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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.
INTRODUCTION: Older patients with acute myeloid leukemia (AML) experience short survival despite intensive chemotherapy. Azacitidine has promising activity in patients with low proliferating AML. The aim of this dose-finding part of this trial was to evaluate feasibility and safety of azacitidine combined with a cytarabine- and daunorubicin-based chemotherapy in older patients with AML.
TRIAL DESIGN: Prospective, randomised, open, phase II trial with parallel group design and fixed sample size.
PATIENTS AND METHODS: Patients aged 61 years or older, with untreated acute myeloid leukemia with a leukocyte count of <20,000/µl at the time of study entry and adequate organ function were eligible. Patients were randomised to receive azacitidine either 37.5 (dose level 1) or 75 mg/sqm (dose level 2) for five days before each cycle of induction (7+3 cytarabine plus daunorubicine) and consolidation (intermediate-dose cytarabine) therapy. Dose-limiting toxicity was the primary endpoint.
RESULTS: Six patients each were randomised into each dose level and evaluable for analysis. No dose-limiting toxicity occurred in either dose level. Nine serious adverse events occurred in five patients (three in the 37.5 mg, two in the 75 mg arm) with two fatal outcomes. Two patients at the 37.5 mg/sqm dose level and four patients at the 75 mg/sqm level achieved a complete remission after induction therapy. Median overall survival was 266 days and median event-free survival 215 days after a median follow up of 616 days.
CONCLUSIONS: The combination of azacitidine 75 mg/sqm with standard induction therapy is feasible in older patients with AML and was selected as an investigational arm in the randomised controlled part of this phase-II study, which is currently halted due to an increased cardiac toxicity observed in the experimental arm.
We have sampled atmospheric ice nuclei (IN) and aerosol in Germany and in Israel during spring 2010. IN were analyzed by the static vapor diffusion chamber FRIDGE, as well as by electron microscopy. During the Eyjafjallajökull volcanic eruption of April 2010 we have measured the highest ice nucleus number concentrations (>600 l−1) in our record of 2 yr of daily IN measurements in central Germany. Even in Israel, located about 5000 km away from Iceland, IN were as high as otherwise only during desert dust storms. The fraction of aerosol activated as ice nuclei at −18 °C and 119% rhice and the corresponding area density of ice-active sites per aerosol surface were considerably higher than what we observed during an intense outbreak of Saharan dust over Europe in May 2008.
Pure volcanic ash accounts for at least 53–68% of the 239 individual ice nucleating particles that we collected in aerosol samples from the event and analyzed by electron microscopy. Volcanic ash samples that had been collected close to the eruption site were aerosolized in the laboratory and measured by FRIDGE. Our analysis confirms the relatively poor ice nucleating efficiency (at −18 °C and 119% ice-saturation) of such "fresh" volcanic ash, as it had recently been found by other workers. We find that both the fraction of the aerosol that is active as ice nuclei as well as the density of ice-active sites on the aerosol surface are three orders of magnitude larger in the samples collected from ambient air during the volcanic peaks than in the aerosolized samples from the ash collected close to the eruption site. From this we conclude that the ice-nucleating properties of volcanic ash may be altered substantially by aging and processing during long-range transport in the atmosphere, and that global volcanism deserves further attention as a potential source of atmospheric ice nuclei.
The pT-differential inclusive production cross section of the prompt charm-strange meson Ds+ in the rapidity range |y|<0.5 was measured in proton–proton collisions at s=7 TeV at the LHC using the ALICE detector. The analysis was performed on a data sample of 2.98×108 events collected with a minimum-bias trigger. The corresponding integrated luminosity is Lint=4.8 nb−1. Reconstructing the decay Ds+→ϕπ+, with ϕ→K−K+, and its charge conjugate, about 480 Ds± mesons were counted, after selection cuts, in the transverse momentum range 2<pT<12 GeV/c. The results are compared with predictions from models based on perturbative QCD. The ratios of the cross sections of four D meson species (namely D0, D+, D⁎+ and Ds+) were determined both as a function of pT and integrated over pT after extrapolating to full pT range, together with the strangeness suppression factor in charm fragmentation. The obtained values are found to be compatible within uncertainties with those measured by other experiments in e+e−, ep and pp interactions at various centre-of-mass energies.
he first measurements of the invariant differential cross sections of inclusive π0 and η meson production at mid-rapidity in proton–proton collisions at s=0.9 TeV and s=7 TeV are reported. The π0 measurement covers the ranges 0.4<pT<7 GeV/c and 0.3<pT<25 GeV/c for these two energies, respectively. The production of η mesons was measured at s=√7 TeV in the range 0.4<pT<15 GeV/c. Next-to-Leading Order perturbative QCD calculations, which are consistent with the π0 spectrum at s=0.9 TeV, overestimate those of π0 and η mesons at s=√7 TeV, but agree with the measured η/π0 ratio at s=√7 TeV.
