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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]

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]

Introduction: Second-generation basal insulins like glargine 300 U/mL (Gla-300) have a longer duration of action and less daily fluctuation and interday variability than first-generation ones, such as glargine 100 U/mL (Gla-100). The EF-BI study, a nationwide observational, retrospective study, was designed to compare persistence, acute care complications, and healthcare costs associated with the initiation of such basal insulins (BI) in a real-life setting in France. Methods: This study was conducted using the French healthcare claims database (SNDS). Adult patients living with type 1 or type 2 diabetes mellitus (T1DM or T2DM) initiating Gla-300 or Gla-100 ± other hypoglycemic medications between January 1, 2016 and December 31, 2020, and without any insulin therapy over the previous 6 months were included. Persistence was defined as remaining on the same insulin therapy until discontinuation defined by a 6 month period without insulin reimbursement. Hospitalized acute complications were identified using ICD-10 codes. Total collective costs were established for patients treated continuously with each basal insulin over 1–3 years. All comparisons were adjusted using a propensity score based on initial patient/treatment characteristics. Results: A total of 235,894 patients with T2DM and 6672 patients with T1DM were included. Patients treated with Gla-300 were 83% (T1DM) and 44% (T2DM) less likely to discontinue their treatment than those treated with Gla-100 after 24 months (p < 0.0001). The annual incidence of acute hospitalized events in patients with T2DM treated with Gla-300 was 12% lower than with Gla-100 (p < 0.0001) but similar in patients with T1DM. Comparison of overall costs showed moderate but statistically significant differences in favor of Gla-300 versus Gla-100 for all patients over the first year, and in T2DM only over a 3-year follow-up. Conclusion: Use of Gla-300 resulted in a better persistence, less acute hospitalized events at least in T2DM, and reduced healthcare expenditure. These real-life results confirmed the potential interest of using Gla-300 rather than Gla-100. [ABSTRACT FROM AUTHOR]

We use an agnostic information-theoretic approach to investigate the statistical properties of natural images. We introduce the Multiscale Relevance (MSR) measure to assess the robustness of images to compression at all scales. Starting in a controlled environment, we characterize the MSR of synthetic random textures as function of image roughness H and other relevant parameters. We then extend the analysis to natural images and find striking similarities with critical ( H ≈ 0 ) random textures. We show that the MSR is more robust and informative of image content than classical methods such as power spectrum analysis. Finally, we confront the MSR to classical measures for the calibration of common procedures such as color mapping and denoising. Overall, the MSR approach appears to be a good candidate for advanced image analysis and image processing, while providing a good level of physical interpretability. [ABSTRACT FROM AUTHOR]

We use an agnostic information-theoretic approach to investigate the statistical properties of natural images. We introduce the Multiscale Relevance (MSR) measure to assess the robustness of images to compression at all scales. Starting in a controlled environment, we characterize the MSR of synthetic random textures as function of image roughness H and other relevant parameters. We then extend the analysis to natural images and find striking similarities with critical ( H ≈ 0 ) random textures. We show that the MSR is more robust and informative of image content than classical methods such as power spectrum analysis. Finally, we confront the MSR to classical measures for the calibration of common procedures such as color mapping and denoising. Overall, the MSR approach appears to be a good candidate for advanced image analysis and image processing, while providing a good level of physical interpretability. [ABSTRACT FROM AUTHOR]

Background: Because often introduced without proper validation studies, so-called "add-ons" to IVF have adversely affected in vitro fertilization (IVF) outcomes worldwide. All-freeze cycles (embryo banking, EB) with subsequently deferred thaw cycles are such an "add-on" and, because of greatly diverging reported outcomes, have become increasingly controversial. Based on "modeling" with selected patient populations, we in this study investigated whether reported outcome discrepancies may be the consequence of biased patient selection. Results: In four distinct retrospective case control studies, we modeled in four cohort pairings how cryopreservation with subsequent thaw cycles affects outcomes differently in good-, average- and poor-prognosis patients: (i) 127 fresh vs. 193 frozen donor-recipient cycles to model best-prognosis patients; (ii) 741 autologous fresh non-donor IVF cycles vs. 217 autologous frozen non-donor IVF cycles to model average prognosis patients; (iii) 143 favorably selected autologous non-donor IVF cycles vs. the same 217 frozen autologous cycles non-donor to monitor good- vs. average-prognosis patients; and (iv) 598 average and poor-prognosis autologous non-donor cycles vs. the same 217 frozen autologous non-donor cycles to model poor vs. average prognosis patients. In best-prognosis patients, EB marginally improved IVF outcomes. In unselected patients, EB had no effects. In poor-prognosis patients, EB adversely affected IVF outcomes. Unexpectedly, the study also discovered independent-of-age-associated chromosomal abnormalities, a previously unreported effect of recipient age on miscarriage risk in donor-egg recipients. Conclusions: In poor-prognosis patients, EB cycles should be considered contraindicated. In intermediate-prognosis patients EB does not appear to change outcomes, not warranting additional cost and time delays. Therefore, only good-prognosis patients are candidates for EB, though they will experience only marginal benefits that may not be cost-effective. [ABSTRACT FROM AUTHOR]

Due to their cardiovascular protective effect, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) represent breakthrough therapies for type 2 diabetes mellitus (T2DM). In this review article, we discuss the mechanistic and clinical synergies that make the combined use of GLP-1RAs and SGLT2is appealing in patients with T2DM. Overall, the presented cumulative evidence supports the benefits of GLP-1RA plus SGLT2i combination therapy on metabolic-cardiovascular-renal disease in patients with T2DM, with a low hypoglycemia risk. Accordingly, we encourage the adoption of GLP-1RA plus SGLT2i combination therapy in patients with T2DM and established atherosclerotic cardiovascular disease (ASCVD) or multiple risk factors for ASCVD (i.e., age ≥ 55 years, overweight/obesity, dyslipidemia, hypertension, current tobacco use, left ventricular hypertrophy, and/or proteinuria). Regarding renal effects, the evidence of SGLT2is in preventing kidney failure is more abundant than for GLP-1RAs, which showed a beneficial effect on albuminuria but not on hard kidney endpoints. Hence, in case of persistent albuminuria and/or uncontrolled metabolic risks (i.e., inadequate glycemic control, hypertension, overweight/obesity) on SGLT2i therapy, GLP-1RAs should be considered as the preferential add-on therapy in T2DM patients with chronic kidney disease. Despite the potential clinical benefits of GLP-1RA plus SGLT2i combination therapy in patients with T2DM, several factors may delay this combination to become a common practice soon, such as reimbursement and costs associated with polypharmacy. Altogether, when administering GLP-1RA plus SGLT2i combination therapy, it is important to adopt an individualized approach to therapy taking into account individual preferences, costs and coverage, toxicity profile, consideration of kidney function and glucose-lowering efficacy, desire for weight loss, and comorbidities. [ABSTRACT FROM AUTHOR]

