bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetic and pharmacodynamic comparison of hydrofluoroalkane and chlorofluorocarbon formulations of budesonide
Authors: Clearie Karine L. , Williamson Peter. A. , Meldrum Karen , Gillen Michael , Carlsson Lars‐Goran , Carlholm Marie , Ekelund Jan , Lipworth Brian J. 
Published: November 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Chlorofluorocarbons (CFCs) have been implicated in damage to the ozone layer, and are due to be phased out in accordance with the Montreal Protocol.• Hydrofluoroalkane‐134a (HFA) has been found to act as an adequate propellant for pressurized metered‐dose inhaler delivery systems without the same deleterious environmental effects.WHAT THIS STUDY ADDS• This paper presents data from both steady‐state pharmacokinetic and pharmacodynamic assessments of HFAvs.CFC pressurized metered‐dose inhaler formulations of budesonide. It demonstrates that they are therapeutically equivalent in terms of relative lung bioavailability, airway efficacy and systemic effects.AIMSA hydrofluoroalkane formulation of budesonide pressurized metered‐dose inhaler has been developed to replace the existing chlorofluorocarbon one. The aim of this study was to evaluate the pharmacokinetic and pharmacodynamic characteristics of both formulations.METHODSSystemic bioavailability and bioactivity of both hydrofluoroalkane and chlorofluorocarbon pressurized metered‐dose inhaler formulations at 800 µg twice daily was determined during a randomized crossover systemic pharmacokinetic/pharmacodynamic study at steady state in healthy volunteers. Measurements included the following: plasma cortisol AUC24h[area under the concentration‐time curve (0–24 h)], budesonide AUC0–12handCmax. Clinical efficacy was determined during a randomized crossover pharmacodynamic study in asthmatic patients receiving 200 µg followed by 800 µg budesonide via chlorofluorocarbon or hydrofluoroalkane pressurized metered‐dose inhaler each for 4 weeks. Methacholine PC20(primary outcome), exhaled nitric oxide, spirometry, peak expiratory flow and symptoms were evaluated.RESULTSIn the pharmacokinetic study, there were no differences in cortisol, AUC0–12h[area under the concentration‐time curve (0–12 h)],Tmax(time to maximum concentration) orCmax(peak serum concentration) between the hydrofluoroalkane and chlorofluorocarbon pressurized metered‐dose inhaler. The ratio of budesonide hydrofluoroalkanevs.chlorofluorocarbon pressurized metered‐dose inhaler for cortisol AUC24hwas 1.02 (95% confidence interval 0.93–1.11) and budesonide AUC0–12hwas 1.03 (90% confidence interval 0.9–1.18). In the asthma pharmacodynamic study, there was a significant dose response (P< 0.0001) for methacholine PC20(provocative concentration of methacholine needed to produce a 20% fall in FEV1) with a relative potency ratio of 1.10 (95% confidence interval 0.49–2.66), and no difference at either dose. No significant differences between formulations were seen with the secondary outcome variables.CONCLUSIONSHydrofluoroalkane and chlorofluorocarbon formulations of budesonide were therapeutically equivalent in terms of relative lung bioavailability, airway efficacy and systemic effects.
Risk of asthma in adult twins with type 2 diabetes and increased body mass index
Authors: Thomsen S. F. , Duffy D. L. , Kyvik K. O. , Skytthe A. , Backer V. 
Published: November 2010

