University of Augsburg

This research aims to enhance fibre-matrix adhesion in bio-based fibre-reinforced polyolefins without using adhesion promoters. The primary focus is to establish a cross-linking mechanism between cellulose fibres and polyethylene by applying UV irradiation to a UV-transparent matrix and UV-absorbing fibres. The influence of UV treatment on the composite properties is evaluated by tensile, interfacial and interlaminar shear strength tests. The UV irradiation decreases the critical fragment length in single fibre fragmentation tests, indicating an improved fibre-matrix adhesion. The UV-irradiated composites’ tensile strength and Young’s modulus are found to be ~10% (for 3- and 8-minute irradiation) and ~50% (for 8-minute irradiation), respectively, higher than those of the untreated samples. Furthermore, the UV irradiation leads to an improvement in the interlaminar shear strength by 25%. The variation of the UV-irradiation time (3 min and 8 min) and the comparison of the properties of semi-finished composite sheets and composites also reveal chemical and physical changes in the regenerated cellulose fibres due to heat adsorption. The proposed mechanism of interfacial crosslinking is confirmed by FTIR spectroscopy. The results suggest an approach to overcome poor compatibility between hydrophobic polyolefin matrix and hydrophilic cellulose-based fibres, resulting in adhesive-free bio-based composites.

The interplay between European and national law poses considerable problems not only from a legal perspective. Enterprises also face economic challenges as the absence of a European “level playing field” leads to rising transaction costs. This article uses the example of the PRIIP Regulation to illustrate the interplay between the various hierarchical levels of European law and attempts to provide a methodological solution for yet unresolved issues. Finally, the article raises the question whether the PRIIP Regulation has really achieved its legislative objectives.

In this study, the capability of a statistical downscaling model (SDSM) is evaluated to simulate precipitation regarding 37 rain gauge stations (1985–2005) in the North Karun Watershed (NKW), DeZ Watershed (DZW), and KarKheh Watershed (KKW). The fifth generation ECMWF atmospheric reanalysis (ERA5) dataset for calibration (1985–1993) of the model and the outputs of the Norwegian Earth System Model (NorESM1-M) for validation over a historical period (1994–2005) was used. Representative concentration pathways (RCPs) 4.5 and 8.5 scenarios in the near (the 2030s) and mid-term future (the 2060s) using the NorESM1-M model to project precipitation was utilized. Maximum 24-h precipitation (MP24) over the future periods was derived from the projected annual mean precipitation series. The MP24 with generalized normal (GNO) and generalized logistic (GLO) probability distribution functions (PDFs) as the most suitable distribution was then regionalized. The results of the selection predictor stage indicate that precipitation is mainly affected by relative humidity, precipitation rate, and wind in the whole region. Moreover, the results evaluating the performance of the SDSM model at all the stations reveal that the model is classified into good and very good categories. Over both calibration and validation periods, the simulated series are almost close to the observed series. Hence, the SDSM model can potentially downscale future precipitation in the region. The annual precipitation under all scenarios is projected to increase except for scenario RCP8.5 in the 2060s. Comparing the MP24 under scenario RCP4.5 with the baseline period shows a rise in precipitation by about 8% in the 2030s and roughly 9.4% in the 2060s, while under scenario RCP8.5, it will increase by approximately 7.5% and 5.6%, respectively, over the same periods. Overall, the future MP24 in the eastern parts, especially in the northeast and center of the study area, is considerable, which could be due to increased elevation. The MP24 as an extreme event also shows more noticeable changes than annual precipitation under future climatic conditions. In general, extreme precipitation will see a growth in the future, leading to an increase in flood risk in this region.

The European Clozapine Task Force is a group of psychiatrists and pharmacologists practicing in 18 countries under European Medicines Agency (EMA) regulation, who are deeply concerned about the underuse of clozapine in European countries. Although clozapine is the most effective antipsychotic for people with treatment-resistant schizophrenia, a large proportion of them do not have access to this treatment. Concerns about clozapine-induced agranulocytosis and stringent blood monitoring rules are major barriers to clozapine prescribing and use. There is a growing body of evidence that the incidence of clozapine-induced agranulocytosis is very low after the first year of treatment. Maintaining lifelong monthly blood monitoring after this period contributes to unjustified discontinuation of clozapine. We leverage recent and replicated evidence on the long-term safety of clozapine to call for the revision and updating of the EMA's blood monitoring rules, thus aiming to overcome this major barrier to clozapine prescribing and use. We believe the time has come for relaxing the rules without increasing the risks for people using clozapine in Europe.

