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Acute myeloid leukemia (AML) is a complex disease, and its treatment needs to be adjusted to the risk, which is conferred by cytogenetics and molecular markers. Cytarabine is the main drug to treat AML, and it has been suggested that the genotype of cytarabine metabolizing enzymes may have a prognostic relevance in AML. Here we report the association between the 5'-nucleotidase, cytosolic II (NT5C2) rs10883841, cytidine deaminase (CDA) rs2072671 and rs532545 genotypes and the clinical outcome of 477 intermediate-risk cytogenetic AML patients receiving cytarabine-based chemotherapy. Patients younger than 50 years old with the NT5C2 rs10883841 AA genotype had lower overall survival (OS) (p: .003; HR 2.16, 95% CI 1.29-3.61) and lower disease-free survival (DFS) (p: .002; HR 2.45, 95% CI 1.41-4.27), associated to a higher relapse incidence (p: .010; HR 2.23, 95% CI 1.21-4.12). Interestingly, subgroup analysis showed that the negative effect of the NT5C2 rs10883841 AA genotype was detected in all subgroups except in patients with nucleophosmin mutation without high ratio FLT-3 internal tandem duplication. CDA polymorphisms were associated with the complete remission rate after induction chemotherapy, without influencing OS. Further studies are warranted to determine whether this pharmacogenomic approach may be helpful to individualize AML treatment.

Background There is no reliable microbiological marker to guide the indication and the response to antiviral treatment in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the dynamics of subgenomic RNA (sgRNA) in patients with COVID-19 before and after receiving treatment with remdesivir. Methods We included consecutive patients admitted for COVID-19 who received remdesivir according to our institutional protocol and accepted to participate in the study. A nasopharyngeal swab for quantitative reverse transcriptase–polymerase chain reaction (qRT-PCR) was collected at baseline and after 3 and 5 days of treatment with remdesivir. Genomic and sgRNA were analyzed in those samples and main comorbidities and evolution were collected for the analyses. The main outcomes were early discharge (≤10 days) and 30-day mortality. Results A total of 117 patients were included in the study, of whom 24 had a negative sgRNA at baseline, with 62.5% (15/24) receiving early discharge (≤10 days) and no deaths in this group. From the 93 remaining patients, 62 had a negative sgRNA at day 5 with 37/62 (59.6%) with early discharge and a mortality rate of 4.8% (3/62). In the subgroup of 31 patients with positive sgRNA after 5 days of remdesivir, the early discharge rate was 29% (9/31) and the mortality rate was 16.1% (5/31). In multivariable analyses, the variables associated with early discharge were negative sgRNA at day 3 and not needing treatment with corticosteroids or intensive care unit admission. Conclusions Qualitative sgRNA could help in monitoring the virological response in patients who receive remdesivir. Further studies are needed to confirm these findings.

Background Lateral flow immunoassays (LFIA) have shown their usefulness for detecting CTX-M- and carbapenemase-producing Enterobacterales (CPEs) in bacterial cultures. Here, we have developed and validated the BL-DetecTool to detect CTX-M enzymes and carbapenemases directly from clinical samples. Methods The BL-DetecTool is an LFIA that integrates an easy sample preparation device named SPID (Sampling, Processing, Incubation and Detection). It was evaluated in three University hospitals on urine, blood culture (BC) and rectal swab (RS) specimens either of clinical origin or on spiked samples. RS evaluation was done directly and after a 24 h enrichment step. Results The CTX-M BL-DetecTool was tested on 485 samples (154 BC, 150 urines, and 181 RS) and revealed a sensitivity and specificity of 97.04% (95% CI 92.59%–99.19%) and 99.43% (95% CI 97.95%–99.93%), respectively. Similarly, the Carba5 BL-DetecTool was tested on 382 samples (145 BC, 116 urines, and 121 RS) and revealed a sensitivity and specificity of 95.3% (95% CI 89.43%–98.47%) and 100% (95% CI 98.67%–100%), respectively. While with the Carba5 BL-DetecTool five false negatives were observed, mostly in RS samples, with the CTX-M BL-DetecTool, in addition to four false-negatives, two false-positives were also observed. Direct testing of RS samples revealed a sensitivity of 78% and 86% for CTX-M and carbapenemase detection, respectively. Conclusions BL-DetecTool showed excellent biological performance, was easy-to-use, rapid, and could be implemented in any microbiology laboratory around the world, without additional equipment, no need for electricity, nor trained personnel. It offers an attractive alternative to costly molecular methods.

This study aimed to investigate whethehr the diversity and composition of the intestinal microbiota determines the risk of multidrug-resistant organism (MDRO) acquisition, infection, and mortality in patients admitted to a liver intensive care unit (ICU).This prospective study included patients admitted to a 12-bed ICU between July and December 2018. Rectal swabs to detect MDRO intestinal colonization were obtained at ICU admission and weekly thereafter during the ICU stay. The 16S rRNA gene sequencing was performed on 138 rectal swabs from 62 patients. We evaluated the potential association between gut microbiota composition and diversity and the risk of MDRO colonization, infection, and hospital mortality.Of the patients studied, 19 of 62 (30.65%) presented with MDRO colonization at admission, 16 (25.81%) were colonized during their stay, and 27 (43.55%) were not colonized; 45 of 62 patients (72.58%) developed an infection, and mortality was 29.03% (18 of 62). Higher bacterial diversity and abundance of Bacillales Family XI incertae sedis and Prevotella families were associated with a lower risk of colonization by MDRO, infection, and death (linear discriminant analysis effect size score4), whereas the Enterococcaceae family was associated with an increased risk of infection and death (linear discriminant analysis effect size score4). The LASSO regression and multivariate analysis identified Family XI incertae sedis to be associated with a lower risk of infection (OR: 0.997; 95% CI, 0.996-0.999; p = 0.001) and microbial evenness index to be associated with lower mortality risk (OR: 0.68; 95% CI, 0.49-0.95; p = 0.02).Microbial diversity and abundance of certain bacterial taxa could have prognostic value in patients admitted to a critical care unit. Larger perspective studies should address the value of these markers in clinical practice.

