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Abstract Background Unlike other viruses, the pathogenicity of human metapneumovirus (hMPV) in adults remains uncertain. To address this question, a retrospective monocentric cohort including all patients admitted to ICU with hMPV infection between January 1, 2010, and June 30, 2018 was performed. The characteristics of hMPV infected patients were studied and compared to matched influenza infected patients. Consecutively, a systematic review and meta-analyses investigating PUBMED, EMBASE and COCHRANE databases was conducted to explore the hMPV infections in adult patients (PROSPERO number: CRD42018106617). Trials, case series, and cohorts published between January 1, 2008 and August 31, 2019 compiling adults presenting hMPV infections were included. Pediatric studies were excluded. Data were extracted from published reports. Primary endpoint was the rate of low respiratory tract infections (LRTIs) among all hMPV infected patients. Results During the study period, 402 patients were tested positive for hMPV. Among them 26 (6.5%) patients were admitted to the ICU, 19 (4.7%) for acute respiratory failure. Twenty-four (92%) were immunocompromised. Bacterial coinfections were frequent 53.8%. Hospital mortality rate was 30.8%. In the case–control analysis, the clinical and imaging characteristics were not different between hMPV and influenza infected patients. The systematic review identified 156 studies and 69 of them (1849 patients) were eligible for analysis. Although there was heterogeneity between the studies, the rate of hMPV LRTIs was 45% (95% CI 31–60%; I 2 = 98%). Intensive care unit (ICU) admission was required for 33% (95% CI 21–45%; I 2 = 99%). Hospital mortality rate was 10% (95% CI 7–13%; I 2 = 83%) and ICU mortality rate was 23% (95% CI 12–34%; I 2 = 65%). Underlying malignancy was independently associated with increased mortality rate. Conclusions This preliminary work suggested that hMPV may be associated with severe infection and high mortality in patients with underlying malignancies. However, regarding the small size of the cohort and the heterogeneity of the review, more cohort studies are warranted.

Abstract Background Etoposide remains the cornerstone of symptomatic management of critically ill patients with secondary hemophagocytic syndrome (sHS). Risk of healthcare-associated infections (HAIs) in this setting with etoposide has never been assessed. We sought to evaluate the association between etoposide administration, HAIs occurrence and survival in critically ill adult patients with sHS. In this retrospective single-center study conducted in a university hospital ICU between January 2007 and March 2020, all consecutive patients with sHS were included. HAIs were defined as any microbiologically documented infection throughout ICU stay. Competing risk survival analysis was performed to determine factors associated with HAIs. Propensity score-based overlap weighting was performed to adjust for factors associated with etoposide use. Results 168 patients with a median age of 49 [38, 59] were included. Forty-three (25.6%) patients presented with at least 1 microbiologically documented HAI throughout ICU stay. After adjustment, cumulative incidence of HAI was higher in patients receiving etoposide (p = 0.007), while survival was unaffected by etoposide status (p = 0.824). By multivariable analysis, etoposide treatment was associated with a higher incidence of HAIs (sHR 3.75 [1.05, 6.67]), whereas no association with survival (sHR 0.53 [0.20, 1.98]) was found. Other factors associated with increased mortality after adjustment included age, immunodepression, male sex, SOFA score > 13, and occurrence of HAI. Conclusions In patients with sHS, etoposide treatment is independently associated with increased occurrence of HAIs, whereas no association with survival was found. Intensivists should be aware of increased infectious risk, to promptly detect and treat infections in this specific setting. Studies to assess benefits from prophylactic anti-infectious agents in this setting are warranted and the lack of benefit of etoposide on survival needs to be interpreted cautiously.

Abstract Background Internal tandem duplications in the FLT3 gene, termed FLT3-ITDs, are useful molecular markers in acute myeloid leukemia (AML) for patient risk stratification and follow-up. FLT3-ITDs are increasingly screened through high-throughput sequencing (HTS) raising the need for robust and efficient algorithms. We developed a new algorithm, which performs no alignment and uses little resources, to identify and quantify FLT3-ITDs in HTS data. Results Our algorithm (FiLT3r) focuses on the k-mers from reads covering FLT3 exons 14 and 15. We show that those k-mers bring enough information to accurately detect, determine the length and quantify FLT3-ITD duplications. We compare the performances of FiLT3r to state-of-the-art alternatives and to fragment analysis, the gold standard method, on a cohort of 185 AML patients sequenced with capture-based HTS. On this dataset FiLT3r is more precise (no false positive nor false negative) than the other software evaluated. We also assess the software on public RNA-Seq data, which confirms the previous results and shows that FiLT3r requires little resources compared to other software. Conclusion FiLT3r is a free software available at https://gitlab.univ-lille.fr/filt3r/filt3r . The repository also contains a Snakefile to reproduce our experiments. We show that FiLT3r detects FLT3-ITDs better than other software while using less memory and time.

