469 research outputs found
Hybridization-induced magnetism in correlated cerium systems
There is a great change in the nature of the magnetic ordering on going from CeIn3, a local moment antiferromagnetic system, to CePb3, a heavy fermion itinerant antiferromagnetic system, both of which have Cu3Au crystal structure. We have applied ab initio electronic structure calculations, based on the linear-muffin-tin-orbital method, and a phenomenological theory of orbitally driven magnetic ordering, to study the effects of the band-f hybridization-induced interactions and the band-f exchange-induced interactions, pertinent to the magnetic behavior of these systems. The position of the Ce 4 f energy level relative to the Fermi energy and the intra-atomic Coulomb interaction are obtained from a sequence of three total-energy supercell calculations with two, one and zero f electrons in the Ce 4 f core. The calculations elucidate the origins in the electronic structure of the variation of the f-state resonance width characterizing the strength of the hybridization and the density of states at the Fermi energy characterizing the number and character of band states available for hybridization. We present results for the hybridization potential and the hybridization-induced exchange interactions on going from CeIn3 to CePb3, where the only obvious change is the addition of an anion p electron
Multimodal Machine Learning-based Knee Osteoarthritis Progression Prediction from Plain Radiographs and Clinical Data
Knee osteoarthritis (OA) is the most common musculoskeletal disease without a
cure, and current treatment options are limited to symptomatic relief.
Prediction of OA progression is a very challenging and timely issue, and it
could, if resolved, accelerate the disease modifying drug development and
ultimately help to prevent millions of total joint replacement surgeries
performed annually. Here, we present a multi-modal machine learning-based OA
progression prediction model that utilizes raw radiographic data, clinical
examination results and previous medical history of the patient. We validated
this approach on an independent test set of 3,918 knee images from 2,129
subjects. Our method yielded area under the ROC curve (AUC) of 0.79 (0.78-0.81)
and Average Precision (AP) of 0.68 (0.66-0.70). In contrast, a reference
approach, based on logistic regression, yielded AUC of 0.75 (0.74-0.77) and AP
of 0.62 (0.60-0.64). The proposed method could significantly improve the
subject selection process for OA drug-development trials and help the
development of personalized therapeutic plans
Early-life exposure to combustion-derived particulate matter causes pulmonary immunosuppression
Elevated levels of combustion-derived particulate matter (CDPM) are a risk factor for the development of lung diseases such as asthma. Studies have shown that CDPM exacerbates asthma, inducing acute lung dysfunction and inflammation; however, the impact of CDPM exposure on early immunological responses to allergens remains unclear. To determine the effects of early-lifeCDPMexposure on allergic asthma development in infants, we exposed infant mice to CDPM and then induced a mouse model of asthma using house dust mite (HDM) allergen. Mice exposed to CDPMHDM failed to develop a typical asthma phenotype including airway hyper-responsiveness, T-helper type 2 (Th2) inflammation, Muc5ac expression, eosinophilia, and HDM-specific immunoglobulin (Ig) compared with HDM-exposed mice. Although HDM-specific IgE was attenuated, total IgE was twofold higher in CDPMHDM mice compared with HDM mice. We further demonstrate that CDPM exposure during early life induced an immunosuppressive environment in the lung, concurrent with increases in tolerogenic dendritic cells and regulatory T cells, resulting in the suppression of Th2 responses. Despite having early immunosuppression, these mice develop severe allergic inflammation when challenged with allergen as adults. These findings demonstrate a mechanism whereby CDPM exposure modulates adaptive immunity, inducing specific antigen tolerance while amplifying total IgE, and leading to a predisposition to develop asthma upon rechallenge later in life. © 2014 Society for Mucosal Immunology
Recombinant Escherichia coli as a gene delivery vector into airway epithelial cells
Abstract To transfer genes into airway epithelial cells, we have generated auxotrophic dap Escherichia coli BM2710 mutant that expresses the invasin of Yersinia pseudotuberculosis and the listeriolysin of Listeria monocytogenes. E. coli BM2710 harboring a plasmid carrying the gfp gene was incubated with immortalized normal or cystic fibrosis (CF) airway epithelial cells or with primary bronchial epithelial cells grown as an explant-outgrowth cell culture model. Approximately 2% of immortalized cells expressed GFP. Few primary cells were transfected that were always poorly differentiated and located at the edge of the outgrowth. This was consistent with the expression of h1-integrins only on these cells and with the required interaction for cell entry of E. coli expressing the invasin with h1-integrins. The subsequent intracellular trafficking of E. coli BM2710 studied by confocal and electronic microscopy showed that the E. coli-containing phagosomes rapidly matured into phagolysosomes. This is the first demonstration that recombinant bacteria are able to transfer genes into primary airway epithelial cells, provided that they are able to invade the cells
Radical-containing ultrafine particulate matter initiates epithelial-to-mesenchymal transitions in airway epithelial cells
Environmentally persistent free radicals (EPFRs) in combustion generated particulate matter (PM) are capable of inducing pulmonary pathologies and contributing to the development of environmental asthma. In vivo exposure of infant rats to EPFRs demonstrates their ability to induce airway hyperresponsiveness to methacholine, a hallmark of asthma. However, the mechanisms by which combustion-derived EPFRs elicit in vivo responses remain elusive. In this study, we used a chemically defined EPFR consisting of approximately 0.2 μm amorphrous silica containing 3% cupric oxide with the organic pollutant 1,2-dichlorobenzene (DCB-230). DCB-230 possesses similar radical content to urban-collected EPFRs but offers several advantages, including lack of contaminants and chemical uniformity. DCB-230 was readily taken up by BEAS-2B and at high doses (200 μg/cm2) caused substantial necrosis. At low doses (20 μg/cm2), DCB-230 particles caused lysosomal membrane permeabilization, oxidative stress, and lipid peroxidation within 24 hours of exposure. During this period, BEAS-2B underwent epithelial-to-mesenchymal transition (EMT), including loss of epithelial cell morphology, decreased E-cadherin expression, and increased α-smooth muscle actin (α-SMA) and collagen I production. Similar results were observed in neonatal air-liquid interface culture (i.e., disruption of epithelial integrity and EMT). Acute exposure of infant mice to DCB-230 resulted in EMT, as confirmed by lineage tracing studies and evidenced by coexpression of epithelial E-cadherin and mesenchymal α-SMA proteins in airway cells and increased SNAI1 expression in the lungs. EMT in neonatal mouse lungs after EPFR exposure may provide an explanation for epidemiological evidence supporting PM exposure and increased risk of asthma. Copyright © 2013 by the American Thoracic Society
