Selective COX-2 inhibitors and risk of myocardial infarction

Selective inhibitors of cyclooxygenase- 2 ( COX- 2, ` coxibs') are highly effective anti-inflammatory and analgesic drugs that exert their action by preventing the formation of prostanoids. Recently some coxibs, which were designed to exploit the advantageous effects of non- steroidal anti-inflammatory drugs while evading their side effects, have been reported to increase the risk of myocardial infarction and atherothrombotic events. This has led to the withdrawal of rofecoxib from global markets, and warnings have been issued by drug authorities about similar events during the use of celecoxib or valdecoxib/ parecoxib, bringing about questions of an inherent atherothrombotic risk of all coxibs and consequences that should be drawn by health care professionals. These questions need to be addressed in light of the known effects of selective inhibition of COX- 2 on the cardiovascular system. Although COX- 2, in contrast to the cyclooxygenase-1 ( COX- 1) isoform, is regarded as an inducible enzyme that only has a role in pathophysiological processes like pain and inflammation, experimental and clinical studies have shown that COX- 2 is constitutively expressed in tissues like the kidney or vascular endothelium, where it executes important physiological functions. COX- 2- dependent formation of prostanoids not only results in the mediation of pain or inflammatory signals but also in the maintenance of vascular integrity. Especially prostacyclin ( PGI(2)), which exerts vasodilatory and antiplatelet properties, is formed to a significant extent by COX- 2, and its levels are reduced to less than half of normal when COX- 2 is inhibited. This review outlines the rationale for the development of selective COX- 2 inhibitors and the pathophysiological consequences of selective inhibition of COX- 2 with special regard to vasoactive prostaglandins. It describes coxibs that are currently available, evaluates the current knowledge on the risk of atherothrombotic events associated with their intake and critically discusses the consequences that should be drawn from these insights. Copyright (C) 2005 S. Karger AG, Basel

A Multi-cut Formulation for Joint Segmentation and Tracking of Multiple Objects

Recently, Minimum Cost Multicut Formulations have been proposed and proven to be successful in both motion trajectory segmentation and multi-target tracking scenarios. Both tasks benefit from decomposing a graphical model into an optimal number of connected components based on attractive and repulsive pairwise terms. The two tasks are formulated on different levels of granularity and, accordingly, leverage mostly local information for motion segmentation and mostly high-level information for multi-target tracking. In this paper we argue that point trajectories and their local relationships can contribute to the high-level task of multi-target tracking and also argue that high-level cues from object detection and tracking are helpful to solve motion segmentation. We propose a joint graphical model for point trajectories and object detections whose Multicuts are solutions to motion segmentation {\it and} multi-target tracking problems at once. Results on the FBMS59 motion segmentation benchmark as well as on pedestrian tracking sequences from the 2D MOT 2015 benchmark demonstrate the promise of this joint approach

{SHIFT}: {A} Synthetic Driving Dataset for Continuous Multi-Task Domain Adaptation

Adapting to a continuously evolving environment is a safety-critical challenge inevitably faced by all autonomous-driving systems. Existing image- and video-based driving datasets, however, fall short of capturing the mutable nature of the real world. In this paper, we introduce the largest multi-task synthetic dataset for autonomous driving, SHIFT. It presents discrete and continuous shifts in cloudiness, rain and fog intensity, time of day, and vehicle and pedestrian density. Featuring a comprehensive sensor suite and annotations for several mainstream perception tasks, SHIFT allows to investigate how a perception systems' performance degrades at increasing levels of domain shift, fostering the development of continuous adaptation strategies to mitigate this problem and assessing the robustness and generality of a model. Our dataset and benchmark toolkit are publicly available at www.vis.xyz/shift

A fabrication guide for planar silicon quantum dot heterostructures

We describe important considerations to create top-down fabricated planar quantum dots in silicon, often not discussed in detail in literature. The subtle interplay between intrinsic material properties, interfaces and fabrication processes plays a crucial role in the formation of electrostatically defined quantum dots. Processes such as oxidation, physical vapor deposition and atomic-layer deposition must be tailored in order to prevent unwanted side effects such as defects, disorder and dewetting. In two directly related manuscripts written in parallel we use techniques described in this work to create depletion-mode quantum dots in intrinsic silicon, and low-disorder silicon quantum dots defined with palladium gates. While we discuss three different planar gate structures, the general principles also apply to 0D and 1D systems, such as self-assembled islands and nanowires.Comment: Accepted for publication in Nanotechnology. 31 pages, 12 figure

FreeMatch: Self-adaptive Thresholding for Semi-supervised Learning

Pseudo labeling and consistency regularization approaches based on confidencethresholding have made great progress in semi-supervised learning (SSL).However, we argue that existing methods might fail to adopt suitable thresholdssince they either use a pre-defined / fixed threshold or an ad-hoc thresholdadjusting scheme, resulting in inferior performance and slow convergence. Wefirst analyze a motivating example to achieve some intuitions on therelationship between the desirable threshold and model's learning status. Basedon the analysis, we hence propose FreeMatch to define and adjust the confidencethreshold in a self-adaptive manner according to the model's learning status.We further introduce a self-adaptive class fairness regularization penalty thatencourages the model to produce diverse predictions during the early stages oftraining. Extensive experimental results indicate the superiority of FreeMatchespecially when the labeled data are extremely rare. FreeMatch achieves 5.78%,13.59%, and 1.28% error rate reduction over the latest state-of-the-art methodFlexMatch on CIFAR-10 with 1 label per class, STL-10 with 4 labels per class,and ImageNet with 100 labels per class, respectively.<br

