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n this paper we report on the investigation of baryonic resonance production in proton-proton collisions at the kinetic energies of 1.25 GeV and 3.5 GeV, based on data measured with HADES. Exclusive channels npπ+ and ppπ0 as well as ppe+e− were studied simultaneously in the framework of a one-boson exchange model. The resonance cross sections were determined from the one-pion channels for Δ(1232) and N(1440) (1.25 GeV) as well as further Δ and N* resonances up to 2 GeV/c2 for the 3.5 GeV data. The data at 1.25 GeV energy were also analysed within the framework of the partial wave analysis together with the set of several other measurements at lower energies. The obtained solutions provided the evolution of resonance production with the beam energy, showing a sizeable non-resonant contribution but with still dominating contribution of Δ(1232)P33. In the case of 3.5 GeV data, the study of the ppe+e− channel gave the insight on the Dalitz decays of the baryon resonances and, in particular, on the electromagnetic transition form-factors in the time-like region. We show that the assumption of a constant electromagnetic transition form-factors leads to underestimation of the yield in the dielectron invariant mass spectrum below the vector mesons pole. On the other hand, a comparison with various transport models shows the important role of intermediate ρ production, though with a large model dependency. The exclusive channels analysis done by the HADES collaboration provides new stringent restrictions on the parameterizations used in the models.
his contribution aims to give a basic overview of the latest results regarding the production of resonances in different collision systems. The results were extracted from experimental data collected with HADES that is a multipurpose detector located at the GSI Helmholtzzentrum, Darmstadt. The main points discussed here are: the properties of the strange resonances Λ(1405) and Σ(1385), the role of Δ’s as a source of pions in the final state, the production dynamics reflected in form of differential cross sections, and the role of the ϕ meson as a source for K− particles.
The neutron capture cross section of 58Ni was measured at the neutron time of flight facility n_TOF at CERN, from 27 meV to 400 keV neutron energy. Special care has been taken to identify all the possible sources of background, with the so-called neutron background obtained for the first time using high-precision GEANT4 simulations. The energy range up to 122 keV was treated as the resolved resonance region, where 51 resonances were identified and analyzed by a multilevel R-matrix code SAMMY. Above 122 keV the code SESH was used in analyzing the unresolved resonance region of the capture yield. Maxwellian averaged cross sections were calculated in the temperature range of kT = 5 – 100 keV, and their astrophysical implications were investigated.
Background: The introduction of modern troponin assays has facilitated diagnosis of acute myocardial infarction due to improved sensitivity with corresponding loss of specificity. Atrial fibrillation (AF) is associated with elevated levels of troponin. The aim of the present study was to evaluate the diagnostic performance of troponin I in patients with suspected acute coronary syndrome and chronic AF.
Methods: Contemporary sensitive troponin I was assayed in a derivation cohort of 90 patients with suspected acute coronary syndrome and chronic AF to establish diagnostic cut-offs. These thresholds were validated in an independent cohort of 314 patients with suspected myocardial infarction and AF upon presentation. Additionally, changes in troponin I concentration within 3 hours were used.
Results: In the derivation cohort, optimized thresholds with respect to a rule-out strategy with high sensitivity and a rule-in strategy with high specificity were established. In the validation cohort, application of the rule-out cut-off led to a negative predictive value of 97 %. The rule-in cut-off was associated with a positive predictive value of 88 % compared with 71 % if using the 99th percentile cut-off. In patients with troponin I levels above the specificity-optimized threshold, additional use of the 3-hour change in absolute/relative concentration resulted in a further improved positive predictive value of 96 %/100 %.
Conclusions: Troponin I concentration and the 3-hour change in its concentration provide valid diagnostic information in patients with suspected myocardial infarction and chronic AF. With regard to AF-associated elevation of troponin levels, application of diagnostic cut-offs other than the 99th percentile might be beneficial.
Protein turnover and quality control by the proteasome is of paramount importance for cell homeostasis. Dysfunction of the proteasome is associated with aging processes and human diseases such as neurodegeneration, cardiomyopathy, and cancer. The regulation, i.e. activation and inhibition of this fundamentally important protein degradation system, is still widely unexplored. We demonstrate here that the evolutionarily highly conserved type II triple-A ATPase VCP and the proteasome inhibitor PSMF1/PI31 interact directly, and antagonistically regulate proteasomal activity. Our data provide novel insights into the regulation of proteasomal activity.
