Laminar shear stress elicit distinct endothelial cell e‐selectin expression pattern via TNFα and IL‐1β activation

The ability to discriminate cell adhesion molecule expression between healthy and inflamed endothelium is critical for therapeutic intervention in many diseases. This study explores the effect of laminar flow on TNFα‐induced E‐selectin surface expression levels in human umbilical vein endothelial cells (HUVECs) relative to IL‐1β‐induced expression via flow chamber assays. HUVECs grown in static culture were either directly (naïve) activated with cytokine in the presence of laminar shear or pre‐exposed to 12 h of laminar shear (shear‐conditioned) prior to simultaneous shear and cytokine activation. Naïve cells activated with cytokine in static served as control. Depending on the cell shear history, fluid shear is found to differently affect TNFα‐induced relative to IL‐1β‐induced HUVEC expression of E‐selectin. Specifically, E‐selectin surface expression by naïve HUVECs is enhanced in the 8–12 h activation time range with simultaneous exposure to shear and TNFα (shear‐TNFα) relative to TNFα static control whereas enhanced E‐selectin expression is observed in the 4–24 h range for shear‐IL‐1β treatment relative to IL‐1β static control. While exposure of HUVECs to shear preconditioning mutes shear‐TNFα‐induced E‐selectin expression, it enhances or down‐regulates shear‐IL‐1β‐induced expression dependent on the activation period. Under dual‐cytokine‐shear conditions, IL‐1β signaling dominates. Overall, a better understanding of E‐selectin expression pattern by human ECs relative to the combined interaction of cytokines, shear profile and history can help elucidate many disease pathologies. Biotechnol. Bioeng. 2013; 110: 999–1003. © 2012 Wiley Periodicals, Inc. Naïve or shear‐preconditioned endothelial cell (EC) monolayers were exposed to TNFα or IL‐1β in static or in the presence of high laminar shear. Simultaneous presence of shear generally enhanced E‐selectin expression relative to static activation in naïve ECs in response to either TNFα or IL‐1β stimulation. Prior exposure to shear preconditioning mutes E‐selectin expression with shear‐TNFα activation, while enhancing or down‐regulating shear‐IL‐1b induced expression, dependent on the activation period.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96255/1/24746_ftp.pd

Investigating and learning lessons from early experiences of implementing ePrescribing systems into NHS hospitals:a questionnaire study

Background: ePrescribing systems have significant potential to improve the safety and efficiency of healthcare, but they need to be carefully selected and implemented to maximise benefits. Implementations in English hospitals are in the early stages and there is a lack of standards guiding the procurement, functional specifications, and expected benefits. We sought to provide an updated overview of the current picture in relation to implementation of ePrescribing systems, explore existing strategies, and identify early lessons learned.Methods: a descriptive questionnaire-based study, which included closed and free text questions and involved both quantitative and qualitative analysis of the data generated.Results: we obtained responses from 85 of 108 NHS staff (78.7% response rate). At least 6% (n = 10) of the 168 English NHS Trusts have already implemented ePrescribing systems, 2% (n = 4) have no plans of implementing, and 34% (n = 55) are planning to implement with intended rapid implementation timelines driven by high expectations surrounding improved safety and efficiency of care. The majority are unclear as to which system to choose, but integration with existing systems and sophisticated decision support functionality are important decisive factors. Participants highlighted the need for increased guidance in relation to implementation strategy, system choice and standards, as well as the need for top-level management support to adequately resource the project. Although some early benefits were reported by hospitals that had already implemented, the hoped for benefits relating to improved efficiency and cost-savings remain elusive due to a lack of system maturity.Conclusions: whilst few have begun implementation, there is considerable interest in ePrescribing systems with ambitious timelines amongst those hospitals that are planning implementations. In order to ensure maximum chances of realising benefits, there is a need for increased guidance in relation to implementation strategy, system choice and standards, as well as increased financial resources to fund local activitie

Unsupervised Deep Representation Learning Enables Phenotype Discovery For Genetic association Studies of Brain Imaging

Understanding the genetic architecture of brain structure is challenging, partly due to difficulties in designing robust, non-biased descriptors of brain morphology. Until recently, brain measures for genome-wide association studies (GWAS) consisted of traditionally expert-defined or software-derived image-derived phenotypes (IDPs) that are often based on theoretical preconceptions or computed from limited amounts of data. Here, we present an approach to derive brain imaging phenotypes using unsupervised deep representation learning. We train a 3-D convolutional autoencoder model with reconstruction loss on 6130 UK Biobank (UKBB) participants\u27 T1 or T2-FLAIR (T2) brain MRIs to create a 128-dimensional representation known as Unsupervised Deep learning derived Imaging Phenotypes (UDIPs). GWAS of these UDIPs in held-out UKBB subjects (n = 22,880 discovery and n = 12,359/11,265 replication cohorts for T1/T2) identified 9457 significant SNPs organized into 97 independent genetic loci of which 60 loci were replicated. Twenty-six loci were not reported in earlier T1 and T2 IDP-based UK Biobank GWAS. We developed a perturbation-based decoder interpretation approach to show that these loci are associated with UDIPs mapped to multiple relevant brain regions. Our results established unsupervised deep learning can derive robust, unbiased, heritable, and interpretable brain imaging phenotypes

