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Brain state-dependent transcranial magnetic stimulation (TMS) holds promise for enhancing neuromodulatory effects by synchronizing stimulation with specific features of cortical oscillations derived from real-time electroencephalography (EEG). However, conventional approaches rely on open-loop systems with static stimulation parameters, assuming that pre-determined EEG features universally indicate high or low excitability states. This one-size-fits-all approach overlooks individual neurophysiological differences and the dynamic nature of brain states, potentially compromising therapeutic efficacy. We present a supervised machine learning framework that predicts individual motor excitability states from pre-stimulus EEG features. Our approach combines established biomarkers with a comprehensive set of spectral and connectivity measures, implementing multi-scale feature selection within a nested cross-validation scheme. Validation across multiple classifiers, feature sets, and experimental protocols in 50 healthy participants demonstrated a mean prediction accuracy of $71 \; \pm \; 7$ %. Hierarchical clustering of top predictive EEG features revealed two distinct participant subgroups. The first subgroup, comprising approximately 50% of participants, showed predictive features predominantly in alpha and low-beta bands in sensorimotor regions of the stimulated hemisphere, aligning with traditional associations of motor excitability and the sensorimotor $\mu $ -rhythm. The second subgroup exhibited predictive features primarily in low and high gamma bands in parietal regions, suggesting that motor excitability is influenced by broader neural dynamics for these individuals. Our data-driven framework effectively identifies personalized motor excitability biomarkers, holding promise to optimize TMS interventions in clinical and research settings. Additionally, our approach provides a versatile platform for biomarker discovery and validation across diverse neuromodulation paradigms and brain signal classification tasks.

RESUMO Ecossistema de inovação representa uma série de atores que possuem parcerias e envolvimento para disseminar conhecimento e tecnologia. A teoria das trocas sociais é constituída por elementos que incentivam as pessoas a pensarem nos benefícios e riscos potenciais de seus relacionamentos. Visto que há uma lacuna na literatura referente à baixa quantidade de artigos que relacionem ecossistema de inovação com a teoria das trocas sociais, o objetivo do estudo foi analisar as contribuições teóricas e gerenciais e as indicações de estudos futuros de artigos científicos que relacionaram os temas para propor categorias de análise. A revisão sistemática da literatura ocorreu por meio de análise bibliométrica e de conteúdo com auxílio do software Iramuteq®. As categorias propostas foram: planejamento geral; atores do ecossistema; ações dos atores; tecnologia e pesquisa; e características das trocas sociais no ecossistema de inovação. O relacionamento entre atores de um ecossistema por meio de seus profissionais promove interação, confiança, cooperação e colaboração - trocas sociais -, que possibilitam um ambiente propício à inovação. A cooperação para a transferência de conhecimento e o compartilhamento se mostram como oportunidade ou suporte para novos produtos e serviços.

Abstract Background Neurological emergencies are one of the major diagnosis groups in the Emergency Medical Services (EMS) with the highest rate of misdiagnosis. Despite the knowledge of time sensitivity and the importance of prehospital factors, prehospital delay is common. Although several stroke triage scales have been developed, a gold standard in the prehospital setting is lacking. Objectives Our aim was to evaluate the perception of neurological emergencies by EMS personnel and to identify current problems, difficulties and opportunities for improvement in the prehospital management of stroke, seizure, non-specific neurological symptoms, and paediatric neurological emergencies. Methods The study was conducted as an online survey through SoSci Survey and was made available from March 1st to June 30th 2023 to all personnel working in emergency medical services. The access link was distributed through snowballing, social media, and through a QR code on a promotional poster. The survey was completed anonymously. The final survey consisted of 30 questions in German on the topics of neurological emergencies, general neurological assessment, specific neurological examination including paediatric assessment, stroke, and seizures, and finally suggestions for improvement. Results The largest group of participants were paramedics, who estimated to encounter neurological emergencies at a general rate of 20–60%. When unease was felt, the main reasons were ambiguity of symptoms and insufficient admission capacity of hospitals. The biggest challenges were highly varied. Almost 80% of participants assumed that the neurological assessment would be omitted in difficult patient groups such as demented, intoxicated or children. 75% felt uncomfortable making a paediatric assessment, 50% were unfamiliar with the Paediatric Glasgow Coma Scale. Conclusions Support through more standardized practical training and defined, uniform guidelines is needed. There was also a clear need for peer collaboration, feedback and case sharing. Digitalization, the usage of telemedicine and updated versions of the documentation protocols including paediatric adaptations to current guidelines could further improve current neurological assessment in the prehospital setting.

Neonatal apneas and hypopneas present a serious risk for healthy infant development. Treating these adverse events requires frequent manual stimulation by skilled personnel, which can lead to alarm fatigue. This study aims to develop and validate an interpretable model that can predict apneas and hypopneas. Automatically predicting these adverse events before they occur would enable the use of methods for automatic intervention. We propose a neural additive model to predict individual occurrences of neonatal apnea and hypopnea and apply it to a physiological dataset from infants with Robin sequence at risk of upper airway obstruction. The dataset will be made publicly available together with this study. Our proposed model allows the prediction of individual apneas and hypopneas, achieving an average AuROC of 0.80 when discriminating segments of polysomnography recordings starting 15 seconds before the onset of apneas and hypopneas from control segments. Its additive nature makes the model inherently interpretable, which allowed insights into how important a given signal modality is for prediction and which patterns in the signal are discriminative. For our problem of predicting apneas and hypopneas in infants with Robin sequence, prior irregularities in breathing-related modalities as well as decreases in SpO2 levels were especially discriminative. Our prediction model presents a step towards an automatic prediction of neonatal apneas and hypopneas in infants at risk for upper airway obstruction. Together with the publicly released dataset, it has the potential to facilitate the development and application of methods for automatic intervention in clinical practice.

Abstract In the framework of the Multidisciplinary drifting Observatory for the Study of Arctic Climate Polarstern expedition, the Leibniz Institute for Tropospheric Research, Leipzig, Germany, operated the shipborne OCEANET-Atmosphere facility for cloud and aerosol observations throughout the whole year. OCEANET-Atmosphere comprises, amongst others, a multiwavelength Raman lidar, a microwave radiometer, and an optical disdrometer. A cloud radar was operated aboard Polarstern by the US Atmospheric Radiation Measurement program. These measurements were processed by applying the so-called Cloudnet methodology to derive cloud properties. To gain a comprehensive view of the clouds, lidar and cloud radar capabilities for low- and high-altitude observations were combined. Cloudnet offers a variety of products with a spatiotemporal resolution of 30 s and 30 m, such as the target classification, and liquid and ice microphysical properties. Additionally, a lidar-based low-level stratus retrieval was applied for cloud detection below the lowest range gate of the cloud radar. Based on the presented dataset, e.g., studies on cloud formation processes and their radiative impact, and model evaluation studies can be conducted.

The Virtual Special Issue investigates the relationship between social entrepreneurship, creative territories, and responsible consumption. These three fields have grown quickly in the last two decades and have attracted the attention of many researchers. The issue contributes to current research by exploring various aspects of creative territories, responsible business and consumption, and social entrepreneurship. This editorial presents the five articles included in this Special Volume. Two papers are more strongly related to creative territories and sustainable supply chain innovation, while the other three focus on social entrepreneurship and responsible consumption in the footwear, healthcare, and processing industries. Furthermore, pathways for future research are formulated, calling for more dedicated research on the above three areas to create solid theory-building via sophisticated research methods.

LEIA project aims to contribute to the development of the next generation of central receiver power plants focusing on validating a combination and integration of pre-commercial solar field control and O&M solutions for the central tower receiver technology using molten salts, as the most promising cost-effective solution with the highest market penetration potential. To effectively remove the existing technical and industrial barriers to optimize central receiver and heliostat field operation & maintenance and thus to improve overall CSP performance, the following innovations are being developed: 1) Smart heliostat field control, 2) Smart control systems, 3) Solar Field Operation and Maintenance control strategies. These developments will be tested and demonstrated in three flagship operational environments: a) Cerro Dominador (Chile), b) CIEMAT – PSA (Spain), and c) CENER – Tudela (Spain).

