Using Topological Data Analysis for diagnosis pulmonary embolism

Pulmonary Embolism (PE) is a common and potentially lethal condition. Most patients die within the first few hours from the event. Despite diagnostic advances, delays and underdiagnosis in PE are common.To increase the diagnostic performance in PE, current diagnostic work-up of patients with suspected acute pulmonary embolism usually starts with the assessment of clinical pretest probability using plasma d-Dimer measurement and clinical prediction rules. The most validated and widely used clinical decision rules are the Wells and Geneva Revised scores. We aimed to develop a new clinical prediction rule (CPR) for PE based on topological data analysis and artificial neural network. Filter or wrapper methods for features reduction cannot be applied to our dataset: the application of these algorithms can only be performed on datasets without missing data. Instead, we applied Topological data analysis (TDA) to overcome the hurdle of processing datasets with null values missing data. A topological network was developed using the Iris software (Ayasdi, Inc., Palo Alto). The PE patient topology identified two ares in the pathological group and hence two distinct clusters of PE patient populations. Additionally, the topological netowrk detected several sub-groups among healthy patients that likely are affected with non-PE diseases. TDA was further utilized to identify key features which are best associated as diagnostic factors for PE and used this information to define the input space for a back-propagation artificial neural network (BP-ANN). It is shown that the area under curve (AUC) of BP-ANN is greater than the AUCs of the scores (Wells and revised Geneva) used among physicians. The results demonstrate topological data analysis and the BP-ANN, when used in combination, can produce better predictive models than Wells or revised Geneva scores system for the analyzed cohortComment: 18 pages, 5 figures, 6 tables. arXiv admin note: text overlap with arXiv:cs/0308031 by other authors without attributio

Experimental thermal performance comparison of pure and metal foam-loaded PCMs

The thermal performance of latent heat thermal energy storage (LHTES) systems considerably depends on thermal conductivity of adopted phase change materials (PCMs). To increase the low thermal conductivity of these materials, pure PCMs can be loaded with metal foams. In this study, the melting process of pure and metal-foam loaded phase change materials placed in a rectangular shape case is experimentally investigated by imposing a constant heat flux at the top. Two different paraffin waxes with melting point of about 35°C are tested. The results obtained with pure PCM are compared with those achieved from the use of PCM combined with two different porous metals: a 10 PPI aluminum foam with 96% porosity and a 20 PPI copper foam with 95% porosity. The results demonstrate how metal foams lead to a significant improvement of conduction heat transfer reducing significantly the melting time and the temperature difference between the heater and PCM

Short-Term Repeatability of Noninvasive Aortic Pulse Wave Velocity Assessment: Comparison between Methods and Devices

BACKGROUND Aortic pulse wave velocity (PWV) is an indirect index of arterial stiffness and an independent cardiovascular risk factor. Consistency of PWV assessment over time is thus an essential feature for its clinical application. However, studies providing a comparative estimate of the reproducibility of PWV across different noninvasive devices are lacking, especially in the elderly and in individuals at high cardiovascular risk. METHODS Aimed at filling this gap, short-term repeatability of PWV, estimated with 6 different devices (Complior Analyse, PulsePen-ETT, PulsePen-ET, SphygmoCor Px/Vx, BPLab, and Mobil-O-Graph), was evaluated in 102 high cardiovascular risk patients hospitalized for suspected coronary artery disease (72 males, 65 ± 13 years). PWV was measured in a single session twice, at 15-minute interval, and its reproducibility was assessed though coefficient of variation (CV), coefficient of repeatability, and intraclass correlation coefficient. RESULTS The CV of PWV, measured with any of these devices, was <10%. Repeatability was higher with cuff-based methods (BPLab: CV = 5.5% and Mobil-O-Graph: CV = 3.4%) than with devices measuring carotid-femoral PWV (Complior: CV = 8.2%; PulsePen-TT: CV = 8.0%; PulsePen-ETT: CV = 5.8%; and SphygmoCor: CV = 9.5%). In the latter group, PWV repeatability was lower in subjects with higher carotid-femoral PWV. The differences in PWV between repeated measurements, except for the Mobil-O-Graph, did not depend on short-term variations of mean blood pressure or heart rate. CONCLUSIONS Our study shows that the short-term repeatability of PWV measures is good but not homogenous across different devices and at different PWV values. These findings, obtained in patients at high cardiovascular risk, may be relevant when evaluating the prognostic importance of PW

