[18F]-sodium fluoride autoradiography imaging of nephrocalcinosis in donor kidneys and explanted kidney allografts

Nephrocalcinosis is present in up to 43% of kidney allograft biopsies at one-year after transplantation and is associated with inferior graft function and poor graft survival. We studied [18F]-sodium fluoride ([18F]-NaF) imaging of microcalcifications in donor kidneys (n = 7) and explanted kidney allografts (n = 13). Three µm paraffin-embedded serial sections were used for histological evaluation of calcification (Alizarin Red; Von Kossa staining) and ex-vivo [18F]-NaF autoradiography. The images were fused to evaluate if microcalcification areas corresponded with [18F]-NaF uptake areas. Based on histological analyses, tubulointerstitial and glomerular microcalcifications were present in 19/20 and 7/20 samples, respectively. Using autoradiography, [18F]-NaF uptake was found in 19/20 samples, with significantly more tracer activity in kidney allograft compared to deceased donor kidney samples (p = 0.019). Alizarin Red staining of active microcalcifications demonstrated good correlation (Spearman's rho of 0.81, p < 0.001) and Von Kossa staining of consolidated calcifications demonstrated significant but weak correlation (0.62, p = 0.003) with [18F]-NaF activity. This correlation between ex-vivo [18F]-NaF uptake and histology-proven microcalcifications, is the first step towards an imaging method to identify microcalcifications in active nephrocalcinosis. This may lead to better understanding of the etiology of microcalcifications and its impact on kidney transplant function

Aorto-Iliac Artery Calcification and Graft Outcomes in Kidney Transplant Recipients

While the association of vascular calcification with inferior patient outcomes in kidney transplant recipients is well-established, the association with graft outcomes has received less attention. With this dual-centre cohort study, we aimed to determine the clinical impact of recipient pre-transplant aorto-iliac calcification, measured on non-contrast enhanced computed tomography (CT)-imaging within three years prior to transplantation (2005&ndash;2018). We included 547 patients (61.4% male, age 60 (interquartile range 51&ndash;68) years), with a median follow-up of 3.1 (1.4&ndash;5.2) years after transplantation. The aorto-iliac calcification score (CaScore) was inversely associated with one-year estimated-glomerular filtration rate (eGFR) in univariate linear regression analysis (standard &beta; &minus;3.3 (95% CI &minus;5.1 to &minus;1.5, p &lt; 0.0001), but not after adjustment for potential confounders, including donor and recipient age (p = 0.077). In multivariable Cox regression analyses, a high CaScore was associated with overall graft failure (p = 0.004) and death with a functioning graft (p = 0.002), but not with death-censored graft failure and graft function decline. This study demonstrated that pre-transplant aorto-iliac calcification is associated with one-year eGFR in univariate, but not in multivariable linear regression analyses. Moreover, this study underlines that transplantation in patients with a high CaScore does not result in earlier transplant function decline or worse death censored graft survival, although ongoing efforts for the prevention of death with a functioning graft remain essential

Aorto-Iliac Artery Calcification Prior to Kidney Transplantation

As vascular calcification is common in kidney transplant candidates, aorto-iliac vessel imaging is performed for surgical planning. The aim of the present study was to investigate whether a novel non-contrast enhanced computed tomography-based quantification technique for aorto-iliac calcification can be used for cardiovascular risk stratification prior to kidney transplantation. In this dual-center cohort study, we measured the aorto-iliac calcium score (CaScore) of 547 patients within three years prior to transplantation (2005-2018). During a median (interquartile range) follow-up of 3.1 (1.4, 5.2) years after transplantation, 80 (14.7%) patients died, of which 32 (40.0%) died due to cardiovascular causes, and 84 (15.5%) patients had a cardiovascular event. Kaplan-Meier survival curves showed significant differences between the CaScore tertiles for cumulative overall-survival (Log-rank testp<0.0001), cardiovascular survival (p<0.0001), and cardiovascular event-free survival (p<0.001). In multivariable Cox regression, the aorto-iliac CaScore was associated with all-cause mortality (hazard ratio 1.53, 95%CI 1.14-2.06,p= 0.005), cardiovascular mortality (2.04, 1.20-3.45,p= 0.008), and cardiovascular events (1.35, 1.01-1.80,p= 0.042). These independent associations of the aorto-iliac CaScore with the outcome measures can improve the identification of patients at risk for (cardiovascular) death and those who could potentially benefit from stringent cardiovascular monitoring to improve their prognosis after transplantation

The relationship of peritubular capillary density with glomerular volume and kidney function in living kidney donors

Background: Peritubular capillary rarefaction plays an important role in the progression of chronic kidney disease. Little is known about the relation between peritubular capillary density, glomerular volume and filtration rate in the healthy kidney. Methods: In this single-center study, we included 69 living kidney donors who donated between 2005 and 2008 and had representative renal biopsies available. In all donors, glomerular filtration rate was measured using 125I-Iothalamate before donation and at five years after donation. Before donation, the increase in glomerular filtration rate after dopamine stimulation was measured. Glomerular volume and peritubular capillary density were determined in biopsies taken at the time of transplantation. Pearson’s correlation coefficient and linear regression were used to assess relations between parameters.Results: Mean donor age was 52 ± 11 years and mean measured glomerular filtration rate was 119 ± 22 mL/min before donation and 82 ± 15 mL/min at five years after donation. While peritubular capillary density (measured by either number of peritubular capillaries/50,000 μm2 or number of peritubular capillaries/tubule) was not associated with measured glomerular filtration rate before or after donation, number of peritubular capillaries/tubule was associated with the increase in measured glomerular filtration rate after dopamine stimulation (St.β = 0.33, p = 0.004), and correlated positively with glomerular volume (R = 0.24, p = 0.047). Glomerular volume was associated with unstimulated measured glomerular filtration rate before donation (St.β = 0.31, p = 0.01) and at five years (St.β = 0.30, p = 0.01) after donation, independent of age.Conclusions: In summary, peritubular capillary density was not related to unstimulated kidney function before or after kidney donation, in contrast to glomerular volume. However, number of peritubular capillaries/tubule correlated with the increase in glomerular filtration rate after dopamine stimulation in healthy kidneys, and with glomerular volume. These findings suggest that peritubular capillary density and glomerular volume differentially affect kidney function in healthy living kidney donors. Graphical abstract: [Figure not available: see fulltext.]</p

