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With increasing mpox cases in Maricopa County, Arizona, the county’s health department launched a survey on July 11, 2022, to gather eligibility and contact data and provide clinic information to those interested in JYNNEOS as postexposure prophylaxis (PEP) or expanded postexposure prophylaxis(PEP++). Survey data were matched to case and vaccination data. Overall, 343 of the 513 respondents (66.9%) who reported close contact with an mpox case patient received PEP and 1712 of the 3379 respondents (50.7%) who were unsure of their contact status received PEP++. This outreach intervention connected potential close contacts unknown to MCDPH with PEP or PEP++. (Am J Public Health. 2023;113(5):504–508. https://doi.org/10.2105/AJPH.2023.307224 )

We utilize high-resolution cosmological simulations to reveal that high-redshift galaxies tend to undergo a robust `wet compaction' event when near a `golden' stellar mass of $\sim 10^{10} M_{\odot}$. This is a gaseous shrinkage to a compact star-forming phase, a `blue nugget' (BN), followed by central quenching of star formation to a compact passive stellar bulge, a `red nugget' (RN), and a buildup of an extended gaseous disc and ring. Such nuggets are observed at cosmic noon and seed today's early-type galaxies. The compaction is triggered by a drastic loss of angular momentum due to, e.g., wet mergers, counter-rotating cold streams, or violent disc instability. The BN phase marks drastic transitions in the galaxy structural, compositional and kinematic properties. The transitions are from star-forming to quenched inside-out, from diffuse to compact with an extended disc-ring and a stellar envelope, from dark matter to baryon central dominance, from prolate to oblate stellar shape, from pressure to rotation support, from low to high metallicity, and from supernova to AGN feedback. The central black hole growth, first suppressed by supernova feedback when below the golden mass, is boosted by the compaction, and the black hole keeps growing once the halo is massive enough to lock in the supernova ejecta., 33 pages, 26 figures in the main body (49 pages, 45 figures including appendix)

Bullying research has shown repeatedly that victims of bullying have an increased risk for later internalizing problems and bullies have an increased risk for later externalizing problems. Bullying involvement is often, either explicitly or implicitly, presented as part of a causal mechanism for maladjustment. However, genetic vulnerability may confound the reported associations. This study examined to what extent genetic vulnerability can account for the reported associations between bullying involvement (age 11-14) and later internalizing and externalizing problems (age 16), using data from the TRacking Adolescents' Individual Lives Survey (n = 1604). Because polygenic scores capture only a fraction of the total genetic effect, they were extrapolated to the size of single-nucleotide polymorphism and twin heritability estimates to examine genetic confounding while controlling for (hypothetical) polygenic scores that fully capture the genetic effect. Genetic vulnerability for internalizing and externalizing problems confounded, respectively, the association between bullying victimization and later internalizing problems, and the association between bullying perpetration and later externalizing problems. As such, this study showcases a method that can be broadly used to assess the magnitude of genetic confounding. Caution is, however, warranted in interpreting particularly the less straightforward extrapolations of polygenic scores to the size of twin heritability estimates.

ZusammenfassungDie Behandlung von peripheren Nervenverletzungen und Kompressionssyndromen erfordert eine rasche und präzise Diagnose. Nervenpathologien korrekt zu identifizieren ist klinisch jedoch oft diffizil, womit wichtige Zeit bis zur fachgerechten Therapie verlorengeht. In diesem Positionspaper der deutschsprachigen Arbeitsgemeinschaft für Mikrochirurgie (DAM) wird der derzeitige Status Quo zur Diagnostik von peripheren Nerven bei traumatischen Läsionen und Kompressionssyndromen analysiert. Hierbei wurde der Stellenwert der klassischen klinischen Diagnostik in Zusammenschau mit Elektrophysiologie, hochauflösendem Nervenultraschall und Magnetresonanz-Neurographie bewertet sowie die Mitglieder der DAM zu ihrem diagnostischen Zugang befragt. Die beschriebenen Inhalte wurden im Zuge eines Konsensusworkshops anlässlich der 42. Jahrestagung der DAM 2021 in Graz erarbeitet.

Personal Privacy Assistants (PPAs) can support users in managing their privacy. Conducting a user study, we provide qualitative and quantitative insights into how users imagine their PPA and how PPAs designs can appear for different user groups. We highlight five aspects derived from the literature that are essential when designing a PPA: What features should the PPA have? How should the PPA learn the users’ preferences? What level of user involvement in its decisions should the PPAs have? Which vendor should offer the PPA? What data are users willing to disclose to their PPA? Our results provide a holistic view of user perceptions of PPAs. We identify two user groups that differ in their characteristics, such as technology affinity and privacy concerns, and have different ideas of a PPA in terms of automation level and provider, for example. We discuss our results in relation to the literature and derive recommendations for designing PPAs to fulfill user needs.

The advancing digitalisation is one of the great challenges of our times. Related activities also concern the wastewater sector. In the field of building construction, one emerging approach is building information modelling (BIM). The presented work investigates to which extent BIM practices have already found their way to wastewater management, and what kind of benefits and constraints are incorporated. Information is collected by means of a literature review and international expert surveys. Results indicate that several BIM-related key elements are already well established in the sector, but not necessarily in the intended manner. Consequently, the digital transition in the wastewater sector is not about replacing existing procedures and techniques but to rethink and optimise them. This primarily concerns data and information management in combination with the application of digital tools. Furthermore, wastewater management requires more integrated approaches, involving interdisciplinary/collaborative concepts and life cycle perspectives. Appropriate change management is necessary to give support and guidance to employees during the transition process. Furthermore, also from the political side, a clear definition and communication of the pursued digital vision is important. This article aims at stimulating discussion and research to optimise wastewater management from the digital perspective.

