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The tetrapyrazolylpyridyl diborate (B2Pz4Py) ligand provides a suitable platform for the isolation of heterobimetallic main-group element compounds as well as homotetrametallic copper complexes. The heterobimetallic tin(II)–lithium(I) (1) and tin(II)–thallium(I) (2) complexes have been synthesized, isolated, and fully characterized including single-crystal X-ray diffraction analysis. When reacted with copper(I) sources, complex 2grants access to a homotetrametallic copper(I) complex (4). Upon subsequent oxidation, 4gives rise to the bimetallic copper(II) complex 5, in which the two copper(II) centers are connected viaa bridging bromido ligand (CuII–μ-Br–CuII).

Background and objective: Persistent prostatic specific antigen (PSA) represents a poor prognostic factor for recurrence after radical prostatectomy (RP). However, the impact of persistent PSA on oncologic outcomes in patients undergoing salvage RP is unknown. To investigate the impact of persistent PSA after salvage RP on long-term oncologic outcomes. Material and methods: Patients who underwent salvage RP for recurrent prostate cancer between 2000 and 2021 were identified from twelve high-volume centers. Only patients with available PSA after salvage RP were included. Kaplan-Meier analyses and multivariable Cox regression models were used to test the effect of persistent PSA on biochemical recurrence (BCR), metastasis and any death after salvage RP. Persistent PSA was defined as a PSA-value ≥ 0.1 ng/ml, at first PSA-measurement after salvage RP. Results: Overall, 580 patients were identified. Of those, 42% (n = 242) harbored persistent PSA. Median follow-up after salvage RP was 38 months, median time to salvage RP was 64 months and median time to first PSA after salvage RP was 2.2 months. At 84 months after salvage RP, BCR-free, metastasis-free, and overall survival was 6.6 vs. 59%, 71 vs. 88% and 77 vs. 94% for patients with persistent vs. undetectable PSA after salvage RP (all p < 0.01). In multivariable Cox models persistent PSA was an independent predictor for BCR (HR: 5.47, p < 0.001) and death (HR: 3.07, p < 0.01). Conclusion: Persistent PSA is common after salvage RP and represents an independent predictor for worse oncologic outcomes. Patients undergoing salvage RP should be closely monitored after surgery to identify those with persistent PSA.

The dark red semiconductor Cu(Sb2S3)Cl was obtained by leaching the layered precursor Cu(Sb2S3)[AlCl4] in a 0.1 M aqueous HCl solution. The selective extraction of AlCl3yielded a mica-like lamellar product of poor crystallinity. Misalignment of lamellae down to the nanoscale prevented structure determination by conventional single-crystal X-ray diffraction, but a combination of transmission electron microscopy, selected area electron diffraction, and selected area electron precession diffraction tomography on a nanoscale spot with largely ordered crystalline lamellae revealed the crystal structures of two intergrown modifications. Orthorhombic o-Cu(Sb2S3)Cl and monoclinic m-Cu(Sb2S3)Cl have similar layers to the precursor and differ only in the stacking of the layers. These consist of uncharged Sb2S3strands, whose sulfide ions, together with chloride ions, coordinate the copper(I) cations. Only one chloride ion remained from the [AlCl4]−group. DFT calculations confirm the structure solution for the orthorhombic form and suggest that the monoclinic structure is metastable against transformation to o-Cu(Sb2S3)Cl.

Individuals with ultrarare disorders pose a structural challenge for healthcare systems since expert clinical knowledge is required to establish diagnoses. In TRANSLATE NAMSE, a 3-year prospective study, we evaluated a novel diagnostic concept based on multidisciplinary expertise in Germany. Here we present the systematic investigation of the phenotypic and molecular genetic data of 1,577 patients who had undergone exome sequencing and were partially analyzed with next-generation phenotyping approaches. Molecular genetic diagnoses were established in 32% of the patients totaling 370 distinct molecular genetic causes, most with prevalence below 1:50,000. During the diagnostic process, 34 novel and 23 candidate genotype–phenotype associations were identified, mainly in individuals with neurodevelopmental disorders. Sequencing data of the subcohort that consented to computer-assisted analysis of their facial images with GestaltMatcher could be prioritized more efficiently compared with approaches based solely on clinical features and molecular scores. Our study demonstrates the synergy of using next-generation sequencing and phenotyping for diagnosing ultrarare diseases in routine healthcare and discovering novel etiologies by multidisciplinary teams.

