bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrative review of international nursing research in Mainland China
Authors: Li M. , Wei L. , Liu H. , Tang L.
Published: February 2009

Background:  Nursing research in Mainland China is divided into two parts: domestic nursing research, comprising all publications in Chinese; and international nursing research, comprising all publications in English. Domestic nursing research has been developing rapidly, demonstrated by the increase in new national or regional journals and publications. However, little is known about the extent of international research.

Aims:  To outline the development of international nursing research publications in Mainland China and to provide suggestions for future development.

Method:  All of the papers were retrieved from PubMed. The key search phase was ‘China or P.R.China NOT Hong Kong NOT Taiwan NOT Macao [AD]’, with the limits of ‘English’, ‘nursing journals’ as well as the published date up to ‘2007/09/30’.

Findings:  PubMed recorded 57 English papers that were originally conducted in Mainland China during the search period from 1989 to 30 September 2007. Thirty‐seven of the total 57 (65%) publications were contributed by Beijing, Shanghai and Hubei. Forty‐four of the 57 publications were conducted with collaborators from Hong Kong, the USA, the UK and Canada. Thirteen publications were funded by international societies, while only three were funded by the Chinese government. The research topics mainly focused on clinical research, nursing education and nursing management.

Conclusions and Implications:  This study indicates that international nursing research has been growing slowly in Mainland China along with provincial variations. The suggestions to improve nursing research include the reform of nursing education, the enhancement of the collaboration with the international societies and the establishment of research priorities.
Understanding of speaker certainty and false‐belief reasoning: a comparison of Japanese and German preschoolers
Authors: Matsui Tomoko , Rakoczy Hannes , Miura Yui , Tomasello Michael
Published: February 2009

It has been repeatedly shown that when asked to identify a protagonist's false belief on the basis of his false statement, English‐speaking 3‐year‐olds dismiss the statement and fail to attribute to him a false belief. In the present studies, we tested 3‐year‐old Japanese children in a similar task, using false statements accompanied by grammaticalized particles of speaker (un)certainty, as in everyday Japanese utterances. The Japanese children were directly compared with same‐aged German children, whose native language does not have grammaticalized epistemic concepts. Japanese children profited from the explicit statement of the protagonist's false belief when it was marked with the attitude of certainty in a way that German children did not – presumably because Japanese but not German children must process such marking routinely in their daily discourse. These results are discussed in the broader context of linguistic and theory of mind development.
Gesturing Gives Children New Ideas About Math
Authors: Goldin-Meadow Susan , Cook Susan Wagner , Mitchell Zachary A.
Published: February 2009

How does gesturing help children learn? Gesturing might encourage children to extract meaning implicit in their hand movements. If so, children should be sensitive to the particular movements they produce and learn accordingly. Alternatively, all that may matter is that children move their hands. If so, they should learn regardless of which movements they produce. To investigate these alternatives, we manipulated gesturing during a math lesson. We found that children required to produce correct gestures learned more than children required to produce partially correct gestures, who learned more than children required to produce no gestures. This effect was mediated by whether children took information conveyed solely in their gestures and added it to their speech. The findings suggest that body movements are involved not only in processing old ideas, but also in creating new ones. We may be able to lay foundations for new knowledge simply by telling learners how to move their hands.
Managing technological transitions through R&D alliances
Authors: Riccaboni Massimo , Moliterni Rocco
Published: February 2009

Technological and market transitions are difficult to manage, and collaborations can be viewed as either resources or constraints in dynamic settings. In the biopharmaceutical industry, a paradigmatic shift in the relevant knowledge bases occurred in the mid‐1990s, inducing a structural change in the network of R&D collaborations. Search and relational strategies oriented toward exploration versus exploitation have prevailed in different phases of the network evolution. Therefore, biotechnology firms have experienced overwhelming difficulties in reorienting their learning strategies throughout paradigmatic shifts and ambidextrous organizations have been able to attain superior performances in terms of stability and centralization in the R&D network.
The value of a ‘failed’ R&D project: an emerging evaluation framework for building innovative capabilities1
Authors: Elmquist Maria , Le Masson Pascal
Published: February 2009

In literature and R&D organizations alike, project success consists in minimizing the deviations from set targets in terms of quality, cost and time. The main management task is to execute and monitor progress to reduce risks – assuming that project attributes are known, necessary resources can be estimated and a reasonable time table can be agreed upon. In such a context, evaluating project success is easy. However, in an innovative context, setting project targets initially is difficult and the contributions of the projects sometimes are of an unexpected nature. This paper investigates if projects can be evaluated in terms of how they contribute to the building of innovative capabilities of the firm instead of independently. Based on a case study at the Régie Autonome des Transports Parisians and the theoretical framework of innovation fields, a framework for evaluating projects from an additional perspective is proposed. Based on the following four criteria: financial resources, the development of a structured, refined and expanded strategic vision, developed competences (with related suppliers) and identification of knowledge gaps (occasionally with related partners for knowledge production), this framework shows how seemingly failed R&D projects can instead be considered as invaluable to the overall innovation process.
Kernel‐based Generalized Cross‐validation in Non‐parametric Mixed‐effect Models
Authors: XU WANGLI , ZHU LIXING
Published: February 2009

