1,011 research outputs found

    The development of an automated sentence generator for the assessment of reading speed

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    Reading speed is an important outcome measure for many studies in neuroscience and psychology. Conventional reading speed tests have a limited corpus of sentences and usually require observers to read sentences aloud. Here we describe an automated sentence generator which can create over 100,000 unique sentences, scored using a true/false response. We propose that an estimate of the minimum exposure time required for observers to categorise the truth of such sentences is a good alternative to reading speed measures that guarantees comprehension of the printed material. Removing one word from the sentence reduces performance to chance, indicating minimal redundancy. Reading speed assessed using rapid serial visual presentation (RSVP) of these sentences is not statistically different from using MNREAD sentences. The automated sentence generator would be useful for measuring reading speed with button-press response (such as within MRI scanners) and for studies requiring many repeated measures of reading speed

    Maternal obesity has little effect on the immediate offspring but impacts on the next generation

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    Maternal obesity during pregnancy has been linked to an increased risk of obesity and cardiometabolic disease in the offspring, a phenomenon attributed to developmental programming. Programming effects may be transmissible across generations through both maternal and paternal inheritance, although the mechanisms remain unclear. Using a mouse model, we explored the effects of moderate maternal diet-induced obesity (DIO) on weight gain and glucose-insulin homeostasis in first-generation (F1) and second-generation offspring. DIO was associated with insulin resistance, hyperglycemia and dyslipidemia before pregnancy. Birth weight was reduced in female offspring of DIO mothers (by 6%, P = .039), and DIO offspring were heavier than controls at weaning (males by 47%, females by 27%), however there were no differences in glucose tolerance, plasma lipids, or hepatic gene expression at 6 months. Despite the relative lack of effects in the F1, we found clear fetal growth restriction and persistent metabolic changes in otherwise unmanipulated second-generation offspring with effects on birth weight, insulin levels, and hepatic gene expression that were transmitted through both maternal and paternal lines. This suggests that the consequences of the current dietary obesity epidemic may also have an impact on the descendants of obese individuals, even when the phenotype of the F1 appears largely unaffected

    Visual population receptive fields in people with schizophrenia have reduced inhibitory surrounds

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    People with schizophrenia (SZ) experience abnormal visual perception on a range of visual tasks, which have been linked to abnormal synaptic transmission and an imbalance between cortical excitation and inhibition. However differences in the underlying architecture of visual cortex neurons, which might explain these visual anomalies, have yet to be reported in vivo. Here, we probe the neural basis of these deficits by using functional MRI (fMRI) and population receptive field (pRF) mapping to infer properties of visually responsive neurons in people with SZ. We employed a Difference-of-Gaussian (DoG) model to capture the centre-surround configuration of the pRF, providing critical information about the spatial scale of the pRFs inhibitory surround. Our analysis reveals that SZ is associated with reduced pRF size in early retinotopic visual cortex as well as a reduction in size and depth of the inhibitory surround in V1, V2 and V4. We consider how reduced inhibition might explain the diverse range of visual deficits reported in SZ. SIGNIFICANCE STATEMENT: People with schizophrenia (SZ) experience abnormal perception on a range of visual tasks, which has been linked to abnormal synaptic transmission and an imbalance between cortical excitation/inhibition. However associated differences in the underlying architecture of visual cortex neurons have yet to be reported in vivo. We used fMRI and population receptive field (pRF) mapping to demonstrate that the fine-grained functional architecture of visual cortex in people with SZ differs from unaffected controls. SZ is associated with reduced pRF size in early retinotopic visual cortex, largely due to reduced inhibitory surrounds. An imbalance between cortical excitation and inhibition could drive such a change in the centre-surround pRF configuration, and ultimately explain the range of visual deficits experienced in SZ

    Forecast or Fall: Prediction's Importance to Postural Control

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    To interact successfully with an uncertain environment, organisms must be able to respond to both unanticipated and anticipated events. For unanticipated events, organisms have evolved stereotyped motor behaviors mapped to the statistical regularities of the environment, which can be trigged by specific sensory stimuli. These “reflexive” responses are more or less hardwired to prevent falls and represent, maybe, the best available solution to maintaining posture given limited available time and information. With the gift of foresight, however, motor behaviors can be tuned or prepared in advance, improving the ability of the organism to compensate for, and interact with, the changing environment. Indeed, foresight's improvement of our interactive capacity occurs through several means, such as better action selection, processing, and conduction delay compensation and by providing a prediction with which to compare our actual behaviors to, thereby facilitating error identification and learning. Here we review the various roles foresight (prediction) plays in maintaining our postural equilibrium. We start by describing some of the more recent findings related to the prediction of instability. Specifically, we cover recent advancements in the understanding of anticipatory postural behaviors that are used broadly to stabilize volitional movement and compensate for impending postural disturbances. We also describe anticipatory changes in the state, or set, of the nervous system that may facilitate anticipatory behaviors. From changes in central set, we briefly discuss prediction of postural instability online before moving into a discussion of how predictive mechanisms, such as internal models, permit us to tune, perhaps our highest level predictive behaviors, namely the priming associated with motor affordances. Lastly, we explore methods best suited to expose the contribution of prediction to postural equilibrium control across a variety of contexts

    Reducing in-stent restenosis therapeutic manipulation of miRNA in vascular remodeling and inflammation

