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Background: Aim of this study was to identify factors associated with patients using the internet to find information about their upcoming surgery in general, and more specifically about anaesthesia. Methods: With Ethics committee approval, 1000 consecutive patients seen before elective surgery in the anaesthesia preoperative clinic of a Swiss Level 2 hospital were asked to complete a questionnaire. Primary outcome were patients using the internet to gather any medical information related to their upcoming hospital stay, secondary outcome patients using the internet to gather information regarding the upcoming anaesthesia. Multiple regression was performed to identify independent factors associated with internet use. Results: Eighty-two percent of the patients (n = 815) participated. 97% of those were ASA physical status 1 or 2; 83% (n = 676) had experience with previous anaesthetics, 86% (n = 700) reported to use the internet in general. Overall, about one-third of the participants used the internet to learn more about their medical condition, 26% regarding their upcoming surgical procedure. Only 7% (n = 55) obtained information about the anaesthetic. In multivariate analyses, factors associated with internet use were generally doing so, and planned moderate compared to minor surgery; not using the internet was associated with previous anaesthetic experience. Of those who did not use the Internet to learn about their anaesthetic, 34% indicated that they would have visited a trusted website. Conclusion: Only few patients used the internet to obtain information about their upcoming procedure and the anaesthetic part played an even smaller role. However, many patients would have appreciated guidance to find trustworthy internet sites. Trial registration: German Clinical Trials Register (DRKS00005434; date of registration: 27th December 2013); date of enrolment of first patient: 1st August 2013; study retrospectively registered. [ABSTRACT FROM AUTHOR]

When designing utility substations, it is necessary to consider all directional components of the electromagnetic reaction forces during short-circuit faults to properly account for their effects on substation equipment. IEEE 605 assumes straight long parallel conductors in its two-dimensional (2-D) force calculations while ignoring any bends and 3-D placement of conductors. CIGRE's Brochure 105 provides practical information on the mechanical effects of short-circuit currents in HV and EHV open air, conventional substations. Although these computational methods are easy to implement, they have several limitations and are sometimes too conservative. Previously published papers address such conservatism using dynamic analysis approaches that provide more accurate results when compared to experimental data. This paper provides two extensions to IEEE 605 and CIGRE 105 for calculating fault current reaction forces. A closed-form equation defining the simplified 2-D short-circuit force time history during a fault based on CIGRE 105 and a computationally inexpensive numerical 3-D force calculation technique are presented. [ABSTRACT FROM PUBLISHER]

Background: Midazolam is commonly used as a pre-anesthesia anxiolytic. It's elimination may not be fast enough for short procedures. In orally premedicated patients we obtained midazolam plasma concentrations at the end of surgical procedures and compared those to concentrations at anesthesia induction. Methods: The study was conducted prospectively with consent of the local ethics committee (Ethikkomission Kanton Thurgau, Switzerland) and carried out with written informed consent of each patient. Female patients aged 20 to 60 years undergoing elective procedures with general anesthesia were included, and were divided in two groups according to the planned surgical time: group S (<30 min) and group L (90-120 min), respectively. All patients received 7.5 mg Midazolam po as premedication. Blood samples were drawn at anesthesia induction, and at the end of surgery. Data were compared with t-test (independent samples; significance level p <0.05). Results: Twenty-five patients per group were included. Four patients were excluded from analysis, since midazolam was not detectable in any samples. Time of premedication to the 1st blood sample was not statistically different between groups, neither were Midazolam plasma levels at this time point (p = 0.94). None of the patients from group L (n = 24), but five patients in group S (n = 22) did have a higher plasma level of Midazolam at the end of the case compared to the beginning. Conclusions: The elimination half-life of oral Midazolam can lead to higher plasma levels at the end of a short procedure compared to those at induction of anesthesia. Trial registration: German Clinical Trials Register (Deutsches Register Klinischer Studien), DRKS00005429; date of registration 3rd January 2014 [ABSTRACT FROM AUTHOR]

