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

Effects of Cocaine and/or Heroin Use on Resting Cardiovascular Function

Background: Regular cocaine and/or heroin use is associated with major health risks, especially cardiovascular disease (CVD), but confounded by other factors. Objectives: We examined effects of chronic (years of regular use) and recent (past-month) use of cocaine and heroin, controlling for other factors, on resting cardiovascular function. Methods: In a sample of cocaine and/or heroin users (N=292), we obtained data on demographics, body mass index (BMI), history of substance use, and electrocardiogram, heart rate (HR) and blood pressure (BP). Following bivariate correlations, three-block (1: demographics, BMI; 2: tobacco, alcohol, marijuana; 3: cocaine, heroin) regression analyses were conducted to predict cardiovascular measures. Results: Higher BMI predicted increased systolic and diastolic BP (as did older age), increased supine HR, and longer QRS duration, QTc interval, PR interval, and P-wave duration. Recent substance use had more reliable effects than chronic use on cardiovascular measures. Past-month marijuana-use days predicted higher systolic BP, lower supine HR, and greater likelihood of early repolarization and ST elevation, whereas average daily marijuana use predicted shorter QTc interval. Average daily alcohol use predicted higher diastolic BP, higher supine HR and lower likelihood of sinus bradycardia (HRbpm). Past-month tobacco-use days predicted shorter QTc interval and increased likelihood of profound bradycardia (HRbpm). Past-month heroin-use days predicted lower seated HR, greater likelihood of sinus bradycardia and lower likelihood of left ventricular hypertrophy. More years of regular cocaine use and past-month cocaine-use days predicted longer QTc interval. Conclusions: Cocaine and heroin incrementally predicted modest variance in resting bradycardia and QTc interval. Clinicians should first consider demographics and recent use of tobacco, alcohol and marijuana before assuming cocaine and heroin affect these measures

Dynamics of Socioeconomic Risk Factors for Neglected Tropical Diseases and Malaria in an Armed Conflict

Armed conflict and war and infectious diseases are globally among the leading causes of human suffering and premature death. Moreover, they are closely interlinked, as an adverse public health situation may spur violent conflict, and violent conflict may favor the spread of infectious diseases. The consequences of this vicious cycle are increasingly borne by civilians, often as a hidden and hence neglected burden. We analyzed household data that were collected before and after an armed conflict in a rural part of western Côte d'Ivoire, and investigated the dynamics of socioeconomic risk factors for neglected tropical diseases (NTDs) and malaria. We identified a worsening of the sanitation infrastructure, decreasing use of protective measures against mosquito bites, and increasing difficulties to reach public health care infrastructure. In contrast, household crowding, the availability of soap, and the accessibility of comparatively simple means of health care provision (e.g., traditional healers and community health workers) seemed to be more stable. Knowledge about such dynamics may help to increase crisis-proofness of critical infrastructure and public health systems, and hence mitigate human suffering due to armed conflict and war

Offspring's leukocyte telomere length, paternal age, and telomere elongation in sperm.

PublishedJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tThis is the final version of the article. Available from Public Library of Science via the DOI in this record.Leukocyte telomere length (LTL) is a complex genetic trait. It shortens with age and is associated with a host of aging-related disorders. Recent studies have observed that offspring of older fathers have longer LTLs. We explored the relation between paternal age and offspring's LTLs in 4 different cohorts. Moreover, we examined the potential cause of the paternal age on offspring's LTL by delineating telomere parameters in sperm donors. We measured LTL by Southern blots in Caucasian men and women (n=3365), aged 18-94 years, from the Offspring of the Framingham Heart Study (Framingham Offspring), the NHLBI Family Heart Study (NHLBI-Heart), the Longitudinal Study of Aging Danish Twins (Danish Twins), and the UK Adult Twin Registry (UK Twins). Using Southern blots, Q-FISH, and flow-FISH, we also measured telomere parameters in sperm from 46 young (50 years) donors. Paternal age had an independent effect, expressed by a longer LTL in males of the Framingham Offspring and Danish Twins, males and females of the NHLBI-Heart, and females of UK Twins. For every additional year of paternal age, LTL in offspring increased at a magnitude ranging from half to more than twice of the annual attrition in LTL with age. Moreover, sperm telomere length analyses were compatible with the emergence in older men of a subset of sperm with elongated telomeres. Paternal age exerts a considerable effect on the offspring's LTL, a phenomenon which might relate to telomere elongation in sperm from older men. The implications of this effect deserve detailed study.Supported by NIH grants R01-AG021593, R01-AG020132, and P01-AG0876. Support was also provided by NIH contract NOHC25195, the NHLBI cooperative agreement grants U01 HL 67893, U01 HL67894, U01 HL67895, U01 HL67896, U01 HL67897, U01 HL67898, U01 HL67899, U01 HL67900, U01 HL67901, U01 HL67902, U01 HL56563, U01 HL56564, U01 HL56565, U01 HL56566, U01 HL56567, U01 HL56568, and U01 HL56569. Also funded in part by the Wellcome Trust grant (ref 074951)

