Epidemiology of Epstein-Barr Virus Chronic High Viral Load in Kidney Transplant Recipients.

Background: Epstein-Barr virus (EBV) chronic high viral load (CHVL) may be defined by >16 000 copies/mL whole blood or >200 copies/10 peripheral blood mononuclear cells in >50% samples exceeding 6 mo. EBV CHVL has only been characterized in a few small pediatric studies, with heterogeneous results and unclear clinical significance.

Methods: This single-center observational study evaluated adult and pediatric kidney transplant recipients transplanted between 2010 and 2021 on tacrolimus/mycophenolate-based/prednisone immunosuppression.

Immune phenotyping in a pediatric multicenter transplant study: Suitability of a preformulated dry-antibody panel system.

Flow-cytometric immune phenotyping is influenced by cryopreservation and inter-laboratory variability limiting comparability in multicenter studies. We assessed a system of optimized, pre-mixed dry-antibody panel tubes requiring small amounts of whole blood for validity, reliability and challenges in a Canadian multicenter study (POSITIVE) with long-distance sample shipping, using standardized protocols. Thirty-seven children awaiting solid-organ transplant were enrolled for parallel immune-phenotyping with both validated, optimized in-house panels and the dry-antibody system.

Association of BKV viremia and nephropathy with adverse alloimmune outcomes in kidney transplant recipients.

Background: Immunosuppression reduction for BK polyoma virus (BKV) must be balanced against risk of adverse alloimmune outcomes. We sought to characterize risk of alloimmune events after BKV within context of HLA-DR/DQ molecular mismatch (mMM) risk score.

Methods: This single-center study evaluated 460 kidney transplant patients on tacrolimus-mycophenolate-prednisone from 2010-2021.

A rational approach to guide cost-effective de novo donor-specific antibody surveillance with tacrolimus immunosuppression.

De novo donor-specific antibody (dnDSA) after renal transplantation has been shown to correlate with antibody-mediated rejection and allograft loss. However, the lack of proven interventions and the time and cost associated with annual screening for dnDSA are difficult to justify for all recipients. We studied a well-characterized consecutive cohort (n = 949) with over 15 years of prospective dnDSA surveillance to identify risk factors that would help institute a resource-responsible surveillance strategy.

Attosecond Real-Time Observation of Recolliding Electron Trajectories in Helium at Low Laser Intensities.

Laser-driven recollision physics is typically accessible only at field intensities high enough for tunnel ionization. Using an extreme ultraviolet pulse for ionization and a near-infrared (NIR) pulse for driving of the electron wave packet lifts this limitation. This allows us to study recollisions for a broad range of NIR intensities with transient absorption spectroscopy, making use of the reconstruction of the time-dependent dipole moment.

XUV-Initiated Dissociation Dynamics of Molecular Oxygen (O).

We performed a time-resolved spectroscopy experiment on the dissociation of oxygen molecules after the interaction with intense extreme-ultraviolet (XUV) light from the free-electron laser in Hamburg at Deutsches Elektronen-Synchrotron. Using an XUV-pump/XUV-probe transient-absorption geometry with a split-and-delay unit, we observe the onset of electronic transitions in the O cation near 50 eV photon energy, marking the end of the progression from a molecule to two isolated atoms. We observe two different time scales of 290 ± 53 and 180 ± 76 fs for the emergence of different ionic transitions, indicating different dissociation pathways taken by the departing oxygen atoms.

The negative impact of T cell-mediated rejection on renal allograft survival in the modern era.

The prevalence and long-term impact of T cell-mediated rejection (TCMR) is poorly defined in the modern era of tacrolimus/mycophenolate-based maintenance therapy. This observational study evaluated 775 kidney transplant recipients with serial histology and correlated TCMR events with the risk of graft loss. After a ~30% incidence of a first Banff Borderline or greater TCMR detected on for-cause (17%) or surveillance (13%) biopsies, persistent (37.

Care processes and structures associated with higher medication adherence in adolescent and young adult transplant recipients.

Background: We aimed to identify care processes and structures that were independently associated with higher medication adherence among young transplant recipients.

Methods: We conducted a prospective, observational cohort study of 270 prevalent kidney, liver, and heart transplant recipients 14-25 years old. Patients were ≥3 months post-transplant, ≥2 months post-discharge, and followed in one of 14 pediatric or 14 adult transplant programs in Canada.