This study addresses the timely issues of modelling, and defining selection criteria for, a solid-state fault isolation device (FID) intended for use in power electronics-based distribution systems (PEDS). This work subsequently derives the FID parameters by mapping the characteristics of a conventional medium-voltage distribution system onto that of the PEDS envisioned under a new multi-university Engineering Research Centre. When conventional circuit breakers are used in distribution systems, they have a relatively long clearing time, causing the voltage to collapse for a significant time. A semiconductor circuit breaker, however, is expected to be able to switch fast enough to keep a voltage disturbance within acceptable limits. The main focus of this study is to address the operational issues of the interaction between the power electronic converters and the solid-state FID. The utilisation of rate of current decrease (di/dt) control during turn-off in conjunction with passive clamping devices to manage the overvoltage that results from very fast circuit breaker operation is introduced. In contrast to a simple conventional RC-snubber circuit, the proposed overvoltage management avoids high leakage current, which is the undesirable drawback of RC-snubber circuits. The presented prototype is experimentally verified with low and medium-voltage test circuits. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) is a well-defined inflammation whereby alveolar macrophages play a crucial role as effector cells. As shown previously in numerous experimental approaches, volatile anaesthetics might reduce the degree of injury in pre- or post-conditioning set-ups. Therefore, we were interested to evaluate the effect of the application of the volatile anaesthetic sevoflurane on alveolar macrophages regarding the expression of inflammatory mediators upon lipopolysaccharide (LPS) stimulation in vitro. Alveolar macrophages were stimulated with LPS. Two hours later, cells were exposed additionally to air (control) or to sevoflurane-containing air for 4, 6, 8, 12 or 24 h. Tumour necrosis factor (TNF)-α, cytokine-induced neutrophil chemoattractant-1 (CINC-1), macrophage-inflammatory protein-2 (MIP-2) and monocyte chemoattractant protein-1 (MCP-1) proteins were determined and chemotaxis assays were performed. To evaluate possible cellular signalling pathways phosphorylation of the kinases extracellular-regulated kinase (ERK) and Akt was assessed. In the early phase of sevoflurane post-conditioning expression of TNF-α, CINC-1, MIP-2 and MCP-1 was attenuated, leading to a diminished chemotaxis reaction for neutrophils. Phosphorylation of ERK seems to be a possible cellular mechanism in the sevoflurane-induced protection in vitro. Pharmacological post-conditioning of alveolar macrophages with sevoflurane immunmodulates the inflammatory response upon stimulation with endotoxin. This might be a possible option for a therapeutical approach in ALI. [ABSTRACT FROM AUTHOR]

Aims: Pancreatic adenocarcinoma is an aggressive gastrointestinal malignancy with only a few long-term survivors even after radical surgery. Patients with ampullary cancer have a better prognosis but adjuvant therapy needs further improvement. Epithelial cell adhesion molecule (Ep-CAM) is strongly expressed in a variety of epithelial cancers and represents a promising target for immunological tumour therapy. Thus, the aim of this study was to investigate Ep-CAM expression and its potential prognostic impact in pancreatic and ampullary carcinomas. Methods: Ep-CAM expression was investigated retrospectively by immunohistochemistry in paraffin-embedded primary tumour tissue samples from a series of consecutive patients with pancreatic (n = 153) and ampullary cancer (n = 34). Results: Ep-CAM overexpression was observed in 85 of 153 pancreatic cancer specimens (56%) and in 29 of 34 ampullary cancer samples (85%). Overall, Ep-CAM failed to be an independent prognostic marker. However, subgroup analyses showed that Ep-CAM overexpression correlated with shorter overall survival among patients with ampullary cancer and advanced stage pancreatic cancer. In the latter subgroup, survival gradually worsened with increasing Ep-CAM scores. Furthermore, in ampullary cancer, Ep-CAM overexpression was found to correlate with tumour stage. Conclusions: Ep-CAM overexpression was detectable in the majority of cases with pancreatic and ampullary cancer, Therefore, Ep-CAM represents an attractive target for immune-based therapeutic interventions in these tumour entities. However, the prognostic value of Ep-CAM overexpression remains undetermined. [ABSTRACT FROM AUTHOR]