The ALICE Collaboration has measured inclusive J/ψ production in pp collisions at a center-of-mass energy √s=2.76 TeV at the LHC. The results presented in this Letter refer to the rapidity ranges |y|<0.9 and 2.5<y<4 and have been obtained by measuring the electron and muon pair decay channels, respectively. The integrated luminosities for the two channels are Linte=1.1 nb−1 and Lintμ=19.9 nb−1, and the corresponding signal statistics are NJ/ψe+e−=59±14 and NJ/ψμ+μ−=1364±53. We present dσJ/ψ/dy for the two rapidity regions under study and, for the forward-y range, d2σJ/ψ/dydpt in the transverse momentum domain 0<pt<8 GeV/c. The results are compared with previously published results at s=7 TeV and with theoretical calculations.
The ALICE experiment has measured low-mass dimuon production in pp collisions at √s=7 TeV in the dimuon rapidity region 2.5<y<4. The observed dimuon mass spectrum is described as a superposition of resonance decays (η,ρ,ω,η′,ϕ) into muons and semi-leptonic decays of charmed mesons. The measured production cross sections for ω and ϕ are σω(1<pt<5 GeV/c,2.5<y<4)=5.28±0.54(stat)±0.49(syst) mb and σϕ(1<pt<5 GeV/c,2.5<y<4)=0.940±0.084(stat)±0.076(syst) mb. The differential cross sections d2σ/dydpt are extracted as a function of pt for ω and ϕ. The ratio between the ρ and ω cross section is obtained. Results for the ϕ are compared with other measurements at the same energy and with predictions by models.
Identical neutral kaon pair correlations are measured in √s=7 TeV pp collisions in the ALICE experiment. One-dimensional Ks0Ks0 correlation functions in terms of the invariant momentum difference of kaon pairs are formed in two multiplicity and two transverse momentum ranges. The femtoscopic parameters for the radius and correlation strength of the kaon source are extracted. The fit includes quantum statistics and final-state interactions of the a0/f0 resonance. Ks0Ks0 correlations show an increase in radius for increasing multiplicity and a slight decrease in radius for increasing transverse mass, mT, as seen in ππ correlations in pp collisions and in heavy-ion collisions. Transverse mass scaling is observed between the Ks0Ks0 and ππ radii. Also, the first observation is made of the decay of the f2′(1525) meson into the Ks0Ks0 channel in pp collisions.
Heavy flavour decay muon production at forward rapidity in proton–proton collisions at √s=7 TeV
(2012)
The production of muons from heavy flavour decays is measured at forward rapidity in proton–proton collisions at √s=7 TeV collected with the ALICE experiment at the LHC. The analysis is carried out on a data sample corresponding to an integrated luminosity Lint=16.5 nb−1. The transverse momentum and rapidity differential production cross sections of muons from heavy flavour decays are measured in the rapidity range 2.5<y<4, over the transverse momentum range 2<pt<12 GeV/c. The results are compared to predictions based on perturbative QCD calculations.
Harmonic decomposition of two particle angular correlations in Pb–Pb collisions at √sNN=2.76 TeV
(2012)
Angular correlations between unidentified charged trigger (t) and associated (a) particles are measured by the ALICE experiment in Pb–Pb collisions at √sNN=2.76 TeV for transverse momenta 0.25<pTt,a<15 GeV/c, where pTt>pTa. The shapes of the pair correlation distributions are studied in a variety of collision centrality classes between 0 and 50% of the total hadronic cross section for particles in the pseudorapidity interval |η|<1.0. Distributions in relative azimuth Δϕ≡ϕt−ϕa are analyzed for |Δη|≡|ηt−ηa|>0.8, and are referred to as “long-range correlations”. Fourier components VnΔ≡〈cos(nΔϕ)〉 are extracted from the long-range azimuthal correlation functions. If particle pairs are correlated to one another through their individual correlation to a common symmetry plane, then the pair anisotropy VnΔ(pTt,pTa) is fully described in terms of single-particle anisotropies vn(pT) as VnΔ(pTt,pTa)=vn(pTt)vn(pTa). This expectation is tested for 1⩽n⩽5 by applying a global fit of all VnΔ(pTt,pTa) to obtain the best values vn{GF}(pT). It is found that for 2⩽n⩽5, the fit agrees well with data up to pTa∼3–4 GeV/c, with a trend of increasing deviation as pTt and pTa are increased or as collisions become more peripheral. This suggests that no pair correlation harmonic can be described over the full 0.25<pT<15 GeV/c range using a single vn(pT) curve; such a description is however approximately possible for 2⩽n⩽5 when pTa<4 GeV/c. For the n=1 harmonic, however, a single v1(pT) curve is not obtained even within the reduced range pTa<4 GeV/c.
