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In this paper we develop test cases to adjudicate between dual-process and the causal mapping explanations of order effects. Using dilemmas with minimized emotional force, we explore new conditions for order effects to occur. Overall, the results support causal model theory. We produced novel evidence that order effects extend not only to cases with low emotional engagement, but also to specialized judgements about whether an action violates a rule. However, when objects are sacrificed instead of persons the order effect either disappears orbecomes symmetrical, contrary to previous theorizing that it is an asymmetrical transfer effect.Causal model theory needs to be developed to include interplays between the moral status of sacrificed entities and computational models of causal mapping. Symmetric order effects remain a puzzle, motivating future research. Though we do not know how to explain them yet, we discuss how symmetric order effects can influence policy decision making.

Objective:The purpose of this study was to provide an overview of the current literature regarding the vocational rehabilitation services found effective in promoting employment among transition-age youth with disabilities as well as identifying factors affecting the effectiveness of those services.Methods:This study utilized the Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines to theoretically and methodologically ground the systematic review. Through a three-stage filtering process, 35 studies were identified that helped identify common and effective vocational rehabilitation services for transition-aged youth.Findings:Three major themes were observed in the review of literature: validated vocational rehabilitation services, vocational rehabilitation counselor factors, and demographic variables.Conclusions:Additional research is needed in the role of disability severity as a variable of successful service provision. Further identifying successful vocational services for varying levels of disability severity will provide vocational rehabilitation consumers with more individualized options and has the potential to increase positive case closure rates. Lastly, research indicated a need for continued training of VR counselors to ensure they are meeting the needs of their consumers.

Objective To evaluate the usability and use of human factors (HF)–based clinical decision support (CDS) implemented in the emergency department (ED). Background Clinical decision support can improve patient safety; however, the acceptance and use of CDS has faced challenges. Following a human-centered design process, we designed a CDS to support pulmonary embolism (PE) diagnosis in the ED. We demonstrated high usability of the CDS during scenario-based usability testing. We implemented the HF-based CDS in one ED in December 2018. Method We conducted a survey of ED physicians to evaluate the usability and use of the HF-based CDS. We distributed the survey via Qualtrics, a web-based survey platform. We compared the computer system usability questionnaire scores of the CDS between those collected in the usability testing to use of the CDS in the real environment. We asked physicians about their acceptance and use of the CDS, barriers to using the CDS, and areas for improvement. Results Forty-seven physicians (56%) completed the survey. Physicians agreed that diagnosing PE is a major problem and risk scores can support the PE diagnostic process. Usability of the CDS was reported as high, both in the experimental setting and the real clinical setting. However, use of the CDS was low. We identified several barriers to the CDS use in the clinical environment, in particular a lack of workflow integration. Conclusion Design of CDS should be a continuous process and focus on the technology’s usability in the context of the broad work system and clinician workflow.

Background Extremity replantation as well as allotransplantation aim to restore form and function of the amputated limb. Both approaches, however, are clearly limited by the ischemic time. Ex vivo perfusion (EVP), already well-established in the field of solid organ transplantation, represents a promising tool to overcome this restriction. Methods We have currently established the technical requirements to provide EVP to severed limbs in a clinical hospital setting and hereby report of a 48-hour hypothermic EVP (EVP48) of an upper extremity amputated at the level of the proximal humerus, followed by a 2-hour simulated reperfusion (2SR) with donor blood. Results Muscle biopsies revealed histopathologically well preserved, vital muscle tissue after EVP24, and partially grouped muscle fiber necrosis with predominantly vital muscle tissue after EVP48 and 2SR. Analyses of perfusate samples showed a marked decline of biochemical muscle damage markers during EVP48. Cytokine analysis disclosed an isolated increase of the proinflammatory cytokines, interleukine-6, monocyte chemotactic protein-1, and interferon-γ, during EVP and 2SR. Magnetic resonance imaging, performed after EVP48, indicated partial muscle necrosis of the intrinsic hand muscles only, while no signs for infection or inflammation were present. Conclusion Our single case experience shows the general feasibility of an amputated limb ex vivo salvage perfusion setting to allow for delayed replantation up to 24 hours. Nevertheless, an accurate prior planning is crucial to ensure successful implementation of EVP in the acute clinical setting.

In the present paper, we propose a novel single-fiber model which exploits a description of fibers as a sequence of bond and torsion angles. Using the Frenet–Serret formulas, this representation can be translated into three-dimensional (3D) space and vice-versa. While the precise locations of points along a fiber do not directly convey information about the inner material properties of the fiber, the distribution of bond, and torsion angles may be related to various material characteristics and, thus, our model may form a direct link between inner material properties and emerging microstructure properties. More precisely, we model curved fibers in the 3D Euclidean space R3 as polygonal tracks that we represent by their local curvature and torsion at each sampling point. The 2D sequences of curvatures and torsions obtained in this way are then considered as realizations of a Markov chain with finite memory which takes its values in R2. The transition kernel of this Markov chain is given by a family of conditional multivariate probability distributions. They are constructed using so-called R-vine copulas, which are fitted and validated by means of experimental data.

PurposeThis study aims to examine whether and how voluntary accounting disclosures can repair individual donors’ trust in a charity after negative events.Design/methodology/approachThe authors adopt a qualitative research approach and conduct 32 semi-structured interviews with active Australian individual donors, with a hypothetical vignette design. Hypothetical negative events and corresponding accounting disclosures are presented to participants during interviews.FindingsThree types of individual donors are identified based on their decision-making patterns after negative events and primary trust relations with a charity-reasoned donor (giving-decision based on their analysis of the situation, competence-based trust), generalist donors (giving-decision based on trust in the charitable sector, institution-based trust) and emotional donors (giving-decision based on feelings and emotions about the charity, integrity-based trust). The research suggests that accounting disclosures can repair trust damage for reasoned donors and support institution-based trust for generalist donors, but do not seem able to repair trust damage for emotional donors and can potentially damage trust further.Practical implicationsOverall, the findings suggest that a one-size-fits-all approach to communicating with individual donors after negative events is not likely to be very effective in repairing trust. Instead, charities may need to adapt disclosures to their different types of individual donors.Originality/valueWhile prior accounting studies have largely focussed on how charity managers themselves grapple with accountability or how negative events impact charitable donations, the authors demonstrate how accounting disclosures can play different roles in the trust-repairing process for different types of individual donors.

Implant-based reconstruction (IBR) is the most frequently performed breast reconstruction procedure in the USA. As the US population ages, an increasing number of these patients suffer from comorbidities requiring the use of chronic antithrombotic therapy. Outcomes following IBR in patients prescribed these medications are not well understood.An all-payor administrative claims database (52 million patients) was queried for patients undergoing IBR from 2010 through 2018. Patients who were prescribed therapeutic antithrombotic therapy, and those who were not, were matched in a one-to-one fashion for comorbidities independently associated with bleeding and thrombo-ischemic events following first-stage IBR. Cox proportional hazards models investigated the 90-day risk of bleeding and major thrombo-ischemic events following IBR.Of the 36,379 patients found to have undergone IBR, 2,024 patients were perfectly matched for age and high-risk comorbidities. Patients prescribed antithrombotic drugs had increased 90-day risk for all thrombo-ischemic complications (HR: 5.62, 95% CI: 3.53-8.95, p0.0001), as well as a significantly increased risk for 90-day DVT, 90-day PE, 90-day myocardial infarction, and 90-day stroke. Patients specifically prescribed antiplatelet drugs, direct oral anticoagulants (DOAC), and warfarin had a significantly increased risk for transfusion.Patients prescribed antithrombotic therapy had a significantly increased risk for life-threatening thrombotic events and transfusion following elective IBR. This suggests a role for further monitoring and a potential role for multi- and interdisciplinary interventions to help mitigate this risk. These interventions can be the subject of future prospective studies.

Threat and error management in complex systems has historically centered around failures rather than successes. This has led to an unbalanced view of risk within organizations in that information regarding resiliency within the system (those factors which help to negate failure) are typically ignored. Currently, the National Aeronautics and Space Administration (NASA) employs the Human Factors Analysis and Classification System (HFACS) to both identify human error involved in mishaps and assess those events which prevented more serious consequences from occurring. This paper demonstrates a Red Light/Green Light analysis of a case study, EVA 23, to outline an incident in which an astronaut came dangerously close to drowning in space due to the collection of water in his helmet.

In this work, we present a workflow for semi-automatic extraction of geo-references and motion events from the book "The Travels of Marco Polo". These are then used to create 3D renderings of the space and movement which allows readers to visually trace Marco Polo's route themselves to provide the exprience of the entirety of the journey.

Society faces existential challenges, such as global warming, demographic change and digital innovations. Standards help solving problems and reaping opportunities. They have long been recognised as important, from technological, business, and economic perspectives, but clear evidence about their societal impact is still missing. Against this background, the XXM Partners commissioned this project to get a clearer view of how standards impact society. The project was carried out by researchers from Eindhoven University of Technology and Rotterdam School of Management, Erasmus University between November 2021 and November 2022. We conducted a pre-study of 48 standards, reviewed academic literature on standards’ impact and its measurement. We carried out eight in-depth case studies of particular standards with 86 expert interviews, relevant documents, and other sources. In doing so, we reached all five goals that were agreed in the project contract: Goal 1: Overview over dimensions of standards impacts Societal impact has many dimensions, which relate, e.g., to public health, education, or the environment. Our literature review identified the 17 United Nations Sustainable Development Goals (SDGs) as the most suitable framework for our project. The SDGs are goals, agreed upon in global consensus, on which society should focus and improve. A growing global movement has formed around them to address societal challenges. In a pre-study, we conducted desk research to explore potential impacts of 48 standards. They cover the breadth of subject areas, and include standards with societal, environmental, technical and/or business purposes. We find that these standards can be linked to all SDGs. Often one standard affects multiple SDGs, going beyond intended impacts. Goal 2: Overview over scientific literature on standards’ impacts Standards are important for society. This is widely recognised in academic literature. However, there is relatively limited research on how they impact society. Most of this limited research focuses on two standards: ISO 9001 (quality management systems) and ISO 14001 (environmental management systems). Our review reveals a research focus on business/economic (both standards) and environmental (ISO 14001) impacts. Some evidence exists on non-environmental societal impacts (e.g., workplace safety), but this remains limited. We extended our review to other fields, especially addressing best practice for impact measurement. We compared multiple approaches, selected the Logic Model for understanding impact, and adapted it to standards. This model helps understand impact by tracing it in five steps: (1) inputs (including standards), (2) activities for standard implementation, (3) outputs (a situation reflecting what a standard prescribes), (4) outcomes (changes for stakeholders), and eventually (5) long-term impact. Goal 3: Evidence of standards’ societal impacts – empirical research Under the project team’s guidance, master students carried out eight in-depth studies in Norway (two studies), Sweden (two studies), Finland (two studies), Denmark and Austria. Standards were selected in consultation with the XXM Partners. They cover a broad range of important areas, e.g., greenhouse gas (GHG) emissions reporting (ISO 14064-1), clinical trials for medical devices (ISO 14155), and information security management (ISO 27001). Our studies led to findings about (1) specific societal changes caused by the investigated standards, (2) what drives standards’ impacts in general, and (3) measuring standards’ impact (see Goal 4 below). Findings about standards’ specific societal changes Two standards in our study are particularly successful in creating positive impact: • EN 16516 (emissions of construction products into indoor air) promotes the availability of low-emission construction products, thereby contributing to healthy indoor air. • ISO 14155 (clinical investigations for medical devices) contributes to safer clinical trials and availability of innovative medical devices for patients. In the other cases, we observe strong potential for positive societal impact. However, this is not achieved, e.g., due to standards not being implemented at large scale, not meeting potential users’ expectations, and/or competing with other standards. In two cases (ISO 14064-1, GHG emissions accounting; ISO 14044, life-cycle assessment), foreseeable abuse of the standard may even provide opportunities for greenwashing. All investigated standards have broader (potential) impacts on the SDGs than identified by ISO. E.g., ISO 14155 does not only contribute to SDG 3 (“Good Health and Wellbeing”), but also to SDG 9 (“Industry, Innovation and Infrastructure”) and the institutional aspect of SDG 16 (“Peace, Justice and Strong Institutions”). Findings about drivers behind standards’ impacts: importance of their ecosystems All investigated standards are deeply embedded in their ecosystems. A remarkable finding concerns the large extent, to which (mis)alignment with this context drives their impact. This also makes it challenging to isolate the standard’s impact from that of its entire ecosystem. Where we observed positive impact, this was largely due to a standard serving a clear purpose in its ecosystem (e.g., meeting market needs, supporting certification, alignment with regulatory requirements). In the cases where potentials for positive impact have not yet been realised, our data show how this is driven by misaligned ecosystems and standards. We have recommendations for how to address this (see Goal 5 below) Goal 4: Applied methodology for demonstrating societal impacts In the course of the project, we developed a methodology for measuring standard’s societal impacts. It consists of a six-step process, which is based on four essential frameworks/tools: 1. Stakeholder analysis, 2. A checklist for analysing a standard’s ecosystem, 3. The logic model for standards, 4. The SDGs as a framework for classifying impact. We recommend this methodology for systematically studying further standards’ impacts. Goal 5: Recommendations to National Standard Bodies (NSBs) Our results have clear implications for the XXM Partners, ISO/IEC, CEN/CENELEC, and their members. Based on these implications, we provide recommendations on (1) communicating standards’ impacts to policymakers and other stakeholders, and (2) enhancing standards’ positive impact. Section 9.5 (p.102) specifies these recommendations in detail. Communicating standards’ impact • To policymakers: Emphasise standards’ functions as essential instruments for change in their respective ecosystems. • To other stakeholders: Focus on standards’ contributions to the SDGs, while acknowledging that the full potential is not yet achieved. • Ensure standards’ inclusion in frameworks for measuring societal impact: Engage in dialogue with the impact measurement community. Ensure that increasingly influential approaches to measuring societal impact include standards. This would support clearer communication about standards’ impacts and contribute to frameworks’ accuracy. Enhancing standards’ positive impact • Already address societal impacts during the standardisation process. We provide two tools, which may be used for this. • Improve standards’ relevance and quality in line with their ecosystems’ expectations (positioning standards relative to competing and/or complementary standards, clarity of requirements, quality of translations, withdrawing unused standards). • Need for future research in six directions: (1) Studies at the level of standard families and/or ecosystems. (2) Large-scale replication. (3) Understanding standard competition. (4) Reflecting ongoing developments in impact measurement. (5) Effects of societal change on standards’ role in society. (6) Starting from the “grand- societal challenges”. Conclusion Our work makes a novel contribution to knowledge about standards’ impacts. By doing so, we offer concrete insights, which the XXM Partners can use in communicating the benefits of standards. We also identify key factors affecting standards’ societal impacts, and offer tools and methods that are relevant for practitioners and researchers alike. The XXM Partners can use these insights in their work to further maximise standards’ value to society, and limit any potential negative effects.

OBJECTIVE The prevalence of chronic kidney disease (CKD) in the United States is 13% of the general population. Among those with CKD, diabetic nephropathy is the leading cause of end-stage renal disease. This is a retrospective study examining the effect of long-term use of dipeptidyl peptidase-4 (DPP-4) inhibitors on all-cause mortality and progression of renal disease in the veteran population. METHODS Data was extracted using the Veterans Administration Informatics and Computing Infrastructure. A large cohort of veterans diagnosed with type 2 diabetes mellitus were used to identify patients on DPP-4 inhibitors and without DPP-4 inhibitors. Groups were compared to determine the effect of DPP-4 inhibitors on the progression of CKD and all-cause mortality. Data were analyzed using SAS. RESULTS Subjects in the treatment group (n = 40 558) had baseline variables (age, body mass index, race) similar to the control group (n = 40 558). Diabetes control improved in the treatment group (HgbA1c, 8.3% [67 mmol/mol] to 7.8% [62 mmol/mol]; P < .001) but not in the control group (HgbA1c, 7.4% [57 mmol/mol] to 7.3% [56 mmol/mol]). New diagnoses of heart failure and coronary artery bypass grafts were clinically significant (odds ratios = 0.66 and 0.52). No change in progression of CKD was seen in either group. All-cause mortality was reduced by 59%. CONCLUSION We conclude that DPP-4 inhibitors are associated with a significant reduction in all-cause mortality independent of glucose control, albeit with no clear cause, including obtainable cardiovascular outcomes. Our data is consistent with prior trials in that DPP-4 inhibitors did not show a significant change in serum creatinine or microalbuminuria.

The underlying mechanisms of chronic pruritus (CP), which is often very debilitating for patients, are still not well understood. Over the past few years, peripheral and central mechanisms involving different classes of pruriceptive and nociceptive neuron (e.g., C- and Aδ-fibers), immune cells (e.g., eosinophils, basophils, Th1, Th2, and mast cells) and epithelial cells (e.g., keratinocytes) have been investigated. Based on these, numerous promising target-specific therapies are under development. In this review, we highlight the cells, key mediators, and receptors involved in itch perception and CP, and conclude by summarizing the therapies developed for these conditions.

BACKGROUND Emergency department (ED) providers are important collaborators in preventing falls for older adults because they are often the first healthcare providers to see a patient after a fall and because at-home falls are often preceded by previous ED visits. Previous work has shown that ED referrals to falls interventions can reduce the risk of an at-home fall by 38%. Screening patients at risk for a fall can be time-consuming and difficult to implement in the ED setting. Machine learning (ML) and clinical decision support (CDS) offer the potential of automating the screening process. However, it remains unclear whether automation of screening and referrals can reduce the risk of future falls among older patients. OBJECTIVE The goal of this paper to is describe a research protocol for evaluating effectiveness of an automated screening and referral intervention. These findings will inform ongoing discussions about the use of machine learning and artificial intelligence to augment medical decision making. METHODS To assess effectiveness of our program for patients receiving the falls risk intervention, our primary analysis will be to obtain referral completion rate at three different EDs. We use a quasi-experimental design known as a sharp regression discontinuity with regards to intent-to-treat, since the intervention is administered to patients whose risk score falls above some threshold. A conditional logistic regression model will be built to describe six-month fall risk at each site as a function of the intervention, patient demographics, and risk score. The odds ratio of return visit for fall and its 95% confidence interval will be estimated comparing those that identified as high risk by the ML-based CDS (ML-CDS) and those who were not but had a similar risk profile. RESULTS The ML-CDS tool under study has been implemented at two of the three EDs in our study. As of April 2023, a total of 1326 patient encounters have been flagged for providers, and 339 unique patients have been referred to the mobility and falls clinic. To date, 45 (15%) patients have scheduled an appointment with the clinic. CONCLUSIONS This study seeks to quantify the impact of an ML-CDS intervention on patient behavior and outcomes. Our end-to-end dataset allows for a more meaningful analysis of patient outcomes than other studies focused on interim outcomes, and our multi-site implementation plan will demonstrate applicability to a broad population and possibility to adapt intervention to other emergency departments and achieve similar results. Our statistical methodology, regression discontinuity design, allows for causal inference from observational data and staggered implementation strategy allows for the identification of secular trends that could affect causal association and mitigate as necessary. CLINICALTRIAL This observational quasi-experiment is registered with clinicaltrials.gov as NCT05810064

The overall survival rate of extracorporeal life support (ECLS) remains at 60%. Research and development has been slow, in part due to the lack of sophisticated experimental models. This publication introduces a dedicated rodent oxygenator (“RatOx”) and presents preliminary in vitro classification tests. The RatOx has an adaptable fiber module size for various rodent models. Gas transfer performances over the fiber module for different blood flows and fiber module sizes were tested according to DIN EN ISO 7199. At the maximum possible amount of effective fiber surface area and a blood flow of 100 mL/min, the oxygenator performance was tested to a maximum of 6.27 mL O2/min and 8.2 mL CO2/min, respectively. The priming volume for the largest fiber module is 5.4 mL, while the smallest possible configuration with a single fiber mat layer has a priming volume of 1.1 mL. The novel RatOx ECLS system has been evaluated in vitro and has demonstrated a high degree of compliance with all pre-defined functional criteria for rodent-sized animal models. We intend for the RatOx to become a standard testing platform for scientific studies on ECLS therapy and technology.

Background: Using idiographic network models in psychotherapy has been a growing area of interest. However, little is known about the perceived clinical utility of network models. The present study aims to explore therapists’ experiences with network model-based feedback within the context of the TheraNet Project. Methods: Therapists who had received network-based feedback were invited to retrospective focus groups. The focus group questions related to how participation in the study influenced the therapeutic relationship, how the networks were used, and what might improve their clinical utility. The transcribed focus groups were analyzed descriptively using qualitative content analysis. Results: Most therapists mentioned using the feedback to solidify their case concept, while fewer therapists discussed the feedback directly with the patients. Several barriers to using the feedback were discussed, as well as various suggestions for how to make it more clinically useful. Many therapists reported skepticism with regards to research in the outpatient training center in general, though they were also all pleasantly surprised by being involved, having their opinions heard, and showing a readiness to adapt research to their needs/abilities. Conclusions: This study highlights the gap between researchers’ and therapists’ perceptions about what useful feedback should look like. The TheraNet therapists’ interest in adapting the feedback and building more informative feedback systems signals a general openness to the implementation of clinically relevant research. We provide suggestions for future implementations of network-based feedback systems in the outpatient clinical training center setting.

