62 research outputs found
Direct data-driven filter design for automotive controlled suspensions
This paper investigates the filter design problem for automotive controlled suspensions when no mathematical model of the system is available, but a set of initial experiments can be performed, where also the variable to be estimated is measured. The problem of designing suitable linear time-invariant filters is here investigated, focusing the attention on the estimation of the relative vertical speed between chassis and wheel, using the data provided by two accelerometers measuring the chassis and wheel accelerations. Disturbances and noises are supposed to be norm-bounded and optimality refers to the minimization of the induced norm from disturbances to the estimation error. A Set Membership formulation is followed and, for classes of filters with exponentially decaying impulse response, an approximating set is determined guaranteed to contain all the solutions to the optimal filtering problem. A method is proposed for designing almost-optimal filters with finite impulse response, whose worst-case estimation error is at most twice the lowest achievable one. Numerical simulations using standard "benchmark" road profiles illustrate the effectiveness of the proposed solutions
Direct data-driven filter design for automotive controlled suspensions
This paper investigates the filter design problem for automotive controlled suspensions when no mathematical model of the system is available, but a set of initial experiments can be performed, where also the variable to be estimated is measured. The problem of designing suitable linear time-invariant filters is here investigated, focusing the attention on the estimation of the relative vertical speed between chassis and wheel, using the data provided by two accelerometers measuring the chassis and wheel accelerations. Disturbances and noises are supposed to be norm-bounded and optimality refers to the minimization of the induced norm from disturbances to the estimation error. A Set Membership formulation is followed and, for classes of filters with exponentially decaying impulse response, an approximating set is determined guaranteed to contain all the solutions to the optimal filtering problem. A method is proposed for designing almost-optimal filters with finite impulse response, whose worst-case estimation error is at most twice the lowest achievable one. Numerical simulations using standard "benchmark" road profiles illustrate the effectiveness of the proposed solutions
Genomic variability of host factors in AIDS: role of antimicrobial peptides resistance to lentiviral infections.
2006/2007LâAIDS è una delle maggiori pandemie in corso sulla Terra. Sfortunatamente lâelevato tasso di mutazioni del virus impedisce agli immunologi di trovare un vaccino efficiente contro il suo agente eziologico: il virus HIV-1.
I peptidi antimicrobici sono una classe di importanti molecole coinvolte nella risposta immunitaria innata caratterizzati sia da attivitĂ sia antibatterica che antimicrobica e che, visto il loro ruolo come barriera primaria contro i patogeni, probabilmente ricoprouno un ruolo rilevante nella trasmissione e nellâinfezione da HIV-1, probabilmente intervenendo nel sito dellâinfezione per fornire una prima barriera contro lâingresso del virus. Molti studi hanno evidenziato il ruolo anti-HIV-1 dei peptidi antimicrobici; nonostante ciò nessuno degli studi fatti prende in considerazione il fatto che differenti classi di peptidi antimicrobici possano cooperare in maniera sinergica, essendo presenti contemporaneamente sul sito dellâinfezione.
Nel nostro lavoro siamo stati in grado di studiare il ruolo di polimorfismi (SNP) a carico di differenti geni dellâimmunitĂ innata nellâinfezione e nella trasmissione verticale in un gruppo di bambini brasiliani provenienti dalle zone piĂš povere di Recife e dei suoi sobborghi.
I gruppi che abbiamo studiato sono stati: controlli sani con la stessa origine etnica dei pazienti (lâorigine etnica è stata verificata mediante sequenziamento della regione D-loop mitocondriale), pazienti infetti nati da madri sieropositive e bambini esposti al virus che nonostante siano nati da madri HIV-1 positive non hanno contratto il virus. In nessun caso le madri sono state sottoposte a taglio cesareo o a terapia antiretrovirale prima del parto per ridurre il rischio di trasmissione virale.
Siamo stati in grado di dimostrare che due polimorfismi nella regione 5âUTR del gene DEFB1, e precisamente il -20(G/A) ed il -52(G/A), sono in grado di influenzare la suscettibilitĂ allâinfezione da HIV-1.
Inoltre abbiamo evidenziato, mediante studi in vitro, che questi polimorfismi, assieme al polimorfismo -44(G/C), possiedono unâattivitĂ funzionale sulla trascrizione del gene.
Siamo anche stati in grado di mostrare che un polimorfismo nel gene LTF, codificante la proteina lattoferrina, è fortemente correlato con una protezione dallâinfezione da HIV-1. Il polimorfismo in questione, lâR29K, conferisce una maggiore attivitĂ antimicrobica alla lattoferrina e modifica la sequenza aminoacidica della regione N-terminale della proteina, la lattoferricina.
Gli studi sulla sequenza del gene hCAP18, codificante per lâunica catelicidina umana conosciuta, LL37, non hanno dato risultati significativi. Non siamo riusciti ed evidenziare alcun polimorfismo non-sinonimo nei pazienti presi in esame. Siamo tuttavia stati in grado di identificare alcune nuove mutazioni che, sfortunatamente, sono troppo rare per avere una significativitĂ statistica.
Il locus defensinico 8p23 è conosciuto per essere soggetto ad un elevato tasso di ricombinazione. Di conseguenza molti dei geni delle defensine umane possono essere presenti in un numero di copie variabile, fatto che può influenzare lâespressione proteica di questi geni.
