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Small amounts of water (tens to hundreds of parts per million) can have a profound effect on the properties of mantle peridotites, including viscosities, conductivities, and melting temperatures. Measuring the water content of nominally anhydrous minerals (NAMs) has provided insight into the amounts of water contained within mantle rocks. However, converting from NAM water contents to the activity of H2O is non-trivial. Equilibria involving amphibole can be used to determine values of the activity of H2O (aH2O) at the time of mineral equilibration. This approach yields low values of the activity of H2O (<0.3) for four peridotite xenoliths from Southeastern Australia. These four xenoliths also record values of oxygen fugacity (fO2) that range from −0.2 to −1.2 log units below the fayalitemagnetite-quartz buffer. All these values of fO2 are inconsistent with the presence of a CH4-rich fluid (too oxidizing), and the lowest value of oxygen fugacity, as recorded by one sample, is inconsistent with the presence of a CO2-rich fluid. [ABSTRACT FROM AUTHOR]

Purpose: Understanding the mechanism and extent of preoperative deformity in revision procedures may provide data to prevent future failures in lumbar spinal fusion patients. Methods: ASD patients without prior spine surgery (PRIMARY) and with prior short (SHORT) and long (LONG) fusions were included. SHORT patients were stratified into modes of failure: implant, junctional, malalignment, and neurologic. Baseline demographics, spinopelvic alignment, offset from alignment targets, and patient-reported outcome measures (PROMs) were compared across PRIMARY and SHORT cohorts. Segmental lordosis analyses, assessing under-, match, or over-correction to segmental and global lordosis targets, were performed by SRS-Schwab coronal curve type and construct length. Results: Among 785 patients, 430 (55%) were PRIMARY and 355 (45%) were revisions. Revision procedures included 181 (23%) LONG and 174 (22%) SHORT corrections. SHORT modes of failure included 27% implant, 40% junctional, 73% malalignment, and/or 28% neurologic. SHORT patients were older, frailer, and had worse baseline deformity (PT, PI-LL, SVA) and PROMs (NRS, ODI, VR-12, SRS-22) compared to primary patients (p < 0.001). Segmental lordosis analysis identified 93%, 88%, and 62% undercorrected patients at LL, L1-L4, and L4-S1, respectively. SHORT patients more often underwent 3-column osteotomies (30% vs. 12%, p < 0.001) and had higher ISSG Surgical Invasiveness Score (87.8 vs. 78.3, p = 0.006). Conclusions: Nearly half of adult spinal deformity surgeries were revision fusions. Revision short fusions were associated with sagittal malalignment, often due to undercorrection of segmental lordosis goals, and frequently required more invasive procedures. Further initiatives to optimize alignment in lumbar fusions are needed to avoid costly and invasive deformity corrections. Level of evidence: IV Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding. [ABSTRACT FROM AUTHOR]

Background: Scaling is typically discussed as a way to amplify or expand a health innovation. However, there is limited knowledge about the specific techniques that can enhance access to or improve the quality of innovations, aiming to increase their positive impacts for the public good. We sought to identify, compare, and contrast scaling frameworks to advance the science and practice of scaling. Methods: Using a scoping review we asked: 1) What are the attributes of scaling frameworks for innovations that support health outcomes? and 2) What are the similarities and differences of these attributes? Inclusion criteria were 1) primary studies or review articles, 2) a primary focus on scaling innovations for health and social care, 3) articles that developed a framework, and 4) articles were concerned with a health outcome. Starting from an umbrella review, we identified relevant studies and extracted data about the characteristics of the articles, attributes of framework development, attributes of framework components, transferability, and the framework’s underlying ethical lens. Grey literature was included through expert consultation. Data were summarized using frequencies and qualitative description. Results: From 94 potentially eligible articles, we identified 9 unique frameworks and included 4 additional frameworks from the grey literature, resulting in a total of 13 frameworks. Seven frameworks include a definition of scaling, and eight are designed for public health settings. Five of the frameworks were developed for the US/Canada/UK and Australia. Six of the lead authors’ primary institutional affiliation are from North America. Framework developers involved diverse stakeholders in a number of ways to develop their framework. Eight frameworks were developed, but not yet tested or applied, while the remaining frameworks were in the process of being applied or had already been applied to cases. All frameworks use a consequentialist-utilitarian ethical lens. Lastly, a comparison between frameworks found in the grey or published literature show important differences. Conclusion: Much may be learned through further support for, and development of, scaling frameworks by primary authors affiliated with the Global South. Important aspects of framework development were identified, especially understanding the nuances of diverse stakeholder involvement in development. [ABSTRACT FROM AUTHOR]