The synthesis of spiro compounds featuring seven- and six-membered rings in the spirobicyclic motif is successfully achieved through a cascade process encompassing a rhodium(I)-catalyzed cycloisomerization followed by a highly selective Diels-Alder homodimerization. The scope of the reaction is analyzed based on a series of synthetic substrates, and control experiments and DFT calculations led us to justify the exquisite degree of selectivity observed We are grateful for financial support from the Ministerio de Ciencia e Innovación (PID2020-113711GB-I00 MCIN/AEI/ 10.13039/501100011033), the Generalitat de Catalunya (Project 2017-SGR-39), and the UdG for an IF predoctoral grant to J.V. Open Access funding provided thanks to the CRUE-CSIC agreement with ACS

How are carbon dioxide assimilation by photosynthesis and (shallow) cumulus clouds connected? What is the local interaction between rainforest evapotranspiration and cloud formation modulated by incoming regional air masses? These interrelated questions were the main drivers of the experimental campaign CloudRoots-Amazonia22 that took place at the ATTO/Campina supersites in the pristine Amazon rainforest during August 2022 (dry season). CloudRoots-Amazonia22 collected observational data to derive relationships between leaf level processes to canopy scales and connected them to the diurnal evolution of the clear to cloudy atmospheric boundary layer. At leaf level, first results indicate a diurnal asymmetry of the leaf conductance with maximum openings before midday. These observations are related to radiative energy fluxes to study the partitioning into sensible and latent heating and of plant-soil carbon dioxide exchnages. By coupling measurements of carbon and water stable isotopologues by fast laser instruments to turbulence measurements we aim to quantify flux variations related to the radiation fluctuations driven by clouds. These observations are integrated with 75 soundings of state variables and greenhouse gas profiles taken by flights below, through and above the cloud layers. We investigate what controls the transition from shallow to deep convection and the causality between the surface-cloud shear and the moisture transport at the interface between the different atmospheric layers. The observational analysis is completed with conceptual modelling and systematic large-eddy simulation experiments, which include dynamic vegetation models to advance our understanding of the diurnal energy, water and carbon cycles over the Amazon rainforest.

Validation of gas exchange fluxes in models has been challenging due to the lack of ecosystem scale exchange fluxes partitioned into soil, plant and atmospheric components. One promising method to partition turbulent fluxes uses the exchange process dependent fractionation of molecules like CO2 and H2O. When applying this method to short spatiotemporal scales, an isotope flux (δ-flux) needs to be resolved. Few have attempted to measure this δ-flux as the required instrumentation only became available in recent years. In our presentation we will discuss observations made during the LIAISE 2021 field campaign using an EC system, Picarro L-2130i H2O isotope analyser, and Aerodyne TILDAS-CS CO2 isotope analyser. This campaign took place in the summer of 2021 in the heavily irrigated Ebro River basin near Lleida, Spain embedded in a semi-arid region.We will present procedures to estimate and scrutinize the central δ-flux variable. To this end we calculated co-spectra of the relevant signals and compared their frequency dependent contributions. One relevant finding is that mole fractions and isotope ratios measured with the same instrument can be offset in time by more than a minute, thereby impacting the resulting δ-fluxes. Additionally, we found asymmetric signal loss between net ecosystem fluxes and δ-fluxes. We will show that such effects impact flux partitioning severely and indicate how they can be tackled using physically sound corrections. Only when such corrections and verifications are made, ecosystem flux partitioning can be applied to validate conceptual land-atmosphere exchange models. Such models will calculate the diurnal variability of CO2 and H2O isotopologue concentrations, and link local to regional scales, all with the purpose of better constraining current and future exchange fluxes.

IntroductionBiofilm production is an important yet currently overlooked aspect of diagnostic microbiology that has implications for antimicrobial stewardship. In this study, we aimed to validate and identify additional applications of the BioFilm Ring Test® (BRT) for Pseudomonas aeruginosa (PA) isolates from patients with bronchiectasis (BE).Materials and methodsSputa were collected from BE patients who had at least one PA positive culture in the previous year. We processed the sputa to isolate both mucoid and non-mucoid PA, and determined their susceptibility pattern, mucA gene status, and presence of ciprofloxacin mutations in QRDR genes. The Biofilm production index (BPI) was obtained at 5 and 24 hours. Biofilms were imaged using Gram staining.ResultsWe collected 69 PA isolates, including 33 mucoid and 36 non-mucoid. A BPI value below 14.75 at 5 hours predicted the mucoid PA phenotype with 64% sensitivity and 72% specificity.ConclusionOverall, our findings suggest that the fitness-cost associated with the mucoid phenotype or ciprofloxacin resistance is shown through a time-dependent BPI profile. The BRT has the potential to reveal biofilm features with clinical implications.

Background Our aim in this study was to evaluate the clinical and prognostic impact of communicating microbiological information in real time for adult patients with bloodstream infections (BSIs). Methods We retrospectively reviewed 6225 clinical episodes of bacteremia in a teaching hospital from January 2013 to December 2019. Bacteremia-associated mortality was compared when blood culture results were relayed to the infectious diseases specialist (IDS) in real time and periods when results were relayed the following morning. The impact of information availability using mortality at 30 days was used as the main outcome of the study. Results The initial analysis (all microorganisms included) did not show an association of mortality and information delay to the IDS (odds ratio [OR], 1.18; 95% confidence interval [CI], .99–1.42). However, information delay of BSIs caused by fast-growing microorganisms such as Enterobacterales was associated with a significant increase in the odds of death at 30 days both in the univariate (OR, 1.76; 95% CI, 1.30–2.38) and multivariate analysis (OR, 2.22; 95% CI, 1.50–3.30). Similar results were found with mortality at 14 days and 7 days in the univariate (OR, 1.54; 95% CI, 1.08–2.20 and OR, 1.56; 95% CI, 1.03–2.37, respectively) and the multivariate analysis (OR, 2.05; 95% CI, 1.27–3.32 and OR, 1.92; 95% CI, 1.09–3.40, respectively). Conclusions Information delivered in real time has prognostic relevance and is likely to improve survival of patients with documented BSIs. Future studies should address the prognostic impact of adequate resource allocation (microbiologist/IDS with 24/7 coverage) in BSIs.