C6orf10 low-frequency and rare variants in italian multiple sclerosis patients

In light of the complex nature of multiple sclerosis (MS) and the recently estimated contribution of low-frequency variants into disease, decoding its genetic risk components requires novel variant prioritization strategies. We selected, by reviewing MS Genome Wide Association Studies (GWAS), 107 candidate loci marked by intragenic single nucleotide polymorphisms (SNPs) with a remarkable association (p-value <= 5 x 10(-6)). A whole exome sequencing (WES)-based pilot study of SNPs with minor allele frequency (MAF) <= 0.04, conducted in three Italian families, revealed 15 exonic low-frequency SNPs with affected parent-child transmission. These variants were detected in 65/120 Italian unrelated MS patients, also in combination (22 patients). Compared with databases (controls gnomAD, dbSNP150, ExAC, Tuscany-1000 Genome), the allelic frequencies of C6orf10 rs 16870005 and IL2RA rs12722600 were significantly higher (i.e., controls gnomAD, p = 9.89 x 10(-7) and p < 1 x 10(-20)). TET2 rs61744960 and TRAF3 rs138943371 frequencies were also significantly higher, except in Tuscany-1000 Genome. Interestingly, the association of C6orf10 rs16870005 (Ala431Thr) with MS did not depend on its linkage disequilibrium with the HLA-DRB1 locus. Sequencing in the MS cohort of the C6orf10 3' region revealed 14 rare mutations (10 not previously reported). Four variants were null, and significantly more frequent than in the databases. Further, the C6orf10 rare variants were observed in combinations, both intra-locus and with other low-frequency SNPs. The C6orf10 Ser389Xfr was found homozygous in a patient with early onset of the MS. Taking into account the potentially functional impact of the identified exonic variants, their expression in combination at the protein level could provide functional insights in the heterogeneous pathogenetic mechanisms contributing to MS.In light of the complex nature of multiple sclerosis (MS) and the recently estimated contribution of low-frequency variants into disease, decoding its genetic risk components requires novel variant prioritization strategies. We selected, by reviewing MS Genome Wide Association Studies (GWAS), 107 candidate loci marked by intragenic single nucleotide polymorphisms (SNPs) with a remarkable association (p-value ≤ 5 × 10−6). A whole exome sequencing (WES)-based pilot study of SNPs with minor allele frequency (MAF) ≤ 0.04, conducted in three Italian families, revealed 15 exonic low-frequency SNPs with affected parent-child transmission. These variants were detected in 65/120 Italian unrelated MS patients, also in combination (22 patients). Compared with databases (controls gnomAD, dbSNP150, ExAC, Tuscany-1000 Genome), the allelic frequencies of C6orf10 rs16870005 and IL2RA rs12722600 were significantly higher (i.e., controls gnomAD, p = 9.89 × 10−7 and p < 1 × 10−20). TET2 rs61744960 and TRAF3 rs138943371 frequencies were also significantly higher, except in Tuscany-1000 Genome. Interestingly, the association of C6orf10 rs16870005 (Ala431Thr) with MS did not depend on its linkage disequilibrium with the HLA-DRB1 locus. Sequencing in the MS cohort of the C6orf10 3′ region revealed 14 rare mutations (10 not previously reported). Four variants were null, and significantly more frequent than in the databases. Further, the C6orf10 rare variants were observed in combinations, both intra-locus and with other low-frequency SNPs. The C6orf10 Ser389Xfr was found homozygous in a patient with early onset of the MS. Taking into account the potentially functional impact of the identified exonic variants, their expression in combination at the protein level could provide functional insights in the heterogeneous pathogenetic mechanisms contributing to MS

Neurological involvement in Ile68Leu (p.Ile88Leu) ATTR amyloidosis: not only a cardiogenic mutation

Ile68Leu transthyretin-related amyloidosis (ATTR) is known as a mainly or exclusively cardiogenic variant. We hypothesized that an accurate specialized neurological evaluation could reveal a consistent frequency of mixed phenotypes.Forty-six consecutive subjects with transthyretin (TTR) Ile68Leu (p.Ile88Leu) mutation (29 patients and 17 unaffected carriers) underwent an in-depth cardiac and neurologic evaluation at a single center.All 29 patients showed cardiac involvement. In 20 (69%) cases, it was associated with neurological abnormalities (i.e. a mixed phenotype): 10 (35% of the total) had signs and symptoms of neuropathy, 5 (17%) had abnormalities at the neurologic specialist examination but without symptoms, and 5 (17%) had abnormal nerve conduction study only. None of the asymptomatic carriers showed neurological abnormalities or cardiac involvement. The Neuropathy Impairment Score was5 in seven patients at baseline, and became5 in six more patients during follow-up. The probability of experiencing a major adverse cardiac event (MACE) during follow-up was higher in the mixed than cardiologic phenotype (At least two-thirds of patients with Ile68Leu ATTR and amyloidotic cardiomyopathy show an associated - definite or probable - neurologic impairment of variable degree if accurately evaluated in a neurologic setting. This proportion can rise during follow-up. The mixed phenotype carries a worse prognosis compared to the exclusively cardiologic one. These observations show that more patients could be eligible for treatment with gene silencers than currently indicated and highlight the need for an in-depth and continuous multidisciplinary evaluation of Ile68Leu ATTR patients

