72 research outputs found

    Individual Investors and Portfolio Diversification in Late Victorian Britain: How Diversified Were Victorian Financial Portfolios?

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    This article investigates Victorian investor financial portfolio strategies in England and Wales during the second half of the nineteenth century. We find that investors held on average about half of their gross wealth in the form of four or five liquid financial securities, but were reluctant to adopt fully contemporary financial advice to invest equal amounts in securities or to spread risk across the globe. They generally held under-diversified portfolios and proximity to their investments may have been an alternative to diversification as a means of risk reduction, especially for the less wealthy

    The effectiveness of cognitive behavioural therapy versus antidepressants for treatment of post-stroke depression in adults

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    Stroke is a common disorder with profound lasting effects and is the UK’s fourth leading cause of morbidity. One important after-effect is post-stroke depression (PSD). PSD can impact overall recovery, however treatment guidelines remain unclear. Usual care generally consists of antidepressants despite cognitive behavioural therapy (CBT) being a first-line treatment for depression. This evidence review aims to assess the effectiveness of CBT compared with antidepressants for treating PSD in adult stroke patients. Evidence searches of MEDLINE, PUBMED, The Cochrane Library, PsycINFO and NICE Evidence Search were conducted using strict search terms. The results were screened and appraised. A reference list search was carried out on included reviews with these results also screened and appraised. Appraisals used the AGREE II tool for guidelines and the CASP systematic review and randomised controlled trial (RCT) frameworks. Each stage was carried out by two independent reviewers, with disagreements resolved by a third reviewer. After applying inclusion and exclusion criteria, two guidelines, four reviews and one RCT were included in the synthesis. One review found CBT effective for treating PSD. Two reviews found CBT combined with antidepressants more effective than antidepressants alone. One review concluded CBT was ineffective for treating PSD. A single RCT found CBT more effective than antidepressants if PSD onset was nine months post-stroke, but PSD onset six months post-stroke was most effectively treated by antidepressants. Results for less than six months post-stroke were inconclusive. The findings of this evidence review suggest it is not possible to definitively conclude whether CBT is more or less effective than antidepressants. A combination of both is likely to be most effective. Lack of research means conclusions for clinical practice are difficult to draw. More research is needed before specific guidelines can be compiled

    Financial diversification strategies before World War I: Buy-and-hold versus naïve portfolio selection

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    This study contributes to a growing volume of scholarship that highlights the importance of financial diversification in business history. It shows that, pre-WWI, financial advice for equal portfolio weighting, the so-called naïve diversification, then called scientific investment or geographical distribution of risk, was a sophisticated strategy for Victorian investors and not suboptimal to Markowitz optimization. Drawing upon a unique dataset of 507 individual portfolios at death, this study shows that, although Victorian investors, in particular wealthy investors, did diversify investment risk across a number of securities, they did not hold equally weighted portfolios. It explores possible reasons for the unbalanced nature of investor portfolios and dismisses socio economic factors, illiquidity, passive ‘buy the market’ and market timing strategies as possible explanatory factors. The results rather point to a strategy of naïve diversification spread over time, a ‘buy as you go and hold strategy’, buying new securities as savings allowed and holding them until death

    Minimizing the impact of biologging devices: Using computational fluid dynamics for optimizing tag design and positioning

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    Biologging devices are used ubiquitously across vertebrate taxa in studies of movement and behavioural ecology to record data from organisms without the need for direct observation. Despite the dramatic increase in the sophistication of this technology, progress in reducing the impact of these devices to animals is less obvious, notwithstanding the implications for animal welfare. Existing guidelines focus on tag weight (e.g. the ‘5% rule'), ignoring aero/hydrodynamic forces in aerial and aquatic organisms, which can be considerable. Designing tags to minimize such impact for animals moving in fluid environments is not trivial, as the impact depends on the position of the tag on the animal, as well as its shape and dimensions. We demonstrate the capabilities of computational fluid dynamics (CFD) modelling to optimize the design and positioning of biologgers on marine animals, using the grey seal (Halichoerus grypus) as a model species. Specifically, we investigate the effects of (a) tag form, (b) tag size, and (c) tag position and quantify the impact under frontal hydrodynamic forces, as encountered by seals swimming at sea. By comparing a conventional versus a streamlined tag, we show that the former can induce up to 22% larger drag for a swimming seal; to match the drag of the streamlined tag, the conventional tag would have to be reduced in size by 50%. For the conventional tag, the drag induced can differ by up to 11% depending on the position along the seal's body, whereas for the streamlined tag this difference amounts to only 5%. We conclude by showing how the CFD simulation approach can be used to optimize tag design to reduce drag for aerial and aquatic species, including issues such as the impact of lateral currents (unexplored until now). We also provide a step-by-step guide to facilitate the implementation of CFD in biologging tag design

