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The aim of this study was to examine the impact of features of dysmetabolism on liver disease severity, evolution, and clinical outcomes in a real-life cohort of patients treated with direct acting antivirals for chronic hepatitis C virus (HCV) infection. To this end, we considered 7,007 patients treated between 2014 and 2018, 65.3% with advanced fibrosis, of whom 97.7% achieved viral eradication (NAVIGATORE-Lombardia registry). In a subset (n=748), liver stiffness measurement (LSM) was available at baseline and follow-up. Higher body mass index (BMI; odds ratio [OR] 1.06 per kg/m2, 1.03-1.09) and diabetes (OR 2.01 [1.65-2.46]) were independently associated with advanced fibrosis at baseline, whereas statin use was protective (OR 0.46 [0.35-0.60]; P&nbsp

AIM The aim of this study was to compare early and late injections of intravitreal dexamethasone implant in patients affected by central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO) with a six-months follow-up. We assessed whether an earlier treatment start (within seven days from diagnosis) could be more beneficial than a delayed (or late) treatment start (after seven days). MATERIALS AND METHODS The study included 81 patients (81 eyes) affected by retinal vein occlusion. Best corrected visual acuity was assessed through Early Treatment Diabetic Retinopathy Study (ETDRS) while central macular thickness (CMT) was measured by spectral-domain optical coherence tomography. RESULTS Both types of patients had a positive therapeutic response to dexamethasone, with an increase in visual acuity (ETDRS) and CMT reduction. CRVO patients were characterized by lower ETDRS values at baseline and at the end of the follow-up as compared to BRVO. CRVO patients showed higher CMT values at baseline, after three and six months from injection. No significant differences in therapeutic response to dexamethasone were observed between patients treated early or late, regardless of RVO type. CONCLUSIONS This study demonstrates that the therapeutic properties of dexamethasone implant are not significantly influenced by an early or late treatment start in patients affected by BRVO and CRVO, although its therapeutic efficacy seems greater in the former type.

In the last decades, the traditional understanding of organized crime (OC) has been widely challenged. As the United Nations Office on Drugs and Crime (UNODC), Europol, as well as German authorities have extensively highlighted, hierarchical criminal organizations coexist and overlap with new forms of liquid networked criminality. These criminal networks are composed of flexible alliances between professionals acting worldwide that regulate themselves based on market logic rather than violent conflicts. While appearing "dis-organized," these criminal networks are highly resilient to law enforcement intervention due to their redundancy. Their capacity for infiltrating the legitimate economy and the estimated sums of money they launder globally, which amounts to between 2 and 5 percent of global GDP yearly (UNODC), are alarming. Therefore, not only law enforcement and policymakers, but also the private sector cannot afford to drop their guard. National interventions often just push criminal activities into other countries; hence, effective strategies should address global markets' dynamics. (SWP Comments)

Immer wieder wird das traditionelle Verständnis von Organisierter Kriminalität (OK) in Frage gestellt. Das Büro der Vereinten Nationen für Drogen- und Verbrechensbekämpfung (UNODC), das EU-Polizeiamt Europol und auch deutsche Behörden wie Bundeskriminalamt, Bundesinnenministerium und Bundesjustizministerium betonen, dass neben hierarchischen kriminellen Vereinigungen neue Formen krimineller Netzwerke existieren, die sich mit alten überlappen. Es handelt sich um weltweit agierende Zusammenschlüsse, die eher einer Marktlogik folgen, statt sich in gewaltsame Konflikte zu verstricken. Für die Strafverfolgungsbehörden sind sie schwer zu fassen, weil sie locker und flexibel organisiert sind. Alarmierend sind vor allem ihre Fähigkeit, die legale Wirtschaft zu infiltrieren, und das enorme Maß an Geldwäsche, welches das UNODC auf zwei bis fünf Prozent des weltweiten Bruttoinlandsprodukts schätzt. Deshalb sollten nicht nur Strafverfolgungsbehörden und Politiker, sondern auch der Privatsektor besonders wachsam sein. Oft treibt nationale Strafverfolgung kriminelle Aktivitäten nur über die nächste Grenze. Um erfolgreich zu sein, sollten Gegenstrategien daher an globalen Marktdynamiken ansetzen. (author's abstract)

Ship Reporting Systems (SRSs) have been standardized with the goal of enforcing safety in navigation. Automatic Identification System (AIS) is the most known SRS but, given the limited available bandwidth, it supports a simple, basic set of services without dealing with security aspects. Specifically to address such weaknesses, this paper explores a possible backward-compatible solution aimed at increasing the safety and flexibility provided by the current AIS systems: the proposed solution exploits a complementary channel set in the TV White Space frequencies; the paper also presents the integration work which led to the prototyping, together with a first set of practical tests.

