1,698 research outputs found

    X-ray Fluorescence Analysis of Feldspars and Silicate Glass: Effects of Melting Time on Fused Bead Consistency and Volatilisation

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    Reproducible preparation of lithium tetraborate fused beads for XRF analysis of glass and mineral samples is of paramount importance for analytical repeatability. However, as with all glass melting processes, losses due to volatilisation must be taken into account and their effects are not negligible. Here the effects of fused bead melting time have been studied for four Certified Reference Materials (CRM’s: three feldspars, one silicate glass), in terms of their effects on analytical variability and volatilisation losses arising from fused bead preparation. At melting temperatures of 1065 °C, and for feldspar samples, fused bead melting times shorter than approximately 25 min generally gave rise to a greater deviation of the XRF-analysed composition from the certified composition. This variation might be due to incomplete fusion and/or fused bead inhomogeneity but further research is needed. In contrast, the shortest fused bead melting time for the silicate glass CRM gave an XRF-analysed composition closer to the certified values than longer melting times. This may suggest a faster rate of glass-in-glass dissolution and homogenization during fused bead preparation. For all samples, longer melting times gave rise to greater volatilisation losses (including sulphates and halides) during fusion. This was demonstrated by a linear relationship between SO3 mass loss and time1/2, as predicted by a simple diffusion-based model. Iodine volatilisation displays a more complex relationship, suggestive of diffusion plus additional mechanisms. This conclusion may have implications for vitrification of iodine-bearing radioactive wastes. Our research demonstrates that the nature of the sample material impacts on the most appropriate fusion times. For feldspars no less than ~25 min and no more than ~60 min of fusion at 1065 °C, using Li2B4O7 as the fusion medium and in the context of feldspar samples and the automatic fusion equipment used here, strikes an acceptable (albeit non-ideal) balance between the competing factors of fused bead quality, analytical consistency and mitigating volatilisation losses. Conversely, for the silicate glass sample, shorter fusion times of less than ~30 min under the same conditions provided more accurate analyses whilst limiting volatile losses

    Thoracic endovascular aneurysm repair, race, and volume in thoracic aneurysm repair

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    BackgroundVolume-based disparities in surgical care are often associated with poorer results in African American patients. We examined the effect of treatment patterns and outcomes, by race, for isolated thoracic aortic aneurysm (TAA).MethodsUsing Medicare claims (1999-2007), we studied all patients undergoing repair of TAAs, via open surgery or thoracic endovascular aneurysm repair (TEVAR). We studied 30-day mortality and complications by race, procedure type, and hospital volume.ResultsWe studied 12,573 patients who underwent open TAA repair (4% of whom were black) and 2732 patients who underwent TEVAR (8% of whom were black). In open repair, black patients had higher 30-day mortality than white patients (18% vs 10%; P < .001), while mortality rates were similar with TEVAR (8% black vs 9% white; P = .56). For open repair, black patients were more likely to undergo surgery at low-volume hospitals, where overall operative mortality was highest (14% at very low-volume hospitals, 7% at very high-volume hospitals; P < .001). However, for TEVAR, black patients were not more likely to undergo repair at low-volume hospitals, and mortality differences were not evident across volume strata (9% at very low-volume hospitals, 7% at very high-volume hospitals; P = .328). Multivariable analyses adjusting for age, sex, race, comorbidity, and volume confirmed that increased perioperative mortality was associated with black race for open surgery (OR, 2.0, 95% CI, 1.5-2.5; P < .001) but not TEVAR (OR, 0.9, 95% CI, 0.6-1.5; P = .721).ConclusionsWhile racial disparities in surgical care have a significant effect on mortality with open thoracoabdominal aortic aneurysm repair, black patients undergoing TEVAR obtain similar outcomes as white patients. New technology can limit the effect of racial disparities in surgical care

    Variation in thromboembolic complications among patients undergoing commonly performed cancer operations

