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BackgroundThe unrestricted use of linezolid has been linked to the emergence of linezolid-resistantStaphylococcus epidermidis(LRSE). We report the effects of combined antibiotic stewardship and infection control measures on the spread of LRSE in an intensive care unit (ICU).MethodsMicrobiological data were reviewed to identify all LRSE detected in clinical samples at an ICU in southwest Germany. Quantitative data on the use of antibiotics with Gram-positive coverage were obtained in defined daily doses (DDD) per 100 patient-days (PD). In addition to infection control measures, an antibiotic stewardship intervention was started in May 2019, focusing on linezolid restriction and promoting vancomycin, wherever needed. We compared data from the pre-intervention period (May 2018–April 2019) to the post-intervention period (May 2019–April 2020). Whole-genome sequencing (WGS) was performed to determine the genetic relatedness of LRSE isolates.ResultsIn the pre-intervention period, LRSE were isolated from 31 patients (17 in blood cultures). The average consumption of linezolid and daptomycin decreased from 7.5 DDD/100 PD and 12.3 DDD/100 PD per month in the pre-intervention period to 2.5 DDD/100 PD and 5.7 DDD/100 PD per month in the post-intervention period (p = 0.0022 and 0.0205), respectively. Conversely, vancomycin consumption increased from 0.2 DDD/100 PD per month to 4.7 DDD/100 PD per month (p ConclusionsComplementing infection control measures by targeted antibiotic stewardship interventions was beneficial in containing the spread of LRSE in an ICU.

Background; : Liberal PCR testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is key to contain the coronavirus disease 2019 (COVID-19) pandemic. Combined multi-sample testing in pools instead of single tests might enhance laboratory capacity and reduce costs, especially in low- and middle-income countries.; Objective; : The purpose of our study was to assess the value of a simple questionnaire to guide and further improve pooling strategies for SARS-CoV-2 laboratory testing.; Methods; : Pharyngeal swabs for SARS-CoV-2 testing were obtained from healthcare and police staff, hospital inpatients, and nursing home residents in the southwestern part of Germany. We designed a simple questionnaire, which included questions pertaining to a suggestive clinical symptomatology, recent travel history, and contact with confirmed cases to stratify an individual's pre-test probability of having contracted COVID-19. The questionnaire was adapted repeatedly in face of the unfolding pandemic in response to the evolving epidemiology and observed clinical symptomatology. Based on the response patterns, samples were either tested individually or in multi-sample pools. We compared the pool positivity rate and the number of total PCR tests required to obtain individual results between this questionnaire-based pooling strategy and randomly assembled pools.; Findings; : Between March 11 and July 5, 2020, we processed 25,978 samples using random pooling (n = 6,012; 23.1%) or questionnaire-based pooling (n = 19,966; 76.9%). The overall prevalence of SARS-CoV-2 was 0.9% (n = 238). Pool positivity (14.6% vs. 1.2%) and individual SARS-CoV-2 prevalence (3.4% vs. 0.1%) were higher in the random pooling group than in the questionnaire group. The average number of PCR tests needed to obtain the individual result for one participant was 0.27 tests in the random pooling group, as compared to 0.09 in the questionnaire-based pooling group, leading to a laboratory capacity increase of 73% and 91%, respectively, as compared to single PCR testing.; Conclusions; : Strategies that combine pool testing with a questionnaire-based risk stratification can increase laboratory testing capacities for COVID-19 and might be important tools, particularly in resource-constrained settings.

