953 research outputs found
Do Hedged Mutual Funds Hedge?
Mutual funds using hedge fund strategies, known as “hedged mutual funds,” have experienced rapid growth in recent years. In theory, these funds should provide a source of diversification for retail investors however the 2008 credit crisis negated the expected benefits of many equity diversifiers. Between 2004 and 2009, hedged mutual funds underperform hedge funds using similar strategies. In contrast, hedged mutual funds outperform the S&P 500 although funds with a market neutral strategy underperform the risk-free rate. These findings suggest that, when compared to a long-only equity strategy, hedged mutual funds offer retail investors improved performance in bear markets
Joseph E Johnston and the defense of Richmond
This study examines Confederate military operations in Virginia from February 17-May 31, 1862, focusing specifically on the role of Joseph E. Johnston as commander of the Department of Northern Virginia. It includes a detailed consideration of Confederate grand strategy, Johnston\u27s withdrawal from the Potomac River, the redeployment of the army to Yorktown, the siege of Yorktown, and the Battles of Williamsburg and Seven Pines.;In February, 1862, following the surrender of Fort Donelson, President Jefferson Davis reoriented strategy in Virginia from a defense of the frontiers to a closer defense of Richmond; he also recalled General Robert E. Lee from South Carolina to coordinate that defense. But the strategic concepts of Davis, Lee, and Joseph Johnston (the senior field commander in Virginia) often differed a great deal, leading to confrontation and discord.;This study concentrates on following Johnston\u27s point of view during the campaign, especially on his role as a field army commander. The conclusion suggests that Johnston was a superior strategist, administrator, and operational commander, but suffered from serious deficiencies as in tactical supervision of his own subordinates and an inability to deal tactfully with his superiors
The Guayule Plant: A Renewable, Domestic Source of Binder Materials for Flexible Pavement Mixtures
Due to the rising price of crude oil, flexible pavement costs have increased significantly. This price pressure has resulted in the increased use of reclaimed asphalt pavement (RAP) and/or reclaimed asphalt roofing shingles (RAS) because of the binder (asphalt cement) they contain. This has increased demand for recycling (rejuvenating) agents which return the RAP/RAS binders to their original state by 1) restoring maltenes (petroleum oils and resins) that have been depleted due to age-hardening/oxidation, and 2) reducing their viscosity. The project concept was to design a flexible pavement mixture (FPM) produced with little-to-no virgin petroleumbased binder which implied the use of high percentages of RAP and/or RAS, and a bio-based virgin binder. The potential impacts of a renewable (bio-based), domestic source of FPM binder on highway construction could be lower costs and, perhaps more importantly, a decreased dependence on foreign oil
Sustainable Development for Canada's Arctic and Subarctic Communities: A Backcasting Approach to Churchill, Manitoba
Backcasting has been used to evaluate sustainable development in several communities in Canada, Europe, and the United States, but no research has applied it to a remote northern community. This first such effort, which took place in Churchill, Manitoba, evaluated the environmental, social, and economic aspects of a small Subarctic community. As part of the backcasting approach, a community survey identified local issues and concerns, such as tundra vehicle damage, alcohol abuse, and the future economic viability of the Hudson Bay Port Company. Community residents also identified potential growth areas, including the establishment of Nunavut and increased tourism opportunities. The application of the backcasting approach in Canada's northern regions will have benefits for research and management by identifying local issues and building strategies for sustainable development.L'analyse rétrospective a été utilisée pour évaluer le développement durable dans diverses communautés du Canada, d'Europe et des États-Unis, mais aucun travail de recherche ne l'a appliquée à une communauté isolée du Grand Nord. Cette première tentative du genre, qui s'est déroulée à Churchill, au Manitoba, a évalué les facettes environnementales, sociales et économiques d'une petite collectivité subarctique. Dans le cadre de la méthode de l'analyse rétrospective, un sondage auprès de la communauté a permis d'identifier les préoccupations et enjeux locaux, tels que les dommages à la toundra causés par les véhicules, l'abus d'alcool et la future viabilité économique de la Compagnie du port de la baie d'Hudson. Les résidents de la communauté ont également identifié des zones de croissance potentielle, y compris l'établissement du Nunavut et des ouvertures accrues sur le plan touristique. L'application de la technique de l'analyse rétrospective dans les régions nordiques du Canada sera bénéfique pour la recherche et la gestion en identifiant les enjeux locaux et en édifiant des stratégies visant le développement durable
Prognosis of refractory neurosarcoidosis altered by thalidomide: a case report
Introduction:
Sarcoidosis is a multisystem disease characterized by noncaseating granulomas in the lungs, skin, lymph nodes, and, rarely, the nervous system. Granuloma formation in sarcoidosis is mediated by increased secretion of interferon-gamma, interleukin-2, and tumor necrosis factor-alpha. 25% of patients with neurosarcoidosis are steroid resistant and another 20–40% are resistant to any conventional immunosuppression, but the typical agents suppress the immune system in a non-specific fashion. Thalidomide has been shown to have activity specific to the inflammatory mediators of sarcoidosis, has been shown to be beneficial in cutaneous sarcoidosis, and provides an interesting observation in our patient with refractory neurosarcoidosis.
Case presentation:
A 40 year old African-american female presented with refractory neurosarcoidosis. Over the course of several years, the patient was treated with high dose steroids, imuran, cytoxan, and cyclosporine without benefit. Then, the patient received thalidomide, slowly escalating to 650 mg. After 2 months radiologic improvement was noted and after 6 months clinical stabilization and improvement became apparent.
