Search

Purpose: To develop a generic radial sampling scheme that combines the advantages of golden ratio sampling with simplicity of equidistant angular patterns. The irrational angle between consecutive spokes in golden ratio‐based sampling schemes enables a flexible retrospective choice of temporal resolution, while preserving good coverage of k‐space for each individual bin. Nevertheless, irrational increments prohibit precomputation of the point‐spread function (PSF), can lead to numerical problems, and require more complex processing steps. To avoid these problems, a new sampling scheme based on a rational approximation of golden angles (RAGA) is developed. Methods: The theoretical properties of RAGA sampling are mathematically derived. Sidelobe‐to‐peak ratios (SPR) are numerically computed and compared to the corresponding golden ratio sampling schemes. The sampling scheme is implemented in the BART toolbox and in a radial gradient‐echo sequence. Feasibility is shown for quantitative imaging in a phantom and a cardiac scan of a healthy volunteer. Results: RAGA sampling can accurately approximate golden ratio sampling and has almost identical PSF and SPR. In contrast to golden ratio sampling, each frame can be reconstructed with the same equidistant trajectory using different sampling masks, and the angle of each acquired spoke can be encoded as a small index, which simplifies processing of the acquired data. Conclusion: RAGA sampling provides the advantages of golden ratio sampling while simplifying data processing, rendering it a valuable tool for dynamic and quantitative MRI. [ABSTRACT FROM AUTHOR]

Objective: To quantify the variation, triggers and impact on quality of life of symptom flares in women with chronic pelvic pain (CPP). Design: Cross‐sectional questionnaire within the Translational Research in Pelvic Pain clinical cohort study. Setting: Women with CPP, with subgroups of women with endometriosis (EAP), interstitial cystitis/bladder pain syndrome (BPS), comorbid endometriosis and interstitial cystitis/bladder pain syndrome (EABP), and those with pelvic pain without endometriosis or interstitial cystitis/bladder pain syndrome (PP). Population or Sample: A total of 100 participants. Methods: Descriptive and comparative analysis from flares questionnaire. Main Outcome Measures: The prevalence, characteristics and triggers of short, medium and long symptom flares in CPP. Results: We received 100 responses of 104 questionnaires sent. Seventy‐six per cent of women with CPP have ever experienced symptom flares of at least one length (short, medium and/or long). Flares are associated with painful and non‐painful symptoms. There is large variation for the frequency, duration, symptoms and triggers for flares. Over 60% of participants reported flares as stopping them from doing things they would usually do, >80% reported thinking about symptoms of flares and >80% reported flares being bothersome. Conclusions: Flares are prevalent and clinically very important in CPP. More research is needed to elucidate the mechanisms and characteristics underlying flares. Clinical practice should include an enquiry into flares with the aim of finding strategies to lessen their burden. [ABSTRACT FROM AUTHOR]

Background: Inflammatory processes can trigger acute coronary syndromes (ACS) which may increase core body temperature (BT), a widely available low‐cost marker of systemic inflammation. Herein, we aimed to delineate baseline characteristics of ST‐segment elevation myocardial infarction (STEMI) and non‐ST‐segment elevation ACS (NSTE‐ACS) patients stratified by initial BT and to assess its predictive utility towards major adverse cardiovascular events (MACE) after the index ACS. Methods: From 2012 until 2017, a total of 1044 ACS patients, 517 with STEMI and 527 with NSTE‐ACS, were prospectively recruited at the University Hospital Zurich. BT was measured by digital tympanic thermometer along with high‐sensitivity C‐reactive protein (hs‐CRP) and cardiac troponin‐T (hs‐cTnT) levels prior to coronary angiography. Patients were stratified according to initial BT and uni‐ and multivariable regression models were fit to assess associations of BT with future MACE risk. Results: Among patients with STEMI, BT was not predictive of 1‐year MACE, but a U‐shaped relationship between BT and MACE risk was noted in those with NSTE‐ACS (p =.029), translating into a 2.4‐fold (HR, 2.44, 95% CI, 1.16–5.16) increased 1‐year MACE risk in those with BT >36.8°C (reference: 36.6–36.8°C). Results remained robust in multivariable‐adjusted analyses accounting for sex, age, diabetes, renal function and hs‐cTnT. However, when introducing hs‐CRP, the BT‐MACE association did not prevail. Conclusions: In prospectively recruited patients with ACS, initial BT shows a U‐shaped relationship with 1‐year MACE risk among those with NSTE‐ACS, but not in those with STEMI. BT is a broadly available low‐cost marker to identify ACS patients with high inflammatory burden, at high risk for recurrent ischaemic events, and thus potentially suitable for an anti‐inflammatory intervention. Registration: ClinicalTrials.gov Identifier: NCT01000701. [ABSTRACT FROM AUTHOR]

Objectives: Although serum screening for aneuploidies has become less prevalent, maternal‐serum alpha‐fetoprotein (MSAFP) screening for body‐wall defects remains widespread. We explored whether MSAFP screening is associated with earlier omphalocele detection than ultrasound alone. Methods: This is a retrospective cohort study of prenatally detected omphalocele cases at our center from 2007 to 2023. We explored the association between MSAFP screening, gestational age at omphalocele detection, and clinical outcomes. Results: Among 101 pregnancies with prenatally diagnosed omphalocele, 27 (26.7%) had MSAFP screening. The median gestational age at MSAFP screening was 17 weeks 4 days. Of those who received MSAFP screening, 11 (41%) had values ≥2.5 multiples of the median (MoM) and 16 (59%) were not elevated. MSAFP results did not correlate with omphalocele size and were not associated with prenatal or postnatal outcomes. MSAFP screening did not result in earlier suspicion for or confirmation of omphalocele (P =.97 and P =.87, respectively). In contrast, first‐trimester ultrasound screening was associated with earlier suspicion for and confirmation of omphalocele (P <.01 and P =.01, respectively). There were no clinical or demographic differences between those who received MSAFP screening and those who did not (including body mass index or commute distance to an urban center). Conclusion: MSAFP screening is not associated with earlier omphalocele detection. Furthermore, in pregnancies with prenatally diagnosed omphalocele, the results of MSAFP screening are not predictive of clinical outcomes. [ABSTRACT FROM AUTHOR]

In line with calls to stimulate methodological diversity and support evidence‐based human resource development (HRD) through quantitative competencies, we present a methods demonstration leveraging open‐source tools and lesser‐known quantitative research methods to support the HRD research community and applied HRD in the workplace. In this paper, we provide an informative introduction to partial least squares structural equation modeling (PLS‐SEM). We discuss PLS‐SEM application trends in the field of HRD, present key characteristics of the method, and demonstrate up‐to‐date metrics and evaluation guidelines using an illustrative model. Our PLS‐SEM demonstration and explanations can serve as a valuable resource for practitioners concerned with substantiating results for organizational stakeholders and support researchers in methodological decision‐making while avoiding common pitfalls associated with less familiar methods. Our step‐by‐step demonstration is conducted in open‐source software and accompanied by explicitly coded operations so that readers can easily replicate the illustrative analyses presented. [ABSTRACT FROM AUTHOR]

Objectives: The aim was to assess the developmental attributes of sphenoid sinuses affected by fungal balls and describe a surgical approach which reestablishes gravity‐dependent drainage to compensate for any mucociliary dysfunction. Methods: A within‐patient case–control analysis was performed on sphenoid sinus dimensions from patients with sphenoid sinus fungal ball (SSFB). Radiological dimensions were assessed to determine the dominant or larger sinus by volume and width. Pneumatization in the sagittal and lateral extent was assessed. The influence of sinus size and pneumatization variants within a patient was analyzed. Patency and the presence of mucostasis from radical reshaping of the sinus cavity were documented at least 3 months after surgery. Complications (bleeding, cerebrospinal fluid leak, and cranial nerve palsy) were recorded. Results: Twenty‐three patients (59 ± 19 years, 86% female, 46 sphenoid sinuses) were assessed. Fungal ball was more common in the smaller (non‐dominant) sinus, by width (78% vs. 22%, p < 0.01) and by proportion of total sphenoid volume (0.39 ± 0.16 vs. 0.61 ± 0.16, p < 0.01). Pneumatization variants did not influence the development of SSFB within a patient. All patients had patency and the absence of mucostasis or persistent inflammation at last follow‐up. No complications were reported. Conclusion: The smaller or nondominant sphenoid sinus is more affected by SSFB. Surgical reshaping of the sphenoid to prevent mucostasis is favorable in managing the smaller affected sinus cavity. Level of Evidence: 4 Laryngoscope, 134:4888–4892, 2024 [ABSTRACT FROM AUTHOR]

