bluuebunny/crossref_metadata_2025 huggingface dataset:
Generating price‐effective intermodal routes
Authors: Gromicho Joaquim A.S. , Oudshoorn Erwin , Post Gerhard
Published: May 2011

We describe the problem of intermodal international freight transport that is faced by some logistic service providers and the solution that ORTEC's logistic suite offers to these customers. This solution is based on a state of the art k‐shortest path algorithm for directed networks. Our focus is on the modeling aspects of the problem. In particular, we propose an approach in two phases and methods to reduce the size of the network, so as to obtain a solution within an acceptable calculation time.
Properties of Preliminary Test Estimators and Shrinkage Estimators for Evaluating Multiple Exposures—Application to Questionnaire Data from the ‘Study of Nevi in Children’
Authors: Satagopan Jaya M. , Zhou Qin , Oliveria Susan A. , Dusza Stephen W. , Weinstock Martin A. , Berwick Marianne , Halpern Allan C.
Published: May 2011

Epidemiology studies increasingly examine multiple exposures in relation to disease by selecting the exposures of interest in a thematic manner. For example, sun exposure, sunburn and sun protection behaviour could be themes for an investigation of sun-related exposures. Several studies now use predefined linear combinations of the exposures pertaining to the themes to estimate the effects of the individual exposures. Such analyses may improve the precision of the exposure effects, but they can lead to inflated bias and type I errors when the linear combinations are inaccurate. We investigate preliminary test estimators and empirical Bayes-type shrinkage estimators as alternative approaches when it is desirable to exploit the thematic choice of exposures, but the accuracy of the predefined linear combinations is unknown. We show that the two types of estimator are intimately related under certain assumptions. The shrinkage estimator that is derived under the assumption of an exchangeable prior distribution gives precise estimates and is robust to misspecifications of the user-defined linear combinations. The precision gains and robustness of the shrinkage estimation approach are illustrated by using data from the ‘Study of nevi in children’, where the exposures are the individual questionnaire items and the outcome is log(total back naevus count).
Workload Portfolio Optimization for Virtualized Computer Systems Based on Semiparametric Quantile Function Estimation
Authors: Li Ta-Hsin
Published: May 2011

The latest technologies of server virtualization allow multiple computer workloads to share the same physical system dynamically while protecting them from interference from each other. Consolidation of workloads from stand-alone systems into virtualized systems requires accurate capacity sizing and optimal portfolio design to maximize the benefit of virtualization. This requirement often translates into a demand for accurate estimation of high quantiles from a limited amount of data for hundreds of workloads with diverse statistical characteristics. To deal with the problem, a semiparametric method of quantile function estimation is considered. The method employs the generalized Pareto distribution to model the high quantiles that exceed a certain threshold and retains the sample quantiles below the threshold. An automatic procedure is proposed for adaptive threshold and estimator selection and for adaptive data trimming. A simulation study shows that the procedure proposed is superior to the non-parametric sample quantile method for a variety of distributions. The procedure is applied to a portfolio optimization problem for computer workload consolidation with real data.
Bayesian Estimation of Extent of Recovery for Aspects of Verbal Memory in Women Undergoing Adjuvant Chemotherapy Treatment for Breast Cancer
Authors: Rolfe Margaret I. , Mengersen Kerrie L. , Vearncombe Katharine J. , Andrew Brooke , Beadle Geoffrey F.
Published: May 2011

Decline in cognitive function can be experienced by up to 50% of women while undergoing adjuvant chemotherapy with a subset of patients experiencing long-term effects. Bayesian latent basis longitudinal random-effects and latent class growth models were used to assess the degree of verbal memory recovery for learning, immediate retention and delayed recall in women undergoing chemotherapy for early stage breast cancer and who were assessed before, and at 1, 6 and 18 months post chemotherapy. The latent basis model, with the initial time point fixed to 1 and the second to 0, enabled the estimation of the degree of recovery at times 3 and 4. In the single-class model, three prior distributions for the random effects were used, resulting in minimal differences in parameter estimation. These models resulted in a near complete recovery for learning, and 57–60% for immediate retention and delayed recall at 18 months post chemotherapy. A range of two- to five-class Bayesian mixture models were fitted, with classes differing for baseline and degree of recovery. In the three-class model, the ‘Low’ class indicated 29.0%, 11.0% and 9.6% recovery at 18 months post treatment for the three outcome measures respectively, indicating an extended time of reduced verbal memory function.
EXECUTIVE PAY DETERMINATION AND FIRM PERFORMANCE—EMPIRICAL EVIDENCE FROM A COMPRESSED WAGE ENVIRONMENT*
Authors: DALE‐OLSEN HARALD
Published: May 2011

Using representative register and questionnaire data on Norwegian firms and workplaces we study the relationship between firm performance, CEO compensation schemes and the level of executive compensation. On average no relationship is found between executive performance pay and firm productivity. These relationships vary between industries, and CEO performance pay is strongly associated with high‐productivity manufacturing firms. On average CEOs receive higher earnings under performance pay than under fixed pay, even controlled for productivity and industry differences. Thus the earnings of executives appear more strongly related to the choice of executive remuneration scheme than that of the performance of firms.
Extending home ownership before the First World War: the case of the Co‐operative Permanent Building Society, 1884–19131
Authors: SAMY LUKE
Published: May 2011

