Regional regime complexity is on the rise. The 73 regional international organizations (RIOs) increasingly overlap with respect to member states and policy competencies. The corresponding risk of maladaptation and ineffective regional governance, e.g., in the form of wasted resources or incompatible policies, can be countered when overlapping RIOs engage in adaptation by inter-organizational cooperation. Adaptation can be minimalist, geared towards avoiding negative externalities by information-sharing or consultation (“problem-avoiding adaptation”). Alternatively, “synergy-creating adaptation” is geared towards creating added values for the cooperating RIOs, for instance by joint decision-making or implementation and other joint activities. When do overlapping RIOs choose problem-avoidance and when do they opt for synergy-creating adaptation? We use a novel dataset (IOCA) and institutionalist approaches to identify potential exogenous and endogenous driving forces for adaptation. The quantitative analysis shows that the propensity for adaptation in regime complexes in Africa, Asia, the Americas and Europe is furthered by endogenous causes (extent of overlap, duration of overlap, prior cooperation experiences) while exogenous factors play out differently in different contexts. Moreover, RIOs are more prone to opt for synergy-creating adaptation the more similar they are in ideological terms in American, Asian and European regional regime complexes, while this factor has the opposite effect in the African regional regime complex.

In business-to-business settings, purchasing dominantly takes place within customer-supplier relationships. Therefore, from a supplier perspective, it is important to understand what drives customers' rebuy decisions. Here, the value in use that individual representatives of a customer organization, based on the achievement of their individual and collective goals, experience in their usage processes has an important impact on the firm's loyalty. However, only little is known about how the various users in a customer firm, the members of a business usage center (BUC), perceive value in use and how these perceptions are influenced by their interactions. In two studies with 18 interviewees using the repertory grid technique in combination with means-end chaining, this paper investigates how actors' self-concepts influence their attributed reasons for actions of other BUC members and in turn the perceptions of their behaviors. Eleven attributed reasons for action are elicited that are grouped into four clusters covering competence profile, emotional profile, job requirements, and personal motivation. The findings of this study complement existing research that mainly uses hierarchical positions and organizational roles to explain individual assessments and decision-making specifically related to business buying behavior. Based on these insights, theoretical as well as managerial implications are discussed and avenues for further research are presented.

During the Covid-19 crisis, most OECD countries used short-time work (subsidised reductions in working hours) to preserve employment. This paper documents that short-time work affects the behaviour of firms (supply) and households (demand). First, using household survey data from Germany, we show that the consumption risk of short-time work is lower than that of unemployment. Second, we construct a New Keynesian model with heterogeneous workers and firms, incomplete asset markets, and labour market frictions. Short-time work weakens workers’ precautionary savings motive and lowers labour costs. This reduces the level and volatility of both the separation and unemployment rate at the cost of tying workers to less productive firms.

This article explores how salespeople in business markets communicate customer value propositions (CVPs) to the different actors involved in organizational purchase decisions. As a result, the authors introduce a novel, buying-center-member-based framework of CVP adaptive communication. This framework categorizes CVP adaptive communication as an operational selling behavior among salespeople comprising three consecutive steps: (1) perceiving cues from buying-center members, (2) reacting to these cues through changes in CVP communication, and (3) addressing particular customer goals as CVP communication ends. The authors propose two complementary approaches that explain the heterogeneity in how CVP communication is adapted, building on means-end chaining and revealing that CVP adaptive communication arises from a set of 15 buying-center member perception cues. Using configurational analyses, the study reveals that salespeople identify constellations of buyer types that are consistently addressed through the same CVP communication. These configurational results indicate four buyer types: two types for whom salespeople address customers’ collective value in use and two types for whom salespeople address customers’ individual value in use. Generally, the study helps offer a new understanding of value communication rooted in an outside-in perspective on the CVP that considers customers as external triggers of CVP communication changes.

