The linear and nonlinear evolutions of the tearing instability in a collisionless plasma with a strong guide field are analysed on the basis of a two-field Hamiltonian gyrofluid model. The model is ...valid for a low ion temperature and a finite $\beta _e$. The finite $\beta _e$ effect implies a magnetic perturbation along the guide field direction, and electron finite Larmor radius effects. A Hamiltonian derivation of the model is presented. A new dispersion relation of the tearing instability is derived for the case $\beta _e=0$ and tested against numerical simulations. For $\beta _e \ll 1$ the equilibrium electron temperature is seen to enhance the linear growth rate, whereas we observe a stabilizing role when electron finite Larmor radius effects become more relevant. In the nonlinear phase, stall phases and faster than exponential phases are observed, similarly to what occurs in the presence of ion finite Larmor radius effects. Energy transfers are analysed and the conservation laws associated with the Casimir invariants of the model are also discussed. Numerical simulations seem to indicate that finite $\beta _e$ effects do not produce qualitative modifications in the structures of the Lagrangian invariants associated with Casimirs of the model.
Ageing implicates a remodeling of our immune system, which is a consequence of the physiological senescence of our cells and tissues coupled with environmental factors and chronic antigen exposure. ...An immune system that senesces includes more differentiated cells with accumulation of highly differentiated CD4 and CD8 T cells. The pool of naive T cells decreases with the exponential thymic involution induced by age. Differentiated T cells have similar, if not higher, functional capacities but scarce studies are looking at the impact of senescence among specific T cells. After a stimulation, other immune cells (monocytes, dendritic cells and NK) are functionally altered during ageing. It is as if the immune system was more efficient at the basal level, but less efficient after a stimulation in the old compared to young people, likely due to less reserve. Concerning the clinical impact, older people are more prone to certain pathogens and their clinical manifestations differ from the younger people. Severe flu and VZV reactivation are more frequent with an altered cellular response to vaccination. Vaccination failure can have detrimental consequences in people presenting frailty criteria. Old people frailty is majored by their comorbidities and diseases like cancer. Thus, chemotherapies are employed with circumspection in older patients. The use of anti-PD-1/PD-L1 immunotherapies is therefore attractive, because of less side effects with a better response compared to chemotherapy. Old persons inclusion is lacking in current studies and clinical trials. Some subgroups or pooled analyses confirm the gain in response without increased toxicities in older patients but their inclusion criteria differ from the real-life practice. Specific studies focusing on this population are needed because of the increasing cancer incidence with age and the overall ageing of the population.
Summary
The objective of this study was to explore whether ketamine prevents or exacerbates acute or post‐traumatic stress disorders in military trauma patients. We conducted a retrospective study of ...a database from the French Military Health Service, including all soldiers surviving a war injury in Afghanistan (2010–2012). The diagnosis of post‐traumatic stress disorder was made by a psychiatrist and patients were analysed according to the presence or absence of this condition. Analysis included the following covariables: age; sex; acute stress disorder; blast injury; associated fatality; brain injury; traumatic amputation; Glasgow coma scale; injury severity score; administered drugs; number of surgical procedures; physical, neurosensory or aesthetic sequelae; and the development chronic pain. Covariables related to post‐traumatic and acute stress disorders with a p ≤ 0.10 were included in a multivariable logistic regression model. The data from 450 soldiers were identified; 399 survived, of which 274 were analysed. Among these, 98 (36%) suffered from post‐traumatic stress disorder and 89 (32%) had received ketamine. Fifty‐four patients (55%) in the post‐traumatic stress disorder group received ketamine vs. 35 (20%) in the no PTSD group (p < 0.001). The 89 injured soldiers who received ketamine had a median (IQR range) injury severity score of 5 (3–13 1–26) vs. 3 (2–4 1–6 in the 185 patients who did not (p < 0.001). At multivariable analysis, only acute stress disorder and total number of surgical procedures were independently associated with the development of post‐traumatic stress disorder. In this retrospective study, ketamine administration was not a risk factor for the development of post‐traumatic stress disorder in the military trauma setting.
There are many isolated sources of NOx emissions across the western United States, including electrical power generation plants and urban areas. In this manuscript, two satellite instruments ...measuring NO2 vertical columns over these sources and an atmospheric chemical‐transport model are used to evaluate bottom‐up NOx emission inventories, model assumptions, and satellite retrieval algorithms. We carried out simulations with the Weather Research and Forecasting‐Chemistry (WRF‐Chem) model for the western U.S. domain during the summer of 2005 using measured power plant NOx emissions. Model NO2 vertical columns are compared with a retrieval of the Scanning Imaging Absorption Spectrometer for Atmospheric Chartography (SCIAMACHY) satellite instrument data by the University of Bremen and retrievals of the Ozone Monitoring Instrument (OMI) data by the U.S. National Aeronautics and Space Administration (NASA) and a modified version of the NASA OMI retrieval produced by the University of Bremen. For areas dominated by power plant NOx emissions, the model NO2 columns serve as a comparison standard for satellite retrievals because emissions are continuously monitored at all large U.S. power plants. An extensive series of sensitivity tests of the assumptions in both the satellite retrievals and the model are carried out over the Four Corners and San Juan power plants, two adjacent facilities in the northwest corner of New Mexico that together represent the largest NOx point source in the United States. Overall, the SCIAMACHY and OMI NO2 columns over western U.S. power plants agree well with model NO2 columns, with differences between the two being within the variability of the model and satellite. In contrast to regions dominated by power plant emissions, model NO2 columns over large urban areas along the U.S. west coast are approximately twice as large as satellite NO2 columns from SCIAMACHY and OMI retrievals. The discrepancies in urban areas are beyond the sensitivity ranges in the model simulations and satellite observations, implying overestimates of these cities' bottom‐up NOx emissions, which are dominated by motor vehicles. Taking the uncertainties in the satellite retrievals into account, our study demonstrates that the tropospheric columns of NO2 retrieved from space‐based observations of backscattered solar electromagnetic radiation can be used to evaluate and improve bottom‐up emission inventories.