Abstract. Although generalized cross‐validation (GCV) has been frequently applied to select bandwidth when kernel methods are used to estimate non‐parametric mixed‐effect models in which non‐parametric mean functions are used to model covariate effects, and additive random effects are applied to account for overdispersion and correlation, the optimality of the GCV has not yet been explored. In this article, we construct a kernel estimator of the non‐parametric mean function. An equivalence between the kernel estimator and a weighted least square type estimator is provided, and the optimality of the GCV‐based bandwidth is investigated. The theoretical derivations also show that kernel‐based and spline‐based GCV give very similar asymptotic results. This provides us with a solid base to use kernel estimation for mixed‐effect models. Simulation studies are undertaken to investigate the empirical performance of the GCV. A real data example is analysed for illustration.
Bayesian Semiparametric Modelling in Quantile Regression
Authors: KOTTAS ATHANASIOS , KRNJAJIĆ MILOVAN
Published: February 2009

Abstract.  We propose a Bayesian semiparametric methodology for quantile regression modelling. In particular, working with parametric quantile regression functions, we develop Dirichlet process mixture models for the error distribution in an additive quantile regression formulation. The proposed non‐parametric prior probability models allow the shape of the error density to adapt to the data and thus provide more reliable predictive inference than models based on parametric error distributions. We consider extensions to quantile regression for data sets that include censored observations. Moreover, we employ dependent Dirichlet processes to develop quantile regression models that allow the error distribution to change non‐parametrically with the covariates. Posterior inference is implemented using Markov chain Monte Carlo methods. We assess and compare the performance of our models using both simulated and real data sets.
The Meaning Structure of Social Networks
Authors: Fuhse Jan A.
Published: February 2009

This essay proposes to view networks as sociocultural structures. Following authors from Leopold von Wiese and Norbert Elias to Gary Alan Fine and Harrison White, networks are configurations of social relationships interwoven with meaning. Social relationships as the basic building blocks of networks are conceived of as dynamic structures of reciprocal (but not necessarily symmetric) expectations between alter and ego. Through their transactions, alter and ego construct an idiosyncratic “relationship culture” comprising symbols, narratives, and relational identities. The coupling of social relationships to networks, too, is heavily laden with meaning. The symbolic construction of persons is one instance of this coupling. Another instance is the application of social categories (like race or gender), which both map and structure social networks. The conclusion offers an agenda for research on this “meaning structure of social networks.”
Seizures in patients with symptomatic cervical artery occlusion by dissection and by atherosclerosis
Authors: De Reuck J. , Van Maele G.
Published: February 2009

Background and purpose: The outcome of patients with occlusion by cervical dissection (OCD) is considered to be better than of those with atherosclerotic occlusion (ATO) of cervical arteries. The present observational retrospective study investigates whether there are also differences in the occurrence of seizures between OCD and ATO patients.

Methods: The characteristics and the occurrence of seizures in 199 consecutive patients with a stroke due to a cervical artery occlusion are determined. Forty patients with OCD and 159 with ATO are compared.

Results: Occlusion by cervical dissection patients are significantly younger and have less vascular risk factors than those with ATO. Stroke type, vascular territory, NIHS score and outcome are similar. Three (7.5%) OCD and 29 (18.2%) ATO patients developed seizures. However, this difference is not statistically significant (P = 0.146). On multiple logistic regression analysis, ageing and arterial hypertension are independent variables.

Discussion: This study suggests a lower incidence of seizures in patients with OCD compared to those with ATO, although not statistically proven, due to the small sample size. Age and arterial hypertension can explain this difference.
Economic Incentives, Business Cycles, and Long‐Term Sickness Absence
Authors: NORDBERG MORTEN , RØED KNUT
Published: February 2009

We investigate long‐term absenteeism in Norway, on the basis of register data covering 8 years and more than two million absence spells. Key findings are that: (1) a tighter labor market yields lower work resumption rates for persons who are absent, and higher relapse rates for persons who have already resumed work; and (2) the work resumption rates increase when sickness benefits are exhausted, but work resumptions at this stage tend to be short‐lived.
Who Is at Risk of Losing and Gaining Health Insurance?
Authors: FAIRLIE ROBERT W. , LONDON REBECCA A.
Published: February 2009

In this study, we examine annual transitions into and out of health insurance coverage using matched data from the 1996 to 2004 Current Population Survey (CPS). We find evidence of several characteristics that are strongly associated with the likelihood of losing or gaining health insurance including race, education, unemployment, part‐time employment status, employment size, and self‐employment.
Identifying Minimum Wage Effects: New Evidence from Monthly CPS Data
Authors: SABIA JOSEPH J.
Published: February 2009

The appropriateness of including year effects in employment models has been a contentious issue in the minimum wage literature. Using monthly data from the 1979–2004 Current Population Surveys, I find consistent evidence of adverse labor demand effects for teenagers across specifications preferred by those on each side of this debate. Estimated employment elasticities range from –0.2 to –0.3 and unconditional hours elasticities from –0.4 to –0.5.
Product Market Competition and Human Resource Practices in the Retail Food Sector
Authors: DAVIS ELIZABETH , FREEDMAN MATTHEW , LANE JULIA , MCCALL BRIAN , NESTORIAK NICOLE , PARK TIMOTHY
Published: February 2009

