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Background: Biliary atresia (BA) is a rare condition of unknown origin in newborns with jaundice. In BA bile ducts are non-functional, causing neonatal cholestasis and following liver fibrosis and failure. Methods: This retrospective study included liver biopsies of 14 infants with BA aged [mean ± SD] 63 ± 23 days. Patients were grouped according to the clinical course (jaundice-free vs recurrent jaundice vs required liver transplantation or liver fibrosis (Ishak fibrosis score)) and followed for 1.61–5.64 years (mean 4.03). Transcriptome profiles were assessed using a panel of 768 fibrosis-specific genes, reanalyzed via qRT-PCR, and confirmed via immunostaining. Plasma from an additional 30 BA infants and 10 age-matched controls were used for amyloid precursor protein (APP) quantification by ELISA. Results: Different clinical outcome groups showed a homogeneous mRNA expression. Altered amyloid-metabolism-related gene expression was found between cases with Ishak fibrosis score greater than 4. Immunostaining confirmed a distinct presence of APP in the livers of all BA subjects. APP plasma levels were higher in BA than in age-matched controls and correlated with the histological fibrosis grade. Conclusions: These results suggest that amyloidosis may contribute to BA and liver fibrosis, indicating that APP could serve as a potential liquid biomarker for these conditions. Impact:

Biliary atresia patients with higher fibrosis scores according to Ishak have higher hepatic expression of amyloid-related genes while amyloid precursor protein accumulates in the liver and increases in the circulation.

After a recent study revealed beta-amyloid deposition as a mechanism potentially involved in biliary atresia, we were able to correlate amyloid-metabolism-related transcript levels as well as amyloid precursor protein tissue and plasma levels with the degree of hepatic fibrosis.

These findings suggest that amyloid precursor protein is a fibrosis marker in infants with biliary atresia, reinforcing the role of amyloid metabolism in the pathogenesis of this serious disease.

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The Forbes article discusses the journey of Howard Schultz, the former CEO of Starbucks, from growing up in subsidized housing to amassing a personal fortune of $3 billion. Schultz's career at Starbucks began in 1982 when he became the marketing director, eventually leading a boardroom coup to reinstate himself as CEO in 2008. Despite stepping down multiple times, Schultz's perseverance led Starbucks to report $36.2 billion in net revenue in 2024. The article highlights Schultz's resilience and determination in building Starbucks into an international success. [Extracted from the article]

Background: Postoperative delirium (POD) is a serious complication following deep brain stimulation (DBS) but only received little attention. Its main risk factors are higher age and preoperative cognitive deficits. These are also main risk factors for long-term cognitive decline after DBS in Parkinson’s disease (PD).Objective: To identify risk factors for POD severity after DBS surgery in PD.Methods: 57 patients underwent DBS (21 female; age 60.2±8.2; disease duration 10.5±5.9 years). Preoperatively, general, PD– and surgery-specific predictors were recorded. Montreal Cognitive Assessment and the neuropsychological test battery CANTAB ConnectTMwere used to test domain-specific cognition. Volumes of the cholinergic basal forebrain were calculated with voxel-based morphometry. POD severity was recorded with the delirium scales Confusion Assessment Method for Intensive Care Unit (CAM-ICU) and Nursing Delirium Scale (NU-DESC). Spearman correlations were calculated for univariate analysis of predictors and POD severity and linear regression with elastic net regularization and leave-one-out cross-validation was performed to fit a multivariable model.Results: 21 patients (36.8%) showed mainly mild courses of POD following DBS. Correlation between predicted and true POD severity was significant (spearman rho?=?0.365, p?=?0.001). Influential predictors were age (p?

Hintergrund: Schlafschwierigkeiten im Kindesalter sind weit verbreitet. Etwa zwei Drittel aller Kinder und Jugendlichen erleben im Laufe ihres Heranwachsens belastende schlafbezogene Ängste. Dies allein ist keine Diagnose, hat jedoch weitreichende Folgen, da sich die Prävalenz für Folgestörungen wie beispielsweise Angststörungen und Insomnie erhöht. Methoden: 19 Kinder im Alter von 4,5–7 Jahren und deren Eltern wurden in einem Vorher-Nachher-Design mit Baseline und Follow-up vor und nach dem Lesen ausgewählter Bilderbücher nach ihren Ängsten und ihrem Zubettgehverhalten befragt. Jede Familie erhielt ein gleiches Set aus vier Bilderbüchern sowie standardisierten Instruktionen zum Vorleseverhalten. Zur Befragung wurden Schlafprotokolle, Interviews, Fremdbeurteilungs- und Selbstbeurteilungsinstrumente eingesetzt. Nach einer zweiwöchigen Baseline folgte eine zweiwöchige Testphase und nach vier Wochen eine Nachbefragung. Ergebnisse: Die Ergebnisse zeigen eine signifikante Verbesserung der schlafbezogenen Ängste und einiger problematischer Verhaltensweisen beim Zubettgehen im Prä-Post-Vergleich. Die Anzahl der geäußerten Ängste, der Widerstand beim Zubettgehen sowie die Häufigkeit des nächtlichen Erwachens wurden signifikant reduziert. Die Veränderungen blieben vier Wochen nach der Testphase stabil.

