A distributed combustion solver for engine simulations on grids

AbstractMulti-dimensional models for predictive simulations of modern engines are an example of multi-physics and multi-scale mathematical models, since lots of thermofluiddynamic processes in complex geometrical configurations have to be considered. Typical models involve different submodels, including turbulence, spray and combustion models, with different characteristic time scales. The predictive capability of the complete models depends on the accuracy of the submodels as well as on the reliability of the numerical solution algorithms. In this work we propose a multi-solver approach for reliable and efficient solution of the stiff Ordinary Differential Equation (ODE) systems arising from detailed chemical reaction mechanisms for combustion modeling. Main aim was to obtain high-performance parallel solution of combustion submodels in the overall procedure for simulation of engines on distributed heterogeneous computing platforms. To this aim we interfaced our solver with the CHEMKIN-II package and the KIVA3V-II code and carried out multi-computer simulations of realistic engines. Numerical experiments devoted to test reliability of the simulation results and efficiency of the distributed combustion solver are presented and discussed

A Parallel Implementation of the Network Identification by Multiple Regression (NIR) Algorithm to Reverse-Engineer Regulatory Gene Networks

The reverse engineering of gene regulatory networks using gene expression profile data has become crucial to gain novel biological knowledge. Large amounts of data that need to be analyzed are currently being produced due to advances in microarray technologies. Using current reverse engineering algorithms to analyze large data sets can be very computational-intensive. These emerging computational requirements can be met using parallel computing techniques. It has been shown that the Network Identification by multiple Regression (NIR) algorithm performs better than the other ready-to-use reverse engineering software. However it cannot be used with large networks with thousands of nodes - as is the case in biological networks - due to the high time and space complexity. In this work we overcome this limitation by designing and developing a parallel version of the NIR algorithm. The new implementation of the algorithm reaches a very good accuracy even for large gene networks, improving our understanding of the gene regulatory networks that is crucial for a wide range of biomedical applications

Comparison of local injection of methotrexate and linear salpingostomy in the conservative laparoscopic treatment of ectopic pregnancy

STUDY OBJECTIVE: To compare local injection of metothrexate (MTX) and linear salpingostomy in the conservative laparoscopic treatment of ectopic pregnancy. DESIGN: Prospective, nonrandomized study, July 1991 to May 1994. SETTING: Department of obstetrics and gynecology in a university hospital. PATIENTS: Fourteen women with unruptured ectopic pregnancies without documented fetal heart motion and size below 50 mm as measured by ultrasound. INTERVENTIONS: All 14 women underwent the laparoscopic treatment by either local injection of MTX or linear salpingostomy (7 patients each). MEASUREMENTS AND MAIN RESULTS: Both treatments were successful in all patients. Mean length of operation was 32 +/- 5 minutes (range 25-35 min) in the MTX group versus 67 +/- 15 minutes (range 50-90 min) in the salpingostomy group. Mean length of hospital stay was 2.7 days (range 1-5 days) and 1.7 days (range 1-3 days), respectively. No intraoperative complications occurred, and the postoperative course was uneventful in all women. Mean disappearance time of serum beta-human chorionic gonadotropin (hCG) levels was similar in both groups, although in the linear salpingostomy group the decrease was immediate. No difference in tubal patency on follow-up hysterosalpingography was observed between the two groups. CONCLUSIONS: Although this is a preliminary report with a small number of patients, both types of treatment were safe and effective. An advantage of linear salpingostomy was the predictable and consistent decline of circulating beta-hCG, and consequently a reduced need for a close follow-up. Local MTX injection was safe, economic, effective, and easy to perform, and in our experience the surgical time was statistically shorter than that for linear salpingostomy. Therefore, in selected patients, local injection of MTX could be the treatment of choice for unruptured ectopic pregnancy, avoiding a longer and potentially more dangerous procedure. Long-term outcomes do not seem to differ between the two types of treatment

A community-based resource for automatic exome variant-calling and annotation in Mendelian disorders

BACKGROUND: Mendelian disorders are mostly caused by single mutations in the DNA sequence of a gene, leading to a phenotype with pathologic consequences. Whole Exome Sequencing of patients can be a cost-effective alternative to standard genetic screenings to find causative mutations of genetic diseases, especially when the number of cases is limited. Analyzing exome sequencing data requires specific expertise, high computational resources and a reference variant database to identify pathogenic variants. RESULTS: We developed a database of variations collected from patients with Mendelian disorders, which is automatically populated thanks to an associated exome-sequencing pipeline. The pipeline is able to automatically identify, annotate and store insertions, deletions and mutations in the database. The resource is freely available online http://exome.tigem.it. The exome sequencing pipeline automates the analysis workflow (quality control and read trimming, mapping on reference genome, post-alignment processing, variation calling and annotation) using state-of-the-art software tools. The exome-sequencing pipeline has been designed to run on a computing cluster in order to analyse several samples simultaneously. The detected variants are annotated by the pipeline not only with the standard variant annotations (e.g. allele frequency in the general population, the predicted effect on gene product activity, etc.) but, more importantly, with allele frequencies across samples progressively collected in the database itself, stratified by Mendelian disorder. CONCLUSIONS: We aim at providing a resource for the genetic disease community to automatically analyse whole exome-sequencing samples with a standard and uniform analysis pipeline, thus collecting variant allele frequencies by disorder. This resource may become a valuable tool to help dissecting the genotype underlying the disease phenotype through an improved selection of putative patient-specific causative or phenotype-associated variations

Lamin A/C sustains PcG protein architecture, maintaining transcriptional repression at target genes

