A new and improved setup of the SF6 retrieval together with a newly calibrated version of MIPAS-ENVISAT level 1b spectra (version 5, ESA data version 5.02/5.06) was used to obtain a new global SF6 ...data set, covering the total observational period of MIPAS from July 2002 to April 2012 for the first time. Monthly and zonally averaged SF6 profiles were converted into mean age of air using a tropospheric SF6-reference curve. The obtained data set of age of air was compared to airborne age of air measurements. The temporal evolution of the mean age of air was then investigated in 10° latitude and 1–2 km altitude bins. A regression model consisting of a constant and a linear trend term, two proxies for the quasi-biennial oscillation variation, sinusoidal terms for the seasonal and semiannual variation and overtones was fitted to the age of air time series. The annual cycle for particular regions in the stratosphere was investigated and compared to other studies. The age of air trend over the total MIPAS period consisting of the linear term was assessed and compared to previous findings of Stiller et al. (2012). While the linear increase of mean age is confirmed to be positive for the northern midlatitudes and southern polar middle stratosphere, differences are found in the northern polar upper stratosphere, where the mean age is now found to increase as well. The magnitude of trends in the northern midlatitude middle stratosphere is slightly lower compared to the previous version and the trends fit remarkably well to the trend derived by Engel et al. (2009). Negative age of air trends found by Stiller et al. (2012) are confirmed for the lowermost tropical stratosphere and lowermost southern midlatitudinal stratosphere. Differences to the previous data versions occur in the middle tropical stratosphere around 25 km, where the trends are now negative. Overall, the new latitude–altitude distribution of trends appears to be less patchy and more coherent than the previous one. The new data provide evidence of an accelerating shallow branch of the Brewer–Dobson circulation, at least in the Southern Hemisphere. Finally the age of air decadal trends are compared to trends calculated with simulated SF6 values by the Karlsruhe Simulation Model of the Middle Atmosphere (KASIMA) and good agreement is found. The hemispheric asymmetry in the trends found in the MIPAS data is also indicated in the trends calculated with simulated SF6 values by the KASIMA model.
We have used the Whole Atmosphere Community Climate Model (WACCM), with an updated treatment of loss processes, to determine the atmospheric lifetime of sulfur hexafluoride (SF6). The model includes ...the following SF6 removal processes: photolysis, electron attachment and reaction with mesospheric metal atoms. The Sodankylä Ion Chemistry (SIC) model is incorporated into the standard version of WACCM to produce a new version with a detailed D region ion chemistry with cluster ions and negative ions. This is used to determine a latitude- and altitude-dependent scaling factor for the electron density in the standard WACCM in order to carry out multi-year SF6 simulations. The model gives a mean SF6 lifetime over an 11-year solar cycle (τ) of 1278 years (with a range from 1120 to 1475 years), which is much shorter than the currently widely used value of 3200 years, due to the larger contribution (97.4 %) of the modelled electron density to the total atmospheric loss. The loss of SF6 by reaction with mesospheric metal atoms (Na and K) is far too slow to affect the lifetime. We investigate how this shorter atmospheric lifetime impacts the use of SF6 to derive stratospheric age of air. The age of air derived from this shorter lifetime SF6 tracer is longer by 9 % in polar latitudes at 20 km compared to a passive SF6 tracer. We also present laboratory measurements of the infrared spectrum of SF6 and find good agreement with previous studies. We calculate the resulting radiative forcings and efficiencies to be, on average, very similar to those reported previously. Our values for the 20-, 100- and 500-year global warming potentials are 18 000, 23 800 and 31 300, respectively.