La simulation du contrôle non destructif (CND) par ultrasons joue un rôle important dans les évaluations et contrôles des structures en béton. Le béton est un milieu composite : la présence d’hétérogénéités conduit à la dispersion et à l’atténuation des ondes ultrasonores. Cela a un effet important sur le contrôle. Par conséquent, il est important de modéliser avec précision l’atténuation des ondes due à la diffusion par les différents composants présents dans le béton (granulats, porosités, microfissures…). Les méthodes ultrasonores classiquement utilisées reposent sur l’étude de l’onde cohérente caractérisée par sa vitesse et son atténuation. Cette onde peut être simulée à l’aide de modèles numériques ou analytiques. Les modèles numériques sont plus performants mais très couteux dans le cas 3D, et le besoin de mettre en place une simulation rapide de contrôles conduit à une nécessité d’améliorer les modèles analytiques 3D simplifiés. Ces derniers considèrent une distribution uniforme de granulats dans une matrice de ciment mais le champ ultrasonore total dépend fortement des positions des obstacles. Notre étude porte sur la fonction de corrélation qui décrit la distribution de ces positions. La simplification de cette fonction qui suppose l’uniformité de la distribution peut conduire à des erreurs dans l’estimation de l’atténuation. En guise d’amélioration des modèles analytiques, on cherche à les adapter à une fonction de corrélation plus réaliste. Le travail présenté dans cette communication vise à établir un modèle analytique 2D et 3D amélioré pour la diffusion multiple intégrant une fonction de corrélation plus réaliste entre les diffuseurs. Une comparaison entre le modèle analytique dans sa version 2D et le code éléments finis ONDO développé par le CEA List sera présentée. La validation au cas 2D permet l’emploi de fonctions de corrélation similaires pour le cas 3D.

Summary: In current IVF practice, metaphase-2 (M2) oocytes are considered most efficient in producing good quality embryos. Maximizing their number at all ages is standard clinical practice, while immature germinal vesicle (GV) oocytes are mostly automatically discarded. We present preliminary evidence that oocyte maturity grades with advancing age significantly change in their abilities to produce good quality embryos, with M2 oocytes significantly declining, GV oocytes improving, and M1 oocytes staying the same. These data contradict the over-40-year-old dogma that oocyte grades functionally do not change with advancing age, supporting potential changes to current IVF practice: (1) Stimulation protocols and timing of oocyte retrieval can be adjusted to a patient’s age and ovarian function. (2) In older and younger women with prematurely aging ovaries, GV oocytes may no longer be automatically discarded. (3) In some infertile women, rescue in vitro maturation of immature oocytes may delay the need for third-party egg donation.

This Special Issue of Applied Sciences focuses on advancing modeling methods for the ultrasonic Non-destructive Testing (NDT) of materials [...]

PURPOSE:Critical Care Nephrology is an emerging sub-specialty of Critical Care. Despite increasing awareness about the serious impact of acute kidney injury (AKI) and renal replacement therapy (RRT), important knowledge gaps persist. This report represents a summary of a 1-day meeting of the AKI section of the European Society of Intensive Care Medicine (ESICM) identifying priorities for future AKI research. METHODS:International Members of the AKI section of the ESICM were selected and allocated to one of three subgroups: "AKI diagnosis and evaluation", "Medical management of AKI" and "Renal Replacement Therapy for AKI." Using a modified Delphi methodology, each group identified knowledge gaps and developed potential proposals for future collaborative research. RESULTS:The following key research projects were developed: Systematic reviews: (a) epidemiology of AKI with stratification by patient cohorts and diagnostic criteria; (b) role of higher blood pressure targets in patients with hypertension admitted to the Intensive Care Unit, and (c) specific clearance characteristics of different modalities of continuous renal replacement therapy (CRRT). Observational studies: (a) epidemiology of critically ill patients according to AKI duration, and (b) current clinical practice of CRRT. Intervention studies:( a) Comparison of different blood pressure targets in critically ill patients with hypertension, and (b) comparison of clearance of solutes with various molecular weights between different CRRT modalities. CONCLUSION:Consensus was reached on a future research agenda for the AKI section of the ESICM.

