bluuebunny/crossref_metadata_2025 huggingface dataset:
ON THE PROBABILITY OF ERROR WHEN USING A GENERAL AKAIKE‐TYPE CRITERION TO ESTIMATE AUTOREGRESSION ORDER
Authors: Hall Peter , Hart Jeffrey D.
Published: May 2008

Abstract.A general Akaike‐type procedure is studied where the additive penalty is proportional to the autoregression order but the constant of proportionality has a general valueγ. For the procedure to be weakly consistent it is necessary and sufficient thatγ→0 andnγ∝ asn∝, wherendenotes the sample size. Ifn1‐εγ∝ for some ε>0 then the probability of erring when estimating the autoregression order converges to zero at a raten‐c, for allc>0, asn→∝. However, several procedures suggested for practical use haven1‐εγ→0 for each ε>0; in particular, they haveγ=n‐1lognorγ=n‐1log logn. To elucidate the properties of error probabilities in these circumstances we study the case of an AR(1) process. It is shown that in this case the probability of underestimating order is usually substantially less then the chance of overestimation, unless the autoregressive constant is particularly small (in fact, of size 2γ1/2).
BAYESIAN THRESHOLD AUTOREGRESSIVE MODELS FOR NONLINEAR TIME SERIES
Authors: Geweke John , Terui Nobuhiko
Published: May 2008

Abstract.This paper provides a Bayesian approach to statistical inference in the threshold autoregressive model for time series. The exact posterior distribution of the delay and threshold parameters is derived, as is the multi‐step‐ahead predictive density. The proposed methods are applied to the Wolfe's sunspot and Canadian lynx data sets.
ON THE UNIMODALITY OF THE EXACT LIKELIHOOD FUNCTION FOR NORMAL AR(2) SERIES
Authors: Minozzo M. , Azzalini A.
Published: May 2008

Abstract. For stationary second‐order autoregressive normal processes, the conjecture of uniqueness of the solution of the exact likelihood equations is examined. A sufficient condition for uniqueness is given; this condition is satisfied with very high probability if the number of observations is not extremely small. Moreover, it is shown that not more than two maxima may exist. Examples of data which actually produce a likelihood function with two local maxima are given.
NON‐SINGULARITY OF FISHER INFORMATION FOR AUTOREGRESSIVE MOYING‐AVERAGE PROCESSES
Authors: Wang Xiaobao
Published: May 2008

Abstract. The average Fisher information about the parameter of a finite‐order ARMA process is non‐singular if and only if the parameter is identifiable.
ESTIMATION AND BLIND DECONVOLUTION OF AUTOREGRESSIVE SYSTEMS WITH NONSTATIONARY BINARY INPUTS
Authors: Li Ta‐Hsin
Published: May 2008

Abstract. The problem of parameter estimation and blind deconvolution of auto‐regressive (AR) systems with independent nonstationary binary inputs is considered. The estimation procedure consists of applying a moving‐average filter (equalizer) to the observed data and adjusting the parameters of the filter so as to minimize a criterion that measures the binariness of its output. The output sequence itself serves as an estimate of the unobservable binary input of the AR system. Without assuming stationarity of the inputs, it is shown that the proposed method produces a consistent estimator of the AR system not only in the sense of converging to the true parameter as the sample size increases, but also in the sense of attaining the true parameter of the AR system for a sufficiently large sample size. For noisy data, the estimation criterion is modified on the basis of an asymptotic analysis of the effect of the noise. It is shown that the modified criterion is also consistent (in the usual sense) and its variability depends upon the filtered noise. Some simulation results are presented to demonstrate the performance of the proposed method for parameter estimation as well as for blind deconvolution.
RANDOM AGGREGATION OF UNIVARIATE AND MULTIVARIATE LINEAR PROCESSES
Authors: Kadi A. , Oppenheim G. , Viano M. C.
Published: May 2008

Abstract. The paper is devoted to random aggregation of multivariate autoregressive moving‐average (ARMA) processes. We derive second‐order characteristics of random aggregate models. We show that random aggregation preserves the ARMA structure. Moreover, we specify a functional relation between the initial model poles and aggregate ones. We then examine the case of univariate ARMA processes. Theorem 4 shows that, if the initial process is ARMA(p, q), the random aggregate process is an ARMA(p*, q*) model with p* at most equal to p; * depends, among other things, on the sampling distribution L. This theorem generalizes the well‐known results on the topic of time interval aggregation without overlapping.
ESTIMATION OF THE LONG‐MEMORY PARAMETER, BASED ON A MULTIVARIATE CENTRAL LIMIT THEOREM
Authors: Beran Jan , Terrin Norma
Published: May 2008

Abstract.Long memory is known to occur in many fields of statistical application. Stationary processes whose correlations decay asymptotically like ‖k‖2H‐2, wherekis the lag andHε (0.5, 1), provide useful parsimonious models with long memory. The parameterHcharacterizes the long‐memory features of the data. For long time series, maximum likelihood estimation ofHcan be costly in terms of CPU time. In this paper, we show that, for disjoint stretches of the data, estimates ofHand other parameters that characterize the dependence structure are asymptotically independent. Averaging these estimates leads to a fast and efficient approximate maximum likelihood method.
ESTIMATION OF THE FRACTIONAL DIFFERENCE PARAMETER IN THE ARIMA(p, d, q) MODEL USING THE SMOOTHED PERIODOGRAM
Authors: Reisen Valderio A.
Published: May 2008