Beyond its role in providing structure to the nuclear envelope, lamin A/C is involved in transcriptional regulation. However, its cross talk with epigenetic factors--and how this cross talk influences physiological processes--is still unexplored. Key epigenetic regulators of development and differentiation are the Polycomb group (PcG) of proteins, organized in the nucleus as microscopically visible foci. Here, we show that lamin A/C is evolutionarily required for correct PcG protein nuclear compartmentalization. Confocal microscopy supported by new algorithms for image analysis reveals that lamin A/C knock-down leads to PcG protein foci disassembly and PcG protein dispersion. This causes detachment from chromatin and defects in PcG protein-mediated higher-order structures, thereby leading to impaired PcG protein repressive functions. Using myogenic differentiation as a model, we found that reduced levels of lamin A/C at the onset of differentiation led to an anticipation of the myogenic program because of an alteration of PcG protein-mediated transcriptional repression. Collectively, our results indicate that lamin A/C can modulate transcription through the regulation of PcG protein epigenetic factors

Minimally invasive simple prostatectomy: Robotic-assisted versus laparoscopy. A comparative study

Purpose: Robotic-assisted simple prostatectomy (RASP) is a novel surgical procedure for the management of obstructive symptoms caused by enlarged prostate glands. Before the introduction of minimally invasive techniques, the standard approach was the open simple prostatectomy (OSP). The aim of our study was to compare intraoperative and perioperative outcomes of robotic (RASP) and laparoscopic (LSP) simple prostatectomy. Methods: We retrospectively analyzed data from patients who underwent minimally invasive simple prostatectomy at the Urological Department of Portogruaro Hospital, Portogruaro, and at the Urological Department of "San Bassiano" Hospital, in Bassano del Grappa, from March 2015 to December 2020. Data collected from medical records included age, body mass index, prostate volume, operative time, preoperative International Prostatic Symptoms Score (IPSS), postoperative IPSS, time with drainage, blood transfusion, intraoperative complications, perioperative complications and length of hospital stay. Results: Robotic-assisted (n = 25) and laparoscopic simple prostatectomy (n = 25) were performed with a transvesical approach. No significant differences were observed regarding baseline characteristics, body mass index, prostate volume and IPSS. Operative time was lower in the laparoscopic group (122 min vs 139 min) (p = 0.024), while hospital stay was lower in the robotic group (4 days vs 6 days) (p = 0.047). Conclusions: Robotic-assisted simple prostatectomy is a safe technique with results comparable to laparoscopic simple prostatectomy, encompassing the advantage of a shorter hospitalization. Considering the costs and the limited availability of robotic-assisted simple prostatectomy, laparoscopic simple prostatectomy is a valid and safe alternative for experienced surgeons

Sarilumab plus standard of care vs standard of care for the treatment of severe COVID-19: a phase 3, randomized, open-labeled, multi-center study (ESCAPE study)

Background Among interleukin-6 inhibitors suggested for use in COVID-19, there are few robust evidences for the efficacy of sarilumab. Herein, we evaluated the efficacy and safety of sarilumab in severe COVID-19.Methods In this phase 3, open-labeled, randomized clinical trial, conducted at 5 Italian hospitals, adults with severe COVID-19 pneumonia (excluding mechanically ventilated) were randomized 2:1 to receive intravenous sarilumab (400 mg, repeatable after 12 h) plus standard of care (SOC) (arm A) or to continue SOC (arm B). Randomization was web-based. As post-hoc analyses, the participants were stratified according to baseline inflammatory parameters. The primary endpoint was analysed on the modified Intention-To-Treat population, including all the randomized patients who received any study treatment (sarilumab or SOC). It was time to clinical improvement of 2 points on a 7-points ordinal scale, from baseline to day 30. We used Kaplan Meier method and log-rank test to compare the primary outcome between two arms, and Cox regression stratified by clinical center and adjusted for severity of illness, to estimate the hazard ratio (HR). The trial was registered with EudraCT (2020-001390-76).Findings Between May 2020 and May 2021, 191 patients were assessed for eligibility, of whom, excluding nine dropouts, 176 were assigned to arm A (121) and B (55). At day 30, no significant differences in the primary endpoint were found (88% [95% CI 81-94] in arm A vs 85% [74-93], HR 1.07 [0.8-1.5] in arm B; log-rank p = 0.50). After stratifying for inflammatory parameters, arm A showed higher probability of improvement than B without statistical significance in the strata with C reactive protein (CRP) < 7 mg/dL (88% [77-96] vs 79% [63-91], HR 1.55 [0.9-2.6]; log-rank p = 0.049) and in the strata with lymphocytes <870/mmc (90% [79-96]) vs (73% [55-89], HR 1.53 [0.9-2.7]; log-rank p = 0.058). Overall, 39/121 (32%) AEs were reported in arm A and 14/55 (23%) in B (p = 0.195), while serious AEs were 22/121 (18%) and 7/55 (11%), respectively (p = 0.244). There were no treatment-related deaths.Interpretation The efficacy of sarilumab in severe COVID-19 was not demonstrated both in the overall and in the stratified for severity analysis population. Exploratory analyses suggested that subsets of patients with lower CRP values or lower lymphocyte counts might have had benefit with sarilumab treatment, but this finding would require replication in other studies. The relatively low rate of concomitant corticosteroid use, could partially explain our results.Funding This study was supported by INMI "Lazzaro Spallanzani" Ricerca Corrente Linea 1 on emerging and ree-merging infections, funded by Italian Ministry of Health.Copyright (c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362