Quest for a Nuclear Georeactor

Knowledge about the interior of our planet is mainly based on the interpretation of seismic data from earthquakes and nuclear explosions, and of composition of meteorites. Additional observations have led to a wide range of hypotheses on the heat flow from the interior to the crust, the abundance of certain noble gases in gasses vented from volcanoes and the possibility of a nuclear georeactor at the centre of the Earth. This paper focuses on a proposal for an underground laboratory to further develop antineutrinos as a tool to map the distribution of radiogenic heat sources, such as the natural radionuclides and the hypothetical nuclear georeactor.Comment: Invited talk presented at the International Symposium on Radiation Physics, Cape Town, 2003. Manuscript is submitted to Radiation Physics and Chemistr

Легочная гипертензия при диастолической дисфункции левого желудочка у больных с ишемической кардиомиопатией

На основании данных эхокардиографического исследования выявлена взаимосвязь между степенью легочной гипертензии и тяжестью диастолической дисфункции левого желудочка у больных с ишемической кардиомиопатией. Показано, что рестриктиное наполнение левого желудочка наблюдается в основном при выраженной легочной гипертензии.The findings of echocardiography were used to reveal interrelation between the degree of pulmonary hypertension and severity of diastolic dysfunction of the left ventricle in patients with ischemic cardiomyopathy. Restrictive filling of the left ventricle is shown to be observed in marked pulmonary hypertension

Cell-free microRNAs as early predictors of graft viability during ex vivo normothermic machine perfusion of human donor livers

Background: Cell-free microRNAs (miRs) have emerged as early and sensitive biomarkers for tissue injury and function. This study aimed to investigate whether the release of hepatocyte-derived microRNAs (HDmiRs) and cholangiocyte-derived miRs (CDmiRs) correlates with hepato-cholangiocellular injury and function during oxygenated, normothermic machine perfusion (NMP) of human liver grafts. Methods: Donor livers (n = 12), declined for transplantation, were subjected to oxygenated NMP (6 hours) after a period of static cold storage (median 544 minutes (IQR 421-674)). Perfusate and bile samples were analyzed by qRT-PCR for HDmiR-122 and CDmiR-222. Spearman correlations were performed between miR levels and currently available indicators and classic markers. Results: Both HDmiR-122 and CDmiR-222 levels in perfusate at 30 minutes of NMP strongly correlated with hepatocyte injury (peak perfusate AST) and cholangiocyte injury (peak biliary LDH). In bile, only CDmiR-222 correlated with these injury markers. For hepato-cholangiocellular function, both miRs in perfusate correlated with total bilirubin, while HDmiR-122 (in perfusate) and CDmiR-222 (in bile) correlated with bicarbonate secretion. Both the relative ratio of HDmiR-122/CDmiR-222 and AST in perfusate at 30 minutes significantly correlated with cumulative bile production, but only the relative ratio was predictive of histopathological injury after 6 hours NMP. Conclusion: Early levels of HDmiR-122 and CDmiR-222, in perfusate and/or bile, are predictive of excretory functions and hepato-cholangiocellular injury after 6 hours NMP. These miRs may represent new biomarkers for graft viability and function during machine perfusion

Diurnal variation in P-glycoprotein-mediated transport and cerebrospinal fluid turnover in the brain.

Nearly all bodily processes exhibit circadian rhythmicity. As a consequence, the pharmacokinetic and pharmacodynamic properties of a drug may also vary with time of day. The objective of this study was to investigate diurnal variation in processes that regulate drug concentrations in the brain, focusing on P-glycoprotein (P-gp). This efflux transporter limits the distribution of many drugs in the brain. To this end, the exposure to the P-gp substrate quinidine was determined in the plasma and brain tissue after intravenous administration in rats at six different time points over the 24-h period. Our results indicate that time of administration significantly affects the exposure to quinidine in the brain. Upon inhibition of P-gp, exposure to quinidine in brain tissue is constant over the 24-h period. To gain more insight into processes regulating brain concentrations, we used intracerebral microdialysis to determine the concentration of quinidine in brain extracellular fluid (ECF) and cerebrospinal fluid (CSF) after intravenous administration at two different time points. The data were analyzed by physiologically based pharmacokinetic modeling using NONMEM. The model shows that the variation is due to higher activity of P-gp-mediated transport from the deep brain compartment to the plasma compartment during the active period. Furthermore, the analysis reveals that CSF flux is higher in the resting period compared to the active period. In conclusion, we show that the exposure to a P-gp substrate in the brain depends on time of administration, thereby providing a new strategy for drug targeting to the brain.Pharmacolog

