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The results of a combined experimental and computational investigation of the structural evolution of Au81Si19, Pd82Si18, and Pd77Cu6Si17 metallic glass forming liquids are presented. Electrostatically levitated metallic liquids are prepared, and synchrotron x-ray scattering studies are combined with embedded atom method molecular dynamics simulations to probe the distribution of relevant structural units. Metal–metalloid based metallic glass forming systems are an extremely important class of materials with varied glass forming ability and mechanical processibility. High quality experimental x-ray scattering data are in poor agreement with the data from the molecular dynamics simulations, demonstrating the need for improved interatomic potentials. The first peak in the x-ray static structure factor in Pd77Cu6Si17 displays evidence for a Curie–Weiss type behavior but also a peak in the effective Curie temperature. A proposed order parameter distinguishing glass forming ability, 1 / S T , q 1 − 1 , shows a peak in the effective Curie temperature near a crossover temperature established by the behavior of the viscosity, TA. [ABSTRACT FROM AUTHOR]

The results of a combined structural and dynamical study of Cu–Zr–Al metallic glass forming liquids are presented. Containerless high-energy x-ray scattering experiments made using electrostatic levitation are combined with molecular dynamics simulations to probe the onset of rapid structural ordering as well as the temperature-dependent diffusivity and viscosity in three liquids: Cu49Zr45Al6, Cu47Zr45Al8, and Cu43Zr45Al12. These compositions were chosen because they are reported to have dramatically different glass forming-ability. Experimental data show that the first peak in the x-ray static structure factor displays evidence for a Curie–Weiss type behavior, but also a peak in the effective Curie temperature. The evidence provided here for the onset of cooperativity, marked by a crossover temperature, TA (which is usually above the liquidus temperature), is accompanied by the onset of development of more spatially extended structural order in the liquids. Based on the molecular dynamics simulations, each of the liquids exhibits a clear breakdown of the Stokes–Einstein relation at a temperature near, but below, the crossover temperature, TA. The breakdown is manifest as a rapid reduction in the relative diffusion coefficients between Cu, Zr, and Al. [ABSTRACT FROM AUTHOR]

Abstract To determine the prevalence of functional, respiratory and renal impairments and of post-intensive-care-syndrome (PICS) among patients who had attended a post-ICU multidisciplinary consultation (post-ICU-MC) around 3 months after ICU discharge, we performed a retrospective, monocentric observational study, at Clermont Ferrand University hospital, France. We included patients who had attended a post-ICU-MC. Their characteristics during ICU stay and at the post-ICU-MC were collected. Functional status was assessed by the 6-min-walking test, handgrip test and peak inspiratory pressure, respiratory function by exploratory functional outcomes, mental status by SF-36 score, and quality of life by SF-36 score and European Quality of Life 5 Dimensions questionnaire. Overall, we enrolled 67 patients, of whom 70%, 74%, and 68% had functional, respiratory, and renal impairments, respectively, at the post-ICU-MC. Additionally, 40%, 28%, 19%, and 2.5% had three, two, one, and none of these impairments, respectively. All patients experienced mental disorders and a decline in quality of life. Functional impairment correlated with frailty score and sex, and respiratory function with age. To conclude, the prevalence of PICS in our cohort was high, as was that of functional, respiratory and renal failure.

