Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

(No) Return to the Roman Greek-Catholic Church, between Adhesion and Religious Transmission

The author analyses the individual and collective motives which have pushed some of the Greek-Catholics to Join their former Church since 1989. The Romanian Greek-Catholic Church, founded in 1687, was outlawed by the communist party between 1948 and 1989. After it became legal again, the Church tried to reorganize itself. The author analyses such a return, in the light of the notions of conversion, membership and of religious transmission, and proposes to take the factor of the uniqueness of God into account, as it allows to complement the analyses in terms of religious identity and of religious market-place''

Putting Direct Perpetrators on Trial: the Ovcara Massacre Trial in Belgrade

This paper is based on ethnographical fieldwork conducted in The Hague, Croatia and Serbia. It addresses the distinction between command and individual responsibility on the one hand, and between individual responsibility and collective guilt on the other, by focusing on the two trials related to the Ovcara massacre, the one in the International Criminal Tribunal for the former Yugoslavia (ICTY) and the one in Belgrade, and on non-juridical attempts to deal with the past in Serbia. My main question here is the following: are trials held in the territory of the former Yugoslavia more likely than the trials held in The Hague to contribute to the two major features of restorative justice, i.e. to repair the harm suffered by the victims and to reintegrate the offenders into their community. On the basis of the meetings I had with the association Vukovarske Majke, it seems that the victims’ families expect more from local trials than from the ICTY: even though, and maybe because, the indictees are the direct killers of their relatives, they are the ones who can give details about the circumstances of the massacre, and information about the location of the still missing corpses. Yet they all underlined that local trials would never have happened without the existence of the ICTY. In addition, in a situation of such massive crimes, courtrooms are not the only spaces were justice can be dispensed. The essential work of dealing with the past outside the courtrooms, as the example of Novi Sad’s Helsinki Committee for Human Rights presented in this paper shows, is an important step towards restorative justice

Investigation of the consistency of the recent CH4 increase derived from NDACC-FTIR, ACE-FTS and GEOS-Chem

We present an update on the status of the recent methane increase study based on six FTIR ground-based sites, ACE-FTS satellite occultations and GEOS-Chem simulation

Identifying long-range transport of wildfire emissions to the Arctic using a network of ground-based FTIR spectrometers, satellite observations, and transport models

International audienceWe present a multi-year time series of the total column amounts of carbon monoxide (CO), hydrogen cyanide (HCN) and ethane (C2H6) obtained by Fourier Transform Infrared (FTIR) spectrometer measurements at ten sites. Six are high-latitude sites: Eureka, Nunavut (80.05°N, 86.42°W); Ny Alesund, Norway (78.92°N, 11.93°E); Thule, Greenland (76.53°N, 68.74°W); Kiruna, Sweden (67.84°N, 20.41°E); Poker Flat, Alaska (65.11°N, 147.42°W); St. Petersburg, Russia (59.88°N, 29.83°E) and four are mid-latitude sites: Bremen,Germany (53.1°N, 8.8°E); Zugspitze, Germany (47.42°N, 10.98°E); Jungfraujoch, Switzerland (46.55°N, 7.98°E) and Toronto, Ontario (43.66°N, 79.40°W).For each site, enhancements of total column amounts above seasonal means are identified and attributed to wildfire events using HYSPLIT and FLEXPART back-trajectories. Wildfire source locations are identified using the Moderate Resolution Imaging Spectroradiometer (MODIS) fire hot spot dataset while satellite measurements of CO total columns from the Infrared Atmospheric Sounding Interferometer (IASI) illustrate transport of the smoke plume and allow for further confirmation of the observed enhancement. Using the multi-year time series, inter-annual variability of wildfire events is observed. Differences in travel times of the smoke plume between sites allow for ageing of the plume to be determined, providing a means to infer the physical and chemical processes affecting the loss of each species during transport. The varying lifetimes of the species and independent measurements at all sites, along with sensitivities to various source regions given by FLEXPART allow for the transport pathways to the Arctic to be investigated. By accounting for the effect of the ageing of the smoke plumes, the measured FTIR enhancement ratios are corrected to obtain emission ratios and emission factors, which are needed to improve the simulation of fire emissions in chemical transport models

