In Memoriam: James Lyons Chesnut, D.D.

https://digitalcommons.cedarville.edu/cedarville_village_history/1004/thumbnail.jp

Topics in Mathematical Pharmacology

Mathematical analysis of pharmacological models is becoming increasingly rel- evant for drug development. Emphasis on mechanistic models has grown and qualitative understanding of complex biological systems has improved a great deal. In this paper we present two examples of basic modular processes which are involved in a wide range of physiological systems. The first model concerns the interaction of a drug with its target, the way the compounds bind and then elicit an effect. The second model is central in signal trans- duction across the cell wall. Both models demonstrate the complex and interesting dynamics which is directly relevant for the impact of the drug. Analysis and Stochastic

Ionic current changes underlying action potential repolarization responses to physiological pacing and adrenergic stimulation in adult rat ventricular myocytes

This study aimed to simulate ventricular responses to elevations in myocyte pacing and adrenergic stimulation using a novel electrophysiological rat model and investigate ion channel responses underlying action potential (AP) modulations. Peak ion currents and AP repolarization to 50% and 90% of full repolarization (APD50-90) were recorded during simulations at 1–10 Hz pacing under control and adrenergic stimulation conditions. Further simulations were performed with incremental ion current block (L-type calcium current, ICa; transient outward current, Ito; slow delayed rectifier potassium current, IKs; rapid delayed rectifier potassium current, IKr; inward rectifier potassium current, IK1) to identify current influence on AP response to exercise. Simulated APD50-90 closely resembled experimental findings. Rate-dependent increases in IKs (6%–101%), IKr (141%–1339%), and ICa (0%–15%) and reductions in Ito (11%–57%) and IK1 (1%–9%) were observed. Meanwhile, adrenergic stimulation triggered moderate increases in all currents (23%–67%) except IK1. Further analyses suggest AP plateau is most sensitive to modulations in Ito and ICa while late repolarization is most sensitive to IK1, ICa, and IKs, with alterations in IKs predominantly stimulating the greatest magnitude of influence on late repolarization (35%–846% APD90 prolongation). The modified Leeds rat model (mLR) is capable of accurately modeling APs during physiological stress. This study highlights the importance of ICa, Ito, IK1, and IKs in controlling electrophysiological responses to exercise. This work will benefit the study of cardiac dysfunction, arrythmia, and disease, though future physiologically relevant experimental studies and model development are required

Exotic smooth structures and symplectic forms on closed manifolds

We give a short proof of the (known) result that there are no Kaehler structures on exotic tori. This yields a negative solution to a problem posed by Benson and Gordon. W discuss the symplectic version of the problem and analyze results which yield an evidence for the conjecture that there are no symplectic structures on exotic tori.Comment: AMSLaTeX, 16 pages, a new version. A survey of the symplectic version of the problem is adde

Atenolol versus losartan in children and young adults with Marfan's syndrome

BACKGROUND : Aortic-root dissection is the leading cause of death in Marfan's syndrome. Studies suggest that with regard to slowing aortic-root enlargement, losartan may be more effective than beta-blockers, the current standard therapy in most centers. METHODS : We conducted a randomized trial comparing losartan with atenolol in children and young adults with Marfan's syndrome. The primary outcome was the rate of aortic-root enlargement, expressed as the change in the maximum aortic-root-diameter z score indexed to body-surface area (hereafter, aortic-root z score) over a 3-year period. Secondary outcomes included the rate of change in the absolute diameter of the aortic root; the rate of change in aortic regurgitation; the time to aortic dissection, aortic-root surgery, or death; somatic growth; and the incidence of adverse events. RESULTS : From January 2007 through February 2011, a total of 21 clinical centers enrolled 608 participants, 6 months to 25 years of age (mean [+/- SD] age, 11.5 +/- 6.5 years in the atenolol group and 11.0 +/- 6.2 years in the losartan group), who had an aorticroot z score greater than 3.0. The baseline-adjusted rate of change (+/- SE) in the aortic-root z score did not differ significantly between the atenolol group and the losartan group (-0.139 +/- 0.013 and -0.107 +/- 0.013 standard-deviation units per year, respectively; P = 0.08). Both slopes were significantly less than zero, indicating a decrease in the degree of aortic-root dilatation relative to body-surface area with either treatment. The 3-year rates of aortic-root surgery, aortic dissection, death, and a composite of these events did not differ significantly between the two treatment groups. CONCLUSIONS : Among children and young adults with Marfan's syndrome who were randomly assigned to losartan or atenolol, we found no significant difference in the rate of aorticroot dilatation between the two treatment groups over a 3-year period

Psychometric assessment of the short-form Child Perceptions Questionnaire: an international collaborative study.

