Introduction: The minor in question Boutaghou, Maya; Jean-François, Emmanuel Bruno
Cultural dynamics,
02/2020, Letnik:
32, Številka:
1-2
Journal Article
Recenzirano
Dedicated to “the minor in question,” this issue of Cultural Dynamics investigates the renewed potential and conceptual valence of the “minor,” both as a critical category and a methodological ...framework, for thinking through questions of positionality and performance, of agency and ways of being, for marginal subjects whose creative and expressive cultures circumvent dominant influences and hierarchical systems of power. Grounded in the work of comparative literature and theory, the volume gathers contributions by scholars from a variety of disciplines in the Humanities, whose works lie at the intersection of various linguistic expressions, geographical arrangements, cultural formations, and so-called minor orientations within established area studies programs. Considering how aesthetic forms convey the “minor” as a cultural entity, they approach it both as a dynamic category and a fluid positionality, not only to uncover the diverse forms that violence, domination, and inequalities take across multiple contexts, but also to challenge static representations of minor subjects and communities as passive, isolated, and/or disempowered.
Severe community-acquired pneumonia caused by Streptococcus pneumoniae is associated with high morbidity and mortality rates. CAL02, a novel antitoxin agent with an unprecedented mode of action, ...consists of liposomes that capture bacterial toxins known to dysregulate inflammation, cause organ damage, and impede immune defence. We aimed to assess the safety of CAL02 as an add-on therapy to antibiotics.
This randomised, double-blind, multicentre, placebo-controlled trial was done in ten intensive care units (ICUs) in France and Belgium (but only six units enrolled patients), in patients with severe community-acquired pneumococcal pneumonia who required ICU admission and had been identified as being infected with S pneumoniae. We randomly assigned participants in two stages—the first stage randomly assigned six patients (1:1) to either low-dose CAL02 or placebo, and the second stage randomly assigned 18 patients (14:4) to either high-dose CAL02 or placebo, and stratified in four blocks (4:1, 4:1, 3:1, and 3:1), in addition to standard of care. Block randomisation was done with a computer-generated random number list. Participants, investigators, other site study personnel, the sponsor, and the sponsor's designees involved in study management and monitoring were masked to the randomisation list and treatment assignment. Patients were treated with low-dose (4 mg/kg) or high-dose (16 mg/kg) CAL02 or placebo (saline), in addition to standard antibiotic therapy. Two intravenous doses of study treatment were infused, with a 24 h interval, at a concentration of 10 mg/mL, stepwise, over a maximum of 2 h on days 1 and 2. The primary objective of the study was to assess the safety and tolerability of low-dose and high-dose CAL02 in patients with severe community-acquired pneumonia treated with standard antibiotic therapy, and the primary analysis was done on the safety population (all patients who received at least one dose of the study treatment). Efficacy was a secondary outcome. This trial is registered with ClinicalTrials.gov, number NCT02583373.
Between March 21, 2016, and Jan 13, 2018, we screened 280 patients with community-acquired pneumonia. 19 patients were enrolled and randomly assigned, resulting in 13 patients in the CAL02 groups (three assigned to low-dose CAL02 and ten assigned to high-dose CAL02) and six in the placebo group. One patient randomly assigned to placebo was allocated to the wrong treatment group and received high-dose CAL02 instead of placebo. Thus, 14 patients received CAL02 (three received low-dose CAL02 and 11 received high-dose CAL02) and five patients received placebo, constituting the safety population. At baseline, the mean APACHE II score for the total study population was 21·5 (SD 4·9; 95% CI 19·3–23·7) and 11 (58%) of 19 patients had septic shock. Adverse events occurred in 12 (86%) of 14 patients in the CAL02 treatment groups combined and all five (100%) patients in the placebo group. Serious adverse events occurred in four (29%) of 14 patients in the CAL02 treatment groups combined and two (40%) of five patients in the placebo group. One non-serious adverse event (mild increase in triglycerides) in a patient in the high-dose CAL02 group was reported as related to study drug. However, analysis of the changes in triglyceride levels in the CAL02 groups compared with the placebo group revealed no correlation with administration of CAL02. No adverse events were linked to local tolerability events. All patients, apart from one who died in the low CAL02 group (death not related to the study drug) achieved clinical cure at the test of cure visit between days 15 and 22. The sequential organ failure assessment score decreased by mean 65·0% (95% CI 50·7–79·4) in the combined CAL02 groups compared with 29·2% (12·8–45·5) in the placebo group between baseline and day 8.
The nature of adverse events was consistent with the profile of the study population and CAL02 showed a promising safety profile and tolerability. However, the difference between high-dose and low-dose CAL02 could not be assessed in this study. Efficacy was in line with the expected benefits of neutralising toxins. The results of this study support further clinical development of CAL02 and provide a solid basis for a larger clinical study.
