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

Evaluation of individual dosimetry in mixed neutron and photon radiation fields (EVIDOS). Part II: conclusions and recommendations

The paper presents the main conclusions and recommendations derived from the EVIDOS project, which is supported by the European Commission within the 5th Framework Programme. EVIDOS aims at evaluating state of the art neutron dosimetry techniques in representative workplaces of the nuclear industry with complex mixed neutron-photon radiation fields. This analysis complements a series of individual papers which present detailed results and it summarises the main findings from a practical point of view. Conclusions and recommendations are given concerning characterisation of radiation fields, methods to derive radiation protection quantities and dosemeter result

Genetic Risk Score for Serum 25-Hydroxyvitamin D Concentration Helps to Guide Personalized Vitamin D Supplementation in Healthy Finnish Adults

Background Genetic factors modify serum 25-hydroxyvitamin D [25(OH)D] concentration and can affect the optimal intake of vitamin D. Objectives We aimed to personalize vitamin D supplementation by applying knowledge of genetic factors affecting serum 25(OH)D concentration. Methods We performed a genome-wide association study of serum 25(OH)D concentration in the Finnish Health 2011 cohort (n = 3339) using linear regression and applied the results to develop a population-matched genetic risk score (GRS) for serum 25(OH)D. This GRS was used to tailor vitamin D supplementation for 96 participants of a longitudinal Digital Health Revolution (DHR) Study. The GRS, serum 25(OH)D concentrations, and personalized supplementation and dietary advice were electronically returned to participants. Serum 25(OH)D concentrations were assessed using immunoassays and vitamin D intake using FFQs. In data analyses, cross-sectional and repeated-measures statistical tests and models were applied as described in detail elsewhere. Results GC vitamin D-binding protein and cytochrome P450 family 2 subfamily R polypeptide 1 genes showed genome-wide significant associations with serum 25(OH)D concentration. One single nucleotide polymorphism from each locus (rs4588 and rs10741657) was used to develop the GRS. After returning data to the DHR Study participants, daily vitamin D supplement users increased from 32.6% to 60.2% (P = 6.5 x 10(-6)) and serum 25(OH)D concentration from 64.4 +/- 20.9 nmol/L to 68.5 +/- 19.2 nmol/L (P = 0.006) between August and November. Notably, the difference in serum 25(OH)D concentrations between participants with no risk alleles and those with 3 or 4 risk alleles decreased from 20.7 nmol/L to 8.0 nmol/L (P = 0.0063). Conclusions We developed and applied a population-matched GRS to identify individuals genetically predisposed to low serum 25(OH)D concentration. We show how the electronic return of individual genetic risk, serum 25(OH)D concentrations, and factors affecting vitamin D status can be used to tailor vitamin D supplementation. This model could be applied to other populations and countries.Peer reviewe

Evaluation of individual dosimetry in mixed neutron and photon radiation fields (EVIDOS). Part I: scope and methods of the project

Supported by the European Commission, the EVIDOS project started in November 2001 with the broad goal of evaluating state of the art dosimetry techniques in representative workplaces of the nuclear industry. Seven European institutes joined efforts with end users at nuclear power plants, at fuel processing and reprocessing plants, and at transport and storage facilities. A comprehensive programme was devised to evaluate capabilities and limitations of standard and innovative personal dosemeters in relation to the mixed neutron-photon fields of concern to the nuclear industry. This paper describes the criteria behind the selection of dosimetry techniques and workplaces that were analysed, as well as the organisation of the measurement campaigns. Particular emphasis was placed on the evaluation of a variety of electronic personal dosemeters, either commercially available or previously developed by the partners. The estimates provided by these personal dosemeters were compared to reference values of dose equivalent quantities derived from spectrometry and fluence-to-dose equivalent conversion coefficients. Spectrometry was performed both with conventional multisphere and with some original instrumentation providing energy and direction resolution, based on silicon detectors and superheated drop detectors mounted on or in spherical moderators. The results were collected in a large, searchable database and are intended to be used in the harmonisation of dosimetric procedures for mixed radiation fields and for the approval of dosimetry services in Europ

Genetic Risk Score for Serum 25-Hydroxyvitamin D Concentration Helps to Guide Personalized Vitamin D Supplementation in Healthy Finnish Adults