Data-driven approaches have gained interest recently in the field of wind energy. Data-driven online estimators have been investigated and demonstrated in several applications such as online loads estimation, wake center position estimations, online damage estimation. The present work demonstrates the application of machine learning algorithms to formulate an estimator of the internal loads acting on the bearings of the drivetrain of onshore wind turbines. The loads estimator is implemented as a linear state-space model that is augmented with a non-linear feed-forward neural network. The estimator infers the loads time series as a function of the standard measurements from the SCADA and condition monitoring systems (CMS). A formal analysis of the available data is carried out to define the structure of the virtual sensor regarding the order of the models, number of states, architecture of neural networks. Correlation coefficient of 98% in the time domain and matching of the frequency signature are achieved. Several applications are mentioned and discussed in this work such as online estimation of the forces for monitoring and model predictive control applications.

PurposeThe objective of this research is to analyze the microfoundations of dynamic capabilities used by microbreweries in Porto Alegre (Brazil) in their coopetition strategies.Design/methodology/approachA case study with a qualitative approach was developed. Data were collected during interviews with owners of 11 microbreweries, via analysis of documents and nonparticipatory observation. The authors used the content analysis technique to infer knowledge.FindingsThe authors identified the microfoundations of dynamic coopetition capabilities including collective purchases, shared distribution expenses, shared production, education of consumers and other beer producers, group interaction and a business roundtable with entrepreneurs from the food and drink sector in the hospitality industry.Research limitations/implicationsThe authors developed a framework that considers the relationship between the microfoundations of dynamic capabilities and coopetition regarding the paradox between competition and cooperation. It is relevant to identify different actors’ movements and the potential outcomes of coopetitive strategies, which yield a competitive advantage for the cluster.Practical implicationsTogether, the microfoundations of dynamic capabilities contribute to the competitive advantage of the cluster.Originality/valueThe study highlights how small companies can jointly develop competitive advantage in a market dominated by a large company.

Funding Information: We want to thank all cooperation associates in the framework of this manuscript. Further, we especially thank the Institut Laue-Langevin for the synthesis of the TMPT materials and Gabriele Es-Samlaoui for the preparation of TEM samples used in this work. This work was supported by the German Science Foundation (DFG), project CRC 1279 (project number 316249678), projects KR 4866/8-1, and the collaborative research center “Chemistry of Synthetic 2D Materials” SFB-1415-417590517. This work was supported by a project funded by the Carl Zeiss foundation. The computational support from the Technical University of Dresden computing cluster (TAURUS) and High-Performance Computing Center (HLRS) in Stuttgart is gratefully appreciated. M.K.K. acknowledges funding from the Deutsche Forschungsgemeinschaft (DFG) within the project DFG: KI 2546/1-1. Publisher Copyright: © 2023 The Authors. Published by American Chemical Society. 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 MnPS3 by local structural transformations via electron irradiation in a transmission electron microscope and by thermal annealing under vacuum. In both cases we find that MnS1-xPx phases (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 initio calculations 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.

ZusammenfassungDer Klimawandel stellt urbane Räume durch vermehrte Trockenperioden und Starkregenereignisse vor große Herausforderungen und fordert Maßnahmen, um die Lebensqualität aufrecht zu erhalten. Urbane Begrünung spielt als Klimawandelanpassungsmaßnahme eine wichtige Rolle – allerdings können Pflanzen nur bei ausreichender Bewässerung einen mikroklimatischen Kühleffekt erzielen. Aktuell wird vorrangig Trinkwasser zur Bewässerung herangezogen, was langfristig als nicht nachhaltig einzustufen ist. Im urbanen Raum stehen weitere Wasserressourcen, wie Regenwasser, Abwasser oder Grauwasser (Abwasser ohne Fäkalien) als Brauchwasser, beispielsweise zur Bewässerung, zur Verfügung. Diese Wasserressourcen haben ein großes Potenzial zur kreislauforientierten Wiedernutzung, welches jedoch in Österreich aktuell nicht ausgeschöpft wird. Daher stellt sich die Frage, inwiefern Wasserwiedernutzung in österreichischen Strategien zur Klimawandelanpassung berücksichtigt wird und welche Potenziale sich daraus ergeben. Dazu werden in diesem Artikel Strategien zur Klimawandelanpassung auf Bundes- und Landesebene analysiert, das qualitative und quantitative Potenzial von Regen- und gereinigtem Grauwasser aufgezeigt und Herausforderungen in der praktischen Umsetzung von Wasserwiedernutzung identifiziert. Die Ergebnisse zeigen, dass der Brauchwasserbedarf mit urbanen Wasserressourcen gedeckt werden kann (mit variierendem Deckungsgrad je nach Ressource) und damit eine nutzungsorientierte Verwendung dieser Ressourcen ein hohes Potenzial aufweist. Auch wird eine Brauchwasserversorgung als Teil des Maßnahmenpakets zur Anpassung an den Klimawandel gesehen. Allerdings zeigt sich, dass in der Praxis einige Herausforderungen bei der Umsetzung von und der Schaffung der Voraussetzungen für Wasserwiedernutzung gesehen werden. Diese Lücke zwischen der Vision einer klimawandelangepassten Zukunft und den identifizierten Herausforderungen in der Praxis muss geschlossen werden, um langfristig Brauchwasserbedarf – wo möglich – mit urbanen Wasserressourcen zu decken und die wertvolle Ressource Trinkwasser für den tatsächlichen Trinkwasserbedarf zu sichern.