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    ObjectiveThere is widespread evidence that cancer confers an increased risk of deep venous thrombosis (DVT). This risk is thought to vary among different cancer types. The purpose of this study is to better define the incidence of thrombotic complications among patients undergoing surgical treatment for a spectrum of prevalent cancer diagnoses in contemporary practice.MethodsAll patients undergoing one of 11 cancer surgical operations (breast resection, hysterectomy, prostatectomy, colectomy, gastrectomy, lung resection, hepatectomy, pancreatectomy, cystectomy, esophagectomy, and nephrectomy) were identified by Current Procedural Terminology and International Classification of Diseases, Ninth Revision codes using the American College of Surgeons National Surgical Quality Improvement Program database (2007-2009). The study endpoints were DVT, pulmonary embolism (PE), and overall postoperative venous thromboembolic events (VTE) within 1 month of the index procedure. Multivariate logistic regression was utilized to calculate adjusted odds ratios for each endpoint.ResultsOver the study interval, 43,808 of the selected cancer operations were performed. The incidence of DVT, PE, and total VTE within 1 month following surgery varied widely across a spectrum of cancer diagnoses, ranging from 0.19%, 0.12%, and 0.28% for breast resection to 6.1%, 2.4%, and 7.3%, respectively, for esophagectomy. Compared with breast cancer, the incidence of VTE ranged from a 1.31-fold increase in VTE associated with gastrectomy (95% confidence interval, 0.73-2.37; P = .4) to a 2.68-fold increase associated with hysterectomy (95% confidence interval, 1.43-5.01; P = .002). Multivariate logistic regression revealed that inpatient status, steroid use, advanced age (≥60 years), morbid obesity (body mass index ≥35), blood transfusion, reintubation, cardiac arrest, postoperative infectious complications, and prolonged hospitalization were independently associated with increased risk of VTE.ConclusionsThe incidence of VTE and thromboembolic complications associated with cancer surgery varies substantially. These findings suggest that both tumor type and resection magnitude may impact VTE risk. Accordingly, such data support diagnosis and procedural-specific guidelines for perioperative VTE prophylaxis and can be used to anticipate the risk of potentially preventable morbidity

    Blood-Based Transcriptomic Biomarkers Are Predictive of Neurodegeneration Rather Than Alzheimer\u27s Disease

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    Alzheimer\u27s disease (AD) is a growing global health crisis affecting millions and incurring substantial economic costs. However, clinical diagnosis remains challenging, with misdiagnoses and underdiagnoses being prevalent. There is an increased focus on putative, blood-based biomarkers that may be useful for the diagnosis as well as early detection of AD. In the present study, we used an unbiased combination of machine learning and functional network analyses to identify blood gene biomarker candidates in AD. Using supervised machine learning, we also determined whether these candidates were indeed unique to AD or whether they were indicative of other neurodegenerative diseases, such as Parkinson\u27s disease (PD) and amyotrophic lateral sclerosis (ALS). Our analyses showed that genes involved in spliceosome assembly, RNA binding, transcription, protein synthesis, mitoribosomes, and NADH dehydrogenase were the best-performing genes for identifying AD patients relative to cognitively healthy controls. This transcriptomic signature, however, was not unique to AD, and subsequent machine learning showed that this signature could also predict PD and ALS relative to controls without neurodegenerative disease. Combined, our results suggest that mRNA from whole blood can indeed be used to screen for patients with neurodegeneration but may be less effective in diagnosing the specific neurodegenerative disease

    Establishing effective conservation management strategies for a poorly known endangered species: A case study using Australia’s night parrot (Pezoporus occidentalis)

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    An evidence-based approach to the conservation management of a species requires knowledge of that species’ status, distribution, ecology, and threats. Coupled with budgets for specific conservation strategies, this knowledge allows prioritisation of funding toward activities that maximise benefit for the species. However, many threatened species are poorly known, and determining which conservation strategies will achieve this is difficult. Such cases require approaches that allow decision-making under uncertainty. Here we used structured expert elicitation to estimate the likely benefit of potential management strategies for the Critically Endangered and, until recently, poorly known Night Parrot (Pezoporus occidentalis). Experts considered cat management the single most effective management strategy for the Night Parrot. However, a combination of protecting and actively managing existing intact Night Parrot habitat through management of grazing, controlling feral cats, and managing fire specifically to maintain Night Parrot habitat was thought to result in the greatest conservation gains. The most cost-effective strategies were thought to be fire management to maintain Night Parrot habitat, and intensive cat management using control methods that exploit local knowledge of cat movements and ecology. Protecting and restoring potentially suitable, but degraded, Night Parrot habitat was considered the least effective and least cost-effective strategy. These expert judgements provide an informed starting point for land managers implementing on-ground programs targeting the Night Parrot, and those developing policy aimed at the species’ longer-term conservation. As a set of hypotheses, they should be implemented, assessed, and improved within an adaptive management framework that also considers the likely co-benefits of these strategies for other species and ecosystems. The broader methodology is applicable to conservation planning for the management and conservation of other poorly known threatened species