Combioxin.
Les enjeux nergtiques et environnementaux sont l'origine d'une forte croissance de la production d'lectricit partir d'nergies renouvelables depuis le dbut du XXIe sicle. Le concept de dveloppement ...durable et le souci des gnrations futures nous interpellent au quotidien permettant l'mergence de nouvelles technologies de production d'nergie, et de nouveaux comportements d'utilisation de ces nergies. L'mergence rapide de nouvelles technologies peut rendre la comprhension et donc la perception de celle-ci difficile. Ce livre a pour but de contribuer une meilleure connaissance de ces nouvelles technologies de production d'lectricit en s'adressant un public vari. Il prsente les enjeux, les sources et leurs moyens de conversion en lectricit suivant une approche gnrale et dveloppe les notions scientifiques de base permettant d'en apprhender les principales caractristiques techniques avec une vision d'ensemble. Des systmes de production d'lectricit partir de ressources nergtiques renouvelables de petites et moyennes puissances sont prsents. La deuxime dition de cet ouvrage, revue et augmente, met jour les nombreuses donnes caractrisant le dveloppement de ces nergies renouvelables, aborde les nouvelles technologies mergentes photovoltaques et marmotrices exploitant les courants marins, le dveloppement de l'olien offshore, et les dveloppements rcents concernant l'intgration de ces sources dans le rseau lectrique, ainsi que le dveloppement de l'autoproduction et de l'autoconsommation. Plusieurs exercices sont proposs au lecteur des fins d'valuation.
This paper deals with the transient stability of a grid-forming converter while embedding a current reference saturation strategy. The novelty of this work consists in investigating the impact of the ...current reference angle on the transient stability. In case of a balanced voltage sag, analytical formulas to estimate the critical clearing angle (CCA) and critical clearing time (CCT) while considering different values of the current reference angle are derived. It is demonstrated that the choice of this angle is constrained by the ability of the power converter to switch back to the voltage control mode. Based on that, its optimal value that enhances the transient stability and allows a switching from the saturated current control mode to the voltage control mode is calculated. Thereafter, the effectiveness of this optimal choice to guarantee the stability in case of a phase shift caused by a line re-closing event is verified. Time-domain simulations and experimental tests validate the correctness of the presented theoretical approaches.
Background
The objective of this study was to evaluate the ability of endothelial biomarkers to early predict clinical deterioration of patients admitted to the emergency department (ED) with a ...suspected sepsis. This was a prospective, multicentre, international study conducted in EDs. Adult patients with suspected acute bacterial infection and sepsis were enrolled but only those with confirmed infection were analysed. The kinetics of biomarkers and organ dysfunction were collected at T0, T6 and T24 hours after ED admission to assess prognostic performances of sVEGFR2, suPAR and procalcitonin (PCT). The primary outcome was the deterioration within 72 h and was defined as a composite of relevant outcomes such as death, intensive care unit admission and/or SOFA score increase validated by an independent adjudication committee.
Results
After adjudication of 602 patients, 462 were analysed including 124 who deteriorated (27%). On admission, those who deteriorated were significantly older (73 60–82 vs 63 45–78 y-o,
p
<
0.001
) and presented significantly higher SOFA scores (2.15 ± 1.61 vs 1.56 ± 1.40,
p
=
0.003
). At T0, sVEGFR2 (5794 5026–6788 vs 6681 5516–8059,
p
<
0.0001
), suPAR (6.04 4.42–8.85 vs 4.68 3.50–6.43,
p
<
0.0001
) and PCT (7.8 ± 25.0 vs 5.4 ± 17.9 ng/mL,
p
=
0.001
) were associated with clinical deterioration. In multivariate analysis, low sVEGFR2 expression and high suPAR and PCT levels were significantly associated with early deterioration, independently of confounding parameters (sVEGFR2, OR = 1.53 1.07–2.23,
p
<
0.001
; suPAR, OR = 1.57 1.21–2.07,
p
=
0.003
; PCT, OR = 1.10 1.04–1.17,
p
=
0.0019
). Combination of sVEGFR2 and suPAR had the best prognostic performance (AUC = 0.7 0.65–0.75) compared to clinical or biological variables.
Conclusions
sVEGFR2, either alone or combined with suPAR, seems of interest to predict deterioration of patients with suspected bacterial acute infection upon ED admission and could help front-line physicians in the triage process.
Abstract
Background
Except in a few retrospective studies mainly including patients under chemotherapy, information regarding the impact of immunosuppressive therapy on the prognosis of patients ...admitted to the intensive care unit (ICU) for septic shock is scarce. Accordingly, the PACIFIC study aimed to asses if immunosuppressive therapy is associated with an increased mortality in patients admitted to the ICU for septic shock.
