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Through a multiple-case study of seven German providers, we explore the architecture of commercial offerings of consumer experiences, such as wine-tastings, craft workshops, or wellness activities, which have both digital and physical components. Physical-digital experiences offer participants an opportunity to encounter many different sensations of an experience, as not all (e.g. taste, smell, touch) can be converted to digital form and not all are possible to experience physically (e.g. visual depictions of distant lands). Our empirical study shows that experience providers combine both physical and digital offering architectures by augmenting, substituting, porting, and excluding physical and digital components, a process that changes the value these experiences create for consumers and provides new means by which providers capture value from these offerings. We develop a theoretical model that explains value creation and value capture through the design and provision of physical-digital experiential consumer offerings that leverage physical-digital hybridity at multiple levels to enhance existing or generate new value pathways. [ABSTRACT FROM AUTHOR]

Introduction: This article examines the productivity of dissonance in the development of alternative crisis intervention methods, using the German example of the "Open Dialogue Leipzige.V." The research provides detailed insights into the development of the association and the adaptation of the OD approach to local circumstances. Methods: The presentation is based on a participatory research process, primarily processing interview data using the Grounded Theory Method. It analyzes the specific practices of implementing Open Dialogue within the association and the organizational and contextual conditions corresponding with it. Results: Despite the challenges accompanying the introduction and sustainability of Open Dialogue in the German healthcare system, the organizational structure of the association—characterized by grassroots democratic principles and a community driven by a strong willingness to change—enables a successful application of Open Dialogue principles. Discussion: The article critically illuminates how engagement, professionalization, and participatory learning mutually influence each other through the organizational form of the association, bringing forth an innovative crisis intervention that could potentially serve as a model for other contexts. [ABSTRACT FROM AUTHOR]

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Entrepreneurial grit, defined as passion and perseverance for long-term goals, has repeatedly been linked to higher venture performance. In this paper, we theorize that higher levels of grit may also lead to more nonfinancial success and stronger societal impact for entrepreneurs and that anxiety is a negative moderator in these relationships. We test our model among 1,398 German entrepreneurs in a broad range of industries and find support for our hypotheses. We contribute by uncovering grit as a novel determinant for the nonfinancial success measures of personal fulfillment and workplace relationships, as well as for societal impact, and by shedding light on the role of negative emotions as attenuators in these relationships. [ABSTRACT FROM AUTHOR]

Background: The traditional binary classification of diabetes into Type 1 and Type 2 fails to capture the heterogeneity among diabetes patients. This study aims to identify and characterize diabetes subtypes within the German FoCus cohort, using the ANDIS cohort's classification framework, and to explore subtype-specific variations in metabolic markers, gut microbiota, lifestyle, social factors, and comorbidities. Methods: We utilized data from 416 participants (208 with diabetes and 208 matched metabolically healthy controls) from the German FoCus cohort. Participants were classified into five subtypes: severe autoimmune diabetes (SAID)-like, severe insulin-deficient diabetes (SIDD)-like, severe insulin-resistant diabetes (SIRD)-like, mild obesity-related diabetes (MOD)-like, and mild age-related diabetes (MARD)-like. Comprehensive characterization included anthropometric measurements, dietary and physical activity questionnaires, blood biomarker analysis, and gut microbiota profiling. Results: The subtype distribution in the FoCus cohort accounted to SAID-like: 2.84%, SIDD-like: 30.81%, SIRD-like: 32.23%, MOD-like: 17.54%, MARD-like: 16.59%. Of interest, inflammatory markers (C-reactive protein (CRP) and Interleukin-6 (IL-6)) and glucagon-like peptide-1 (GLP-1) levels were similarly elevated across all subtypes compared to controls, indicating common aspects in Type 2 diabetes molecular pathology despite different clinical phenotypes. While the gut microbiota and dietary patterns only showed minor differences, smoking status, sleep duration, physical activity and psychological aspects varied significantly between the subtypes. In addition, we observed a lower educational status especially for SIDD-like and SIRD-like groups, which should be considered in establishing future diabetes-related patient education programs. In respect to the development of cardio-metabolic comorbidities, we observe not only significant differences in the presence of the diseases but also for their age-of onset, highlighting the need for early preventive intervention strategies. Conclusions: The study validates the ANDIS classification framework's applicability not only at the time point of manifestation but also in cohorts with pre-existing diabetes. While we did not find major differences regarding the classical metabolic, microbial and nutritional parameters, we identified several significant associations with lifestyle factors. Our findings underscore the importance of personalized, subtype-specific therapies not solely focusing on anthropometric and laboratory markers but comprehensively addressing the patient's own personality and situation of life. [ABSTRACT FROM AUTHOR]

Network models are widely applied to describe connectivity and flow in diverse systems. In contrast, the fact that many connected systems move through space as the result of dynamic restructuring has received little attention. Therefore, we introduce the concept of 'traveling networks', and we analyze a tree-based model where the leaves are stochastically manipulated to grow, branch, and retract. We derive how these restructuring rates determine key attributes of network structure and motion, enabling a compact understanding of higher-level network behaviors such as multiscale search. These networks self-organize to the critical point between exponential growth and decay, allowing them to detect and respond to environmental signals with high sensitivity. Finally, we demonstrate how the traveling network concept applies to real-world systems, such as slime molds, the actin cytoskeleton, and human organizations, exemplifying how restructuring rules and rates in general can select for versatile search strategies in real or abstract spaces. Complex networks are relevant to wide range of areas, from biology to social sciences and economics, however the aspect that networks can move through space has not been elaborated. The authors propose a concept of traveling networks that can dynamically restructure themselves in space and perform search tasks. [ABSTRACT FROM AUTHOR]

Introduction: Data science training has the potential to propel environmental health research efforts into territories that remain untapped and holds immense promise to change our understanding of human health and the environment. Though data science training resources are expanding, they are still limited in terms of public accessibility, user friendliness, breadth of content, tangibility through real-world examples, and applicability to the field of environmental health science. Methods: To fill this gap, we developed an environmental health data science training resource, the inTelligence And Machine lEarning (TAME) Toolkit, version 2.0 (TAME 2.0). Results: TAME 2.0 is a publicly available website that includes training modules organized into seven chapters. Training topics were prioritized based upon ongoing engagement with trainees, professional colleague feedback, and emerging topics in the field of environmental health research (e.g., artificial intelligence and machine learning). TAME 2.0 is a significant expansion upon the original TAME training resource pilot. TAME 2.0 specifically includes training organized into the following chapters: (1) Data management to enable scientific collaborations; (2) Coding in R; (3) Basics of data analysis and visualizations; (4) Converting wet lab data into dry lab analyses; (5) Machine learning; (6) Applications in toxicology and exposure science; and (7) Environmental health database mining. Also new to TAME 2.0 are "Test Your Knowledge" activities at the end of each training module, in which participants are asked additional module-specific questions about the example datasets and apply skills introduced in the module to answer them. TAME 2.0 effectiveness was evaluated via participant surveys during graduate-level workshops and coursework, as well as undergraduate-level summer research training events, and suggested edits were incorporated while overall metrics of effectiveness were quantified. Discussion: Collectively, TAME 2.0 now serves as a valuable resource to address the growing demand of increased data science training in environmental health research. TAME 2.0 is publicly available at: https://uncsrp.github.io/TAME2/. [ABSTRACT FROM AUTHOR]