Background: Various trivalent radiometals are well suited for labeling of DOTA-conjugated variants of Glu-ureido-based prostate-specific membrane antigen (PSMA) inhibitors. The DOTA-conjugate PSMA-617 has proven high potential in PSMA radioligand therapy (PSMA-RLT) of prostate cancer as well as PET imaging when labeled with lutetium-177 and gallium-68 respectively. Considering the relatively short physical half-life of gallium-68 this positron emitter precludes prolonged acquisition periods, as required for pre-therapeutic dosimetry or intraoperative applications. In this context, the positron emitter scandium-44 is an attractive alternative for PET imaging. We report the synthesis of [44Sc]Sc-PSMA-617 as radiopharmaceutical with generator produced scandium-44, its in vitro characterization and clinical translation as part of a first in-human study. Methods: Scandium-44 was obtained from a 44Ti/44Sc radionuclide generator. PSMA-617 was labeled with 142.4±12.7 MBq of scandium-44 in analogy to [68Ga]Ga-PSMA-617 and evaluated in vitro and in cell studies using PSMA+ LNCaP cells. A first-in-human investigation was subsequently carried out in a cohort of 4 patients (mean age 70±1.8 a) registered for [177Lu]Lu-PSMA-617 therapy. 50.5±9.3 MBq (40 µg, 38.4 nmol) [44Sc]Sc-PSMA-617 were applied via intravenous injection (i.v.), respectively. A Siemens Biograph 2 PET/CT system was used to acquire initial dynamic PET data (30 min) of abdomen in list mode followed by static PET/CT data (skull to mid-thigh) at 45 min, 2 and 18 h post-injection (p.i.). For quantitative analysis, dynamic images were reconstructed as 6 data sets of 300 s each. The noise ratio was measured in liver, lung and an additional region outside the body. SUV values in different organs and lesions were measured and compared to [68Ga]Ga-PSMA-11 data of the same patients. Residence times and organ absorbed doses were calculated using OLINDA/EXM software. Results: Quantitative radiochemical yields of ≥98 % were achieved using 18 nmol of PSMA-617 after 20 min at 95 °C with apparent molar activity of 6.69±0.78 MBq/nmol. Following purification, >99 % radiochemical purity was obtained. [44Sc]Sc-PSMA-617 showed high stability (>95 %) in serum for 24 h. The binding affinity and internalization fraction were determined in PSMA+ LNCaP cells (IC50 = 4.72±0.7 nM and internalization fraction: 15.78±2.14 % IA/106 LNCaP cells) and compared to [68Ga]Ga-PSMA-11 (12.0±2.8 nM and 9.47±2.56 % IA/106 LNCaP cells). Physiological tracer uptake was observed in kidneys, liver, spleen, small intestine, urinary bladder, and salivary glands and pathological uptake in both soft and skeletal metastases. SUV values were significantly lower in the kidneys (14.0) compared to [68Ga]Ga-PSMA-11 OET (30.5). All other measured SUV values did not show a statistically significant difference. Tumor to liver ratios were found to lie between 1.9 and 8.3 for [68Ga]Ga-PSMA-11 and between 2.5 and 8.8 for [44Sc]Sc-PSMA-617 after 120 min. For [44Sc]Sc-PSMA-617 the ratios were higher and no statistically significant differences were observed. Total and % activity were highest in liver followed by kidneys, spleen, small intestine and salivary glands. Rapid wash out was seen in liver and spleen and gradually over time in kidneys. Kidneys received the highest radiation absorbed dose of 0.354 (0.180-0.488) mSv/MBq. No adverse pharmacological effects were observed. Conclusion: In conclusion [44Sc]Sc-PSMA-617 PET is suitable for PET imaging of prostate cancer tissue. [44Sc]Sc-PSMA-617 shows promise to enable pre-therapeutic dosimetry in clinical settings. However, the clinical advantages for individual dosimetry or other applications like intraoperative applications have to be investigated in further studies.

Prostate-specific membrane antigen (PSMA) is highly expressed on prostate epithelial cells and strongly up-regulated in prostate cancer (PC), making it an optimal target for the treatment of metastasized PC. Radioligand therapy (RLT) with 177Lu-PSMA-DKFZ-617 (Lu-PSMA) is a targeted therapy for metastatic PC. In this study, we retrospectively analyzed the side effects and the response rate of 24 hormone and/or chemorefractory PC patients with a mean age of 75.2 years (range: 64–82) with distant metastases and progressive disease according to the PSA level, who were treated with Lu-PSMA. Median PSA was 522 ng/ml (range: 17–2360). Forty-six cycles of Lu-PSMA were performed. Of the 24 patients, 22 received two cycles. Eight weeks after the first cycle of Lu-PSMA therapy 79.1% experienced a decline in PSA level. Eight weeks after the second cycle of Lu-PSMA therapy 68.2% experienced a decline in PSA relative to the baseline value. Apart from two cases of grade 3 anemia, there was no relevant hemato- or nephrotoxicity (grade 3 or 4). These results confirmed that Lu-PSMA is a safe treatment option for metastatic PC patients and has a low toxicity profile. A positive response to therapy in terms of decline in PSA occurs in about 70% of patients.

