Nuclear factor-kappa B in the liver of patients with chronic hepatitis C: decreased RelA expression is associated with enhanced fibrosis progression

The mechanisms of liver damage in chronic hepatitis C virus (HCV) infection are poorly understood. The transcription factor, nuclear factor-kappa B (NF-kappa B), regulates the expression of genes involved in apoptosis, inflammation, and antiviral response. It plays a protective role in several forms of liver damage. In this study, we analyzed NF-kappa B by gel mobility shift assay and immunohistochemistry in liver biopsies from HCV-infected patients, and we have determined the hepatic levels of the components of the NF-kappa B system by semiquantitative polymerase chain reaction (PCR). We found that NF-kappa B was activated in the liver of patients with chronic hepatitis C. Neither NF-kappa B activity nor the RNA levels of NF-kappa B subunits showed correlation with liver inflammatory activity, viral load, or HCV genotype. By contrast, hepatic mRNA values of RelA, the main element of active NF-kappa B, correlated inversely with apoptosis (r = -.68; P <.05) and with the rate of fibrosis progression (r = -.51; P <.04). In intermediate/rapid fibrosers, RelA mRNA levels were significantly decreased as compared with slow fibrosers (P <.003) and with normal livers (P <.03). In conclusion, we found that NF-kappa B is activated in chronic HCV-infected livers, and that the expression of RelA is inversely correlated with liver cell apoptosis and with the rate of fibrosis progression. Our data thus suggest that RelA expression may protect against liver fibrosis and hepatocellular damage

Examining modification of the associations between air pollution and birth outcomes by neighborhood deprivation in a North Carolina birth cohort, 2011–2015

Background: Evidence from studies of air pollutants and birth outcomes suggests an association, but uncertainties around geographical variability and modifying factors still remain. As neighborhood-level social characteristics are associated with birth outcomes, we assess whether neighborhood deprivation level is an effect measure modifier on the association between air pollution and birth outcomes in a North Carolina birth cohort. Methods: Using birth certificate data, all North Carolina residential singleton live births from 1 January 2011 to 31 December 2015 with gestational ages of 20–44 weeks (n = 566,799) were examined for birth defect diagnoses and preterm birth. Exposures were daily average fine particulate matter (PM2.5), daily 8-h maximum nitrogen dioxide (NO2), and daily 8-h maximum ozone (O3) modeled concentrations, and the modifier of interest was the neighborhood deprivation index (NDI). Linear binomial models were used to estimate the prevalence differences and 95% confidence intervals (CI) for the association between ambient air pollution and birth defect diagnoses. Modified Poisson regression models were used to estimate risk differences (RDs) and 95% CIs for air pollution and preterm birth. Models were stratified by the neighborhood deprivation index group (low, medium, or high) to assess potential modification by NDI. Results: Approximately 3.1% of the study population had at least one birth defect and 8.18% were born preterm. For preterm birth, associations with PM2.5 and O3 did not follow a conclusive pattern and there was no evidence of modification by NDI. The associations between NO2 and preterm birth were generally negative across exposure windows except for a positive association with NO2 and preterm birth for high NDI [RD: 34.70 (95% CI 4.84–64.56)] for entire pregnancy exposure. There was no evidence of associations between pollutants examined and birth defects. Conclusions: There may be differences in the association between NO2 exposure and preterm birth by NDI but we did not observe any evidence of associations for birth defects. Our results support the public health protection afforded by reductions in air pollution, even in areas of neighborhood deprivation, but future research conducted in areas with higher levels of air pollution and evaluating the potential for modification by neighborhood deprivation level would be informative

Applying spatial reasoning to topographical data with a grounded geographical ontology

Grounding an ontology upon geographical data has been pro- posed as a method of handling the vagueness in the domain more effectively. In order to do this, we require methods of reasoning about the spatial relations between the regions within the data. This stage can be computationally expensive, as we require information on the location of points in relation to each other. This paper illustrates how using knowledge about regions allows us to reduce the computation required in an efficient and easy to understand manner. Further, we show how this system can be implemented in co-ordination with segmented data to reason abou

Análisis de las notificaciones de ototoxicidad, con sintomatología de acúfenos, en la base de datos del sistema español de farmacovigilancia de medicamentos de uso humano