Formed in the mid‐nineteenth century, the building societies grew rapidly from their humble beginnings as localized ‘self‐help’ institutions to become the dominant players in the house mortgage market by the interwar period. Throughout their early history, the societies presented themselves as champions of home ownership among the working classes, but historians of housing have generally disputed the role that building societies played, or could have played, in extending home ownership before the First World War. The case study presented in this article shows that it was possible for a building society to lend to working‐class borrowers, and that home ownership before the First World War was not beyond the grasp of such people. While it was undoubtedly an exception within the movement, the Co‐operative Permanent Building Society showed a genuine commitment to working‐class owner‐occupation, providing the majority of its loans to both skilled and unskilled workers on easy repayment terms. How it was able to overcome the adverse selection and moral hazard risks involved in lending to such groups of people is the focus of this article.
Legal institutions, social norms, and entrepreneurship in Britain (c.1890–c.1939)1
Authors: DI MARTINO PAOLO
Published: May 2011

This article analyses the functioning of debt‐discharge procedures in England and Wales in the light of the debate on entrepreneurial failure in the years between the late Victorian age and the interwar period. Using an original dataset and an empirical approach, it is argued that social norms, cultural elements, and class considerations influenced the outcome of decisions in a way that could have reduced the incentives for economic agents to engage with productive activity. Results show that over the entire period judges paid disproportionate attention to moral issues, and often gave lighter sentences to members of the elite who went into bankruptcy for personal reasons, and tougher ones to entrepreneurs who failed because of engagement with economic activity.
Consumer policy and consumer empowerment: comparing the historic development in Finland and Germany
Authors: Wahlen Stefan , Huttunen Kaisa
Published: May 2011

This article traces the trajectories of consumer policy in Finland and Germany in the light of a comparative history in order to reflect upon the notion of consumer empowerment in public policy. The principle developments of contemporary consumer policy can be traced back to the post‐war political and economic integrations arising from the initial idea of free markets and individual freedom emphasized in classical liberalism. The article explores this development in Finland and Germany to the point of the establishment of a joint European Union (EU) consumer policy to reveal the notion of consumer empowerment. This approach creates an understanding of the peculiarities of consumer policy in EU member states despite the presence of a joint European policy area. Nowadays, both Finnish and German consumers find EU regulations excessive. It is important to acknowledge the influence of this historic development in order to understand what consumer empowerment meant in the past and thus to further develop policy action on a joint level.
Why do states enfranchise citizens abroad? Comparative insights from Mexico, Italy and Belgium
Authors: LAFLEUR JEAN‐MICHEL
Published: May 2011

Over the past two decades, sending states have greatly increased their interest in maintaining strong connections with their citizens abroad. The worldwide adoption of external voting – understood not only as an electoral procedure that allows some citizens to cast their vote outside the national territory but also as an acknowledgement that an emigrant status is compatible with polity membership – illustrates this phenomenon. Why do states enfranchise citizens abroad? In this article, I seek to answer this question by comparing the evolution of the debates on the extension of voting privileges to citizens residing abroad in Mexico, Italy and Belgium. My central argument is that a combination of variables shapes the development of external voting in different parts of the world, as well as the content of these laws. These include emigrant lobbying, home states' desires to stimulate emigrant loyalty for economic purposes and, most importantly, the evolution of domestic politics. In discussing these variables, I also shed light on how one can shape the adoption of external voting legislation to control the impact of votes cast abroad.
Tracking extranigral degeneration in animal models of Parkinson’s disease: quest for effective therapeutic strategies
Authors: Knaryan Varduhi H. , Samantaray Supriti , Le Gal Charlene , Ray Swapan K. , Banik Naren L.
Published: May 2011

J. Neurochem. (2011) 118, 326–338.

Sporadic Parkinson’s disease (PD) is now interpreted as a complex nervous system disorder in which the projection neurons are predominantly damaged. Such an interpretation is based on mapping of Lewy body and Lewy neurite pathology. Symptoms of the human disease are much widespread, which span from pre‐clinical non‐motor symptoms and clinical motor symptoms to cognitive discrepancies often seen in advanced stages. Existing symptomatic treatments further complicate with overt drug‐irresponsive symptoms. PD is better understood by assimilation of extranigral degenerative pathways with nigrostriatal degenerative mechanisms. The term ‘extranigral’ appeared first in the 1990s to more rigorously define the nigral pathology by process of elimination. However, as clinicians progressively identified PD symptoms unresponsive to the gold standard drug l‐DOPA, definitions of PD symptoms were redefined. Non‐motor symptoms prodromal to motor symptoms just as pre‐clinical to clinical, and conjointly emerged the concept of nigral versus extranigral degeneration in PD. While nigrostriatal degeneration is responsible for the neurobiological substrates of extrapyramydal motor features, extranigral degeneration corroborates a vast majority of other changes in discrete central, peripheral, and enteric nervous system nuclei, which together account for global symptoms of the human disease. As an extranigral site, spinal cord degeneration has also been implicated in PD progression. Interconnected to the upper CNS structures with descending and ascending pathways, spinal neurons participate in movement and sensory circuits, controlling movement and reflexes. Several clinical and in vivo studies have demonstrated signs of parkinsonism‐related degenerative processes in spinal cord, which led to recent consideration of spinal cord as an area of potential therapeutic target. In a nutshell, this review explores how the existing animal models can actually reflect the human disease in order to facilitate PD research. Evolution of extranigral degeneration studies has been succinctly revisited, followed by a survey on animal models in light of recent findings in clinical PD. Together, it may help to develop effective therapeutic strategies for PD.
Glaucoma blind registration in Fife (2000–2009) – a retrospective cohort study
Authors: O’Colmain Una , Anijeet Deepa , Vosoughi Marcus , Sinclair Anne , Sanders Roshini
Published: May 2011

Citation information: O’Colmain U, Anijeet D, Vosoughi M, Sinclair A & Sanders R. Glaucoma blind registration in Fife (2000–2009) – a retrospective cohort study. Ophthalmic Physiol Opt 2011, 31, 360–366. doi: 10.1111/j.1475‐1313.2011.00849.x

Purpose:  To collate information on patients registered blind secondary to glaucoma between 2000 and 2009 and compare findings to an identical study completed a decade earlier between 1990 and 1999.

