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    European Respiratory Society Statement on preschool wheezing disorders: updated definitions, knowledge gaps, and proposed future research directions.

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    Since the publication of the European Respiratory Society (ERS) Task Force reports on the management of preschool wheezing in 2008 and 2014, a large body of evidence has accumulated suggesting the clinical phenotypes that were proposed, episodic (viral) wheezing and multiple-trigger wheezing, do not relate to underlying airway pathology and may not help determine response to treatment. Specifically, using clinical phenotypes alone may no longer be appropriate, and new approaches that can be used to inform clinical care are needed for future research. This ERS Task Force reviewed the literature published after 2008 related to preschool wheezing and has suggested the criteria used to define wheezing disorders in preschool children should include age of diagnosis (0 to <6 years), confirmation of wheezing on at least one occasion, and more than one episode of wheezing ever.Furthermore, diagnosis and management may be improved by identifying treatable traits, including inflammatory biomarkers (blood eosinophils, aeroallergen sensitisation) associated with type-2 immunity and differential response to inhaled corticosteroids, lung function parameters, and airway infection. However, more comprehensive use of biomarkers/treatable traits in predicting the response to treatment requires prospective validation. There is evidence that specific genetic traits may help guide management, but these must be adequately tested. In addition, the Task Force identified an absence of caregiver-reported outcomes, caregiver/self-management options, and features that should prompt specialist referral for this age group. Priorities for future research include a focus on identifying i) mechanisms driving preschool wheezing, ii) biomarkers of treatable traits and efficacy of interventions in those without allergic sensitisation/eosinophilia, iii) the need to include both objective outcomes and caregiver-reported outcomes in clinical trials, iv) the need for a suitable action plan for children with preschool wheezing and v) a definition of severe/difficult-to-treat preschool wheezing

    Recent warming and increasing CO2 stimulate growth of dominant trees under no water limitation in South Korea.

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    Increases of temperatures and atmospheric CO2 concentration influence the growth performance of trees worldwide. The direction and intensity of tree growth and physiological responses to changing climate do, however, vary according to environmental conditions. Here we present complex, long-term, tree-physiological responses to unprecedented temperature increase in East Asia. For this purpose, we studied radial growth and isotopic (δ13C and δ18O) variations using tree-ring data for the past 100 years of dominant Quercus mongolica trees from the cool-temperate forests from Hallasan, South Korea. Overall, we found that tree stem basal area increment, intercellular CO2 concentration, and intrinsic water-use efficiency significantly increased over the last century. We observed, however, short-term variability in the trends of these variables among four periods identified by change point analysis. In comparison, δ18O did not show significant changes over time, suggesting no major hydrological changes in this precipitation-rich area. The strength and direction of growth-climate relationships also varied during the past 100 years. Basal Area Increment (BAI) did not show significant relationships with the climate over 1924-1949 and 1975-1999 periods. However, over 1950-1974 BAI was negatively affected by both temperature and precipitation, while after 2000 a temperature stimulus was observed. Finally, over the last two decades, the increase in Q. mongolica tree growth accelerated and was associated with high spring-summer temperatures and atmospheric CO2 concentrations and decreasing intrinsic water-use efficiency, δ18O, and VPD, suggesting that the photosynthetic rate continued increasing under no water limitations. Our results indicate that the performance of dominant trees of one of the most widely distributed species in East Asia has benefited from recent global changes, mainly over the last two decades. Such findings are essential for projections of forest dynamics and carbon sequestration under climate change

    Temporal evolution of living donor liver transplantation survival - A UNOS registry study.