Ethane rise associated with North American oil and gas exploitation

Ethane (C2H6) is mainly emitted in the atmosphere from leakage during production and transport of natural gas, biofuel consumption and biomass burning. As it shares concurrent anthropogenic emission sources with methane (CH4), a better understanding of the atmospheric distribution of C2H6 and any trends in its abundance can be used to better constrain the sources of CH4 from oil and gas activities.Until very recently, the C2H6 abundance in the atmosphere has been declining due to the reduction of fugitive emissions as a result of air pollution abatement measures. However, a renewal of the atmospheric C2H6 burden has been detected over North America and Europe from 2009 onwards. It is attributed to the unprecedented growth in the exploitation of shale gas and tight oil reservoirs in North America. Using time series of C2H6 abundance derived from ground-based high-resolution infrared solar absorption spectra recorded at complementary NDACC FTIR sites, we present here sharp C2H6 rises in the Northern Hemisphere, of up to 5 %/yr since 2009.Using model simulations, we show that the HTAP2 bottom-up inventories for anthropogenic emissions greatly underestimate the observed pre-increase C2H6 abundances and that they are too low by a factor two. We also evaluate new top-down emissions of C2H6 from the North American oil and gas activities, biofuel consumption and biomass burning, derived from space-borne observations of CH4 from GOSAT. We find a good agreement with the observations at the North American mid-latitudinal sites, close to regions with high drilling productivity, but an overestimation at remote sites. We also estimate that the North American C2H6 emissions have increased by 75% over the past six years (2009-2014), annihilating the benefits of more than two decades of successful anthropogenic emission reduction, and that the associated annual CH4 emissions from the North American oil and gas sector grew from 20 to 35 Tg/yr over the same period.info:eu-repo/semantics/nonPublishe

Detection of the long-range transport of wildfire pollution to the Arctic using a network of ground-based FTIR spectrometers, satellite observations and model result

International audienceWe present a multi-year time series of the total columns of carbon monoxide (CO), hydrogen cyanide (HCN) and ethane (C2H6) obtained by Fourier Transform Infrared (FTIR) spectrometer measurements at nine sites. Six are high-latitude sites: Eureka, Nunavut; Ny Alesund, Norway; Thule, Greenland; Kiruna, Sweden; Poker Flat, Alaska and St. Petersburg, Russia and three are mid-latitude sites; Zugspitze, Germany; Jungfraujoch, Switzerland and Toronto, Ontario. For each site, the inter-annual trends and seasonal variabilities of the CO total column time series are accounted for, allowing ambient concentrations to be determined. Enhancements above ambient levels are then used to identify possible wildfire pollution events. Since the abundance of each trace gas species emitted in a wildfire event is specific to the type of vegetation burned and the burning phase, correlations of CO to the other long-lived wildfire tracers HCN and C2H6 allow for further confirmation of the detection of wildfire pollution. Back-trajectories from HYSPLIT and FLEXPART as well as fire detections from the Moderate Resolution Spectroradiometer (MODIS) allow the source regions of the detected enhancements to be determined while satellite observations of CO from the Measurement of Pollution in the Troposphere (MOPITT) and Infrared Atmospheric Sounding Interferometer (IASI) instruments can be used to track the transport of the smoke plume. Differences in travel times between sites allows ageing of biomass burning plumes to be determined, providing a means to infer the physical and chemical processes affecting the loss of each species during transport. Comparisons of ground-based FTIR measurements to GEOS-Chem chemical transport model results are used to investigate these processes, evaluate wildfire emission inventories and infer the influence of wildfire emissions on the Arctic