Abstract. In recent work on time series analysis considerable interest has been focused on series having the property of long memory. Long memory is a characteristic of time series in which the dependence between distant observations is not negligible. The model that has been most frequently studied, which in some situations shows properties of long memory, is based on the autoregressive integrated moving‐average ARIMA(p, d, q) process. Hosking (Fractional differencing, Biometrika 68 (1) (1981), 165–76) generalized this model by permitting the degree of differencing d to take fractional values. He then demonstrated that for d in the range 0 < d < 0.5 the process is stationary and possesses the long memory property. Our study is based on the ARIMA(p, d, q) model when d takes any real non‐integer value in the interval (‐0.5, 0.5). The main aim of our study is to examine methods for estimating the parameters of this model. For estimating d we suggest an estimator based on the smoothed periodogram. Using an empirical approach we compare this estimator with other which are well known in the literature of long memory models, e.g. the raw periodogram regression method and the Hurst coefficient method.
THE NUMBER OF PEAKS IN A STATIONARY SAMPLE AND ORTHANT PROBABILITIES
Authors: Ku Simon , Seneta Eugene
Published: May 2008

Abstract. The essence of this paper is the exact evaluation of var Sn, where Sn is the number of peaks in a segment of n readings from a stationary Gaussian autoregressive moving‐average (ARMA) process, and of the asymptotic normality of (Sn–ESn)/(var Sn)1/2. The emphasis is on the AR(1) and MA(1) cases, motivated by Stigler (Estimating serial correlation by visual inspection of diagnostic plots. Am. Statistician 40 (1986), 111–16). The evaluation of var Sn is based on a discussion of closed‐form calculation of orthant probabilities for a zero mean quadrivariate normal with correlation structure new to the literature. Related issues are the power of the peaks test against stationary alternatives and the good fit of the normal even for small n. validated by simulation.
RECURSIVE ESTIMATION IN SWITCHING AUTOREGRESSIONS WITH A MARKOV REGIME
Authors: Holst Ulla , Lindgren Georg , Holst Jan , Thuvesholmen Mikael
Published: May 2008

Abstract. A hidden Markov regime is a Markov process that governs the time or space dependent distributions of an observed stochastic process. We propose a recursive algorithm for parameter estimation in a switching autoregressive process governed by a hidden Markov chain. A common approach to the recursive estimation problem is to base the estimation on suboptimal modifications of Kalman filtering techniques. The main idea in this paper is to use the maximum likelihood method and from this develop a recursive EM algorithm.
A NEW WAY TO ESTIMATE ORDERS IN TIME SERIES
Authors: Zhang Hu‐Ming , Wang Ping
Published: May 2008

Abstract.In this paper we propose the order determination quantity (ODQ) as a new way to solve order estimation problems in time series analysis. We estimate orders according to ODQ > 0 or ODQ < 0 instead of by minimizing. Theoretical analysis and simulation have shown that the ODQ has higher identifiability for unknown true orders, provides clear separation points and requires less computational effort than the existing order estimation criteria such as Akaike's information criterion (AIC), Bayes information criterion (BIC),φand predictive least squares (PLS).
ESTIMATION OF COEFFICIENTS OF TIME SERIES REGRESSION WITH A NONSTATIONARY ERROR PROCESS
Authors: Usami Yoshihiro , Huzii Mituaki
Published: May 2008

Abstract. We treat a problem of estimating unknown coefficients of a time series regression when the variance of the error changes with time, i.e. when a process which the error term obeys is nonstationary. First, we show the weak consistency of the ordinary least squares estimator for the coefficients of a polynomial regression under some assumptions on the covariance structure of the error process. Next, we propose a nonparametric method for estimating the variance of the error process and a weighted least squares estimator of the regression coefficients, which is constructed by using the estimator of the variance. We investigate statistical properties of our proposed estimator in the following way. We consider the prediction of a future value of a linear trend by using our proposed estimator and evaluate its prediction error. By simulation studies, we compare the prediction error of the predictor constructed by using our proposed estimator with the prediction errors obtained for other estimators including the ordinary least squares estimator when the variance of the error process increases with time and the sample sizes are small. As a result, our proposed estimator seems to be reasonable.
THE IDENTIFICATION OF SEASONAL AUTOREGRESSIVE MODELS
Authors: Koreisha Sergio G. , Pukkila Tarmo
Published: May 2008

Abstract.In this paper we present a new approach for identifying seasonal autoregressive models and the degree of differencing required to induce stationarity in the data. The identification method is iterative and consists in systematically fitting increasing order models to the data and then verifying that the resulting residuals behave like white noise using a two‐stage autoregressive order determination criterion. Once the order of the process is determined the identified structure is tested to see if it can be simplified. Simulation experiments based on different model structures with varying numbers of observations and parameter values as well as some macroeconomic data are used to evaluate the performance of the procedure.
ESTIMATION OF THE MULTIVARIATE AUTOREGRESSIVE MOVING AVERAGE HAVING PARAMETER RESTRICTIONS AND AN APPLICATION TO ROTATIONAL SAMPLING
Authors: Shin Dong Wan , Sarkar Sahadeb
Published: May 2008