Background: One of the adverse drug reactions (ADR) can be the Ototoxicity, either in a cochlear level or in a vestibular one. This may cause an incapacitating symptomatology due to a hearing impairment or deafness, tinnitus, or a vertiginous syndrome. The objective of this work was to analyze the notifications of ototoxic ADRs registered in the FEDRA database of the Spanish Pharmacovigilance System for Medicinal products for Human Use (SEFV-H), manifested as tinnitus, describing epidemiological and prognostic factors, as well as active principles and associated therapeutic groups. Methods: An observational retrospective study based on the incoming registers in the FEDRA database of the SEFV-H, with tinnitus symptomatology due to ototoxicity between 1984 and 2017 has been earned out. SPSS v.20.0 program has been used for the descriptive and inferential statistics searching elements related to the emergence, seriousness or recuperation of the tinnitus. Results: A total of 662 patients notifications were obtained with 899 suspected drugs. 64% of the patients were women. The average age was 55.8 years old. An 8.5% of the tinnitus were classified as serious, meaning a significant and persistent disability. Evaluating the causality through the modified Karch-Lasagna algorithm (SEFV-H algorithm). a causal group credible or well defined, was discovered in 48.6% In the ATC ranking, the most frequent group of cause drugs was the N. nervous system. It was concluded. among others, that the seriousness is more significant in men and that the elder group have a great influence in the tinnitus recovery. Conclusions: The appearance of tinnitus brought on by medical ototoxicity may determine an important limitation on the patient. A vestibular and cochlear function monitoring must he carried out on patients under treatment with high ototoxicity drugs. The task of the pharmacovigilance seems to be essential. by spreading its results and stimulating the ADR notifications in order to identify pharmacological threats

Characterization of Patients with Chronic Diseases and Complex Care Needs: A New High-Risk Emergent Population

Background: To analyze the prevalence and main epidemiological, clinical and outcome features of in-Patients with Complex Chronic conditions (PCC) in internal medicine areas, using a pragmatic working definition. Methods: Prospective study in 17 centers from Spain, with 97 in-hospital, monthly prevalence cuts. A PCC was considered when criteria of polypathological patient (two or more major chronic diseases) were met, or when a patient suffered one major chronic disease plus one or more of nine predefined complexity criteria like socio-familial risk, alcoholism or malnutrition among others (PCC without polypathology). A complete set of baseline features as well as 12-months survival were collected. Then, we compared clinical, outcome variables, and PROFUND index accuracy between polypathological patients and PCC without polypathology. Results: The global prevalence of PCC was 61% (40% of them were polypathological patients, and 21% PCC withouth polypathology) out of the 2178 evaluated patients. Their median age was 82 (59.5% men), suffered 2.3 ± 1.1 major diseases (heart diseases (70.5%), neurologic (41.5%), renal (36%), and lung diseases (26%)), 5.5 ± 2.5 other chronic conditions, met 2.5 ± 1.5 complexity criteria, and presented functional decline (Barthel index 55 (25-90)). Compared to polypathological patients, the subgroup of PCC without polypathology were younger, with a different pattern of major diseases and comorbidities, a better functional status, and lower 12-months mortality rates ((36.2% vs 46.8%; p = .003; OR 0.7(0.48-0.86). The PROFUND index obtained adequate calibration and discrimination power (AUC-ROC 0.67 (0.63-0.69)) in predicting 12-month mortality of PCC. Conclusion: Patients with complex chronic conditions are highly prevalent in internal medicine areas; their clinical pattern has changed in parallel to socio-epidemiological modifications, but their death-risk is still adequately predicted by PROFUND index

Sources, seasonality, and trends of southeast US aerosol: an integrated analysis of surface, aircraft, and satellite observations with the GEOS-Chem chemical transport model

