141 research outputs found

    Random walks on randomly evolving graphs

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    A random walk is a basic stochastic process on graphs and a key primitive in the design of distributed algorithms. One of the most important features of random walks is that, under mild conditions, they converge to a stationary distribution in time that is at most polynomial in the size of the graph. This fundamental property, however, only holds if the graph does not change over time; on the other hand, many distributed networks are inherently dynamic, and their topology is subjected to potentially drastic changes. In this work we study the mixing (i.e., convergence) properties of random walks on graphs subjected to random changes over time. Specifically, we consider the edge-Markovian random graph model: for each edge slot, there is a two-state Markov chain with transition probabilities p (add a non-existing edge) and q (remove an existing edge). We derive several positive and negative results that depend on both the density of the graph and the speed by which the graph changes

    Equity In Health care financing in low-and middle-income countries: A systematic review of evidence from studies using benefit and financing incidence analyses

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    © 2016 Asante et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Introduction: Health financing reforms in low-and middle-income countries (LMICs) over the past decades have focused on achieving equity in financing of health care delivery through universal health coverage. Benefit and financing incidence analyses are two analytical methods for comprehensively evaluating how well health systems perform on these objectives. This systematic review assesses progress towards equity in health care financing in LMICs through the use of BIA and FIA. Methods and Findings: Key electronic databases including Medline, Embase, Scopus, Global Health, CinAHL, EconLit and Business Source Premier were searched. We also searched the grey literature, specifically websites of leading organizations supporting health care in LMICs. Only studies using benefit incidence analysis (BIA) and/or financing incidence analysis (FIA) as explicit methodology were included. A total of 512 records were obtained from the various sources. The full texts of 87 references were assessed against the selection criteria and 24 were judged appropriate for inclusion. Twelve of the 24 studies originated from sub-Saharan Africa, nine from the Asia-Pacific region, two from Latin America and one from the Middle East. The evidence points to a pro-rich distribution of total health care benefits and progressive financing in both sub-Saharan Africa and Asia-Pacific. In the majority of cases, the distribution of benefits at the primary health care level favoured the poor while hospital level services benefit the better-off. A few Asian countries, namely Thailand, Malaysia and Sri Lanka, maintained a pro-poor distribution of health care benefits and progressive financing. Conclusion: Studies evaluated in this systematic review indicate that health care financing in LMICs benefits the rich more than the poor but the burden of financing also falls more on the rich. There is some evidence that primary health care is pro-poor suggesting a greater investment in such services and removal of barriers to care can enhance equity. The results overall suggest that there are impediments to making health care more accessible to the poor and this must be addressed if universal health coverage is to be a reality

    Protection from Experimental Cerebral Malaria with a Single Dose of Radiation-Attenuated, Blood-Stage Plasmodium berghei Parasites

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    BACKGROUND: Whole malaria parasites are highly effective in inducing immunity against malaria. Due to the limited success of subunit based vaccines in clinical studies, there has been a renewed interest in whole parasite-based malaria vaccines. Apart from attenuated sporozoites, there have also been efforts to use live asexual stage parasites as vaccine immunogens. METHODOLOGY AND RESULTS: We used radiation exposure to attenuate the highly virulent asexual blood stages of the murine malaria parasite P. berghei to a non-replicable, avirulent form. We tested the ability of the attenuated blood stage parasites to induce immunity to parasitemia and the symptoms of severe malaria disease. Depending on the mouse genetic background, a single high dose immunization without adjuvant protected mice from parasitemia and severe disease (CD1 mice) or from experimental cerebral malaria (ECM) (C57BL/6 mice). A low dose immunization did not protect against parasitemia or severe disease in either model after one or two immunizations. The protection from ECM was associated with a parasite specific antibody response and also with a lower level of splenic parasite-specific IFN-γ production, which is a mediator of ECM pathology in C57BL/6 mice. Surprisingly, there was no difference in the sequestration of CD8+ T cells and CD45+ CD11b+ macrophages in the brains of immunized, ECM-protected mice. CONCLUSIONS: This report further demonstrates the effectiveness of a whole parasite blood-stage vaccine in inducing immunity to malaria and explicitly demonstrates its effectiveness against ECM, the most pathogenic consequence of malaria infection. This experimental model will be important to explore the formulation of whole parasite blood-stage vaccines against malaria and to investigate the immune mechanisms that mediate protection against parasitemia and cerebral malaria

