IntroductionObservational evidence suggests physiological benefits and lower mortality with lower chloride solutions; however, 0.9% saline remains the most widely used fluid worldwide. Given ...uncertainty regarding the association of lower chloride on mortality, it is unlikely that practice will change without direct randomised clinical trial (RCT) evidence. This pilot RCT will investigate the feasibility of a large-scale trial directly comparing low chloride with high chloride fluids in patients with septic shock.Methods and analysisThis is a randomised, concealed, blinded parallel-group multicentre pilot trial. We will include adult critically ill patients with septic shock, defined as ongoing hypotension despite 1 L of fluid, or a serum lactate >4 mmol/L, who are within 6 hours of hospital presentation or rapid response team activation. We will exclude patients if they have an aetiology of shock other than sepsis, if they have acute burn injury, elevated intracranial pressure, intent to withdraw life support or previous enrolment in this or a competing trial. Following informed consent, patients will be randomised to a low chloride fluid strategy or a high chloride fluid strategy for the duration of their ICU stay or until 30 days postrandomisation. Clinicians, patients, families and research staff will be blinded. The primary outcome for this trial will be feasibility, assessed by consent rate, recruitment success and protocol adherence. Patient-important clinical outcomes include mortality, receipt of renal replacement therapy, intensive care unit and hospital lengths of stay and surrogate outcomes of incidence of acidosis, hyperkalaemia and acute kidney injury.Ethics and disseminationThis pilot trial will test the feasibility of conducting the main trial, which will examine the effect of high versus low chloride fluids in patients with septic shock on patient-important outcomes.Trial registration numberNCT02748382, registered 8 April 2016.Protocol date1 July 2016.
IntroductionMost solid organ transplants originate from donors meeting criteria for death by neurological criteria (DNC). Within the organ donor, physiological responses to brain death increase the ...risk of ischaemia reperfusion injury and delayed graft function. Donor preconditioning with calcineurin inhibition may reduce this risk.Methods and analysisWe designed a multicentre placebo-controlled pilot randomised trial involving nine organ donation hospitals and all 28 transplant programmes in the Canadian provinces of Ontario and Québec. We planned to enrol 90 DNC donors and their approximately 324 organ recipients, totalling 414 participants. Donors receive an intravenous infusion of either tacrolimus 0.02 mg/kg over 4 hours prior to organ retrieval, or a matching placebo, while monitored in an intensive care unit for any haemodynamic changes during the infusion. Among all study organ recipients, we record measures of graft function for the first 7 days in hospital and we will record graft survival after 1 year. We examine the feasibility of this trial with respect to the proportion of all eligible donors enrolled and the proportion of all eligible transplant recipients consenting to receive a CINERGY organ transplant and to allow the use of their health data for study purposes. We will report these feasibility outcomes as proportions with 95% CIs. We also record any barriers encountered in the launch and in the implementation of this trial with detailed source documentation.Ethics and disseminationWe will disseminate trial results through publications and presentations at participating sites and conferences. This study has been approved by Health Canada (HC6-24-c241083) and by the Research Ethics Boards of all participating sites and in Québec (MP-31-2020-3348) and Clinical Trials Ontario (Project #3309).Trial registration numberNCT05148715.
Interpretation: A minority of Canadian hospitals enrolled the majority of participants in CIHR-funded studies on COVID-19. This analysis sheds light on the Canadian health research ecosystem and ...provides information for multiple key partners to consider ways to realize the full research potential of Canada's health systems.
OBJECTIVES:Mechanisms underlying sepsis-associated encephalopathy remain unclear, but reduced cerebral blood flow, alone or in conjunction with altered autoregulation, is reported as a potential ...contributor. We compared cerebral blood flow of control subjects and vasopressor-dependent septic patients.
DESIGN:Randomized crossover study.
SETTING:MRI with arterial spin labeling.
PATIENTS:Ten sedated septic patients on mechanical ventilation (four with controlled chronic hypertension) and 12 control subjects (six with controlled chronic hypertension) were enrolled. Mean ± SD ages were 61.4 ± 10.2 and 44.2 ± 12.8 years, respectively (p = 0.003). Mean Acute Physiology and Chronic Health Evaluation II score of septic patients at ICU admission was 27.7 ± 6.6.
INTERVENTIONS:To assess the potential confounding effects of sedation and mean arterial pressure, we measured cerebral blood flow with and without sedation with propofol in control subjects and at a target mean arterial pressure of 65 mm Hg and greater than or equal to 75 mm Hg in septic patients. The sequence of sedation versus no sedation and mean arterial pressure targets were randomized.