This article discusses a new bioinformatics research tool that is being developed to identify genes involved in prenatal syndromes based on ultrasound phenotypes. The tool uses an internal database that links ultrasound fetal phenotypes to genes curated by experts in prenatal diagnosis of rare diseases. The tool was tested on 10 cases of CHARGE Syndrome and accurately identified the gene and syndrome in 90% of the cases. Comparative analyses with other available solutions showed that the research tool outperformed other apps in finding the correct gene and/or syndrome. The article concludes that early gene detection of rare syndromes can be significantly improved using research tools specifically designed for prenatal phenotypes. [Extracted from the article]

A correction is presented to the article "Basal Insulinotherapy in Patients Living with Diabetes in France: The EF‑BI Study" which appeared in the previous issue of the periodical.

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%; I2 = 98%). Intensive care unit (ICU) admission was required for 33% (95% CI 21–45%; I2 = 99%). Hospital mortality rate was 10% (95% CI 7–13%; I2 = 83%) and ICU mortality rate was 23% (95% CI 12–34%; I2 = 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 FROM AUTHOR]

This study aims to assess whether increased utilization for preimplantation genetic testing for aneuploidy (PGT-A) relates to improved live birth rates in IVF and whether IVF clinic ownership relates to PGT-A utilization. In a retrospective cohort study involving > 90% of US IVF clinics reporting to the Center for Disease Control and Prevention (CDC), stratified for ages (< 35, 35–37, 38–40, 41–42, and ≥ 43 years), and with reference point cycle start, we investigated whether PGT-A utilization related to live birth rates and ownership format as either physician-, academic/hospital/military, or equity/venture capital (VC) owned clinics. The lowest PGT-A-utilizing clinics reported significantly better live birth rates than the highest-utilizing clinics. Youngest patients (under age 35) were most adversely affected by high PGT-A utilization. Clinic ownership, moreover, is significantly related to the utilization of PGT-A, with equity and/or venture capital (VC)-owned clinics being significantly overrepresented among high-utilizing clinics in comparison to clinics owned by private physicians or by academia, hospitals, and the military. PGT-A, overall, reduces live birth chances in IVF, with the risks of adverse outcome effects increasing with growing PGT-A utilization in primarily younger women under age 35. Equity/VC ownership favors increasing PGT-A utilization in comparison to private physician and academic/hospital/military clinic ownership. These findings suggest intervention strategies to reverse excessive PGT-A utilization. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Identifying patients who will receive renal replacement therapy (RRT) during intensive care unit (ICU) stay is a major challenge for intensivists. The objective of this study was to evaluate the performance of physicians in predicting the need for RRT at ICU admission and at acute kidney injury (AKI) diagnosis. Methods: Prospective, multicenter study including all adult patients hospitalized in 16 ICUs in October 2020. Physician prediction was estimated at ICU admission and at AKI diagnosis, according to a visual Likert scale. Discrimination, risk stratification and benefit of physician estimation were assessed. Mixed logistic regression models of variables associated with risk of receiving RRT, with and without physician estimation, were compared. Results: Six hundred and forty-nine patients were included, 270 (41.6%) developed AKI and 77 (11.8%) received RRT. At ICU admission and at AKI diagnosis, a model including physician prediction, the experience of the physician, SOFA score, serum creatinine and diuresis to determine need for RRT performed better than a model without physician estimation with an area under the ROC curve of 0.90 [95% CI 0.86–0.94, p < 0.008 (at ICU admission)] and 0.89 [95% CI 0.83–0.93, p = 0.0014 (at AKI diagnosis)]. In multivariate analysis, physician prediction was strongly associated with the need for RRT, independently of creatinine levels, diuresis, SOFA score and the experience of the doctor who made the prediction. Conclusion: As physicians are able to stratify patients at high risk of RRT, physician judgement should be taken into account when designing new randomized studies focusing on RRT initiation during AKI. [ABSTRACT FROM AUTHOR]

Background: CAR-T cell (chimeric antigen receptor T) therapy has emerged as an effective treatment of refractory hematological malignancies. Intensive care management is intrinsic to CAR-T cell therapy. We aim to describe and to assess outcomes in critically ill CAR-T cell recipients. Study design and methods: Hospital-wide retrospective study. Consecutive CAR-T cell recipients requiring ICU admission from July 2017 and December 2020 were included. Results: 71 patients (median age 60 years [37–68]) were admitted to the ICU 6 days [4–7] after CAR-T cell infusion. Underlying malignancies included diffuse large B cell lymphoma (n = 53, 75%), acute lymphoblastic leukemia (17 patients, 24%) and multiple myeloma (n = 1, 1.45%). Performance status (PS) was 1 [1–2]. Shock was the main reason for ICU admission (n = 40, 48%). Isolated cytokine release syndrome (CRS) was the most common complication (n = 33, 46%), while 21 patients (30%) had microbiologically documented bacterial infection (chiefly catheter-related infection). Immune effector cell-associated neurotoxicity syndrome was reported in 26 (37%) patients. At ICU admission, vasopressors were required in 18 patients (25%) and invasive mechanical ventilation in two. Overall, 49 (69%) and 40 patients (56%) received tocilizumab or steroids, respectively. Determinant of mortality were the reason for ICU admission (disease progression vs. sepsis or CRS (HR 4.02 [95%CI 1.10–14.65]), Performance status (HR 1.97/point [95%CI 1.14–3.41]) and SOFA score (HR 1.16/point [95%CI 1.01–1.33]). Conclusions: Meaningful survival could be achieved in up to half the CAR-T cell recipients. The severity of organ dysfunction is a major determinant of death, especially in patients with altered performance status or disease progression. [ABSTRACT FROM AUTHOR]

