87 research outputs found

    A combinatorial approach to geometric rough paths and their controlled paths

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    We develop the structure theory for transformations of weakly geometric rough paths of bounded 1<p1 < p-variation and their controlled paths. Our approach differs from existing approaches as it does not rely on smooth approximations. We derive an explicit combinatorial expression for the rough path lift of a controlled path, and use it to obtain fundamental identities such as the associativity of the rough integral, the adjunction between pushforwards and pullbacks, and a change of variables formula for rough differential equations (RDEs). As applications we define rough paths, rough integration and RDEs on manifolds, extending the results of [CDL15] to the case of arbitrary pp

    Fact or Factitious? A Psychobiological Study of Authentic and Simulated Dissociative Identity States

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    BACKGROUND: Dissociative identity disorder (DID) is a disputed psychiatric disorder. Research findings and clinical observations suggest that DID involves an authentic mental disorder related to factors such as traumatization and disrupted attachment. A competing view indicates that DID is due to fantasy proneness, suggestibility, suggestion, and role-playing. Here we examine whether dissociative identity state-dependent psychobiological features in DID can be induced in high or low fantasy prone individuals by instructed and motivated role-playing, and suggestion. METHODOLOGY/PRINCIPAL FINDINGS: DID patients, high fantasy prone and low fantasy prone controls were studied in two different types of identity states (neutral and trauma-related) in an autobiographical memory script-driven (neutral or trauma-related) imagery paradigm. The controls were instructed to enact the two DID identity states. Twenty-nine subjects participated in the study: 11 patients with DID, 10 high fantasy prone DID simulating controls, and 8 low fantasy prone DID simulating controls. Autonomic and subjective reactions were obtained. Differences in psychophysiological and neural activation patterns were found between the DID patients and both high and low fantasy prone controls. That is, the identity states in DID were not convincingly enacted by DID simulating controls. Thus, important differences regarding regional cerebral bloodflow and psychophysiological responses for different types of identity states in patients with DID were upheld after controlling for DID simulation. CONCLUSIONS/SIGNIFICANCE: The findings are at odds with the idea that differences among different types of dissociative identity states in DID can be explained by high fantasy proneness, motivated role-enactment, and suggestion. They indicate that DID does not have a sociocultural (e.g., iatrogenic) origin

    Metformin Prevents Nigrostriatal Dopamine Degeneration Independent of AMPK Activation in Dopamine Neurons

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    Metformin is a widely prescribed drug used to treat type-2 diabetes, although recent studies show it has wide ranging effects to treat other diseases. Animal and retrospective human studies indicate that Metformin treatment is neuroprotective in Parkinson’s Disease (PD), although the neuroprotective mechanism is unknown, numerous studies suggest the beneficial effects on glucose homeostasis may be through AMPK activation. In this study we tested whether or not AMPK activation in dopamine neurons was required for the neuroprotective effects of Metformin in PD. We generated transgenic mice in which AMPK activity in dopamine neurons was ablated by removing AMPK beta 1 and beta 2 subunits from dopamine transporter expressing neurons. These AMPK WT and KO mice were then chronically exposed to Metformin in the drinking water then exposed to MPTP, the mouse model of PD. Chronic Metformin treatment significantly attenuated the MPTP-induced loss of Tyrosine Hydroxylase (TH) neuronal number and volume and TH protein concentration in the nigrostriatal pathway. Additionally, Metformin treatment prevented the MPTP-induced elevation of the DOPAC:DA ratio regardless of genotype. Metformin also prevented MPTP induced gliosis in the Substantia Nigra. These neuroprotective actions were independent of genotype and occurred in both AMPK WT and AMPK KO mice. Overall, our studies suggest that Metformin’s neuroprotective effects are not due to AMPK activation in dopaminergic neurons and that more research is required to determine how metformin acts to restrict the development of PD

    Multiple M. tuberculosis Phenotypes in Mouse and Guinea Pig Lung Tissue Revealed by a Dual-Staining Approach