    A Common Anterior Insula Representation of Disgust Observation, Experience and Imagination Shows Divergent Functional Connectivity Pathways

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    Similar brain regions are involved when we imagine, observe and execute an action. Is the same true for emotions? Here, the same subjects were scanned while they (a) experience, (b) view someone else experiencing and (c) imagine experiencing gustatory emotions (through script-driven imagery). Capitalizing on the fact that disgust is repeatedly inducible within the scanner environment, we scanned the same participants while they (a) view actors taste the content of a cup and look disgusted (b) tasted unpleasant bitter liquids to induce disgust, and (c) read and imagine scenarios involving disgust and their neutral counterparts. To reduce habituation, we inter-mixed trials of positive emotions in all three scanning experiments. We found voxels in the anterior Insula and adjacent frontal operculum to be involved in all three modalities of disgust, suggesting that simulation in the context of social perception and mental imagery of disgust share a common neural substrates. Using effective connectivity, this shared region however was found to be embedded in distinct functional circuits during the three modalities, suggesting why observing, imagining and experiencing an emotion feels so different

    Interoception in anxiety and depression

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    We review the literature on interoception as it relates to depression and anxiety, with a focus on belief, and alliesthesia. The connection between increased but noisy afferent interoceptive input, self-referential and belief-based states, and top-down modulation of poorly predictive signals is integrated into a neuroanatomical and processing model for depression and anxiety. The advantage of this conceptualization is the ability to specifically examine the interface between basic interoception, self-referential belief-based states, and enhanced top-down modulation to attenuate poor predictability. We conclude that depression and anxiety are not simply interoceptive disorders but are altered interoceptive states as a consequence of noisily amplified self-referential interoceptive predictive belief states

    Risky Decisions and Their Consequences: Neural Processing by Boys with Antisocial Substance Disorder

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    Adolescents with conduct and substance problems ("Antisocial Substance Disorder" (ASD)) repeatedly engage in risky antisocial and drug-using behaviors. We hypothesized that, during processing of risky decisions and resulting rewards and punishments, brain activation would differ between abstinent ASD boys and comparison boys.We compared 20 abstinent adolescent male patients in treatment for ASD with 20 community controls, examining rapid event-related blood-oxygen-level-dependent (BOLD) responses during functional magnetic resonance imaging. In 90 decision trials participants chose to make either a cautious response that earned one cent, or a risky response that would either gain 5 cents or lose 10 cents; odds of losing increased as the game progressed. We also examined those times when subjects experienced wins, or separately losses, from their risky choices. We contrasted decision trials against very similar comparison trials requiring no decisions, using whole-brain BOLD-response analyses of group differences, corrected for multiple comparisons. During decision-making ASD boys showed hypoactivation in numerous brain regions robustly activated by controls, including orbitofrontal and dorsolateral prefrontal cortices, anterior cingulate, basal ganglia, insula, amygdala, hippocampus, and cerebellum. While experiencing wins, ASD boys had significantly less activity than controls in anterior cingulate, temporal regions, and cerebellum, with more activity nowhere. During losses ASD boys had significantly more activity than controls in orbitofrontal cortex, dorsolateral prefrontal cortex, brain stem, and cerebellum, with less activity nowhere.Adolescent boys with ASD had extensive neural hypoactivity during risky decision-making, coupled with decreased activity during reward and increased activity during loss. These neural patterns may underlie the dangerous, excessive, sustained risk-taking of such boys. The findings suggest that the dysphoria, reward insensitivity, and suppressed neural activity observed among older addicted persons also characterize youths early in the development of substance use disorders