Background. The objectives of this study were (1) to determine factors associated with impaired sleep and (2) to evaluate the relationship between impaired sleep and the outcome. Methods. Secondary analysis of a prospective observational cohort study in 54 intensive care units in France and Belgium. Sleep quality was quantified by the patients with a semi-quantitative scale. Results. Among the 389 patients included, 40% reported poor sleep during the first night in the ICU and the median (interquartile) total sleep time was 4 h (2–5). Factors independently associated with poor sleep quality were the SOFA score (odds ratio [OR] 0.90, p = 0.037), anxiety (OR 0.43, p = 0.001) and the presence of air leaks (OR 0.52, p = 0.013). Factors independently associated with short-estimated sleep duration (<4 h) were the SOFA score (1.13, p = 0.005), dyspnea on admission (1.13, p = 0.031) and the presence of air leaks (1.92, p = 0.008). Non-invasive ventilation failure was independently associated with poor sleep quality (OR 3.02, p = 0.021) and short sleep duration (OR 0.77, p = 0.001). Sleep quality and duration were not associated with an increase in mortality or length of stay. Conclusions. The sleep of patients with ARF requiring NIV is impaired and is associated with a high rate of NIV failure. [ABSTRACT FROM AUTHOR]

World War II caused a significant problem of missing persons. It is estimated that it resulted in between 8 and 10 million missing in Europe alone. This article examines three categories of missing – civilians, children, and Jews – and assesses the phenomenon's short-term effects. Facing the need to deal with the problem, the Allied armies and the humanitarian organizations came to the realization that it must be dealt with as an issue with political implications. It is suggested that missing persons should be included as a third category in the results of the war, in addition to the living and the dead. [ABSTRACT FROM AUTHOR]

Transcatheter aortic valve implantation (TAVI) has established as a gold standard in the treatment of elderly patients with severe aortic stenosis. Vascular access marks the first step in a TAVI procedure where the transfemoral access is preferred. Therefore, vascular complications are one of the main concerns of operators. With the increasing number of TAVIs performed, the focus is on the prevention and management of vascular complications. Illustrated by a clinical case, this article attempts to review the main vascular complications, their management and how to prevent them. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy is a powerful and widely used technique for the treatment of solid tumors. Beyond its ability to destroy tumor cells, it has been demonstrated that radiotherapy can stimulate the anti-tumor immune response. Unfortunately, this effect is mainly restricted to the irradiated lesion, as tumor control outside the treated field (called the 'abscopal effect') is rarely obtained. In addition, many pro-tumoral factors prevent this anti-tumor immune response from being sustained and efficient. We previously reported that radiotherapy-activated NBTXR3 produced a significant CD8-dependent abscopal effect in immunocompetent mice bearing CT26.WT tumors, while radiotherapy failed to generate such a response. Methods: To identify the mechanisms that may explain this response, we evaluated the capacity of radiotherapy-activated NBTXR3 to modulate the immunogenicity of tumor cells by analysis of immunogenic cell death biomarkers and immunopeptidome sequencing. In vivo, we analyzed treated tumors for CD4+, CD8 + and CD68 + cell infiltrates by immunohistochemistry and digital pathology and sequenced the T cell receptor (TCR) repertoire in both treated and untreated distant tumors. Results: We showed that NBTXR3 activated by radiotherapy both increased immunogenic cell death biomarkers and modulated the immunopeptidome profile of CT26.WT cells. Immunohistochemistry analysis of treated tumors revealed a significant increase in CD4+, CD8 + and CD68 + cell infiltrates for NBTXR3 activated by radiotherapy group, compared to radiotherapy. We also measured significant modifications in TCR repertoire diversity in the radiotherapy-activated NBTXR3 group, both in treated and distant untreated tumors, compared to radiotherapy alone. Conclusions: These results indicate that radiotherapy-activated NBTXR3 can act as an effective immunomodulator, modifying tumor cell immunogenicity and impacting the lymphocyte population. [ABSTRACT FROM AUTHOR]

Aims: The aim of this multicentre study was to harmonize programmed death‐ligand 1 (PD‐L1) immunohistochemistry (IHC) and melanoma scoring. To provide a reference for PD‐L1 expression independently of the IHC protocol, PD‐L1 mRNA expression was compared with IHC. Methods and results: Standardized PD‐L1 assays (22C3, 28–8, SP142, SP263) and laboratory‐developed tests (QR1, 22C3) were evaluated on three IHC platforms with a training set (seven cases). mRNA expression was determined by RNAscope (CD274/PD‐L1 probe) and analysed with image analysis. PD‐L1 IHC findings were scored by seven blinded pathologists using the tumour proportion score (TPS), the combined positive score (CPS), and the MELscore. This method was validated by three blinded pathologists on 40 metastatic melanomas. Concordances among various antibody/platforms were high across antibodies [intraclass correlation coefficient (ICC) >0.80 for the CPS], except for SP142. Two levels of immunostaining intensity were observed: high (QR1 and SP263) and low (28–8, 22C3, and SP142). Reproducibilities across pathologists were higher for QR1 and SP263 (ICC ≥0.87 and ICC ≥0.85 for the TPS and the CPS, respectively). QR1, SP263 and 28–8 showed the highest concordance with mRNA expression. We developed a standardized method for PD‐L1 immunodetection and scoring, tested on 40 metastatic melanomas. Concordances among antibodies were excellent for all criteria, and concordances among pathologists were better for the MELscore than for other scores. Conclusion: Harmonization of PD‐L1 staining and scoring in melanomas with good concordance is achievable with the PD‐L1 IHC protocols applied to other cancers; this reproducible approach can simplify daily practice. [ABSTRACT FROM AUTHOR]

Background We describe the epidemiological, clinical, and prognostic aspects of 177 tularemia cases diagnosed at the National Reference Center for rickettsioses, coxiellosis, and bartonelloses between 2008 and 2017. Methods All patients with a microbiological diagnosis of tularemia made in the laboratory were included. Clinical and epidemiological data were collected retrospectively from clinicians in charge of patients using a standardized questionnaire. Diagnostic methods used were indirect immunofluorescence serology, real-time polymerase chain reaction (PCR), and universal PCR targeting the 16S ribosomal ribonucleic acid gene. Results The series included 54 females and 123 males (sex ratio, 2.28; mean age, 47.38 years). Eighty-nine (50.2%) were confirmed as having tularemia on the basis of a positive Francisella tularensis PCR or seroconversion, and 88 (49.8%) were considered as probable due to a single positive serum. The regions of France that were most affected included Pays de la Loire (22% of cases), Nouvelle Acquitaine (18.6% of cases), and Grand Est (12.4% of cases). Patients became infected mainly through contact with rodents or game (38 cases, 21.4%), through tick-bites (23 cases, 12.9%), or during outdoor leisure activities (37 cases, 20.9%). Glandular and ulceroglandular forms were the most frequent (109 cases, 61.5%). Two aortitis, an infectious endocarditis, a myocarditis, an osteoarticular infection, and a splenic hematoma were also diagnosed. Tularemia was discovered incidentally in 54.8% of cases. Seventy-eight patients were hospitalized, and no deaths were reported. Conclusions Our data suggest that in an endemic area and/or in certain epidemiological contexts, tularemia should be sought to allow an optimized antibiotic therapy and a faster recovery. [ABSTRACT FROM AUTHOR]