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    A unique hallmark of tuberculosis is the granulomatous lesions formed in the lung. Granulomas can be heterogeneous in nature and can develop a necrotic, hypoxic core which is surrounded by an acellular, fibrotic rim. Studying bacilli in this in vivo microenvironment is problematic as Mycobacterium tuberculosis can change its phenotype and also become acid-fast negative. Under in vitro models of differing environments, M. tuberculosis alters its metabolism, transcriptional profile and rate of replication. In this study, we investigated whether these phenotypic adaptations of M. tuberculosis are unique for certain environmental conditions and if they could therefore be used as differential markers. Bacilli were studied using fluorescent acid-fast auramine-rhodamine targeting the mycolic acid containing cell wall, and immunofluorescence targeting bacterial proteins using an anti-M. tuberculosis whole cell lysate polyclonal antibody. These techniques were combined and simultaneously applied to M. tuberculosis in vitro culture samples and to lung sections of M. tuberculosis infected mice and guinea pigs. Two phenotypically different subpopulations of M. tuberculosis were found in stationary culture whilst three subpopulations were found in hypoxic culture and in lung sections. Bacilli were either exclusively acid-fast positive, exclusively immunofluorescent positive or acid-fast and immunofluorescent positive. These results suggest that M. tuberculosis exists as multiple populations in most conditions, even within seemingly a single microenvironment. This is relevant information for approaches that study bacillary characteristics in pooled samples (using lipidomics and proteomics) as well as in M. tuberculosis drug development

    O lugar ocupado pela assistência fisioterapêutica: representações sociais de trabalhadores com DORT

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    INTRODUÇÃO: Os distúrbios osteomusculares relacionados ao trabalho (DORT) articulam-se diretamente à realização de atividades ocupacionais e às condições de trabalho. OBJETIVO: O artigo origina-se de uma pesquisa qualitativa que analisou as representações sociais da assistência fisioterapêutica entre trabalhadores portadores de Distúrbios Osteomusculares Relacionados ao Trabalho (DORT), frequentadores do Centro de Referência em Saúde do Trabalhador (CEREST), pelo Departamento de Saúde do Trabalhador (DSAT), Juiz de Fora (MG). MATERIAIS E MÉTODOS: O recurso de apreensão das informações foi a entrevista semiestruturada, realizada com 12 trabalhadoras com idades entre 29 e 55 anos. RESULTADOS: As informações submetidas à análise temática apontaram que a assistência fisioterapêutica recebida repercute em períodos longos de tratamento e na insatisfação dos resultados, por meio de uma prática curativista, segmentada e pouco resolutiva, na qual prevalece a utilização de equipamentos em detrimento das manobras corporais e holísticas. CONCLUSÃO: Diante dos relatos, verificamos a necessidade de uma atenção humanizada, integral e equânime com responsabilização e vínculo, além da valorização dos trabalhadores e usuários, promovendo melhor qualidade de vida. É imprescindível a realização de novos estudos que possibilitem melhor compreensão e aprofundamento teórico e prático da relação entre a atuação do fisioterapeuta e as representações sociais envolvidas

    Shedding Light on the Galaxy Luminosity Function

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    From as early as the 1930s, astronomers have tried to quantify the statistical nature of the evolution and large-scale structure of galaxies by studying their luminosity distribution as a function of redshift - known as the galaxy luminosity function (LF). Accurately constructing the LF remains a popular and yet tricky pursuit in modern observational cosmology where the presence of observational selection effects due to e.g. detection thresholds in apparent magnitude, colour, surface brightness or some combination thereof can render any given galaxy survey incomplete and thus introduce bias into the LF. Over the last seventy years there have been numerous sophisticated statistical approaches devised to tackle these issues; all have advantages -- but not one is perfect. This review takes a broad historical look at the key statistical tools that have been developed over this period, discussing their relative merits and highlighting any significant extensions and modifications. In addition, the more generalised methods that have emerged within the last few years are examined. These methods propose a more rigorous statistical framework within which to determine the LF compared to some of the more traditional methods. I also look at how photometric redshift estimations are being incorporated into the LF methodology as well as considering the construction of bivariate LFs. Finally, I review the ongoing development of completeness estimators which test some of the fundamental assumptions going into LF estimators and can be powerful probes of any residual systematic effects inherent magnitude-redshift data.Comment: 95 pages, 23 figures, 3 tables. Now published in The Astronomy & Astrophysics Review. This version: bring in line with A&AR format requirements, also minor typo corrections made, additional citations and higher rez images adde

    Epidemiology and etiology of Parkinson’s disease: a review of the evidence

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