Background: Anti‐inflammatory effects of incretin signaling through the glucagon‐like peptide‐1 receptor (GLP‐1R) and the glucose‐dependent insulinotropic polypeptide receptor (GIPR) in mice have been reported. Therefore, we hypothesized that signaling through the endogenous GLP‐1R and the GIPR individually decreases allergic airway inflammation and that the combination of GLP‐1R and GIPR signaling together additively inhibits allergen‐induced lung and airway inflammation. Methods: WT (C57BL/6J), GLP‐1R knockout (KO), GIPR KO, and GLP‐1R/GIPR double KO (DKO) mice were challenged intranasally with Alternaria alternata extract (Alt‐Ext) or vehicle to evaluate the impact of signaling through these receptors on the innate allergen‐induced inflammatory response that is primarily driven by group 2 innate lymphoid cells (ILC2). Results: Alt‐Ext‐induced IL‐33 release in the bronchoalveolar lavage fluid (BALF) was not different between the mouse strains, but thymic stromal lymphopoietin (TSLP) was significantly increased in GLP‐1R/GIPR DKO mice challenged with Alt‐Ext compared to the other strains. Furthermore, Alt‐Ext‐induced protein expression of IL‐5, IL‐13, CCL11, and CCL24 in the lung homogenates, the number of eosinophils, lymphocytes, and neutrophils in the BALF, and the number of lung GATA3+ ILC2 were significantly increased in GLP‐1R/GIPR DKO mice compared to the other 3 strains. Furthermore, ICAM‐1 expression on lung epithelial cells was increased in GLP‐1R/GIPR DKO mice challenged with Alt‐Ext compared to the other 3 strains. Conclusions: Deficiency of both GLP‐1R and GIPR signaling together increased TSLP release, ILC2 activation, and early type 2 innate immune responses to aeroallergen exposure. Combined GLP‐1R and GIPR signaling should be explored for the treatment of asthma. [ABSTRACT FROM AUTHOR]

Objective: Determining the pathogenicity of missense variants in clinical genetic tests for individuals with epilepsy is crucial for guiding personalized treatment. However, achieving a definitive pathogenic classification remains challenging, with most missense variants still classified as variants of uncertain significance (VUS) and with the availability of many computational tools which may provide conflicting predictions. Here, we aim to evaluate the performance of state‐of‐the‐art computational tools in pathogenicity prediction of missense variants in epilepsy‐associated genes. This will assist in selecting the most appropriate tool and critically assess their use in clinical setting. Methods: We assessed the performance of nine in silico pathogenicity prediction tools for missense variants in epilepsy‐associated genes on three carefully curated data sets. The first two data sets comprise missense variants in epilepsy associated genes that have been uploaded to ClinVar in the last year and were, therefore, not part of the training set of any of the nine considered tools. These two data sets are based on two different lists of epilepsy‐associated genes and comprise ~700 and ~ 250 missense variants, respectively. The third data set includes ~400 missense variants within epilepsy‐associated genes for which the functional effects have been determined experimentally and are therefore used here to infer pathogenicity. These three data sets represent the best available approximation to blind and independent test sets. Results: Among the nine assessed tools, AlphaMissense (area under the curve [AUC]:.93,.88, and.95) and REVEL (AUC:.93,.88, and.93) showed the best classification performance, also outperforming other tools in the number of classified variants. Significance: We show which recently developed prediction tools achieve higher performance in epilepsy‐associated genes and should be integrated, therefore, into the American College of Medical Genetics and Genomics/Association of Molecular Pathology (AGMC/AMP) variant classification process. Periodic reevaluation of genetic test results with newly developed or updated tools should be incorporated into standard clinical practice to improve diagnostic yield and better inform precision medicine. [ABSTRACT FROM AUTHOR]

ABSTRACT Enhanced recovery after surgery (ERAS) pathways have been shown to improve patient outcomes, increase patient satisfaction, and decrease costs. First created and implemented in the adult population, these pathways are now commonplace and continue to expand in the pediatric realm. While there are many proven benefits to ERAS pathways, there continue to be challenges to their proper implementation and long‐term success. This article aims to explore common challenges in pediatric ERAS development and implementation, along with strategies to avoid potential pitfalls. Key themes include departmental and institutional support, stakeholder engagement, awareness of pathways, data management and dissemination, and long‐term maintenance including Plan‐Do‐Study‐Act (PDSA) cycles. Pathway development teams should be aware of these considerations and potential pitfalls, and focusing on them can promote long‐term success for a well‐designed pathway. [ABSTRACT FROM AUTHOR]

Background: Hypertension and exercise testing are essential for cardiovascular risk assessment. However, an exact description of blood pressure (BP) in patients with a hypertensive response during exercise (HRE), especially in the recovery phase is lacking. Herein, we aimed to analyse BP and heart rate during exercise testing and recovery in patients with an HRE. Methods: 800 patients aged 17–90 with an HRE during a standardized bicycle ergometry test were recruited. The BP behaviour during exercise testing was correlated with clinical data. Furthermore, data were analysed according to the presence of pre‐existent hypertension. Results: Of the 800 patients included in this study 497 (62%) were previously diagnosed with hypertension. Analysis of covariance showed a significantly faster systolic (β [95% CI] 8.0 [4.9–11.1]) and diastolic (2.4 [0.4–4.4]) BP recovery 3 min after maximal exercise in patients without hypertension in univariable models. These results remained robust in fully adjusted models taking into account age, sex, body mass index, cardiovascular disease, and antihypertensive treatment for systolic (5.3 [1.2–9.4]) and diastolic BP (4.5 [1.9–7.0]). Furthermore, patients with hypertension displayed higher systolic BP during maximal exercise in univariable (3.8 [0.1–7.5]) and fully adjusted (5.5 [1.1–10.0]) models. There was no difference in maximum diastolic BP between groups. Conclusion: In this large cohort study, patients without hypertension showed a faster systolic and diastolic BP recovery and lower maximal systolic BP compared to patients with hypertension. Overall, this study provides new insights into cardiovascular health during recovery phase. [ABSTRACT FROM AUTHOR]

Objective: To develop evidence‐based recommendations to guide the surgical management and postoperative follow‐up of adults with primary hyperparathyroidism. Methods: Representatives from relevant Australian and New Zealand Societies used a systematic approach for adaptation of guidelines (ADAPTE) to derive an evidence‐informed position statement addressing eight key questions. Results: Diagnostic imaging does not determine suitability for surgery but can guide the planning of surgery in suitable candidates. First‐line imaging includes ultrasound and either parathyroid 4DCT or scintigraphy, depending on local availability and expertise. Minimally invasive parathyroidectomy is appropriate in most patients with concordant imaging. Bilateral neck exploration should be considered in those with discordant/negative imaging findings, multi‐gland disease and genetic/familial risk factors. Parathyroid surgery, especially re‐operative surgery, has better outcomes in the hands of higher volume surgeons. Neuromonitoring is generally not required for initial surgery but should be considered for re‐operative surgery. Following parathyroidectomy, calcium and parathyroid hormone levels should be re‐checked in the first 24 h and repeated early if there are risk factors for hypocalcaemia. Eucalcaemia at 6 months is consistent with surgical cure; parathyroid hormone levels do not need to be re‐checked in the absence of other clinical indications. Longer‐term surveillance of skeletal health is recommended. Conclusions: This position statement provides up‐to‐date guidance on evidence‐based best practice surgical and postoperative management of adults with primary hyperparathyroidism. [ABSTRACT FROM AUTHOR]

