Heart transplantation and left ventricular assist systems: not too early, not too late

Editorial commen

Oxidative Damage to DNA and Lipids as Biomarkers of Exposure to Air Pollution

Ba c k g r o u n d: Air pollution is thought to exert health effects through oxidative stress, which causes damage to DNA and lipids. Obj e c t i v e: We determined whether levels of oxidatively damaged DNA and lipid peroxidation products in cells or bodily fluids from humans are useful biomarkers of biologically effective dose in studies of the health effects of exposure to particulate matter (PM) from combustion processes. Data s o u r c e s: We identified publications that reported estimated associations between environmental exposure to PM and oxidative damage to DNA and lipids in PubMed and EMBASE. We also identified publications from reference lists and articles cited in the Web of Science. Data extraction: For each study, we obtained information on the estimated effect size to calculate the standardized mean difference (unitless) and determined the potential for errors in exposure assessment and analysis of each of the biomarkers, for total and stratified formal meta-analyses. Data synthesis: In the meta-analysis, the standardized mean differences (95 % confidence interval) between exposed and unexposed subjects for oxidized DNA and lipids were 0.53 (0.29–0.76) and 0.73 (0.18–1.28) in blood and 0.52 (0.22–0.82) and 0.49 (0.01–0.97) in urine, respectively. The standardized mean difference for oxidized lipids was 0.64 (0.07–1.21) in the airways. Restricting analyses to studies unlikely to have substantial biomarker or exposure measurement error, studies likely to have biomarker and/or exposure error, or studies likely to have both sources of error resulted in standardized mean differences of 0.55 (0.19–0.90), 0.66 (0.37–0.95), and 0.65 (0.34–0.96), respectively. Co n c l u s i o n s: Exposure to combustion particles is consistenly associated with oxidatively damaged DNA and lipids in humans, suggesting that it is possible to use these measurements as biomarkers of biologically effective dose. Key w o r d s: biomarker, DNA damage, lipid peroxidation products, oxidative stress, particulate matter. Environ Health Perspect 118:1126–1136 (2010). doi:10.1289/ehp.0901725 [Onlin

Transit Timing and Duration Variations for the Discovery and Characterization of Exoplanets

Transiting exoplanets in multi-planet systems have non-Keplerian orbits which can cause the times and durations of transits to vary. The theory and observations of transit timing variations (TTV) and transit duration variations (TDV) are reviewed. Since the last review, the Kepler spacecraft has detected several hundred perturbed planets. In a few cases, these data have been used to discover additional planets, similar to the historical discovery of Neptune in our own Solar System. However, the more impactful aspect of TTV and TDV studies has been characterization of planetary systems in which multiple planets transit. After addressing the equations of motion and parameter scalings, the main dynamical mechanisms for TTV and TDV are described, with citations to the observational literature for real examples. We describe parameter constraints, particularly the origin of the mass/eccentricity degeneracy and how it is overcome by the high-frequency component of the signal. On the observational side, derivation of timing precision and introduction to the timing diagram are given. Science results are reviewed, with an emphasis on mass measurements of transiting sub-Neptunes and super-Earths, from which bulk compositions may be inferred.Comment: Revised version. Invited review submitted to 'Handbook of Exoplanets,' Exoplanet Discovery Methods section, Springer Reference Works, Juan Antonio Belmonte and Hans Deeg, Eds. TeX and figures may be found at https://github.com/ericagol/TTV_revie

Analysis of optimal phenotypic space using elementary modes as applied to Corynebacterium glutamicum

BACKGROUND: Quantification of the metabolic network of an organism offers insights into possible ways of developing mutant strain for better productivity of an extracellular metabolite. The first step in this quantification is the enumeration of stoichiometries of all reactions occurring in a metabolic network. The structural details of the network in combination with experimentally observed accumulation rates of external metabolites can yield flux distribution at steady state. One such methodology for quantification is the use of elementary modes, which are minimal set of enzymes connecting external metabolites. Here, we have used a linear objective function subject to elementary modes as constraint to determine the fluxes in the metabolic network of Corynebacterium glutamicum. The feasible phenotypic space was evaluated at various combinations of oxygen and ammonia uptake rates. RESULTS: Quantification of the fluxes of the elementary modes in the metabolism of C. glutamicum was formulated as linear programming. The analysis demonstrated that the solution was dependent on the criteria of objective function when less than four accumulation rates of the external metabolites were considered. The analysis yielded feasible ranges of fluxes of elementary modes that satisfy the experimental accumulation rates. In C. glutamicum, the elementary modes relating to biomass synthesis through glycolysis and TCA cycle were predominantly operational in the initial growth phase. At a later time, the elementary modes contributing to lysine synthesis became active. The oxygen and ammonia uptake rates were shown to be bounded in the phenotypic space due to the stoichiometric constraint of the elementary modes. CONCLUSION: We have demonstrated the use of elementary modes and the linear programming to quantify a metabolic network. We have used the methodology to quantify the network of C. glutamicum, which evaluates the set of operational elementary modes at different phases of fermentation. The methodology was also used to determine the feasible solution space for a given set of substrate uptake rates under specific optimization criteria. Such an approach can be used to determine the optimality of the accumulation rates of any metabolite in a given network