Of particular concern to designers of HTS machines are potential heating effects in the superconducting windings due to AC losses caused by load fluctuations encountered in real-life operating conditions. A 5 MW HTS synchronous prototype ship propulsion motor has been tested extensively under steady-state and dynamic load conditions in the Advanced Test Facility of the Center for Advanced Power Systems at Florida State University. This paper presents results from two tests of rotor heating effects, one employing single frequency torque oscillations and the other more realistic load modeling of sea-states by means of Hardware-in-the-Loop (HIL) real-time simulations. Temperature results from 4 different torque oscillation tests and 12 different sea-state tests provide rotor-heating information, obtained from multiple temperature sensor data within the HTS rotor, and are compared with data obtained from steady-state runs. [ABSTRACT FROM AUTHOR]

A letter to the editor discussing the prognostic value of the adhesion molecules CD44 and E-cadherin in myelodysplastic syndromes, is presented.

Superconducting electrical machines are increasingly of interest for diverse applications such as generators, synchronous condensers and motors. These machines' dynamic behavior differs from that of conventional machines in significant ways due, to certain time constants and reactances being very different. These differences can present difficulties when conventional testing procedures are applied. A 5 MW superconducting rotor machine designed and built by American Superconductor Corporation is currently being tested in the Advanced Test Facility of the Center for Advanced Power Systems at Florida State University. A variety of test procedures are being applied to determine the machine's dynamic performance and the effectiveness of these tests when applied to a superconducting machine is being assessed. In this paper, two means of analysing test data and extracting machine parameters arc described. [ABSTRACT FROM AUTHOR]

A model for the SCFCL suitable for use in real time computer simulation is presented. The model accounts for the highly nonlinear quench behavior of BSCCO and includes the thermal aspects of the transient phenomena when the SCFCL is activated. Implemented in the RTDS real-time simulation tool the model has been validated against published BSCCO characteristics. As an example for an application in protection system studies, the effect of an SCFCL on a utility type impedance relay has been investigated using a real lime hardware-in-the-loop (RT-HIL) experiment. The test setup is described and initial results are presented. They illustrate the effect of how the relay misinterprets the dynamically changing SCFCL impedance as an apparently more distant fault location. It is expected that the new real-time SCFCL model will provide a valuable tool not only for further protection system studies but for a wide range of RT-HIL experiments of power systems. [ABSTRACT FROM AUTHOR]

Investigates the electrical and thermodynamic requirements to be fulfilled by a high temperature superconductor if the fault current limiter (FCL) is of a hybrid type. Concept of the hybrid resistive-type superconducting FCL; Basis of the concept; Critical current density; Feasibility of superconductor cooling by gaseous nitrogen.

The article analyzes how naturally occurring CD4+ CD25+ T cells (Treg) modulate the haematopoietic potential of human stem cells in vitro. Included in the article are multiple graphs and images which depict this phenomenon. The researchers suggest that the extent of interaction between Treg within bone marrow and haematopoietic stem cells remains elusive.