A hypertensive response to exercise is a precursor leading to hypertension, which is a major risk factor for the development of heart failure and diastolic dysfunction. Herein, we aimed to assess blood pressure (BP) in patients with a hypertensive response to exercise and different degrees of diastolic dysfunction. Between January 2009 and December 2014, 373 patients with a hypertensive response to exercise (HRE) and echocardiographic data assessing diastolic function were enrolled at the University Hospital of Zurich. ANCOVA was used to assess the changes in BP response during exercise testing in individuals with different degrees of diastolic dysfunction. Normalization of systolic BP was blunted in patients with grade II and III diastolic dysfunction after 3 min of recovery in univariable [β (95%) ‐ 9.2 (‐13.8 to ‐ 4.8) p <.001, ‐16.0 (‐23.0 to 9.0) p <.001, respectively] and adjusted models. In fully adjusted models, when taking maximal effort into account, there were no differences with regard to systolic BP during exercise. Patients without diastolic dysfunction achieved higher heart rates (HRs) [both in absolute terms (p <.001) and as a percentage of the calculated maximum (p =.003)] and greater wattage (p <.001) at maximum exertion. The findings of this cross‐sectional study suggest that exercise capacity is compromised in patients with diastolic dysfunction. A hypertensive response to exercise and the finding of a blunted BP recovery may help identify patients at risk of developing heart failure. [ABSTRACT FROM AUTHOR]

Scientific research demands robust findings, yet variability in results persists due to researchers' decisions in data analysis. Despite strict adherence to state‐of the‐art methodological norms, research results can vary when analyzing the same data. This article aims to explore this variability by examining the impact of researchers' analytical decisions when using different approaches to structural equation modeling (SEM), a widely used method in innovation management to estimate cause–effect relationships between constructs and their indicator variables. For this purpose, we invited SEM experts to estimate a model on absorptive capacity's impact on organizational innovation and performance using different SEM estimators. The results show considerable variability in effect sizes and significance levels, depending on the researchers' analytical choices. Our research underscores the necessity of transparent analytical decisions, urging researchers to acknowledge their results' uncertainty, to implement robustness checks, and to document the results from different analytical workflows. Based on our findings, we provide recommendations and guidelines on how to address results variability. Our findings, conclusions, and recommendations aim to enhance research validity and reproducibility in innovation management, providing actionable and valuable insights for improved future research practices that lead to solid practical recommendations. [ABSTRACT FROM AUTHOR]

Slag fuming (SF) is a metallurgical process designed to recycle Zn‐containing slags derived from various industrial residues. To protect the reactor from corrosive molten slag, a deliberate as‐solidified slag layer, known as a freeze lining (FL), is formed on the reactor walls using intense water‐cooled jackets. In this article, a computational‐fluid‐dynamics‐based model capable of simulating FL formation in a SF furnace is presented. To capture the complex multiphase flow dynamics, heat transfer, and FL formation during SF, a volume‐of‐fluid model is coupled with a mixture continuum solidification model. Three phases are considered: gas, liquid bulk slag, and solid slag (FL). Moreover, two types of FL are distinguished: one that solidifies on the reactor wall in the bulk slag region and another that solidifies on the reactor wall in the freeboard region owing to slag splashing. Comparisons between calculated FL thickness and heat fluxes and corresponding industrial data demonstrate satisfactory agreement. In this outcome, the robustness of the model is underscored and confidence in its accuracy is instilled. In the simulation results, valuable insights are provided into the evolution of the fuming process, particularly regarding the slag bath temperature, slag splashing dynamics, FL formation, local heat fluxes through the reactor wall, and global net energy balance. [ABSTRACT FROM AUTHOR]

Reliable forecasts of quasi‐stationary, recurrent, and persistent large‐scale atmospheric circulation patterns—so‐called weather regimes—are crucial for various socio‐economic sectors, including energy, health, and agriculture. Despite steady progress, probabilistic weather regime predictions still exhibit biases in the exact timing and amplitude of weather regimes. This study thus aims at advancing probabilistic weather regime predictions in the North Atlantic–European region through ensemble post‐processing. Here, we focus on the representation of seven year‐round weather regimes in sub‐seasonal to seasonal reforecasts of the European Centre for Medium‐Range Weather Forecasts (ECMWF). The manifestation of each of the seven regimes can be expressed by a continuous weather regime index, representing the projection of the instantaneous 500‐hPa geopotential height anomalies (Z500A) onto the respective mean regime pattern. We apply a two‐step ensemble post‐processing involving first univariate ensemble model output statistics and second ensemble copula coupling, which restores the multivariate dependence structure. Compared with current forecast calibration practices, which rely on correcting the Z500 field by the lead‐time‐dependent mean bias, our approach extends the forecast skill horizon for daily/instantaneous regime forecasts moderately by 1 day (from 13.5 to 14.5 days). Additionally, to our knowledge our study is the first to evaluate the multivariate aspects of forecast quality systematically for weather regime forecasts. Our method outperforms current practices in the multivariate aspect, as measured by the energy and variogram score. Still, our study shows that, even with advanced post‐processing, weather regime prediction becomes difficult beyond 14 days, which likely points towards intrinsic limits of predictability for daily/instantaneous regime forecasts. The proposed method can easily be applied to operational weather regime forecasts, offering a neat alternative for cost‐ and time‐efficient post‐processing of real‐time weather regime forecasts. [ABSTRACT FROM AUTHOR]

The morphogenesis of higher plants requires communication among distant organs throughout vascular tissues (xylem and phloem). Numerous investigations have demonstrated that phloem also act as a distribution route for signalling molecules being observed that different macromolecules translocated by the sap, including nucleic acids and proteins, change under stress situations. The participation of extracellular vesicles (EVs) in this communication has been suggested, although little is known about their role. In fact, in the last decade, the presence of EVs in plants has originated a great controversy, where major concerns arose from their origin, isolation methods, and even the appropriate nomenclature for plant nanovesicles. Phloem sap exudates from melon plants, either aphid‐free or infested with Aphis gossypii, were collected by stem incision. After sap concentration (Amicon), phloem EVs (PhlEVs) were isolated by size exclusion chromatography. PhlEVs were characterised using Nanoparticle Tracking Analysis, Transmission electron microscopy and proteomic analysis. Here we confirm the presence of EVs in phloem sap in vivo and the detection of changes in the particles/protein ratio and composition of PhlEVs in response to insect feeding, revealing the presence of typical defence proteins in their cargo as well as components of the proteasome complex. PhlEVs from infested plants showed lower particles/protein ratio and almost two times more proteolytic activity than PhlEVs from aphid‐free plants. In both cases, such activity was inhibited in a dose‐dependent manner by the proteasome inhibitor MG132. Our results suggest that plants may use this mechanism to prepare themselves to receive infectious agents and open up the possibility of an evolutionary conserved mechanism of defence against pathogens/stresses in eukaryotic organisms. [ABSTRACT FROM AUTHOR]

AlphaFold2 has revolutionized structural biology by offering unparalleled accuracy in predicting protein structures. Traditional methods for determining protein structures, such as X‐ray crystallography and cryo‐electron microscopy, are often time‐consuming and resource‐intensive. AlphaFold2 provides models that are valuable for molecular replacement, aiding in model building and docking into electron density or potential maps. However, despite its capabilities, models from AlphaFold2 do not consistently match the accuracy of experimentally determined structures, need to be validated experimentally and currently miss some crucial information, such as post‐translational modifications, ligands and bound ions. In this paper, the advantages are explored of collecting X‐ray anomalous data to identify chemical elements, such as metal ions, which are key to understanding certain structures and functions of proteins. This is achieved through methods such as calculating anomalous difference Fourier maps or refining the imaginary component of the anomalous scattering factor f′′. Anomalous data can serve as a valuable complement to the information provided by AlphaFold2 models and this is particularly significant in elucidating the roles of metal ions. [ABSTRACT FROM AUTHOR]