In different health care settings, such as patients from emergency surgery, rapid detection of SARS-CoV-2 is needed. The QuantuMDx Q-POC is an automatized fast workflow platform based on detection of three genes: two genes encoding structural proteins that can be used to differentiate SARS-CoV-2 from other coronavirus and a third target gene encoding a nonstructural region that is unique for SARS-CoV-2 such as the open reading frame ( ORF1 ).

The Kalman filter (KF) loses its optimality properties when the system model is misspecified to a certain extent, that is, when the assumed system knowledge does not perfectly match the true system dynamics, which in turn can severely impact its performance in real-life applications. The same goes for its extended counterpart (EKF). Linear constraints were recently shown to be a possible way to mitigate the impact of system model mismatch, which led to the derivation of a linearly constrained KF and EKF (LC-KF and LC-EKF). In this contribution, we build on these new robust filters to provide their information form counterparts, the so-called linearly constrained (extended) information filters (LC-IF and LC-EIF). In the unconstrained case, both IF and EIF are mathematically equivalent to the KF and EKF, respectively, but better suited to systems without priors or with a measurement dimension much larger than the state one. Actually only the IF and EIF can be used for large-scale real-time dynamic systems in which computational time and memory are at a premium. Hence the essential need of IF forms of the LC-KF and LC-EKF for such systems, which are introduced in this article. Furthermore, LC-(E)IF still adapts to systems without priors, even though some restrictions apply. Their computational advantages are shown through representative applications, i.e., large array processing and multi-sensor localisation.

Standard state estimation techniques require a perfect knowledge of the system’s model, that is, process and measurement equations, inputs and the corresponding noise statistics. In practice this assumption does not hold and therefore robust filtering methods must be accounted for. A new approach to tackle a potential model mismatch via linear constraints within the Kalman filter, and its extended version (EKF), has been recently shown to be a very promising solution. This letter further explores robust linearly constrained filtering in the context of the Invariant EKF (InEKF). With respect to the EKF, the InEKF is a recent filtering technique which has been shown to better handle the particular structure of a class of problems through the use of Lie groups. In this contribution, a new robust linearly constrained InEKF is introduced, together with particular parametric mismatched models and mitigation strategies through linear constraints. Numerical results for an illustrative navigation example are provided to show the performance improvement and support the discussion.

Parameter estimation is a problem of interest when designing new remote sensing instruments, and the corresponding lower performance bounds are a key tool to assess the performance of new estimators. In global navigation satellite systems reflectometry (GNSS-R), a noncoherent averaging is applied to reduce speckle and thermal noise, and subsequently the parameters of interest are estimated from the resulting waveform. This approach has been long regarded as suboptimal with respect to the optimal coherent one, which is true in terms of detection capabilities, but no analysis exists on the corresponding parameter estimation performance exploiting GNSS signals. First, we show that for certain signal models, both coherent and noncoherent Cramer-Rao bounds are equivalent, and therefore, any maximum likelihood estimation coherent/noncoherent combination scheme is efficient (optimal) at high signal-to-noise ratios. This is validated for an illustrative GNSS-R estimation problem. In addition, it is shown that considering the joint delay/Doppler/phase estimation problem, the noncoherent performance for the delay is still optimal, which is of practical importance for instance in altimetry applications.

It is well known that the Kalman filter (KF) performance is clearly degraded in real-life applications where the system model is misspecified to a certain extent, that is, when the assumed knowledge does not perfectly match the true system dynamics. A possible way to mitigate the impact of a system model mismatch is to resort to linear constraints. In that perspective, a general linearly constrained KF (LCKF) formulation has been recently derived and shown to provide an effective robust filtering solution. In this contribution, we extend the LCKF framework to linear smoothers. Adapting the Fixed-Interval (FI) smoother is easy with sequential state augmentation, but the obtained linearly constrained FI (LCFI) has quadratic complexity in the interval length. Hence the need for an efficient alternative: the linearly constrained Rauch-Tung-Striebel (LCRTS) smoother. Introduced in an intuitive manner, its consistency is proved by showing that the LCFI and LCRTS coincide. The mismatch mitigation capabilities and performance of the LCRTS, with respect to unconstrained smoothers, are shown through illustrative examples with different types of mismatch in both measurement and process equations.

In the last decades, microbiology laboratories have undergone unprecedented technological changes which have revolutionized the diagnosis of infectious diseases. They have last generation technology which allows precise, rapid and effective diagnosis of a wide range of infectious diseases, while also providing valuable information on the antibiotic sensitivity/resistance of the causal microorganism, thereby notably reducing the morbidity and mortality of the patients and at the same time improving in-hospital patient management. Several studies have shown that with the increase in the use of rapid diagnostic techniques this technological advancement has a greater impact when accessibility to the microbiology laboratory is possible beyond the usual 7 h workday. This document discusses the need for clinical microbiology services to work 24 h a day, 7 days a week (24/7).