In this paper, we report the results of three high-powered replication studies in experimental philosophy, which bear on an alleged instability of folk philosophical intuitions: the purported susceptibility of epistemic intuitions about the Truetemp case (Lehrer, Theory of knowledge. Westview Press, Boulder, 1990) to order effects. Evidence for this susceptibility was first reported by Swain et al. (Philos Phenomenol Res 76(1):138–155, 2008); further evidence was then found in two studies by Wright (Cognition 115(3):491–503. https://doi.org/10.1016/j.cognition.2010.02.003, 2010) and Weinberg et al. (Monist 95(2):200–222, 2012). These empirical results have been quite influential in the recent metaphilosophical debate about the method of cases. However, none of Swain et al.’s (2008) predictions concerning order effects with Truetemp cases could be consistently and robustly replicated in our three experiments, and it is thus at best unclear whether Truetemp intuitions are in fact unstable. So, if proponents of the negative program in experimental philosophy still want to use order effects to challenge the reliability of philosophical case judgments, they would be well advised to look elsewhere instead. In any case, given the more robust empirical evidence that we present in this paper, the metaphilosophical flurry created by Swain et al. (2008) and Wright’s (2010) influential studies looks like mere alarmism in hindsight.

The overall survival rate of extracorporeal life support (ECLS) remains at 60%. Research and development has been slow, in part due to the lack of sophisticated experimental models. This publication introduces a dedicated rodent oxygenator (“RatOx”) and presents preliminary in vitro classification tests. The RatOx has an adaptable fiber module size for various rodent models. Gas transfer performances over the fiber module for different blood flows and fiber module sizes were tested according to DIN EN ISO 7199. At the maximum possible amount of effective fiber surface area and a blood flow of 100 mL/min, the oxygenator performance was tested to a maximum of 6.27 mL O2/min and 8.2 mL CO2/min, respectively. The priming volume for the largest fiber module is 5.4 mL, while the smallest possible configuration with a single fiber mat layer has a priming volume of 1.1 mL. The novel RatOx ECLS system has been evaluated in vitro and has demonstrated a high degree of compliance with all pre-defined functional criteria for rodent-sized animal models. We intend for the RatOx to become a standard testing platform for scientific studies on ECLS therapy and technology.

Mosquitoes have profoundly affected human history and continue to threaten human health through the transmission of a diverse array of viruses and pathogens. Because mosquitoes are also highly diverse and globally widespread, their phylogeny has remained either little known or difficult to discern. Here, we used phylogenomic analysis of 709 orthologous nuclear gene sequences from 256 mosquito species to produce a strongly supported phylogeny that resolves the position of the major disease vector species and the major mosquito lineages. Our tree supports an origin of mosquitoes in the early Triassic (~217 mya) with species diversification and host-use patterns within major lineages coinciding in earth history both with major geologic events and with the diversification of vertebrate classes.

Biallelic loss-of-function variants in SMPD4 cause a rare and severe neurodevelopmental disorder with progressive congenital microcephaly and early death. SMPD4 encodes a sphingomyelinase that hydrolyses sphingomyelin into ceramide at neutral pH and can thereby affect membrane lipid homeostasis. SMPD4 localizes to the membranes of the endoplasmic reticulum and nuclear envelope and interacts with nuclear pore complexes (NPC). We refine the clinical phenotype of loss-of-function SMPD4 variants by describing five individuals from three unrelated families with longitudinal data due to prolonged survival. All individuals surviving beyond infancy developed insulin-dependent diabetes, besides presenting with a severe neurodevelopmental disorder and microcephaly, making diabetes one of the most frequent age-dependent non-cerebral abnormalities. We studied the function of SMPD4 at the cellular and organ levels. Knock-down of SMPD4 in human neural stem cells causes reduced proliferation rates and prolonged mitosis. Moreover, SMPD4 depletion results in abnormal nuclear envelope breakdown and reassembly during mitosis and decreased post-mitotic NPC insertion. Fibroblasts from affected individuals show deficient SMPD4-specific neutral sphingomyelinase activity, without changing (sub)cellular lipidome fractions, which suggests a local function of SMPD4 on the nuclear envelope. In embryonic mouse brain, knockdown of Smpd4 impairs cortical progenitor proliferation and induces premature differentiation by altering the balance between neurogenic and proliferative progenitor cell divisions. We hypothesize that, in individuals with SMPD4-related disease, nuclear envelope bending, which is needed to insert NPCs in the nuclear envelope, is impaired in the absence of SMPD4 and interferes with cerebral corticogenesis and survival of pancreatic beta cells.