The COVID-19 pandemic is an ongoing global health threat, yet our understanding of the dynamics of early cellular responses to this disease remains limited1. Here in our SARS-CoV-2 human challenge study, we used single-cell multi-omics profiling of nasopharyngeal swabs and blood to temporally resolve abortive, transient and sustained infections in seronegative individuals challenged with pre-Alpha SARS-CoV-2. Our analyses revealed rapid changes in cell-type proportions and dozens of highly dynamic cellular response states in epithelial and immune cells associated with specific time points and infection status. We observed that the interferon response in blood preceded the nasopharyngeal response. Moreover, nasopharyngeal immune infiltration occurred early in samples from individuals with only transient infection and later in samples from individuals with sustained infection. High expression of HLA-DQA2before inoculation was associated with preventing sustained infection. Ciliated cells showed multiple immune responses and were most permissive for viral replication, whereas nasopharyngeal T cells and macrophages were infected non-productively. We resolved 54 T cell states, including acutely activated T cells that clonally expanded while carrying convergent SARS-CoV-2 motifs. Our new computational pipeline Cell2TCR identifies activated antigen-responding T cells based on a gene expression signature and clusters these into clonotype groups and motifs. Overall, our detailed time series data can serve as a Rosetta stone for epithelial and immune cell responses and reveals early dynamic responses associated with protection against infection.

Die stetig steigende Adipositasprävalenz stellt eine der größten (gesundheitsökonomischen) Herausforderungen unseres Jahrhunderts dar. In den letzten Jahren hat sich durch intensivierte Forschung nicht nur das wissenschaftlich-medizinische Verständnis der Erkrankung Adipositas grundlegend verändert, sondern es konnten hierdurch auch neue Therapieoptionen entwickelt werden. Basierend auf der Erkenntnis, dass Adipositas eine durch Veränderungen des zentralen Nervensystems geprägte Erkrankung ist, stellen unter den konservativen Therapieoptionen die medikamentöse Therapie mit GLP-1-Analoga (GLP-1: glukagonähnliches Peptid 1), spezielle Patientenschulungsprogramme und digitale Gesundheitsanwendungen (DiGA) die Hauptschwerpunkte dar. Neben den genannten Behandlungsansätzen stehen eine adäquate evidenzbasierte Patientenaufklärung und -edukation hinsichtlich der Erkrankung im Vordergrund.

Verschiedene Rahmenwerke des Qualitätsmanagements betonen die Relevanz kompetenter Mitarbeiter:innen für den Unternehmenserfolg. Unternehmen müssen erfolgskritische Kompetenzen bestimmen und bewerten sowie Maßnahmen zur Kompetenzentwicklung umsetzen. Dieser Beitrag stellt einen Ansatz vor, der Unternehmen dabei unterstützt, anhand von prozessorientierten Skill-Profilen und einer KI-basierten Lernplattform diese Aufgaben zu bewerkstelligen. Im Mittelpunkt stehen dabei adaptive Lernpfade der Beschäftigten. Das Fallbeispiel der FBT Feinblechtechnik GmbH demonstriert die Anwendung des Ansatzes in der Praxis.

The study and application of procedures that result in stimulus relations via relational frame theory (RFT) and stimulus equivalence (applied as equivalence-based instruction; EBI), have made tremendous strides in contemporary behavior analysis. However, applications at scale lag basic and translational research. We turn our attention inward to investigate potential causes. We replicated and extended Enoch and Nicholson (Behavior Analysis in Practice, 13(3), 609–617, 2020) by conducting a survey of behavior analysts (n= 129) to determine their perceptions, experiences, and barriers in carrying out research and practice based on RFT and EBI. Participants indicated an interest in RFT and EBI, and mostly perceive both within the scope of behavior analysis. A majority of behavior analysts reported formal education in EBI (78.3%), in contrast to a minority in RFT (15.5%). Adoption of procedures derived from RFT and EBI may be in proportion to formal education. Compounded with a lack of accuracy on basic knowledge questions, there is a potential gap in capacity in the field in addressing behavior related to complex verbal behavior.

With their variety of skills and competencies, humans are an important resource in logistics. To prevent workload-related diseases, improve work design, and maintain productivity in manual processes as order picking, an optimization approach to integrate ergonomics into resource planning is introduced. The objective is to evenly distribute physical workload among workers in a shift. Applying the Design Science Research Method, this paper presents the conceptual process design of the developed ergonomic order assignment. An assessment of the individual workload per order and worker combination is introduced, considering individual characteristics of typical orders. It is followed by a reference implementation.

