Analyzing and Modeling the Performance of the HemeLB Lattice-Boltzmann Simulation Environment

We investigate the performance of the HemeLB lattice-Boltzmann simulator for cerebrovascular blood flow, aimed at providing timely and clinically relevant assistance to neurosurgeons. HemeLB is optimised for sparse geometries, supports interactive use, and scales well to 32,768 cores for problems with ~81 million lattice sites. We obtain a maximum performance of 29.5 billion site updates per second, with only an 11% slowdown for highly sparse problems (5% fluid fraction). We present steering and visualisation performance measurements and provide a model which allows users to predict the performance, thereby determining how to run simulations with maximum accuracy within time constraints.Comment: Accepted by the Journal of Computational Science. 33 pages, 16 figures, 7 table

Myocardial Function Maturation in Very-Low-Birth-Weight Infants and Development of Bronchopulmonary Dysplasia

Background: Myocardial function in very-low-birth-weight infants (VLBWIs) develops during early postnatal life, but different patterns of temporal evolution that might be related to the development of bronchopulmonary dysplasia (BPD) are not completely understood. Methods: A prospective cohort study including VLBWIs admitted to our NICU from January 2015 to 2017 was conducted. Plasma N-terminal pro B type natriuretic peptide (NTproBNP) levels were measured, and echocardiograms were performed at 24 and 72 h of life and weekly thereafter until 36 weeks of postmenstrual age (PMA). We measured the tricuspid annular plane systolic excursion (TAPSE) by M-mode; the lateral tricuspid E', A', and S' waves; and the myocardial performance index (MPI) by tissue doppler imaging (TDI). The subjects were divided into non-BPD and BPD groups. Results: We included 101 VLBWIs. The TAPSE and E', A', and S' waves increased while MPI-TDI decreased over time. Birth gestational age (GA) and postnatal PMA impacted these parameters, which evolved differently in those who developed BPD compared to those in the non-BPD group. The NTproBNP levels at 14 days of life and different echocardiographic parameters were associated with the development of BPD in different multivariate models. Conclusion: TAPSE and TDI values depend on GA and PMA and follow a different temporal evolution that is related to the later development of BPD. Combined biochemical and echocardiographic biomarkers can help identify which VLBWIs are at higher risk of developing BDP