Small-molecule conversion of toxic oligomers to nontoxic β-sheet-rich amyloid fibrils

Several lines of evidence indicate that prefibrillar assemblies of amyloid-{beta} (A{beta}) polypeptides, such as soluble oligomers or protofibrils, rather than mature, end-stage amyloid fibrils cause neuronal dysfunction and memory impairment in Alzheimer's disease. These findings suggest that reducing the prevalence of transient intermediates by small molecule-mediated stimulation of amyloid polymerization might decrease toxicity. Here we demonstrate the acceleration of A{beta} fibrillogenesis through the action of the orcein-related small molecule O4, which directly binds to hydrophobic amino acid residues in A{beta} peptides and stabilizes the self-assembly of seeding-competent, {beta}-sheet-rich protofibrils and fibrils. Notably, the O4-mediated acceleration of amyloid fibril formation efficiently decreases the concentration of small, toxic A{beta} oligomers in complex, heterogeneous aggregation reactions. In addition, O4 treatment suppresses inhibition of long-term potentiation by A{beta} oligomers in hippocampal brain slices. These results support the hypothesis that small, diffusible prefibrillar amyloid species rather than mature fibrillar aggregates are toxic for mammalian cells

Antecedents and consequences of effectuation and causation in the international new venture creation process

The selection of the entry mode in an international market is of key importance for the venture. A process-based perspective on entry mode selection can add to the International Business and International Entrepreneurship literature. Framing the international market entry as an entrepreneurial process, this paper analyzes the antecedents and consequences of causation and effectuation in the entry mode selection. For the analysis, regression-based techniques were used on a sample of 65 gazelles. The results indicate that experienced entrepreneurs tend to apply effectuation rather than causation, while uncertainty does not have a systematic influence. Entrepreneurs using causation-based international new venture creation processes tend to engage in export-type entry modes, while effectuation-based international new venture creation processes do not predetermine the entry mod

Usefulness of C-reactive protein as a marker of early post-infarct left ventricular systolic dysfunction

Objective To assess the usefulness of in-hospital measurement of C-reactive protein (CRP) concentration in comparison to well-established risk factors as a marker of post-infarct left ventricular systolic dysfunction (LVSD) at discharge. Materials and methods Two hundred and four consecutive patients with ST-segment-elevation myocardial infarction (STEMI) were prospectively enrolled into the study. CRP plasma concentrations were measured before reperfusion, 24 h after admission and at discharge with an ultra-sensitive latex immunoassay. Results CRP concentration increased significantly during the first 24 h of hospitalization (2.4 ± 1.9 vs. 15.7 ± 17.0 mg/L; p\0.001) and persisted elevated at discharge (14.7 ± 14.7 mg/L), mainly in 57 patients with LVSD (2.4 ± 1.8 vs. 25.0 ± 23.4 mg/L; p\0.001; CRP at discharge 21.9 ± 18.6 mg/L). The prevalence of LVSD was significantly increased across increasing tertiles of CRP concentration both at 24 h after admission (13.2 vs. 19.1 vs. 51.5 %; p\0.0001) and at discharge (14.7 vs. 23.5 vs. 45.6 %; p\0.0001). Multivariate analysis demonstrated CRP concentration at discharge to be an independent marker of early LVSD (odds ratio of 1.38 for a 10 mg/L increase, 95 % confidence interval 1.01–1.87; p\0.04). Conclusion Measurement of CRP plasma concentration at discharge may be useful as a marker of early LVSD in patients after a first STEMI

Hyperfeatures - multilevel local coding for visual recognition

International audienceHistograms of local appearance descriptors are a popular representation for visual recognition. They are highly discriminant and have good resistance to local occlusions and to geometric and photometric variations, but they are not able to exploit spatial co-occurrence statistics at scales larger than their local input patches. We present a new multilevel visual representation, ‘hyperfeatures', that is designed to remedy this. The starting point is the familiar notion that to detect object parts, in practice it often suffices to detect co-occurrences of more local object fragments – a process that can be formalized as comparison (e.g. vector quantization) of image patches against a codebook of known fragments, followed by local aggregation of the resulting codebook membership vectors to detect co-occurrences. This process converts local collections of image descriptor vectors into somewhat less local histogram vectors – higher-level but spatially coarser descriptors. We observe that as the output is again a local descriptor vector, the process can be iterated, and that doing so captures and codes ever larger assemblies of object parts and increasingly abstract or ‘semantic' image properties. We formulate the hyperfeatures model and study its performance under several different image coding methods including clustering based Vector Quantization, Gaussian Mixtures, and combinations of these with Latent Dirichlet Allocation. We find that the resulting high-level features provide improved performance in several object image and texture image classification tasks