In the last years, two main ICT enablers have been massively explored to enforce vehicular safety: GNSS-based positioning and wireless communications. In fact, by exchanging information on their respective positions, vehicles are expected to be timely aware of the hazards around them and, consequently, to be able to promptly react, hopefully decreasing the rate of accidents. Both wireless communications and positioning are unfortunately far from being ideal, especially on board: however, as recently proposed, they may both significantly benefit from the integration of the emerging Light-Fidelity (Li-Fi) technology. The paper discusses the Li-Fi perspective, shedding light on its potential benefits and issues, also with practical consideration.

Wireless in shop-floors is a bet: it outlines the possibility of making automation more flexible and to simplify plant reconfiguration. However, the specific context subtends several challenging requirements, which the available off-the-shelf solutions are not 100%-ready to cope with. By the way, the potential benefits of wireless for automation are so significant that it is worth investigating novel techniques to enforce the available wireless transceivers, so as to make them suitable for factories. The Italian regional project Wi-Fact is putting under close scrutiny the context of wireless automation to identify the most significant threats and proposing solutions to stem them. This paper take stock of the project achievements at its mid-term turning point.

Most of the emerging applications for road safety and traffic management rely on the frequent exchange of awareness messages among vehicles. Unfortunately, the 802.11 protocol poorly behaves under congested scenarios and cannot guarantee the reliability and timeliness demands of massively transmitted broadcast messages, leading to the severe degradation of safety. Recently, there has been a consensus from academia, automotive industries and standardization bodies in adapting transmission parameters (e.g., rate, transmission power) according to the channel load status. Although the objective of controlling channel load can be met with local load measurements only, the participation and fairness principles require the dissemination and sharing of load information among vehicles. In this paper, we aim to shed light on the dynamics of the channel busy ratio (CBR) metrics (locally measured and shared over one/two hops), commonly used in the literature and at the basis of the Decentralized Congestion Control (DCC) standard, under different density and mobility settings.

a b s t r a c t Background: Data on the efficacy of Peg-interferon/ribavirin therapy for chronic hepatitis C are mostly derived from treatment of selected patients enrolled in clinical trials. This study aimed to assess the effectiveness of Peg-interferon/ribavirin therapy in “real world” chronic hepatitis C patients in Italy. Methods: Independent observational multicentre study including consecutive patients receiving Peginterferon/ribavirin in the 18 months before (retrospective phase) and after (prospective phase) the start of the study. Results: 4176 patients were eligible. The final study population consisted of 2051 patients in the retrospective and 2073 in the prospective phase. Sustained virological response was achieved by 1036 patients (50.5%) during the retrospective phase: 325 were genotypes 1/4 (34.1%) and 684 were genotypes 2/3 (67.2%) and by 800 patients (38.6%) during the prospective phase: 300 were genotypes 1/4 (28.4%) and 473 were genotypes 2/3 (51.5%). During multivariate analysis genotypes 2/3 were significantly associated with higher sustained virological response rates; cirrhosis and -glutamil-transpeptidase >2 times the normal limit were associated with poorer response. Conclusions: The response to Peg-interferon/ribavirin therapy in “real world” clinical practice is distinctly lower than in registration trials. The difference in response rates was more pronounced among easy-totreat than among difficult-to-treat hepatitis C virus genotypes.