Abstract. The vector autoregressive moving average model with nonlinear parametric restrictions is considered. A simple and easy‐to‐compute Newton‐Raphson estimator is proposed that approximates the restricted maximum likelihood estimator which takes full advantage of the information contained in the restrictions. In the case when there are no parametric restrictions, our Newton‐Raphson estimator is equivalent to the estimator proposed by Reinsel et al. (Maximum likelihood estimators in the multivariate autoregressive moving‐average model from a generalized least squares view point. J. Time Ser. Anal. 13 (1992), 133–45). The Newton‐Raphson estimation procedure also extends to the vector ARMAX model. Application of our Newton‐Raphson estimation method in rotational sampling problems is discussed. Simulation results are presented for two different restricted models to illustrate the estimation procedure and compare its performance with that of two alternative procedures that ignore the parametric restrictions.
ON THE RELATIONSHIP BETWEEN GENERALIZED LEAST SQUARES AND GAUSSIAN ESTIMATION OF VECTOR ARMA MODELS
Authors: Poskitt D. S. , Salau M. O.
Published: May 2008

Abstract.This paper investigates theoretical aspects of the relationship between the generalized least squares and Gaussian estimation schemes for vector autoregressive moving‐average models. The asymptotic convergence of the generalized least squares estimator to the Gaussian estimator is established and an alternative numerical method for implementing the generalized least squares scheme is proposed. Finally, some simulation results are presented to illustrate the theory.
MODEL SELECTION AND ORDER DETERMINATION FOR TIME SERIES BY INFORMATION BETWEEN THE PAST AND THE FUTURE
Authors: Li Lei , Xie Zhongjie
Published: May 2008

Abstract.In this paper, the information between the past and the future of a Gaussian stationary sequence is calculated either by its spectral density or by its autocovariances, and is related to the problem of model fitting. It is demonstrated that the criterion of minimum mutual information is the generalization of that of maximum entropy. By employing the above information quantity, we propose a procedure, which is called LIC for simplicity, to obtain consistent estimate of the order of the Bloomfield model or the autoregressive model. In Monte Carlo studies, we illustrate the LIC procedure by several examples, and also estimate the spectral density of time series by the Bloomfield model and LIC method.
BEVERIDGE‐NELSON‐TYPE TRENDS FOR I(2) AND SOME SEASONAL MODELS
Authors: Newbold Paul , Vougas Dimttrios
Published: May 2008

Abstract. Beveridge and Nelson (A new approach to decomposition of economic time series into permanent and transitory components with particular attention to measurement of the business cycle. J. Monet. Econ. 7 (1981), 151–74) introduced a decomposition into trend plus irregular components for time series generated by models that are integrated of order one. The components are functions of current and past, but not future, values of the series. Therefore, these components can be viewed as estimates available to an agent at the time. Moreover, the decomposition exists whenever the generating process is stationary after first differencing. In this paper we extend the decomposition to generating processes that are integrated of order two, and to the seasonal models of Box and Jenkins (Time Series Analysis, Forecasting and Control. San Francisco:Holden Day, 1970). The analysis leads to the estimation of stochastic growth rates, as well as component series. The methodology is applied to monthly UK industrial production data.
TESTING SERIAL INDEPENDENCE USING THE SAMPLE DISTRIBUTION FUNCTION
Authors: Delgado Miguel A.
Published: May 2008

Abstract. This paper presents and discusses a nonparametric test for detecting serial dependence. We consider a Cramèer‐von Mises statistic based on the difference between the joint sample distribution and the product of the marginals. Exact critical values can be approximated from the asymptotic null distribution, or by resampling, randomly permuting the original series. A Monte Carlo experiment illustrates the test performance with small sample sizes. The paper also includes an application, testing the random walk hypothesis of exchange rate returns for several currencies.
OPTIMAL PREDICTION OF CATASTROPHES IN AUTOREGRESSIVE MOVING‐AVERAGE PROCESSES
Authors: Svensson A. , Holst J. , Lindquist R. , Lindgren G.
Published: May 2008

Abstract. This paper presents an optimal predictor of level crossings, catastrophes, for autoregressive moving‐average processes, and investigates the performance of the predictor. The optimal catastrophe predictor is the predictor that gives a minimal number of false alarms for a fixed detection probability. As a tool for evaluating, comparing and constructing the predictors a method using operating characteristics, i.e. the probability of correct alarm and the probability of detecting a catastrophe for the predictor, is used. An explicit condition for the optimal catastrophe predictor based on linear prediction of future process values is given and compared with a naive catastrophe predictor, which alarms when the predicted process values exceed a given level, and with some different approximations of the optimal predictor. Simulations of the different algorithms are presented, and the performance is shown to agree with the theoretical results. All results indicate that the optimal catastrophe predictor is far better than the naive predictor. They also show that it is possible to construct an approximate catastrophe predictor requiring fewer computations without losing too much of the optimal predictor performance.
BIAS AND COVARIANCE OF THE RECURSIVE LEAST SQUARES ESTIMATOR WITH EXPONENTIAL FORGETTING IN VECTOR AUTOREGRESSIONS
Authors: Lindoff B. , Holst J.
Published: May 2008

Abstract. The recursive least squares (RLS) estimation algorithm with exponential forgetting is commonly used to estimate time‐varying parameters in stochastic systems. The statistical properties of the RLS estimator are often hard to find, since they depend in a non‐linear way on the time‐varying characteristics. In this paper the RLS estimator with exponential forgetting factor is applied to stationary Gaussian vector autoregres‐sions and the asymptotic bias and covariance function of the parameter estimates are derived.
Labour Demand, Flexible Contracts and Financial Factors: Firm‐Level Evidence from Spain*
Authors: Benito Andrew , Hernando Ignacio
Published: May 2008

