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The TYK2 gene is associated with development of type 1 diabetes. Here the authors show that TYK2 regulates β-cell development, but at the same time TYK2 inhibition in the islets prevents IFNα responses and enhances their survival against CD8+ T-cell cytotoxicity; representing a potent therapeutic target to halt T1D progression.

Abstract Objective To investigate the treatment decision-making process after an anterior cruciate ligament (ACL) injury from patients’, orthopaedic surgeons’ and physiotherapists’ perspectives. Methods The study is a part of the NACOX study, which is designed to describe the natural corollaries after ACL injury. For the present study, a subgroup 101 patients were included. Patients, their orthopaedic surgeons and their physiotherapists, answered a Shared Decision-Making Process (SDMP) questionnaire, when treatment decision for ACL reconstruction surgery (ACLR) or non-reconstruction (non-ACLR) was taken. The SDMP questionnaire covers four topics: “ informed patient”, “ to be heard”, “ involvement” and “ agreement”. Results Most (75–98%) patients considered their needs met in terms of being heard and agreement with the treatment decision. However, fewer in the non-ACLR group compared to the ACLR group reported satisfaction with information from the orthopaedic surgeon (67% and 79%), or for their own involvement in the treatment decision process (67% and 97%). Conclusion and practice implications Most patients and caregivers considered that patients’ needs to be informed, heard and involved, and to agree with the decision about the treatment process, were fulfilled to a high extent. However, patients where a non-ACLR decision was taken experienced being involved in the treatment decision to a lower extent. This implies that the non-ACLR treatment decision process needs further clarification, especially from the patient involvement perspective.

Introduction: The use of virtual reality technology to deliver exposure therapy in the treatment of phobic anxiety (i.e., social anxiety disorder, agoraphobia, and specific phobia) has been proposed to be advantageous compared with in-vivo exposure therapy. These supposed advantages depend on the features of the virtual reality technology and how it is used therapeutically. Therefore, the aim of this study was to provide a comprehensive overview of the features of the hardware and software used in studies examining virtual reality exposure therapy studies for phobic anxiety disorders.Methods: 70 studies using virtual reality exposure therapy to treat social anxiety disorder, agoraphobia and/or specific phobia, were systematically reviewed for 46 data points relating to these features.Results: We found that studies generally did not utilize contemporary virtual reality technology and that hardware and software features were inconsistently delineated.Discussion: The implications of these findings are that the use of modern virtual reality technology represents a relevant frontier in anxiety treatment and that a framework for reporting technical features of virtual reality exposure interventions would benefit the field.

Abstract Background Protein truncating variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2 are associated with increased breast cancer risk, but risks associated with missense variants in these genes are uncertain. Methods We analyzed data on 59,639 breast cancer cases and 53,165 controls from studies participating in the Breast Cancer Association Consortium BRIDGES project. We sampled training (80%) and validation (20%) sets to analyze rare missense variants in ATM (1146 training variants), BRCA1 (644), BRCA2 (1425), CHEK2 (325), and PALB2 (472). We evaluated breast cancer risks according to five in silico prediction-of-deleteriousness algorithms, functional protein domain, and frequency, using logistic regression models and also mixture models in which a subset of variants was assumed to be risk-associated. Results The most predictive in silico algorithms were Helix (BRCA1, BRCA2 and CHEK2) and CADD (ATM). Increased risks appeared restricted to functional protein domains for ATM (FAT and PIK domains) and BRCA1 (RING and BRCT domains). For ATM, BRCA1, and BRCA2, data were compatible with small subsets (approximately 7%, 2%, and 0.6%, respectively) of rare missense variants giving similar risk to those of protein truncating variants in the same gene. For CHEK2, data were more consistent with a large fraction (approximately 60%) of rare missense variants giving a lower risk (OR 1.75, 95% CI (1.47–2.08)) than CHEK2 protein truncating variants. There was little evidence for an association with risk for missense variants in PALB2. The best fitting models were well calibrated in the validation set. Conclusions These results will inform risk prediction models and the selection of candidate variants for functional assays and could contribute to the clinical reporting of gene panel testing for breast cancer susceptibility.

