bluuebunny/crossref_metadata_2025 huggingface dataset:
Resettling Refugees in Rural and Regional Australia: Learning from Recent Policy and Program Initiatives
Authors: McDonald‐Wilmsen Brooke , Gifford Sandra M. , Webster Kim , Wiseman John , Casey Sue
Published: March 2009

Conscious policy and program support for the resettlement of refugees in regional and rural areas is a relatively recent trend in Australia. Resettlement is a complex process that hinges on the establishment of viable communities. This review suggests that its outcomes, especially for refugee communities, are potentially mixed. However, an appropriately resourced, well managed and well planned refugee resettlement program can potentially provide beneficial outcomes for refugees and host communities. This article draws on existing empirical data and contributions made at a VicHealth Roundtable in late 2007 to thematically explore the challenges facing rural and regional resettlement programs. Given that settlement is a dynamic process and the approaches to rural and regional settlement are evolving, this article provides 12 propositions for a more effective and integrated approach to policy and practice.
Unpacking a Wicked Problem: Enablers/Impediments to Regional Engagement
Authors: Christie Michael J. , Rowe Patricia A. , Pickernell David
Published: March 2009

A case study approach is applied to review Local Government Authorities (LGA) regional engagement in the Australian context. We address the question ‘What are the key LGA enablers/impediments to regional engagement?’ by applyingLeydesdorff's (2000)proposition that triple helix type network systems exhibit patterns of complex behaviour if the interaction factors that trigger enablers are reflexively declared. The three strands of the LGA triple helix network system are institutions, industry and government. In this case study the LGA's overall management of its regional stakeholder relationships resulted in impediments that limit strong regional engagement. Importantly, the findings inform practitioners, policy‐makers and research audiences of the nature of impediments and, by inference, the nature of enablers in LGA triple helix network systems.
The Cult of Collaboration in Public Policy
Authors: O'Flynn Janine
Published: March 2009

A ‘cult of collaboration’ is emerging in Australian public policy circles. In this article I argue this reflects a misunderstanding of the concept and its distinctive characteristics. Here I reintroduce collaboration vis‐à‐vis other forms of ‘working together’ and question whether we have taken a collaborative turn in public policy. In doing so I hope to contribute to a debate on the relevance of collaboration for public policy.
Public Service Neutrality in Hong Kong: Problems and Prospects
Authors: Cheung Chor‐yung
Published: March 2009

Before 2002, Hong Kong's higher civil servants were required to play the dual role of quasi‐ministers and civil servants. In such a context, can we make sense of the claim that Hong Kong's civil service has all along been politically neutral? What role has neutrality played in the governance of Hong Kong? Informed by Kernaghan's model of political neutrality and Oakeshott's idea of civil association, this article argues that the public service should not be regarded solely as an effective instrument of the government in power. In conclusion, this article proposes some institutional measures to strengthen the neutrality of the public service in Hong Kong and argues that properly understanding this will help prevent excessive or illegitimate partisan political power.
The Dilemma of Developing Financial Accountability without Election – A Study of China's Recent Budget Reforms
Authors: Ma Jun
Published: March 2009

Until recently, the discussion on political accountability focused on accountability in democratic systems with free and regular elections. Using China as a case study, this article contends that there exists a possibility of financial accountability without election. However, as election serves the important function of potentially changing the chain of accountability, the route of creating financial accountability without election has its limitations.
The Effect of Compensation Committee Quality on the Association between CEO Cash Compensation and Accounting Performance
Authors: Sun Jerry , Cahan Steven
Published: March 2009

Manuscript Type: Empirical

Research Question/Issue: We examine the effect of compensation committee quality on the association between CEO cash compensation and accounting earnings and the moderating effects of growth opportunities and earnings status.

Research Findings/Insights: Using a sample of 812 US firms, we find that CEO cash compensation is more positively associated with accounting earnings when firms have high compensation committee quality. We also find that the positive effect of compensation committee quality on the association between CEO cash compensation and accounting earnings is less for high growth firms or loss‐making firms.

Theoretical Implications: We contribute to the agency‐based research on CEO compensation by: 1) directly examining the impact of compensation committee quality on the sensitivity of CEO cash compensation to accounting earnings; 2) examining whether the role of compensation committee quality varies across firms; and 3) developing a broader and richer measure of compensation committee quality.