Drug-induced liver injury (DILI) is a relatively infrequent form of adverse drug reaction, its incidence being between 1 : 1000 and 1 : 100 000; however, it accounts for approximately 10% of all cases of acute hepatitis, is the leading cause of acute liver failure, mainly due to acetaminophen overdose, and is the main reason for approved drug withdrawal from the market [1]. It is rarely predictable, in the majority of cases resulting from an idiosyncratic reaction, and some risk factors have been recognized (alcohol, diabetes, advanced age and female sex). Herein we describe a patient who developed DILI while taking telmisartan-hydrochlorothiazide. A 72-year-old woman was referred to our department with a 7-day history of weakness, anorexia, nausea, progressive jaundice, dark-coloured urine and pruritus. The patient had a past medical history of arterial hypertension, and had been taking lercanidipine for about 5 years; 4 weeks before admission she was prescribed telmisartan/hydrochlorothiazide because of uncontrolled blood pressure values. She denied blood transfusion, recent surgery, alcohol abuse and relevant family history. Physical examination showed a 2 cm hepatomegaly, other than jaundice. Laboratory testing on admission showed total serum bilirubin to be 15.6 mg/dl (range: 0–1), direct bilirubin 14.8 mg/dl, aspartate (AST) and alanine (ALT) transaminases 33 IU/l and 87 IU/l, respectively (range: 0–32), alkaline phosphatase (AP) 183 IU/l (range: 35–105), γ-glutamyl transpeptidase 552 IU/l (range: 5–36); complete blood count, serum albumin level and coagulation profile, serum iron and ferritin, amylase, copper and ceruloplasmin were normal. Anti-nuclear, anti-smooth muscle, anti-mitochondrial and anti-liver/kidney microsome antibodies as well as viral serologic markers (anti-HAV IgM, HBsAg, anti-HBc IgM, anti-HCV and HCV-RNA, anti-CMV and anti-EBV IgM and IgG) were all negative. An upper abdominal ultrasound and computed tomography revealed a scleroatrophic gallbladder with normal liver structure and intrahepatic bile ducts. A percutaneous liver biopsy was performed eight days after admission; liver histopathology showed mild mononuclear inflammatory infiltrates in portal tracts without hepatocyte necrosis. Drug-induced liver injury (DILI) was suspected and telmisartan/hydrochlorothiazide was stopped seven days after admission. Serum bilirubin remained substantially unchanged for the first ten days after discontinuation, then gradually began to decrease (Figure 1). Direct bilirubin at discharge (20 days after admission) was 10.3 mg/dl and returned to normal levels within the next 15 days. Figure 1 Evolution of indirect bilirubin levels Telmisartan is the angiotensin II receptor antagonist (ARB) with the highest affinity for the angiotensin II type 1 receptor and with the longest half-life. Furthermore, telmisartan acts as an agonist of peroxisome proliferator-activated receptor gamma (PPAR-γ): the consequent expression modulation of genes involved in carbohydrate and lipid metabolism could be the basis for possible metabolic effects of the drug [2]. A marketed combination, frequently used to enhance the antihypertensive effect of ARBs, is telmisartan plus hydrochlorothiazide, a diuretic drug which belongs to the thiazidic class. This patient was diagnosed with DILI on the basis of 1990 Consensus Meeting criteria [3]: the time to onset of jaundice from the beginning of drugs (25 days) was suggestive, the patient was female and more than 55 years old, alternative causes had been ruled out and the course of the reaction was highly suggestive (although rechallenge has not been performed for either drug). Acute DILI can have a varying pattern of expression [4]: hepatocellular, which mainly affects parenchymal cells; cholestatic, mainly affecting canalicular and/or ductular cells; and mixed cytotoxic/cholestatic. Our case fulfils the diagnostic criteria of cholestatic DILI [3]: although serum AP activity was not significantly increased, the ratio between serum ALT and serum AP activities was below 2. The patient did not report fever, chills or abdominal pain and liver histology showed only minimal inflammatory portal infiltrates: we can therefore more properly define our case as pure cholestasis, in contrast to the more common form of acute cholestatic hepatitis [5]. ARB-induced cholestatic hepatitis has been reported only during treatment with irbesartan [6], while other forms of hepatotoxicity (hepatocellular, mixed) have been reported also with valsartan [7] and losartan [8, 9]. On the other hand, two cases of hydrochlorothiazide-related cholestatic injury have been reported in the literature [10, 11]. Although rare, an acute DILI should therefore be taken into account in the presence of acute hepatotoxicity with negative anamnestic and serological data in hypertensive patients treated with ARB and/or hydrochlorothiazide.

Many cooperative applications designed to improve road safety rely on the frequent exchange of awareness messages among vehicles. Therefore, under high vehicle density, the channel medium is expected to get congested. To tackle this situation, the European Telecommunications Standards Institute (ETSI) specified a set of Decentralized Congestion Control (DCC) mechanisms that adapt the transmission parameters based on channel load measures. Due to some concerns about its effectiveness and stability, DCC and its overall philosophy are currently being revised and extended: all in all, DCC deserves additional investigations. For this purpose, in this paper a simulation analysis is presented, aiming at enriching the insight into the DCC behaviour, under a variety of channel load conditions and through the definition of both link- and application-layer performance metrics. Achieved results show that the DCC techniques are not really effective with the currently specified parameters settings; hence some hints are given to improve their performance.