Abstract Introduction While functional near‐infrared spectroscopy (fNIRS) can provide insight into motor‐cognitive deficits during ecologically valid gait conditions, the feasibility of using fNIRS during complex walking remains unknown. We tested the process and scientific feasibility of using an fNIRS device to measure cortical activity during complex walking tasks consisting of straight walking and navigated walking under single and dual‐task (DT) conditions. Methods Nineteen healthy people from 18 to 64 years (mean age: 45.7 years) participated in this study which consisted of three complex walking protocols: (i) straight walking, DT walking (walking while performing an auditory Stroop task) and single‐task auditory Stroop, (ii) straight and navigated walking, and (iii) navigated walking and navigated DT walking. A rest condition (standing still) was also included in each protocol. Process feasibility outcomes included evaluation of the test procedures and participant experience during and after each protocol. Scientific feasibility outcomes included signal quality measures, and the ability to measure changes in concentration of deoxygenated and oxygenated hemoglobin in the prefrontal cortex. Results All participants were able to complete the three protocols with most agreeing that the equipment was comfortable (57.9%) and that the testing duration was adequate (73.7%). Most participants did not feel tired (94.7%) with some experiencing pain (42.1%) during the protocols. The signal qualities were high for each protocol. Compared to the rest condition, there was an increase in oxygenated hemoglobin in the prefrontal cortex when performing dual‐task walking and navigation. Conclusion We showed that our experimental setup was feasible for assessing activity in the prefrontal cortex with fNIRS during complex walking. The experimental setup was deemed acceptable and practicable. Signal quality was good during complex walking conditions and findings suggest that the different tasks elicit a differential brain activity, supporting scientific feasibility.

Abstract Surface melt forces summertime ice‐flow accelerations on glaciers and ice sheets. Here, we show that large meltwater‐forced accelerations also occur during wintertime in Greenland. We document supraglacial lakes (SGLs) draining in cascades at unusually high elevation, causing an expansive flow acceleration over a ∼5,200 km2 region during winter. The three‐component interferometric surface velocity field and decomposition modeling reveal the underlying flood propagation with unprecedented detail as it traveled over 160 km from the drainage site to the margin, providing novel constraints on subglacial water pathways, drainage morphology, and links with basal sliding. The triggering SGLs continuously grew over 40 years and suddenly released decades of stored meltwater, demonstrating surface melting can impact dynamics well beyond melt production. We show these events are likely common and thus their cumulative impact on dynamics should be further evaluated.

In welfare-policy studies, conditions are often depicted at a national level. This is the case not least in studies of young people's paths and detours to working life. Studies at a high aggregation level have their advantages when it comes to distinguishing differences in living conditions between countries at similar economic development levels and examining the degree to which these differences can be related to institutional inequalities, differences in so-called welfare-policy regimes. But there is also a risk that studies of national regimes obscure the differences in socio-geographical conditions that exist in all countries. In this article we show how the socio-geographical conditions, to a great degree, affect young people's ability to find work on the Swedish labor market with good development and support possibilities. A starting point is that the image of the Swedish transition regime as universalistic, as is often depicted in comparative research on young people's transitions, obscures significant differences in young people's transition and establishment patterns that are related to geographical residence. The Swedish universalistic regime encompasses a large and, over time, growing socio-geographically related spread of establishment opportunities for youths and young adults. We illustrate the circumstances by presenting comparable data in the form of an establishment index on the conditions for youths and young adults in Sweden's 290 municipalities.

In spite of their important roles in many ecosystems, data regarding population structure and biogeographic patterns of leeches are scarce. To begin to address this knowledge gap, we herein perform a phylogeographic analysis of the North American medicinal leech, Macrobdella decora (Say, 1824). A total of 224 M. decora specimens were collected from 35 localities across large swaths of USA and Canada and covering most of the known range of the species. Using four loci (mitochondrial cytochrome c oxidase subunit I [COI] and NADH dehydrogenase I [ND1], as well as nuclear 18S rRNA [18S] and 28S rRNA [28S]), we construct phylogenetic trees using several optimality criteria and superimpose geographic patterns onto the trees in order to tease out any potential structure among the populations. Rather surprisingly, given the large geographic range of the species and abundance of potential geographic barriers to gene flow, the analyses showed a conspicuous lack of structure among the different populations of M. decora. However, an AMOVA did show statistically significant differences between the genetic variation within populations and between populations (COI: FST = 0.65412, p < .00001; ND1: FST = 0.69245, p < .00001), which was largely driven by only 6 out of the 35 populations, and indicated a potential barrier for dispersal across the Appalachian Mountains. Finally, a Mantel test showed a weak, but significant, correlation between geographic distance and genetic distance (COI: r = 0.209, p = .027; ND1: r = 0.1289, p = .030); however, this correlation was primarily driven by a single locality. The overall weak structure suggests that M. decora is panmictic throughout its range, and we discuss this in light of previous population level studies in both bloodfeeding and non‐bloodfeeding species, concluding that the lack of structure in M. decora might be due to its high capacity for dispersal via hosts. [ABSTRACT FROM AUTHOR]