    The Neuronal Correlates of Digits Backward Are Revealed by Voxel-Based Morphometry and Resting-State Functional Connectivity Analyses

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    Digits backward (DB) is a widely used neuropsychological measure that is believed to be a simple and effective index of the capacity of the verbal working memory. However, its neural correlates remain elusive. The aim of this study is to investigate the neural correlates of DB in 299 healthy young adults by combining voxel-based morphometry (VBM) and resting-state functional connectivity (rsFC) analyses. The VBM analysis showed positive correlations between the DB scores and the gray matter volumes in the right anterior superior temporal gyrus (STG), the right posterior STG, the left inferior frontal gyrus and the left Rolandic operculum, which are four critical areas in the auditory phonological loop of the verbal working memory. Voxel-based correlation analysis was then performed between the positive rsFCs of these four clusters and the DB scores. We found that the DB scores were positively correlated with the rsFCs within the salience network (SN), that is, between the right anterior STG, the dorsal anterior cingulate cortex and the right fronto-insular cortex. We also found that the DB scores were negatively correlated with the rsFC within an anti-correlation network of the SN, between the right posterior STG and the left posterior insula. Our findings suggest that DB performance is related to the structural and functional organizations of the brain areas that are involved in the auditory phonological loop and the SN

    The Golden Beauty: Brain Response to Classical and Renaissance Sculptures

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    Is there an objective, biological basis for the experience of beauty in art? Or is aesthetic experience entirely subjective? Using fMRI technique, we addressed this question by presenting viewers, naïve to art criticism, with images of masterpieces of Classical and Renaissance sculpture. Employing proportion as the independent variable, we produced two sets of stimuli: one composed of images of original sculptures; the other of a modified version of the same images. The stimuli were presented in three conditions: observation, aesthetic judgment, and proportion judgment. In the observation condition, the viewers were required to observe the images with the same mind-set as if they were in a museum. In the other two conditions they were required to give an aesthetic or proportion judgment on the same images. Two types of analyses were carried out: one which contrasted brain response to the canonical and the modified sculptures, and one which contrasted beautiful vs. ugly sculptures as judged by each volunteer. The most striking result was that the observation of original sculptures, relative to the modified ones, produced activation of the right insula as well as of some lateral and medial cortical areas (lateral occipital gyrus, precuneus and prefrontal areas). The activation of the insula was particularly strong during the observation condition. Most interestingly, when volunteers were required to give an overt aesthetic judgment, the images judged as beautiful selectively activated the right amygdala, relative to those judged as ugly. We conclude that, in observers naïve to art criticism, the sense of beauty is mediated by two non-mutually exclusive processes: one based on a joint activation of sets of cortical neurons, triggered by parameters intrinsic to the stimuli, and the insula (objective beauty); the other based on the activation of the amygdala, driven by one's own emotional experiences (subjective beauty)

    Steroids in kidney transplant patients

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    Any evaluation of steroids in kidney transplantation is hampered by individual variability in metabolism, the lack of clinically available steroid blood levels, and overall little attention to steroid exposure. Many feel that steroids were an essential part of chronic immunosuppression in past decades but may no longer be necessary in low-risk populations when our newer and more potent drugs are used. Potential differences in long-term outcome will be unapparent in short-term antibody induction studies in low-risk patients, particularly with low on steroid doses, as may have happened in the recent, well-done Astellas trial. In many studies, the evidence for the superiority of mycophenolate (MMF) and tacrolimus (TAC) was not as strong as the evidence for the benefit of steroids in the Canadian cyclosporine study. As the practice of steroid withdrawal has increased, we have not seen the improvement in long-term graft survival that many expected with our newer agents. Steroids have immunosuppressive effects even in doses that are low by historic standards, and side effects may not justify their abandonment
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