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    Living donor liver transplantation (LDLT) is a curative treatment for various liver diseases, reducing waitlist times and associated mortality. We aimed to assess the overall survival (OS), identify predictors for mortality, and analyze differences in risk factors over time. Adult patients undergoing LDLT were selected from the United Network for Organ Sharing database from inception (1987) to 2023. The Kaplan-Meier method was used for analysis, and multivariable Cox proportional hazard models were conducted. 7,257 LDLT recipients with a median age of 54years (IQR:45,61), 54% male, 80% non-Hispanic White, BMI 26.3kg/m2 (IQR:23.2,30.0), and MELD 15 (IQR:11,19) were included. The median cold ischemic time was 1.6hours (IQR:1.0,2.3) with 88% right-lobe-grafts. The follow-up was 4.0years (IQR:1.0,9.2). The contemporary reached median overall survival was 17.0years (95%CI:16.1,18.1) with OS estimates: 1-year 95%, 3-years 89%, 5-years OS 84%, 10-years 72%, 15-years 56% and 20-years 43%. Nine independent factors associated with mortality were identified, with an independent improved OS in the recent time era (aHR 0.53; 95%CI:0.39,0.71). The median center-caseload per year was 5 (IQR:2,10) with observed center-specific improvement of OS. LDLT is a safe procedure with excellent OS. Its efficacy has improved despite an increase of risk parameters, suggesting its limits are yet to be met

    Novel Surgeon-Modified Fenestrated Iliac Stent Graft.

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    PURPOSE We describe the feasibility and early results of a novel endovascular approach with a surgeon-modified fenestrated iliac stent graft to preserve pelvic perfusion in patients with iliac aneurysms not suitable for iliac branch devices (IBDs). TECHNIQUE Seven high-risk patients, median age 76 years (range 63-83), with a complex aortoiliac anatomy with contraindications for commercially available IBDs were treated with a novel surgeon-modified fenestrated iliac stent graft between August 2020 and November 2021. The modified device was built using an iliac limb stent graft (Endurant II Stent Graft; Medtronic), which was partially deployed, surgically fenestrated with a scalpel, reinforced, re-sheathed, and inserted via femoral access. The internal iliac artery was cannulated and bridged with a covered stent. Technical success rate was 100%. After a median follow-up period of 10 months, there was 1 type II endoleak and no migrations, stent fractures, or loss of device integrity. One iliac limb occlusion occurred after 7 months, which needed a secondary endovascular intervention, restoring patency. CONCLUSION Surgeon-modified fenestrated iliac stent graft is feasible and might be used as an alternative in patients with a complex iliac anatomy not suitable to commercially available IBDs. Long-term follow-up is needed to evaluate stent graft patency and potential complications. CLINICAL IMPACT Surgeon modified fenetrated iliac stent grafts might be a promising alternative to iliac branch devices, extending endovascular solutions to a broader patient population with complex aorto-iliac anatomies preserving antegrade internal iliac artery perfusion. It is possible to treat small iliac bifurcations and large angulations of the iliac bifurcation safely and there is no need for a contralateral or upper-extremity access

    Combining Glucose Monitoring and Insulin Infusion in an Integrated Device: A Narrative Review of Challenges and Proposed Solutions.

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    The introduction of automated insulin delivery (AID) systems has enabled increasing numbers of individuals with type 1 diabetes (T1D) to improve their glycemic control largely. However, use of AID systems is limited due to their complexity and costs associated. The user must wear both a continuously monitoring glucose system and an insulin infusion pump. The glucose sensor and the insulin catheter must be inserted at two different body sites using different insertion devices. In addition, the user must pair and manage the different systems. These communicate with the AID software implemented on the pump or on a third device such as a dedicated display device or smart phone application. These components might be developed and commercialized by different manufacturers, which in turn can cause difficulties for patients seeking technical support. A possible solution to these challenges would be to integrate the glucose sensor and insulin catheter into a single device. This would allow the glucose sensor and insulin catheter to be inserted simultaneously, eliminating the need for pairing, and simplifying system management. In recent years, different technologies have been developed and evaluated in clinical investigations that combine the glucose sensor and the insulin catheter in one platform. The consistent finding of all these studies is that integration has no adverse effect on insulin infusion and glucose measurements provided that certain conditions are met. In this review, we discuss the perceived challenges of such an approach and discuss possible solutions that have been proposed

    External Validation of the SI2NCAL2C Score for Outcomes Following Cerebral Venous Thrombosis.