Die Computertomographie (CT) ist mit einer Sensitivitat von mehr als 99 % und annahernd hoher Spezifitat das Mittel der Wahl zur Diagnose und Klassifikation von Dens-axis-Frakturen. In dieser Kasuistik berichten wir uber 4 Falle, bei welchen ein Bewegungsartefakt der CT-Untersuchung eine Anderson-Typ-II-Fraktur imitiert und somit zu einer falschen initialen Diagnose gefuhrt hat. Diese Kasuistik weist darauf hin, dass ubersehene CT-Bewegungsartefakte zu schwerwiegenden Konsequenzen fuhren konnen und sensibilisiert den Leser auf radiologische Zeichen dieser Artefakte.

Fur Patienten mit Lungenkarzinom ist ein prazises Staging von Lymphknoten- und Fernmetastasen die entscheidende Grundlage fur die Therapieplanung und insbesondere fur die Wahl des Operationsverfahrens. Die FDG-PET / CT stellt im Rahmen des diagnostischen Lungenkrebs-Algorithmus beim potentiell kurativem Therapieansatz das zentrale bildgebende Verfahren dar. Bei Patienten mit histologisch gesichertem Lungenkarzinom kann die FDG-PET / CT gegenuber der alleinigen CT die Genauigkeit des Lymphknoten- und Fernmetastasenstagings signifikant erhohen und als Ganzkorperuntersuchung zudem oft weitere Untersuchungen ersetzen. Prospektive Studien zeigen auch, dass durch den Einsatz der FDG-PET in der praoperativen Abklarung bei Patienten mit Lungenkarzinom die Anzahl unnotiger Thorakotomien und Mediastinoskopien signifikant reduziert werden kann.

Neuroendokrine Tumoren sind insgesamt selten. Sie konnen grundsatzlich in allen Organen auftreten und zeigen bezuglich ihres biologischen Verhaltens eine grose Heterogenitat in Abhangigkeit von Ursprungsorgan, klinischer Symptomatik und Histomorphologie. Neben ausgesprochen seltenen Lokalisationen (z. B. Larynx, Cervix uteri, Ovar, Gallenblase, Leber, Niere) sind neuroendokrine Tumoren uberwiegend im Gastrointestinaltrakt und in der Lunge zu finden. Nach ihrer embryonalen Genese teilt man sie ein in neuroendokrine Tumoren des Vorderdarms (Magen, Duodenum, Pankreas, Lunge), des Mitteldarms (Jejunum, Ileum, Appendix, rechtsseitiger Anteil des Kolons) und des Enddarms (linksseitiger Anteil des Kolons, Rektum). Die Rolle der Bildgebung besteht vor allem in der Lokalisation und Darstellung des Primartumors sowie dem Nachweis von Metastasen. In der Diagnostik von neuroendokrinen Tumoren kommen neben radiologischen Verfahren wie der Computertomografie (CT) und der Magnetresonanztomografie (MRT) auch nuklearmedizinische Techniken wie die Somatostatinrezeptorszintigrafie (SRS) und die Positronenemissionstomografie (PET) unter Verwendung radioaktiv markierter Somatostatinanaloga als Tracer zum Einsatz. Dieser Artikel gibt eine Ubersicht uber charakteristische Befunde von neuroendokrinen Tumoren des Gastrointestinaltrakts in den unterschiedlichen bildgebenden Modalitaten.

A novel 18F-labeled tracer, LMI1195 (N-[3-bromo-4-(3-18F-fluoro-propoxy)-benzyl]-guanidine), is being developed for sympathetic nerve imaging; its high specificity for neural uptake-1 mechanism has previously been demonstrated in cell associative studies and in rabbit and nonhuman primate studies assessing heart uptake. The aim of this study was to investigate the mechanisms of 18F-LMI1195 cardiac uptake in the rat, which is known to contain norepinephrine uptake mechanisms beyond uptake-1. Methods: Tracer accumulation in the heart was studied over time after intravenous administration of 18F-LMI1195 in healthy male Wistar rats by quantitative in vivo PET imaging. The uptake mechanism was assessed by pretreatment with the nonselective norepinephrine uptake-1 and norepinephrine uptake-2 inhibitor phenoxybenzamine (50 mg/kg intravenously; n = 4), the selective norepinephrine uptake-1 inhibitor desipramine (2 mg/kg intravenously; n = 4), or saline control (intravenously; n = 4). Results:18F-LMI1195 produced high and sustained heart uptake allowing clear delineation of the left ventricular wall over 60 min after tracer administration. Pretreatment with phenoxybenzamine markedly reduced the 18F-LMI1195 cardiac uptake when compared with controls. In contrast, there was preserved 18F-LMI1195 uptake after desipramine pretreatment. Conclusion: In rats, cardiac uptake of 18F-LMI1195 was significantly inhibited by phenoxybenzamine but not desipramine, suggesting 18F-LMI1195 is a substrate for the uptake-2 mechanism and is consistent with the rat heart having a dominant level of the mechanism.