Many QCD based and phenomenological models predict changes of hadron properties in a strongly interacting environment. The results of these models differ significantly and the experimental determination of hadron properties in nuclear matter is essential. In this paper we present a review of selected physics results obtained at GSI Helmholtzzentrum für Schwerionenforschung GmbH by HADES (High-Acceptance Di-Electron Spectrometer). The e+e− pair emission measured for proton and heavy-ion induced collisions is reported together with results on strangeness production. The future HADES activities at the planned FAIR facility are also discussed.
The High Acceptance DiElectron Spectrometer HADES [1] is installed at the Helmholtzzentrum für Schwerionenforschung (GSI) accelerator facility in Darmstadt. It investigates dielectron emission and strangeness production in the 1-3 AGeV regime. A recent experiment series focusses on medium-modifications of light vector mesons in cold nuclear matter. In two runs, p+p and p+Nb reactions were investigated at 3.5 GeV beam energy; about 9·109 events have been registered. In contrast to other experiments the high acceptance of the HADES allows for a detailed analysis of electron pairs with low momenta relative to nuclear matter, where modifications of the spectral functions of vector mesons are predicted to be most prominent. Comparing these low momentum electron pairs to the reference measurement in the elementary p+p reaction, we find in fact a strong modification of the spectral distribution in the whole vector meson region.
The neutron sensitivity of the C6D6 detector setup used at n_TOF facility for capture measurements has been studied by means of detailed GEANT4 simulations. A realistic software replica of the entire n_TOF experimental hall, including the neutron beam line, sample, detector supports and the walls of the experimental area has been implemented in the simulations. The simulations have been analyzed in the same manner as experimental data, in particular by applying the Pulse Height Weighting Technique. The simulations have been validated against a measurement of the neutron background performed with a natC sample, showing an excellent agreement above 1 keV. At lower energies, an additional component in the measured natC yield has been discovered, which prevents the use of natC data for neutron background estimates at neutron energies below a few hundred eV. The origin and time structure of the neutron background have been derived from the simulations. Examples of the neutron background for two different samples are demonstrating the important role of accurate simulations of the neutron background in capture cross-section measurements.
Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by problems in social behaviour, which are sometimes similar to some symptoms of autism-spectrum disorders (ASD). However, neuronal mechanisms of ASD-like deficits in ADHD have rarely been studied. The processing of biological motion–recently discussed as a marker of social cognition–was found to be disrupted in ASD in several studies. Thus in the present study we tested if biological motion processing is disrupted in ADHD. We used 64-channel EEG and spatio-temporal source analysis to assess event-related potentials associated with human motion processing in 21 children and adolescents with ADHD and 21 matched typically developing controls. On the behavioural level, all subjects were able to differentiate between human and scrambled motion. But in response to both scrambled and biological motion, the N200 amplitude was decreased in subjects with ADHD. After a spatio-temporal dipole analysis, a human motion specific activation was observable in occipital-temporal regions with a reduced and more diffuse activation in ADHD subjects. These results point towards neuronal determined alterations in the processing of biological motion in ADHD.
Background: Hepatitis B coinfection is common in HIV-positive individuals and as antiretroviral therapy has made death due to AIDS less common, hepatitis has become increasingly important. Several drugs are available to treat hepatitis B. The most potent and the one with the lowest risk of resistance appears to be tenofovir (TDF). However there are several questions that remain unanswered regarding the use of TDF, including the proportion of patients that achieves suppression of HBV viral load and over what time, whether suppression is durable and whether prior treatment with other HBV-active drugs such as lamivudine, compromises the efficacy of TDF due to possible selection of resistant HBV strains.
Methods: A systematic review and meta-analysis following PRISMA guidelines and using multilevel mixed effects logistic regression, stratified by prior and/or concomitant use of lamivudine and/or emtricitabine.
Results: Data was available from 23 studies including 550 HBV/HIV coinfected patients treated with TDF. Follow up was for up to seven years but to ensure sufficient power the data analyses were limited to three years. The overall proportion achieving suppression of HBV replication was 57.4%, 79.0% and 85.6% at one, two and three years, respectively. No effect of prior or concomitant 3TC/FTC was shown. Virological rebound on TDF treatment was rare.