Conclusion:
Our case report presents a difficult, refractory case of neurosarcoidosis that demonstrates an altered prognosis based on the addition of thalidomide
Human TBX22 expression and protein-DNA interactions
Cleft palate is one of the most common birth abnormalities. Figures published in 2006 by the American Centres for Disease Control and Prevention, report the incidence of those born in the United States with a cleft palate without the presence of a cleft lip (CPI) to be 6.39 for every 10000 in the three years between 1999 to 2001 and for cleft lip in association with a cleft palate (CLP) to be even greater - 10.48 per 10000 live births. In 2001, Braybrook and colleagues reported that mutations in the TBX22 gene cause X-linked cleft palate (CPX), a disease characterised by a cleft of the secondary palate and is often seen in association with ankyloglossia (tongue-tie) (Braybrook et al. 2001). A cleft of the secondary palate arises as a consequence of disturbance to correct development during palatogenesis: an anomaly in palatal shelf growth; delayed or failed shelf elevation; defective shelf fusion or a failure of medial edge epithelium cell death. This thesis reveals that the expression of TBX22 during these key developmental events in human embryos is consistent with the phenotype seen in CPX. To enable an investigation for TBX22 target genes, a DNA binding sequence is determined for the TBX22 protein. This sequence is used to generate a generic TBX22 DNA binding site, the presence of which is screened for in promoter regions, defined as 2kb upstream of transcription start sites. 132 genes were selected as candidate TBX22 targets on the basis that they underlie human disorders that include a cleft palate. The screen shows that 28 of these genes have at least one perfect or near perfect match to the generic TBX22 DNA binding site. Of these, only two both contained a perfect TBX22 generic DNA binding site and mouse mutants also had cleft palates: SUMO1 and MSX1. Interaction between SUMO1 and TBX22 has already been shown (Andreou et al. 2007). This study investigated MSX1 as a downstream target of TBX22 using a luciferase reporter gene construct in vitro. The results showed that in the presence of TBX22, the luciferase signal was reduced and support MSX1 being a downstream target gene of TBX22. These findings further the understanding of the molecular networks regulating craniofacial development. Unravelling these complex interactions is crucial to identifying the mechanisms of oro-facial clefting, important steps towards improved methods of counselling, treatment and prevention of these common birth disorders.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
Firm ESG reputation risk and debt choice
Using a novel sample covering 3783 US public firms from 2007 to 2020, we examine how negative media coverage of firm‐level environmental, social, and governance (ESG) practices affects a firm's debt choice. We find that firms with higher ESG reputation risk rely more on public bond than bank loan. The social and governance components, in particular, matter. Moreover, firms that receive more negative news coverage display a higher propensity to issue new bonds as opposed to securing new bank debt. Overall, our study presents empirical evidence on the relation between firm ESG reputation risk and debt financing
The gravitational S-matrix
We investigate the hypothesized existence of an S-matrix for gravity, and
some of its expected general properties. We first discuss basic questions
regarding existence of such a matrix, including those of infrared divergences
and description of asymptotic states. Distinct scattering behavior occurs in
the Born, eikonal, and strong gravity regimes, and we describe aspects of both
the partial wave and momentum space amplitudes, and their analytic properties,
from these regimes. Classically the strong gravity region would be dominated by
formation of black holes, and we assume its unitary quantum dynamics is
described by corresponding resonances. Masslessness limits some powerful
methods and results that apply to massive theories, though a continuation path
implying crossing symmetry plausibly still exists. Physical properties of
gravity suggest nonpolynomial amplitudes, although crossing and causality
constrain (with modest assumptions) this nonpolynomial behavior, particularly
requiring a polynomial bound in complex s at fixed physical momentum transfer.
We explore the hypothesis that such behavior corresponds to a nonlocality
intrinsic to gravity, but consistent with unitarity, analyticity, crossing, and
causality.Comment: 46 pages, 10 figure
Pilot Safety Evaluation of Varenicline for the Treatment of Methamphetamine Dependence.
Despite the worldwide extent of methamphetamine dependence, no medication has been shown to effectively treat afflicted individuals. One relatively unexplored approach is modulation of cholinergic system function. Animal research suggests that enhancement of central cholinergic activity, possibly at nicotinic acetylcholine receptors (nAChRs), can reduce methamphetamine-related behaviors. Further, preliminary findings indicate that rivastigmine, a cholinesterase inhibitor, may reduce craving for methamphetamine after administration of the drug in human subjects. We therefore performed a double-blind, placebo-controlled, crossover pilot study of the safety and tolerability of varenicline in eight methamphetamine-dependent research subjects. Varenicline is used clinically to aid smoking cessation, and acts as a partial agonist at α4β2 nAChRs with full agonist properties at α7 nAChRs. Oral varenicline dose was titrated over 1 week to reach 1 mg bid, and then was co-administered with 30 mg methamphetamine, delivered in ten intravenous infusions of 3 mg each. Varenicline was found to be safe in combination with IV methamphetamine, producing no cardiac rhythm disturbances or alterations in vital sign parameters. No adverse neuropsychiatric sequelae were detected either during varenicline titration or following administration of methamphetamine. The results suggest that varenicline warrants further investigation as a potential treatment for methamphetamine dependence
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