In the wake of Wal‐Mart and other mass merchandisers’ entry into food retailing, the nature of competition in the industry has changed radically. Using longitudinal data on workers and firms to construct measures of compensation and churning for traditional food retailers, this paper examines how these measures change in response to mass merchandiser entry. While there is considerable heterogeneity across retail food establishments, human resource practices are persistent even in the face of new external competition.
Theoretical Considerations and Empirical Evidence on Brain Drain Grounding the Review of Albania’s and Bulgaria’s Experience1
Authors: Glytsos Nicholas P.
Published: February 2009

The objectives of this paper are: first, to briefly review the different theoretical aspects of brain drain and its potential positive or negative, direct or indirect effects on the economy of the home country; second, to highlight the limited empirical research on some of these issues; and third, to discuss on this grounding the empirical evidence on the nature and size of brain drain, as well as its impact on the economies of Albania and Bulgaria.

As it appears, the evidence for these two countries and its evaluation as to whether brain drain has been or can be a threat to their development is contradictory and confusing, as it comes out from different casual observations without a convincing analysis. The relevant discussion has not escaped the stereotype way of thinking that the economy and society of these two countries would have been better had emigration of educated persons not taken place, or had those who migrated just returned. The conclusion on policy for brain drain and brain return is that merely hindering the emigration of educated people or trying to motivate their return cannot by itself elevate education and research to higher quality levels and promote development and growth. Without simultaneously developing a friendly and comprehensive institutional and pragmatic framework, such measures are often ineffective or even counterproductive.
The Reverse and Return Transfer of Technology (RRTT): Towards a Comprehensive Model of the Migration of African Experts
Authors: Logan B. Ikubolajeh
Published: February 2009

The emigration of experts from Africa to the developed world is often analysed in terms of the reverse transfer of technology (RTT), a process typically described as one in which the skills embedded in an expert become part of a reverse flow of technology from the less developed to the developed world. In the reverse flow or brain gain, the African home country obtains the embedded skills of the returning expert and is able to use them towards national development efforts. The objectives of this paper are to investigate the RTT from the conceptual, empirical, and policy perspectives. At the conceptual level, the objective is to review the insights to the RTT provided in the globalization, the New Diaspora and the New Brain Drain paradigms. Empirically, the paper uses available data to make the case that even though the RTT has been marginalized in recent scholarship, it is a persistent development problem that continues to warrant scholarly and policy attention. Building on this argument, the paper outlines a model of expert migration, termed the reverse and return transfer of technology (RRTT). This model explores the decision‐making of migrating experts, especially in terms of source‐destination pathways and the choice of locations as either temporary or permanent homes. The policy implications of this reformulation are assessed in terms of the brain drain, the brain gain and remittances.
A validated photonumeric cellulite severity scale
Authors: Hexsel DM , Dal’Forno T , Hexsel CL
Published: February 2009

Background  With recent advances in the treatment of cellulite and localized fat, a comprehensive objective method of measuring cellulite can be potentially useful, especially since important morphological aspects of cellulite are not part of the current classification.

Objective  To develop and to validate a new photonumeric cellulite severity.

Methods  Based on standardized photographs of 55 patients with cellulite, five key morphological aspects of cellulite were identified. A new photonumeric severity scale was developed and validated.

Results  The five key morphological features of cellulite were identified and included the number of depressions, depth of depressions, clinical appearance of evident raised lesions, and presence of flaccidity and the grade of cellulite. Each item was graded from 0 to 3, allowing final classification of cellulite as mild, moderate, and severe. Results for validation of the scale are statistically significant (P < 0.05) and are as follows: intraclass correlation coefficient > 0.7; correlation item‐total > 0.7, with the exception of the right buttock; intraclass correlation coefficients 0.881–0.922; Cronbach's alpha 0.851–0.989 and factor analysis 68–76%.

Conclusion  The proposed photonumeric scale is a consistent, comprehensive, reliable, and reproducible tool for the standardized and objective assessment of the severity of cellulite.

Conflicts of interest

The authors hereby affirm that neither the manuscript nor any part of it has been published or is being considered for publication elsewhere.
Loss of language in early development of autism and specific language impairment
Authors: Pickles Andrew , Simonoff Emily , Conti‐Ramsden Gina , Falcaro Milena , Simkin Zoë , Charman Tony , Chandler Susie , Loucas Tom , Baird Gillian
Published: February 2009

Background: Several authors have highlighted areas of overlap in symptoms and impairment among children with autism spectrum disorder (ASD) and children with specific language impairment (SLI). By contrast, loss of language and broadly defined regression have been reported as relatively specific to autism. We compare the incidence of language loss and language progression of children with autism and SLI.

Methods: We used two complementary studies: the Special Needs and Autism Project (SNAP) and the Manchester Language Study (MLS) involving children with SLI. This yielded a combined sample of 368 children (305 males and 63 females) assessed in late childhood for autism, history of language loss, epilepsy, language abilities and nonverbal IQ.