Interpretation: TDF suppresses HBV to undetectable levels in the majority of HBV/HIV coinfected patients with the proportion fully suppressed continuing to increase during continuous treatment. Prior treatment with 3TC/FTC does not compromise efficacy of TDF treatment. The use of combination treatment with 3TC/FTC offers no significant benefit over TDF alone.
The international research project RECONCILE has addressed central questions regarding polar ozone depletion, with the objective to quantify some of the most relevant yet still uncertain physical and chemical processes and thereby improve prognostic modelling capabilities to realistically predict the response of the ozone layer to climate change. This overview paper outlines the scope and the general approach of RECONCILE, and it provides a summary of observations and modelling in 2010 and 2011 that have generated an in many respects unprecedented dataset to study processes in the Arctic winter stratosphere. Principally, it summarises important outcomes of RECONCILE including (i) better constraints and enhanced consistency on the set of parameters governing catalytic ozone destruction cycles, (ii) a better understanding of the role of cold binary aerosols in heterogeneous chlorine activation, (iii) an improved scheme of polar stratospheric cloud (PSC) processes that includes heterogeneous nucleation of nitric acid trihydrate (NAT) and ice on non-volatile background aerosol leading to better model parameterisations with respect to denitrification, and (iv) long transient simulations with a chemistry-climate model (CCM) updated based on the results of RECONCILE that better reproduce past ozone trends in Antarctica and are deemed to produce more reliable predictions of future ozone trends. The process studies and the global simulations conducted in RECONCILE show that in the Arctic, ozone depletion uncertainties in the chemical and microphysical processes are now clearly smaller than the sensitivity to dynamic variability.
Sulphuric acid, ammonia, amines, and oxidised organics play a crucial role in nanoparticle formation in the atmosphere. In this study, we investigate the composition of nucleated nanoparticles formed from these compounds in the CLOUD (Cosmics Leaving Outdoor Droplets) chamber experiments at CERN (Centre européen pour la recherche nucléaire). The investigation was carried out via analysis of the particle hygroscopicity, ethanol affinity, oxidation state, and ion composition. Hygroscopicity was studied by a hygroscopic tandem differential mobility analyser and a cloud condensation nuclei counter, ethanol affinity by an organic differential mobility analyser and particle oxidation level by a high-resolution time-of-flight aerosol mass spectrometer. The ion composition was studied by an atmospheric pressure interface time-of-flight mass spectrometer. The volume fraction of the organics in the particles during their growth from sizes of a few nanometers to tens of nanometers was derived from measured hygroscopicity assuming the Zdanovskii–Stokes–Robinson relationship, and compared to values gained from the spectrometers. The ZSR-relationship was also applied to obtain the measured ethanol affinities during the particle growth, which were used to derive the volume fractions of sulphuric acid and the other inorganics (e.g. ammonium salts). In the presence of sulphuric acid and ammonia, particles with a mobility diameter of 150 nm were chemically neutralised to ammonium sulphate. In the presence of oxidation products of pinanediol, the organic volume fraction of freshly nucleated particles increased from 0.4 to ~0.9, with an increase in diameter from 2 to 63 nm. Conversely, the sulphuric acid volume fraction decreased from 0.6 to 0.1 when the particle diameter increased from 2 to 50 nm. The results provide information on the composition of nucleated aerosol particles during their growth in the presence of various combinations of sulphuric acid, ammonia, dimethylamine and organic oxidation products.
Biomarkers and bacterial pneumonia risk in patients with treated HIV infection: a case-control study
(2013)
Background: Despite advances in HIV treatment, bacterial pneumonia continues to cause considerable morbidity and mortality in patients with HIV infection. Studies of biomarker associations with bacterial pneumonia risk in treated HIV-infected patients do not currently exist.
Methods: We performed a nested, matched, case-control study among participants randomized to continuous combination antiretroviral therapy (cART) in the Strategies for Management of Antiretroviral Therapy trial. Patients who developed bacterial pneumonia (cases) and patients without bacterial pneumonia (controls) were matched 1:1 on clinical center, smoking status, age, and baseline cART use. Baseline levels of Club Cell Secretory Protein 16 (CC16), Surfactant Protein D (SP-D), C-reactive protein (hsCRP), interleukin-6 (IL-6), and d-dimer were compared between cases and controls.