Methods:  The records of all people registered as blind via the Fife Society for the Blind between 2000 and 2009 were retrospectively examined and those with glaucoma as the primary cause were studied in detail. We compared these results with the results of our previous study, in which we examined the same documents for the preceding decade, 1990–1999.

Results:  The glaucoma blind registration rate was reduced by 31% in the current study compared to the previous one (60 vs 87 patients, p = 0.013). At the same time, there was a 6% increase in blindness registrations due to all causes (881 vs 938, p = 0.62). Patients were referred with significantly fewer visual symptoms (33% vs 60%, p = 0.002) and glaucoma surgery rates increased from 44% to 62% in the current study (p = 0.013). In the later decade, more patients were offered partial sight registration before blind registration (37% vs 10%, p < 0.0001) and sustained independent living at the time of blind registration in this study (66% vs 33%, p < 0.0001). Nearly one‐third of patients in the study group had cognitive impairment and/or hearing loss and this was similar to the first study.

Conclusions:  The study demonstrates a downward trend in the rates of blind registration due to glaucoma, compared to stable rates of registration for all diseases. Over the time period of the two studies there were refinements in the way glaucoma is managed medically by the hospital eye service and in the community, with a high level of input maintained from the local low vision service.
A WATER ABSORPTION ANALYSIS OF NABATEAN, NORTH AFRICAN AND OTHER CLAY LAMP FABRICS UNEARTHED AT THE RED SEA PORT OF ROMANAILA(AQABA, JORDAN)*
Authors: LAPP E. C.
Published: May 2011

A water absorption analysis was conducted on 103 clay lamp samples to determine whether the fabrics of this pottery type are porous. If so, this would lend further support to the long‐standing assumption that lamp makers coated their lighting vessels with slip—not just for decorative purposes, but as a means of preventing oil seepage of the fuel chamber. The samples were excavated at the Red Sea port of RomanAila(modern Aqaba, Jordan) and belong to 10 different types originating from Arabia, Palestine, Egypt, Tunisia and Gaul. The results of the experiment reveal that clay lamp fabrics are porous, and comparatively more so than a reference group of non‐lamp pottery from Pella (Jordan). Petrographic thin‐section analysis of select fabrics confirms the presence of pores, cracks and propagating veins indicative of thermal stress resulting from repeated lamp use. Meandering veins identified in a nozzle fragment were created by the diffusion of vapours, probably originating from the burning lamp oil itself. Ancient lamp makers understood that, given its direct exposure to the extreme temperature of the flame, the nozzle was particularly vulnerable to breakage as a result of thermal shock. A porous lamp fabric, however, helped limit crack propagation, allowing the nozzle and the lamp body to expand and contract to avoid breakage.
Rethinking the sovereign in sovereign wealth funds
Authors: Dixon Adam D , Monk Ashby H B
Published: May 2011

Nation‐states are increasingly sharing sovereignty, both with other states and with supranational and non‐governmental institutions. This is partly due to a long period of economic and financial globalisation, which has undercut territorial notions of sovereignty and varieties of capitalism. In trying to understand this phenomenon, we are drawn to sovereign wealth funds (SWFs), as they offer a unique lens into the changing dynamics of contemporary capitalism, global economic integration and state sovereignty. Indeed, the SWF provides governments with a tool for both engaging with new spatial forms as well as resisting them. While politicians may conceptualise the objective of such funds in the most practical terms, they serve an under‐appreciated role in maintaining state sovereignty in a globalised world. In this paper, we build on emerging interdisciplinary scholarship concerning the rise of SWFs by broadening the interpretation of the utility of SWFs for the sponsoring government in relation to the practice and constitution of sovereignty, explicitly bridging political and economic geography. To this end, we offer an innovative, stylised typology of SWFs in relation to the state and sovereignty. The objective is to better understand the potential long‐term significance of SWFs and the factors that might underpin further development of new SWFs in different countries in the future. Moreover, we believe SWFs can be differentiated according to the role they play in sovereignty and what underlies their claims to legitimacy within their respective nation‐state. By understanding the rise and purpose of SWFs, we hope to better understand the sovereign in SWFs.
Decreased production of neuronal NOS‐derived hydrogen peroxide contributes to endothelial dysfunction in atherosclerosis
Authors: Capettini LSA , Cortes SF , Silva JF , Alvarez‐Leite JI , Lemos VS
Published: May 2011

BACKGROUND AND PURPOSE Reduced NO availability has been described as a key mechanism responsible for endothelial dysfunction in atherosclerosis. We previously reported that neuronal NOS (nNOS)‐derived H2O2 is an important endothelium‐derived relaxant factor in the mouse aorta. The role of H2O2 and nNOS in endothelial dysfunction in atherosclerosis remains undetermined. We hypothesized that a decrease in nNOS‐derived H2O2 contributes to the impaired vasodilatation in apolipoprotein E‐deficient mice (ApoE−/−).