Background and aims: The effects of direct oral anticoagulants (DOACs) in patients with non-valvular atrial fibrillation (NVAF) and liver disease remain poorly understood. Our multinational cohort study assessed the effectiveness and safety of DOACs in this high-risk population. Methods: We assembled two population-based cohorts in United Kingdom and in Québec of NVAF patients with liver disease initiating DOACs or vitamin K antagonists (VKAs) between 2011 and 2020. Using an as-treated exposure definition, we compared DOACs to VKAs and apixaban to rivaroxaban. After inverse probability of treatment weighting, Cox proportional hazards models estimated site-specific hazard ratios (HRs) and 95 % confidence intervals (CIs) of ischemic stroke and major bleeding. Site-specific estimates were pooled using random-effects models. Analyses were repeated among NVAF patients with cirrhosis. Results: There were 11,881 NVAF patients with liver disease (2683 with cirrhosis). Among those, 8815 initiated DOACs (4414 apixaban, 2497 rivaroxaban) and 3696 VKAs. The HRs (95 % CIs) for DOACs compared to VKAs were 1.01 (0.76-1.34) for ischemic stroke and 0.87 (0.77-0.99) for major bleeding. Results were consistent among patients with cirrhosis. The HRs (95 % CIs) for apixaban compared to rivaroxaban were 0.85 (0.60-1.20) for ischemic stroke and 0.80 (0.68-0.95) for major bleeding. This decreased bleeding risk was not observed among patients with cirrhosis (HR, 1.01; 95 % CI 0.72-1.43). Conclusions: Among NVAF patients with liver disease, DOACs were as effective and slightly safer than VKAs, and apixaban was as effective but safer than rivaroxaban. The safety benefit with apixaban was not present among patients with cirrhosis.

Background: Liver transplantation is a life-saving therapy for end -stage liver disease patients, but acute cellular rejection (ACR) and graft complications remain significant postoperative challenges. Early and accurate diagnosis is crucial for timely intervention and improved patient outcomes, but their diagnosis rely currently on invasive biopsy sampling, thus prompting the search for non-invasive Biomarkers. MicroRNA (miRNA) have emerged as promising biomarkers in various pathological conditions, and their potential utility in diagnosing acute cellular rejection after liver transplantation has gained significant interest. Methods: This systematic review of PubMed, Web of Science, and the ClinicalTrials.gov registry analyzes studies exploring miRNA as biomarkers for ACR and graft dysfunction in liver transplantation (PROSPERO ID CRD42023465278). The Cochrane Collaboration tool for assessing risk of bias was employed. Population data, identified miRNA and their dynamic regulation, as well as event prediction were compared. Data extraction and quality assessment were performed independently by two reviewers. Results: Thirteen studies were included in this systematic review. Various investigated miRNAs were upregulated in association with acute cellular rejection, like miR-122, miR-155, miR-181, miR-483-3p, and miR-885-5p, demonstrating great biomarker potential. Additionally, several studies conducted target gene analysis, revealing insights into cellular mechanisms linked to ACR. Moreover, various miRNA were also capable of predicting different organ complications following transplantation, expanding their versatility. Remaining challenges include the standardization of miRNA profiling, the need for functional validation, and the necessity for long-term studies. Conclusion: The results highlight the potential of miRNA as specific, non-invasive biomarkers for ACR and graft dysfunction following liver transplantation. However, further research is needed to validate these findings and establish standardized diagnostic panels to incorporate them into clinical practice and explore miRNA-based therapies in the future.

Selenium (Se) is an essential trace element, which is inserted as selenocysteine (Sec) into selenoproteins during biosynthesis, orchestrating their expression and activity. Se is associated with both beneficial and detrimental health effects; deficient supply or uncontrolled supplementation raises concerns. In particular, Se was associated with an increased incidence of type 2 diabetes (T2D) in a secondary analysis of a randomized controlled trial (RCT). In this review, we discuss the intricate relationship between Se and diabetes and the limitations of the available clinical and experimental studies. Recent evidence points to sexual dimorphism and an association of Se deficiency with gestational diabetes mellitus (GDM). We highlight the emerging evidence linking high Se status with improved prognosis in patients with T2D and lower risk of macro- vascular complications.