    Protein restriction during pregnancy alters Cdkn1c silencing, dopamine circuitry and offspring behaviour without changing expression of key neuronal marker genes

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    We tracked the consequences of in utero protein restriction in mice throughout their development and life course using a luciferase-based allelic reporter of imprinted Cdkn1c. Exposure to gestational low-protein diet (LPD) results in the inappropriate expression of paternally inherited Cdkn1c in the brains of embryonic and juvenile mice. These animals were characterised by a developmental delay in motor skills, and by behavioural alterations indicative of reduced anxiety. Exposure to LPD in utero resulted in significantly more tyrosine hydroxylase positive (dopaminergic) neurons in the midbrain of adult offspring as compared to age-matched, control-diet equivalents. Positron emission tomography (PET) imaging revealed an increase in striatal dopamine synthesis capacity in LPD-exposed offspring, where elevated levels of dopamine correlated with an enhanced sensitivity to cocaine. These data highlight a profound sensitivity of the developing epigenome to gestational protein restriction. Our data also suggest that loss of Cdkn1c imprinting and p57KIP2 upregulation alters the cellular composition of the developing midbrain, compromises dopamine circuitry, and thereby provokes behavioural abnormalities in early postnatal life. Molecular analyses showed that despite this phenotype, exposure to LPD solely during pregnancy did not significantly change the expression of key neuronal- or dopamine-associated marker genes in adult offspring

    Biliary epithelium and liver B cells exposed to bacteria activate intrahepatic MAIT cells through MR1

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    Background & AimsMucosal-Associated Invariant T (MAIT) cells are innate-like T cells characterised by the invariant TCR-chain, Vα7.2-Jα33, and are restricted by MR1, which presents bacterial vitamin B metabolites. They are important for antibacterial immunity at mucosal sites; however, detailed characteristics of liver-infiltrating MAIT (LI-MAIT) and their role in biliary immune surveillance remain unexplored.MethodsThe phenotype and intrahepatic localisation of human LI-MAIT cells was examined in diseased and normal livers. MAIT cell activation in response to E. coli-exposed macrophages, biliary epithelial cells (BEC) and liver B cells was assessed with/without anti-MR1.ResultsIntrahepatic MAIT cells predominantly localised to bile ducts in the portal tracts. Consistent with this distribution, they expressed biliary tropic chemokine receptors CCR6, CXCR6, and integrin αEβ7. LI-MAIT cells were also present in the hepatic sinusoids and possessed tissue-homing chemokine receptor CXCR3 and integrins LFA-1 and VLA-4, suggesting their recruitment via hepatic sinusoids. LI-MAIT cells were enriched in the parenchyma of acute liver failure livers compared to chronic diseased livers. LI-MAIT cells had an activated, effector memory phenotype, expressed α4β7 and receptors for IL-12, IL-18, and IL-23. Importantly, in response to E. coli-exposed macrophages, liver B cells and BEC, MAIT cells upregulated IFN-γ and CD40 Ligand and degranulated in an MR1-dependent, cytokine-independent manner. In addition, diseased liver MAIT cells expressed T-bet and RORγt and the cytokines IFN-γ, TNF-α, and IL-17.ConclusionsOur findings provide the first evidence of an immune surveillance effector response for MAIT cells towards BEC in human liver; thus they could be manipulated for treatment of biliary disease in the future

    Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

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    The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods - recursive partitioning and regression - to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; Pcombined = 2.01 × 10-19 and 2.35 × 10-13, respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes. ©2007 Nature Publishing Group
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