Cardiac affection constitutes a major limiting condition in systemic sarcoidosis. We performed cardiovascular magnetic resonance (CMR) imaging and somatostatin receptor scintigraphy to define the course in cardiac sarcoidosis (CS). In a pilot study, we identified cardiac involvement – diagnosed by CMR imaging – to be present in 29 of 188 patients (15.4%) with histologically proven, extracardiac sarcoidosis. Out of these initial 29 CS-positive patients, 27 patients (49.9 ± 11.8 years, 59.3% male) were presently re-examined and underwent a second CMR-study. 68 Ga-DOTATOC PET/CT was performed when clinically indicated (17 patients). Within a median follow-up period of 2.6 years, none of the initial 29 patients deceased or experienced aborted sudden cardiac death. Among the 27 re-examined cardiac sarcoidosis patients, pathological CMR-findings persisted in 14 of 27 patients (51.9%): 7 patients (25.9% of total study population) exhibited myocardial scar; 1 patient (3.7%) showed increased relative gadolinium enhancement as well as myocardial oedema, as markers of acute inflammatory injury. Both acute and chronic phase cardiac involvement was present in 6 patients (22.2%). Standard CS evaluation parameters as well as laboratory testing failed to recognize CS-persistence. 68 Ga-DOTATOC PET/CT identified 2 patients with regions of raised tracer uptake that concorded with acute inflammatory changes, as assessed by CMR. Cardiac sarcoid affection persisted in barely half the patients and was not afflicted with cardiac death. Additional 68 Ga-DOTATOC PET/CT-imaging allowed for visualization of acute myocardial inflammation and might represent a sensitive CS imaging tool.

// Constantin Lapa 1, * , Theresa Reiter 2, 3, * , Malte Kircher 1 , Andreas Schirbel 1 , Rudolf A. Werner 1 , Theo Pelzer 2 , Carmen Pizarro 4 , Dirk Skowasch 4 , Lena Thomas 5 , Ulrike Schlesinger-Irsch 6 , Daniel Thomas 6 , Ralph A. Bundschuh 5 , Wolfgang R. Bauer 2, 3, * , Florian C. Gartner 5, * 1 Department of Nuclear Medicine, University Hospital Wurzburg, Wurzburg, Germany 2 Department of Internal Medicine, University Hospital Wurzburg, Wurzburg, Germany 3 Comprehensive Heart Failure Center, University Wurzburg, Wurzburg, Germany 4 Department of Internal Medicine II - Pneumology/Cardiology, University Hospital Bonn, Bonn, Germany 5 Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany 6 Department of Radiology, University Hospital Bonn, Bonn, Germany * These authors have contributed equally to this work Correspondence to: Constantin Lapa, email: lapa_c@ukw.de Keywords: sarcoidosis, DOTATOC, SSTR, somatostatin receptor, PET Received: September 01, 2016 Accepted: October 12, 2016 Published: October 21, 2016 ABSTRACT Diagnosis of cardiac sarcoidosis is often challenging. Whereas cardiac magnetic resonance imaging (CMR) and positron emission tomography/computed tomography (PET/CT) with 18 F-fluorodeoxyglucose (FDG) are most commonly used to evaluate patients, PET/CT using radiolabeled somatostatin receptor (SSTR) ligands for visualization of inflammation might represent a more specific alternative. This study aimed to investigate the feasibility of SSTR–PET/CT for detecting cardiac sarcoidosis in comparison to CMR. 15 patients (6 males, 9 females) with sarcoidosis and suspicion on cardiac involvement underwent SSTR-PET/CT imaging and CMR. Images were visually scored. The AHA 17-segment model of the left myocardium was used for localization and comparison of inflamed myocardium for both imaging modalities. In semi-quantitative analysis, mean (SUV mean ) and maximum standardized uptake values (SUV max ) of affected myocardium were calculated and compared with both remote myocardium and left ventricular (LV) cavity. SSTR-PET was positive in 7/15, CMR in 10/15 patients. Of the 3 CMR + /PET - subjects, one patient with minor involvement (

