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Radio frequency (rf) accelerating system noise can have a detrimental impact on the Large Hadron Collider (LHC) performance through longitudinal motion and longitudinal emittance growth. A theoretical formalism has been developed to relate the beam and rf station dynamics with the bunch length growth [T. Mastorides et al., Phys. Rev. ST Accel. Beams 13, 102801 (2010)PRABFM1098-440210.1103/PhysRevSTAB.13.102801]. Measurements were conducted at LHC to determine the performance limiting rf components and validate the formalism through studies of the beam diffusion dependence on rf noise. As a result, a noise threshold was established for acceptable performance which provides the foundation for beam diffusion estimates for higher energies and intensities. Measurements were also conducted to determine the low level rf noise spectrum and its major contributions, as well as to validate models and simulations of this system.

The Large Hadron Collider rf station-beam interaction strongly influences the longitudinal beam dynamics, both single-bunch and collective effects. Nonlinearities and noise generated within the radio frequency (rf) accelerating system interact with the beam and contribute to beam motion and longitudinal emittance blowup. Thus, the noise power spectrum of the rf accelerating voltage strongly affects the longitudinal beam distribution. Furthermore, the coupled-bunch instabilities are also directly affected by the rf components and the configuration of the low level rf (LLRF) feedback loops. In this work we present a formalism relating the longitudinal beam dynamics with the rf system configurations, an estimation of collective effects stability margins, and an evaluation of longitudinal sensitivity to various LLRF parameters and configurations.

The Positron-Electron Project II (PEP-II) B Factory collider ended the final phase of operation at nearly twice the design current and 4X the design luminosity. In the ultimate operation state, eight 1.2 MW radio-frequency (rf) klystrons and 12 accelerating cavities were added beyond the original implementation, and the two storage rings were operating with longitudinal instability growth rates roughly 5X in excess of the original design estimates. From initial commissioning there has been continual adaptation of the low level rf (LLRF) control strategies, configuration tools, and some new hardware in response to unanticipated technical challenges. This paper offers a perspective on the original LLRF and longitudinal instability control design, and highlights via two examples the system evolution from the original design estimates through to the final machine with 1.2×10^{34} luminosity. The impact of unanticipated signals in the coupled-bunch longitudinal feedback and the significance of nonlinear processing elements in the LLRF systems are presented. We present valuable “lessons learned” which are of interest to designers of next generation feedback and impedance controlled LLRF systems.

A dynamics simulation model is used to estimate limits of performance of the positron-electron project (PEP-II). The simulation captures the dynamics and technical limitations of the low level radio frequency (LLRF) system, the high-power rf components, and the low-order mode coupled-bunch longitudinal beam dynamics. Simulation results showing the effect of nonlinearities on the LLRF loops, and studies of the effectiveness of technical component upgrades are reported, as well as a comparison of these results with PEP-II measurements. These studies have led to the estimation of limits and determining factors in the maximum stored current that the low energy ring/high energy ring (LER/HER) can achieve, based on system stability for different rf station configurations and upgrades. In particular, the feasibility of the PEP-II plans to achieve the final goal in luminosity, which required an increase of the beam currents to 4 A for LER and 2.2 A for HER, is studied. These currents are challenging in part because they would push the longitudinal low-order beam mode stability to the limit, and the klystron forward power past a level of satisfactory margin. An acceptable margin is defined in this paper, which in turn determines the corresponding klystron forward power limitation.

A time domain dynamic modeling and simulation tool for beam-cavity interactions in the Low Energy Ring (LER) and High Energy Ring (HER) at the Positron-Electron Project (PEP-II) is presented. Dynamic simulation results for PEP-II are compared to measurements of the actual machine. The motivation for this tool is to explore the stability margins and performance limits of PEP-II radio-frequency (RF) systems at future higher currents and upgraded RF configurations. It also serves as a test bed for new control algorithms and can define the ultimate limits of the low-level RF (LLRF) architecture. The time domain program captures the dynamic behavior of the beam-cavity-LLRF interaction based on a reduced model. The ring current is represented by macrobunches. Multiple RF stations in the ring are represented via one or two macrocavities. Each macrocavity captures the overall behavior of all the 2 or 4 cavity RF stations. Station models include nonlinear elements in the klystron and signal processing. This enables modeling the principal longitudinal impedance control loops interacting via the longitudinal beam model. The dynamics of the simulation model are validated by comparing the measured growth rates for the LER with simulation results. The simulated behavior of the LER at increased operation currents is presented via low-mode instability growth rates. Different control strategies are compared and the effects of both the imperfections in the LLRF signal processing and the nonlinear drivers and klystrons are explored.