The INTENTAS project aims to develop an atomic sensor utilizing entangled Bose-Einstein condensates (BECs) in a microgravity environment. This key achievement is necessary to advance the capability for measurements that benefit from both entanglement-enhanced sensitivities and extended interrogation times. The project addresses significant challenges related to size, weight, and power management (SWaP) specific to the experimental platform at the Einstein-Elevator in Hannover. The design ensures a low-noise environment essential for the creation and detection of entanglement. Additionally, the apparatus features an innovative approach to the all-optical creation of BECs, providing a flexible system for various configurations and meeting the requirements for rapid turnaround times. Successful demonstration of this technology in the Einstein-Elevator will pave the way for a future deployment in space, where its potential applications will unlock high-precision quantum sensing. [ABSTRACT FROM AUTHOR]

Rho-associated kinase (ROCK) inhibitors have gained popularity as novel treatment options in the management of glaucoma and corneal endothelial disorders. Among the various ocular side effects, reticular corneal epithelial edema has been most frequently reported, mainly after treatment with netarsudil. To explain the potential mechanisms, we comparatively analyzed the effects of ripasudil and netarsudil on corneal endothelial and epithelial function in vitro. Primary human corneal endothelial and epithelial cells were incubated with netarsudil dihydrochloride and ripasudil hydrochloride dihydrate for up to 7 days. Gene and protein expression analyses were performed by real-time PCR and immunocytochemistry. Functional assays assessed the cell migration, proliferation, viability, Na+/K+-ATPase activity, transcellular electrical resistance, and FITC–dextran permeability. Reticular bullous corneal epithelial edema was observed in a patient following netarsudil 0.02%/latanoprost 0.005% ophthalmic solution (Roclanda®) for elevated intraocular pressure. In the subsequent laboratory analyses, both netarsudil and ripasudil were found to improve the corneal endothelial pump and barrier function, but they showed differential effects on corneal epithelial cells. Whereas ripasudil improved the epithelial barrier function by upregulating major components of the tight and adherens junctions and reducing paracellular permeability, netarsudil had no or even adverse effects on the epithelial barrier properties by downregulating the expression levels of cell-junction-associated genes. The expression changes normalized after discontinuation of ROCK inhibitors. The findings support the concept that ROCK inhibitors can act as a double-edged sword by having beneficial effects on corneal endothelial cells and adverse effects on epithelial cells. [ABSTRACT FROM AUTHOR]

Background Urinary tract infection (UTI) is a common disease with a significant risk of relapse. Deliberate bladder colonization with asymptomatic Escherichia coli is being explored as a potential strategy to fend off invading uropathogens, thereby mitigating the risk of symptomatic UTI. Currently, one major obstacle is the low success rates for achieving persistent bladder colonization with asymptomatic bacteria and experimental challenge studies are lacking. Here, we assessed the influence of an indwelling bladder catheter on the ability of asymptomatic E. coli to colonize the bladder and to assess the protective efficacy of such colonization against experimental UTI with uropathogenic E. coli. Methods Pigs with or without indwelling bladder catheters were experimentally inoculated with the asymptomatic E. coli strain 83972 and subsequently challenged by inoculation with a uropathogenic E. coli isolate, UTI89. The animals were monitored with regular urine and blood samples and bladders and kidneys were harvested at termination. Results All pigs with indwelling catheters were colonized by E. coli 83972 in response to inoculation, compared to pigs without catheters in which only 1 of 8 animals were colonized. When removing the catheter, E. coli 83972 were spontaneously cleared. Colonization with E. coli 83972 prevented experimental infection in 50% of animals, whereas all control animals became infected. Conclusions The presence of indwelling bladder catheters strongly facilitates the colonization of E. coli 83972, indicating that individuals with catheters may be particularly suited for receiving this treatment. The research supports prophylactic colonization with E. coli 83972 as a potential strategy to reduce the risk of UTIs. [ABSTRACT FROM AUTHOR]

Alkenylbenzenes occur as natural constituents in a variety of edible plants, in particular those herbs and spices used to give a distinctive flavor to a range of food and feed items. Some alkenylbenzenes with relevance for food, such as estragole and methyleugenol, are known to be genotoxic and carcinogenic in rodents. However, the genotoxic and carcinogenic potential of other structurally related alkenylbenzenes, such as myristicin and elemicin, is still under scientific discussion. Here, we investigated the potential of myristicin and elemicin to induce micronuclei (MN) in V79 cells in comparison to that of estragole and methyleugenol. In addition, we determined the impact of these alkenylbenzenes on cell viability and on the induction of apoptosis and necrosis. All tested alkenylbenzenes affected cell viability in a concentration-dependent manner, albeit to varying degrees. Regarding MN formation, elemicin induced a weak but statistically significant response at 100 µM and 500 µM in the absence of an exogenous metabolizing system (S9 mix). Negative results were obtained for estragole and myristicin at the highest tested non-cytotoxic concentration of 10 µM and 100 µM, respectively. For methyleugenol, the MN assay results were considered equivocal, since the observed change in MN induction was rather small and not supported by a concentration-related trend. These findings indicate that traditional in vitro test systems utilizing exogenous metabolizing systems have limited explanatory power with regard to the genotoxic potential of alkenylbenzenes. [ABSTRACT FROM AUTHOR]

The nonlinear interaction between the tip of a scanning probe microscope (SPM) and a sample is manifested in the emergence of bifurcations and unstable branches in the frequency response of a driven cantilever. While extensively investigated theoretically, exploring the unstable branch in an actual SPM experiment is lacking so far, reflecting the broader challenge in studying mechanical nanojunction oscillators under strongly varying external forces. Here we demonstrate experimental tracking of unstable periodic orbits between two saddle-node bifurcation points in the attractive regime, revealing the full set of stationary oscillatory states. This is achieved by a minimally invasive control scheme based on fast adaptive phase extraction and Fourier discretisation of the tip dynamics. Stabilization of unstable branches of oscillating AFM cantilevers opens avenues for novel experimental modes, potentially enabling ultrasensitive surface detection at considerably large amplitudes with minimal tip-surface interaction, new insights in tip-surface interaction mechanisms, as well as new AFM modes enabling arbitrary setpoint choice while inherently avoiding discontinuities. Unstable dynamic states are of technological importance, however, increasingly smaller systems, down to the nanoscale, are challenging to control due to fast time constants. In this work, the authors present an easy to implement way of accessing unstable branches of an oscillating microcantilever tip in the vicinity of a surface and explore possible applications in the context of Scanning Force Microscopy. [ABSTRACT FROM AUTHOR]