EXPERIMENTAL APPROACH Changes in isometric tension were recorded on a myograph; simultaneously, NO and H2O2 were measured using carbon microsensors. Antisense oligodeoxynucleotides were used to knockdown eNOS and nNOS in vivo. Western blot and confocal microscopy were used to analyse the expression and localization of NOS isoforms.

KEY RESULTS Aortas from ApoE−/− mice showed impaired vasodilatation paralleled by decreased NO and H2O2 production. Inhibition of nNOS with L‐ArgNO2‐L‐Dbu, knockdown of nNOS and catalase, which decomposes H2O2 into oxygen and water, decreased ACh‐induced relaxation by half, produced a small diminution of NO production and abolished H2O2 in wild‐type animals, but had no effect in ApoE−/− mice. Confocal microscopy showed increased nNOS immunostaining in endothelial cells of ApoE−/− mice. However, ACh stimulation of vessels resulted in less phosphorylation on Ser852 in ApoE−/− mice.

CONCLUSIONS AND IMPLICATIONS Our data show that endothelial nNOS‐derived H2O2 production is impaired and contributes to endothelial dysfunction in ApoE−/− aorta. The present study provides a new mechanism for endothelial dysfunction in atherosclerosis and may represent a novel target to elaborate the therapeutic strategy for vascular atherosclerosis.
Cellular pharmacokinetic mechanisms of adriamycin resistance and its modulation by 20(S)‐ginsenoside Rh2 in MCF‐7/Adr cells
Authors: Zhang Jingwei , Zhou Fang , Wu Xiaolan , Zhang Xiaoxuan , Chen Yuancheng , Zha Beth S , Niu Fang , Lu Meng , Hao Gang , Sun Yuan , Sun Jianguo , Peng Ying , Wang Guangji
Published: May 2011

BACKGROUND AND PURPOSE Intracellular pharmacokinetics of anticancer drugs in multi‐drug resistance (MDR) cancer cells is hugely important in the evaluation and improvement of drug efficacy. By using adriamycin as a probe drug in MDR cancer cells, we developed a cellular pharmacokinetic‐pharmacodynamic (PK‐PD) model to reveal the correlation between cellular pharmacokinetic properties and drug resistance. In addition, the ability of 20(S)‐ginsenoside Rh2 (20(S)‐Rh2) to reverse MDR was further investigated.

EXPERIMENTAL APPROACH The cellular pharmacokinetics of adriamycin were analysed visually and quantitatively in human breast cancer cells MCF‐7 and in adriamycin‐resistant MCF‐7 (MCF‐7/Adr) cells. Mitochondria membrane potential was assayed to evaluate the apoptotic effect of adriamycin. Subsequently, a PK‐PD model was developed via MATLAB.

KEY RESULTS Visual and quantitative data of the dynamic subcellular distribution of adriamycin revealed that it accumulated in cells, especially nuclei, to a lesser and slower extent in MCF‐7/Adr than in MCF‐7 cells. 20(S)‐Rh2 increased the rate and amount of adriamycin entering cellular/subcellular compartments in MCF‐7/Adr cells through inhibition of P‐glycoprotein (P‐gp) activity, in turn augmenting adriamycin‐induced apoptosis. The integrated PK‐PD model mathematically revealed the pharmacokinetic mechanisms of adriamycin resistance in MCF‐7/Adr cells and its reversal by 20(S)‐Rh2.

CONCLUSIONS AND IMPLICATIONS P‐gp, which is overexpressed and functionally active at cellular/subcellular membranes, influences the cellular pharmacokinetic and pharmacological properties of adriamycin in MCF‐7/Adr cells. Inhibition of P‐gp activity represents a key mechanism by which 20(S)‐Rh2 attenuates adriamycin resistance. Even more importantly, our findings provide a new strategy to explore the in‐depth mechanisms of MDR and evaluate the efficacy of MDR modulators.
Δ9‐Tetrahydrocannabinol (Δ9‐THC) attenuates mouse sperm motility and male fecundity
Authors: Morgan Daniel J , Muller Charles H , Murataeva Natalia A , Davis Brian J , Mackie Ken
Published: May 2011

BACKGROUND AND PURPOSE Numerous studies have shown that N‐arachidonoylethanolamine (AEA) can inhibit sperm motility and function but the ability of cannabinoids to inhibit sperm motility is not well understood. We investigated the effects of WIN 55,212‐2, a CB1 cannabinoid receptor agonist, and Δ9‐tetrahydracannabinol (Δ9‐THC) on the ATP levels and motility of murine sperm in vitro. In addition, the effects of acute administration of Δ9‐THC on male fecundity were determined.

EXPERIMENTAL APPROACH Effects of Δ9‐THC on basal sperm kinematics were determined using computer‐assisted sperm analysis (CASA). Stop‐motion imaging was performed to measure sperm beat frequency. The effect of Δ9‐THC on sperm ATP was determined using a luciferase assay. Male fertility was determined by evaluating the size of litters sired by Δ9‐THC‐treated males.

KEY RESULTS Pretreatment of sperm for 15 min with 1 µM Δ9‐THC reduced their basal motility and attenuated the ability of bicarbonate to stimulate flagellar beat frequency. Treatment with 5 µM WIN 55,212‐2 or 10 µM Δ9‐THC for 30 min reduced sperm ATP levels. In sperm lacking CB1 receptors this inhibitory effect of WIN 55,212‐2 on ATP was attenuated whereas that of Δ9‐THC persisted. Administration of 50 mg·kg−1Δ9‐THC to male mice just before mating caused a 20% decrease in embryonic litter size.