    Evaluation of variants in the selectin genes in age-related macular degeneration

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    <p>Abstract</p> <p>Background</p> <p>Age-related macular degeneration (AMD) is a common disease of the elderly that leads to loss of the central visual field due to atrophic or neovascular events. Evidence from human eyes and animal models suggests an important role for macrophages and endothelial cell activation in the pathogenesis of AMD. We sought to determine whether common ancestral variants in genes encoding the selectin family of proteins are associated with AMD.</p> <p>Methods</p> <p>Expression of E-selectin, L-selectin and P-selectin was examined in choroid and retina by quantitative PCR and immunofluorescence. Samples from patients with AMD (n = 341) and controls (n = 400) were genotyped at a total of 34 SNPs in the <it>SELE</it>, <it>SELL </it>and <it>SELP </it>genes. Allele and genotype frequencies at these SNPs were compared between AMD patients and controls as well as between subtypes of AMD (dry, geographic atrophy, and wet) and controls.</p> <p>Results</p> <p>High expression of all three selectin genes was observed in the choroid as compared to the retina. Some selectin labeling of retinal microglia, drusen cores and the choroidal vasculature was observed. In the genetic screen of AMD versus controls, no positive associations were observed for <it>SELE </it>or <it>SELL</it>. One SNP in <it>SELP </it>(rs3917751) produced p-values < 0.05 (uncorrected for multiple measures). In the subtype analyses, 6 SNPs (one in <it>SELE</it>, two in <it>SELL</it>, and three in <it>SELP</it>) produced p-values < 0.05. However, when adjusted for multiple measures with a Bonferroni correction, only one SNP in <it>SELP </it>(rs3917751) produced a statistically significant p-value (p = 0.0029).</p> <p>Conclusions</p> <p>This genetic screen did not detect any SNPs that were highly associated with AMD affection status overall. However, subtype analysis showed that a single SNP located within an intron of <it>SELP </it>(rs3917751) is statistically associated with dry AMD in our cohort. Future studies with additional cohorts and functional assays will clarify the biological significance of this discovery. Based on our findings, it is unlikely that common ancestral variants in the other selectin genes (<it>SELE </it>and <it>SELL</it>) are risk factors for AMD. Finally, it remains possible that sporadic or rare mutations in <it>SELE</it>, <it>SELL</it>, or <it>SELP </it>have a role in the pathogenesis of AMD.</p

    Randomized Trial of Anticoagulation Strategies for Noncritically Ill Patients Hospitalized With COVID-19.

