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Background: Membranes with increasing pore size are introduced to enhance removal of large uremic toxins with regular hemodialysis. These membranes might theoretically have higher permeability for bacterial degradation products. In this paper, permeability for bacterial degradation products of membranes of comparable composition with different pore size was investigated with a new in vitro set-up that represents clinical flow and pressure conditions. Methods: Dialysis was simulated with an AK200 machine using a low-flux, high-flux, medium cut-off (MCO) or high cut-off (HCO) device (n = 6/type). A polyvinylpyrrolidone-solution (PVP) was recirculated at blood side. At dialysate side, a challenge solution containing a filtrated lysate of two water-borne bacteria (Pseudomonas aeruginosa and Pelomononas saccharophila) was infused in the dialysate flow (endotoxin >= 4EU/ml). Blood and dialysate flow were set at 400 and 500 ml/min for 60 min. PVP was sampled before (PVPpre) and after (PVPpost) the experiment and dialysate after 5 and 55 min. Limulus Amebocyte Lysate (LAL) test was performed. Additionally, samples were incubated with a THP-1 cell line (24 h) and IL-1 beta levels were measured evaluating biological activity. Results: The LAL-assay confirmed presence of 9.5 +/- 7.4 EU/ml at dialysate side. For none of the devices the LAL activity in PVPpre vs. PVPpost was significantly different. Although more blood side PVP solutions had a detectable amount of endotoxin using a highly sensitive LAL assay in the more open vs traditional membranes, the permeability for endotoxins of the 4 tested dialysis membranes was not significantly different but the number of repeats is small. None of the PVP solutions induced IL-1 beta in the THP-1 assay. Conclusions: A realisitic in vitro dialysis was developed to assess membrane translocation of bacterial products. LAL activity on the blood side after endotoxin exposure did not change for all membranes. Also, none of the PVPpost solutions induced IL-1 beta in the THP-1 bio-assay.

The purpose of this work is to provide the complex methodology for the identification of typical consumption patterns for particular consumer and to research its behavioral features based on daily activity and seasonal consumption properties to assign the consumer to approved specific billing power consumption category with similar acceptance behavior. Selection of the optimal billing category for consumers is based on comparison of their actual power consumption profiles with standard load profiles corresponding to respective billing group. The developed algorithm allows the distribution company to choose the most appropriate power consumption categories for their consumers and thus rationalize energy costs, as well as optimize the strategic and production planning of electricity purchases.

The purpose of this work is to provide the algorithm for the identification of typical consumption patterns, the research of behavioral models based on daily activity and seasonal indicators (season, month, weekdays and weekends), characteristic of a particular consumer category and its operation modes. Selection of the optimal power consumption group for consumers based on real consumption profiles (given by smart meter measurements over a certain time period) facilitates the distribution company to rationalize its costs, as well as optimize the strategic and production planning of electricity purchases.

A fast mathematical model simulation module based on LabVIEW graphical programming environment has been developed. The module will be used for gas turbine and electrical power system co-simulation, and for testing automation of gas turbine automatic control systems.

Model on the basis of logistic regression according with Knowledge Discovery in Databases (KDD) process by means of statistical programming language R, open source integrated development environment RStudio and software for predictive analytics RapidMiner has been considered. The approach takes into account interconnections of key factors based on analysis of the different measurable parameters. The main feature of the developed model is specificity and adaptiveness. E.g., in finance aspects microloans have their own characteristics in contrast to bank loans hence standard approaches are ineffective. The developed model solves this problem.