Abbiamo quindi impiegato la tecnica dellâMLPA per studiare lâinfluenza del numero di copie dei seguenti geni: DEFA4, DEFA5, DEFA6, DEFB1, DEFB4, DEFB107B, DEFB108, DEFA3, DEFA7, DEFB4, DEFB103A, DEFB104, DEFB105, DEFB106, e DEFB107B.
Abbiamo mostrato come un basso numero di copie del gene DEFB104 aumenta significativamente il rischio di infezione da HIV-1.
Studi funzionali hanno poi evidenziato come lâespressione dellâmRNA sia linearmente dipendente dal numero di copie del gene DEFB104 presenti nel genoma.
Non câera alcun tipo di correlazione tra gli altri geni studiati e lâinfezione o la trasmissione verticale del virus HIV-1.
Inoltre, per rafforzare il nostro studio, abbiamo svolto delle indagini su altri geni dellâimmunitĂ innata, diversi da quelli delle defensine: MBL2 e la sua serin-proteasi associata (MASP2).
Siamo stati in grado di evidenziare come gli aplotipi di MBL2 caratterizzati da una maggiore produzione di MBL siano protettivi nei confronti dellâinfezione da HIV-1. I polimorfismi studiati sono stati il 52 Arg-Cys, il 54 Glu-Asp ed il 57 Glu-Gly nel primo esone di MBL2 e il -550(G/C) ed il -221(G/C) nel promotore del gene.
Abbiamo anche genotipizzato i nostri gruppo per polimorfismi nel gene . 52 Arg-Cys, 54 Glu-Asp and 57 Glu-Gly, che è funzionalmente complementare ad MBL. Non abbimo trovato genotipi o aplotipi di rischio per i polimorfismi D105G e R99K.
In conclusione siamo stati in grado di dimostrare che polimorfismi in molti geni dellâimmunitĂ innata possono influenzare lâinfezione da HIV-1 e la sua trasmissione da madre a figlio, fornendo quindi un obiettivo per studiare nuove strategie per combattere la diffusione dellâHIV-1.
Bisogna notare, tuttavia, che non si può dedurre una regola generale dai dati ottenuti, in quanto sembra che, almeno nel caso dellâHIV-1, lâimmunitĂ innata può ricoprire un ruolo duplice, in quanto una ridotta espressione genica a volte inibisce lâattivitĂ di HIV-1 e a volte la promuove
Evolution of the hepcidin gene in primates
<p>Abstract</p> <p>Background</p> <p>Hepcidin/LEAP-1 is an iron regulatory hormone originally identified as an antimicrobial peptide. As part of a systematic analysis of the evolution of host defense peptides in primates, we have sequenced the orthologous gene from 14 species of non-human primates.</p> <p>Results</p> <p>The sequence of the mature peptide is highly conserved amongst all the analyzed species, being identical to the human one in great apes and gibbons, with a single residue conservative variation in Old-World monkeys and with few substitutions in New-World monkeys.</p> <p>Conclusion</p> <p>Our analysis indicates that hepcidin's role as a regulatory hormone, which involves interaction with a conserved receptor (ferroportin), may result in conservation over most of its sequence, with the exception of the stretch between residues 15 and 18, which in New-World monkeys (as well as in other mammals) shows a significant variation, possibly indicating that this structural region is involved in other functions.</p
Reduced long-term overall mortality in heart failure patients with prolonged QRS treated with CRT combined with ICD vs. heart failure patients with narrow QRS treated with ICD only
n/
Machine learning in clinical and epidemiological research: isn't it time for biostatisticians to work on it?
In recent years, there has been a widespread cross-fertilization between Medical Statistics and Machine Learning (ML) techniques
Guidelines for the use and interpretation of diagnostic methods in adult food allergy
Food allergy has an increasing prevalence in the general population and in Italy concerns 8 % of people with allergies. The spectrum of its clinical manifestations ranges from mild symptoms up to potentially fatal anaphylactic shock. A number of patients can be diagnosed easily by the use of first- and second-level procedures (history, skin tests and allergen specific IgE). Patients with complex presentation, such as multiple sensitizations and pollen-food syndromes, frequently require a third-level approach including molecular diagnostics, which enables the design of a component-resolved sensitization profile for each patient. The use of such techniques involves specialists' and experts' skills on the issue to appropriately meet the diagnostic and therapeutic needs of patients. Particularly, educational programs for allergists on the use and interpretation of molecular diagnostics are needed
Defining Kawasaki disease and pediatric inflammatory multisystem syndrome-temporally associated to SARS-CoV-2 infection during SARS-CoV-2 epidemic in Italy: results from a national, multicenter survey
Background: There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities.
Methods: The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group - KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients' outcome were collected in an online anonymized database (RedCAPÂŽ). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste; AOU Meyer, Florence; IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups.
Results: One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p = 0.04 and 71,9% vs 43,4%; p = 0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p < 0.0001). SARS-CoV-2 assay more often resulted positive in KCG than in KDG (75,5% vs 20%; p < 0.0001). Short-term follow data showed minor complications. Comparing KDG with a KD-Historical Italian cohort (598 patients), no statistical difference was found in terms of clinical manifestations and laboratory data.
Conclusion: Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths
Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both
Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPDâ+âHF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPDâ+âHF. Patients with COPDâ+âHF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPDâ+âHF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPDâ+âHF for all causes (pâ=â0.010), respiratory causes (pâ=â0.006), cardiovascular causes (pâ=â0.046) and respiratory plus cardiovascular causes (pâ=â0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population
- âŚ