A randomized trial of bevacizumab for newly diagnosed glioblastoma.

BACKGROUND: Concurrent treatment with temozolomide and radiotherapy followed by maintenance temozolomide is the standard of care for patients with newly diagnosed glioblastoma. Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor A, is currently approved for recurrent glioblastoma. Whether the addition of bevacizumab would improve survival among patients with newly diagnosed glioblastoma is not known. METHODS: In this randomized, double-blind, placebo-controlled trial, we treated adults who had centrally confirmed glioblastoma with radiotherapy (60 Gy) and daily temozolomide. Treatment with bevacizumab or placebo began during week 4 of radiotherapy and was continued for up to 12 cycles of maintenance chemotherapy. At disease progression, the assigned treatment was revealed, and bevacizumab therapy could be initiated or continued. The trial was designed to detect a 25% reduction in the risk of death and a 30% reduction in the risk of progression or death, the two coprimary end points, with the addition of bevacizumab. RESULTS: A total of 978 patients were registered, and 637 underwent randomization. There was no significant difference in the duration of overall survival between the bevacizumab group and the placebo group (median, 15.7 and 16.1 months, respectively; hazard ratio for death in the bevacizumab group, 1.13). Progression-free survival was longer in the bevacizumab group (10.7 months vs. 7.3 months; hazard ratio for progression or death, 0.79). There were modest increases in rates of hypertension, thromboembolic events, intestinal perforation, and neutropenia in the bevacizumab group. Over time, an increased symptom burden, a worse quality of life, and a decline in neurocognitive function were more frequent in the bevacizumab group. CONCLUSIONS: First-line use of bevacizumab did not improve overall survival in patients with newly diagnosed glioblastoma. Progression-free survival was prolonged but did not reach the prespecified improvement target. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00884741.)

Manganese Superoxide Dismutase: Guardian of the Powerhouse

The mitochondrion is vital for many metabolic pathways in the cell, contributing all or important constituent enzymes for diverse functions such as β-oxidation of fatty acids, the urea cycle, the citric acid cycle, and ATP synthesis. The mitochondrion is also a major site of reactive oxygen species (ROS) production in the cell. Aberrant production of mitochondrial ROS can have dramatic effects on cellular function, in part, due to oxidative modification of key metabolic proteins localized in the mitochondrion. The cell is equipped with myriad antioxidant enzyme systems to combat deleterious ROS production in mitochondria, with the mitochondrial antioxidant enzyme manganese superoxide dismutase (MnSOD) acting as the chief ROS scavenging enzyme in the cell. Factors that affect the expression and/or the activity of MnSOD, resulting in diminished antioxidant capacity of the cell, can have extraordinary consequences on the overall health of the cell by altering mitochondrial metabolic function, leading to the development and progression of numerous diseases. A better understanding of the mechanisms by which MnSOD protects cells from the harmful effects of overproduction of ROS, in particular, the effects of ROS on mitochondrial metabolic enzymes, may contribute to the development of novel treatments for various diseases in which ROS are an important component

Prove That a Faulty Multiplier is Faulty!?

Formal verification of integer multipliers was an open problem for a long time as the size of any reduced ordered binary decision diagram (BDD) [1] which represents integer multiplication is exponential in the width of the operands [2]. In 1995, Bryant and Chen [4] introduced multiplicative binary moment diagrams (*BMD) which is a canonical data structure for pseudo Boolean functions allowing a linear representation of integer multipliers. Based on this data structure, Bryant/Chen [4] and Hamaguchi et.al. experimentally showed [5] that integer multipliers up to a word size of 64 bits can be formally verified. However, all these results only handle the problem of proving a faultless integer multiplier to be correct. But, what happens if the multiplier is faulty? Does the backward construction method stop after a short time? After what time can I be sure that the integer multiplier under consideration is faulty? In this paper, we show that these questions are relevant in practice. In particular, we investigate simple add-step multipliers and show that simple design errors can lead to exponential growth of the *BMDs occuring during backward construction. This proves that the backward construction method can only be applied as filter during formal logic combinational verification unless sharp upper bounds for the sizes of the *BMDs occuring during the backward construction have been proven for the various circuit types as Keim et.al. [6] did it for Wallace Tree multipliers

DataLines, a framework for building streaming data applications

Abstract. Network and security engineers have been struggling with the problems of monitoring the deluge of data generated by network equipment, traffic taps, process logs, intrusion detection systems, and sensor events. Each data source requires learning a different set of tools as well as ad-hoc scripting or programming to generate site-specific report data. An even bigger problem is that many of the processing tools were not designed to work in a streaming context. In research communities such as machine learning and data-mining that focus on streaming data, many of the proposed solutions are built without much thought to how the implementation might actually be used in a production environment. We are currently developing a framework, DataLines, that allows one to build streaming data applications dynamically. DataLines provides a common framework for reading and processing data, and for controlling data flow within an application. It not only frees engineers and application developers from the reoccurring tedium of needing to write code to read, parse, process, and control data flow, but it also serves as a mechanism to bring one’s research into a production environment. The DataLines framework comes with a wide variety of processors to operate (e.g. filter, log, visualize, summarize etc.) on data. In many situations, no application specific code needs to be written–only an XMLbased configuration. This configuration forms the basis of all DataLines applications and can be dropped into several containers such that one can deploy a DataLines application as a command-line driven tool, a gui-based tool, or as part of a web application. We are using DataLines for many of our network and security monitoring efforts, as well as in several research projects. The framework is described and our experience with using DataLines to correlate several different network data sources is presented

Biofilm plaque and hydrodynamic effects on mass transfer, fluoride delivery and caries.

Dental plaque is a dynamic community of microor-ganisms, developing continually and reshaping the microenvironment in which they live.1,2 Bacteria and other organisms in the plaque take nutrients from our saliva and the food we eat to proliferate. Immediately after tooth cleaning, bacteria left on the tooth surface and those attaching to the tooth surface from other parts of the oral cavity such as the tongue, gingivae and cheek mucosa begin to regrow. As the biofilm grows, it forms an irregular heterogeneous structure containing clusters of cells surrounded by channels through which liquid, such as saliva, can flow.3,4 Aerobic organisms on the periphery of the cell clusters remove dissolved oxygen (DO) rapidly, creating favorable microniches for pathogenic anaerobic bacteria to thrive. Thus, as the biofilm develops, it may be thought of as an ecosystem, containing many habitats and organisms. Bacteria modify the local environment through the production of acid from the fermentation of sucrose and other fermentable sugars in the diet, which then may increase demineralization of the enamel surface, leading to, or accelerating, the development of caries.5 The literature contains many excellent reviews regarding the microbial ecology and management of dental plaque biofilms.1,2,6 However, it is the goal of this review to concentrate on the effect that the interactions between biofilm and hydrodynamics have on the delivery of fluoride ion (F–) to the tooth surface, and the effect that F– might have on biofilm physiology and, consequently, the cariogenic process