Background: The incidence of post-discharge nausea and vomiting (PDNV) after ambulatory anaesthesia using total intravenous anaesthesia with a risk-stratified anti-emetic approach is not well documented in the literature. In this study, we outline such an approach. The goal was to achieve an acceptably low rate of PDNV both immediately and the day after surgery.Methods: With ethics committee approval, adult patients undergoing outpatient surgery received a Propofol-based general anaesthetic plus standardised PONV-prophylaxis corresponding to their Apfel risk-score (0-4); ondansetron (risk-score 2), additional dexamethasone (risk-score 3), and additional droperidol (risk-score 4). On post-operative days one and two, patients scored PDNV and pain (numeric rating scale (NRS); 0 = none at all; 10 = worst imaginable). On post-operative day two, patients indicated the level of interference of PDNV and/or pain with their quality of life. Data are descriptive (%) or mean.Results: There were 222 patients included (age 43 years, 44% female, anaesthesia time 95 min). On the day of surgery, 69.4% of patients did not experience any nausea, 10.4% complained about severe (NRS > 6) nausea, 6.3% experienced vomiting or retching. On the first and second postoperative day, nausea was absent in 88.7% of patients and 97.3%, respectively. Quality of life was impacted (NRS ≥ 4) more by pain (32.8% of cases), than by PDNV (13.6%).Conclusion: Acceptably low rates of PDNV were achieved with the proposed standardised approach to PDNV prophylaxis. For almost 90% of patients, PDNV was not an issue the first day after surgery. Pain after discharge was a more common problem. [ABSTRACT FROM AUTHOR]

The extremely low hearing threshold of the mammalian ear suggests the presence of a special amplifying mechanism, because the stereocilia of the outer hair cells (OHCs) are not likely to be sensitive enough themselves, although their mechanical embedding may provide some amplification. In the past decades, biophysicists have increasingly turned to the chaos theory for explanation, a theory the implications of which are considerable. One of its major tenets, self-organization, is not easily understood at first glance, but is easily reproducible mathematically. With self-organization, the processes involving the OHCs can readily be simulated: Self-organization can help to explain why OHCs vibrate at amplitudes much higher than those of the exciting stimulus. To further our understanding of the process of hearing, vibratory processes, which presumably occur in normal and damaged OHC clusters, are described and compared with a mathematical analysis of data sets obtained from normal subjects using an extremely sensitive microphone. [ABSTRACT FROM AUTHOR]

A novel approach to power quality assessment based on real-time (RT) hardware-in-the-loop (HIL) simulation is proposed. The RT-HIL platform is being used for power quality studies of NAVY all-electric ships. The sensitivity for power quality deviations of a variable speed drive controller card was tested in the platform. The successful experiment has contributed to the conceptual design of a universal power quality test bed, which would have the function of testing the immunity of electric components and equipment and the consequent impact on ac distribution systems. [ABSTRACT FROM PUBLISHER]

This retrospective study evaluated the benefit of alemtuzumab monotherapy in unselected patients with advanced B-cell chronic lymphocytic leukemia (CLL) and prolymphocytic leukemia (B-PLL) to definitely describe the impact of this antibody in clinical routine use. Data were collected from 208 consecutive, mainly pretreated, patients with CLL ( n = 202), and B-PLL ( n = 6) who had received alemtuzumab. Response, progression-free survival (PFS), and overall survival (OS) in various settings were assessed, and toxicities were documented. In these routine patients, a comparably low cumulative dose of alemtuzumab (median, 403 mg) was applied. In CLL, overall response rate was 32 %, and various pre-therapeutic parameters were predictive for inferior response, among them, the prior administration of ≥3 therapy lines ( P < 0.001), refractoriness to fludarabine ( P = 0.002), and bulky lymphadenopathy ( P = 0.003). PFS and OS after start of alemtuzumab were 6.2 and 21.0 months, respectively. Bulky lymphadenopathy was the prominent risk factor for both inferior PFS ( P < 0.001) and OS ( P = 0.002). In B-PLL, four patients experienced a fatal outcome, whereas two patients had some benefit with alemtuzumab. The main adverse effects were CMV reactivation (20 %) and a broad spectrum of infections, which together were the main reasons for treatment interruption and/or premature termination. In conclusion, alemtuzumab administered even at low dose levels was effective but overall considerably toxic in routine CLL patients. We emphasize that alemtuzumab remains an important therapeutic option in subsets of CLL patients. [ABSTRACT FROM AUTHOR]