An Integrated Clinical and Genetic Prediction Model for Tacrolimus Levels in Pediatric Solid Organ Transplant Recipients.

Background: There are challenges in achieving and maintaining therapeutic tacrolimus levels after solid organ transplantation (SOT). The purpose of this genome-wide association study was to generate an integrated clinical and genetic prediction model for tacrolimus levels in pediatric SOT.

Methods: In a multicenter prospective observational cohort study (2015-2018), children <18 years old at their first SOT receiving tacrolimus as maintenance immunosuppression were included (455 as discovery cohort; 322 as validation cohort).

XUV pump-XUV probe transient absorption spectroscopy at FELs.

The emergence of ultra-intense extreme-ultraviolet (XUV) and X-ray free-electron lasers (FELs) has opened the door for the experimental realization of non-linear XUV and X-ray spectroscopy techniques. Here we demonstrate an experimental setup for an all-XUV transient absorption spectroscopy method for gas-phase targets at the FEL. The setup combines a high spectral resolving power of E/ΔE ≈ 1500 with sub-femtosecond interferometric resolution, and covers a broad XUV photon-energy range between approximately 20 and 110 eV.

Measuring the frequency chirp of extreme-ultraviolet free-electron laser pulses by transient absorption spectroscopy.

High-intensity ultrashort pulses at extreme ultraviolet (XUV) and x-ray photon energies, delivered by state-of-the-art free-electron lasers (FELs), are revolutionizing the field of ultrafast spectroscopy. For crossing the next frontiers of research, precise, reliable and practical photonic tools for the spectro-temporal characterization of the pulses are becoming steadily more important. Here, we experimentally demonstrate a technique for the direct measurement of the frequency chirp of extreme-ultraviolet free-electron laser pulses based on fundamental nonlinear optics.

Evidence for the alloimmune basis and prognostic significance of Borderline T cell-mediated rejection.

Prognostic biomarkers of T cell-mediated rejection (TCMR) have not been adequately studied in the modern era. We evaluated 803 renal transplant recipients and correlated HLA-DR/DQ molecular mismatch alloimmune risk categories (low, intermediate, high) with the severity, frequency, and persistence of TCMR. Allograft survival was reduced in recipients with Banff Borderline (hazard ratio [HR] 2.

Strong-Field Extreme-Ultraviolet Dressing of Atomic Double Excitation.

We report on the experimental observation of a strong-field dressing of an autoionizing two-electron state in helium with intense extreme-ultraviolet laser pulses from a free-electron laser. The asymmetric Fano line shape of this transition is spectrally resolved, and we observe modifications of the resonance asymmetry structure for increasing free-electron-laser pulse energy on the order of few tens of Microjoules. A quantum-mechanical calculation of the time-dependent dipole response of this autoionizing state, driven by classical extreme-ultraviolet (XUV) electric fields, evidences strong-field-induced energy and phase shifts of the doubly excited state, which are extracted from the Fano line-shape asymmetry.

Nonlinear Coherence Effects in Transient-Absorption Ion Spectroscopy with Stochastic Extreme-Ultraviolet Free-Electron Laser Pulses.

We demonstrate time-resolved nonlinear extreme-ultraviolet absorption spectroscopy on multiply charged ions, here applied to the doubly charged neon ion, driven by a phase-locked sequence of two intense free-electron laser pulses. Absorption signatures of resonance lines due to 2p-3d bound-bound transitions between the spin-orbit multiplets ^{3}P_{0,1,2} and ^{3}D_{1,2,3} of the transiently produced doubly charged Ne^{2+} ion are revealed, with time-dependent spectral changes over a time-delay range of (2.4±0.

Attosecond precision in delay measurements using transient absorption spectroscopy.

Accessing attosecond (as) dynamics directly in the time domain has been achieved by several pioneering experiments over the course of the last decade. Extreme ultraviolet (XUV) group delays and, later, ionization time delays on the order of a few attoseconds have been extracted by photoemission or high-harmonic spectroscopy. Here, we present and benchmark an approach based on attosecond transient absorption spectroscopy to quantify deliberately induced delays by employing resonant photoexcitation of three XUV transitions with a precision of less than 5 as.

XUV-beamline for attosecond transient absorption measurements featuring a broadband common beam-path time-delay unit and in situ reference spectrometer for high stability and sensitivity.