Acting on diet is one of the changes required – in combination with actions on food production, transformation, and waste – to address the challenges of reducing the environmental impact of our food systems and eliminating all forms of malnutrition. The number of studies exploring how to move towards a more sustainable diet has exploded over the past decades, but there is a need to facilitate their understanding and use by policy makers and all other stakeholders possibly influencing diet sustainability. The aim of the present article is to propose a categorization of studies into 4 approaches, based on the type of methodology used to explore diet sustainability, and to highlight the principles, advantages, and limitations of each approach in order to help study users in their interpretation. The 4 approaches are: assessment of sustainability characteristics of hypothetical diets (approach 1) or existing diets (approach 2), identification of existing "positive deviants" (approach 3), and design of more sustainable diets with constrained optimization (approach 4). Specificities and key findings drawn from each approach are described, and challenges for future studies are discussed. [ABSTRACT FROM AUTHOR]

Purpose: Growth hormone (GH) supplementation in association with in vitro fertilization (IVF) is worldwide again increasing, even though study outcomes have been discrepant. Since GH acts via insulin-like growth factor-1 (IGF-1), its utilization in IVF would only seem to make sense with low IGF-1. We, therefore, determined whether IGF-I levels affect IVF outcomes. Methods: Retrospectively, 302 consecutive first fresh, non-donor IVF cycles were studied, excluding patients on GH supplementation. Patients were divided into 3 subgroups: IGF-1 in lower 25th percentile (group A, < 132 ng/mL, n = 64); 25th–75th percentile (B, 133–202 ng/mL, n = 164), and upper 25th percentile (C, > 202 ng/mL, n = 74). IGF-1 was tested immunochemiluminometric with normal range at 78–270 ng/mL. Because of the study patients' adverse selection and low pregnancy chances, the main outcome measure for the study was cycle cancellation. Secondary outcomes were oocyte numbers, embryos transferred, pregnancies, and live births. Results: Group A was significantly older than B and C (P = 0.019). IGF-1 decreased with increasing age per year by 2.2 ± 0.65 ng/mL (P = 0.0007). FSH was best in group B and worst in A (trend, P = 0.085); AMH was best in B and worst in A (N.S.). Cycle cancellations were lowest in C (11.6%) and highest in A (25.0%; P = 0.042). This significance further improved with age adjustment (P = 0.021). Oocytes, embryo numbers, pregnancies, and live birth rates did not differ, though oocyte numbers trended highest in B. Conclusions: Here presented results support the hypothesis that IGF-1 levels affect IVF outcomes. GH treatments, therefore, may be effective only with low IGF-1. [ABSTRACT FROM AUTHOR]

Context Collective gardens are increasingly considered a tool to promote health and well-being. Objective In this systematic review, we critically appraise quantitative studies exploring the potential health benefits of urban collective garden participation. Data Sources Articles published between January 2000 and August 2020 were used. Data Extraction All original research studies reporting at least 1 health outcomes associated with urban collective gardening in free-living adults from Western and other high-income countries were included. Of 1261 articles identified, 15 were included in the systematic review. Methodological quality was assessed by applying the criteria of the Quantitative Study Quality Assessment Tool. Analysis A wide range of health indicators was used. Collective gardening was associated with higher fruit and vegetable consumption than was nongardening. Mixed results were found for physical activity and physiological health. A positive association was found in most studies with mental health and social health. However, the vast majority of included studies were cross-sectional and presented selection bias (n = 13 of 15 for both) and very few used objective measurement methods (n = 3 of 15). Conclusions Longitudinal studies allowing the exploration of causal relationships are needed before the health benefits of collective garden participation suggested by existing studies can be confirmed. [ABSTRACT FROM AUTHOR]

The arithmetic , p-arithmetic , and incoherent intersections between pairs of closed geodesics on a modular or Shimura curve are defined, and some of their expected algebraicity and factorisation properties are examined. These properties follow in a special case from the conjectures of [DV] on the RM values of rigid meromorphic cocycles, and are inspired from the recent work of James Rickards [Ri] and Xavier Guitart, Marc Masdeu and Xavier Xarles [GMX] in the quaternionic setting. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) remains associated with short- and long-term mortality and morbidity. Doppler-based renal resistive index (RI) is a rapid and non-invasive tool that was proposed to assess renal perfusion, identify early risk of AKI, or predict renal recovery course. Central venous pressure and mean perfusion pressure have been associated with risk of AKI in observational studies but may reflect macrovascular perfusion and congestion rather than intra-renal hemodynamic dysregulation [[1]]. Although magnetic resonance imaging (MRI) may assess renal perfusion and oxygenation changes, relevancy of this technique at bedside for critically ill patients is debatable [[3]]. [Extracted from the article]

Whether enjoying the lucid prose of a favourite author or slogging through some other writer's cumbersome, heavy-set prattle (full of parentheses, em dashes, compound adjectives, and Oxford commas), readers will notice stylistic signatures not only in word choice and grammar but also in punctuation itself. Indeed, visual sequences of punctuation from different authors produce marvellously different (and visually striking) sequences. Punctuation is a largely overlooked stylistic feature in stylometry, the quantitative analysis of written text. In this paper, we examine punctuation sequences in a corpus of literary documents and ask the following questions: Are the properties of such sequences a distinctive feature of different authors? Is it possible to distinguish literary genres based on their punctuation sequences? Do the punctuation styles of authors evolve over time? Are we on to something interesting in trying to do stylometry without words, or are we full of sound and fury (signifying nothing)? In our investigation, we examine a large corpus of documents from Project Gutenberg (a digital library with many possible editorial influences). We extract punctuation sequences from each document in our corpus and record the number of words that separate punctuation marks. Using such information about punctuation-usage patterns, we attempt both author and genre recognition, and we also examine the evolution of punctuation usage over time. Our efforts at author recognition are particularly successful. Among the features that we consider, the one that seems to carry the most explanatory power is an empirical approximation of the joint probability of the successive occurrence of two punctuation marks. In our conclusions, we suggest several directions for future work, including the application of similar analyses for investigating translations and other types of categorical time series. [ABSTRACT FROM AUTHOR]