CONCLUSIONS AND IMPLICATIONS Δ9‐THC inhibits both basal and bicarbonate‐stimulated sperm motility in vitro and reduces male fertility in vivo. High concentrations of WIN 55,212‐2 or Δ9‐THC inhibit ATP production in sperm; this effect of WIN 55,212‐2 is CB1 receptor‐dependent whereas that of Δ9‐THC is not.

LINKED ARTICLES This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue‐8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue‐7
Exercise Capacity in Patients Supported With Rotary Blood Pumps Is Improved by a Spontaneous Increase of Pump Flow at Constant Pump Speed and by a Rise in Native Cardiac Output
Authors: Jacquet Luc , Vancaenegem Olivier , Pasquet Agnès , Matte Pascal , Poncelet Alain , Price Joel , Gurné Olivier , Noirhomme Philippe
Published: May 2011

Exercise capacity is improved in patients supported with continuous flow rotary blood pumps (RP). The aim of this study was to investigate the mechanisms underlying this improvement. Ten patients implanted with a RP underwent cardiopulmonary exercise testing (CPET) at 6 months after surgery with hemodynamic and metabolic measurements (RP group). A group of 10 matched heart failure patients were extracted from our heart transplant database, and the results of their last CPET before transplantation were used for comparison (heart failure [HF] group). Peak VO2 was significantly higher in RP than in HF patients (15.8 ± 6.2 vs. 10.9 ± 3 mL O2/kg.min) reaching 52 ± 16% of their predicted peak VO2. The total output measured by a Swan‐Ganz catheter increased from 5.6 ± 1.6 to 9.2 ± 1.8 L/min in the RP group and was significantly higher at rest and at peak exercise than in the HF group, whose output increased from 3.5 ± 0.4 to 5.6 ±  1.6 L/min. In the RP group, the estimated pump flow increased from 5.3 ± 0.4 to 6.2 ± 0.8, whereas the native cardiac output increased from 0.0 ± 0.5 to 3 ± 1.7 L/min. Cardiac output at peak exercise was inversely correlated with age (r = −0.86, P = 0.001) and mean pulmonary artery pressure (r = −0.75, P = 0.012). Maximal exercise capacity is improved in patients supported by RP as compared to matched HF patients and reaches about 50% of the expected values. Both a spontaneous increase of pump flow at constant pump speed and an increase of the native cardiac output contribute to total flow elevation. These findings may suggest that an automatic pump speed adaptation during exercise would further improve the exercise capacity. This hypothesis should be examined.
Health Care Costs in Patients with Fibromyalgia on Pregabalin vs. Duloxetine
Authors: Burke James P. , Sanchez Robert J. , Joshi Ashish V. , Cappelleri Joseph C. , Kulakodlu Mahesh , Halpern Rachel
Published: May 2011

Background:  The economic burden associated with fibromyalgia in the U.S. is substantial. The objective of this study was to compare changes in health care costs in fibromyalgia patients initiated on pregabalin and duloxetine in real‐world settings.

Methods:  Patients (≥ 18 years old) initiating pregabalin or duloxetine between June 1, 2007 and December 31, 2008 were identified using a U.S. managed care database. Patients were selected if they had ≥ 2 medical claims for fibromyalgia (ICD‐9‐CM, 729.1) at least 90 days apart or ≥ 1 claim for fibromyalgia followed within 30 days by a pharmacy claim for pregabalin. The date of the first pregabalin or duloxetine prescription was defined as the index date, and continuous enrollment for 6‐month pre‐ and postindex periods was required.

Results:  A total of 1,616 pregabalin and 207 duloxetine patients were identified. Treatment differences between pregabalin and duloxetine in the pre‐/postindex change in mean [SD] all‐cause total health care costs ($1,307 [16,747] vs. −$158 [17,337]; P = 0.24) or fibromyalgia‐related total health care costs ($584 [3,834] vs. $759 [2,133]; P = 0.32) were not significant. Multivariate analysis using difference‐in‐differences models showed no significant difference in all‐cause costs (mean cost ratio = 1.05, 95% CI: 0.84 to 1.31) or fibromyalgia‐related costs (0.85, 95% CI: 0.61 to 1.18) between treatments during the postindex period.

Conclusion:  No significant differences were found between pregabalin and duloxetine in the pre‐ to postindex change in mean all‐cause or fibromyalgia‐related total health care costs.
Financial Distress and the Cross‐section of Equity Returns
Authors: GARLAPPI LORENZO , YAN HONG
Published: May 2011

We explicitly consider financial leverage in a simple equity valuation model and study the cross‐sectional implications of potential shareholder recovery upon resolution of financial distress. Our model is capable of simultaneously explaining lower returns for financially distressed stocks, stronger book‐to‐market effects for firms with high default likelihood, and the concentration of momentum profits among low credit quality firms. The model further predicts (i) a hump‐shaped relationship between value premium and default probability, and (ii) stronger momentum profits for nearly distressed firms with significant prospects for shareholder recovery. Our empirical analysis strongly confirms these novel predictions.
Estimation and Evaluation of Conditional Asset Pricing Models
Authors: NAGEL STEFAN , SINGLETON KENNETH J.
Published: May 2011

We find that several recently proposed consumption‐based models of stock returns, when evaluated using an optimal set of managed portfolios and the associated model‐implied conditional moment restrictions, fail to capture key features of risk premiums in equity markets. To arrive at these conclusions, we construct an optimal Generalized Method of Moments (GMM) estimator for models in which the stochastic discount factor (SDF) is a conditionally affine function of a set of priced risk factors, and we show that there is an optimal choice of managed portfolios to use in testing a null model against a proposed alternative generalized SDF.
Transseptal Left Ventricular Endocardial Pacing Reduces Dispersion of Ventricular Repolarization
Authors: SCOTT PAUL A. , YUE ARTHUR M. , WATTS EDD , ZEB MEHMOOD , ROBERTS PAUL R. , MORGAN JOHN M.
Published: May 2011

Background:
 Cardiac resynchronization therapy (CRT) may be proarrhythmic in some patients. This may be due to the effect of left ventricular (LV) epicardial pacing on ventricular repolarization. The purpose of this study was to evaluate the effect of endocardial versus epicardial LV biventricular pacing on surface electrocardiogram (ECG) parameters that are known markers of arrhythmogenic repolarization.