Background The purpose of this study is to evaluate the impact of switching from sterile water to 5 % glucose (G5W) for the administration of yttrium-90 (90Y)-resin microspheres on the total activity of 90Y administered (expressed as a proportion of the prescribed/calculated activity), as well as the number of cases of stasis and the reported incidence of discomfort during the selective internal radiation therapy (SIRT) procedure. Methods In December 2013, we switched from sterile water to G5W for the administration of SIRT using 90Y resin microspheres in all patients. This retrospective observational single-center case series describes our experience in the months preceding and after the switch. Apart from the change in administration medium, the protocol for SIRT was otherwise identical. Results One hundred and four SIRT procedures were performed on 78 patients (45 male, mean age: 63 years, range: 31–87 years) with either unresectable hepatocellular carcinoma, cholangiocarcinoma, or chemorefractory liver-dominant metastatic cancer. Compared with sterile water, the whole prescribed activity was administered in significantly more procedures with G5W: 85 vs. 22 %; p

Background -The underlying mechanism of the chronic inflammatory process in atherosclerosis is still unknown. As a possible trigger, several studies in recent years have suggested that different viruses and bacteria are associated with atherosclerotic diseases. Methods - We applied polymerase chain reaction to analyse whether Epstein-Barr virus (EBV), herpes simplex virus (HSV), and cytomegalovirus (CMV) DNA could be detected in CD14 + cells from 184 patients with angiographically documented coronary artery disease (CAD) (74 patients with stable angina (SAP), 51 patients with unstable angina (UAP), and 59 patients with myocardial infarction (Ml)) and from 52 healthy controls. Results - In two patients (one patient with SAP, one patient with UAP) with CAD and one healthy control, DNA from CMV was found (p = 0.469). HSV DNA was detected in one patient (SAP) but not in any controls (p = 0.644). EBV DNA was found in nine patients (three patients with SAP, one patient with DAP, five patients with Ml), and two controls (p = 0.752). Conclusion - Our data do not support the hypothesis that herpesvirus-infected monocytes are related to the incidence of human coronary atherosclerosis.

Tracheobronchiale Verletzungen bei stumpfem Thoraxtrauma sind sehr selten (Haufigkeit

Epstein-Barr-Virus-(EBV-)assoziierte Lymphoproliferationen (PTLD) nach Stammzelltransplantation (SCT) sind mit einem oft fulminanten Verlauf und einer hohen Mortalitat verbunden.Hauptrisikofaktoren sind die EBV-Primarinfektion nach Transplantation, T-Zell-depletiertes Transplantat,T-Zell-Antikorper (OKT3,ATG,ALG) und die Fremdspendertransplantation oder die Familienspende mit mindestens 2 HLA-Antigen-Differenzen. Die EBV-Lastmessung hat sich - mit gewissen Limitationen - als taugliches Mittel zur fruhzeitigen Diagnose und zum Therapiemonitoring etabliert.Therapeutische Optionen, die insbesondere auch in der Prophylaxe erfolgreich sind, umfassen im Wesentlichen die Verabreichung von monoklonalen Anti-CD-20-Antikorpern (Rituximab) und den adoptiven T-Zell-Transfer.Zukunftige Ziele waren in der Standardisierung der EBV-Lastmessung, der Etablierung einer immunologischen Diagnostik und in der Prophylaxe der PTLD zu sehen.

The controlled clinical trial reported here is part of a multicenter clinical and basic research project, sponsored by the German Federal Minister of Science and Technology, directed by a standing commission of the president of the Max-Planck-Gesellschaft, and coordinated by the Max-Planck-Institut fur Biochemie, Munchen. Overall, 249 patients with rheumatoid arthritis (RA) were enrolled by 16 participating hospitals. In addition to NSAID treatment, patients were randomly given either interferon gamma (IFN-γ) or placebo. In the IFN-γ group, 107 patients were evaluated and in the control group, 116 patients were evaluated. The response rate after 3 months of treatment, according to joint pain indexes, was significantly higher in the IFN-γ group with an error probability of 1%. IFN-γ was able to reduce the quantity of corticosteroids administered. Compared with the control group, the IFN-γ group benefited considering all parameters measured. Most important side effects were transient fever and transient influenza-like symptoms; all other adverse events were comparable in both groups.