Adequate fluid therapy is crucial to maintain organ function after burn trauma. Major burns lead to a systemic response with fluid loss and cardiac dysfunction. To guide fluid therapy, measurement of cardiac pre- and afterload is helpful. Whereas cardiac function is usually measured after admission to intensive care unit (ICU), in this study, hemodynamic monitoring was performed directly after arrival at hospital. We conducted a prospective cohort study with inclusion of 19 patients (male/female 13/6, 55 ± 18 years, mean total body surface area 36 ± 19%). Arterial waveform analysis (PulsioFlexProAqt®, Getinge) was implemented immediately after admission to hospital to measure cardiac pre- and afterload and to guide resuscitation therapy. Cardiac parameters 3.75 (2.67-6.0) h after trauma were normal regarding cardiac index (3.45 ± 0.82) L/min/m², systemic vascular resistance index (1749 ± 533) dyn sec/cm5 m2, and stroke volume (SV; 80 ± 20) mL. Stroke volume variation (SVV) was increased (21 ± 7) % and associated with mortality (mean SVV survivors vs nonsurvivors 18.92 (±6.37) % vs 27.6 (±5.68) %, P =.017). Stroke volume was associated with mortality at the time of ICU-admission (mean SV survivors vs nonsurvivors 90 (±20) mL vs 50 (±0) mL, P =.004). Changes after volume challenge were significant for SVV (24 ± 9 vs19 ± 8%, P =.01) and SV (68 ± 24 vs 76 ± 26 mL, P =.03). We described association of SVV and SV with survival of severely burned patients in an observational study. This indicates high valence of those parameters in the early postburn period. The use of an autocalibrated device enables a very early monitoring of parameters relevant to burn shock survival. [ABSTRACT FROM AUTHOR]

This study evaluates the Dual Language Program (DLP) implemented at a Title I public school in Baltimore City during the 2019–2020 and 2020–2021 school years. Building on previous research, the DLP's implementation, sustainability, and effects on students' learning outcomes were examined. Utilizing a mixed-methods approach, the study's second phase included participants from the school's mainstream, English-only program (MP), enriching the overall understanding of the school community's perception of the program. Data were collected through surveys, classroom observations, and standardized assessments—the DIBELS and the iReady Diagnostic assessments. Findings showed challenges with curriculum standardization and prevalent misconceptions about bilingualism. Nevertheless, the program's successes were evident in DLP students' enhanced engagement, parental involvement, and community support. Despite the challenges of the COVID-19 pandemic, the DLP demonstrated its capacity for scaleability and sustainability. During the 2020–2021 school year, regardless of virtual learning, DLP students not only maintained but, in the case of Cohort 1, showed greater growth in reading skills compared to MP students, with Cohort 3 DLP students improving to reach statistically similar performance levels to their MP peers. Findings indicate that the DLP has the potential to serve as a sustainable educational program, fostering both dual language proficiency and academic outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Equine atypical myopathy is a severe intoxication caused by protoxins synthesised by certain maple trees, notably sycamore maple (Acer pseudoplatanus). These protoxins are activated into harmful toxins that disrupt lipid metabolism by inhibiting specific steps of fatty acid β-oxidation, leading to the accumulation of acylcarnitines in the blood. This activation process is catalysed mainly by specific mitochondrial enzymes, which are also present in some bacteria. Horses grazing in close proximity to affected animals have shown differences in their faecal microbiota composition, suggesting that the role of gut microbiota in atypical myopathy could be more substantial than previously understood. Recently, blood analyses have demonstrated the existence of subclinical cases among these cograzers. The present study compares the faecal bacteria of horses affected by atypical myopathy, their cograzers, and a group of toxin-free horses serving as a control group. Results show significant differences in faecal bacterial diversity and composition between groups, particularly for certain bacterial genera. Additionally, blood levels of specific compounds appear to be associated with these bacterial changes. The theoretical presence of the enzymes involved in the protoxin activation process was also studied. These results highlight the importance of comprehensively studying intestinal microbiota to better understand its role in this generally fatal poisoning. Hypoglycin A and methylenecyclopropylglycine are protoxins responsible for atypical myopathy in equids. These protoxins are converted into toxins that inhibit fatty acid β-oxidation, leading to blood accumulation of acylcarnitines and toxin conjugates, such as methylenecyclopropylacetyl-carnitine. The enzymes involved in this activation are also present in some prokaryotic cells, raising questions about the potential role of intestinal microbiota in the development of intoxication. Differences have been noted between the faecal microbiota of cograzers and atypical myopathy-affected horses. However, recent blood acylcarnitines profiling revealed subclinical cases among cograzers, challenging their status as a control group. This study investigates the faecal microbiota of horses clinically affected by atypical myopathy, their cograzers, and a control group of toxin-free horses while analysing correlations between microbiota composition and blood parameters. Faecal samples were analysed using 16S amplicon sequencing, revealing significant differences in α-diversity, evenness, and β-diversity. Notable differences were found between several genera, especially Clostridia_ge, Bacteria_ge, Firmicutes_ge, Fibrobacter, and NK4A214_group. Blood levels of methylenecyclopropylacetyl-carnitine and C14:1 correlated with variations in faecal microbial composition. The theoretical presence of enzymes in bacterial populations was also investigated. These results underscore the critical need to investigate the potential role of intestinal microbiota in this poisoning and may provide insights for developing prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to assess the initial experience, technical success, and clinical benefit of AneuFix (TripleMed, Geleen, the Netherlands), a novel biocompatible and non-inflammatory elastomer that is directly injected into the aneurysm sac by a translumbar puncture in patients with a type II endoleak and a growing aneurysm. Materials and Methods: A multicenter, prospective, pivotal study was conducted (ClinicalTrials.gov:NCT02487290). Patients with a type II endoleak and aneurysm growth (>5 mm) were included. Patients with a patent inferior mesenteric artery connected to the endoleak were excluded for initial safety reasons. The endoleak cavity was translumbar punctured with cone-beam computed tomography (CT) and software guidance. Angiography of the endoleak was performed, all lumbar arteries connected to the endoleak were visualized, and AneuFix elastomer was injected into the endoleak cavity and short segment of the lumbar arteries. The primary endpoint was technical success, defined as successful filling of the endoleak cavity with computed tomography angiography (CTA) assessment within 24 hours. Secondary endpoints were clinical success defined as the absence of abdominal aortic aneurysm (AAA) growth at 6 months on CTA, serious adverse events, re-interventions, and neurological abnormalities. Computed tomography angiography follow-up was performed at 1 day and at 3, 6, and 12 months. This analysis reports the initial experience of the first 10 patients treated with AneuFix. Results: Seven men and 3 women with a median age of 78 years (interquartile range (IQR), 74-84) were treated. Median aneurysm growth after endovascular aneurysm repair (EVAR) was 19 mm (IQR, 8–23 mm). Technical success was 100%; it was possible to puncture the endoleak cavity of all treated patients and to inject AneuFix. Clinical success at 6 months was 90%. One patient showed 5 mm growth with persisting endoleak, probably due to insufficient endoleak filling. No serious adverse events related to the procedure or AneuFix material were reported. No neurological disorders were reported. Conclusion: The first results of type II endoleak treatment with AneuFix injectable elastomer in a small number of patients with a growing aneurysm show that it is technically feasible, safe, and clinically effective at 6 months. Clinical Impact: Effective and durable embolization of type II endoleaks causing abdominal aortic aneurysms (AAA) growth after EVAR is challenging. A novel injectable elastic polymer (elastomer) was developed, specifically designed to treat type II endoleaks (AneuFix, TripleMed, Geleen, the Netherlands). Embolization of the type II endoleak was performed by translumbar puncture. The viscosity changes from paste-like during injection, into an elastic implant after curing. The initial experience of this multicentre prospective pivotal trial demonstrated that the procedure is feasible and safe with a technical success of 100%. Absence of AAA growth was observed in 9 out of 10 treated patients at 6 months. [ABSTRACT FROM AUTHOR]