In response to global warming, the Brewer–Dobson circulation in the stratosphere is expected to accelerate and the mean transport time of air along this circulation to decrease. This would imply a ...negative stratospheric age of air trend, i.e. an air parcel would need less time to travel from the tropopause to any point in the stratosphere. Age of air as inferred from tracer observations, however, shows zero to positive trends in the northern mid-latitude stratosphere and zonally asymmetric patterns. Using satellite observations and model calculations we show that the observed latitudinal and vertical patterns of the decadal changes of age of air in the lower to middle stratosphere during the period 2002–2012 are predominantly caused by a southward shift of the circulation pattern by about 5°. After correction for this shift, the observations reveal a hemispherically almost symmetric decrease of age of air in the lower to middle stratosphere up to 800 K of up to −0.25 years over the 2002–2012 period with strongest decrease in the northern tropics. This net change is consistent with long-term trends from model predictions.
Axillary clearance in early breast cancer aims to improve locoregional control and provide staging information but is associated with undesirable morbidity. We therefore investigated whether avoiding ...axillary surgery in older women would result in improved quality of life (QL) with similar disease-free survival (DFS) and overall survival (OS).
Between 1993 and 2002, women > or = 60 years old with clinically node-negative operable breast cancer in whom adjuvant tamoxifen was considered indicated regardless of pathologic nodal status were randomly assigned to primary surgery plus axillary clearance (Sx + Ax) followed by tamoxifen (Tam) versus Sx without Ax followed by Tam for 5 consecutive years. The primary end point was QL reported by the patient and by physician assessment.
A total of 473 patients (234 to Sx + Ax, 239 to Sx) were randomly assigned. The median age was 74 years; 80% had estrogen receptor-positive disease. In both the patients' subjective assessment of their QL and the physicians' perception of the patients' QL, the largest adverse QL effects of Ax were observed from baseline to the first postoperative assessment, but the differences tended to disappear in 6 to 12 months. At a median follow-up of 6.6 years, results for Sx + Ax and Sx yielded similar DFS (6-year DFS, 67% v 66%; hazard ratio HR Sx + Ax/Sx, 1.06; 95% CI, 0.79 to 1.42; P = .69) and OS (6-year OS, 75% v 73%; HR Sx + Ax/Sx, 1.05; 95% CI, 0.76 to 1.46; P = .77).
Avoiding axillary clearance for women > or = 60 years old who have clinically node-negative disease and receive Tam for endocrine-responsive disease yields similar efficacy with better early QL.
The European critical levels (CLs) for ozone (O
3) to protect crops, natural and semi-natural vegetation, as well as forest trees, are expressed as an Accumulated exposure Over a Threshold of 40 ppb ...(AOT40). In principle, this exposure index should represent the O
3 concentrations at the upper boundary of the quasi-laminar layer of the plant canopy. However, in reality, those values cannot be measured and, therefore, must be estimated by micrometeorological models. Nevertheless, inappropriate calculation of AOT40 for ambient conditions using O
3 levels actually measured at some reference height above the canopy leads to predictions of unrealistic crop yield losses. At the present time, CL to protect crops from long-term effects and yield losses, is based on open-top chamber experiments, mainly with spring wheat. In addition to concerns associated with the experimental methodologies used in these studies, a correct application of CL should include simulation of phenological stages of a representative wheat canopy. The present paper describes a model for simulation of leaf area index and canopy height development, based on algorithms adopted from a widely validated agrometeorological model of the German Weather Service. Because, O
3 concentrations at the upper boundary of the quasi-laminar layer of the crop canopy are not unambiguouly connected with plant stomatal uptake, a correction of the actually simulated concentrations is needed to provide toxicologically effective O
3 concentrations (effective AOT40). A comparison of results from the application of effective AOT40, with the observations of yield by the farmers, suggests that the estimated crop losses using the effective dose are within the bounds of probability. However, at the present time, for plants other than wheat, the data base is too small to derive meaningful and reliable effective dose–response relationships. Taking into account the definition of AOT40, soil–vegetation–atmosphere-transfer models must be generally applied. Future research efforts should address the important need for flux-orientated concepts which lead to a derivation of critical absorbed doses for O
3 to protect vegetation (critical loads).