Summary: Background & Aims: Sarcopenia and myosteatosis are proving to be major factors to predict mortality in intensive care patients. Few studies are currently focusing on evaluating the functional impact after intensive care discharge and none has considered sarcopenia and myosteatosis as prognostic factors.The aim of our study was to determine whether sarcopenia and myosteatosis are reliable prognostic factors for mid-term functional impact in critical patients a few months after intensive care discharge. Methods: We carried out a retrospective monocentric study using computed-tomography scanner performed on intensive care admission and/or three months after discharge to assess sarcopenia and myosteatosis in 43 patients with critical illnesses who underwent a multidisciplinary evaluation on a multidisciplinary consultation's day hospital.We used L3 and/or T4 computed-tomography-scan levels to assess sarcopenia with the skeletal muscle index and myosteatosis with skeletal muscle density. These data were compared with main patient characteristics on intensive care admission and during intensive care stay and with functional assessments at the post intensive care multidisciplinary consultations, based on hand grip strength test, 6-minute walking test, and peak inspiratory pressure. Results: We found a good correlation of both skeletal muscle index and skeletal muscle density for T4 and L3 levels. Skeletal muscle index was correlated with hand grip strength test, and skeletal muscle density with 6-minute walking test, which are both functional tests recommended in the algorithm of the European Working Group on Sarcopenia in Older People to diagnose sarcopenia. Peak inspiratory pressure was correlated with both skeletal muscle index and skeletal muscle density and also with other functional tests. Conclusions: We confirmed the reliability of thoracic computed-tomography-scan to assess sarcopenia and myosteatosis. We found that skeletal muscle index and skeletal muscle density are independent but complementary predictive factors for functional impact at mid-term in intensive care patients. Peak inspiratory pressure could be a useful tool for the assessment and management of sarcopenia.

Abstract Regional citrate anticoagulation use in intermittent hemodialysis is limited by the increased risk of metabolic complications due to faster solute exchanges than with continuous renal replacement therapies. Several simplifications have been proposed. The objective of this study was to validate a mathematical model of hemodialysis anticoagulated with citrate that was then used to evaluate different prescription scenarios on anticoagulant effectiveness (free calcium concentration in dialysis filter) and calcium balance. A study was conducted in hemodialyzed patients with a citrate infusion into the arterial line and a 1.25 mmol/L calcium dialysate. Calcium and citrate concentrations were measured upstream and downstream of the citrate infusion site and in the venous line. The values measured in the venous lines were compared with those predicted by the model using Bland and Altman diagrams. The model was then used with 22 patients to make simulations. The model can predict the concentration of free calcium, bound to citrate or albumin, accurately. Irrespective of the prescription scenario a decrease in free calcium below 0.4 mmol/L was obtained only in a fraction of the dialysis filter. A zero or slightly negative calcium balance was observed, and should be taken into account in case of prolonged use.

Abstract Background The honey bee reference genome, HAv3.1, was produced from a commercial line sample that was thought to have a largely dominant Apis mellifera ligustica genetic background. Apis mellifera mellifera, often referred to as the black bee, has a separate evolutionary history and is the original type in western and northern Europe. Growing interest in this subspecies for conservation and non-professional apicultural practices, together with the necessity of deciphering genome backgrounds in hybrids, triggered the necessity for a specific genome assembly. Moreover, having several high-quality genomes is becoming key for taking structural variations into account in pangenome analyses. Results Pacific Bioscience technology long reads were produced from a single haploid black bee drone. Scaffolding contigs into chromosomes was done using a high-density genetic map. This allowed for re-estimation of the recombination rate, which was over-estimated in some previous studies due to mis-assemblies, which resulted in spurious inversions in the older reference genomes. The sequence continuity obtained was very high and the only limit towards continuous chromosome-wide sequences seemed to be due to tandem repeat arrays that were usually longer than 10 kb and that belonged to two main families, the 371 and 91 bp repeats, causing problems in the assembly process due to high internal sequence similarity. Our assembly was used together with the reference genome to genotype two structural variants by a pangenome graph approach with Graphtyper2. Genotypes obtained were either correct or missing, when compared to an approach based on sequencing depth analysis, and genotyping rates were 89 and 76% for the two variants. Conclusions Our new assembly for the Apis mellifera mellifera honey bee subspecies demonstrates the utility of multiple high-quality genomes for the genotyping of structural variants, with a test case on two insertions and deletions. It will therefore be an invaluable resource for future studies, for instance by including structural variants in GWAS. Having used a single haploid drone for sequencing allowed a refined analysis of very large tandem repeat arrays, raising the question of their function in the genome. High quality genome assemblies for multiple subspecies such as presented here, are crucial for emerging projects using pangenomes.