Background Minimally invasive tissue sampling (MITS), a postmortem procedure that uses core needle biopsy samples and does not require opening the body, may be a valid alternative to complete autopsy (CA) in highly infectious diseases such as coronavirus disease-19 (COVID-19). This study aimed to (1) compare the performance of MITS and CA in a series of COVID-19 deaths and (2) evaluate the safety of the procedure. Methods From October 2020 to February 2021, MITS was conducted in 12 adults who tested positive before death for COVID-19, in a standard, well-ventilated autopsy room, where personnel used reinforced personal protective equipment. In 9 cases, a CA was performed after MITS. A thorough histological evaluation was conducted, and the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was evaluated by real-time reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. Results The diagnoses provided by MITS and CA matched almost perfectly. In 9 patients, COVID-19 was in the chain of events leading to death, being responsible for diffuse alveolar damage and mononuclear T-cell inflammatory response in the lungs. No specific COVID-19 features were identified. Three deaths were not related to COVID-19. All personnel involved in MITS repeatedly tested negative for COVID-19. SARS-CoV-2 was identified by RT-PCR and immunohistochemistry in the MITS samples, particularly in the lungs. Conclusions MITS is useful for evaluating COVID-19–related deaths in settings where a CA is not feasible. The results of this simplified and safer technique are comparable to those of CA.

Nitrogen oxides (NO x ) play a central role in catalyzing tropospheric ozone formation. Nitrogen dioxide (NO 2 ) has recently reemerged as a key target for air pollution control measures, and observational evidence points toward a limited understanding of ozone in high-NO x environments. A complete understanding of the mechanisms controlling the rapid atmospheric cycling between ozone (O 3 )–nitric oxide (NO)–NO 2 in high-NO x regimes at the surface is therefore paramount but remains challenging because of competing dynamical and chemical effects. Here, we present long-term eddy covariance measurements of O 3 , NO, and NO 2 , over an urban area, that allow disentangling important physical and chemical processes. When generalized, our findings suggest that the depositional O 3 flux near the surface in urban environments is negligible compared to the flux caused by chemical conversion of O 3 . This leads to an underestimation of the Leighton ratio and is a key process for modulating urban NO 2 mixing ratios. As a consequence, primary NO 2 emissions have been significantly overestimated.

Smoke from wildfires or burning biomass directly affects air quality and weather through modulating cloud microphysics and radiation. A simple wildfire emission coupling of black carbon (BC) and organic carbon (OC) with microphysics was implemented using the Weather Research and Forecasting model's fire module. A set of large-eddy simulations inspired by unique surface and upper atmospheric observations from the 2021 Santa Coloma de Queralt Fire (Spain) were conducted to investigate the influence of background conditions and interactions between atmospheric and fire processes such as fire smoke, ambient moisture, and latent heat release on the formation and evolution of pyroconvective clouds. While the microphysical impact of BC and OC emissions on the dynamics of fire behavior is minimal on short time scales (

Remdesivir (RDV) was the first antiviral drug approved by the FDA to treat severe coronavirus disease-2019 (COVID-19) patients. RDV inhibits SARS-CoV-2 replication by stalling the non structural protein 12 (nsp12) subunit of the RNA-dependent RNA polymerase (RdRp). No evidence of global widespread RDV-resistance mutations has been reported, however, defining genetic pathways to RDV resistance and determining emergent mutations prior and subsequent antiviral therapy in clinical settings is necessary. This study identified 57/149 (38.3%) patients who did not respond to one course (5-days) (n = 36/111, 32.4%) or prolonged (5 to 20 days) (n = 21/38, 55.3%) RDV therapy by subgenomic RNA detection. Genetic variants in the nsp12 gene were detected in 29/49 (59.2%) non responder patients by Illumina sequencing, including the de novo E83D mutation that emerged in an immunosuppressed patient after receiving 10 + 8 days of RDV, and the L838I detected at baseline and/or after prolonged RDV treatment in 9/49 (18.4%) non responder subjects. Although 3D protein modeling predicted no interference with RDV, the amino acid substitutions detected in the nsp12 involved changes on the electrostatic outer surface and in secondary structures that may alter antiviral response. It is important for health surveillance to study potential mutations associated with drug resistance as well as the benefit of RDV retreatment, especially in immunosuppressed patients and in those with persistent replication. IMPORTANCE This study provides clinical and microbiologic data of an extended population of hospitalized patients for COVID-19 pneumonia who experienced treatment failure, detected by the presence of subgenomic RNA (sgRNA). The genetic variants found in the nsp12 pharmacological target of RDV bring into focus the importance of monitoring emergent mutations, one of the objectives of the World Health Organization (WHO) for health surveillance. These mutations become even more crucial as RDV keeps being prescribed and new molecules are being repurposed for the treatment of COVID-19. The present article offers new perspectives for the clinical management of non responder patients treated and retreated with RDV and emphasizes the need of further research of the benefit of combinatorial therapies and RDV retreatment, especially in immunosuppressed patients with persistent replication after therapy. This work was financed by a Gilead Sciences grant (IN-ES-540-6089) and CIBER Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, España (CB21/13/00081). This work was financed by ad hoc patronage funds for research on COVID-19 from donations from citizens and organizations to the Hospital Clínic de Barcelona-Fundació Clínic per a la Recerca Biomèdica. Sí

The immense impact of the COVID-19 pandemic on health systems has motivated the scientific community to search for clinical prognostic factors for SARS-CoV-2 infection. Low cycle threshold values (Ct) of diagnostic real-time RT-PCR assays in hospitalized patients have been associated with a poor prognosis in several studies, whereas other studies did not find this association. We explored whether SARS-CoV-2 Ct values at diagnosis were associated with a poor outcome (admission to hospital and death) in 604 community patients diagnosed at primary health centers. Although lower Ct values were found in patients who died of COVID-19, the Ct value was not significantly associated with a worse outcome in a multivariate analysis, while age remained an independent prognostic factor. We did not find evidence to support the role of Ct values as a prognostic factor of COVID-19 in community cases.