Three carvotacetones (1 – 3) isolated from Sphaeranthus africanus were screened in 60 cancer cell lines at the National Cancer Institute (NCI) within the Developmental Therapeutics Program (DTP). At the concentration of 10−5 M, compound 1 (3,5-diangeloyloxy-7-hydroxycarvotacetone) turned out to be the most active compound against ACHN and UO-31 renal cancer cell lines with growth percent values of − 100% (all cells dead). Compound 2 (3-angeloyloxy-5-[2″,3″-epoxy-2″-methylbutanoyloxy]-7-hydroxycarvotacetone) showed strong effects in SK-MEL-5 melanoma and ACHN renal cancer cells with inhibition values of 93% and 97%, respectively. Compound 3 (3-angeloyloxy-5-[3″-chloro-2″-hydroxy-2″-methylbutanoyloxy]-7-hydroxy-carvotacetone) exhibited a quite strong effect on renal cancer cells with a growth inhibitory effect of 96% against ACHN and UO-31 cells. When treated with five different concentrations of 1 (1 × 10−8, 1 × 10−7, 1 × 10−6, 1 × 10−5, and 1 × 10−4 M), HOP-92 cells were found to be most sensitive with GI50, TGI, and LC50 values of 0.17, 0.40, and 0.96 µM, respectively. When using the ApoTox-Glo triplex assay to evaluate the apoptosis inducing effects of seven carvotacetones isolated from S. africanus in CCRF-CEM cells, compounds 1 – 6 increased caspase-3/7 activity with 1, 2, and 4 (3-angeloyloxy-5,7-dihydroxycarvotacetone) exhibiting the highest activitiy, indicating induction of caspase-dependent apoptosis.

Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental condition impacting children and adults. Current treatments are limited and there is increasing interest in the use of mindfulness, which is growing in popularity. Previous systematic reviews have typically focused on specific ages, outcome measures or interventions. The current review aimed to take a more comprehensive approach. Title and abstract searches were performed in five databases for randomized and non-randomized controlled trials or pre-post studies with participants with an ADHD diagnosis or a score above a clinically relevant cut-off on a validated ADHD measure. Studies had to measure symptoms of ADHD, global or social functioning. Extraction of key information including participant status (i.e., diagnosis, scale scores, comorbidities, medication use), study design, and outcome measures was conducted. Effect sizes (Hedge’s g) were calculated and where a measure had been used in at least three studies with the same population, meta-analyses were considered. Twenty-nine studies were initially identified, with seven deemed poor quality and removed from further analysis leaving, 22 studies containing data from 1237 children and adults with ADHD along with data from 525 family members. The data indicate possible benefits of mindfulness on self-compassion, quality of life, wellbeing, depression, and anxiety. The findings also suggest that mindfulness may also improve ADHD symptoms, executive function, problematic behaviours, and emotional dysregulation, although results vary by age of patient and measures used. Parent stress and parenting style have received limited attention, highlighting the need for more studies in these areas. Whilst the data presented suggest that mindfulness may be beneficial, the evidence base is not as strong as the popularity of the approach. Many of the studies lacked blind assessment, adequate randomization, or suitable control conditions. As such high-quality controlled studies considering medication, other psychosocial interventions, use of active and in active controls and comorbidity as well as longer follow-up periods, are needed to confirm this.

The genus Ctenomys has been widely used in karyotype evolution studies due to the variation in their diploid numbers. Ctenomys minutus is characterized by intraspecific variation in diploid number (2 n = 42, 46, 48, and 50), which makes it an interesting model to investigate genomic rearrangements mechanisms that could lead to different cytotypes in this species. Thereupon, it has been already shown that DNA methylation may participate in chromosome structure. Therefore, we aimed to investigate whether telomeres and global DNA methylation had a role in the genome rearrangements that led to this variation in C. minutus. We also realized an analysis for the presence of intrachromosomal telomeric repeats (ITRs) by fluorescence in situ hybridization. Our study demonstrated that neither telomere length nor DNA methylation had significant differences among the cytotypes. However, if only females were considered, there were significant differences for telomere length and methylation. Young individuals, regardless of their cytotypes, had the most methylated DNA. Regarding the ITRs, we found a signal on chromosome 1 in 2 n = 50b. No evidence was found that telomere length or methylation could have influenced chromosomal rearrangements, although new cytotypes seem to have emerged within the distribution of parental cytotypes by the accumulation of different chromosomal rearrangements.

Radiomics promises to enhance the discriminative performance for clinically significant prostate cancer (csPCa), but still lacks validation in real-life scenarios. This study investigates the classification performance and robustness of machine learning radiomics models in heterogeneous MRI datasets to characterize suspicious prostate lesions for non-invasive prediction of prostate cancer (PCa) aggressiveness compared to conventional imaging biomarkers.A total of 142 patients with clinical suspicion of PCa underwent 1.5T or 3T biparametric MRI (7 scanner types, 14 institutions) and exhibited suspicious lesions [prostate Imaging Reporting and Data System (PI-RADS) score ≥3] in peripheral or transitional zones. Whole-gland and index-lesion segmentations were performed semi-automatically. A total of 1,482 quantitative morphologic, shape, texture, and intensity-based radiomics features were extracted from T2-weighted and apparent diffusion coefficient (ADC)-images and assessed using random forest and logistic regression models. Five-fold cross-validation performance in terms of area under the ROC curve was compared to mean ADC (mADC), PI-RADS and prostate-specific antigen density (PSAD). Bias mitigation techniques targeting the high-dimensional feature space and inherent class imbalance were applied and robustness of results was systematically evaluated.Trained models showed mean area under the curves (AUCs) ranging from 0.78 to 0.83 in csPCa classification. Despite using mitigation techniques, high performance variability of results could be demonstrated. Trained models achieved on average numerically higher classification performance compared to clinical parameters PI-RADS (AUC =0.78), mADC (AUC =0.71) and PSAD (AUC =0.63).Radiomics models' classification performance of csPCa was numerically but not significantly higher than PI-RADS scoring. Overall, clinical applicability in heterogeneous MRI datasets is limited because of high variability of results. Performance variability, robustness and reproducibility of radiomics-based measures should be addressed more transparently in future research to enable broad clinical application.