Key content: All patients with ovarian endometriosis should be offered an individualised, shared decision‐making approach informed by clinical history, symptoms and fertility status.Surgical management of ovarian endometriosis can be effective in treating endometriosis‐associated pelvic pain and infertility, but there is no current evidence that surgery for ovarian endometriosis increases the success of in vitro fertilisation (IVF) treatment.Ovarian reserve tests should be considered before any ovarian surgery and can help guide the patient towards the optimal treatment.The Endometriosis Fertility Index should be incorporated into pre‐operative consultations as a validated tool that estimates the likelihood of spontaneous conception following surgical intervention.Surgeons should be trained in different surgical techniques, types of diathermy and haemostatic agents that can minimise the risk of inadvertent injury to normal ovarian cortex. Learning objectives: To facilitate informed decision‐making regarding the treatment of ovarian endometriosis.To gain insight into the possible surgical techniques available to manage ovarian endometriosis and the evidence behind them.To understand the impact of each technique on endometriosis‐associated pain, fertility outcomes and recurrence rates. Ethical considerations: Should fertility preservation be offered to all women of reproductive age with fertility aspirations and a diagnosis of endometriomas?Should integrated care boards (ICBs) devise specific criteria to offer funding for fertility preservation as an option before surgery for ovarian endometriosis? [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusions To assess the effect of allergen immunotherapy (AIT) on patients with central compartment atopic disease (CCAD) and house dust mite (HDM) sensitization post‐surgery.A retrospective cohort of surgically treated, HDM‐sensitized CRSwNP patients phenotyped as CCAD was assessed. Patients were divided into two groups based on whether they had AIT commenced as part of their surgical care. All AIT patients started immunotherapy prior to their surgery. The primary endpoint was reformation of middle turbinate (MT) edema 12 months postsurgery. Secondary endpoints were corticosteroid irrigation use (<4 times/week vs. ≥4 times/week, %) and the rhinologic domain of the 22‐item sino‐nasal outcome test (SNOT‐22). Demographic characteristics, concomitant asthma, smoking status, history of aspirin‐exacerbated respiratory disease, conjunctival symptoms, polysensitization, serum eosinophils (cell × 109/L), tissue eosinophilia (% > 100/HPF), and serum IgE (kU/L) were also recorded.Eighty‐six CCAD patients were assessed (41 ± 14 yrs, 64% female). AIT was applied in 37% (n = 32). Baseline features were similar apart from greater conjunctival symptoms (72 vs. 45%, p = 0.02) in the AIT group. At 12 months post‐surgery, the AIT group has less MT edema (% ≥ diffuse 15.6 vs. 52.9, p < 0.01). Patients on AIT also had less pharmacotherapy requirements at 12 months (% ≥ 4/week, 37.5 vs. 79.6%, p < 0.01). The rhinologic symptoms were similar (21.1 ± 17.1 vs. 20.1 ± 21.6, p = 0.83).Surgery and pharmacotherapy are effective in managing CCAD, but the addition of AIT improved allergic phenomenon and allowed de‐escalation of topical therapy. Longer term studies are required to demonstrate further immunomodulation. [ABSTRACT FROM AUTHOR]

Self‐promoted glycosylations with trichloroacetimidate glycosyl donors are demonstrated on solid‐phase‐anchored peptides orthogonally deprotected and tosylcarbamoylated on the side‐chains of cysteine and serine, respectively. The donor scope included glucosyl as well as mannosyl trichloroacetimidates, carrying benzyl, acetyl, or isopropylidene protecting groups. Isopropylidene groups were found to be removed under the acidic conditions used for release of the neoglycopeptides from the solid support, yielding neoglycopeptides with unprotected hydroxyl groups. Glycosylation of a peptide containing a carbamoylated tyrosine was attempted as well, but the desired neoglycopeptide could not be synthesized due to thermal instability of the carbamate. [ABSTRACT FROM AUTHOR]

Intermetallic nanocrystals are emerging materials for energy, catalysis, and biomedical applications, but combining two or more metals at the nanoscale remains challenging. The amalgamation reaction represents a convenient method for hundreds of intermetallic compositions, as it relies on fast and efficient alloying of liquid metals into presynthesized metallic seeds. Here, Pd–Zn nanocrystals, prepared via Zn amide thermolysis on the surface of Pd nanocrystals and subsequent amalgamation alloying, are investigated. Size‐uniform nanocrystals and control over a wide range of Pd–Zn compositions are achieved. This allows deriving a phase diagram at the nanoscale, in which miscibility gaps and three phases with broad solid solutions are detected. Furthermore, the formation of homogeneous ZnO shells for Pd–Zn compositions extending beyond phase solubility limits is observed. Full chemistry control for Pd–Zn nanocrystals enables a rational choice of materials for selected energy applications, achieveing an extended lifetime of Zn‐ion batteries for Zn‐rich PdZn2 stoichiometry, superior electrocatalytic properties for nearly stoichiometric PdZn halite phase, and the stability and efficiency of high‐voltage cathodes benefiting from ZnO shell protection around Pd3Zn10 nanocrystals are reported. This paper exemplifies the multifunctionality of intermetallics Pd–Zn nanocrystals, while this methodology can be extended to many other bimetallic nanomaterials. [ABSTRACT FROM AUTHOR]

Hypoxic–ischemic encephalopathy (HIE) occurs in up to 7 out of 1000 births and accounts for almost a quarter of neonatal deaths worldwide. Despite the name, many newborns with HIE have little evidence of perinatal hypoxia. We hypothesized that some infants with HIE have genetic disorders that resemble encephalopathy. We reviewed genetic results for newborns with HIE undergoing exome or genome sequencing at a clinical laboratory (2014–2022). Neonates were included if they had a diagnosis of HIE and were delivered ≥35 weeks. Neonates were excluded for cardiopulmonary pathology resulting in hypoxemia or if neuroimaging suggested postnatal hypoxic–ischemic injury. Of 24 patients meeting inclusion criteria, six (25%) were diagnosed with a genetic condition. Four neonates had variants at loci linked to conditions with phenotypic features resembling HIE, including KIF1A, GBE1, ACTA1, and a 15q13.3 deletion. Two additional neonates had variants in genes not previously associated with encephalopathy, including DUOX2 and PTPN11. Of the six neonates with a molecular diagnosis, two had isolated HIE without apparent comorbidities to suggest a genetic disorder. Genetic diagnoses were identified among neonates with and without sentinel labor events, abnormal umbilical cord gasses, and low Apgar scores. These results suggest that genetic evaluation is clinically relevant for patients with perinatal HIE. [ABSTRACT FROM AUTHOR]

Pediatric melanomas are rare tumors that have clinical and histological differences from adult melanomas. In adult melanoma, the immunohistochemical marker PRAME is increasingly employed as a diagnostic adjunct. PRAME is also under investigation as a target structure for next‐generation immunotherapies including T‐cell engagers. Little is known about the characteristics of PRAME expression in pediatric melanoma. In this retrospective study, samples from 25 pediatric melanomas were compared with control groups of melanomas in young adults (18–30 years; n = 32), adult melanoma (>30 years, n = 30), and benign melanocytic nevi in children (0–18 years; n = 30) with regard to the immunohistochemical expression of PRAME (diffuse PRAME expression >75%/absolute expression). Pediatric melanomas show lower diffuse PRAME expression (4%) and lower absolute PRAME expression (25%) compared to young adult melanomas (15.6%/46.8%) and adult melanomas (50%/70%). A significant age‐dependent expression could be observed. An analysis of event‐free survival shows no prognostic role for PRAME in pediatric melanoma and young adult melanoma, but a significant association with diffuse PRAME expression in adulthood. The age dependency of PRAME expression poses a potential pitfall in the diagnostic application of melanocytic tumors in young patients and may limit therapeutic options within this age group. The immunohistochemical expression of the tumor‐associated antigen PRAME is an increasingly important diagnostic marker for melanocytic tumors and is gaining attention as a possible immunotherapeutic target in melanoma. As the available data primarily stem from adult melanoma, and given the clinical and histological distinctions in pediatric melanomas, our understanding of PRAME expression in this specific patient group remains limited. The age‐dependent low PRAME expression shown here constrains the use of this marker in pediatric melanoma and may also limit the use of immunotherapeutic strategies against PRAME in young patients. [ABSTRACT FROM AUTHOR]

