexes when investigating the mechanisms that mediate the negative consequences of exposure to such stressor.

Orographic gravity waves (i.e., mountain waves) can potentially lead to cross-isentropic fluxes of trace gases via the generation of turbulence. During the DEEPWAVE (Deep Propagating Gravity Wave Experiment) campaign in July 2014, we performed tracer measurements of carbon monoxide (CO) and nitrous oxide (N2O) above the Southern Alps during periods of gravity wave activity. The measurements were taken along two stacked levels at 7.9 km in the troposphere and 10.9 km in the stratosphere. A detailed analysis of the observed wind components shows that both flight legs were affected by vertically propagating gravity waves with momentum deposition and energy dissipation between the two legs. Corresponding tracer measurements indicate turbulent mixing in the region of gravity wave occurrence. For the stratospheric data, we identified mixing leading to a change of the cross-isentropic tracer gradient of N2O from the upstream to the downstream region of the Southern Alps. Based on the quasi-inert tracer N2O, we identified two distinct layers in the stratosphere with different chemical composition on different isentropes as given by constant potential temperature Θ. The CO–N2O relationship clearly indicates that irreversible mixing between these two layers occurred. Further, we found a significant change of the vertical profiles of N2O with respect to Θ from the upstream to the downstream side above the Southern Alps just above the tropopause. A scale-dependent gradient analysis reveals that this cross-isentropic gradient change of N2O is triggered in the region of gravity wave occurrence. The power spectra of the in situ measured vertical wind, Θ, and N2O indicate the occurrence of turbulence above the mountains associated with the gravity waves in the stratosphere. The estimated eddy dissipation rate (EDR) based on the measured three-dimensional wind indicates a weak intensity of turbulence in the stratosphere above the mountain ridge. The Θ–N2O relation downwind of the Alps modified by the gravity wave activity provides clear evidence that trace gas fluxes, which were deduced from wavelet co-spectra of vertical wind and N2O, are at least in part cross-isentropic. Our findings thus indicate that orographic waves led to turbulent mixing on both flight legs in the troposphere and in the stratosphere. Despite only weak turbulence during the stratospheric leg, the cross-isentropic gradient and the related composition change on isentropic surfaces from upstream to downstream of the mountain unambiguously conserves the effect of turbulent mixing by gravity wave activity on the trace gas distribution prior to the measurements. This finally leads to irreversible trace gas fluxes across isentropes and thus has a persistent effect on the upper troposphere and lower stratosphere (UTLS) trace gas composition.

This paper presents the results of a diachronic and multidisciplinary investigation into the production and consumption of cooking ware in the ancient city of Priene (Turkey). Three major chronological horizons are considered, covering the fourth to the first century BCE: the late Classical/early Hellenistic period, the middle Hellenistic period, and the late Hellenistic/early Roman Imperial period. Following a thorough typological and macroscopic study of fabrics, an integrated analytical approach combining petrography and elemental analysis (wavelength dispersive X-ray fluorescence) was applied to investigate the main macroscopic types and fabrics that characterised cooking wares. Integration of the results from the typological study with the subsequent analyses of 90 representative samples has provided high-resolution insights into cooking ware production and consumption at Priene over the study period. In addition to tracing transformations in local and regional manufacture over time, the results show that cooking wares were imported to the city from several places and, moreover, at a scale at least equivalent to that for other categories of ceramic vessels at that time. Changes in the manufacturing technology of local and regional products and the origin of imports are discussed in the context of significant historical developments that took place in this region over the period covered by the study.