Central nervous system (CNS) infections such as meningitis and encephalitis are medical emergencies that require rapid diagnosis of the causative pathogen to guide early and adequate treatment since a delay in implementing an adequate antimicrobial therapy can lead to death. The current microbiological diagnostic methods based on culture or antigen detection have important limitations in their capacity to accurately identify the different potential pathogens causing CNS and, in the time, to obtaining results. Rapid syndromic molecular arrays have been developed. The main advantage of using a meningoencephalitis panel based in a multiplex test is that includes bacteria, viruses and fungi, covering the most prevalent microorganisms causing meningitis and encephalitis and the turn-around time is circa 1h. The use of these multiplex-PCR based tools is reviewed and the advantages and disadvantages of this technique are discussed.

Background The use of remdesivir has demonstrated a significant reduction in the time to recovery in patients with COVID-19. However, the impact on mortality is still controversial. Therefore, it is necessary to evaluate whether there is a specific subgroup of patients in whom an active antiviral therapy also reduces the mortality. Methods Patients admitted for >48 h in our hospital for a SARS-CoV-2 confirmed or suspected infection from February 2020 to February 2021 were retrospectively analysed. The primary outcome of the study was mortality at 30 days. Univariate and multivariate analyses were performed to identify predictors of mortality. Results In total, 2607 patients (438 receiving remdesivir and 2169 not) were included with a median (IQR) age of 65 (54–77) years and 58% were male. Four hundred and seventy-six were admitted to the ICU (18.3%) and 264 required invasive mechanical ventilation (10.1%). The global 30 day mortality rate was 10.7%. Pre-admission symptom duration of 4–6 days and ≤3 days was associated with a 1.5- and 2.5-fold increase in the mortality rate, respectively, in comparison with >6 days and treatment with remdesivir was independently associated with a lower mortality rate (OR = 0.382, 95% CI = 0.218–0.671). The analysis showed that the major difference was among patients with shorter pre-admission symptom duration ( Conclusions Patients with ≤3 days and 4–6 days from symptom onset to admission are associated with a 2.5- and 1.5-fold higher risk of death, respectively. Remdesivir was associated with 62% reduced odds of death versus standard-of-care and its survival benefit increased with shorter duration of symptoms.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction (RT-PCR) provides a highly variable cycle threshold (Ct) value that cannot distinguish viral infectivity. Subgenomic ribonucleic acid (sgRNA) has been used to monitor active replication. Given the importance of long RT-PCR positivity and the need for work reincorporation and discontinuing isolation, we studied the functionality of normalized viral loads (NVLs) for patient monitoring and sgRNA for viral infectivity detection. Methods The NVLs measured through the Nucleocapsid and RNA-dependent-RNA-polymerase genes and sgRNA RT-PCRs were performed in 2 consecutive swabs from 84 healthcare workers. Results The NVLs provided similar and accurate quantities of both genes of SARS-CoV-2 at 2 different timepoints of infection, overcoming Ct-value and swab collection variability. Among SARS-CoV-2-positive samples, 51.19% were sgRNA-positive in the 1st RT-PCR and 5.95% in the 2nd RT-PCR. All sgRNA-positive samples had >4 log10 RNA copies/1000 cells, whereas samples with ≤1 log10 NVLs were sgRNA-negative. Although NVLs were positive until 29 days after symptom onset, 84.1% of sgRNA-positive samples were from the first 7 days, which correlated with viral culture viability. Multivariate analyses showed that sgRNA, NVLs, and days of symptoms were significantly associated (P Conclusions The NVLs and sgRNA are 2 rapid accessible techniques that could be easily implemented in routine hospital practice providing a useful proxy for viral infectivity and coronavirus disease 2019 patient follow-up.

Resumen Los programas de optimizacion del diagnostico microbiologico (PRODIM) promueven actuaciones coordinadas orientadas a optimizar el uso de las tecnicas diagnosticas, propiciando la toma de decisiones terapeuticas, clinicas y preventivas adecuadas y «coste-efectivas». La implementacion de los PRODIM debe sustentarse en la creacion de comites multidisciplinares liderados por microbiologos clinicos para el diseno de algoritmos diagnosticos, la adecuacion del sistema informatico del laboratorio para el control de la pertinencia de las pruebas diagnosticas solicitadas, la puesta en marcha de un sistema de control de calidad, el diseno y realizacion de estudios de analisis de coste-efectividad, la educacion del peticionario y del personal tecnico y de enfermeria y la evaluacion continua del programa. La incorporacion de PRODIM en la rutina asistencial reporta beneficios tangibles para el paciente a la vez que afianza el papel clave del microbiologo clinico en el manejo de las enfermedades infecciosas.

International audience; Background - Infective endocarditis (IE) is a common and serious complication in patients receiving chronic hemodialysis (HD). Objectives - This study sought to investigate whether there are significant differences in complications, cardiac surgery, relapses, and mortality between IE cases in HD and non-HD patients. Methods - Prospective cohort study (International Collaboration on Endocarditis databases, encompassing 7,715 IE episodes from 2000 to 2006 and from 2008 to 2012). Descriptive analysis of baseline characteristics, epidemiological and etiological features, complications and outcomes, and their comparison between HD and non-HD patients was performed. Risk factors for major embolic events, cardiac surgery, relapses, and in-hospital and 6-month mortality were investigated in HD-patients using multivariable logistic regression. Results - A total of 6,691 patients were included and 553 (8.3%) received HD. North America had a higher HD-IE proportion than the other regions. The predominant microorganism was Staphylococcus aureus (47.8%), followed by enterococci (15.4%). Both in-hospital and 6-month mortality were significantly higher in HD versus non-HD-IE patients (30.4% vs. 17% and 39.8% vs. 20.7%, respectively; p

The atmospheric oxidation of biogenic volatile organic compounds (BVOC) by OH radicals over tropical rainforests impacts local particle production and the lifetime of globally distributed harmful and radiatively active gases. For the pristine Amazon rainforest during the dry season, we empirically determined the diurnal OH radical variability at the forest-atmosphere interface region between 80 and 325m from 07:00 to 15:00 LT using BVOC measurements. A dynamic time warping approach was applied showing that median averaged transport times between 80 m to 325 m decrease from 105 to 15 minutes over this time period. The inferred OH concentrations show evidence for an early morning OH peak (07:00–08:00 LT) and an OH maximum (13:00–14:00LT) reaching 1x106 ± 1.1x106 molecules cm− 3 controlled by the coupling between BVOC emission fluxes, convective turbulence, air chemistry and photolysis rates. The results were evaluated against a turbulence resolving transport (DALES), a regional scale (WRF-Chem) and a global (EMAC) atmospheric chemistry model.

