1,550 research outputs found

    Derivative pricing under the possibility of long memory in the supOU stochastic volatility model

    Get PDF
    We consider the supOU stochastic volatility model which is able to exhibit long-range dependence. For this model we give conditions for the discounted stock price to be a martingale, calculate the characteristic function, give a strip where it is analytic and discuss the use of Fourier pricing techniques. Finally, we present a concrete specification with polynomially decaying autocorrelations and calibrate it to observed market prices of plain vanilla options

    Readers as research detectives

    Get PDF
    Flaws in research papers are common but it may require arduous detective work to unravel them. Checklists are helpful, but many inconsistencies will only be revealed through repeated cross-checks of every little detail, just like in a crime case. As a major deterrent for dishonesty, raw data from all trials should be posted on a public website. This would also make it much easier to detect errors and flaws in publications, and it would allow many research projects to be performed without collecting new data. The prevailing culture of secrecy and ownership to data is not in the best interests of patients

    Involvement of a Natural Fusion of a Cytochrome P450 and a Hydrolase in Mycophenolic Acid Biosynthesis

    Get PDF
    Mycophenolic acid (MPA) is a fungal secondary metabolite and the active component in several immunosuppressive pharmaceuticals. The gene cluster coding for the MPA biosynthetic pathway has recently been discovered in Penicillium brevicompactum, demonstrating that the first step is catalyzed by MpaC, a polyketide synthase producing 5-methylorsellinic acid (5-MOA). However, the biochemical role of the enzymes encoded by the remaining genes in the MPA gene cluster is still unknown. Based on bioinformatic analysis of the MPA gene cluster, we hypothesized that the step following 5-MOA production in the pathway is carried out by a natural fusion enzyme MpaDE, consisting of a cytochrome P450 (MpaD) in the N-terminal region and a hydrolase (MpaE) in the C-terminal region. We verified that the fusion gene is indeed expressed in P. brevicompactum by obtaining full-length sequence of the mpaDE cDNA prepared from the extracted RNA. Heterologous coexpression of mpaC and the fusion gene mpaDE in the MPA-nonproducer Aspergillus nidulans resulted in the production of 5,7-dihydroxy-4-methylphthalide (DHMP), the second intermediate in MPA biosynthesis. Analysis of the strain coexpressing mpaC and the mpaD part of mpaDE shows that the P450 catalyzes hydroxylation of 5-MOA to 4,6-dihydroxy-2-(hydroxymethyl)-3-methylbenzoic acid (DHMB). DHMB is then converted to DHMP, and our results suggest that the hydrolase domain aids this second step by acting as a lactone synthase that catalyzes the ring closure. Overall, the chimeric enzyme MpaDE provides insight into the genetic organization of the MPA biosynthesis pathway

    A participatory physical and psychosocial intervention for balancing the demands and resources among industrial workers (PIPPI): study protocol of a cluster-randomized controlled trial

    Get PDF
    Background: Need for recovery and work ability are strongly associated with high employee turnover, well-being and sickness absence. However, scientific knowledge on effective interventions to improve work ability and decrease need for recovery is scarce. Thus, the present study aims to describe the background, design and protocol of a cluster randomized controlled trial evaluating the effectiveness of an intervention to reduce need for recovery and improve work ability among industrial workers. Methods/Design: A two-year cluster randomized controlled design will be utilized, in which controls will also receive the intervention in year two. More than 400 workers from three companies in Denmark will be aimed to be cluster randomized into intervention and control groups with at least 200 workers (at least 9 work teams) in each group. An organizational resources audit and subsequent action planning workshop will be carried out to map the existing resources and act upon initiatives not functioning as intended. Workshops will be conducted to train leaders and health and safety representatives in supporting and facilitating the intervention activities. Group and individual level participatory visual mapping sessions will be carried out allowing team members to discuss current physical and psychosocial work demands and resources, and develop action plans to minimize strain and if possible, optimize the resources. At all levels, the intervention will be integrated into the existing organization of work schedules. An extensive process and effect evaluation on need for recovery and work ability will be carried out via questionnaires, observations, interviews and organizational data assessed at several time points throughout the intervention period. Discussion: This study primarily aims to develop, implement and evaluate an intervention based on the abovementioned features which may improve the work environment, available resources and health of industrial workers, and hence their need for recovery and work ability

    Prognostic impact of matched preoperative plasma and serum VEGF in patients with primary colorectal carcinoma

    Get PDF
    In serum, the major part of vascular endothelial growth factor derives from in vitro degranulation of granulocytes and platelets. Therefore, plasma may be preferred for vascular endothelial growth factor measurements. However, which specimen is the best predictor of survival is still debated. The present study analyzed the prognostic value of matched preoperative serum and plasma vascular endothelial growth factor concentrations in patients with colorectal cancer. To establish the reference range among healthy people, vascular endothelial growth factor was analyzed in 50 matched EDTA-plasma and serum samples from healthy blood donors. Preoperatively, in 524 patients with colorectal cancer, matched plasma and serum vascular endothelial growth factor concentrations were analyzed. In the colorectal cancer patients, the median plasma vascular endothelial growth factor concentration (44 pg ml−1) was significantly (P=0.01) higher than the median plasma vascular endothelial growth factor concentration (30 pg ml−1) in the healthy blood donors. In serum, no significant (P=0.30) difference in the median vascular endothelial growth factor concentration was found between colorectal cancer patients (268 pg ml−1) and healthy blood donors (220 pg ml−1). The preoperative vascular endothelial growth factor concentrations were dichotomized by the 95th percentile of the healthy blood donors (plasma=112 pg ml−1, serum=533 pg ml−1). In univariate survival analyses, both high plasma vascular endothelial growth factor (>112 pg ml−1) and high serum vascular endothelial growth factor (>533 pg ml−1) predicted a reduced survival. In multivariate survival analyses, high serum vascular endothelial growth factor (>533 pg ml−1) independently predicted a reduced survival (HR=1.65, P=0.015), while high plasma vascular endothelial growth factor (>112 pg ml−1) did not (HR=1.27, P=0.23). This study indicates that preoperative serum vascular endothelial growth factor apparently is a better predictor of overall survival than the preoperative plasma vascular endothelial growth factor