The following chapter gives an overview on how nutrition can influence the skin. The first part of the chapter gives background information on the skin, its functions and the skin ageing process. In the second part, nutrients and their possible effects on skin are presented. This is followed by examples on how to incorporate these nutrients into food formulations, taking both food regulations and technological challenges into account. In the last part, an outlook for possible future trends with regard to consumer expectations as well as technologies is given.

If the data collected within a sensor network is valuable or should be kept confidential then security measures should protect the access to this data. We first determine security issues in the context of access control in sensor networks especially focusing on the problem of node capture, i.e., the possibility that an attacker can completely take over some of the sensor nodes. We then introduce the notion of t-robust sensor networks which can withstand capture of up to t nodes and consider three basic security concepts for such networks: (1) t-robust storage, a mechanism to securely store data within a set of sensors such that capture of any t sensors does not reveal that data to the adversary; (2) n-authentication which ensures that authentication is achieved with every uncompromised sensor in the broadcast range of a client (n denotes the number of nodes in that broadcast range); and (3) n-authorization, an authorization primitive with similar properties like n-authentication. We present a generic t-robust protocol for implementing access control using these primitives.

This paper proposes that the healthcare domain can serve as an archetypical field of research in pervasive computing. We present this area from a technological perspective, arguing that it provides a wide range of possible applications of pervasive computing technology. We further recognize that pervasive computing technology is likely to create concerns about the security of healthcare systems, due to increased data aggregation, ubiquitous access, and increasing dependency on technical solutions. But we also justify why the same technology can help building more robust, more dependable systems that increase the quality of healthcare. We identify building blocks that are necessary to achieve this goal: a pervasive middleware, appropriate handling of exceptional situations, and dependability assertions for small devices.

We present an evaluation of advanced routing algorithms for content-based publish/subscribe systems that focuses on the inherent characteristics of routing algorithms (routing table sizes and filter forwarding overhead) instead of system-specific parameters (CPU load etc.). The evaluation is based on a working prototype instead of simulations and compares several routing algorithms to each other. Moreover, the effects of locality among the interests of the consumers are investigated. The results offer new insights into the behavior of content-based routing algorithms. Firstly, advanced routing algorithms can be considered mandatory in large-scale publish/subscribe systems. Secondly, the use of advertisements considerably improves scalability. Thirdly, advanced routing algorithms operate efficiently in more dynamic environments than was previously thought. Finally, the good behavior of the algorithms improves even if the interests of the consumers are not evenly distributed, which can be expected in practice.

Recently, research has focused on enabling fair exchange between payment and electronically shipped items. The reason for this is the growing importance of electronic commerce and the increasing number of applications in this area. Although a considerable number of fair exchange protocols exist, they usually have been defined for special scenarios and thus only work under particular assumptions. Furthermore, these protocols provide different degrees of fairness and cause different communication overhead. The purpose of the paper is to present a unifying solution to the problem. We do this by defining a suite of protocol modules which allow us to compose protocols where the achieved degree of fairness can be enhanced step by step. The advantage of the stepwise approach is that after each step one can decide if the provided degree of fairness is acceptable or if one is willing to spend more in order to reach a higher degree of fairness. We show the applicability of our approach by deriving a novel efficient fair exchange protocol.

Usually, load distribution schemes for replicated servers are based on a many-to-one mapping between client and server meaning that, while a server may serve many clients, a client has a single specific server which it queries at any point in time. In some cases, however it is desirable that the number of accesses of a client may be distributed over multiple servers, thus yielding a many-to-many mapping between clients and servers. We present a simple method to efficiently realize such a many-to-many mapping between clients and servers. For the sake of transparency we add a component called "distribution module" to the communication interface of client and server. This module is responsible for distributing server accesses over multiple target machines in a well defined way. We present algorithms for the client and server component and show that they are self-stabilizing, meaning that they converge to a stable state once the access pattern becomes regular. Due to this property, the components can tolerate any internal transient fault in a non-masking way. Additionally, our approach is highly modular since servers may run an off-the-shelf load distribution algorithm and replica consistency is not affected.