Hypoxic microenvironments induce widespread metabolic changes that have been shown to be critical in regulating innate and adaptive immune responses. Hypoxia-induced changes include the generation of extracellular adenosine followed by subsequent signaling through adenosine receptors on immune cells. This evolutionarily conserved "hypoxia-adenosinergic" pathway of hypoxia → extracellular adenosine → adenosine receptor signaling has been shown to be critical in limiting and redirecting T cell responses including in tumor microenvironments and the gut mucosa. However, the question of whether hypoxic microenvironments are involved in the development of B cell responses has remained unexplored until recently. The discovery that germinal centers (GC), the anatomic site in which B cells undergo secondary diversification and affinity maturation, develop a hypoxic microenvironment has sparked new interest in how this evolutionarily conserved pathway affects antibody responses. In this review we will summarize what is known about hypoxia-adenosinergic microenvironments in lymphocyte development and ongoing immune responses. Specific focus will be placed on new developments regarding the role of the hypoxia-adenosinergic pathway in regulating GC development and humoral immunity. [ABSTRACT FROM AUTHOR]

Background: Patients with kidney failure often lack robust evidence because they are excluded from randomized trials. Trial emulation provides an alternative approach to derive treatment effect estimates when randomized trials cannot be conducted. Critical questions about the comparative efficacy and safety of interventions in kidney failure are now being answered using this approach or parts of it. However, variations and inconsistencies in reporting cast doubt on the reliability and validity of effect estimates not derived from randomized trials. The aim of this methodological systematic review is to understand the extent to which the target study approach is used in kidney failure and the appropriateness of this approach. By identifying and evaluating studies that qualify as emulating a target trial, compared with studies that did not apply the principles. We aim to provide more specific methodological guidance to increase the clarity and reliability of reporting treatment effect estimates when running a trial in kidney failure is not feasible. Methods: This protocol is developed in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses Protocols (PRISMA-P) statement. MEDLINE, Embase, and reference lists (backwards citation chasing) will be searched up until 1st July 2023 and the search updated prior to publication to identify all studies evaluating patient outcomes in late-stage kidney disease and failure that use target trial emulation as the primary approach for analysis. Two authors (A. A., P. K.) will select articles based on title and abstract and then full text, with a third reviewer settling disagreements (J. P.). The prespecified variables will be extracted, and the risk of bias will be assessed by at least two authors (A. A., P. K., A. N.) using prespecified data forms. This will enable the determination of the robustness of the methodological quality of observational studies in using the whole or elements of the target trial approach. We will thereby assess their ability to reliably report treatment effect estimates. Discussion: We will provide specific methodological recommendations on how to design target trials and model assumptions for emulation to get reliable treatment effect estimates for therapeutic interventions in kidney failure. Methodological systematic review registration: Open Science Framework: Identifier https://doi.org/10.17605/OSF.IO/Z4Y29. [ABSTRACT FROM AUTHOR]

Background and aims: Several non-invasive tests for detecting bladder cancer (BC) are commercially available and are based on detecting small panels of BC-associated mutations and/or methylation changes in urine DNA. However, it is not clear which type of biomarker is best, or if a combination of the two is needed. In this study we address this question by taking a 23-gene mutation panel (GALEAS™ Bladder, GB) and testing if adding a panel of methylation markers improves the sensitivity of BC detection. Methods: Twenty-three methylation markers were assessed in urine DNA by bisulphite conversion, multiplex PCR, and next generation sequencing in 118 randomly selected haematuria patients with pre-existing GB data (56 BCs and 62 non-BCs), split into training and test sets. We also analysed an additional 16 GB false-negative urine DNAs. Results: The methylation panel detected bladder cancer in haematuria patients with 69% sensitivity at 96% specificity (test set results, 95% CIs 52-87% and 80-99%, respectively). Corresponding sensitivity and specificity for GB were 92% and 89%. Methylation and mutation markers were highly concordant in urine, with all GB false-negative samples also negative for methylation markers. Conclusions and limitations: Our data show that, with a comprehensive mutation panel, any gains from adding methylation markers are, at best, marginal. It is likely that low tumour content is the commonest cause of false-negative urine test results. Our study does have a limited sample size and other methylation markers might behave differently to the those studied here. [ABSTRACT FROM AUTHOR]

Although next‐generation sequencing has enabled diagnoses for many patients with Mendelian disorders, the majority remain undiagnosed. Here, we present a sibling pair who were clinically diagnosed with Escobar syndrome, however targeted gene testing was negative. Exome sequencing (ES), and later genome sequencing (GS), revealed compound heterozygous TTN variants in both siblings, a maternally inherited frameshift variant [(NM_133378.4):c.36812del; p.(Asp12271Valfs*10)], and a paternally inherited missense variant [(NM_133378.4):c.12322G > A; p.(Asp4108Asn)]. This result was considered nondiagnostic due to poor clinical fit and limited pathogenicity evidence for the missense variant of uncertain significance (VUS). Following initial nondiagnostic RNA sequencing (RNAseq) on muscle and further pursuit of other variants detected on the ES/GS, a reanalysis of noncanonical splice sites in the muscle transcriptome identified an out‐of‐frame exon retraction in TTN, near the known VUS. Interim literature included reports of patients with similar TTN variants who had phenotypic concordance with the siblings, and a diagnosis of a congenital titinopathy was given 4 years after the TTN variants had been initially reported. This report highlights the value of reanalysis of RNAseq with a different approach, expands the phenotypic spectrum of congenital titinopathy and also illustrates how a perceived phenotypic mismatch, and failure to consider known variants, can result in a prolongation of the diagnostic journey. [ABSTRACT FROM AUTHOR]