How people in long-term recovery (clinical and personal) in first-episode psychosis (schizophrenia and bipolar spectrum disorders) experience the mental health and welfare services they interact with is not frequently studied but has significant implications. We therefore aimed to explore which aspects of these services people with FEP evaluate as important for their long-term recovery. Twenty participants in clinical and/or personal recovery from two Norwegian long-term follow-up studies after FEP (TOP 10-year and TIPS 20-year) were sampled for this interview-based qualitative study. The research-team included service user experience. A deductive analysis based on personal accounts of recovery generated five service aspects. Few specific types of interventions were reported to promote recovery although medications, psychotherapy and employment support were mentioned. Participants valued services based in collaboration and that focused on their resources rather than limitations. The importance of long-term follow-up with a consistent aim was highlighted, as was the inclusion of caregivers and peers. Welfare services contributed to recovery by supporting basic needs and safety, but some experienced social exclusion when not participating in the labor market. This study is unique in exploring the role of services, including welfare, in long-term FEP recovery from service user perspectives. Participants evaluated that services played a more indirect role in long-term recovery by supporting their personal resources, although what they needed from services had frequently not been offered. Their expertise by experience contributes valuable knowledge. Better service coordination and consistent implementation of this knowledge are crucial to support recovery in FEP. [ABSTRACT FROM AUTHOR]

Finding a robust and efficient solver for (non-)symmetric systems that arise in incompressible Computational Fluid Dynamics (CFD) is of great interest to both academia and industry. We consider the Compatible Discrete Operator (CDO) discretization that has recently been devised for CFD simulations in the context of incompressible Stokes and Navier–Stokes flows. The discrete problems resulting from CDO schemes yield large saddle-point systems that require relevant numerical methods suitable to deal with large indefinite and poorly conditioned linear systems. In this paper, we focus on two segregated methods: the augmented Lagrangian Uzawa method and the generalized Golub–Kahan bidiagonalization, as well as a monolithic method based on an algebraic transformation by change of variables. We also employ algebraic multigrid (AMG) preconditioned Krylov solvers such as the Flexible Conjugate Gradient (FCG) method, and the Flexible Generalized Minimal Residual (FGMRES) method, to solve the linear systems. Using the CFD software code_saturne, we compare the numerical performance with respect to the choice of linear solvers and numerical strategies for the saddle-point problem. In the numerical experiments, the AMG preconditioned Krylov methods show robustness in test cases of Stokes and Navier–Stokes problems. [ABSTRACT FROM AUTHOR]

Background: The newborn transphyseal fracture of the distal humerus is frequently misdiagnosed with an elbow dislocation due to the absence of the lateral condyle ossification node. No consensus has been reported either for the diagnosis or the management of these rare fractures. This study aimed to analyze a series of newborns with transphyseal distal humerus fractures. Methods: All consecutive infants treated between 2005 and 2020 for a transphyseal fracture of the distal humerus before the age of 6 months were retrospectively included. All radiological examinations were analyzed (X-ray, ultrasound, and magnetic resonance imaging (MRI)) as well as the therapeutic management (orthopedic or surgical treatment). The patients were seen at outpatient clinic visits with a minimum of 2-year follow-up. Results: Nine newborns were treated. The main cause was an obstetrical traumatism (n = 8). The diagnosis was made on physical examination and addressed by obstetric departments with standard biplanar radiographs in four cases. The fracture was suspected on physical examination in the remaining five cases and confirmed by complementary imaging (ultrasound (2), MRI (1), and both (3)). A total of six patients were treated conservatively and three surgically with an open reduction. At a mean follow-up of 79 months, two complications occurred: one axillary abscess due to the cast and one cubitus varus deformity. All children had a full functional recovery. Conclusions: The transphyseal fracture of the distal humerus in newborns is a rare entity that should be managed conservatively. Additional imaging examinations are recommended to clarify the diagnosis. Level of evidence: Level IV, cohort study. [ABSTRACT FROM AUTHOR]

Introduction: ONWARDS 5 evaluated the effectiveness and safety of insulin icodec (icodec) titrated with a dosing guide app (icodec with app) versus once-daily insulin analogs in insulin-naive adults with type 2 diabetes. The insulin glargine U300 (glargine U300) stratum was too small to enable a robust post hoc efficacy comparison. Augmentation methodology was applied to increase the glargine U300 group size using real-world data (RWD), to facilitate efficacy comparisons of icodec with app versus glargine U300, and to demonstrate the potential of the augmentation methodology to strengthen underpowered treatment comparisons (AUGMENT study). Methods: ONWARDS 5 data were augmented with RWD collected from the US Ambulatory Electronic Medical Records database. Randomized and augmented comparisons (propensity-score-matched) between icodec with app and glargine U300 were weighted to provide a fully augmented estimate of the primary outcome (change in glycated hemoglobin [HbA1c] after 52 weeks). Data were adjusted for trial effects. Sensitivity analyses were conducted. Results: The nonaugmented randomized estimated treatment difference (ETD; 95% CI) between icodec with app and glargine U300 (trial stratum) for change in HbA1c was − 0.21 (− 0.70 to 0.28) percentage points. After adjusting for trial effects, the overall fully augmented ETD (95% CI) was − 0.33 (− 0.68 to 0.01) percentage points numerically in favor of icodec with app, although not statistically significant. Sensitivity analyses supported the findings. Conclusions: Using augmented data, the precision of the change in HbA1c estimate was increased compared with the trial stratum analysis alone. These findings help to validate the principle of utilizing augmentation to strengthen trial outcomes. Trial Registration Number: The ONWARDS 5 trial is registered with ClinicalTrials.gov (NCT04760626). [ABSTRACT FROM AUTHOR]

Discrete time stochastic optimal control problems and Markov decision processes (MDPs), respectively, serve as fundamental models for problems that involve sequential decision making under uncertainty and as such constitute the theoretical foundation of reinforcement learning. In this article we study the numerical approximation of MDPs with infinite time horizon, finite control set, and general state spaces. Our set-up in particular covers infinite-horizon optimal stopping problems of discrete time Markov processes. A key tool to solve MDPs are Bellman equations which characterize the value functions of the MDPs and determine the optimal control strategies. By combining ideas from the full-history recursive multilevel Picard approximation method, which was recently introduced to solve certain nonlinear partial differential equations, and ideas from Q-learning we introduce a class of suitable nonlinear Monte Carlo methods and prove that the proposed methods do not suffer from the curse of dimensionality in the numerical approximation of the solutions of Bellman equations and the associated discrete time stochastic optimal control problems. [ABSTRACT FROM AUTHOR]

