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

Local partnerships for the development of coastal regions: A review of Fisheries Local Action Groups with focus on the Mediterranean

In the last programming period of the European Maritime Fisheries Fund, Fisheries Local Action Groups (FLAGs) have been in charge of meeting the objectives of Union Priority 4, aimed at boosting territorial cohesion and employment in European coastal areas. These local partnerships have hence received support for the elaboration of local development strategies that should promote both territorial and sectorial projects, balancing the interests of the different stakeholders involved. This article provides for a literature review of the scientific contributions on FLAGs, organizing the main findings according to the six dimensions of the Porter’s Diamond Model in the context of the cluster analysis on coastal communities’ competitiveness. Moreover, by focusing on FLAGs from Italy, Spain and France, the paper discusses the orientation towards sectoral and territorial interests in the Mediterranean. It emerges that while the literature has mostly emphasized their territorial functions, FLAGs ‒ especially those in areas with relatively higher incidence of employment in fisheries-related sectors ‒ have prior-itized projects of sectorial scope

Food security and migration in Africa: A validation of theoretical links using case studies from literature

The connection between food security and migration is increasingly discussed by both international agencies and academic literature. However, despite several improvements, we continue to know little about the complex causal-effect relations that link these aspects and, in particular, how much migration patterns are affected by food security issues and how much, as a feedback, migration can affect food security, on both the origin and destination areas. This paper aims firstly to draw a general framework of this nexus and then to validate it using empirical literature on the African continent. A few common points can be emphasized for the continent: due to structural and familiar characteristics, different strategies based on opportunity costs or risk minimization (including food security aspects) may emerge; individuals often migrate following household strategies; multi-nodal households are emerging; land grabbing and land tenure security represent important drivers to be considered; emergencies or critical situations often cause the erosion of women rights. In many situations, the poverty trap prevents most food insecure households to leave marginal lands

Very Low Alcohol Consumption Is Associated with Lower Prevalence of Cirrhosis and Hepatocellular Carcinoma in Patients with Non-Alcoholic Fatty Liver Disease

The role of moderate alcohol consumption in the evolution of NAFLD is still debated. The aim of this study is to evaluate the impact of current and lifelong alcohol consumption in patients with NAFLD. From 2015 to 2020, we enrolled 276 consecutive patients fulfilling criteria of NAFLD (alcohol consumption up to 140 g/week for women and 210 g/week for men). According to their current alcohol intake per week, patients were divided in: abstainers, very low consumers (C1: <70 g/week) and moderate consumers (C2). We created a new tool, called LACU (Lifetime Alcohol Consuming Unit) to estimate the alcohol exposure across lifetime: 1 LACU was defined as 7 alcohol units per week for 1 drinking year. Patients were divided into lifelong abstainers and consumers and the latter furtherly divided into quartiles: Q1-Q4. Stratification according to alcohol intake, both current and cumulative as estimated by LACU, showed that very low consumers (C1 and Q1-Q3) displayed lower frequency of cirrhosis and hepatocellular carcinoma compared to abstainers and moderate consumers (C2 and Q4). We can speculate that up to one glass of wine daily in the context of a Mediterranean diet may be a long-term useful approach in selected NAFLD patients

Colored Group Field Theory

Group field theories are higher dimensional generalizations of matrix models. Their Feynman graphs are fat and in addition to vertices, edges and faces, they also contain higher dimensional cells, called bubbles. In this paper, we propose a new, fermionic Group Field Theory, posessing a color symmetry, and take the first steps in a systematic study of the topological properties of its graphs. Unlike its bosonic counterpart, the bubbles of the Feynman graphs of this theory are well defined and readily identified. We prove that this graphs are combinatorial cellular complexes. We define and study the cellular homology of this graphs. Furthermore we define a homotopy transformation appropriate to this graphs. Finally, the amplitude of the Feynman graphs is shown to be related to the fundamental group of the cellular complex

Is there coherence in the European Union's strategy to guarantee the supply of fish products from abroad?

The European Union (EU) fisheries in internal waters and aquaculture are not sufficient to satisfy the EU's fish demand. For this reason, the EU's consumption depends on catches of distant water fisheries through fisheries agreements with third countries and on the import of fish products. This paper analyzes the coherence of the EU policy by focusing on four case studies. In particular, this paper attempts to identify the main synergies and conflicts amongst the varying objectives of the EU and different actors affected by the external dimension of the common fisheries policy (CFP). Results appear to show that fisheries agreements, particularly those concerning demersal resources, are more difficult to renew due to competition with local fleets, pressure from environmentalist lobbies, and budgetary issues. Thus, the EU market will increasingly be dependent on imports due to a liberalization climate encouraged by the EU processors that require raw material and fishing companies established in third countries (joint ventures). The role of the Council of the European Union, the European Parliament, and the European Commission, along with their positions of contradictory objectives, is highlighted

Price-quantity relations and choice of the geographical market size in Italian fresh seafood products

A correct planning and management of the fishing activities cannot ignore the market response to fish production. A wrong assumption about the market size during the empirical investigation can induce to errors in the preparation of the management plans. The purpose of this paper is to provide indications on the real extension (and therefore on the response) of the markets for some of the principal seafood species in Italy. An inverse system framework is followed to empirically investigate the price-quantity relations using a panel of five markets along the coast of the Adriatic Sea. The results confirm that considering only a large geographical size (e.g. national level) can be misleading if the markets are not integrated at this level (for example in the case of cuttlefish), while considering too limited geographical sizes (e.g. local level) can be misleading because the potential market integrations at regional (as in the case of hakes), national (anchovies) or intemationallevel are ignored

Consumer Sentiments and Emotions in New Seafood Product Concept Development: A Co-Creation Approach Using Online Discussion Rooms in Croatia, Italy and Spain

Growing Mediterranean seafood consumption, increasing consumers' awareness of food safety and quality, and changing food lifestyles are leading to the development of new food products. However, the majority of new food products launched on the market are expected to fail within the first year. One of the most effective ways to enhance new product success is by involving consumers during the first phases of New Product Development (NPD), using the so-called co-creation approach. Based on data collected through online discussion rooms, two new seafood product concepts-sardine fillets and sea burgers-were evaluated by a set of potential consumers in three Mediterranean countries-Italy, Spain, and Croatia. Textual information was analyzed by first using the topic modeling technique. Then, for each main topic identified, sentiment scores were calculated, followed by the identification of the main related emotions that were evoked. Overall, consumers seem to positively evaluate both proposed seafood product concepts, and three recurrent positive emotions (trust, anticipation, joy) were identified in relation to the main topics aroused during the discussions. The results of this study will be useful to guide future researchers and actors in this industry in the next development steps of the targeted seafood products in Mediterranean countries

The external and commercial dimensions of the EU fisheries policy: An institutional approach applied to the whitefish case

This paper discusses the connections that exist between several policy areas concerning fisheries, namely fisheries management and regulations in internal and external waters as well as commercial policies. An institutional approach isused to describe the system by indicating the causal interactions and feedbacks that exist between rules, stocks, catches, imports, and prices.The European Union,as one of the major players in the fishing industry and market, is considered as the case study. The key argument of the paper is that when catches decrease, essentially because of the use of inappropriate management tools and strategy, national interest moves from fishers to other categories such as processors and consumers, which involves several changes to external policies. Theanalys is presented here in shows that this is exactly what is happening in the case of whitefish. Furthermore, the changing habits and preferences of EU consumers have resulted in increasing substitution possibilities between different species, most of which are imported. This fact combined with there duced level of EU catches means that the EU is decreasingly able to affect international prices