Aim and hypotheses: The THEMIS randomized trial compared ticagrelor plus aspirin versus placebo plus aspirin for patients with stable coronary artery disease and type 2 diabetes mellitus (CAD-T2DM), and without prior myocardial infarction (MI) or stroke. The aim of the study was to quantify the size of the CAD-T2DM population without prior MI or stroke population in a real-world setting, and more specifically populations with similar THEMIS selection criteria (THEMIS-like and THEMIS-PCI-like populations), as well as their risk of major outcomes in current practice. Methods: A 2-year follow-up cohort study included all CAD-T2DM without MI/stroke prevalent patients on January 1st, 2014 in the SNDS French nationwide claims database. The THEMIS-like population concerned those ≥ 50 years of age with similar THEMIS inclusion and exclusion criteria. Prevalence was standardized to the European population. The cumulative incidence function was used to estimate the incidence of clinical outcomes (MI, ischemic stroke, and major bleeding according to the TIMI classification) with death as competing risk, and the Kaplan–Meier estimate for all-cause death and a composite outcome of MI, stroke and all-cause death. Results: From a population of about 50 million adults, the prevalence of CAD-T2DM without MI/stroke, THEMIS-like and THEMIS-PCI-like populations was respectively at 6.04, 1.50 and 0.27 per 1000 adults, with a mean age of 72.7, 72.3 and 70.9 years and less comorbidities and diabetic complications for the THEMIS-like and THEMIS-PCI-like population. The 2-year cumulative incidence was respectively 1.7%, 1.3% and 1.6% for MI, 1.7%, 1.5% and 1.4% for stroke, 4.8%, 3.1% and 2.9% for major bleeding, 13.6%, 9.7% and 6.8% for all-cause death, and 16.2%, 12.0% and 9.5% for the composite outcome. Conclusion: THEMIS-like prevalence was estimated at 1.50 per 1,000 adults, representing about a quarter of CAD-T2DM without MI/stroke patients, and 0.27 per 1000 adults for the THEMIS-PCI-like populations. In current French practice, the median age of both these populations was about 5–6 years older than in the THEMIS trial, with a 2-year incidence of major outcomes between two or four time above the ones of the placebo arm of the THEMIS trial using very close definitions. Registration No. EUPAS27402 (http://www.ENCEPP.eu). [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is now recognized as a heterogeneous syndrome that not only affects acute morbidity and mortality, but also a patient's long-term prognosis. In this narrative review, an update on various aspects of AKI in critically ill patients will be provided. Focus will be on prediction and early detection of AKI (e.g., the role of biomarkers to identify high-risk patients and the use of machine learning to predict AKI), aspects of pathophysiology and progress in the recognition of different phenotypes of AKI, as well as an update on nephrotoxicity and organ cross-talk. In addition, prevention of AKI (focusing on fluid management, kidney perfusion pressure, and the choice of vasopressor) and supportive treatment of AKI is discussed. Finally, post-AKI risk of long-term sequelae including incident or progression of chronic kidney disease, cardiovascular events and mortality, will be addressed. [ABSTRACT FROM AUTHOR]

Many patients develop acute kidney injury (AKI), the causes of which may be directly related to the cancer, its associated therapies, or non-cancer related factors [[3]] (Fig. Thus, the complex issues that arise in critically ill patients with underlying cancer require multidisciplinary care with a focus on patient-centered outcomes. Malignancy associated AKI Although the main risk factors for AKI in the ICU setting are common to the general ICU population, several causes related to malignancy are relatively unique. AKI is common in patients with tumor lysis syndrome (TLS), (> 80%) and in critically ill patients with myeloma (80-90%) [[5]]. [Extracted from the article]

Background: While acute kidney injury (AKI) is frequent in severe SARS-CoV2-related pneumonia ICU patients, few data are still available about its risk factors. Methods: Retrospective observational study performed in four university affiliated hospitals in Paris. AKI was defined according to the KIDGO guidelines. Factors associated with AKI were picked up using multivariable mixed-effects logistic regression. Independent risk factors of day 28 mortality were assessed using Cox model. Results: 379 patients (median age 62 [53,69], 77% of male) were included. Half of the patients had AKI (n = 195, 52%) including 58 patients (15%) with AKI stage 1, 44 patients (12%) with AKI stage 2, and 93 patients (25% with AKI stage 3). Chronic kidney disease (OR 7.41; 95% CI 2.98–18.4), need for invasive mechanical ventilation at day 1 (OR 4.83; 95% CI 2.26–10.3), need for vasopressors at day 1 (OR 2.1; 95% CI 1.05–4.21) were associated with increased risk of AKI. Day 28 mortality in the cohort was 26.4% and was higher in patients with AKI (37.4 vs. 14.7%, P < 0.001). Neither AKI (HR 1.35; 95% CI 0.78–2.32) nor AKI stage were associated with mortality (HR [95% CI] for stage 1, 2 and 3 when compared to no AKI of, respectively, 1.02 [0.49–2.10], 1.73 [0.81–3.68] and 1.42 [0.78–2.58]). Conclusion: In this large cohort of SARS-CoV2-related pneumonia patients admitted to the ICU, AKI was frequent, mostly driven by preexisting chronic kidney disease and life sustaining therapies, with unclear adjusted relationship with day 28 outcome. [ABSTRACT FROM AUTHOR]

Aim: To investigate the association between routine use of dipeptidyl peptidase‐4 (DPP‐4) inhibitors and the severity of coronavirus disease 2019 (COVID‐19) infection in patient with type 2 diabetes in a large multicentric study. Materials and Methods: This study was a secondary analysis of the CORONADO study on 2449 patients with type 2 diabetes (T2D) hospitalized for COVID‐19 in 68 French centres. The composite primary endpoint combined tracheal intubation for mechanical ventilation and death within 7 days of admission. Stabilized weights were computed for patients based on propensity score (DPP‐4 inhibitors users vs. non‐users) and were used in multivariable logistic regression models to estimate the average treatment effect in the treated as inverse probability of treatment weighting (IPTW). Results: Five hundred and ninety‐six participants were under DPP‐4 inhibitors before admission to hospital (24.3%). The primary outcome occurred at similar rates in users and non‐users of DPP‐4 inhibitors (27.7% vs. 28.6%; p =.68). In propensity analysis, the IPTW‐adjusted models showed no significant association between the use of DPP‐4 inhibitors and the primary outcome by Day 7 (OR [95% CI]: 0.95 [0.77–1.17]) or Day 28 (OR [95% CI]: 0.96 [0.78–1.17]). Similar neutral findings were found between use of DPP‐4 inhibitors and the risk of tracheal intubation and death. Conclusions: These data support the safety of DPP‐4 inhibitors for diabetes management during the COVID‐19 pandemic and they should not be discontinued. [ABSTRACT FROM AUTHOR]