Results: Cases (n = 72) and controls (n = 72) were 25.7% female, 51.4% black, 65.3% current smokers, 9.7% diabetic, 36.1% co-infected with Hepatitis B/C, and 75.0% were on cART at baseline. Median (IQR) age was 45 (41, 51) years with CD4+ count of 553 (436, 690) cells/mm3. Baseline CC16 and SP-D were similar between cases and controls, but hsCRP was significantly higher in cases than controls (2.94 µg/mL in cases vs. 1.93 µg/mL in controls; p = 0.02). IL-6 and d-dimer levels were also higher in cases compared to controls, though differences were not statistically significant (p-value 0.06 and 0.10, respectively).
Conclusions: In patients with cART-treated HIV infection, higher levels of systemic inflammatory markers were associated with increased bacterial pneumonia risk, while two pulmonary-specific inflammatory biomarkers, CC16 and SP-D, were not associated with bacterial pneumonia risk.
RP1 (synonym: MAPRE2, EB2) is a member of the microtubule binding EB1 protein family, which interacts with APC, a key regulatory molecule in the Wnt signalling pathway. While the other EB1 proteins are well characterized the cellular function and regulation of RP1 remain speculative to date. However, recently RP1 has been implicated in pancreatic cancerogenesis. CK2 is a pleiotropic kinase involved in adhesion, proliferation and anti-apoptosis. Overexpression of protein kinase CK2 is a hallmark of many cancers and supports the malignant phenotype of tumor cells. In this study we investigate the interaction of protein kinase CK2 with RP1 and demonstrate that CK2 phosphorylates RP1 at Ser236 in vitro. Stable RP1 expression in cell lines leads to a significant cleavage and down-regulation of N-cadherin and impaired adhesion. Cells expressing a Phospho-mimicking point mutant RP1-ASP236 show a marked decrease of adhesion to endothelial cells under shear stress. Inversely, we found that the cells under shear stress downregulate endogenous RP1, most likely to improve cellular adhesion. Accordingly, when RP1 expression is suppressed by shRNA, cells lacking RP1 display significantly increased cell adherence to surfaces. In summary, RP1 phosphorylation at Ser236 by CK2 seems to play a significant role in cell adhesion and might initiate new insights in the CK2 and EB1 family protein association.
Background & Aims: Genetic variations near the interferon lambda 3 gene (IFNL3, IL28B) are the most powerful predictors for sustained virologic response (SVR) in patients with chronic hepatitis C virus (HCV) infection, compared to other biochemical or histological baseline parameters. We evaluated whether the interplay of both IFNL3 polymorphisms rs12979860 and rs8099917 together with non-genetic clinical factors contributes to the predictive role of these genetic variants.
Methods: The cohort comprised 1,402 patients of European descent with chronic HCV type 1 infection. 1,298 patients received interferon-based antiviral therapy, and 719 (55%) achieved SVR. The IFNL3 polymorphisms were genotyped by polymerase chain reaction and melting curve analysis.
Results: A significant correlation was found between the IFNL3 polymorphisms and biochemical as well as virologic predictors of treatment outcome such as ALT, GGT, cholesterol, and HCV RNA levels. In multivariate regression analysis, IFLN3 SNPs, HCV RNA levels, and the GGT/ALT ratio were independent predictors of SVR. Dependent on the GGT/ALT ratio and on the HCV RNA concentration, significant variations in the likelihood for achieving SVR were observed in both, carriers of the responder as well as non-responder alleles.
Conclusions: Our data support a clear association between IFNL3 genotypes and baseline parameters known to impact interferon responsiveness. Improved treatment outcome prediction was achieved when these predictors were considered in combination with the IFNL3 genotype.
Background: 15-20% of all patients initially diagnosed with colorectal cancer develop metastatic disease and surgical resection remains the only potentially curative treatment available. Current 5-year survival following R0-resection of liver metastases is 28-39%, but recurrence eventually occurs in up to 70%. To date, adjuvant chemotherapy has not improved clinical outcomes significantly. The primary objective of the ongoing LICC trial (L-BLP25 In Colorectal Cancer) is to determine whether L-BLP25, an active cancer immunotherapy, extends recurrence-free survival (RFS) time over placebo in colorectal cancer patients following R0/R1 resection of hepatic metastases. L-BLP25 targets MUC1 glycoprotein, which is highly expressed in hepatic metastases from colorectal cancer. In a phase IIB trial, L-BLP25 has shown acceptable tolerability and a trend towards longer survival in patients with stage IIIB locoregional NSCLC.