This article presents a theory and analysis of the social aesthetics of digital diplomacy. Drawing inspiration from the sociology of taste and visual theory, we conceptualize social aesthetics as the encoding of social norms and hierarchies into visual representations. Through this lens, we examine how the multitude of images uploaded by diplomats on social media daily contribute to the symbolic authority of their profession, ritually conveying ideals of international mediation and sovereign equality. Using advancements in computer vision methods, we analyze over 55,000 images sourced from tweets by more than 1,000 ambassadors globally. In contrast to prevailing research highlighting how social media images disrupt traditional diplomatic norms, facilitate strategic nation-branding, or promote individuals, our large-scale analysis reveals a remarkable uniformity in these images across diplomats from different countries. We demonstrate how diplomatic images perpetuate a Western visual canon, thereby reinforcing structures of power and distinction, and delineating the normative boundaries of diplomacy as a global institution. The article contributes to debates about diplomacy, aesthetics, taste, rituals, and power in international relations. Furthermore, it underscores the value of computer vision and convolutional neural networks in uncovering large-scale social patterns and relationships within practices previously perceived as highly personalized or strategic. [ABSTRACT FROM AUTHOR]

Aim: To investigate what happens to cross‐sectionally identified root‐filled teeth over a 6‐year period, regardless of the time that elapsed since primary root canal treatment, in a cohort of adult patients regularly attending a Public Dental Service. A secondary aim was to investigate how the cumulative events affecting root‐filled teeth over the same time were associated with variables obtained from a baseline examination. Methodology: Adult patients with ≥1 previously root‐filled tooth and regularly attending the Public Dental Service in Örebro County were enrolled for study participation in 2015. General dental practitioners examined all identified root‐filled teeth in this cohort at baseline using a standardized protocol and were also responsible for further decision‐making and treatments. After six years, information on events of the root‐filled teeth was collected from dental records. The highest rating (most invasive treatment) on a 5‐point ordinal scale was used in the analyses. Regression analyses with stepwise selection were performed for associations between patient‐ and tooth‐related factors and events. Results: A total of 445 patients with 1007 root‐filled teeth were followed the entire observation time. Twenty (2.0%) of the root‐filled teeth had endodontic retreatment and 150 (14.9%) were extracted over six years. Among teeth with periapical radiolucency or pain, the majority did not undergo retreatment or extraction; however, the multivariate analysis demonstrated that retreatment or extraction was associated with baseline recordings of teeth with periapical radiolucency (p <.0001), tenderness to percussion (p <.0001), and poor coronal restoration (p <.0001). Conclusions: This study corroborates the notion that in general dentistry, root‐filled teeth with radiological signs of apical disease often remain untreated over time. Furthermore, it also reveals that root‐filled teeth presenting with mild pain do not necessarily receive any intervention. However, teeth with baseline signs of apical periodontitis, pain, or inadequate coronal restoration were more likely to have received intervention during the six‐year period. [ABSTRACT FROM AUTHOR]

Background/Objectives: Given the complex nature of Anterior Cruciate Ligament (ACL) injury, it is important to analyze its etiology with suitable approaches in order to formulate intervention strategies for effective prevention. The present study employs system thinking techniques to develop a Causal Loop Diagram (CLD) Model for investigating the risk factors for ACL Injury (CLD-ACLI), through a Group Model Building approach. Methods: A two-stage procedure was applied involving a comprehensive literature review followed by several systems thinking group-modeling co-creation workshops with stakeholders. Results: Based on input from experts and stakeholders, combined with the latest scientific findings, the derived CLD-ACLI model revealed a series of interesting complex nonlinear interrelationships causal loops between the likelihood of ACL injury and the number of risk factors. Particularly, the interaction among institutional, psychological, neurocognitive, neuromuscular, malalignment factors, and trauma history seem to affect neuromuscular control, which subsequently may alter the biomechanics of landing, predisposing the ACL to injury. Further, according to the proposed CLD-ACLI model, the risk for injury may increase further if specific environmental and anatomical factors affect the shear forces imposed on the ACL. Conclusions: The proposed CLD-ACLI model constitutes a rigorous useful conceptual presentation agreed upon among experts on the dynamic interactions among potential intrinsic and extrinsic risk factors for ACL injury. The presented causal loop model constitutes a vital step for developing a validated quantitative system dynamics simulation model for evaluating ACL injury-prevention strategies prior to implementation. [ABSTRACT FROM AUTHOR]

