Graft Neutrophil Sequestration and Concomitant Tissue Plasminogen Activator Release During Reperfusion in Clinical Kidney Transplantation

Background. Inflammation, coagulation, and fibrinolysis are tightly linked together. Reperfusion after transient ischemia activates both neutrophils, coagulation, and fibrinolysis. Experimental data suggest that tissue plasminogen activator (tPA) regulates renal neutrophil influx in kidney ischemia and reperfusion injury. Methods. In 30 patients undergoing kidney transplantation, we measured renal neutrophil sequestration and tPA release from blood samples drawn from the supplying artery and renal vein early after reperfusion. tPA antigen levels were measured using a commercial enzyme-linked immunosorbent assay kit. For each parameter, transrenal difference (Delta) was calculated by subtracting the value of the arterial sample (ingoing blood) from the value of the venous sample (outgoing blood). Results. Positive transrenal gradients of tPA antigen occurred at 1 minute [Delta = 14 (3-46) ng/mL, P <.01] and 5 minutes [Delta = 5 (-3 to 27) ng/mL, P <.01] after reperfusion. At 5 minutes after reperfusion, a negative transrenal gradient of neutrophils was observed [Delta = -0.17 (-1.45 to 0.24) x 10E9 cells/L, P <.001]. At 1 minute after reperfusion, neutrophil sequestration into the kidney (ie, negative transrenal neutrophil count) correlated significantly with tPA release from the kidney (ie, positive transrenal tPA concentration), (R = -0.513 and P = .006). Conclusions. The findings suggest a proinflammatory role for tPA in ischemia and reperfusion injury in human kidney transplantation.Peer reviewe

Oxidation of HMGB1 Causes Attenuation of Its Pro-Inflammatory Activity and Occurs during Liver Ischemia and Reperfusion

High mobility group box 1 (HMGB1) is a nuclear transcription factor. Once HMGB1 is released by damaged cells or activated immune cells, it acts as danger molecule and triggers the inflammatory signaling cascade. Currently, evidence is accumulating that posttranslational modifications such as oxidation may modulate the pro-inflammatory potential of danger signals. We hypothesized that oxidation of HMGB1 may reduce its pro-inflammatory potential and could take place during prolonged ischemia and upon reperfusion

Evaluation of bottom-up and top-down strategies for aggregated forecasts: state space models and arima applications

Abstract. In this research, we consider monthly series from the M4 competition to study the relative performance of top-down and bottom-up strategies by means of implementing forecast automation of state space and ARIMA models. For the bottomup strategy, the forecast for each series is developed individually and then these are combined to produce a cumulative forecast of the aggregated series. For the top-down strategy, the series or components values are first combined and then a single forecast is determined for the aggregated series. Based on our implementation, state space models showed a higher forecast performance when a top-down strategy is applied. ARIMA models had a higher forecast performance for the bottom-up strategy. For state space models the top-down strategy reduced the overall error significantly. ARIMA models showed to be more accurate when forecasts are first determined individually. As part of the development we also proposed an approach to improve the forecasting procedure of aggregation strategies

High-growth firms and productivity:evidence from the United Kingdom

Abstract There is considerable evidence that high-growth firms (HGFs) contribute significantly to employment and economic growth. However, the literature so far does not adequately explore the link between HGFs and productivity. This paper investigates the empirical link between total factor productivity (TFP) growth and HGFs, defined in terms of sales growth, in the United Kingdom over the period 2001-2010, by examining two related research questions. Firstly, does higher TFP growth lead to HGF status and secondly, does HGF experience help firms achieve faster TFP growth? Our findings reveal that firms in both the manufacturing and services sectors are more likely to become HGFs when they exhibit higher TFP growth. In addition, firms that have had HGF experience tend to enjoy faster TFP growth following the high-growth episodes. Policy implications are drawn based on the self-reinforcing process of the high-growth phenomenon that is revealed by our results

Minimum Wages and Youth Employment: Evidence from the Finnish Retail Trade Sector

Following an agreement between the trade unions and the employer organisations, Finnish employers could pay less than the existing minimum wage for young workers between 1993 and 1995. We examine the effects of these minimum wage exceptions by comparing the changes in wages and employment of the groups whose minimum wages were reduced with simultaneous changes among slightly older workers for whom the minimum wage regulation was still binding. Our analysis is based on the payroll record data and minimum wage agreements from the retail trade sector over the period 1990-2005. We discover that average wages in the eligible group declined only modestly despite the fact that the excess supply of labour during high unemployment should make it relatively easy to attract workers even with low wages. The minimum wage exceptions had no positive effects on employment