Left ventricular myocardial performance

Recentemente Tei e collaboratori, hanno proposto un nuovo indice Doppler-derivato in grado di valutare simultaneamente la funzione sistolica e diastolica. Questo indice di performance cardiaca (MPI), definito come la somma del tempo di contrazione isovolumetrica e tempo di rilasciamento isovolumetrico diviso per il tempo di eiezione ventricolare sinistro, è considerato di facile esecuzione, non dipendente dalla geometria ventricolare, non invasivo, riproducibile e indipendente dalla frequenza cardiaca e dalla pressione arteriosa. L’MPI ha dimostrato di avere un’importante utilità clinica. È infatti prolungato in molte malattie cardiache, anche in assenza di segni clinici. Studi hanno dimostrato che l’MPI correla bene con misure invasive di funzione sistolica e diastolica, fornendo informazioni prognostiche su morbilità e mortalità nei pazienti con cardiopatia ischemica, amiloidosi cardiaca, cardiomiopatia dilatativa, ipertensione polmonare primitiva e variazioni di funzione ventricolare sinistra come risultato di terapie farmacologiche. L’MPI risulta essere modificato anche in pazienti asintomatici che presentano fattori di rischio come il diabete mellito e l’ipertensione arteriosa. Orem et al. ha registrato variazioni dell’MPI in una popolazione diabetica con diversi gradi di albuminuria. Più recentemente, l’MPI ha mostrato risultati promettenti nella valutazione della funzione ventricolare prenatale e in bambini e adulti con malattie cardiache congenite. L'obiettivo di questa tesi è quello di analizzare le applicazioni cliniche dell’ MPI in diverse condizioni fisiologiche e patologiche, chiarendo alcuni aspetti della dinamica ventricolare sinistra. Nel primo studio, abbiamo dimostrato che la geometria ventricolare sinistra rappresenta un fattore determinante della performance del miocardio. In realtà, i nostri dati dimostrano una correlazione tra MPI e spessore relativo di parete ma non con la massa indicizzata con la superficie corporea. La dipendenza dell’MPI dalla geometria di camera ventricolare deve essere presa in considerazione durante l'applicazione dell’indice per la valutazione della performance miocardica come marcatore prognostico nella malattia cardiaca in cui la geometria ventricolare può essere modificata. Nel secondo studio l’MPI è stato valutato per l’identificazione delle anomalie cardiache subcliniche in un gruppo omogeneo di pazienti asintomatici con diabete mellito tipo 2, di recente diagnosi, con o senza ipertensione arteriosa. L’incremento dell’MPI è dovuto principalmente ad un prolungamento della IRT. Una correlazione tra MPI e il valore di HbA1c è risultata significativa indicando il suo ruolo come marker precoce di controllo metabolico. I nostri risultati potrebbero avere importanti implicazioni cliniche. In primo luogo, questo indice potrebbe rappresentare un facile approccio per individuare una fase precoce di cardiomiopatia diabetica che preceda la disfunzione diastolica, quindi monitorare la storia naturale della malattia diabetica stessa. In secondo luogo, l’MPI potrebbe essere utile per valutare indirettamente il controllo metabolico o suggerire un rapido avvio di specifici trattamenti farmacologici che possano aiutare il decorso clinico della cardiomiopatia diabetica. Una diagnosi precoce di cardiomiopatia diabetica tramite l’MPI non è solo importante, ma può anche rivelarsi essenziale per testare nuovi approcci terapeutici in corso di malattia diabetica. Infine, nel terzo studio, l’MPI sembra essere una tecnica non invasiva sensibile per l’individuazione sub-clinica di una disfunzione ventricolare sinistra in pazienti con sclerosi multipla trattati con basse dosi di mitoxantrone, un agente antineoplastico della famiglia degli antracenedioni. Tale indice sembra fornire migliori informazioni prognostiche per quanto concerne il rischio di cardiotossicità, rispetto alle misurazioni ecocardiografiche convenzionali. Pensiamo che l’MPI possa essere un parametro aggiuntivo all'ecocardiografia convenzionale nel monitoraggio degli effetti collaterali cardiaci, in grado di individuare una cardiotossicità subclinica da mitoxantrone. In conclusione, una semplice misura Doppler-derivata in grado di esprimere la performance globale del miocardio, è correlata alla complessa funzione cardiaca e sembra essere un indicatore utile di risultati clinici, rappresentando un indice aggiuntivo per la diagnosi e per la gestione clinica dei pazienti con molte malattie non solo cardiache ma anche sistemiche.Recently, a conceptually new Doppler index that combines the assessment of systolic and diastolic left ventricular (LV) performance was proposed by Tei and co-workers. This Myocardial Performance Index (MPI), which is defined as the sum of isovolumetric contraction time and isovolumetric relaxation time divided by the ejection time, was reported to be simple, non-geometrical, non-invasive, reproducible and independent of the heart rate and blood pressure. The MPI has been shown to have significant clinical utility. It is prolonged in many cardiac diseases even in the absence of clinical signs. Studies have demonstrated that MPI correlates well with invasive measures of both systolic and diastolic function in adults and provides prognostic information about morbidity and mortality in patients with ischemic heart disease, cardiac amyloidosis, dilated cardiomyopathy, primary pulmonary hypertension and detects early LV functional improvement as a result of drug therapy. MPI is also abnormal in individuals without overt cardiac disease who have risk factors such as diabetes mellitus and treated and untreated hypertension. Orem et al. demonstrated progressively more abnormal MPI with increasing degrees of albuminuria in a diabetic population. More recently, the MPI has shown promise in the assessment of right ventricular function in fetus, children and adults with various heart disease. The aim of this thesis was to analyse the LV myocardial performance, applying the MPI in various physiological and pathological conditions to elucidate some aspects of LV myocardial dynamic. In the first study, we demonstrated that LV geometry represents an important determinant of the myocardial performance. In fact, our data demonstrates a correlation between MPI and RWT but not with LVM/BSA. The MPI geometry-dependence must be taken into consideration during the application of the Index for the evaluation of myocardial performance, and when used as a prognostic marker in cardiac disease where the LV geometry could be modified. In the second study the MPI has been confirmed able to identify the earliest abnormalities of cardiac performance at echocardiography in a homogeneous group of uncomplicated asymptomatic type 2 diabetic patients with very short duration of disease with or without hypertension. The MPI increase was mainly due to a prolongation of IRT. A correlation between MPI and the HbA1c value, was found indicating its role as an early marker of metabolic control. Our findings may have important clinical implications. First, this index could provide an easy approach to detect an earliest phase of diabetic cardiomyopathy that precede diastolic dysfunction, and to monitor the natural history of the diabetic disease. Second, MPI could be useful for indirectly assess the metabolic control or suggest an early start of specific pharmacological treatments that may help the clinical course of diabetic cardiomyopathy. Most importantly, whether such abnormalities may be reverted by optimal metabolic control and/or pharmacologic treatments could be determined. Diagnosing pre-clinical diabetic cardiomyopathy early through MPI is not only important but also may turn out to be essential for the appropriate clinical testing of new therapeutic approaches to diabetic disease. Finally, the MPI appears to be a sensitive noninvasive technique for detecting significant subclinical left ventricular dysfunction, in patients with multiple sclerosis treated with low dose of mitoxantrone, an antracenedione antineoplastic agent. Besides, provides important prognostic information for the risk of future cardiotoxicity, beyond other conventional echocardiographic measurements. We expect that MPI may be an adjunctive parameter to the conventional echocardiography in monitoring cardiac side effects and for detecting sub-clinical cardiotoxicity of mitoxantrone. In conclusion, a simple measure of Doppler index, combining systolic and diastolic time interval as an expression of global myocardial performance, correlates with overall cardiac function, seem to be a useful predictor of clinical outcome and could be an adjunctive index for the diagnosis and for the clinical management of patients with many cardiac and systemic disease

ModHMM: A Modular Supra-Bayesian Genome Segmentation Method

Genome segmentation methods are powerful tools to obtain cell type or tissue-specific genome-wide annotations and are frequently used to discover regulatory elements. However, traditional segmentation methods show low predictive accuracy and their data-driven annotations have some undesirable properties. As an alternative, we developed ModHMM, a highly modular genome segmentation method. Inspired by the supra-Bayesian approach, it incorporates predictions from a set of classifiers. This allows to compute genome segmentations by utilizing state-of-the-art methodology. We demonstrate the method on ENCODE data and show that it outperforms traditional segmentation methods not only in terms of predictive performance, but also in qualitative aspects. Therefore, ModHMM is a valuable alternative to study the epigenetic and regulatory landscape across and within cell types or tissues