Pseudoentropic Isometries: A New Framework for Fuzzy Extractor Reusability

Fuzzy extractors (Dodis \textit{et al.}, Eurocrypt 2004) turn a noisy secret into a stable, uniformly distributed key. \textit{Reusable} fuzzy extractors remain secure when multiple keys are produced from a single noisy secret (Boyen, CCS 2004). Boyen proved that any information-theoretically secure reusable fuzzy extractor is subject to strong limitations. Simoens \textit{et al.} (IEEE S\&P, 2009) then showed deployed constructions suffer severe security breaks when reused. Canetti \textit{et al.} (Eurocrypt 2016) proposed using computational security to sidestep this problem. They constructed a computationally secure reusable fuzzy extractor for the Hamming metric that corrects a \emph{sublinear} fraction of errors. We introduce a generic approach to constructing reusable fuzzy extractors. We define a new primitive called a \emph{reusable pseudoentropic isometry} that projects an input metric space to an output metric space. This projection preserves distance and entropy even if the same input is mapped to multiple output metric spaces. A reusable pseudoentropy isometry yields a reusable fuzzy extractor by 1) randomizing the noisy secret using the isometry and 2) applying a traditional fuzzy extractor to derive a secret key. We propose reusable pseudoentropic isometries for the set difference and Hamming metrics. The set difference construction is built from composable digital lockers (Canetti and Dakdouk, Eurocrypt 2008) yielding the first reusable fuzzy extractor that corrects a {\it linear} fraction of errors. For the Hamming metric, we show that the second construction of Canetti \textit{et al.} (Eurocrypt 2016) can be seen as an instantiation of our framework. In both cases, the pseudoentropic isometry\u27s reusability requires noisy secrets distributions to have entropy in each symbol of the alphabet. Lastly, we implement our set difference solution and describe two use cases

Influenza and associated co-infections in critically ill immunosuppressed patients

Abstract Background It is unclear whether influenza infection and associated co-infection are associated with patient-important outcomes in critically ill immunocompromised patients with acute respiratory failure. Methods Preplanned secondary analysis of EFRAIM, a prospective cohort study of 68 hospitals in 16 countries. We included 1611 patients aged 18 years or older with non-AIDS-related immunocompromise, who were admitted to the ICU with acute hypoxemic respiratory failure. The main exposure of interest was influenza infection status. The primary outcome of interest was all-cause hospital mortality, and secondary outcomes ICU length of stay (LOS) and 90-day mortality. Results Influenza infection status was categorized into four groups: patients with influenza alone (n = 95, 5.8%), patients with influenza plus pulmonary co-infection (n = 58, 3.6%), patients with non-influenza pulmonary infection (n = 820, 50.9%), and patients without pulmonary infection (n = 638, 39.6%). Influenza infection status was associated with a requirement for intubation and with LOS in ICU (P < 0.001). Patients with influenza plus co-infection had the highest rates of intubation and longest ICU LOS. On crude analysis, influenza infection status was associated with ICU mortality (P < 0.001) but not hospital mortality (P = 0.09). Patients with influenza plus co-infection and patients with non-influenza infection alone had similar ICU mortality (41% and 37% respectively) that was higher than patients with influenza alone or those without infection (33% and 26% respectively). A propensity score-matched analysis did not show a difference in hospital mortality attributable to influenza infection (OR = 1.01, 95%CI 0.90–1.13, P = 0.85). Age, severity scores, ARDS, and performance status were all associated with ICU, hospital, and 90-day mortality. Conclusions Category of infectious etiology of respiratory failure (influenza, non-influenza, influenza plus co-infection, and non-infectious) was associated with ICU but not hospital mortality. In a propensity score-matched analysis, influenza infection was not associated with the primary outcome of hospital mortality. Overall, influenza infection alone may not be an independent risk factor for hospital mortality in immunosuppressed patients

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Treg cells and the TNFR2pos Treg subset play a major role in sepsis-induced CD4+ T cell impairment