Methods:
 ECG markers of repolarization (QT dispersion, QTD; T peak to end, Tpeak‐end; Tpeak‐end dispersion, Tpeak‐endD; QTc) were retrospectively measured before and after CRT in seven patients with transseptal LV endocardial leads (TS group), 28 matched patients with coronary sinus (CS) LV leads (CS group), and eight patients with surgical LV epicardial leads (SUR group). All ECGs were scanned and analyzed using digital callipers.

Results:
 Compared to the CS group, the TS group CRT was associated with a significant postpacing reduction in QTD (−45.2 ± 35.6 vs −4.3 ± 43.6 ms, P = 0.03) and Tpeak‐end (−24.2 ± 22.1 vs 3.4 ± 26.7 ms, P = 0.02). There was a nonsignificant post‐CRT reduction in both Tpeak‐endD (−11.3 ± 31.0 vs 2.4 ± 28.9 ms, P = 0.27) and QTc (−50.0 ± 46.4 vs 4.4 ± 70.2 ms, P = 0.06) in the TS versus the CS group. In contrast, there were no differences between the SUR and CS groups in terms of the effect of CRT on these repolarization parameters.

Conclusions:
 CRT with (atrial transseptal) endocardial LV lead placement is associated with repolarization characteristics that are considered to be less arrhythmogenic than those generated by CS (epicardial) LV lead placement. Further work is needed to determine whether these changes translate to a reduction in proarrhythmia. (PACE 2011; 34:1258–1266)
Long‐term Arrhythmia Variability after Monomorphic Ventricular Tachycardia in Patients with an Implantable Cardioverter Defibrillator
Authors: CLEMENS MARCELL , NAGY‐BALÓ EDINA , HERCZKU CSABA , KUN CSABA , ÉDES ISTVÁN , CSANÁDI ZOLTÁN
Published: May 2011

Background:
 Arrhythmia burden in patients receiving an implantable cardioverter defibrillator (ICD) after monomorphic ventricular tachycardia (mVT) is higher than in patients with other indications. We investigated the long‐term arrhythmia profile in this subset of patients.

Methods:
 Fifty‐two patients with an ICD implanted after mVT were followed up for at least 3 months. The cycle lengths (CLs) of the tachycardias recovered from the device memory were compared with the CL of the index arrhythmia. Morphological analysis of the intracardiac electrograms was performed and the response to antitachycardia pacing (ATP) was also assessed.

Results:
 A total of 833 mVT episodes with intracardiac electrograms occurred during the follow‐up (3–58 months; mean: 30.3 months) in 41 of the 52 patients analyzed. mVTs with different CLs as compared with the index mVT were found in 26 (50.0%), and at least two different mVT morphologies were observed in 28 (53.8%) patients. Multiple mVT morphologies were predictive of lower ATP efficacy (95.6%, 85.0%, and 70.3% in the patients with 1, 2, and 3 or more mVT morphologies, respectively; P < 0.0001) and a higher shock burden (4.2%, 19.3%, and 24.7% in the patients with 1, 2, and 3 or more mVT morphologies, respectively; P < 0.0001).

Conclusion:
 A high mVT burden was demonstrated with marked variability of the arrhythmias as concerns both CL and morphology in patients with an ICD implanted for mVT. Multiple mVT morphologies during the follow‐up were predictive of lower ATP efficacy and a higher shock burden. (PACE 2011; 34:1185–1191)
Growth of Intricate ZnO Nanorod Networks on α‐Fe2O3‐Coated Si Substrate: Growth Mechanism and Optical Properties
Authors: Cui Yinfang , Wang Cong , Wu Sujuan , Jia Yuping , Zhang Fangfang , Wang Tianmin , Liu Gang
Published: May 2011

Intricate ZnO nanorod networks grown on α‐Fe2O3‐coated Si substrate were synthesized by low‐temperature solution synthesis method. The obtained samples and α‐Fe2O3 thin film were characterized by Field Emission Scanning Electron Microscope and X‐ray diffraction. The results show that the polar‐surface of the (110) preferred orientation of α‐Fe2O3 thin film is inclined to the Si substrate, which plays a critical role in the formation of the intricate ZnO nanorod networks. The schematic diagram for the formation process of the intricate ZnO nanorod networks has also been proposed. Furthermore, its photoluminescence displays a pronounced UV and green emission.
Melatonin promotes differentiation of 3T3‐L1 fibroblasts
Authors: González Alicia , Alvarez‐García Virginia , Martínez‐Campa Carlos , Alonso‐González C. , Cos Samuel
Published: May 2011