We estimate models of labour demand for a panel of 3,400 Spanish manufacturing firms over the period 1985–2001. We examine the roles of fixed‐term contracts, financial factors and a policy reform in 1997 affecting permanent contracts by lowering payroll taxes and dismissal costs. Compared with permanent employment, the demand for flexible labour displays: (i) greater sensitivity to financial factors; (ii) greater cyclical sensitivity; (iii) a larger average wage elasticity; and (iv) less inertia. Our analysis of the 1997 policy reform suggests that a 5 percentage point reduction in the payroll tax is associated with an 8% increase in permanent labour demand.
IS AN EXPORT SUBSIDY A ROBUST TRADE POLICY RECOMMENDATION TOWARD A UNIONIZED DUOPOLY?
Authors: MA JIE
Published: May 2008

Brander and Spencer (1988) and Bandyopadhyay et al. (2000) imply that the robust trade policy recommendation toward a unionized duopoly is an export subsidy. In this paper, we show that we cannot get such a result even in the linear case if the opportunity cost of public funds is sufficiently high. However, if we consider the case where the domestic firm and the trade union lobby the government to set favorable trade policies by giving the government political contributions, then the result of robustness will be restored if the government cares about political contributions sufficiently relative to national welfare.
Lipoprotein(a) in patients initiating antiretroviral therapy
Authors: Mauss S , Berger F , Schmutz G , Henke J , Richter WO
Published: May 2008

Objectives

The interaction between lipoprotein(a), an emerging cardiovascular risk factor, and antiretrovirals (ARVs) has been less well studied than the interaction between either cholesterol or triglycerides and these drugs. In this study we assessed the effect of initiating antiretroviral therapy (ART) on lipoprotein(a) levels.

Methods

Fasting samples from 95 patients initiating ART with nucleoside/nucleotide reverse transcriptase inhibitors plus nonnucleoside reverse transcriptase inhibitors or protease inhibitors were obtained. Lipids and lipoproteins were determined until week 48.

Results

As in the general population, the study population showed a highly skewed lipoprotein(a) distribution (median 9.9 mg/dL, range 0.1–110 mg/dL). The study population was divided into individuals with lipoprotein(a) ≥30 mg/dL at baseline (n=28) and those with <30 mg/dL (n=67). Almost exclusively, patients with high lipoprotein(a) at baseline (median 51.6 mg/dL) showed a profound increase of median 26.7 mg/dL (week 24). This effect was not associated with specific ARVs and was independent of changes in other lipids. The low‐lipoprotein(a) group (baseline median 7 mg/dL) showed a small increase of median 2.6 mg/dL (week 24).

Conclusions

Marked increases in lipoprotein(a) after initiation of ART were mainly restricted to patients with high baseline levels. This may have clinical implications as patients with high lipoprotein(a) are at higher risk for myocardial infarction and stroke.
Adrenal suppression and Cushing's syndrome secondary to an interaction between ritonavir and fluticasone: a review of the literature
Authors: Foisy MM , Yakiwchuk EMK , Chiu I , Singh AE
Published: May 2008

Objective

The purpose of this article is to provide a systematic overview of the literature on adrenal suppression and Cushing's syndrome secondary to an interaction between inhaled/intranasal fluticasone and ritonavir. The clinical presentation, diagnosis and management will be discussed.

Methods

A literature search using Medline and EMBASE and a search of abstracts of the three previous years of major HIV‐related conferences were carried out.

Results

There were 25 cases (15 adult and 10 paediatric) of significant adrenal suppression secondary to an interaction between ritonavir and inhaled fluticasone, and three cases involving ritonavir and intranasal fluticasone. Cases with other steroids were not reported; however, there were cases of adrenal suppression with itraconazole [also a potent cytochrome p (CYP) 3A4 inhibitor] and inhaled budesonide. Clinicians need to differentiate between antiretroviral‐induced lipodystrophy syndrome and iatrogenic Cushing's syndrome secondary to glucocorticoid use. Long‐term fluticasone and ritonavir should be avoided. If ritonavir is required, another inhaled steroid such as low‐dose budesonide or beclomethasone can be used cautiously. Upon discontinuation of inhaled corticosteroids, close monitoring for symptoms of adrenal insufficiency is warranted. The need for steroid replacement therapy at physiological doses should be assessed.

Conclusions

The combination of ritonavir and fluticasone should be avoided. Budesonide, beclomethasone, triamcinolone and flunisolide appear to be safer options.
A STACKELBERG MODEL OF CHILD SUPPORT AND WELFARE*
Authors: Roff Jennifer
Published: May 2008

This article models the child support and welfare decisions of never‐married parents on welfare as a Stackelberg game. The mother chooses whether to exit welfare, report paternity, and to obtain a formal child support order. If a child support order is obtained, the father chooses whether to comply with the order. Simulation results from the structural parameters indicate that increasing the child support disregard increases paternal compliance slightly and affects maternal paternity reporting more significantly; effects are limited, however, by low paternal incomes. Results also indicate that high award amounts can decrease expected child support payments to women on welfare.
Explaining Attitudes towards Self‐employment among Immigrants: A Canadian Case Study
Authors: Bauder Harald
Published: May 2008

