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Multiplicity is a ubiquitous characteristic of massive stars. Multiple systems offer us a unique observational constraint on the formation of high-mass systems. Herschel 36 A is a massive triple system composed of a close binary (Ab1-Ab2) and an outer component (Aa). We measured the orbital motion of the outer component of Herschel 36 A using infrared interferometry with the AMBER and PIONIER instruments of ESO's Very Large Telescope Interferometer. Our immediate aims are to constrain the masses of all components of this system and to determine if the outer orbit is co-planar with the inner one. Reported spectroscopic data for all two components of this system and our interferometric data allow us to derive full orbital solutions for the outer orbit Aa-Ab and the inner orbit Ab1-Ab2. For the first time, we derive the absolute masses of m Aa = 22.3 ± 1.7, m Ab1  = 20.5 ± 1.5, and m Ab2  = 12.5 ± 0.9 M⊙. Despite not being able to resolve the close binary components, we infer the inclination of their orbit by imposing the same parallax as the outer orbit. Inclinations derived from the inner and outer orbits imply a modest difference of about 22° between the orbital planes. We discuss this result and the formation of Herschel 36 A in the context of Core Accretion and Competitive Accretion models, which make different predictions regarding the statistic of the relative orbital inclinations. [ABSTRACT FROM AUTHOR]

The O9.7 V star HD 54879 is currently the only massive magnetic star whose magnetic field geometry and rotation period are not constrained. Over the last 3 yr, we gathered additional observations of this star, obtained using various instruments at several astronomical facilities, with the aim to constrain the rotation period and the magnetic field geometry. The new data include the first full Stokes vector observations with the Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI), installed at the Large Binocular Telescope. The acquired spectropolarimetric observations show a very slow magnetic field variability related to the extremely slow rotation of HD 54879, which is also indicated in a dynamical spectrum, displaying variability of the Hα line. The most intriguing result of our study is the discovery of differences in longitudinal magnetic field strengths measured using different least-squares deconvolution (LSD) masks containing lines belonging to different elements. It is the first time that such a differential analysis of the field strength in dependence of the used lines is carried out for a magnetic O-type star. Since the LSD Stokes  I profiles of the studied O, Si, and He line masks remain stable over all observing epochs, we conclude that the detection of different field strengths using lines belonging to these elements is related to the different formation depths, with the He lines formed much higher in the stellar atmosphere compared to the silicon and the oxygen lines, and non-local thermodynamic equilibrium (NLTE) effects. Our numerical magnetospherical model suggests the presence of enhanced gas density that fills the volume inside the field lines close to the star. [ABSTRACT FROM AUTHOR]

The objective of this study was to analyze the expression and prognostic role of methylthioadenosine phosphorylase (MTAP) in mesothelioma. MTAP protein expression by immunohistochemistry was analyzed in 113 mesotheliomas (60 pleural and 53 peritoneal), consisting of 36 effusions and 77 surgical specimens. MTAP expression was fully lost in 38 tumors and partially lost in 8 tumors. Loss of expression was significantly more common in effusions compared with biopsies/surgical resection specimens (20/36 vs. 26/77; P =0.017), and in pleural compared with peritoneal mesotheliomas (35/60 vs. 11/53; P <0.001). MTAP performed less robustly than BAP1 in comparative analysis of 57 tumors previously analyzed for expression of the latter protein (46 vs. 25 cases with loss of expression). In survival analysis for 69 patients with partial clinical data, male gender was significantly associated with shorter overall survival (OS; P =0.042), whereas loss of MTAP was associated with a trend for shorter OS ( P =0.058), with no prognostic role for patient age ( P =0.379) or anatomic site ( P =0.381). The association between loss of MTAP and poor OS became significant when survival analysis was limited to patients with pleural mesothelioma ( P =0.018). In conclusion, loss of MTAP expression is more frequent in pleural compared with peritoneal mesothelioma and has limited diagnostic relevance at the latter anatomic site. More frequent loss in effusion specimens suggests a role for this marker in effusion cytology. MTAP loss in pleural mesothelioma is associated with poor survival., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Nomenclature in the field of neurodegenerative diseases presents a challenging problem. Inconsistent use of terms such as Alzheimer disease and dementia has compromised progress in clinical care, research, and development of therapeutics. Dementia-associated stigma further contributes to inconsistent and imprecise language. The result is a lack of clarity that produces confusion with patients and the general public and presents communication challenges among researchers. Therefore, the Advisory Council on Research, Care, and Services of the National Plan to Address Alzheimer's Disease authorized a committee to make recommendations for improvement., Objective: To establish a systematic neurodegenerative disease framework for information collection and communication to standardize language usage for research, clinical, and public health purposes., Evidence Review: The Dementia Nomenclature Initiative organized into 3 major stakeholder working groups: clinicians, researchers, and the public (including individuals living with dementia and family caregivers). To inform the work, the initiative completed a narrative literature review of dementia nomenclature evolution over the last century across the PubMed, CINAHL, PsycInfo, and Scopus databases (January 1, 2000, through July 31, 2020). Initiative working groups used the results as a foundation for understanding current challenges with dementia nomenclature and implications for research, clinical practice, and public understanding. The initiative obtained additional input via focus groups with individuals living with dementia and caregivers, with separate groups for race and ethnicity (American Indian or Alaska Native, Asian or Pacific Islander, Black or African American, Hispanic or Latino, and White) as an initial assessment of the meaning of dementia-related terms to these groups., Findings: From working group deliberations, the literature review, and focus group input, the initiative developed a framework clearly separating the clinical syndromic presentation experienced by affected individuals from possible underlying pathophysiologies. In the framework, domains of clinical impairment, such as cognitive, behavioral, motor, and other neurologic features, are graded by level of impairment between none and severe. Next, biomarker information describes underlying disease processes, explains the syndrome, and identifies possible disease labels: Alzheimer disease, frontotemporal degeneration, dementia with Lewy bodies, or vascular cognitive impairment dementia., Conclusions and Relevance: The Dementia Nomenclature Initiative established a framework to guide communication about cognitive impairment among older adults. Wider testing and refinement of the framework will subsequently improve the information used in communicating about cognitive impairment and the way in which the information is used in clinical, research, and public settings.