We study the problem of the transformation of a given reactant species into an immiscible product species, as they flow through a chemically active porous medium. We derive the equation governing the evolution of the volume fraction of the species, in a one-dimensional macroscopic description, identify the relevant dimensionless numbers, and provide simple models for capillary pressure and relative permeabilities, which are quantities of crucial importance when tackling multiphase flows in porous media. We set the domain of validity of our models and discuss the importance of viscous coupling terms in the extended Darcy's law. We investigate numerically the steady regime and demonstrate that the spatial transformation rate of the species along the reactor is non-monotonous, as testified by the existence of an inflection point in the volume fraction profiles. We obtain the scaling of the location of this inflection point with the dimensionless lengths of the problem. Eventually, we provide key elements for optimization of the reactor. [ABSTRACT FROM AUTHOR]

Respiratory complications of solid organ transplant (SOT) are a diagnostic and therapeutic challenge when requiring intensive care unit (ICU) admission. We aimed at describing this challenge in a prospective cohort of SOT recipients admitted in the ICU. In this post hoc analysis of an international cohort of immunocompromised patients admitted in the ICU for an acute respiratory failure, we analyzed all SOT recipients and compared their severity, etiologic diagnosis, prognosis, and outcome according to the performance of an invasive diagnostic strategy (encompassing a fiber-optic bronchoscopy and bronchoalveolar lavage), the type of transplanted organ, and the need of invasive ventilation at day 1. Among 1611 patients included in the primary study, 142 were SOT recipients (kidney, n = 73; 51.4%; lung, n = 33; 23.2%; liver, n = 29; 20.4%; heart, n = 7; 4.9%). Lung transplant recipients were younger than other SOT recipients, and severity did not differ across type of received organ. An invasive diagnostic strategy was more frequently performed in lung transplant recipients with a trend toward a higher rate of bacterial etiology in lung than kidney transplant recipients. Overall ICU survival of SOT recipients was 75.4%. Invasive diagnostic strategy, type of transplanted organ, and need of invasive mechanical ventilation at day 1 did not affect ICU prognosis. ICU management of hypoxemic acute respiratory failure in SOT recipients translated into a low ICU mortality rate, whatever the transplanted organ or the acute respiratory failure cause. The post-ICU burden of acute respiratory failure SOT recipients remains to be investigated. [ABSTRACT FROM AUTHOR]

Automated communication bots follow deterministic local rules that either respond to programmed instructions or learned patterns. On the microlevel, their automated and reactive behavior makes certain parts of the communication dynamic more predictable. Studying communicative turns in the editing history of Wikipedia, we find that on the macrolevel, the overall emergent communication process becomes both more complex and less predictable. The increased presence of bots is the main explanatory variable for these seemingly contradictory tendencies. In short, individuals introduce bots to make communication more simple and predictable but end up with a large-scale dynamic that is more complex and more uncertain. We explain our results with the information processing nature of complex systems. The article also serves as a showcase for the use of information-theoretic measures from dynamical systems theory to assess changes in communication dynamics provoked by algorithms. [ABSTRACT FROM AUTHOR]

Following the publication of the COMPASS trial, the European Medicines Agency has approved a regimen of combination of rivaroxaban 2.5 mg twice daily and a daily dose of 75–100 mg acetylsalicylic acid (ASA) for patients with coronary artery disease (CAD) or symptomatic peripheral artery disease (PAD) at high risk of ischemic events. However, the applicability of such a therapeutic strategy in France is currently unknown. To describe the proportion of patients eligible to COMPASS in France, their baseline clinical characteristics and the rate of major adverse cardiovascular events, using the REACH registry. From the the REduction of Atherothrombosis for Continued Health (REACH) registry database, a large international registry of patients with, or at risk, of atherothrombosis, we analyzed patients included in France with either established CAD and/or PAD and fulfilling the inclusion and exclusion criteria of the COMPASS trial. The ischemic outcome was a composite of cardiovascular (CV) death, myocardial infarction (MI), or stroke, and serious bleeding were defined as haemorrhagic stroke or bleeding leading to hospitalization or transfusion. Among more than 65000 patients enrolled in REACH, 2.012 patients were evaluable and enrolled in France. Among them, 1194 patients (59.3%) were eligible to COMPASS. The main reasons for exclusion of the COMPASS trial, were high bleeding risk (59.1%), anticoagulant use (43.4%), requirement for dual antiplatelet therapy within 1 year of an ACS or PCI (24.7%). In the "COMPASS eligible population", the rate of MACE (CV, MI and stroke) at 4 years follow-up was 13.4% [11.3–15.8], and serious bleeding was 2.5% at 4 years [1.6–3.4]. Patients with polyvascular disease (n = 219) had the highest rate of MACE, compared with patients with CAD only and PAD only (19.1% [13.9–26.1] vs. 11.6% [9.1–14.8] vs 13.2% [9.2–18.8], P < 0.0001, respectively). The COMPASS therapeutic strategy in France appears to be applicable to more than half of CAD or PAD patients. This population appears at high residual risk of atherothrombotic events, and patients with polyvascular disease experienced the highest rate of events. [ABSTRACT FROM AUTHOR]

Mathematical optimisation of diets is generally used to translate nutrient‐based recommendations into healthy food choices but can also be used to assess the possible impact of food‐based dietary guidelines (FBDG) on nutrient intakes. Optimisation of individual diets, which allows individual variability of food consumption to be taken into account, generates more robust results and more realistic diets than population diet optimisation. It was used to simulate the impact on nutrient intakes of complying with the new French FBDGs. For each observed diet of adults in the French INCA2 survey, a new isoenergetic diet was designed to meet all food consumption frequencies recommended by the new French FBDGs, as interpreted by the constraints included in a model called DP2. Because the dairy food group is the only one whose guideline has been reduced (from 3 to 2 portions/day) compared to the previous FBDGs, an alternative model, called DP3, imposing 3 daily portions of dairy products instead of 2 was also tested. Diets optimised with the DP2 model had lower energy density and higher nutrient density than the observed diets, and inadequate intakes decreased for most vitamins and minerals. With the alternative DP3 model, the decrease in saturates was less pronounced than with 2 portions/day of dairy products (13.8%, 11.9% and 12.8% energy in observed diets and in DP2 and DP3, respectively), but calcium adequacy was improved instead of being worsened (51%, 58% and 16% of inadequacy in observed diets and in diets modelled with 2 portions/day and 3 portions/day of dairy products, respectively). Individual diet optimisation is a powerful tool for assessing the nutritional relevance of existing FBDGs and to test possible alternatives.comment="AUTHOR: Please suggest whether the term 'population-diet optimisation' can be changed as 'population-diet optimisation' throughout the article."comment="Change as you want"comment="AUTHOR: Please suggest whether the term 'Individual-diet optimisation' can be changed as 'Individual diet optimisation' throughout the article."comment="Change as you want" [ABSTRACT FROM AUTHOR]