Measuring bound-state quantum dynamics, excited and driven by strong fields, is achievable by time-resolved absorption spectroscopy. Here, a vacuum beamline for spectroscopy in the attosecond temporal and extreme ultraviolet (XUV) spectral range is presented, which is a tool for observing and controlling nonequilibrium electron dynamics. In particular, we introduce a technique to record an XUV absorption signal and the corresponding reference simultaneously, which greatly improves the signal quality.

Pediatric Outcomes in Transplant: PersOnaliSing Immunosuppression To ImproVe Efficacy (POSITIVE Study): The Collaboration and Design of a National Transplant Precision Medicine Program.

Background: Despite age-related differences in biology, physiology, and behavior, transplant immunosuppression is not tailored by age. This likely contributes to high graft failure and posttransplant complications. We present the aims, design, and methods of the Pediatric Outcomes in Transplant: PersOnaliSing Immunosuppression To ImproVe Efficacy Study aimed at personalizing posttransplant immunosuppression in children and young adults.

Cellularity in low-grade Pseudomyxoma peritonei impacts recurrence-free survival following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Purpose: Documentation of cellularity in Pseudomyxoma peritonei (PMP) is not performed on a regular basis in everyday clinical practice, but is recommended by the PSOGI (Peritoneal Surface Oncology Group International). We investigated the impact of cellularity in PMP following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on recurrence-free survival.

Methods: Data from 25 patients with low-grade (American Joint Committee on Cancer grade G1) PMP were retrospectively evaluated.

HLA-DR/DQ molecular mismatch: A prognostic biomarker for primary alloimmunity.

Alloimmune risk stratification in renal transplantation has lacked the necessary prognostic biomarkers to personalize recipient care or optimize clinical trials. HLA molecular mismatch improves precision compared to traditional antigen mismatch but has not been studied in detail at the individual molecule level. This study evaluated 664 renal transplant recipients and correlated HLA-DR/DQ single molecule eplet mismatch with serologic, histologic, and clinical outcomes.

Real-Time Reconstruction of the Strong-Field-Driven Dipole Response.

The reconstruction of the full temporal dipole response of a strongly driven time-dependent system from a single absorption spectrum is demonstrated, only requiring that a sufficiently short pulse is employed to initialize the coherent excitation of the system. We apply this finding to the time-domain observation of Rabi cycling between doubly excited atomic states in the few-femtosecond regime. This allows us to pinpoint the breakdown of few-level quantum dynamics at the critical laser intensity near 2  TW/cm^{2} in doubly excited helium.

Class II Eplet Mismatch Modulates Tacrolimus Trough Levels Required to Prevent Donor-Specific Antibody Development.

Despite more than two decades of use, the optimal maintenance dose of tacrolimus for kidney transplant recipients is unknown. We hypothesized that HLA class II donor-specific antibody (DSA) development correlates with tacrolimus trough levels and the recipient's individualized alloimmune risk determined by HLA-DR/DQ epitope mismatch. A cohort of 596 renal transplant recipients with 50,011 serial tacrolimus trough levels had HLA-DR/DQ eplet mismatch determined using HLAMatchmaker software.

Evaluation of C1q Status and Titer of De Novo Donor-Specific Antibodies as Predictors of Allograft Survival.

De novo donor-specific antibodies (dnDSAs) that develop after renal transplantation are independent predictors of allograft loss. However, it is unknown if dnDSA C1q status or titer at the time of first detection can independently predict allograft loss. In a consecutive cohort of 508 renal transplant recipients, 70 developed dnDSAs.

Time-resolved four-wave-mixing spectroscopy for inner-valence transitions.

Noncollinear four-wave-mixing (FWM) techniques at near-infrared (NIR), visible, and ultraviolet frequencies have been widely used to map vibrational and electronic couplings, typically in complex molecules. However, correlations between spatially localized inner-valence transitions among different sites of a molecule in the extreme ultraviolet (XUV) spectral range have not been observed yet. As an experimental step toward this goal, we perform time-resolved FWM spectroscopy with femtosecond NIR and attosecond XUV pulses.

Rates and determinants of progression to graft failure in kidney allograft recipients with de novo donor-specific antibody.

Understanding rates and determinants of clinical pathologic progression for recipients with de novo donor-specific antibody (dnDSA), especially subclinical dnDSA, may identify surrogate endpoints and inform clinical trial design. A consecutive cohort of 508 renal transplant recipients (n = 64 with dnDSA) was studied. Recipients (n = 388) without dnDSA or dysfunction had an eGFR decline of -0.