BackgroundThe current literature identifies several potential benefits of artificial intelligence models for populations’ health and health care systems' efficiency. However, there is a lack of understanding on how the risk of bias is considered in the development of primary health care and community health service artificial intelligence algorithms and to what extent they perpetuate or introduce potential biases toward groups that could be considered vulnerable in terms of their characteristics. To the best of our knowledge, no reviews are currently available to identify relevant methods to assess the risk of bias in these algorithms. The primary research question of this review is which strategies can assess the risk of bias in primary health care algorithms toward vulnerable or diverse groups? ObjectiveThis review aims to identify relevant methods to assess the risk of bias toward vulnerable or diverse groups in the development or deployment of algorithms in community-based primary health care and mitigation interventions deployed to promote and increase equity, diversity, and inclusion. This review looks at what attempts to mitigate bias have been documented and which vulnerable or diverse groups have been considered. MethodsA rapid systematic review of the scientific literature will be conducted. In November 2022, an information specialist developed a specific search strategy based on the main concepts of our primary review question in 4 relevant databases in the last 5 years. We completed the search strategy in December 2022, and 1022 sources were identified. Since February 2023, two reviewers independently screened the titles and abstracts on the Covidence systematic review software. Conflicts are solved through consensus and discussion with a senior researcher. We include all studies on methods developed or tested to assess the risk of bias in algorithms that are relevant in community-based primary health care. ResultsIn early May 2023, almost 47% (479/1022) of the titles and abstracts have been screened. We completed this first stage in May 2023. In June and July 2023, two reviewers will independently apply the same criteria to full texts, and all exclusion motives will be recorded. Data from selected studies will be extracted using a validated grid in August and analyzed in September 2023. Results will be presented using structured qualitative narrative summaries and submitted for publication by the end of 2023. ConclusionsThe approach to identifying methods and target populations of this review is primarily qualitative. However, we will consider a meta-analysis if quantitative data and results are sufficient. This review will develop structured qualitative summaries of strategies to mitigate bias toward vulnerable populations and diverse groups in artificial intelligence models. This could be useful to researchers and other stakeholders to identify potential sources of bias in algorithms and try to reduce or eliminate them. Trial RegistrationOSF Registries qbph8; https://osf.io/qbph8 International Registered Report Identifier (IRRID)DERR1-10.2196/46684

Attention to inequality is increasingly taking centerstage in the fight against climate change and environmental devastation. More and more scholars and activists emphasize the need to put the reduction of inequality at the core of environmental and climate politics, and more and more propose a (socially just) "sufficiency" approach and politics to do so. Just sufficiency is presented as the new desirable societal pact, tasked with taking over from the current dominant growth pact driving "excess," and replacing it with a politics of "enough," through "collectively defined self-limitation." However, an excess/enough lens misses the dynamics of production of inequality in the first place, with important political implications. This article thus seeks to contribute a tighter critical theoretical understanding of the inequality-unsustainability relation as a nexus historically powered by specific mechanisms of fossil, metabolic, as well as "green" accumulation. Through the theorization of these relations, one can better apprehend how inequality is not only a question of unfair distribution or exclusion from affluence demanding to be addressed through social and environmental justice, but also the condition for the modes of extraction and exploitation that produce and reproduce unsustainability. I argue that the counterhegemonic struggle must be waged on that terrain: putting limitations (not self-limitations) on the accumulation machine and its inequality-unsustainability nexus. This reading, which builds on critical theory and Marxist and feminist political ecology, is related to notions of class as structured not only by exploitation, but also, crucially by dispossession and status hierarchization. Adopting a nexus approach to inequality and unsustainability offers a critical theoretical method that can hopefully shift the assessments and orientations of the sufficiency movement away from the moral terrain of self-limitation (whose self?) toward the class politics of limits on capital needed today for socio-ecological transformation. [ABSTRACT FROM AUTHOR]

