302 research outputs found

    A consistent two-factor model for pricing temperature derivatives

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    We analyze a consistent two-factor model for pricing temperature derivatives that incorporates the forward looking information available in the market by specifying a model for the dynamics of the complete meteorological forecast curve. The two-factor model is a generalization of the Nelson-Siegel curve model by allowing factors with mean-reversion to a stochastic mean for structural changes and seasonality for periodic patterns. Based on the outcomes of a statistical analysis of forecast data we conclude that the two-factor model captures well the stylized features of temperature forecast curves. In particular, a functional principal component analysis reveals that the model re ects reasonably well the dynamical structure of forecast curves by decomposing their shapes into a tilting and a bending factor. We continue by developing an estimation procedure for the model, before we derive explicit prices for temperature derivatives and calibrate the market price of risk (MPR) from temperature futures derivatives (CAT, HDD, CDD) traded at the Chicago Mercantile Exchange (CME). The factor model shows that the behavior of the implied MPR for futures traded in and out of the measurement period is more stable than other estimates obtained in the literature. This confirms that at least parts of the irregularity of the MPR is not due to irregular risk perception but rather due to information misspecification. Similar to temperature derivatives, this approach can be used for pricing other non-tradable assets

    Influence of Running and Walking on Hormonal Regulators of Appetite in Women

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    Nine female runners and ten walkers completed a 60 min moderate-intensity (70% VO2max) run or walk, or 60 min rest in counterbalanced order. Plasma concentrations of the orexogenic peptide ghrelin, anorexogenic peptides peptide YY (PYY), glucagon-like peptide-1 (GLP-1), and appetite ratings were measured at 30 min interval for 120 min, followed by a free-choice meal. Both orexogenic and anorexogenic peptides were elevated after running, but no changes were observed after walking. Relative energy intake (adjusted for cost of exercise/rest) was negative in the meal following running (−194 ± 206 kcal) versus walking (41 ± 196 kcal) (P = 0.015), although both were suppressed (P < 0.05) compared to rest (299 ± 308 and 284 ± 121 kcal, resp.). The average rate of change in PYY and GLP-1 over time predicted appetite in runners, but only the change in GLP-1 predicted hunger (P = 0.05) in walkers. Results provide evidence that exercise-induced alterations in appetite are likely driven by complex changes in appetite-regulating hormones rather than change in a single gut peptide

    Coming Out to Care: Caregivers of Gay and Lesbian Seniors in Canada

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    Purpose: This article reports on the findings of a study whose purpose was to explore the experiences of caregivers of gay and lesbian seniors living in the community and to identify issues that emerged from an exploration of access to and equity in health care services for these populations. Design and Methods: The study used a qualitative methodology based upon principles of grounded theory in which open-ended interviews were undertaken with 17 caregivers living in three different cities across Canada. Results: Findings indicated several critical themes, including the impact of felt and anticipated discrimination, complex processes of coming out, the role of caregivers, self-identification as a caregiver, and support. Implications:  We consider several recommendations for change in light of emerging themes, including expanding the definition of caregivers to be more inclusive of gay and lesbian realities, developing specialized services, and advocating to eliminate discrimination faced by these populations

    Human skeletal muscle drug transporters determine local exposure and toxicity of statins

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    Rationale: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, are important drugs used in the treatment and prevention of cardiovascular disease. Although statins are well tolerated, many patients develop myopathy manifesting as muscle aches and pain. Rhabdomyolysis is a rare but severe toxicity of statins. Interindividual differences in the activities of hepatic membrane drug transporters and metabolic enzymes are known to influence statin plasma pharmacokinetics and risk for myopathy. Interestingly, little is known regarding the molecular determinants of statin distribution into skeletal muscle and its relevance to toxicity. Objective: We sought to identify statin transporters in human skeletal muscle and determine their impact on statin toxicity in vitro. Methods and Results: We demonstrate that the uptake transporter OATP2B1 (human organic anion transporting polypeptide 2B1) and the efflux transporters, multidrug resistance-associated protein (MRP)1, MRP4, and MRP5 are expressed on the sarcolemmal membrane of human skeletal muscle fibers and that atorvastatin and rosuvastatin are substrates of these transporters when assessed using a heterologous expression system. In an in vitro model of differentiated, primary human skeletal muscle myoblast cells, we demonstrate basal membrane expression and drug efflux activity of MRP1, which contributes to reducing intracellular statin accumulation. Furthermore, we show that expression of human OATP2B1 in human skeletal muscle myoblast cells by adenoviral vectors increases intracellular accumulation and toxicity of statins and such effects were abrogated when cells overexpressed MRP1. Conclusions: These results identify key membrane transporters as modulators of skeletal muscle statin exposure and toxicity. © 2010 American Heart Association, Inc

    Evaluation of four Cameroonian medicinal plants for anticancer, antigonorrheal and antireverse transcriptase activities