It has been shown that baseline health-related quality of life (HRQOL) is a valuable prognostic indicator of survival outcomes for various metastatic cancers, but there is no evidence on the prognostic value of baseline HRQOL for patients with bladder cancer undergoing radical cystectomy (RC) and ileal conduit (IC) or orthotopic ileal neobladder (ONB) with curative intent.To assess the association between baseline HRQOL and survival outcomes following RC.The study included 407 patients with prospectively assessed baseline HRQOL before RC. Patients were stratified according to the Global Health Status (GHS) domain of the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire, with good general HRQOL defined as GHS ≥70 on the basis of validated cutoff levels. A propensity score-matched analysis of 357 patients (1:2 ratio; 125 patients with GHS ≥70 vs 232 with GHS70) was performed.RC with IC or ONB.The primary endpoint was cancer-specific survival (CSS). The secondary endpoints were overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meier and multivariate Cox regression models were constructed to assess the prognostic value of baseline GHS for prediction of survival outcomes.Median follow-up was 40.5 mo. The rates of 5-yr CSS (82% vs 65%; p = 0.001), 5-yr OS (76% vs 53%; p = 0.001), and 5-yr RFS (50% vs 39%; p = 0.04) were significantly higher in the GHS ≥70 cohort. GHS ≥70 was confirmed as an independent predictor for CSS (hazard ratio [HR] 0.37, 95% confidence interval [CI] 0.18-0.73; p = 0.004), OS (HR 0.45, 95% CI 0.26-0.79; p = 0.005), and RFS (HR 0.50, 95% CI 0.30-0.83; p = 0.008) in multivariate analyses. Study limitations include the retrospective analysis of prospectively collected data and use of a HRQOL questionnaire not specifically for bladder cancer.Our findings suggest that preoperative baseline HRQOL has significant predictive value for outcomes of RC with curative intent for bladder cancer. We found that good general HRQOL at baseline accurately predicts greater CSS, OS, and RFS.We assessed the association between health-related quality of life at baseline and survival outcomes after radical cystectomy for bladder cancer. We found that good general health-related quality of life at baseline predicts better survival outcomes and that higher baseline scores were associated with greater cancer-specific survival.

Key Points:We conceptualise innovation as new interactions being created by the digital platform, in contrast to coordination which facilitates existing interactions or market transactions.We apply this framework to the DMA to assess two of the most contentious practices: self-preferencing and data-sharing.We show that these practices differ hugely in the extent to which they replace existing interactions (little to negative innovation effect), sustain existing interactions (moderate, positive innovation effect), or trigger new interactions (large, positive innovation spillovers).We thus derive that the business model agnostic approach to digital platforms taken in the DMA risks treating practices that increase the value created by an interaction equally to those that simply shift the distribution of value.

Asymmetrical distribution of melanomas in favor of the left body half has been repeatedly described.In a prospective cross-sectional study, we investigated the distribution of melanocytic nevi between the left and right halves of the body in 702 patients. In 2,004 consecutive cases with melanomas, we retrospectively determined left to right (L/R) ratios of primary melanomas, lymph node metastases, and melanocytic nevi in sentinel lymph nodes (SN).The L/R ratios for cutaneous nevi and melanomas were 1.23 (95 % confidence interval [CI] 1.12-1.36) and 1.6 (95 % CI 1.37-1.88), respectively. In both cutaneous nevi and melanomas, the left-sided excess was mainly found in intermittently light-exposed skin. Of the nevus patients, 92.4 % were right-handed. Breslow thickness and rates of ulceration did not differ significantly between the two body halves.Melanocytic nevi and melanomas are more frequently found on the left body half. We assume asymmetric solar radiation as the causative factor. The vast majority of right-handed people might unconsciously align their posture during outdoor activities so that the light falls in from the left. This avoids shadow cast by the dominant arm, shoulder, or head.

Individual differences in child and adolescent social development are due to a combination of variation in genetic propensity and environmental conditions. That is, variation in social domains like bullying-victimization, loneliness and pro- and antisocial behaviour is genetically influenced to a substantial extent. That is not to say that social contexts also do not play an important role in shaping social development. Indeed, parenting and parent–child relationship quality have been associated with various aspects of social development. What complicates matters is that environmental conditions – including parenting – are under genetic influence as well. Genetic influence on parenting has not received sufficient attention in the literature on social development although it likely biases estimates of parental effects on offspring social development. To change this situation, I review recent twin and molecular research on genetic influence on parenting and discuss why genetically-informed studies improve and enrich contemporary research into social development. The aim of this topic review is to provide an accessible introduction to genetics of parenting and encourage genetically-informed research into social development.