ObjectivePrimary sclerosing cholangitis (PSC) is characterised by bile duct strictures and progressive liver disease, eventually requiring liver transplantation. Although the pathogenesis of PSC remains incompletely understood, strong associations with HLA-class II haplotypes have been described. As specific HLA-DP molecules can bind the activating NK-cell receptor NKp44, we investigated the role of HLA-DP/NKp44-interactions in PSC.DesignLiver tissue, intrahepatic and peripheral blood lymphocytes of individuals with PSC and control individuals were characterised using flow cytometry, immunohistochemical and immunofluorescence analyses. HLA-DPA1 and HLA-DPB1 imputation and association analyses were performed in 3408 individuals with PSC and 34 213 controls. NK cell activation on NKp44/HLA-DP interactions was assessed in vitro using plate-bound HLA-DP molecules and HLA-DPB wildtype versus knock-out human cholangiocyte organoids.ResultsNKp44+NK cells were enriched in livers, and intrahepatic bile ducts of individuals with PSC showed higher expression of HLA-DP. HLA-DP haplotype analysis revealed a highly elevated PSC risk for HLA-DPA1*02:01~B1*01:01(OR 1.99, p=6.7×10−50). Primary NKp44+NK cells exhibited significantly higher degranulation in response to plate-bound HLA-DPA1*02:01-DPB1*01:01 compared with control HLA-DP molecules, which were inhibited by anti-NKp44-blocking. Human cholangiocyte organoids expressing HLA-DPA1*02:01-DPB1*01:01 after IFN-γ-exposure demonstrated significantly increased binding to NKp44-Fc constructs compared with unstimulated controls. Importantly, HLA-DPA1*02:01-DPB1*01:01-expressing organoids increased degranulation of NKp44+NK cells compared with HLA-DPB1-KO organoids.ConclusionOur studies identify a novel PSC risk haplotype HLA-DP A1*02:01~DPB1*01:01and provide clinical and functional data implicating NKp44+NK cells that recognise HLA-DPA1*02:01-DPB1*01:01 expressed on cholangiocytes in PSC pathogenesis.

Naturalistic observation of verbal behavior on social media is a method of gathering data on the acceptability of topics of social interest. In other words, online social opinion may be a modern-day measure of social validity. We sought to gain an objective understanding of online discourse related to the field of applied behavior analysis (ABA). We analyzed Twitter posts related to ABA (e.g., #ABA, #BehaviorAnalysis, #appliedbehavioranalysis). Our initial sample consisted of 119,911 tweets from 2012 to 2022. We selected a random subset (n= 11,000) for further analysis using a stratified sampling procedure to ensure that tweets across years were adequately represented. Two observers were trained to code tweets for relevance and sentiment toward the field. A total of 5,408 relevant tweets were identified and analyzed, with an arithmetic mean of 492 tweets per year. Tweets were categorized as having neutral (51.41%), positive (43.81%), or negative (4.79%) sentiment. Negative sentiment tweets received approximately three times higher engagement scores compared to positive and neutral tweets. Positive sentiment tweets commonly used hashtags related to special education, therapy, behavior analysis, autism, and specific individuals. Negative sentiment tweets focused on the harmful effects of ABA, disability, variations of ABA, and promoting alternatives to ABA. Our results suggest that there is a small but vocal minority that has the potential to shape the narrative on ABA. We suggest a path forward for behavior analysts in the study of the online discourse on ABA.

Machine learning, a subfield of artificial intelligence (AI), relies on large corpora of data as input for learning algorithms, resulting in trained models that can perform a variety of tasks. While data or information are not subject matter within copyright law, almost all materials used to construct corpora for machine learning are protected by copyright law: texts, images, videos, and so on. There are global policy moves to address the copyright implications of machine learning, in particular in the context of so-called “foundation models” that underpin generative AI. This paper takes a step back, exploring empirically three technological settings through detailed case studies. We set out the established industry methodology of a lifecycle of AI (collecting data, organising data, model training, model operation) to arrive at descriptions suitable for legal analysis. This will allow an assessment of the challenges for a harmonisation of rights, exceptions and disclosure under EU copyright law. The three case studies are:Machine learning for scientific purposes, in the context of a study of regional short-term letting markets;Natural Language Processing (NLP), in the context of large language models;Computer vision, in the context of content moderation of images.