Background: Neurolymphomatosis refers to infiltration of the peripheral nervous system (PNS) by non-Hodgkin lymphoma (NHL). Diagnostic intervals in neurolymphomatosis and factors delaying diagnosis have not been evaluated. We therefore aimed to analyze diagnostic intervals in a large cohort. Methods: The quality control database at Yale Cancer Center, Section of Neuro-Oncology, was searched for neurolymphomatosis cases diagnosed between 2001 and 2021. Univariate analyses were performed to identify parameters influencing diagnostic intervals. Results: We identified 22 neurolymphomatosis cases including 7 with primary and 15 with secondary disease, which occurred a median (range: 4–144) of 16 months after initial NHL diagnosis. Patients typically presented with painful polyneuropathy (73%), that was asymmetrical and rapidly progressive. Diagnosis was based on PNS biopsy (50%) or integration of neuroimaging findings (50%) with NHL history and diagnostic cerebrospinal fluid examinations. Median interval from symptom onset to diagnosis was 3 months (range: 1–12). Secondary neurolymphomatosis compared to primary disease (median 2 vs. 6 months, p = 0.02), and cases with rapidly-progressive asymmetrical neuropathy as opposed to other presentations (median 2 vs. 6 months; p < 0.001) were diagnosed earlier. Upfront conventional CT compared to other modalities (median 2 vs. 5 months p = 0.04) and nerve root localization as opposed to other disease sites (median 1.5 vs. 4 months; p = 0.04) delayed diagnosis. Conclusions: NL type and localization, neuropathy course and distribution, and imaging modality selected for initial evaluation influence diagnostic intervals in neurolymphomatosis. Knowledge of this rare entity is critical for early suspicion, and diagnosis. [ABSTRACT FROM AUTHOR]

The NIH Toolbox Cognitive Battery (NIHTB-CB) was developed as a common-metric, computerized cognitive screener for research. Although extensively normed and validated in Americans of different ethnicities, there is little data on how generalizable such results would be when used outside of the United States. The objective of this study was to assess measurement invariance (MI) of the NIHTB-CB across Jamaican and African-American samples and determine appropriateness of comparisons across groups. Multi-group confirmatory factor analyses using a single-factor model were conducted using five tests of fluid cognitive abilities from the NIHTB-CB, which assess working memory, episodic memory, processing speed, and executive function. MI was tested sequentially for configural, metric and scalar invariance. 125 Jamaican and 154 American adults of African descent were included. The Jamaican mean age was 31.6 ± 8.6 years (57% males) compared to 43.5 ± 15.5 years (25% males) for the African-American group. The Jamaicans had on average 11.3 ± 2.7 years of education compared to 13.9 ± 2.6 years for the African-Americans. We found metric and configural invariance across both samples but not scalar invariance. These findings suggest that the single factor emerging from the NIHTB-CB measures the same construct, i.e. fluid cognitive ability, in both groups and hence the battery is appropriate for assessments within cultures. However, lack of scalar invariance indicates that direct cross-cultural comparisons of performance levels should be interpreted with caution, also suggesting that U.S. normative standards are not generalizable to the Jamaican population. [ABSTRACT FROM AUTHOR]

Background: In the search for effective treatments for refractive obsessive–compulsive disorder (OCD), deep brain stimulation (DBS) serves as an alternative option for those with minimal response to pharmacotherapy. The rarity of reports regarding DBS use for OCD is attributed to the invasive nature of the procedure: placement of electrodes within targeted areas of the brain to provide neuromodulation. This treatment of last resort may decrease functional impairment and pharmacologic complications for a debilitating mental illness. This study compares the pharmacotherapy utilization and treatment outcomes of five treatment-refractory OCD patients after the placement of DBS with those of a matched cohort. Methods: This retrospective, single-center, case–cohort study reviewed the electronic medical records of five subjects treated with DBS for treatment-refractory OCD and compared them to a similar treatment-refractory cohort whose OCD was treated without the use of DBS. Control subjects were matched by age, sex, years since diagnosis, number of previous medication class trials, and additional clinical factors. Inclusion criteria were defined as those that are at least eighteen years of age, assigned a primary diagnosis of OCD per the ICD-10 classification, and received DBS treatment for refractory OCD. Exclusion criteria included comorbid psychotic disorders, unstable neurological or coagulation disorder(s), and/or an eating disorder diagnosis. The primary endpoint was the change in the number of psychotropic medications two years after implantation for the DBS cohort and two years after psychiatric decompensation for the comparator cohort. Secondary endpoints included: Y-BOCS (the Yale–Brown Obsessive–Compulsive Scale) changes over time, duration quantity of psychotropic medication classes prescribed, and additional symptomology scale changes. Results: Patients receiving DBS were more likely to be on fewer medications and trialed fewer medications after treatment. One out of the five patients was found to be a responder in Y-BOCS scoring after DBS treatment. A reduction in anxiety and depression symptoms was also seen in the HAM-A and HAM-D scales for those that received DBS. Conclusions: A reduction in psychiatric medications trialed during therapy was observed, as well as varying reductions in OCD, anxiety, and depression symptomology following DBS. Results from this study indicate that DBS implantation may contribute to a reduction in polypharmacy while displaying DBS's potential impact on comorbid anxiety and depression symptoms. Given that the small sample size limits generalizability, additional prospective, randomized trials comparing the efficacy of DBS for OCD-specific symptomology and its overall impact on pharmacotherapy are needed in order to further establish the role of DBS as an accepted treatment option for OCD. [ABSTRACT FROM AUTHOR]

