Ultrasound shear wave elastography for liver disease. A critical appraisal of the many actors on the stage

In the last 12\u200a-\u200a18 months nearly all ultrasound manufacturers have arrived to implement ultrasound shear wave elastography modality in their equipment for the assessment of chronic liver disease; the few remaining players are expected to follow in 2016.When all manufacturers rush to a new technology at the same time, it is evident that the clinical demand for this information is of utmost value. Around 1990, there was similar demand for color Doppler ultrasound; high demand for contrast-enhanced ultrasonography was evident at the beginning of this century, and around 2010 demand increased for strain elastography. However, some issues regarding the new shear wave ultrasound technologies must be noted to avoid misuse of the resulting information for clinical decisions. As new articles are expected to appear in 2016 reporting the findings of the new technologies from various companies, we felt that the beginning of this year was the right time to present an appraisal of these issues. We likewise expect that in the meantime EFSUMB will release a new update of the existing guidelines 1 2.The first ultrasound elastography method became available 13 years ago in the form of transient elastography with Fibroscan(\uae) 3. It was the first technique providing non-invasive quantitive information about the stiffness of the liver and hence regarding the amount of fibrosis in chronic liver disease 3. The innovation was enormous, since a non-invasive modality was finally available to provide findings otherwise achievable only by liver biopsy. In fact, prior to ultrasound elastography, a combination of conventional and Doppler ultrasound parameters were utilized to inform the physician about the presence of cirrhosis and portal hypertension 4. However, skilled operators were required, reproducibility and diagnostic accuracy were suboptimal, and it was not possible to differentiate the pre-cirrhotic stages of fibrosis. All these limitations were substantially improved by transient elastography, performed with Fibroscan(\uae), a technology dedicated exclusively to liver elastography. Since then, more than 1300 articles dealing with transient elastography have been listed in PubMed, some describing results with more than 10,000 patients 5. The technique has been tested in nearly all liver disease etiologies, with histology as the reference standard. Meta-analysis of data, available in many etiologies 6, showed good performance and reproducibility as well as some situations limiting reliability 5. Thresholds for the different fibrosis stages (F0 to F4) have been provided by many large-scale studies utilizing histology as the reference standard 7. Transient elastography tracks the velocity of shear waves generated by the gentle hit of a piston on the skin, with the resulting compression wave traveling in the liver along its longitudinal axis. The measurement is made in a 4\u200acm long section of the liver, thus able to average slightly inhomogeneous fibrotic deposition.In 2008 a new modality became available, Acoustic Radiation Force Impulse (ARFI) quantification, and classified by EFSUMB 1 as point shear wave elastography (pSWE), since the speed of the shear wave (perpendicular to the longitudinal axis) is measured in a small region (a "point", few millimeters) at a freely-choosen depth within 8\u200acm from the skin. This technology was the first to be implemented in a conventional ultrasound scanner by Siemens(\uae) 8. Several articles have been published regarding this technology, most with the best reference standards 9, some including findings on more than 1000 hepatitis C patients 10 or reporting meta-analysis of data 11. Although the correlation between Siemens pSWE and transient elastography appeared high 12 13, the calculated thresholds for the different fibrosis stages and the stiffness ranges between the two techniques are not superimposable.Interestingly, pSWE appears to provide greater applicability than transient elastography for measuring both liver 13 and spleen stiffness, which is a new application of elastography 14, of interest for the prediction of the degree of portal hypertension 15 16.Nowadays other companies have started producing equipment with pSWE technology, but only very few articles have been published so far, for instance describing the use of Philips(\uae) equipment, which was the second to provide pSWE. These articles show preliminary good results also in comparison with TE 17 18. Not enough evidence is currently available in the literature about the elastographic performance of the products most recently introduced to the market. Furthermore, with some products the shear wave velocities generated by a single ultrasound acoustic push pulse can be measured in a bidimensional area (a box in the range of 2\u200a-\u200a3\u200acm per side) rather than in a single small point, producing a so-called bidimensional 2D-SWE 1. The stiffness is depicted in color within the area and refreshing of the measurement occurs every 1\u200a-\u200a2 seconds. Once the best image is acquired, the operator chooses a Region Of Interest (ROI) within the color box, where the mean stiffness is then calculated. 