Implant-supported hybrid prostheses have become popular solutions when treating patients with terminal dentitions or who are completely edentulous. Since the implementation of osseointegrated dental implants to treat edentulism, multiple prosthetic designs and materials have been used for full-arch fixed hybrid prostheses. While these restorations can be highly successful, the most common restorative failures are attributed to lack of prosthetic space or a framework without passive fit, consequently leading to possible chippings, delamination, and/or fractures. This article reviews the clinical and laboratory steps for fabrication of definitive implant-supported hybrid prostheses with the implementation of bone reduction guides, implant osteotomy guides, and immediate provisionalization using digital manufacturing technologies.

Background: The risk of early surgical complications of liver transplantation (LT) is higher in children when compared with adults. The aims of the present retrospective study from a single center cohort/single surgeon were to identify the predictive factors for surgical complications after pediatric LT., Methods: All children receiving a first LT from October 1990 to October 2010 in our center were included., Results: Included 151 children (boys 55.0%), with a mean age of 4.8 ± 4.8 years, and a mean weight of 17.9 ± 14.4 kg. Thirty-seven patients were transplanted within the first year, and 59 patients had a body weight below 10 kg. The main initial liver disease was biliary atresia (49.0%). Living donor LT was performed in 39 cases (25.8%), cadaveric whole liver LT in 50 cases (33.1%), and cadaveric partial liver LT in 62 cases (41.1%). Early surgical complications included reoperation (37.8%), vascular complications (8.6%), i.e. arterial (3.3%) or portal thrombosis/stenosis (7.3%) within the first month, and biliary complications in the first 90 days occurred in 22.5% of the cases. The main indications for surgical revision were abdominal bleeding, treatment of a biliary complication, and bowel perforation. Multivariate analysis disclosed that only graft type (split and moreover from a living donor) was significantly and independently associated with the occurrence of biliary complication, and that indication for LT, period, graft type, and operative time were significantly and independently associated with the necessity of surgical revision., Conclusion: Our results emphasize that surgical complications are frequent and strongly depend on patient/graft characteristics., Competing Interests: Declaration of Competing Interest None of the authors have any conflict of interest disclosures to make., (Copyright © 2023. Published by Elsevier Masson SAS.)