International audience; This article investigates new strategies to compute accurate low‐complexity log‐likelihood ratio (LLR) values based on the Bayesian formulation under uncorrelated fading channels for both antipodal and code shift keying modulations when no channel state information (CSI) is available at the receiver. These LLR values are then used as input to modern error‐correcting schemes used in the data decoding process of last‐generation Global Navigation Satellite System signals. Theoretical analysis based on the maximum achievable rate is presented for the different methods in order to evaluate the performance degradation with respect to the optimal CSI channel. Finally, the frame error rate simulation results are shown, validating the appropriate performance of the proposed LLR approximation methods.

International audience; State estimation is a fundamental task in many engineering fields, and therefore robust nonlinear filtering techniques able to cope with misspecified, uncertain and/or corrupted models must be designed for real-life applicability. In this contribution we explore nonlinear Gaussian filtering problems where measurements may be corrupted by outliers,and propose a new robust variational-based filtering methodology able to detect and mitigate their impact. This method generalizes previous contributions to the case of multiple outlier indicators for both independent and dependent observation models. An illustrative example is provided to support the discussion and show the performance improvement.

Introduction Acinetobacter is a genus that comprises a group of opportunistic pathogens responsible for a variety of nosocomial infections. The Acinetobacter calcoaceticus–Acinetobacter baumannii (Acb) complex includes some species of clinical importance, mainly A. baumannii, A. pittii and A. nosocomialis, which share phenotypic similarities that make it very difficult to distinguish between them using a phenotypic approach. The aim of this study was to evaluate two commercial matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) systems for the identification of different Acinetobacter species, with a special focus among those belonging to the Acb complex. Methods One hundred and fifty-six Acinetobacter spp. clinical strains, identified by amplified ribosomal DNA restriction analysis (ARDRA) and rpoB gene sequencing, were analysed by two different MALDI-TOF systems. Results Considering only the 144 strains of the Acb complex evaluated in this study, the Vitek-MS™ and Microflex LT™ systems correctly identified 129 (89.6%) and 143 (99.3%) strains, respectively. Conclusion After analysing 156 strains belonging to Acinetobacter spp., both Vitek-MS™ and Microflex LT™ proved to be rapid and accurate systems for the identification of Acb complex species showing a good correlation. However, both manufacturers should improve their databases to include new species in them.

Objectives To characterize the clonal spread of carbapenem-resistant Klebsiella pneumoniae and Escherichia coli isolates between different healthcare institutions in Catalonia, Spain. Methods Antimicrobial susceptibility was tested by disc diffusion. MICs were determined by gradient diffusion or broth microdilution. Carbapenemase production was confirmed by lateral flow. PCR and Sanger sequencing were used to identify the allelic variants of resistance genes. Clonality studies were performed by PFGE and MLST. Plasmid typing, conjugation assays, S1-PFGE plus Southern blotting and MinION Oxford Nanopore sequencing were used to characterize resistance plasmids. Results Twenty-nine carbapenem-resistant isolates recovered from three healthcare institutions between January and November 2016 were included: 14 K. pneumoniae isolates from a tertiary hospital in the south of Catalonia (hospital A); 2 K. pneumoniae isolates from a nearby healthcare centre; and 12 K. pneumoniae isolates and 1 E. coli isolate from a tertiary hospital in Barcelona (hospital B). The majority of isolates were resistant to all antimicrobial agents, except colistin, and all were NDM producers. PFGE identified a major K. pneumoniae clone (n = 27) belonging to ST147 and co-producing NDM-1 and CTX-M-15, with a few isolates also harbouring blaOXA-48. Two sporadic isolates of K. pneumoniae ST307 and E. coli ST167 producing NDM-7 were also identified. blaNDM-1 was carried in two related IncR plasmid populations and blaNDM-7 in a conjugative 50 kb IncX3 plasmid. Conclusions We report the inter-hospital dissemination of XDR high-risk clones of K. pneumoniae and E. coli associated with the carriage of small, transferable plasmids harbouring blaNDM genes.

The main objective of this study was to compare in vitro activities of a novel fluoroquinolone (FQ), UB-8902, with ofloxacin (OFX), levofloxacin (LFX), and moxifloxacin (MOX) against Mycobacterium ...

International audience; Ionospheric scintillation is the physical phenomena affecting radio waves coming from the space through the ionosphere. Such disturbance is caused by ionospheric electron‐density irregularities and is a major threat in Global Navigation Satellite Systems (GNSS). From a signal‐processing perspective, scintillation is one of the most challenging propagation scenarios, particularly affecting high‐precision GNSS receivers and safety critical applications where accuracy, availability, continuity, and integrity are mandatory. Under scintillation, GNSS signals are affected by amplitude and phase variations, which mainly compromise the synchronization stage of the receiver. To counteract these effects, one must resort to advanced signal‐processing techniques such as adaptive/robust methods, machine learning, or parameter estimation. This contribution reviews the signal‐processing landscape in GNSS receivers, with emphasis on different detection, monitoring, and mitigation problems. New results using real data are provided to support the discussion. To conclude, future perspectives of interest to the GNSS community are discussed.

