Murine lymphoid procoagulant activity induced by bacterial lipopolysaccharide and immune complexes is a monocyte prothrombinase

Murine lymphoid cells respond rapidly to bacterial lipopolysaccharide or antigen-antibody complexes to initiate or accelerate the blood coagulation pathways. The monocyte or macrophage has been identified as the cellular source, although lymphocyte collaboration is required for the rapid induction of the procoagulant response. This procoagulant activity is identified in the present study as a direct prothrombin activator, i.e., a prothrombinase. Studies with plasmas deficient in single coagulation factors demonstrate that the induced murine procoagulant activity effector molecule does not require factors XII, VIII, VII, X, or V, but does require prothrombin to transform fibrinogen to fibrin. This enzyme(s) produces limited proteolysis of prothrombin to yield thrombin or thrombinlike products that are functionally capable of converting fibrinogen to fibrin. The prothrombinase is undetectable in freshly isolated Murine lymphoid cells respond rapidly to bacterial lipopolysaccharide or antigen-antibody complexes to initiate or accelerate the blood coagulation pathways. The monocyte or macrophage has been identified as the cellular source, although lymphocyte collaboration is required for the rapid induction of the procoagulant response. This procoagulant activity is identified in the present study as a direct prothrombin activator, i.e., a prothrombinase. Studies with plasmas deficient in single coagulation factors demonstrate that the induced murine procoagulant activity effector molecule does not require factors XII, VIII, VII, X, or V, but does require prothrombin to transform fibrinogen to fibrin. This enzyme(s) produces limited proteolysis of prothrombin to yield thrombin or thrombinlike products that are functionally capable of converting fibrinogen to fibrin. The prothrombinase is undetectable in freshly isolate

A class of well-posed parabolic final value problems

This paper focuses on parabolic final value problems, and well-posedness is proved for a large class of these. The clarification is obtained from Hilbert spaces that characterise data that give existence, uniqueness and stability of the solutions. The data space is the graph normed domain of an unbounded operator that maps final states to the corresponding initial states. It induces a new compatibility condition, depending crucially on the fact that analytic semigroups always are invertible in the class of closed operators. Lax--Milgram operators in vector distribution spaces constitute the main framework. The final value heat conduction problem on a smooth open set is also proved to be well posed, and non-zero Dirichlet data are shown to require an extended compatibility condition obtained by adding an improper Bochner integral.Comment: 16 pages. To appear in "Applied and numerical harmonic analysis"; a reference update. Conference contribution, based on arXiv:1707.02136, with some further development

Local and global modes of drug action in biochemical networks

It becomes increasingly accepted that a shift is needed from the traditional target-based approach of drug development to an integrated perspective of drug action in biochemical systems. We here present an integrative analysis of the interactions between drugs and metabolism based on the concept of drug scope. The drug scope represents the set of metabolic compounds and reactions that are potentially affected by a drug. We constructed and analyzed the scopes of all US approved drugs having metabolic targets. Our analysis shows that the distribution of drug scopes is highly uneven, and that drugs can be classified into several categories based on their scopes. Some of them have small scopes corresponding to localized action, while others have large scopes corresponding to potential large-scale systemic action. These groups are well conserved throughout different topologies of the underlying metabolic network. They can furthermore be associated to specific drug therapeutic properties

Selling Health Promotion to Corporate America: Uses and Abuses of the Economic Argument

Economic considerations constitute a significant factor in businesses' interest in adopting health promotion (HP) programs and in the wellness community's attempts to sell such programming to business. Substantial elements of both the business and wellness communities believe that HP programs are financially profitable, in addition to, and as a result of, improving employees' health. Examination of the foundation of this belief, however, leads to the conclusion that underlying analyses have been techni cally flawed and have ignored important costs of HP programs. This article discusses the limitations of these analyses and outlines the framework of a model that could provide a sound assessment of the economics of workplace HP programs. In general, it is expected that resultant analyses would find less direct profit potential in work place HP programs but would emphasize the cost-effectiveness of many such efforts. The latter would force recognition that health, and not profit, is the principal benefit of health promotion programming. The distinction between the cost-effectiveness and cost-saving potential of health promotion is one that all interested parties should master.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66785/2/10.1177_109019818701400106.pd

Edging your bets: advantage play, gambling, crime and victimisation

Consumerism, industrial development and regulatory liberalisation have underpinned the ascendance of gambling to a mainstream consumption practice. In particular, the online gambling environment has been marketed as a site of ‘safe risks’ where citizens can engage in a multitude of different forms of aleatory consumption. This paper offers a virtual ethnography of an online ‘advantage play’ subculture. It demonstrates how advantage players have reinterpreted the online gambling landscape as an environment saturated with crime and victimisation. In this virtual world, advantage play is no longer simply an instrumental act concerned with profit accumulation to finance consumer desires. Rather, it acts as an opportunity for individuals to engage in a unique form of edgework, whereby the threat to one’s well-being is tested through an ability to avoid crime and victimisation. This paper demonstrates how mediated environments may act as sites for edgeworking and how the potential for victimisation can be something that is actively engaged with