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    BACKGROUND Prior studies of therapeutic-dose anticoagulation in patients with COVID-19 have reported conflicting results. OBJECTIVES We sought to determine the safety and effectiveness of therapeutic-dose anticoagulation in noncritically ill patients with COVID-19. METHODS Patients hospitalized with COVID-19 not requiring intensive care unit treatment were randomized to prophylactic-dose enoxaparin, therapeutic-dose enoxaparin, or therapeutic-dose apixaban. The primary outcome was the 30-day composite of all-cause mortality, requirement for intensive care unit-level of care, systemic thromboembolism, or ischemic stroke assessed in the combined therapeutic-dose groups compared with the prophylactic-dose group. RESULTS Between August 26, 2020, and September 19, 2022, 3,398 noncritically ill patients hospitalized with COVID-19 were randomized to prophylactic-dose enoxaparin (n = 1,141), therapeutic-dose enoxaparin (n = 1,136), or therapeutic-dose apixaban (n = 1,121) at 76 centers in 10 countries. The 30-day primary outcome occurred in 13.2% of patients in the prophylactic-dose group and 11.3% of patients in the combined therapeutic-dose groups (HR: 0.85; 95% CI: 0.69-1.04; P = 0.11). All-cause mortality occurred in 7.0% of patients treated with prophylactic-dose enoxaparin and 4.9% of patients treated with therapeutic-dose anticoagulation (HR: 0.70; 95% CI: 0.52-0.93; P = 0.01), and intubation was required in 8.4% vs 6.4% of patients, respectively (HR: 0.75; 95% CI: 0.58-0.98; P = 0.03). Results were similar in the 2 therapeutic-dose groups, and major bleeding in all 3 groups was infrequent. CONCLUSIONS Among noncritically ill patients hospitalized with COVID-19, the 30-day primary composite outcome was not significantly reduced with therapeutic-dose anticoagulation compared with prophylactic-dose anticoagulation. However, fewer patients who were treated with therapeutic-dose anticoagulation required intubation and fewer died (FREEDOM COVID [FREEDOM COVID Anticoagulation Strategy]; NCT04512079).Dr Stone has received speaker honoraria from Medtronic, Pulnovo, Infraredx, Abiomed, and Abbott; has served as a consultant to Daiichi-Sankyo, Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Cardiomech, Gore, Amgen, Adona Medical, and Millennia Biopharma; and has equity/ options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter; his daughter is an employee at IQVIA; and his employer, Mount Sinai Hospital, receives research support from Abbott, Abiomed, Bioventrix, Cardiovascular Systems Inc, Phillips, BiosenseWebster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave. Dr Farkouh has received institutional research grants from Amgen, AstraZeneca, Novo Nordisk, and Novartis; has received consulting fees from Otitopic; and has received honoraria from Novo Nordisk. Dr Lala has received consulting fees from Merck and Bioventrix; has received honoraria from Zoll Medical and Novartis; has served on an advisory board for Sequana Medical; and is the Deputy Editor for the Journal of Cardiac Failure. Dr Moreno has received honoraria from Amgen, Cuquerela Medical, and Gafney; has received payment for expert testimony from Koskoff, Koskoff & Dominus, Dallas W. Hartman, and Riscassi & Davis PC; and has stock options in Provisio. Dr Goodman has received institutional research grants from Bristol Myers Squibb/Pfizer Alliance, Bayer, and Boehringer Ingelheim; has received consulting fees from Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, Ferring Pharmaceuticals, HLS Therapeutics, Novartis, Pendopharm/Pharmascience, Pfizer, Regeneron, and Sanofi; has received honoraria from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Ferring Pharmaceuticals, HLS Therapeutics, JAMP Pharma, Merck, Novartis, Pendopharm/Pharmascience, Pfizer, Regeneron, Sanofi, and Servier; has served on Data Safety and Monitoring boards for Daiichi-Sankyo/American Regent and Novo Nordisk A/C; has served on advisory boards for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, Eli Lilly, Ferring Pharmaceuticals, HLS Therapeutics, JAMP Pharma, Merck, Novartis, Pendopharm/Pharmascience, Pfizer, Regeneron, Sanofi, Servier, and Tolmar Pharmaceuticals; has a leadership role in the Novartis Council for Heart Health (unpaid); and otherwise has received salary support or honoraria from the Heart and Stroke Foundation of Ontario/University of Toronto (Polo) Chair, Canadian Heart Failure Society, Canadian Heart Research Centre and MD Primer, Canadian VIGOUR Centre, Cleveland Clinic Coordinating Centre for Clinical Research, Duke Clinical Research Institute, New York University Clinical Coordinating Centre, PERFUSE Research Institute, and the TIMI Study Group (Brigham Health). Dr Ricalde has received consulting fees from Medtronic, Servier, and Boston Scientific; has received honoraria from Medtronic, Pfizer, Merck, Boston Scientific, Biosensors, and Bayer; has served on an advisory board for Medtronic; and has leadership roles in SOLACI and Kardiologen. Dr Payro has received consulting fees from Bayer Mexico; has received honoraria from Bayer, Merck, AstraZeneca, Medtronic, and