Abstract Purpose Despite that early integration of palliative care is recommended in advanced cancer patients, referrals to outpatient specialised palliative care (SPC) frequently occur late. Well-defined referral criteria are still missing. We analysed indicators associated with early (ER) and late referral (LR) to SPC of an high volume outpatient unit of a comprehensive cancer center. Methods Characteristics, laboratory parameters and symptom burden of 281 patients at first SPC referral were analysed. Timing of referral was categorized as early, intermediate and late (> 12, 3–12 and

Germany's 2018–2020 consecutive drought events resulted in multiple sectors – including agriculture, forestry, water management, energy production, and transport – being impacted. High-resolution information systems are key to preparedness for such extreme drought events. This study evaluates the new setup of the one-kilometer German drought monitor (GDM), which is based on daily soil moisture (SM) simulations from the mesoscale hydrological model (mHM). The simulated SM is compared against a set of diverse observations from single profile measurements, spatially distributed sensor networks, cosmic-ray neutron stations, and lysimeters at 40 sites in Germany. Our results show that the agreement of simulated and observed SM dynamics in the upper soil (0–25 cm) are especially high in the vegetative active period (0.84 median correlation R) and lower in winter (0.59 median R). The lower agreement in winter results from methodological uncertainties in both simulations and observations. Moderate but significant improvements between the coarser 4 km resolution setup and the ≈ 1.2 km resolution GDM in the agreement to observed SM dynamics is observed in autumn (+0.07 median R) and winter (+0.12 median R). Both model setups display similar correlations to observations in the dry anomaly spectrum, with higher overall agreement of simulations to observations with a larger spatial footprint. The higher resolution of the second GDM version allows for a more detailed representation of the spatial variability of SM, which is particularly beneficial for local risk assessments. Furthermore, the results underline that nationwide drought information systems depend both on appropriate simulations of the water cycle and a broad, high-quality, observational soil moisture database.

Objective Climate change increases the frequency, intensity and length of heatwaves, which puts a particular strain on the health of vulnerable population groups. General practitioners (GPs) could reach these people and provide advice on protective health behaviour against heat. Data is lacking on whether and what topic of GP advice people are interested in, and whether specific person characteristics are associated with such interests.Design Cross-sectional, nationwide, face-to-face household survey, conducted during winter 2022/2023.Setting Germany.Participants Population-based sample of 4212 respondents (aged 14–96 years), selected by using multistratified random sampling (50%) combined with multiquota sampling (50%).Main outcome measure Interest in receiving GP advice on health protection during heatwaves (yes/no), and the topic people find most important (advice on drinking behaviour, nutrition, cooling, cooling rooms, physical activity or medication management). Associations between predefined person characteristics and the likelihood of interest were estimated using adjusted logistic regressions.Results A total of 4020 respondents had GP contact and provided data on the outcome measure. Of these, 23% (95% CI=22% to 25%) expressed interest in GP advice. The likelihood of expressing interest was positively associated with being female, older age (particularly those aged 75+ years: 38% were interested), having a lower level of educational attainment, having a migration background, living in a more urban area, and living in a single-person household. It was negatively associated with increasing income. Advice on medication management received highest interest (25%).Conclusions During winter season 2022/2023, around one quarter of the German population with GP contact—and around 40% of those aged 75+ years—was estimated to have a stated interest in receiving GP advice on protective health behaviour during heatwaves, especially on medication management. Climate change is creating new demands for healthcare provision in general practice. This study provides initial relevant information for research and practice aiming to address these demands.

The PSI Positron Production (P^{3} or P-cubed) experiment is a e^{+} source and capture system with the potential to increase by an order of magnitude the state-of-the-art e^{+} yield normalized to the drive linac energy, a highly desirable goal for future colliders. The experiment is framed in the FCC-ee injector study and will be hosted at SwissFEL, located at the Paul Scherrer Institute in Switzerland. This paper presents the P^{3} project at an advanced stage, with an emphasis on a capture system featuring a novel e^{+} matching device based on high-temperature superconducting solenoids, followed by two large aperture rf cavities surrounded by normal-conducting solenoids. The diagnostics design is also introduced, including monitors of charge, energy spectrum, and bunch-by-bunch longitudinal profile simultaneously for secondary e^{+} and e^{-}. The last chapter of the text overviews the currently ongoing installation at SwissFEL, including the beam transfer line, rf network, radiation protection, and other relevant activities toward the operation with e^{+} in the coming years.

