Automated analysis of quantitative image data using isomorphic functional mixed models, with application to proteomics data

Image data are increasingly encountered and are of growing importance in many areas of science. Much of these data are quantitative image data, which are characterized by intensities that represent some measurement of interest in the scanned images. The data typically consist of multiple images on the same domain and the goal of the research is to combine the quantitative information across images to make inference about populations or interventions. In this paper we present a unified analysis framework for the analysis of quantitative image data using a Bayesian functional mixed model approach. This framework is flexible enough to handle complex, irregular images with many local features, and can model the simultaneous effects of multiple factors on the image intensities and account for the correlation between images induced by the design. We introduce a general isomorphic modeling approach to fitting the functional mixed model, of which the wavelet-based functional mixed model is one special case. With suitable modeling choices, this approach leads to efficient calculations and can result in flexible modeling and adaptive smoothing of the salient features in the data. The proposed method has the following advantages: it can be run automatically, it produces inferential plots indicating which regions of the image are associated with each factor, it simultaneously considers the practical and statistical significance of findings, and it controls the false discovery rate.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS407 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

MK-0448, a Specific Kv1.5 Inhibitor: Safety, Pharmacokinetics and Pharmacodynamic Electrophysiology in Experimental Animal Models and in Humans.

BACKGROUND: -We evaluated the viability of I(Kur) as a target for maintenance of sinus rhythm in patients with a history of atrial fibrillation through the testing of MK-0448, a novel I(Kur) inhibitor. METHODS AND RESULTS: -In vitro MK-0448 studies demonstrated strong inhibition of I(Kur) with minimal off-target activity. In vivo MK-0448 studies in normal anesthetized dogs demonstrated significant prolongation of the atrial refractory period compared with vehicle controls without affecting the ventricular refractory period. In studies of a conscious dog heart failure model, sustained AF was terminated with bolus intravenous MK-0448 doses of 0.03 and 0.1 mg/kg. These data led to a two-part first-in-human study: Part I evaluated safety and pharmacokinetics, and Part II was an invasive electrophysiologic (EP) study in healthy subjects. MK-0448 was well-tolerated with mild adverse experiences, most commonly irritation at the injection site. During the EP study, ascending doses of MK-0448 were administered, but no increases in atrial or ventricular refractoriness were detected despite achieving plasma concentrations in excess of 2 μM. Follow-up studies in normal anesthetized dogs designed to assess the influence of autonomic tone demonstrated that prolongation of atrial refractoriness with MK-0448 was markedly attenuated in the presence of vagal nerve simulation, suggesting that the effects of I(Kur) blockade on atrial repolarization may be negated by enhanced parasympathetic neural tone. CONCLUSIONS: -The contribution of I(Kur) to human atrial electrophysiology is less prominent than in preclinical models and therefore is likely to be of limited therapeutic value for the prevention of atrial fibrillation

Affirmative actions in terms of special rights:Confronting structural violence in Brazilian higher education

Made available in DSpace on 2019-10-04T12:14:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-07-01Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)In this article, the authors interpret affirmative actions with reference to structural violence, which is accompanied by legitimizing discourses that tend to make discrimination appear natural and unquestionable. They illustrate the extension of structural violence in Brazilian society with particular reference to access to higher education. It has been common to talk about some groups of students as having special needs. However, the authors see groups of students suffering structural violence as being groups with special rights, and explore affirmative actions through the notion of special rights. The authors find that special-rights terminology establishes the discussion of affirmative actions in higher education in a broader and, at the same time, more profound conceptual framework related to interpretations of social justice. Simultaneously, special-rights terminology brings an educational specificity to the discussion of affirmative actions. Thus, the authors see affirmative actions as being both a general sociopolitical and specific educational challenge.Univ Fed Alfenas, Dept Math, 700th Gabriel Monteiro da Silva St, BR-37130001 Alfenas, MG, BrazilAalborg Univ, Dept Learning & Philosophy, Aalborg, DenmarkState Univ Sao Paulo, Dept Math Educ, Sao Paulo, BrazilState Univ Sao Paulo, Dept Math Educ, Sao Paulo, BrazilCAPES: 2014/05584-

MK-801 inhibits the development of morphine tolerance at spinal sites

The (NMDA) receptor antagonist MK-801 has been shown to attenuate tolerance development in rats. In this study, we show that MK-801 inhibits tolerance to the antinociceptive effects of morphine, as assessed by the tail-flick test, in spinalized rats. These results suggest that NMDA receptor antagonists inhibit opiate tolerance at spinal sites, and also provide strong evidence that the effects of MK-801 are not due to its ability to interfere with associative learning, but instead to inhibition of non-associative mechanisms of opiate tolerance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30508/1/0000137.pd