Implicit in Canada's immigration policies is that some immigrants are endowed with a particular entrepreneurial spirit, and that this spirit relates to immigrants’ origin. This paper examines whether attitudes towards entrepreneurship indeed relate to origin, or whether they can be explained through labour market circumstances at the place of settlement and/or Canada's immigrant selection procedure. The empirical study focuses on the reported attitudes towards entrepreneurship. A survey of 509 Vancouver residents of a predominantly Chinese immigrant neighbourhood, a predominantly South Asian immigrant neighbourhood, and a neighbourhood of non‐immigrants reveals that ethnic origin is a weak indicator of entrepreneurial attitudes. Instead, urban or rural background emerges as a more powerful predictor. The results also raise doubts about whether the Canadian government's immigration policy, which selects immigrants on the basis of economic potential, indeed selects immigrants with a greater desire to become self‐employed. Furthermore, the amount of time immigrants have spent in Canada does not significantly affect attitudes towards entrepreneurship.
History of the Use of Ergotamine and Dihydroergotamine in Migraine From 1906 and Onward
Authors: Tfelt-Hansen PC , Koehler PJ
Published: May 2008

Dale showed in 1906 in a seminal work that ergot inhibits the pressor effect of adrenaline. Stoll at Sandoz isolated ergotamine from ergot in 1918. Based on the belief that migraine was due to increased sympathetic activity, ergotamine was first used in the acute treatment of migraine by Maier in Switzerland in 1925. In 1938 Graham and Wolff demonstrated the parallel decrease of temporal pulsations and headache after ergotamine i.v. This inspired the vascular theory of Wolff: an initial cerebral vasoconstriction followed by an extracranial vasodilation. Dihydroergotamine (DHE) was introduced as an adrenolytic agent in 1943. It is still in use parenterally and by the nasal route. Before the triptan era ergotamine and DHE had widespread use as the only specific antimigraine drugs. From 1950 the world literature on ergotamine was dominated by two adverse events: ergotamine overuse headache and the relatively rare overt ergotism. Recently, oral ergotamine, which has an oral bioavailability of < 1%, has been inferior to oral triptans in randomized clinical trials. A European Consensus in 2000 concluded that ergotamine is not a drug of first choice. In an American review of 2003 it was suggested that ergotamine may be considered in the treatment of selected patients with moderate to severe migraine.
Francis Kilvert (1840–1879): An Early Self-Report of Cluster Headache?
Authors: Larner AJ
Published: May 2008

The published selections from the diary of the clergyman Francis Kilvert, dating from the 1870s, were systematically searched for accounts of headache, face ache and face pain. Although limited, as all such retrospective studies with restricted documentation must be, nonetheless illustrative quotations from the diaries suggest he may have suffered from cluster headache. This may be one of the earliest accounts by a patient, rather than a physician, of cluster headache.
Consumption of foods and foodstuffs processed with hazardous chemicals: a case study of Bangladesh
Authors: Hossain Md. Motaher , Heinonen Visa , Islam K. M. Zahidul
Published: May 2008

Determining the best way to persuade consumers to consume more healthy foods is challenging. In Bangladesh, however, daily newspapers consistently show that various hazardous chemicals (e.g. calcium carbide, sodium cyclamate, cyanide and formalin, etc.) are mixed with or added to foods and foodstuffs. These chemicals are very dangerous to humans. This present study examines the reasons behind the use of hazardous chemicals in foods as well as the extent to which food producers/sellers use such chemicals. In addition, this study assesses consumer perceptions of and attitudes towards these contaminated food items and explores how adulterated foods and foodstuffs affect consumer health. The empirical data were collected from 110 consumers, 25 sellers or producers, seven doctors and seven pharmacists in Dhaka, the capital of Bangladesh. This study shows that nearly every consumer (93.7%) is aware that various foods and foodstuffs contain hazardous chemicals, and that 95.5% of consumers are aware that these adulterated foods and foodstuffs are harmful to their health. This paper explores the myriad reasons why consumers nevertheless feel compelled to consume such chemically treated foods.
Effects of retinoic acids on the dendritic morphology of cultured hippocampal neurons
Authors: Liu Ying , Kagechika Hiroyuki , Ishikawa Junko , Hirano Hitoshi , Matsukuma Satoshi , Tanaka Kazuko , Nakamura Shoji
Published: May 2008

Vitamin A‐derived retinoic acids (RAs) are known to exert a variety of biological actions, including modulatory effects on cell differentiation and apoptosis. A recent study has demonstrated that 13‐cis‐RA and all‐trans‐RA suppressed neurogenesis in the dentate gyrus of the hippocampus in adult mice. The present experiments were performed to see whether 13‐cis‐RA and all‐trans‐RA could alter the dendritic morphology of cultured hippocampal neurons via RA receptors: retinoic acid receptor (RAR) and retinoid X receptor (RXR). High doses of 13‐cis‐RA and all‐trans‐RA exerted a negative effect on the cultured hippocampal neurons, while a low dose of 13‐cis‐RA but not all‐trans‐RA caused a positive effect. The negative changes induced by 13‐cis‐RA and all‐trans‐RA were antagonized by RXR antagonists and RAR antagonists, respectively. The positive changes induced by a low dose of 13‐cis‐RA were blocked by both RXR antagonists and RAR antagonists. These results suggest that RAs at high concentrations cause a negative effect on the dendritic morphology of cultured hippocampal neurons through RA receptors, while RAs at low concentrations exert a positive influence on cultured hippocampal neurons.
Neuroadaptive changes in the mesocortical glutamatergic system during chronic nicotine self‐administration and after extinction in rats
Authors: Wang Fan , Chen Hao , Sharp Burt M.
Published: May 2008