Inducing a magnetic gap at the Dirac point of the topological surface state (TSS) in a three-dimensional (3D) topological insulator (TI) is a route to dissipationless charge and spin currents. Ideally, magnetic order is present only at the surface, as through proximity of a ferromagnetic (FM) layer. However, experimental evidence of such a proximity-induced Dirac mass gap is missing, likely due to an insufficient overlap of TSS and the FM subsystem. Here, we take a different approach, namely ferromagnetic extension (FME), using a thin film of the 3D TI Bi_{2}Te_{3}, interfaced with a monolayer of the lattice-matched van der Waals ferromagnet MnBi_{2}Te_{4}. Robust 2D ferromagnetism with out-of-plane anisotropy and a critical temperature of T_{c}≈15 K is demonstrated by x-ray magnetic dichroism and electrical transport measurements. Using angle-resolved photoelectron spectroscopy, we observe the opening of a sizable magnetic gap in the 2D FM phase, while the surface remains gapless in the paramagnetic phase above T_{c}. Ferromagnetic extension paves the way to explore the interplay of strictly 2D magnetism and topological surface states, providing perspectives for realizing robust quantum anomalous Hall and chiral Majorana states.

Abstract The Black Lives Matter Movement, which gained unprecedented global momentum in mid‐2020, triggered critical reflection on systemic discrimination of disadvantaged groups across many domains of society. It prompted us, as early‐career researchers (ECRs) in conservation science, to examine our own awareness of ongoing injustices within our field, the role we play in perpetuating or countering these injustices, and how to move forward. Colonialist ideologies and power dynamics throughout the history of conservation practice and research have left a long‐lasting legacy of inequality and systemic racism. While improvements have been made, these legacies continue to influence teaching and practice today. In this perspective piece, we reflect on the impacts of conservation’s colonial past and how the sector has developed. We then explore how current traditional routes into conservation, and the dominance of these approaches, can leave ECRs underprepared to address modern‐day conservation issues due to a limited understanding of conservation’s history and key theories from other fields. We end by offering a set of suggestions encouraging others to learn and practise fairer and more inclusive conservation practices. Read the free Plain Language Summary for this article on the Journal blog.

Abstract Background The COVID-19 pandemic has made it more difficult to maintain high quality in medical education. As online formats are often considered unsuitable, interactive workshops and seminars have particularly often been postponed or cancelled. To meet the challenge, we converted an existing interactive undergraduate elective on safety culture into an online event. In this article, we describe the conceptualization and evaluation of the elective. Methods The learning objectives of the safety culture elective remained unchanged, but the teaching methods were thoroughly revised and adapted to suit an online setting. The online elective was offered as a synchronous two-day course in winter semester 2020/21 during the “second wave” of the COVID-19 pandemic in Germany. At the end of each day, participating students evaluated the elective by completing an online survey. Items were rated on a six-point Likert scale. We used SPSS for data analysis. Results Twenty medical undergraduates completed the elective and rated it extremely positively (1.1 ± 0.2). Students regard safety culture as very important and felt the learning objectives had been achieved. Moreover, they were very satisfied with the design and content of the elective, and especially with interactive elements like role-play. Around 55% of participants would recommend continuing to offer the online elective after the pandemic. Conclusions It makes sense to offer undergraduate medical students online elective courses on safety culture, especially during a pandemic. The elective described here can serve as a best practice example of how to teach safety culture to undergraduates, especially when physical presence is unfeasible. Electives requiring a high degree of interaction can also function well online.