How are financial incentives and innovative activity linked? We analyze how firms’ use of financial incentives is associated with their employees’ innovative activity. The presence and transparency of financial incentives matter for the link between incentives and innovative activity, just like the activity profile of those receiving incentives. In a study of managers and workers in small German manufacturers, we find that financial incentives and explorative and exploitative innovative activity do interact. Financial incentives for managers (workers) are positively (negatively) associated with exploitative innovative activity, and negatively with exploratory innovative activity for both groups of employees. Furthermore, a transparent compensation system counteracts the negative association of financial incentives for workers on innovation activity, especially exploration. Our study qualifies the claim that extrinsic motivation crowds out innovative activity and specifies under which conditions the use of financial incentives in a firm is associated with different degrees of organizational exploitative and explorative innovative activity.

OBJECTIVE: To evaluate the relationship between pre-operative PSA value, 68Ga-prostate-specific-membrane-antigen (PSMA) PET performance and oncologic outcomes after salvage lymph node dissection (sLND) for biochemical recurrent prostate cancer (PCa). PATIENTS AND METHODS: The study included 164 patients diagnosed with ≤2 pelvic lymph-node recurrence(s) of PCa documented on 68Ga-PSMA PET scan and treated with pelvic ± retroperitoneal sLND at 11 high-volume centres between 2012 and 2019. Pathologic findings were correlated to PSA values at time of sLND, categorized in early (1.5 ng/ml). Clinical recurrence (CR)-free survival after sLND was calculated using multivariable analyses and plotted over pre-operative PSA value. RESULTS: Median [interquartile range (IQR)] PSA at sLND was 1.1 (0.6, 2.0) ng/ml, and 131 (80%) patients had one positive spot at PET scan. All patients received pelvic sLND, whereas 91 (55%) men received also retroperitoneal dissection. Median (IQR) number of node removed was 15 (6, 28). The rate of positive pathology increased as a function of pre-operative PSA value, with highest rates for patients with pre-operative PSA > 1.5 ng/ml (pelvic-only sLNDs: 84%; pelvic + retroperitoneal sLNDs: 90%). After sLND, PSA ≤ 0.3 ng/ml was detected in 67 (41%) men. On multivariable analyses, pre-operative PSA was associated with PSA response (p

Many platforms rely on volunteer contributions for value creation. Thus, unpaid contributors are valuable to the platform, but control over their activities is limited. We study whether and how volunteer communities can provide a competitive advantage and ask how contributor behavior depends on a platform's competitive position. We propose two channels: First, a stronger competitive position facilitates contributor coordination, leading to a larger active community. Second, a platform's competitive position is related to contributor motivation, which drives how much individuals contribute. Studying two competing game wiki platforms, we find that a platform's stronger competitive position is associated with higher activity, primarily driven by the number of contributors, which in turn triggers increased contributions by existing contributors. Further, high-productivity contributors are especially active on a stronger platform.

Background With the introduction of several drugs for the therapy of transthyretin-related amyloidosis (ATTR) which slow down the disease, early detection of polyneuropathy (PNP) is becoming increasingly of interest. [99mTc]-3,3-Diphosphono-1,2-Propanodicarboxylic Acid (DPD) bone scintigraphy, which is used for the diagnosis of cardiac (c)ATTR, can possibly make an important contribution in the identification of patients at risk for PNP. Methods Fifty patients with cATTR, who underwent both planar whole-body DPD scintigraphy and nerve conduction studies (NCS) were retrospectively evaluated. A subgroup of 22 patients also underwent quantitative SPECT/CT of the thorax from which Standardized Uptake Values (SUVpeak) in the subcutaneous fat tissue of the left axillar region were evaluated. Results The Perugini score was significantly increased in patients with cATTR and additional diagnosis of PNP compared to patients without (2.51 ± 0.51 vs 2.13 ± 0.52; P = 0.03). Quantitative SPECT/CT revealed that DPD uptake in the subcutaneous fat of the left axillar region was significantly increased in cATTR patients with compared to patients without (1.36 ± 0.60 vs 0.74 ± 0.52; P = 0.04). Conclusion This study suggests that DPD bone scintigraphy is a useful tool for identification of patients with cATTR and a risk for PNP due to increased DPD soft tissue uptake.

Healthy eating habits are related to a lower prevalence of chronic diseases. Objective: Verify the relationship between eating behaviors and self-perceived health (SPH) in young, middle-aged, and older adults. Materials and methods: This is a cross-sectional study with 52166 Brazilian adults aged 18 years and over. The dependent variable was positive SPH, whereas the independent variable was the eating behavior (exchanging lunch for snacks; exchanging dinner for snacks; intake of beans, ultra-processed food the previous day, fruits, vegetables, and processed juices/soft drinks). Poisson regression with robust adjustment for variance was used in the data analysis. Results: The relationship between eating behaviors and SPH was similar between genders. However, a more evident relationship was observed among young adults, regarding the age group. The consumption of fruits and vegetables was most clearly associated with SPH among the investigated behaviors. Furthermore, the higher the number of positive eating behaviors, the higher the prevalence of positive SPH in both genders and all age groups. Conclusion: The findings of this study reinforce the importance of healthy eating behaviors for health and indicate a more direct relationship between these and positive SPH in young adults and as a habit of regularly consuming fruits and vegetables.

Many plant-associated fungi are obligate biotrophs that depend on living hosts to proliferate. However, little is known about the molecular basis of the biotrophic lifestyle, despite the impact of fungi on the environment and food security. In this work, we show that combinations of organic acids and glucose trigger phenotypes that are associated with the late stage of biotrophy for the maize pathogen Ustilago maydis . These phenotypes include the expression of a set of effectors normally observed only during biotrophic development, as well as the formation of melanin associated with sporulation in plant tumors. U. maydis and other hemibiotrophic fungi also respond to a combination of carbon sources with enhanced proliferation. Thus, the response to combinations of nutrients from the host may be a conserved feature of fungal biotrophy.