    Prevalence of Peripheral Artery Disease is Higher in Persons Living with HIV Compared to Uninfected Controls

    Get PDF
    OBJECTIVE: Ankle-brachial index (ABI) is an excellent tool for diagnosing peripheral artery disease (PAD). We aimed to determine the prevalence and risk factors for PAD in people living with HIV (PLWH) compared to uninfected controls. We hypothesized that prevalence of PAD would be higher among PLWH than among controls independent of traditional cardiovascular disease (CVD) risk factors. METHODS: PLWH aged ≥40 were recruited from the Copenhagen comorbidity in HIV infection (COCOMO) study. Sex and age matched uninfected controls were recruited from the Copenhagen General Population Study. We defined PAD as ankle-brachial index (ABI) ≤ 0.9 and assessed risk factors for PAD using logistic regression adjusting for age, sex, smoking status, dyslipidemia, diabetes, hypertension and hsCRP. RESULTS: Among 908 PLWH and 11,106 controls, PAD was detected in 112 (12% CI [95% 10-14]) and 623 (6% [95% 5-6]), respectively (p<0.001); odds ratio (OR)=2.4 [95% 1.9-2.9], adjusted OR=1.7 [95% 1.3-2.3, p<.001]. Traditional CVD risk factors, but not HIV-related variables were associated with PAD. The strength of the association between PAD and HIV tended to be higher with older age (p=0.052, adjusted test for interaction). CONCLUSION: Prevalence of PAD is higher among PLWH compared to uninfected controls, especially among older persons, and remains so after adjusting for traditional CVD risk factors. Our findings expand the evidence base that PLWH have excess arterial disease to also include PAD. The exact biological mechanisms causing this excess risk remain to be elucidated. Until then, focus on management of modifiable traditional risk factors is important

    The Development of a Point of Care Clinical Guidelines Mobile Application Following a User-Centred Design Approach

    Get PDF
    This paper describes the development of a point of care clinical guidelines mobile application. A user-centred design approach was utilised to inform the design of a smartphone application, this included: Observations; a survey; focus groups and an analysis of popular apps utilised by clinicians in a UK NHS Trust. Usability testing was conducted to inform iterations of the application, which presents clinicians with a variety of integrated tools to aid in decision making and information retrieval. The study found that clinicians use a mixture of technology to retrieve information, which is often inefficient or has poor usability. It also shows that smartphone application development for use in UK hospitals needs to consider the variety of users and their clinical knowledge and work pattern. This study highlights the need for applying user-centred design methods in the design of information presented to clinicians and the need for clinical information delivery that is efficient and easy to use at the bedside

    Allometric Scaling of the Active Hematopoietic Stem Cell Pool across Mammals

    Get PDF
    BACKGROUND: Many biological processes are characterized by allometric relations of the type Y = Y (0) M(b) between an observable Y and body mass M, which pervade at multiple levels of organization. In what regards the hematopoietic stem cell pool, there is experimental evidence that the size of the hematopoietic stem cell pool is conserved in mammals. However, demands for blood cell formation vary across mammals and thus the size of the active stem cell compartment could vary across species. METHODOLOGY/PRINCIPLE FINDINGS: Here we investigate the allometric scaling of the hematopoietic system in a large group of mammalian species using reticulocyte counts as a marker of the active stem cell pool. Our model predicts that the total number of active stem cells, in an adult mammal, scales with body mass with the exponent ¾. CONCLUSION/SIGNIFICANCE: The scaling predicted here provides an intuitive justification of the Hayflick hypothesis and supports the current view of a small active stem cell pool supported by a large, quiescent reserve. The present scaling shows excellent agreement with the available (indirect) data for smaller mammals. The small size of the active stem cell pool enhances the role of stochastic effects in the overall dynamics of the hematopoietic system

    “Excellence R Us”: university research and the fetishisation of excellence

    Get PDF
    The rhetoric of “excellence” is pervasive across the academy. It is used to refer to research outputs as well as researchers, theory and education, individuals and organisations, from art history to zoology. But does “excellence” actually mean anything? Does this pervasive narrative of “excellence” do any good? Drawing on a range of sources we interrogate “excellence” as a concept and find that it has no intrinsic meaning in academia. Rather it functions as a linguistic interchange mechanism. To investigate whether this linguistic function is useful we examine how the rhetoric of excellence combines with narratives of scarcity and competition to show that the hypercompetition that arises from the performance of “excellence” is completely at odds with the qualities of good research. We trace the roots of issues in reproducibility, fraud, and homophily to this rhetoric. But we also show that this rhetoric is an internal, and not primarily an external, imposition. We conclude by proposing an alternative rhetoric based on soundness and capacity-building. In the final analysis, it turns out that that “excellence” is not excellent. Used in its current unqualified form it is a pernicious and dangerous rhetoric that undermines the very foundations of good research and scholarship
    corecore