Methods: This is a multinational, phase II, multicenter, randomized, double-blind, placebo-controlled trial with a sample size of 159 patients from 20 centers in 3 countries. Patients with stage IV colorectal adenocarcinoma limited to liver metastases are included. Following curative-intent complete resection of the primary tumor and of all synchronous/metachronous metastases, eligible patients are randomized 2:1 to receive either L-BLP25 or placebo. Those allocated to L-BLP25 receive a single dose of 300 mg/m2 cyclophosphamide (CP) 3 days before first L-BLP25 dose, then primary treatment with s.c. L-BLP25 930 mug once weekly for 8 weeks, followed by s.c. L-BLP25 930 mug maintenance doses at 6-week (years 1&2) and 12-week (year 3) intervals unless recurrence occurs. In the control arm, CP is replaced by saline solution and L-BLP25 by placebo. Primary endpoint is the comparison of recurrence-free survival (RFS) time between groups. Secondary endpoints are overall survival (OS) time, safety, tolerability, RFS/OS in MUC-1 positive cancers. Exploratory immune response analyses are planned. The primary endpoint will be assessed in Q3 2016. Follow-up will end Q3 2017. Interim analyses are not planned.
Discussion: The design and implementation of such a vaccination study in colorectal cancer is feasible. The study will provide recurrence-free and overall survival rates of groups in an unbiased fashion. Trial Registration EudraCT Number 2011-000218-20
The knowledge of baryonic resonance properties and production cross sections plays an important role for the extraction and understanding of medium modifications of mesons in hot and/or dense nuclear matter. We present and discuss systematics on dielectron and strangeness production obtained with HADES on p+p, p+A and A+A collisions in the few GeV energy regime with respect to these resonances.
Significant reductions in stratospheric ozone occur inside the polar vortices each spring when chlorine radicals produced by heterogeneous reactions on cold particle surfaces in winter destroy ozone mainly in two catalytic cycles, the ClO dimer cycle and the ClO/BrO cycle. Chlorofluorocarbons (CFCs), which are responsible for most of the chlorine currently present in the stratosphere, have been banned by the Montreal Protocol and its amendments, and the ozone layer is predicted to recover to 1980 levels within the next few decades. During the same period, however, climate change is expected to alter the temperature, circulation patterns and chemical composition in the stratosphere, and possible geo-engineering ventures to mitigate climate change may lead to additional changes. To realistically predict the response of the ozone layer to such influences requires the correct representation of all relevant processes. The European project RECONCILE has comprehensively addressed remaining questions in the context of polar ozone depletion, with the objective to quantify the rates of some of the most relevant, yet still uncertain physical and chemical processes. To this end RECONCILE used a broad approach of laboratory experiments, two field missions in the Arctic winter 2009/10 employing the high altitude research aircraft M55-Geophysica and an extensive match ozone sonde campaign, as well as microphysical and chemical transport modelling and data assimilation. Some of the main outcomes of RECONCILE are as follows: (1) vortex meteorology: the 2009/10 Arctic winter was unusually cold at stratospheric levels during the six-week period from mid-December 2009 until the end of January 2010, with reduced transport and mixing across the polar vortex edge; polar vortex stability and how it is influenced by dynamic processes in the troposphere has led to unprecedented, synoptic-scale stratospheric regions with temperatures below the frost point; in these regions stratospheric ice clouds have been observed, extending over >106km2 during more than 3 weeks. (2) Particle microphysics: heterogeneous nucleation of nitric acid trihydrate (NAT) particles in the absence of ice has been unambiguously demonstrated; conversely, the synoptic scale ice clouds also appear to nucleate heterogeneously; a variety of possible heterogeneous nuclei has been characterised by chemical analysis of the non-volatile fraction of the background aerosol; substantial formation of solid particles and denitrification via their sedimentation has been observed and model parameterizations have been improved. (3) Chemistry: strong evidence has been found for significant chlorine activation not only on polar stratospheric clouds (PSCs) but also on cold binary aerosol; laboratory experiments and field data on the ClOOCl photolysis rate and other kinetic parameters have been shown to be consistent with an adequate degree of certainty; no evidence has been found that would support the existence of yet unknown chemical mechanisms making a significant contribution to polar ozone loss. (4) Global modelling: results from process studies have been implemented in a prognostic chemistry climate model (CCM); simulations with improved parameterisations of processes relevant for polar ozone depletion are evaluated against satellite data and other long term records using data assimilation and detrended fluctuation analysis. Finally, measurements and process studies within RECONCILE were also applied to the winter 2010/11, when special meteorological conditions led to the highest chemical ozone loss ever observed in the Arctic. In addition to quantifying the 2010/11 ozone loss and to understand its causes including possible connections to climate change, its impacts were addressed, such as changes in surface ultraviolet (UV) radiation in the densely populated northern mid-latitudes.
