A fast stratospheric chemistry solver: the E4CHEM submodel for the atmospheric chemistry global circulation model EMAC

The atmospheric chemistry general circulation model ECHAM5/MESSy (EMAC) and the atmospheric chemistry box model CAABA are extended by a computationally very efficient submodel for atmospheric chemistry, E4CHEM. It focuses on stratospheric chemistry but also includes background tropospheric chemistry. It is based on the chemistry of MAECHAM4-CHEM and is intended to serve as a simple and fast alternative to the flexible but also computationally more demanding submodel MECCA. In a model setup with E4CHEM, EMAC is now also suitable for simulations of longer time scales. The reaction mechanism contains basic O3, CH4, CO, HOx, NOx, and ClOx gas phase chemistry. In addition, E4CHEM includes optional fast routines for heterogeneous reactions on sulphate aerosols and polar stratospheric clouds (substituting the existing submodels PSC and HETCHEM), and scavenging (substituting the existing submodel SCAV). We describe the implementation of E4CHEM into the MESSy structure of CAABA and EMAC. For some species the steady state in the box model differs by up to 100% when compared to results from CAABA/MECCA due to different reaction rates. After an update of the reaction rates in E4CHEM the mixing ratios in both boxmodel and 3-D model simulations are in satisfactory agreement with the results from a simulation where MECCA with a similar chemistry scheme was employed. Finally, a comparison against a simulation with a more complex and already evaluated chemical mechanism is presented in order to discuss shortcomings associated with the simplification of the chemical mechanism

3066 consecutive Gamma Nails. 12 years experience at a single centre

<p>Abstract</p> <p>Background</p> <p>Fixation of trochanteric hip fractures using the Gamma Nail has been performed since 1988 and is today well established and wide-spread. However, a number of reports have raised serious concerns about the implant's complication rate. The main focus has been the increased risk of a subsequent femoral shaft fracture and some authors have argued against its use despite other obvious advantages, when this implant is employed.</p> <p>Through access to a uniquely large patient data base available, which is available for analysis of trochanteric fractures; we have been able to evaluate the performance of the Gamma Nail over a twelve year period.</p> <p>Methods</p> <p>3066 consecutive patients were treated for trochanteric fractures using Gamma Nails between 1990 and 2002 at the Centre de Traumatologie et de l'Orthopedie (CTO), Strasbourg, France. These patients were retrospectively analysed. Information on epidemiological data, intra- and postoperative complications and patients' outcome was retrieved from patient notes. All available radiographs were assessed by a single reviewer (AJB).</p> <p>Results</p> <p>The results showed a low complication rate with the use of the Gamma Nail. There were 137 (4.5%) intraoperative fracture-related complications. Moreover 189 (6.2%) complications were detected postoperatively and during follow-up. Cut-out of the lag screw from the femoral head was the most frequent mechanical complication (57 patients, 1.85%), whereas a postoperative femoral shaft fracture occurred in 19 patients (0.6%). Other complications, such as infection, delayed healing/non-union, avascular femoral head necrosis and distal locking problems occurred in 113 patients (3.7%).</p> <p>Conclusions</p> <p>The use of the Gamma Nail in trochanteric hip fractures is a safe method with a low complication rate. In particular, a low rate of femoral shaft fractures was reported. The low complication rate reported in this series can probably be explained by strict adherence to a proper surgical technique.</p

Arthroscopy vs. MRI for a detailed assessment of cartilage disease in osteoarthritis: diagnostic value of MRI in clinical practice

<p>Abstract</p> <p>Background</p> <p>In patients with osteoarthritis, a detailed assessment of degenerative cartilage disease is important to recommend adequate treatment. Using a representative sample of patients, this study investigated whether MRI is reliable for a detailed cartilage assessment in patients with osteoarthritis of the knee.</p> <p>Methods</p> <p>In a cross sectional-study as a part of a retrospective case-control study, 36 patients (mean age 53.1 years) with clinically relevant osteoarthritis received standardized MRI (sag. T1-TSE, cor. STIR-TSE, trans. fat-suppressed PD-TSE, sag. fat-suppressed PD-TSE, Siemens Magnetom Avanto syngo MR B 15) on a 1.5 Tesla unit. Within a maximum of three months later, arthroscopic grading of the articular surfaces was performed. MRI grading by two blinded observers was compared to arthroscopic findings. Diagnostic values as well as intra- and inter-observer values were assessed.</p> <p>Results</p> <p>Inter-observer agreement between readers 1 and 2 was good (kappa = 0.65) within all compartments. Intra-observer agreement comparing MRI grading to arthroscopic grading showed moderate to good values for readers 1 and 2 (kappa = 0.50 and 0.62, respectively), the poorest being within the patellofemoral joint (kappa = 0.32 and 0.52). Sensitivities were relatively low at all grades, particularly for grade 3 cartilage lesions. A tendency to underestimate cartilage disorders on MR images was not noticed.</p> <p>Conclusions</p> <p>According to our results, the use of MRI for precise grading of the cartilage in osteoarthritis is limited. Even if the practical benefit of MRI in pretreatment diagnostics is unequivocal, a diagnostic arthroscopy is of outstanding value when a grading of the cartilage is crucial for a definitive decision regarding therapeutic options in patients with osteoarthritis.</p

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Energetic particle precipitation in ECHAM5/MESSy – Part 2: Solar proton events

The atmospheric chemistry general circulation model ECHAM5/MESSy (EMAC) has been extended by processes that parameterize particle precipitation. Several types of particle precipitation that directly affect NOy and HOx concentrations in the middle atmosphere are accounted for and discussed in a series of papers. In part 1, the EMAC parameterization for NOx produced in the upper atmosphere by low-energy electrons is presented. Here, we discuss production of NOy and HOx associated with Solar Proton Events (SPEs). A submodel that parameterizes the effects of precipitating protons, based on flux measurements by instruments on the IMP or GOES satellites, was added to the EMAC model. Production and transport of NOy and HOx, as well as effects on other chemical species and dynamics during the 2003 Halloween SPEs are presented. Comparisons with MIPAS/ENVISAT measurements of a number of species affected by the SPE are shown and discussed. There is good agreement for NO2, but a severe disagreement is found for N2O similar to other studies. We discuss the effects of an altitude dependence of the N/NO production rate on the N2O and NOy changes during the SPE. This yields a modified parameterization that shows mostly good agreement between MIPAS and model results for NO2, N2O, O3, and HOCl. With the ability of EMAC to relax the model meteorology to observations, accurate assessment of total column ozone loss is also possible, yielding a loss of approximately 10 DU at the end of November. Discrepancies remain for HNO3, N2O5, and ClONO2, which are likely a consequence from the missing cluster ion chemistry and ion-ion recombination in the EMAC model as well as known issues with the model's NOy partitioning