In follicular lymphoma (FL) and mantle cell lymphoma (MCL) the monoclonal antibody rituximab (R) improves the prognosis when combined with chemotherapy. The present study investigated R-maintenance ...after R-chemotherapy. Patients with recurring or refractory FL and MCL were randomized to 4 courses of fludarabine, cyclophosphamide, and mitoxantrone (FCM) alone or combined with R (R-FCM). Responding patients underwent a second randomization for R-maintenance comprising 2 further courses of 4-times-weekly doses of R after 3 and 9 months. The first randomization was stopped after 147 patients, when R-FCM revealed a significantly better outcome. All subsequent patients received R-FCM. Of the 176 patients who are currently evaluable (as of October 2005), 138 received R-FCM for remission induction. Response duration was significantly prolonged by R-maintenance after R-FCM, with the median not being reached in this evaluation versus an estimated median of 16 months (P = .001). This beneficial effect was also observed when analyzing FL (P = .035) and MCL (P = .049) separately. Hence, R-maintenance is effective after salvage with R-chemotherapy and significantly prolongs response duration in patients with recurring or refractory FL or MCL.
The distribution of methane (CH4) in the stratosphere can be a major driver of spatial variability in the dry-air column-averaged CH4 mixing ratio (XCH4), which is being measured increasingly for the ...assessment of CH4 surface emissions. Chemistry-transport models (CTMs) therefore need to simulate the tropospheric and stratospheric fractional columns of XCH4 accurately for estimating surface emissions from XCH4. Simulations from three CTMs are tested against XCH4 observations from the Total Carbon Column Network (TCCON). We analyze how the model–TCCON agreement in XCH4 depends on the model representation of stratospheric CH4 distributions. Model equivalents of TCCON XCH4 are computed with stratospheric CH4 fields from both the model simulations and from satellite-based CH4 distributions from MIPAS (Michelson Interferometer for Passive Atmospheric Sounding) and MIPAS CH4 fields adjusted to ACE-FTS (Atmospheric Chemistry Experiment Fourier Transform Spectrometer) observations. Using MIPAS-based stratospheric CH4 fields in place of model simulations improves the model–TCCON XCH4 agreement for all models. For the Atmospheric Chemistry Transport Model (ACTM) the average XCH4 bias is significantly reduced from 38.1 to 13.7 ppb, whereas small improvements are found for the models TM5 (Transport Model, version 5; from 8.7 to 4.3 ppb) and LMDz (Laboratoire de Météorologie Dynamique model with zooming capability; from 6.8 to 4.3 ppb). Replacing model simulations with MIPAS stratospheric CH4 fields adjusted to ACE-FTS reduces the average XCH4 bias for ACTM (3.3 ppb), but increases the average XCH4 bias for TM5 (10.8 ppb) and LMDz (20.0 ppb). These findings imply that model errors in simulating stratospheric CH4 contribute to model biases. Current satellite instruments cannot definitively measure stratospheric CH4 to sufficient accuracy to eliminate these biases. Applying transport diagnostics to the models indicates that model-to-model differences in the simulation of stratospheric transport, notably the age of stratospheric air, can largely explain the inter-model spread in stratospheric CH4 and, hence, its contribution to XCH4. Therefore, it would be worthwhile to analyze how individual model components (e.g., physical parameterization, meteorological data sets, model horizontal/vertical resolution) impact the simulation of stratospheric CH4 and XCH4.
Musculoskeletal disorders of the trunk and neck are common among cleaners. Vacuum cleaning is a demanding activity. The aim of this study was to present the movement profile of the trunk and neck ...during habitual vacuuming. The data were collected from 31 subjects (21f./10 m) using a 3D motion analysis system (Xsens). 10 cycles were analysed in vacuuming PVC and carpet floors with 8 vacuum cleaners. The joint angles and velocities were represented statistically descriptive. When vacuuming, the trunk is held in a forwardly inclined position by a flexion in the hip and rotated from this position. In the joint angles and velocities of the spine, the rotation proved to be dominant. A relatively large amount of movement took place in the cervical spine and also in the lumbar spine. The shown movement profile is rather a comfort area of vacuuming which may serve as a reference for ergonomics in vacuuming.
