Processing Radio Astronomical Data Using the PROCESS Software Ecosystem

In this paper we discuss our efforts in "unlocking" the Long Term Archive (LTA) of the LOFAR radio telescope using the software ecosystem developed in the PROCESS project. The LTA is a large (>50 PB) archive that expands with about 7 PB per year by the ingestion of new observations. It consists of coarsely calibrated "visibilities", i.e. correlations between signals from LOFAR stations. Converting these observations into sky maps (images), which are needed for astronomy research, can be challenging due to the data sizes of the observations and the complexity and compute requirements of the software involved. Using the PROCESS software environment and testbed, we enable a simple point-and-click-reduction of LOFAR observations into sky maps for users of this archive. This work was performed as part of the PROCESS project which aims to provide generalizable open source solutions for user friendly exascale data processing

Real-time visualization of renal microperfusion using laser speckle contrast imaging

Significance: Intraoperative parameters of renal cortical microperfusion (RCM) have been associated with postoperative ischemia/reperfusion injury. Laser speckle contrast imaging (LSCI) could provide valuable information in this regard with the advantage over the current standard of care of being a non-contact and full-field imaging technique. Aim: Our study aims to validate the use of LSCI for the visualization of RCM on ex vivo perfused human-sized porcine kidneys in various models of hemodynamic changes. Approach: A comparison was made between three renal perfusion measures: LSCI, the total arterial renal blood flow (RBF), and sidestream dark-field (SDF) imaging in different settings of ischemia/reperfusion. Results: LSCI showed a good correlation with RBF for the reperfusion experiment (0.94 +/- 0.02; p < 0.0001) and short- and long-lasting local ischemia (0.90 +/- 0.03; p < 0.0001 and 0.81 +/- 0.08; p < 0.0001, respectively). The correlation decreased for low flow situations due to RBF redistribution. The correlation between LSCI and SDF (0.81 +/- 0.10; p < 0.0001) showed superiority over RBF (0.54 +/- 0.22; p < 0.0001). Conclusions: LSCI is capable of imaging RCM with high spatial and temporal resolutions. It can instantaneously detect local perfusion deficits, which is not possible with the current standard of care. Further development of LSCI in transplant surgery could help with clinical decision making. (C) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License

Real-time, multi-spectral motion artefact correction and compensation for laser speckle contrast imaging

Abstract Laser speckle contrast imaging (LSCI) is so sensitive to motion that it can measure the movement of red blood cells. However, this extreme sensitivity to motion is also its pitfall as the clinical translation of LSCI is slowed down due to the inability to deal with motion artefacts. In this paper we study the effectiveness of a real-time, multi-spectral motion artefact correction and compensation by subduing an in vitro flow phantom and ex vivo porcine kidney to computer-controlled motion artefacts. On the in vitro flow phantom, the optical flow showed a good correlation with the total movement. This model results in a better signal-to-noise ratios for multiple imaging distances and the overestimation of perfusion was reduced. In the ex vivo kidney model, the perfusion overestimation was also reduced and we were still able to distinguish between ischemia and non-ischemia in the stabilized data whereas this was not possible in the non-stabilized data. This leads to a notably better perfusion estimation that could open the door to a multitude of new clinical applications for LSCI

Prolonged Organ Extraction Time Negatively Impacts Kidney Transplantation Outcome

Main Problem: Following cold aortic flush in a deceased organ donation procedure, kidneys never reach the intended 0–4°C and stay ischemic at around 20°C in the donor’s body until actual surgical retrieval. Therefore, organ extraction time could have a detrimental influence on kidney transplant outcome. Materials and Methods: We analyzed the association between extraction time and kidney transplant outcome in multicenter data of 5,426 transplant procedures from the Dutch Organ Transplantation Registry (NOTR) and 15,849 transplant procedures from the United Network for Organ Sharing (UNOS). Results: Extraction time was grouped per 10-min increment. In the NOTR database, extraction time was independently associated with graft loss [HR 1.027 (1.004–1.050); p = 0.022] and with DGF [OR 1.043 (1.021–1.066); p 80 min was associated with a 27.4% higher hazard rate of graft failure [HR 1.274 (1.080–1.502); p = 0.004] and such kidneys had 43.8% higher odds of developing DGF [OR 1.438, (1.236–1.673); p 30 min was associated with 14.5% higher odds of developing DGF [OR 1.145 (1.063–1.233); p < 0.005]. Discussion: Prolonged kidney extraction time negatively influenced graft survival in Dutch donors and increased DGF risk in all deceased donor recipients

Loss of Endothelial Glycocalyx During Normothermic Machine Perfusion of Porcine Kidneys Irrespective of Pressure and Hematocrit