It is plausible that peer aggression—like general forms of aggression—is transmitted from one generation to the next. As such, parental behavior in childhood and adolescence may be associated with offspring aggressive behavior against peers. This study used 1970 British Cohort Study data to test intergenerational transmission of peer aggression. The baseline sample consisted of 13,135 participants. At the first assessment that was used in this study, participants were on average 4.95 years old (SD = 0.79; 48.20% female). At the last assessment, participants were on average 33.88 years old (SD = 0.36; 52.1% female). Models were computed for early and middle childhood, and adolescence. Significant associations between parents’ and offspring peer aggression were found in most models – especially when correlating aggression in similar developmental periods for parents and children. Other transmission mechanisms such as genetic transmission may be relevant and should be taken into account in future studies.

Zusammenfassung 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.

Background: Besides second-generation hormone therapy (sHT), upfront docetaxel along with androgen deprivation therapy is the current standard of care for metastasized hormone-sensitive prostate cancer (mHSPC). Evidence on second-line therapy upon progression on chemohormonal treatment outside clinical trials is scarce. Objective: To comparatively assess the efficacy of subsequent therapy after upfront docetaxel in mHSPC in a real-world setting. Design, setting, and participants: This is a retrospective multicenter analysis. Males with mHSPC on androgen-deprivation therapy progressed to castration-resistant prostate cancer (CRPC) after upfront docetaxel. Outcome measurements and statistical analysis: Overall survival (OS), progression-free survival 2 (PFS2), and time to progression 2 (TTP2) were assessed. Chi-square test and Mann-Whitney U test were used for univariate comparison between the sHT and non-sHT (other therapies) cohorts. Median time to event was tested by Kaplan-Meier method and log-rank test. Univariate and multivariate analysis regression was performed with the Cox proportional-hazard model. Results and limitations: Sixty-five patients were included in the final analysis. Median TTP2 was 20 mo, median PFS2 was 29 mo, and median OS was not reached; sHT was an independent predictor of favorable PFS2 as compared with non-sHT. Time to CRPC was also confirmed to be the strongest predictor for novel endpoints PFS2 and TTP2. Time to CRPC >18 mo conferred advantage to sHT over non-sHT in relation to PFS2 and OS. Second-line therapies were well tolerated. The analysis is prone to inherent flaws and biases due to its retrospective nature. Conclusions: In real-world patients progressing after upfront docetaxel, sHT is independently associated with favorable PFS2 favoring drug class switch. Longer time to CRPC predicts strongly for superior PFS2 and TTP2. Further prospective research is warranted in order to guide treatment sequencing and improve outcomes and quality of life of males with metastasized prostate cancer. Patient summary: We analyzed the efficacy of second-line therapy after docetaxel in hormone-dependent metastatic prostate cancer. Novel hormone therapy appears to be a preferable option for deferring progression optimally. Larger patient databases are eagerly awaited. In real-world patients progressing after upfront docetaxel, second-generation hormone therapy is independently associated with superior progression-free survival 2 (PFS2) favoring drug class switch. Longer time to castration-resistant prostate cancer predicts strongly for superior PFS2 and time to progression 2.

IntroductionKeratinocytes form a multilayer barrier that protects the skin from invaders or injuries. The barrier function of keratinocytes is in part mediated by the production of inflammatory modulators that promote immune responses and wound healing. Skin commensals and pathogens such as Staphylococcus aureus secrete high amounts of phenol-soluble modulin (PSM) peptides, agonists of formyl-peptide receptor 2 (FPR2). FPR2 is crucial for the recruitment of neutrophils to the sites of infection, and it can influence inflammation. FPR1 and FPR2 are also expressed by keratinocytes but the consequences of FPR activation in skin cells have remained unknown.MethodsSince an inflammatory environment influences S. aureus colonization, e. g. in patients with atopic dermatitis (AD), we hypothesized that interference with FPRs may alter keratinocyte-induced inflammation, proliferation, and bacterial colonization of the skin. To assess this hypothesis, we investigated the effects of FPR activation and inhibition in keratinocytes with respect to chemokine and cytokine release as well as proliferation and skin wound gap closure.ResultsWe observed that FPR activation induces the release of IL-8, IL-1α and promotes keratinocyte proliferation in a FPR-dependent manner. To elucidate the consequence of FPR modulation on skin colonization, we used an AD-simulating S. aureus skin colonization mouse model using wild-type (WT) or Fpr2-/- mice and demonstrate that inflammation enhances the eradication of S. aureus from the skin in a FPR2-dependent way. Consistently, inhibition of FPR2 in the mouse model or in human keratinocytes as well as human skin explants promoted S. aureus colonization.DiscussionOur data indicate that FPR2 ligands promote inflammation and keratinocyte proliferation in a FPR2-dependent manner, which is necessary for eliminating S. aureus during skin colonization.