Background: The role of adjuvant chemotherapy in postmenopausal patients with lymph node-negative breast cancer is controversial. After demonstrating the efficacy of chemotherapy combined with ...tamoxifen for postmenopausal patients with lymph node-positive disease, the International Breast Cancer Study Group launched a randomized trial (Trial IX) to evaluate the role of adjuvant chemotherapy preceding treatment with tamoxifen for patients with lymph node-negative disease. Methods: After stratification by estrogen receptor (ER) status, patients were randomly assigned to receive three 28-day courses of “classical” adjuvant CMF chemotherapy (cyclophosphamide at 100 mg/m2 on days 1–14, orally; methotrexate at 40 mg/m2 on days 1 and 8, intravenously; and 5-fluorouracil at 600 mg/m2 on days 1 and 8, intravenously) followed by tamoxifen (20 mg/day, orally for 57 months) (CMF→tamoxifen) or to receive tamoxifen alone (20 mg/day, orally for 60 months). We enrolled 1669 eligible patients, 382 (23%) with ER-negative tumors, 1217 (73%) with ER-positive tumors, and 70 (4%) with unknown ER status. The median follow-up was 71 months. All statistical tests were two-sided. Results: The added benefit of CMF followed by tamoxifen over tamoxifen alone was statistically significantly dependent on ER status (tests for interaction: P = .01 for disease-free survival DFS and P = .07 for overall survival OS). For patients with ER-negative tumors, the addition of CMF statistically significantly improved DFS (5-year DFS = 84% for CMF→tamoxifen versus 69% for tamoxifen alone; difference = 15%; 95% confidence interval CI = 6% to 24%; risk ratio RR = 0.52; 95% CI = 0.34 to 0.79; P = .003) and OS (5-year OS = 89% for CMF→tamoxifen versus 81% for tamoxifen alone; difference = 8%; 95% CI = 0% to 16%; RR = 0.51; 95% CI = 0.30 to 0.87; P = .01). By contrast, for patients with ER-positive tumors, addition of CMF provided no benefit in terms of DFS (5-year DFS = 84% for CMF→tamoxifen versus 85% for tamoxifen alone; difference = –1; 95% CI = –6% to 4%; RR = 0.99; 95% CI = 0.75 to 1.30; P = .92) or OS (5-year OS = 95% for CMF→tamoxifen versus 93% for tamoxifen alone; difference = 2%; 95% CI = –1% to 5%; RR = 0.95; 95% CI = 0.64 to 1.40; P = .80). Conclusions: Postmenopausal patients with lymph node-negative breast cancer benefited substantially from adjuvant chemotherapy if their cancer was ER-negative (i.e., endocrine-nonresponsive). In contrast, if their cancer was ER-positive (i.e., endocrine-responsive), they obtained no benefit from the combination treatment compared with tamoxifen alone.
Chronic myeloid leukemia (CML)-study IV was designed to explore whether treatment with imatinib (IM) at 400 mg/day (n=400) could be optimized by doubling the dose (n=420), adding interferon (IFN) ...(n=430) or cytarabine (n=158) or using IM after IFN-failure (n=128). From July 2002 to March 2012, 1551 newly diagnosed patients in chronic phase were randomized into a 5-arm study. The study was powered to detect a survival difference of 5% at 5 years. After a median observation time of 9.5 years, 10-year overall survival was 82%, 10-year progression-free survival was 80% and 10-year relative survival was 92%. Survival between IM400 mg and any experimental arm was not different. In a multivariate analysis, risk group, major-route chromosomal aberrations, comorbidities, smoking and treatment center (academic vs other) influenced survival significantly, but not any form of treatment optimization. Patients reaching the molecular response milestones at 3, 6 and 12 months had a significant survival advantage. For responders, monotherapy with IM400 mg provides a close to normal life expectancy independent of the time to response. Survival is more determined by patients' and disease factors than by initial treatment selection. Although improvements are also needed for refractory disease, more life-time can currently be gained by carefully addressing non-CML determinants of survival.