The aim of this study was to evaluate in vitro the relationship between polymerization shrinkage and microleakage in dentin-bordered restorations.Four light-cured restorative materials in combination with their respective dental bonding agents (DBA) were investigated: Tetric Ceram/Syntac classic (Vivadent), Solitaire/Gluma Solid bond (Heraeus Kulzer), Definite/EtchPrime 3.0 (Degussa), Solitaire 2/Gluma Solid bond (Heraeus Kulzer). The chemically cured resin Degufill sc microhybrid (Degussa) in combination with ART Bond (Coltène) was also included. Polymerization shrinkage of the restorative materials was measured using three different methods (dilatometer, linometer, buoyancy method) and analyzed with ANOVA. For the determination of microleakage, caries-free human molars were embedded in acrylic resin and subsequently abraded with a wet abrasion machine to produce four level dentin surfaces. One hundred sixty cavities (3 mm diameter/1.5 mm deep) were randomly assigned to four groups of equal size. The groups were restored without (group 1 and 2) and with DBA (group 3 and 4), and either not subjected (group 1 and 3) or subjected (group 2 and 4) to 2000 cycles from 5-55 degrees C. Each group was further divided into five material subgroups of eight cavities each. Microleakage was determined using a dye penetration test assessed at depths of 200, 400 and 600 microm into the fillings. Data were analyzed with the Kruskal-Wallis and the Mann-Whitney test.All three methods of measuring polymerization shrinkage (PS) generated the same, statistically secured ranking for the four light-cured restorative materials: PS DefinitePS Tetric CeramPS Solitaire 2PS Solitaire. In the microleakage study, only a few statistically significant differences were observed. EtchPrime 3.0/Definite in group 3 and Solid Bond/Solitaire 2 in group 4 tended to exhibit the least microleakage. Correlation coefficients between aggregated shrinkage and microleakage data were 0.3 for group 3 and -0.2 for group 4.The results do not suggest any correlation between polymerization shrinkage and microleakage in dentin of direct adhesive restorations.

Event-based systems are developed and used as a coordination model to integrate components in loosely coupled systems. Research and product development focused so far on efficiency issues but neglected methodological support to build such systems. In this paper, we present the modular design and implementation of an event system which supports scopes and event mappings, two new and powerful structuring methods that facilitate engineering and coordination of components in event-based systems. The approach is based on a trace-based specification method adapted from temporal logic.

Fair exchange protocols ensure that the participating parties, customer and vendor, can engage in electronic commerce transactions without the risk of suffering a disadvantage. This means that neither of them delivers his digital item without receiving the other party's item. In general, fair exchange cannot be solved without the help of a trusted third party (TTP), a dedicated computer which is trusted by both participants. Trust can be established by carefully securing the TTP or even better by introducing tamper-proof hardware. However, if the communication to the TTP is unreliable or disrupted, then the exchange cannot be performed in a timely fashion or not at all. Up to now, this has been a problem especially for the exchange of time-sensitive items, i.e., items which lose value over time. We present a novel approach to perform fair exchange using tamper-poof hardware on the customer's side. More specifically, co-located to the customer's machine we use a smart card which partially takes over the role of the TTP. The challenge of designing protocols in this environment lies in the fact that the communication between the smart card and the vendor is under control of the customer. Our approach has the following benefits: It supports the exchange in mobile environments where customers frequently experience a disconnection from the network. Furthermore, our approach is the first to handle time-sensitive items properly.

Mobile agents have been advocated to support electronic commerce over the Internet. While being a promising paradigm, many intricate problems need to be solved to make this vision reality. The problem of fair exchange between two agents is one such fundamental problem. Informally speaking, this means to exchange two electronic items in such a way that neither agent suffers a disadvantage. We study the problem of fair exchange in the mobile agent paradigm. We show that while existing protocols for fair exchange can be substantially simplified in the context of mobile agents, there are still many problems related to security which remain difficult to solve. We propose three increasingly flexible solutions to the fair exchange problem and show how to implement them using existing agent technology. The basis for ensuring the security properties of fair exchange is a tamper-proof hardware device called a trusted processing environment.

Patients on renal replacement therapy, haemodialysis (HD), or after kidney transplantation (TX), are known to be at risk of acquiring blood-borne infections (HBV, HCV). GBV-C/Hepatitis G virus (HGV) has been described recently and is considered to cause blood-borne infections. The aim of this study was to analyse the risk for the medical staff of HD and TX patients to acquire HGV infection.Eighty-five HD patients and 86 TX recipients were compared with 49 health-care workers and 64 blood donors as controls. The HGV prevalence was determined by RT-PCR and antibodies to E2 protein.A high prevalence of HGV was found in the medical staff (24%) which nearly corresponded to the prevalence of the patients (TX 36%, HD 25%) but not to the controls (9%). In contrast, the prevalence of HCV was low in the medical staff (2%) and controls (0%) but high in HD (13%) and TX (13%). Age and duration of employment in the department did not significantly influence the HGV prevalence in staff. The number of viraemic subjects in staff was high, possibly indicating a more recent infection.An occupational risk for HGV exists in medical staff of dialysis and transplant patients. Further routes of transmission than only parenteral may play a role in this setting.