Results: language loss occurred in just 1% of children with SLI but in 15% of children classified as having autism or autism spectrum disorder. Loss was more common among children with autism rather than milder ASD and is much less frequently reported when language development is delayed. For children who lost language skills before their first phrases, the phrased speech milestone was postponed but long‐term language skills were not significantly lower than children with autism but without loss. For the few who experienced language loss after acquiring phrased speech, subsequent cognitive performance is more uncertain.

Conclusions: Language loss is highly specific to ASD. The underlying developmental abnormality may be more prevalent than raw data might suggest, its possible presence being hidden for children whose language development is delayed.
Orienting of visual attention among persons with autism spectrum disorders: reading versus responding to symbolic cues
Authors: Landry Oriane , Mitchell Peter L. , Burack Jacob A.
Published: February 2009

Background:  Are persons with autism spectrum disorders (ASD) slower than typically developing individuals to read the meaning of a symbolic cue in a visual orienting paradigm?

Methods:  Participants with ASD (n = 18) and performance mental age (PMA) matched typically developing children (n = 16) completed two endogenous orienting conditions in which the cue exposure time and response preparation time were manipulated within a consistent series of cue‐target stimulus onset asynchronies (SOAs).

Results:  Participants with ASD displayed facilitation effects at all SOAs, whereas typically developing children displayed facilitation effects only at shorter SOAs. The magnitude of the facilitation effect was greater for the group with ASD at 400ms SOA. Both groups showed similar effects of condition, with similar patterns of facilitation in both conditions.

Conclusion:  Persons with ASD were not slower to read the symbolic cue, as the effect was elicited by brief cues within longer SOAs before target onset. The participants with ASD were also less efficient in using the predictability of the cues to guide responding. The difficulties of participants with ASD on endogenous orienting occur at the response selection level, not the perceptual level.
Genetic and environmental influence on attachment disorganization
Authors: Spangler Gottfried , Johann Monika , Ronai Zsolt , Zimmermann Peter
Published: February 2009

Background:  Empirical studies demonstrate that maternal sensitivity is associated with attachment security in infancy, while maternal frightening/frightened behavior is related to attachment disorganization. However, attachment disorganization is also predicted by individual dispositions in infancy. Indeed, recent studies indicate a link between attachment disorganization and DRD4 gene polymorphisms, thus suggesting a genetic vulnerability for attachment disorganization. The aims of our study were twofold, to test a) a possible direct link between molecular genetic variations and attachment disorganization, and b) a possible gene–environment interaction with a moderating effect of early maternal caregiving.

Methods:  Attachment security and disorganization, as well as quality of maternal behavior were assessed in the infants of the Regensburg Longitudinal Study IV (N = 106) at the age of 12 months. DNA samples were collected in order to assess the exon III repeat polymorphism in the coding region and the −521 C/T single nucleotide polymorphism (SNP) in the regulatory region of the DRD4 gene and a repeat polymorphism (5‐HTTLPR) in the promoter region of the serotonin transporter gene.

Results:  Significant associations were found between attachment disorganization and the short polymorphism of the serotonin transporter gene. Also, a gene–environment interaction indicated that this genetic association was only valid for infants of mothers exhibiting low responsiveness. No other significant genetic associations with attachment disorganization were apparent.

Conclusions:  The study suggests a gene–environment interaction whereby biological determinants of attachment disorganization are moderated by social experiences. Different pathways of the development of attachment disorganization are discussed based on a bio‐behavioral model of development.
Iatrogenic effect of juvenile justice
Authors: Gatti Uberto , Tremblay Richard E. , Vitaro Frank
Published: February 2009

Background:  The present study uses data from a community sample of 779 low‐SES boys to investigate whether intervention by the juvenile justice system is determined, at least in part, by particular individual, familial and social conditions, and whether intervention by the juvenile courts during adolescence increases involvement in adult crime.

Method:  The study considers self‐reported crime in childhood and adolescence, and introduces individual, familial and social variables into its analysis.

Results:  The results show that youths who are poor, impulsive, poorly supervised by their parents, and exposed to deviant friends are more likely, for the same degree of antisocial behavior, to undergo intervention by the Juvenile Court, and that this intervention greatly increases the likelihood of involvement with the penal system in adulthood. The results also show that the various measures recommended by the Juvenile Court exert a differential criminogenic effect; those that involve placement have the most negative impact.
Growth and demography of a re‐introduced population of White‐tailed Eagles Haliaeetus albicilla
Authors: EVANS RICHARD J. , WILSON JEREMY D. , AMAR ARJUN , DOUSE ANDREW , MACLENNAN ALISON , RATCLIFFE NORMAN , WHITFIELD D. PHILIP
Published: February 2009