Background Genetic factors modify serum 25-hydroxyvitamin D [25(OH)D] concentration and can affect the optimal intake of vitamin D. Objectives We aimed to personalize vitamin D supplementation by applying knowledge of genetic factors affecting serum 25(OH)D concentration. Methods We performed a genome-wide association study of serum 25(OH)D concentration in the Finnish Health 2011 cohort (n = 3339) using linear regression and applied the results to develop a population-matched genetic risk score (GRS) for serum 25(OH)D. This GRS was used to tailor vitamin D supplementation for 96 participants of a longitudinal Digital Health Revolution (DHR) Study. The GRS, serum 25(OH)D concentrations, and personalized supplementation and dietary advice were electronically returned to participants. Serum 25(OH)D concentrations were assessed using immunoassays and vitamin D intake using FFQs. In data analyses, cross-sectional and repeated-measures statistical tests and models were applied as described in detail elsewhere. Results GC vitamin D-binding protein and cytochrome P450 family 2 subfamily R polypeptide 1 genes showed genome-wide significant associations with serum 25(OH)D concentration. One single nucleotide polymorphism from each locus (rs4588 and rs10741657) was used to develop the GRS. After returning data to the DHR Study participants, daily vitamin D supplement users increased from 32.6% to 60.2% (P = 6.5 x 10(-6)) and serum 25(OH)D concentration from 64.4 +/- 20.9 nmol/L to 68.5 +/- 19.2 nmol/L (P = 0.006) between August and November. Notably, the difference in serum 25(OH)D concentrations between participants with no risk alleles and those with 3 or 4 risk alleles decreased from 20.7 nmol/L to 8.0 nmol/L (P = 0.0063). Conclusions We developed and applied a population-matched GRS to identify individuals genetically predisposed to low serum 25(OH)D concentration. We show how the electronic return of individual genetic risk, serum 25(OH)D concentrations, and factors affecting vitamin D status can be used to tailor vitamin D supplementation. This model could be applied to other populations and countries.Peer reviewe

Neutron area survey instrument measurements in the EVIDOS project

Neutron survey instruments have been exposed at all the measurement locations used in the EVIDOS project. These results have an important impact in the interpretation of the results from the project, since operationally the survey instrument will be used for an initial assessment of and routine monitoring of the ambient dose equivalent dose rate. Additionally, since the response of these instruments is in some cases very well characterised, their systematic deviations from the reference quantities provide an important verification of the determination of those quantitie

Electronic neutron personal dosemeters: their performance in mixed radiation fields in nuclear power plants

This work describes spectral distributions of neutrons obtained as function of energy and direction at four workplace fields at the Krümmel reactor in Germany. Values of personal dose equivalent Hp(10) and effective dose E are determined for different directions of a person's orientation in these fields and readings of personal neutron dosemeters—especially electronic dosemeters—are discussed with respect to Hp(10) and

Summary of personal neutron dosemeter results obtained within the EVIDOS project

Within the EC project EVIDOS (‘Evaluation of Individual Dosimetry in Mixed Neutron and Photon Radiation Fields'), different types of active neutron personal dosemeters (and some passive ones) were tested in workplace fields at nuclear installations in Europe. The results of the measurements which have been performed up to now are summarised and compared to our currently best estimates of the personal dose equivalent Hp(10). Under- and over-readings by more than a factor of two for the same dosemeter in different workplace fields indicate that in most cases the use of field-specific correction factors is require

Three independently deleted regions at chromosome arm 16q in human prostate cancer: allelic loss at 16q24.1–q24.2 is associated with aggressive behaviour of the disease, recurrent growth, poor differentiation of the tumour and poor prognosis for the patient

Loss of heterozygosity at chromosome arm 16q is a frequent event in human prostate cancer. In this study, loss of heterozygosity at 16q was studied in 44 prostate cancer patients exhibiting various clinical features. Fifteen polymorphic polymerase chain reaction (PCR) markers were used to identify the separately deleted areas and the findings were compared with clinicopathological variables and 5-year survival of the patients. The results indicated that there are at least three independently deleted regions at 16q. Allelic losses at the central and distal areas were associated significantly with aggressive behaviour of the disease (16q24.1–q24.2, P< 0.01, and 16q24.3–qter, P< 0.05), and the central area of deletion was further significantly associated with poorly differentiated tumour cells (P< 0.05) and with recurrent (P< 0.01) growth of the tumour. During the follow-up period, 28% of the patients initially with M0 disease developed distant metastases. Of the patients showing allelic loss at 16q24.1–q24.2, distant metastasis were found in 45% during the 5-year follow-up period, and 31% of the patients showing loss at 16q21.1 also developed distant metastases. After the 5-year follow-up period, 14 (32%) of the patients remained alive, whereas 19 (43%) had died because of their prostate cancer. The overall survival rate of the patients showing allelic loss at 16q21.1 or 16q24.1–q24.2 was significantly lower than that of the patients with retained heterozygosity. © 1999 Cancer Research Campaig