Background Prurigo nodularis (PN) is a debilitating, difficult-to-treat, intensely pruritic, chronic inflammatory skin disease characterized by hyperkeratotic skin nodules. The pathogenesis of PN is not well understood but is believed to involve cross talk between sensory nerve fibers, immune cells, and the epidermis. It is centered around the neuroimmune cytokine IL-31, driving an intractable itch–scratch cycle. Objective We sought to provide a comprehensive view of the transcriptomic changes in PN skin and characterize the mechanism of action of the anti–IL-31 receptor inhibitor nemolizumab. Method RNA sequencing of biopsy samples obtained from a cohort of patients treated with the anti–IL-31 receptor inhibitor nemolizumab and taken at baseline and week 12. Generation and integration of patient data with RNA-Seq data generated from reconstructed human epidermis stimulated with IL-31 and other proinflammatory cytokines. Results Our results demonstrate that nemolizumab effectively decreases IL-31 responses in PN skin, leading to effective suppression of downstream inflammatory responses including TH2/IL-13 and TH17/IL-17 responses. This is accompanied by decreased keratinocyte proliferation and normalization of epidermal differentiation and function. Furthermore, our results demonstrate how transcriptomic changes associated with nemolizumab treatment correlate with improvement in lesions, pruritus, stabilization of extracellular matrix remodeling, and processes associated with cutaneous nerve function. Conclusion These data demonstrate a broad response to IL-31 receptor inhibition with nemolizumab and confirm the critical upstream role of IL-31 in PN pathogenesis.

Objective This study investigates the rates of obesity-related cancers in patients undergoing vertical sleeve gastrectomy (VSG), Roux-en-Y gastric bypass (RYGB), or no surgical intervention. Summary background data Obesity has been previously associated with increased rates of cancers; however, weight loss surgeries have not been explored to demonstrate their potential risk reduction impact. Methods Patients meeting bariatric eligibility criteria between January 2010 and December 2018 were identified. Exact 1:1:1 matching based on baseline patient demographics and comorbidities was used to create three groups with identical covariates: patients undergoing VSG, RYGB, and no surgery. Results A total of 28,908 bariatric-eligible patients equally split into patients undergoing VSG (n = 9,636, 33.3%), RYGB (n = 9,636, 33.3%), and those with no surgical intervention (n = 9,636, 33.3%). Bariatric-eligible patients that did not undergo surgical intervention had significantly higher rates and odds of developing numerous cancer types included in our study when compared to either surgical cohorts, with any cancer type (4.61%), uterine (0.86%), colorectal (0.57%), and lung cancers (0.50%) being most common. Individuals undergoing RYGB were significantly less likely to develop colorectal cancer compared to patients without any surgical intervention (OR 0.47, 95% CI 0.30-0.75). Additionally, those undergoing VSG were significantly less likely to develop lung cancer than the bariatric eligible no surgery cohort (OR 0.42, 95% CI 0.25-0.70). Conclusion Postoperative rates of any cancer type, lung, ovarian, and uterine cancer were significantly lower in obese patients undergoing either vertical sleeve gastrectomy (VSG) or Roux-en-Y gastric bypass (RYGB) compared to bariatric-eligible patients without any surgical intervention.

Artificial membrane lungs are composed of hollow fiber membranes. Blood flows with low velocities in the membrane bundle, forming a laminar boundary layer near the membrane surfaces that limits gas transfer. Passive blood mixing within the fiber array is utilized to overcome this limitation. Nevertheless, it is unclear to which extent blood mixing and fiber configuration contribute to the performance of membrane oxygenators. This study aims to evaluate the effect of fiber configuration and replacement on the gas exchange performance of membrane oxygenators to contribute to a better understanding of the influence of blood mixing to gas transfer and the mechanisms of gas exchange in blood. Furthermore, designs in which hollow fibers of different functions could be combined in highly integrated membrane lungs are provided. We analyzed the gas transfer performance of membrane oxygenators in a perpendicular configuration with 100%, 75%, or 50% of fibers open, and in a crossed configuration with 100% or 67% of fibers open. 95%–100% of the oxygen transfer of a fully open oxygenator could be maintained in our prototypes with 25% of gas exchange fibers closed in a perpendicular configuration, indicating that several fibers contributed to gas exchange by mixing the blood flow. Closing fibers in a perpendicular configuration resulted in a lower decrease in oxygen transfer. This study contributes to the development of novel membrane oxygenators integrating fibers of different functionalities (e.g. oxygenation and dialysis) maintaining high gas exchange efficiency.

Forecasting spielt eine zunehmend wichtige Rolle für Unternehmen. Die Qualität von Forecasts ist dabei aber häufig von Unsicherheit sowie unterschiedlichen Interessen geprägt. In diesem Beitrag diskutieren wir, wie in dezentralisierten Unternehmen Business Unit Controller in Interaktionen mit dem Corporate Controlling dazu beitragen können, dass lokale Forecasts als glaubwürdig akzeptiert werden.