White‐tailed Eagles Haliaeetus albicilla became extinct in Britain in 1918 following prolonged persecution. Intensive conservation efforts since the 1970s have included the re‐introduction of the species to Britain through two phases of release of Norwegian fledglings in western Scotland in 1975–85 and 1993–98. Population growth and breeding success have been monitored closely to the present day, aided by the use of patagial tags to individually mark most released birds as well as a high proportion of wild‐bred nestlings. This study reviews the growth and demography of this re‐introduced population, and makes comparisons with other European populations. For the first time, we compare the demographic rates of released and wild‐bred birds in the Scottish population. Breeding success in the Scottish population has increased over time as the average age and experience of individuals in the population have increased, and success tends to be higher where one or both adults are wild‐bred. Current levels of breeding success remain low compared with some other populations in Europe, but similar to those in Norway where weather conditions and food availability are likely to be most similar. Survival rates in Scotland are similar to those recorded elsewhere, but survival rates of released birds are lower than those of wild‐bred birds, especially during the first 3 years of life. Despite the effect of lower survival rates of released birds in limiting overall population growth rate, the recent rate of growth of the Scottish population remains high relative to other recovering populations across Europe. Differences in demographic rates of wild‐bred and released birds suggest that in future re‐introduction programmes, steps to maximize the success and output of the earliest breeding attempts would help ensure the most rapid shift to a population composed largely of wild‐bred birds, which should then have a higher rate of increase.
The Predictive Content of Aggregate Analyst Recommendations
Authors: HOWE JOHN S. , UNLU EMRE , YAN XUEMIN (STERLING)
Published: February 2009

Using more than 350,000 sell‐side analyst recommendations from January 1994 to August 2006, this paper examines the predictive content of aggregate analyst recommendations. We find that changes in aggregate analyst recommendations forecast future market excess returns after controlling for macroeconomic variables that have been shown to influence market returns. Similarly, changes in industry‐aggregated analyst recommendations predict future industry returns. Changes in aggregate analyst recommendations also predict one‐quarter‐ahead aggregate earnings growth. Overall, our results suggest that analyst recommendations contain market‐ and industry‐level information about future returns and earnings.
Diadenosine pentaphosphate is a potent activator of cardiac ryanodine receptors revealing a novel high‐affinity binding site for adenine nucleotides
Authors: Song L , Carter SM , Chen Y , Sitsapesan R
Published: February 2009

Background and purpose:  Diadenosine polyphosphates are normally present in cells at low levels, but significant increases in concentrations can occur during cellular stress. The aim of this study was to investigate the effects of diadenosine pentaphosphate (Ap5A) and an oxidized analogue, oAp5A on the gating of sheep cardiac ryanodine receptors (RyR2).

Experimental approach:  RyR2 channel function was monitored after incorporation into planar bilayers under voltage‐clamp conditions.

Key results:  With10 µmol·L−1 cytosolic Ca2+, a significant ‘hump’ or plateau at the base of the dose–response relationship to Ap5A was revealed. Open probability (Po) was significantly increased to a plateau of approximately 0.2 in the concentration range 100 pmol·L−1–10 µmol·L−1. High Po values were observed at >10 µmol·L−1 Ap5A, and Po values close to 1 could be achieved. Nanomolar levels of ATP and adenosine also revealed a hump at the base of the dose–response relationships, although GTP did not activate at any concentration, indicating a common, high‐affinity binding site on RyR2 for adenine‐based compounds. The oxidized analogue, oAp5A, did not significantly activate RyR2 via the high‐affinity binding site; however, it could fully open the channel with an EC50 of 16 µmol·L−1 (Ap5A EC50 = 140 µmol·L−1). Perfusion experiments suggest that oAp5A and Ap5A dissociate slowly from their binding sites on RyR2.

Conclusions and implications:  The ability of Ap5A compounds to increase Po even in the presence of ATP and their slow dissociation from the channel may enable these compounds to act as physiological regulators of RyR2, particularly under conditions of cellular stress.
Statins and fenofibrate affect skeletal muscle chloride conductance in rats by differently impairing ClC‐1 channel regulation and expression
Authors: Pierno S , Camerino GM , Cippone V , Rolland J‐F , Desaphy J‐F , De Luca A , Liantonio A , Bianco G , Kunic JD , George Jr. AL , Conte Camerino D
Published: February 2009

Background and purpose: Statins and fibrates can produce mild to life‐threatening skeletal muscle damage. Resting chloride channel conductance (gCl), carried by the ClC‐1 channel, is reduced in muscles of rats chronically treated with fluvastatin, atorvastatin or fenofibrate, along with increased resting cytosolic calcium in statin‐treated rats. A high gCl, controlled by the Ca2+‐dependent protein kinase C (PKC), maintains sarcolemma electrical stability and its reduction alters muscle function. Here, we investigated how statins and fenofibrate impaired gCl.

Experimental approach: In rats treated with fluvastatin, atorvastatin or fenofibrate, we examined the involvement of PKC in gCl reduction by the two intracellular microelectrodes technique and ClC‐1 mRNA level by quantitative real time‐polymerase chain reaction. Direct drug effects were tested by patch clamp analysis on human ClC‐1 channels expressed in human embryonic kidney (HEK) 293 cells.

Key results: Chelerythrine, a PKC inhibitor, appliedin vitroon muscle dissected from atorvastatin‐treated rats fully restored gCl, suggesting the involvement of this enzyme in statin action. Chelerythrine partially restored gCl in muscles from fluvastatin‐treated rats but not in those from fenofibrate‐treated rats, implying additional mechanisms for gCl impairment. Accordingly, a decrease of ClC‐1 channel mRNA was found in both fluvastatin‐ and fenofibrate‐treated rat muscles. Fenofibric acid, thein vivometabolite of fenofibrate, but not fluvastatin, rapidly reduced chloride currents in HEK 293 cells.