Background: Insomnia in children is common and causes many mental health problems. Nevertheless, only little is known about influencing factors for sleep help-seeking behavior of parents with children with insomnia. Objective: The aim of this study was to evaluate the duration and severity of insomnia in children as well as to assess the influence of additional mental disorders on insomnia duration and severity. The influence of a child’s insomnia duration and severity on parental sleep help-seeking behavior was examined. Materials and methods: Patients at three German outpatient sleep clinics were evaluated. A self-developed parental sleep interview according to the third edition of the International Classification of Sleep Disorders (ICSD-3) criteria was conducted for each child. Additionally, information about insomnia severity and duration, the number of sleep help-seeking efforts, and mental disorders were retrieved from the family registration form. Results: A total of 175 children (4–11 years) with a mean insomnia duration of 54 months were included. Insomnia severity was high, with no differences between children with and without comorbid mental disorders. Most parents (88.6%) had made efforts to seek sleep-related help for their child’s insomnia before contacting one of our outpatient sleep clinics. Pediatricians are the most frequently consulted professionals for child sleep problems. Insomnia severity ratings significantly correlated with the number of times professional help had been sought, but not with the number of self-help efforts. Insomnia duration was not correlated with any of the help-seeking measures. Conclusion: Insomnia severity, but not insomnia duration, is associated with help-seeking behavior in parents. In the current sample, most parents sought professional help from their pediatrician beside their own efforts to elicit change. In sum, there were no differences between children with and without comorbid mental disorders, neither in terms of insomnia duration nor for insomnia severity. It seems necessary to promote awareness of the consequences of insomnia in children and therefore support earlier parental help-seeking behavior.

Eine 45-jährige Patientin erhielt in der 39. Schwangerschaftswoche bei suspektem Kardiotokogramm in der Austreibungsphase nach Geburtseinleitung eine Rapid Sequence Induction (RSI) zur Notsectio.

Zusammenfassung: Der Mangel an kurativen Behandlungskonzepten zur Therapie des metastasierten Prostatakarzinoms erfordert die Entwicklung von neuen, effektiven Therapiestrategien. Durch Fortschritte auf dem Gebiet der immunologischen und translationalen Forschung stellen Vakzinierungen eine neue, viel versprechende Behandlungsmodalität des Prostatakarzinoms dar. Die Immunisierung von Patienten mit hormonrefraktärem Prostatakarzinom mit einer allogenen, IL-2- und IFN-γ-sezernierenden Tumorzellvakzine ist ein sicherer Therapieansatz ohne dosislimitierende oder autoimmune Toxizität. Eine Reduktion der PSA-Progression sowie vakzineinduzierte Immunantworten konnten bei behandelten Patienten nachgewiesen werden. Trotz dieser Ergebnisse weisen aktuelle Vakzinestrategien nur einen limitierten klinischen Erfolg auf. Es konnte nachgewiesen werden, dass mehrere immunsuppressive Mechanismen, wie regulatorische T-Zellen oder myeloide Suppressorzellen eine antitumoröse Immunantwort unterdrücken und die Aktivität von immuntherapeutischen Ansätzen abschwächen können. Ein besseres Verständnis von regulatorischen Zusammenhängen des Immunsystems bietet neue Möglichkeiten, die vakzineinduzierte antitumoröse Immunantwort zu verbessern, indem eine tumorbedingte Immunsuppression rückgängig gemacht wird, bevor die Immuntherapie bei Tumorpatienten erfolgreich eingesetzt werden kann.

Citizen participation is generally considered crucial to ensuring that policies effectively address public needs. But there is a long-running debate over how far such participation should go. This article focuses on one of the most far-reaching forms of citizen participation in public policy making– direct legislation– and asks to what extent it can bring about good governance outcomes in the political, economic and social spheres. Focusing on the case of Switzerland, where direct legislation is established and frequent, the article draws on existing studies to discuss long-term impacts of citizen participation in public policy-making. The evidence shows that, in the Swiss case, direct legislation contributed to consensual politics, a favourable environment for economic development, as well as high citizen satisfaction. The conclusion discusses to what extent these findings generalise beyond the Swiss case.

AbstractA methodology is introduced that allows to determine the reliability of railway bridges subject to freight trains and which comply with code based assessment according to the Swiss structural code SIA 269. The methodology uses probabilistic models for section forces from freight trains. These models are based on a large database of wheel load measurements. A case study demonstrates how the methodology is applied to determine the reliability of generic bridges and subsequently allows the assessment of the reliability for a portfolio of railway bridges. The results show that the target reliability is achieved according to SIA 269 considering the code format and current set of partial safety factors. The study identifies potential load bearing reserves for bridges with longer spans.

Travel diaries are a state-of-the-art method to capture peoples’ travel behavior. However, traditional approaches are burdensome for respondents resulting in fatigue and attrition, whereas new methods such as GPS-tracking are costly and fraught with issues of respondents’ privacy of personal data. In this paper, we present an interactive, web-based travel diary, that improves the reporting process while minimizing efforts for survey designers. In a pilot study we show that the approach ensures to record detailed spatial trip information, but still guarantees respondents’ data privacy. The open-source design allows a cost-efficient integration in any survey engine that supports HTML and JavaScript.