Practical Implications: Our findings imply that shareholders and directors should be concerned about the composition of compensation committees as we find that compensation committee quality varies depending on compensation committee size and other characteristics of the committee members. Our findings also imply that for compensation committee members, there are greater challenges in monitoring CEO compensation contracts for firms with high growth or that incur losses. Further, our findings imply that even when all compensation committees are regulated to be fully independent, there are still quality differences among these independent compensation committees.
State Control, Legal Investor Protection, and Ownership Concentration: Evidence from China
Authors: Wu Shinong , Xu Nianhang , Yuan Qingbo
Published: March 2009

Manuscript Type: Empirical

Research Question/Issue: To control for the omitted‐variables and aggregation biases problem existing in previous cross‐country studies, our paper investigates the relationship of ownership concentration and legal investor protection across regions and over time in one emerging economy, China, during the period 1992 to 2003. Moreover, this paper examines whether state control affects this relationship.

Research Findings/Results: For state‐controlled firms, we cannot find the typical inverse relationship between ownership concentration and legal investor protection documented by La Porta, Lopez‐de‐Silanes, Shleifer, and Vishny (1998), since state per se works as a substitute for formal legal investor protection in protecting property rights by exploiting political power. However, for non‐state‐controlled firms, the inverse relationship does hold.

Theoretical Implications: Our findings suggest that the nature of the controlling shareholder should be taken into account when examining the relationship between ownership concentration and legal investor protection. Moreover, our findings give new insights, especially to the study on other emerging economies that share similar characteristics with China in terms of legal development and government control. Finally, the cross‐region study within one country provides a new perspective on the research in this area.

Practitioner Implications: First, to provide a level playing field for different types of investors, the state's dual role of controlling shareholder and political power holder should be separated. Second, it is important to build up a good legal system to protect investors in order for a country to develop its capital markets, especially for the development of the non‐state sector.
The Link Between Board Composition and Corporate Diversification in Australian Corporations
Authors: Chen Rongrong , Dyball Maria Cadiz , Wright Sue
Published: March 2009

Manuscript Type: Empirical

Research Question/Issue: This study investigates the association between the composition of the board of directors and corporate diversification, to explore the role of the board in corporate strategic choice.

Research Findings/Results: Based on a sample of 101 Australian publicly listed firms in 2005, this study finds that there is no link between corporate decisions on product and/or geographic diversification and two aspects of board composition – board independence and institutional representation. However, there is a positive link between total diversification and a third aspect of board composition – the proportion of directors who have ties to boards of corporations in other industries.

Theoretical Implications: The results provide support for the managerial hegemony and the resource dependency theories. Corporate strategic decisions regarding diversification are more likely to be made by management than boards of directors, and to be encouraged by interlocking directors with extra‐industry ties.

Practical Implications: Contrary to the requirement or recommendation in many jurisdictions that boards be more independent, these results indicate that shareholders' interests, represented by lower levels of diversification, are not promoted under such circumstances. Interlocking directors appear to effectively link the corporation to the external business environment and to encourage diversification. Existing recommendations and regulations to align management with shareholders' interests through independent boards should be revised. Board composition should also consider directors' knowledge, relevant expertise, availability, and length of tenure.
Getting Even or Getting Equal? Retributive Desires and Transitional Justice
Authors: David Roman , Choi Susanne Y. P.
Published: March 2009

This article examines the effect that different policy interventions of transitional justice have on the desires of the victims of human rights violations for retribution. The retributive desires assessed in this article are conceptualized as individual, collective, and abstract demands for the imposition of a commensurate degree of suffering upon the offender. We suggest a plausible way of reducing victims’ retributive desires. Instead of “getting even” in relation to the suffering, victims and perpetrators may “get equal” in relation to their respective statuses, which were affected by political crimes. The article hypothesizes that the three classes of transitional justice: (1) reparation that empowers victims by financial compensation, truth telling, and social acknowledgment; (2) retribution that inflicts punishment upon perpetrators; and (3) reconciliation that renews civic relationship between victims and perpetrators through personal contact, apology, and forgiveness; each contributes to restoring equality between victims and perpetrators, and in so doing decreases the desires that victims have for retribution. In order to test our hypotheses, we conducted a survey of former political prisoners in the Czech Republic. Results from the regression analysis reveal that financial compensation, social acknowledgement, punishment, and forgiveness are likely to reduce victims’ retributive desires.
Beyond “Practical” Reconciliation: Intergroup Inequality and the Meaning of Non‐Indigenous Identity
Authors: Subašić Emina , Reynolds Katherine J.
Published: March 2009