A number of unprecedented extreme late spring frosts has recently hit Western Europe, especially France, causing severe impacts on vineyards that had already undergone bud burst. Whether climate change may have contributed to making these events more likely is poorly understood, since it depends on a subtle balance between how much the phenological cycle anticipates due to winter warming and how much cold spring nights warm. Here we shed more light on the key driving factors behind observed changes by taking a novel approach in which the different components of past warming trends, i.e. mean warming, seasonal cycle changes, diurnal temperature changes and frequency of cold snaps, are isolated and separately analysed. Bud burst date is determined using a previously tested phenological model based on growing degree days. A statistical model is introduced to modulate the different components of warming and generate thousands of sample of plausible realisations of internal climate variability. The statistical model is fit to daily mean and night minimum temperature data in 1950-2022 from the ERA5 reanalysis and EOBS. We show that in large parts of Europe even a simple seasonally and daily uniform warming leads to an increase in the risk of frosts after vineyard bud bursts. However, such simple thermodynamic effect is small compared to the observed changes in the frequency of such events. Including the effect of changes in the seasonal cycle, i.e. the winter warming amplification, and in the diurnal temperature range further increases frost risk, but it still explains only up to a third of the observed changes in the frost events. Likewise, changes in internal atmospheric variability are also insufficient to explain the observed trends. We demonstrate that only the increased frequency in an intra-seasonal atmospheric circulation pattern causing warm winters followed by spring cold snaps, and acting on a warmed seasonal cycle, can explain the observed trends. We then analyse CMIP6 historical simulations to attribute the role of climate change versus internal climate variability. While mean warming and seasonal cycle changes are strongly influenced by climate change, the winter to spring swing in atmospheric circulation is more difficult to attribute and it may result from an extreme realisation of internal variability. We suggest that storylines can be used to illustrate plausible future risks for vineyards depending on the rate of regional warming and the type of circulation changes.

The proposed drivers of wintertime North American cold spells are multifarious, including modes of climate variability, planetary wave patterns and regional-to-continental-scale weather regimes. The Arctic stratospheric polar vortex has also been reported as a potential remote driver. One proposed coupling mechanism between the stratospheric polar vortex and the troposphere is upward-propagating planetary waves being reflected downward by the polar vortex. Here, we present a physically interpretable regional stratospheric wave reflection detection metric and identify the tropospheric circulation anomalies over North America associated with prolonged periods of wave reflection. The stratospheric reflection events show a systematic evolution from a Pacific Trough regime – associated on average with positive temperature anomalies and a near-complete absence of anomalously cold temperatures in North America – to an Alaskan Ridge regime, which favours low temperatures over much of the continent. The most striking feature of the stratospheric reflection events is thus a systematic shift in the tropospheric circulation in North America, associated with a rapid, continental-scale decrease in temperatures. These emerge as continental-scale cold spells by the end of the reflection events. Stratospheric reflection events are thus highly relevant in a tropospheric predictability perspective.

Long-chain fatty acids with antimicrobial properties are abundant on the skin and mucosal surfaces, where they are essential to restrict the proliferation of opportunistic pathogens such asStaphylococcus aureus. These antimicrobial fatty acids (AFAs) elicit bacterial adaptation strategies, which have yet to be fully elucidated. Characterizing the pervasive mechanisms used byS. aureusto resist AFAs could open new avenues to prevent pathogen colonization. Here, we identify theS. aureuslipase Lip2 as a novel resistance factor against AFAs. Lip2 detoxifies AFAs via esterification with cholesterol. This is reminiscent of the activity of the fatty acid-modifying enzyme (FAME), whose identity has remained elusive for over three decades.In vitro, Lip2-dependent AFA-detoxification was apparent during planktonic growth and biofilm formation. Our genomic analysis revealed that prophage-mediated inactivation of Lip2 was more common in blood and nose isolates than in skin strains, suggesting a particularly important role of Lip2 for skin colonization. Accordingly, in a mouse model ofS. aureusskin colonization, bacteria were protected from sapienic acid - a human-specific AFA - in a cholesterol- and lipase-dependent manner. These results suggest Lip2 is the long-sought FAME that exquisitely manipulates environmental lipids to promote bacterial growth. Our data support a model in whichS. aureusexploits and/or exacerbates lipid disorders to colonize otherwise inhospitable niches.

The increasing number and quality of numerical groundwater models worldwide represent a great source of knowledge for local, regional, and international scientists as well as water managers and decision makers. This development is facilitated by recent advancements in computational tools and access to open software. At the same time, scientific journals stress the importance of sharing model codes and data upon publishing, setting a new publishing standard. Altogether, these developments in the groundwater modelling field create a richer and more dynamic environment, fostering model reproducibility. Such an environment calls for a global, integrated, and standardized database of groundwater models to help members of the groundwater modelling community to search, deposit, and analyse groundwater model information. Unfortunately, despite attempts in the past, such a database is not yet constructed and made available to the public. This is why multiple universities and institutes from different countries came together to create the Groundwater Model Portal (GroMoPo), where groundwater model information can be collected and shared easily. The process of building GroMoPo started by collecting information about individual groundwater models via an online form where various information was compiled by researchers from the institutes involved in the project. Apart from simple information such as names of model developers, year of model development, and country of origin, we also collected information on model implementation (e.g. software used, time and area covered, calibration and validation data availability). The collected data is stored at the Consortium of Universities for the Advancement of Hydrologic Science, Inc. (CUAHSI) HydroShare environment. The collected data are freely accessible via a web portal, which allows the user to query and visualize groundwater model information and to contribute new models. This web portal also allows new users to submit groundwater model information and explore previously collected data. Furthermore, we plan to keep GroMoPo updated in the future as an ongoing service, with CUAHSI’s help, for the hydrological community. We collected information from more than 500 groundwater models in our first phase. This number might appear large, but we estimate that it captures only a few percent of published peer-reviewed articles that include a groundwater model. Therefore, we wish to invite the groundwater modelling community to contribute to and use GroMoPo, expanding our group even further to ensure that more data is collected and shared in the future. With such community involvement, we hope to facilitate meta-analysis and comparative studies, enable broader sensitivity and uncertainty analysis, avoid duplication or replication in groundwater modelling efforts, increase the visibility of existing models and associated publications, and create a teaching tool for aspiring groundwater modelers.