Background While some memory decline in old age is “normal”, there are some older individuals with maintained high cognitive performance. Using a multimodal approach including neuroimaging, fitness, genetic and questionnaire data (Fig1A), we aimed to identify factors that are related to successful cognitive aging and whether these differ between sexes. Method We analyzed 165 cognitively normal older adults age = 60 years from an ongoing study (SFB1436) (age = 71±8years, 43% female). For all participants, we determined plasma Abeta1‐42/Abeta1‐40. Temporal lobe tau burden was estimated by [18F]PI‐2620 in a subsample (see Fig.1A for sample sizes). We assessed global white matter hyperintensity (WMH) volumes and gray matter thickness for medial temporal lobe (MTL), anterior cingulate cortex (ACC) and whole brain. We measured aerobic and muscular capacity (and blood pressure) by fitness assessment and trait/state anxiety by self‐reports. Genetic profiling included KLOTHO and KIBRA polymorphisms and APOE genotype. To phenotype successful cognitive aging, we i) grouped individuals age = 79.5 years into SuperAgers (N = 18) based on delayed verbal recall performance = normative values at age of 50‐60 years versus typical agers (N = 19). For the whole sample we ii) calculated cognitive age gap (CAG) as the difference between cognition‐predicted age and chronological age (Fig.3A). We assessed how markers of pathology, brain structure, fitness, mental health and genetics were related to CAG, covarying for chronological age, sex and education. Result SuperAgers and typical agers did not differ in age, sex, education, fitness, anxiety or Abeta42/40 (all p‐values>0.1). However, SuperAgers had less WMH volume, higher ACC thickness, lower blood pressure and less temporal lobe tau‐tracer binding (small subgroup;). In the whole sample, younger cognitive age related to higher MTL and global cortical thickness, less temporal tau‐tracer binding, less anxiety (all p<0.05; Figure 3B) and marginally to higher muscular capacity (p = .06). Only the association between anxiety measures and CAG was moderated by sex (Fig.3B). CAG was not related to genotype. Conclusion Our results suggest that successful cognitive aging is related to resistance against age‐related pathology and higher brain integrity. Younger cognitive age is linked to better mental health, especially in females.

Objectives The purpose of this study was to evaluate whether the iodine contrast in blood and solid organs differs between men and women and to evaluate the effect of BMI, height, weight, and blood volume (BV) on sex-specific contrast in staging CT. Materials and methods Patients receiving a venous-phase thoracoabdominal Photon-Counting Detector CT (PCD-CT) scan with 100- or 120-mL CM between 08/2021 and 01/2022 were retrospectively included in this single-center study. Image analysis was performed by measuring iodine contrast in the liver, portal vein, spleen, left atrium, left ventricle, pulmonary trunk, ascending and descending aorta on spectral PCD-CT datasets. Univariable and multivariable analyses were performed to assess the impact of sex, age, BMI, height, weight, and BV on the iodine contrast. Results A total of 274 patients were included (mean age 68 years ± 12 SD, 168 men). Iodine contrast in organs and blood attenuation was significantly higher in women when using the same volume of CM. Sex, age, BMI, height, weight, and BV significantly influenced iodine contrast. After adjusting for confounding variables, sex remained a significant factor, with women having higher parenchymal and vascular iodine contrast. Conclusion Standardized or weight-adapted use of CM in venous-phase thoracoabdominal CT scans results in significantly higher contrast in women compared to men. Customizing the CM dose to the patient’s BV could result in a similar contrast between sexes. This approach has the potential to reduce the amount of CM, resulting in cost savings, and to decrease the risks associated with CM, particularly for the female sex. Key Points Question This study addresses whether current standardized iodinated contrast media protocols lead to systematically higher iodine enhancement in women than in men during thoracoabdominal CT. Findings Women consistently show greater iodine enhancement in blood and abdominal organs compared to BMI-matched men when receiving identical volumes of contrast media. Clinical relevance Adjusting contrast media dosage based on blood volume in venous-phase CT scans could equalize parenchymal and intravascular iodine enhancement across sexes. This approach may reduce unnecessary contrast exposure in women, lower associated risks, and optimize healthcare resource allocation.