Electronic Outbreak Surveillance in Germany: A First Evaluation for Nosocomial Norovirus Outbreaks

BACKGROUND: In Germany, surveillance for infectious disease outbreaks is integrated into an electronic surveillance system. For 2007, the national surveillance database contains case-based information on 201,224 norovirus cases, three-quarters of which are linked to outbreaks. We evaluated the data quality of the national database in reflecting nosocomial norovirus outbreak (NNO) data available in 19 Hessian local public health authorities (LPHAs) and the influence of differences between LPHA's follow-up procedures for laboratory notifications of Norovirus positive stool samples on outbreak underascertainment. METHODS: Data on NNO beginning in 2007 and notified to the 19 LPHAs were extracted from the national database, investigated regarding internal validity and compared to data collected from LPHAs for a study on NNO control. LPHAs were questioned whether they routinely contacted all persons for whom a laboratory diagnosis of norovirus infection was notified. The number of outbreaks per 1,000 hospital beds and the number of cases within NNOs for acute care and rehabilitation hospitals were compared between counties with and without complete follow-up. RESULTS: The national database contained information on 155 NNOs, including 3,115 cases. Cases were missed in the national database in 58 (37%) of the outbreaks. Information on hospitalisation was incorrect for an estimated 47% of NNO cases. Information on county of infection was incorrect for 24% (199/820) of cases being forwarded between LPHAs for data entry. Reported NNO incidence and number of NNO cases in acute care hospitals was higher in counties with complete follow-up (incidence-rate ratio (IRR) 2.7, 95% CI 1.4-5.7, p-value 0.002 and IRR 2.1, 95% CI 1.9-2.4, p-value 0.001, respectively). CONCLUSIONS: Many NNOs are not notified by hospitals and differences in LPHA procedures have an impact on the number of outbreaks captured in the surveillance system. Forwarding of case-by-case data on Norovirus outbreak cases from the local to the state and national level should not be required

QGP Theory: Status and Perspectives

The current status of Quark-Gluon-Plasma Theory is reviewed. Special emphasis is placed on QGP signatures, the interpretation of current data and what to expect from RHIC in the near future.Comment: 20 pages, invited overview talk at the 4th International Conference on the Physcis and Astrophysics of the Quark-Gluon-Plasma, November 2001, Jaipur, India, to appear in Praman

Tinnitus Intensity Dependent Gamma Oscillations of the Contralateral Auditory Cortex

Non-pulsatile tinnitus is considered a subjective auditory phantom phenomenon present in 10 to 15% of the population. Tinnitus as a phantom phenomenon is related to hyperactivity and reorganization of the auditory cortex. Magnetoencephalography studies demonstrate a correlation between gamma band activity in the contralateral auditory cortex and the presence of tinnitus. The present study aims to investigate the relation between objective gamma-band activity in the contralateral auditory cortex and subjective tinnitus loudness scores. In unilateral tinnitus patients (N = 15; 10 right, 5 left) source analysis of resting state electroencephalographic gamma band oscillations shows a strong positive correlation with Visual Analogue Scale loudness scores in the contralateral auditory cortex (max r = 0.73, p<0.05). Auditory phantom percepts thus show similar sound level dependent activation of the contralateral auditory cortex as observed in normal audition. In view of recent consciousness models and tinnitus network models these results suggest tinnitus loudness is coded by gamma band activity in the contralateral auditory cortex but might not, by itself, be responsible for tinnitus perception

The Role of Age and Exposure to Plasmodium falciparum in the Rate of Acquisition of Naturally Acquired Immunity: A Randomized Controlled Trial