To cite this article: Thomsen SF, Duffy DL, Kyvik KO, Skytthe A, Backer V. Risk of asthma in adult twins with type 2 diabetes and increased body mass index. Allergy 2011; 66: 562–568.AbstractAim:  To examine the relationship between asthma, type 2 diabetes and increased body mass index (BMI) in adult twins.Methods:  We performed record linkage between questionnaire‐defined asthma and BMI, and hospital discharge diagnoses of type 2 diabetes in 34 782 Danish twins, 20–71 years of age.Results:  The risk of asthma was increased in subjects with type 2 diabetes relative to nondiabetic subjects both in men (13.5%vs 7.5%), P = 0.001 and in women (16.6%vs 9.6%), P = 0.001. The result remained significant after adjustment for age, BMI, smoking, symptoms of chronic bronchitis, marital status and zygosity, men: OR = 1.70 (1.07–2.70), P = 0.026; women: OR = 1.88 (1.24–2.85), P = 0.003. In this analysis, BMI remained a highly significant predictor for asthma independently of diabetes status in women, P < 0.000 but not in men, P = 0.336. Significant positive genetic correlations were found between asthma and type 2 diabetes, 0.20 (0.01–0.40), P = 0.047; between asthma and BMI in women, 0.15 (0.07–0.22), P < 0.000; and between BMI and type 2 diabetes, 0.40 (0.29–0.43), P < 0.000.Conclusions:  Asthma, type 2 diabetes and increased BMI are strongly associated in adults, particularly in women. These results suggest a common aetiology for asthma and metabolic syndrome.
Production of prenylated flavonoids in tomato fruits expressing a prenyltransferase gene from Streptomyces coelicolor A3(2)
Authors: Koeduka T. , Shitan N. , Kumano T. , Sasaki K. , Sugiyama A. , Linley P. , Kawasaki T. , Ezura H. , Kuzuyama T. , Yazaki K. 
Published: November 2010

AbstractFlavonoids are natural compounds found in many plants, including the important fruit crop, tomato. Prenylated flavonoids consist of a large group of compounds, which often exhibit antitumour, antibacterial and/or anti‐androgen activities. In this study, we engineered the biosynthesis of prenylated flavonoids using a Streptomyces prenyltransferase HypSc (SCO7190) possessing broad‐range substrate specificity, in tomato as a host plant. LC/MS/MS analysis demonstrated the generation of 3′‐dimethylallyl naringenin in tomato fruits when recombinant HypSc protein was targeted to the plastids, whereas the recombinant protein hardly produced this compound in vitro. This is the first report confirming the accumulation of a prenylated flavonoid using a bacterial prenyltransferase in transgenic plants, and our results suggest that the product specificities of prenyltransferases can be significantly influenced by the host plant.
Heat shock protein 90 mediates cytoprotection by H2S against chemical hypoxia‐induced injury in PC12 cells
Authors: Meng Jin‐Lan , Mei Wei‐Yi , Dong Yan‐Fen , Wang Jian‐Hong , Zhao Chun‐Mei , Lan Ai‐Ping , Yang Chun‐Tao , Chen Pei‐Xi , Feng Jian‐Qiang , Hu Chen‐Heng 
Published: November 2010

Summary1. Increasing evidence indicates that hydrogen sulphide (H2S) may serve as an important biological cytoprotective agent. Heat shock protein (Hsp) 90 can attenuate stress‐induced injury. However, whether Hsp90 mediates the cytoprotective effect of H2S against chemical hypoxia‐induced injury in PC12 cells is not known.2. In the present study, CoCl2 (a chemical hypoxia mimetic) was used to treat PC12 cells to create a model of chemical hypoxia. To explore the role of Hsp90 in the cytoprotection afforded by H2S against chemical hypoxia‐induced injury, 2 μmol/L 17‐allylaminogeldanamycin (17‐AAG), a selective inhibitor of Hsp90, was administered for 30 min prior to preconditioning with 400 μmol/L NaHS, followed by chemical hypoxia.3. Cobalt chloride reduced cell viability (by 52.7 ± 1.5%), increased PC12 cell apoptosis (by 42.1 ± 1.5%), induced reactive oxygen species (ROS) by 3.79% compared with control and induced the dissipation of mitochondrial membrane potential (MMP) by 2.56% compared with control.4. Pretreatment of PC12 cells with 100–400 μmol/L sodium hydrosulphide (NaHS), an H2S donor, for 3 h prior to exposure to 600 μmol/L CoCl2 provided significant, concentration‐dependant protection to PC12 cells against CoCl2‐induced cytotoxicity. Specifically, pretreatment of PC12 cells with 400 μmol/L NaHS decreased apoptosis to 16.77 ± 1.77% and blocked the CoCl2‐induced increase in ROS production and loss of MMP.5. At 400 μmol/L, NaHS upregulated Hsp90 in a time‐dependant manner (over the period 0–180 min). In addition to its effects on Hsp90 expression, NaHS pretreatment of PC12 cells augmented the overexpression of Hsp90 induced by 600 μmol/L CoCl2 by 1.38‐fold (P < 0.01).6. Treatment of PC12 cells with 2 μmol/L 17‐AAG for 30 min prior to NaHS pretreatment blocked the overexpression of Hsp90 induced by NaHS preconditioning, as evidenced by decreased cell viability (by 54.2 + 1.2%; P < 0.01), increased PC12 cell apoptosis (by 36.6 ± 1.2%; P < 0.01) and increasing ROS production.7. The findings of the present study provide novel evidence that Hsp90 mediates H2S‐induced neuroprotection against chemical hypoxia‐induced injury via anti‐oxidant and anti‐apoptotic effects.
Six years’ experience with high‐intensity focused ultrasonography for prostate cancer: oncological outcomes using the new ‘Stuttgart’ definition for biochemical failure
Authors: Ripert Thomas , Azémar Marie‐Dominique , Ménard Johann , Barbe Coralie , Messaoudi Rabah , Bayoud Younes , Pierrevelcin Jean , Duval François , Staerman Frédéric 
Published: November 2010