Objective: HIV/AIDS disproportionately affects Black and Latino people in the United States, yet there is a lack of research on predictors of neurocognitive outcomes in these groups. We examined neurocognitive performance and its key predictors across White, Black, and Latino people with HIV (PWH). Method: Participants included 586 PWH of White, Black, and Latino (English- and Spanish-speaking) background. Neurocognition was assessed via demographically-adjusted Fluid Cognition Composite T-scores from the NIH-Toolbox cognition battery, and individual tests comprising this composite. Predictors examined included sociodemographic and HIV disease characteristics, and medical, psychiatric and substance comorbidities. Results: Compared to White PWH, English-speaking Latino PWH had lower T-scores on the Fluid Cognition Composite, as well as Flanker Inhibition and Picture Sequence Memory tests. While there were no other significant group differences on Fluid Cognition, both Latino PWH language groups performed worse than Black PWH on Flanker Inhibition, and Black PWH performed worse than White PWH on List Sorting. Separate multivariable linear regression models by ethnic/racial/language group showed that significant correlates of worse Fluid Cognition included depressive symptoms among White PWH; hepatitis C co-infection among Black PWH; hypertension among English-speaking Latino PWH; and higher estimated duration of HIV disease and depressive symptoms in Spanish-speaking Latino PWH. Conclusions: Findings suggest worse neurocognition among English-speaking Latino PWH compared to Whites. Predictors of neurocognitive function among PWH differ across ethnic/racial and language groups. Consideration of these HIV disease characteristics and comorbidities may be valuable in developing targeted culturally-relevant interventions aimed at ameliorating neurocognitive dysfunction among diverse PWH. [ABSTRACT FROM AUTHOR]

Introduction: Gestational diabetes mellitus (GDM) continues to increase particularly for non‐European women. This study aimed to identify and quantify risk factors for women diagnosed with gestational diabetes in New Zealand to identify women at higher risk. Methods: A national dataset of 601,166 eligible women who had ≥ 1 birth in New Zealand between January 2001 and December 2010 identified 11,459 women with gestational diabetes of whom 11,447 were randomly matched with 57,235 control women for age and year of delivery. Results: Adjusted odds ratios (95% CI) showed higher odds of gestational diabetes for Asian (3.60, 3.39–3.82), Pacific (2.76, 2.57–2.96) and Māori (1.23, 1.15–1.31) women compared with European/Other women. Women most economically disadvantaged (1.44, 1.34–1.56), not registered with a lead maternity carer (1.16, 1.04–1.30) and those identified as smokers (1.20, 1.11–1.31) were more likely than control women to develop gestational diabetes. In contrast, women residing in rural (0.83, 0.77–0.88) and remote areas (0.68, 0.60–0.77) were less likely to develop gestational diabetes compared with women living in urban areas, and similarly for non‐New Zealand resident women (0.78, 0.72–0.85) compared with resident women. Conclusions: Women who were diagnosed with gestational diabetes were more likely to be non‐European, economically disadvantaged, residing in urban areas, unregistered with a lead maternity carer and more likely to smoke. In addition to universal screening for pre‐existing diabetes, all women at risk of gestational diabetes should be identified and supported to undertake to a 75 g glucose challenge test between 24 and 28 weeks. [ABSTRACT FROM AUTHOR]

E-cigarettes have gained notable popularity among youth in recent years, posing a serious societal issue that has elicited much concern from public health professionals and legislators. The increase in e-cigarette consumption among adolescents can be ascribed to assertive marketing strategies employed by corporations that focus on appealing to young consumers through flavored offerings and aesthetically pleasing designs. This rise is concerning because of the possible long-term health ramifications linked to vaping, such as nicotine addiction and exposure to hazardous chemicals found in numerous e-cigarette formulations. The normalization of e-cigarette usage in social contexts may result in heightened peer pressure and the endorsement of detrimental conduct. To properly address this issue, government agencies must enforce stronger rules on e-cigarette sales and marketing directed at minors, while schools and community organizations should educate youth about the risks of vaping. [ABSTRACT FROM AUTHOR]

