Lawrence Livermore National Laboratory capabilities in multiphase dynamics

The computer codes at LLNL with capabilities for numerical analysis for multiphase flow; phenomenology and constitutive theory and modeling; advanced diagnostics, advanced test beds, facilities, and data bases; and multiphase flow applications are listed, with brief descriptions

Premorbid levels of high-sensitivity cardiac troponin T and natriuretic peptide and prognosis after incident myocardial infarction

High-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) at the time of myocardial infarction (MI) are strong predictors of prognosis. However, whether their premorbid (before MI occurrence) levels are associated with prognosis after incident MI is unknown. Methods: In 1,054 participants from the Atherosclerosis Risk in Communities Study with incident MI, we evaluated premorbid levels of hs-cTnT and NT-proBNP measured on median 5.8 (interquartile interval 3.0-11.5 [mean 5.5]) years prior to incident MI and their associations with subsequent composite and individual outcomes of all-cause mortality, cardiovascular mortality, recurrent MI, heart failure, and stroke. Results: During a median follow-up of 3.0 years after MI, 801 participants developed the composite outcome. Both hs-cTnT and NT-proBNP were independently associated with the composite outcome after incident MI. Among individual outcomes, all-cause mortality, cardiovascular mortality, and heart failure showed significant associations with both cardiac markers. Overall, NT-proBNP demonstrated a more evident relationship than hs-cTnT. Indeed, the addition of premorbid NT-proBNP alone, but not hs-cTnT alone, to conventional predictors at incident MI significantly improved risk prediction of the composite outcome after incident MI (∆c-statistic 0.013 [95% CI 0.005-0.022] from 0.691 with conventional predictors). Conclusions: Premorbid levels of hs-cTnT and NT-proBNP assessed on average 6 years prior to incident MI were associated with adverse outcomes after incident MI. These results further highlight the importance of cardiac health at an earlier stage of life

Wilson Loop and Dimensional Reduction in Non-Commutative Gauge Theories

Using the AdS/CFT correspondence we study UV behavior of Wilson loops in various noncommutative gauge theories. We get an area law in most cases and try to identify its origin. In D3 case, we may identify the the origin as the D1 dominance over the D3: as we go to the boundary of the AdS space, the effect of the flux of the D3 charge is highly suppressed, while the flux due to the D1 charge is enhenced. So near the boundary the theory is more like a theory on D1 brane than that on D3 brane. This phenomena is closely related to the dimensional reduction due to the strong magnetic field in the charged particle in the magnetic field. The linear potential is not due to the confinement by IR effect but is the analogue of Coulomb's potential in 1+1 dimension.Comment: v2: references added, v3:include comparison with hep-th/0010256. v4=v3(mailer error), v5= to appear in pr

In vitro and in vivo antimycobacterial activities of ketone and amide derivatives of quinoxaline 1,4-di-N-oxide

Abstract: Objectives: To evaluate a novel series of quinoxaline 1,4-di-N-oxides for in vitro activity against Mycobacterium tuberculosis and for efficacy in a mouse model of tuberculosis (TB). Methods: Ketone and amide derivatives of quinoxaline 1,4-di-N-oxide were evaluated in in vitro and in vivo tests including: (i) activity against M. tuberculosis resistant to currently used antitubercular drugs including multidrug-resistant strains (MDR-TB resistant to isoniazid and rifampicin); (ii) activity against non-replicating persistent (NRP) bacteria; (iii) MBC; (iv) maximum tolerated dose, oral bioavailability and in vivo efficacy in mice; and (v) potential for cross-resistance with another bioreduced drug, PA-824. Results: Ten compounds were tested on single drug-resistant M. tuberculosis. In general, all compounds were active with ratios of MICs against resistant and non-resistant strains of <= 4.00. One compound, 5, was orally active in a murine model of TB, bactericidal, active against NRP bacteria and active on MDR-TB and poly drug-resistant clinical isolates (resistant to 3-5 antitubercular drugs). Conclusions: Quinoxaline 1,4-di-N-oxides represent a new class of orally active antitubercular drugs. They are likely bioreduced to an active metabolite, but the pathway of bacterial activation was different from PA-824, a bioreducible nitroimidazole in clinical trials. Compound 5 was bactericidal and active on NRP organisms indicating that activation occurred in both growing and non-replicating bacteria leading to cell death. The presence of NRP bacteria is believed to be a major factor responsible for the prolonged nature of antitubercular therapy. If the bactericidal activity and activity on non-replicating bacteria in vitro translate to in vivo conditions, quinoxaline 1,4-di-N-oxides may offer a path to shortened therapy

Efficacy of quinoxaline-2-carboxylate 1,4-di-N-oxide derivatives in experimental tuberculosis

This study extends earlier reports regarding the in vitro efficacies of the 1,4-di-N-oxide quinoxaline derivatives against Mycobacterium tuberculosis and has led to the discovery of a derivative with in vivo efficacy in the mouse model of tuberculosis. Quinoxaline-2-carboxylate 1,4-di-N-oxide derivatives were tested in vitro against a broad panel of single-drug-resistant M. tuberculosis strains. The susceptibilities of these strains to some compounds were comparable to those of strain H(37)Rv, as indicated by the ratios of MICs for resistant and nonresistant strains, supporting the premise that 1,4-di-N-oxide quinoxaline derivatives have a novel mode of action unrelated to those of the currently used antitubercular drugs. Specific derivatives were further evaluated in a series of in vivo assays, including evaluations of the maximum tolerated doses, the levels of oral bioavailability, and the efficacies in a low-dose aerosol model of tuberculosis in mice. One compound, ethyl 7-chloro-3-methylquinoxaline-2-carboxylate 1,4-dioxide, was found to be (i) active in reducing CFU counts in both the lungs and spleens of infected mice following oral administration, (ii) active against PA-824-resistant Mycobacterium bovis, indicating that the pathway of bioreduction/activation is different from that of PA-824 (a bioreduced nitroimidazole that is in clinical trials), and (iii) very active against nonreplicating bacteria adapted to low-oxygen conditions. These data indicate that 1,4-di-N-oxide quinoxalines hold promise for the treatment of tuberculosis

THE GROWING THREAT OF ARBOVIRUS TRANSMISSION AND OUTBREAKS IN KENYA: A REVIEW

Objective: To review the trend in arbovirus outbreaks and activity in Kenya in the last tenyears.Data source: Published reports of past outbreak investigations and more recent dataavailable at the Arbovirology and Viral haemorrhagic fevers reference centre, Centre forVirus Research, Nairobi.Study selection: Past and recent outbreaks and active tr:tnsmission reports of arboviruses ofmedical importance in Kenya including Yellow fever (Y F), Rift Valley Fever (RVF), Dengueand Crimean Congo haemorrhagic fever.Synthesis: Each of the viruses was reviewed providing c -itical information on classification,incidence, outbreak, and activity in Kenya, mode of transmission, recognition of cases,management and control.Conclusion: There is increased frequency of outbreaks and detection of arbovirus activity inhumansand vectors in the last ten years including re-emergenceof Y F virus as a public healthconcern in Kenya. The importance of recognition of cases and diagnosis (especially inmalaria endemic areas) is critical to management a ~ ~ d control. Effective countrywidesurveillance backed by diagnostic centres is highly recommended