Conclusions and implications: Our data suggest multiple mechanisms underlie the effect of statins and fenofibrate on ClC‐1 channel conductance. While statins promote Ca2+‐mediated PKC activation, fenofibrate directly inhibits ClC‐1 channels and both fluvastatin and fenofibrate impair expression of mRNA for ClC‐1.
Low‐dose oral sirolimus reduces atherogenesis, vascular inflammation and modulates plaque composition in mice lacking the LDL receptor
Authors: Zhao L , Ding T , Cyrus T , Cheng Y , Tian H , Ma M , Falotico R , Praticò D
Published: February 2009

Background and purpose:  Chronic proliferative responses of different vascular cell types have been involved in the pathogenesis of atherosclerosis. However, their functional role remains to be established. Sirolimus reduces neointimal proliferation after balloon angioplasty and chronic graft vessel disease. These studies were undertaken to investigate the effects of this anti‐proliferative drug on atherogenesis.

Experimental approach:  Low‐density lipoprotein receptor‐deficient (LDL r‐KO) mice on a cholesterol‐rich diet were randomized to receive placebo or sirolimus (0.1; 0.3; or 1 mg·kg−1) in their diet for 8 or 16 weeks.

Results:  In both studies, plasma levels of the drug increased in a dose‐dependent fashion, animals gained weight normally and, among groups, plasma lipids levels did not differ significantly. Compared with placebo, plasma levels of interleukin‐6, monocyte chemoattractant protein‐1, interferon γ, tumour necrosis factor α and CD40, and their mRNA levels in aortic tissue were significantly reduced in sirolimus‐treated mice. This effect resulted in a significant and dose‐dependent reduction in atherosclerotic lesions, in both the root and aortic tree. Also these lesions contained less monocyte/macrophages and smooth muscle cells, but more collagen.

Conclusions and implications:  The present results demonstrated that at low doses, sirolimus was an effective and safe anti‐atherogenic agent in the LDL r‐KO mice. It attenuated the progression of atherosclerosis and modulated the plaque phenotype by reducing the pro‐inflammatory vascular responses typical of the disease.

British Journal of Pharmacology (2009) doi:10.1111/j.1476‐5381.2008.00080.x
The endocannabinoid system as a target for the treatment of motor dysfunction
Authors: Fernández‐Ruiz Javier
Published: February 2009

There is evidence that cannabinoid‐based medicines that are selective for different targets in the cannabinoid signalling system (e.g. receptors, inactivation mechanism, enzymes) might be beneficial in basal ganglia disorders, namely Parkinson's disease (PD) and Huntington's disease (HD). These benefits not only include the alleviation of specific motor symptoms [e.g. choreic movements with cannabinoid receptor type 1 (CB1)/transient receptor potential vanilloid type 1 agonists in HD; bradykinesia with CB1antagonists and tremor with CB1agonists in PD], but also the delay of disease progression due to the neuroprotective properties demonstrated for cannabinoids (e.g. CB1agonists reduce excitotoxicity; CB2agonists limit the toxicity of reactive microglia; and antioxidant cannabinoids attenuate oxidative damage). In addition, extensive biochemical, anatomical, physiological and pharmacological studies have demonstrated that: (i) the different elements of the cannabinoid system are abundant in basal ganglia structures and they are affected by these disorders; (ii) the cannabinoid system plays a prominent role in basal ganglia function by modulating the neurotransmitters that operate in the basal ganglia circuits, both in healthy and pathological conditions; and (iii) the activation and/or inhibition of the cannabinoid system is associated with important motor responses that are maintained and even enhanced in conditions of malfunctioning and/or degeneration. In this article we will review the available data regarding the relationship between the cannabinoid system and basal ganglia activity, both in healthy and pathological conditions and will also try to identify future lines of research expected to increase current knowledge about the potential therapeutic benefits of targeting this system in PD, HD and other basal ganglia disorders.
Ca2+‐calmodulin can activate and inactivate cardiac ryanodine receptors
Authors: Sigalas C , Bent S , Kitmitto A , O'Neill S , Sitsapesan R
Published: February 2009

Background and purpose: Ca2+‐calmodulin (Ca2+CaM) is widely accepted as an inhibitor of cardiac ryanodine receptors (RyR2); however, the effects of physiologically relevant CaM concentrations have not been fully investigated.

Experimental approach: We investigated the effects of low concentrations of Ca2+CaM (50–100 nmol·L−1) on the gating of native sheep RyR2, reconstituted into bilayers. Suramin displaces CaM from RyR2 and we have used a gel‐shift assay to provide evidence of the mechanism underlying this effect. Finally, using suramin to displace endogenous CaM from RyR2 in permeabilized cardiac cells, we have investigated the effects of 50 nmol·L−1CaM on sarcoplasmic reticulum (SR) Ca2+‐release.