The long‐standing policy of “practical reconciliation” between Australian Indigenous and Non‐Indigenous people has actively disregarded the need to redress past injustice as the basis of current intergroup inequality. While this approach has received extensive critique from reconciliation scholars, its implications for Non‐Indigenous involvement in reconciliation have been neglected. When Indigenous disadvantage is divorced from its social and historical context it is also more likely to be seen as having little to do with “us” as Non‐Indigenous Australians. In contrast, when inequality is seen as stemming from the past and present reality of intergroup relations, and as such shapes the meaning of Non‐Indigenous identity, it will be seen as more illegitimate, in need of change, and is more likely to motivate political engagement in the reconciliation process. The current study tests and finds support for this idea. Importantly, controlling for the contributions of perceived legitimacy of inequality and need for social change, Non‐Indigenous identity meaning continued to significantly predict intentions to vote and engage in political action in support of reconciliation.
INDIVISIBILITIES, SYNERGY AND PROXIMITY: THE NEED FOR AN INTEGRATED APPROACH TO AGGLOMERATION ECONOMIES
Authors: CAPELLO ROBERTA
Published: March 2009

The aim of the paper is to present a review of the literature on agglomeration economies in a light such that it is possible to uncover the building blocks for use in a multidimentional approach to agglomeration economies. The paper claims that the different conceptual dimensions – industrial, socio‐cultural/cognitive and geographic – build upon the three micro‐foundations of agglomeration economies – indivisibility, synergy and proximity – and explain their nature, scope and intensity. The paper stresses two main issues. The first is that a socio‐cultural/cognitive perspective still today ignored by mainstream approaches to agglomeration economies is an additional important conceptual dimension on which to understand the complex mechanisms whereby exchanges of knowledge, labour or intermediate goods take place in agglomerated areas. The second is that a multidimensional approach comprising the three different dimensions in the study of agglomeration economies makes it possible to overcome a deterministic approach to agglomeration economies and move instead towards a stochastic interpretation which opens the black box of this complex phenomenon.
THE DIFFERENCE BETWEEN BI‐REGIONAL AND FULL NETWORKS WHEN ANALYSING AGGLOMERATION EFFECTS
Authors: THISSEN MARK , HILBERS HANS , VAN DE COEVERING PAUL
Published: March 2009

Agglomeration economies explain why productivity increases as the size of agglomeration increases, and thereby partly explain the importance of location and space in economic development. Agglomeration economies are based on the distance between firms, labour and the market. Infrastructure investment can be a tool used by governments to affect this distance, where, in doing so, they induce agglomeration economies and increase economic growth. In this paper, we will discuss the importance of considering types of networks when analysing agglomeration economies using multiregional new economic geography (NEG)‐based spatial general equilibrium models. These models typically use abstract bi‐regional origin‐destination networks to describe the cost of transporting or commuting between regions. These abstract networks are like tunnels between regions and do not take into account the actual roads in real infrastructure networks used for transport and traffic between destinations. In other words, in real infrastructure networks, which we label full networks, people and goods move from one region to another via actual roads and possibly via third regions. In the empirical economic literature, there is a significant difference between the economic effect of changes in a bi‐regional origin‐destination network and the economic effect of changes in a full network. To date, no systematic explanation has been given for this difference in the size of the effects. Lack of an explanation for this difference may lead to confusion among policy‐makers who have to decide on infrastructure investment. In this methodological paper, we discuss the reason for this difference. We do not discuss the absolute size of the agglomeration effects, only the relative difference that exists when using different types of networks. In order to explain the difference, we introduce a methodology that translates the effects in a bi‐regional origin‐destination network into similar effects in a full network, making it possible to systematically compare the economic importance of all links (roads) in such a network. This is highly relevant to policy‐makers, who can now interpret the model results on a real full infrastructure network. We will also show the mathematical relationship between the importance of agglomeration economies on a link in a full network and the importance of agglomeration economies on a link in a bi‐regional origin‐destination network. Finally, the methodology is illustrated with a case study from the Netherlands.
SOCIAL NETWORKS AND COMPETITIVE GROWTH OF UNIVERSITY SPIN‐OFF FIRMS: A TALE OF TWO CONTRASTING CITIES
Authors: SOETANTO DANNY P. , VAN GEENHUIZEN MARINA
Published: March 2009