Pharmacokinetics, Pharmacodynamics, and Safety of Lisinopril in Pediatric Kidney Transplant Patients: Implications for Starting Dose Selection

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111964/1/cpt127.pd

Endoscopists attitudes on the publication of "quality" data for endoscopic procedures: a cross-sectional survey

<p>Abstract</p> <p>Background</p> <p>Whilst the public now have access to mortality & morbidity data for cardiothoracic surgeons, such "quality" data for endoscopy are not generally available. We studied endoscopists' attitudes to and the practicality of this data being published.</p> <p>Methods</p> <p>We sent a questionnaire to all consultant gastrointestinal (GI) surgeons, physicians and medical GI specialist registrars in the Northern region who currently perform GI endoscopic procedures (n = 132). We recorded endoscopist demographics, experience and current data collection practice. We also assessed the acceptability and utility of nine items describing endoscopic "quality" (e.g. mortality, complication & completion rates).</p> <p>Results</p> <p>103 (78%) doctors responded of whom 79 were consultants (77%). 61 (59%) respondents were physicians. 77 (75%) collect any "quality" data. The most frequently collected item was colonoscopic completion rate. Data were most commonly collected for appraisal, audit or clinical governance. The majority of doctors (54%) kept these data only available to themselves, and just one allowed the public to access this. The most acceptable data item was annual number of endoscopies and the least was crude upper GI bleeding mortality. Surgeons rated information less acceptable and less useful than physicians. Acceptability and utility scores were not related to gender, length of experience or current activity levels. Only two respondents thought all items totally unacceptable and useless.</p> <p>Conclusion</p> <p>The majority of endoscopists currently collect "quality" data for their practice although these are not widely available. The endoscopists in this study consider the publication of their outcome data to be "fairly unacceptable/not very useful" to "neutral" (score 2–3). If these data were made available to patients, consideration must be given to both its value and its acceptability.</p

Measuring V_ub and probing SUSY with double ratios of purely leptonic decays of B and D mesons

The experimental prospects for precise measurements of the leptonic decays B_u -> tau nu / mu nu, B_s -> mu+ mu-, D -> mu nu and D_s -> mu nu / tau nu are very promising. Double ratios involving four of these decays can be defined in which the dependence on the values of the decay constants is essentially eliminated, thus enabling complementary measurements of the CKM matrix element V_ub with a small theoretical error. We quantify the experimental error in a possible future measurement of |V_ub| using this approach, and show that it is competitive with the anticipated precision from the conventional approaches. Moreover, it is shown that such double ratios can be more effective than the individual leptonic decays as a probe of the parameter space of supersymmetric models. We emphasize that the double ratios have the advantage of using |V_ub| as an input parameter (for which there is experimental information), while the individual decays have an uncertainty from the decay constants (e.g. f_B_s), and hence a reliance on theoretical techniques such as lattice QCD.Comment: 21 pages, 4 figure

Three-dimensional localization of ultracold atoms in an optical disordered potential

We report a study of three-dimensional (3D) localization of ultracold atoms suspended against gravity, and released in a 3D optical disordered potential with short correlation lengths in all directions. We observe density profiles composed of a steady localized part and a diffusive part. Our observations are compatible with the self-consistent theory of Anderson localization, taking into account the specific features of the experiment, and in particular the broad energy distribution of the atoms placed in the disordered potential. The localization we observe cannot be interpreted as trapping of particles with energy below the classical percolation threshold.Comment: published in Nature Physics; The present version is the initial manuscript (unchanged compared to version 1); The published version is available online at http://www.nature.com/nphys/journal/vaop/ncurrent/full/nphys2256.htm

T Wave Alternans in high arrhythmic risk patients: Analysis in time and frequency domains: A pilot study

BACKGROUND: T wave alternans (TA) is a repolarisation phenomenon manifesting as a microvolt beat to beat change in the amplitude of the T wave and ST segment. TA has been shown to be a predictor of arrhythmic risk in unselected myocardial infarction populations. TA has not been used to differentiate risk within the ischaemic cardiomyopathy population. METHODS: The subjects investigated comprised, Group 1: 7 stable patients with remote (>20 months) extensive myocardial scarring and no arrhythmic events (NYHA 3 and 4). Group2: 9 post infarction patients with malignant arrhythmia and implantable defibrillator. During breath holding, 20 continuous QRST complexes from each patients X, Y and Z leads were digitally recorded. Time domain, resultant absolute difference vectors (ATA), were calculated for alternate resultant T wave sequences. Group differences between the magnitude and temporal distribution of mean ATAs and their spectral and cross-spectral analysis were compared. RESULTS: Group 1 v Group 2 mean ATAs were 10.7 (7.17) v 11.7 (8.48) respectively, not significant. Each group had a homogenous temporal distribution of ATAs. Both group's largest mean ATA frequency components were between 0 to 25 Hz, the largest ATA component being at the DC frequency. Cross spectral analysis showed no significant differences in group ATA frequency content. CONCLUSION: The frequency content and microvolt magnitude of T wave alternans was not significantly different in these two groups. The specificity of T wave alternans for differentiating arrhythmic risk in post infarction scarring and heart failure needs investigation