Clinical translation and implementation of optical imaging agents for precision image-guided cancer surgery

Introduction The field of tumor-specific fluorescence-guided surgery has seen a significant increase in the development of novel tumor-targeted imaging agents. Studying patient benefit using intraoperative fluorescence-guided imaging for cancer surgery is the final step needed for implementation in standard treatment protocols. Translation into phase III clinical trials can be challenging and time consuming. Recent studies have helped to identify certain waypoints in this transition phase between studying imaging agent efficacy (phase I-II) and proving patient benefit (phase III). Trial initiation Performing these trials outside centers of expertise, thus involving motivated clinicians, training them, and providing feedback on data quality, increases the translatability of imaging agents and the surgical technique. Furthermore, timely formation of a trial team which oversees the translational process is vital. They are responsible for establishing an imaging framework (camera system, imaging protocol, surgical workflow) and clinical framework (disease stage, procedure type, clinical research question) in which the trial is executed. Providing participating clinicians with well-defined protocols with the aim to answer clinically relevant research questions within the context of care is the pinnacle in gathering reliable trial data. Outlook If all these aspects are taken into consideration, tumor-specific fluorescence-guided surgery is expected be of significant value when integrated into the diagnostic work-up, surgical procedure, and follow-up of cancer patients. It is only by involving and collaborating with all stakeholders involved in this process that successful clinical translation can occur. Aim Here, we discuss the challenges faced during this important translational phase and present potential solutions to enable final clinical translation and implementation of imaging agents for image-guided cancer surgery.Surgical oncolog

Deformation effects in 56^{56}Ni nuclei produced in 28^{28}Si+28^{28}Si at 112 MeV

Velocity and energy spectra of the light charged particles (protons and $\alpha$-particles) emitted in the $^{28}$Si(E$_{lab}$ = 112 MeV) + $^{28}$Si reaction have been measured at the Strasbourg VIVITRON Tandem facility. The ICARE charged particle multidetector array was used to obtain exclusive spectra of the light particles in the angular range 15 - 150 degree and to determine the angular correlations of these particles with respect to the emission angles of the evaporation residues. The experimental data are analysed in the framework of the statistical model. The exclusive energy spectra of $\alpha$-particles emitted from the $^{28}$Si + $^{28}$Si compound system are generally well reproduced by Monte Carlo calculations using spin-dependent level densities. This spin dependence approach suggests the onset of large deformations at high spin. A re-analysis of previous $\alpha$-particle data from the $^{30}$Si + $^{30}$Si compound system, using the same spin-dependent parametrization, is also presented in the framework of a general discussion of the occurrence of large deformation effects in the A$_{CN}$ ~ 60 mass region.Comment: 25 pages, 6 figure

Incident gallstones during somatostatin analog treatment are associated with acute biliary complications especially after discontinuation

Introduction Gallstones are a known adverse effect of somatostatin analogs, but the exact incidence and clinical implications are unknown.Objectives The aim of this study was to investigate the incidence of gallstones on imaging and related complications in unbiased trial data.Methods Data from the DIPAK 1 trial, in which 305 polycystic kidney disease patients were randomized to standard of care (SoC) or lanreotide for 120 weeks, were used. Magnetic resonance imaging (MRI) was performed at baseline and end of treatment and was assessed for the presence, number, and size of gallstones. For all patients who had gallstones at the end of the trial, we obtained follow-up after the trial.Results Of 249 patients with data available, 11 patients randomized to lanreotide and four randomized to SoC had gallstones at baseline. During the study, new gallstones were formed in 19/124 patients using lanreotide (15%) and 1/125 patients receiving SoC (1%). The odds ratio for gallstone formation with lanreotide use was 25.9 (95% confidence interval 3.37-198.8; p 20 stones in 69% of patients) and small (<= 3 mm in 63% of patients). Of the 19 patients with incident gallstones during lanreotide treatment, 9 experienced gallstone-associated complications, 8 of whom experienced gallstone-associated complications after discontinuation of treatment (median time after discontinuation 2.5 years). In patients with gallstones at baseline and in patients receiving SoC, no complications occurred.Conclusions Treatment with a somatostatin analog leads to the formation of multiple, small gallstones that are associated with severe complications, especially after discontinuation of therapy.Functional Genomics of Systemic Disorder