Study Type – Therapy (outcomes research)Level of Evidence 2bOBJECTIVE• To determine oncological outcomes after high‐intensity focused ultrasonography (HIFU) treatment in patients with localized prostate cancer using a new, more accurate, definition (‘Stuttgart’ definition) of biochemical failure.PATIENTS AND METHODS• We performed a retrospective review of all patients in our centre who received first‐line treatment with a second‐generation AblathermTM device (EDAP‐TMS, Lyon, France).• Oncological failure was given either by biochemical failure (prostate‐specific antigen, PSA, nadir plus 1.2 g/mL) (Stuttgart definition) or the start of salvage therapy because of a persistently positive biopsy after the HIFU procedure.• The 5‐year biochemical‐free survival rate and 5‐year disease‐free survival rate were calculated.RESULTS• In total, 53 patients were included (mean age, 72.5 ± 4.5 years, range 60–79 years; 28 low risk and 25 intermediate risk). None had undergone previous hormonal therapy. Mean ±sd follow‐up was 45.4 ± 15.5 months (range 16–71 years). Mean (range) pre‐treatment PSA was 8.5 ± 4 (0.29–18) ng/mL. The median (range) PSA nadir value was 1 (0.01–14) ng/mL and occurred after a mean (range) of 5.09 (3–24) months.• Overall, 36 patients (67.9%) experienced oncological failure.• These included 33 cases (62.2%) of biochemical failure. A PSA nadir of ≤0.2, 0.21–1.0 and >1 ng/mL was reached in 20.8%, 30.2% and 49% of patients, respectively, and was associated with biochemical failure in 9.1%, 30.3% and 60.6%, respectively.• The 5‐year biochemical‐free survival rate and disease‐free survival rate were 21.7% and 13.5%, respectively. In multivariate analysis, a PSA nadir of >1 ng/mL was significantly associated with a risk of biochemical and oncological failure (P= 0.002 and P < 0.001).• Oncological failure was not associated with any risk group.• No patient died from prostate cancer.CONCLUSIONS• In our experience, AblathermTM treatment for clinically localized prostate cancer was associated with a high rate of biochemical failure as determined by the ‘Stuttgart’ definition, and did not achieve effective cancer control.• The PSA nadir value after HIFU treatment was a significant predictor of treatment failure.
Examining Autonomy’s Boundaries: A Follow‐up Review of Perinatal Mortality Cases in UK Independent Midwifery
Authors: Symon Andrew , Winter Clare , Donnan Peter T. , Kirkham Mavis 
Published: November 2010