We present an approach for detecting early signs for upcoming forest damages by training a Convolutional Neural Network (CNN) for the pixel-wise prediction of the remaining life-time (RLT) of trees in forests based on Sentinel-2 imagery. We focus on a scenario in which reference data are only available for a related task, namely for a bi-temporal pixel-wise classification of forest degradation. This reference is used to train a CNN for the pixel-wise prediction of forest degradation. In this context, we propose a new sub-sampling-based approach for compensating the effects of a heavy class imbalance in the training data. Using the resulting classification model, we predict semi-labels for images of a Sentinel-2 time series, from which training data for a CNN designed to regress the RLT can be derived after some label cleansing. However, due to data gaps in the time series, e.g. caused by clouds, only intervals can be derived for the target variable to be regressed, and for some training pixels one of the interval limits may even be unknown. Consequently, we propose a new loss function for training a CNN for regressing the RLT that only requires the known interval limits. The method is evaluated on a data set in Germany, covering a time-span of 5 years. We show that the proposed sub-sampling strategy for dealing with strong label imbalance when training the classifier significantly reduces the training time compared to other approaches. We further show that our model predicts the RLT with a maximum error of two months for 80% of the forest pixels that die within one year from the acquisition date of the Sentinel-2 image.

Geostatistics as a subfield of statistics accounts for the spatial correlations encountered in many applications of, for example, earth sciences. Valuable information can be extracted from these correlations, also helping to address the often encountered burden of data scarcity. Despite the value of additional data, the use of geostatistics still falls short of its potential. This problem is often connected to the lack of user-friendly software hampering the use and application of geostatistics. We therefore present GSTools, a Python-based software suite for solving a wide range of geostatistical problems. We chose Python due to its unique balance between usability, flexibility, and efficiency and due to its adoption in the scientific community. GSTools provides methods for generating random fields; it can perform kriging, variogram estimation and much more. We demonstrate its abilities by virtue of a series of example applications detailing their use.

In this paper two simple synthetic aperture radar (SAR) methods are applied on data from a 24 GHz FMCW radar implemented on a linear drive for educational purposes. The data of near and far range measurements are evaluated using two different SAR signal processing algorithms featuring 2D-FFT and frequency back projection (FBP) method (Moreira et al., 2013). A comparison of these two algorithms is performed concerning runtime, image pixel size, azimuth and range resolution. The far range measurements are executed in a range of 60 to 135 m by monitoring cars in a parking lot. The near range measurement from 0 to 5 m are realised in a measuring chamber equipped with absorber foam and nearly ideal targets like corner reflectors. The comparison of 2D-FFT and FBP algorithm shows that both deliver good and similar results for the far range measurements but the runtime of the FBP algorithm is up to 150 times longer as the 2D-FFT runtime. In the near range measurements the FBP algorithm displays a very good azimuth resolution and targets which are very close to each other can be separated easily. In contrast to that the 2D-FFT algorithm has a lower azimuth resolution in the near range, thus targets which are very close to each other, merge together and cannot be separated.

Distributed environmental models such as land surface models (LSMs) require model parameters in each spatial modeling unit (e.g., grid cell), thereby leading to a high-dimensional parameter space. One approach to decrease the dimensionality of the parameter space in these models is to use regularization techniques. One such highly efficient technique is the multiscale parameter regionalization (MPR) framework that translates high-resolution predictor variables (e.g., soil textural properties) into model parameters (e.g., porosity) via transfer functions (TFs) and upscaling operators that are suitable for every modeled process. This framework yields seamless model parameters at multiple scales and locations in an effective manner. However, integration of MPR into existing modeling workflows has been hindered thus far by hard-coded configurations and non-modular software designs. For these reasons, we redesigned MPR as a model-agnostic, stand-alone tool. It is a useful software for creating graphs of NetCDF variables, wherein each node is a variable and the links consist of TFs and/or upscaling operators. In this study, we present and verify our tool against a previous version, which was implemented in the mesoscale hydrologic model (mHM; https://www.ufz.de/mhm, last access: 16 January 2022). By using this tool for the generation of continental-scale soil hydraulic parameters applicable to different models (Noah-MP and HTESSEL), we showcase its general functionality and flexibility. Further, using model parameters estimated by the MPR tool leads to significant changes in long-term estimates of evapotranspiration, as compared to their default parameterizations. For example, a change of up to 25 % in long-term evapotranspiration flux is observed in Noah-MP and HTESSEL in the Mississippi River basin. We postulate that use of the stand-alone MPR tool will considerably increase the transparency and reproducibility of the parameter estimation process in distributed (environmental) models. It will also allow a rigorous uncertainty estimation related to the errors of the predictors (e.g., soil texture fields), transfer function and its parameters, and remapping (or upscaling) algorithms.