Multiple sclerosis (MS) is a T cell-driven autoimmune disease that attacks the myelin of the central nervous system (CNS) and currently has no cure. MS etiology is linked to both the gut flora and external environmental factors but this connection is not well understood. One immune system regulator responsive to nonpathogenic external stimuli is the aryl hydrocarbon receptor (AHR). The AHR, which binds diverse molecules present in the environment in barrier tissues, is a therapeutic target for MS. However, AHR's precise function in T lymphocytes, the orchestrators of MS, has not been described. Here, we show that in a mouse model of MS, T cell-specific Ahr knockout leads to recovery driven by a decrease in T cell fitness. At the mechanistic level, we demonstrate that the absence of AHR changes the gut microenvironment composition to generate metabolites that impact T cell viability, such as bile salts and short chain fatty acids. Our study demonstrates a newly emerging role for AHR in mediating the interdependence between T lymphocytes and the microbiota, while simultaneously identifying new potential molecular targets for the treatment of MS and other autoimmune diseases., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Merchak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The role of protocol liver biopsies (PLB) in the follow-up of pediatric liver transplant recipients remains questionable. This single-center retrospective study aimed to evaluate their clinical impact on the long-term management of pediatric liver transplant recipients., Methods: We described histopathological lesions and clinical consequences for patient management of PLB performed 1, 5, 10, 15, 20, and 25 years after pediatric liver transplantation (LT)., Results: A total of 351 PLB performed on 133 patients between 1992 and 2021 were reviewed. PLB found signs of rejection in 21.7% of cases (76/351), and moderate to severe fibrosis in 26.5% of cases (93/351). Overall, 264 PLB (75.2%) did not cause any changes to patient care. Immunosuppression was enhanced after 63 PLB, including 23 cases of occult rejection. The 1-year PLB triggered significantly more changes, while biopsies at 15, 20, and 25 years produced the lowest rates of subsequent modifications. PLB had a significantly higher probability of inducing therapeutic changes if the patient had abnormal biological or imaging results (odds ratio [OR] 2.82 and 2.06), or a recent history of rejection or bacterial infection (OR 2.22 and 2.03)., Conclusion: Our results suggest that, although it often does not prompt any treatment changes, PLB could be performed because of its ability to detect silent rejection requiring an increase in immunosuppression. PLB could be carried out 1, 5, and 10 years after LT and then every 10 years in patients with normal biological and imaging results and no recent complications, while other patients could be kept on a 5-year protocol., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Oligodendrocyte progenitor cells (OPCs) account for approximately 5% of the adult brain and have been historically studied for their role in myelination. In the adult brain, OPCs maintain their proliferative capacity and ability to differentiate into oligodendrocytes throughout adulthood, even though relatively few mature oligodendrocytes are produced post-developmental myelination. Recent work has begun to demonstrate that OPCs likely perform multiple functions in both homeostasis and disease and can significantly impact behavioral phenotypes such as food intake and depressive symptoms. However, the exact mechanisms through which OPCs might influence brain function remain unclear. The first step in further exploration of OPC function is to profile the transcriptional repertoire and assess the heterogeneity of adult OPCs. In this work, we demonstrate that adult OPCs are transcriptionally diverse and separate into two distinct populations in the homeostatic brain. These two groups show distinct transcriptional signatures and enrichment of biological processes unique to individual OPC populations. We have validated these OPC populations using multiple methods, including multiplex RNA in situ hybridization and RNA flow cytometry. This study provides an important resource that profiles the transcriptome of adult OPCs and will provide a toolbox for further investigation into novel OPC functions., (© 2022. The Author(s).)

Maternal health and diet can have important consequences for offspring nutrition and metabolic health. During lactation, signals are communicated from the mother to the infant through milk via macronutrients, hormones, and bioactive molecules. In this study we designed experiments to probe the mother-milk-infant triad in the condition of normal maternal health and upon exposure to high fat diet (HFD) with or without concurrent metformin exposure. We examined maternal characteristics, milk composition and offspring metabolic parameters on postnatal day 16, prior to offspring weaning. We found that lactational HFD increased maternal adipose tissue weight, mammary gland adipocyte size, and altered milk lipid composition causing a higher amount of omega-6 (n6) long chain fatty acids and lower omega-3 (n3). Offspring of HFD dams were heavier with more body fat during suckling. Metformin (Met) exposure decreased maternal blood glucose and several milk amino acids. Offspring of met dams were smaller during suckling. Gene expression in the lactating mammary glands was impacted to a greater extent by metformin than HFD, but both metformin and HFD altered genes related to muscle contraction, indicating that these genes may be more susceptible to lactational stressors. Our study demonstrates the impact of common maternal exposures during lactation on milk composition, mammary gland function and offspring growth with metformin having little capacity to rescue the offspring from the effects of a maternal HFD during lactation., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Melanoma is a potentially deadly type of skin cancer that has been increasing in incidence but is curable if found in the early stages. Family physicians are in an ideal situation to examine the skin during routine visits, but studies indicate they are not well trained to detect or treat skin cancers. We piloted a structured, longitudinal, hands-on procedural curriculum to improve family medicine residents' ability to identify and manage skin cancers. Family medicine residency programs wishing to improve the diagnosis and management of skin cancer by family physicians might consider trialing our structured curriculum and procedure clinic., Competing Interests: None to Declare, (© 2021 Rivet, Motamedi, Burns, Archibald; licensee Synergies Partners.)