Purpose: Accurate prediction of extraprostatic extension (EPE) is pivotal for surgical planning. Herein, we aimed to provide an updated model for predicting EPE among patients diagnosed with MRI-targeted biopsy. Materials and methods: We analyzed a multi-institutional dataset of men with clinically localized prostate cancer diagnosed by MRI-targeted biopsy and subsequently underwent prostatectomy. To develop a side-specific predictive model, we considered the prostatic lobes separately. A multivariable logistic regression analysis was fitted to predict side-specific EPE. The decision curve analysis was used to evaluate the net clinical benefit. Finally, a regression tree was employed to identify three risk categories to assist urologists in selecting candidates for nerve-sparing, incremental nerve sparing and non-nerve-sparing surgery. Results: Overall, data from 3169 hemi-prostates were considered, after the exclusion of prostatic lobes with no biopsy-documented tumor. EPE was present on final pathology in 1,094 (34%) cases. Among these, MRI was able to predict EPE correctly in 568 (52%) cases. A model including PSA, maximum diameter of the index lesion, presence of EPE on MRI, highest ISUP grade in the ipsilateral hemi-prostate, and percentage of positive cores in the ipsilateral hemi-prostate achieved an AUC of 81% after internal validation. Overall, 566, 577, and 2,026 observations fell in the low-, intermediate- and high-risk groups for EPE, as identified by the regression tree. The EPE rate across the groups was: 5.1%, 14.9%, and 48% for the low-, intermediate- and high-risk group, respectively. Conclusion: In this study we present an update of the first side-specific MRI-based nomogram for the prediction of extraprostatic extension together with updated risk categories to help clinicians in deciding on the best approach to nerve-preservation.

Transition-metal phosphorus trichalcogenides (TMPTs) are inorganic materials with exciting properties, such as inherent magnetism combined with the electronic band gap. Due to their layered structure, these materials can be exfoliated into ultrathin sheets, which show properties different from their bulk counterparts. In this work, we present an experimental study supported by first-principles calculations focused on tuning the properties of freestanding few-layer MnPSe3by local structural transformations stimulated by electron beam irradiation and thermal annealing under high vacuum conditions in a transmission electron microscope (TEM). In both cases, we observe the emergence of α- or γ-MnSe crystal structures. Using different TEM methods, we systematically investigate the irradiation-induced structural modifications. The results are rationalized with the help of ab initio calculations, which predict that the elastic knock-on threshold for removing selenium is significantly higher than that for phosphorus. Nevertheless, an increased sputtering rate of Se compared to P was detected by complementary spectroscopic experiments in this ternary compound, indicating that inelastic damage mechanisms play the dominant role within the low-voltage region. Moreover, the locally formed MnSe phases arise after the complete degradation of the host MnPSe3structure. First-principles calculations predict that the electronic and magnetic properties of 2D MnSe structures depend on the crystal types, facets, that is, orientation of the crystallographic planes of the parent bulk material, and crystallite thickness.

The nanospace of the van der Waals (vdW) gap between structural units of two-dimensional (2D) materials serves as a platform for growing unusual 2D systems through intercalation and studying their properties. Various kinds of metal chlorides have previously been intercalated for tuning the properties of host layered materials, but the atomic structure of the intercalants remains still unidentified. In this study, we investigate the atomic structural transformation of molybdenum(V) chloride (MoCl5) after intercalation into bilayer graphene (BLG). Using scanning transmission electron microscopy, we found that the intercalated material represents MoCl3networks, MoCl2chains, and Mo5Cl10rings. Giant lattice distortions and frequent structural transitions occur in the 2D MoClxthat have never been observed in metal chloride systems. The trend of symmetric to nonsymmetric structural transformations can cause additional charge transfer from BLG to the intercalated MoClx, as suggested by our density functional theory calculations. Our study deepens the understanding of the behavior of matter in the confined space of the vdW gap in BLG and provides hints at a more efficient tuning of material properties by intercalation for potential applications, including transparent conductive films, optoelectronics, and energy storage.

As digital technologies emerge and improve rapidly, firms face changing tradeoffs in terms of their technology infrastructure and strategic direction. Hence, many of them adopt new digital technology and develop new business models and strategies. The literature on strategic alignment of IT suggests that firms need to synchronize these different domains of choice. We therefore, ask how far firms renew their strategy as they adopt new technologies. In this article, we study this question empirically by assessing if the adoption of new digital technologies is associated with, or even leads to, changes to firm strategy using a detailed survey-based dataset on firms’ strategy renewal and their adoption of digital technologies. We observe a strong positive association between the extent of strategy change and the stage of adoption of advanced digital technologies overall, suggesting a tight coupling between (technological) structure and strategy. Further, using instrumental variable regressions to disentangle the two effects, we find that the adoption of new technologies may lead to a large and robust effect on strategy change: the more extensive the adoption, the larger the change in strategy. This result is robust to various specifications and across industries. However, we notice substantial differences across technologies, potentially pointing at heterogeneity in their strategic nature or maturity level.