Alzheimer's disease (AD) and schizophrenia (SCZ) represent two major neuropathological conditions with a high disease burden. Despite their distinct etiologies, patients suffering from AD or SCZ share a common burden of disrupted memory functions unattended by current therapies. Recent preclinical analyses highlight cell-type-specific contributions of parvalbumin interneurons (PVIs), particularly the plasticity of their cellular excitability, towards intact neuronal network function (cell-to-network plasticity) and memory performance. Here we argue that deficits of PVI cell-to-network plasticity may underlie memory deficits in AD and SCZ, and we explore two therapeutic avenues: the targeting of PVI-specific neuromodulation, including by neuropeptides, and the recruitment of network synchrony in the gamma frequency range (40 Hz) by external stimulation. We finally propose that these approaches be merged under consideration of recent insights into human brain physiology.

Objectives: Partial cystectomy (PC) has been proposed as a less invasive alternative to radical cystectomy (RC) for the treatment localized muscle-invasive bladder cancer (MIBC). The aim of this study was to evaluate the outcome of PC in a contemporary patient cohort to identify potential risk factors for this procedure. Methods: Data from 58 MIBC patients who underwent PC were retrospectively analyzed. Demographics, tumor characteristics, clinical outcomes, and pathology results were collected. Statistical analysis was performed using Cox regression and Kaplan-Meier method to determine survival rates and risk factors. Results: The cohort consisted of 58 patients with MIBC with a median age of 71 years. The 5-year overall survival (OS), cancer specific survival (CSS) and recurrence-free survival (RFS) rates were 55%, 67% and 51%, respectively. Clinical suspicion for lymph node metastases (HR 3.82, CI 1.09-13.39, P = 0.036), advanced T-stages (HR 3.80, CI 1.38-10.49, P = 0.010), a higher grading (HR 6.57, CI 0.76 -49.19, P = 0.010), positive resection margins (HR 1.81, CI 1.10-2.96, P = 0.012), lymphovascular invasion (HR 5.14, CI 1.77-14.88, P = 0.003), vascular invasion (HR 6.62, CI 2.16-20.27, P = 0. 001), and longer time from initial diagnosis to surgery (HR 1.003, CI 1.001 -1.01, days, P = 0.010) were associated with decreased OS. Complications within the first 30 and 90 postoperative days were observed 31% and 36% of patients, respectively. 4% experienced a Clavien-Dino grade III/IV complication. One patient developed acute respiratory distress syndrome and died 46 days after surgery. Conclusion: Partial cystectomy appears to be a safe bladder-sparing approach for highly selected MIBC patients with favorable oncologic outcomes and acceptable complication rates. Patient selection and assessment of tumor characteristics are essential for successful outcomes. Prospective randomized controlled trials are needed.

Background: The aim of this study was to analyze four pre -operative physical frailty indicators from a geriatric assessment (GA) independently and combined in a physical frailty index, in their ability to predict postoperative 30 d -complications. Materials and methods: In this secondary analysis of data from the published PERATECS study (ClinicalTrials.gov: NCT01278537), the predictive value of four physical frailty indicators from a defined GA battery was examined with univariable and multivariate logistic regression models in a sample of 493 onco-geriatric surgical patients. The primary endpoint was incidence of major (Clavien -Dindo >= grade 2 [CD >= 2]) complications within 30 postoperative days. Predictors of the first model included self -reported exhaustion (SRE), body mass index (BMI), Timed Up -and -Go (TUG) and handgrip strength (HGS) independently, and a second model combined these four items as a Physical Frailty Index (4i-PFI). Both regression models were adjusted for age, gender, American Society of Anesthesiologists (ASA) status, tumor sites, duration of surgery time and Mini Nutritional Assessment (MNA) score. Results: A total of 233 patients (47 %) developed CD >= 2 complications. In addition to ASA score, length of surgery, and gynecological and upper gastrointestinal tumor sites, the first model showed that SRE (OR 1.866) predicted CD >= 2 complications, but not TUG, BMI and HGS. In the second model, the 4i-PFI predicted CD >= 2 complications (OR pre -frail = 1.808, frail = 3.787). Conclusions: Physical frailty indicators as SRE revealed a better ability to predict CD >= 2 complications than BMI, TUG and HGS. However, prediction of CD >= 2 complications was enhanced when these parameters were combined in a novel 4i-PFI.