Background: Liver transplantation (LT) is a standard-of-care therapeutic modality for selected patients with life-threatening liver disease, including children. In addition to specific clinical characteristics of pediatric LT recipients due to initial liver disease (and related comorbidities) and level of liver failure, early postoperative outcome may be dependent on the surgical technique used, related to the type of organ donor and graft. Therefore, the aims of the present retrospective study from a large single centre cohort were to identify the prognostic factors for both 1-year patient and graft survival., Methods: Between October 1990 and October 2010, 151 children underwent a first LT in our centre., Results: The mean age was 5.3 ± 7.4 years, and the main indication was biliary atresia (BA) (49.0%). Living donor liver transplantation (LDLT) was performed in 39 cases (25.8%). Cadaveric liver graft was a whole liver in 50 cases (33.1%) and a partial liver (reduced or split) in 62 cases (41.1%). One-year patient and graft survival rates were 88.7% and 86.1%, respectively. Multivariate analysis disclosed that initial liver disease, location at time of LT, donor/recipient (D/R) delta age, early post-transplant hemodialysis and initial immunosuppression (induction) were significantly associated with patient survival and that D/R delta age, primary non-function, early post-transplant hemodialysis and initial immunosuppression (induction) were significantly associated with graft survival., Conclusion: The results of our single-centre experience of pediatric LT emphasize that early patient and graft survivals depend on pre-operative/operative factors such as initial liver disease, D/R delta age and immunosuppressive regimen. Awareness of these factors can help in the decision making for children requiring LT., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Competing Interests: C. Rivet déclare n’avoir aucun lien d’intérêts.

Background: Pandemics disrupt traditional health care operations by overwhelming system resource capacity but also create opportunities for care innovation., Objective: To describe the development and rapid deployment of a virtual hospital program, Atrium Health hospital at home (AH-HaH), within a large health care system., Design: Prospective case series., Setting: Atrium Health, a large integrated health care organization in the southeastern United States., Patients: 1477 patients diagnosed with coronavirus disease 2019 (COVID-19) from 23 March to 7 May 2020 who received care via AH-HaH., Intervention: A virtual hospital model providing proactive home monitoring and hospital-level care through a virtual observation unit (VOU) and a virtual acute care unit (VACU) in the home setting for eligible patients with COVID-19., Measurements: Patient demographic characteristics, comorbid conditions, treatments administered (intravenous fluids, antibiotics, supplemental oxygen, and respiratory medications), transfer to inpatient care, and hospital outcomes (length of stay, intensive care unit [ICU] admission, mechanical ventilation, and death) were collected from electronic health record data., Results: 1477 patients received care in either the AH-HaH VOU or VACU or both settings, with a median length of stay of 11 days. Of these, 1293 (88%) patients received care in the VOU only, with 40 (3%) requiring inpatient hospitalization. Of these 40 patients, 16 (40%) spent time in the ICU, 7 (18%) required ventilator support, and 2 (5%) died during their hospital admission. In total, 184 (12%) patients were ever admitted to the VACU, during which 21 patients (11%) required intravenous fluids, 16 (9%) received antibiotics, 40 (22%) required respiratory inhaler or nebulizer treatments, 41 (22%) used supplemental oxygen, and 24 (13%) were admitted as an inpatient to a conventional hospital. Of these 24 patients, 10 (42%) required ICU admission, 1 (3%) required a ventilator, and none died during their hospital admission., Limitation: Generalizability is limited to patients with a working telephone and the ability to comply with the monitoring protocols., Conclusion: Virtual hospital programs have the potential to provide health systems with additional inpatient capacity during the COVID-19 pandemic and beyond., Primary Funding Source: Atrium Health.