The ALICE Collaboration reports the measurement of the relative J/ψ yield as a function of charged particle pseudorapidity density dNch/dη in pp collisions at √s=7 TeV at the LHC. J/ψ particles are detected for pt>0, in the rapidity interval |y|<0.9 via decay into e+e−, and in the interval 2.5<y<4.0 via decay into μ+μ− pairs. An approximately linear increase of the J/ψ yields normalized to their event average (dNJ/ψ/dy)/〈dNJ/ψ/dy〉 with (dNch/dη)/〈dNch/dη〉 is observed in both rapidity ranges, where dNch/dη is measured within |η|<1 and pt>0. In the highest multiplicity interval with 〈dNch/dη(bin)〉=24.1, corresponding to four times the minimum bias multiplicity density, an enhancement relative to the minimum bias J/ψ yield by a factor of about 5 at 2.5<y<4 (8 at |y|<0.9) is observed.
A measurement of the multi-strange Ξ− and Ω− baryons and their antiparticles by the ALICE experiment at the CERN Large Hadron Collider (LHC) is presented for inelastic proton–proton collisions at a centre-of-mass energy of 7 TeV. The transverse momentum (pT) distributions were studied at mid-rapidity (|y|<0.5) in the range of 0.6<pT<8.5 GeV/c for Ξ− and Ξ¯+ baryons, and in the range of 0.8<pT<5 GeV/c for Ω− and Ω¯+. Baryons and antibaryons were measured as separate particles and we find that the baryon to antibaryon ratio of both particle species is consistent with unity over the entire range of the measurement. The statistical precision of the current data has allowed us to measure a difference between the mean pT of Ξ− (Ξ¯+) and Ω− (Ω¯+). Particle yields, mean pT, and the spectra in the intermediate pT range are not well described by the PYTHIA Perugia 2011 tune Monte Carlo event generator, which has been tuned to reproduce the early LHC data. The discrepancy is largest for Ω− (Ω¯+). This PYTHIA tune approaches the pT spectra of Ξ− and Ξ¯+ baryons below pT<0.85 GeV/c and describes the Ξ− and Ξ¯+ spectra above pT>6.0 GeV/c. We also illustrate the difference between the experimental data and model by comparing the corresponding ratios of (Ω−+Ω¯+)/(Ξ−+Ξ¯+) as a function of transverse mass.
The ALICE Collaboration has made the first measurement at the LHC of J/ψ photoproduction in ultra-peripheral Pb–Pb collisions at sNN=2.76 TeV. The J/ψ is identified via its dimuon decay in the forward rapidity region with the muon spectrometer for events where the hadronic activity is required to be minimal. The analysis is based on an event sample corresponding to an integrated luminosity of about 55 μb−1. The cross section for coherent J/ψ production in the rapidity interval −3.6<y<−2.6 is measured to be dσJ/ψcoh/dy=1.00±0.18(stat)−0.26+0.24(syst) mb. The result is compared to theoretical models for coherent J/ψ production and found to be in good agreement with those models which include nuclear gluon shadowing.
Background and Aims: The prevalence of hepatitis C virus (HCV) antibodies in Germany has been estimated to be in the range of 0.4–0.63%. Screening for HCV is recommended in patients with elevated ALT levels or significant risk factors for HCV transmission only. However, 15–30% of patients report no risk factors and ALT levels can be normal in up to 20–30% of patients with chronic HCV infection. The aim of this study was to assess the HCV seroprevalence in patients visiting two tertiary care emergency departments in Berlin and Frankfurt, respectively.
Methods: Between May 2008 and March 2010, a total of 28,809 consecutive patients were screened for the presence of anti-HCV antibodies. Anti-HCV positive sera were subsequently tested for HCV-RNA.