Purpose: To assess the efficacy and safety of computed tomography (CT)-guided high-dose-rate HDR) brachytherapy in treating recurrent hepatocellular carcinoma (HCC) not amenable to repeated resection or radiofrequency ablation. Materials and methods: From January 2010 to January 2022, 38 patients (mean age, 70.1 years; SD +/- 9.0 years) with 79 nodular and four diffuse intrahepatic HCC recurrences not amenable to repeated resection or radiofrequency ablation underwent CT-guided HDR brachytheapy in our department. Tumor response was evaluated by cross-sectional imaging 6 weeks after CT-guided HDR brachytherapy and every 3 months thereafter. Local tumor control (LTC), progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meier curves (KPCs). Severity of procedure-related complications (PRCs) was classified as recommended by the Society of Interventional Radiology (SIR). Results: Patients were available for MRI evaluation for a mean follow-up of 33.1 months (SD, +/- 21.6 mm, range 4-86 months; median 29 months). Patients had a mean of 2.3 (SD, +/- 1.4) intrahepatic tumors. Mean tumor diameter was 43.2 mm (SD, +/- 19.6 mm). 13 of 38 (34.2%) patients showed local tumor progression after CTguided HDR brachytherapy. Mean LTC was 29.3 months (SD, +/- 22.1). Distant tumor progression was seen in 12 patients (31.6%). The mean PFS was 20.8 months (SD, +/- 22.1). Estimated 1-, 3-, and 5-year PFS rates were 65.1%, 35.1% and 22.5%, respectively. 13 patients died during the follow-up period. Mean OS was 35.4 months (SD, +/- 21.7). Estimated 1-, 3-, and 5-year OS rates were 91.5%, 77.4% and 58.0%, respectively. SIR grade 1 complications were recorded in 8.6% (5/38) and SIR grade 2 complications in 3.4% (2/58) of interventions. Conclusion: CT-guided HDR brachytherapy is a safe and efficient therapeutic option for managing large or critically located HCC recurrences in the remaining liver after prior hepatic resection.

Maternal immunisation is a powerful tool to protect both pregnant women and their children. A new maternal RSV vaccine holds promise to protect newborns from RSV-associated illness in the first few months of life, but no official recommendation has been made in Germany. Since RSV causes a significant burden of paediatric hospital admissions, we consider it a pertinent opportunity to review barriers to maternal vaccination in Germany, which might also apply to other settings. Access to vaccination for pregnant women in Germany is shaped by an interplay of legal, regulatory, institutional, and sociocultural factors, with a less permissive clinical research environment, delays in recommendation and roll-out, and lower acceptance by healthcare professionals and the population. Actionable recommendations to improve availability and uptake include coordination with other national regulatory bodies to reduce delays, awareness and literacy campaigns for health professionals and the general public, and capacity building for vaccine clinical research.

