30 research outputs found

    Measuring portfolio performance using a modified measure of risk

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    This paper reports the results of an investigation into the properties of a theoretical modification of beta proposed by Leland (1999) and based on earlier work of Rubinstein (1976). It is shown that when returns are elliptically symmetric, beta is the appropriate measure of risk and that there are other situations in which the modified beta will be similar to the traditional measure based on the capital asset pricing model. For the case where returns have a normal distribution, it is shown that the criterion either does not exist or reduces exactly to the conventional beta. It is therefore conjectured that the modified measure will only be useful for portfolios that have nonstandard return distributions which incorporate skewness. For such situations, it is shown how to estimate the measure using regression and how to compare the resulting statistic with a traditional estimated beta using Hotelling's test. An empirical study based on stocks from the FTSE350 does not find evidence to support the use of the new measure even in the presence of skewness.Journal of Asset Management (2007) 7, 388-403. doi:10.1057/palgrave.jam.225005

    Interaction of Pattern Recognition Receptors with Mycobacterium Tuberculosis.

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    Tuberculosis (TB) is considered a major worldwide health problem with 10 million new cases diagnosed each year. Our understanding of TB immunology has become greater and more refined since the identification of Mycobacterium tuberculosis (MTB) as an etiologic agent and the recognition of new signaling pathways modulating infection. Understanding the mechanisms through which the cells of the immune system recognize MTB can be an important step in designing novel therapeutic approaches, as well as improving the limited success of current vaccination strategies. A great challenge in chronic disease is to understand the complexities, mechanisms, and consequences of host interactions with pathogens. Innate immune responses along with the involvement of distinct inflammatory mediators and cells play an important role in the host defense against the MTB. Several classes of pattern recognition receptors (PRRs) are involved in the recognition of MTB including Toll-Like Receptors (TLRs), C-type lectin receptors (CLRs) and Nod-like receptors (NLRs) linked to inflammasome activation. Among the TLR family, TLR1, TLR2, TLR4, and TLR9 and their down-stream signaling proteins play critical roles in the initiation of the immune response in the pathogenesis of TB. The inflammasome pathway is associated with the coordinated release of cytokines such as IL-1β and IL-18 which also play a role in the pathogenesis of TB. Understanding the cross-talk between these signaling pathways will impact on the design of novel therapeutic strategies and in the development of vaccines and immunotherapy regimes. Abnormalities in PRR signaling pathways regulated by TB will affect disease pathogenesis and need to be elucidated. In this review we provide an update on PRR signaling during M. tuberculosis infection and indicate how greater knowledge of these pathways may lead to new therapeutic opportunities

    Simvastatin: A Risk Factor for Angioedema?

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    Atypical cerebral and cerebellar language organisation: a case study

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    BACKGROUND: In the majority of right-handed subjects, language processing is subserved by a close interplay between the left cerebral hemisphere and right cerebellum. Within this network, the dominant fronto-insular region and the contralateral posterior cerebellum are crucially implicated in oral language production. CASE PRESENTATION: We report atypical anatomoclinical findings in a right-handed patient with an extensive right cerebellar infarction and an older left fronto-insular stroke. Standardised neurolinguistic and neurocognitive test batteries were performed. In addition, fMRI, DTI, and SPECT results are reported. In this patient, disruption of the cerebellocerebral language network due to vascular damage in the left fronto-insular region and right posterior inferior cerebellar artery (PICA) territory did not induce any speech or language deficits. By contrast, executive and behavioural disturbances were found after the right cerebellar stroke. Evidence from fMRI and DTI suggests atypical bilateral language representation (Laterality Index = +0,11). At the cerebellar level, fMRI showed more activated voxels in the left than in the right hemisphere (Laterality Index = +0,66). CONCLUSION: We hypothesise congenital bilateral language representation in this patient which might be more advantageous than a typically lateralised distribution of linguistic functions to compensate acute damage to critical language regions. The more activated left cerebellum possibly compensated the functional loss in the right cerebellum after acute damage due to bilateral organisation of language function. However, more research is needed to confirm this hypothesis

    Disabled-2 Determines Commitment of a Pre-adipocyte Population in Juvenile Mice

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    Disabled-2 (Dab2) is a widely expressed clathrin binding endocytic adaptor protein and known for the endocytosis of the low-density lipoprotein (LDL) family receptors. Dab2 also modulates endosomal Ras/MAPK (Erk1/2) activity by regulating the disassembly of Grb2/Sos1 complexes associated with clathrin-coated vesicles. We found that the most prominent phenotype of Dab2 knockout mice was their striking lean body composition under a high fat and high caloric diet, although the weight of the mutant mice was indistinguishable from wild-type littermates on a regular chow. The remarkable difference in resistance to high caloric diet-induced weight gain of the dab2-deleted mice was presented only in juvenile but not in mature mice. Investigation using Dab2-deficient embryonic fibroblasts and mesenchymal stromal cells indicated that Dab2 promoted adipogenic differentiation by modulation of MAPK (Erk1/2) activity, which otherwise suppresses adipogenesis through the phosphorylation of PPARγ. The results suggest that Dab2 is required for the excessive calorie-induced differentiation of an adipocyte progenitor cell population that is present in juvenile but depleted in mature animals. The finding provides evidence for a limited pre-adipocyte population in juvenile mammals and the requirement of Dab2 in the regulation of Ras/MAPK signal in the commitment of the precursor cells to adipose tissues
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