Abstract Background About 20% of patients with acute pancreatitis develop a necrotising form with a worse prognosis due to frequent appearance of organ failure(s) and/or infection of necrosis. Aims of the present study was to evaluate the “step up” approach treatment of infected necrosis in terms of: feasibility, success in resolving infection, morbidity of procedures, risk factors associated with death and long-term sequels. Methods In this observational retrospective monocentric study in the real life, necrotizing acute pancreatitis at the stage of infected walled-off necrosis were treated as follow: first step with drainage (radiologic and/or endoscopic-ultrasound-guided with lumen apposing metal stent); in case of failure, minimally invasive necrosectomy sessions(s) by endoscopy through the stent and/or via retroperitoneal surgery (step 2); If necessary open surgery as a third step. Efficacy was assessed upon to a composite clinical-biological criterion: resolution of organ failure(s), decrease of at least two of clinico-biological criteria among fever, CRP serum level, and leucocytes count). Results Forty-one consecutive patients were treated. The step-up strategy: (i) was feasible in 100% of cases; (ii) allowed the infection to be resolved in 33 patients (80.5%); (iii) Morbidity was mild and rapidly resolutive; (iv) the mortality rate at 6 months was of 19.5% (significant factors: SIRS and one or more organ failure(s) at admission, fungal infection, size of the largest collection ≥ 16 cm). During the follow-up (median 72 months): 27% of patients developed an exocrine pancreatic insufficiency, 45% developed or worsened a previous diabetes, 24% had pancreatic fistula and one parietal hernia. Conclusions Beside a very good feasibility, the step-up approach for treatment of infected necrotizing pancreatitis in the real life displays a clinico-biological efficacy in 80% of cases with acceptable morbidity, mortality and long-term sequels regarding the severity of the disease.

Summary: Background: We apply endoscopic ultrasound-guided fine needle aspiration biopsy to cytopathologically diagnose and sample nucleic acids from primary tumours regardless of the disease stage. Methods: 397 patients with proven pancreatic adenocarcinoma were included and followed up in a multicentre prospective study. DNA and mRNA were extracted from materials of primary tumours obtained by endoscopic ultrasound-guided fine needle aspiration biopsy and analysed using targeted deep sequencing and RNAseq respectively. Findings: The variant allele frequency of the KRAS mutation was used to evaluate the tumour cellularity, ranging from 15 to 20% in all cells, regardless of the tumour stage. The molecular profile of metastatic primary tumours significantly differed from other types of tumours, more frequently having TP53 mutations (p = 0.0002), less frequently having RNF43 mutations, and possessing more basal-like mRNA component (p = 0.001). Molecular markers associated with improved overall survival were: mutations in homologous recombination deficiency genes in patients who received first-line platinum-based chemotherapy (p = 0.025) and wild-type TP53 gene in patients with locally advanced tumours who received radio-chemotherapy (p = 0.01). The GemPred transcriptomic profile was associated with a significantly better overall survival in patients with locally advanced or metastatic pancreatic cancer who received a gemcitabine-based first-line treatment (p = 0.019). Interpretation: The combination of genomic and transcriptomic analyses of primary pancreatic tumours enables us to distinguish metastatic tumours from other tumour types. Our molecular strategy may assist in predicting overall survival outcomes for platinum or gemcitabine-based chemotherapies, as well as radio-chemotherapy. Funding: Institut National Du Cancer (BCB INCa_7294), CHU of Toulouse, Inserm and Ligue Nationale Contre le Cancer (CIT program).

Underutilized sheep and goat breeds can adapt to challenging environments due to their genetics. Integrating publicly available genomic datasets with new data will facilitate genetic diversity analyses; however, this process is complicated by data discrepancies, such as outdated assembly versions or different data formats. Here, we present the SMARTER-database, a collection of tools and scripts to standardize genomic data and metadata, mainly from SNP chip arrays on global small ruminant populations, with a focus on reproducibility. SMARTER-database harmonizes genotypes for about 12,000 sheep and 6,000 goats to a uniform coding and assembly version. Users can access the genotype data via File Transfer Protocol and interact with the metadata through a web interface or using their custom scripts, enabling efficient filtering and selection of samples. These tools will empower researchers to focus on the crucial aspects of adaptation and contribute to livestock sustainability, leveraging the rich dataset provided by the SMARTER-database. Availability and implementation The code is available as open-source software under the MIT license at https://github.com/cnr-ibba/SMARTER-database.