This paper presents an overview of the functionalities and applications of Exasim, an open-source code for generating high-order discontinuous Galerkin codes to numerically solve parametrized partial differential equations (PDEs). The software combines high-level and low-level languages to construct parametrized PDE models via Julia, Python or Matlab scripts and produce high-performance C++ codes for solving the PDE models on CPU and Nvidia GPU processors with distributed memory. Exasim provides matrix-free discontinuous Galerkin discretization schemes together with scalable reduced basis preconditioners and Newton-GMRES solvers, making it suitable for accurate and efficient approximation of wide-ranging classes of PDEs., 19 pages, 4 figures, 3 tables

Objectives Protegrins are a family of natural peptides from the innate immune system of vertebrates, with broad-spectrum antimicrobial activity. However, the toxicity and haemolysis of protegrin-1 (PG-1) at low concentrations renders it useless for therapeutic application. We rationally designed PLP-3, a novel synthetic PG-1-like peptide, comprising key activity features of protegrins in a constrained bicyclic structure. Our main objective was to investigate PLP-3’s activity against MDR strains of Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae and to analyse its haemolysis and cytotoxicity. Methods Peptide synthesis was performed via solid phase and intramolecular ligation in solution, and the correct folding of the peptide was verified by circular dichroism. Antimicrobial activity was performed through broth microdilution. The test panel contained 45 bacterial strains belonging to A. baumannii, P. aeruginosa and K. pneumoniae (15 strains per species) comprising colistin-resistant and MDR strains. Cytotoxicity was assessed by XTT cell viability assays using HeLa and A549 cells and haemolysis of human erythrocytes. Results PLP-3 was successfully synthesized, and its antiparallel β-sheet conformation was confirmed. Antimicrobial activity screening showed MIC90 values of 2 mg/L for A. baumannii, 16 mg/L for K. pneumoniae and 8 mg/L for P. aeruginosa. The haemolysis IC50 value was 48.53 mg/L. Cytotoxicity against human HeLa and A549 cells showed values of ca. 200 mg/L in both cell lines resulting in a 100-fold selectivity window for bacterial over human cells. Conclusions PLP-3 has potent antimicrobial activity, especially against A. baumannii, while maintaining low haemolysis and toxicity against human cell lines at antimicrobial concentrations. These characteristics make PLP-3 a promising peptide with an interesting therapeutic window.

A combined morphological and molecular genetic study of the European species within the /Rhombisporum clade of the genus Entoloma reveals a high species diversity. This group comprises typical grassland species with pronounced and well-differentiated cheilocystidia, and a wide range of spore shapes varying from rhomboid to five-angled. To fix the concept of the classical species E. rhombisporum, a neotype is designated. Nine species are described as new to science based on the result of nrDNA ITS phylogeny with additional gap coding, and morphological characterization: E. caulocystidiatum, E. lunare, E. pararhombisporum, E. pentagonale, E. perrhombisporum, E. rhombiibericum, E. rhombisporoides, E. sororpratulense, and E. subcuboideum. The ITS sequences of the holotypes of previously described species belonging to the /Rhombisporum clade, viz., E. laurisilvae and E. pratulense have also been generated and are published here for the first time. Since many of the above-mentioned species have been misidentified as E. cocles, it seemed opportune to also study this species and to designate a neotype to fix its current concept. A key including European species is presented. As most of the species are potentially important indicators for threatened grassland communities, the 130 ITS barcodes newly generated for this study may be useful as a reference in conservation and metabarcoding projects.

Objectives To detect a potential hidden dissemination of the blaOXA-48 gene among Proteus mirabilis isolates obtained from a single centre. Methods P. mirabilis from diverse clinical samples presenting an ESBL phenotype or obtained from blood cultured from 2017 to 2019 were evaluated. Bacterial identification was performed using MALDI-TOF MS. MICs were determined using International Organization for Standardization (ISO) standard microdilution and interpreted following EUCAST guidelines. WGS was performed using both short- and long-read technologies and assemblies were done using Unicycler. Resistomes were assessed using the ResFinder database. SNPs were detected using the PATRIC bioinformatics platform. Cloning experiments were performed using the pCRII-TOPO cloning kit. Results Thirty-one out of 108 (28.7%) isolates were positive for blaOXA-48 and blaCTX-M-15. Twenty-nine out of 31 of the isolates were susceptible to temocillin, piperacillin/tazobactam, ertapenem and meropenem, whereas only 2/31 showed a resistance phenotype against these antibiotics. Both blaOXA-48 and blaCTX-M-15 genes were detected within the same chromosomally integrated new transposon in all isolates. The resistant isolates displayed a single mutation located in the putative promoter upstream of blaOXA-48. Cloning experiments confirmed that the mutation was responsible for the resistance phenotype. Conclusions The presence of a chromosomal copy of blaOXA-48 did not confer resistance to carbapenems, but a single mutation in the promoter could lead to an increase in resistance. This study shows a hidden circulation of OXA-48-positive, but carbapenem- and piperacillin/tazobactam-susceptible, P. mirabilis isolates that can become resistant to β-lactams after a single mutation.

CARB-ES-19 is a comprehensive, multicenter, nationwide study integrating whole-genome sequencing (WGS) in the surveillance of carbapenemase-producingIn total, 71 hospitals, representing all 50 Spanish provinces, collected the first 10 isolates per hospital (February to May 2019); CPE isolates were first identified according to EUCAST (meropenem MIC0.12 mg/L with immunochromatography, colorimetric tests, carbapenem inactivation, or carbapenem hydrolysis with MALDI-TOF). Prevalence and incidence were calculated according to population denominators. Antibiotic susceptibility testing was performed using the microdilution method (EUCAST). All 403 isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis.In total, 377 (93.5%) CP-Kpn and 26 (6.5%) CP-Eco isolates were collected from 62 (87.3%) hospitals in 46 (92%) provinces. CP-Kpn was more prevalent in the blood (5.8%, 50/853) than in the urine (1.4%, 201/14,464). The cumulative incidence for both CP-Kpn and CP-Eco was 0.05 per 100 admitted patients. The main carbapenemase genes identified in CP-Kpn wereThis study serves as a first step toward WGS integration in the surveillance of carbapenemase-producing Enterobacterales in Spain. We detected important epidemiological changes, including increased CP-Kpn and CP-Eco prevalence and incidence compared to previous studies, wide interregional dissemination, and increased dissemination of high-risk clones, such as ST307/OXA-48 and ST512/KPC-3.

