Benchmark based on application signature to analyze and predict their behavior

Currently, there are benchmark sets that measure the performance of HPC systems under specific computing and communication properties. These benchmarks represent the kernels of applications that measure specific hardware components. If the user’s application is not represented by any benchmark, it is not possible to obtain an equivalent performance metric. In this work, we propose a benchmark based on the signature of an MPI application obtained by the PAS2P method. PAS2P creates the application signature in order to predict the execution time, which we believe will be very adjusted in relation to the execution time of the full application. The signature has two performance qualities: the bounded time to execute it (a benchmark property) and the quality of prediction. Therefore, we propose to extend the signature by giving the benchmark capacities such as the efficiency of the application over the HPC system. The performance metrics will be performed by the benchmark proposed. The experimentation validates our proposal with an average error of prediction close to 7%.Instituto de Investigación en Informátic

FibroScan-aspartate aminotransferase (FAST) score for monitoring histological improvement in non-alcoholic steatohepatitis activity during semaglutide treatment: post-hoc analysis of a randomised, double-blind, placebo-controlled, phase 2b trial

\ua9 2023Background: Currently, assessment of candidate pharmacotherapies in patients with non-alcoholic steatohepatitis (NASH) involves invasive liver biopsy. Non-invasive scores, such as the FibroScan-aspartate aminotransferase (FAST) score, are used to identify candidates for therapy, but their ability to assess disease progression or treatment effect is unknown. We aimed to assess the association between FAST score and histological endpoints. Methods: We conducted a post-hoc analysis using data from a prior randomised, double-blind, placebo-controlled, phase 2b trial at 143 sites across 16 countries. Patients (aged 18–75 years) with biopsy-confirmed NASH, fibrosis stage 1–3, and a Non-alcoholic fatty liver disease Activity Score (NAS) ≥4 were enrolled between January 2017 and September 2018, and randomly assigned to receive once-daily subcutaneous semaglutide 0.1, 0.2, or 0.4 mg or placebo for 72 weeks. A subgroup analysis of patients with FAST score and histological data in the pooled semaglutide treatment and placebo arms at baseline and week 72 was performed. The original trial is registered at ClinicalTrials.gov, NCT02970942. Findings: A total of 122 patients were included in this post-hoc analysis (93 received semaglutide and 29 received placebo). FAST score reduction was associated with achieving the primary endpoint of NASH resolution without worsening of fibrosis in the pooled semaglutide group (area under the receiver operating curve 0.69; 95% confidence interval [CI] 0.58, 0.81). Mean FAST score reduction from baseline to week 72 was greatest in patients who met the primary endpoint vs those who did not in both the semaglutide (−0.40 [95% CI –0.84, 0.04] vs −0.22 [95% CI –0.74, 0.30] points; p = 0.002) and placebo groups (−0.25 [95% CI –0.72, 0.23] vs 0.00 [95% CI –0.50, 0.50] points; p = 0.047). Similarly, mean reductions in FAST score at week 72 were greater in those with NAS improvement vs those without in the semaglutide and placebo groups (≥1 point, −0.36 [95% CI –0.82, 0.11] vs −0.08 [95% CI –0.53, 0.38] points [p < 0.001] and −0.25 [95% CI –0.64, 0.14] vs −0.06 [95% CI –0.40, 0.53] points [p = 0.001]; ≥2 points, −0.40 [95% CI –0.86, 0.06] vs −0.14 [95% CI –0.56, 0.28] points [p < 0.001] and −0.29 [95% CI –0.67, 0.09] vs −0.05 [95% CI –0.40, 0.50] points; [p < 0.001]). A FAST score reduction of more than 0.22 points after semaglutide treatment was associated with meeting the primary endpoint (sensitivity 78%; specificity 60%; positive likelihood ratio 1.26; negative likelihood ratio 0.25; odds ratio 4.93). Interpretation: The potential of the FAST score as a non-invasive monitoring tool to identify histological changes following treatment requires further evaluation and validation. Funding: Novo Nordisk A/S

Diagnosis, pathogenesis and outcome in leucocyte chemotactic factor 2 (ALECT2) amyloidosis

Introduction: Renal biopsy series from North America suggest that leucocyte chemotactic factor 2 (ALECT2) amyloid is the third most common type of renal amyloid. We report the first case series from a European Centre of prevalence, clinical presentation and diagnostic findings in ALECT2 amyloidosis and report long-term patient and renal outcomes for the first time. Methods: We studied the clinical features, diagnostic investigations and the outcome of all patients with ALECT2 amyloidosis followed systematically at the UK National Amyloidosis Centre (NAC) between 1994 and 2015. Results: Twenty-four patients, all non-Caucasian, were diagnosed with ALECT2 amyloidosis representing 1.3% of all patients referred to the NAC with biopsy-proved renal amyloid. Diagnosis was made at median age of 62 years, usually from renal histology; immunohistochemical staining was definitive for ALECT2 fibril type. Median estimated glomerular filtration rate (GFR) at diagnosis was 33 mL/min/1.73 m2 and median proteinuria was 0.5 g/24 h. Hepatic amyloid was evident on serum amyloid P component (SAP) scintigraphy in 11/24 cases but was not associated with significant derangement of liver function. No patient had evidence of cardiac amyloidosis or amyloid neuropathy. Median follow-up was 4.8 (range 0.5–15.2) years, during which four patients died and four progressed to end-stage renal disease. The mean rate of GFR loss was 4.2 (range 0.5–9.6) mL/min/year and median estimated renal survival from diagnosis was 8.2 years. Serial SAP scans revealed little or no change in total body amyloid burden. Conclusions: ALECT2 amyloidosis is a relatively benign type of renal amyloid, associated with a slow GFR decline, which is reliably diagnosed on renal histology. Neither the molecular basis nor the factors underlying the apparent restriction of ALECT2 amyloidosis to non-Caucasian populations have been determined