Der Artikel beschreibt zunächst die aktuellen technischen und regulatorischen Rahmenbedingungen für Lastverschiebung im Prosumer-Haushalt. Seit Ende 2023 sind alle Rahmenbedingungen weitestgehend definiert, um in den nächsten Jahren automatisierte tarifbasierte Lastverschiebungen in den Markt einzuführen. Die vom Gesetzgeber geforderten flexiblen Tarife als Anreiz zur Lastverschiebung werden näher analysiert. Ein besonderer Fokus liegt dabei auf dynamischen Tarifen, bei denen die Vertriebspreise dynamisch an die Marktergebnisse der Strombörse gekoppelt werden. Auf Basis einer Marktübersicht und der Ergebnisse einer qualitativen Expertenbefragung von 12 Stadtwerken und Lieferanten erfolgt eine Bewertung dynamischer Tarife. Es wird ein alternatives Tarifkonzept auf Basis des Tarifanwendungsfalles 5 (ereignisvariabler Tarif) vorgestellt. Bei diesem Tarif werden drei bzw. vier Tarifstufen dynamisch an den Börsenpreis angepasst. Dieses Tarifkonzept ist datensparsamer und einfacher in den IT-Systemen umzusetzen als die notwendige Zählerstandsgangmessung (Tarifanwendungsfall 7) mit einem Messwert pro ¼ h bzw. h bei dynamischen Tarifen. Auch weist der ereignisvariable Tarif eine geringere Komplexität sowie ein geringeres Kostenrisiko für die Endverbraucher auf. Der Beitrag beschreibt die dafür notwendige Signalisierung zwischen dem Messstellenbetreiber (Gateway-Administrator), dem Smart Meter Gateway und einem Home Energy Management System zur automatischen Übermittlung der Tarifsignale. In einem quantitativen Vergleich auf Basis der Börsenstrompreise des Jahres 2023 werden verschiedene Ausgestaltungsvarianten des ereignisvariablen Tarifs mit einem dynamischen Tarif und einem Einheitspreistarif verglichen.

Extreme weather events are occurring more frequently, and research has shown that plant diversity can help mitigate the impacts of climate change by increasing plant productivity and ecosystem stability. Although soil temperature and its stability are key determinants of essential ecosystem processes, no study has yet investigated whether plant diversity buffers soil temperature fluctuations over long-term community development. Here we have conducted a comprehensive analysis of a continuous 18-year dataset from a grassland biodiversity experiment with high spatial and temporal resolutions. Our findings reveal that plant diversity acts as a natural buffer, preventing soil heating in hot weather and cooling in cold weather. This diversity effect persists year-round, intensifying with the aging of experimental communities and being even stronger under extreme climate conditions, such as hot days or dry years. Using structural equation modelling, we found that plant diversity stabilizes soil temperature by increasing soil organic carbon concentrations and, to a lesser extent, plant leaf area index. Our results suggest that, in lowland grasslands, the diversity-induced stabilization of soil temperature may help to mitigate the negative effects of extreme climatic events such as soil carbon decomposition, thus slowing global warming.

When applying to a university, students and their parents devote considerable time acquiring information about university programs in order to form preferences. We explore ways to reduce wasteful information acquisition, that is, to help students avoid acquiring information about out‐of‐reach schools or universities, using a market design approach. Focusing on markets where students are ranked by universities based on exam scores, we find that, both theoretically and experimentally, a sequential serial dictatorship mechanism leads to higher student welfare than a direct serial dictatorship mechanism. This is because the sequential mechanism informs students about which universities are willing to admit them, thereby directing their search. Our experiments also show that the sequential mechanism has behavioral advantages because subjects deviate from the optimal search strategy less frequently than under the direct mechanism. Furthermore, providing historical cutoff scores under the direct mechanism can increase student welfare, especially when the information costs are high, although the observed effect is weaker than that of a sequential mechanism.

With the rise of China and the deepening of China-EU interactions, it is crucial for both China and the EU to know the Chinese public perceptions of the EU and what factors influence the formation of perceptions, to enhance mutual understanding. Given the increasing role of social media in the political process, this study hypothesizes that social media use is a strong predictor for Chinese public perceptions of the EU and China-EU relations. We analyze the effects by utilizing original public opinion survey data collected in China in 2020. Our findings show that social media use as well as socioeconomic factors together predict Chinese public perceptions of the EU and China-EU relations. However, social media use effects vary across different social media platforms.

Die kraniofaziale Mikrosomie hat eine Inzidenz von 1:3000–1:5000, ist aber dennoch eine der häufigsten angeborenen kraniofazialen Erkrankungen. Ihre Ausprägung ist variabel und geht mit Anomalien der Kiefer, Ohren, Gesichtsweichteile, Augenhöhlen und Gesichtsnerven sowie weiteren extrakraniellen Malformationen einher. Die exakte Genese ist unklar, diskutiert werden pränatale Expositionen und genetische Anomalien. Die Komplexität dieser Erkrankung erschwert die Diagnostik und erfordert ein inter- und multidisziplinäres Therapiekonzept. In dieses sind u. a. die Fachrichtungen Mund‑, Kiefer- und Gesichtschirurgie, Neurochirurgie, Kieferorthopädie, Pädiatrie, Ophthalmologie, Otorhinolaryngologie sowie Logopädie und Ernährungsberatung eingebunden.

The complexity of planning and implementing peacebuilding processes has been discussed using various approaches, for example, adaptive peacebuilding, and the “local turn” in peacebuilding. These theories argue that peacebuilding is a nonlinear and contextual process, contrary to the linear, static conception of the liberal peace paradigm. This paper contributes to this field and seeks to learn how peacebuilding processes can be planned better, by integrating the concepts of adaptive and urban peacebuilding. Using action research and organizational ethnographic analysis of an EU-funded peacebuilding process between Palestinians and Israelis in Jerusalem, this article lays out four general steps to improve planning for future peacebuilding initiatives: (1) integrate flexibility; (2) balance inherent asymmetries; (3) “localize” planning; and (4) plan for indirect alternatives. In conclusion, we discuss the implications for peacebuilding processes in other contested and settler-colonial cities.

In recent years, innovative city logistic concepts for courier, express, and parcel (CEP) shipments have raised particular interest in contributing to a more sustainable transportation system. One solution can be the utilization of existing urban rail infrastructure. A so-called ‘cargo tram’ transports goods to an intermodal city hub, where cargo bikes cover the last leg to the receiver. Although conceptional or economic studies exist, detailed analyses of the transport-related effects, e.g., through freight demand models, still need to be carried out. Hence, in this study, we develop a methodology to integrate urban rail-based parcel transport in terms of a cargo tram into the existing agent-based freight, i.e., parcel, demand model logiTopp. Instead of a single mode choice, a two-stage selection model based on transport chains is developed, comprising a rule-based and utility-based stage. The proposed methodology is implemented in logiTopp, and the model is applied to the city of Karlsruhe, Germany, where the overall effects of rail-based parcel transport are simulated and evaluated in proof-of-concept scenarios. The analysis shows that the proposed transport chain selection model produces overall reasonable results. Moreover, they indicate that the realization of a rail-based parcel transport can reduce the overall mileage and number of trips caused by CEP shipments. However, the potential is driven by several factors, such as the number and location of city hubs, the maximum range of cargo bikes, and the overall evaluation of the cargo tram. Additional empirical investigations are necessary to validate the results from the proof-of-concept scenarios.

Successful urbanization fosters socio-economic growth when accompanied by sufficient urban infrastructure, often constructed using sand-based materials, such as concrete. However, mining sand necessary to make these materials has detrimental socio-enviro-economic consequences. Africa, one of the world’s most rapidly urbanizing regions, lacks the infrastructure to support this urbanization. Although sand can be used to build missing infrastructure and thus enable successful urbanization, the relationship between African sand mining and urbanization remains poorly understood. We create a continental mapping of African sand mining and a spatial detection model showing that, like other African point-source resources, sand mining correlates with urbanization but does not necessarily improve socio-economic outcomes, such as contributing to local infrastructure development, in African communities. Rather, we find that urbanization increases the viable area for, and thus the potential consequences of, sand mining. These findings highlight the imperativeness of critically examining sand's role in future African urban and socio-economic development.

One of the challenges for automated abusive language detection is combating unintended bias, which can be easily introduced through the annotation process, especially when what is (not) considered abusive is subjective and heavily context dependent. Our study incorporates a fine-grained, socio-pragmatic perspective to data modeling by taking into consideration contextual elements that impact the quality of abusive language corpora. We use a fine-grained annotation scheme that distinguishes between different types of non-abuse along with explicit and implicit abuse. We include the following non-abusive categories: meta, casual profanity, argumentative language, irony, and non-abusive language. Experts and minimally trained annotators use this scheme to manually re-annotate instances originally considered abusive by crowdsourced annotators in a standard corpus. After re-annotation, we investigate discrepancies between experts and minimally trained annotators. Our investigation shows that minimally trained annotators have difficulty interpreting contextual aspects and distinguishing between content performing abuse and content about abuse or instances of casual profanity. It also demonstrates how missing information or contextualization cues are often a source of disagreement across all types of annotators and poses a significant challenge for developing robust, nuanced corpora and annotation guidelines for abusive language detection.

Digital Twins are seen as one of the core technologies and enablers of Industrie 4.0. There are various definitions of the term Digital Twin, but most agree that they are digital representations supporting the real production system throughout its lifecycle by providing models, data-integration and online-optimization. Currently, there are no implementations of Digital Twins to be used productively, which fulfill all parts of this definition. This work focuses on the simulation part of Digital Twins and the real-time requirements which arises from an online calculation. An approach that uses models of virtual commissioning, which are integrated in an industrial controller to tackle the problem of real-time calculation is presented. To enable the online simulation of complex and multi-physical models the simulation is parallelized and calculated on a multicore processor.