Results: The overall HCV seroprevalence was 2.6% (95% CI: 2.4–2.8; 2.4% in Berlin and 3.5% in Frankfurt). HCV-RNA was detectable in 68% of anti-HCV positive cases. Thus, the prevalence of chronic HCV infection in the overall study population was 1.6% (95% CI 1.5–1.8). The most commonly reported risk factor was former/current injection drug use (IDU; 31.2%) and those with IDU as the main risk factor were significantly younger than patients without IDU (p<0.001) and the male-to-female ratio was 72% (121 vs. 46 patients; p<0.001). Finally, 18.8% of contacted HCV-RNA positive patients had not been diagnosed previously.
Conclusions: The HCV seroprevalence was more than four times higher compared to current estimates and almost one fifth of contacted HCV-RNA positive patients had not been diagnosed previously.
2011 wurden Gräben der Oberrheinebene auf ihren Makrophytenbestand untersucht. Die Mehrzahl der Gräben wies keine bemerkenswerten Pflanzenvorkommen auf. Callitriche obtusangula gehört allerdings zu den im Gebiet offenbar relativ weit verbreiteten Arten. Bemerkenswert ist der Bereich innerhalb einer Altrheinschlinge zwischen Geinsheim, Leeheim und Wallerstädten, wo in kleinen Gräben, deren Umgebung intensiv ackerbaulich genutzt wird, bemerkenswerte Arten wie Nitella capillaris, Ranunculus lingua, Samolus valerandi und Utricularia vulgaris vorkommen. Die Neuanlage von Gräben in diesem Bereich wird empfohlen.
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.
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.
Background: Simultaneous pancreas kidney transplantation (SPK), pancreas transplantation alone (PTA) or pancreas transplantation after kidney (PAK) are the only curative treatment options for patients with type 1 (juvenile) diabetes mellitus with or without impaired renal function. Unfortunately, transplant waiting lists for this indication are increasing because the current organ acceptability criteria are restrictive; morbidity and mortality significantly increase with time on the waitlist. Currently, only pancreas organs from donors younger than 50 years of age and with a body mass index (BMI) less than 30 are allocated for transplantation in the Eurotransplant (ET) area. To address this issue we designed a study to increase the available donor pool for these patients.
Methods/Design: This study is a prospective, multicenter (20 German centers), single blinded, non-randomized, two armed trial comparing outcome after SPK, PTA or PAK between organs with the currently allowed donor criteria versus selected organs from donors with extended criteria. Extended donor criteria are defined as organs procured from donors with a BMI of 30 to 34 or a donor age between 50 and 60 years. Immunosuppression is generally standardized using induction therapy with Myfortic, tacrolimus and low dose steroids. In principle, all patients on the waitlist for primary SPK, PTA or PAK are eligible for the clinical trial when they consent to possibly receiving an extended donor criteria organ. Patients receiving an organ meeting the current standard criteria for pancreas allocation (control arm) are compared to those receiving extended criteria organ (study arm); patients are blinded for a follow-up period of one year. The combined primary endpoint is survival of the pancreas allograft and pancreas allograft function after three months, as an early relevant outcome parameter for pancreas transplantation.
Discussion: The EXPAND Study has been initiated to investigate the hypothesis that locally allocated extended criteria organs can be transplanted with similar results compared to the currently allowed standard ET organ allocation. If our study shows a favorable comparison to standard organ allocation criteria, the morbidity and mortality for patients waiting for transplantation could be reduced in the future.
Trial registered at: NCT01384006
Recent clinical data support the clinical use of oral lavender oil in patients suffering from subsyndromal anxiety. We identified the molecular mechanism of action that will alter the perception of lavender oil as a nonspecific ingredient of aromatherapy to a potent anxiolytic inhibiting voltage dependent calcium channels (VOCCs) as highly selective drug target. In contrast to previous publications where exorbitant high concentrations were used, the effects of lavender oil in behavioral, biochemical, and electrophysiological experiments were investigated in physiological concentrations in the nanomolar range, which correlate to a single dosage of 80 mg/d in humans that was used in clinical trials. We show for the first time that lavender oil bears some similarities with the established anxiolytic pregabalin. Lavender oil inhibits VOCCs in synaptosomes, primary hippocampal neurons and stably overexpressing cell lines in the same range such as pregabalin. Interestingly, Silexan does not primarily bind to P/Q type calcium channels such as pregabalin and does not interact with the binding site of pregabalin, the α2δ subunit of VOCCs. Lavender oil reduces non-selectively the calcium influx through several different types of VOCCs such as the N-type, P/Q-type and T-type VOCCs. In the hippocampus, one brain region important for anxiety disorders, we show that inhibition by lavender oil is mainly mediated via N-type and P/Q-type VOCCs. Taken together, we provide a pharmacological and molecular rationale for the clinical use of the oral application of lavender oil in patients suffering from anxiety.