515 research outputs found

    Fluid Flow Property Estimation from Seismic Scattering Data

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    We present a methodology for relating seismic scattering signals from fractures to the fluid permeability field of the fracture network. The workflow is used to interpret seismic scattering signals for the reservoir permeability of the Emilio Field in the Adriatic Sea.Eni-MIT Energy Initiative Founding Member Progra

    Permeability Estimates of Self-Affine Fracture Faults Based on Generalization of the Bottle Neck Concept

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    We propose a method for calculating the effective permeability of two-dimensional self-affine permeability fields based on generalizing the one-dimensional concept of a bottleneck. We test the method on fracture faults where the local permeability field is given by the cube of the aperture field. The method remains accurate even when there is substantial mechanical overlap between the two fracture surfaces. The computational efficiency of the method is comparable to calculating a simple average and is more than two orders of magnitude faster than solving the Reynolds equations using a finite-difference scheme

    Building up a collaborative network for the surveillance of HIV genetic diversity in Italy. A pilot study

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    introduction. Prevalence of infection with HIV-1 non-B subtypes in Italy has been reported to raise, due to increased migration flows and travels. HIV-1 variants show different biological and immunological properties that impact on disease progression rate, response to antiretroviral therapy (ART) and sensitivity of diagnostic tests with important implications for public health. Therefore, a constant surveillance of the dynamics of HIV variants in Italy should be a high public health priority. Organization of surveillance studies requires building up a platform constituted of a network of clinical centers, laboratories and institutional agencies, able to properly collect samples for the investigation of HIV subtypes heterogeneity and to provide a database with reliable demographic, clinical, immunological and virological data. Aim. We here report our experience in building up such a platform, co-ordinated by the National AIDS Center of the Istituto Superiore di Sanità, taking advantage of a pilot study aimed at evaluating HIV subtypes diversity in populations of HIV-infected migrant people in Italy. Materials and methods. Four hundred and thirty four HIV-infected migrants were enrolled in 9 Italian clinical centers located throughout the Italian territory. Standard Operating Procedures (SOPs) for sample collection were provided by the National AIDS Center to each clinical center. In addition, clinical centers were required to fill up a case report form (crf) for each patient, which included demographic, clinical, immunological and virological information. Results. All centers properly collected and stored samples from each enrolled individual. Overall, the required information was correctly provided for more than 90% of the patients. However, some fields of the crf, particularly those including information on the last HIV-negative antibody test and presence of co-infections, were properly filled up in less than 80% of the enrolled migrants. Centers from Northern and Central Italy showed a better tendency to report correct information in the crf than centers from the South. These results provide evidence that procedures for establishing a platform for the surveillance of HIV subtype heterogeneity are affordable by all the components of the network and lay the ground for the organization of a broader HIV subtypes surveillance in Italy

    Long-term kidney function recovery and mortality after COVID-19-associated acute kidney injury: An international multi-centre observational cohort study

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    Background While acute kidney injury (AKI) is a common complication in COVID-19, data on post-AKI kidney function recovery and the clinical factors associated with poor kidney function recovery is lacking. Methods A retrospective multi-centre observational cohort study comprising 12,891 hospitalized patients aged 18 years or older with a diagnosis of SARS-CoV-2 infection confirmed by polymerase chain reaction from 1 January 2020 to 10 September 2020, and with at least one serum creatinine value 1–365 days prior to admission. Mortality and serum creatinine values were obtained up to 10 September 2021. Findings Advanced age (HR 2.77, 95%CI 2.53–3.04, p \u3c 0.0001), severe COVID-19 (HR 2.91, 95%CI 2.03–4.17, p \u3c 0.0001), severe AKI (KDIGO stage 3: HR 4.22, 95%CI 3.55–5.00, p \u3c 0.0001), and ischemic heart disease (HR 1.26, 95%CI 1.14–1.39, p \u3c 0.0001) were associated with worse mortality outcomes. AKI severity (KDIGO stage 3: HR 0.41, 95%CI 0.37–0.46, p \u3c 0.0001) was associated with worse kidney function recovery, whereas remdesivir use (HR 1.34, 95%CI 1.17–1.54, p \u3c 0.0001) was associated with better kidney function recovery. In a subset of patients without chronic kidney disease, advanced age (HR 1.38, 95%CI 1.20–1.58, p \u3c 0.0001), male sex (HR 1.67, 95%CI 1.45–1.93, p \u3c 0.0001), severe AKI (KDIGO stage 3: HR 11.68, 95%CI 9.80–13.91, p \u3c 0.0001), and hypertension (HR 1.22, 95%CI 1.10–1.36, p = 0.0002) were associated with post-AKI kidney function impairment. Furthermore, patients with COVID-19-associated AKI had significant and persistent elevations of baseline serum creatinine 125% or more at 180 days (RR 1.49, 95%CI 1.32–1.67) and 365 days (RR 1.54, 95%CI 1.21–1.96) compared to COVID-19 patients with no AKI. Interpretation COVID-19-associated AKI was associated with higher mortality, and severe COVID-19-associated AKI was associated with worse long-term post-AKI kidney function recovery

    Niemann–Pick type C disease as proof-of-concept for intelligent biomarker panel selection in neurometabolic disorders