Sulphuric acid, ammonia, amines, and oxidised organics play a crucial role in nanoparticle formation in the atmosphere. In this study, we investigate the composition of nucleated nanoparticles formed from these compounds in the CLOUD chamber experiments at CERN. The investigation is carried out via analysis of the particle hygroscopicity, ethanol affinity, oxidation state, and ion composition. Hygroscopicity was studied by a hygroscopic tandem differential mobility analyser and a cloud condensation nuclei counter, ethanol affinity by an organic differential mobility analyser and particle oxidation level by a high-resolution time-of-flight aerosol mass spectrometer. The ion composition was studied by an atmospheric pressure interface time-of-flight mass spectrometer. The volume fraction of the organics in the particles during their growth from sizes of a few nanometers to tens of nanometers was derived from measured hygroscopicity assuming the Zdanovski-Stokes-Robinson relationship, and compared to values gained from the spectrometers. The ZSR-relationship was also applied to obtain the measured ethanol affinities during the particle growth, which were used to derive the volume fractions of sulphuric acid and the other inorganics (e.g. ammonium salts). In the presence of sulphuric acid and ammonia, particles with a mobility diameter of 150 nm were chemically neutralised to ammonium sulphate. In the presence of oxidation products of pinanediol, the organic volume fraction of freshly nucleated particles increased from 0.4 to ∼0.9, with an increase in diameter from 2 to 63 nm. Conversely, the sulphuric acid volume fraction decreased from 0.6 to 0.1 when the particle diameter increased from 2 to 50 nm. The results provide information on the composition of nucleated aerosol particles during their growth in the presence of various combinations of sulphuric acid, ammonia, dimethylamine and organic oxidation products.
New results on the differential cross section in deuteron-proton elastic scattering are obtained at the deuteron kinetic energy of 2.5 GeV with the HADES spectrometer. The angular range of 69° – 125° in the center of mass system is covered. The obtained results are compared with the relativistic multiple scattering model calculation using the CD-Bonn deuteron wave function. The data at fixed scattering angles in the c.m. are in qualitative agreement with the constituent counting rules prediction.
Background: Chronic renal disease is a serious complication of long-term intravenous drug use (IVDU). Recent reports have postulated a changing pattern of underlying nephropathy over the last decades.
Methods: Retrospective investigation including all patients with prior or present IVDU that underwent renal biopsy because of chronic kidney disease between 01.04.2002 and 31.03.2012 in the city of Frankfurt/Main, Germany.
Results: Twenty four patients with IVDU underwent renal biopsy because of progressive chronic kidney disease or proteinuria. Renal AA-amyloidosis was the predominant cause of renal failure in 50% of patients. Membranoproliferative glomerulonephritis (GN) was the second most common cause found in 21%. Patients with AA-amyloidosis were more likely to be HIV infected (67 vs.17%; p=0.036) and tended to have a higher rate of repeated systemic infections (92 vs. 50%; p=0.069). Patients with AA-amyloidosis presented with progressive renal disease and nephrotic-range proteinuria but most patients had no peripheral edema or systemic hypertension. Development of proteinuria preceded the decline of GFR for approximately 1--2 years.
Conclusions: AA-amyloidosis was the predominant cause of progressive renal disease in the last 10 years in patients with IVDU. The highest rate of AA-amyloidosis observed was seen in HIV infected patients with IVDU. We speculate that chronic HIV-infection as well as the associated immunosuppression might promote development of AA-amyloidosis by increasing frequency and duration of infections acquired by IVDU.