Background Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common adverse event of CD19-directed chimeric antigen receptor (CAR) T cell therapy. Other neurological adverse events, however, have not methodically been described and studied. Furthermore, safety data on CAR-T cell therapy in patients with central nervous system (CNS) lymphoma remain limited.Main body We here report occurrence of a Guillain-Barré-like syndrome (GBS) and central diabetes insipidus (cDI) following tisagenlecleucel therapy for relapsed high-grade lymphoma with CNS involvement. Both complications were refractory to standard treatment of ICANS. Weakness of respiratory muscles required mechanical ventilation and tracheostomy while cDI was treated with desmopressin substitution for several weeks. Muscle-nerve biopsy and nerve conduction studies confirmed an axonal pattern of nerve damage. T cell-rich infiltrates and detection of the CAR transgene in muscle-nerve sections imply a direct or indirect role of CAR-T cell-mediated inflammation. In line with current treatment guidelines for GBS, intravenous immunoglobulin was administered and gradual but incomplete recovery was observed over the course of several months.Conclusions This case report highlights the risk of rare but severe neurological adverse events, such as acute GBS or cDI, in patients treated with CAR-T cells. It further underlines the importance of appropriate patient surveillance and systematic reporting of rare complications to eventually improve treatment.

Abstract Substantial sex differences have been reported in the physiological response to stress at multiple levels, including the release of the stress hormone, cortisol. Here, we explore the genomic variants in 93 females and 196 males regulating the initial transcriptional response to cortisol via glucocorticoid receptor (GR) activation. Gene expression levels in peripheral blood were obtained before and after GR-stimulation with the selective GR agonist dexamethasone to identify differential expression following GR-activation. Sex stratified analyses revealed that while the transcripts responsive to GR-stimulation were mostly overlapping between males and females, the quantitative trait loci (eQTLs) regulation differential transcription to GR-stimulation was distinct. Sex-stratified eQTL SNPs (eSNPs) were located in different functional genomic elements and sex-stratified transcripts were enriched within postmortem brain transcriptional profiles associated with Major Depressive Disorder (MDD) specifically in males and females in the cingulate cortex. Female eSNPs were enriched among SNPs linked to MDD in genome-wide association studies. Finally, transcriptional sensitive genetic profile scores derived from sex-stratified eSNPS regulating differential transcription to GR-stimulation were predictive of depression status and depressive symptoms in a sex-concordant manner in a child and adolescent cohort (n = 584). These results suggest the potential of eQTLs regulating differential transcription to GR-stimulation as biomarkers of sex-specific biological risk for stress-related psychiatric disorders.

Abstract Background Relatively little is known about protective factors and the emergence and maintenance of positive outcomes in the field of adolescents with chronic conditions. Therefore, the primary aim of the study is to acquire a deeper understanding of the dynamic process of resilience factors, coping strategies and psychosocial adjustment of adolescents living with chronic conditions. Methods/design We plan to consecutively recruit N = 450 adolescents (12–21 years) from three German patient registries for chronic conditions (type 1 diabetes, cystic fibrosis, or juvenile idiopathic arthritis). Based on screening for anxiety and depression, adolescents are assigned to two parallel groups – “inconspicuous” (PHQ-9 and GAD-7

