Whole-body 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) for accurate staging of Hodgkin's disease

BACKGROUND: Staging of Hodgkin's disease (HD) is accomplished by a variety of invasive and non-invasive modalities. This prospective study was undertaken to investigate the value of whole-body positron emission tomography (PET) with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) in defining regions involved by lymphoma compared with conventional staging methods in patients with HD. PATIENTS AND METHODS: Fourty-four newly diagnosed patients with HD underwent FDG-PET as part of their initial staging work-up. PET findings were correlated with findings of conventional staging including computed tomography, ultrasound, bone scanning, bone marrow biopsy, liver biopsy and laparotomy. When results of FDG-PET differed to those obtained by conventional methods reevaluation was performed by biopsy, if possible, or magnetic resonance imaging. RESULTS: The results of FDG-PET were compared with three hundred twenty-one conventional staging procedures performed in 44 patients. FDG-PET was positive in 38 of 44 (86%) patients at sites of documented disease. PET detected additional lesions in five cases previously not identified by conventional staging methods. In another case a nodal lesion suspect on CT was negative at FDG-PET and was settled as true negative by biopsy. As a consequence of PET findings five patients had to be upstaged and one patient had to be downstaged, resulting in changes in treatment strategy in all six cases (14%). FDG-PET failed to visualize sites of HD in four patients. In two of our patients a false positive PET result was obtained. CONCLUSIONS: Our data indicate that FDG-PET provides an imaging technique that appears to visualize involved lesions in most patients with HD and is useful in the management of these patients.     

Effects of cholestanol feeding and cholestyramine treatment on the tissue sterols in the rabbit

Rabbits were fed diets enriched with cholestanol or cholestereol (3.5 g/wk) for 4–12 weeks. During cholestanol feeding, the concentration of cholestanol in blood serum, liver, heart and aorta increased 15–30 times. In serum and liver, the concentration of cholesterol also increased. Cholestanol-fed rabbits developed inflammatory changes in the liver, with proliferation of small bile ducts. Liver tests were only slightly abnormal. Morphological atherosclerosis of the aorta was only occasionally seen in rabbits receiving cholestanol for eight weeks or less. During cholesterol feeding, the amounts of cholesterol in different tissues increased dramatically, most in the aorta. Morphological atherosclerosis in the aorta was found in all rabbits fed cholesterol-enriched diets for more than four weeks. Brain cholestanol was doubled in rabbits fed cholestanol for eight weeks, whereas brain sterols did not change significantly during cholesterol feeding. After an additional regression period with cholestyramine for eight weeks, the increased content of cholestanol in the brain was unchanged in cholestanol-fed rabbits. These observations are discussed in relation to the cholestanolosis of the brain that develops in the rare inherited human disease cerebrotendinous xanthomatosis.     

Mapping feature models onto domain models: ensuring consistency of configured domain models

We present an approach to model-driven software product line engineering which is based on feature models and domain models. A feature model describes both common and varying properties of the instances of a software product line. The domain model is composed of a structural model (package and class diagrams) and a behavioral model (story diagrams). Features are mapped onto the domain model by annotating elements of the domain model with features. An element of a domain model is specific to the features included in its feature annotation. An instance of the product line is defined by a set of selected features (a feature configuration). A configuration of the domain model is built by excluding all elements whose feature set is not included in the feature configuration. To ensure consistency of the configured domain model, we define constraints on the annotations of inter-dependent domain model elements. These constraints guarantee that a model element may be selected only when the model elements are also included on which it depends. Violations of dependency constraints may be removed automatically with the help of an error repair tool which propagates features to dependent model elements.     

Performance modeling and analysis of message-oriented event-driven systems

Message-oriented event-driven systems are becoming increasingly ubiquitous in many industry domains including telecommunications, transportation and supply chain management. Applications in these areas typically have stringent requirements for performance and scalability. To guarantee adequate quality-of-service, systems must be subjected to a rigorous performance and scalability analysis before they are put into production. In this paper, we present a comprehensive modeling methodology for message-oriented event-driven systems in the context of a case study of a representative application in the supply chain management domain. The methodology, which is based on queueing Petri nets, provides a basis for performance analysis and capacity planning. We study a deployment of the SPECjms2007 standard benchmark on a leading commercial middleware platform. A detailed system model is built in a step-by-step fashion and then used to predict the system performance under various workload and configuration scenarios. After the case study, we present a set of generic performance modeling patterns that can be used as building blocks when modeling message-oriented event-driven systems. The results demonstrate the effectiveness, practicality and accuracy of the proposed modeling and prediction approach.     