2D-SWE can be performed as a "one shot" technique or as a semi-"real-time" technique for a few seconds (at about 1 frame per second) in order to obtain a stable elastogram. With either technique, there should be no motion/breathing during image acquisition. A bidimensional averaged area should overcome the limitation of pSWE to inadvertently investigate small regions of greater or lesser stiffness than average. A shear wave quality indicator could be useful to provide real-time feedback and optimize placement of the sampling ROIs, a technology recently presented by Toshiba(\uae), but which is still awaiting validation in the literature.Supersonic Imagine by Aixplorer(\uae) which works with a different modality of insonation and video analysis compared to the the previously-mentioned three techniques (i.\u200ae., transient elastography, pSWE and 2D-SWE), leading to a bidimensional assessment of liver stiffness in real time up to 5\u200aHz and in larger regions; thus this technique is also termed real-time 2\u200aD SWE. It has been available on the market for a few years 19 20, and many articles have been published showing stiffness values quite similar to those of Fibroscan(\uae) 21; likewise, defined thresholds based on histological findings have appeared in several articles 19 20 21.After this brief summary of the technological state of the art we would like to mention the following critical issues that we believe every user should note prior to providing liver stiffness reports. \ub7 The thresholds obtained from the "oldest" techniques for the various fibrosis stages based on hundreds of patients with histology as reference standard cannot be straightforwardly applied to the new ultrasound elastography techniques, even if based on the same principle (e.\u200ag. pSWE). In fact, the different manufacturers apply proprietary patented calculation modes, which might result in slightly to moderately different values. It should be kept in mind that the range for intermediate fibrosis stages (F1 to F3) is quite narrow, in the order of 2\u200a-\u200a3 kilopascal (over a total range spanning 2 to 75 kPa with Fibroscan), so that slightly different differences in outputs could shift the assessment of patients from one stage to another. Comparative studies using phantoms and healthy volunteers, as well as patients, are eagerly awaited. In fact, the equipment might not produce linear correlations of measurements at different degrees of severity of fibrosis. As a theoretical example, some equipment might well correlate in their values with an older technique, such as transient elastography, at low levels of liver fibrosis, but not as well in cases of more advanced fibrosis or vice versa. Consequentely, when elastography data are included in a report, the equipment utilized for the measurement should be clearly specified, and conclusions about the fibrosis stage should be withheld if an insufficient number of comparative studies with solid reference standards are available for that specific equipment.. \ub7 Future studies using histology as a reference might be biased in comparison to previous studies, since nowadays fewer patients with chronic hepatitis C or hepatitis B undergo biopsy. In fact, due to wide availability of effective drugs as well as the use of established elastography methods for patients with viral hepatitis, most cases submitted to biopsy today have uncertain etiology or inconsistent and inconclusive clinical data. Therefore, extrapolated thresholds from such inhomogeneous populations applied to more ordinary patients with viral hepatitis might become problematic in the future, although no better solution is currently anticipated. This situation might lead to the adoption of a standard validated elastographic method as reference, but this has to be agreed-upon at an international level.. \ub7 Ultrasound elastography embedded in conventional scanners usually allows the choice of where to place the ROI within the color stiffness box and whether to confirm or exclude each single measurement when determining the final value. Thus, the operator has a greater potential to influence the final findings than with Fibroscan\uae, where these choices are not available. This has to be kept in mind to avoid the possibility that an operator could, even inadvertently, tend to confirm an assumption about that specific patient or to confirm the patient's expectations.. \ub7 Quality criteria for the new technologies following transient elastography are absent (depending on the manufacturer) or have not been satisfactorily defined, so that the information potentially inserted in a report cannot currently be judged for its reliability by the clinician.. (ABSTRACT TRUNCATED