Comparison Between Invasive and Noninvasive Methods to Estimate Subendocardial Oxygen Supply and Demand Imbalance

Background Estimation of the balance between subendocardial oxygen supply and demand could be a useful parameter to assess the risk of myocardial ischemia. Evaluation of the subendocardial viability ratio (SEVR, also known as Buckberg index) by invasive recording of left ventricular and aortic pressure curves represents a valid method to estimate the degree of myocardial perfusion relative to left ventricular workload. However, routine clinical use of this parameter requires its noninvasive estimation and the demonstration of its reliability. Methods and Results Arterial applanation tonometry allows a noninvasive estimation of SEVR as the ratio of the areas directly beneath the central aortic pressure curves obtained during diastole (myocardial oxygen supply) and during systole (myocardial oxygen demand). However, this "traditional" method does not account for the intra-ventricular diastolic pressure and proper allocation to systole and diastole of left ventricular isometric contraction and relaxation, respectively, resulting in an overestimation of the SEVR values. These issues are considered in the novel method for SEVR assessment tested in this study. SEVR values estimated with carotid tonometry by "traditional" and "new" method were compared with those evaluated invasively by cardiac catheterization. The "traditional" method provided significantly higher SEVR values than the reference invasive SEVR: average of differences +/- SD= 44 +/- 11% (limits of agreement: 23% - 65%). The noninvasive "new" method showed a much better agreement with the invasive determination of SEVR: average of differences +/- SD= 0 +/- 8% (limits of agreement: -15% to 16%). Conclusions Carotid applanation tonometry provides valid noninvasive SEVR values only when all the main factors determining myocardial supply and demand flow are considered

InSAR Monitoring of Italian Coastline Revealing Natural and Anthropogenic Ground Deformation Phenomena and Future Perspectives

In this work, we use X and C-band SAR data provided by the COSMO-SkyMed and ENVISAT missions to detect and measure some ground deformation phenomena along six coastal areas of Italy. In particular, we exploit multi-temporal interferometric synthetic aperture radar (InSAR), i.e., small baseline subsets (SBAS) and interferometric point target analysis (IPTA) methods, to retrieve the deformation rate maps and time series for each investigated area. Multi-temporal InSAR analysis revealed local subsidence and uplifting effects in Ravenna Coastal Areas, Fiumicino, Campi Flegrei, Sibari Plain, Augusta Bay, and Taranto Gulf. Our work is meant as a demonstrator to show how InSAR-based analysis can provide a detailed understanding of the coastal hazards. Such analysis also opens up new monitoring scenarios such as the possibility of designing a near real-time surveillance service based on Sentinel-1 SAR data.Publishedid 31522T. Deformazione crostale attivaJCR Journa

SARS-CoV-2-Associated ssRNAs Activate Human Neutrophils in a TLR8-Dependent Fashion

COVID-19 disease is characterized by a dysregulation of the innate arm of the immune system. However, the mechanisms whereby innate immune cells, including neutrophils, become activated in patients are not completely understood. Recently, we showed that GU-rich RNA sequences from the SARS-CoV-2 genome (i.e., SCV2-RNA1 and SCV2-RNA2) activate dendritic cells. To clarify whether human neutrophils may also represent targets of SCV2-RNAs, neutrophils were treated with either SCV2-RNAs or, as a control, R848 (a TLR7/8 ligand), and were then analyzed for several functional assays and also subjected to RNA-seq experiments. Results highlight a remarkable response of neutrophils to SCV2-RNAs in terms of TNFα, IL-1ra, CXCL8 production, apoptosis delay, modulation of CD11b and CD62L expression, and release of neutrophil extracellular traps. By RNA-seq experiments, we observed that SCV2-RNA2 promotes a transcriptional reprogramming of neutrophils, characterized by the induction of thousands of proinflammatory genes, similar to that promoted by R848. Furthermore, by using CU-CPT9a, a TLR8-specific inhibitor, we found that SCV2-RNA2 stimulates neutrophils exclusively via TLR8-dependent pathways. In sum, our study proves that single-strand RNAs from the SARS-CoV-2 genome potently activate human neutrophils via TLR8, thus uncovering a potential mechanism whereby neutrophils may contribute to the pathogenesis of severe COVID-19 disease