Use of Intravenous Albumin:A Guideline From the International Collaboration for Transfusion Medicine Guidelines
Background: Albumin is used commonly across a wide range of clinical settings to improve hemodynamics, to facilitate fluid removal, and to manage complications of cirrhosis. The International Collaboration for Transfusion Medicine Guidelines developed guidelines for the use of albumin in patients requiring critical care, undergoing cardiovascular surgery, undergoing kidney replacement therapy, or experiencing complications of cirrhosis. Study Design and Methods: Cochairs oversaw the guideline development process and the panel included researchers, clinicians, methodologists, and a patient representative. The evidence informing this guideline arises from a systematic review of randomized clinical trials and systematic reviews, in which multiple databases were searched (inception through November 23, 2022). The panel reviewed the data and formulated the guideline recommendations using Grading of Recommendations Assessment, Development, and Evaluation methodology. The guidelines were revised after public consultation. Results: The panel made 14 recommendations on albumin use in adult critical care (three recommendations), pediatric critical care (one recommendation), neonatal critical care (two recommendations), cardiovascular surgery (two recommendations), kidney replacement therapy (one recommendation), and complications of cirrhosis (five recommendations). Of the 14 recommendations, two recommendations had moderate certainty of evidence, five recommendations had low certainty of evidence, and seven recommendations had very low certainty of evidence. Two of the 14 recommendations suggested conditional use of albumin for patients with cirrhosis undergoing large-volume paracentesis or with spontaneous bacterial peritonitis. Twelve of 14 recommendations did not suggest albumin use in a wide variety of clinical situations where albumin commonly is transfused. Interpretation: Currently, few evidence-based indications support the routine use of albumin in clinical practice to improve patient outcomes. These guidelines provide clinicians with actionable recommendations on the use of albumin.</p
Superhard Phases of Simple Substances and Binary Compounds of the B-C-N-O System: from Diamond to the Latest Results (a Review)
The basic known and hypothetic one- and two-element phases of the B-C-N-O
system (both superhard phases having diamond and boron structures and
precursors to synthesize them) are described. The attention has been given to
the structure, basic mechanical properties, and methods to identify and
characterize the materials. For some phases that have been recently described
in the literature the synthesis conditions at high pressures and temperatures
are indicated.Comment: Review on superhard B-C-N-O phase
Use of albumin infusion for cirrhosis-related complications. An international position statement
Background & Aims: Numerous studies have evaluated the role of human albumin (HA) in managing various liver cirrhosis-related complications. However, their conclusions remain partially controversial, probably because HA was evaluated in different settings, including indications, patient characteristics, and dosage and duration of therapy. Methods: Thirty-three investigators from 19 countries with expertise in the management of liver cirrhosis-related complications were invited to organise an International Special Interest Group. A three-round Delphi consensus process was conducted to complete the international position statement on the use of HA for treatment of liver cirrhosis-related complications. Results: Twelve clinically significant position statements were proposed. Short-term infusion of HA should be recommended for the management of hepatorenal syndrome, large volume paracentesis, and spontaneous bacterial peritonitis in liver cirrhosis. Its effects on the prevention or treatment of other liver cirrhosis-related complications should be further elucidated. Long-term HA administration can be considered in specific settings. Pulmonary oedema should be closely monitored as a potential adverse effect in cirrhotic patients receiving HA infusion. Conclusions: Based on the currently available evidence, the international position statement suggests the potential benefits of HA for the management of multiple liver cirrhosis-related complications and summarises its safety profile. However, its optimal timing and infusion strategy remain to be further elucidated. Impact and implications: Thirty-three investigators from 19 countries proposed 12 position statements on the use of human albumin (HA) infusion in liver cirrhosis-related complications. Based on current evidence, short-term HA infusion should be recommended for the management of HRS, LVP, and SBP; whereas, long-term HA administration can be considered in the setting where budget and logistical issues can be resolved. However, pulmonary oedema should be closely monitored in cirrhotic patients who receive HA infusion
Need and importance of health protection training in Nepal
By investing in health protection, the health of the nation can be safeguarded from future threats of uncontrolled infectious disease epidemics and disasters
Design and in vitro studies of a needle-type glucose sensor for subcutaneous monitoring
International audienceA new miniaturized glucose oxidase based needle-type glu¬ cose mlcrosensor has been developed for subcutaneous glu¬ cose monitoring. The sensor Is equivalent In shape and size to a 26-gauge needle (0.45-mm o.d.) and can be Implanted with ease without any Incision. The novel configuration greatly facilitates the deposition of enzyme and polymer films so that sensors with characteristics suitable for In vivo use (upper limit of linear range > 15 mM, response time 60%). The sensor response is largely Independent of ox¬ ygen tension In the normal physiological range. It also ex¬ hibits good selectivity against common interferences except for the exogenous drug acetaminophen
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