Key results: Ca2+CaM activated or inhibited single RyR2, but activation was much more likely at low (50–100 nmol·L−1) concentrations. Also, suramin displaced CaM from a peptide of the CaM binding domain of RyR2, indicating that, like the skeletal isoform (RyR1), suramin directly competes with CaM for its binding site on the channel. Pre‐treatment of rat permeabilized ventricular myocytes with suramin to displace CaM, followed by addition of 50 nmol·L−1CaM to the mock cytoplasmic solution caused an increase in the frequency of spontaneous Ca2+‐release events. Application of caffeine demonstrated that 50 nmol·L−1CaM reduced SR Ca2+content.

Conclusions and implications: We describe for the first time how Ca2+CaM is capable, not only of inactivating, but also of activating RyR2 channels in bilayers in a CaM kinase II‐independent manner. Similarly, in cardiac cells, CaM stimulates SR Ca2+‐release and the use of caffeine suggests that this is a RyR2‐mediated effect.
Histamine H1 receptor blockade predominantly impairs sensory processes in human sensorimotor performance
Authors: Van Ruitenbeek P , Vermeeren A , Smulders FTY , Sambeth A , Riedel WJ
Published: February 2009

Background and purpose:  Centrally active antihistamines impair cognitive performance, particularly sensorimotor performance. The aim of the present study was to further elucidate the scarcely studied subprocesses involved in sensorimotor performance, which may be affected by H1 receptor blockade. Better knowledge about the cognitive deficits associated with histamine dysfunction can contribute to better treatment of clinical disorders in which histamine hypofunction may be a contributing factor, such as in schizophrenia.

Experimental approach:  Interactions of dexchlorpheniramine with specific task manipulations in a choice reaction time task were studied. Task demands were increased at the level of sensory subprocesses by decreasing stimulus quality, and at the level of motor subprocesses by increasing response complexity. A total of 18 healthy volunteers (9 female) aged between 18 and 45 years participated in a three‐way, double‐blind, crossover design. Treatments were single oral doses of 4 mg dexchlorpheniramine, 1 mg lorazepam and placebo. Behavioural effects were assessed by measuring reaction times and effects on brain activity by event‐related potentials.

Key results:  Dexchlorpheniramine significantly slowed reaction times, but did not significantly interact with task manipulations. However, it did significantly interact with stimulus quality, as measured by event‐related potentials. Lorazepam slowed reaction times and interacted with perceptual manipulations, as shown by effects on reaction times.

Conclusions and implications:  The results confirm that the histamine system is involved in sensory information processing and show that H1 blockade does not affect motoric information processing. Histamine hypofunction in clinical disorders may cause impaired sensory processing, which may be a drug target.
A retrospective analysis of radiation therapy for the treatment of feline vaccine‐associated sarcoma*
Authors: Eckstein C. , Guscetti F. , Roos M. , Martín de las Mulas J. , Kaser‐Hotz B. , Rohrer Bley C.
Published: February 2009

We retrospectively evaluated predictive prognostic factors in 73 cats with vaccine‐associated sarcoma given postsurgical curative (n = 46, most with clean margins) or coarse fractionated radiotherapy (n = 27, most with either macroscopic disease or dirty margins). The former animals displayed a median survival of 43 months and a median progression free interval (PFI) of 37 months, the latter reached a median survival of 24 months and a median PFI of 10 months. In cats undergoing coarse fractionated therapy, factors predictive of a better outcome included lack of visible mass (n = 10) as opposed to macroscopic disease (n = 17, survival: 30 versus 7 months,P = 0.025; PFI: 20 versus 4 months,P = 0.01), adjuvant chemotherapy for gross disease (n = 5/17, survival: 29 versus 5 months,P = 0.04) and a smaller number of surgeries preceding radiation therapy (coeff = 0.41,P = 0.03). The Ki67 index was not predictive for survival. We concluded that postsurgical curative and coarse fractionated radiotherapy are effective legitimate options for managing vaccine‐associated sarcomas.
Impact of Recent Prior Opioid Use on Rizatriptan Efficacy. A Post Hoc Pooled Analysis
Authors: Ho Tony W. , Rodgers Anthony , Bigal Marcelo E.
Published: February 2009

Background.— Limited evidence suggests that, in individuals with migraine, prior use of opioids reduces responsiveness to treatment with subsequent acute migraine therapies. The evidence is more robust with regard to opioids as a risk factor for chronic migraine.

Objectives.— To explore whether recent prior opioid use influenced treatment response, in a post hoc pooled analysis of rizatriptan clinical trials.

Methods.— We included rizatriptan 10 mg and placebo data from phase 3 moderate/severe migraine studies as well as from the rizatriptan “Treat a Migraine Early” (TAME) studies. As part of the clinical assessment, medication usage for migraine and other reasons in the 30 days prior to a screening visit and up to the time of taking study drug was captured via patient's self‐report. The influence of recent prior opioid use on the endpoint of pain freedom at 2 hours was assessed via logistic regression. We further explored the influence of gender and disability on treatment response.

Results.— In the moderate/severe migraine studies of 2068 individuals treated with rizatriptan, 284 (13.7%) reported recent prior use of opioids. Of those treated with placebo (1258), 12.5% recently used opioids. In the TAME studies, the proportions were lower, 3.9% and 5.3%, respectively. The pretreatment and demographic characteristics were similar across the study groups. In the moderate/severe studies, recent prior opioid use was associated with reduced 2‐hour pain freedom. Although the influence of recent prior opioid use was assessed independently of treatment, the finding was driven primarily by rizatriptan (recent prior use vs no use: 34% vs 42% for rizatriptan and 10% vs 10% for placebo; P = .013). In the TAME studies, recent prior opioid use was also predictive of reduced efficacy (recent prior use vs no use: 41% vs 59% for rizatriptan and 13% vs 32% for placebo; P = .007).