Introduction: The clinical role of lymphadenectomy (LAD) as part of hepatic resection for malignancies of the liver remains unclear. In this study, we aimed to report on the use cases and postoperative outcomes of liver resection and simultaneous LAD for hepatic malignancies (HM). Materials and methods: Clinicopathological data from patients who underwent surgery at 13 German centers from 2017 to 2022 (n = 3456) was extracted from the StuDoQ'Liver registry of the German Society of General and Visceral Surgery. Propensity-score matching (PSM) was performed to account for the extent of liver resection and patient demographics. Results: LAD was performed in 545 (16%) cases. The most common indication for LAD was cholangiocarcinoma (CCA), followed by colorectal liver metastases (CRLM) and hepatocellular carcinoma (HCC). N+ status was found in 7 (8%), 59 (35%), and 56 cases (35%) for HCC, CCA, and CRLM, respectively (p < 0.001). The LAD rate was highest for robotic-assisted resections (28%) followed by open (26%) and laparoscopic resections (13%), whereas the number of resected lymph nodes was equivalent between the techniques (p = 0.303). LAD was associated with an increased risk of liver-specific postoperative complications, especially for patients with HCC. Conclusion: In this multicenter registry study, LAD was found to be associated with an increased risk of liverspecific complications. The highest rate of LAD was observed among robotic liver resections.

Background: The Prostate Imaging-Reporting and Data System (PI-RADS) calls for reporting the prostate index lesion and the location within the transition (TZ) or peripheral zone (PZ) and location on a corresponding sector map. The aim of this study was to train a deep learning DL-based algorithm for automatic prostate sector mapping and to validate its' performance. Methods: An automatic 24-sector grid-map (ASG) of the prostate was developed, based on an automatic zone-specific deep learning segmentation of the prostate. To evaluate the efficacy of the method, fiducials for random locations within the prostate were placed, and the corresponding sectors were determined for 50 mpMRI datasets. The reference standard was defined in a consensus read by two expert uroradiologists. Annotated fiducial locations were evaluated automatically by the ASG and by four radiologists in two reads with and without the help of a superimposed sector grid-map and the success rate was compared. Results: The ASG algorithm identified the correct prostate sector of the annotated lesions in 80 % (40/50 reads) of the cases and outperformed readings of the four radiologists with 55 % (109/200), p < 0.0001. The added use of the 24 ASG map significantly improved the rate of correct sector annotation for the four radiologists to 71 % (141/200), p < 0.004. Conclusion: The 24 ASG map was effective for prostate sector segmentation and significantly improved location reporting of prostate lesions.

The concentration of air pollution is gradually increasing every year so that daily skin exposure is unavoidable. Dietary supplements and topical formulations currently represent the protective strategies to guard against the effects of air pollution on the body and the skin. Unfortunately, there are not yet enough methods available to measure the effectiveness of anti-pollution products on skin. Here, we present two ex vivo methods for measuring the protective effect against air pollution of different cream formulations on the skin: Electron paramagnetic resonance (EPR) spectroscopy and autofluorescence excited by 785 nm using a confocal Raman microspectrometer (CRM). Smoke from one cigarette was used as a model pollutant. EPR spectroscopy enables the direct measurement of free radicals in excised porcine skin after smoke exposure. The autofluorescence in the skin was measured ex vivo, which is an indicator of oxidative stress. Two antioxidants and a chelating agent in a base formulation and a commercial product containing an antioxidant mixture were investigated. The ex vivo studies show that the antioxidant epigallocatechin-3-gallate (EGCG) in the base cream formulation provided the best protection against oxidative stress from smoke exposure for both methods.

