Management of HCV Infection and Liver Transplantation

A major challenge facing liver transplant recipients and their physicians is recurrence of hepatitis C virus infection following otherwise technically successful liver transplantation. Recurrent infection leads to diminished graft and patient survival. Although a number or predictors of severe recurrence have been identified, no definitive strategy has been developed to prevent recurrence. Generally the tempo of hepatitis C recurrence is gauged by serial liver biopsies with the decision to intervene with antiviral therapy based on local philosophy and expertise. Treating hepatitis C in this population has a number of major challenges including diminished patient tolerance for side-effects as well as managing the patient's immunesuppression. However sustained viral responses are possible with the potential to reduce the impact of recurrent hepatitis on the graft. However recurrent hepatitis C virus infection will remain the most frequent form of recurrent disease in liver transplant programs for the foreseeable future

Hand-worn Haptic Interface for Drone Teleoperation

Drone teleoperation is usually accomplished using remote radio controllers, devices that can be hard to master for inexperienced users. Moreover, the limited amount of information fed back to the user about the robot's state, often limited to vision, can represent a bottleneck for operation in several conditions. In this work, we present a wearable interface for drone teleoperation and its evaluation through a user study. The two main features of the proposed system are a data glove to allow the user to control the drone trajectory by hand motion and a haptic system used to augment their awareness of the environment surrounding the robot. This interface can be employed for the operation of robotic systems in line of sight (LoS) by inexperienced operators and allows them to safely perform tasks common in inspection and search-and-rescue missions such as approaching walls and crossing narrow passages with limited visibility conditions. In addition to the design and implementation of the wearable interface, we performed a systematic study to assess the effectiveness of the system through three user studies (n = 36) to evaluate the users' learning path and their ability to perform tasks with limited visibility. We validated our ideas in both a simulated and a real-world environment. Our results demonstrate that the proposed system can improve teleoperation performance in different cases compared to standard remote controllers, making it a viable alternative to standard Human-Robot Interfaces.Comment: Accepted at the IEEE International Conference on Robotics and Automation (ICRA) 202

DISCUS: the distributed core for ubiquitous broadband access

A new end to end architecture based on Long-Reach Passive Optical Network (LR-PON) with wireless integration, a distributed core built of optical transparency islands and an OpenFlow-based control plane, which is being developed in the EU project DISCUS, is described in this paper. The main technological advances and the network modelling and optimization approach are reported

4D flow MRI in abdominal vessels: prospective comparison of k-t accelerated free breathing acquisition to standard respiratory navigator gated acquisition

Volumetric phase-contrast magnetic resonance imaging with three-dimensional velocity encoding (4D flow MRI) has shown utility as a non-invasive tool to examine altered blood flow in chronic liver disease. Novel 4D flow MRI pulse sequences with spatio-temporal acceleration can mitigate the long acquisition times of standard 4D flow MRI, which are an impediment to clinical adoption. The purpose of our study was to demonstrate feasibility of a free-breathing, spatio-temporal (k-t) accelerated 4D flow MRI acquisition for flow quantification in abdominal vessels and to compare its image quality, flow quantification and inter-observer reproducibility with a standard respiratory navigator-gated 4D flow MRI acquisition. Ten prospectively enrolled patients (M/F: 7/3, mean age = 58y) with suspected portal hypertension underwent both 4D flow MRI acquisitions. The k-t accelerated acquisition was approximately three times faster (3:11 min ± 0:12 min/9:17 min ± 1:41 min, p < 0.001) than the standard respiratory-triggered acquisition. Vessel identification agreement was substantial between acquisitions and observers. Average flow had substantial inter-sequence agreement in the portal vein and aorta (CV < 15%) and poorer agreement in hepatic and splenic arteries (CV = 11-38%). The k-t accelerated acquisition recorded reduced velocities in small arteries and reduced splenic vein flow. Respiratory gating combined with increased acceleration and spatial resolution are needed to improve flow measurements in these vessels

DISCUS: end-to-end network design for ubiquitous high speed broadband services

Fibre-to-the-premises (FTTP) has been long sought as the ultimate solution to satisfy the demand for broadband access in the foreseeable future, and offer distance-independent data rate within access network reach. However, currently deployed FTTP networks have in most cases only replaced the transmission medium, without improving the overall architecture, resulting in deployments that are only cost efficient in densely populated areas (effectively increasing the digital divide). In addition, the large potential increase in access capacity cannot be matched by a similar increase in core capacity at competitive cost, effectively moving the bottleneck from access to core. DISCUS is a European Integrated Project that, building on optical-centric solutions such as Long-Reach Passive Optical access and flat optical core, aims to deliver a cost-effective architecture for ubiquitous broadband services. One of the key features of the project is the end-to-end approach, which promises to deliver a complete network design and a conclusive analysis of its economic viability

DISCUS : an end-to-end solution for ubiquitous broadband optical access

Fiber to the premises has promised to increase the capacity in telecommunications access networks for well over 30 years. While it is widely recognized that optical-fiber-based access networks will be a necessity in the shortto medium-term future, its large upfront cost and regulatory issues are pushing many operators to further postpone its deployment, while installing intermediate unambitious solutions such as fiber to the cabinet. Such high investment cost of both network access and core capacity upgrade often derives from poor planning strategies that do not consider the necessity to adequately modify the network architecture to fully exploit the cost benefit that a fiber-centric solution can bring. DISCUS is a European Framework 7 Integrated Project that, building on optical-centric solutions such as long-reach passive optical access and flat optical core, aims to deliver a cost-effective architecture for ubiquitous broadband services. DISCUS analyzes, designs, and demonstrates end-to-end architectures and technologies capable of saving cost and energy by reducing the number of electronic terminations in the network and sharing the deployment costs among a larger number of users compared to current fiber access systems. This article describes the network architecture and the supporting technologies behind DISCUS, giving an overview of the concepts and methodologies that will be used to deliver our end-to-end network solution

A randomized, placebo-controlled, phase II study of obeticholic acid for primary sclerosing cholangitis

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Efficacy and safety of mycophenolate mofetil and tacrolimus as second-line therapy for patients with autoimmune hepatitis

Background: Predniso(lo)ne, alone or in combination with azathioprine, is the standard of care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy for patients with AIH. Patients and methods: We performed a retrospective study of data (from 19 centres in Europe, the United States, Canada, and China) from 201 patients with AIH who received second-line therapy (121 received MMF and 80 received tacrolimus), for a median of 62 months (range, 6–190 months). Patients were categorized according to their response to SOC. Patients in group 1 (n=108) had a complete response to the SOC, but were switched to second line therapy due to side effects of predniso(lo)ne or azathioprine, whereas patients in group 2 (n=93) had not responded to SOC. Results: There was no significant difference in the proportion of patients with a complete response to MMF (69.4%) vs tacrolimus (72.5%) (P=.639). In group 1, MMF and tacrolimus maintained a biochemical remission in 91.9% and 94.1% of patients, respectively (P=.682). Significantly more group 2 patients given tacrolimus compared to MMF had a complete response (56.5 % vs. 34%, P=.029) There were similar proportions of liver-related deaths or liver transplantation among patients given MMF (13.2%) vs tacrolimus (10.3%) (log-rank, P=.472). Ten patients receiving MMF (8.3%) and 10 patients receiving tacrolimus (12.5%) developed side effects that required therapy withdrawal. Conclusions: Long-term therapy with MMF or tacrolimus was generally well tolerated by patients with AIH. The agents were equally effective in previous complete responders who did not tolerate SOC therapy. Tacrolimus led to a complete response in a greater proportion of previous non-responder patients compared to MMF

Sofosbuvir and Ribavirin Prevent Recurrence of HCV Infection After Liver Transplantation: An Open-Label Study

Background & AimsPatients with detectable hepatitis C virus (HCV) RNA at the time of liver transplantation universally experience recurrent HCV infection. Antiviral treatment before transplantation can prevent HCV recurrence, but existing interferon-based regimens are poorly tolerated and are either ineffective or contraindicated in most patients. We performed a trial to determine whether sofosbuvir and ribavirin treatment before liver transplantation could prevent HCV recurrence afterward.MethodsIn a phase 2, open-label study, 61 patients with HCV of any genotype and cirrhosis (Child–Turcotte–Pugh score, ≤7) who were on waitlists for liver transplantation for hepatocellular carcinoma, received up to 48 weeks of sofosbuvir (400 mg) and ribavirin before liver transplantation. The primary end point was the proportion of patients with HCV-RNA levels less than 25 IU/mL at 12 weeks after transplantation among patients with this HCV-RNA level at their last measurement before transplantation.ResultsSixty-one patients received sofosbuvir and ribavirin, and 46 received transplanted livers. The per-protocol efficacy population consisted of 43 patients who had HCV-RNA level less than 25 IU/mL at the time of transplantation. Of these 43 patients, 30 (70%) had a post-transplantation virologic response at 12 weeks, 10 (23%) had recurrent infection, and 3 (7%) died (2 from nonfunction of the primary graft and 1 from complications of hepatic artery thrombosis). Of all 61 patients given sofosbuvir and ribavirin, 49% had a post-transplantation virologic response. Recurrence was related inversely to the number of consecutive days of undetectable HCV RNA before transplantation. The most frequently reported adverse events were fatigue (in 38% of patients), headache (23%), and anemia (21%).ConclusionsAdministration of sofosbuvir and ribavirin before liver transplantation can prevent post-transplant HCV recurrence. ClinicalTrials.gov: NCT01559844

An intermediate-effect size variant in UMOD confers risk for chronic kidney disease

The kidney-specific gene UMOD encodes for uromodulin, the most abundant protein excreted in normal urine. Rare large-effect variants in UMOD cause autosomal dominant tubulointerstitial kidney disease (ADTKD), while common low-impact variants strongly associate with kidney function and the risk of chronic kidney disease (CKD) in the general population. It is unknown whether intermediate-effect variants in UMOD contribute to CKD. Here, candidate intermediate-effect UMOD variants were identified using large-population and ADTKD cohorts. Biological and phenotypical effects were investigated using cell models, in silico simulations, patient samples, and international databases and biobanks. Eight UMOD missense variants reported in ADTKD are present in the Genome Aggregation Database (gnomAD), with minor allele frequency (MAF) ranging from 10(−5) to 10(−3). Among them, the missense variant p.Thr62Pro is detected in ∼1/1,000 individuals of European ancestry, shows incomplete penetrance but a high genetic load in familial clusters of CKD, and is associated with kidney failure in the 100,000 Genomes Project (odds ratio [OR] = 3.99 [1.84 to 8.98]) and the UK Biobank (OR = 4.12 [1.32 to 12.85). Compared with canonical ADTKD mutations, the p.Thr62Pro carriers displayed reduced disease severity, with slower progression of CKD and an intermediate reduction of urinary uromodulin levels, in line with an intermediate trafficking defect in vitro and modest induction of endoplasmic reticulum (ER) stress. Identification of an intermediate-effect UMOD variant completes the spectrum of UMOD-associated kidney diseases and provides insights into the mechanisms of ADTKD and the genetic architecture of CKD