Abstract Background X-chromosome inactivation (XCI) is an epigenetic process that occurs during early development in mammalian females by randomly silencing one of two copies of the X chromosome in each cell. The preferential inactivation of either the maternal or paternal copy of the X chromosome in a majority of cells results in a skewed or non-random pattern of X inactivation and is observed in over 25% of adult females. Identifying skewed X inactivation is of clinical significance in patients with suspected rare genetic diseases due to the possibility of biased expression of disease-causing genes present on the active X chromosome. The current clinical test for the detection of skewed XCI relies on the methylation status of the methylation-sensitive restriction enzyme (Hpall) binding site present in proximity of short tandem polymorphic repeats on the androgen receptor (AR) gene. This approach using one locus results in uninformative or inconclusive data for 10–20% of tests. Further, recent studies have shown inconsistency between methylation of the AR locus and the state of inactivation of the X chromosome. Herein, we develop a method for estimating X inactivation status, using exome and transcriptome sequencing data derived from blood in 227 female samples. We built a reference model for evaluation of XCI in 135 females from the GTEx consortium. We tested and validated the model on 11 female individuals with different types of undiagnosed rare genetic disorders who were clinically tested for X-skew using the AR gene assay and compared results to our outlier-based analysis technique. Results In comparison to the AR clinical test for identification of X inactivation, our method was concordant with the AR method in 9 samples, discordant in 1, and provided a measure of X inactivation in 1 sample with uninformative clinical results. We applied this method on an additional 81 females presenting to the clinic with phenotypes consistent with different hereditary disorders without a known genetic diagnosis. Conclusions This study presents the use of transcriptome and exome sequencing data to provide an accurate and complete estimation of X-inactivation and skew status in a cohort of female patients with different types of suspected rare genetic disease.

Quantifying the role of clouds in the earth's radiation budget is essential for improving our understanding of the drivers and feedback mechanisms of climate change. This holds in particular for the Arctic, the region currently undergoing the most rapid changes. This region, however, also poses significant challenges to remote-sensing retrievals of clouds and radiative fluxes, introducing large uncertainties in current climate data records. In particular, low-level stratiform clouds are common in the Arctic but are, due to their low altitude, challenging to observe and characterize with remote-sensing techniques. The availability of reliable ground-based observations as reference is thus of high importance. In the present study, radiative transfer simulations using state-of-the-art ground-based remote sensing of clouds are contrasted with surface radiative flux measurements to assess their ability to constrain the cloud radiative effect. Cloud radar, lidar, and microwave radiometer observations from the PS106 cruise in the Arctic marginal sea ice zone in summer 2017 were used to derive cloud micro- and macrophysical properties by means of the instrument synergy approach of Cloudnet. Closure of surface radiative fluxes can only be achieved by a realistic representation of the low-level liquid-containing clouds in the radiative transfer simulations. The original, most likely erroneous, representation of these low-level clouds in the radiative transfer simulations led to errors in the cloud radiative effect of 54 W m−2. In total, the proposed method could be applied to 11 % of the observations. For the data, where the proposed method was utilized, the average relative error decreased from 109 % to 37 % for the simulated solar and from 18 % to 2.5 % for the simulated terrestrial downward radiative fluxes at the surface. The present study highlights the importance of jointly improving retrievals for low-level liquid-containing clouds which are frequently encountered in the high Arctic, together with observational capabilities both in terms of cloud remote sensing and radiative flux observations. Concrete suggestions for achieving these goals are provided.

Drones are becoming a common tool for animal monitoring; however, sound emitted from drones may disturb animals and bias survey results. Understanding noise levels produced by different flight maneuvers, altitudes (i.e., above ground level (AGL)), and drone models could mitigate animal disturbance during surveys. We measured maximum sound (dB) emitted during three flight maneuvers (hovering, flyover, and turning) among eight AGLs (15–120 m) and two vertical maneuvers (ascending and descending) for four commercially available quadcopter drone models (DJI Matrice 300, Matrice 200, Phantom 3, and Autel Evo II), accounting for wind speed and comparing to ambient (background) noise. Ascending, descending, and hovering produced more noise compared to flyover and turning maneuvers. One large drone (Matrice 200, 4.7 kg) produced more noise than the two smaller drones (Evo II, 1.2 kg and Phantom 3, 1.1 kg). However, the largest drone (Matrice 300, 6.4 kg) produced noise similar to smaller models and was the quietest among all models from 75 to 120 m AGL, providing potential size advantages with less noise disturbance. Our results indicate that flights consisting of flyover and turning maneuvers likely cause less noise disturbance than surveys with prolonged hovering over animals.

This paper addresses semiotic elements of ritual in human encounter. The notion of an essential ritual presence in the existential/communicative connection of persons has been established in the work of Langer, Gadamer, and Jakobson. Yet, as Richard Lanigan maintains, vital aspects of Jakobson’s model of communication are typically missed in the application of his work, a consequence of which is that social science no longer differentiates between “communication” and “information”. As such, everything perceived as meaningful is reducible to “message”, and thus, effective communication means merely “finding the right message”. The regression to our current cybernetic world, along with the intellectual paradigms enabling it, was never a foregone conclusion, but the entrenchment of social science in information theory makes it clear that an epistemological commitment to a semiotic phenomenology of communicative existence—and the visibility of ritual life—may well be our only way out.

Creative territories are geographic spaces of collaboration between different social actors, driving innovations and requiring regulatory mechanisms for sustainability and growth. This paper aims to synthesize available evidence on creative territories through a systematic literature review to analyze the significant actors in creative territories, the type of partnerships between them, the kind of innovations in creative territories, and the regulatory mechanisms for supporting these territories. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed to ensure a transparent and systematic approach. A comprehensive search in the Scopus database, employing predefined search terms and inclusion criteria, included 86 articles. The findings revealed several key topics within the existing academic literature on creative territories, including i) the individual social players in creative territories and partnerships and collaborations among them, ii) the various innovations in these territories and sectors, iii) the regulatory mechanisms applied by government and non-government actors. These topics or aspects were further analyzed and categorized to provide a comprehensive overview of the research landscape. The discussion section presents a critical analysis and synthesis of the findings, highlighting that the government supports creative territories through 16 regulatory mechanisms, while the literature highlights at least 5 levels of government intervention. Additionally, private social actors can positively impact creative territories through various regulatory mechanisms, including firm self-regulation, industry self-regulation, and civil regulation, with at least 21 social actors classified into 5 groups collaborating through six types/forms of collaboration. Furthermore, several circumstances and factors should be available to prosper in a particular partnership/collaboration like a clear definition of responsibilities, well-defined rules, mutual benefits, equal collaboration, and solid authority. The findings underscore the importance of creative territories and serve as a valuable resource for researchers, practitioners, and policymakers, offering insights and directions for future research endeavors.

Neural oscillations are ubiquitously observed in many brain areas. One proposed functional role of these oscillations is that they serve as an internal clock, or 'frame of reference'. Information can be encoded by the timing of neural activity relative to the phase of such oscillations. In line with this hypothesis, there have been multiple empirical observations of such phase codes in the brain. Here we ask: What kind of neural dynamics support phase coding of information with neural oscillations? We tackled this question by analyzing recurrent neural networks (RNNs) that were trained on a working memory task. The networks were given access to an external reference oscillation and tasked to produce an oscillation, such that the phase difference between the reference and output oscillation maintains the identity of transient stimuli. We found that networks converged to stable oscillatory dynamics. Reverse engineering these networks revealed that each phase-coded memory corresponds to a separate limit cycle attractor. We characterized how the stability of the attractor dynamics depends on both reference oscillation amplitude and frequency, properties that can be experimentally observed. To understand the connectivity structures that underlie these dynamics, we showed that trained networks can be described as two phase-coupled oscillators. Using this insight, we condensed our trained networks to a reduced model consisting of two functional modules: One that generates an oscillation and one that implements a coupling function between the internal oscillation and external reference. In summary, by reverse engineering the dynamics and connectivity of trained RNNs, we propose a mechanism by which neural networks can harness reference oscillations for working memory. Specifically, we propose that a phase-coding network generates autonomous oscillations which it couples to an external reference oscillation in a multi-stable fashion.

Abstract Interface engineering in complex oxide superlattices is a growing field, enabling manipulation of the exceptional properties of these materials, and also providing access to new phases and emergent physical phenomena. Here we demonstrate how interfacial interactions can induce a complex charge and spin structure in a bulk paramagnetic material. We investigate a superlattice (SLs) consisting of paramagnetic LaNiO3 (LNO) and highly spin-polarized ferromagnetic La2/3Ca1/3MnO3 (LCMO), grown on SrTiO3 (001) substrate. We observed emerging magnetism in LNO through an exchange bias mechanism at the interfaces in X-ray resonant magnetic reflectivity. We find non-symmetric interface induced magnetization profiles in LNO and LCMO which we relate to a periodic complex charge and spin superstructure. High resolution scanning transmission electron microscopy images reveal that the upper and lower interfaces exhibit no significant structural variations. The different long range magnetic order emerging in LNO layers demonstrates the enormous potential of interfacial reconstruction as a tool for tailored electronic properties.

Abstract Background Stroke is one of the leading causes of death and the main cause of long-term disability in the United States. The significant risk factors of stroke among Hispanics are well-documented. The majority of stroke survivors return home following a stroke and are cared for by family caregivers. Due to the abrupt nature of strokes, caregivers experience unexpected changes and demands that oftentimes lead to caregiver burden and depression. Given the significant risk factors for stroke in Hispanics and the influence of culture in family norms and family management, we developed a telephone and online problem-solving intervention for Spanish-speaking stroke caregivers. This study tests the impact of a telephone and online problem-solving intervention for Spanish-speaking stroke caregivers on caregiver outcomes. Methods The design is a two-arm parallel randomized clinical trial with repeated measures. We will enroll 290 caregivers from 3 Veterans Affairs (VA) medical centers. Participants randomized into the intervention arm receive a problem-solving intervention that uses telephone and online education and care management tools on the previously developed and nationally available RESCUE en Español Caregiver website. In the usual care group, participants receive the information and/or support caregivers of veterans with stroke normally receive through existing VA resources (e.g., stroke-related information and support). The primary outcome is change in caregiver’s depressive symptoms at 1- and 12-weeks post-intervention. Secondary outcomes include changes in stroke caregivers’ burden, self-efficacy, problem-solving, and health-related quality of life (HRQOL) and veterans’ functional abilities. We will also determine the budgetary impact, the acceptability of the intervention and participation barriers and facilitators for Spanish-speaking stroke caregivers. Discussion This is an ongoing study. It is the first known randomized controlled trial testing the effect of a telephone and online problem-solving intervention in Spanish for caregivers of veterans post-stroke. If successful, findings will support an evidence-based model that can be transported into clinical practice to improve the quality of caregiving post-stroke. Trial registration ClinicalTrials.gov: NCT03142841— Spanish Intervention for Caregivers of Veterans with Stroke (RESCUE Español). Registered on February 23, 2018. Protocol version 8. 08.11.2022.

Recent advances in connectomics research enable the acquisition of increasing amounts of data about the connectivity patterns of neurons. How can we use this wealth of data to efficiently derive and test hypotheses about the principles underlying these patterns? A common approach is to simulate neuronal networks using a hypothesized wiring rule in a generative model and to compare the resulting synthetic data with empirical data. However, most wiring rules have at least some free parameters, and identifying parameters that reproduce empirical data can be challenging as it often requires manual parameter tuning. Here, we propose to use simulation-based Bayesian inference (SBI) to address this challenge. Rather than optimizing a fixed wiring rule to fit the empirical data, SBI considers many parametrizations of a rule and performs Bayesian inference to identify the parameters that are compatible with the data. It uses simulated data from multiple candidate wiring rule parameters and relies on machine learning methods to estimate a probability distribution (the 'posterior distribution over parameters conditioned on the data') that characterizes all data-compatible parameters. We demonstrate how to apply SBI in computational connectomics by inferring the parameters of wiring rules in an in silico model of the rat barrel cortex, given in vivo connectivity measurements. SBI identifies a wide range of wiring rule parameters that reproduce the measurements. We show how access to the posterior distribution over all data-compatible parameters allows us to analyze their relationship, revealing biologically plausible parameter interactions and enabling experimentally testable predictions. We further show how SBI can be applied to wiring rules at different spatial scales to quantitatively rule out invalid wiring hypotheses. Our approach is applicable to a wide range of generative models used in connectomics, providing a quantitative and efficient way to constrain model parameters with empirical connectivity data.

For understanding Arctic climate change, it is critical to quantify and address uncertainties in climate data records on clouds and radiative fluxes derived from long-term passive satellite observations. A unique set of observations collected during the PS106 expedition of the research vessel Polarstern (28 May to 16 July 2017) by the OCEANET facility, is exploited here for this purpose and compared with the CERES SYN1deg ed. 4.1 satellite remote-sensing products. Mean cloud fraction (CF) of 86.7 % for CERES SYN1deg and 76.1 % for OCEANET were found for the entire cruise. The difference of CF between both data sets is due to different spatial resolution and momentary data gaps, which are a result of technical limitations of the set of shipborne instruments. A comparison of radiative fluxes during clear-sky (CS) conditions enables radiative closure (RC) for CERES SYN1deg products by means of independent radiative transfer simulations. Several challenges were encountered to accurately represent clouds in radiative transfer under cloudy conditions, especially for ice-containing clouds and low-level stratus (LLS) clouds. During LLS conditions, the OCEANET retrievals were particularly compromised by the altitude detection limit of 155 m of the cloud radar. Radiative fluxes from CERES SYN1deg show a good agreement with ship observations, having a bias (standard deviation) of −6.0 (14.6) and 23.1 (59.3) W m−2 for the downward longwave (LWD) and shortwave (SWD) fluxes, respectively. Based on CERES SYN1deg products, mean values of the radiation budget and the cloud radiative effect (CRE) were determined for the PS106 cruise track and the central Arctic region (70–90∘ N). For the period of study, the results indicate a strong influence of the SW flux in the radiation budget, which is reduced by clouds leading to a net surface CRE of −8.8 and −9.3 W m−2 along the PS106 cruise and for the entire Arctic, respectively. The similarity of local and regional CRE supports the consideration that the PS106 cloud observations can be representative of Arctic cloudiness during early summer.

Abstract Background Stroke is one of the most frequent diseases, and half of the stroke survivors are left with permanent impairment. Prediction of individual outcome is still difficult. Many but not all patients with stroke improve by approximately 1.7 times the initial impairment, that has been termed proportional recovery rule. The present study aims at identifying factors predicting motor outcome after stroke more accurately than before, and observe associations of rehabilitation treatment with outcome. Methods The study is designed as a multi-centre prospective clinical observational trial. An extensive primary data set of clinical, neuroimaging, electrophysiological, and laboratory data will be collected within 96 h of stroke onset from patients with relevant upper extremity deficit, as indexed by a Fugl-Meyer-Upper Extremity (FM-UE) score ≤ 50. At least 200 patients will be recruited. Clinical scores will include the FM-UE score (range 0–66, unimpaired function is indicated by a score of 66), Action Research Arm Test, modified Rankin Scale, Barthel Index and Stroke-Specific Quality of Life Scale. Follow-up clinical scores and applied types and amount of rehabilitation treatment will be documented in the rehabilitation hospitals. Final follow-up clinical scoring will be performed 90 days after the stroke event. The primary endpoint is the change in FM-UE defined as 90 days FM-UE minus initial FM-UE, divided by initial FM-UE impairment. Changes in the other clinical scores serve as secondary endpoints. Machine learning methods will be employed to analyze the data and predict primary and secondary endpoints based on the primary data set and the different rehabilitation treatments. Discussion If successful, outcome and relation to rehabilitation treatment in patients with acute motor stroke will be predictable more reliably than currently possible, leading to personalized neurorehabilitation. An important regulatory aspect of this trial is the first-time implementation of systematic patient data transfer between emergency and rehabilitation hospitals, which are divided institutions in Germany. Trial registration This study was registered at ClinicalTrials.gov ( NCT04688970 ) on 30 December 2020.

Previous work from our laboratories has identified multiple defects in endocytosis, protein trafficking, and secretion, along with altered Golgi function after alcohol administration. Manifestation of alcohol‐associated liver disease (ALD) is associated with an aberrant function of several hepatic proteins, including asialoglycoprotein receptor (ASGP‐R), their atypical distribution at the plasma membrane (PM), and secretion of their abnormally glycosylated forms into the bloodstream, but trafficking mechanism is unknown. Here we report that a small GTPase, Rab3D, known to be involved in exocytosis, secretion, and vesicle trafficking, shows ethanol (EtOH)–impaired function, which plays an important role in Golgi disorganization. We used multiple approaches and cellular/animal models of ALD, along with Rab3D knockout (KO) mice and human tissue from patients with ALD. We found that Rab3D resides primarily in trans‐ and cis‐faces of Golgi; however, EtOH treatment results in Rab3D redistribution from trans‐Golgi to cis‐medial‐Golgi. Cells lacking Rab3D demonstrate enlargement of Golgi, especially its distal compartments. We identified that Rab3D is required for coat protein I (COPI) vesiculation in Golgi, and conversely, COPI is critical for intra‐Golgi distribution of Rab3D. Rab3D/COPI association was altered not only in the liver of patients with ALD but also in the donors consuming alcohol without steatosis. In Rab3D KO mice, hepatocytes experience endoplasmic reticulum (ER) stress, and EtOH administration activates apoptosis. Notably, in these cells, ASGP‐R, despite incomplete glycosylation, can still reach cell surface through ER‐PM junctions. This mimics the effects seen with EtOH‐induced liver injury. Conclusion: We revealed that down‐regulation of Rab3D contributes significantly to EtOH‐induced Golgi disorganization, and abnormally glycosylated ASGP‐R is excreted through ER‐PM connections, bypassing canonical (ER→Golgi→PM) anterograde transportation. This suggests that ER‐PM sites may be a therapeutic target for ALD.

Purpose – Governance is a polysemous concept that has been gaining the attention of social scientists and humanists over the last three decades. Tourism governance studies have mirrored the knowledge developed within traditional disciplines to analyse processes in different spheres of action. This paper aims to perceive how tourism governance has been applied in scientific research over recent decades, in terms of its conceptualization, territorial scale and the type of territory studied. Design – Using a literature review, we present an analysis of governance in tourism studies and we show the potential of textual statistics for the analysis of huge amounts of textual data. Methodology – Data were extracted from SCOPUS, from 1999 to 2020, based on the keywords ‘governance’ and ‘tourism’. All abstracts were encoded and analysed using ALCESTE software. Findings – The findings reveal a great concern with sustainability, especially with the environmental and social impacts generated by tourism, and destination management, with an emphasis on the performance of the public sector through local and regional institutions and their relations with local tourism stakeholders. Originality of the research – The novelty of this work is the analysis of the conceptual framework and implementation practises in governance and tourism using an innovative software tool for textual analysis.

Objective: this study analyses how international literature informs the discussion of sustainability within career scope. Method: we conducted a systematic literature review through the Web of Science database and analyzed 152 papers with the sustainable-career-related keywords: resilience, systems, and ecosystem. By exploring the conceptual foundations of these concepts that have evolved in the context of career sustainability over the last three decades, we identified six clusters of different theoretical approaches. Results: these are the interplay of social spaces in the development of sustainable or unsustainable career paths; need for an open-systems perspective for organizational career management; significance of personal attributes and individual behaviors in career sustainability development; addressing satisfaction and well-being in work and life spheres; external and internal career mobility in complex environments; and contemporary sustainability challenges and their implications for careers, cities, and governments. Conclusion: based on the findings, we established six assumptions that may guide future empirical research in this field.

In this work we report the new technical feasibility of combining a large-scale screw pressing facility with an industrial-scale pulsed electric field (PEF) system for a great increase in the yields of plant juice and crude protein extracted from freshly harvested blends of perennial ryegrass (Lolium perenne) (70%) and white clover (30%). A disk separator has been successfully utilized for continuous separation of 400 L of raw juice and successive protein precipitated at pH 5.0 and 60 °C. The yields of pressed juice and crude protein were increased by around 25% and 31%, respectively. The crude protein content reached 37.3 g/100 g in dry matter. In addition to the crude protein, the precipitated sediment contained minerals like Ca, K, Na, Mg and P, which are essential for health and promisingly interesting for future applications such as food alternatives. Microbial status, chemical compositions, macromolecular sizes and fat-protein microstructures of the samples collected at different process steps were explored, which allows for a better understanding of pilot-scale extraction processes and optimization. This study indicated a great potential for protein extraction from green biomass and for future food applications.

This research aimed to analyze the role of local education programs in Passo Fundo (Brazil) to develop sustainable cities. In this analysis, we sought to describe the management of public policies in the area of education in the city of Passo Fundo; identify the characteristics of a sustainable city present in Passo Fundo; and propose a set of actions in the area of public education for the city of Passo Fundo, in the direction of the concept of sustainable cities. Initially, a theoretical approach was made, starting from articles and books that deal with the subject. A descriptive, exploratory, qualitative research was carried out, with semi-structured interviews with five municipal managers linked to the education area of the chosen city – Passo Fundo. Data were computed, analyzed, and interpreted using content analysis. The results show that the notion and recognition of education and the sustainable city are evidenced, with the importance of citizen participation and education as a formative agent for the effectiveness of sustainable city development. It can be verified concerning management practices in education the practices of events to condition a sustainable city, the International Folklore Festival, the Book Fair, and the Literary Journey.

An advanced multiwavelength polarization Raman lidar was operated aboard the icebreaker Polarstern during the MOSAiC (Multidisciplinary drifting Observatory for the Study of Arctic Climate) expedition to continuously monitor aerosol and cloud layers in the central Arctic up to 30 km height. The expedition lasted from September 2019 to October 2020 and measurements were mostly taken between 85 and 88.5∘ N. The lidar was integrated into a complex remote-sensing infrastructure aboard the Polarstern. In this article, novel lidar techniques, innovative concepts to study aerosol–cloud interaction in the Arctic, and unique MOSAiC findings will be presented. The highlight of the lidar measurements was the detection of a 10 km deep wildfire smoke layer over the North Pole region between 7–8 km and 17–18 km height with an aerosol optical thickness (AOT) at 532 nm of around 0.1 (in October–November 2019) and 0.05 from December to March. The dual-wavelength Raman lidar technique allowed us to unambiguously identify smoke as the dominating aerosol type in the aerosol layer in the upper troposphere and lower stratosphere (UTLS). An additional contribution to the 532 nm AOT by volcanic sulfate aerosol (Raikoke eruption) was estimated to always be lower than 15 %. The optical and microphysical properties of the UTLS smoke layer are presented in an accompanying paper (Ohneiser et al., 2021). This smoke event offered the unique opportunity to study the influence of organic aerosol particles (serving as ice-nucleating particles, INPs) on cirrus formation in the upper troposphere. An example of a closure study is presented to explain our concept of investigating aerosol–cloud interaction in this field. The smoke particles were obviously able to control the evolution of the cirrus system and caused low ice crystal number concentration. After the discussion of two typical Arctic haze events, we present a case study of the evolution of a long-lasting mixed-phase cloud layer embedded in Arctic haze in the free troposphere. The recently introduced dual-field-of-view polarization lidar technique was applied, for the first time, to mixed-phase cloud observations in order to determine the microphysical properties of the water droplets. The mixed-phase cloud closure experiment (based on combined lidar and radar observations) indicated that the observed aerosol levels controlled the number concentrations of nucleated droplets and ice crystals.

Abstract Background The development of persistent endoplasmic reticulum (ER) stress is one of the cornerstones of prostate carcinogenesis; however, the mechanism is missing. Also, alcohol is a physiological ER stress inducer, and the link between alcoholism and progression of prostate cancer (PCa) is well documented but not well characterized. According to the canonical model, the mediator of ER stress, ATF6, is cleaved sequentially in the Golgi by S1P and S2P proteases; thereafter, the genes responsible for unfolded protein response (UPR) undergo transactivation. Methods Cell lines used were non-malignant prostate epithelial RWPE-1 cells, androgen-responsive LNCaP, and 22RV1 cells, as well as androgen-refractory PC-3 cells. We also utilized PCa tissue sections from patients with different Gleason scores and alcohol consumption backgrounds. Several sophisticated approaches were employed, including Structured illumination superresolution microscopy, Proximity ligation assay, Atomic force microscopy, and Nuclear magnetic resonance spectroscopy. Results Herein, we identified the trans-Golgi matrix dimeric protein GCC185 as a Golgi retention partner for both S1P and S2P, and in cells lacking GCC185, these enzymes lose intra-Golgi situation. Progression of prostate cancer (PCa) is associated with overproduction of S1P and S2P but monomerization of GCC185 and its downregulation. Utilizing different ER stress models, including ethanol administration, we found that PCa cells employ an elegant mechanism that auto-activates ER stress by fragmentation of Golgi, translocation of S1P and S2P from Golgi to ER, followed by intra-ER cleavage of ATF6, accelerated UPR, and cell proliferation. The segregation of S1P and S2P from Golgi and activation of ATF6 are positively correlated with androgen receptor signaling, different disease stages, and alcohol consumption. Finally, depletion of ATF6 significantly retarded the growth of xenograft prostate tumors and blocks production of pro-metastatic metabolites. Conclusions We found that progression of PCa associates with translocation of S1P and S2P proteases to the ER and subsequent ATF6 cleavage. This obviates the need for ATF6 transport to the Golgi and enhances UPR and cell proliferation. Thus, we provide the novel mechanistic model of ATF6 activation and ER stress implication in the progression of PCa, suggesting ATF6 is a novel promising target for prostate cancer therapy.

BackgroundAntibiotic susceptibility of Helicobacter pylori to antibiotics may vary among different niches of the stomach. The progression of chronic H. pylori gastritis to atrophy changes intragastric physiology that may influence selection of resistant strains.AimTo study the antibiotic resistance of H. pylori taking the severity of atrophic gastritis in antrum and corpus into account.MethodsHelicobacter pylori-positive patients (n = 110, m = 32, mean age 52.6 ± 13.9 years) without prior H. pylori eradication undergoing upper gastrointestinal (GI) endoscopy for dyspeptic symptoms were included in a prospective study. Patients were stratified into three groups depending on the grade of atrophy: no atrophy (OLGA Stage 0), mild atrophy (OLGA Stage I–II) and moderate/severe atrophy (OLGA Stage III–IV). Two biopsies each from the antrum and the corpus and one from the angulus were taken and assessed according to the updated Sydney system. H. pylori strains were isolated from antrum and corpus biopsies and tested for antibiotic susceptibility (AST) for amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, and rifampicin by the agar dilution methods. A Chi-square test of independence with a 95% confidence interval was used to detect differences in the proportion of patients with susceptible and resistant H. pylori strains.ResultsAmong 110 patients, primary clarithromycin resistance (R) was 30.0%, both in the antrum and corpus; metronidazole resistance accounted for 36.4 and 34.5% in the antrum and corpus; and levofloxacin was 19.1 and 22.7% in the antrum and corpus, respectively. Resistance rates to amoxicillin, tetracycline, and rifampicin were below 5%. Dual antibiotic resistance rate was 21.8%, and triple resistance rate was 9.1%. There was a significant difference in the resistance rate distribution in antrum (p

The modification of an existing cloud property retrieval scheme for the Spinning Enhanced Visible and Infrared Imager (SEVIRI) instrument on board the geostationary Meteosat satellites is described to utilize its high-resolution visible (HRV) channel for increasing the spatial resolution of its physical outputs. This results in products with a nadir spatial resolution of 1×1 km2 compared to the standard 3×3 km2 resolution offered by the narrowband channels. This improvement thus greatly reduces the resolution gap between current geostationary and polar-orbiting meteorological satellite imagers. In the first processing step, cloudiness is determined from the HRV observations by a threshold-based cloud masking algorithm. Subsequently, a linear model that links the 0.6 µm, 0.8 µm, and HRV reflectances provides a physical constraint to incorporate the spatial high-frequency component of the HRV observations into the retrieval of cloud optical depth. The implementation of the method is described, including the ancillary datasets used. It is demonstrated that the omission of high-frequency variations in the cloud-absorbing 1.6 µm channel results in comparatively large uncertainties in the retrieved cloud effective radius, likely due to the mismatch in channel resolutions. A newly developed downscaling scheme for the 1.6 µm reflectance is therefore applied to mitigate the effects of this scale mismatch. Benefits of the increased spatial resolution of the resulting SEVIRI products are demonstrated for three example applications: (i) for a convective cloud field, it is shown that significantly better agreement between the distributions of cloud optical depth retrieved from SEVIRI and from collocated MODIS observations is achieved. (ii) The temporal evolution of cloud properties for a growing convective storm at standard and HRV spatial resolutions are compared, illustrating an improved contrast in growth signatures resulting from the use of the HRV channel. (iii) An example of surface solar irradiance, determined from the retrieved cloud properties, is shown, for which the HRV channel helps to better capture the large spatiotemporal variability induced by convective clouds. These results suggest that incorporating the HRV channel into the retrieval has potential for improving Meteosat-based cloud products for several application domains.

Marcus Örgel,1 Manfred Gogol,1 Tilman Graulich,1 Mohamed Omar,1 Alexander Ranker,2 Christian Böttcher,1 Emmanouil Liodakis,1 Christian Krettek,1 Christian Macke1 1Trauma Department, Hannover Medical School, Hanover, Germany; 2Department of Rehabilitation Medicine, Hannover Medical School, Hanover, GermanyCorrespondence: Marcus ÖrgelDepartment for Traumatology, Hannover Medical School (MHH), Carl – Neuberg – Straße 1, Hannover, 30625, GermanyTel +49 511 532 2099Email Oergel.Marcus@mh-hannover.deIntroduction: This retrospective cohort analysis examines the impact of the COVID-19 pandemic in the prehospital setting in Germany. The data of two emergency physician response units of a northern German region with 1.2 million citizens was analyzed retrospectively.Materials and Methods: We analyzed the period March 16 to April 16 for the year 2020 when the lockdown took place in Germany and compare the results for the same period for the year 2019 and 2018. 1004 patients were included. Demographic data, the type of rescue missions, the number of missions per day, the National Advisory Committee for Aeronautics Score (NACA-score), the frequency of respiratory emergencies (COVID-19 and non-COVID-19 associated), as well as the number of deaths were documented.Results: Mean age was 62.3± 24.8 years and 576 (56.5%) were male. Number of missions were 397, 403 and 333 in 2018, 2019 and 2020 respectively. The control room registered a 22% reduction of rescue missions for the year 2020. Even the amount of emergency calls via the emergency number 112 was reduced by 17.4% between 2018 and 2020. 150 (14.9%) missions were due to respiratory emergencies. In 2020 10 missions (28.6% of respiratory emergencies) were COVID-19 related. In 2020 the NACA score increased significantly.Conclusion: We found a decreasing effect of the COVID-19 pandemic in Germany on the number of emergency calls as well as missions, and an increase of the severity of cases in preclinical care for a northern German region with 1.2 million citizens. The effect of these findings caused by COVID-19 on the health care system remains to be seen.Keywords: emergency medicine, SARS-CoV-2, COVID-19, prehospital care, emergency physician response units, pandemic

Abstract Background Achalasia‐addisonianism‐alacrima syndrome, frequently referred to as Allgrove syndrome or Triple A syndrome, is a multisystem disorder resulting from homozygous or compound heterozygous pathogenic variants in the gene encoding aladin (AAAS). Aladin is a member of the WD‐repeat family of proteins and is a component of the nuclear pore complex. It is thought to be involved in nuclear import and export of molecules. Here, we describe an individual with a paternally inherited truncating variant and a maternally inherited, novel missense variant in AAAS presenting with alacrima, achalasia, anejaculation, optic atrophy, muscle weakness, dysarthria, and autonomic dysfunction. Methods Whole‐exome sequencing was performed in the proband, sister, and parents. Variants were confirmed by Sanger sequencing. The localization of aladin to the nuclear pore was assessed in cells expressing the patient variant. Results Functional testing of the maternally inherited variant, p.(Arg270Pro), demonstrated decreased localization of aladin to the nuclear pore in cells expressing the variant, indicating a deleterious effect. Follow‐up testing in the proband's affected sister revealed that she also inherited the biallelic AAAS variants. Conclusions Review of the patient's clinical, pathological, and genetic findings resulted in a diagnosis of Triple A syndrome.

Inferring parameters of computational models that capture experimental data is a central task in cognitive neuroscience. Bayesian statistical inference methods usually require the ability to evaluate the likelihood of the model—however, for many models of interest in cognitive neuroscience, the associated likelihoods cannot be computed efficiently. Simulation-based inference (SBI) offers a solution to this problem by only requiring access to simulations produced by the model. Previously, Fengler et al. introduced likelihood approximation networks (LANs, Fengler et al., 2021) which make it possible to apply SBI to models of decision-making but require billions of simulations for training. Here, we provide a new SBI method that is substantially more simulation efficient. Our approach, mixed neural likelihood estimation (MNLE), trains neural density estimators on model simulations to emulate the simulator and is designed to capture both the continuous (e.g., reaction times) and discrete (choices) data of decision-making models. The likelihoods of the emulator can then be used to perform Bayesian parameter inference on experimental data using standard approximate inference methods like Markov Chain Monte Carlo sampling. We demonstrate MNLE on two variants of the drift-diffusion model and show that it is substantially more efficient than LANs: MNLE achieves similar likelihood accuracy with six orders of magnitude fewer training simulations and is significantly more accurate than LANs when both are trained with the same budget. Our approach enables researchers to perform SBI on custom-tailored models of decision-making, leading to fast iteration of model design for scientific discovery.

O objetivo deste artigo é identificar o impacto das práticas de gestão sustentável de recursos humanos (GSRH) no comprometimento organizacional (CO). O estudo utilizou uma amostra de 290 funcionários vinculados a seis empresas classificadas no Índice de Sustentabilidade Empresarial da Bovespa. As hipóteses de pesquisa foram testadas com base em um modelo estrutural, utilizando a técnica de modelagem de equações estruturais (MEE). Os resultados mostram que as práticas de GSRH são representadas por três dimensões: atração e retenção de profissionais, manutenção de profissionais saudáveis e motivados e desenvolvimento de competências dos profissionais. Essas práticas têm um impacto significativo e positivo no comprometimento afetivo (CA) e no comprometimento normativo (CN). Além disso, o CA se destaca como um mediador parcial da relação entre as práticas de GSRH e o CN.

From 25 May to 21 July 2017, the research vessel Polarstern performed the cruise PS106 to the high Arctic in the region north and northeast of Svalbard. The mobile remote-sensing platform OCEANET was deployed aboard Polarstern. Within a single container, OCEANET houses state-of-the-art remote-sensing equipment, including a multiwavelength Raman polarization lidar PollyXT and a 14-channel microwave radiometer HATPRO (Humidity And Temperature PROfiler). For the cruise PS106, the measurements were supplemented by a motion-stabilized 35 GHz cloud radar Mira-35. This paper describes the treatment of technical challenges which were immanent during the deployment of OCEANET in the high Arctic. This includes the description of the motion stabilization of the cloud radar Mira-35 to ensure vertical-pointing observations aboard the moving Polarstern as well as the applied correction of the vessels heave rate to provide valid Doppler velocities. The correction ensured a leveling accuracy of ±0.5∘ during transits through the ice and an ice floe camp. The applied heave correction reduced the signal induced by the vertical movement of the cloud radar in the PSD of the Doppler velocity by a factor of 15. Low-level clouds, in addition, frequently prevented a continuous analysis of cloud conditions from synergies of lidar and radar within Cloudnet, because the technically determined lowest detection height of Mira-35 was 165 m above sea level. To overcome this obstacle, an approach for identification of the cloud presence solely based on data from the near-field receiver of PollyXT at heights from 50 m and 165 m above sea level is presented. We found low-level stratus clouds, which were below the lowest detection range of most automatic ground-based remote-sensing instruments during 25 % of the observation time. We present case studies of aerosol and cloud studies to introduce the capabilities of the data set. In addition, new approaches for ice crystal effective radius and eddy dissipation rates from cloud radar measurements and the retrieval of aerosol optical and microphysical properties from the observations of PollyXT are introduced.

Abstract Background Proximal femoral fractures are a major socioeconomic burden and they occur mainly in geriatric patients. High mortality and complication rates are reported. To reduce the mortality and morbidity of these patients, co-management with geriatricians has been recommended. Most previous studies have focused on relatively comprehensive care models. Models with only a few additions to the usual care have not been extensively evaluated. Methods This retrospective observational study included all patients aged ≥70 years (mean age: 84.5 ± 7.1 years, 70% women) with an isolated proximal femoral fracture treated surgically in our institution from May 2018 to October 2019. In the first 9 months, patients were treated with the usual care (control group, n = 103). In the second 9 months, patients were treated with our multidisciplinary care model (intervention group, n = 104), which included the usual care, plus: (1) one multidisciplinary ward round per week and (2) one “elective” operation slot per day reserved for proximal femoral fractures. Baseline characteristics and outcome measures of the hospital stay were extracted from electronic health records. A 3-month follow-up was conducted by phone. Results Baseline characteristics were comparable between groups (p > 0.05). The hospital stay was shorter in the intervention group than in the control group (7.8 ± 4.3 vs. 9.1 ± 4.5; p = 0.022). The intervention reduced the waiting time for surgery by more than 10 h (intervention: 25.4 ± 24.5 vs. control: 35.8 ± 34.1 h; p = 0.013). A structured phone interview was not performed in 30.9% of the cases. The model reduced the overall dissatisfaction rate by more than half (12.9% vs. 32.4%; p = 0.008). On the other hand, the groups had similar perioperative complication rates (25% vs. 24.3%; p > 0.9999) and mortality (4.8% vs. 3.9%; p > 0.9999) and they remained similar at the 3-month follow-up (complications: 20.3% vs. 17.6% p = 0.831, mortality: 18.2% vs. 15.0% p = 0.573). Conclusion We found that two additions to the usual proximal femoral fracture regimen could significantly improve the overall satisfaction rate, reduce the length of hospital stay and shorten the waiting time for surgery. In contrast to previous studies, we observed no significant improvements in complication or mortality rates. Further changes in the standard care might be needed for this purpose.

The role of clouds in recent Arctic warming is not fully understood, including their effects on the solar radiation and the surface energy budget. To investigate relevant small-scale processes in detail, the intensive Physical feedbacks of Arctic planetary boundary layer, Sea ice, Cloud and AerosoL (PASCAL) drifting ice floe station field campaign was conducted during early summer in the central arctic. During this campaign, the small-scale spatiotemporal variability of global irradiance was observed for the first time on an ice floe with a dense network of autonomous pyranometers. A total of 15 stations were deployed covering an area of 0.83 km×1.59 km from 4–16 June 2017. This unique, open-access dataset is described here, and an analysis of the spatiotemporal variability deduced from this dataset is presented for different synoptic conditions. Based on additional observations, five typical sky conditions were identified and used to determine the values of the mean and variance of atmospheric global transmittance for these conditions. Overcast conditions were observed 39.6 % of the time predominantly during the first week, with an overall mean transmittance of 0.47. The second most frequent conditions corresponded to multilayer clouds (32.4 %), which prevailed in particular during the second week, with a mean transmittance of 0.43. Broken clouds had a mean transmittance of 0.61 and a frequency of occurrence of 22.1 %. Finally, the least frequent sky conditions were thin clouds and cloudless conditions, which both had a mean transmittance of 0.76 and occurrence frequencies of 3.5 % and 2.4 %, respectively. For overcast conditions, lower global irradiance was observed for stations closer to the ice edge, likely attributable to the low surface albedo of dark open water and a resulting reduction of multiple reflections between the surface and cloud base. Using a wavelet-based multi-resolution analysis, power spectra of the time series of atmospheric transmittance were compared for single-station and spatially averaged observations and for different sky conditions. It is shown that both the absolute magnitude and the scale dependence of variability contains characteristic features for the different sky conditions.