Background: Current treatment for head and neck squamous cell carcinoma (HNSCC) involves surgery, radiotherapy, and chemotherapy. Despite aggressive multimodal approaches, tumour recurrence occurs in 40-60 % of cases, leading to poor survival outcomes. HNSCC lacks common genetic drivers for tailored therapies, and reliable biomarkers for treatment selection are scarce. We investigated the procedural requirements for incorporating drug- and radiosensitivity screens in patient-derived organoids (PDOs) within a clinical trial framework. Patients and methods: Fresh tumour samples (N = 198) from 186 HNSCC patients were included. Success rates of organoid establishment were correlated with clinical and procedural parameters. Timelines for establishment of PDO cultures were determined, and their long-term growth potential assessed by serial passaging. Additionally, we conducted whole exome sequencing on matched tumour-organoid pairs. Three PDO models were employed to establish radiosensitivity assays. Results: In total, PDO models displaying histomorphological features and genomic alterations of parental tumours were successfully established for 35 % of patient tumours. Success rates rose to 77 % for samples with a tumour cell content of 30 % or higher. Advanced patient age, prior radiotherapy, and delays in tissue processing were identified as negative predictors for engraftment. The estimated time interval needed for screens was compatible with PDO-guided selection of curative-intent radiotherapy regimens. Conclusions: Our findings suggest that with high-quality samples and efficient tissue processing, PDO screens can be successfully performed in 77 % of HNSCC patients. Given the procedural challenges involved, future clinical trials aiming to the utility of PDOs for guiding treatment decisions should consider implementing centralised PDO screening.

OBJECTIVE: This prospective study assesses the acceptance and usefulness of augmented 360° virtual reality (VR) videos for early student education and preparation in the field of neurosurgery. METHODS: Thirty-five third-year medical students participated. Augmented 360° VR videos depicting three neurosurgical procedures (lumbar discectomy, brain metastasis resection, clipping of an aneurysm) were presented during elective seminars. Multiple questionnaires were employed to evaluate conceptual and technical aspects of the videos. The analysis utilized ordinal logistic regression to identify crucial factors contributing to the learning experience of the videos. RESULTS: The videos were consistently rated as good to very good in quality, providing detailed demonstrations of intraoperative anatomy and surgical workflow. Students found the videos highly useful for their learning and preparation for surgical placements, and they strongly supported the establishment of a VR lounge for additional self-directed learning. Notably, 81% reported an increased interest in neurosurgery, and 47% acknowledged the potential influence of the videos on their future choice of specialization. Factors associated with a positive impact on students' interest and learning experience included high technical quality and comprehensive explanations of the surgical steps. CONCLUSIONS: This study demonstrated the high acceptance of augmented 360 degrees VR videos as a valuable tool for early student education in neurosurgery. While handson training remains indispensable, these videos promote conceptual knowledge, ignite interest in neurosurgery, and provide a much-needed orientation within the operating room. The incorporation of detailed explanations throughout the surgeries with augmentation using superimposed elements, offers distinct advantages over simply observing live surgeries.

OBJECTIVE: Precise planning and execution is key for neuroendoscopic interventions, which can be based on different available aiding technologies. The aim of this retrospective study is to report a case -based use of guided neuroendoscopy and to develop a stratification algorithm for the available technologies. METHODS: We reviewed consecutive neuroendoscopic cases performed at our center from 2016 to 2018. We distinguished between patients receiving a new burr hole (group A) and those with a preexisting burr hole (group B). Case -specific technical requirements for procedure planing and execution, complication rate, surgical outcome, and possible subsequent surgery were evaluated. From this experience, a stratification system was developed to tailor the available guiding technologies. RESULTS: A total of 309 neuroendoscopic interventions in 243 patients were included in the present study. The cases included hydrocephalic (81.6%) and nonhydrocephalic (18.4%) conditions. The interventions were supported by coordinate -based (group A, n = 49; group B, n = 67), guidebased (group A, n = 42; group B, n = 0), ultrasound -guided (group A, n = 50; group B, n = 7), or navigated augmented reality -guided (group A, n = 85; group B, n = 9) techniques. The overall complication rate was 4.5%. Stratified by the surgical indication, fontanel status, entry point localization, presence of a preexisting burr hole, ventricular size, and n umber of targets, an approach toward image -guided neuroendoscopy is suggested. CONCLUSIONS: Planning and technical guidance is essential in neuroendoscopic procedures. The stratified decision -making algorithm for different available technologies aims to achieve lower cost and time consumption, which was found to be safe and efficient. Further investigations are warranted to deliver solid data on procedure efficiency.