Nanobodies (Nbs) hold great potential to replace conventional antibodies in various biomedical applications. However, conventional methods for their discovery can be time-consuming and expensive. We have developed a reliable protein selection strategy that combines magnetic activated cell sorting (MACS)-based screening of yeast surface display (YSD) libraries and functional ligand-binding identification by Tat-based recognition of associating proteins (FLI-TRAP) to isolate antigen-specific Nbs from synthetic libraries. This combined process enabled isolation of three unique Nb clones (NbT15, NbT21, and NbT22) that all bound specifically to a target antigen, namely proprotein convertase subtilisin/kexin type 9 (PCSK9) as well as a gain-of-function PCSK9 mutant (D374Y). All three clones bound to PCSK9 and blocked the interaction between the low-density lipoprotein receptor (LDLR) and either wild-type PCSK9 or the D374Y mutant. Overall, our combined protein selection method enables rapid and straightforward identification of potent antigen-specific Nbs in a manner that can be executed in a basic laboratory setting without the need for specialized equipment. We anticipate that our strategy will be a valuable addition to the protein engineering toolkit, allowing development of Nbs or virtually any other synthetic binding protein for a wide range of applications. [ABSTRACT FROM AUTHOR]

Adaptive cycling holds potential for promoting physical and mental health among individuals with disabilities, who often face barriers to traditional cycling and other forms of exercise. This scoping review systematically examines existing scientific literature to assess the effects of adaptive cycling on the physical and mental health of individuals with disabilities. Following a widely recognized methodological scoping review framework, 35 qualitative and quantitative studies were identified through comprehensive database searches and manual screenings. The review highlights the positive impacts of adaptive cycling on cardiovascular fitness, muscle strength, and overall physical well-being, as well as improvements in mental health and quality of life. Despite these benefits, significant research gaps remain, particularly concerning adaptive cycling modalities, such as sociable cycles, chair transporters, and power-assisted bikes, which were underrepresented in the existing literature. This review underscores the need for further studies to provide a comprehensive understanding on the effects of different adaptive cycling modalities. Such studies are essential to improve accessibility and ultimately support the health and social inclusion of individuals with disabilities. [ABSTRACT FROM AUTHOR]

Ultrasound imaging is widely valued for its safety, non-invasiveness, and real-time capabilities but is often limited by operator variability, affecting image quality and reproducibility. Robot-assisted ultrasound may provide a solution by delivering more consistent, precise, and faster scans, potentially reducing human error and healthcare costs. Effective force control is crucial in robotic ultrasound scanning to ensure consistent image quality and patient safety. However, existing robotic ultrasound systems rely heavily on expensive commercial force sensors or the integrated sensors of commercial robotic arms, limiting their accessibility. To address these challenges, we developed a cost-effective, lightweight, 3D-printed force sensor and a hybrid position–force control strategy tailored for robotic ultrasound scanning. The system integrates patient-to-robot registration, automated scanning path planning, and multi-sensor data fusion, allowing the robot to autonomously locate the patient, target the region of interest, and maintain optimal contact force during scanning. Validation was conducted using an ultrasound-compatible abdominal aortic aneurysm (AAA) phantom created from patient CT data and healthy volunteer testing. For the volunteer testing, during a 1-min scan, 65% of the forces were within the good image range. Both volunteers reported no discomfort or pain during the whole procedure. These results demonstrate the potential of the system to provide safe, precise, and autonomous robotic ultrasound imaging in real-world conditions. [ABSTRACT FROM AUTHOR]

Objectives: To survey physicians' views on the risks and benefits of computed tomography (CT) in the management of septic patients and indications for and contraindications to contrast media use in searching for septic foci. Methods: A web-based questionnaire was administered to physicians at a large European university medical center in January 2022. A total of 371 questionnaires met the inclusion criteria and were analyzed with physicians' work experience, workplace, and medical specialty as independent variables. Chi-square tests were used for exploratory analysis. Results: While physicians with all levels of work experience were included, the largest group (35.0%, n = 130/371) had 3–7 years of experience. Most physicians agreed that the benefits of CT outweigh its potential adverse effects in septic patients (90.5%, n = 336/371). Responders saw the strongest indication for contrast media administration in septic patients for (1) CT examinations of the abdomen (92.7%, n = 333/359) and (2) combined CT examinations of the chest, abdomen, and pelvis (94.1%, n = 337/358). While radiologists were most likely to consider manifest hyperthyroidism an absolute contraindication to contrast media administration (43.8%, n = 14/32), most other groups of physicians opted for appropriate preparation before contrast media administration in this subset of septic patients. Conclusion: In this survey, most participating physicians considered CT an essential diagnostic modality to detect an infectious focus in septic patients. Whereas the risk of ionizing radiation was regarded as justifiable by most physicians, different specialties varied in their assessment of the risks of contrast media administration. Key Points: Physicians recognize CT as a relevant imaging modality in the diagnostic management of patients with sepsis. There is an interdisciplinary consensus that the use of ionizing radiation is justified in septic patients. There is disagreement about indications for and contraindications to contrast media administration among physicians from different medical specialties. [ABSTRACT FROM AUTHOR]

Background: Paenibacillus polymyxa, is a Gram-positive, plant growth promoting bacterium, known for producing 98% optically pure 2,3-butanediol, an industrially valuable chemical for solvents, plasticizers and resins. Immobilization of Paenibacillus polymyxa has been proposed to improve the cell stability and efficiency of the fermentation process, reduce contamination and provide easy separation of butanediol in the culture broth as compared to conventional bioprocesses. This research aimed to explore the potential of Paenibacillus polymyxa with immobilization technique to produce 2,3-butanediol. Results: We investigated different immobilization methods with natural biopolymers like alginate, chitosan and carrageenan-chitosan-based immobilization. These methods were further investigated for their immobilization efficiency and yield in 2,3-butanediol production. Carrageenan-chitosan beads enabled a higher cell concentration and demonstrated superior cell retention to calcium-alginate-chitosan beads. Carrageenan-chitosan immobilization preserved 2,3-butanediol production in bacteria and increased the product formation rate. Conclusion: Carrageenan-chitosan immobilization enables non-pathogenic Paenibacillus polymyxa to be a capable 2,3-butanediol producer with increased product formation rate, which has not been previously reported. This novel strategy offers promising alternative to traditional fermentation processes using pathogenic strains and can be further applied in co-cultivations for metabolite production, wastewater management and bioremediation. [ABSTRACT FROM AUTHOR]