MEASUREMENTS AND MAIN RESULTS:In septic patients, cerebral blood flow measured at a mean arterial pressure target of 65 mm Hg (40.4 ± 10.9 mL/100 g/min) was not different from cerebral blood flow measured at a mean arterial pressure target of greater than or equal to 75 mm Hg (41.3 ± 9.8 mL/100 g/min; p = 0.65). In control subjects, we observed no difference in cerebral blood flow measured without and with sedation (24.8 ± 4.2 vs 24.9 ± 5.9 mL/100 g/min; p = 0.93). We found no interaction between chronic hypertension and the effect of sedation or mean arterial pressure targets. Cerebral blood flow measured in sedated septic patients (mean arterial pressure target 65 mm Hg) was 62% higher than in sedated control subjects (p = 0.001).
CONCLUSIONS:In septic patients, cerebral blood flow was higher than in sedated control subjects and did not vary with mean arterial pressure targets. Further research is required to understand the clinical significance of cerebral hyperperfusion in septic patients on vasopressors and to reassess the neurologic effects of current mean arterial pressure targets in sepsis.
Introduction En contexte de transition numérique des systèmes éducatifs, il est très pertinent que Peraya et Fiévez (2022) s’intéressent à l’importance du plan stratégique numérique des universités, ...comme le fait le Québec depuis 2018. Plus précisément, c’est en 2018 que le ministère de l’Éducation et de l’Enseignement supérieur du Québec (MEES) s’est doté de son Plan d’action numérique (PAN), document contenant un ensemble de 33 mesures qui visent l’optimisation de l’intégration et l’exploit...
Successive hydrazone/thioether orthogonal ligations of a dendrimeric lysine core with antigenic peptides and mannoside derivatives are described (see scheme). This method provides a flexible one‐pot ...synthesis for artificial conjugates of clustered carbohydrate receptor ligands bearing antigens.
Cet article éclaire, d’un point de vue essentiellement théorique, le phénomène de la souffrance enseignante dans une perspective empruntée à la sociologie et la philosophie sociale des principaux ...représentants de la première génération de l’École de Francfort, Max Horkheimer et Theodor Adorno : ses objectifs sont de mettre en lumière les articulations possibles entre les manifestations microsociologiques de la souffrance vécue dans le cadre du travail enseignant (problèmes d’adaptation, stress, désenchantement face au métier, remaniements identitaires professionnels et personnels) et le concept macrosociologique de rationalisation instrumentale du système éducatif. Quels sont les impacts de ce processus de rationalisation, au cœur de la pensée horkheimerienne et adornienne, sur les différentes manifestations de la souffrance enseignante ? Comment le concept de souffrance chez les deux philosophes permet-il de mieux comprendre les fondements et rouages des difficultés enseignantes ?
This article aims to understand the phenomenon of teaching difficulties and suffering from a theoretical point of view, through the sociological and philosophical perspectives of Frankfurt School’s first generation theorists Max Horkheimer and Theodor Adorno. Its main goal is to highlight the possible relation between the microsociological manifestations of suffering experienced in teaching work (adaptation problems, stress, disenchantment vis-à-vis the profession, professional and personal identity changes) and the concept of the instrumental rationalization of the educational systems. What are the possible impacts of this process of rationalization, central to Horkheimer and Adorno’s theories, on the different manifestations of teacher suffering? More specifically, how does the concept of suffering in the two philosopher’s theories allow us to better comprehend the difficulties facing teachers in their work? These are some of the questions that this article aims to answer.
In humans, sterile immunity against malaria can be consistently induced through exposure to the bites of thousands of irradiated infected mosquitoes. The same level of protection has yet to be ...achieved using subunit vaccines. Recent studies have indicated an essential function for intrahepatic parasites, the stage after the mosquito bite, and thus for antigens expressed during this stage. We report here the identification of liver-stage antigen 3, which is expressed both in the mosquito and liver-stage parasites. This Plasmodium falciparum 200-kilodalton protein is highly conserved, and showed promising antigenic and immunogenic properties. In chimpanzees (Pan troglodytes), the primates most closely related to humans and that share a similar susceptibility to P. falciparum liver-stage infection, immunization with LSA-3 induced protection against successive heterologous challenges with large numbers of P. falciparum sporozoites.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
We describe novel peptide−protein microarrays, which were fabricated using semicarbazide glass slides that permitted the immobilization of glyoxylyl peptides by site-specific ligation and the ...immobilization of proteins by physisorption. The arrays permitted the simultaneous serodetection of antibodies directed against hepatitis C virus (HCV core p21 15−45 peptide, NS4 1925−1947 peptide, core, NS3, NS4, and mixture of core, NS3, NS4, and NS5 antigens), hepatitis B virus (HBc, HBe, and HBs), human immunodeficiency virus (Gp41 and Gp120 for HIV-I and Gp36 for HIV-II), Epstein−Barr virus (VCAp18 153-176 peptide), and syphilis (rTpN47 and rTpN17) antigens using an immunofluorescence assay. Peptide−protein microarrays displayed high signal-to-noise ratios, sensitivities, and specificities for the detection of antibodies as revealed by the analysis of a collection of human sera referenced against these five pathogens.
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