Lynch Syndrome: Its Impact on Urothelial Carcinoma

Lynch syndrome, known as hereditary nonpolyposis colorectal cancer (HNPCC), is an autosomal-dominant familial cancer syndrome with an increased risk for urothelial cancer (UC). Mismatch repair (MMR) deficiency, due to pathogenic variants in MLH1, MSH2, MSH6, and PMS2, and microsatellite instability, are known for development of Lynch syndrome (LS) associated carcinogenesis. UC is the third most common cancer type in LS-associated tumors. The diversity of germline variants in the affected MMR genes and their following subsequent function loss might be responsible for the variation in cancer risk, suggesting an increased risk of developing UC in MSH2 mutation carriers. In this review, we will focus on LS-associated UC of the upper urinary tract (UUT) and bladder, their germline profiles, and outcomes compared to sporadic UC, the impact of genetic testing, as well as urological follow-up strategies in LS. In addition, we present a case of metastatic LS-associated UC of the UUT and bladder, achieving complete response during checkpoint inhibition since more than 2 years.     

Hypolipidemic activity of the surfactants aminimides,and their effects on lipid metabolism of rodents

A series of short chain fatty acid derivatives of aminimides were shown to possess hypolipidemic activity in rats and mice. Most of the agents tested lowered both serum cholesterol and triglyceride levels by at least 30% in mice and were effective in hyperlipidemic induced mice. 1,1-Dimethyl-1-(2-hydroxypropyl)-amine mersitimide lowered serum cholesterol levels 41% and serum triglyceride levels 56% at 20 mg/kg/day I.P. after 16 days. The same agent was active orally when administered to rats with a 38% reduction in serum cholesterol and a 52% reduction in serum triglycerides after 14 days. The agents inhibited liver acetyl CoA synthetase, ATP dependent citrate lyase and phosphatidate phosphohydrolase activities in vitro and in vivo. Reduction of cholesterol, triglycerides, neutral lipids and phospholipid levels were noted in the livers of mice treated for 16 days. In rat studies, cholesterol, triglyceride and phospholipid levels were reduced in liver, small intestine and the feces after two weeks' dosing. The cholesterol content was reduced in the very low density lipoprotein (VLDL) and low density lipoprotein (LDL) fractions but elevated in the high density lipoproteins (HDL). Triglyceride levels were lowered in the VLDL, and neutral lipid levels were reduced in the chylomicron and VLDL fractions.     

Group psychotherapy with the elderly: Problems and prospects.

Examines the development, since 1950, of group psychotherapy with the elderly. The strengths and weaknesses of the research generated during this period are highlighted, with particular attention to the critical elements of group psychotherapy that make it effective for use with both institutionalized and community-dwelling elderly. (74 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hypolipidemic activity of 3- and 4-phenyl-piperidine-2,6-diones and selected N-substituted derivatives

Three- and 4-phenyl-piperidine-2,6-dione derivatives were investigated for hypolipidemic activity at 20 mg/kg/day intraperitoneally in rodents. The 3-phenyl compound afforded the best activity and effectiveness in both normal and hyperlipidemia-induced mice. The agent lowered lipids by blocking the de novo hepatic synthesis of cholesterol and triglycerides, specifically at the sites of ATP-dependent citrate lyase, acetyl CoA synthetase,sn-glycerol-3-phosphate acyl transferase and phosphatidylate phosphohydrolase. The agent caused a more rapid clearance of cholesterol by the fecal route. Cholesterol levels of the chylomicrons, very low density lipoprotein and low density lipoprotein (LDL) were reduced, whereas high density lipoprotein cholesterol was significantly elevated after drug administration. Triglyceride content was lowered in the chylomicron and LDL fractions. These modulations of lipid content of serum lipoproteins by the drug suggest a favorable situation for treatment of hyperlipidemic states.     

Heuristics for the capacitated dispersion problem

In this paper, we investigate the adaptation of the greedy randomized adaptive search procedure (GRASP) and variable neighborhood descent (VND) methodologies to the capacitated dispersion problem. Dispersion and diversity problems arise in the placement of undesirable facilities, workforce management, and social media, among others. Maximizing diversity deals with selecting a subset of elements from a given set in such a way that the distance among the selected elements is maximized. We target here a realistic variant with capacity constraints for which a heuristic with a performance guarantee was previously introduced. In particular, we propose a hybridization of GRASP and VND implementing within the strategic oscillation framework. To evaluate the performance of our heuristic, we perform extensive experimentation to first set key search parameters, and then compare the final method with the previous heuristic. Additionally, we propose a mathematical model to obtain optimal solutions for small‐sized instances, and compare our solutions with the well‐known LocalSolver software.     

View Planning for Multi-View Stereo 3D Reconstruction Using an Autonomous Multicopter

Multi-view stereo algorithms are an attractive technique for the digital reconstruction of outdoor sites. Concerning the data acquisition process a vertical take off and landing UAV carrying a digital camera is a suitable platform in terms of mobility and flexibility in viewpoint placement. We introduce an automated UAV based data acquisition and outdoor site reconstruction system. A special focus is set on the problem of model based view planning using a coarse digital surface model (DSM) with minimal data preprocessing. The developed view planning heuristic considers a coverage, a maximum view angle and an overlapping constraint imposed by multi-view stereo reconstruction techniques. The time complexity of the algorithm is linear with respect to the size of the area of interest. We demonstrate the efficiency of the entire system in two scenarios, a building and a hillside.     

Predicting users' return to virtual worlds: a social perspective

Virtual worlds or three‐dimensional computer‐based simulated environments have received considerable attention as platforms for entertainment, education and commerce. In contrast to a web site, for example, where a user interacts with a two‐dimensional site, virtual worlds provide a platform in which users can interact with other individuals, sometimes including strangers, within three‐dimensional environments. Virtual worlds afford a form of ‘socialness’ unlike many other technologies, often motivating a user – by virtue of these social experiences – to return. Drawing on the Spatial Model of Interaction and Awareness‐Attention Theory, we demonstrate that besides social aspects, which include social awareness and social perception, flow experience, which is the mental state of being fully absorbed and somewhat lost in time, is an essential ingredient in an individual's decision to return to a virtual world. We also demonstrate how characteristics of the technology are linked to the social aspects experienced in virtual worlds. A laboratory study conducted in a virtual world, Second Life, supports our assertions and identifies state predictors of flow that influence individuals' intentions to return to the virtual world environment.     

Utilizing domain models for application design and validation

Domain analysis enables identifying families of applications and capturing their terminology in order to assist and guide system developers to design valid applications in the domain. One major way of carrying out the domain analysis is modeling. Several studies suggest using metamodeling techniques, feature-oriented approaches, or architectural-based methods for modeling domains and specifying applications in those domains. However, these methods mainly focus on representing the domain knowledge, providing insufficient guidelines (if any) for creating application models that satisfy the domain rules and constraints. In particular, validation of the application models which include application-specific knowledge is insufficiently dealt. In order to fill these lacks, we propose a general approach, called Application-based DOmain Modeling (ADOM), which enables specifying domains and applications similarly, (re)using domain knowledge in application models, and validating the application models against the relevant domain models. In this paper we present the ADOM approach, demonstrating its application to UML 2.0 class and sequence diagrams.