This task force paper presents multi-domain tools and their interfacing issues to perform simulations that require expertise in multiple areas of physics, such as electrothermal, electromechanical, electrochemical, and electromagnetic simulations, etc. Features of single multi-domain simulation tools, which are capable of simulating more than one system such as electrical chemical, mechanical, etc., are discussed. In addition, programs that are not capable of performing multi-domain simulation independently but can be interfaced with other programs to perform multi-domain simulation are also covered. Two case studies are reported where multi-domain simulations are performed in offline and real-time environments through the interfacing of more than one simulation tool. [ABSTRACT FROM PUBLISHER]

This paper deals with the current state-of-the-art in interfacing issues related to real-time digital simulators employed in the simulation of power systems and power-electronic systems. This paper provides an overview of technical challenges encountered and their solutions as the real-time digital simulators evolved. Hardware-in-the-loop interfacing for controller hardware and power apparatus hardware are also presented. [ABSTRACT FROM AUTHOR]

Intravenous administration of fluids, electrolytes and glucose are the most common interventions in hospitalized pediatric patients. Parenteral fluid administration can be life-saving, however, if used incorrectly it also carries substantial risks. Perioperatively, adequate hydration, prevention of electrolyte imbalances and maintenance of normoglycemia are the main goals of parenteral fluid therapy. Conceptionally, the distinction between maintenance requirements, deficits and ongoing loss is helpful. Although the pathophysiological basis for parenteral fluid therapy was clarified in the first half of the 20th century, some aspects still remain controversial. In newborn infants, rational parenteral fluid therapy must take into account large insensible fluid losses, adaptive changes of renal function in the first days of life and the fact that neonates do not tolerate prolonged periods of fasting. In older infants the occurrence of iatrogenic hyponatremia with the use of hypotonic solutions has led to a critical reappraisal of the validity of the Holliday-Segar method for calculating maintenance fluid requirements in the postoperative period. Pragmatically, only isotonic solutions should be used in clinical situations which are known to be associated with increases in antidiuretic hormone (ADH) secretion. In this context, it is important to realize that in contrast to lactated Ringer's solution, the use of normal saline can lead to hyperchloremic acidosis in a dose-dependent fashion. Although there is no convincing evidence that colloids are better than crystalloids, there are clinical situations where the use of the more expensive colloids seems justified. It may be reasonable to choose a solution for fluid replacement which has a composition comparable to the composition of the fluid which must be replaced. Although hypertonic saline can reduce an elevated intracranial pressure, this therapy cannot be recommended as a routine procedure because there is currently no evidence that this intervention improves long-term outcome in pediatric patients with traumatic brain injury. [ABSTRACT FROM AUTHOR]

Objectives: To assess clinically relevant difference in hepatic iron quantification using R2* relaxometry with (FS) and without (non-FS) fat saturation for the evaluation of patients with suspected hepatic iron overload. Methods: We prospectively enrolled 134 patients who underwent 1.5-T MRI R2* relaxometry with FS and non-FS gradient echo sequences (12 echoes, initial TE = 0.99 ms). Proton density fat fraction for the quantification of steatosis was assessed. Linear regression analyses and Bland-Altman plots including Lin's concordance correlation coefficient were performed for correlation of FS R2* with non-FS R2*. Patients were grouped into 4 severity classes of iron overload (EASL based), and agreement was evaluated by contingency tables and the proportion of overall agreement. Results: A total of 41.8% of patients showed hepatic iron overload; 67.9% had concomitant steatosis; and 58.2% revealed no iron overload of whom 60.3% had steatosis. The mean R2* value for all FS data was 102.86 1/s, for non-FS 108.16 1/s. Linear regression resulted in an R-squared value of 0.99 (p < 0.001); Bland-Altman plot showed a mean R2* difference of 5.26 1/s (SD 17.82). The concordance correlation coefficient was only slightly lower for patients with steatosis compared with non-steatosis (0.988 vs. 0.993). The overall agreement between FS and non-FS R2* measurements was 94.8% using either method to classify patients according to severity of iron storage. No correlation between R2* and proton density fat fraction was found for both methods. Conclusion: R2* relaxometry showed an excellent overall agreement between FS and non-FS acquisition. Both variants can therefore be used in daily routine. However, clinically relevant differences might result when switching between the two methods or during patient follow-up, when fat content changes over time. We therefore recommend choosing a method and keeping it straight in the context of follow-up examinations. Key Points: • Both variants of R2* relaxometry (FS and non-FS) may be used in daily routine. • Clinically relevant differences might result when switching between the two methods or during patient follow-up, when fat content changes over time. • It seems advisable choosing one method and keeping it straight in the context of follow-up examinations. [ABSTRACT FROM AUTHOR]

