OBJECTIVE:The objective was to evaluate the association between age-related comorbidities (ARCs) and 5-year HIV-related excess mortality in people living with HIV aged ≥60 years.DESIGN:Cohort study using relative survival analysis (Estève's model).SETTING:The French multicentre prospective Dat'AIDS cohort that involves 12 French hospitals.PARTICIPANTS:Inclusion of 1415 HIV-1 infected patients actively followed aged ≥60 years on January 2008, with a 5-year follow-up period in the late combination antiretroviral therapy era.RESULTS:Among 1415 patients included, 154 died. By multivariable analysis, factors predictive of 5-year HIV-related excess mortality were non-AIDS-related cancer (adjusted excess HR (aEHR)=2.94; 95% CI 1.32 to 6.57), cardiovascular disease (aEHR=6.00; 95% CI 2.45 to 14.65), chronic renal disease (aEHR=4.86; 95% CI 2.24 to 10.53), cirrhosis (aEHR=3.58; 95% CI 1.25 to 10.28), hepatitis C co-infection (aEHR=3.63; 95% CI 1.44 to 9.12), body mass index<18.5 kg/m² (aEHR=4.10; 95% CI 1.61 to 10.48) and having a CD4 cell count ≤200/mm3 (aEHR=5.79; 95% CI 2.28 to 14.69).CONCLUSIONS:ARCs, particularly cardiovascular disease and chronic renal disease, are predictive of HIV-related excess mortality, with an increase in hazard similar to that of CD4 cell count.TRIAL REGISTRATION NUMBER:NCT02898987.

Objective: Anterior chest thrusts (with the subject sitting or standing and thrusts applied to the lower sternum) are recommended by the Australian Resuscitation Council as part of the sequence for clearing upper airway obstruction by a foreign body. Lateral chest thrusts (with the victim lying on their side) are no longer recommended due to a lack of evidence. We compared anterior, lateral chest and abdominal thrusts in the generation of airway pressures using a suitable animal model.Methods: This was a repeated-measures, cross-over, clinical trial of eight anaesthetised, intubated, adult pigs. For each animal, ten trials of each technique were undertaken with the upper airway obstructed. A chest/abdominal pressure transducer, a pneumotachograph and an intra-oesophageal balloon catheter recorded chest/abdominal thrust, expiratory air flows, airway and intrapleural pressures, respectively.Results: The mean (SD) thrust pressures generated for the anterior, lateral and abdominal techniques were 120.9 (11.0), 135.2 (20.0), and 142.4 (27.3) cmH(2)O, respectively (p < 0.0001). The mean (SD) peak expiratory airway pressures were 6.5 (3.0), 18.0 (5.5) and 13.8 (6.7) cmH(2)O, respectively (p < 0.0001). The mean (SD) peak expiratory intrapleural pressures were 5.4 (2.7), 13.5 (6.2) and 10.3 (8.5) cmH(2)O, respectively (p < 0.0001). At autopsy, no rib, intra-abdominal or intra-thoracic injury was observed.Conclusion: Lateral chest and abdominal thrust techniques generated significantly greater airway and pleural pressures than the anterior thrust technique. We recommend further research to provide additional evidence that may inform management guidelines for clearing foreign body upper airway obstruction. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Severe community- and hospital-acquired pneumonia is caused by Legionella pneumophila. Lung airway and alveolar epithelial cells comprise an important sentinel system in airborne infections. Although interleukin (IL)-6 is known as a central regulator of the immune response in pneumonia, its regulation in the lung is widely unknown. Herein, we demonstrate that different L. pneumophila strains induce delayed expression of IL-6 in comparison with IL-8 by human lung epithelial cells. IL-6 expression depended, at early time points, on flagellin recognition by Toll-like receptor (TLR)5, activity of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK)1 and p38 mitogen-activated protein (MAP) kinase, and, at later time points, on the type-IV secretion system. In the same manner, but more rapidly, the recently described transcription factor IκBζ was induced by Legionella infection and, binding to the nuclear factor (NF)-κB subunit p50 - recruited to the il6 promoter together with CCAAT-enhancer-binding protein β and phosphorylated activator protein-1 subunit cJun. Similarly, histone modifications and NF-κB subunit p65/RelA appeared at the iκbζ and subsequently at the il6 gene promoter, thereby initiating gene expression. Gene silencing of IκBζ reduced Legionella-related IL-6 expression by 41%. Overall, these data indicate a sequence of flagellin/TLR5- and type IV-dependent IκBζ expression, recruitment of IκBζ/p50 to the il6 promoter, chromatin remodelling and subsequent IL-6 transcription in L. pneumophila-infected lung epithelial cells.