Retrospective analysis for evaluation of the value of contrast-enhanced MRI in patients treated with breast conservative therapy

Purpose The aim of this study was to assess the value of contrast-enhanced (c.-e.) MRI in the follow-up of patients with conservatively treated breast cancer since detection and exclusion of malignancy may interfere significantly with posttherapeutic changes within the treated breast. Material and methods A total of 207 patients with a history of limited surgery and radiation therapy underwent MR imaging, 40 patients were examined 0–12 months and 167 patients were examined later than 12 months after radiotherapy. Suspicious or indeterminate findings were suggested by clinical examination or conventional imaging in 80 studies. In 127 women, MRI was performed within breast tissue that was difficult to assess due to scarring or dense breast tissue. Results Recurrent carcinoma was confirmed in 27 patients by surgical biopsy. All 27 carcinomas, except for one with a slow signal increase, demonstrated early rise of signal intensity on dynamic T1-weighted contrast enhanced images. During the first year after therapy, the diagnostic accuracy could not be improved by additional use of c.-e. MRI. Differentiation between posttherapeutic changes and recurrent carcinoma was frequently not possible because of strong and sometimes early and ill-circumscribed enhancement. Later than 12 months after therapy enhancement decreased significantly, thus the false positive calls could be reduced from 49 (conventional imaging) to 12 (conventional imaging plus MRI). A total of 12 of 26 recurrences and multifocality in 4/5 cases were diagnosed by MR imaging alone at this time interval. Conclusion In the first year after therapy, c.-e. MRI is only indicated in selected cases. The results later than 12 months emphasize that c.-e. MRI may contribute significant additional information. It allows better distinction of posttherapeutic fibrosis from recurrent carcinoma and proved to be able to detect recurrent disease more sensitive and at an earlier stage.     

Identification and Optimization of the First Highly Selective GLUT1 Inhibitor BAY‐876

Despite the long‐known fact that the facilitative glucose transporter GLUT1 is one of the key players safeguarding the increase in glucose consumption of many tumor entities even under conditions of normal oxygen supply (known as the Warburg effect), only few endeavors have been undertaken to find a GLUT1‐selective small‐molecule inhibitor. Because other transporters of the GLUT1 family are involved in crucial processes, these transporters should not be addressed by such an inhibitor. A high‐throughput screen against a library of ～3 million compounds was performed to find a small molecule with this challenging potency and selectivity profile. The N‐(1H‐pyrazol‐4‐yl)quinoline‐4‐carboxamides were identified as an excellent starting point for further compound optimization. After extensive structure–activity relationship explorations, single‐digit nanomolar inhibitors with a selectivity factor of >100 against GLUT2, GLUT3, and GLUT4 were obtained. The most promising compound, BAY‐876 [N⁴‐[1‐(4‐cyanobenzyl)‐5‐methyl‐3‐(trifluoromethyl)‐1H‐pyrazol‐4‐yl]‐7‐fluoroquinoline‐2,4‐dicarboxamide], showed good metabolic stability in vitro and high oral bioavailability in vivo.     

Full-wafer technology-A new approach to large-scale laserfabrication and integration

A concept for full-wafer processing (FWP) and full-wafer testing (FWT) for semiconductor laser fabrication in the AlGaAs-GaAs material system is presented. The approach is based on chemically assisted ion beam etching for the laser-mirror formation. Record values for mirror scattering, optimum mirror reflectivity, and equivalence to cleaved mirrors in terms of laser threshold and efficiency have been achieved. Promising results for uniformity and reproducibility for major laser diode characteristics on processed 2-in wafers have been found. The FWP technology has been extensively used for designing test sites to determine various materials, process, and laser parameters, such as sheet resistance, ridge dimensions, lithographic alignment errors, mirror surface leakage, etc