Given the important role of clouds in our planet’s climate system, it is crucial to further improve our understanding of their governing processes as well as the resulting spatio-temporal variability of their properties. This co-variability of different cloud optical properties is adequately represented through the well-established concept of cloud regimes. The focus of the present study lies on the creation of a cloud regime dataset over Europe, named “Cloud Regime dAtAset based on the CLAAS-2.1 climate data record” (CRAAS), in order to analyze their variability and their changes at different spatio-temporal scales. In addition, co-occurrences between the cloud regimes and large-scale weather patterns are investigated. The CLoud property dAtAset using Spinning Enhanced Visible and Infrared (SEVIRI) edition 2.1 (CLAAS-2.1) data record, which is produced by the Satellite Application Facility on Climate Monitoring (CM SAF), was used as the basis for the derivation of the cloud regimes over Europe for a 14-year period (2004–2017). In particular, the cloud optical thickness (COT) and cloud top pressure (CTP) products of CLAAS-2.1 were used in order to compute 2D histograms. Then, the k-means clustering algorithm was applied to the generated 2D histograms in order to derive the cloud regimes. Eight cloud regimes were identified, which, along with the geographical distribution of their frequency of occurrence, assisted in providing a detailed description of the climate of the cloud properties over Europe. The annual and diurnal variabilities of the eight cloud regimes were studied, and trends in their frequency of occurrence were also examined. Larger changes in the frequency of occurrence of the produced cloud regimes were found for a regime associated to alto- and nimbo-type clouds and for a regime connected to shallow cumulus clouds and fog (−0.65% and +0.70% for the time period of the study, respectively).

Do personality traits in highly intelligent individuals relate to their work engagement? Seemingly little is known about the relationship between personality and work engagement for gifted individuals. In what may be the first study to do so, a Swedish Mensa sample (n = 353) was explored with a two-part aim: to assess psychometric personality properties and to investigate the relationship between personality traits (Mini-IPIP6) and work engagement (UWES-9). The results of the Mensa members and the Mturk sample (1.4 SD lower in cognitive ability based on ICAR-16) were compared using a confirmatory factor analysis (CFA) and a regression. The findings indicated that the Mensa sample had higher openness (d = .50) and honesty-humility (d = .65) and that personality traits were similarly related to work engagement in both groups, with the exception that neither openness nor honesty-humility were related to work engagement in the Mensa sample. The characteristics of intellectually gifted individuals are further discussed.

The realistic representation of low-level clouds, including their radiative effects, in atmospheric models remains challenging. A sensitivity study is presented to establish a conceptual approach for the evaluation of low-level clouds and their radiative impact in a highly resolved atmospheric model. Considering simulations for six case days, the analysis supports the notion that the properties of clouds more closely match the assumptions of the sub-adiabatic rather than the vertically homogeneous cloud model, suggesting its use as the basis for evaluation. For the considered cases, 95.7 % of the variance in cloud optical thickness is explained by the variance in the liquid water path, while the droplet number concentration and the sub-adiabatic fraction contribute only 3.5 % and 0.2 % to the total variance, respectively. A mean sub-adiabatic fraction of 0.45 is found, which exhibits strong inter-day variability. Applying a principal component analysis and subsequent varimax rotation to the considered set of nine properties, four dominating modes of variability are identified, which explain 97.7 % of the total variance. The first and second components correspond to the cloud base and top height, and to liquid water path, optical thickness, and cloud geometrical extent, respectively, while the cloud droplet number concentration and the sub-adiabatic fraction are the strongest contributors to the third and fourth components. Using idealized offline radiative transfer calculations, it is confirmed that the shortwave and longwave cloud radiative effects exhibit little sensitivity to the vertical structure of clouds. This reconfirms, based on an unprecedented large set of highly resolved vertical cloud profiles, that the cloud optical thickness and the cloud top and bottom heights are the main factors dominating the shortwave and longwave radiative effect of clouds and should be evaluated together with radiative fluxes using observations to attribute model deficiencies in the radiative fluxes to deficiencies in the representation of clouds. Considering the different representations of cloud microphysical processes in atmospheric models, the analysis has been further extended and the deviations between the radiative impact of the single- and double-moment schemes are assessed. Contrasting the shortwave cloud radiative effect obtained from the double-moment scheme to that of a single-moment scheme, differences of about ∼40 W m−2 and significant scatter are observed. The differences are attributable to a higher cloud albedo resulting from the high values of droplet number concentration in particular in the boundary layer predicted by the double-moment scheme, which reach median values of around ∼600 cm−3.

Abstract In this study Lagrangian large‐eddy simulation of cloudy mixed layers in evolving warm air masses in the Arctic is constrained by in situ observations from the recent PASCAL field campaign. A key novelty is that time dependence is maintained in the large‐scale forcings. An iterative procedure featuring large‐eddy simulation on microgrids is explored to calibrate the case setup, inspired by and making use of the typically long memory of Arctic air masses for upstream conditions. The simulated mixed‐phase clouds are part of a turbulent mixed layer that is weakly coupled to the surface and is occasionally capped by a shallow humidity layer. All eight simulated mixed layers exhibit a strong time evolution across a range of time scales, including diurnal but also synoptic fingerprints. A few cases experience rapid cloud collapse, coinciding with a rapid decrease in mixed‐layer depth. To gain insight, composite budget analyses are performed. In the mixed‐layer interior the heat and moisture budgets are dominated by turbulent transport, radiative cooling, and precipitation. However, near the thermal inversion the large‐scale vertical advection also contributes significantly, showing a distinct difference between subsidence and upsidence conditions. A bulk mass budget analysis reveals that entrainment deepening behaves almost time‐constantly, as long as clouds are present. In contrast, large‐scale subsidence fluctuates much more strongly and can both counteract and boost boundary‐layer deepening resulting from entrainment. Strong and sudden subsidence events following prolonged deepening periods are found to cause the cloud collapses, associated with a substantial reduction in the surface downward longwave radiative flux.

Background: Due to demographic changes, proximal femoral fractures (PFF) in the elderly rise constantly. The standard diagnostic tool is still the X-ray of the pelvis/hip in two planes. Our hypothesis was that the lateral-view X-ray has little influence on classification, planning of the operative procedure, and choice of implant in geriatric patients.Methods: Retrospective analysis of all initial X-rays of PFF in geriatric patients (≥70 years) from May 2018 until August 2019 in a Level I Trauma center. Three experienced consultants categorized the fractures on the ap pelvis view and performed Garden and Pauwels classification as well as a two-staged classification displaced/nondisplaced [for femoral neck fractures (FNF)] or AO Classification [for intertrochanteric fractures (ITF)]. Afterward, they decided the operative strategy as well as implant choice [dynamic hip screw (DHS), intramedullary nail (IMN), or arthroplasty]. After 4 weeks, they categorized all fractures again with now available lateral view X-rays in a different order.Results: Two hundred seven patients (146 female, 61 male; 70.5 vs. 29.5%) with 90 FNF and 117 ITF (43.5 vs. 56.5%) could be included. Age was 84.6 ± 6.9 years. The treatment was in 45 cases DHS, in 82 cases IMN, and for the other 80 cases arthroplasty. The interobserver reliability of the classifications were poor, except for the two-staged classification [Fleiss-κ ap view only = 0.708 (CI 95% 0.604, 0.812) vs. additional lateral = 0.756 (CI 95% 0.644, 0.869)]. Moreover, independent from the classification, there were no significant changes in management and choice of implant with additional lateral view.Conclusions: Regarding our results, we consider the lateral view dispensable for standard X-ray of displaced PFF in geriatric patients. In nondisplaced fractures, it could be added secondary.