Legionella pneumophila is an intracellular pathogen which can cause severe pneumonia called Legionnaires' disease. Host innate immune responses to L. pneumophila depend on (I) the Toll-like receptors, (II), the NAIP5/IPAF inflammasome and (III) IFNγ-mediated antibacterial mechanisms. In our study we investigate a further innate defense mechanism potentially directed against Legionella infection, which is governed by type I IFNs (IFNα/β). Our results showed that both wildtype (wt) and the flagellin-deficient L. pneumophila induced IFNβ production in murine bone marrow macrophages (BMMs) dependent on MAVS, IRF3 and on the bacterial T4 S S. While in C57 B L/6 BMMs growth of wt Legionella was rapidly terminated, BMMs lacking IRF3 or the type I IFN receptor IFNAR allowed substantial bacterial replication. We also observed increased bacterial replication of Legionella ΔflaA in IRF3-/- and IFNAR-/- BMMs compared to C57 B L/6 BMMs, while growth was restricted in C57 B L/6 BMMs upon treatment with IFNβ. Endogenous IFNα/β as well as exogenous IFNβ negatively affected bacterial numbers in replication vacuoles which appeared to be dependent on immunity-related GTPases, but did not influence ER recruitment to the vacuole or its fusion with lysosomes. Ongoing studies examine the role of type I IFNs in L. pneumophila infection in mice in vivo. Taken together, IFNα/β-mediated mechanisms might contribute to the host innate immune response against L. pneumophila infection.

Legionella pneumophila verursacht schwere ambulant oder im Krankenhaus erworbene Pneumonien. Lungenepithelzellen stellen ein wichtiges Warnsystem gegen Atemwegskeime dar.

We undertook a retrospective cohort study of 16 experienced recreational scuba divers and 16 matched non-diver controls to determine the prevalence of hearing loss and, if present, the likely causes of this loss. Each subject was required to be aged 55 years or less and to have no history or likelihood of hearing loss. An audiologist, blinded to each subject's group status, undertook all examinations. There were no significant differences in group demographics. All divers were highly experienced (median number of dives 725). Comparison of mean hearing thresholds (range 250-8000 Hz) revealed no significant differences between divers and non-divers for both air and bone conduction studies. The only exception was at 6000 Hz where the air conduction threshold was significantly higher in divers than in non-divers (p=0.03). However, there were no significant differences in Pure Tone and High Frequency averages. We conclude that experienced recreational scuba divers do not have elevated hearing threshold levels overall when compared to non-diver controls. This conclusion differs from that of investigators who have examined the hearing of experienced professional divers. Further investigation is indicated to further investigate this discrepancy and to determine whether the apparent hearing loss among the divers at 6000Hz was an isolated departure from normal hearing thresholds or, in fact, the result of diving.

Background/aims: The development of an electro-transformation system and the construction of shuttle plasmids for Actinobacillus actinomycetemcomitans have enhanced the molecular analysis of virulence factors. However, inefficient transformation is frequently encountered. This study investigated the efficiency of electro-transformation and expression of Green Fluorescent Protein (GFP) in 12 different A. actinomycetemcomitans strains. The influence of the plasmid vector, serotype, and phenotype were the major factors taken into consideration.Material and methods: Twelve serotyped A. actinomycetemcomitans strains were independently electro-transformed with two different Escherichia coli-A. actinomycetemcomitans shuttle plasmids (pVT1303 and pVT1304), both containing an identical ltx-GFPmut2 gene construct but a different backbone (pDMG4 and pPK1, respectively). The transformation efficiency, transformation frequency, and electro-transformation survival rate were determined by culture techniques. GFP expression was observed at the colony level by fluorescence microscopy.Results: All strains could be transformed with both plasmids. However, major differences were observed for the transformation efficiency, transformation frequency, and electro-transformation survival rate between strains. The data demonstrated that plasmid vector, serotype, and phenotype are key players for obtaining a successful transformation. An inverted relationship between the electro-transformation survival rate and tranformation frequency was also observed. GFP expression was also influenced by phenotype, serotype and plasmid vector.Conclusions: The serotype of A. actinomycetemcomitans has an important influence on its survival after electro-transformation and on transformation frequency. The expression of GFP is strain and plasmid vector dependent.