Abstract:  Background:  An earlier matched cohort study in the United Kingdom found a significantly higher perinatal mortality rate for births booked under an independent midwife compared with births in National Health Service units (1.7% [25/1,508] vs 0.6% [45/7,366]). This study examined independent midwives’ management and decision making in the 15 instances of perinatal death that occurred at term.Methods:  Thematic analysis of independent midwives’ case notes was performed in instances of perinatal mortality. Semi‐structured interviews were conducted with the midwives concerned.Results:  Home birth was attempted in 13 of the 15 cases. Significant (often multiple) antenatal risk factors were identified in 13 cases, including twin pregnancy, planned vaginal births after cesarean section, breech presentations, and maternal illness. Several women had declined some or all routine antenatal screening. Three deaths occurred before labor onset. Postmortem results were known in only four cases; many causes of death remained unexplained. Professional consensus was that seven deaths were unpreventable; elective cesarean section may have changed the outcome in eight cases. However, the pregnant women had declined this option; some were reported to be avoiding National Health Service care because of previous bad experiences. Transfer to hospital care, when it occurred, was often problematic. Care management was judged to be clinically acceptable within the parameters set by the mothers’ choices.Conclusions:  Information about clinical processes (and outcomes) is essential if informed decisions are to be made. The women in this review had reportedly accepted the potential consequences of their high‐risk situations. If reality is to match rhetoric about “patient” autonomy, such decision making in high‐risk situations must be accepted. (BIRTH 37:4 December 2010)
Exploring Dental Care Misconceptions and Barriers in Pregnancy
Authors: Detman Linda A. , Cottrell Barbara H. , Denis‐Luque Marie F. 
Published: November 2010

Abstract:  Background:  Poor oral health is increasingly linked to adverse pregnancy outcomes, including preterm birth and low‐birthweight infants. Little is known about childbearing women’s experiences in obtaining dental care. The objective of this study was to explore Florida women’s experience of barriers in obtaining dental care before and during their pregnancies.Methods:  Study data were derived from a larger data set of a study that examined barriers to prenatal care. One month after giving birth face‐to‐face interviews were conducted with 253 African American women, 18 to 35 years old, who were residents of one of three Florida counties. Interview questions about women’s experiences on obtaining oral health care before and during pregnancy, and recall of guidance about oral health care during prenatal visits were transcribed and analyzed qualitatively. Through subject‐level content analysis, key themes were assessed about the participants’ perspectives on obtaining oral health care before and during pregnancy.Results:  Most participants did not obtain dental care and did not recall receiving dental information during prenatal visits. Barriers to dental care included lack of insurance, difficulty in finding a dentist, low priority given to dental care, misconceptions about the safety and appropriateness of dental care during pregnancy, and sporadic anticipatory guidance during prenatal care.Conclusions:  Misconceptions about the appropriateness of oral health care during pregnancy may affect women’s access to and use of this care. Given the implications of poor oral health on possible adverse birth outcomes and its larger connection with the general health of mothers and babies, attention to oral health misconceptions and barriers is warranted. (BIRTH 37:4 December 2010)
The Private Market for Long‐Term Care Insurance in the United States: A Review of the Evidence
Authors: Brown Jeffrey R. , Finkelstein Amy 
Published: November 2010

AbstractThis article reviews the growing literature on the market for private long‐term care insurance, a market notable for its small size despite the fact that long‐term care expenses are potentially large and highly uncertain. After summarizing long‐term care utilization and insurance coverage in the United States, the article reviews research on the supply of and the demand for private long‐term care insurance. It concludes that demand‐side factors impose important limits on the size of the private market and that we currently have a limited understanding of how public policies could be designed to encourage the growth of this market.
Housing, Health, and Annuities
Authors: Davidoff Thomas 
Published: November 2010

AbstractAnnuities, long‐term care insurance (LTCI), and reverse mortgages appear to offer important consumption smoothing benefits to the elderly, yet private markets for these products are small. A prominent idea is to combine LTCI and annuities to alleviate both supply (selection) and demand (liquidity) problems in these markets. This article shows that if consumers typically liquidate home equity only in the event of illness or very old age, then LTCI and annuities become less attractive and may become substitutes rather than complements. The reason is that the marginal utility of wealth drops when an otherwise illiquid home is sold, an event correlated with the payouts of both annuities and LTCI. Simulations confirm that demand for LTCI and annuities is highly sensitive to the liquidity and magnitude of home equity.
The Aggregate Demand for Private Health Insurance Coverage in the United States
Authors: Ahking Francis W. , Giaccotto Carmelo , Santerre Rexford E. 
Published: November 2010

AbstractThis article estimates the aggregate demand for private health insurance coverage in the United States using an error correction model for the period 1966–1999. Both short‐ and long‐run price and income elasticities of demand are estimated. The empirical findings indicate that both private insurance enrollment and the completeness of insurance are relatively inelastic with respect to changes in price and income in the short and long run. Moreover, the results suggest that an increase in the number cyclically and frictionally uninsured generates less welfare loss than an increase in the number of structurally uninsured.
Adverse Selection, Moral Hazard, and Outlier Payment Policy
Authors: Mougeot Michel , Naegelen Florence 
Published: November 2010

