457 research outputs found
MANOVA modelling of a chiropractic longitudinal study using multiple imputation
No full textThe purpose of this report is to present the detailed statistical analysis of a randomised, placebo-controlled trial comparing two different treatment modalities to an intervention of no known benefit for people with acute or subacute thoracic spine pain.
The therapy arms consist of Spinal Manipulative Therapy (SMT) and Graston Technique (GT) and the placebo is a non-functional ultrasound. A placebo group was utilised because at present there are no proven treatments for non-specific thoracic pain. This trial is registered with the Australia and New Zealand Clinical Trials Registry. Ethics approval has been granted by Murdoch University Human Research and Ethics Committee, number 2007/274.
The aim of this three arm trial was to test the efficacy of SMT and GT as independent modalities compared to detuned ultrasound for the outcomes of pain and disability. The latter were measured using the Visual Analogue Scale (VAS) and a modified Oswestry Back Pain Disability Index. The study was conducted at the Murdoch University Chiropractic student clinic in Perth, Australia, and the protocol published in Crothers et al (2008).
In this report, Section 2 provides an initial exploratory analysis of the data, Section 3 outlines the statistical models used in the final analysis, Section 4 defines these models in mathematical terms, Section 5 discusses the management of missing values via multiple imputation and Section 6 presents the results of the statistical modelling and hypothesis tests. The clinical study will be published in full elsewhere
Bridging the gap: Defining the molecular mechanisms of CEP290 disease pathogenesis
No full textMutations in the gene CEP290 cause an array of debilitating and phenotypically distinct human diseases, ranging in severity from the devastating blinding disease Leber congenital amaurosis (LCA) to Senior Løken Syndrome, Joubert syndrome, and the embryonically lethal Meckel-Grüber syndrome. The pathology observed in these diseases is thought to be due to CEP290\u27s essential role in the development and maintenance of the primary cilium, but despite its critical role in biology and disease we know only little about CEP290\u27s function. Here we identify four novel functional domains of the protein, showing that CEP290 directly binds to cellular membranes through an N-terminal domain that includes a highly conserved amphipathic helix motif, and to microtubules through a domain located within its myosin-tail homology domain. Furthermore, CEP290 activity was found to be regulated by two novel autoinhibitory domains within its N- and C-termini, both of which were also found to play critical roles in regulating ciliogenesis. Disruption of the microtubule-binding domain in the rd16 mouse LCA model was found to be sufficient to induce significant deficits in cilium formation leading to retinal degeneration. Taking these findings into account, we developed a novel model that accurately predicts patient CEP290 protein levels in a mutation-specific fashion. Predicted CEP290 protein levels were found to robustly correlate with disease severity for all reported CEP290 patients. All these data implicate CEP290 as an integral structural and regulatory component of the primary cilium and provide insight into the pathological mechanisms of LCA and related ciliopathies. Our findings also suggest novel strategies for therapeutic intervention in the treatment of CEP290-based disease that, if fully realized, would be the first treatment available for the many patients suffering the devastating effects of CEP290 dysfunction
The Bionic Retina: A Small Molecule with Big Potential for Visual Restoration
No full textIn this issue of Neuron, Polosukhina et al. (2012) intravitreally deliver the light-activatable molecule acrylamide-azobenzene-quaternary ammonium (AAQ) to the eyes of mice with end-stage retinal degeneration. Results show that, with the appropriate illumination, AAQ restores light sensitivity and visual behavior
An alternative definition of economic regions in the U.S. based on similarities in state business cycles
No full textSince the 1950s the Bureau of Economic analysis (BEA) has grouped the states into eight regions based primarily on cross-sectional similarities in their socioeconomic characteristics. This is the most frequently used grouping of states in the U.S. for economic analysis. Since several recent studies concentrate on similarities and differences in regional business cycles, this paper groups states into regions based not on a broad set of socioeconomic characteristics but on the similarities in their business cycles. The analysis makes use of a consistent set of coincident indexes estimated from a Stock and Watson-type model. The author applies k-means cluster analysis to the cyclical components of these indexes to group the 48 contiguous states into eight regions with similar cycles. Having grouped the states into regions, the author determines the relative strength of cohesion among the states in the various regions. Finally, the author compares the regions defined in this paper with the BEA regions.Business cycles ; Regional economics
Sci Transl Med