The aim of this study was to compare different analysis methods of 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography (FDG-PET) and magnetic resonance imaging (MRI) data for prediction of histopathological response (HPR) to neoadjuvant radiochemotherapy (RCTx) in patients with advanced rectal cancer.Twenty-eight patients of a previously published clinical trial underwent serial FDG-PET/computed tomography scans at baseline, 14 days after initiation, and after completion of RCTx. In addition, MRI was performed at baseline and after the end of therapy. Response prediction was correlated with different image analysis algorithms comprising pure metabolic parameters taking into account the FDG uptake, volume-based parameters measuring the lesion volume in either MRI or PET data, and integrated parameters combining metabolic and volumetric information. The established two-dimensional (2D) regions of interest (ROI; diameter 1.5 cm) served as standard of reference. Changes between the parameters at the defined time points were calculated and analyzed for their potential to predict HPR to RCTx using receiver operating characteristic (ROC) analysis. Additionally, the interobserver reliability of fixed-size algorithms was analyzed.Histopathology classified eight of 28 patients as non-responders and 20 patients as responders to RCTx. ROC analysis of the standard 2D ROI technique revealed areas under the curve (AUCs) of 0.64 and 0.71 for the early and late time points. Corresponding AUCs for three-dimensional (3D) volume of interest technique resulted in AUCs of 0.75 for both early and late time points, respectively. Volumetric parameters showed AUCs ranging from 0.52 to 0.57 (early time points) and 0.46 to 0.76 (later time points), respectively. Corresponding AUCs for the integrated parameters were ranging between 0.70 and 0.73 (early time points) and 0.66 and 0.76 (late time points). Analysis of intra-class correlation coefficients (ICC) for three different readers resulted in the best intra-class correlation values for the changes of 3D standard uptake value (SUV(3D)), for both early (ICC = 0.96) and late (ICC = 0.96) time points, respectively.Our study emphasizes that 3D-based approaches for assessing SUV values consistently belonged to the group of parameters with the highest AUC values for prediction of HPR to neoadjuvant RCTx in patients with rectal cancer. MRI was not a good predictor for therapy response; hence, the MRI information derived from combined anatomic and metabolic parameters showed unsatisfying results too.

Glycemic control of intensive care patients can be beneficial for this patient group but the continuous determination of their glucose concentration is challenging. Current continuous glucose monitoring systems based on the measurement of interstitial fluid glucose concentration struggle with sensitivity losses, resulting from biofouling or inflammation reactions. Their use as decision support systems for the therapeutic treatment is moreover hampered by physiological time delays as well as gradients in glucose concentration between plasma and interstitial fluid. To overcome these drawbacks, we developed and clinically evaluated a system based on microdialysis of whole blood. Venous blood is heparinised at the tip of a double lumen catheter and pumped through a membrane based micro-fluidic device where protein-free microdialysate samples are extracted. Glucose recovery as an indicator of long term stability was studied in vitro with heparinised bovine blood and remained highly stable for 72 h. Clinical performance was tested in a clinical trial in eight healthy volunteers undergoing an oral glucose tolerance test. Glucose concentrations of the new system and the reference method correlated at a level of 0.96 and their mean relative difference was 1.9 +/- 11.2%. Clinical evaluation using Clark's Error Grid analysis revealed that the obtained glucose concentrations were accurate and clinically acceptable in 99.6% of all cases. In conclusion, results of the technical and clinical evaluation suggest that the presented device delivers microdialysate samples suitable for accurate and long term stable continuous glucose monitoring in blood.

Background Time to cardiopulmonary resuscitation (CPR) is a main determinant of survival after out-of-hospital cardiac arrest. Only widespread implementation of training courses for laypersons can decrease response time. Methods and results In this prospective randomized trial, we evaluated how laypersons retained CPR skills and skills in using the automated external defibrillator (AED). A total of 1095 volunteers were randomly assigned to receive CPR/AED-training courses of 2 h (375 persons), 4 h (378 persons) or 7 h (342 persons) duration. Courses were held in accordance with the guidelines for CPR. All trainees were tested immediately after the initial class in a standardized test scenario using an AED and a manikin. Either at 6 or at 12 months, retests were given to 164 and 206 volunteers, respectively. In 479 volunteers, retesting was completed at both 6- and 12-month intervals. At the immediate tests, the 7-h training group showed a slightly higher rate of correct responses (7 h: 96%, 4 h: 94%, 2 h: 92%) (p

The commercial application of membranes in dialysis treatment has started already 40 years ago. Today, dialysis is the application in medicine using the largest number of membrane surface area per year. Integration of the membrane production process into dialyzer manufacturing was the key element in the successful transition from small scale production to large scale dialyzer manufacturing. Automatization techniques are heavily integrated into this process to fulfill the high quality and safety demands in medical technology. This paper gives an overview on the different membrane applications in medical industry. The material selection for manufacturing dialysis membranes and the different membrane morphologies are discussed. In the second part the different manufacturing steps in dialyzer production are presented. Polymermembranen fur medizinische Anwendungen Die kommerzielle Anwendung von Dialysemembranen fand ihren Anfang vor uber 40 Jahren. Der groste Anteil der jahrlich weltweit produzierten Membranflache wird heute in der Dialyse eingesetzt. Die Integration des Membranherstellungsprozesses in die Dialysatorfertigung war das Schlusselelement bei der erfolgreichen Umstellung von der Kleinserienproduktion hin zur Massenfertigung von Dialysatoren. Um hochste Sicherheits- und Qualitatsanspruche bei der Fertigung von Medizinprodukten zu gewahrleisten, ist es erforderlich, den integrierten Herstellungsprozess vollstandig zu automatisieren. Diese Arbeit gibt eine Ubersicht uber die unterschiedlichen Membrananwendungen in der Medizintechnik. Die Materialauswahl zur Herstellung von Dialysemembranen sowie die unterschiedlichen Strukturen der Dialysemembranen werden detailliert beschrieben. In einem zweiten Abschnitt wird insbesondere auf die unterschiedlichen Herstellungsschritte in der Dialysatorfertigung eingegangen.

