Evaluation of patients treated with natalizumab for progressive multifocal leukoencephalopathy

Background: Progressive multifocal leukoencephalopathy (PML) was reported to have developed in three patients treated with natalizumab. We conducted an evaluation to determine whether PML had developed in any other treated patients. Methods: We invited patients who had participated in clinical trials in which they received recent or long-term treatment with natalizumab for multiple sclerosis, Crohn's disease, or rheumatoid arthritis to participate. The clinical history, physical examination, brain magnetic resonance imaging (MRI), and testing of cerebrospinal fluid for JC virus DNA were used by an expert panel to evaluate patients for PML. We estimated the risk of PML in patients who completed at least a clinical examination for PML or had an MRI. Results: Of 3417 patients who had recently received natalizumab while participating in clinical trials, 3116 (91 percent) who were exposed to a mean of 17.9 monthly doses underwent evaluation for PML. Of these, 44 patients were referred to the expert panel because of clinical findings of possible PML, abnormalities on MRI, or a high plasma viral load of JC virus. No patient had detectable JC virus DNA in the cerebrospinal fluid. PML was ruled out in 43 of the 44 patients, but it could not be ruled out in one patient who had multiple sclerosis and progression of neurologic disease because data on cerebrospinal fluid testing and follow-up MRI were not available. Only the three previously reported cases of PML were confirmed (1.0 per 1000 treated patients; 95 percent confidence interval, 0.2 to 2.8 per 1000). Conclusions: A detailed review of possible cases of PML in patients exposed to natalizumab found no new cases and suggested a risk of PML of roughly 1 in 1000 patients treated with natalizumab for a mean of 17.9 months. The risk associated with longer treatment is not known

Orbitopal Fixing

The topic of this paper are integer programming models in which a subset of 0/1-variables encode a partitioning of a set of objects into disjoint subsets. Such models can be surprisingly hard to solve by branch-and-cut algorithms if the order of the subsets of the partition is irrelevant, since this kind of symmetry unnecessarily blows up the search tree. We present a general tool, called orbitopal fixing, for enhancing the capabilities of branch-and-cut algorithms in solving such symmetric integer programming models. We devise a linear time algorithm that, applied at each node of the search tree, removes redundant parts of the tree produced by the above mentioned symmetry. The method relies on certain polyhedra, called orbitopes, which have been introduced bei Kaibel and Pfetsch (Math. Programm. A, 114 (2008), 1-36). It does, however, not explicitly add inequalities to the model. Instead, it uses certain fixing rules for variables. We demonstrate the computational power of orbitopal fixing at the example of a graph partitioning problem.Comment: 22 pages, revised and extended version of a previous version that has appeared under the same title in Proc. IPCO 200

A hybrid constraint programming and semidefinite programming approach for the stable set problem

This work presents a hybrid approach to solve the maximum stable set problem, using constraint and semidefinite programming. The approach consists of two steps: subproblem generation and subproblem solution. First we rank the variable domain values, based on the solution of a semidefinite relaxation. Using this ranking, we generate the most promising subproblems first, by exploring a search tree using a limited discrepancy strategy. Then the subproblems are being solved using a constraint programming solver. To strengthen the semidefinite relaxation, we propose to infer additional constraints from the discrepancy structure. Computational results show that the semidefinite relaxation is very informative, since solutions of good quality are found in the first subproblems, or optimality is proven immediately.Comment: 14 page

Cracking the code of oscillatory activity

Neural oscillations are ubiquitous measurements of cognitive processes and dynamic routing and gating of information. The fundamental and so far unresolved problem for neuroscience remains to understand how oscillatory activity in the brain codes information for human cognition. In a biologically relevant cognitive task, we instructed six human observers to categorize facial expressions of emotion while we measured the observers' EEG. We combined state-of-the-art stimulus control with statistical information theory analysis to quantify how the three parameters of oscillations (i.e., power, phase, and frequency) code the visual information relevant for behavior in a cognitive task. We make three points: First, we demonstrate that phase codes considerably more information (2.4 times) relating to the cognitive task than power. Second, we show that the conjunction of power and phase coding reflects detailed visual features relevant for behavioral response-that is, features of facial expressions predicted by behavior. Third, we demonstrate, in analogy to communication technology, that oscillatory frequencies in the brain multiplex the coding of visual features, increasing coding capacity. Together, our findings about the fundamental coding properties of neural oscillations will redirect the research agenda in neuroscience by establishing the differential role of frequency, phase, and amplitude in coding behaviorally relevant information in the brai

The detection of temporally defined objects does not require focused attention.