The effects of the land-cover (LC) type on the surface fluxes have been investigated using observational data and numerical weather prediction models in numerous studies. Most of these works stress the need for a realistic and accurate representation of the LC within the models, including appropriate soil and vegetation parameters. This is needed to obtain more realistic near-surface atmospheric processes, leading to better forecasts of atmospheric variables of common interest (2-m temperature, 10-m wind speed, relative humidity, etc.). In a previous work, we have studied these effects focusing on a fair-weather day in a heterogeneous area of southern France. To this aim, we used the Weather Research and Forecasting (WRF) model at 1 km with an improved (30-m and more realistic) representation of the LC, configured with four land surface models (LSM): Noah, Noah-MP, CLM4 and RUC.The results showed that the influence of LC on surface fluxes were important but differed depending on the LSM, displaying some extreme flux values for specific LC categories (e.g., urban and conifer). This opened the question of how these effects impacted the development of the atmospheric boundary layer (ABL), which motivated the present work. To this aim, we analysed the ABL height (zi) simulated by WRF in each LC category using the different LSM. These values were compared to those observed with multiple instrumentation (radiosoundings, unmanned aerial vehicles, wind profilers, etc.) available during the Boundary Layer Late Afternoon and Sunset Turbulence (BLLAST) field campaign, which took place in the area of study in summer 2011.The zi simulated values were similar in magnitude and in temporal evolution than those observed, indicating a good performance of the model for the 4 LSMs. However, some LSM displayed a higher variability in the simulated zi depending on the sensible/latent heat partitioning and on the type of LC. These results indicate that the important effects of the LC type on the surface fluxes are transferred to the top of the PBL, affecting zi even from an analysis of this variable at a model resolution of 1x1 km.In order to disentangle whether the spatial variability of the modelled zi is close to the reality, for future works we highlight the importance of intensive and frequent zi measurements at the field over different nearby sites with contrasting LC. This will help to continue understanding how the surface forcing affects the PBL development and to what extent the processes reproduced in the model differ from those observed in the reality.

The tropical rainforest is the largest source of VOCs to the global atmosphere [1], where they are oxidized primarily by the hydroxyl radical (OH) [2]. In-situ measurements of OH are rare, especially from tropical forests, but indirect OH estimates can be made using VOC concentrations measured from aircraft or towers. For this it is necessary to measure the vertical change in concentration of a specific VOC with a known OH rate coefficient, within a known reaction time. In this study volatile organic compounds (VOC) were measured on the Amazon Tall Tower Observatory (ATTO) from 3 heights (80, 150 and 325 m) above the Amazon rainforest with a PTR-TOF-MS 4000 (IONICON Analytik GmbH). Typically to estimate OH, the convective timescale of the boundary layer is taken as the approximate reaction time. However, here we have developed a new method to determine the vertical transport based on the dynamic time warping technique. Median averaged transport times from 80 m to 325 m ranged from 105 to 15 minutes with decreasing values throughout the day from 06:00 to 15:00 as thermal and shear driven convection increases. We apply this method to determine effective OH concentrations between 80-325 m using isoprene and its oxidation products (methyl vinyl ketone, methacrolein and ISOPOOH) and compare these empirically derived values to values from the large-eddy simulation DALES [3]. The timescales of turbulent mixing and OH chemistry are similar, so both govern the vertical change in concentration.[1] Guenther, Alex. “Biological and Chemical Diversity of Biogenic Volatile Organic Emissions into the Atmosphere.” ISRN Atmospheric Sciences 2013 (2013): 1–27. https://doi.org/10.1155/2013/786290.[2] Lelieveld, Jos, Sergey Gromov, Andrea Pozzer, and Domenico Taraborrelli. “Global Tropospheric Hydroxyl Distribution, Budget and Reactivity.” Atmospheric Chemistry and Physics 16, no. 19 (2016): 12477–93. https://doi.org/10.5194/acp-16-12477-2016.[3] Vilà-Guerau de Arellano, J., X. Wang, X. Pedruzo-Bagazgoitia, M. Sikma, A. Agustí-Panareda, S. Boussetta, G. Balsamo, et al. “Interactions Between the Amazonian Rainforest and Cumuli Clouds: A Large-Eddy Simulation, High-Resolution ECMWF, and Observational Intercomparison Study.” Journal of Advances in Modeling Earth Systems 12, no. 7 (2020): 1–33. https://doi.org/10.1029/2019MS001828.

Microbiological diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a challenge. Although real-time reverse transcription PCR (RT-PCR) represents the gold standard method, strategies that allow rapid and simple diagnosis are necessary for the early identification of cases. In this study, we evaluated the diagnostic performance of six different commercial rapid antigen tests (Coronavirus antigen [Ag] rapid test cassette [Healgen Scientific, Houston, TX, USA], COVID-19 Ag FIA [Vircell, SD Biosensor Inc., Gyeonggi-do, Republic of Korea], Clinitest rapid COVID-19 antigen test [Siemens, Healthineers, Erlangen, Germany], SARS-CoV-2 rapid antigen test [SD Biosensor; Roche Diagnostics, Basel, Switzerland], Panbio COVID-19 Ag rapid test device [Abbott, Chicago, IL, USA], and SARS-CoV-2 test [MonLab, Barcelona, Spain]) in 130 nasopharyngeal swab samples tested previously by RT-PCR. The overall sensitivity of the rapid tests ranged from 65% to 79%, and the specificity was 100% for all of them. The sensitivity was higher for those samples with RT-PCR cycle threshold (