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    Methanol extracts from the leaves, bark and roots of four Cameroonian medicinal plants, Bersama engleriana, Cupressus lusitanica, Vitellaria paradoxa and Guibourtia tessmannii were tested for their in vitro cytotoxicity, antigonorrheal and antireverse transcriptase activities. The XTT (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxyanilide inner salt) assay, the dilution method and reverse transcriptase (RT) assay were used for the investigations. Preliminary phytochemical analysis of the extracts was also conducted using standard methods. Results showed that all extracts contained compounds belonging to the classes of phenols and terpenoids. They were also able to reduce in dose dependent manner, the proliferation of the cancer THP-1, DU145, HeLa, MCF-7, HepG2 and the normal Vero cells. IC50 values below 30 μg/ml were noted with extract from the three parts of B. engleriana on at least two of the five studied cancer cell lines, the lowest value of 5.9 μg/ml being obtained with sample from the bark. IC50 values below 30 μg/ml were also recorded with extracts from the leaves (on HeLa cells) and bark (on MCF-7) of G. tessmanii, and that from the bark of C. lusitanica on MCF-7. Extracts from B. engleriana and those from the bark of V. paradoxa gave the minimal inhibitory concentrations (MIC) values below 100 μg/ml on most of the 10 tested Nesseria gonorrhoeae strains. Extracts from B. engleriana also inhibited more than 80% the activity of the Human Immuno-deficiency Virus (HIV) enzyme. Finally, the results of the present study provide baseline information for the use of B. engleriana, C. lusitanica, G. tessmanii, V. paradoxa.http://www.elsevier.com/locate/etapnf201

    Body temperature, activity patterns and hunting in free-living cheetah : biologging reveals new insights

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    As one of the few felids that is predominantly diurnal, cheetahs (Acinonyx jubatus) can be exposed to high heat loads in their natural habitat. Little is known about long‐term patterns of body temperature and activity (including hunting) in cheetahs because long‐term concurrent measurements of body temperature and activity have never been reported for cheetahs, or, indeed, for any free‐living felid. We report here body temperature and locomotor activity measured with implanted data loggers over 7 months in 5 free‐living cheetahs in Namibia. Air temperature ranged from a maximum of 39 °C in summer to −2 °C in winter. Cheetahs had higher (∼0.4 °C) maximum 24‐h body temperatures, later acrophase (∼1 h), with larger fluctuations in the range of the 24‐h body temperature rhythm (approximately 0.4 °C) during a hot‐dry period than during a cool‐dry period, but maintained homeothermy irrespective of the climatic conditions. As ambient temperatures increased, the cheetahs shifted from a diurnal to a crepuscular activity pattern, with reduced activity between 900 and 1500 hours and increased nocturnal activity. The timing of hunts followed the general pattern of activity; the cheetahs hunted when they were on the move. Cheetahs hunted if an opportunity presented itself; on occasion they hunted in the midday heat or in total darkness (new moon). Biologging revealed insights into cheetah biology that are not accessible by traditional observer‐based techniques.Supplementary Material: Table S1 Prey identified after 38 successful hunts. Figure S1 An original record of 10‐min recordings of body temperature from a single free‐living female cheetah (female 1, panel B) and the prevailing black globe temperature recorded at a nearby weather station (panel A) over the 7‐month study period (October to May).The National Research Foundation of South Africa and a Carnegie Large Research Grant.https://onlinelibrary.wiley.com/journal/17494877hj2020Paraclinical Science

    Prophylactic evaluation of verubecestat on disease- and symptom-modifying effects in 5XFAD mice.

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    Introduction: Alzheimer\u27s disease (AD) is the most common form of dementia. Beta-secretase (BACE) inhibitors have been proposed as potential therapeutic interventions; however, initiating treatment once disease has significantly progressed has failed to effectively stop or treat disease. Whether BACE inhibition may have efficacy when administered prophylactically in the early stages of AD has been under-investigated. The present studies aimed to evaluate prophylactic treatment of the BACE inhibitor verubecestat in an AD mouse model using the National Institute on Aging (NIA) resources of the Model Organism Development for Late-Onset Alzheimer\u27s Disease (MODEL-AD) Preclinical Testing Core (PTC) Drug Screening Pipeline. Methods: 5XFAD mice were administered verubecestat ad libitum in chow from 3 to 6 months of age, prior to the onset of significant disease pathology. Following treatment (6 months of age), in vivo imaging was conducted with 18F-florbetapir (AV-45/Amyvid) (18F-AV45) and 18-FDG (fluorodeoxyglucose)-PET (positron emission tomography)/MRI (magnetic resonance imaging), brain and plasma amyloid beta (Aβ) were measured, and the clinical and behavioral characteristics of the mice were assessed and correlated with the pharmacokinetic data. Results: Prophylactic verubecestat treatment resulted in dose- and region-dependent attenuations of 18F-AV45 uptake in male and female 5XFAD mice. Plasma Aβ40 and Aβ42 were also dose-dependently attenuated with treatment. Across the dose range evaluated, side effects including coat color changes and motor alterations were reported, in the absence of cognitive improvement or changes in 18F-FDG uptake. Discussion: Prophylactic treatment with verubecestat resulted in attenuated amyloid plaque deposition when treatment was initiated prior to significant pathology in 5XFAD mice. At the same dose range effective at attenuating Aβ levels, verubecestat produced side effects in the absence of improvements in cognitive function. Taken together these data demonstrate the rigorous translational approaches of the MODEL-AD PTC for interrogating potential therapeutics and provide insight into the limitations of verubecestat as a prophylactic intervention for early-stage AD
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