Perceptual grouping is crucial to distinguish objects from their background. Recent studies have shown that observers can detect an object that does not have any unique qualities other than unique temporal properties. A crucial question is whether focused attention is needed for this type of grouping. In two visual search experiments, we show that searching for an object defined by temporal grouping can occur in parallel. These findings suggest that focused attention is not needed for temporal grouping to occur. It is proposed that temporal grouping may occur because the neurons representing the changing object elements adopt firing frequencies that cause the visual system to bind these elements together without the need for focused attention. © 2008 The Experimental Psychology Society

Configurational asymmetry in vernier offset detection

Two psychophysical experiments were conducted at the horizontal and vertical orientations respectively, demonstrating substantial main effect of configuration, but no effect of offset direction on vernier acuity. In Experiment 1, a pair of horizontal bars were arranged side by side with a large gap between them. The observers were, on average, significantly better at discriminating a vertical offset if the right-hand bar was below the left-hand bar than vice versa, regardless of which bar they experienced as displaced and which as constant. A similar asymmetry was evident in Experiment 2 where observers judged horizontal offset for a pair of vertically oriented bars, where one was placed above the other. In this case average performance was better if the upper bar was on the right of the lower bar rather than on its left. There were large individual variations in the asymmetrical trend, but the effect could not be explained by subjective response bias. Furthermore, vernier acuity improved significantly and the asymmetry decreased more or less as a function of training. The average asymmetrical trend was consistent across training days and across two orientations, which indicates that the processing of line vernier stimuli is possibly configuration-specific in the cardinal orientation

The N2pc Is Increased by Perceptual Learning but Is Unnecessary for the Transfer of Learning

Background: Practice improves human performance in many psychophysical paradigms. This kind of improvement is thought to be the evidence of human brain plasticity. However, the changes that occur in the brain are not fully understood. Methodology/Principal Findings: The N2pc component has previously been associated with visuo-spatial attention. In this study, we used event-related potentials (ERPs) to investigate whether the N2pc component changed during long-term visual perceptual learning. Thirteen subjects completed several days of training in an orientation discrimination task, and were given a final test 30 days later. The results showed that behavioral thresholds significantly decreased across training sessions, and this decrement was also present in the untrained visual field. ERPs showed training significantly increased the N2pc amplitude, and this effect could be maintained for up to 30 days. However, the increase in N2pc was specific to the trained visual field. Conclusion/Significance: Training caused spatial attention to be increasingly focused on the target positions. However, this process was not transferrable from the trained to the untrained visual field, which suggests that the increase in N2pc ma

Enhanced Memory for Scenes Presented at Behaviorally Relevant Points in Time

What determines whether a scene is remembered or forgotten? Our results show how visual scenes are encoded into memory at behaviorally relevant points in time

The Spatial Origin of a Perceptual Transition in Binocular Rivalry

When the left and the right eye are simultaneously presented with incompatible images at overlapping retinal locations, an observer typically reports perceiving only one of the two images at a time. This phenomenon is called binocular rivalry. Perception during binocular rivalry is not stable; one of the images is perceptually dominant for a certain duration (typically in the order of a few seconds) after which perception switches towards the other image. This alternation between perceptual dominance and suppression will continue for as long the images are presented. A characteristic of binocular rivalry is that a perceptual transition from one image to the other generally occurs in a gradual manner: the image that was temporarily suppressed will regain perceptual dominance at isolated locations within the perceived image, after which its visibility spreads throughout the whole image. These gradual transitions from perceptual suppression to perceptual dominance have been labeled as traveling waves of perceptual dominance. In this study we investigate whether stimulus parameters affect the location at which a traveling wave starts. We varied the contrast, spatial frequency or motion speed in one of the rivaling images, while keeping the same parameter constant in the other image. We used a flash-suppression paradigm to force one of the rival images into perceptual suppression. Observers waited until the suppressed image became perceptually dominant again, and indicated the position at which this breakthrough from suppression occurred. Our results show that the starting point of a traveling wave during binocular rivalry is highly dependent on local stimulus parameters. More specifically, a traveling wave most likely started at the location where the contrast of the suppressed image was higher than that of the dominant one, the spatial frequency of the suppressed image was lower than that of the dominant one, and the motion speed of the suppressed image was higher than that of the dominant one. We suggest that a breakthrough from suppression to dominance occurs at the location where salience (the degree to which a stimulus element stands out relative to neighboring elements) of the suppressed image is higher than that of the dominant one. Our results further show that stimulus parameters affecting the temporal dynamics during continuous viewing of rival images described in other studies, also affect the spatial origin of traveling waves during binocular rivalry

Short-Term Compassion Training Increases Prosocial Behavior in a Newly Developed Prosocial Game

Compassion has been suggested to be a strong motivator for prosocial behavior. While research has demonstrated that compassion training has positive effects on mood and health, we do not know whether it also leads to increases in prosocial behavior. We addressed this question in two experiments. In Experiment 1, we introduce a new prosocial game, the Zurich Prosocial Game (ZPG), which allows for repeated, ecologically valid assessment of prosocial behavior and is sensitive to the influence of reciprocity, helping cost, and distress cues on helping behavior. Experiment 2 shows that helping behavior in the ZPG increased in participants who had received short-term compassion training, but not in participants who had received short-term memory training. Interindividual differences in practice duration were specifically related to changes in the amount of helping under no-reciprocity conditions. Our results provide first evidence for the positive impact of short-term compassion training on prosocial behavior towards strangers in a training-unrelated task