Transport in biological systems is controlled by membranes functioning as barriers between compartments with various degrees of specificity. In 1972, Singer andNicolson [1] introduced a breakthrough view on structures of cell membranes with their fluid mosaic model. Their findings emerged along colloid chemistrybased organization of hydrophilic–hydrophobic polymer molecules and structures to form the cell membrane. Obviously, these principles also influenced the design of artificial membranes for therapeutic purposes. The general functional features involved in membrane separation processes, whether a natural cell membrane or an artificial membrane, concern either the process or the structure of the barrier, i.e. diffusion and convection of solutes along a pressure or concentration gradient, adsorption to generate a barrier for certain molecules, patch-like or mosaic-like structures to prevent or limit unspecific interaction, short transport channels for fast transport, nanoand micro-dimensions to suppress unspecific interaction and enable selectivity, narrow pore distribution to sharpen cut-off profiles, and optimized cross-filtration flux. In biological organisms, a number of additional functional elements of membranes are applied: active epithelial layers supported by basement membrane structures such as glomerular membranes, confluent tightly connected layers of endothelial cells, and strictly ordered hydrophilic–hydrophobic molecular arrangements in cellular bi-layer membranes. The function of the artificial kidney has relied from the beginning on principles laid down in renal physiology or, later, in biophysical principles in synthetic membranes whose functions were approaching those of the human glomerular membrane. Diffusion and convection predominantly have been combined to achieve the desired blood purification. Today, haemodialysis is basically divided into two categories: blood purification by low-flux and high-flux dialysis membranes [2–13]. Low-flux dialysis includes the standard haemodialysis technique in which dialysers with low hydraulic permeability are utilized. Blood and dialysate flows are at 250 and 500ml/min, respectively, and the average duration is 4 h. When dialyser surface area is increased, blood and dialysate flows are increased up to 400 and 800ml/min, respectively, and the treatment is defined in these circumstances as high efficiency haemodialysis. In this treatment, the clearance for small molecules is remarkably increased and the treatment time can generally be shortened, but the clearance for medium to large molecules is still very low due to the sieving characteristics of the membrane [14–30]. Classic cellulosic membranes such as Cuprophan were typically hydrogel-type low-flux membranes (i.e. permeability to water in the range of 5–6ml/h mmHg m), strongly hydrophilic and remarkably thin (6–12 mm) to permit an optimal utilization in diffusive transport of water-soluble solutes for treatments such as haemodialysis. On the other hand, classic high-flux synthetic membranes were originally fully hydrophobic, strongly asymmetric and with a wall thickness of 40–60 mm. They were originally employed in convective therapies such as haemofiltration [31] due to their high hydraulic permeability (i.e. 30–40ml/h mmHg m) and their elevated sieving coefficients. In a subsequent step, membrane structures have been adapted to fulfil the demand for increased diffusive permeability matched with tailored convective properties. This was achieved by (i) using polymer blends of hydrophilic and hydrophobic polymers; (ii) reduction of the wall thickness; and (iii) structural modifications Correspondence and offprint requests to: Claudio Ronco, Department of Nephrology, St Bortolo Hospital, Viale Rodolfi, 36100 Vicenza, Italy. E-mail: cronco@goldnet.it

Introduction The mortality risk of dialysis patients is still elevated. Even though there is continuous improvement in the biocompatibility of dialysis devices and treatments, there is clinical evidence of a negative inflammatory impact. One dialysis-related risk factor to be considered in this regard may be the repeated blood exposure to foreign filter surfaces. Standard test methods do not allow differences to be shown between most of the common dialysis devices. Methods A new highly sensitive in vitro test system was developed by analyzing the response of leukocytes to surface contact in dialysis filter devices by means of quantitative real time PCR and flow cytometry. Membrane surface studies provided additional physical data. Results An increase in the transcription level of specific pro-inflammatory genes, particularly IL-1β, TNF alpha, and IL-8, was observed after blood contact to the filter devices. In two sets of pairwise filter comparisons, radiation-sterilized filters showed stronger cell activation, more hydrophilic membranes, and rougher surfaces. Conclusions Quantitative real time RT-PCR was shown to be a new in vitro test method with increased sensitivity for detecting differences in activation levels of leukocytes upon membrane contact. Correlating leukocyte activation levels with surface properties opens new opportunities for understanding leukocyte activation upon membrane contact and thus guides further improvements in the biocompatibility of dialysis filter devices.