Le sepsis est fréquemment responsable d’une immunosuppression induite par l'inflammation, qui est une cause importante de pneumonie acquise à l'hôpital. Une altération sévère des lymphocytes CD4+ est une caractéristique de l'IS post-septique. Nous avons cherché à déterminer comment les cellules Treg modifient les lymphocytes T CD4+ et leur rôle dans l’augmentation de susceptibilité de l’hôte à une pneumopathie bactérienne secondaire. Tout d'abord, nous avons montré dans la souris que le ratio Treg (lymphocytes Treg/CD4+) est augmenté pendant le sepsis par une diminution importante des lymphocytes T CD4+ plutôt que par une augmentation du nombre de Treg. Les Treg provenant d'animaux septiques présentaient un phénotype activé (expression CTLA4). En utilisant des souris DEREG et OTII, nous avons confirmé que les Treg au cours du sepsis contribuaient à une altération des lymphocytes T CD4+ et altéraient les défenses contre une pneumopathie secondaire.Sepsis causes inflammation-induced immunosuppression (IS), which is an important cause of hospital-acquired pneumonia. A severe depletion of the CD4+ lymphocytes compartment is a hallmark of post-septic IS and we sought to investigate whether and how Treg cells alter the CD4+ T cell compartment and render the septic host prone to a secondary bacterial pneumonia. First we showed in mice that the Treg ratio (Treg/CD4+ T lymphocytes) is enhanced during sepsis through a dramatic decrease of CD4+ T cells rather than an increased number of Treg. Treg from septic animals presented an activated phenotype (CTLA4 expression). Using DEREG and OTII mice, we confirmed that Treg induce a CD4+ T cell impairment and alter the defenses against pneumonia

Table Ronde Recherche & Conchyliculture #3 2022

La production d’huîtres creuses est une des principales ressources aquacoles dans le monde. La France en est la principale productrice en Europe. Depuis ses débuts au tournant du XXe siècle, la production a toujours connu des épisodes de mortalité. Ainsi, les huîtres classiquement rencontrées sur nos côtes (Ostrea edulis) ont connu des mortalités massives dans les années 1920, puis ce fut le tour de l’huître portugaise à la fin des années 1960. L’introduction et la bonne adaptation des huîtres japonaises (Crassostrea gigas) dans les années 1970 se sont également accompagnées de divers épisodes depuis les années 1990, notamment liés au virus de l’herpès (OsHV-1) et aux bactéries Vibrio. Aujourd’hui, deux maladies touchent particulièrement les élevages ostréicoles. Le POMS d’une part, qui associe virus et bactéries, cause le syndrome de mortalité des juvéniles d’huître. Moins bien connue, la maladie des adultes est pour sa part due à Vibrio aesturianus. L’état des connaissances sur ces maladies a été présenté et discuté lors de la table-ronde du 16 mars 2022 (Mieux connaître l’état de santé des cheptels). La table-ronde du 11 mai 2022 s’est quant à elle focalisée sur les conséquences de ces mortalités dans le milieu ainsi que sur les travaux menés pour trouver des solutions pratiques permettant de les limiter. Ce qu’il faut retenir La présence d’huîtres moribondes et de chairs en décomposition dans la lagune lors des épisodes de mortalité n’est pas sans conséquences pour le milieu puisque des transferts de bactéries, virus, ammonium et phosphate ainsi que des changements de communautés planctoniques sont observés à proximité des lanternes d’huîtres. Côté solutions, plusieurs pistes prometteuses ont été présentées : la stimulation immunitaire, la sélection (épigénétique), la prise de probiotiques ainsi que certains changements de pratiques zootechniques, notamment l’exondation

Population Pharmacokinetic Study of Cefazolin Dosage Adaptation in Bacteremia and Infective Endocarditis Based on a Nomogram

International audienceOptimal dosing of continuous-infusion cefazolin can be challenging in patients being treated for bacteremia or infective endocarditis. The aim of this work is to describe and analyze the pharmacokinetics of cefazolin in those patients using a population pharmacokinetics modeling approach and to establish a nomogram to determine the optimal daily dose. Population pharmacokinetics were modeled using the Pmetrics package for R. Plasma concentrations were collected retrospectively from patients treated with continuous-infusion cefazolin for bacteremia or infective endocarditis. The influence of multiple parameters, including renal function, total body weight, body mass index, body surface area (BSA), ideal weight, lean body weight, height, and age, was tested. The probabilities of target attainment for selected target concentrations (40, 60, and 80 mg/liter) were calculated. A dosing nomogram was then developed, using the absolute value of the glomerular filtration rate (aGFR), to determine the optimal daily dose required to achieve the target concentrations in at least 90% of patients. In total, 346 cefazolin plasma concentrations from 162 patients were collected. A one-compartment model best described the data set. The only covariate was aGFR, calculated according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula and the patient's body surface area, for the rate of elimination. Using the nomogram, achieving a cefazolin concentration target of 40 mg/liter with a success rate of at least 90% and with an aGFR of 30, 60, 90, and 120 ml/min requires a daily dose of 2.6, 4.3, 6.1, and 8.0 g/day, respectively. These results confirm the interest of posology adaptation of cefazolin according to aGFR