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    OBJECTIVES Prognostication for cerebral venous thrombosis (CVT) remains difficult. We sought to validate the SI2NCAL2C score in an international cohort. MATERIALS AND METHODS The SI2NCAL2C score was originally developed to predict poor outcome (modified Rankin Scale (mRS) 3-6) at 6 months, and mortality at 30 days and 1 year using data from the International CVT Consortium. The SI2NCAL2C score uses 9 variables: the absence of any female-sex-specific risk factors, intracerebral hemorrhage, central nervous system infection, focal neurological deficits, coma, age, lower level of hemoglobin, higher level of glucose, and cancer. The ACTION-CVT study was an international retrospective study that enrolled consecutive patients across 27 centers. The poor outcome score was validated using 90-day mRS due to lack of follow-up at the 6-month time-point in the ACTION-CVT cohort. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration plots. Missing data were imputed using the additive regression and predictive mean matching methods. Bootstrapping was performed with 1000 iterations. RESULTS Mortality data were available for 950 patients and poor outcome data were available for 587 of 1,025 patients enrolled in ACTION-CVT. Compared to the International CVT Consortium, the ACTION-CVT cohort was older, less often female, and with milder clinical presentation. Mortality was 2.5% by 30 days and 6.0% by one year. At 90-days, 16.7% had a poor outcome. The SI2NCAL2C score had an AUC of 0.74 [95% CI 0.69-0.79] for 90-day poor outcome, 0.72 [0.60-0.82] for mortality by 30 days, and 0.82 [0.76-0.88] for mortality by one year. CONCLUSIONS The SI2NCAL2C score had acceptable to good performance in an international external validation cohort. The SI2NCAL2C score warrants additional validation studies in diverse populations and clinical implementation studies

    Chronic insomnia, REM sleep instability and emotional dysregulation: A pathway to anxiety and depression?

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    The world-wide prevalence of insomnia disorder reaches up to 10% of the adult population. Women are more often afflicted than men, and insomnia disorder is a risk factor for somatic and mental illness, especially depression and anxiety disorders. Persistent hyperarousals at the cognitive, emotional, cortical and/or physiological levels are central to most theories regarding the pathophysiology of insomnia. Of the defining features of insomnia disorder, the discrepancy between minor objective polysomnographic alterations of sleep continuity and substantive subjective impairment in insomnia disorder remains enigmatic. Microstructural alterations, especially in rapid eye movement sleep ("rapid eye movement sleep instability"), might explain this mismatch between subjective and objective findings. As rapid eye movement sleep represents the most highly aroused brain state during sleep, it might be particularly prone to fragmentation in individuals with persistent hyperarousal. In consequence, mentation during rapid eye movement sleep may be toned more as conscious-like wake experience, reflecting pre-sleep concerns. It is suggested that this instability of rapid eye movement sleep is involved in the mismatch between subjective and objective measures of sleep in insomnia disorder. Furthermore, as rapid eye movement sleep has been linked in previous works to emotional processing, rapid eye movement sleep instability could play a central role in the close association between insomnia and depressive and anxiety disorders

    Virtuous outlaws: Affective claims to value in professional speechwriters’ discourse

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    Implementation of triple-scan protocol to evaluate the fit of complete-arch implant-supported fixed prostheses.

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    Passive fit is essential for multiple-unit implant-supported prostheses. Conventional methods to assess the passivity of complete-arch implant-supported prostheses do not allow 3-dimensional (3D) visualization and quantification of misfit. This report describes the marginal and internal fit evaluation of a complete-arch implant-supported prosthesis by using the triple-scan protocol involving a scanner and a 3D analysis freeware. This technique allows researchers, clinicians, or dental technicians to detect and quantify 3D prosthetic misfit, which may facilitate the preparation for dental appointments and objective measurement of misfit for research studies

    Verifying the seating of a 3D-printed removable die using elastomeric matrices: A dental technique.

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    Computer-aided design and computer-aided manufacturing systems enable digital designing and 3-dimensional (3D) printing of definitive casts with removable dies. However, the fit of the removable dies should be without interferences for their accurate positioning in the cast. Given that the accuracy of additive manufacturing depends on design- and manufacturing-related factors, verifying the accuracy of the position of 3D-printed removable dies in their cast is essential to fabricate positionally accurate definitive prostheses, which would enable minimal or no laboratory and clinical adjustments. This dental technique article presents a straightforward approach to verify the seating of a 3D-printed removable die by using verification matrices made of a polyvinylsiloxane interocclusal registration material

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