ACS catalysis 12, 3256 - 3268 (2022). doi:10.1021/acscatal.1c05169, Co oxides and oxyhydroxides have been studied extensively in the past as promising electrocatalysts for the oxygen evolution reaction (OER) in neutral to alkaline media. Earlier studies showed the formation of an ultrathin CoO$_x$(OH)$_y$ skin layer on Co$_3$O$_4$ at potentials above 1.15 V vs reversible hydrogen electrode (RHE), but the precise influence of this skin layer on the OER reactivity is still under debate. We present here a systematic study of epitaxial spinel-type Co$_3$O$_4$ films with defined (111) orientation, prepared on different substrates by electrodeposition or physical vapor deposition. The OER overpotential of these samples may vary up to 120 mV, corresponding to two orders of magnitude differences in current density, which cannot be accounted for by differences in the electrochemically active surface area. We demonstrate by a careful analysis of operando surface X-ray diffraction measurements that these differences are clearly correlated with the average thickness of the skin layer. The OER reactivity increases with the amount of formed skin layer, indicating that the entire three-dimensional skin layer is an OER-active interphase. Furthermore, a scaling relationship between the reaction centers in the skin layer and the OER activity is established. It suggests that two lattice sites are involved in the OER mechanism., Published by ACS, Washington, DC

Am 10. April 1912 ging Elisabeth Walton Allen an Bord der „Titanic“, um ihr Hab und Gut nach England zu holen. Eines Nachts wurde sie von ihrer aufgelösten Tante geweckt, deren Kajüte unter Wasser stand. Wie steht es um Elisabeths Chancen und hätte man selbst das Unglück damals überlebt? Das Titanic-Orakel ist eine algorithmusbasierte App, die entsprechende Prognosen aufstellt und im Rahmen des Kurses „Data Science“ am Department Information der HAW Hamburg entstanden ist. Dieser Beitrag zeigt Schritt für Schritt, wie die App unter Verwendung freier Software entwickelt wurde. Code und Daten werden zur Nachnutzung bereitgestellt.

Theorists in the debate about how to define lying disagree whether it is possible to lie with pictures. At the same time, they agree that definitions of lying should be consistent with how laypersons use the term ‘lie’. This calls for an empirical perspective on whether ordinary usage allows for pictorial lies. The present paper provides some initial data on this question by reporting an exper-iment with 623 participants investigating layperson judgements about cases of insincere linguistic and pictorial communication. The results indicate that ordi-nary usage of ‘lie’ does permit pictorial lies.

Although aligning care with patient goals is fundamental to critical care, this process is often delayed and leads to conflict among patients, families, and intensive care unit (ICU) teams. Interprofessional collaboration within ICU teams is an opportunity to improve goal-aligned care, yet this collaboration is poorly understood. A better understanding of how ICU team members work together to provide goal-aligned care may identify new strategies for improvement.Transactive memory systems is a theory of group mind that explains how high-performing teams use a shared memory and collective cognition. We applied this theory to characterize the process of interprofessional collaboration within ICU teams and its relationship with goal-aligned care.We conducted a secondary analysis of focus group (n = 10) and semi-structured interview (n = 8) transcripts, gathered during a parent study at two academic medical centers on the process of ICU care delivery in acute respiratory failure. Participants (N = 70) included interprofessional ICU and palliative care team members, surrogates, and patient survivors. We used directed content analysis, applying transactive memory systems theory and its major components (specialization, coordination, credibility) to examine ICU team collaboration.Participants described each ICU profession as having a specialized role in aligning care with patient goals. Different professions have different opportunities to gather knowledge about patient goals and priorities, which results in dispersion of this knowledge among different team members. To share and use this dispersed knowledge, ICU teams rely on an informal coordination process and "side conversations." This process is a workaround for formal channels (e.g., health records, interprofessional rounds) that do not adequately convey knowledge about patient goals. This informal process does not occur if team members are discouraged from asserting their knowledge because of hierarchy or lack of psychological safety. Conversely, coordination succeeds when team members recognize each other as credible sources of valued knowledge.We found that ICU team members work together to align care with patient goals and priorities, using transactive memory systems. The successful function of these systems can be disrupted or promoted by ICU organizational and cultural factors, which are potential targets for efforts to increase goal-aligned care.

Towards the establishment of a long-term lung-assist device to be used both as a bridge and as an alternative to lung transplantation according to final destination therapy, we develop the biohybrid lung (BHL) on the technical basis of contemporary extracorporeal membrane oxygenation (ECMO). Here, to overcome the significant drawbacks of ECMO, in particular the missing hemocompatibility of the artificial surfaces, all blood-contacting areas need to be endothelialized sufficiently. In continuation of our recent accomplishments, demonstrating the feasibility of establishing a physiological acting endothelial cell (EC) monolayer on the hollow fiber membranes (HFMs) of the ECMO in vitro, the next step towards BHL translation is the endothelialization of the complete oxygenator, consisting of HFMs and the surrounding housing. Therefore, we assessed EC seeding inside our model oxygenator (MOx), which simulated the conditions in the assembled HFM oxygenators in order to identify the most important factors influencing efficient endothelialization, such as cell seeding density, cell distribution, incubation time and culture medium consumption. Overall, upon adjusting the concentration of infused ECs to 15.2 × 104/cm2 and ensuring optimal dispersion of cells in the MOx, viable and confluent EC monolayers formed on all relevant surfaces within 24 h, even though they comprised different polymers, i.e., the fibronectin-coated HFMs and the polysulfone MOx housing. Periodic medium change ensured monolayer survival and negligible apoptosis rates comparable to the reference within the assembled system. By means of these results, revealing essential implications for BHL development, their clinical translation is coming one step closer to reality.