Many CuIcomplexes have luminescent triplet charge-transfer excited states with diverse applications in photophysics and photochemistry, but for isoelectronic ZnIIcompounds, this behavior is much less common, and they typically only show ligand-based fluorescence from singlet π–π* states. We report two closely related tetrahedral ZnIIcompounds, in which intersystem crossing occurs with appreciable quantum yields and leads to the population of triplet excited states with intraligand charge-transfer (ILCT) character. In addition to showing fluorescence from their initially excited 1ILCT states, these new compounds therefore undergo triplet–triplet energy transfer (TTET) from their 3ILCT states and consequently can act as sensitizers for photo-isomerization reactions and triplet–triplet annihilation upconversion from the blue to the ultraviolet spectral range. The photoactive 3ILCT state furthermore facilitates photoinduced electron transfer. Collectively, our findings demonstrate that mononuclear ZnIIcompounds with photophysical and photochemical properties reminiscent of well-known CuIcomplexes are accessible with suitable ligands and that they are potentially amenable to many different applications. Our insights seem relevant in the greater context of obtaining photoactive compounds based on abundant transition metals, complementing well-known precious-metal-based luminophores and photosensitizers.

Background: Prostate cancer (PCa) is the most frequent cancer in men. The prognosis of PCa is heterogeneous with many clinically indolent tumors and rare highly aggressive cases. Reliable tissue markers of prognosis are lacking. Active cholesteryl ester synthesis has been associated with prostate cancer aggressiveness. Sterol-O-Acyl transferases (SOAT) 1 and 2 catalyze cholesterol esterification in humans. Objective: To investigate the value of SOAT1 and SOAT2 tissue expression as prognostic markers in high risk PCa. Patients and methods: Formalin-fixed paraffin-embedded tissue samples from 305 high risk PCa cases treated with radical prostatectomy were analyzed for SOAT1 and SOAT2 protein expression by semi-quantitative immunohistochemistry. The Kaplan–Meier method and Cox proportional hazards modeling were used to compare outcome. Main outcome measure: Biochemical recurrence (BCR) free survival. Results: SOAT1 expression was high in 73 (25%) and low in 219 (75%; not evaluable: 13) tumors. SOAT2 was highly expressed in 40 (14%) and at low levels in 249 (86%) samples (not evaluable: 16). By Kaplan–Meier analysis, we found significantly shorter median BCR free survival of 93 months (95% confidence interval 23.6–123.1) in patients with high SOAT1 vs. 134 months (112.6–220.2, Log-rank p< 0.001) with low SOAT1. SOAT2 expression was not significantly associated with BCR. After adjustment for age, preoperative PSA, tumor stage, Gleason score, resection status, lymph node involvement and year of surgery, high SOAT1 but not SOAT2 expression was associated with shorter BCR free survival with a hazard ratio of 2.40 (95% CI 1.57–3.68, p< 0.001). Time to clinical recurrence and overall survival were not significantly associated with SOAT1 and SOAT2 expression Conclusions: SOAT1 expression is strongly associated with BCR free survival alone and after multivariable adjustment in high risk PCa. SOAT1 may serve as a histologic marker of prognosis and holds promise as a future treatment target.

The lymphocyte genome is prone to many threats, including programmed mutation during differentiation1, antigen-driven proliferation and residency in diverse microenvironments. Here, after developing protocols for expansion of single-cell lymphocyte cultures, we sequenced whole genomes from 717 normal naive and memory B and T cells and haematopoietic stem cells. All lymphocyte subsets carried more point mutations and structural variants than haematopoietic stem cells, with higher burdens in memory cells than in naive cells, and with T cells accumulating mutations at a higher rate throughout life. Off-target effects of immunological diversification accounted for approximately half of the additional differentiation-associated mutations in lymphocytes. Memory B cells acquired, on average, 18 off-target mutations genome-wide for every on-target IGHVmutation during the germinal centre reaction. Structural variation was 16-fold higher in lymphocytes than in stem cells, with around 15% of deletions being attributable to off-target recombinase-activating gene activity. DNA damage from ultraviolet light exposure and other sporadic mutational processes generated hundreds to thousands of mutations in some memory cells. The mutation burden and signatures of normal B cells were broadly similar to those seen in many B-cell cancers, suggesting that malignant transformation of lymphocytes arises from the same mutational processes that are active across normal ontogeny. The mutational landscape of normal lymphocytes chronicles the off-target effects of programmed genome engineering during immunological diversification and the consequences of differentiation, proliferation and residency in diverse microenvironments.

Eine 45-jährige Patientin erhielt in der 39. Schwangerschaftswoche bei suspektem Kardiotokogramm in der Austreibungsphase nach Geburtseinleitung eine Rapid Sequence Induction (RSI) zur Notsectio.