The accurate prediction of intense precipitation events is one of the main objectives of operational weather services. This task is even more relevant nowadays, with the rapid progression of global warming which intensifies these events. Numerical weather prediction models have improved continuously over time, providing uncertainty estimation with dynamical ensembles. However, direct precipitation forecasting is still challenging. Greater availability of machine‐learning tools paves the way to a hybrid forecasting approach, with the optimal combination of physical models, event statistics, and user‐oriented postprocessing. Here we describe a specific chain, based on a random‐forest (RF) pipeline, specialised in recognising favourable synoptic conditions leading to precipitation extremes and subsequently classifying extremes into predefined types. The application focuses on northern and central Italy, taken as a testbed region, but is seamlessly extensible to other regions and time‐scales. The system is called MaLCoX (Machine Learning model predicting Conditions for eXtreme precipitation) and is running daily at the Italian regional weather service of ARPAE Emilia‐Romagna. MalCoX has been trained with the ARCIS gridded high‐resolution precipitation dataset as the target truth, using the last 20 years of the European Centre for Medium‐Range Weather Forecasts (ECMWF) reforecast dataset as input predictors. We show that, with a long enough training period, the optimal blend of larger‐scale information with direct model output improves the probabilistic forecast accuracy of extremes in the medium range. In addition, with specific methods, we provide a useful diagnostic to convey to forecasters the underlying physical storyline which makes a meteorological event extreme. [ABSTRACT FROM AUTHOR]

Carbon-based electrodes are used in flow batteries to provide active centers for vanadium redox reactions. However, strong controversy exists about the exact origin of these centers. This study systematically explores the influence of structural and functional groups on the vanadium redox reactions at carbon surfaces. Pyridine, phenol and butyl containing groups are attached to carbon felt electrodes. To establish a unique comparison between the model and real-world behavior, both non-activated and commercially used thermally activated felts serve as a substrate. Results reveal enhanced half-cell performance in non-activated felt with introduced hydrophilic functionalities. However, this cannot be transferred to the thermally activated felt. Beyond a decrease in electrochemical activity, a reduced long-term stability can be observed. This work indicates that thermal treatment generates active sites that surpass the effect of functional groups and are even impeded by their introduction. [ABSTRACT FROM AUTHOR]

Articular cartilage and meniscus transfer and distribute mechanical loads in the knee joint. Degeneration of these connective tissues occurs during the progression of knee osteoarthritis, which affects their composition, microstructure, and mechanical properties. A deeper understanding of disease progression can be obtained by studying them simultaneously. Time‐resolved synchrotron‐based X‐ray phase‐contrast tomography (SR‐PhC‐µCT) allows to capture the tissue dynamics. This proof‐of‐concept study presents a rheometer setup for simultaneous in situ unconfined compression and SR‐PhC‐µCT of connective knee tissues. The microstructural response of bovine cartilage (n = 16) and meniscus (n = 4) samples under axial continuously increased strain, or two steps of 15% strain (stress–relaxation) is studied. The chondrocyte distribution in cartilage and the collagen fiber orientation in the meniscus are assessed. Variations in chondrocyte density reveal an increase in the top 40% of the sample during loading, compared to the lower half. Meniscus collagen fibers reorient perpendicular to the loading direction during compression and partially redisperse during relaxation. Radiation damage, image repeatability, and image quality assessments show little to no effects on the results. In conclusion, this approach is highly promising for future studies of human knee tissues to understand their microstructure, mechanical response, and progression in degenerative diseases. [ABSTRACT FROM AUTHOR]

Background: International osteoporosis guidelines have recommended treatment approaches based on fracture risk stratification, in particular, anabolic therapy for patients with very high risk (VHR) of fragility fracture. Aim: To summarise Australian clinicians' perceptions of patients at VHR of fracture. Methods: Australian clinicians invited to educational webinars on anabolic treatments for osteoporosis were surveyed in March and April 2021 about a typical patient they had most recently seen and identified as at VHR of fracture. Results: Of the 268 clinician attendees who were invited to complete the post‐webinar surveys, 67 (25%) responded and permitted the publication of aggregated data. A typical patient perceived to have a VHR of fracture was a woman in her 80's, living at home, who had been diagnosed with osteoporosis between 5 and 10 years ago, and received treatment for 1–5 years' duration, most commonly denosumab. The patient frequently had a T‐score below −3.0 SD (standard deviation), multiple fragility fractures and most commonly suffered a vertebral fracture in the past 12 months, whereas on an adequate regimen of osteoporosis medication. There was a mismatch between the patient being eligible for anabolic therapy (64.2%) and actually having been prescribed an anabolic treatment in the past (20.9%). Conclusions: Australian clinicians' perceptions of patients with a VHR of fracture and the use of anabolic agents appear to be heavily influenced by local reimbursement criteria. The mismatch between patients deemed eligible for reimbursed anabolic therapy and those prescribed an anabolic agent suggests treatment inertia. [ABSTRACT FROM AUTHOR]

Background: Pectus excavatum repair is associated with significant discomfort, and pain is a primary contributor to postoperative hospital length of stay. Recent advances in postoperative pain control include the use of intercostal cryoablation techniques that may now make it possible to discharge patients on the day of surgery. Unnecessary variation in patient care and noncompliance with care bundles may be a factor in extended length of stay. The global aim of this quality improvement initiative was to successfully implement an enhanced recovery after surgery (ERAS) pathway on patients undergoing pectus excavatum repair. The SMART aim was to have a greater than 70% compliance for the perioperative bundle elements within 1 year of the pathway implementation. Methods: Multiple Plan‐Do‐Study‐Act (PDSA) cycles were designed to create and implement an ERAS pathway for patients undergoing a pectus bar insertion procedure. This multidisciplinary pathway was designed, managed, and implemented with key stakeholders from the Departments of Evidence Based Practice, Surgery, Anesthesiology, and Perioperative Nursing. Patient characteristics, outcomes, and compliance with elements of the pathway were measured for analysis for both the baseline and post‐intervention groups with monthly automated reports. Results: After implementation of the ERAS pathway, data on the first 50 patients showed a 90% compliance with the perioperative bundle elements. Mean length of stay was significantly decreased from 33 h (95% CI [28.76, 37.31]) to 18 h (95% CI [14.54, 21.70]). There were zero readmissions within 24 hours for patients who were discharged on the day of surgery. Conclusion: Employing a multidisciplinary approach in both planning and execution that standardized clinician practices and minimized unnecessary variation in patient care, an ERAS pathway for pectus bar insertion has been successfully established at our institution. [ABSTRACT FROM AUTHOR]