Background: To perform a comprehensive study on the relationship between vitamin D metabolism and the response to interferon-α-based therapy of chronic hepatitis C.
Methodology/Principal Findings: Associations between a functionally relevant polymorphism in the gene encoding the vitamin D 1α-hydroxylase (CYP27B1-1260 rs10877012) and the response to treatment with pegylated interferon-α (PEG-IFN-α) and ribavirin were determined in 701 patients with chronic hepatitis C. In addition, associations between serum concentrations of 25-hydroxyvitamin D3 (25[OH]D3) and treatment outcome were analysed. CYP27B1-1260 rs10877012 was found to be an independent predictor of sustained virologic response (SVR) in patients with poor-response IL28B genotypes (15% difference in SVR for rs10877012 genotype AA vs. CC, p = 0.02, OR = 1.52, 95% CI = 1.061–2.188), but not in patients with favourable IL28B genotype. Patients with chronic hepatitis C showed a high prevalence of vitamin D insufficiency (25[OH]D3<20 ng/mL) during all seasons, but 25(OH)D3 serum levels were not associated with treatment outcome.
Conclusions/Significance: Our study suggests a role of bioactive vitamin D (1,25[OH]2D3, calcitriol) in the response to treatment of chronic hepatitis C. However, serum concentration of the calcitriol precursor 25(OH)D3 is not a suitable predictor of treatment outcome.
Poster presentation: Purpose of the study The aim of the Rainbow Cohort is to assess the tolerability and efficacy of initiating treatment with, or switching treatment to the saquinavir (SQV) 500 mg film-coated tablet formulation. We present the final 48-week subgroup analysis of PI-experienced, but SQV-naïve patients. ...
Poster presentation: Purpose of the study The aim of the Rainbow Cohort is to assess the tolerability and efficacy of initiating treatment with, or switching treatment to saquinavir (SQV) 500 mg film-coated tablet formulation. We present the final 48-week subgroup analysis of antiretroviral therapy (ART)-naïve patients. ...
This study presents an evaluation of a pulse height condensation particle counter (PH-CPC) and an expansion condensation particle counter (E-CPC) in terms of measuring ambient and laboratory-generated molecular and ion clusters. Ambient molecular cluster concentrations were measured with both instruments as they were deployed in conjunction with an ion spectrometer and other aerosol instruments in Hyytiälä, Finland at the SMEAR II station between 1 March and 30 June 2007. The observed cluster concentrations varied and ranged from some thousands to 100 000 cm -3. Both instruments showed similar (within a factor of ~5) concentrations. An average size of the detected clusters was approximately 1.8 nm. As the atmospheric measurement of sub 2-nm particles and molecular clusters is a challenging task, we conclude that most likely we were unable to detect the smallest clusters. Nevertheless, the reported concentrations are the best estimates to date for minimum cluster concentrations in a boreal forest environment.
The ambient and laboratory molecular and ion clusters were investigated. Here we present data on the ambient concentrations of both charged and uncharged molecular clusters as well as the performance of a pulse height condensation particle counter (PH-CPC) and an expansion condensation particle counter (E-CPC). The ambient molecular cluster concentrations were measured using both instruments, and they were deployed in conjunction with ion spectrometers and other aerosol instruments in Hyytiälä, Finland at the SMEAR II station during 1 March to 30 June 2007. The observed cluster concentrations varied and were from ca. 1000 to 100 000 cm−3. Both instruments showed similar concentrations. The average size of detected clusters was approximately 1.8 nm. As the atmospheric measurements at sub 2-nm particles and molecular clusters are a challenging task, and we were most likely unable to detect the smallest clusters, the reported concentrations are our best estimates for minimum cluster concentrations in boreal forest environment.
Poster presentation: Purpose of the study To compare the virological, immunological and clinical response to three boosted double protease inhibitor (PI) regimens of saquinavir and ritonavir in combination with lopinavir (LOPSAQ), atazanavir (ATSAQ) or fosamprenavir (FOSAQ) without reverse transcriptase inhibitors (RTI) in HIV-positive patients with limited RTI treatment options. ...
Poster presentation: Purpose of the study To compare the lipometabolic profiles of three double-boosted protease inhibitor (PI) regimens at standard dose, containing saquinavir and ritonavir in combination with lopinavir (LOPSAQ), atazanavir (ATSAQ) or fosamprenavir (FOSAQ) in HIV-positive patients, treated without reverse transcriptase inhibitors (RTI). ...