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    Background: Drug-eluting stents reduce the incidence of in-stent restenosis, but they result in delayed arterial healing and are associated with a chronic inflammatory response and hypersensitivity reactions. Identifying novel interventions to enhance wound healing and reduce the inflammatory response may improve long-term clinical outcomes. Micro–ribonucleic acids (miRNAs) are noncoding small ribonucleic acids that play a prominent role in the initiation and resolution of inflammation after vascular injury.<p></p> Objectives: This study sought to identify miRNA regulation and function after implantation of bare-metal and drug-eluting stents.<p></p> Methods: Pig, mouse, and in vitro models were used to investigate the role of miRNA in in-stent restenosis.<p></p> Results: We documented a subset of inflammatory miRNAs activated after stenting in pigs, including the miR-21 stem loop miRNAs. Genetic ablation of the miR-21 stem loop attenuated neointimal formation in mice post-stenting. This occurred via enhanced levels of anti-inflammatory M2 macrophages coupled with an impaired sensitivity of smooth muscle cells to respond to vascular activation.<p></p> Conclusions: MiR-21 plays a prominent role in promoting vascular inflammation and remodeling after stent injury. MiRNA-mediated modulation of the inflammatory response post-stenting may have therapeutic potential to accelerate wound healing and enhance the clinical efficacy of stenting

    On the Creation of Acceptable Conjoint Analysis Experimental Designs

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    Conjoint analysis studies typically utilize orthogonal fractional factorial experimental designs to construct a set of hypothetical stimuli. Occasionally, these designs include environmentally correlated attributes that can lead to stimulus profiles that are not representative of the subject's environment. To date, no one has proposed a remedy well-grounded in statistical theory. This note presents a new methodology utilizing combinatorial optimization procedures for creating modified fractional factorial designs that are as “orthogonal” as possible, which do not contain nonrepresentative stimulus profiles.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72641/1/j.1540-5915.1991.tb00357.x.pd

    Nucleon-Nucleon Scattering under Spin-Isospin Reversal in Large-N_c QCD

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    The spin-flavor structure of certain nucleon-nucleon scattering observables derived from the large N_c limit of QCD in the kinematical regime where time-dependent mean-field theory is valid is discussed. In previous work, this regime was taken to be where the external momentum was of order N_c which precluded the study of differential cross sections in elastic scattering. Here it is shown that the regime extends down to order N_c^{1/2} which includes the higher end of the elastic regime. The prediction is that in the large N_c limit, observables describable via mean-field theory are unchanged when the spin and isospin of either nucleon are both flipped. This prediction is tested for proton-proton and neutron-proton elastic scattering data and found to fail badly. We argue that this failure can be traced to a lack of a clear separation of scales between momentum of order N_c^{1/2} and N_c^1 when N_c is as small as three. The situation is compounded by an anomalously low particle production threshold due to approximate chiral symmetry.Comment: 5 pages, 1 figur

    Macrophage Sub-Populations and the Lipoxin A4 Receptor Implicate Active Inflammation during Equine Tendon Repair

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    Macrophages (Mϕ) orchestrate inflammatory and reparatory processes in injured connective tissues but their role during different phases of tendon healing is not known. We investigated the contribution of different Mϕ subsets in an equine model of naturally occurring tendon injury. Post mortem tissues were harvested from normal (uninjured), sub-acute (3–6 weeks post injury) and chronically injured (>3 months post injury) superficial digital flexor tendons. To determine if inflammation was present in injured tendons, Mϕ sub-populations were quantified based on surface antigen expression of CD172a (pan Mϕ), CD14highCD206low (pro-inflammatory M1Mϕ), and CD206high (anti-inflammatory M2Mϕ) to assess potential polarised phenotypes. In addition, the Lipoxin A4 receptor (FPR2/ALX) was used as marker for resolving inflammation. Normal tendons were negative for both Mϕ and FPR2/ALX. In contrast, M1Mϕ predominated in sub-acute injury, whereas a potential phenotype-switch to M2Mϕ polarity was seen in chronic injury. Furthermore, FPR2/ALX expression by tenocytes was significantly upregulated in sub-acute but not chronic injury. Expression of the FPR2/ALX ligand Annexin A1 was also significantly increased in sub-acute and chronic injuries in contrast to low level expression in normal tendons. The combination of reduced FPR2/ALX expression and persistence of the M2Mϕ phenotype in chronic injury suggests a potential mechanism for incomplete resolution of inflammation after tendon injury. To investigate the effect of pro-inflammatory mediators on lipoxin A4 (LXA4) production and FPR2/ALX expression in vitro, normal tendon explants were stimulated with interleukin-1 beta and prostaglandin E2. Stimulation with either mediator induced LXA4 release and maximal upregulation of FPR2/ALX expression after 72 hours. Taken together, our data suggests that although tenocytes are capable of mounting a protective mechanism to counteract inflammatory stimuli, this appears to be of insufficient duration and magnitude in natural tendon injury, which may potentiate chronic inflammation and fibrotic repair, as indicated by the presence of M2Mϕ

    Excited Baryon Decay Widths in Large N_c QCD

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    We study excited baryon decay widths in large N_c QCD. It was suggested previously that some spin-flavor mixed-symmetric baryon states have strong couplings of O(N_c^{-1/2}) to nucleons [implying narrow widths of O(1/N_c)], as opposed to the generic expectation based on Witten's counting rules of an O(N_c^0) coupling. The calculation obtaining these narrow widths was performed in the context of a simple quark-shell model. This paper addresses the question of whether the existence of such narrow states is a general property of large N_c QCD. We show that a general large N_c QCD analysis does not predict such narrow states; rather they are a consequence of the extreme simplicity of the quark model.Comment: 9 page
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