Many cephalopods escape detection using camouflage1. This behaviour relies on a visual assessment of the surroundings, on an interpretation of visual-texture statistics2–4and on matching these statistics using millions of skin chromatophores that are controlled by motoneurons located in the brain5–7. Analysis of cuttlefish images proposed that camouflage patterns are low dimensional and categorizable into three pattern classes, built from a small repertoire of components8–11. Behavioural experiments also indicated that, although camouflage requires vision, its execution does not require feedback5,12,13, suggesting that motion within skin-pattern space is stereotyped and lacks the possibility of correction. Here, using quantitative methods14, we studied camouflage in the cuttlefish Sepia officinalisas behavioural motion towards background matching in skin-pattern space. An analysis of hundreds of thousands of images over natural and artificial backgrounds revealed that the space of skin patterns is high-dimensional and that pattern matching is not stereotyped—each search meanders through skin-pattern space, decelerating and accelerating repeatedly before stabilizing. Chromatophores could be grouped into pattern components on the basis of their covariation during camouflaging. These components varied in shapes and sizes, and overlay one another. However, their identities varied even across transitions between identical skin-pattern pairs, indicating flexibility of implementation and absence of stereotypy. Components could also be differentiated by their sensitivity to spatial frequency. Finally, we compared camouflage to blanching, a skin-lightening reaction to threatening stimuli. Pattern motion during blanching was direct and fast, consistent with open-loop motion in low-dimensional pattern space, in contrast to that observed during camouflage.

AbstractEvidence about the influence of different business models (BMs) on the performance of small and medium enterprises (SMEs) is scarce and contradictory. In this paper, a meta-analytical study of the quantitative literature regarding BMs and SMEs is developed which overcomes biases commonly found in other, more limited works. We found that both innovation-based BMs (I-BMs) and efficiency-based BMs (E-BMs) positively affect the performance of SMEs, but also that, in countries with higher levels of entrepreneurial capabilities, the positive impact of I-BMs increases. We also identified that, while the existence of stronger capabilities in firms affects I-BMs positively, the size of SMEs impacts E-BMs favorably. Finally, key contributions of these findings for practitioners and scholars interested in the usefulness of BMs and their impact on SMEs are discussed.

Quasi-two-dimensional (2D) manganese phosphorus trisulfide, MnPS3, which exhibits antiferromagnetic ordering, is a particularly interesting material in the context of magnetism in a system with reduced dimensionality and its potential technological applications. Here, we present an experimental and theoretical study on modifying the properties of freestanding MnPS3by local structural transformations via electron irradiation in a transmission electron microscope and by thermal annealing under vacuum. In both cases we find that MnS1–xPxphases (0 ≤ x< 1) form in a crystal structure different from that of the host material, namely that of the α- or γ-MnS type. These phase transformations can both be locally controlled by the size of the electron beam as well as by the total applied electron dose and simultaneously imaged at the atomic scale. For the MnS structures generated in this process, our ab initiocalculations indicate that their electronic and magnetic properties strongly depend on both in-plane crystallite orientation and thickness. Moreover, the electronic properties of the MnS phases can be further tuned by alloying with phosphorus. Therefore, our results show that electron beam irradiation and thermal annealing can be utilized to grow phases with distinct properties starting from freestanding quasi-2D MnPS3.

Die Klärschlammbewirtschaftung in Österreich befindet sich im Umbruch. Künftig soll die Phosphorrückgewinnung forciert werden, gleichzeitig verliert die landwirtschaftliche Ausbringung immer weiter an Bedeutung. Aktuelle politische Konzepte fokussieren sich primär auf die (wenigen) größeren Kläranlagen, allerdings haben auch die (vielen) kleinen Anlagen einen Bedarf an tragfähigen Lösungen für die Zukunft. Um einen Überblick über die aktuelle Praxis der Klärschlammbewirtschaftung unter spezieller Berücksichtigung von Kleinkläranlagen und kleinen Kläranlagen zu schaffen, wird in diesem Beitrag am Beispiel von Oberösterreich ein Inventar aller Kläranlagen im Land erstellt und darauf aufbauend anlagenspezifisch der Klärschlammanfall dargestellt und wichtige derzeit gängige Verwertungspfade genauer beleuchtet. Die präsentierten Erkenntnisse sollen dazu beitragen, die Fachwelt sowie die politischen Entscheidungsträger in Bezug auf die Bedürfnisse der „kleineren“ Kläranlagen zu sensibilisieren, damit auch diese bei der Entwicklung von geeigneten und tragfähigen Zukunftskonzepten der Klärschlammbewirtschaftung Berücksichtigung finden.