This dataset covers national and subnational non-pharmaceutical interventions (NPI) to combat the COVID-19 pandemic in the Americas. Prior to the development of a vaccine, NPI were governments' primary tools to mitigate the spread of COVID-19. Variation in subnational responses to COVID-19 is high and is salient for health outcomes. This dataset captures governments' dynamic, varied NPI to combat COVID-19 for 80% of Latin America's population from each country's first case through December 2021. These daily data encompass all national and subnational units in Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Mexico, and Peru. The dataset includes individual and aggregate indices of nine NPI: school closures, work suspensions, public event cancellations, public transport suspensions, information campaigns, local travel restrictions, international travel controls, stay-at-home orders, and restrictions on the size of gatherings. We also collected data on mask mandates as a separate indicator. Local country-teams drew from multiple data sources, resulting in high-quality, reliable data. The dataset thus allows for consistent, meaningful comparisons of NPI within and across countries during the pandemic., (© 2023. Springer Nature Limited.)

Tungsten (W)-based shots are considered more environmentally safe than lead (Pb)-based shots, but knowledge about the W-shot fate in the soil environment is still limited, especially in terms of minor constituents such as iron, copper, and nickel (Ni). Contaminant behaviour in soil strongly depends on pH; in turn, the corrosion of metal composites may affect the pH locally. The aim of this study was to compare Pb- and W-shot weathering dynamics in soil (silt loam, pH 6.3) and reveal the interplay of shot weathering-induced pH-changes on the mobility of elements using in situ chemical imaging (Diffusive gradients in thin films for labile elements, planar optodes for soil pH) and batch incubation experiments over time (16 months). Despite our expectation to find acidification due to W oxidation, we observed a pH increase by 0.2 units in extracted soil solutions and by 0.6 units in the soil around W-shots as Ni dissolved from the binder phase of the shot. After 10 weeks, release of labile Ni was 3-times higher compared to W despite the low Ni content in the shot (7 %, m/m). Pb-shot oxidation increased soil solution pH by 0.5 units which likely supported mobility of Pb-shot-derived antimony (Sb). Steep gradients of labile W and Pb and soil solution concentrations <0.8 μmol L -1 indicated that transfer from shot to soil was low. Contrastingly, labile Ni and Sb were found up to ~4 mm from the shot surface and in higher soil solution concentrations as suggested by the shot constitution, indicating higher mobility of minor as compared to major shot constituents. After 16 months, 36 % of total Ni were dissolved in the soil solution highlighting the environmental relevance of minor shot constituents in Pb-shot alternatives after short term weathering in soil., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Whereas directed evolution and rational design by structural inspection are established tools for enzyme redesign, computational methods are less mature but have the potential to predict small sets of mutants with desired properties without laboratory screening of large libraries. We have explored the use of computational enzyme redesign to change the enantioselectivity of a highly thermostable alcohol dehydrogenase from Thermus thermophilus in the asymmetric reduction of ketones. The enzyme reduces acetophenone to (S)-1-phenylethanol. To invert the enantioselectivity, we used an adapted CASCO workflow which included Rosetta for enzyme design and molecular dynamics simulations for ranking. To correct for unrealistic binding modes, we used Boltzmann weighing of binding energies computed by a linear interaction energy approach. This computationally cheap method predicted four variants with inverted enantioselectivity, each with 6-8 mutations around the substrate-binding site, causing only modest reduction (2- to 7-fold) of k cat /K M values. Laboratory testing showed that three variants indeed had inverted enantioselectivity, producing (R)-alcohols with up to 99 % enantiomeric excess. The broad substrate range allowed reduction of acetophenone derivatives with full conversion to highly enantioenriched alcohols. The results demonstrate the use of computational methods to control ketoreductase stereoselectivity in asymmetric transformations with minimal experimental screening., (© 2023 The Authors. ChemBioChem published by Wiley-VCH GmbH.)