Pandemics cause business disruptions that have serious implications for the design and delivery of services, leading to adverse performance consequences for services industries. Focusing on the restaurant industry, the authors present a conceptual framework of restaurants’ resilience during a pandemic that is grounded in existing services and strategy research, secondary and qualitative sources, and insights obtained from social media data. This framework is tested via an empirical analysis of the Yelp COVID-19 data set. Several interesting trends in consumer preferences are identified including a rapid shift toward third-party app delivery models. Surprisingly, the analysis shows that partnering with third-party app delivery services before COVID improved firms’ resilience, whereas during the pandemic, these partnerships have a negative impact on restaurant survival. Furthermore, the study documents some important differences between the drivers of restaurant survival before versus during the pandemic, highlighting critical changes in consumer preferences that may shape the industry in the future.

Word embeddings have recently been applied to detect and explore changes in word meaning on large historical corpora. While word embeddings are useful in many Natural Language Processing tasks, there are a number of questions that need to be addressed concerning accuracy and applicability of these methods for historical data. There is a scarce literature on the stability and replicability of these embeddings, especially on small corpora, which are common in historical work. It also remains unclear whether methods used to evaluate embeddings in contemporary data can also be used for historical data sets. Our overarching goal is to use word embeddings for investigating semantic shifts in the history of Spanish. In the work presented here, we focus on methodological questions that arise. We first examine the stability and applicability of three commonly used word embeddings models on a small corpus of medieval and classical Spanish. Comparing our results with a study on the word algoas a test case, we show that a rank-averaging method can produce more stable results from the embeddings. We corroborate previous theoretical work while demonstrating the applicability of our method when training word embeddings on small corpora for the analysis of semantic change. Second, we investigate how best to evaluate different embeddings models. We show that an existing analogy test cannot be used without modification. Our new analogy test, consisting of roughly 10,000 questions for medieval and classical Spanish, will be released with the article.

Reinforcement Learning algorithms find more and more application in fields where complex tasks need to be solved. The automation of production systems is one of those fields. Normally, programming a control system defines the automation strategy. Previous contributions by the authors have shown that a so-called agent can learn automation strategies for production systems using a Reinforcement Learning setup. However, the development of the reward function for the agent can be challenging and needs Reinforcement Learning domain knowledge. This paper introduces a novel approach in combining Test-Driven Development with Reinforcement Learning in order to solve the problem of a suitable reward function. In the presented approach predefined test cases are used to derive rewards for the agent. The use of an automated test framework allows for continuous learning sequences until all test cases are passed. An application example of a robot cell is used to demonstrate the novel approach and verify its suitability and usability. The first application shows promising results for further examination towards more application scenarios.

Microglia have emerged as important players in brain aging and pathology. To understand how genetic risk for neurological and psychiatric disorders is related to microglial function, large transcriptome studies are essential. Here we describe the transcriptome analysis of 255 primary human microglial samples isolated at autopsy from multiple brain regions of 100 individuals. We performed systematic analyses to investigate various aspects of microglial heterogeneities, including brain region and aging. We mapped expression and splicing quantitative trait loci and showed that many neurological disease susceptibility loci are mediated through gene expression or splicing in microglia. Fine-mapping of these loci nominated candidate causal variants that are within microglia-specific enhancers, finding associations with microglial expression of USP6NLfor Alzheimer’s disease and P2RY12for Parkinson’s disease. We have built the most comprehensive catalog to date of genetic effects on the microglial transcriptome and propose candidate functional variants in neurological and psychiatric disorders.

Background: The medical challenges caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV‑2) pose a tremendous burden on the healthcare system. This study aimed to analyze the effects of a SARS-CoV‑2 infections or disease progression on inpatient mortality of geriatric patients after proximal femoral fracture surgery. Methods: A retrospective analysis was conducted in all patients with a proximal femoral fracture surgically treated in an urban regional trauma center from 01/01/2020 to 01/31/2021. According to PCR test results detecting SARS-CoV‑2, the patients were divided into two groups (SARS-CoV‑2 positive vs. SARS-CoV‑2 negative). Patient data, disease progression data, and treatment-related information were evaluated for all patients. Statistical data analysis was performed using unpaired Student’s ttest or non-parametric Mann-Whitney Utest. Results: A total of 311 patients (women: 70.4%, age: 82.0 ± 11.0 years) were included in this study. Of these 3.9% (12/311) had a positive test result for SARS-CoV‑2. Significantly more deceased patients were found in the group tested positive for SARS-CoV‑2 (SARS-CoV‑2 positive: 41.7%, SARS-CoV‑2 negative: 5.4%, p< 0.001). In addition, the number of proximal femoral fracture associated deaths correlated with the number of positive test results performed in the Clinic. The length of stay of SARS-CoV‑2 COVID-19 survivors tended to be greater than in those who were tested negative (SARS-CoV‑2 COVID-19 positive: 15.6 ± 13.1 days, SARS-CoV‑2 COVID-19 negative: 11.5 ± 6.5 days, p= 0.683). Furthermore, a significant difference in age was found in SARS-CoV‑2 survivors and SARS-CoV‑2 decedents (deceased: 95.5 ± 7.5 years, alive: 83.5 ± 7.3 years, p= 0.020). Conclusion: The study was conducted before the introduction of SARS-CoV‑2 vaccination. The results therefore refer to immune naive (unvaccinated) patients. In our study, more than 40% of all patients with proximal femoral fractures who tested positive for SARS-CoV‑2 died during hospitalization. An additional, critical factor in this respect was the age of the infected patients. Nonetheless, a positive correlation was demonstrated between the mortality rate and the number of positive SARS-CoV‑2 detections. Regarding the greater length of stay of patients tested positive for SARS-CoV‑2, the limited transfer options (further rehabilitation, skilled nursing facility) of the infected ones can be considered as causal. Particularly the vulnerable older patients are increasingly endangered by a combination of proximal femoral fracture and SARS-CoV‑2.