The hippocampal dentate gyrus is an important relay conveying sensory information from the entorhinal cortex to the hippocampus proper. During exploration, the dentate gyrus has been proposed to act as a pattern separator. However, the dentate gyrus also shows structured activity during immobility and sleep. The properties of these activity patterns at cellular resolution, and their role in hippocampal-dependent memory processes have remained unclear. Using dual-color in vivo two-photon Ca2+ imaging, we show that in immobile mice dentate granule cells generate sparse, synchronized activity patterns associated with entorhinal cortex activation. These population events are structured and modified by changes in the environment; and they incorporate place- and speed cells. Importantly, they are more similar than expected by chance to population patterns evoked during self-motion. Using optogenetic inhibition, we show that granule cell activity is not only required during exploration, but also during immobility in order to form dentate gyrus-dependent spatial memories.

BackgroundThe majority of stroke survivors return to their homes and need assistance from family caregivers to perform activities of daily living. These increased demands coupled with the lack of preparedness for their new roles lead to a high risk for caregivers developing depressive symptoms and other negative outcomes. Follow-up home support and problem-solving interventions with caregivers are crucial for maintaining stroke survivors in their homes. Problem-solving interventions are effective but are underused in practice because they require large amounts of staff time to implement and are difficult for caregivers logistically. ObjectiveThe aim of this study is to test a problem-solving intervention for stroke caregivers that can be delivered over the telephone during the patient’s transitional care period (time when the stroke survivor is discharged to home) followed by 8 asynchronous online sessions. MethodsThe design is a two-arm parallel randomized clinical trial with repeated measures. We will enroll 240 caregivers from eight Veterans Affairs (VA) medical centers. Participants randomized into the intervention arm receive a modified problem-solving intervention that uses telephone and web-based support and training with interactive modules, fact sheets, and tools on the previously developed and nationally available Resources and Education for Stroke Caregivers’ Understanding and Empowerment Caregiver website. In the usual care group, no changes are made in the information, discharge planning, or care the patients who have had a stroke normally receive, and caregivers have access to existing VA resources (eg, caregiver support line, self-help materials). The primary outcome is a change in caregiver depressive symptoms at 11 and 19 weeks after baseline data collection. Secondary outcomes include changes in stroke caregivers’ burden, knowledge, positive aspects of caregiving, self-efficacy, perceived stress, health-related quality of life, and satisfaction with care and changes in stroke survivors’ functional abilities and health care use. The team will also determine the budgetary impact, facilitators, barriers, and best practices for implementing the intervention. Throughout all phases of the study, we will collaborate with members of an advisory panel. ResultsStudy enrollment began in June 2015 and is ongoing. The first results are expected to be submitted for publication in 2021. ConclusionsThis is the first known study to test a transitional care and messaging center intervention combined with technology to decrease caregiver depressive symptoms and to improve the recovery of stroke survivors. If successful, findings will support an evidence-based model that can be transported into clinical practice to improve the quality of caregiving post stroke. Trial RegistrationClinicalTrials.gov NCT01600131; https://www.clinicaltrials.gov/ct2/show/NCT01600131 International Registered Report Identifier (IRRID)DERR1-10.2196/21799

Mechanistic modeling in neuroscience aims to explain observed phenomena in terms of underlying causes. However, determining which model parameters agree with complex and stochastic neural data presents a significant challenge. We address this challenge with a machine learning tool which uses deep neural density estimators—trained using model simulations—to carry out Bayesian inference and retrieve the full space of parameters compatible with raw data or selected data features. Our method is scalable in parameters and data features and can rapidly analyze new data after initial training. We demonstrate the power and flexibility of our approach on receptive fields, ion channels, and Hodgkin–Huxley models. We also characterize the space of circuit configurations giving rise to rhythmic activity in the crustacean stomatogastric ganglion, and use these results to derive hypotheses for underlying compensation mechanisms. Our approach will help close the gap between data-driven and theory-driven models of neural dynamics.

Abstract Background RNA polymerase III (Pol III)‐related disorders are autosomal recessive neurodegenerative disorders caused by variants in POLR3A or POLR3B. Recently, a novel phenotype of adult‐onset spastic ataxia was identified in individuals with the c.1909+22G>A POLR3A variant in compound heterozygosity. Methods Whole‐exome sequencing was performed in the proband and parents. Variants were confirmed by Sanger sequencing. RNA sequencing was performed to evaluate splicing implications. Results A 42‐year‐old female was evaluated for unexplained neurological findings with a slow progressive decline in gait and walking speed since adolescence. WES revealed a novel missense variant (c.3593A>C, p.Lys1198Arg) in exon 27 of POLR3A in compound heterozygosity with the c.1909+22G>A variant. Summary of previously reported clinical features from individuals with pathogenic biallelic alterations in POLR3A and adult‐onset phenotype is consistent with our findings. RNA analysis revealed c.3593A>G drives the production of four RNA transcript products each with different functional impacts. Conclusion The novel dual‐class c.3593A>C variant in POLR3A causes an amino acid substitution and complex disruption of splicing. Our report supports the need to investigate variants near splice junctions for proper interpretation. Current interpretation guidelines need to address best practices for inclusion of predicted or measured transcriptional disruption pending functional activity or reliable transcript abundance estimates.

The ability to preferentially stimulate different retinal pathways is an important area of research for improving visual prosthetics. Recent work has shown that different classes of retinal ganglion cells (RGCs) have distinct linear electrical input filters for low-amplitude white noise stimulation. The aim of this study is to provide a statistical framework for characterizing how RGCs respond to white-noise electrical stimulation. We used a nested family of Generalized Linear Models (GLMs) to partition neural responses into different components—progressively adding covariates to the GLM which captured non-stationarity in neural activity, a linear dependence on the stimulus, and any remaining non-linear interactions. We found that each of these components resulted in increased model performance, but that even the non-linear model left a substantial fraction of neural variability unexplained. The broad goal of this paper is to provide a much-needed theoretical framework to objectively quantify stimulus paradigms in terms of the types of neural responses that they elicit (linear vs. non-linear vs. stimulus-independent variability). In turn, this aids the prosthetic community in the search for optimal stimulus parameters that avoid indiscriminate retinal activation and adaptation caused by excessively large stimulus pulses, and avoid low fidelity responses (low signal-to-noise ratio) caused by excessively weak stimulus pulses.

International human resources management encompasses expatriation consisting of the transfer of employees between the units of the organization in different countries for a specific period. To achieve the expatriation results, an important process is adjustment, which involves adapting to the new context. One of the factors influencing the adjustment in the country is the organizational socialization, understood as the integration of the individual with the organization. The aim of this research was to analyze the relationship between organizational tactics and the process of organizational socialization of expatriates. Through a quantitative approach and a descriptive character, the data collection took place in an online questionnaire. The sample consisted of expatriates working in international companies. The results were analyzed through descriptive statistics and linear regression. It was shown that companies use institutionalized tactics to adjust employees. It was identified that 14% of the process of organizational socialization is explained by the tactics, being that the greater impact of these tactics are perceived in the dimension of the task, that is, the role that the employee will act. The number of times the expatriate has performed international missions may alter the perception of the tactics used for his adjustment, which is an important finding of this research.

In spite of the growing interest in the role of the gut microbiome (GM) in host physiology and health, the mechanisms governing its assembly and its effects on the environment are poorly understood. In this article, we show that the host genotype and the GM of Daphnia influence the community structure of the surrounding bacterioplankton (BPK). When Daphnia genotypes were placed in an identical environment, both the GM and BPK showed a genotype and diet-dependent taxonomic composition. Overall, the GM strongly differed from the BPK in taxonomic composition and was characterized by a lower α-diversity, suggesting a selective rejecting of bacteria from the regional species pool. In a microbiome transplant experiment, the assembly of both the GM and BPK was strongly affected by the host genotype and the inoculum to which germ-free Daphnia were exposed. The combination of these results suggests a strong interaction between the host genotype, its GM and free-living microbial communities. Currently, it is generally assumed that an animal’s diet has a strong effect on the animal’s GM, but only a negligible (if any) effect on the surrounding environment. However, our results indicate that the diet/microbiome inocula have a small effect on the gut community and a large effect on the community in the surrounding environment. This structuring genotype × microbiome × environment effect is an essential prerequisite that could indicate that microbiomes play an important role in eco-evolutionary processes.