Background: The rate of acquisition of naturally acquired immunity (NAI) against malaria predominantly depends on transmission intensity and age, although disentangling the effects of these is difficult. We used chemoprophylaxis to selectively control exposure to P. falciparum during different periods in infancy and explore the effect of age in the build-up of NAI, measured as risk of clinical malaria.\ud \ud Methods and Findings: A three-arm double-blind randomized placebo-controlled trial was conducted in 349 infants born to Mozambican HIV-negative women. The late exposure group (LEG) received monthly Sulfadoxine-Pyrimethamine (SP) plus Artesunate (AS) from 2.5–4.5 months of age and monthly placebo from 5.5–9.5 months; the early exposure group (EEG) received placebo from 2.5–4.5 months and SP+AS from 5.5–9.5 months; and the control group (CG) received placebo from 2.5–9.5 months. Active and passive case detection (PCD) were conducted from birth to 10.5 and 24 months respectively. The primary endpoint was time to first or only episode of malaria in the second year detected by PCD. The incidence of malaria during the second year was of 0.50, 0.51 and 0.35 episodes/PYAR in the LEG, EEG and CG respectively (p = 0.379 for the adjusted comparison of the 3 groups). The hazard ratio of the adjusted comparison between the LEG and the CG was 1.38 (0.83–2.28, p = 0.642) and that between the EEG and the CG was 1.35 (0.81–2.24, p = 0.743).\ud \ud Conclusions: After considerably interfering with exposure during the first year of life, there was a trend towards a higher risk of malaria in the second year in children who had received chemoprophylaxis, but there was no significant rebound. No evidence was found that the age of first exposure to malaria affects the rate of acquisition of NAI. Thus, the timing of administration of antimalarial interventions like malaria vaccines during infancy does not appear to be a critical determinant

Dirac-Born-Infeld-Volkov-Akulov and deformation of supersymmetry

We deform the action and the supersymmetry transformations of the d = 10 and d = 4 Maxwell supermultiplets so that at each order of the deformation the theory has 16 Maxwell multiplet deformed supersymmetries as well as 16 Volkov-Akulov type non-linear supersymmetries. The result agrees with the expansion in the string tension of the explicit action of the Dirac-Born-Infeld model and its supersymmetries, extracted from D9 and D3 superbranes, respectively. The half-maximal Dirac-Born-Infeld models with 8 Maxwell supermultiplet deformed supersymmetries and 8 Volkov-Akulov type supersymmetries are described by a new class of d = 6 vector branes related to chiral (2,0) supergravity, which we denote as 'Vp-branes'. We use a space-filling V5 superbrane for the d = 6 model and a V3 superbrane for the d = 4 half-maximal Dirac-Born-Infeld (DBI) models. In this way we present a completion to all orders of the deformation of the Maxwell supermultiplets with maximal 16+16 supersymmetries in d = 10 and 4, and half-maximal 8+8 supersymmetries in d = 6 and 4.</p

Magnetic-field-induced charge-stripe order in the high temperature superconductor YBa2Cu3Oy

Electronic charges introduced in copper-oxide planes generate high-transition temperature superconductivity but, under special circumstances, they can also order into filaments called stripes. Whether an underlying tendency of charges to order is present in all cuprates and whether this has any relationship with superconductivity are, however, two highly controversial issues. In order to uncover underlying electronic orders, magnetic fields strong enough to destabilise superconductivity can be used. Such experiments, including quantum oscillations in YBa2Cu3Oy (a notoriously clean cuprate where charge order is not observed) have suggested that superconductivity competes with spin, rather than charge, order. Here, using nuclear magnetic resonance, we demonstrate that high magnetic fields actually induce charge order, without spin order, in the CuO2 planes of YBa2Cu3Oy. The observed static, unidirectional, modulation of the charge density breaks translational symmetry, thus explaining quantum oscillation results, and we argue that it is most likely the same 4a-periodic modulation as in stripe-ordered cuprates. The discovery that it develops only when superconductivity fades away and near the same 1/8th hole doping as in La2-xBaxCuO4 suggests that charge order, although visibly pinned by CuO chains in YBa2Cu3Oy, is an intrinsic propensity of the superconducting planes of high Tc cuprates.Comment: For a final version, see http://www.nature.com/nature/journal/v477/n7363/full/nature10345.htm