This paper wishes to explain, using qualitative sociology, an epidemiological finding: that the extent of recovery following stroke is class-based and that patients from the working classes and lower socioeconomic groups are more vulnerable to functional impairments following stroke than those from higher socioeconomic groups. Based on a 15-month ethnographic study of neurology and rehabilitation units, the paper shows that hospital rehabilitation after stroke is shaped by a "school form," and that it therefore proves far more efficient with patients who have scholastic dispositions, more frequently associated with people from the middle and upper classes with considerable cultural capital. "What is lost" during a stroke and "what is regained" after is not only a question of location in the brain and how serious the neurological incident was, but also correlates with class-based dispositions and attitudes towards practice, as well as language and learning situations. The notion of "school form" can be useful outside the school context per se when it comes to understanding social inequalities, since it can, in this case, explain the class-based processes through which health inequalities arise. [ABSTRACT FROM AUTHOR]

The recent results of Cardiovascular Outcomes Trials (CVOTs) in type 2 diabetes have clearly established the cardiovascular (CV) safety or even the benefit of two therapeutic classes, Glucagon-Like Peptide-1 receptor agonists (GLP-1 RA) and Sodium-Glucose Co-Transporter-2 inhibitors (SGLT-2i). Publication of the latest CVOTs for these therapeutic classes also led to an update of ESC guidelines and ADA/EASD consensus report in 2019, which considers using GLP-1 RA or SGLT-2i with proven cardiovascular benefit early in the management of type 2 diabetic patient with established cardiovascular disease (CVD) or at high risk of atherosclerotic CVD. The main beneficial results of these time-to event studies are supported by conventional statistical measures attesting the effectiveness of GLP-1 RA or SGLT2i on cardiovascular events (absolute risk, absolute risk difference, relative risk, relative risk reduction, odds ratio, hazard ratio). In addition, another measure whose clinical meaning appears to be easier, the Number Needed to Treat (NNT), is often mentioned while discussing the results of CVOTs, in order to estimating the clinical utility of each drug or sometimes trying to establish a power ranking. While the value of the measure is admittedly of interest, the subtleties of its computation in time-to-event studies are little known. We provide in this article a clear and practical explanation on NNT computation methods that should be used in order to estimate its value, according to the type of study design and variables available to describe the event of interest, in any randomized controlled trial. More specifically, a focus is made on time-to-event studies of which CVOTs are part, first to describe in detail an appropriate and adjusted method of NNT computation and second to help properly interpreting NNTs with the example of CVOTs conducted with GLP-1 RA and SGLT-2i. We particularly discuss the risk of misunderstanding of NNT values in CVOTs when some specific parameters inherent in each study are not taken into account, and the following risk of erroneous comparison between NNTs across studies. The present paper highlights the importance of understanding rightfully NNTs from CVOTs and their clinical impact to get the full picture of a drug's effectiveness. [ABSTRACT FROM AUTHOR]

Objective: To identify food choices allowing the fulfillment of nutritionally adequate diets resembling actual food patterns at the lowest cost achievable for the Brazilian population, stratified by income level. Methods: Food consumption and prices were obtained from the Household Budget Survey (n = 55,970 households) and National Dietary Survey (n = 32,749 individuals). The sample was stratified into capitals of the states and further by income levels according to the official minimum wage (totaling 108 geographic-economic strata, or GES). Linear programming models were performed for each GES in order to find the lowest cost of diets that meet a set of nutritional constraints. In order to find realistic diets, constraints referring to preferences were introduced in the models allowing optimized food quantities to depart progressively from the current intake for each food and food group. The impact of meeting each target nutrient was assessed by performing models removing each nutrient at the time. Results: The observed and optimized diet costs were US$2.16 and US$2.58 per capita/day. The highest cost increment and the greatest food shifts were observed in the lowest income level. The nutrient adequacy was reached by mainly increasing fruits and vegetables, beans, fish and seafood, dairy, nuts, and eggs; and reducing red and processed meat, chicken, margarine and butter, cookies, cakes, sugar-sweetened beverages, and sauces. As the departure from the current intakes increase, the optimized healthy diet cost reduced. In the lowest income, the lowest cost increment was about US$ 0.10; in the higher income levels, it tended to be cheaper than the observed cost. Calcium was the most expensive nutrient to meet adequacy. Conclusion: Nutritionally adequate diets are possible but costlier than the observed. [ABSTRACT FROM AUTHOR]

A stochastic model is proposed to simulate the propagation of an acoustic wave in a random medium characterized by weak velocity fluctuations. After the acoustic wave propagation through a random velocity field, the propagation field becomes itself a random field. In the developed stochastic approach, the wave field in such random medium is modeled by the combination of the wave field in a mean homogeneous medium and of fluctuation corrections. These corrections are provided by a random field generator whose inputs are the statistical moments of the travel times. Using this stochastic modeling, the propagation of both an incident plane wave and an acoustic realistic beam generated by a real transducer in a random velocity field is calculated and the corresponding simulations are validated by comparison with those obtained with a deterministic model based on geometrical optics. [ABSTRACT FROM AUTHOR]

• A new model is proposed for 2D elastic wave diffraction by a stress-free wedge. • The developed spectral functions method is valid for any wedge angle. • The numerical scheme for the spectral functions method is detailed. • The proposed model has been validated against two different numerical models. 2D elastic plane wave diffraction by a stress-free wedge is a canonical problem of interest to researchers in many different fields. To our knowledge, no fully analytical resolution has been found and semi-analytical evaluations of asymptotic approximations have therefore become a common approach. In this paper, a method called the spectral functions method is developed in the aforementioned 2D configuration. This method has the advantage of being valid for wedge angles lower and higher than π. The diffracted displacement field is expressed as an integral in terms of two unknown functions called the spectral functions. These functions are decomposed into two parts: one which can be computed analytically and the other which is approached numerically using a collocation method. The details of the corresponding numerical scheme are given and the method is validated numerically for all wedge angles. [ABSTRACT FROM AUTHOR]