The concentrations of H-2, O-2, CO2, and concentrations and isotopic composition of the noble gases (including Rn-222), N-2, CH4, and higher hydrocarbons dissolved in 4000 m deep-seated fluids from a 12-month fluid production test in the KTB pilot hole were analyzed. This determination of the gas geochemistry during the test in combination with the knowledge of the hydraulic data provides relevant information about the fluid hydraulics of the deep system. All gas concentrations and isotopic signatures, except for Rn-222, showed constancy during the course of the test. This, in combination with large fluid flow rates at a moderate water table drawdown, imply an almost infinite fluid reservoir in 4000 m depth. From the change in Rn-222-activity as a function of pump rate, the contribution of smaller and wider pores to the overall fluid flow in an aquifer can be deduced. This Rn-222-activity monitoring proved therefore to be a valuable instrument for the qualitative observation of the scavenging of pore and fracture surfaces, a hydraulic feature invisible to standard hydraulic testing tools. The observance of this scavenging effect is due to (i) the continuous on-line geochemical monitoring, (ii) the durability of the test, (iii) a change in pump rate during the course of the test, and (iv) due to the short half-life of Rn-222. The fluids have a 5.9% mantle He component, and a delta(21)Ne excess of 14%, and a noble gas model age of about (5.5-6.2) +/- 2.0 Myr. The mean N-2/Ar-ratio of 516 and delta(15)N-data of about +1.57parts per thousand indicates sedimentary or metamorphic origin of N-2. The hydrocarbons, amounting to 33 vol.% in the gas phase, are derived from thermal decomposition of marine organic matter of low maturity. But a key question, the identification of the potential source region of the fluids and the migration pathway, is still unidentified.

OBJECTIVE:The authors had for aim to evaluate the clinical and biological evolution in HIV-infected patients with viraemia lower than 30,000 copies/mL having decided to interrupt their treatment.PATIENTS AND METHODS:Patients with highly active antiretroviral therapy (HAART) for more than 3 months followed by treatment interruption longer than 1 month were included in a retrospective analysis.RESULTS:Forty-six patients having stopped treatment between November 1999 and July 2003 were included. The median duration of treatment interruption was 9.5 months. During the study, no clinical event occurred for 21 patients, and at least 1 clinical event occurred for the 25 others. The median CD4(+) cell counts (CD4) before and at the end of treatment interruption were 597/mm(3) and 437/mm(3), respectively (P<0.001). The median values of viral load before and at the end of treatment interruption were <50 and 23749 copies/mL, respectively (P<0.001). Among the 26 patients having started a new HAART, pre-treatment interruption and post-new HAART median CD4 (with a median delay after HAART of 9.7 months) were 548 and 432.5/mm(3) (P=0.02). Pre-treatment interruption and post-new HAART median viral load were 131.5 and 94.5 copies/mL (NS).CONCLUSIONS:Treatment interruption must be used with caution in spite of the absence of virological impact, because CD4 cell count after new HAART is lower than CD4 preceding treatment interruption. Treatment interruption is contraindicated for patients with AIDS. Physicians must carefully follow other patients who decide on a treatment interruption.

Objective. - The authors had for aim to evaluate the clinical and biological evolution in HIV-infected patients with viraemia lower than 30,000 copies/mL having decided to interrupt their treatment. Patients and methods. -Patients with highly active antiretroviral therapy (HAART) for more than 3 months followed by treatment interruption longer than 1 month were included in a retrospective analysis.Results. - Forty-six patients having stopped treatment between November 1999 and July 2003 were included. The median duration of treatment interruption was 9.5 months. During the study, no clinical event occurred for 21 patients, and at least 1 clinical event occur-red for the 25 others. The median CD4(+) cell counts (CD4) before and at the end of treatment interruption were 597/mm(3) and 437/mm(3), respectively (P < 0.001). The median values of viral load before and at the end of treatment interruption were < 50 and 23749 copies/mL, respectively (P < 0.001). Among the 26 patients having started a new HAART, pre-treatment interruption and post-new HAART median CD4 (with a median delay after HAART of 9.7 months) were 548 and 432.5/mm(3) (P=0.02). Pre-treatment interruption and post-new HAART median viral load were 131.5 and 94.5 copies/mL (NS).Conclusions. - Treatment interruption must be used with caution in spite of the absence of virological impact, because CD4 cell count after new HAART is lower than CD4 preceding treatment interruption. Treatment interruption is contraindicated for patients with AIDS. Physicians must carefully follow other patients who decide on a treatment interruption. (c) 2005 Elsevier SAS. Tous droits reserves.