Conclusion.— Recent prior opioid use was associated with lower triptan response. Because of the post hoc nature of the analysis and limitations in capturing amount of opioid used, as well as to adjust for disability levels, these findings require replication in prospective studies.
Pathology type does not predict language lateralization in children with medically intractable epilepsy
Authors: Kadis Darren S. , Kerr Elizabeth N. , Rutka James T. , Snead III O. Carter , Weiss Shelly K. , Smith Mary Lou
Published: February 2009

Purpose:  We examined potential differences in the effects of pathology type on language lateralization in pediatric epilepsy.

Methods:  We examined findings from intracarotid sodium amobarbital procedure (IAP/Wada) in a large consecutive sample of children with refractory epilepsy. Subjects were assigned to one of three pathology groups: developmental (n = 28), acquired (n = 26), and tumor (n = 20); groups were compared for language lateralization.

Results:  Rates of atypical language lateralization did not differ across groups. Greater than half of the subjects with left hemisphere insults and seizure onset before 6 years of age had atypical language lateralization, independent of pathology type.

Discussion:  Atypical language lateralization may occur in the context of developmental, acquired, and/or tumor pathology.
BIODIVERSITY OF CORALLINE ALGAE IN THE NORTHEASTERN ATLANTIC INCLUDING CORALLINA CAESPITOSA SP. NOV. (CORALLINOIDEAE, RHODOPHYTA)1
Authors: Walker Rachel H. , Brodie Juliet , Russell Stephen , Irvine Linda M. , Orfanidis Sotiris
Published: February 2009

The Corallinoideae (Corallinaceae) is represented in the northeastern Atlantic by Corallina officinalis L.; Corallina elongata J. Ellis et Sol.; Haliptilon squamatum (L.) H. W. Johans., L. M. Irvine et A. M. Webster; and Jania rubens (L.) J. V. Lamour. The delimitation of these geniculate coralline red algae is based primarily on morphological characters. Molecular analysis based on cox1 and 18S rRNA gene phylogenies supported the division of the Corallinoideae into the tribes Janieae and Corallineae. Within the Janieae, a sequence difference of 46–48 bp (8.6%–8.9%) between specimens of H. squamatum and J. rubens in the cox1 phylogeny leads us to conclude that they are congeneric. J. rubens var. rubens and J. rubens var. corniculata (L.) Yendo clustered together in both phylogenies, suggesting that for those genes, there was no genetic basis for the morphological variation. Within the Corallineae, it appears that in some regions, the name C. elongata has been misapplied. C. officinalis samples formed two clusters that differed by 45–54 bp (8.4%–10.0%), indicating species‐level divergence, and morphological differences were sufficient to define two species. One of these clusters was consistent with the morphology of the type specimen of C. officinalis (LINN 1293.9). The other species cluster is therefore described here as Corallina caespitosa sp. nov. This study has demonstrated that there is a clear need for a revision of the genus Corallina to determine the extent of “pseudocryptic” diversity in this group of red algae.
SEASONAL CHANGES IN SIZE STRUCTURE OFSARGASSUMANDTURBINARIAPOPULATIONS (PHAEOPHYCEAE) ON TROPICAL REEF FLATS IN THE SOUTHERN RED SEA1
Authors: Ateweberhan Mebrahtu , Bruggemann J. Henrich , Breeman Anneke M.
Published: February 2009

Seasonal variation in density, thallus length and biomass, population size structure, and allometric length‐biomass relationships was investigated in populations ofSargassum ilicifolium(Turner) C. Agardh,Sargassum subrepandum(Forssk.) C. Agardh, andTurbinaria triquetra(J. Agardh) Kütz. (Phaeophyceae) on shallow reef flats in the southern Red Sea. Thallus length and biomass varied strongly with season, with the highest values occurring in the cooler months. Thallus densities showed no significant temporal variation. Log‐total biomass versus log‐density relationships were positive throughout the growth season without any decrease in the slope of the relationship. In two populations, biomass‐density combinations approached the interspecific biomass‐density line, but the massive annual shedding of modules occurred before self‐thinning would set in. Allometric length‐biomass relationships varied with season in all populations and were associated with seasonal module initiation, growth, and shedding. Evidence of a strong asymmetric competition was found in two high‐density populations. These populations showed a predominance of small thalli during peak development, asymmetrical Lorenz curves, increasing Gini coefficients, and increasing thallus length relative to biomass during the main growth phase. In two other less crowded populations, small thalli were absent during peak development, Lorenz curves were symmetrical, and Gini coefficients decreased during the main growth phase. In these populations, size equalization appears to be due to responses at the modular level rather than size‐dependent mortality. We conclude that changes in size structure in this highly seasonal environment are determined by module dynamics, modified by asymmetric competition in some populations, with a minor role of recruitment and no regulatory effect of self‐thinning.