Major depressive disorders are global health problems that affect more than 6% of the U.S. population. Despite years of research, the etiology of depression remains unclear. Historically, it was believed that depression started within the central nervous system (CNS), but alternative hypotheses have recently challenged this dogma. Indeed, experimental and clinical evidence show that the gut microbiome could be an active player in depression initiation. The composition of bacterial species in depressed patients is significantly different from control microbiomes, and the transfer of the microbiome from depressed patients is sufficient to initiate depressive symptoms in animals. Additionally, the gut microbiome is known to change in the presence of depression risk factors such as chronic stress. While there is strong evidence delineating a role for microbial dysbiosis in depression, the initiating event for this dysbiosis remains unknown. Within the gut, microbiota reside in the mucus layer, a critical gel-like barrier involved in protecting the host from unwanted pathogen interactions, as well as regulating the immune system. Though the mucus layer is often ignored in the face of dysbiosis, it represents a dynamic and important piece of host machinery that has the potential to impact a wide variety of biological processes. Here, we review evidence supporting the novel concept that stress can modify the delicate mucus-microbiome balance, initiating dysbiosis, and ultimately leading to depression., (Copyright © 2020 Rivet-Noor and Gaultier.)

There are limited clinical data regarding prolonged-release tacrolimus (PR-T) use in pediatric transplant recipients. This Phase 2 study assessed the efficacy and safety of PR-T in stable pediatric kidney, liver, and heart transplant recipients (aged ≥5 to ≤16 years) over 1 year following conversion from immediate-release tacrolimus (IR-T), on a 1:1 mg total-daily-dose basis. Endpoints included the incidence of acute rejection (AR), a composite endpoint of efficacy failure (death, graft loss, biopsy-confirmed AR, and unknown outcome), and safety. Tacrolimus dose and whole-blood trough levels (target 3.5-15 ng/ml) were also evaluated. Overall, 79 patients (kidney, n = 48; liver, n = 29; heart, n = 2) were assessed. Following conversion, tacrolimus dose and trough levels remained stable; however, 7.6-17.7% of patients across follow-up visits had trough levels below the target range. Two (2.5%) patients had AR, and 3 (3.8%) had efficacy failure. No graft loss or deaths were reported. No new safety signals were identified. Drug-related treatment-emergent adverse events occurred in 28 patients (35.4%); most were mild, and all resolved. This study suggests that IR-T to PR-T conversion is effective and well tolerated over 1 year in pediatric transplant recipients and highlights the importance of therapeutic drug monitoring to maintain target tacrolimus trough levels., (© 2019 Astellas Pharma Europe. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.)