Nicotine self‐administration causes adaptation in the mesocorticolimbic glutamatergic system, including the up‐regulation of ionotropic glutamate receptor subunits. We therefore determined the effects of nicotine self‐administration and extinction on NMDA‐induced glutamate neurotransmission between the medial prefrontal cortex (mPFC) and ventral tegmental area (VTA). On day 19 of nicotine SA, both regions were microdialyzed for glutamate while mPFC was sequentially perfused with Kreb’s Ringer buffer (KRB), 200 μM NMDA, KRB, 500 μM NMDA, KRB, and 100 mM KCl. Basal glutamate levels were unaffected, but nicotine self‐administration significantly potentiated mPFC glutamate release to 200 μM NMDA, which was ineffective in controls. Furthermore, in VTA, nicotine self‐administration significantly amplified glutamate responses to both mPFC infusions of NMDA. This hyper‐responsive glutamate neurotransmission and enhanced glutamate subunit expression were reversed by extinction. Behavioral studies also showed that a microinjection of 2‐amino‐5‐phosphonopentanoic acid (NMDA‐R antagonist) into mPFC did not affect nicotine or sucrose self‐administration. However, in VTA, NBQX (AMPA‐R antagonist) attenuated both nicotine and sucrose self‐administration. Collectively, these studies indicate that mesocortical glutamate neurotransmission adapts to chronic nicotine self‐administration and VTA AMPA‐R may be involved in the maintenance of nicotine self‐administration.
Leptin neuroprotection in the CNS: mechanisms and therapeutic potentials
Authors: Signore Armando P. , Zhang Feng , Weng Zhongfang , Gao YanQin , Chen Jun
Published: May 2008

Leptin is well known as a hormone important in the central control of appetitive behaviors via receptor‐mediated actions in the hypothalamus, where leptin adjusts food intake to maintain homeostasis with the body’s energy stores. Recent evidence has shown that leptin and its receptors are widespread in the CNS and may provide neuronal survival signals. This review summarizes our current knowledge of how leptin functions in the brain and then focuses on the ability of leptin to mitigate neuronal damage in experimental models of human neurological disorders. Damage to the brain by acute events such as stroke, or long‐term loss of neurons associated with neurodegenerative diseases, including Parkinson’s and Alzheimer’s disease, may be amenable to treatment using leptin to limit death of susceptible cells. Leptin‐mediated pro‐survival signaling is now known to prevent the death of neurons in these models. The signaling cascades that leptin generates are shared by other neuroprotective molecules including insulin and erythropoietin, and are thus a component of the neurotrophic effects mediated by endogenous hormones. Coupled with evidence that leptin dysregulation in human disease also results in enhanced neuronal susceptibility to damage, development of leptin as a therapeutic methodology is an attractive and viable possibility.
Lovastatin effect in rat neuroblasts of the CNS: inhibition of cap‐dependent translation
Authors: Santa‐Catalina Marta Olivera , Garcia‐Marin Luis Jesus , Bragado María Julia
Published: May 2008

Mevalonate biosynthesis pathway is important in cell growth and survival and its blockade by 3‐hydroxy‐3‐methylglutaryl CoA reductase inhibitors, statins, arrest brain neuroblasts growth and induce apoptosis. Translation is among the main biochemical mechanisms that controls gene expression and therefore cell growth or apoptosis. In the CNS, translation regulates synaptic plasticity. Thus, our aim was to investigate the effect of lovastatin in protein translation in rat neuroblasts of the CNS and the biochemical pathways involved. Lovastatin treatment in rat brain neuroblasts causes a significant time‐ and concentration‐inhibition of protein synthesis, which is partially mediated by phosphatydilinositol 3‐kinase/mammalian target of rapamycin (mTOR) pathway inhibition. Lovastatin treatment decreases the phosphorylation state of mTOR substrates, p70S6K and eukaryotic translation initiation factor (eIF) 4E‐binding protein 1 and simultaneously increases eIF4E‐binding protein 1 in a time‐dependent manner. Concomitantly, lovastatin causes a decrease in eIF4G cellular amount, which is partially mediated by caspase(s) activity excluding caspase 3. These biochemical pathways affected by lovastatin might explain the protein translation inhibition observed in neuroblasts. Cycloheximide treatment, which blocked protein synthesis, does not induce neuroblasts apoptosis. Therefore, we suggest that lovastatin‐induced protein synthesis inhibition might not contribute to the concomitant neuroblasts apoptosis previously observed.
The ketogenic diet increases mitochondrial glutathione levels
Authors: Jarrett Stuart G. , Milder Julie B. , Liang Li‐Ping , Patel Manisha
Published: May 2008

The ketogenic diet (KD) is a high‐fat, low carbohydrate diet that is used as a therapy for intractable epilepsy. However, the mechanism(s) by which the KD achieves neuroprotection and/or seizure control are not yet known. We sought to determine whether the KD improves mitochondrial redox status. Adolescent Sprague–Dawley rats (P28) were fed a KD or control diet for 3 weeks and ketosis was confirmed by plasma levels of β‐hydroxybutyrate (BHB). KD‐fed rats showed a twofold increase in hippocampal mitochondrial GSH and GSH/GSSG ratios compared with control diet‐fed rats. To determine whether elevated mitochondrial GSH was associated with increased de novo synthesis, the enzymatic activity of glutamate cysteine ligase (GCL) (the rate‐limiting enzyme in GSH biosynthesis) and protein levels of the catalytic (GCLC) and modulatory (GCLM) subunits of GCL were analyzed. Increased GCL activity was observed in KD‐fed rats, as well as up‐regulated protein levels of GCL subunits. Reduced CoA (CoASH), an indicator of mitochondrial redox status, and lipoic acid, a thiol antioxidant, were also significantly increased in the hippocampus of KD‐fed rats compared with controls. As GSH is a major mitochondrial antioxidant that protects mitochondrial DNA (mtDNA) against oxidative damage, we measured mitochondrial H2O2 production and H2O2‐induced mtDNA damage. Isolated hippocampal mitochondria from KD‐fed rats showed functional consequences consistent with the improvement of mitochondrial redox status i.e. decreased H2O2 production and mtDNA damage. Together, the results demonstrate that the KD up‐regulates GSH biosynthesis, enhances mitochondrial antioxidant status, and protects mtDNA from oxidant‐induced damage.
Cerebellar granule cells cultured from adolescent rats express functional NMDA receptors: anin vitromodel for studying the developing cerebellum
Authors: Popp R. Lisa , Reneau Jason C. , Dertien Janet S.
Published: May 2008