Order and Stochastic Dynamics in Drosophila Planar Cell Polarity

Cells in the wing blade of Drosophila melanogaster exhibit an in-plane polarization causing distal orientation of hairs. Establishment of the Planar Cell Polarity (PCP) involves intercellular interactions as well as a global orienting signal. Many of the genetic and molecular components underlying this process have been experimentally identified and a recently advanced system-level model has suggested that the observed mutant phenotypes can be understood in terms of intercellular interactions involving asymmetric localization of membrane bound proteins. Among key open questions in understanding the emergence of ordered polarization is the effect of stochasticity and the role of the global orienting signal. These issues relate closely to our understanding of ferromagnetism in physical systems. Here we pursue this analogy to understand the emergence of PCP order. To this end we develop a semi-phenomenological representation of the underlying molecular processes and define a “phase diagram” of the model which provides a global view of the dependence of the phenotype on parameters. We show that the dynamics of PCP has two regimes: rapid growth in the amplitude of local polarization followed by a slower process of alignment which progresses from small to large scales. We discuss the response of the tissue to various types of orienting signals and show that global PCP order can be achieved with a weak orienting signal provided that it acts during the early phase of the process. Finally we define and discuss some of the experimental predictions of the model

Diagnosis of Esophagitis Based on Face Recognition Techniques

Face recognition technology has evolved over years with the Principal Component Analysis (PCA) method being the benchmark for recognition efficiency. The face recognition techniques take care of variation of illumination, pose and other features of the face in the image. We envisage an application of these face recognition techniques for classification of medical images. The motivating factor being, given a condition of an organ it is represented by some typical features. In this paper we report the use of the face recognition techniques to classify the type of Esophagitis, a condition of inflammation of the esophagus. The image of the esophagus is captured in the process of endoscopy. We test PCA, Fisher Face method and Independent Component Analysis techniques to classify the images of the esophagus. Esophagitis is classified into four categories. The results of classification for each method are reported and the results are compared

FibroScan-AST (FAST) score for the non-invasive identification of patients with non-alcoholic steatohepatitis with significant activity and fibrosis: a prospective derivation and global validation study

BACKGROUND The burden of non-alcoholic fatty liver disease (NAFLD) is increasing globally, and a major priority is to identify patients with non-alcoholic steatohepatitis (NASH) who are at greater risk of progression to cirrhosis, and who will be candidates for clinical trials and emerging new pharmacotherapies. We aimed to develop a score to identify patients with NASH, elevated NAFLD activity score (NAS≥4), and advanced fibrosis (stage 2 or higher [F≥2]). METHODS This prospective study included a derivation cohort before validation in multiple international cohorts. The derivation cohort was a cross-sectional, multicentre study of patients aged 18 years or older, scheduled to have a liver biopsy for suspicion of NAFLD at seven tertiary care liver centres in England. This was a prespecified secondary outcome of a study for which the primary endpoints have already been reported. Liver stiffness measurement (LSM) by vibration-controlled transient elastography and controlled attenuation parameter (CAP) measured by FibroScan device were combined with aspartate aminotransferase (AST), alanine aminotransferase (ALT), or AST:ALT ratio. To identify those patients with NASH, an elevated NAS, and significant fibrosis, the best fitting multivariable logistic regression model was identified and internally validated using boot-strapping. Score calibration and discrimination performance were determined in both the derivation dataset in England, and seven independent international (France, USA, China, Malaysia, Turkey) histologically confirmed cohorts of patients with NAFLD (external validation cohorts). This study is registered with ClinicalTrials.gov, number NCT01985009. FINDINGS Between March 20, 2014, and Jan 17, 2017, 350 patients with suspected NAFLD attending liver clinics in England were prospectively enrolled in the derivation cohort. The most predictive model combined LSM, CAP, and AST, and was designated FAST (FibroScan-AST). Performance was satisfactory in the derivation dataset (C-statistic 0·80, 95% CI 0·76–0·85) and was well calibrated. In external validation cohorts, calibration of the score was satisfactory and discrimination was good across the full range of validation cohorts (C-statistic range 0·74–0·95, 0·85; 95% CI 0·83–0·87 in the pooled external validation patients' cohort; n=1026). Cutoff was 0·35 for sensitivity of 0·90 or greater and 0·67 for specificity of 0·90 or greater in the derivation cohort, leading to a positive predictive value (PPV) of 0·83 (84/101) and a negative predictive value (NPV) of 0·85 (93/110). In the external validation cohorts, PPV ranged from 0·33 to 0·81 and NPV from 0·73 to 1·0. INTERPRETATION The FAST score provides an efficient way to non-invasively identify patients at risk of progressive NASH for clinical trials or treatments when they become available, and thereby reduce unnecessary liver biopsy in patients unlikely to have significant disease

Spin Caloritronics

This is a brief overview of the state of the art of spin caloritronics, the science and technology of controlling heat currents by the electron spin degree of freedom (and vice versa).Comment: To be published in "Spin Current", edited by S. Maekawa, E. Saitoh, S. Valenzuela and Y. Kimura, Oxford University Pres

International Veterinary Epilepsy Task Force consensus proposal: Medical treatment of canine epilepsy in Europe

In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors’ experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible