On Dynamic Lifting and Effect Typing in Circuit Description Languages

In the realm of quantum computing, circuit description languages represent a valid alternative to traditional QRAM-style languages. They indeed allow for finer control over the output circuit, without sacrificing flexibility nor modularity. We introduce a generalization of the paradigmatic lambda-calculus Proto-Quipper-M, which models the core features of the quantum circuit description language Quipper. The extension, called Proto-Quipper-K, is meant to capture a very general form of dynamic lifting. This is made possible by the introduction of a rich type and effect system in which not only computations, but also the very types are effectful. The main results we give for the introduced language are the classic type soundness results, namely subject reduction and progress

Circuit Width Estimation via Effect Typing and Linear Dependency (Long Version)

Circuit description languages are a class of quantum programming languages in which programs are classical and produce a description of a quantum computation, in the form of a quantum circuit. Since these programs can leverage all the expressive power of high-level classical languages, circuit description languages have been successfully used to describe complex and practical quantum algorithms, whose circuits, however, may involve many more qubits and gate applications than current quantum architectures can actually muster. In this paper, we present Proto-Quipper-R, a circuit description language endowed with a linear dependent type-and-effect system capable of deriving parametric upper bounds on the width of the circuits produced by a program. We prove both the standard type safety results and that the resulting resource analysis is correct with respect to a big-step operational semantics. We also show that our approach is expressive enough to verify realistic quantum algorithms.Comment: 21 pages (excluding references), 21 figure

Extended Adhesion-Sparing Liver Eversion during Kasai Portoenterostomy for Infants with Biliary Atresia

Background: Despite the fact that Kasai portoenterostomy (KPE) is the primary treatment for biliary atresia (BA), liver transplantation (LT) remains the ultimate surgery for two-thirds of these patients. Their true survival rate with the native liver reflects the original KPE and the burden of post-operative complications. We report an original modification of the adhesion-sparing liver eversion (ASLE) technique during KPE that facilitates the total native hepatectomy at time of transplantation. Methods: All consecutive patients with BA who underwent KPE at our department and subsequent LT at Paediatric Liver Transplant Centre at Papa Giovanni XXIII Hospital between 2010-2018 were retrospectively enrolled. All patients underwent ASLE during KPE. Patients' demographic data, type of KPE, total transplant time (TTT), hepatectomy time (HT), intra-operative packed red blood cells and plasma transfusions, intra- and post-operative complications were noted. Results: 44 patients were enrolled. Median TTT and HT were 337 and 57 min, respectively. The median volume of packed red blood cell transfusion was 95 mL. No patients presented bowel perforation during the procedure or in the short post-operative course. No mortality after LT was recorded. Conclusions: In addition to the well-known advantages of the standard liver eversion technique, ASLE reduces the formation of intra-abdominal adhesions, lowering significantly the risk of bowel perforation and bleeding when liver transplantation is performed for failure of KPE

Pharmacokinetics of prolonged-release tacrolimus versus immediate-release tacrolimus in de novo liver transplantation: A randomized phase III substudy

Background With the same dose of tacrolimus, lower systemic exposure on the first day of dosing has been reported for prolonged-release tacrolimus compared with immediate-release tacrolimus, prompting investigation of differing initial doses. Methods This sub-study of a double-blind, randomized, phase III trial in de novo liver transplant recipients compared the pharmacokinetics of once-daily prolonged-release tacrolimus (initial dose: 0.2mg/kg/day) versus twice-daily immediate-release tacrolimus (initial dose: 0.1mg/kg/day) during the first 2 weeks post-transplant. Results Pharmacokinetic data were analysed from patients receiving prolonged-release tacrolimus (n=13) and immediate-release tacrolimus (n=12). Mean systemic exposure (AUC0–24) was higher with prolonged-release versus immediate-release tacrolimus. Dose-normalized AUC0–24 (normalized to 0.1mg/kg/day) showed generally lower exposure with prolonged-release tacrolimus versus immediate-release tacrolimus. There was good correlation between AUC0–24 and concentration at 24 hours after the morning dose (r=0.96 and r=0.86, respectively), and the slope of the line of best fit was similar for both formulations. Conclusions Doubling the initial starting dose of prolonged-release tacrolimus compared with immediate-release tacrolimus overcompensated for lower exposure on Day 1. A 50% higher starting dose of prolonged-release tacrolimus than immediate-release tacrolimus may be required for similar systemic exposure. However, doses of both formulations can be optimized using the same trough-level monitoring system. (ClinicalTrials . gov number: NCT00189826) Discipline liver transplantation/hepatology, immunosuppression/immune modulation. This article is protected by copyright. All rights reserved