In the developing rat cerebellum functional NMDA receptors (NMDARs) expressing the NR2C subunit have been identified on or after postnatal day 19. We obtained primary cultured cells from 19‐ to 35‐day‐old rat cerebellum that expressed few oligodendrocytes or astrocytes. Cultured cells were immunoreactive for neuron‐specific proteins thus indicating a neuronal population. The primary neuron present was the granule cell as indicated by immunofluorescence for the GABAAalpha 6 subunit. Whole‐cell patch‐clamp experiments indicated that functional NMDARs were present. Functional characteristics of NMDARs expressed in cerebellar granule cells (CGCs) obtained from adolescent animals were similar to those previously reported for NMDARs expressed in CGCs obtained from neonatal rats. Cultured CGCs obtained from older animals contained NMDARs that were inhibited by EtOH and were less sensitive to the NR2B subunit‐specific antagonist Ro 25‐6981. Furthermore, NMDA‐induced currents were smaller than those observed in CGCs. Western blot analysis indicated the presence of the NMDA NR2A and NR2C subunits, but not the NR2B in cultures obtained from the adolescent rats. CGCs obtained from adolescent rats express functional NMDARs consistent with a developmental profile observedin vivo.
Does Doctor–Patient Communication Affect Patient Satisfaction with Hospital Care? Results of an Analysis with a Novel Instrumental Variable
Authors: Clever Sarah L. , Jin Lei , Levinson Wendy , Meltzer David O.
Published: May 2008

Objective. To determine the relationship between physicians' communication behaviors and patients' overall satisfaction with hospital care using a novel instrumental variable to address possible confounding of this association by patient attributes.

Data Sources/Study Setting. Administrative records and postdischarge survey data were obtained from patients discharged from the General Medicine service at an urban tertiary‐care academic hospital between July 1, 1997 and June 30, 2000. Administrative data included comorbidities, demographic data, and payer status. In the discharge survey, patients rated their attending physician on four communication behaviors, other aspects of their hospital stay, and their overall hospital care.

Study Design. The primary outcome was patients' ratings of their overall satisfaction with hospital care, and the primary independent variable was patients' ratings of their physicians' communication behaviors. To remove possible confounding of the association between patient ratings of physician communication and overall satisfaction by other patient‐specific attributes, we created an instrumental variable (IV) in a two‐stage linear regression. The IV was the mean of the communication ratings given to each physician by the other patients cared for by that physician.

Principle Findings/Conclusions. Three thousand one hundred and twenty‐three patients were included in the analysis. In the ordinary least squares regression, there was a significant positive relationship between overall satisfaction and overall ratings of attendings' communication behaviors, with an increase in overall satisfaction of 0.58 points on a 5‐point scale for each 1‐point increase in overall attendings' communication behaviors, p<.001. This relationship was maintained but attenuated in the IV regression, with a coefficient of 0.40, p=.046. Although we find that the relationship between patient communication ratings and overall patient satisfaction may be confounded by patient‐level factors, we nevertheless continue to find evidence of a statistically significant and sizable relationship between physicians' communication behaviors and overall patient satisfaction after controlling for such factors.
Pesticides, Preference Heterogeneity and Environmental Taxes
Authors: Chalak Ali , Balcombe Kelvin , Bailey Alastair , Fraser Iain
Published: May 2008

In this paper we present results from two choice experiments (CE), designed to take account of the different negative externalities associated with pesticide use in agricultural production. For cereal production, the most probable impact of pesticide use is a reduction in environmental quality. For fruit and vegetable production, the negative externality is on consumer health. Using latent class models we find evidence of the presence of preference heterogeneity in addition to reasonably high willingness to pay (WTP) estimates for a reduction in the use of pesticides for both environmental quality and consumer health. To place our WTP estimates in a policy context we convert them into an equivalent pesticide tax by type of externality. Our tax estimates suggest that pesticide taxes based on the primary externality resulting from a particular mode of agricultural production are a credible policy option that warrants further consideration.
The use of hyperbaric oxygen therapy to treat chronic wounds: A review
Authors: Thackham Jennifer A. , McElwain D.L. Sean , Long Robert J.
Published: May 2008