Background: Treatment with vaginal progesterone reduces the risk of miscarriage and preterm birth in selected high‐risk women. The hypothesis that vaginal progesterone can reduce the risk of hypertensive disorders of pregnancy (HDP) is unexplored. Objectives: To summarise the evidence on the effectiveness of vaginal progesterone to reduce the risk of HDP. Search strategy: We searched Embase (OVID), MEDLINE (OVID), PubMed, CENTRAL and clinicaltrials.gov from inception until 20 June 2023. Selection criteria: We included placebo‐controlled randomised trials (RCTs) of vaginal progesterone for the prevention or treatment of any pregnancy complications. Data collection and analysis: We extracted absolute event numbers for HDP and pre‐eclampsia in women receiving vaginal progesterone or placebo, and meta‐analysed the data with a random effects model. We appraised the certainty of the evidence using GRADE methodology. Main results: The quantitative synthesis included 11 RCTs, of which three initiated vaginal progesterone in the first trimester, and eight in the second or third trimesters. Vaginal progesterone started in the first trimester of pregnancy lowered the risk of any HDP (risk ratio [RR] 0.71, 95% confidence interval [CI] 0.53–0.93, 2 RCTs, n = 4431 women, I2 = 0%; moderate‐certainty evidence) and pre‐eclampsia (RR 0.61, 95% CI 0.41–0.92, 3 RCTs, n = 5267 women, I2 = 0%; moderate‐certainty evidence) when compared with placebo. Vaginal progesterone started in the second or third trimesters was not associated with a reduction in HDP (RR 1.19, 95% CI 0.67–2.12, 3 RCTs, n = 1602 women, I2 = 9%; low‐certainty evidence) or pre‐eclampsia (RR 0.97, 95% CI 0.71–1.31, 5 RCTs, n = 4274 women, I2 = 0%; low‐certainty evidence). Conclusions: Our systematic review found first‐trimester initiated vaginal micronised progesterone may reduce the risk of HDP and pre‐eclampsia. [ABSTRACT FROM AUTHOR]

In recent years, there has been growing evidence that latent heat release in midlatitude weather systems such as warm conveyor belts (WCBs) contributes significantly to the onset and maintenance of blocking anticyclones (blocked weather regimes). Still, numerical weather prediction (NWP) and climate models struggle to correctly predict and represent atmospheric blocking in particular over Europe. Here, we elucidate the representation of WCB activity in 20 years of extended winter (1997–2017) of European Centre for Medium‐Range Weather Forecast's IFS reforecasts around the onset of blocking over Europe (EuBL) employing different perspectives. First, we show that the model struggles to predict EuBL onsets already at 10–14 days lead time in line with a misrepresentation of WCB activity in the ensemble mean. However, we also find cases with accurate EuBL forecasts even in pentad 4 (15–19 days). This subset of successful forecasts at extended‐range lead times goes in line with accurate WCB forecasts over the North Atlantic several days prior to the blocking onset. Second, investigating the time‐lagged relationship of blocking onset and WCB activity, we find that WCB activity over the North Atlantic emerges well prior to the onset of the block and that different pathways into EuBL exist in the reforecasts compared to reanalysis. Finally, we find indication of predictability associated with a Rossby wave train emerging from the North Pacific. Although our study can not disentangle the roles of intrinsic predictability limits and model deficiencies, we show that correct predictions of EuBL go along with distinct patterns of WCB activity. Plain Language Summary: Warm conveyor belts (WCBs) are weather systems associated with low pressure systems which occur predominantly over the ocean regions of the midlatitudes. Several recent studies highlight the role of latent heat release due to cloud formation in WCBs for the development of long‐lived high pressure systems. However, current weather prediction and climate models struggle to accurately predict these high pressure systems, particularly over Europe (EuBL). This study, based on 20 years (1997–2017) of forecast data, reveals challenges in predicting WCB activity together with the onset of EuBL, especially within a lead time of 10–14 days. Successful predictions at extended lead times (15–19 days) align with precise forecasts of WCB activity over the North Atlantic and North Pacific, indicating a connection between these regions. Examining the timing of the onset of EuBL and WCB activity, we show that WCB activity over the North Atlantic precedes EuBL. Additionally, we identify both correct and incorrect pathways leading to EuBL and suggest that predictability of EuBL may arise from specific atmospheric patterns, particularly related to Rossby waves in the North Pacific. Key Points: Warm conveyor belt (WCB) activity around the onset of atmospheric blocking over Europe (EuBL) is analyzed in reanalysis and sub‐seasonal reforecastsCorrect WCB prediction provides a sub‐seasonal window of forecast opportunity for EuBL onsetSynoptic activity over the North Pacific supports the development of a teleconnection that affects EuBL onset [ABSTRACT FROM AUTHOR]

Despite the prevalence of exposure to potentially traumatic events (PTEs) among children involved with the child welfare system (CWS), trauma screening is not yet a common practice. The purpose of this study was to assess the impact of embedding a formal trauma screening process in statewide multidisciplinary evaluations for CWS‐involved youth. A retrospective record review was conducted with two random samples of cases reflecting both pre‐ and postimplementation of formal screening procedures (n = 70 preimplementation, n = 100 postimplementation). Findings from the record review indicate statistically significant improvements in the documentation of general, χ2(1, N = 170) = 18.8, p <.001, and specific, χ2(1, N = 170) = 10.7, p =.001, details of children's reactions associated with PTE exposure, as well as increases in providers' recommendations, χ2(1, N = 170) = 18.1, p <.001, and referrals, χ2(1, N = 170) = 4.5, p =.034, for trauma‐focused services. The early identification of trauma‐related symptoms may help connect children more promptly to trauma‐informed evidence‐based interventions, which may avert or mitigate the long‐term sequelae of child maltreatment and CWS involvement. [ABSTRACT FROM AUTHOR]

Objective: To characterize the short‐term outcomes of patients undergoing surgical repair of lateral skull base cerebrospinal fluid (CSF) leaks followed by a shortened length of stay (LOS) protocol. Study Design: Retrospective study. Setting: Tertiary medical center. Methods: A total of 156 adult patients from July 2016 to December 2022 who underwent repair of CSF leaks via transmastoid (TM), middle cranial fossa (MCF), or combined (TM/MCF) approaches were included. Data collected included: LOS, presentation to the emergency department (ED), need for readmission, major neurologic complications (stroke, seizure, and meningitis), and CSF leak recurrence. Results: Approximately half of patients underwent a TM repair (49.4%), whereas the other half underwent either an MCF (3.8%) or combined TM/MCF repair (46.8%). No peri‐/postoperative lumbar drains were used and only 2 (1.3%) patients were admitted to the intensive care unit after surgery. Mean LOS for the cohort was 1.1 ± 0.7 days and was longer for surgeries involving MCF (1.3 ± 0.6) compared to TM (0.8 ± 0.7). Ninety‐two percent of TM cases were discharged within 24 hours (32% on the same day) while for cases involving an MCF approach, 72.2% of patients were discharged within 24 hours. Of the patients in the study, 6 (3.8%) presented to an ED for minor complications and no patient required readmission. Revision surgery was required for 3 (1.9%) patients for recurrent CSF leak. Conclusion: Our findings suggest that short LOS after surgical repair of lateral skull base defects in the treatment of CSF leak is safe and effective. [ABSTRACT FROM AUTHOR]

Mineral dust, the most abundant atmospheric aerosol by mass, interacts with radiation directly and alters cloud properties indirectly. Many operational numerical weather prediction models account for aerosol direct effects by using climatological mean concentrations and neglect indirect effects. This simplification may lead to shortcomings in model forecasts during outbreaks of Saharan dust towards Europe, when climatological mean dust concentrations deviate strongly from actual concentrations. This study investigates errors in model analyses and short‐range forecasts during such events. We investigate a pronounced dust event in March 2021 using the pre‐operational ICOsahedral Nonhydrostatic weather and climate model with Aerosols and Reactive Trace gases (ICON‐ART) with prognostic calculation of dust and the operational European Centre for Medium‐Range Weather Forecasts (ECMWF) Integrated Forecasting System (IFS) model, which deploys a dust climatology. We compare model analysis and forecast with measurements from satellite and in situ instruments. We find that inclusion of prognostic aerosol and direct radiative effects from dust improves forecasts of surface radiation during clear‐sky conditions. However, dust‐induced cirrus clouds are strongly underestimated, highlighting the importance of representing indirect effects adequately. These findings are corroborated by systematic quantification of forecast errors against satellite measurements. For this we construct an event catalogue with 49 dust days over Central Europe between January 2018 and March 2022. We classify model cells by simulated and observed cloudiness and simulated dustiness in the total atmospheric column. We find significant overestimations of brightness temperature for cases with dust compared with cases without dust. For surface shortwave radiation, we find median overestimations of 6.2% during cloudy conditions with dust optical depth greater than 0.1, however these are not significant compared with cloudy conditions without dust. Our findings show that the pre‐operational ICON‐ART and the operational IFS model still do not reproduce cloudiness adequately during events with Saharan dust over Central Europe. Missing implementations of prognostic dust, particularly of indirect effects on cloud formation, lead to significant underestimations of cloudiness and potentially overestimations of surface radiation. [ABSTRACT FROM AUTHOR]