Rationale: Allogeneic hematopoietic stem-cell transplantation (Allo-HSCT) recipients are still believed to be poor candidates for ICU management. Methods: We investigated outcomes and determinants of mortality in a large multicenter retrospective cohort of Allo-HSCT patients admitted between January 1, 2015, and December 31, 2020, to 14 French ICUs. The primary endpoint was 90-day mortality. Measurements and Main Results: In total, 1,164 patients were admitted throughout the study period. At the time of ICU admission, 765 (66%) patients presented with multiple organ dysfunction, including acute respiratory failure in 40% (n = 461). The median sepsis-related organ failure assessment score was 6 (interquartile range, 4–8). Invasive mechanical ventilation, renal replacement therapy, and vasopressors were required in 438 (38%), 221 (19%), and 468 (41%) patients, respectively. ICU mortality was 26% (302 deaths). Ninety-day, 1-year, and 3-year mortality rates were 48%, 63%, and 70%, respectively. By multivariable analysis, age > 56 years (odds ratio [OR], 2.0 [95% confidence interval (CI), 1.53–2.60]; P < 0.001), time from Allo-HSCT to ICU admission between 30 and 90 days (OR, 1.68 [95% CI, 1.17–2.40]; P = 0.005), corticosteroid-refractory acute graft-versus-host disease (OR, 1.63 [95% CI, 1.38–1.93]; P < 0.001), need for vasopressors (OR, 1.9 [95% CI, 1.42–2.55]; P < 0.001), and mechanical ventilation (OR, 3.1 [95% CI, 2.29–4.18]; P < 0.001) were independently associated with 90-day mortality. In patients requiring mechanical ventilation, mortality rates ranged from 39% (no other risk factors for mortality) to 100% (four associated risk factors for mortality). Conclusions: Most critically ill Allo-HSCT recipients survive their ICU stays, including those requiring mechanical ventilation, with an overall 90-day survival rate reaching 51.8%. A careful assessment of goals of care is required in patients with two or more risk factors for mortality. [ABSTRACT FROM AUTHOR]

The values of the Dedekind--Rademacher cocycle at certain real quadratic arguments are shown to be global p-units in the narrow Hilbert class field of the associated real quadratic field, as predicted by the conjectures of Darmon--Dasgupta (2006) and Darmon--Vonk (2021). The strategy for proving this result combines the approach of prior work of the authors (2021) with one crucial extra ingredient: the study of infinitesimal deformations of irregular Hilbert Eisenstein series of weight 1 in the anti-parallel direction. [ABSTRACT FROM AUTHOR]

Background Racial disparities in treatment and outcomes of rectal cancer have been attributed to patients' differential access to care. We aimed to study treatment and outcomes of rectal cancer in the equal access Military Health System (MHS) to better understand potential racial disparities. Methods We accessed the MilCanEpi database to study a cohort of patients aged 18 and older who were diagnosed with rectal adenocarcinoma between 1998 and 2014. Receipt of guideline recommended treatment per tumor stage, cancer recurrence, and all-cause death were compared between non-Hispanic White and Black patients using multivariable regression models with associations expressed as odds (AORs) or hazard ratios (AHRs) and their 95% confidence intervals (CIs). Results The study included 171 Black and 845 White patients with rectal adenocarcinoma. Overall, there were no differences in receipt of guideline concordant treatment (AOR = 0.76, 95% CI = 0.45 to 1.29), recurrence (AHR = 1.34, 95% CI = 0.85 to 2.12), or survival (AHR = 1.08, 95% CI = 0.77 to 1.54) for Black patients compared with White patients. However, Black patients younger than 50 years of age at diagnosis (AOR = 0.34, 95% CI = 0.13 to 0.90) or with stage III or IV tumors (AOR = 0.28, 95% CI = 0.12 to 0.64) were less likely to receive guideline recommended treatment than White patients in stratified analysis. Conclusions In the equal access MHS, although there were no overall racial disparities in rectal cancer treatment or clinical outcomes between Black and White patients, disparities among those with early-onset or late-stage rectal cancers were noted. This suggests that factors other than access to care may play a role in the observed disparities and warrants further research. [ABSTRACT FROM AUTHOR]