BACKGROUND: Normothermic machine perfusion (NMP) is a promising modality for marginal donor kidneys. However, little is known about the effects of NMP on causing endothelial glycocalyx (eGC) injury. This study aims to evaluate the effects of NMP on eGC injury in marginal donor kidneys and whether this is affected by perfusion pressures and hematocrits.METHODS: Porcine slaughterhouse kidneys (n = 6/group) underwent 35 min of warm ischemia. Thereafter, the kidneys were preserved with oxygenated hypothermic machine perfusion for 3 h. Subsequently, 4 h of NMP was applied using pressure-controlled perfusion with an autologous blood-based solution containing either 12%, 24%, or 36% hematocrit. Pressures of 55, 75, and 95 mm Hg were applied in the 24% group. Perfusate, urine, and biopsy samples were collected to determine both injury and functional parameters.RESULTS: During NMP, hyaluronan levels in the perfusate increased significantly ( P &lt; 0.0001). In addition, the positivity of glyco-stained glycocalyx decreased significantly over time, both in the glomeruli ( P = 0.024) and peritubular capillaries ( P = 0.003). The number of endothelial cells did not change during NMP ( P = 0.157), whereas glomerular endothelial expression of vascular endothelial growth factor receptor-2 decreased significantly ( P &lt; 0.001). Microthrombi formation was significantly increased after NMP. The use of different pressures and hematocrits did not affect functional parameters during perfusion. CONCLUSIONS: NMP is accompanied with eGC and vascular endothelial growth factor receptor-2 loss, without significant loss of endothelial cells. eGC loss was not affected by the different pressures and hematocrits used. It remains unclear whether endothelial injury during NMP has harmful consequences for the transplanted kidney.</p

Nitric oxide and long-term outcomes after kidney transplantation:Results of the TransplantLines cohort study

Impaired endogenous nitric oxide (NO) production may contribute to graft failure and premature mortality in kidney transplant recipients (KTR). We investigated potential associations of 24-h urinary NOx (NO3- + NO2-) excretion (uNOx) with long-term outcomes. uNOx was determined by HPLC and GC-MS in 698 KTR and in 132 kidney donors before and after donation. Additionally, we measured urinary nitroso species (RXNO) by gas-phase chemiluminescence. Median uNOx was lower in KTR compared to kidney donors (688 [393-1076] vs. 1301 [868-1863] before donation and 1312 [982-1853] μmol/24 h after donation, P < 0.001). During median follow-up of 5.4 [4.8-6.1] years, 150 KTR died (61 due to cardiovascular disease) and 83 experienced graft failure. uNOx was inversely associated with all-cause mortality (HR per doubling of uNOx: 0.84 [95% CI 0.75-0.93], P < 0.001) and cardiovascular mortality (HR 0.78 [95% CI 0.67-0.92], P = 0.002). The association of uNOx with graft failure was lost when adjusted for renal function (HR per doubling of uNOx: 0.89 [95% CI 0.76-1.05], P = 0.17). There were no significant associations of urinary RXNO with outcomes. Our study suggests that KTR have lower NO production than healthy subjects and that lower uNOx is associated with a higher risk of all-cause and cardiovascular mortality

Hydrogen sulphide-induced hypometabolism in human-sized porcine kidneys

Background Since the start of organ transplantation, hypothermia-forced hypometabolism has been the cornerstone in organ preservation. Cold preservation showed to protect against ischemia, although post-transplant injury still occurs and further improvement in preservation techniques is needed. We hypothesize that hydrogen sulphide can be used as such a new preservation method, by inducing a reversible hypometabolic state in human sized kidneys during normothermic machine perfusion. Methods Porcine kidneys were connected to an ex-vivo isolated, oxygen supplemented, normothermic blood perfusion set-up. Experimental kidneys (n = 5) received a 85mg NaHS infusion of 100 ppm and were compared to controls (n = 5). As a reflection of the cellular metabolism, oxygen consumption, mitochondrial activity and tissue ATP levels were measured. Kidney function was assessed by creatinine clearance and fractional excretion of sodium. To rule out potential structural and functional deterioration, kidneys were studied for biochemical markers and histology. Results Hydrogen sulphide strongly decreased oxygen consumption by 61%, which was associated with a marked decrease in mitochondrial activity/function, without directly affecting ATP levels. Renal biological markers, renal function and histology did not change after hydrogen sulphide treatment. Conclusion In conclusion, we showed that hydrogen sulphide can induce a controllable hypometabolic state in a human sized organ, without damaging the organ itself and could thereby be a promising therapeutic alternative for cold preservation under normothermic conditions in renal transplantation

Ischemia targeted therapies during critical periods of organ preservation

Ischemic tissue damage resulting from the surgical extraction procedure of donor kidneys remains an important clinical problem in kidney transplantation. This thesis aims to gain insight and find potential solutions to mitigate the impact of ischemic injury. In addition to quantification of the impact of the duration of ischemia, also the role of temperature during this ischemic period was investigated. Furthermore, the effect of temperature on mitochondrial function and reactive oxygen species production were determined and new strategies to decrease ischemic injury were evaluated. These strategies include the use of hydrogen sulphide, oxygen and glucose during the flush-out at the start of extraction procedure. Hydrogen sulphide showed interesting capacities in inducing a hypometabolic state and reducing inflammatory markers but failed to prevent ischemic injury. The use of oxygen and glucose improved the energy status of the kidneys after the flush-out. Lastly, a new way of visualizing renal cortical microperfusion was studied, thereby improving the assessment of damage resulting from ischemia and getting better insight into organ quality