No full textGenetic pleiotropy, the phenomenon by which mutations in the same gene result in markedly different disease phenotypes, has proven difficult to explain with traditional models of disease pathogenesis. We have developed a model of pleiotropic disease that explains, through the process of basal exon skipping, how different mutations in the same gene can differentially affect protein production, with the total amount of protein produced correlating with disease severity. Mutations in the centrosomal protein of 290 kDa (CEP290) gene are associated with a spectrum of phenotypically distinct human diseases (the ciliopathies). Molecular biologic examination of CEP290 transcript and protein expression in cells from patients carrying CEP290 mutations, measured by quantitative polymerase chain reaction and Western blotting, correlated with disease severity and corroborated our model. We show that basal exon skipping may be the mechanism underlying the disease pleiotropy caused by CEP290 mutations. Applying our model to a different disease gene, CC2D2A (coiled-coil and C2 domains-containing protein 2A), we found that the same correlations held true. Our model explains the phenotypic diversity of two different inherited ciliopathies and may establish a new model for the pathogenesis of other pleiotropic human diseases.1DP2OD007483/OD/NIH HHS/United States1F30AG044078-01A1/AG/NIA NIH HHS/United States1R24 EY019861-01A1/EY/NEI NIH HHS/United States8DP1EY023177/DP/NCCDPHP CDC HHS/United StatesDP1 EY023177/EY/NEI NIH HHS/United StatesDP1 OD008267/OD/NIH HHS/United StatesR24EY019861/EY/NEI NIH HHS/United StatesHoward Hughes Medical Institute/United States2016-06-10T00:00:00Z26062849PMC448648
Sacrifice in the Eucharist in the texts of the fathers from the New Testament to the council of Chalcedon
No full textThis thesis examines the evidence for the notion of Eucharistic Sacrifice which is found in the original texts of all the principal Fathers and ecclesiastical authors of the Early Church. The period covered is from the time of the writing of the New Testament to the Council of Chalcedon in 451 A.D. Each of the principal Fathers is examined in historical order, as far as this is possible, except when there is another link between them such as their city of origin. Apart from a few exceptions, the texts are presented in their Greek or Latin original in the footnotes, but an English translation is supplied for every case in the main text of the thesis. The aim of the thesis is not to provide an exhaustive analysis of the above data, but to present them in an orderly way and to make initial exploratory comments on the texts themselves and of the work of various scholars. The final conclusion resulting from this exercise is that, although there is indisputable evidence that the notion of Eucharistic sacrifice was widely upheld by Patristic authors, its actual content varied from author to author and presents a richness which it is not easy to classify
Family altruism and incentives
No full textThe author builds on the altruistic model of the family, to explore the strategic interaction between altruistic parents, and selfish children, when children's efforts are endogenous. If there is uncertainty about the amount of income the children will realize, and if parents have imperfect information, the children have an incentive to exert little effort, and to rely on their parent's altruistically motivated transfers. Because of this, parents face a tradeoff between the insurance that bequests implicitly provide their children, and the disincentive to work prompted by their altruism. The author shows that if parents can credibly commit to a pattern of transfers, they will choose not to compensate children in bad outcomes, as much as predicted by the standard (no uncertainty, no asymmetric information) dynastic model of the family. Alternatively, parents may choose to forgo any insurance, and offer a fixed level of bequest, to elicit greater effort from their children. The optimal transfers structure that the author derives, reconciles the predictions of the altruistic family model, with much of the existing evidence on inter-generational transfers, which suggests that parents compensate only partially, or not at all, for earnings differentials among their children. Moreover, the author shows that Ricardian equivalence holds in this setup, except when non-negativity constraints are binding.Economic Theory&Research,Environmental Economics&Policies,Health Economics&Finance,Educational Sciences,Safety Nets and Transfers
Landscape-painter as landscape-gardener : the case of Alfred Parsons R.A.
No full textIn 2 vols.Available from British Library Document Supply Centre-DSC:DXN016830 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo
A New Framework for the Citation Indexing Paradigm
No full textA new citation indexing paradigm is proposed: the cascading citation indexing framework (c2IF, for short). It improves the way research publications are assessed for their impact in promoting science and technology. Given a collection of articles and their citation graph, citations are considered at the (article, author) level. Each one article is uniquely identified by means of the Digital Object Identifier (DOI, http://www.doi.org). To identify each one author uniquely, a Universal Author Identifier (UAI) scheme is established. In addition to the citations directly made to a given (article, author) pair, citation paths that target each one citing article are also considered. The granularity of the paradigm is further increased by introducing the concept of the chord, whereby a citation path of length one co-exists with paths of length two or higher, involving the same source- and target- articles. The c2IF output emerges in the form
of a medal standings table, analogous to the one that ranks teams at athletic events: when two (article, author) pairs receive the same number of (direct) citations, the one that is cited by more popular articles (i.e. articles that comprise targets to a larger number of paths in the citation graph), is assigned a higher rank value
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