Subvisible cirrus clouds (SVCs) may contribute to dehydration close to the tropical tropopause. The higher and colder SVCs and the larger their ice crystals, the more likely they represent the last efficient point of contact of the gas phase with the ice phase and, hence, the last dehydrating step, before the air enters the stratosphere. The first simultaneous in situ and remote sensing measurements of SVCs were taken during the APE-THESEO campaign in the western Indian ocean in February/March 1999. The observed clouds, termed Ultrathin Tropical Tropopause Clouds (UTTCs), belong to the geometrically and optically thinnest large-scale clouds in the Earth's atmosphere. Individual UTTCs may exist for many hours as an only 200–300 m thick cloud layer just a few hundred meters below the tropical cold point tropopause, covering up to 105 km2. With temperatures as low as 181 K these clouds are prime representatives for defining the water mixing ratio of air entering the lower stratosphere.
Mechanisms by which subvisible cirrus clouds (SVCs) might contribute to dehydration close to the tropical tropopause are not well understood. Recently Ultrathin Tropical Tropopause Clouds (UTTCs) with optical depths around 10−4 have been detected in the western Indian ocean. These clouds cover thousands of square kilometers as 200–300 m thick distinct and homogeneous layer just below the tropical tropopause. In their condensed phase UTTCs contain only 1–5% of the total water, and essentially no nitric acid. A new cloud stabilization mechanism is required to explain this small fraction of the condensed water content in the clouds and their small vertical thickness. This work suggests a mechanism, which forces the particles into a thin layer, based on upwelling of the air of some mm/s to balance the ice particles, supersaturation with respect to ice above and subsaturation below the UTTC. In situ measurements suggest that these requirements are fulfilled. The basic physical properties of this mechanism are explored by means of a single particle model. Comprehensive 1-D cloud simulations demonstrate this stabilization mechanism to be robust against rapid temperature fluctuations of +/−0.5 K. However, rapid warming (ΔT>2 K) leads to evaporation of the UTTC, while rapid cooling (ΔT<−2 K) leads to destabilization of the particles with the potential for significant dehydration below the cloud.
Subvisible cirrus clouds (SVCs) may contribute to dehydration close to the tropical tropopause. The higher and colder SVCs and the larger their ice crystals, the more likely they represent the last efficient point of contact of the gas phase with the ice phase and, hence, the last dehydrating step, before the air enters the stratosphere. The first simultaneous in situ and remote sensing measurements of SVCs were taken during the APE-THESEO campaign in the western Indian ocean in February/March 1999. The observed clouds, termed Ultrathin Tropical Tropopause Clouds (UTTCs), belong to the geometrically and optically thinnest large-scale clouds in the Earth´s atmosphere. Individual UTTCs may exist for many hours as an only 200--300 m thick cloud layer just a few hundred meters below the tropical cold point tropopause, covering up to 105 km2. With temperatures as low as 181 K these clouds are prime representatives for defining the water mixing ratio of air entering the lower stratosphere.
Mechanisms by which subvisible cirrus clouds (SVCs) might contribute to dehydration close to the tropical tropopause are not well understood. Recently Ultrathin Tropical Tropopause Clouds (UTTCs) with optical depths around 10-4 have been detected in the western Indian ocean. These clouds cover thousands of square kilometers as 200-300 m thick distinct and homogeneous layer just below the tropical tropopause. In their condensed phase UTTCs contain only 1-5% of the total water, and essentially no nitric acid. A new cloud stabilization mechanism is required to explain this small fraction of the condensed water content in the clouds and their small vertical thickness. This work suggests a mechanism, which forces the particles into a thin layer, based on upwelling of the air of some mm/s to balance the ice particles, supersaturation with respect to ice above and subsaturation below the UTTC. In situ measurements suggest that these requirements are fulfilled. The basic physical properties of this mechanism are explored by means of a single particle model. Comprehensive 1-D cloud simulations demonstrate this stabilization mechanism to be robust against rapid temperature fluctuations of +/- 0.5 K. However, rapid warming (Delta T > 2 K) leads to evaporation of the UTTC, while rapid cooling (Delta T < -2 K) leads to destabilization of the particles with the potential for significant dehydration below the cloud