Aim: The aim of the study was to identify the nature and extent of scientific research addressing continuing education for advanced practice nurses. Design: A scoping review. Review Methods: The Joanna Briggs Institute's methodology for scoping reviews. Data Sources: Electronic search was conducted on 17 September 2023 via CINAHL, PsycINFO, PubMed, Scopus, Web of Science, Cochrane Library and the Joanna Briggs Institute's Evidence‐Based Practice Database for research articles published between 2012 and 2023. Results: Nineteen papers were included in this review. Scientific research on continuing education for advanced practice nursing roles (i.e. nurse practitioner, clinical nurse specialist) has primarily been conducted in the United States and mostly addresses online‐delivered continuing education interventions for clinical care competency. Most of the interventions targeted nurse practitioners. Conclusion: Continuing education has a pivotal role in supporting advanced practice nursing competency development. In addition to clinical care, future continuing education research should focus on other advanced practice nursing competencies, such as education, leadership, supporting organizational strategies, research and evidence implementation. Implications for the Profession and/or Patient Care: Continuing education programmes for advanced practice nurses should be rigorously developed, implemented and evaluated to support the quality and effectiveness of patient care. Impact: Continuing education for advanced practice nursing roles is an understudied phenomenon. This review highlights future research priorities and may inform the development of continuing education programmes. Reporting Method: PRISMA‐ScR. [ABSTRACT FROM AUTHOR]

Background Surgical stress may lead to postsurgical hypercoagulability, endothelial dysfunction and systemic inflammation, which can impact on patient recovery. Remote ischaemic preconditioning is a procedure that activates the body's endogenous defences against ischaemia and reperfusion injury. Studies have suggested that remote ischaemic preconditioning has antithrombotic, antioxidative and anti-inflammatory effects. The hypothesis was that remote ischaemic preconditioning reduces surgery-induced systemic stress response. Method During a 24-month period (2019–2021), adult patients undergoing subacute laparoscopic cholecystectomy due to acute cholecystitis were randomized to remote ischaemic preconditioning or control. Remote ischaemic preconditioning was performed less than 4 h before surgery on the upper arm. It consisted of four cycles of 5 min ischaemia and 5 min reperfusion. The gene expression of 750 genes involved in inflammatory processes, oxidative stress and endothelial function was investigated preoperatively and 2–4 h after surgery in both groups. In addition, changes in 20 inflammation- and vascular trauma–associated proteins were assessed preoperatively, 2–4 h after surgery and 24 h after surgery. Results A total of 60 patients were randomized. There were no statistically significant differences in gene expression 2–4 h after surgery between the groups (P > 0.05). Remote ischaemic preconditioning did not affect concentrations of circulating proteins up to 24 h after surgery (P > 0.05). Conclusion The study did not demonstrate any effect of remote ischaemic preconditioning on expression levels of the chosen genes or in circulating immunological cytokines and vascular trauma–associated proteins up to 24 h after subacute laparoscopic cholecystectomy in patients with acute cholecystitis. [ABSTRACT FROM AUTHOR]

Aim: To investigate the decisional needs in Denmark of people with kidney failure, relatives, and health professionals when planning end‐of‐life care. Design: A qualitative interview study. Methods: Individual semi‐structured interviews were carried out with people with kidney failure, relatives and health professionals from November 2021 to June 2022. Malterud's systematic text condensation was used to analyse transcripts. Results: A total of 13 patients, 10 relatives, and 12 health professionals were interviewed. Overall, four concepts were agreed on: (1) Talking about end of life is difficult, (2) Patients and relatives need more knowledge and information, (3) Health professionals need more tools and training, and (4) Experiencing busyness as a barrier to conversations about end of life. Conclusion: People with kidney failure, relatives, and health professionals shared certain decisional needs while also having some different decisional needs about end‐of‐life care. To meet these various needs, end‐of‐life conversations should be systematic and organized according to the patients' needs and wishes. Impact: Non‐systematic end‐of‐life care decision‐making processes limit patients' involvement. Patients and relatives need more knowledge about end‐of‐life care, and health professionals need more competences and time to discuss decisional needs. A shared decision‐making intervention for people with kidney failure when making end‐of‐life care decisions will be developed. Reporting Method: This empirical qualitative research is reported according to the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist. Patient or Public Contribution: Patients, relatives, and health professionals have been involved throughout the research process as part of the research team and advisory board. The patients are people with kidney failure and the relatives are relatives of a person with kidney failure. For this study, the advisory board has particularly contributed to the validation of the invitation letter for participation, the interview guides and the preparation of the manuscript. [ABSTRACT FROM AUTHOR]