Zusammenfassung Die Differenzierung von benignen und malignen Halszysten stellt für den HNO-Arzt eine Herausforderung dar. Die Inzidenz von Karzinomen in initial benigne eingestuften Halszysten liegt bei bis zu 24%. Das Ziel dieser Studie war es, über die Malignitätsrate von zystischen zervikalen Läsionen zu berichten und mittels aktueller Leitlinien eine Differenzierung von zervikalen Metastasen im Vergleich zu benignen Halszysten zu erleichtern. Zwischen 2013 und 2023 wurden insgesamt 155 Patienten mit der Verdachtsdiagnose einer lateralen Halszyste in der Abteilung für Hals-, Nasen- und Ohrenheilkunde des Universitätsklinikums Heidelberg behandelt. Bei allen Patienten wurde eine Zystenexstirpation mit oder ohne Panendoskopie durchgeführt. Bei 21,9% der Patienten zeigte sich histologisch eine Lymphknotenmetastase ipsilateral zum Primarius. Das Durchschnittsalter dieser Patienten lag statistisch signifikant höher als das der Patienten mit benignen Läsionen (64,0±12,8 versus 41,0±15,8; p<0,001). Während die Wahrscheinlichkeit einer Malignität bei Patienten unter 54 Jahren selten war (11%), stieg sie in der Altersgruppe von 60–69 Jahren auf 80% an. Die klinische Sensitivität bei Initialverdacht einer benignen Halszyste lag bei 60,3%, die Spezifität bei 48,7%. Zur frühzeitigen Diagnose und Therapie einer unilateralen Halszyste gehört eine individuelle Vorgehensweise, welche durch multiple Faktoren (Anamnese, klinische Befunde, Bildgebung sowie klinikeigene Kompetenzen) getroffen werden muss. Unabhängig davon empfehlen wir bei Patienten über 40 Jahren ein bildmorphologisches Staging, eine „No-touch“-Panendoskopie und eine histologische Sicherung.

Background Dropout from healthcare interventions can negatively affect patients and healthcare providers through impaired trust in the healthcare system and ineffective use of resources. Research on this topic is still largely missing on refugees and asylum seekers. The current study aimed to characterize predictors for dropout in the Mental Health in Refugees and Asylum Seekers (MEHIRA) study, one of the largest multicentered controlled trials investigating the effectiveness and cost-effectiveness of a nationwide stepped and collaborative care model. Methods Predictors were multiply imputed and selected for descriptive modelling using backward elimination. The final variable set was entered into logistic regression. Results The overall dropout rate was 41,7%. Dropout was higher in participants in group therapy ( p = 0.001; OR = 10.7), with larger satisfaction with social relationships ( p = 0.017; OR = 1.87), with difficulties in maintaining personal relationships ( p = 0.005; OR = 4.27), and with higher depressive symptoms ( p = 0.029; OR = 1.05). Participants living in refugee accommodation ( p = 0.040; OR = 0.45), with a change in social status ( p = 0.008; OR = 0.67) and with conduct ( p = 0.020; OR = 0.24) and emotional problems ( p = 0.013; OR = 0.31) were significantly less likely to drop out of treatment. Conclusion Overall, the outcomes of this study suggest that predictors assessing social relationships, social status, and living conditions should be considered as topics of psychological treatment to increase adherence and as predictors for future research studies (including treatment type).

Dissolved oxygen is crucial for metabolism, growth, and other complex physiological and pathological processes; however, standard physiological models (such as organ-on-chip systems) often use ambient oxygen levels, which do not...