Objectives: To assess if the administration of gadoxetate disodium (Gd-EOB-DTPA) significantly affects hepatic magnetic resonance elastography (MRE) measurements in the delayed hepatobiliary phase (DHBP).Methods: A total of 47 patients (15 females, 32 males; age range 23-78 years, mean 54.28 years) were assigned to standard hepatic magnetic resonance imaging (MRI) with application of Gd-EOB-DTPA and hepatic MRE. MRE was performed before injection of Gd-EOB-DTPA and after 40-50 min in the DHBP. Liver stiffness values were obtained before and after contrast media application and differences between pre- and post-Gd-EOB-DTPA values were evaluated using a Bland-Altman plot and the Mann-Whitney-Wilcoxon test. In addition, the data were compared with regard to the resulting fibrosis classification.Results: Mean hepatic stiffness for pre-Gd-EOB-DTPA measurements was 4.01 kPa and post-Gd-EOB-DTPA measurements yielded 3.95 kPa. We found a highly significant individual correlation between pre- and post-Gd-EOB-DTPA stiffness values (Pearson correlation coefficient of r = 0.95 (p < 0.001) with no significant difference between the two measurements (p =0.49)). Bland-Altman plot did not show a systematic effect for the difference between pre- and post-stiffness measurements (mean difference: 0.06 kPa, SD 0.81). Regarding the classification of fibrosis stages, the overall agreement was 87.23% and the intraclass correlation coefficient was 96.4%, indicating excellent agreement.Conclusions: Administration of Gd-EOB-DTPA does not significantly influence MRE stiffness measurements of the liver in the DHBP. Therefore, MRE can be performed in the DHBP.Key Points: • MRE of the liver can reliably be performed in the delayed hepatobiliary phase. • Gd-EOB-DTPA does not significantly influence MRE stiffness measurements of the liver. • MRE performed in the delayed hepatobiliary-phase is reasonable in patients with reduced liver function. [ABSTRACT FROM AUTHOR]

Purpose: To prospectively evaluate a prototypical 3D turbo-spin-echo proton-density-weighted sequence with compressed sensing and free-stop scan mode for preventing motion artefacts (3D-PD-CS-SPACE free-stop) for knee imaging in a clinical setting.Methods and Materials: 80 patients underwent 3T magnetic resonance imaging (MRI) of the knee with our 2D routine protocol and with 3D-PD-CS-SPACE free-stop. In case of a scan-stop caused by motion (images are calculated nevertheless) the sequence was repeated without free-stop mode. All scans were evaluated by 2 radiologists concerning image quality of the 3D-PD-CS-SPACE (with and without free-stop). Important knee structures were further assessed in a lesion based analysis and compared to our reference 2D-PD-fs sequences.Results: Image quality of the 3D-PD-CS-SPACE free-stop was found optimal in 47/80, slightly compromised in 21/80, moderately in 10/80 and severely in 2/80. In 29/80, the free-stop scan mode stopped the 3D-PD-CS-SPACE due to subject motion with a slight increase of image quality at longer effective acquisition times. Compared to the 3D-PD-CS-SPACE with free-stop, the image quality of the acquired 3D-PD-CS-SPACE without free-stop was found equal in 6/29, slightly improved in 13/29, improved with equal contours in 8/29, and improved with sharper contours in 2/29. The lesion based analysis showed a high agreement between the results from the 3D-PD-CS-SPACE free-stop and our 2D-PD-fs routine protocol (overall agreement 96.25%-100%, Cohen's Kappa 0.883-1, p < 0.001).Conclusion: 3D-PD-CS-SPACE free-stop is a reliable alternative for standard 2D-PD-fs protocols with acceptable acquisition times. [ABSTRACT FROM AUTHOR]

