Railway Systems and the 'Universal Good of the State': Technologies of Government in the 19th-Century Papal State

Informed by Foucault’s concept of governmentality, the paper focuses on nineteenth-century General Commissariat for the Railroad Industry in the Papal State. Unlike in liberal States, where government intervention in the affairs of railway companies was limited, the pressing need to reinforce the Pope’s pastoral power, strengthen the bond between the believers and the Holy See and ensure equity and the efficiency of the new infrastructure meant that the Commissariat acted as a governmental centre of calculation. Accounting technologies in the form of budgets, cost accounting systems and penetrating audits enabled the government to intervene in the operations of private railway companies. The study analyses the role of accounting and auditing practices in the pursuit of non-liberal goals in an industry which is traditionally perceived as critical to the development of a liberal economy, one in which accounting was traditionally used to maintain investors’ confidence in the capitalist system

Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods: We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings: Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. Interpretation: This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. Funding: Sanofi and Regeneron Pharmaceuticals

AGILE detection of a rapid γ-ray flare from the blazar PKS 1510-089 during the GASP-WEBT monitoring

We report the detection by the AGILE satellite of a rapid gamma-ray flare from the powerful gamma-ray quasar PKS 1510-089, during a pointing centered on the Galactic Center region from 1 March to 30 March 2008. This source has been continuosly monitored in the radio-to-optical bands by the GLAST-AGILE Support Program (GASP) of the Whole Earth Blazar Telescope (WEBT). Moreover, the gamma-ray flaring episode triggered three ToO observations by the Swift satellite in three consecutive days, starting from 20 March 2008. In the period 1-16 March 2008, AGILE detected gamma-ray emission from PKS 1510-089 at a significance level of 6.2-sigma with an average flux over the entire period of (84 +/- 17) x 10^{-8} photons cm^{-2} s^{-1} for photon energies above 100 MeV. After a predefined satellite re-pointing, between 17 and 21 March 2008, AGILE detected the source at a significance level of 7.3-sigma, with an average flux (E > 100 MeV) of (134 +/- 29) x 10^{-8} photons cm^{-2} s^{-1} and a peak level of (281 +/- 68) x 10^{-8} photons cm^{-2} s^{-1} with daily integration. During the observing period January-April 2008, the source also showed an intense and variable optical activity, with several flaring episodes and a significant increase of the flux was observed at millimetric frequencies. Moreover, in the X-ray band the Swift/XRT observations seem to show an harder-when-brighter behaviour of the source spectrum. The spectral energy distribution of mid-March 2008 is modelled with a homogeneous one-zone synchrotron self Compton emission plus contributions from inverse Compton scattering of external photons from both the accretion disc and the broad line region. Indeed, some features in the optical-UV spectrum seem to indicate the presence of Seyfert-like components, such as the little blue bump and the big blue bump

AGILE detection of extreme γ -ray activity from the blazar PKS 1510-089 during March 2009: Multifrequency analysis

We report on the extreme gamma-ray activity from the FSRQ PKS 1510-089 observed by AGILE in March 2009. In the same period a radio-to-optical monitoring of the source was provided by the GASP-WEBT and REM. Moreover, several Swift ToO observations were triggered, adding important information on the source behaviour from optical/UV to hard X-rays. We paid particular attention to the calibration of the Swift/UVOT data to make it suitable to the blazars spectra. Simultaneous observations from radio to gamma rays allowed us to study in detail the correlation among the emission variability at different frequencies and to investigate the mechanisms at work. In the period 9-30 March 2009, AGILE detected an average gamma-ray flux of (311+/-21)x10^-8 ph cm^-2 s^-1 for E>100 MeV, and a peak level of (702+/-131)x10^-8 ph cm^-2 s^-1 on daily integration. The gamma-ray activity occurred during a period of increasing activity from near-IR to UV, with a flaring episode detected on 26-27 March 2009, suggesting that a single mechanism is responsible for the flux enhancement observed from near-IR to UV. By contrast, Swift/XRT observations seem to show no clear correlation of the X-ray fluxes with the optical and gamma-ray ones. However, the X-ray observations show a harder photon index (1.3-1.6) with respect to most FSRQs and a hint of harder-when-brighter behaviour, indicating the possible presence of a second emission component at soft X-ray energies. Moreover, the broad band spectrum from radio-to-UV confirmed the evidence of thermal features in the optical/UV spectrum of PKS 1510-089 also during high gamma-ray state. On the other hand, during 25-26 March 2009 a flat spectrum in the optical/UV energy band was observed, suggesting an important contribution of the synchrotron emission in this part of the spectrum during the brightest gamma-ray flare, therefore a significant shift of the synchrotron peak