Background There are hardly any data on the extent to which nursing home residents are provided with palliative homecare. We want to add evidence by comparing nursing home residents (who had been living in a nursing home for at least one year) and nursing-care-dependent community dwellers in terms of utilization and quality of palliative homecare. Methods We conducted a population-based study with nationwide claims data from deceased beneficiaries of a large German health insurance provider. First, we compared utilization rates of primary palliative care [PPC], specialized palliative homecare [SPHC], and no palliative care [noPC] between nursing home residents and community dwellers, both descriptively and adjusted for covariates. Second, we analyzed the (adjusted) relationship between PPC-only and SPHC (both: starting ≥ 30 days before death), and noPC with healthcare indicators (death in hospital, hospitalization, emergencies, intensive care treatment within the last 30 days of life), and compared these relationships between nursing home residents and community dwellers. Analyses were conducted using simple and multiple logistic regression. Data were standardized by age and gender. Results From 117,436 decedents in 2019, 71,803‬ could be included in the first, 55,367‬ in the second analysis. The rate of decedents with noPC was higher in nursing home residents (61.3%) compared to community dwellers (56.6%). Nursing home residents received less SPHC (10.7% vs. 23.2%) but more PPC (30.3% vs. 27.0%) than community dwellers, and achieved better outcomes across all end-of-life healthcare indicators. Adjusted for covariates, both types of palliative homecare were associated with beneficial outcomes, in nursing home residents as well as in community dwellers, with generally better outcomes for SPHC than PPC-only. For most outcomes, the associations with palliative homecare were equal or smaller in nursing home residents than in community dwellers. Conclusions The overall better performance in quality of end-of-life care in nursing home residents than in community dwellers may be due to the institutionally provided nursing and general practitioner care within nursing homes. This may also explain higher rates of PPC and lower rates of SPHC in nursing home residents, and why the relationship with both PPC and SPHC are smaller in nursing home residents. Trial registration German Clinical Trials Register (DRKS): [DRKS00024133, Date of registration: 28.06.2021].

The Habsburg Empire dissolved after World War One. A new world order of nation‐states was emerging that acknowledged and distributed civic rights to non‐titular nations based on national minority status. How did Jewish communities in the former Kingdom of Hungary respond to the gradual change of sovereignty, the ethnicisation of everyday life and the escalating antisemitic violence? Focusing on the turbulent months between October 1918 and March 1919, this study examines the transformation of loyalty patterns among various Jewish communities at the local, regional, national and international levels. A pivotal aspect of the chaotic transition from empire to nation‐state was the intensified nationalism and the growing interest in models accommodating ethno‐confessional diversity. Amid the emerging solutions to the minority question in East‐Central Europe and worldwide, this paper focuses on the model of non‐territorial autonomy within Jewish communities in the territories that became part of Romania and Czechoslovakia.

Within the material family of metal–organic frameworks (MOFs) the subclass of flexible MOFs (flexMOFs) has attracted great attention, showing structural flexibility as a response to external stimuli such as guest adsorption, temperature, and pressure. Hybrid composites like nanoparticle (NP) loaded flexible MOFs, which stand to potentially combine advantageous properties of both are yet largely unexplored. Here the synthesis of flexMOFs with surface mounted nanoparticles, e. g. NP@Zn2(BME‐bdc)2dabco composites (NP = Pt and SiO2 nanoparticles, BME‐bdc²⁻ = 2,5‐bismethoxyethoxy‐1,4‐benzenedicarboxylate, dabco = 1,4‐diazabicyclo[2.2.2]octane) is reported, studying the impact of nanoparticles on the stimulus‐responsiveness of a flexMOF. It is shown that CO2 physisorption triggered flexibility of the MOF is retained and reversible for all NP@flexMOF composites. Additionally, it is observed that NPs stabilize the large pore state of the MOF, slightly increasing and shifting the switching pressure window. This effect is also observed during temperature‐induced switching but Pt@flexMOF composites partially lose long‐range order during the reversion to their narrow pore state, while attached SiO2 NPs allow for a fully reversible transition. These findings suggest that the total exerted material strain triggering the switching is heavily dependent on NP size and the applied stimulus and that guest‐induced switchability can be fully realized in NP@flexMOF hybrid materials.