Abstract Background To investigate patients’ perspectives on polypharmacy and the use of a digital decision support system to assist general practitioners (GPs) in performing medication reviews. Methods Qualitative interviews with patients or informal caregivers recruited from participants in a cluster-randomized controlled clinical trial (cRCT). The interviews were transcribed verbatim and analyzed using thematic analysis. Results We conducted 13 interviews and identified the following seven themes: the patients successfully integrated medication use in their everyday lives, used medication plans, had both good and bad personal experiences with their drugs, regarded their healthcare providers as the main source of medication-related information, discussed medication changes with their GPs, had trusting relationships with them, and viewed the use of digital decision support tools for medication reviews positively. No unwanted adverse effects were reported. Conclusions Despite drug-related problems, patients appeared to cope well with their medications. They also trusted their GPs, despite acknowledging polypharmacy to be a complex field for them. The use of a digital support system was appreciated and linked to the hope that reasons for selecting specific medication regimens would become more comprehensible. Further research with a more diverse sampling might add more patient perspectives. Trial registration ClinicalTrials.gov, NCT03430336 . Registered on February 6, 2018.

Abstract Constantly decreasing costs of high-throughput profiling on many molecular levels generate vast amounts of multi-omics data. Studying one biomedical question on two or more omic levels provides deeper insights into underlying molecular processes or disease pathophysiology. For the majority of multi-omics data projects, the data analysis is performed level-wise, followed by a combined interpretation of results. Hence the full potential of integrated data analysis is not leveraged yet, presumably due to the complexity of the data and the lacking toolsets. We propose a versatile approach, to perform a multi-level fully integrated analysis: The Knowledge guIded Multi-Omics Network inference approach, KiMONo ( https://github.com/cellmapslab/kimono ). KiMONo performs network inference by using statistical models for combining omics measurements coupled to a powerful knowledge-guided strategy exploiting prior information from existing biological sources. Within the resulting multimodal network, nodes represent features of all input types e.g. variants and genes while edges refer to knowledge-supported and statistically derived associations. In a comprehensive evaluation, we show that our method is robust to noise and exemplify the general applicability to the full spectrum of multi-omics data, demonstrating that KiMONo is a powerful approach towards leveraging the full potential of data sets for detecting biomarker candidates.

Radar systems for contactless vital sign monitoring are well known and an actual object of research. These radar-based sensors could be used for monitoring of elderly people in their homes but also for detecting the activity of prisoners and to control electrical devices (light, audio, etc.) in smart living environments. Mostly these sensors are foreseen to be mounted on the ceiling in the middle of a room. In retirement homes the rooms are mostly rectangular and of standardized size. Furniture like beds and seating are found at the borders or the corners of the room. As the propagation path from the center of the room ceiling to the borders and corners of a room is 1.4 and 1.7 time longer the power reflected by people located there is 6 or even 10 dB lower than if located in the center of the room. Furthermore classical antennas in microstrip technology are strengthening radiation in broadside direction. Radar systems with only one single planar antenna must be mounted horizontally aligned when measuring in all directions. Thus an antenna pattern which is increasing radiation in the room corners and borders for compensation of free space loss is needed. In this contribution a specification of classical room sizes in retirement homes are given. A method for shaping the antenna gain in the E-plane by an one-dimensional series-fed traveling wave patch array and in the H-plane by an antenna feeding network for improvement of people detection in the room borders and corners is presented for a 24 GHz digital beamforming (DBF) radar system. The feeding network is a parallel-fed power divider for microstrip patch antennas at 24 GHz. Both approaches are explained in theory. The design parameters and the layout of the antennas are given. The simulation of the antenna arrays are executed with CST MWS. Simulations and measurements of the proposed antennas are compared to each other. Both antennas are used for the transmit and the receive channel either. The sensor topology of the radar system is explained. Furthermore the measurement results of the protoype are presented and discussed.