Concentrations and isotopic ratios of dissolved noble gases, Cl-36, deltaD and delta(18)O in water samples from the ultra-deep gold mines (0.718 to 3.3 km below the surface) in the Witwatersrand Basin, South Africa, were investigated to quantify the dynamics of these ultra deep crustal fluids. The mining activity has a significant impact on the concentrations of dissolved gases, as the associated pressure release causes the degassing of the fissure water. The observed under saturation of the atmospheric noble gases in the fissure water samples (70-98%, normalized to ASW at 20degreesC and 1013 mbar) is reproduced by a model that considers diffusive degassing and solubility equilibration with a gas phase at sampling temperature. Corrections for degassing result in 4 He concentrations as high as 1.55 (.) 10(-1) cm(3)STP(4)He g(-1), Ar-40/Ar-36 ranging between 806 and 10331, and Xe-134/Xe-132 and Xe-136/Xe-132 ratios above 0.46 and 0.44, respectively. Corrected Xe-134(136)/Xe-132 and Xe-134(136)/He-4-ratios are consistent with their production ratios, whereas the nucleogenic He-4/Ar-40, and Xe-134(136)/Ar-40 ratios generally indicate that these gases are produced in an environment with an average [U + Th]/K-content 2-3 times above that of crustal average. In two scenarios, one considering only accumulation of in situ produced noble gases, the other additionally crustal flux components, the model ages for 14 individual water samples range from 13 to 168 Ma and from 1 to 23 Ma, respectively. The low Cl-36-ratios of (4-37) (.) 10(-15) and comparatively high Cl-36-concentrations of (8-350) (.) 10(-15) atoms Cl-36 l(-1) reflect subsurface production in secular equilibrium indicating an age in excess of 1.5 Ma or 5 times the half-life of Cl-36.In combination, the results suggest residence times of the fluids in fissures in this region (up to 3.3 km depth) are of the order of 1-100 Ma. We cannot exclude the possibility of mixing and that small quantities of younger water have been mixed with the very old bulk. Copyright (C) 2003 Elsevier Ltd.

A cornerstone of applications utilizing in situ cosmogenic nuclides is the ability to scale production rates from the few sites where they are well-established to sites under study. Theoretical scaling models currently used for this purpose (e.g., Lal, 1991; Dunai, 2001) are based on modern measurements of cosmic ray variation with latitude and altitude. However, these models have never been thoroughly tested empirically using significant numbers of geologic samples. The main problem in addressing this issue is the scarcity of samples of well-established age. However, the recent development of a reliable extraction method for in situ cosmogenic C (in situ C) from quartz (Lifton et al., 2001) provides a unique opportunity to test these theoretical models empirically. Unlike other commonly used in situ cosmogenic nuclides, C has a short half-life that allows attainment of secular equilibrium in approximately 15 to 20 ky. In addition, C loss from decay far outstrips loss from erosion in many geomorphic settings. Under such conditions, the measured concentration of in situ C is only a function of its integrated average production rate. These aspects of the in situ C system make a wide range of landscape features suitable archives for production rate determinations. We have sampled along a mid-latitude altitude transect to assess the altitudinal dependence of integrated late Quaternary in situ C production rates. Sampling site altitudes range from near sea level in Death Valley, California, to nearly 3.9 km in the Inyo-White Mountains, California. Low-altitude samples were collected from sites on stable alluvial fan surfaces exhibiting well-developed desert pavements, whereas highaltitude samples were collected from stable bedrock sites with low local relief. We plan to present preliminary results from this transect, providing a significant empirical test of the variation of integrated late Quaternary cosmogenic nuclide production rates over a major altitudinal gradient.

A boundary layer wind profiler with RASS is described operating at 1290 MHz in a quasi-operational mode at the Meteorological Observatory Lindenberg of the German Weather Service (DWD). It provides vertical profiles of wind and temperature from the lower atmosphere with a height resolution of 50m to 400 m and a time resolution of about 1 to 60 minutes. For an estimation of the system reliability, the availability of the measurements for all different height levels is analyzed. With regard to the data quality, a comparison of wind profiler/RASS and rawinsonde data is presented based on 856 wind and 451 temperature profiles. It reveals reasonable conformity of both sounding systems. Finally, case studies are shown, demonstrating the system ability to analyze some characteristic phenomena in the lower troposphere, which are unresolved temporally and spatially by the routine rawinsonde network.

A boundary layer wind profiler with RASS is described operating at 1290 MHz in a quasi-operational mode at the Meteorological Observatory Lindenberg of the German Weather Service (DWD). It provides vertical profiles of wind and temperature from the lower atmosphere with a height resolution of 50m to 400 m and a time resolution of about 1 to 60 minutes. For an estimation of the system reliability, the availability of the measurements for all different height levels is analyzed. With regard to the data quality, a comparison of wind profiler/RASS and rawinsonde data is presented based on 856 wind and 451 temperature profiles. It reveals reasonable conformity of both sounding systems. Finally, case studies are shown, demonstrating the system ability to analyze some characteristic phenomena in the lower troposphere, which are unresolved temporally and spatially by the routine rawinsonde network.