A simple prediction model to estimate obstructive coronary artery disease

BackgroundA simple noninvasive model to predict obstructive coronary artery disease (OCAD) may promote risk stratification and reduce the burden of coronary artery disease (CAD). This study aimed to develop pre-procedural, noninvasive prediction models that better estimate the probability of OCAD among patients with suspected CAD undergoing elective coronary angiography (CAG).MethodsWe included 1262 patients, who had reliable Framingham risk variable data, in a cohort without known CAD from a prospective registry of patients referred for elective CAG. We investigated pre-procedural OCAD (&ge;50% stenosis in at least one major coronary vessel based on CAG) predictors.ResultsA total of 945 (74.9%) participants had OCAD. The final modified Framingham scoring (MFS) model consisted of anemia, high-sensitivity C-reactive protein, left ventricular ejection fraction, and five Framingham factors (age, sex, total and high-density lipoprotein cholesterol, and hypertension). Bootstrap method (1000 times) revealed that the model demonstrated a good discriminative power (c statistic, 0.729&thinsp;&plusmn;&thinsp;0.0225; 95% CI, 0.69&ndash;0.77). MFS provided adequate goodness of fit (P&thinsp;=&thinsp;0.43) and showed better performance than Framingham score (c statistic, 0.703 vs. 0.521; P&thinsp;&lt;&thinsp;0.001) in predicting OCAD, thereby identifying patients with high risks for OCAD (risk score&thinsp;&ge;&thinsp;27) with &ge;70% predictive value in 68.8% of subjects (range, 37.2&ndash;87.3% for low [&le;17] and very high [&ge;41] risk scores).ConclusionOur data suggested that the simple MFS risk stratification tool, which is available in most primary-level clinics, showed good performance in estimating the probability of OCAD in relatively stable patients with suspected CAD; nevertheless, further validation is needed.<br /

Nonequilibrium Dynamics in Noncommutative Spacetime

We study the effects of spacetime noncommutativity on the nonequilibrium dynamics of particles in a thermal bath. We show that the noncommutative thermal bath does not suffer from any further IR/UV mixing problem in the sense that all the finite-temperature non-planar quantities are free from infrared singularities. We also point out that the combined effect of finite temperature and noncommutative geometry has a distinct effect on the nonequilibrium dynamics of particles propagating in a thermal bath: depending on the momentum of the mode of concern, noncommutative geometry may switch on or switch off their decay and thermalization. This momentum dependent alternation of the decay and thermalization rates could have significant impacts on the nonequilibrium phenomena in the early universe at which spacetime noncommutativity may be present. Our results suggest a re-examination of some of the important processes in the early universe such as reheating after inflation, baryogenesis and the freeze-out of superheavy dark matter candidates.Comment: 24 pages, 2 figure

The challenges of implementing packaged hospital electronic prescribing and medicine administration systems in UK hospitals: premature purchase of immature solutions?

The UK National Health Service is making major efforts to implement Hospital Electronic Prescribing and Medicine Administration (HEPMA) to improve patient safety and quality of care. Substantial public investments have attracted a wide range of UK and overseas suppliers offering Commercial-Off –The-Shelf (COTS) solutions. A lack of (UK) implementation experience and weak supplier-user relationships are reflected in systems with limited configurability, poorly matched to the needs and practices of English hospitals. This situation echoes the history of comparable corporate information infrastructures - Enterprise Resource Planning systems - in the 1980s/1990s. UK government intervention prompted a similar swarming of immature, often unfinished, products into the market. This resulted, in both cases, in protracted and difficult implementation processes as vendors and adopters struggled to get the systems to work and match the circumstances of the adopting organisations. An analysis of the influence of the Installed Base on Information Infrastructures should explore how the evolution of COTS solutions is conditioned by the structure of adopter and vendor ‘communities’

On thermodynamics of N=6 superconformal Chern-Simons theory

We study thermodynamics of N=6 superconformal Chern-Simons theory by computing quantum corrections to the free energy. We find that in weakly coupled ABJM theory on R(2) x S(1), the leading correction is non-analytic in the 't Hooft coupling lambda, and is approximately of order lambda^2 log(lambda)^3. The free energy is expressed in terms of the scalar thermal mass m, which is generated by screening effects. We show that this mass vanishes to 1-loop order. We then go on to 2-loop order where we find a finite and positive mass squared m^2. We discuss differences in the calculation between Coulomb and Lorentz gauge. Our results indicate that the free energy is a monotonic function in lambda which interpolates smoothly to the N^(3/2) behaviour at strong coupling.Comment: 29 pages. v2: references added. v3: minor changes, references added, published versio

Relationship between Silent Gastroesophageal Reflux and Food Sensitization in Infants and Young Children with Recurrent Wheezing

It is known that early childhood wheezing associated with sensitization to allergens, including food, has an increased risk of developing asthma later during school age. Gastroesophageal reflux (GER) is well known to be associated with asthma. The purpose of this study was to determine whether there is an association between silent GER and food sensitization in infants and young children with recurrent wheezing. Eighty-five infants or young children with recurrent wheezing, and no gastrointestinal symptoms, underwent 24 hr esophageal pH monitoring, as well as total serum IgE and specific IgE testing for eggs and milk. Among the 85 subjects, 48.2% had significant GER. There was no significant difference in the GER between atopic and non-atopic recurrent wheezers (41.7% and 50.8%, respectively). The sensitization rate to food (eggs or milk) was 12.2% and 20.5% in the GER and non-GER groups, respectively and showed no statistically significant difference between the two groups (P=0.34). In conclusion, about half of infants and young children with recurrent wheezing and no gastrointestinal symptoms have silent GER. The silent GER may not contribute to food sensitization in infants and young children with recurrent wheezing