Little is known about the political determinants of subjective well-being across nations. The objective of the study presented in this article is to single out the importance of a variety of determinants on the perceived quality of life in China, aiming, in particular, to understand the role and the importance of political conditions. Using individual level data from a survey conducted in Ya’an Municipality of Sichuan Province, our analysis shows that not only the personal situation and the local environment, but also the performance of one’s town/township government, as well as political trust are relevant for citizens’ subjective well-being. However, if political trust is important for satisfaction with life, this is predominantly an effect of trust in local government. In the Chinese context, our findings confirm that citizens’ quality of life is influenced by the legitimacy of the political order, conceived in terms of output-legitimacy, i.e., the perception of governmental performance.

The attenuation coefficient provides a quantitative parameter for tissue characterization and can be calculated from optical coherence tomography (OCT) data, but accurate determination requires compensation for the confocal function. We present extensive measurement series for extraction of the focal plane and the apparent Rayleigh length from the ratios of OCT images acquired with different focus depths and compare these results with two alternative approaches. By acquiring OCT images for a range of different focus depths the optimal focus plane difference is determined for intralipid and titanium oxide (TiO_2) phantoms with different scatterer concentrations, which allows for calculation of the attenuation coefficient corrected for the confocal function. The attenuation coefficient is determined for homogeneous intralipid and TiO_2 samples over a wide range of concentrations. We further demonstrate very good reproducibility of the determined attenuation coefficient of layers with identical scatter concentrations in a multi-layered phantom. Finally, this method is applied to in vivo retinal data.

The new World Trade Center complex in New York City rose up into the heights during the last decade. Nine new buildings including 1776 ft tall One WTC and Calatrava’s sculptural Oculus Station cover the 60,000 m2area in the world’s most outstanding construction site. One spot is still under construction and will host “The Ronald O. Perelman Performing Arts Center”—a new kind of multidisciplinary venue with an astonishing smooth facade made from exceptional stone-glass. The cube-shaped building is 49 × 49 m wide and 42 m tall. A steel roof cantilevers from the inner core and holds hot-rolled steel mullions to carry the curtail wall. The total span is 36 m with one intermediate support only. This encloses a large area interior room for public events, arts and theatre performances. As a special feature, the whole building is covered with stone, in particular 4800 stone-glass insulating glass units grouped in aluminum cassettes carrying four glass panes each. The intention is to present a white four-sided landmark structure with distinguished black veining during the day and a glowing amber-like appearance at night when the interior of the building is illuminated. Stone-glass units have never been used in this scale. Standard PVB interlayers were not an option for the product as it cannot be laminated properly. Therefore, the façade supplier accepted the challenge to design and build using alternative materials. The paper presents the project and its facade design. Numerous additional experimental assessments were conducted—from small scale quasi-static air pressure tests of the glass to full scale performance mock-up tests. Finally, a design process was developed that covers all critical demands of an incomparable project.

ABSTRACTThis paper explores the emerging governance patterns in Chinese metropolitan regions (城市群 chengshiqun). In the scholarly debate on city-regional governance in the West, a prominent position holds that governing large urban regions entails a rescaling of state territories. In China, the central government plays a prominent role in the scale-building of China’s metropolitan regions. This is not only evident in the first stage of the post-reform policies, involving major reforms of state scales for the purpose of economic and urban development. Drawing on three case studies (the Yangtze River Delta, Guanzhong–Tianshui and Beijing–Tianjin–Hebei metropolitan regions), it is shown that the Chinese central government also plays a strong role in the current stage of metropolitan regional development. It is argued that the trajectory of metropolitan scale-building in China is a result of the hierarchical administrative system impeding horizontal cooperation between subnational entities of the party-state.