Herein, we report a metal-free, base-promoted route for the synthesis of hybrid molecular scaffolds in which various 1,3-diones and 1,2,4-triazoles are linked by a benzyl bridge. This three-component, one-pot reaction was accomplished by first treating 4-hydroxycoumarin, trans-β-nitrostyrene, and aldehyde hydrazone in the presence of sodium carbonate. Further, this protocol was successfully expanded to other 1,3-diones, such as dimedone and 4-hydroxy-2-quinolone. A broad substrate scope, mild reaction conditions, and the metal and ligand/additive-free approach are the prominent features of this strategy. [ABSTRACT FROM AUTHOR]

Background Staphylococcus aureus bloodstream infection (bacteremia) is traditionally treated with at least 2 weeks of intravenous (IV) antibiotics in adults, 3–7 days in children, and often longer for those with complicated disease. The current practice of treating S. aureus bacteremia (SAB) with prolonged IV antibiotics (rather than oral antibiotics) is based on historical observational research and expert opinion. Prolonged IV antibiotic therapy has significant disadvantages for patients and healthcare systems, and there is growing interest in whether a switch to oral antibiotics following an initial period of IV therapy is a safe alternative for clinically stable patients. Protocol The early oral switch (EOS) domain of the S. aureus Network Adaptive Platform (SNAP) trial will assess early switch to oral antibiotics compared with continued IV treatment in clinically stable patients with SAB. The primary endpoint is 90-day all-cause mortality. Hospitalised SAB patients are assessed at platform day 7 ±2 (uncomplicated SAB) and day 14 ±2 (complicated SAB) to determine their eligibility for randomization to EOS (intervention) or continued IV treatment (current standard of care). Discussion Recruitment is occurring in the EOS domain of the SNAP trial. As of August 2023, 21% of all SNAP participants had been randomized to the EOS domain, a total of 264 participants across 77 centers, with an aim to recruit at least 1000 participants. We describe challenges and facilitators to enrolment in this domain to aid those planning similar trials. [ABSTRACT FROM AUTHOR]

Individuals diagnosed with Parkinson's disease (PD) often exhibit heightened susceptibility to cardiac dysfunction, reflecting a complex interaction between these conditions. The involvement of mitochondrial dysfunction in the development and progression of cardiac dysfunction and PD suggests a plausible commonality in some aspects of their molecular pathogenesis, potentially contributing to the prevalence of cardiac issues in PD. Mitochondria, crucial organelles responsible for energy production and cellular regulation, play important roles in tissues with high energetic demands, such as neurons and cardiac cells. Mitochondrial dysfunction can occur in different and non-mutually exclusive ways; however, some mechanisms include alterations in mitochondrial dynamics, compromised bioenergetics, biogenesis deficits, oxidative stress, impaired mitophagy, and disrupted calcium balance. It is plausible that these factors contribute to the increased prevalence of cardiac dysfunction in PD, suggesting mitochondrial health as a potential target for therapeutic intervention. This review provides an overview of the physiological mechanisms underlying mitochondrial quality control systems. It summarises the diverse roles of mitochondria in brain and heart function, highlighting shared pathways potentially exhibiting dysfunction and driving cardiac comorbidities in PD. By highlighting strategies to mitigate dysfunction associated with mitochondrial impairment in cardiac and neural tissues, our review aims to provide new perspectives on therapeutic approaches. [ABSTRACT FROM AUTHOR]

Mass spectrometry imaging (MSI) is a powerful scientific tool for understanding the spatial distribution of biochemical compounds in tissue structures. In this paper, we introduce three novel approaches in MSI data processing to perform the tasks of data augmentation, feature ranking, and image registration. We use these approaches in conjunction with non-negative matrix factorization (NMF) to resolve two of the biggest challenges in MSI data analysis, namely: 1) the large file sizes and associated computational resource requirements and 2) the complexity of interpreting the very high dimensional raw spectral data. There are many dimensionality reduction techniques that address the first challenge but do not necessarily result in readily interpretable features, leaving the second challenge unaddressed. We demonstrate that NMF is an effective dimensionality reduction algorithm that reduces the size of MSI datasets by three orders of magnitude with limited loss of information, yielding spatial and spectral components with meaningful correlation to tissue structure that may be used directly for subsequent data analysis without the need for additional clustering steps. This analysis is demonstrated on an MSI dataset from female Sprague-Dawley rats for an animal model of comorbid visceral pain hypersensitivity (CPH). We find that high-dimensional MSI data (∼ 100,000 ions per pixel) can be reduced to 20 spectral NMF components with < 20% loss in reconstruction accuracy. The resulting spatial NMF components are reproducible and correlate well with H&E-stained tissue images. These components may also be used to generate images with enhanced specificity for different tissue types. Small patches of NMF data (i.e., 20 spatial NMF components over 20 × 20 pixels) provide an accuracy of ∼ 87% in classifying CPH vs naïve control subjects. This paper presents the novel data processing methodologies that were used to produce these results, encompassing novel data processing pipelines for data augmentation to support training for classification, ranking of features according to their contribution to classification, and image registration to enhance tissue-specific imaging. [ABSTRACT FROM AUTHOR]

We contribute to the higher education returns discourse by examining perceptions among college graduates. Using 2021 U.S. Survey of Household Economics of Decisionmaking data, we observe that over 80% of degree holders perceive that they received positive financial returns from college, while only 7% of college degree holders regret their decision to go to university. However, 39% regret their major choice, and 24% regret their institution choice. Logistic regression reveals perceptions and regrets vary with field of study, gender, type of institution attended, student debt load, and age. [ABSTRACT FROM AUTHOR]

The water‐lily clade represents the second earliest‐diverging branch of angiosperms. Most of its species belong to Nymphaeaceae, of which the "core Nymphaeaceae"—comprising the genera Euryale, Nymphaea and Victoria—is the most diverse clade. Despite previous molecular phylogenetic studies on the core Nymphaeaceae, various aspects of their evolutionary relationships have remained unresolved. The length‐variable introns and intergenic spacers are known to contain most of the sequence variability within the water‐lily plastomes. Despite the challenges with multiple sequence alignment, any new molecular phylogenetic investigation on the core Nymphaeaceae should focus on these noncoding plastome regions. For example, a new plastid phylogenomic study on the core Nymphaeaceae should generate DNA sequence alignments of all plastid introns and intergenic spacers based on the principle of conserved sequence motifs. In this investigation, we revisit the phylogenetic history of the core Nymphaeaceae by employing such an approach. Specifically, we use a plastid phylogenomic analysis strategy in which all coding and noncoding partitions are separated and then undergo software‐driven DNA sequence alignment, followed by a motif‐based alignment inspection and adjustment. This approach allows us to increase the reliability of the character base compared to the default practice of aligning complete plastomes through software algorithms alone. Our approach produces significantly different phylogenetic tree reconstructions for several of the plastome regions under study. The results of these reconstructions underscore that Nymphaea is paraphyletic in its current circumscription, that each of the five subgenera of Nymphaea is monophyletic, and that the subgenus Nymphaea is sister to all other subgenera of Nymphaea. Our results also clarify many evolutionary relationships within the Nymphaea subgenera Brachyceras, Hydrocallis and Nymphaea. In closing, we discuss whether the phylogenetic reconstructions obtained through our motif‐based alignment adjustments are in line with morphological evidence on water‐lily evolution. [ABSTRACT FROM AUTHOR]

Uncertainty attribution in water supply forecasting is crucial to improve forecast skill and increase confidence in seasonal water management planning. We develop a framework to quantify fractional forecast uncertainty and partition it between (1) snowpack quantification methods, (2) variability in post‐forecast precipitation, and (3) runoff model errors. We demonstrate the uncertainty framework with statistical runoff models in the upper Tuolumne and Merced River basins (California, USA) using snow observations at two endmember spatial resolutions: a simple snow pillow index and full‐catchment snow water equivalent (SWE) maps at 50 m resolution from the Airborne Snow Observatories. Bayesian forecast simulations demonstrate a nonlinear decrease in the skill of statistical water supply forecasts during warm snow droughts, when a low fraction of winter precipitation remains as SWE. Forecast skill similarly decreases during dry snow droughts, when winter precipitation is low. During a shift away from snow‐dominance, the uncertainty of forecasts using snow pillow data increases about 1.9 times faster than analogous forecasts using full‐catchment SWE maps in the study area. Replacing the snow pillow index with full‐catchment SWE data reduces statistical forecast uncertainty by 39% on average across all tested climate conditions. Attributing water supply forecast uncertainty to reducible error sources reveals opportunities to improve forecast reliability in a warmer future climate. [ABSTRACT FROM AUTHOR]

The precise control of soft and continuum robots requires knowledge of their shape, which has, in contrast to classical rigid robots, infinite degrees of freedom. To partially reconstruct the shape, proprioceptive techniques use built‐in sensors, resulting in inaccurate results and increased fabrication complexity. Exteroceptive methods so far rely on expensive tracking systems with reflective markers placed on all components, which are infeasible for deformable robots interacting with the environment due to marker occlusion and damage. Here, a regression approach is presented for three‐dimensional key point estimation using a convolutional neural network. The proposed approach uses data‐driven supervised learning and is capable of online markerless estimation during inference. Two images of a robotic system are captured simultaneously at 25 Hz from different perspectives and fed to the network, which returns for each pair the parameterized key point or piecewise constant curvature shape representations. The proposed approach outperforms markerless state‐of‐the‐art methods by a maximum of 4.5% in estimation accuracy while being more robust and requiring no prior knowledge of the shape. Online evaluations on two types of soft robotic arms and a soft robotic fish demonstrate the method's accuracy and versatility on highly deformable systems. [ABSTRACT FROM AUTHOR]

Background: The addition of epinephrine to arthroscopic irrigation fluid has been shown to improve surgeon-rated visual clarity during shoulder arthroscopic surgery. Subacromial injections of epinephrine are also used for this purpose. Purpose/Hypothesis: To assess the influence of a preoperative subacromial epinephrine injection on surgeon visualization during subacromial shoulder arthroscopic surgery. It was hypothesized that the epinephrine injection would improve surgeon-rated visual clarity. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A double-blind randomized controlled trial including adult patients undergoing shoulder arthroscopic surgery in the beach-chair position requiring visualization of the subacromial space was performed. Patients in the epinephrine group (n = 30) received a preoperative subacromial injection of bupivacaine and epinephrine, and those in the control group (n = 30) received a preoperative subacromial injection of bupivacaine. Epinephrine was added to the first 10 L of arthroscopic irrigation fluid in all patients. The primary outcome was surgeon-rated visual clarity throughout the procedure that was recorded at the end of the procedure using a visual analog scale (VAS) scored from 0 (worst) to 10 (best). Secondary outcomes included an increase in pump pressure during the procedure, total operative time, and the intraoperative use of blood pressure–modulating medications. Results: Rotator cuff repair was performed in 88.3% of patients (25/30 epinephrine; 28/30 control), with multiple procedures performed in 85.0% of patients (23/30 epinephrine; 27/30 control). The VAS score for visual clarity was slightly better in the epinephrine group compared with the control group, although the difference was neither statistically nor clinically significant (8.3 ± 1.4 vs 7.5 ± 1.8, respectively; P =.09). There was no difference between the epinephrine and control groups in the need for an increase in pump pressure to improve visualization (8/30 [26.7%] vs 7/30 [23.3%], respectively; P >.99), total operative time (62.0 ± 19.4 vs 64.0 ± 30.1 minutes, respectively; P =.90), or the intraoperative use of blood pressure–modulating medications (20/30 [66.7%] vs 17/30 [56.7%], respectively; P =.60). There were no perioperative adverse events in either group. Conclusion: The addition of a subacromial epinephrine injection before shoulder arthroscopic surgery resulted in a small improvement in visual clarity that was neither statistically nor clinically significant, with no adverse effects reported in this study. Registration: NCT05244525 (ClinicalTrials.gov) [ABSTRACT FROM AUTHOR]

Understanding fundamental life history and ecological attributes of declining endemic fishes is essential for developing effective strategies for their conservation and recovery. In the Great Plains and desert rivers of North America, numerous imperiled leuciscids belong to a unique reproductive ecotype with drifting eggs and larvae (pelagophils). Herein, we synthesize three decades of research on the embryology and early life history of Rio Grande Silvery Minnow Hybognathus amarus, a federally endangered member of this ecotype, and explore how our findings can guide management and conservation of these sensitive taxa. We investigated three early developmental aspects of Hybognathus amarus through aquarium and laboratory studies: 1) egg morphology, development, and density, 2) larval development, growth, and behavior, and 3) morphologic and meristic analysis of larvae and early juveniles. Eggs nearly doubled in size at 10 min post-fertilization, were nonadhesive and nearly neutrally buoyant (specific gravity: 1.0011–1.0024), and hatched within 30 hrs in water about 23°C. Recently emerged protolarvae first transformed to mesolarvae after about one week, to metalarvae after about three weeks, and to juveniles after about six weeks at 20–24°C. Based on six candidate models, larval fish development (i.e., from protolarvae to early juveniles) was best explained by a cubic polynomial growth curve. While most protolarvae developed a gas bladder and began to feed within a week, the complete complement of fin rays (i.e., required for proficient swimming) had not fully formed until about one month post-hatching. Early developmental characteristics (e.g., egg specific gravity and larval fin ray formation), combined with river fragmentation, flow regulation, and habitat loss, can profoundly affect the upstream retention and recruitment of Hybognathus amarus and other native pelagophils. Long-term recovery of these highly imperiled species will depend on restoring sufficient seasonal flows, river and floodplain connectivity, and habitat complexity to promote their successful spawning, growth, and survival. [ABSTRACT FROM AUTHOR]

The wetsalts tiger beetle, Cicindelidia haemorrhagica (LeConte) (Coleoptera: Cicindelidae), is found in several active thermal hot spring areas in Yellowstone National Park (YNP) where substrate surface temperatures can exceed 50 °C. However, relationships between surface temperatures and the time adults spend on them remain poorly understood. Therefore, we characterized thermal profiles of Dragon Spring and Rabbit Creek, 2 thermally active research sites containing C. haemorrhagica in YNP, to quantify the time adults spend at different surface temperatures. We took 58 thermal video recordings of adults over 6 total days of observation ranging from 10 to 15 min for each adult. Thermal video analysis results indicated a positive relationship between the total time adult beetles spent on surface temperatures from Dragon Spring and Rabbit Creek as temperatures increased from 20 °C. Once surface temperatures exceeded 40 °C, the total time spent at those surface temperatures declined. Adults were recorded on substrates exceeding 50 °C at one of the 2 research locations. Rabbit Creek had substantially more instances of adults present with surface temperatures exceeding 40 °C, including one individual on a surface temperature of 61.5 °C. There were 3 instances of beetles spending more than 4 min at a particular surface temperature, all within the preferred range of 30–40 °C. Our thermal profile results and previous behavioral observations suggest that adults may be resistant to the heat produced from the thermal waters that influence the substrate temperatures but may not be subject to high surface temperatures as previously reported. [ABSTRACT FROM AUTHOR]