Dark energy models toward observational tests and data

A huge amount of good quality astrophysical data converges towards the picture of a spatially flat universe undergoing the today observed phase of accelerated expansion. This new observational trend is commonly addressed as Precision Cosmology. Despite of the quality of astrophysical surveys, the nature of dark energy dominating the matter-energy content of the universe is still unknown and a lot of different scenarios are viable candidates to explain cosmic acceleration. Methods to test these cosmological models are based on distance measurements and lookback time toward astronomical objects used as standard candles. I discuss the characterizing parameters and constraints of three different classes of dark energy models pointing out the related degeneracy problem which is the signal that more data at low (z= 0- 1), medium (1<z<10) and high (10 <z< 1000) redshift are needed to definitively select realistic models.Comment: 17 pages, 9 figures, Lectures for 42nd Karpacz Winter School of Theoretical Physics: Current Mathematical Topics in Gravitation and Cosmology, Ladek, Poland, 6-11 Feb 200

Distributed control in virtualized networks

The increasing number of the Internet connected devices requires novel solutions to control the next generation network resources. The cooperation between the Software Defined Network (SDN) and the Network Function Virtualization (NFV) seems to be a promising technology paradigm. The bottleneck of current SDN/NFV implementations is the use of a centralized controller. In this paper, different scenarios to identify the pro and cons of a distributed control-plane were investigated. We implemented a prototypal framework to benchmark different centralized and distributed approaches. The test results have been critically analyzed and related considerations and recommendations have been reported. The outcome of our research influenced the control plane design of the following European R&amp;D projects: PLATINO, FI-WARE and T-NOVA

Improving P300 Speller performance by means of optimization and machine learning

Brain-Computer Interfaces (BCIs) are systems allowing people to interact with the environment bypassing the natural neuromuscular and hormonal outputs of the peripheral nervous system (PNS). These interfaces record a user’s brain activity and translate it into control commands for external devices, thus providing the PNS with additional artificial outputs. In this framework, the BCIs based on the P300 Event-Related Potentials (ERP), which represent the electrical responses recorded from the brain after specific events or stimuli, have proven to be particularly successful and robust. The presence or the absence of a P300 evoked potential within the EEG features is determined through a classification algorithm. Linear classifiers such as stepwise linear discriminant analysis and support vector machine (SVM) are the most used discriminant algorithms for ERPs’ classification. Due to the low signal-to-noise ratio of the EEG signals, multiple stimulation sequences (a.k.a. iterations) are carried out and then averaged before the signals being classified. However, while augmenting the number of iterations improves the Signal-to-Noise Ratio, it also slows down the process. In the early studies, the number of iterations was fixed (no stopping environment), but recently several early stopping strategies have been proposed in the literature to dynamically interrupt the stimulation sequence when a certain criterion is met in order to enhance the communication rate. In this work, we explore how to improve the classification performances in P300 based BCIs by combining optimization and machine learning. First, we propose a new decision function that aims at improving classification performances in terms of accuracy and Information Transfer Rate both in a no stopping and early stopping environment. Then, we propose a new SVM training problem that aims to facilitate the target-detection process. Our approach proves to be effective on several publicly available datasets

Usefulness of omega-3 fatty acid supplementation in addition to mesalazine in maintaining remission in pediatric Crohn's disease: a double-blind, randomized, placebo-controlled study.

AIM: To assess the value of long-chain omega-3 fatty acids (FAs) supplementation in addition to amino-salicylic-acid (5-ASA) in pediatric patients with Crohn's disease (CD). METHODS: Thirty-eight patients (20 males and 18 females, mean age 10.13 years, range 5-16 years) with CD in remission were randomized into two groups and treated for 12 mo. Group I (18 patients) received 5-ASA (50 mg/kg/d)+ omega-3 FAs as triglycerides in gastro-resistant capsules, 3 g/d (eicosapentanoic acid, EPA, 400 mg/g, docosahexaenoic acid, DHA, 200 mg/g). Group II (20 patients) received 5-ASA (50 mg/kg/d)+ olive oil placebo capsules. Patients were evaluated for fatty acid incorporation in red blood cell membranes by gas chromatography at baseline 6 and 12 mo after the treatment. RESULTS: The number of patients who relapsed at 1 year was significantly lower in group I than in group II (P < 0.001). Patients in group I had a significant increase in the incorporation of EPA and DHA (P < 0.001) and a decrease in the presence of arachidonic acids. CONCLUSION: Enteric-coated omega-3 FAs in addition to treatment with 5-ASA are effective in maintaining remission of pediatric CD