Background Second-line treatment options for persistent, recurrent or metastatic (r/m) cervical cancer are limited. We investigated the safety, efficacy, and immunogenicity of the therapeutic DNA-based vaccine VB10.16 combined with the immune checkpoint inhibitor atezolizumab in patients with human papillomavirus (HPV)16-positive r/m cervical cancer. Patients and methods This multicenter, single-arm, phase 2a study ( NCT04405349 , registered 26 May 2020) enrolled adult patients with persistent, r/m HPV16-positive cervical cancer. Patients received 3 mg VB10.16 (every 3 weeks (Q3W) for 12 weeks, hereafter every 6 weeks) combined with 1,200 mg atezolizumab (Q3W) for 48 weeks in total with a 12-month follow-up. The primary endpoints were incidence and severity of adverse events (AEs) and objective response rate (ORR; Response Evaluation Criteria in Solid Tumor V.1.1). ORR was assessed in the efficacy population, being all response-evaluable patients who received any administration of VB10.16 and atezolizumab and had at least one post-baseline imaging assessment. Results Between June 16, 2020, and January 25, 2022, 52 patients received at least one administration of study treatment. Of these, 47 patients had a minimum of one post-baseline tumor assessment. The median follow-up time for survival was 11.7 months. AEs related to VB10.16 were non-serious and mainly mild injection site reactions (9 of 52 patients). There were no signs of new toxicities other than what was already described with atezolizumab. ORR was 19.1% (95% CI 9.1% to 33.3%). Median duration of response was not reached (n.r.) (95% CI 2.2 to n.r.), median progression-free survival was 4.1 months (95% CI 2.1 to 6.2), and median overall survival was 21.3 months (95% CI 8.5 to n.r.). In programmed death-ligand 1 (PD-L1)-positive patients (n=24), ORR was 29.2% (95% CI 12.6 to 51.1). HPV16-specific T-cell responses were analyzed in 36 of 47 patients with an increase observed in 22/36 (61%). Conclusions The therapeutic DNA-based vaccine VB10.16 combined with atezolizumab was safe and well tolerated showing a promising clinically meaningful efficacy with durable responses in patients with persistent, r/m HPV16-positive cervical cancer, especially if PD-L1-positive.

Background There are limited therapeutic options in cases of failed reperfusion (modified thrombolysis in cerebral infarction [mTICI] score < 2b) after stent-retriever and/or aspiration based endovascular treatment (EVT) for acute ischemic stroke. Despite the absence of data supporting its use, rescue therapy (balloon angioplasty and/or stent implantation) is often utilized in such cases. Studies are limited to large vessel occlusions, while the outcomes and complications after rescue therapy in medium/distal vessel occlusions (MDVOs) have not been reported. This study aims to report the outcomes of rescue therapy in MDVO stroke patients. Methods We performed an analysis of the “Blood pressure and Antiplatelet medication management after reScue angioplasty after failed Endovascular treatment in Large and distal vessel occlusions with probable IntraCranial Atherosclerotic Disease” (BASEL ICAD) retrospective registry. All MDVO stroke patients were included in the analysis. Results Out of the 718 registry patients, 87 (12.1%) presented with an MDVO. Fifty-six patients (64.4%) showed an occlusion of the M2 segment of the middle cerebral artery. Rescue stenting was performed in 78 patients (89.7%) while balloon angioplasty alone was performed in 9 patients (10.3%). Successful reperfusion (mTICI score ⩾ 2b) was achieved in 73 (83.9%) patients after rescue therapy. Symptomatic intracranial hemorrhage (sICH) occurred in 8 patients (9.2%) and post-treatment stent occlusion in 12 patients (13.8%). Ninety days mortality was 20.7%. Twenty-eight patients (32.2%) achieved functional independence at 90 days (modified Rankin Scale 0–2). Conclusion Rescue therapy with stenting and/or balloon angioplasty in patients undergoing EVT for isolated MDVO with suspected underlying intracranial atherosclerotic disease is an effective reperfusion strategy but is associated with complications and poor functional outcomes.