Expressing a desire for surgery before participating in first-line osteoarthritis (OA) interventions (patient education and exercise therapy) has been shown to contribute to poorer outcomes from the interventions, but we lack knowledge on how these patients reflect on health care and self-management of OA. To explore and describe patients' perspectives of health care and self-management of OA among those expressing a desire for surgery before participating in first-line OA interventions. Sixteen patients with hip or knee OA referred to participate in a standardized first-line OA intervention program in primary health care in Sweden were included in the study. We used individual semi-structured interviews to collect data, which were analyzed using inductive qualitative content analysis. One theme of meaning "A multifaceted picture of needs, expectations, and individual choices" and five categories were identified as perspectives from the participants regarding health care and self-management of OA: 1) lacking control and needing support; 2) standing alone in an unsupportive environment; 3) going with the flow; 4) having expectations; and 5) taking ownership. Patients who express a desire for surgery before participating in first-line interventions for OA are not a homogeneous group. They describe a broad range of perspectives on how they reason and reflect on health care and self-management of OA based on their own needs, expectations, and choices. Findings from this study strengthen insights on the importance of exploring the patient's perspectives and individualizing OA interventions to achieve the lifestyle changes that first-line interventions strive to accomplish. [ABSTRACT FROM AUTHOR]

To analyze the role of interleukin IL-17A and IL-10 polymorphisms in susceptibility to juvenile idiopathic arthritis (JIA), 98 Finnish children and adolescents with JIA were studied. Data from the 1000 Genomes Project, consisting of 99 healthy Finns, served as the controls. The patients were analyzed for four IL-17A and three IL-10 gene-promoter polymorphisms, and the serum IL-17A, IL-17F, IL-10, and IL-6 levels were determined. The IL-17A rs8193036 variant genotypes (CT/CC) were more common among the patients than controls, especially in those with polyarthritis (OR 1.93, 95% CI 1.11–3.36; p = 0.020). IL-17A rs2275913 minor allele A was more common in patients (OR 1.45, 95% Cl 1.08–1.94; p = 0.014) and especially among patients with oligoarthritis and polyarthritis than the controls (OR 1.61, 95%CI 1.06–2.43; p = 0.024). Carriers of the IL-17A rs4711998 variant genotype (AG/AA) had higher serum IL-17A levels than those with genotype GG. However, carriers of the variant genotypes of IL-17A rs9395767 and rs4711998 appeared to have higher IL-17F levels than those carrying wildtype. IL-10 rs1800896 variant genotypes (TC/CC) were more abundant in patients than in the controls (OR 1.97, 95%CI 1.06–3.70; p = 0.042). Carriers of the IL-10 rs1800896 variant genotypes had lower serum levels of IL-17F than those with wildtype. These data provide preliminary evidence of the roles of IL-17 and IL-10 in the pathogenesis of JIA and its subtypes in the Finnish population. However, the results should be interpreted with caution, as the number of subjects included in this study was limited. [ABSTRACT FROM AUTHOR]

Background: Health‐related quality of life (HRQoL) is a multidimensional concept used to examine the impact of patient‐perceived health status on quality of life. Patients' perception of illness affects outcomes in both medical and elective surgical patients; however, not much is known about how HRQoL effects outcomes in the emergency surgical setting. This study aimed to examine if patient‐reported HRQoL was a predictor of unplanned readmission after emergency laparotomy. Methods: This study included 215 patients who underwent emergency laparotomy at the Copenhagen University Hospital, Herlev, between August 1, 2021, and July 31, 2022. Patient‐reported HRQoL was assessed with the EuroQol group EQ5D index (EQ5D5L descriptive system and EQ‐VAS). The population was followed from 0 to 180 days after discharge, and readmissions and days alive and out of hospital were registered. A Cox proportional hazard model was used to examine HRQoL and the risk of readmission within 30 and 180 days. Results: Within 30 days, 28.4% of patients were readmitted; within 180 days, the number accumulated to 45.1%. Low self‐evaluated HRQoL predicted 180‐day readmission and was significantly associated with fewer days out of hospital within both 90 and 180 days. Low HRQoL and discharge with rehabilitation were independent risk factors for short‐ (30‐day) and long‐term (180‐day) emergency readmission. Conclusion: Patient‐perceived quality of life is an independent predictor of 180‐day readmission, and the number of days out of hospital was correlated to self‐reported HRQoL. [ABSTRACT FROM AUTHOR]