As we enter the exascale computing era, efficiently utilizing power and optimizing the performance of scientific applications under power and energy constraints has become critical and challenging. We propose a low‐overhead autotuning framework to autotune performance and energy for various hybrid MPI/OpenMP scientific applications at large scales and to explore the tradeoffs between application runtime and power/energy for energy efficient application execution, then use this framework to autotune four ECP proxy applications—XSBench, AMG, SWFFT, and SW4lite. Our approach uses Bayesian optimization with a Random Forest surrogate model to effectively search parameter spaces with up to 6 million different configurations on two large‐scale HPC production systems, Theta at Argonne National Laboratory and Summit at Oak Ridge National Laboratory. The experimental results show that our autotuning framework at large scales has low overhead and achieves good scalability. Using the proposed autotuning framework to identify the best configurations, we achieve up to 91.59% performance improvement, up to 21.2% energy savings, and up to 37.84% EDP (energy delay product) improvement on up to 4096 nodes. [ABSTRACT FROM AUTHOR]

Auditory hair cells form precise and sensitive staircase-like actin protrusions known as stereocilia. These specialized microvilli detect deflections induced by sound through the activation of mechano-electrical transduction (MET) channels located at their tips. At rest, a small MET channel current results in a constant calcium influx which regulates the morphology of the actin cytoskeleton in the shorter 'transducing' stereocilia. However, the molecular mechanisms involved in this novel type of activity-driven plasticity in the stereocilium cytoskeleton are currently unknown. Here, we tested the contribution of myosin XVA (MYO15A) isoforms, given their known roles in the regulation of stereocilia dimensions during hair bundle development and the maintenance of transducing stereocilia in mature hair cells. We used electron microscopy to evaluate morphological changes in the cytoskeleton of auditory hair cell stereocilia after the pharmacological blockage of resting MET currents in cochlear explants from mice that lacked one or all isoforms of MYO15A. Hair cells lacking functional MYO15A isoforms did not exhibit MET-dependent remodeling in their stereocilia cytoskeleton. In contrast, hair cells lacking only the long isoform of MYO15A exhibited increased MET-dependent stereocilia remodeling, including remodeling in stereocilia from the tallest 'non-transducing' row of the bundle. We conclude that MYO15A isoforms both enable and fine-tune the MET-dependent remodeling of the actin cytoskeleton in transducing stereocilia, while also contributing to the stability of the tallest row. [ABSTRACT FROM AUTHOR]

Marine heatwaves are starting to occur several times a decade, yet we do not understand the effect this has on corals across biological scales. This study combines tissue-, organism-, and community-level analyses to investigate the effects of a marine heatwave on reef-building corals. Adjacent conspecific pairs of coral colonies of Montipora capitata and Porites compressa that showed contrasting phenotypic responses (i.e., bleached vs. not bleached) were first identified during a marine heatwave that occurred in 2015 in Kāne'ohe Bay, Hawai' i. These conspecific pairs of bleaching-resistant and bleaching-susceptible colonies were sampled for histology and photographed before, during, and after a subsequent marine heatwave that occurred in 2019. Histology samples were quantified for: (i) abundance of mesenterial filaments, (ii) tissue structural integrity, (iii) clarity of epidermis, and (iv) cellular integrity (lack of necrosis/granulation) on a 1–5 scale and averaged for an overall tissue integrity score. Tissue integrity scores revealed a significant decline in overall tissue health during the 2019 heatwave relative to the months prior to the heatwave for individuals of both species, regardless of past bleaching history in 2015 or bleaching severity during the 2019 heatwave. Coral tissue integrity scores were then compared to concurrent colony bleaching severity, which revealed that tissue integrity was significantly correlated with colony bleaching severity and suggests that the stability of the symbiosis is related to host tissue health. Colony partial mortality was also quantified as the cumulative proportion of each colony that appeared dead 2.5 years following the 2019 bleaching event, and tissue integrity during the heatwave was found to be strongly predictive of the extent of partial mortality following the heatwave for M. capitata but not P. compressa, the latter of which suffered little to no mortality. Surprisingly, bleaching severity and partial mortality were not significantly correlated for either species, suggesting that tissue integrity was a better predictor of mortality than bleaching severity in M. capitata. Despite negative effects of heat stress at the tissue- and colony-level, no significant changes in coral cover were detected, indicating resilience at the community level. However, declines in tissue integrity in response to heat stress that are not accompanied by a visible bleaching response may still have long-term consequences for fitness, and this is an important area of future investigation as heat stress is commonly associated with long-term decreases in coral fecundity and growth. Our results suggest that histology is a valuable tool for revealing the harmful effects of marine heatwaves on corals before they are visually evident as bleaching, and may thus improve the predictability of ecosystem changes following climate change-driven heat stress by providing a more comprehensive assessment of coral health. [ABSTRACT FROM AUTHOR]

The article discusses the challenges faced by cardiac surgeons in treating patients with isolated tricuspid valve disease, even after minimally invasive surgery. The study compared outcomes based on the degree of residual tricuspid regurgitation (TR) at discharge in 53 patients. Patients with more than mild TR at discharge had significantly lower one-year survival rates, highlighting the need for further research on the impact of residual TR on patient outcomes. [Extracted from the article]

The article discusses the risks of iatrogenic injuries to the circumflex artery during mitral valve surgery, which occur in 0.3 to 1.8% of cases. The study analyzed mitral anatomy using advanced imaging software in 313 patients who underwent minimally invasive mitral valve surgery. The findings showed that a close location of the circumflex artery to the mitral valve with a distance <4 mm increased the risk of injury, highlighting the importance of preoperative assessment using advanced CT imaging software. [Extracted from the article]

The article compares the outcomes of minimally invasive surgery via right anterolateral mini-thoracotomy (RAMT) access versus complete sternotomy (CS) in patients undergoing replacement of the ascending aorta (AA) and the aortic root. The study found that RAMT had shorter aortic x-clamp time, lower 30-day mortality, and fewer complications such as wound infections, postoperative delirium, and re-intubation compared to CS. The authors recommend adopting the RAMT approach for aortic surgery to reduce sternotomy-associated complications and improve postoperative outcomes. [Extracted from the article]

The article compares the outcomes of minimally invasive surgery for replacing the ascending aorta and aortic root using two different approaches: right anterolateral mini-thoracotomy (RAMT) and partial upper sternotomy (PUS). The study analyzed data from 96 patients and found that RAMT had shorter operation times and lower rates of complications compared to PUS. The authors recommend RAMT as a safe and effective technique for treating these conditions when performed by an experienced team in a high-volume center. [Extracted from the article]

The study published in the journal "Thoracic & Cardiovascular Surgeon" examines the relationship between MELD Score and outcomes in patients undergoing surgery for infective endocarditis. The MELD Score, which assesses liver function, was found to be strongly associated with postoperative mortality and morbidity, with higher scores correlating with increased risk. Patients with a MELD Score over 30 had poor outcomes, indicating futility. The study suggests further research to determine if MELD assessment provides additional benefits compared to traditional assessment methods like EuroSCORE II. [Extracted from the article]