Methods
This was a retrospective epidemiological multicentre study. Eight high enroller centres in septic shock randomised controlled trials (RCTs) participated in the study. Patients in the “exposed” group were selected from the screen failure logs of seven recent RCTs and excluded because of immunosuppressive treatment. The “non-exposed” patients were those included in the placebo arm of the same RCTs. A multivariate logistic regression model was used to estimate the risk of death.
Results
Among the 433 patients enrolled, 103 were included in the “exposed” group and 330 in the “non-exposed” group. Reason for immunosuppressive therapy included organ transplantation (n = 45 44%) or systemic disease (n = 58 56%). ICU mortality rate was 24% in the “exposed” group and 25% in the “non-exposed” group (
p
= 0.9). Neither in univariate nor in multivariate analysis immunosuppressive therapy was associated with a higher ICU mortality (OR: 0.95; 95% CI 0.56–1.58:
p
= 0.86 and 1.13 95% CI 0.61–2.05:
p
= 0.69, respectively) or 3-month mortality (OR: 1.13; 95% CI 0.69–1.82:
p
= 0.62 and OR: 1.36 95% CI 0.78–2.37:
p
= 0.28, respectively).
Conclusions
In this study, long-term immunosuppressive therapy excluding chemotherapy was not associated with significantly higher or lower ICU and 3-month mortality in patients admitted to the ICU for septic shock.
Numerous developments have been dedicated these passed years to demonstrate the use of surface acoustic wave (SAW) devices as passive sensors probed through a wireless radio-frequency link. Giving ...access to physical parameter variations without embedded power supply, recent works have shown that SAW sensors can be used under harsh environments such as temperatures in excess of 300°C and much more. The purpose of this paper is to present a new packaging process for SAW sensors operating under temperature environments up to 600°C. The robustness of this packaging process is first validated at the above-mentioned temperature using a classical temperature probe via wired connection. The reliability of this process applied to differential SAW sensors then is demonstrated by wireless interrogation of a quartz-based SAW differential sensor from room temperature to 480°C. The sensor operation has been validated for several tens of hours without major failure nor significant deviation, although the measurement distance dynamic range is observed to be dramatically reduced with operating on such a wide temperature range.
COVID-19 includes lung infection ranging from mild pneumonia to life-threatening acute respiratory distress syndrome (ARDS). Dysregulated host immune response in the lung is a key feature in ARDS ...pathophysiology. However, cellular actors involved in COVID-19-driven ARDS are poorly understood. Here, in blood and airways of severe COVID-19 patients, we serially analyzed unconventional T cells, a heterogeneous class of T lymphocytes (MAIT, γδT, and iNKT cells) with potent antimicrobial and regulatory functions. Circulating unconventional T cells of COVID-19 patients presented with a profound and persistent phenotypic alteration. In the airways, highly activated unconventional T cells were detected, suggesting a potential contribution in the regulation of local inflammation. Finally, expression of the CD69 activation marker on blood iNKT and MAIT cells of COVID-19 patients on admission was predictive of clinical course and disease severity. Thus, COVID-19 patients present with an altered unconventional T cell biology, and further investigations will be required to precisely assess their functions during SARS-CoV-2-driven ARDS.
Purpose
Nangibotide is a specific TREM-1 inhibitor that tempered deleterious host–pathogens interactions, restored vascular function, and improved survival, in animal septic shock models. This study ...evaluated the safety and pharmacokinetics of nangibotide and its effects on clinical and pharmacodynamic parameters in septic shock patients.
Methods
This was a multicenter randomized, double-blind, two-stage study. Patients received either continuous infusion of nangibotide (0.3, 1.0, or 3.0 mg/kg/h) or placebo. Treatment began < 24 h after shock onset and continued for up to 5 days. Safety primary outcomes were adverse events (AEs), whether serious or not, and death. Exploratory endpoints evaluated nangibotide effects on pharmacodynamics, organ function, and mortality, and were analyzed according to baseline sTREM-1 concentrations.
Results
Forty-nine patients were randomized. All treatment emergent AEs (TEAEs) were collected until Day 28. No significant differences were observed in TEAEs between treatment groups. No drug withdrawal linked to TEAE nor appearance of anti-drug antibodies were reported. Nangibotide pharmacokinetics appeared to be dose-proportional and clearance was dose-independent. Nangibotide did not significantly affect pharmacodynamic markers. Decrease in SOFA score LS mean change (± SE) from baseline to Day 5 in pooled nangibotide groups versus placebo was − 0.7 (± 0.85) in the randomized population and − 1.5 (± 1.12) in patients with high baseline plasma sTREM-1 concentrations (non-significant). This pattern was similar to organ support end points.
Conclusion
No significant increases in TEAEs were detected in nangibotide-treated patients versus placebo. These results encourage further evaluation of nangibotide and further exploration of plasma sTREM-1 concentrations as a predictive efficacy biomarker.
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