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    AIM: Using Niemann-Pick type C disease (NPC) as a paradigm, we aimed to improve biomarker discovery in patients with neurometabolic disorders. METHOD: Using a multiplexed liquid chromatography tandem mass spectrometry dried bloodspot assay, we developed a selective intelligent biomarker panel to monitor known biomarkers N-palmitoyl-O-phosphocholineserine and 3β,5α,6β-trihydroxy-cholanoyl-glycine as well as compounds predicted to be affected in NPC pathology. We applied this panel to a clinically relevant paediatric patient cohort (n = 75; 35 males, 40 females; mean age 7 years 6 months, range 4 days-19 years 8 months) presenting with neurodevelopmental and/or neurodegenerative pathology, similar to that observed in NPC. RESULTS: The panel had a far superior performance compared with individual biomarkers. Namely, NPC-related established biomarkers used individually had 91% to 97% specificity but the combined panel had 100% specificity. Moreover, multivariate analysis revealed long-chain isoforms of glucosylceramide were elevated and very specific for patients with NPC. INTERPRETATION: Despite advancements in next-generation sequencing and precision medicine, neurological non-enzymatic disorders remain difficult to diagnose and lack robust biomarkers or routine functional testing for genetic variants of unknown significance. Biomarker panels may have better diagnostic accuracy than individual biomarkers in neurometabolic disorders, hence they can facilitate more prompt disease identification and implementation of emerging targeted, disease-specific therapies

    Use of an extended KDIGO definition to diagnose acute kidney injury in patients with COVID-19:A multinational study using the ISARIC–WHO clinical characterisation protocol

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    BackgroundAcute kidney injury (AKI) is one of the most common and significant problems in patients with Coronavirus Disease 2019 (COVID-19). However, little is known about the incidence and impact of AKI occurring in the community or early in the hospital admission. The traditional Kidney Disease Improving Global Outcomes (KDIGO) definition can fail to identify patients for whom hospitalisation coincides with recovery of AKI as manifested by a decrease in serum creatinine (sCr). We hypothesised that an extended KDIGO (eKDIGO) definition, adapted from the International Society of Nephrology (ISN) 0by25 studies, would identify more cases of AKI in patients with COVID-19 and that these may correspond to community-acquired AKI (CA-AKI) with similarly poor outcomes as previously reported in this population.Methods and findingsAll individuals recruited using the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC)–World Health Organization (WHO) Clinical Characterisation Protocol (CCP) and admitted to 1,609 hospitals in 54 countries with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection from February 15, 2020 to February 1, 2021 were included in the study. Data were collected and analysed for the duration of a patient’s admission. Incidence, staging, and timing of AKI were evaluated using a traditional and eKDIGO definition, which incorporated a commensurate decrease in sCr. Patients within eKDIGO diagnosed with AKI by a decrease in sCr were labelled as deKDIGO. Clinical characteristics and outcomes—intensive care unit (ICU) admission, invasive mechanical ventilation, and in-hospital death—were compared for all 3 groups of patients. The relationship between eKDIGO AKI and in-hospital death was assessed using survival curves and logistic regression, adjusting for disease severity and AKI susceptibility. A total of 75,670 patients were included in the final analysis cohort. Median length of admission was 12 days (interquartile range [IQR] 7, 20). There were twice as many patients with AKI identified by eKDIGO than KDIGO (31.7% versus 16.8%). Those in the eKDIGO group had a greater proportion of stage 1 AKI (58% versus 36% in KDIGO patients). Peak AKI occurred early in the admission more frequently among eKDIGO than KDIGO patients. Compared to those without AKI, patients in the eKDIGO group had worse renal function on admission, more in-hospital complications, higher rates of ICU admission (54% versus 23%) invasive ventilation (45% versus 15%), and increased mortality (38% versus 19%). Patients in the eKDIGO group had a higher risk of in-hospital death than those without AKI (adjusted odds ratio: 1.78, 95% confidence interval: 1.71 to 1.80, p-value < 0.001). Mortality and rate of ICU admission were lower among deKDIGO than KDIGO patients (25% versus 50% death and 35% versus 70% ICU admission) but significantly higher when compared to patients with no AKI (25% versus 19% death and 35% versus 23% ICU admission) (all p-values <5 × 10−5). Limitations include ad hoc sCr sampling, exclusion of patients with less than two sCr measurements, and limited availability of sCr measurements prior to initiation of acute dialysis.ConclusionsAn extended KDIGO definition of AKI resulted in a significantly higher detection rate in this population. These additional cases of AKI occurred early in the hospital admission and were associated with worse outcomes compared to patients without AKI

    Multinational characterization of neurological phenotypes in patients hospitalized with COVID-19

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    Neurological complications worsen outcomes in COVID-19. To define the prevalence of neurological conditions among hospitalized patients with a positive SARS-CoV-2 reverse transcription polymerase chain reaction test in geographically diverse multinational populations during early pandemic, we used electronic health records (EHR) from 338 participating hospitals across 6 countries and 3 continents (January–September 2020) for a cross-sectional analysis. We assessed the frequency of International Classification of Disease code of neurological conditions by countries, healthcare systems, time before and after admission for COVID-19 and COVID-19 severity. Among 35,177 hospitalized patients with SARS-CoV-2 infection, there was an increase in the proportion with disorders of consciousness (5.8%, 95% confidence interval [CI] 3.7–7.8%, pFDR < 0.001) and unspecified disorders of the brain (8.1%, 5.7–10.5%, pFDR < 0.001) when compared to the pre-admission proportion. During hospitalization, the relative risk of disorders of consciousness (22%, 19–25%), cerebrovascular diseases (24%, 13–35%), nontraumatic intracranial hemorrhage (34%, 20–50%), encephalitis and/or myelitis (37%, 17–60%) and myopathy (72%, 67–77%) were higher for patients with severe COVID-19 when compared to those who never experienced severe COVID-19. Leveraging a multinational network to capture standardized EHR data, we highlighted the increased prevalence of central and peripheral neurological phenotypes in patients hospitalized with COVID-19, particularly among those with severe disease
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