Abstract: Introduction: The number of incidental renal lesions identified in CT scans of the abdomen is increasing. Objective: The aim of this study was to determine whether hyperdense renal lesions without solid components in a portal venous CT scan can be clearly classified as vascular or non-vascular by material decomposition into iodine and water. Methods: This retrospective single-center study included 26 patients (mean age 72 years ± 9; 16 male) with 42 hyperdense renal lesions (>20 HU) in a contrast-enhanced Photon-Counting Detector CT scan (PCD-CT) between May and December 2022. Spectral decomposition into virtual non-contrast (VNC) images and iodine quantification maps was performed, and HU values were quantified within the lesions. Further imaging and histopathological reports served as reference standards. Results: Mean VNC values were 55.7 (±24.2) HU for non-vascular and 32.2 (±11.1) HU for vascular renal lesions. Mean values in the iodine maps were 5.7 (±7.8) HU for non-vascular and 33.3 (±19.0) HU for vascular renal lesions. Using a threshold of >20.3 HU in iodine maps, a total of 7/8 (87.5%) vascular lesions were correctly identified. Conclusion: This proof-of-principle study suggests that the routine use of spectral information acquired in PCD-CT scans might be able to reduce the necessary workup for hyperdense renal lesions without solid components. Further studies with larger patient cohorts are necessary to validate the results of this study and to determine the usefulness of this method in clinical routine.

Purpose: To establish the extent, distribution and frequency of in-vivo vessel wall [⁶⁸Ga]Ga-PentixaFor uptake and to determine its relationship with calcified atherosclerotic plaque burden (CAP) and cardiovascular risk factors (CVRF). Methods: 65 oncological patients undergoing [⁶⁸Ga]Ga-PentixaFor PET/CT were assessed. Radiotracer uptake (target-to-background ratio [TBR]) and CAP burden (including number of CAP sites, calcification circumference and thickness) in seven major vessel segments per patient were determined. We then investigated associations of vessel wall uptake with CAP burden, cardiovascular risk (CVRF and European Society of Cardiology [ESC] SCORE2/SCORE2-OP risk chart) and image noise (determined by coefficient of variation [CoV] from unaffected liver parenchyma). Results: We identified 1292 sites of high focal [⁶⁸Ga]Ga-PentixaFor uptake (PentixaFor+ sites) in the vessel wall in 65/65 (100%) patients, with concomitant calcification in 385/1292 (29.8%) sites. There were no significant associations between vessel wall uptake and CAP burden (number of PentixaFor+ sites: r ≤ 0.18, P ≥ 0.14; PentixaFor+ TBR: r ≤ 0.08, P ≥ 0.54). The number of PentixaFor+ sites showed a moderate correlation with cardiovascular risk (ESC SCORE2/SCORE2-OP, r = 0.30; number of CVRF, r = 0.26; P = 0.04, respectively), but failed to reach significance for PentixaFor+ TBR (r ≤ 0.18, P ≥ 0.22). In univariable regression analysis, body mass index (odds ratio [OR] 1.08, 95%-confidence interval [CI] 1.02-1.14) and CoV (OR, 1.07; CI, 1.05-1.10) were linked to TBR and the number of PentixaFor+ sites (P < 0.01, respectively), while injected activity was only associated with the latter imaging parameter (OR, 0.99; CI, 0.98-1.00; P = 0.04). In multivariable regression, injected activity (OR, 1.00; CI, 0.99-1.00) and CoV (OR, 1.06; CI, 1.06-1.07) remained significantly associated with the number of PentixaFor+ sites (P < 0.01, respectively). CoV, however, was the only parameter significantly linked to PentixaFor+ TBR on multivariable analysis (OR, 1.02; CI, 1.01-1.03; P < 0.01). Conclusion: On a visual and quantitative level, high focal [⁶⁸Ga]Ga-PentixaFor uptake in the arterial tree was not consistently linked to vessel wall calcification or cardiovascular risk. Image noise, however, may account for a substantial portion of apparent vessel wall uptake.