Ischemic preconditioning attenuates portal venous plasma concentrations of purines following warm liver ischemia in man

Background/Aims: Degradation of adenine nucleotides to adenosine has been suggested to play a critical role in ischemic preconditioning (IPC). Thus, we questioned in patients undergoing partial hepatectomy whether (i) IPC will increase plasma purine catabolites and whether (ii) formation of purines in response to vascular clamping (Pringle maneuver) can be attenuated by prior IPC. Methods: 75 patients were randomly assigned to three groups: group I underwent hepatectomy without vascular clamping; group II was subjected to the Pringle maneuver during resection, and group III was preconditioned (10 min ischemia and 10 min reperfusion) prior to the Pringle maneuver for resection. Central, portal venous and arterial plasma concentrations of adenosine, inosine, hypoxanthine and xanthine were determined by high-performance liquid chromatography. Results: Duration of the Pringle maneuver did not differ between patients with or without IPC. Surgery without vascular clamping had only a minor effect on plasma purine transiently increased. After the Pringle maneuver alone, purine plasma concentrations were most increased. This strong rise in plasma purines caused by the Pringle maneuver, however, was significantly attenuated by IPC. When portal venous minus arterial concentration difference was calculated for inosine or hypoxanthine, the respective differences became positive in patients subjected to the Pringle maneuver and were completely prevented by preconditioning. Conclusion: These data demonstrate that (i) IPC increases formation of adenosine, and that (ii) the unwanted degradation of adenine nucleotides to purines caused by the Pringle maneuver can be attenuated by IPC. Because IPC also induces a decrease of portal venous minus arterial purine plasma concentration differences, IPC might possibly decrease disturbances in the energy metabolism in the intestine as well. Copyright (C) 2005 S. Karger AG, Basel

Liver Transplantation in Adults

Human liver transplantation has been possible since 1967. We report our experience in 32 adult patients who received liver transplants at the University of Pittsburgh over a 16‐month period. Survival data, method utilized for patient selection, costs, and morbidity of the procedure are discussed. Copyright © 1982 American Association for the Study of Liver Disease

Using electronic health records to support clinical trials: a report on stakeholder engagement for EHR4CR

Background. The conduct of clinical trials is increasingly challenging due to greater complexity and governance requirements as well as difficulties with recruitment and retention. Electronic Health Records for Clinical Research (EHR4CR) aims at improving the conduct of trials by using existing routinely collected data, but little is known about stakeholder views on data availability, information governance, and acceptable working practices. Methods. Senior figures in healthcare organisations across Europe were provided with a description of the project and structured interviews were subsequently conducted to elicit their views. Results. 37 structured interviewees in Germany, UK, Switzerland, and France indicated strong support for the proposed EHR4CR platform. All interviewees reported that using the platform for assessing feasibility would enhance the conduct of clinical trials and the majority also felt it would reduce workloads. Interviewees felt the platform could enhance trial recruitment and adverse event reporting but also felt it could raise either ethical or information governance concerns in their country. Conclusions. There was clear support for EHR4CR and a belief that it could reduce workloads and improve the conduct and quality of trials. However data security, privacy, and information governance issues would need to be carefully managed in the development of the platform

Cancer gene prioritization by integrative analysis of mRNA expression and DNA copy number data: a comparative review

A variety of genome-wide profiling techniques are available to probe complementary aspects of genome structure and function. Integrative analysis of heterogeneous data sources can reveal higher-level interactions that cannot be detected based on individual observations. A standard integration task in cancer studies is to identify altered genomic regions that induce changes in the expression of the associated genes based on joint analysis of genome-wide gene expression and copy number profiling measurements. In this review, we provide a comparison among various modeling procedures for integrating genome-wide profiling data of gene copy number and transcriptional alterations and highlight common approaches to genomic data integration. A transparent benchmarking procedure is introduced to quantitatively compare the cancer gene prioritization performance of the alternative methods. The benchmarking algorithms and data sets are available at http://intcomp.r-forge.r-project.orgComment: PDF file including supplementary material. 9 pages. Preprin

Nontrivial temporal scaling in a Galilean stick-slip dynamics

We examine the stick-slip fluctuating response of a rough massive non-rotating cylinder moving on a rough inclined groove which is submitted to weak external perturbations and which is maintained well below the angle of repose. The experiments presented here, which are reminiscent of the Galileo's works with rolling objects on inclines, have brought in the last years important new insights into the friction between surfaces in relative motion and are of relevance for earthquakes, differing from classical block-spring models by the mechanism of energy input in the system. Robust nontrivial temporal scaling laws appearing in the dynamics of this system are reported, and it is shown that the time-support where dissipation occurs approaches a statistical fractal set with a fixed value of dimension. The distribution of periods of inactivity in the intermittent motion of the cylinder is also studied and found to be closely related to the lacunarity of a random version of the classic triadic Cantor set on the line.Comment: 7 pages including 6 figure

A European inventory of common electronic health record data elements for clinical trial feasibility

Background: Clinical studies are a necessity for new medications and therapies. Many studies, however, struggle to meet their recruitment numbers in time or have problems in meeting them at all. With increasing numbers of electronic health records (EHRs) in hospitals, huge databanks emerge that could be utilized to support research. The Innovative Medicine Initiative (IMI) funded project ‘Electronic Health Records for Clinical Research’ (EHR4CR) created a standardized and homogenous inventory of data elements to support research by utilizing EHRs. Our aim was to develop a Data Inventory that contains elements required for site feasibility analysis. Methods:The Data Inventory was created in an iterative, consensus driven approach, by a group of up to 30 people consisting of pharmaceutical experts and informatics specialists. An initial list was subsequently expanded by data elements of simplified eligibility criteria from clinical trial protocols. Each element was manually reviewed by pharmaceutical experts and standard definitions were identified and added. To verify their availability, data exports of the source systems at eleven university hospitals throughout Europe were conducted and evaluated. Results: The Data Inventory consists of 75 data elements that, on the one hand are frequently used in clinical studies, and on the other hand are available in European EHR systems. Rankings of data elements were created from the results of the data exports. In addition a sub-list was created with 21 data elements that were separated from the Data Inventory because of their low usage in routine documentation. Conclusion: The data elements in the Data Inventory were identified with the knowledge of domain experts from pharmaceutical companies. Currently, not all information that is frequently used in site feasibility is documented in routine patient care.<br

Fermat's principle of least time in the presence of uniformly moving boundaries and media

The refraction of a light ray by a homogeneous, isotropic and non-dispersive transparent material half-space in uniform rectilinear motion is investigated theoretically. The approach is an amalgamation of the original Fermat's principle and the fact that an isotropic optical medium at rest becomes optically anisotropic in a frame where the medium is moving at a constant velocity. Two cases of motion are considered: a) the material half-space is moving parallel to the interface; b) the material half-space is moving perpendicular to the interface. In each case, a detailed analysis of the obtained refraction formula is provided, and in the latter case, an intriguing backward refraction of light is noticed and thoroughly discussed. The results confirm the validity of Fermat's principle when the optical media and the boundaries between them are moving at relativistic speeds.Comment: 11 pages, 6 figures, RevTeX 4, comments welcome; V2: revised, Fig. 7 added; V3: several typos corrected, accepted for publication in European Journal of Physics (online at: http://stacks.iop.org/EJP/28/933