Hybrid vapor deposition is one of the most appealing processes for perovskite photovoltaics fabrication, thanks to its versatile nature. By using sequentially different vapor deposition processes tailored to the inorganic and organic perovskite precursors' peculiarities, this type of process gives access to the full potential of vapor deposition. While vapor deposition of metal halides is well understood and mastered, vapor deposition of organohalide species is much more delicate (degradation of vapors, high vapor pressure, setup‐specific constraints). Here, a novel close space sublimation system is reported and in‐depth insights on the conversion into perovskite of a metal halide template are provided. In this evolution of the process, the substrate coated with metal halide template and the organohalide source are loaded together in a dedicated holder, then transferred into a vacuum chamber on a heating element already at temperature setpoint. The system enables a simple, fast, low‐cost, and easy‐to‐reproduce organohalide vapor deposition process. The formation of the perovskite in situ and identification different conversion regimes are studied. Furthermore, the influence of the chemical environment and chamber design on the process are discussed. Compositional tuning and additive engineering in the process are processed and fabricate proof of concept photovoltaic devices reaching high fill factors of 80% and 17% power conversion efficiency for a bandgap of 1.63 eV. [ABSTRACT FROM AUTHOR]

Nanostructured palladium (Pd) is a universal catalyst that is widely used in applications ranging from catalytic converters of combustion engine cars to hydrogenation catalysts in industrial processes. Standard protocols for synthesizing such nanoparticles (NPs) typically use bottom‐up approaches. They utilize special and often expensive physical techniques or wet‐chemical methods requiring organic surfactants. These surfactants should often be removed before catalytic applications. In this article, the synthesis of Pd NPs immobilized on carbon support by electrochemical erosion without using any surfactants or toxic materials is reported. The Pd NPs synthesis essentially relies on a Pd bulk pretreatment, which causes material embrittlement and allows the erosion process to evolve more efficiently, producing homogeneously distributed NPs on the support. Moreover, the synthesized catalyst is tested for hydrogen evolution reaction. The activity evaluations identify optimal synthesis parameters related to the erosion procedure. The electrocatalytic properties of the Pd NPs produced with sizes down to 6.4 ± 2.9 nm are compared with a commercially available Pd/C catalyst. The synthesized catalyst outperforms the commercial catalyst within all properties, like specific surface area, geometric activity, mass activity, specific activity, and durability. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to examine the relationship between the decrease in elective procedures and the need for blood donation during the novel coronavirus disease (COVID‐19) pandemic at university hospitals. Background: The COVID‐19 pandemic has immensely impacted transfusion medicine. By cancelling elective surgery, the German government hoped to increase the available resources for patients infected with COVID‐19, especially in intensive care units, and prevent the shortage of blood products. Methods/Materials: Over 26 weeks, from the 3rd of February 2020 to the 2nd of August 2020, during the first phase of the pandemic, we assessed the number of crossmatches, blood group typing, use of donated blood, and case mix indices by retrospectively analysing data from two major university hospitals' information systems in Essen and Hamburg, Germany. Data were pooled, analysed, and compared with that of the same period in the previous year. Results: Following the cessation of elective procedures, the number of requests for crossmatches and blood group typing significantly decreased in 2020 compared to that in 2019. However, the number of blood transfusions required was reduced to a lesser extent. The number of outpatient and inpatient cases significantly decreased, whereas the cases requiring transfusion decreased only. Conclusion: During the initial phase of the pandemic, transfusion medicine, especially in large institutions, faced an almost unchanged high demand for donated blood. This should be considered regarding personnel and blood donation allocations. Therefore, we developed a monitoring system to display the availability of blood products in real‐time. The quick and easy display of in‐stock and expiring blood products can optimise the use of this valuable resource. [ABSTRACT FROM AUTHOR]

Metal halide perovskites (MHPs) have become a widely studied class of semiconductors for various optoelectronic devices. The possibility to tune their bandgap (Eg) over a broad spectral range from 1.2 eV to 3 eV by compositional engineering makes them particularly attractive for light emitting devices and multi‐junction solar cells. In this metadata study, data from Peer‐reviewed publications available in the Perovskite Database (www.perovskitedatabase.com) is used to evaluate the current state of Eg tuning in wideEg MHP semiconductors. Recent literature on wide Eg MHP semiconductors is examined and the data is extracted and uploaded onto the Perovskite Database. Beyond describing recent highlights and scientific breakthroughs, general trends are drawn from 45,000 individual experimental datasets of MHP solar cell devices. The historical evolution of MHP solar cells is recapitulated, and general conclusions are drawn about the current limits of device performance. Three dominant causes are identified and discussed for the degradation of performance relative to the Shockley‐Queisser (SQ) model's theoretical limit for single‐junction solar cells: 1) energetically mismatched selective transport materials for wide Eg MHPs, 2) lower optoelectronic quality of wide Eg MHP absorbers, and 3) dynamically evolving compositional heterogeneity due to light‐induced phase segregation phenomena. [ABSTRACT FROM AUTHOR]

Inorganic materials depleted of heavy stable isotopes are known to deviate strongly in some physicochemical properties from their isotopically natural counterparts. Here we explored for the first time the effect of simultaneous depletion of the heavy carbon, hydrogen, oxygen and nitrogen isotopes on the bacterium E. coli and the enzymes expressed in it. Bacteria showed faster growth, with most proteins exhibiting higher thermal stability, while for recombinant enzymes expressed in depleted media, faster kinetics was discovered. At room temperature, luciferase, thioredoxin and dihydrofolate reductase and Pfu DNA polymerase showed up to a 250 % increase in activity compared to the native counterparts, with an additional ∼50 % increase at 10 °C. Diminished conformational and vibrational entropy is hypothesized to be the cause of the accelerated kinetics. Ultralight enzymes may find an application where extreme reaction rates are required. [ABSTRACT FROM AUTHOR]

Research on infant and toddler reaching has shown evidence for motor planning after the initiation of the reaching action. However, the reach action sequence does not begin after the initiation of a reach but rather includes the initial visual fixations onto the target object occurring before the reach. We developed a paradigm that synchronizes head‐mounted eye‐tracking and motion capture to determine whether the latency between the first visual fixation on a target object and the first reaching movement toward the object predicts subsequent reaching behavior in toddlers. In a corpus of over one hundred reach sequences produced by 17 toddlers, we found that longer fixation‐reach latencies during the pre‐reach phase predicted slower reaches. If the slowness of an executed reach indicates reach difficulty, then the duration of pre‐reach planning would be correlated with reach difficulty. However, no relation was found with pre‐reach planning duration when reach difficulty was measured by usual factors and independent of reach duration. The findings raise important questions about the measurement of reach difficulty, models of motor control, and possible developmental changes in the relations between pre‐planning and continuously unfolding motor plans throughout an action sequence. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to investigate real‐world adherence to intranasal corticosteroid irrigations using pharmacy data and assess factors associated with low adherence. Methods: Patients undergoing treatment with corticosteroid irrigations for any diagnosis during a 2‐year period were prospectively recruited. Subjects completed a one‐time set of questionnaires including the Barriers to Care Questionnaire (BCQ), 22‐item Sino‐Nasal Outcome Test (SNOT‐22), and a questionnaire assessing their experience with corticosteroid irrigations. Pharmacy data was used to calculate the medication possession ratio (MPR), a measure of medication adherence graded from 0 to 1. Results: Seventy‐one patients were enrolled. Patient diagnoses included chronic rhinosinusitis (CRS) without nasal polyps (n = 37), CRS with nasal polyps (n = 24), or a non‐CRS diagnosis, most commonly chronic rhinitis (n = 10). The MPR for the overall group was 0.44 ± 0.33. Just 9.9% of patients had a perfect MPR of 1. Despite low MPR, only 19.7% of patients reported problems taking the medication when directly asked. Lower education resulted in lower MPR (unstandardized B = 0.065, p = 0.046). Increasing BCQ score, indicating higher barriers to care, was associated with lower MPR (unstandardized B = −0.010, p = 0.033). The lower the MPR, the worse the patient SNOT‐22 scores (unstandardized B = −15.980, p = 0.036). Conclusion: Adherence to corticosteroid irrigations was low and patients underreported issues with their medication. Education and barriers to care were associated with lower adherence, which, in turn, was associated with worse sinonasal quality of life. [ABSTRACT FROM AUTHOR]