An analysis of the FROG-ICU database could demonstrate a positive effect on one-year mortality of receiving ACEI/ARBs at ICU discharge in patients with acute kidney disease (AKD) [[16]]. Effect of human recombinant alkaline phosphatase on seven-day creatinine clearance in patients with sepsis-associated acute kidney injury: a randomized clinical trial. 11 Barbar SD, Clere-Jehl R, Bourredjem A. Timing of renal-replacement therapy in patients with acute kidney injury and sepsis. 16 Gayat E, Hollinger A, Cariou A. Impact of angiotensin-converting enzyme inhibitors or receptor blockers on post-ICU discharge outcome in patients with acute kidney injury. [Extracted from the article]

Information dynamics provides a broad set of measures for characterizing how a dynamical system stores, processes, and transmits information. While estimators for these measures are commonly used in applications, the statistical properties of these estimators for finite time series are not well understood. In particular, the precision of a given estimate is generally unknown. We develop confidence intervals for generic information-dynamic parameters using a bootstrap procedure. The bootstrap procedure uses an echo state network, a particular instance of a reservoir computer, as a simulator to generate bootstrap samples from a given time series. We perform a Monte Carlo analysis to investigate the performance of the bootstrap confidence intervals in terms of their coverage and expected lengths with two model systems and compare their performance to a simulator based on the random analog predictor. We find that our bootstrap procedure generates confidence intervals with nominal, or near nominal, coverage of the information-dynamic measures, with smaller expected length than the random analog predictor-based confidence intervals. Finally, we demonstrate the applicability of the confidence intervals for characterizing the information dynamics of a time series of sunspot counts. [ABSTRACT FROM AUTHOR]

Background: The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial found clinical benefit of low-dose rivaroxaban plus aspirin, but at the expense of increased bleeding risk in patients with stable vascular disease.Objectives: This study evaluated the balance of ischemic and bleeding risks according to the presence of ≥1 enrichment criteria in "COMPASS-eligible" patients.Methods: Key COMPASS selection criteria were applied to identify a COMPASS-eligible population (n = 16,875) from the REACH (REduction of Atherothrombosis for Continued Health) Registry of stable atherothrombotic patients. Ischemic outcome was the composite of cardiovascular death, myocardial infarction, or stroke. Bleeding outcome was serious bleeding (hemorrhagic stroke, hospitalization for bleeding, transfusion).Results: Patients were categorized according to the enrichment criteria: age >65 years (81.5%), diabetes (41.0%), moderate renal failure (40.2%), peripheral artery disease (33.7%), current smoker (13.8%), heart failure (13.3%), ischemic stroke (11.1%), and asymptomatic carotid stenosis (8.7%). Each criterion was associated with a consistent increase in ischemic and bleeding events, but no individual subgroup derived a more favorable trade-off. Patients with multiple criteria had a dramatic increase in ischemic risk (7.0% [95% confidence interval (CI): 5.6% to 8.7%], 12.5% [95% CI: 11.1% to 14.1%], 16.6% [95% CI: 14.7% to 18.6%], and 21.8% [95% CI: 19.9% to 23.9%] with 1, 2, 3, and ≥4 enrichment criteria, respectively), but a more modest absolute increase in bleeding risk (1.5% [95% CI: 0.9% to 2.1%], 1.8% [95% CI: 1.3% to 2.2%], 2.0% [95% CI: 1.5% to 2.6%], 3.2% [95% CI: 2.6% to 3.9%]).Conclusions: In a population of stable vascular patients at high risk of atherothrombotic events, the subset with multiple enrichment criteria had a greater absolute increase in ischemic than in bleeding risk and may be good candidates for low-dose rivaroxaban in addition to aspirin. [ABSTRACT FROM AUTHOR]

Purpose: The number of averted deaths due to therapeutic advances in oncology and hematology is substantial and increasing. Survival of critically ill cancer patients has also improved during the last 2 decades. However, these data stem predominantly from unadjusted analyses. The aim of this study was to assess the impact of ICU admission year on short-term survival of critically ill cancer patients, with special attention on those with neutropenia.Methods: Systematic review and meta-analysis of individual data according to the guidelines of meta-analysis of observational studies in epidemiology.Datasource: Pubmed and Cochrane databases.Eligibility Criteria: Adult studies published in English between May 2005 and May 2015.Results: Overall, 7354 patients were included among whom 1666 presented with neutropenia at ICU admission. Median ICU admission year was 2007 (IQR 2004-2010; range 1994-2012) and median number of admissions per year was 693 (IQR 450-1007). Overall mortality was 47.7%. ICU admission year was associated with a progressive decrease in hospital mortality (OR per year 0.94; 95% CI 0.93-0.95). After adjustment for confounders, year of ICU admission was independently associated with hospital mortality (OR for hospital mortality per year: 0.96; 95% CI 0.95-0.97). The association was also seen in patients with neutropenia but not in allogeneic stem cell transplant recipients.Conclusion: After adjustment for patient characteristics, severity of illness and clustering, hospital mortality decreased steadily over time in critically ill oncology and hematology patients except for allogeneic stem cell transplant recipients. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to investigate center effects on hospital mortality of ICU patients with hematologic malignancies and to explore interactions between center and patients characteristics.Design: Multicenter prospective cohort.Setting: Seventeen ICUs across France and Belgium.Patients: One-thousand eleven patients with hematologic malignancies hospitalized in ICUs.Interventions: Reanalysis of the original data using state-of-the-art statistical methods with permutation procedures for testing multiple random effects.Measurements and Main Results: Average crude mortality was 39% and varied from 11% to 58% across centers. There was a significant center effect on the mean hospital mortality, after adjustment on individual prognostic factors (p < 0.001; median adjusted odds ratio for center effect 1.57 [interquartile range, 1.24-2.18]). There was also a quantitative interaction between center and the effect of the Sequential Organ Failure Assessment score: higher scores were associated with higher mortality (odds ratio for 1 point = 1.24 on average; 95% CI, 1.15-1.33) but with a magnitude that depended on center (p = 0.028).Conclusions: Between-center heterogeneity in hospital mortality was confirmed after adjustment for individual prognostic factors. It was partially explained by center experience in treating oncology patients. Interestingly, center effect was similar in magnitude to that of known mortality risk factors. [ABSTRACT FROM AUTHOR]