Chronic wounds, defined as those wounds which fail to proceed through an orderly process to produce anatomic and functional integrity, are a significant socioeconomic problem. A wound may fail to heal for a variety of reasons including the use of corticosteroids, formation of squamous cell carcinoma, persistent infection, unrelieved pressure, and underlying hypoxia within the wound bed. Hypoxia appears to inhibit the wound healing process by blocking fibroblast proliferation, collagen production, and capillary angiogenesis and to increase the risk of infection. Hyperbaric oxygen therapy (HBOT) has been shown to aid the healing of ulcerated wounds and demonstrated to reduce the risk of amputation in diabetic patients. However, the causal reasons for the response of the underlying biological processes of wound repair to HBOT, such as the up‐regulation of angiogenesis and collagen synthesis are unclear and, consequently, current protocols remain empirical. Here we review chronic wound healing and the use of hyperbaric oxygen as an adjunctive treatment for nonhealing wounds. Databases including PubMed, ScienceDirect, Blackwell Synergy, and The Cochrane Library were searched for relevant phrases including HBOT, HBO/HBOT, wound healing, and chronic/nonhealing wounds/ulcers.
Delay of tympanic membrane wound healing in rats with topical application of a tyrosine kinase inhibitor
Authors: Kaftan Holger , Reuther Lars , Miehe Bärbel , Hosemann Werner , Herzog Michael
Published: May 2008

An animal model of chronic tympanic membrane (TM) perforation is needed for experiments on supporting wound healing of TM perforations. The epidermal growth factor receptor (EGFR) has been implicated in the regulation of wound healing. The object of this study was to investigate the efficacy of topical EGFR‐inhibitor (erlotinib) to arrest wound healing of experimental TM perforation in rats. Bilateral instrumental myringotomies were performed in 13 male rats. A solution of erlotinib (10 mg/mL) was applied to one TM of each animal and vehicle only (control group) to the other side. The application procedure was repeated on both sides daily for 12 consecutive days. Thereafter, tympanic membranes were observed weekly for a total of 30 days. The mean healing period was found to be 12.1 days in the group with erlotinib and 6.4 days in the control group. The difference was significant. We observed differences in the histologic parameters between erlotinib group and control group. The inhibition of EGFR by topical application of erlotinib did delay the healing rate of myringotomies but seems not to be suitable to create a chronic TM perforation in rat.
Platelets, but not erythrocytes, significantly affect cytokine release and scaffold contraction in a provisional scaffold model
Authors: Jacobson May , Fufa Duretti , Abreu Eduardo L. , Kevy Sherwin , Murray Martha M.
Published: May 2008

Platelets and erythrocytes are major components of wound provisional scaffolding. In this study, we hypothesized that the concentration of platelets and erythrocytes would significantly affect fibroblast‐mediated contraction of three‐dimensional scaffolds or the release of cytokines from the scaffold. To test this hypothesis, human anterior cruciate ligament fibroblasts were cultured in one of four scaffolds: a collagen matrix, a collagen‐fibrin matrix containing the same concentration of platelets as whole blood, a collagen‐fibrin matrix containing a high platelet concentration, and a collagen–fibrin matrix containing a high platelet concentration and red blood cells. Cytokine release from the four groups of gels and gel contraction were measured over a 10‐day period. The results of these assays supported greater cytokine release, fibroblast proliferation, and gel contraction in scaffolds with higher platelet concentration. In contrast, the addition of erythrocytes did not significantly stimulate or suppress scaffold contraction or growth factor release from the provisional scaffolds. We concluded that while platelet concentration can significantly impact cytokine release and scaffold retraction in a provisional scaffold, the inclusion of erythrocytes does not have a significant effect on these same behaviors. Therefore, while platelets may be an important regulator of repair processes after injury, it is less likely that erythrocytes have a similar function.
Skin cells, but not T cells, are resistant to indoleamine 2, 3‐dioxygenase (IDO) expressed by allogeneic fibroblasts
Authors: Forouzandeh Farshad , Jalili Reza B. , Germain Marc , Duronio Vincent , Ghahary Aziz
Published: May 2008

We have previously demonstrated that indoleamine 2, 3‐dioxygenase (IDO) expressed by dermal fibroblasts generated a tryptophan deficient environment in which immune cells, but not skin cells, undergo apoptosis. However, the mechanism by which primary skin cells such as fibroblasts and keratinocytes are resistant to this culture environment is not elucidated. Here, we asked the question of whether the activity of the general control nonderepressing‐2 (GCN2) kinase pathway in primary immune and skin cells is differently regulated in response to IDO‐induced tryptophan deficient environment. Before addressing this question, the expression of IDO in IDO‐adenoviral infected fibroblasts, as a source of IDO expression, was validated. We then demonstrated a significant immunosuppressive effect of IDO expression in primary human T cells co‐cultured with IDO expressing fibroblasts in the presence of allogeneic pieces of either epidermis or full thickness skin. Evaluating the mechanism by which skin cells, but not T cells, are resistant to IDO induced low tryptophan environment, we then co‐cultured IDO‐expressing fibroblasts with bystander human T cells, the fibroblasts, or keratinocytes for 3 days. The results showed a significant activation of apoptotic pathway as analyzed by caspase‐3 induction as well as the expression of CHOP, a downstream effector of GCN2 kinase pathway in T cells, but not in skin cells.
Understanding the Inputs into Innovation: Do Cities Substitute for Internal Firm Resources?
Authors: Forman Chris , Goldfarb Avi , Greenstein Shane
Published: May 2008

We examine whether there is a trade‐off between employing internal (firm) resources and purchased external (local) resources in process innovation. We draw on a rich dataset of Internet investments by 86,879 US establishments to examine decisions to invest in advanced Internet technology. We show that the marginal contribution of internal resources is greater outside of a major urban area than inside one. Agglomeration is less important for firms with highly capable IT workers. When firms invest in innovative processes they act as if resources available in cities are partial substitutes for both establishment‐level and firm‐level internal resources.