Viatris; has received payments for expert testimony from Bayer; has received travel support from AstraZeneca; has served on an advisory board for Bayer; and his institution has received equipment donated from AstraZeneca. Dr Castellano has received consulting fees and honoraria from Ferrer International, Servier, and Daiichi-Sankyo; and has received travel support from Ferrer International. Dr Hung has served as an advisory board member for Pfizer, Merck, AstraZeneca, Fosun, and Gilead. Dr Nadkarni has received consulting fees from Renalytix, Variant Bio, Qiming Capital, Menarini Health, Daiichi-Sankyo, BioVie, and Cambridge Health; has received honoraria from Daiichi-Sankyo and Menarini Health; has patents for automatic disease diagnoses using longitudinal medical record data, methods, and apparatus for diagnosis of progressive kidney function decline using a machine learning model, electronic phenotyping technique for diagnosing chronic kidney disease, deep learning to identify biventricular structure and function, fusion models for identification of pulmonary embolism, and SparTeN: a novel spatio-temporal deep learning model; has served on a Data Safety and Monitoring Board for CRIC OSMB; has leadership roles for Renalytix scientific advisory board, Pensive Health scientific advisory board, and ASN Augmented Intelligence and Digital Health Committee; has ownership interests in Renalytix, Data2Wisdom LLC, Verici Dx, Nexus I Connect, and Pensieve Health; and his institution receives royalties from Renalytix. Dr Goday has received the Frederick Banting and Charles Best Canada Graduate Scholarship (Doctoral Research Award) from the Canadian Institutes of Health Research. Dr Furtado has received institutional research grants from AstraZeneca, CytoDin, Pfizer, Servier, Amgen, Alliar Diagnostics, and the Brazilian Ministry of Health; has received consulting fees from Biomm and Bayer; has received honoraria from AstraZeneca, Bayer, Servier, and Pfizer; and has received travel support from Servier, AstraZeneca, and Bayer. Dr Granada has received consulting fees, travel support, and stock from Cogent Technologies Corp; and has received stock from Kutai. Dr Contreras has served as a consultant for Merck, CVRx, Novodisk, and Boehringer Ingelheim; and has received educational grants from Alnylam Pharmaceuticals and AstraZeneca. Dr Bhatt has received research funding from Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, Cincor, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer Inc, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89bio; has received royalties from Elsevier; has received consultant fees from Broadview Ventures and McKinsey; has received honoraria from the American College of Cardiology, Baim Institute for Clinical Research, Belvoir Publications, Boston Scientific, Cleveland Clinic, Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine, Novartis, Population Health Research Institute, Rutgers University, Canadian Medical and Surgical Knowledge Translation Research Group, Cowen and Company, HMP Global, Journal of the American College of Cardiology, K2P, Level Ex, Medtelligence/ReachMD, MJH Life Sciences, Oakstone CME, Piper Sandler, Population Health Research Institute, Slack Publications, WebMD, Wiley, Society of Cardiovascular Patient Care; has received fees from expert testimony from the Arnold and Porter law firm; has received travel support from the American College of Cardiology, Society of Cardiovascular Patient Care, American Heart Association; has a patent for otagliflozin assigned to Brigham and Women’s Hospital who assigned to Lexicon; has participated on a data safety monitoring board or advisory board for Acesion Pharma, Assistance Publique-Hôpitaux de Paris, AngioWave, Baim Institute, Bayer, Boehringer Ingelheim, Boston Scientific, Cardax, CellProthera, Cereno Scientific, Cleveland Clinic, Contego Medical, Duke Clinical Research Institute, Elsevier Practice Update Cardiology, Janssen, Level Ex, Mayo Clinic, Medscape Cardiology, Merck, Mount Sinai School of Medicine, MyoKardia, NirvaMed, Novartis, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, Population Health Research Institute, and Stasys; serves as a trustee or director for American College of Cardiology, AngioWave, Boston VA Research Institute, Bristol Myers Squibb, DRS.LINQ, High Enroll, Society of Cardiovascular Patient Care, and TobeSoft; has ownership interests in AngioWave, Bristol Myers Squibb, DRS.LINQ, and High Enroll; has other interests in Clinical Cardiology, the NCDR-ACTION Registry Steering Committee; has conducted unfunded research with FlowCo and Takeda, Contego Medical, American Heart Association Quality Oversight Committee, Inaugural Chair, VA CART Research and Publications Committee; and has been a site co-investigator for Abbott, Biotronik, Boston Scientific, CSI, St Jude Medical (now Abbott), Phillips SpectraWAVE, Svelte, and Vascular Solutions. Dr Fuster declares that he raised $7 million from patients for this study granted to Mount Sinai Heart, unrelated to industry. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.S
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