Plea for multitargeted interventions for severe COVID-19

International audienc

Treatment of Bone and Joint Tuberculosis in France: A Multicentre Retrospective Study

International audienceBackground: Nine percent of all cases of tuberculosis are bone and joint tuberculosis (BJTB). BJTB occurs in two main forms: spinal (STB) and extraspinal (ESTB). The aim of this study was to compare STB with ESTB in terms of diagnosis, treatment and outcomes. Methods: We collected demographic, clinical, microbiological, treatment duration and outcome data for patients with BJTB in a retrospective multicentre study over a 17-year period. Results: Of the 116 patients included in the study, 69 (59.5%) had STB and 47 (40.5%) had ESTB. The median age was higher in the ESTB group. There were significantly more foreign-born patients in the STB group. The median time for diagnosis was longer for ESTB (6 months) than STB (4 months) (p= 0.017). Magnetic resonance imaging was highly reliable for the diagnosis. Direct examination and histology allowed the diagnosis to be made in more than 80% of cases. The median treatment duration of 12 months, regardless of the type of BJTB, was longer than recommended. A favourable outcome was achieved in 91.9% of cases. Conclusion: The management of BJTB remains challenging. An earlier diagnosis should be more effective, reducing the total duration of treatment and leading to better tolerance

Principal component analysis, a useful tool to study cyclin-dependent kinase-inhibitor’s effect on cerebral ischaemia

International audienceAbstract Stroke is a leading cause of acute death related in part to brain oedema, blood–brain barrier disruption and glial inflammation. A cyclin-dependant kinase inhibitor, (S)-roscovitine, was administered 90 min after onset on a model of rat focal cerebral ischaemia. Brain swelling and Evans Blue tissue extravasation were quantified after Evans Blue injection. Combined tissue Evans Blue fluorescence and immunofluorescence of endothelial cells (RECA1), microglia (isolectin-IB4) and astrocytes (glial fibrillary acidic protein) were analysed. Using a Student’s t-test or Mann–Whitney test, (S)-roscovitine improved recovery by more than 50% compared to vehicle (Mann–Whitney, P &lt; 0.001), decreased significantly brain swelling by 50% (t-test, P = 0.0128) mostly in the rostral part of the brain. Main analysis was therefore performed on rostral cut for immunofluorescence to maximize biological observations (cut B). Evans Blue fluorescence decreased in (S)-roscovitine group compared to vehicle (60%, t-test, P = 0.049) and was further supported by spectrophotometer analysis (Mann–Whitney, P = 0.0002) and Evans Blue macroscopic photonic analysis (t-test, P = 0.07). An increase of RECA-1 intensity was observed in the ischaemic hemisphere compared to non-ischaemic hemisphere. Further study showed, in the ischaemic hemisphere that (S)-roscovitine treated group compared to vehicle, showed a decrease of: (i) endothelial RECA-1 intensity of about 20% globally, mainly located in the cortex (−28.5%, t-test, P = 0.03); (ii) Microglia’s number by 55% (t-test, P = 0.006) and modulated reactive astrocytes through a trend toward less astrocytes number (15%, t-test, P = 0.05) and astrogliosis (21%, t-test, P = 0.076). To decipher the complex relationship of these components, we analysed the six biological quantitative variables of our study by principal component analysis from immunofluorescence studies of the same animals. Principal component analysis differentiated treated from non-treated animals on dimension 1 with negative values in the treated animals, and positive values in the non-treated animals. Interestingly, stroke recovery presented a negative correlation with this dimension, while all other biological variables showed a positive correlation. Dimensions 1 and 2 allowed the identification of two groups of co-varying variables: endothelial cells, microglia number and Evans Blue with positive values on both dimensions, and astrocyte number, astrogliosis and brain swelling with negative values on dimension 2. This partition suggests different mechanisms. Correlation matrix analysis was concordant with principal component analysis results. Because of its pleiotropic complex action on different elements of the NeuroVascular Unit response, (S)-roscovitine may represent an effective treatment against oedema in stroke