In order to count the number of smooth cubic hypersurfaces tangent to a prescribed number of lines and passing through a given number of points, we construct a compactification of their moduli space. We term the latter a $1$--\textit{complete variety of cubic hypersurfaces} in analogy to the space of complete quadrics. Paolo Aluffi explored the case of plane cubic curves. Starting from his work, we construct such a space in arbitrary dimension by a sequence of five blow-ups. The counting problem is then reduced to the computation of five Chern classes, climbing the sequence of blow-ups. Computing the last of these is difficult due to the fact that the vector bundle is not given explicitly. Identifying a restriction of this vector bundle, we arrive at the desired numbers in the case of cubic surfaces., 33 pages, comments welcome!

Cell-surface receptors, which are either receptor-like proteins (RLPs) or receptor-like kinases (RLKs), form the first layer of the plant innate immune system. The LRR-RLKs SUPPRESSOR OF BIR1-1 (SOBIR1) and BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED KINASE 1 (BAK1) are the common regulatory co-receptors of LRR-RLPs. The tomato LRR-RLP Cf-4, which specifically detects the apoplastic effector Avr4 that is secreted by the pathogenic intercellular fungusCladosporium fulvum, requires SOBIR1 and BAK1 to mediate resistance against this fungus. It is proposed that phosphorylation events take place between the cytoplasmic kinase domains of SOBIR1 and BAK1, which lead to the initiation of various downstream signaling outputs such as the rapid phosphorylation of receptor-like cytoplasmic kinases (RLCKs), the accumulation of reactive oxygen species (ROS), the activation of mitogen-activated protein kinase (MAPK) cascades, and in some cases, the hypersensitive response (HR). Here, by performingin vitrophosphorylation assays, we show that SOBIR1 directly phosphorylates BAK1, whereas BAK1, in its turn, directly phosphorylates SOBIR1, which results in the full activation of the Cf-4-containing immune complex. We found that threonine 522, present in the activation segment of the SOBIR1 kinase domain ofNicotiana benthamiana(Nb), is required for its intrinsic kinase activity, and is essential for the Avr4/Cf-4/SOBIR1/BAK1-triggered ROS burst, MAPK activation and the HR. Tyrosine residue Y469 was found to be crucial for the Avr4/Cf-4- triggered activation of MAPKs and the HR, but not for ROS production andNbSOBIR1 intrinsic kinase activity. RLCKs are well-recognized to act as the initial cytoplasmic transducers, bridging cell-surface receptor complexes with their downstream signaling partners. By knocking out multiple genes belonging to different RLCK-VII subfamilies inN. benthamianaplants stably expressingCf-4, we show that members of the RLCK-VII subfamilies 6, 7 and 8 are required for the Avr4/Cf-4-triggered ROS production. Typically, the Avr4 protein triggers a biphasic ROS burst in leaf discs obtained fromN. benthamiana:Cf-4plants, in which the first transitory response is followed by a second, sustained ROS burst. Interestingly, the intensities of the first and second phase of the ROS burst are affected in different ways in the variousrlck-viiknock-out plants, indicating that there are different downstream ROS regulatory mechanisms, involving different RLCKs inN. benthamiana. Further studies show that members from RLCK-VII-6, 7 and 8 also play an essential role in regulating the ROS production triggered by flg22, chitin, and the nlp20/RLP23 and the pg13/RLP42 combinations.

Most individuals with rare diseases initially consult their primary care physician. For a subset of rare diseases, efficient diagnostic pathways are available. However, ultra-rare diseases often require both expert clinical knowledge and comprehensive genetic diagnostics, which poses structural challenges for public healthcare systems. To address these challenges within Germany, a novel structured diagnostic concept, based on multidisciplinary expertise at established university hospital centers for rare diseases (CRDs), was evaluated in the three year prospective study TRANSLATE NAMSE. A key goal of TRANSLATE NAMSE was to assess the clinical value of exome sequencing (ES) in the ultra-rare disease population. The aims of the present study were to perform a systematic investigation of the phenotypic and molecular genetic data of TRANSLATE NAMSE patients who had undergone ES in order to determine the yield of both ultra-rare diagnoses and novel gene-disease associations; and determine whether the complementary use of machine learning and artificial intelligence (AI) tools improved diagnostic effectiveness and efficiency.ES was performed for 1,577 patients (268 adult and 1,309 pediatric). Molecular genetic diagnoses were established in 499 patients (74 adult and 425 pediatric). A total of 370 distinct molecular genetic causes were established. The majority of these concerned known disorders, most of which were ultra-rare. During the diagnostic process, 34 novel and 23 candidate genotype-phenotype associations were delineated, mainly in individuals with neurodevelopmental disorders.To determine the likelihood that ES will lead to a molecular diagnosis in a given patient, based on the respective clinical features only, we developed a statistical framework called YieldPred. The genetic data of a subcohort of 224 individuals that also gave consent to the computer-assisted analysis of their facial images were processed with the AI tool Prioritization of Exome Data by Image Analysis (PEDIA) and showed superior performance in variant prioritization.The present analyses demonstrated that the novel structured diagnostic concept facilitated the identification of ultra-rare genetic disorders and novel gene-disease associations on a national level and that the machine learning and AI tools improved diagnostic effectiveness and efficiency for ultra-rare genetic disorders.