Optimized Collaborative Brain-Computer Interfaces for Enhancing Face Recognition

The aim of this study is to maximize group decision performance by optimally adapting EEG confidence decoders to the group composition. We train linear support vector machines to estimate the decision confidence of human participants from their EEG activity. We then simulate groups of different size and membership by combining individual decisions using a weighted majority rule. The weights assigned to each participant in the group are chosen solving a small-dimension, mixed, integer linear programming problem, where we maximize the group performance on the training set. We therefore introduce optimized collaborative brain-computer interfaces (BCIs), where the decisions of each team member are weighted according to both the individual neural activity and the group composition. We validate this approach on a face recognition task undertaken by 10 human participants. The results show that optimal collaborative BCIs significantly enhance team performance over other BCIs, while improving fairness within the group. This research paves the way for practical applications of collaborative BCIs to realistic scenarios characterized by stable teams, where optimizing the decision policy of a single group may lead to significant long-term benefits of team dynamics

Position and frequency shifts induced by massive modes of the gravitational wave background in alternative gravity

Alternative theories of gravity predict the presence of massive scalar, vector, and tensor gravitational wave modes in addition to the standard massless spin~2 graviton of general relativity. The deflection and frequency shift effects on light from distant sources propagating through a stochastic background of gravitational waves, containing such modes, differ from their counterparts in general relativity. Such effects are considered as a possible signature for alternative gravity in attempts to detect deviations from Einstein's gravity by astrophysical means.Comment: 9 pages, 1 figur

TAVI nel trattamento della stenosi aortica degenerativa: stato dell’arte e prospettive

Degenerative aortic stenosis is the most common form of heart valve disease in developed countries and predominantly affects the elderly. Aortic valve replacement (AVR) has been the gold standard, but recently, transcatheter aortic valve implantation has emerged as an effective therapeutic alternative to conventional AVR for high-risk patients. This review analyzed the literature about AVR, with the objective of evaluating the outcomes of transcatheter aortic valve implantation in patients who are not eligible for surgery showing an improvement in quality of life and middle-term outcomes. The crucial point is the lack of studies with long-term follow-up that could give therapeutic importance to percutaneous valve replacemen

Correspondence between Jordan-Einstein frames and Palatini-metric formalisms

We discuss the conformal symmetry between Jordan and Einstein frames considering their relations with the metric and Palatini formalisms for modified gravity. Appropriate conformal transformations are taken into account leading to the evident connection between the gravitational actions in the two mentioned frames and the Hilbert-Einstein action with a cosmological constant. We show that the apparent differences between Palatini and metric formalisms strictly depend on the representation while the number of degrees of freedom is preserved. This means that the dynamical content of both formalism is identical.Comment: 6 pages, to appear in Mod. Phys. Lett.

New insights on final Epigravettian funerary behavior at Arene Candide cave (Western Liguria, Italy)

We gained new insights on Epigravettian funerary behavior at the Arene Candide cave through the osteological and spatial analysis of the burials and human bone accumulations found in the cave during past excavations. Archaeothanathological information on the human skeletal remains was recovered from diaries, field pictures and notes, and data from recent excavations was integrated. The secondary deposits have traditionally been interpreted as older burials that were disturbed to make space for new inhumations. Our results suggest that those disturbances were not casual: older burials were intentionally displaced to bury younger inhumations. Subsequently, some skeletal elements, especially crania, were arranged around the new burial; these were often placed within stone niches. Based on the composition of some clusters, which contain the bones of two individuals displaced together, it is possible that a double burial composed of two adults was originally present at the site. This would be a burial type that had not been recognized at Arene Candide until now. Strikingly, this potential double burial contained an individual showing pathological bowing of the limbs, a finding which is not infrequent in skeletons from Gravettian and Epigravettian multiple burials. In addition, the crania and other skeletal elements derived from this burial were intentionally placed around a new inhumation, whose skeleton possibly shows a milder form of the same disease (possibly hereditary rickets). This and other observations suggest that the five individuals belonging to the second phase of this “cemetery” (AMS dates spanning 12,030 – 11,180 cal BP) might have been buried over a relatively brief time span. Our study demonstrated similar behaviors in the first phase of mortuary use of the cave (12,820 – 12,420 cal BP), indicating a remarkable persistence in Final Epigravettian funerary models despite their archaeologically apparent rarity and intermittent nature