Zebrafish are gaining momentum as a laboratory animal species for the study of anxiety-related disorders in translational research, whereby they serve a fundamental complement to laboratory rodents. Several anxiety-related behavioral paradigms, which rest upon the presentation of live predatorial stimuli, may yield inconsistent results due to fatigue, habituation, or idiosyncratic responses exhibited by the stimulus itself. To overcome these limitations, we designed and manufactured a fully controllable robot inspired by a natural aquatic predator (Indian leaf fish, Nandus nandus) of zebrafish. We report that this robot elicits aversive antipredatorial reactions in a preference test and that data obtained therein correlate with data observed in traditional anxiety- and fear-related tests (light/dark preference and shelter-seeking). Finally, ethanol administration (0.25; 0.50; 1.00%) exerts anxiolytic effects, thus supporting the view that robotic stimuli can be used in the analysis of anxiety-related behaviors in zebrafish.
- Proceedings of the National Academy of Sciences of the United States of America
- Published almost 3 years ago
Floating oil, plastics, and marine organisms are continually redistributed by ocean surface currents. Prediction of their resulting distribution on the surface is a fundamental, long-standing, and practically important problem. The dominant paradigm is dispersion within the dynamical context of a nondivergent flow: objects initially close together will on average spread apart but the area of surface patches of material does not change. Although this paradigm is likely valid at mesoscales, larger than 100 km in horizontal scale, recent theoretical studies of submesoscales (less than ∼10 km) predict strong surface convergences and downwelling associated with horizontal density fronts and cyclonic vortices. Here we show that such structures can dramatically concentrate floating material. More than half of an array of ∼200 surface drifters covering ∼20 × 20 km2 converged into a 60 × 60 m region within a week, a factor of more than 105 decrease in area, before slowly dispersing. As predicted, the convergence occurred at density fronts and with cyclonic vorticity. A zipperlike structure may play an important role. Cyclonic vorticity and vertical velocity reached 0.001 s-1 and 0.01 ms-1, respectively, which is much larger than usually inferred. This suggests a paradigm in which nearby objects form submesoscale clusters, and these clusters then spread apart. Together, these effects set both the overall extent and the finescale texture of a patch of floating material. Material concentrated at submesoscale convergences can create unique communities of organisms, amplify impacts of toxic material, and create opportunities to more efficiently recover such material.
- Quarterly journal of experimental psychology (2006)
- Published almost 8 years ago
Remembering to perform deferred actions when an event is encountered in the future is referred to as event-based prospective memory (PM). We examined whether the failure of individuals to allocate sufficient attentional resources to nonfocal PM tasks can be linked to the response demands inherent in PM paradigms that require the PM task to race for response selection with the speeded ongoing task. In three experiments, participants performed a lexical decision task while being required to make a separate PM response to a specific word (focal), an exemplar of a category (nonfocal), or a syllable (nonfocal). We manipulated the earliest time participants could make task responses by presenting a tone at varying onsets (0-1,600 ms) following stimulus presentation. Improvements in focal PM and nonfocal PM were observed at response delays as brief as 200 ms and 400 ms, respectively. Nonfocal PM accuracy was comparable to focal PM accuracy at delays of 600 ms and 1,600 ms for categorical targets and syllable targets, respectively. Delaying task responses freed the resource-demanding processing operations used on the ongoing task for use on the nonfocal PM task, increasing the probability that the nonfocal PM features of ongoing task stimuli were adequately assessed prior to the ongoing task response.
New paradigms in mantle cell lymphoma: is it time to risk-stratify treatment based on the proliferative signature?