Classical Effective Field Theory for Weak Ultra Relativistic Scattering

Inspired by the problem of Planckian scattering we describe a classical effective field theory for weak ultra relativistic scattering in which field propagation is instantaneous and transverse and the particles' equations of motion localize to the instant of passing. An analogy with the non-relativistic (post-Newtonian) approximation is stressed. The small parameter is identified and power counting rules are established. The theory is applied to reproduce the leading scattering angle for either a scalar interaction field or electro-magnetic or gravitational; to compute some subleading corrections, including the interaction duration; and to allow for non-zero masses. For the gravitational case we present an appropriate decomposition of the gravitational field onto the transverse plane together with its whole non-linear action. On the way we touch upon the relation with the eikonal approximation, some evidence for censorship of quantum gravity, and an algebraic ring structure on 2d Minkowski spacetime.Comment: 29 pages, 2 figures. v4: Duration of interaction is determined in Sec 4 and detailed in App C. Version accepted for publication in JHE

Study protocol to investigate the effect of a lifestyle intervention on body weight, psychological health status and risk factors associated with disease recurrence in women recovering from breast cancer treatment

Background Breast cancer survivors often encounter physiological and psychological problems related to their diagnosis and treatment that can influence long-term prognosis. The aim of this research is to investigate the effects of a lifestyle intervention on body weight and psychological well-being in women recovering from breast cancer treatment, and to determine the relationship between changes in these variables and biomarkers associated with disease recurrence and survival. Methods/design Following ethical approval, a total of 100 patients will be randomly assigned to a lifestyle intervention (incorporating dietary energy restriction in conjunction with aerobic exercise training) or normal care control group. Patients randomised to the dietary and exercise intervention will be given individualised healthy eating dietary advice and written information and attend moderate intensity aerobic exercise sessions on three to five days per week for a period of 24 weeks. The aim of this strategy is to induce a steady weight loss of up to 0.5 Kg each week. In addition, the overall quality of the diet will be examined with a view to (i) reducing the dietary intake of fat to ~25% of the total calories, (ii) eating at least 5 portions of fruit and vegetables a day, (iii) increasing the intake of fibre and reducing refined carbohydrates, and (iv) taking moderate amounts of alcohol. Outcome measures will include body weight and body composition, psychological health status (stress and depression), cardiorespiratory fitness and quality of life. In addition, biomarkers associated with disease recurrence, including stress hormones, estrogen status, inflammatory markers and indices of innate and adaptive immune function will be monitored. Discussion This research will provide valuable information on the effectiveness of a practical, easily implemented lifestyle intervention for evoking positive effects on body weight and psychological well-being, two important factors that can influence long-term prognosis in breast cancer survivors. However, the added value of the study is that it will also evaluate the effects of the lifestyle intervention on a range of biomarkers associated with disease recurrence and survival. Considered together, the results should improve our understanding of the potential role that lifestyle-modifiable factors could play in saving or prolonging lives

Review of in-situ process monitoring and in-situ metrology for metal additive manufacturing

Lack of assurance of quality with additively manufactured (AM) parts is a key technological barrier that prevents manufacturers from adopting AM technologies, especially for high-value applications where component failure cannot be tolerated. Developments in process control have allowed significant enhancement of AM techniques and marked improvements in surface roughness and material properties, along with a reduction in inter-build variation and the occurrence of embedded material discontinuities. As a result, the exploitation of AM processes continues to accelerate. Unlike established subtractive processes, where in-process monitoring is now commonplace, factory-ready AM processes have not yet incorporated monitoring technologies that allow discontinuities to be detected in process. Researchers have investigated new forms of instrumentation and adaptive approaches which, when integrated, will allow further enhancement to the assurance that can be offered when producing AM components. The state-of-the-art with respect to inspection methodologies compatible with AM processes is explored here. Their suitability for the inspection and identification of typical material discontinuities and failure modes is discussed with the intention of identifying new avenues for research and proposing approaches to integration into future generations of AM systems

Strong-coupling expansion and effective hamiltonians

When looking for analytical approaches to treat frustrated quantum magnets, it is often very useful to start from a limit where the ground state is highly degenerate. This chapter discusses several ways of deriving {effective Hamiltonians} around such limits, starting from standard {degenerate perturbation theory} and proceeding to modern approaches more appropriate for the derivation of high-order effective Hamiltonians, such as the perturbative continuous unitary transformations or contractor renormalization. In the course of this exposition, a number of examples taken from the recent literature are discussed, including frustrated ladders and other dimer-based Heisenberg models in a field, as well as the mapping between frustrated Ising models in a transverse field and quantum dimer models.Comment: To appear as a chapter in "Highly Frustrated Magnetism", Eds. C. Lacroix, P. Mendels, F. Mil