Objective: To formulate clinical consensus recommendations on the presentation, assessment, and management of primary hyperparathyroidism (PHPT) in adults. Methods: Representatives from relevant Australian and New Zealand Societies used a systematic approach for adaptation of guidelines (ADAPTE) to derive an evidence‐informed position statement addressing nine key questions. Results: PHPT is a biochemical diagnosis. Serum calcium should be measured in patients with suggestive symptoms, reduced bone mineral density or minimal trauma fractures, and in those with renal stones. Other indications are detailed in the manuscript. In patients with hypercalcaemia, intact parathyroid hormone, 25‐hydroxy vitamin D, phosphate, and renal function should be measured. In established PHPT, assessment of bone mineral density, vertebral fractures, urinary tract calculi/nephrocalcinosis and quantification of urinary calcium excretion is warranted. Parathyroidectomy is the only definitive treatment and is warranted for all symptomatic patients and should be considered for asymptomatic patients without contraindications to surgery and with >10 years life expectancy. In patients who do not undergo surgery, we recommend annual evaluation for disease progression. Where the diagnosis is not clear or the risk‐benefit ratio is not obvious, multidisciplinary discussion and formulation of a consensus management plan is appropriate. Genetic testing for familial hyperparathyroidism is recommended in selected patients. Conclusions: These clinical consensus recommendations were developed to provide clinicians with contemporary guidance on the assessment and management of PHPT in adults. It is anticipated that improved health outcomes for individuals and the population will be achieved at a decreased cost to the community. [ABSTRACT FROM AUTHOR]

An unusually rich and diverse suite of virgianid brachiopods, hitherto poorly known, is systematically described here for the first time from the Ordovician–Silurian boundary interval (late Katian – Aeronian) of North Greenland. The Late Ordovician virgianids comprise typical taxa of the warm‐water Tcherskidium fauna (e.g. Tcherskidium tenuicostatum, Proconchidium schleyi, Holorhynchus giganteus and Deloprosopus dawesi sp. nov.). Among the early Silurian taxa, Virgiana hursti sp. nov. occurs as abundant shell beds, similar to other congeneric species in Laurentia, but has somewhat larger internal skeletal structures, albeit not as extravagantly developed as in the late Katian virgianids; Borealoides balderi gen. et sp. nov. shows extreme thickening of the shell wall and internal structures, approaching the extravagant calcification of Katian virgianids. The highly distinctive mid‐Aeronian stricklandioid brachiopod genus, Kulumbella, characterized by a shell with criss‐cross (divaricate) ribbing, also occurs in North Greenland, represented by K. heimdali sp. nov., which has the largest and most strongly biconvex shells for the genus. Palaeogeographically, the Late Ordovician virgianid fauna of Laurentia was highly distinct, confined to the low–mid tropical latitudes north of the palaeoequator. In comparison, the early Silurian (Rhuddanian) Virgiana and some related taxa in Laurentia spanned the tropics of both hemispheres, forming extensive shell beds in carbonate basins, although Borealis and Borealoides gen. nov. remained confined largely to the northern hemisphere, suggesting a certain level of provincialism extending into the earliest Silurian. A palaeoecological preference for warm‐water carbonate settings would explain the unusual abundance and richness of the virgianid faunas in North Greenland. [ABSTRACT FROM AUTHOR]

Objective: Progressive hepatic fibrosis can be considered the final stage of chronic liver disease. Hepatic stellate cells (HSC) play a central role in liver fibrogenesis. Thyroid hormones (TH, e.g. thyroxine; T4 and triiodothyronine; T3) significantly affect development, growth, cell differentiation and metabolism through activation of TH receptor α and/or β (TRα/β). Here, we evaluated the influence of TH in hepatic fibrogenesis. Design: Human liver tissue was obtained from explanted livers following transplantation. TRα‐deficient (TRα‐KO) and wild‐type (WT) mice were fed a control or a profibrogenic methionine‐choline deficient (MCD) diet. Liver tissue was assessed by qRT‐PCR for fibrogenic gene expression. In vitro, HSC were treated with TGFβ in the presence or absence of T3. HSC with stable TRα knockdown and TRα deficient mouse embryonic fibroblasts (MEF) were used to determine receptor‐specific function. Activation of HSC and MEF was assessed using the wound healing assay, Western blotting, and qRT‐PCR. Results: TRα and TRβ expression is downregulated in the liver during hepatic fibrogenesis in humans and mice. TRα represents the dominant isoform in HSC. In vitro, T3 blunted TGFβ‐induced expression of fibrogenic genes in HSC and abrogated wound healing by modulating TGFβ signalling, which depended on TRα presence. In vivo, TRα‐KO enhanced MCD diet‐induced liver fibrogenesis. Conclusion: These observations indicate that TH action in non‐parenchymal cells is highly relevant. The interaction of TRα with TH regulates the phenotype of HSC via the TGFβ signalling pathway. Thus, the TH–TR axis may be a valuable target for future therapy of liver fibrosis. [ABSTRACT FROM AUTHOR]

Third- and fourth-generation synchrotron light sources with high fluxes and beam energies enable the use of innovative X-ray translucent experimental apparatus. These experimental devices access geologically relevant conditions whilst enabling in situ characterization using the spatial and temporal resolutions accessible at imaging beamlines. Here, Heitt Mjölnir is introduced, a heated miniature triaxial rig based on the design of Mjölnir, but covering a wider temperature range and larger sample volume at similar pressure capacities. This device is designed to investigate coupled thermal, chemical, hydraulic and mechanical processes from grain to centimetre scales using cylindrical samples of 10 mm × 20 mm (diameter × length). Heitt Mjölnir can simultaneously reach confining (hydraulic) pressures of 30 MPa and 500 MPa of axial stress with independently controlled sample pore fluid pressure < 30 MPa. This internally heated apparatus operates to temperatures up to 573 K with a minimal vertical thermal gradient in the sample of <0.3 K mm-1. This new apparatus has been deployed in operando studies at the TOMCAT (Swiss Light Source), I12 JEEP (Diamond Light Source) and PSICHE' (Synchrotron SOLEIL) beamlines for 4D X-ray microtomography with scan intervals of a few minutes. Heitt Mjölnir is portable and modular, allowing a wide range of 4D characterizations of low-grade metamorphism and deformational processes. It enables spatially and temporally resolved fluid-rock interaction studies at conditions of crustal reservoirs and is suitable for characterization of material properties in geothermal, carbonation or subsurface gas storage applications. Technical drawings and an operation guide are included in this publication. [ABSTRACT FROM AUTHOR]

The dynamic structure and composition of lipid membranes need to be tightly regulated to control the vast array of cellular processes from cell and organelle morphology to protein‐protein interactions and signal transduction pathways. To maintain membrane integrity, sense‐and‐response systems monitor and adjust membrane lipid composition to the ever‐changing cellular environment, but only a relatively small number of control systems have been described. Here, we explore the emerging role of the ubiquitin‐proteasome system in monitoring and maintaining membrane lipid composition. We focus on the ER‐resident RNF145 E3 ubiquitin ligase, its role in regulating adiponectin receptor 2 (ADIPOR2), its lipid hydrolase substrate, and the broader implications for understanding the homeostatic processes that fine‐tune cellular membrane composition. [ABSTRACT FROM AUTHOR]