Background: During the past decade, mTOR inhibitors (mTORi), everolimus and sirolimus, have been increasingly used after adult liver transplantation (LT). The aim of the present study was to describe the use of mTORi in pediatric LT recipients., Methods: All pediatric LT recipients who received mTORi before December 2017 from 4 European pediatric LT centers were included and analyzed., Results: The present retrospective study included 30 patients; 21 were male (70%), median age was 9.3 years (range: 1.2-17.1 years) at mTORi introduction. Main indications for mTORi introduction were pre-existing liver malignancy (43.3%), calcineurin inhibitor (CNI) nephrotoxicity (26.7%), or rejection (23.4%). At last follow-up, mTORi CNIs were withdrawn in 10 patients (10/29, 34.5%). The median dose of mTORi was 1.8 mg/day (range: 0.3-5.0) or 0.058 mg/kg/day (range: 0.01-0.26), and the median trough level was 5.1 μg/L (range: 1.0-15.5). After a median follow-up of 2.8 years (range: 0.2-10.0), 50.0% of the patients presented with at least one adverse event. The main adverse events included hyperlipidemia, proteinuria, dermatitis, and mucitis. Overall mTORi discontinuation rate was 23.3% (10.0% because of adverse event). Introduction of mTORi had no significant impact on renal function., Conclusion: Our results suggest that mTORi can be used in pediatric LT recipients in different clinical situations, both to reinforce immunosuppressive therapy, and to reduce CNI and related toxicity., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background & Aims: To identify prognostic factors for liver disease in children with alpha-1 antitrypsin deficiency, irrespective of phenotype, using the DEFI-ALPHA cohort., Methods: Retrospective, then prospective from 2010, multicentre study including children known to have alpha-1 antitrypsin blood concentration below 0.8 g/L, born in France since 1989. Clinical and biological data were collected. Liver disease was classified as "severe" (portal hypertension, liver failure, liver transplantation or death); "moderate" (persistent abnormal liver biology without portal hypertension); and "mild/none" (normal or almost normal liver biology and native liver). Prognostic factors for severe liver disease were evaluated using a Cox semiparametric model., Results: In January 2017, 153 patients from 19 centres had been included; genotypes were PIZZ in 81.9%, PISZ in 8.1%, other in 10.0%. Mean ± SD follow-up was 4.7 ± 2.1 years. Half of patients had moderate liver disease. Twenty-eight children (18.3%) had severe liver disease (mean age 2.5 years, range: 0-11.6): diagnosis of alpha-1 antitrypsin deficiency was made before two months of age in 65.4%, genotypes were PIZZ in 25 (89.3%), PISZ in 2, PIM like Z in 1, 15 children underwent liver transplantation, 1 child died at 3 years of age. Neonatal cholestasis was significantly associated with severe liver disease (P = 0.007)., Conclusion: Alpha-1 antitrypsin-deficient patients presenting with neonatal cholestasis were likely to develop severe liver disease. Some patients with non-homozygous ZZ genotype can develop severe liver disease, such as PISZ and M variants, when associated with predisposing factors. Further genetic studies will help to identify other factors involved in the development of liver complications., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Risk factors for the development of anti-HLA antibodies include blood transfusion, organ transplantation, and pregnancy. Humoral rejection, mediated by donor-specific anti-HLA antibodies (DSA), has been studied in all kind of solid organ transplantations, and several studies have suggested that post-liver transplantation (LT) DSA may play a role in acute and chronic rejection., Objective: The aim of the present study was to assess the impact of pregnancy on the occurrence of DSA and the impact of DSA in a large population of young female LT recipients., Methods: This single center retrospective study included all female patients who underwent a first LT between January 1990 and December 2010 and who were of childbearing age during post-LT follow-up (i.e. 18 to 40 years old)., Results: The study population consisted in 73 patients, and the mean age at LT was 20.9 years (0.6-39.9); 32 patients were transplanted during childhood. The global incidence of de novo DSA was 42.5% (31/73), after a median delay of 15.5 years (1-25) of follow-up after LT. Most de novo DSA were anti-class II alone (90.3%), and included anti-DQ for 80.6%. From the 73 patients, 33 presented at least one pregnancy after LT (45.2%) and before DSA screening. Multivariate analysis disclosed that history of pregnancy (OR = 6.37; 95%CI, 2.17-18.63, p = 0.001) and younger age at LT (OR = 0.96; 95%CI:0.92-0.99, p = 0.033) were significantly associated with de novo DSA. Among the 31 patients who had de novo DSA, the diagnosis of antibody-mediated rejection was made in 8 patients (25.8%), after a median delay of 74 months after LT; 6/8 (75.0%) had history of pregnancy. During follow-up, 3 of these 8 patients lost their liver graft and died., Conclusion: The results of the present study suggest that close monitoring of DSA in young women with history of pregnancy should be recommended regarding the risk of DSA-mediated rejection., (Copyright © 2019 Elsevier B.V. All rights reserved.)