Introduction: Immune checkpoint inhibitors (ICIs) are now standard of care in many cancers. They can generate immune-related adverse events (irAEs), but no biomarkers are available to identify ...patients who are more likely to develop irAEs. We assess the association between pre-existing autoantibodies and occurrence of irAEs. Patients and Methods: We prospectively collected data from consecutive patients receiving ICIs for advanced cancers, in a single center between May 2015 and July 2021. Autoantibodies testing was performed before ICIs initiation including AntiNeutrophil Cytoplasmic Antibodies, Antinuclear Antibodies, Rheumatoid Factor anti-Thyroid Peroxidase and anti-Thyroglobulin. We analyzed the associations of pre-existing autoantibodies with onset, severity, time to irAEs and with survival outcomes. Results: Of the 221 patients included, most had renal cell carcinoma (n = 99; 45%) or lung carcinoma (n = 90; 41%). Grade ≥2 irAEs were more frequent among patients with pre-existing autoantibodies: 64 (50%) vs. 20 (22%) patients (Odds-Ratio= 3.5 95% CI=1.8-6.8; p < 0.001) in the positive vs negative group, respectively. irAEs occurred earlier in the positive group with a median time interval between ICI initiation and irAE of 13 weeks (IQR = 8.8-21.6) vs. 28.5 weeks (IQR=10.6-55.1) in the negative group (p = 0.01). Twelve patients (9.4%) experienced multiple (≥2) irAEs in the positive group vs. 2 (2%) in the negative group (OR = 4.5 95% CI: 0.98-36, p = 0.04). After a median follow-up of 25 months, median PFS and OS were significantly longer among patients experiencing irAE (p = 0.00034 and p = 0.016, respectively). Conclusion: The presence of pre-existing autoantibodies is significantly associated with the occurrence of grade ≥2 irAEs, with earlier and multiple irAEs in patients treated with ICIs.
This study compares recent CO, NOx, NMVOC, SO2, BC, and OC anthropogenic emissions from several state‐of‐the‐art top‐down estimates to global and regional bottom‐up inventories and projections from ...five Shared Socioeconomic Pathways (SSPs) in several regions. Results show that top‐down emissions derived in several recent studies exhibit similar uncertainty as bottom‐up inventories in some regions for certain species and even less in the case of Chinese CO emissions. In general, the largest discrepancies are found outside of regions such as the United States, Europe, and Japan where the most accurate and detailed information on emissions is available. In some regions such as China, which has recently undergone dynamical economic growth and changes in air quality regulations, the top‐down estimates better capture recent emission trends than global bottom‐up inventories. These results show the potential of top‐down estimates to complement bottom‐up inventories and to aide in the development of emission scenarios, particularly in regions where global inventories lack the necessary up‐to‐date and accurate information regarding regional activity data and emission factors such as Africa and India. Areas of future work aimed at quantifying and reducing uncertainty are also highlighted. A regional comparison of recent CO and NOx trends in the five SSPs indicate that SSP126, a strong pollution control scenario, best represents the trends from the top‐down and regional bottom‐up inventories in the United States, Europe, and China, while SSP460, a low‐pollution control scenario, lies closest to actual trends in West Africa. This analysis can be useful for air quality forecasting and near‐future pollution control/mitigation policy studies.
Key Points
Top‐down emissions from several recent studies are within the range of bottom‐up inventories and exhibit a similar level of uncertainty for some regions and species
In China, the United States, and Europe emission trends in the last decade from SSP126 match most closely actual trends from bottom‐up and top‐down estimates
In Western Africa and India recent emission trends from low pollution control scenarios (SSP460 and SSP370, respectively) match most closely actual trends
African biomass burning emission inventories for gaseous and particulate species have been constructed at a resolution of 1 km by 1km with daily coverage for the 2000-2007 period. These inventories ...are higher than the GFED2 inventories, which are currently widely in use. Evaluation specifically focusing on combustion aerosol has been carried out with the ORISAM-TM4 global chemistry transport model which includes a detailed aerosol module. This paper compares modeled results with measurements of surface BC concentrations and scattering coefficients from the AMMA Enhanced Observations period, aerosol optical depths and single scattering albedo from AERONET sunphotometers, LIDAR vertical distributions of extinction coefficients as well as satellite data. Aerosol seasonal and interannual evolutions over the 2004-2007 period observed at regional scale and more specifically at the Djougou (Benin) and Banizoumbou (Niger) AMMA/IDAF sites are well reproduced by our global model, indicating that our biomass burning emission inventory appears reasonable.
Congenital ichthyoses (CI) comprise a heterogeneous group of monogenic genetic skin diseases characterized by diffuse scaling, often associated with skin inflammation. Diagnosis of the individual ...form of ichthyosis is complex and is guided by clinical expertise. CI usually has a major impact on quality of life (QOL) and thus requires lifelong treatment. To date, there are no curative therapies, although various symptomatic treatment options exist. The present protocol for the management of CI has been drawn up in accordance with the recommendations published in 2012 by the French National Authority for Health, based on a literature review, with the help and validation of members of the French network for rare skin diseases (FIMARAD). It provides a summary of evidence and expert-based recommendations and is intended to help clinicians with the management of these rare and often complex diseases.
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