Abstract:  Melatonin inhibits the genesis and growth of breast cancer by interfering at different levels in the estrogen‐signaling pathways. Melatonin inhibits aromatase activity and expression in human breast cancer cells, thus behaving as a selective estrogen enzyme modulator. As the adipose tissue adjacent to the tumor seems to account for most aromatase expression and enzyme activity in breast tumors and also mediates the desmoplastic reaction or accumulation of undifferentiated fibroblasts around malignant epithelial cells, in this work, we studied the effects of melatonin on the conversion of preadipocytes (3T3‐L1) into adipocytes and on the capability of these cells to synthesize estrogens by regulating the expression and enzyme activity of aromatase, one of the main enzymes that participates in the synthesis of estrogens in the peritumoral adipose tissue. Thus, in both differentiating and differentiated 3T3‐L1 adipocytes, high concentrations of melatonin increased intracytoplasmic triglyceride accumulation, an indicator of adipogenic differentiation. Melatonin (1 mm) significantly increased the expression of both CCAAT/enhancer‐binding protein α and peroxisome proliferator‐activated receptor γ, two main regulators of terminal adipogenesis, in 3T3‐L1 cells. The presence of melatonin during differentiation also induced a parallel reduction in aromatase expression and activity and expression of the cells. The effects of melatonin were reversed by luzindole, a melatonin receptor antagonist, indicating that melatonin acts through known receptor‐mediated mechanisms. These findings suggest that, in human breast tumors, melatonin could stimulate the differentiation of fibroblasts and reduce the aromatase activity and expression in both fibroblasts and adipocytes, thereby reducing the number of estrogen‐producing cells proximal to malignant cells.
Water Level Monitoring Pressure Transducers—A Need for Industry‐Wide Standards
Authors: Sorensen James P.R. , Butcher Andrew S.
Published: May 2011

There are currently no industry‐wide standards for the calibration and specification of water‐level monitoring pressure transducers. Consequently, specifications from different manufacturers are currently not directly comparable, and different branded sensors may not perform similarly under the same environmental conditions. This has been highlighted by the varied performance of 14 leading brands of pressure transducers under test conditions. In laboratory tests, transducers generally met product accuracy specifications, although temperature compensation was substandard in five absolute sensors. In a 99‐day field test, accuracy was typically within around ±10 mm for lower range pressure sensors, which exceeded some product specifications. Furthermore, there was evidence for linear and curved forms of instrument drift. As a result of the diverse performance of the transducers, it is recommended that an industry‐wide standard for calibration and specification is introduced. This would eliminate any uncertainty surrounding the current procedures and lead to more informed procurement by the user who would have a greater understanding of comparative instrument performance. Any new standard should also address sensor drift which is currently rarely cited in product specifications.
Comprehensive Analysis of Single‐ and Multi‐Target Activity Cliffs Formed by Currently Available Bioactive Compounds
Authors: Wassermann Anne M. , Dimova Dilyana , Bajorath Jürgen
Published: May 2011

Activity cliffs are formed by structurally similar compounds having large potency differences. Their study is a focal point of SAR analysis. We present a first systematic survey of single‐ and multitarget activity cliffs contained in currently available bioactive compounds. Approximately 12% of all active compounds were involved in the formation of activity cliffs. Perhaps unexpectedly, activity cliffs were found to be similarly distributed over different protein target families. Moreover, only approximately 5% of all activity cliffs were multitarget cliffs. Importantly, we also found that only very few multitarget cliffs were formed by compounds having different target selectivity. In addition, ‘polypharmacological cliffs’, i.e., multitarget activity cliffs involving targets from different protein families, were also only rarely found. Taken together, our findings reveal that only approximately 2% of all pairs of structurally similar compounds sharing the same biological activity form activity cliffs but that, on average, approximately one of 10 active compounds is involved in the formation of one or two single‐target cliffs of large magnitude (with at least 100‐fold difference in potency). These compounds provide a rich source of SAR information and can be identified across many different target families.
Growth Promotion of Bifidobacterium Species by Poultry Bone and Meat Trimming Hydrolyzate
Authors: Lazzi Camilla , Meli Federica , Dossena Arnaldo , Gatti Monica , Neviani Erasmo
Published: May 2011

Abstract:  The growth of bifidobacteria that are employed in the production of functional food is often slow or limited, even on synthetic media. In this study, we investigated whether a peptide hydrolyzate (functional animal protein [FAP]), from poultry bones and meat trimmings, could be a potential source of growth stimulators. The bifidogenic activity of FAP on 18 strains of Bifidobacterium species was assessed via 2 different techniques: turbidimetric measurements and a direct count by fluorescence microscopy. Growth experiments were performed in B12 broth as the basal medium, B12 broth supplemented with N‐acetylglucosamine, and B12 broth supplemented with FAP. FAP supplementation yielded the highest maximum optical density (OD) and count values. The use of the microscopic fluorescence counts allowed for better evaluation of the extent of growth and assessment of the viability of cells. FAP from poultry bones and meat trimmings has potential as a growth stimulator for different bifidobacteria of human origin. FAP is a promising ingredient for inclusion in industrial media that are used to culture probiotic strains, including bifidobacteria, because it supports growth very well and maintains cells at a high level of viability.