PET has been proven to be helpful in the delineation of gross tumour volume (GTV) for external radiation therapy in several tumour entities. The aim of this study was to determine if [(11)C]choline PET could be used to localize the carcinomatous tissue within the prostate in order to specifically target this area for example with high-precision radiation therapy.Included in this prospective study were 20 patients with histological proven prostate carcinoma who underwent [(11)C]choline PET/CT before radical prostatectomy. After surgical resection, specimens were fixed and cut into 5-mm step sections. In each section the area of the carcinoma was delineated manually by an experienced pathologist and digitalized, and the histopathological tumour volume was calculated. Shrinkage due to resection and fixation was corrected using in-vivo and ex-vivo CT data of the prostate. Histopathological tumour location and size were compared with the choline PET data. Different segmentation algorithms were applied to the PET data to segment the intraprostatic lesion volume.A total of 28 carcinomatous lesions were identified on histopathology. Only 13 (46 %) of these lesions had corresponding focal choline uptake. In the remaining lesions, no PET uptake (2 lesions) or diffuse uptake not corresponding to the area of the carcinoma (13 lesions) was found. In the patients with corresponding PET lesions, no suitable SUV threshold (neither absolute nor relative) was found for GTV segmentation to fit the volume to the histological tumour volume.The choline uptake pattern corresponded to the histological localization of prostate cancer in fewer than 50 % of lesions. Even when corresponding visual choline uptake was found, this uptake was highly variable between patients. Therefore SUV thresholding with standard algorithms did not lead to satisfying results with respect to defining tumour tissue in the prostate.

PET and PET/CT have changed the diagnostic algorithm in oncology. Health care systems worldwide have recently approved reimbursement for PET and PET/CT for staging of non-small cell lung cancer and differential diagnosis of solitary pulmonary nodules because PET and PET/CT have been found to be cost-effective for those uses. Additional indications that are covered by health care systems in the United States and several European countries include staging of gastrointestinal tract cancers, breast cancer, malignant lymphoma, melanoma, and head and neck cancers. Regarding these indications, diagnostic effectiveness and superiority over conventional imaging modalities have been shown, whereas cost-effectiveness has been demonstrated only in part. This article reports on the current knowledge of economic evaluations of PET and PET/CT in oncologic applications. Because more economic evaluations are needed for several clinical indications, we also report on the methodologies for conducting economic evaluations of diagnostic tests and suggest an approach toward the implementation of these tests in future clinical studies.

Purpose To assess a threshold for Gluc-Lys[ 18 F]-TOCA positron emission tomography (PET) in target volume delineation of glomus tumors in the skull base and to compare with MRI-based target volume delineation. Methods and Materials The threshold for volume segmentation in the PET images was determined by a phantom study. Nine patients with a total of 11 glomus tumors underwent PET either with Gluc-Lys[ 18 F]-TOCA or with 68 Ga-DOTATOC (in 1 case). All patients were additionally scanned by MRI. Positron emission tomography and MR images were transferred to a treatment-planning system; MR images were analyzed for lesion volume by two observers, and PET images were analyzed by a semiautomated thresholding algorithm. Results Our phantom study revealed that 32% of the maximum standardized uptake value is an appropriate threshold for tumor segmentation in PET-based target volume delineation of gross tumors. Target volume delineation by MRI was characterized by high interobserver variability. In contrast, interobserver variability was minimal if fused PET/MRI images were used. The gross tumor volumes (GTVs) determined by PET (GTV-PET) showed a statistically significant correlation with the GTVs determined by MRI (GTV-MRI) in primary tumors; in recurrent tumors higher differences were found. The mean GTV-MRI was significantly higher than mean GTV-PET. The increase added by MRI to the common volume was due to scar tissue with strong signal enhancement on MRI. Conclusions In patients with glomus tumors, Gluc-Lys[ 18 F]-TOCA PET helps to reduce interobserver variability if an appropriate threshold for tumor segmentation has been determined for institutional conditions. Especially in patients with recurrent tumors after surgery, Gluc-Lys[ 18 F]-TOCA PET improves the accuracy of GTV delineation.