Quick evaluation of the efficacy of irradiation treatment still presents problems; this is especially the case with radiosensitizers, combined irradiation and chemotherapy, hyperthermia, hyperfractionation, and radiation with a high linear energy transfer. Our tests were aimed at finding a method to determine the effect of irradiation on a tumor in vivo at the beginning of treatment. We sought to detect the oncoradiogenic enzyme peak of aldolase [2], i.e., an increase in the serum enzyme level 16–19 h after initial irradiation of patients with bronchial or esophageal carcinoma; we examined the activity of glucose6-phosphate isomerase (GPI; EC 5.3.1.9), an enzyme better suited for clinical laboratory routine, in patients with tumors of various localizations. The enzyme GPI, found in the cytoplasm, is omnipresent in nature and is also contained in human tissue in varying concentrations. Enzyme activity is particularly high in muscular and hepatic tissue and in malignant tumors. The normal range of serum enzyme activity is 0.3–3.0 μoll−1 s−1. Prior to the examination proper, the activity of GPI and creatine kinase (CK) in the serum of 16 healthy subjects was measured at hourly intervals over a period of 24 h. No pathological enzyme activity or significant changes in enzyme activity were observed throughout this period, and preanalytical factors such as food intake or physical activity were found to have no effect. The test was repeated in six patients with malignant tumors; also in this group we found no significant changes in GPI activity in the serum over a period of 24 h, and only higher mean values and greater dispersion were noted.

Publish/subscribe (pub/sub) is considered a valuable middleware architecture that proliferates loose coupling and leverages reconfigurability and evolution. Up to now, existing pub/sub middleware was optimized for static systems where users as well as the underlying system structure was rather fixed. We study the question whether existing pub/sub middleware can be extended to support mobile and location-dependent applications.We first analyze the requirements of such applications and distinguish two orthogonal forms of mobility: the system-centric physical mobility and an application-centric logical mobility (where users are aware that they are changing location). For logical-mobility we introduce location-dependent subscriptions as a suitable means to exploit the power of the event-based paradigm in mobile applications. Briefly spoken, a location-dependent subscription offers to express interest in all events which are related to a user's current location. We present efficient implementations for both forms of mobility within the content-based pub/sub middleware Rebeca. Our solutions draw much of their efficiency from the refined routing capabilities (namely, covering and merging) of the Rebeca system.

Background Radioligand therapy (RLT) with 177Lu-DKFZ-617 PSMA (Lu-PSMA) (prostate-specific membrane antigen) is a novel targeted therapy of metastatic prostate cancer. We analysed retrospectively the early side effects and the response rate in the first patients, who received a therapy with Lu-PSMA in our departments. Methods RLT was performed in ten hormone- and/or chemo-refractory patients with distant metastases and progressive disease (mean age 73.5 years). 68Ga-PSMA HBED-CC PET/CT was performed in all patients prior to RLT. The median PSA level prior to the therapy was 298.5 ng/ml (range 5–853 ng/ml). All patients received CBC, renal and liver function tests the day before and 2 days after application (mean administered activity 5.6 GBq, range 4.1–6.1 GBq), followed by further tests every 2 weeks. All patients were contacted by telephone every week regarding side effects or any positive and negative changes. Results Eight weeks after the therapy, seven patients (70 %) experienced a PSA decline, of whom six experienced more than 30 % and five more than 50 %. Three patients showed a progressive disease according to the PSA increase. No patient experienced any side effects immediately after injection of Lu-PSMA. Relevant hematotoxicity (grade 3 or 4) occurred 7 weeks after the administration in just one patient. The same patient showed a leucopenia grade 2. Two patients showed a disturbance of only 1 hematologic cell line, whereas one patient showed a reduction of grades 1 and 2 in leucocytes and thrombocytes, respectively. Six patients did not show any hematotoxicity during the 8 weeks after therapy. There was no relevant nephrotoxicity (grade 3 or 4). Conclusions Our initial results indicate that RLT with Lu-PSMA is safe and seems to have low early side-effect profile. A relevant PSA decline was detected in 70 % of patients.