AbstractIn this article, we analyze the rationale for introducing outlier payments into a prospective payment system for hospitals under adverse selection and moral hazard. The payer has only two instruments: a fixed price for patients whose treatment cost is below a threshold and a cost‐sharing rule for outlier patients. We show that a fixed‐price policy is optimal when the hospital is sufficiently benevolent. When the hospital is weakly benevolent, a mixed policy solving a trade‐off between rent extraction, efficiency, and dumping deterrence must be preferred. We show how the optimal combination of fixed price and partially cost‐based payment depends on the degree of benevolence of the hospital, the social cost of public funds, and the distribution of patients severity.
Dynamics of the Market for Medical Malpractice Insurance
Authors: Neale Faith R. , Eastman Kevin L. , Peterson Drake Pamela 
Published: November 2010

AbstractPublic attention has been directed recently at the market for medical malpractice insurance, yet disagreement persists over whether this market has changed and, if so, what has caused this change. In this study, we examine factors that affect the market for this insurance, including the growth in premiums, losses, and investment earnings, and loss variability. Our analysis suggests that there was significant deterioration in the market for medical malpractice insurance beginning in 1998 and culminating in 2001. We conclude that insurers' losses are the primary driver of the market deterioration during the period 1998 through 2003.
On the Possibility of Profitable Self‐Selection Contracts in Competitive Insurance Markets
Authors: Snow Arthur 
Published: November 2010

AbstractSeveral studies extend the Rothschild–Stiglitz model of competitive insurance contracting with adverse selection by incorporating additional dimensions of private information and conclude that some insurers may earn positive profit in a separating, self‐selection equilibrium, provided each insurer is restricted to making a single contract offer. The main result of this article is that these profitable configurations are not sustainable when individual insurers can offer multiple contracts. It is also shown that the ability to offer multiple contracts overturns equilibria that have applicants from different risk classes pooled as well as those where profits are dissipated by a fixed entry cost.
Insurance Markets With Differential Information
Authors: Seog S. Hun 
Published: November 2010

AbstractThis article attempts to understand the outcomes when each party of an insurance contract simultaneously has superior information. I assume that policyholders have superior information about specific risks while insurers have superior information about general risks. I find that low‐general‐risk policyholders purchase insurance, while high‐general‐risk policyholders are self‐insured. Among the low‐general‐risk policyholders, high‐specific‐risk policyholders purchase full insurance, while low‐specific‐risk policyholders purchase partial insurance. When insurers can strategically publicize their information, efficiency is improved because high‐general‐risk policyholders purchase actuarially fair insurance. The market segmentation is also found based on the general‐risk type and the publicizing of information.
Evidence of Asymmetric Information in the Automobile Insurance Market: Dichotomous Versus Multinomial Measurement of Insurance Coverage
Authors: Kim Hyojoung , Kim Doyoung , Im Subin , Hardin James W. 
Published: November 2010

AbstractIn the empirical analysis of information asymmetry in automobile insurance markets, prior research used a dichotomous measurement approach that induces excessive bundling in coverage measurements and sample selection biases. To improve on the conditional correlation method for testing information asymmetry, we propose a multinomial measurement approach that constructs coverage categories at ordered multinomial levels. With this approach, we find robust evidence of information asymmetry in both coverage area and coverage amount choices, which we could not find with the dichotomous measurement approach. It thus demonstrates the sensitivity of the empirical findings to the method used to measure insurance coverage.
Multidimensional Credibility With Time Effects: An Application to Commercial Business Lines
Authors: Englund Martin , Gustafsson Jim , Nielsen Jens Perch , Thuring Fredrik 
Published: November 2010

AbstractThis article considers Danish insurance business lines for which the pricing methodology has been dramatically upgraded recently. A costly affair, but nevertheless, the benefits greatly exceed the costs; without a proper pricing mechanism, you are simply not competitive. We show that experience rating improves this sophisticated pricing method as much as it originally improved pricing compared with a trivial flat rate. Hence, it is very important to take advantage of available customer experience. We verify that recent developments in multivariate credibility theory improve the prediction significantly, and we contribute to this theory with new robust estimation methods for time (in‐)dependency.