Hintergrund: Sarkopenie umfasst den altersbedingten oder mit systemischen Krankheiten assoziierten Abbau von Muskelkraft, Muskelmasse und Muskelfunktionen und geht mit einem erhöhten Risiko für Stürze einher. Ziele: Die Diagnostik von Sarkopenie erfordert Referenzwerte für Balance, die Identifikation sarkopenischer Veränderungen sowie Risikovorhersagen für Stürze. Methoden: In einer gesunden Studienkohorte wird die Balancefähigkeit mittels Posturographie auf einem Leonardo Mechanograph® erhoben und alters- und geschlechtsspezifische Referenzwerte für Variablen der posturalen Kontrolle ermittelt. In einer längsschnittlichen Beobachtung dieser Studienkohorte wird der Abbau der Muskelmasse mittels DXA, die Muskelkraft mit einem Handdynamometer und die Muskelleistung auf einem Leonardo Mechanograph® bei Zweibeinsprüngen und dem Chair Rise Test untersucht. Veränderungen werden mit gepaarten t-Tests nach Altersgruppe und Geschlecht analysiert. Varianzanalysen und Dunnett-Tests ermitteln Unterschiede zwischen den Gruppen. In einer Kohorte mit rheumatoider Arthritis werden Assoziationen von Muskelfunktionen, Sarkopenie und prospektiven Stürzen untersucht. Zusätzlich zu den oben genannten Tests werden Gehgeschwindigkeit, SPPB und FICSIT-4 erhoben. Rheumaspezifische Messwerte wie HAQ, Krankheitsdauer und DAS28(CRP) werden erfasst. Sarkopenische Veränderungen werden gemäß der EWGSOP2 und der FNIH bestimmt. Die Teilnehmenden dokumentieren über ein Jahr Stürze in einem Sturztagebuch und berichten diese quartalsweise. Zur Berechnung der Assoziationen mit Sturz finden univariate und multiple logistische Regressionen Anwendung. Ergebnisse: Referenzwerte für Variablen der posturalen Kontrolle stehen für Frauen und Männer zwischen 20 und 86 Jahren in 5-Jahres-Schritten zur Verfügung. Der Abbau von Muskelleistung während Zweibeinsprüngen beginnt in der jüngsten Altersgruppe von 20-39 Jahren (-1,22 % pro Jahr bei Frauen, -1,51 % pro Jahr bei Männern, p, Background: Sarcopenia refers to the loss of muscle strength, muscle mass and neuromuscular functions due to ageing or systemic diseases. Early diagnosis is important to predict risks and prevent adverse outcomes such as falls. Objectives: Sarcopenia screening requires reference values of postural control and indicators for early identification of sarcopenic changes as well as prediction models for falls. Methods: In a healthy study sample postural control is assessed by means of posturography on a Leonardo Mechanograph® and age- and sex-specific reference values for variables of postural control are determined. In a longitudinal observation of this study cohort, the loss of muscle mass is measured using DXA, muscle strength by hand dynamometer and muscle power on a Leonardo Mechanograph® during two-leg jumps (2LJ) and the chair rise test. Changes are analysed with paired t-tests by age group and sex. Differences between groups are calculated using analyses of variance and Dunnett’s tests. In a one-year prospective study of patients with rheumatoid arthritis, associations between neuromuscular variables, sarcopenia and falls are evaluated. At baseline, muscle mass, strength and power are collected. Further, physical function tests such as gait speed, SPPB and FICSIT-4 are assessed. Rheumatism-specific measures including HAQ, disease duration and DAS28CRP are evaluated. Sarcopenic changes are determined according to established definitions by the EWGSOP2 and FNIH. Falls are reported in quarterly falls diaries. Univariate and multiple logistic regression analyses are used to calculate associations with falls. Results: Reference values for variables of postural control are reported for men and women in five-year bands of age between 20 and 86 years. Muscle power measured during 2LJ shows the earliest and highest rate of decline in the youngest age group of 20-39 years in both sexes (-1.22 % per year in women, -1.51 % per year in men, p

In this paper we completely solve the problem of finding the (upper) approximation order with respect to the Kolmogorov, Gel'fand, and linear widths for the embedding of the Sobolev spaces $W^{\alpha,p}$ and $W_{0}^{\alpha,p}$ in the euclidian measure spaces $L_{\nu}^{q}$ for an arbitrary Borel probability measure $\nu$ with support contained in the open $m$-dimensional unit cube and for all possible choices of $1\leq p,q\leq\infty$. We will determine the exact values for the various upper approximation orders in terms of the $L^{q}$-spectrum of $\nu$ only and finally give sufficient conditions imposed on the regularity of the $L^{q}$-spectrum for the approximation orders to exist. We also elucidate some intrinsic connections between the concept of approximation order and the fractal geometric notion of the upper and lower Minkowski dimension of the support of $\nu$., Comment: 23 pages, 2 figures

Ziel unserer Forschung ist die Replikation der Studie „Male Bias in Language? Establishing the Efficiency of Three Different Gender-Fair Language Strategies” von Lindqvist, Renström und Sendén (2018). Sie behandelt, inwiefern unterschiedliche Sprachstrategien einen Einfluss auf die Interpretation und Wahrnehmung des Geschlechts üben und die Geschlechter unter Umständen unterschiedlich stark repräsentieren. Im Hinblick auf die Wichtigkeit inklusiver Sprache leiten sich praktische Implikationen ab, die durch die Replikationsstudie eine weitere Legitimation erfahren könnten. Es wird untersucht, wie unterschiedliche Strategien genderneutraler Personenbeschreibungen sich auf den Male Bias auswirken.