Practical Application:  Proteinaceous hydrolyzate can be considered a promising ingredient for industrial media that are used to culture probiotic strains, including bifidobacteria, because it improves bacterial growth and maintains cells at a high level of viability.
Effect of Irradiation on Salmonella Survival and Quality of 2 Varieties of Whole Green Onions
Authors: Murugesan Latha , Williams‐Hill Donna , Prakash Anuradha
Published: May 2011

Abstract:  Two varieties of green onions, Banner and Baja Verde, were inoculated with a cocktail of 3 Salmonella strains using dip and spot inoculation and irradiated at 0, 0.3, 0.6, 0.9, and 1.2 kGy using electron beam. Salmonella survivors were enumerated using a XLD underlay/TSAYE overlay plating method. The D values were in the range of 0.26 to 0.32 kGy depending on variety but not on the method of inoculation. This indicated that a 5‐log reduction of Salmonella can be achieved at a dose of 1.6 kGy. For the quality study, both varieties of green onions were irradiated at 0, 1.5, 2.0, and 2.5 kGy and evaluated for changes in microbial counts, color, texture, and visual quality during storage at 4 °C. Irradiation reduced total plate counts and psychrotrophs by 3 logs. Although the counts increased during storage, they did not exceed the initial counts of control. No significant difference was observed in color and texture between irradiated samples and control. The control maintained good visual quality for about 13 d as compared to 15 d for 1.5 and 2.5 kGy samples. The 2.0 kGy samples maintained good visual quality for 17 d suggesting that irradiation can increase shelf life by reducing spoilage microorganisms but higher doses can be detrimental to quality. At the dose levels required to achieve a 5‐log reduction in Salmonella, the shelf life of whole green onion can be extended. This study shows that irradiation can be used to enhance safety without adverse effects on quality.
Blood Pressure and Cardiovascular Outcomes in Patients Taking Nonsteroidal Antiinflammatory Drugs
Authors: Krum Henry , Swergold Gary , Gammaitoni Arnold , Peloso Paul M. , Smugar Steven S. , Curtis Sean P. , Brater D. Craig , Wang Hongwei , Kaur Amarjot , Laine Loren , Weir Matthew R. , Cannon Christopher P.
Published: May 2011

Introduction: The increased thrombotic cardiovascular (CV) risk in trials of cyclo‐oxygenase‐2 (COX‐2) inhibitors versus placebo, and the apparent similar risk with nonsteroidal antiinflammatory drugs (NSAIDs), may be related to their potential to elevate blood pressure (BP). Aims: We evaluated the relationship between baseline BP and change in BP on CV events (CVEs) in patients receiving NSAIDs or COX‐2 inhibitors in the prospective randomized, double‐blind, Multinational Etoricoxib and Diclofenac Arthritis Long‐term Program (N = 34,701) comparing etoricoxib 60 or 90 mg or diclofenac 150 mg daily for a mean duration of 18 months. The main outcome measure was confirmed thrombotic CVEs. The Antiplatelet Trialists’ Collaboration endpoint, all‐cause mortality, CV/congestive heart failure (CHF) mortality, and CHF incidence were similarly evaluated. Results: We found that baseline systolic BP (SBP) was associated with significantly higher risk of all events (P < 0.001). Baseline diastolic BP (DBP) was inversely and significantly associated with risk of all events (P < 0.001 to P= 0.016) except CV/CHF mortality (P= 0.054). There was no significant differential effect between etoricoxib and diclofenac in relation to CVEs, except for confirmed CHF, for which the risk was significantly higher with etoricoxib (P= 0.019). Only CHF risk (P= 0.020 for both SBP and DBP change), but not thrombotic endpoints, was significantly associated with change in BP from months 0 to 4. These findings were not meaningfully altered after covariate adjustment for baseline CV risk. Conclusions: Baseline BP, but not change in BP, was significantly associated with risk of thrombotic CVEs through 18 months. The CV risk of COX‐2s and NSAIDs did not appear to be related to the BP‐elevating effects of these agents, although such analyses, i.e., from randomized controlled trials, are unable to definitively exclude such a relationship.
Tenosynovitis of the carpal sheath of the digital flexor tendons associated with tears of the radial head of the deep digital flexor: Observations in 11 horses
Authors: MINSHALL G. J. , WRIGHT I. M.
Published: May 2011

Reasons for performing study:Tears of the radial head of the deep digital flexor (DDF) have not previously been documented.

Objectives:To describe the presentation, clinical, ultrasonographic and tenoscopic features associated with tears of the radial head of the DDF and to report the results of treatment.

Hypotheses:Tears of the radial head of the DDF cause lameness and distension of the carpal sheath of the digital flexor tendons. Removal of disrupted tissue that is extruded into the sheath can result in clinical resolution and restoration of function.

Methods:Case records and diagnostic images of horses in which tearing of the radial head of the DDF was diagnosed were reviewed retrospectively and follow‐up information obtained.

Results:Eleven cases were identified. Clinical, ultrasonographic and tenoscopic commonality was recorded and treatment techniques were documented. All cases returned post operatively to pre‐injury levels of work.

Conclusion:Tearing of the radial head of the DDF is a clinical entity with consistent diagnostic features. Tenoscopic removal of the torn tissue is associated with a good outcome.

Potential relevance:Clinicians evaluating lame horses should include tearing of the radial head of the DDF as a differential diagnosis in animals with distended carpal sheaths. Tenoscopic surgery is a recommended treatment.
Thermodynamic Properties of Ionized Gases at High Temperatures
Authors: Eisazadeh-Far Kian , Metghalchi Hameed , Keck James C.
Published: May 2011

Thermodynamic properties of ionized gases at high temperatures have been calculated by a new model based on local equilibrium conditions. Calculations have been done for nitrogen, oxygen, air, argon, and helium. The temperature range is 300–100,000 K. Thermodynamic properties include specific heat capacity, density, mole fraction of particles, and enthalpy. The model has been developed using statistical thermodynamics methods. Results have been compared with other researchers and the agreement is good.