Signaling in Secret: Pay-for-Performance and the Incentive and Sorting Effects of Pay Secrecy

Key Findings: Pay secrecy adversely impacts individual task performance because it weakens the perception that an increase in performance will be accompanied by increase in pay; Pay secrecy is associated with a decrease in employee performance and retention in pay-for-performance systems, which measure performance using relative (i.e., peer-ranked) criteria rather than an absolute scale (see Figure 2 on page 5); High performing employees tend to be most sensitive to negative pay-for- performance perceptions; There are many signals embedded within HR policies and practices, which can influence employees’ perception of workplace uncertainty/inequity and impact their performance and turnover intentions; and When pay transparency is impractical, organizations may benefit from introducing partial pay openness to mitigate these effects on employee performance and retention

Реконструкция Гусиноозерской ГРЭС

Выпускная квалификационная работа содержит 95 страниц, 39 рисунков, 34 таблицы, 6 источников литературы и всего 4 приложения. Ключевые слова: электрическая станция, элегазовый выключатель, турбогенератор, короткое замыкание, асинхронный режим, «Mustang».The Degree Work contains 95 pages, 39 pictures, 34 tables sheets, 6 information sourses and 4 application. Key words: power station, generator, short curcuit, Mustang, Sulfur hexafluoride switche

Carbon nanoparticles in lateral flow methods to detect genes encoding virulence factors of Shiga toxin-producing Escherichia coli

The use of carbon nanoparticles is shown for the detection and identification of different Shiga toxin-producing Escherichia coli virulence factors (vt1, vt2, eae and ehxA) and a 16S control (specific for E. coli) based on the use of lateral flow strips (nucleic acid lateral flow immunoassay, NALFIA). Prior to the detection with NALFIA, a rapid amplification method with tagged primers was applied. In the evaluation of the optimised NALFIA strips, no cross-reactivity was found for any of the antibodies used. The limit of detection was higher than for quantitative PCR (q-PCR), in most cases between 104 and 105 colony forming units/mL or 0.1–0.9 ng/μL DNA. NALFIA strips were applied to 48 isolates from cattle faeces, and results were compared to those achieved by q-PCR. E. coli virulence factors identified by NALFIA were in very good agreement with those observed in q-PCR, showing in most cases sensitivity and specificity values of 1.0 and an almost perfect agreement between both methods (kappa coefficient larger than 0.9). The results demonstrate that the screening method developed is reliable, cost-effective and user-friendly, and that the procedure is fast as the total time required is <1 h, which includes amplification

Measurement of hadronic shower punchthrough in magnetic field

The total punchthrough probability of showers produced by negative pions, positive pions, positive kaons and protons, has been measured as a function of depth in an absorber in a magnetic field ranging from 0 to 3 Tesla. The incident particle momentum varied from 10 to 300 GeV/c. The lateral shower development and particle multiplicity at several absorber depths have been determined. The measurements are compared with the predictions of Monte Carlo simulation programs

Regionalized Pathology Correlates with Augmentation of mtDNA Copy Numbers in a Patient with Myoclonic Epilepsy with Ragged-Red Fibers (MERRF-Syndrome)

Human patients with myoclonic epilepsy with ragged-red fibers (MERRF) suffer from regionalized pathology caused by a mutation in the mitochondrial DNA (m.8344A→G). In MERRF-syndrome brain and skeletal muscles are predominantly affected, despite mtDNA being present in any tissue. In the past such tissue-specificity could not be explained by varying mtDNA mutation loads. In search for a region-specific pathology in human individuals we determined the mtDNA/nDNA ratios along with the mutation loads in 43 different post mortem tissue samples of a 16-year-old female MERRF patient and in four previously healthy victims of motor vehicle accidents. In brain and muscle we further determined the quantity of mitochondrial proteins (COX subunits II and IV), transcription factors (NRF1 and TFAM), and VDAC1 (Porin) as a marker for the mitochondrial mass. In the patient the mutation loads varied merely between 89–100%. However, mtDNA copy numbers were increased 3–7 fold in predominantly affected brain areas (e.g. hippocampus, cortex and putamen) and in skeletal muscle. Similar increases were absent in unaffected tissues (e.g. heart, lung, kidney, liver, and gastrointestinal organs). Such mtDNA copy number increase was not paralleled by an augmentation of mitochondrial mass in some investigated tissues, predominantly in the most affected tissue regions of the brain. We thus conclude that “futile” stimulation of mtDNA replication per se or a secondary failure to increase the mitochondrial mass may contribute to the regionalized pathology seen in MERRF-syndrome