This study was a Phase II, open-label, multicenter, single-arm, cross-over study comparing the pharmacokinetics (PK) of tacrolimus in stable pediatric kidney, liver, or heart allograft recipients converted from immediate-release tacrolimus (IR-T) to prolonged-release tacrolimus (PR-T). In Days -30 to -1 of screening period, patients received their IR-T-based regimen; during Days 1-7, patients received study IR-T (same dose as screening). On Day 7, the first 24-hours PK profile was taken; patients were then converted to PR-T (1 mg:1 mg), with a second 24-hours PK profile taken on Day 14. The primary end-point was tacrolimus area under the blood concentration-time curve over 24 hours (AUC 24 ); secondary end-points were maximum concentration C max and concentration at 24 hours C 24 . The predefined similarity interval for confidence intervals (CIs) of least squares mean (LSM) ratios was 80%-125%. The PK analysis set comprised 74 pediatric transplant recipients (kidney, n = 45; liver, n = 28; heart, n = 1). PR-T:IR-T LSM ratio (90% CI) was similar overall for AUC 24 , max , and C 24 , and for kidney and liver recipients for AUC 24 (LSM ratio, kidney 91.8%; liver 104.1%) and C 24 (kidney 90.5%; liver 89.9%). Linear relationship was similar between AUC 24 and C 24 , and between PR-T and IR-T (rho 0.89 and 0.84, respectively), suggesting that stable pediatric transplant recipients can be converted from IR-T to PR-T at the same total daily dose, using the same therapeutic drug monitoring method., (© 2019 The Authors. Pediatric Transplantation published by Wiley Periodicals, Inc.)

Background & Aims: Measuring of the relative exchangeable copper seems to be a promising tool for the diagnosis of Wilson disease. The aim of our study is to determine the performance of REC for the diagnosis of Wilson disease in a population of patients with chronic liver diseases., Methods: Measuring of exchangeable serum copper levels and relative exchangeable copper was performed in a group of Wilson disease patients at diagnosis or at clinical deterioration because of non-compliance (group 1, n=9), a group of stable WD patients (group 2, n=40), and two groups of patients (adult and paediatric) followed for non-Wilsonian liver diseases (group 3, n=103 and group 4, n=49 respectively)., Results: Exchangeable serum copper (N: 0.6-1.1 μmol/L) was significantly higher in group 1 (mean 2.2±0.7 μmol/L) compared to the other three groups: group 2=0.9±0.4 μmol/L, group 3=1.2±0.4 μmol/L, group 4=1.1±0.3 μmol/L (P<0.05). Relative exchangeable copper was significantly higher in Wilson disease patients group 1 and 2 (mean 52.6% and 43.8%) compared to patients suffering from other liver diseases (mean 7.1% and 5.9%) (P<0.05)., Conclusions: Our study confirms that the determination of relative exchangeable copper is a highly valuable tool for the diagnosis of Wilson disease., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The prevalence and clinical impact of anti-HLA donor-specific antibodies (DSA) after liver transplantation (LT) have not been extensively studied, especially in pediatric population., Methods: The present cross-sectional study included 100 patients who underwent a first LT in childhood. Anti HLA immunization study was performed at a single time point during routine follow-up using Luminex® single antigen tests with classical anti-IgG conjugate and anti-C3d conjugate., Results: The main indication for LT was biliary atresia (52%) and median age at LT was 4.6years. The median time between LT and DSA assessment was 7.8years (range 1-21years). DSA was identified in twenty-four patients (24%) after LT, with a prevalence of 8%, 28%, 33%, 50%, respectively 0-5years, 5-10years, 10-15years and >15years after LT. DSA were mainly class II (23/24) with a mean MFI of 9.731±5.489 and 18 (79.3%) were C3d-binding DSA. Multivariate analysis disclosed that time elapsed since LT (p<0.01) and history of fulminant hepatitis (p=0.04) were significantly associated with a higher rate of DSA. Liver function tests (at time of DSA assessment) were not different according to the presence or not of DSA (or C3d-binding DSA). Regarding histology, the DSA group had a higher rate of chronic rejection, cirrhosis and centrilobular fibrosis or cirrhosis. In addition, patients with C3d-binding DSA and high MFI (>10,000) had a significant poorer long-term graft survival (p=0.03)., Conclusion: In our pediatric cohort of LT, prevalence of DSA was high and increased regularly with time. Presence of C3d positive-DSA with high MFI was associated with a higher rate of graft loss., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This first observation of donor-transmitted coccidioidomycosis in a pediatric liver-transplant recipient underlines a rare condition in transplanted patients in a nonendemic area. This transmission was observed after a liver split, the patient being contaminated by the left liver while the right-liver recipient was not.