Visualization and quantification of corrosion processes is essential in materials research. Here we present a new approach for 2D spatiotemporal imaging of metal corrosion dynamics in situ. The approach combines time-integrated Mg 2+ flux imaging by diffusive gradients in thin films laser ablation inductively coupled plasma mass spectrometry (DGT LA-ICP-MS) and near real-time pH imaging by planar optodes. The parallel assessment of Mg 2+ flux and pH distributions on a fine-structured, bare Mg alloy (b-WE43) showed intense Mg dissolution with Mg 2+ flux maxima up to 11.9 ng cm -2  s -1 and pH increase >9 during initial corrosion (≤15 min) in aqueous NaNO 3 solution (c = 0.01 mol L -1 ). The techniques visualized the lower initial corrosion rate in buffered synthetic body fluid (Hank's balanced salt solution; pH 7.6) compared to unbuffered NaNO 3 (pH 6.0), but precise localization of Mg corrosion remains challenging under these conditions. To further demonstrate the capability of DGT LA-ICP-MS for spatiotemporal metal flux imaging at the microscale, a coated Mg alloy (c-WE43) with lower reactivity was deployed for ≤120 min. The high spatial resolution (∼10 μm × 80 μm) and low limits of detection (≤0.04 ng cm -2  s -1 , t = 60 min) enabled accurate in situ localization and quantification (U rel  = 20%, k = 2) of distinct Mg 2+ flux increase, showing micro-confined release of Mg 2+ from surface coating defects on c-WE43 samples. The presented approach can be extended to other metal species and applied to other materials to better understand corrosion processes and improve material design in technological engineering., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: While cardiac amyloidosis (CA) classically involves the left ventricle (LV), less is known about its impact on the right ventricle (RV) and pulmonary vasculature. We performed a retrospective analysis to identify the prevalence and types of pulmonary hypertension (PH) profiles in CA and to determine haemodynamic and cardiovascular magnetic resonance (CMR) predictors of major adverse cardiovascular events (MACE)., Methods: Patients with CA who underwent CMR and right heart catheterisation (RHC) within 1 year between 2010 and 2019 were included. Patients were assigned the following haemodynamic profiles based on RHC: no PH, precapillary PH, isolated postcapillary PH (IPCPH), or combined precapillary and postcapillary PH (CPCPH). The relationship between PH profile and MACE (death, heart failure hospitalisation) was assessed using survival analysis. CMR and RV parameters were correlated with MACE using Cox-regression analysis., Results: A total of 52 patients were included (age 69±9 years, 85% men). RHC was performed during biopsy in 44 (85%) and for clinical indications in 8 (15%) patients. Rates of no PH, precapillary PH, IPCPH and CPCPH were 5 (10%), 3 (6%), 29 (55%) and 15 (29%), respectively. Haemodynamic PH profile did not correlate with risk of death (p=0.98) or MACE (p=0.67). Transpulmonary gradient (TPG) (HR 0.88, CI 0.80 to 0.97), RV, (HR 0.95, CI 0.92 to 0.98) and LV ejection fraction (HR 0.95, CI 0.92 to 0.98) were significantly associated with MACE., Conclusions: PH is highly prevalent in CA, even at the time of diagnosis. While IPCPH was most common, CPCPH is not infrequent. TPG and RV ejection fraction (RVEF) are prognostic markers in this population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Nonpharmaceutical interventions such as stay-at-home orders continue to be the main policy response to the COVID-19 pandemic in countries with limited or slow vaccine rollout. Often, nonpharmaceutical interventions are managed or implemented at the subnational level, yet little information exists on within-country variation in nonpharmaceutical intervention policies. We focused on Latin America, a COVID-19 epicenter, and collected and analyzed daily subnational data on public health measures in Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Mexico, and Peru to compare within- and across-country nonpharmaceutical interventions. We showed high heterogeneity in the adoption of these interventions at the subnational level in Brazil and Mexico; consistent national guidelines with subnational heterogeneity in Argentina and Colombia; and homogeneous policies guided by centralized national policies in Bolivia, Chile, and Peru. Our results point to the role of subnational policies and governments in responding to health crises. We found that subnational responses cannot replace coordinated national policy. Our findings imply that governments should focus on evidence-based national policies while coordinating with subnational governments to tailor local responses to changing local conditions.