Idiopathic pulmonary fibrosis (IPF) is an aggressive interstitial lung disease with a high mortality rate. Putative drug targets in IPF have failed to translate into effective therapies at the clinical level. We identify TRAF2- and NCK-interacting kinase (TNIK) as an anti-fibrotic target using a predictive artificial intelligence (AI) approach. Using AI-driven methodology, we generated INS018_055, a small-molecule TNIK inhibitor, which exhibits desirable drug-like properties and anti-fibrotic activity across different organs in vivo through oral, inhaled or topical administration. INS018_055 possesses anti-inflammatory effects in addition to its anti-fibrotic profile, validated in multiple in vivo studies. Its safety and tolerability as well as pharmacokinetics were validated in a randomized, double-blinded, placebo-controlled phase I clinical trial (NCT05154240) involving 78 healthy participants. A separate phase I trial in China, CTR20221542, also demonstrated comparable safety and pharmacokinetic profiles. This work was completed in roughly 18 months from target discovery to preclinical candidate nomination and demonstrates the capabilities of our generative AI-driven drug-discovery pipeline. An AI-generated small-molecule inhibitor treats fibrosis in vivo and in phase I clinical trials. [ABSTRACT FROM AUTHOR]

Background: Proximal phalanx fractures are common, with surgical fixation indicated for unstable fractures. Traditionally, closed reduction percutaneous pinning (CRPP) resulted in decreased stiffness and tendon irritation compared to open reduction internal fixation (ORIF). We hypothesized that more recent studies would have more similar outcomes to CRPP. The purpose of this study was to compare CRPP and ORIF in terms of range of motion, Disabilities of the Arm, Shoulder, and Hand (DASH) scores, and complications. Methods: Four electronic databases were queried from 2010 to present. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, two independent reviewers performed a two-step review process to identify relevant articles. Patient demographics, total active motion (TAM), DASH, and complications were extracted. The methodological quality of each study included was assessed independently. Meta-analysis was performed for comparative trials. Results: Fourteen studies met inclusion criteria including four comparative studies: Thirteen studies included TAM. The weighted average TAM was 228 ± 34° for CRPP and 223 ± 32° for ORIF (P =.07 with 95% confidence interval (CI), −0.5 to 10.5). Seven studies evaluated DASH scores; weighted average was 8.2 ± 8.9 for CRPP and 11.7 ± 6.5 for ORIF (P <.01 with 95% CI, 1.8-5.2). Two studies directly compared CRPP to ORIF, favoring ORIF for both TAM with d = 1.07 and DASH with d = 0.23. Rates of tenolysis or hardware removal were higher for ORIF (P <.01). Conclusions: New literature suggests more equipoise with regard to treatment of proximal phalanx fracture with CRPP versus ORIF. Type of study/level of evidence: Meta-analysis, Level II. [ABSTRACT FROM AUTHOR]

The Preferred Reporting Items for Diagnostic Accuracy Studies in Endodontics (PRIDASE) 2024 guidelines are based on the Standards for Reporting of Diagnostic Accuracy Studies (STARD) 2015 guidelines and the Clinical and Laboratory Images in Publications (CLIP) principles, with the addition of items specifically related to endodontics. The use of the PRIDASE 2024 guidelines by authors and their application by journals during the peer review process will reduce the possibility of bias and enhance the quality of future diagnostic accuracy studies. The PRIDASE 2024 guidelines consist of a checklist containing 11 domains and 66 individual items. The purpose of the current document is to provide an explanation for each item on the PRIDASE 2024 checklist, along with examples from the literature to help readers understand their importance and offer advice to those developing manuscripts. A link to the PRIDASE 2024 explanation and elaboration document is available on the Preferred Reporting Items for study Designs in Endodontology (PRIDE) website (https://pride‐endodonticguidelines.org/pridase/) and on the International Endodontic Journal website (https://onlinelibrary.wiley.com/page/journal/13652591/homepage/pride‐guidelines.htm). [ABSTRACT FROM AUTHOR]

Rationale: Glucagon-like peptide-1 (GLP-1) receptor agonists reduce alcohol consumption in rodents and non-human primates. Semaglutide is a new long-acting GLP-1 receptor agonist, widely used in the clinic against type 2 diabetes and obesity. It is also reported to reduce alcohol intake in rodents. Objectives: This study investigates the possible inhibitory effect of semaglutide on alcohol intake in alcohol-preferring African green monkeys. Methods: We performed a vehicle-controlled study on male monkeys that had demonstrated a preference for alcohol. In the monkeys selected for voluntary alcohol drinking, alcohol consumption was measured for ten days at baseline (Monday to Friday for two weeks). During this period, the monkeys had access to alcohol 4 h per day and free access to water 24 h per day. After two weeks of baseline measurements, the monkeys were randomized to semaglutide or vehicle. Each group consisted of ten monkeys, and the two groups were balanced with respect to baseline alcohol intake. Following the baseline period, the monkeys were treated with escalating doses of semaglutide (up to 0.05 mg/kg) or vehicle subcutaneously twice weekly for two weeks during which period alcohol was not available. After uptitration, the monkeys had access to alcohol 4 h daily for 20 days (Monday to Friday for 4 weeks), and alcohol consumption was measured. During this alcohol exposure period, treatment with semaglutide (0.05 mg/kg twice weekly) or vehicle continued for three weeks followed by a one-week washout period. Results: Compared to the vehicle, semaglutide significantly reduced alcohol intake. There were no signs of emetic events or changes in water intake. Conclusions: These data demonstrate for the first time the potent effect of semaglutide in reducing voluntary alcohol intake in non-human primates and further substantiate the need for clinical trials investigating the effect of semaglutide in patients with alcohol-use disorder. [ABSTRACT FROM AUTHOR]

This research proposes that broad-based employee share ownership (ESO) affects corporate environmental performance (CEP). Drawing upon corporate governance literature, social exchange theory, and stakeholder utility theory, we propose that employees as owners adopt more favorable attitudes toward beneficial outcomes for CEP, and that the broad-based impact of ESO overwhelms the impact of CEO ownership. Also, we propose that these relationships are contingent upon trade union presence as a form of worker voice that amplifies the ESO influence on CEP. The empirical results from U.S. publicly traded companies from 2009 to 2016 indicate that broad-based ESO is linked to positive CEP by companies, and provides some support for all proposed hypotheses. This study provides scholarly and practical implications for the effects of shared capitalist modes of ownership and employee engagement on corporate sustainability. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most common cancer among men and women combined, and the second leading cause of cancer death in the US. The revised USPSTF CRC screening recommendations increased CRC screening needs across health systems, which may create particular challenges for community health centers (CHCs) given their resource constraints. The objective of our study is to assess CRC screening rates across 10 CHCs in Massachusetts and estimate the additional increase in the number of average-risk screening-eligible individuals after the revision in guidelines. CRC screening was defined as being up to date vs. not up to date based on any of the approved screening modalities in the appropriate time frame. Our outcome of interest was CRC screening by age group and the percentage increase in screenings needed to screen individuals 45 to 49 across our partner CHCs after the revision in guidelines. Our analysis included 70,808 individuals aged 45 to 75. The overall CRC screening rate was 35.9% after the USPSTF guideline revision. Screening rates were lowest in those aged 45 to 49 at 9.6%, and highest in those over age 55 at 47.0%. There was a 22.9% increase in additional screenings needed after USPSTF guideline revision. The revised USPSTF guidelines increased screening needs by about 23% without additional funding for CHCs for which demand already outstrips staffing and clinical care resources. Future studies should include cost analyses of screening the population 45 to 49 and identify effective strategies that are low burden and do not add to the workload of CHC providers to improve screening at CHCs. [ABSTRACT FROM AUTHOR]