Although originally classified as a non-coding RNA, the male-specific abdominal (MSA) RNA from the Drosophila melanogaster bithorax complex has recently been shown to code for a micropeptide that plays a vital role in determining how mated females use stored sperm after mating. Interestingly, the MSA transcript is a male-specific version of another transcript produced in both sexes within the posterior central nervous system from an alternative promoter, called the iab-8 lncRNA. However, while the MSA transcript produces a small peptide, it seems that the iab-8 transcript does not. Here, we show that the absence of iab-8 translation is due to a repressive mechanism requiring the two unique 5' exons of the iab-8 lncRNA. Through cell culture and transgenic analysis, we show that this mechanism relies on the presence of upstream open reading frames present in these two exons that prevent the production of proteins from downstream open reading frames. Author summary: The study of genome wide transcriptomes has shown that there are a number of non-coding transcripts that play important biological functions. What keeps these transcripts non-coding is generally thought to be the lack of a suitable open reading frame from which a protein can be translated. However, aside from their non-coding functions, the increased use of techniques like ribosome profiling has shown that many predicted non-coding transcripts are, in fact, bound by ribosomes and also make functional peptides. The male-specific abdominal transcript found within the Drosophila bithorax complex is one of them. This transcript codes for a small peptide in the male accessory gland that plays a role in sperm usage. However, an alternative version of this transcript, called the iab-8 lncRNA, is made in the central nervous system, where it does not seem to produce this peptide. Here, we show that the translation of a biologically functional open reading frames can be regulated in different tissues through regulating translation from upstream open reading frames, using the iab-8 transcript as a model. In doing so, this mechanism could limit potentially detrimental protein misexpression through post-transcriptional means. [ABSTRACT FROM AUTHOR]

Wheat (Triticum aestivum L.) production in the Northern Great Plains of North America has been challenged by wheat stem sawfly (WSS), Cephus cinctus Norton, for a century. Damaging WSS populations have increased, highlighting the need for reliable surveys. Remote sensing (RS) can be used to correlate reflectance measurements with nuanced phenomena like cryptic insect infestations within plants, yet little has been done with WSS. To evaluate interactions between WSS-infested wheat and spectral reflectance, we grew wheat plants in a controlled environment, experimentally infested them with WSS and recorded weekly hyperspectral measurements (350–2500 nm) of the canopies from prior to the introduction of WSS to full senescence. To assess the relationships between WSS infestation and wheat reflectance, we employed sparse multiway partial least squares regression (N-PLS), which models multidimensional covariance structures inherent in multitemporal hyperspectral datasets. Multitemporal hyperspectral measurements of wheat canopies modeled with sparse N-PLS accurately estimated the proportion of WSS-infested stems (R2 = 0.683, RMSE = 13.5%). The shortwave-infrared (1289–1380 nm) and near-infrared (942–979 nm) spectral regions were the most important in estimating infestation, likely due to internal feeding that decreases plant-water content. Measurements from all time points were important, suggesting aerial RS of WSS in the field should incorporate the visible through shortwave spectra collected from the beginning of WSS emergence at least weekly until the crop reaches senescence. [ABSTRACT FROM AUTHOR]

Background The use of adjunctive antibiotics directed against exotoxin production in Staphylococcus aureus bacteremia (SAB) is widespread, and it is recommended in many guidelines, but this is based on limited evidence. Existing guidelines are based on the theoretical premise of toxin suppression, as many strains of S. aureus produce toxins such as leukocidins (eg, Panton-Valentine leukocidin, toxic shock syndrome toxin 1, exfoliative toxins, and various enterotoxins). Many clinicians therefore believe that limiting exotoxin production release by S. aureus could reduce its virulence and improve clinical outcomes. Clindamycin, a protein synthesis inhibitor antibiotic, is commonly used for this purpose. We report the domain-specific protocol, embedded in a large adaptive, platform trial, seeking to definitively answer this question. Methods and Analysis The Staphylococcus aureus Network Adaptive Platform (SNAP) trial is a pragmatic, randomized, multicenter adaptive platform trial that aims to compare different SAB therapies, simultaneously, for 90-day mortality rates. The adjunctive treatment domain aims to test the effectiveness of adjunctive antibiotics, initially comparing clindamycin to no adjunctive antibiotic, but future adaptations may include other agents. Individuals will be randomized to receive either 5 days of adjunctive clindamycin (or lincomycin) or no adjunctive antibiotic therapy alongside standard-of-care antibiotics. Most participants with SAB (within 72 hours of index blood culture and with no contraindications) will be eligible to participate in this domain. Prespecified analyses are defined in the statistical appendix to the core protocol, and domain-specific secondary analyses will be adjusted for resistance to clindamycin, disease phenotype (complicated or uncomplicated SAB) and Panton-Valentine leukocidin–positive isolate. [ABSTRACT FROM AUTHOR]