A main effector mechanism of rituximab (RTX) is the induction of complement-dependent cytotoxicity (CDC). However, this effector function is limited, because CLL cells are protected from complement-induced damage by regulators of complement activation (RCAs). A prominent RCA in fluid phase is factor H (fH), which has not been investigated in this context yet. Here, we show that fH binds to CLL cells and that human recombinant fH-derived short-consensus repeat 18-20 (hSCR18-20) interferes with this binding. In complement-based lysis assays, CLL cells from therapy-naive patients were differently susceptible to RTX-induced CDC and were defined as CDC responder or CDC non-responder, respectively. In CDC responders, but notably also in non-responders, hSCR18-20 significantly boosted RTX-induced CDC. Killing of the cells was specific for CD20+ cells, whereas CD20− cells were poorly affected. CDC resistance was independent of expression of the membrane-anchored RCAs CD55 and CD59, although blocking of these RCAs further boosted CDC. Thus, inhibition of fH binding by hSCR18-20 sensitizes CLL cells to CDC and may provide a novel strategy for improving RTX-containing immunochemotherapy of CLL patients. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukemia (CLL) is the most prevalent lymphoid malignancy in the elderly of the Western world. Although treatment options have improved over the past two decades, 10-15% of patients still have a poor prognosis and are often resistant to therapy. Aberrations in the p53 pathway, such as a deleted (del17p13) or mutated p53 gene, are highly enriched in this class of patients. In an extensive screen for p53-independent apoptosis inducers, actinomycin D was identified from 1496 substances and shown to induce apoptosis in primary CLL cells derived from high-risk patients including those with aberrant p53, revealing a novel p53-independent mechanism of action. Both pro-survival genes BCL2 and MCL1 are targeted by actinomycin D, in contrast to fludarabine the backbone of current treatment schedules. In the well-established TCL1 transgenic mouse model for high-risk CLL, actinomycin D treatment was more effective in reducing tumor load than fludarabine, with no evidence of resistance after three treatment cycles and an overall survival increase of over 300%. Tumor load reduction was coupled to BCL2 downregulation. Our results identify the clinically approved compound actinomycin D as a potentially valuable treatment option for CLL high-risk patients. [ABSTRACT FROM AUTHOR]

This paper presents a detailed model for simulation of a Superconducting Magnetic Energy Storage (SMES) system. SMES technology has the potential to bring real power storage characteristic to the utility transmission and distribution systems. The principle of SMES system operation is reviewed in this paper. To understand transient and dynamic performance of a SMES system, a detailed SMES system benchmark model is given with extensive simulation results. This system is demonstrated using an electromagnetic transient program—PSCAD/EMTDC. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated cyclooxygenase 2 (COX-2) overexpression in various human malignancies, especially in breast cancer, where COX-2 turned out to be a predictor of poor survival. To evaluate the relation of COX-2 and Ep-CAM overexpression and its prognostic significance, we performed a retrospective study on 212 breast cancer patients with a median follow-up time of 10.5 years. Overexpression of COX-2 in tumour tissue samples was assessed by immunohistochemistry. COX-2 overexpression was found in 48.6% of the tumour samples and was predictive for poor disease-free and overall survival. Univariate analysis revealed a strong correlation between COX-2 and Ep-CAM overexpression (P=0.009). Concurrent COX-2 and Ep-CAM overexpression was present in 21.7% of tumour specimens and had an additive negative impact on disease-free and overall survival. Determination of both tumour markers should help in guiding new therapeutic strategies in patients with invasive breast cancer. [ABSTRACT FROM AUTHOR]