The nature of science (NOS) is a fundamental aspect of scientific literacy to support students' understanding of science content, socio-scientific issues, and science media. Unfortunately, NOS is often left out of science instruction or limited to ineffective implicit approaches. The activity described in this article engages students in inquiry and problem-solving as they attempt to uncover the mechanism of a magic trick. While the trick engages students, the accompanying discussions encourage students to think more deeply about the ways scientists work and think. Through explicit questions, we leverage students' experiences to guide students toward deeper thinking about the nature of science. Importantly, this activity is an introduction to key NOS ideas and we return to NOS in the context of our content instruction throughout the year. Yet, activities such as these can lay a strong foundation for those later conversations. [ABSTRACT FROM AUTHOR]

Objective: The objectives of this study were 1) to identify the effects cannabis has on driving performance and individual motor practices when on the freeway compared to placebo and 2) to bring context to the effects of cannabis on driving by comparing effect sizes to those of alcohol. Methods: Data for analysis was collected from a study of fifty-three participants with a history of tetrahydrocannabinol (THC) cannabis use who completed three visits in randomized order (placebo (0% THC), 6.18% THC, and 10.5% THC). Data for the alcohol analysis was from a subset of eighteen of these participants with a history of recent alcohol use that completed a fourth alcohol visit that targeted a.05 g/210L breath alcohol content (BrAC) during the drive. Comparisons were made using an analysis of variance approach with the SAS General Linear Models Procedure. Cohen's d effect sizes were calculated for the cannabis and alcohol conditions relative to placebo for both the full sample and alcohol subset. Results: Standard deviation of lane position (SDLP) for cannabis significantly increased compared to placebo and the effect size was comparable to that of alcohol at.05 BrAC. Lane departures for cannabis significantly increased relative to placebo as did the time out of the lane. Cannabis use resulted in an increased amount of time at 10% or more below the speed limit for the 6.18% THC condition. Relative to alcohol, cannabis produced more time at slower speeds and less time at speeds more than 10% above the speed limit. Conclusions: Multiple factors of lateral and longitudinal vehicle control on the freeway showed statistical significance. Drivers under the influence of cannabis exhibited higher rates of driving errors but also showed more cautious behaviors such as generally lower speeds on the freeway. Compared with alcohol, effect sizes varied. For longitudinal control, there were larger effect sizes for alcohol with speed effects in opposite directions, but relatively equivalent effect sizes for lateral control and driving errors associated with lane keeping. [ABSTRACT FROM AUTHOR]

Neuron navigators (NAVs) are cytoskeleton-associated proteins well known for their role in axonal guidance, neuronal migration, and neurite growth necessary for neurodevelopment. Neuron navigator 3 (NAV3) is one of the three NAV proteins highly expressed in the embryonic and adult brain. However, the role of the NAV3 gene in human disease is not well-studied. Recently, five bi-allelic and three mono-allelic variants in NAV3 were reported in 12 individuals from eight unrelated families with neurodevelopmental disorder (NDD). Here, we report five patients from three unrelated consanguineous families segregating autosomal recessive NDD. Patients have symptoms of dysmorphism, intellectual disability, developmental delay, and behavioral abnormalities. Exome sequencing (ES) was performed on two affected individuals from one large family, and one affected individual from each of the other two families. ES revealed two homozygous nonsense c.6325C > T; p.(Gln2109Ter) and c.6577C > T; p.(Arg2193Ter) and a homozygous splice site (c.243 + 1G > T) variants in the NAV3 (NM_001024383.2). Analysis of single-cell sequencing datasets from embryonic and young adult human brains revealed that NAV3 is highly expressed in the excitatory neurons, inhibitory neurons, and microglia, consistent with its role in neurodevelopment. In conclusion, in this study, we further validate biallelic protein truncating variants in NAV3 as a cause of NDD, expanding the spectrum of pathogenic variants in this newly discovered NDD gene. [ABSTRACT FROM AUTHOR]

Purpose: This research aimed to better understand what influences the acceptability of non-cash incentives to encourage voluntary blood donation among those who have and have not donated blood. Design/methodology/approach: This paper used data from two cross-sectional surveys with Australian blood donors (n = 768) and non-donors (n = 1,087). Findings: Cost-benefit evaluation, embarrassment and deal proneness were found to be important predictors, explaining 4.4%–27.2% of the acceptability of six different types of non-cash incentives, in addition to demographic (age, gender, education, income), geographic (region) and behavioural (blood donor status) characteristics. Cost-benefit evaluation remained the strongest predictor, irrespective of blood donor status. People who were more embarrassed to receive an incentive generally for donating blood were slightly more accepting of health checks and charity donations, and less accepting of deal promotions. People who were more likely to respond to promotional deals generally were also more accepting of all types of incentives for blood donation; interaction effects demonstrated this was particularly true for non-donors. Practical implications: Findings direct attention to factors that will improve the design and implementation of incentive programs to maximise their acceptability and impact without undermining organisational reputation, as well as point to psychographic characteristics that should be considered when evaluating the adoption and effectiveness of incentives for encouraging blood donation. Originality/value: This paper extends our understanding of what explains the acceptability of different incentive types to encourage voluntary blood donation, beyond geographic, demographic and behavioural characteristics of people who do and do not donate blood. [ABSTRACT FROM AUTHOR]

Ytopt is a Python machine-learning-based autotuning software package developed within the ECP PROTEAS-TUNE project. The ytopt software adopts an asynchronous search framework that consists of sampling a small number of input parameter configurations and progressively fitting a surrogate model over the input-output space until exhausting the user-defined maximum number of evaluations or the wall-clock time. libEnsemble is a Python toolkit for coordinating workflows of asynchronous and dynamic ensembles of calculations across massively parallel resources developed within the ECP PETSc/TAO project. libEnsemble helps users take advantage of massively parallel resources to solve design, decision, and inference problems and expands the class of problems that can benefit from increased parallelism. In this paper we present our methodology and framework to integrate ytopt and libEnsemble to take advantage of massively parallel resources to accelerate the autotuning process. Specifically, we focus on using the proposed framework to autotune the ECP ExaSMR application OpenMC, an open source Monte Carlo particle transport code. OpenMC has seven tunable parameters some of which have large ranges such as the number of particles in-flight, which is in the range of 100,000 to 8 million, with its default setting of 1 million. Setting the proper combination of these parameter values to achieve the best performance is extremely time-consuming. Therefore, we apply the proposed framework to autotune the MPI/OpenMP offload version of OpenMC based on a user-defined metric such as the figure of merit (FoM) (particles/s) or energy efficiency energy-delay product (EDP) on Crusher at Oak Ridge Leadership Computing Facility. The experimental results show that we achieve the improvement up to 29.49% in FoM and up to 30.44% in EDP. [ABSTRACT FROM AUTHOR]