Improved survival in liver transplant recipients receiving prolonged-release tacrolimus in the European liver transplant registry

This study was a retrospective analysis of the European Liver Transplant Registry (ELTR) performed to compare long-term outcomes with prolonged-release tacrolimus versus tacrolimus BD in liver transplantation (January 2008-December 2012). Clinical efficacy measures included univariate and multivariate analyses of risk factors influencing graft and patient survival at 3 years posttransplant. Efficacy measures were repeated using propensity score-matching for baseline demographics. Patients with <1 month of follow-up were excluded from the analyses. In total, 4367 patients (prolonged-release tacrolimus: n = 528; BD: n = 3839) from 21 European centers were included. Tacrolimus BD treatment was significantly associated with inferior graft (risk ratio: 1.81; p = 0.001) and patient survival (risk ratio: 1.72; p = 0.004) in multivariate analyses. Similar analyses performed on the propensity score-matched patients confirmed the significant survival advantages observed in the prolonged-release tacrolimus- versus tacrolimus BD-treated group. This large retrospective analysis from the ELTR identified significant improvements in long-term graft and patient survival in patients treated with prolonged-release tacrolimus versus tacrolimus BD in primary liver transplant recipients over 3 years of treatment. However, as with any retrospective registry evaluation, there are a number of limitations that should be considered when interpreting these data

Development and Validation of a Comprehensive Model to Estimate Early Allograft Failure among Patients Requiring Early Liver Retransplant

Importance: Expansion of donor acceptance criteria for liver transplant increased the risk for early allograft failure (EAF), and although EAF prediction is pivotal to optimize transplant outcomes, there is no consensus on specific EAF indicators or timing to evaluate EAF. Recently, the Liver Graft Assessment Following Transplantation (L-GrAFT) algorithm, based on aspartate transaminase, bilirubin, platelet, and international normalized ratio kinetics, was developed from a single-center database gathered from 2002 to 2015. Objective: To develop and validate a simplified comprehensive model estimating at day 10 after liver transplant the EAF risk at day 90 (the Early Allograft Failure Simplified Estimation [EASE] score) and, secondarily, to identify early those patients with unsustainable EAF risk who are suitable for retransplant. Design, Setting, and Participants: This multicenter cohort study was designed to develop a score capturing a continuum from normal graft function to nonfunction after transplant. Both parenchymal and vascular factors, which provide an indication to list for retransplant, were included among the EAF determinants. The L-GrAFT kinetic approach was adopted and modified with fewer data entries and novel variables. The population included 1609 patients in Italy for the derivation set and 538 patients in the UK for the validation set; all were patients who underwent transplant in 2016 and 2017. Main Outcomes and Measures: Early allograft failure was defined as graft failure (codified by retransplant or death) for any reason within 90 days after transplant. Results: At day 90 after transplant, the incidence of EAF was 110 of 1609 patients (6.8%) in the derivation set and 41 of 538 patients (7.6%) in the external validation set. Median (interquartile range) ages were 57 (51-62) years in the derivation data set and 56 (49-62) years in the validation data set. The EASE score was developed through 17 entries derived from 8 variables, including the Model for End-stage Liver Disease score, blood transfusion, early thrombosis of hepatic vessels, and kinetic parameters of transaminases, platelet count, and bilirubin. Donor parameters (age, donation after cardiac death, and machine perfusion) were not associated with EAF risk. Results were adjusted for transplant center volume. In receiver operating characteristic curve analyses, the EASE score outperformed L-GrAFT, Model for Early Allograft Function, Early Allograft Dysfunction, Eurotransplant Donor Risk Index, donor age × Model for End-stage Liver Disease, and Donor Risk Index scores, estimating day 90 EAF in 87% (95% CI, 83%-91%) of cases in both the derivation data set and the internal validation data set. Patients could be stratified in 5 classes, with those in the highest class exhibiting unsustainable EAF risk. Conclusions and Relevance: This study found that the developed EASE score reliably estimated EAF risk. Knowledge of contributing factors may help clinicians to mitigate risk factors and guide them through the challenging clinical decision to allocate patients to early liver retransplant. The EASE score may be used in translational research across transplant centers