Background: Lymph-node (LN) metastasis in prostate cancer (PC) is a main risk factor for tumor recurrence after radical prostatectomy (RP). Molecular analysis facilitates detection of small-volume LN metastases with higher sensitivity than histopathology. We aimed to prospectively evaluate six candidate gene markers for detection of pelvic LN metastases and to determine their ability to predict biochemical recurrence-free survival (bRFS) in patients treated with RP. Methods: The expression of kallikrein 2, 3, and 4 (KLK2, KLK3, and KLK4), prostate-specific membrane antigen (PSMA), transmembrane serine protease 2 (TMPRSS2) and transient receptor potential cation channel subfamily M member 8 (TRPM8) was assessed using qPCR. We analyzed LNs from 111 patients (intermediate PC, n= 32 (29%); high-risk PC, n= 79 (71%)) who underwent RP and extended pelvic lymph-node dissection without neoadjuvant treatment. Results: Overall, 2411 LNs were examined by molecular and histopathologic examination. Histopathology detected 69 LN metastases in 28 (25%) patients. KLK2 and KLK3 diagnostically performed best and classified all pN1-patients correctly as molecular node-positive (molN1/pN1). The concordance on LN level was best for KLK3 (96%). KLK2, KLK3, KLK4, PSMA, TMPRSS2, and TRPM8 reclassified 27 (24%), 32 (29%), 29 (26%), 8 (7%), 13 (12%), and 23 (21%) pN0-patients, respectively, as node-positive (pN0/molN1). On multivariable cox regression analysis molecular LN status (molN1 vs. molN0) using KLK3 (HR 4.0, p= 0.04) and TMPRSS2 (HR 5.1, p= 0.02) were independent predictors of bRFS. Median bRFS was shorter in patients with only molecular positive LNs (molN1/pN0) for KLK3 (24 months, p= 0.001) and for TMPRSS2 (12 months, p< 0.001) compared to patients with negative nodes (molN0/pN0) (median bRFS not reached). Conclusions: For diagnostic purposes, KLK3 showed highest concordance with histopathology for detection of LN metastases in PC patients undergoing RP. For prognostic purposes, KLK3 and TMPRSS2 expression were superior to histopathologic LN status and other transcripts tested for molecular LN status. We suggest a combined KLK3/TMPRSS2 panel as a valuable diagnostic and prognostic tool for molecular LN analysis.

This article presents a case of fulminant macrophage activation syndrome (MAS) as a rare complication of active systemic lupus erythematosus in a 33-year-old female patient. Initial presentation showed severe lupus disease exacerbation with renal involvement, hemolytic anemia, and neuropsychiatric changes. Early therapy focused on broad immunosuppression (high-dose corticosteroids and cyclophosphamide); however, disease remission could not be achieved. After an additional inflammatory focus and underlying malignancy were excluded, the triplet of pancytopenia, fever, and high ferritin levels indicated MAS, a bone marrow biopsy confirmed secondary hemophagocytic histiocytosis. Treatment with an interleukin‑1 antagonist (anakinra) induced a fast, effective therapeutic success.

It is widely hypothesized that noncalcifying macroalgae will be more productive and abundant in increasingly warm and acidified oceans. Macroalgae vary greatly in the magnitudes and interactions of responses of photosynthesis and growth to multiple stressors associated with climate change. A knowledge gap that exists between the qualitative “macroalgae will benefit” hypothesis and the variable outcomes observed is regulation of physiological mechanisms that cause variation in the magnitudes of change in primary productivity, growth, and their covariation. In this context, we developed a model to quantitatively describe physiological responses to coincident variation in temperature, carbonate chemistry and light supply in a representative bicarbonate‐using marine macroalga. The model is based on Ulvaspp., the best understood dissolved inorganic carbon uptake mechanism among macroalgae, with data enabling synthesis across all parameters. At boundary layer pH < 8.7 most inorganic carbon is taken up through the external carbonic anhydrase (CAext) mechanism under all conditions of photosynthetic photon flux density, temperature, and boundary layer thickness. Each 0.1 unit decline in pH causes a 20% increase in the fraction of diffusive uptake of CO2thereby lessening reliance on active transport of bicarbonate. Modeled downregulation of anion exchange‐mediated active bicarbonate transport associated with a 0.4 unit decline in pH under ocean acidification is consistent with enhanced growth up to 4% per day without increasing photosynthetic rate. The model provides a means to quantify magnitudes of change in productivity under factorial combinations of changing temperature, pCO2, and light supply anticipated as climate changes.

There is no better time than now to take stock of the trajectory of “democratic innovations” in Western democracies, amidst the burgeoning clamour of democratic dissatisfaction and the populist threat to liberal democratic institutions. This article takes the opportunity to discuss the concept of democratic innovations, reflecting on what is truly so democratic about democratic innovations when these practices have also emerged in the unlikely places of authoritarian systems. To do so, it briefly revisits the normative assumptions of these democratic innovations, as well as discusses and assesses the conditions under which such novel institutional ideas function. At the same time, a look at democratic innovations in authoritarian systems uncovers a more nuanced discourse. By examining the contributions of democratic innovations beyond the usual democratic systems, this review article provides a thoughtful premise for reconsidering the rationale, motivation, and functions of democratic innovations that—in the end—might not be so different in democratic and non-democratic systems.

Am Fallbeispiel eines 12-jährigen Mädchens wird die Diagnose und Therapie einer idiopathischen Chondrolyse der Hüftgelenke beschrieben. Die Patientin stellte sich mit intermittierenden Schmerzen und hochgradigen Funktionsstörungen beider Hüften vor. Nach klinischer Untersuchung und Beckenübersichtsröntgenaufnahme zeigte die MRT die typischen Veränderungen einer idiopathischen Chondrolyse. Die rein konservative Therapie mit einer konsequenten physiotherapeutischen Behandlung und regelmäßigen Einnahme eines nichtsteroidalen Antirheumatikums hat ein gutes klinisches Ergebnis erbracht.