Within the past few years a newer, more robust type of superconductor known as 2nd Generation High Temperature Superconductor (HTS) wire, has become available in sufficient quantity and lengths for developers to build prototype devices and test their capabilities. This new material offers the potential for revolutionary changes in superconducting transformers and Superconducting Fault Current Limiters to enable better thermal stability and fast quenching capabilities that can meet the stringent demands of large transient faults for distribution and transmission power lines refid="ref1"/ refid="ref2"/refid="ref3"/refid="ref4"/ refid="ref5"/. [ABSTRACT FROM AUTHOR]

A correction to the article "Reduction of complement factor H binding to CLL cells improves the induction of rituximab-mediated complement-dependent cytotoxicity" by D. Windisch and B. Muellauer that was published in the previous issue.

Grundlagen: Für die adäquate Anwendung von anti-CD20-Anti-körper(Mabthera)-Therapien bei CLL stellen die Findung klinisch tolerabler Dosierungsschemata und die Aufklärung der Wirkprinzipien Voraussetzungen für eine erfolgreiche Mono-, aber auch rational begründete Kombinationstherapie dar. Methodik: In einer monozentrischen Phase-I/II-Studie wurden Patienten mit therapierefraktärer B CLL und Behandlungspflicht nach den NCI-Kriterien mit Mabthera in einschleichender und subsequent progressiv gesteigerter Dosierung behandelt. In Parallele zur Analyse der klinischen Wirksamkeit wurden Analysen zum Mechanismus der Wirkung durchgeführt: Ergebnisse: 1) Lymphozytenkinetik im Blut (PBL): Alle Patienten zeigten über den Verlauf von 6wöchentlichen Behandlungszyklen eine deutliche Reduktion der Gesamtleukozyten (100 + 19G/L vs. 32 + 10 G/L). Der maximale zytoreduktive Effekt war während aller Zyklen innerhalb 1h zu beobachten (delta: 44,8+16,2), während innerhalb von 24 h eine partielle Erholung der Leukozytenzahl eintrat (delta +30%). 2) CD20-Expression und Bindung von Mabthera: Basale CD20-Expression, Bindung von Mabthera und Veränderung der CD20-Expression unter Behandlung wurden mit Antikörpern gegen CD20-Oberflächenepitop, murines FAB-Fragment und intrazytoplasmatisches CD20-Epitop in IF-Doppelfärbungen bzw. Western Blot bestimmt. Dabei konnten im 1. Zyklus in vitro, nicht aber in vivo progrediente Beladbarkeit der CLL-Zellen mit Mabthera sowie Abnahme der intrazytoplasmatischen CD20-Färbung nachgewiesen werden. Im Gegensatz zur Erholung der Leukozytenzahl war in 24 h kein rescue der CD20-Expression peripherer B-Zellen nachweisbar. 3) Biologische Auswirkungen der Mabthera-Behandlung: Triple-Färbungen mit PI/AnnexinV und CD19 belegen die Induktion von Apoptose parallel zur Elimination der Leukozytenzahlen im PBL. Schlußfolgerungen: Auch unter geringsten in vivo Dosen von Mabthera (50 mg/m²) treten in 1 h massive Reduktionen der Lymphozyten und Induktion von Apoptose und in 24-h-Dissoziation von CD20-Expression und der Lymphozytenkinetik auf. [ABSTRACT FROM AUTHOR]