OBJECTIVE: To examine the factor structure and other psychometric characteristics of the most commonly used child oral-health-related quality-of-life (OHRQoL) measure (the 16-item short-form CPQ11-14 ) in a large number of children (N = 5804) from different settings and who had a range of caries experience and associated impacts. METHODS: Secondary data analyses used subnational epidemiological samples of 11- to 14-year-olds in Australia (N = 372), New Zealand (three samples: 352, 202, 429), Brunei (423), Cambodia (244), Hong Kong (542), Malaysia (439), Thailand (220, 325), England (88, 374), Germany (1055), Mexico (335) and Brazil (404). Confirmatory factor analysis (CFA) was used to examine the factor structure of the CPQ11-14 across the combined sample and within four regions (Australia/NZ, Asia, UK/Europe and Latin America). Item impact and internal reliability analysis were also conducted. RESULTS: Caries experience varied, with mean DMFT scores ranging from 0.5 in the Malaysian sample to 3.4 in one New Zealand sample. Even more variation was noted in the proportion reporting only fair or poor oral health; this was highest in the Cambodian and Mexican samples and lowest in the German sample and one New Zealand sample. One in 10 reported that their oral health had a marked impact on their life overall. The CFA across all samples revealed two factors with eigenvalues greater than 1. The first involved all items in the oral symptoms and functional limitations subscales; the second involved all emotional well-being and social well-being items. The first was designated the 'symptoms/function' subscale, and the second was designated the 'well-being' subscale. Cronbach's alpha scores were 0.72 and 0.84, respectively. The symptoms/function subscale contained more of the items with greater impact, with the item 'Food stuck in between your teeth' having greatest impact; in the well-being subscale, the 'Felt shy or embarrassed' item had the greatest impact. Repeating the analyses by world region gave similar findings. CONCLUSION: The CPQ11-14 performed well cross-sectionally in the largest analysis of the scale in the literature to date, with robust and mostly consistent psychometric characteristics, albeit with two underlying factors (rather than the originally hypothesized four-factor structure). It appears to be a sound, robust measure which should be useful for research, practice and policy

The rhetoric of the consumer and customer control in China

This article explores the extent to which the rhetoric of the sovereign consumer and the use of the customer as a device of managerial control have been transferred to the subsidiaries of multinational retail firms operating in China. Based upon data drawn from over 200 interviews conducted at UK and Japanese multi-nationals' stores, in this rapidly internationalizing context it was evident that the notion of the sovereign consumer was ubiquitous and procedures designed to inculcate management by customers or consumer control had been implemented. However, it was equally apparent that the rhetoric of the consumer not only served managerial ends, but also provided a rich and fertile resource for shopfloor workers. Meaningful, socially embedded relationships could also play a crucial role in transactions. Moreover, with respect to discipline and control, employees were fully aware that power lay with their managers, rather than disembodied consumers or even actual customers

Large Scale Magnetic Fields and the Number of Cosmic Ray Sources above 10^(19) eV

We present numerical simulations for the two-point correlation function and the angular power spectrum of nucleons above 10^{19} injected by a discrete distribution of sources following a simple approximation to the profile of the Local Supercluster. We develop a method to constrain the number of sources necessary to reproduce the observed sky distribution of ultra-high energy cosmic rays, as a function of the strength of the large scale cosmic magnetic fields in the Local Supercluster. While for fields B < 0.05 micro Gauss the Supercluster source distribution is inconsistent with the data for any number of sources, fields of strength B~0.3 micro Gauss could reproduce the observed data with a number of sources around 10.Comment: 10 latex pages, 17 postscript figures include

Boson-fermion stars: exploring different configurations

We use the flexibility of the concept of a fermion-boson star to explore different configurations, ranging from objects of atomic size and masses of the order $10^{18}$ g, up to objects of galactic masses and gigantic halos around a smaller core, with possible interesting applications to astrophysics and cosmology, particularly in the context of dark matter.Comment: 8 pages. Minor changes, new reference added and a few typos correcte

Measurement of the Bs0→J/ψKS0B_s^0\to J/\psi K_S^0 branching fraction

The $B_s^0\to J/\psi K_S^0$ branching fraction is measured in a data sample corresponding to 0.41$fb^{-1}$ of integrated luminosity collected with the LHCb detector at the LHC. This channel is sensitive to the penguin contributions affecting the sin2$\beta$ measurement from $B^0\to J/\psi K_S^0$ The time-integrated branching fraction is measured to be $BF(B_s^0\to J/\psi K_S^0)=(1.83\pm0.28)\times10^{-5}$. This is the most precise measurement to date