We use an ensemble of surface (EPA CSN, IMPROVE, SEARCH, AERONET), aircraft (SEAC4RS), and satellite (MODIS, MISR) observations over the southeast US during the summer–fall of 2013 to better understand aerosol sources in the region and the relationship between surface particulate matter (PM) and aerosol optical depth (AOD). The GEOS-Chem global chemical transport model (CTM) with 25 × 25 km2 resolution over North America is used as a common platform to interpret measurements of different aerosol variables made at different times and locations. Sulfate and organic aerosol (OA) are the main contributors to surface PM2.5 (mass concentration of PM finer than 2.5 μm aerodynamic diameter) and AOD over the southeast US. OA is simulated successfully with a simple parameterization, assuming irreversible uptake of low-volatility products of hydrocarbon oxidation. Biogenic isoprene and monoterpenes account for 60 % of OA, anthropogenic sources for 30 %, and open fires for 10 %. 60 % of total aerosol mass is in the mixed layer below 1.5 km, 25 % in the cloud convective layer at 1.5–3 km, and 15 % in the free troposphere above 3 km. This vertical profile is well captured by GEOS-Chem, arguing against a high-altitude source of OA. The extent of sulfate neutralization (f = [NH4+]/(2[SO42−] + [NO3−]) is only 0.5–0.7 mol mol−1 in the observations, despite an excess of ammonia present, which could reflect suppression of ammonia uptake by OA. This would explain the long-term decline of ammonium aerosol in the southeast US, paralleling that of sulfate. The vertical profile of aerosol extinction over the southeast US follows closely that of aerosol mass. GEOS-Chem reproduces observed total column aerosol mass over the southeast US within 6 %, column aerosol extinction within 16 %, and space-based AOD within 8–28 % (consistently biased low). The large AOD decline observed from summer to winter is driven by sharp declines in both sulfate and OA from August to October. These declines are due to shutdowns in both biogenic emissions and UV-driven photochemistry. Surface PM2.5 shows far less summer-to-winter decrease than AOD and we attribute this in part to the offsetting effect of weaker boundary layer ventilation. The SEAC4RS aircraft data demonstrate that AODs measured from space are consistent with surface PM2.5. This implies that satellites can be used reliably to infer surface PM2.5 over monthly timescales if a good CTM representation of the aerosol vertical profile is available

Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS

The chi_b(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4 fb^-1, these states are reconstructed through their radiative decays to Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes. This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table, corrected author list, matches final version in Physical Review Letter

Search for displaced vertices arising from decays of new heavy particles in 7 TeV pp collisions at ATLAS

We present the results of a search for new, heavy particles that decay at a significant distance from their production point into a final state containing charged hadrons in association with a high-momentum muon. The search is conducted in a pp-collision data sample with a center-of-mass energy of 7 TeV and an integrated luminosity of 33 pb^-1 collected in 2010 by the ATLAS detector operating at the Large Hadron Collider. Production of such particles is expected in various scenarios of physics beyond the standard model. We observe no signal and place limits on the production cross-section of supersymmetric particles in an R-parity-violating scenario as a function of the neutralino lifetime. Limits are presented for different squark and neutralino masses, enabling extension of the limits to a variety of other models.Comment: 8 pages plus author list (20 pages total), 8 figures, 1 table, final version to appear in Physics Letters

Reducing heterotic M-theory to five dimensional supergravity on a manifold with boundary

This paper constructs the reduction of heterotic $M$-theory in eleven dimensions to a supergravity model on a manifold with boundary in five dimensions using a Calabi-Yau three-fold. New results are presented for the boundary terms in the action and for the boundary conditions on the bulk fields. Some general features of dualisation on a manifold with boundary are used to explain the origin of some topological terms in the action. The effect of gaugino condensation on the fermion boundary conditions leads to a `twist' in the chirality of the gravitino which can provide an uplifting mechanism in the vacuum energy to cancel the cosmological constant after moduli stabilisation.Comment: 16 pages, RevTe

Measurement of the inclusive isolated prompt photon cross-section in pp collisions at sqrt(s)= 7 TeV using 35 pb-1 of ATLAS data

A measurement of the differential cross-section for the inclusive production of isolated prompt photons in pp collisions at a center-of-mass energy sqrt(s) = 7 TeV is presented. The measurement covers the pseudorapidity ranges |eta|<1.37 and 1.52<=|eta|<2.37 in the transverse energy range 45<=E_T<400GeV. The results are based on an integrated luminosity of 35 pb-1, collected with the ATLAS detector at the LHC. The yields of the signal photons are measured using a data-driven technique, based on the observed distribution of the hadronic energy in a narrow cone around the photon candidate and the photon selection criteria. The results are compared with next-to-leading order perturbative QCD calculations and found to be in good agreement over four orders of magnitude in cross-section.Comment: 7 pages plus author list (18 pages total), 2 figures, 4 tables, final version published in Physics Letters