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Published about 6 years ago
The elucidation of crucial biologic pathways of cell survival and proliferation has led to the development of highly effective drugs, some of which have markedly improved mantle cell lymphoma (MCL) therapeutic opportunities in the past 10 years. Moreover, an undeniable clinical heterogeneity in treatment response and disease behavior has become apparent in this neoplasm. Thus, the need for biologic markers stratifying patients with MCL in risk classes deserving different treatment approaches has recently been fervently expressed. Among several newly discovered biomarkers, the dismal predictive value of a high proliferative signature has been broadly recognized in large studies of patients with MCL. Different techniques have been used to assess tumor cell proliferation, including mitotic index, immunostaining with Ki-67 antibody, and gene expression profiling. Ki-67 proliferative index, in particular, has been extensively investigated, and its negative impact on relapse incidence and overall survival has been validated in large prospective clinical trials. However, one important pitfall limiting its widespread use in clinical practice is the reported interobserver variability, due to the previous lack of a standardized approach for quantification among different laboratories. In the present review, we describe some of the major techniques to assess cell proliferation in MCL, focusing in particular on the Ki-67 index and its need for a standardized approach to be used in multicenter clinical trials. The value of MCL biologic prognostic scores (as MIPI-b) is discussed, along with our proposal on how to integrate these scores in the planning of future trials investigating a tailored therapeutic approach for patients with MCL. See all articles in this CCR Focus section, “Paradigm Shifts in Lymphoma.” Clin Cancer Res; 20(20); 5194-206. ©2014 AACR.
Priming reflects an important means of learning that is mediated by implicit memory. Importantly, priming occurs for previously viewed objects (item-specific priming) and their category relatives (category-wide priming). Two distinct neural mechanisms are known to mediate priming, including the sharpening of a neural object representation and the retrieval of stimulus-response mappings. Here, we investigated whether the relationship between these neural mechanisms could help explain why item-specific priming generates faster responses than category-wide priming. Participants studied pictures of everyday objects, and then performed a difficult picture identification task while we recorded event-related potentials (ERP). The identification task gradually revealed random line segments of previously viewed items (Studied), category exemplars of previously viewed items (Exemplar), and items that were not previously viewed (Unstudied). Studied items were identified sooner than Unstudied items, showing evidence of item-specific priming, and importantly Exemplar items were also identified sooner than Unstudied items, showing evidence of category-wide priming. Early activity showed sustained neural suppression of parietal activity for both types of priming. However, these neural suppression effects may have stemmed from distinct processes because while category-wide neural suppression was correlated with priming behavior, item-specific neural suppression was not. Late activity, examined with response-locked ERPs, showed additional processes related to item-specific priming including neural suppression in occipital areas and parietal activity that was correlated with behavior. Together, we conclude that item-specific and category-wide priming are mediated by separate, parallel neural mechanisms in the context of the current paradigm. Temporal differences in behavior are determined by the timecourses of these distinct processes.
Psychiatry as science is underpinned by paradigms. Considering whether a social paradigm may help to advance the current state of psychiatry, the review provides a reference to the rich, but fragmented past of related initiatives in the history of psychiatry and a personal view of themes, challenges and perspectives of using a social paradigm in psychiatry.
For decades, the dominant paradigm for studying decision making-the expected utility framework-has been burdened by an increasing number of empirical findings that question its validity as a model of human cognition and behavior. However, as Kuhn (1962) argued in his seminal discussion of paradigm shifts, an old paradigm cannot be abandoned until a new paradigm emerges to replace it. In this article, we argue that the recent shift in researcher attention toward basic cognitive processes that give rise to decision phenomena constitutes the beginning of that replacement paradigm. Models grounded in basic perceptual, attentional, memory, and aggregation processes have begun to proliferate. The development of this new approach closely aligns with Kuhn’s notion of paradigm shift, suggesting that this is a particularly generative and revolutionary time to be studying decision science.
Reinstatement of dynamic memories requires the replay of neural patterns that unfold over time in a similar manner as during perception. However, little is known about the mechanisms that guide such a temporally structured replay in humans, because previous studies used either unsuitable methods or paradigms to address this question. Here, we overcome these limitations by developing a new analysis method to detect the replay of temporal patterns in a paradigm that requires participants to mentally replay short sound or video clips. We show that memory reinstatement is accompanied by a decrease of low-frequency (8 Hz) power, which carries a temporal phase signature of the replayed stimulus. These replay effects were evident in the visual as well as in the auditory domain and were localized to sensory-specific regions. These results suggest low-frequency phase to be a domain-general mechanism that orchestrates dynamic memory replay in humans.
The concept of patient engagement in health research has received growing international recognition over recent years. Yet despite some critical advancements, we argue that the concept remains problematic as it negates the very real complexities and context of people’s lives. Though patient engagement conceptually begins to disrupt the identity of “researcher,” and complicate our assumptions and understandings around expertise and knowledge, it continues to essentialize the identity of “patient” as a homogenous group, denying the reality that individuals' economic, political, cultural, subjective and experiential lives intersect in intricate and multifarious ways.