A key assumption in agglomeration theory is that knowledge‐based firms benefit from knowledge spillovers in cities. Cities however may have different locations in the national context, such as embedded in a network of nearby cities or relatively isolated. We examine social networks employed by university spin‐off firms in urban environments that contrast in such a way, namely, Delft (the Netherlands) and Trondheim (Norway). A set of growth models is explored with a focus on characteristics of social networks through which knowledge is acquired, such as tightness, strength and spatial orientation. The networks appear to differ in various respects, except for a positive influence on growth of heterogeneity in the social background of partners. The largest difference is observed in strength of relationships: an increase in strength tends to hamper growth in Delft, while it tends to enhance growth in Trondheim.
METROPOLITAN REGIONS IN THE KNOWLEDGE ECONOMY: NETWORK ANALYSIS AS A STRATEGIC INFORMATION TOOL
Authors: BRANDT ARNO , HAHN CLAUDIA , KRÄTKE STEFAN , KIESE MATTHIAS
Published: March 2009

Since the early 1990s, regional networks have received a lot of academic and political attention as vehicles for knowledge‐based economic development. However, this powerful rhetoric has been accompanied by surprisingly little concrete analysis. Economic geography is only recently waking up to the potential of network analysis for interorganisational linkages within and between regions. We discuss network analysis as a strategic information tool for regional knowledge management and apply it to the metropolitan region of Hannover‐Braunschweig‐Göttingen‐Wolfsburg in the northern German state of Lower Saxony. Producing network diagrams and parameters of network size, density, centrality, cohesion and connectivity from a large sample of actors and linkages, our survey shows striking differences between different fields of competence that highlight the potential of network analysis as a powerful tool and a necessary basis for decision‐making to propel metropolitan regions into the knowledge economy. We outline both case‐specific and generic implications for the practice of regional knowledge management. However, a few methodological shortcomings still call for further research to be conducted.
An exploration of genome size diversity in dragonflies and damselflies (Insecta: Odonata)
Authors: Ardila‐Garcia A. M. , Gregory T. R.
Published: March 2009

Like most insect orders, the Odonata (dragonflies and damselflies) remain poorly studied from the perspective of genome size. They exhibit several characteristics that make them desirable targets for analysis in this area, for example a large range in body size, differences in developmental rate, and distinct modes of flight – all of which are related to genome size in at least some animal taxa. The present study provides new genome size estimates and morphometric data for 100 species of odonates, covering about 1/5 of described North American diversity. Significant relationships are reported between genome size and body size (positive in dragonflies, negative in damselflies), and there is also indication that developmental rate and flight are related to genome size in these insects. Genome size is also positively correlated with chromosome number across the order. These findings contribute to an improved understanding of genome size evolution in insects, and raise several interesting questions for future research.
Gravity amplifies and microgravity decreases circumnutations in Arabidopsis thaliana stems: results from a space experiment
Authors: Johnsson A. , Solheim B. G. B. , Iversen T.‐H.
Published: March 2009

DOI: 10.1111/j.1469-8137.2009.02817.xCommentary p 555
Coevolution of metal availability and nitrogen assimilation in cyanobacteria and algae
Authors: GLASS J. B. , WOLFE‐SIMON F. , ANBAR A. D.
Published: March 2009

Marine primary producers adapted over eons to the changing chemistry of the oceans. Because a number of metalloenzymes are necessary for N assimilation, changes in the availability of transition metals posed a particular challenge to the supply of this critical nutrient that regulates marine biomass and productivity. Integrating recently developed geochemical, biochemical, and genetic evidence, we infer that the use of metals in N assimilation – particularly Fe and Mo – can be understood in terms of the history of metal availability through time. Anoxic, Fe‐rich Archean oceans were conducive to the evolution of Fe‐using enzymes that assimilate abiogenicandThe N demands of an expanding biosphere were satisfied by the evolution of biological N2fixation, possibly utilizing only Fe. Trace O2in late Archean environments, and the eventual ‘Great Oxidation Event’c. 2.3 Ga, mobilized metals such as Mo, enabling the evolution of Mo (or V)‐based N2fixation and the Mo‐dependent enzymes forassimilation and denitrification by prokaryotes. However, the subsequent onset of deep‐sea euxinia, an increasingly‐accepted idea, may have kept ocean Mo inventories low and depressed Fe, limiting the rate of N2fixation and the supply of fixed N. Eukaryotic ecosystems may have been particularly disadvantaged by N scarcity and the high Mo requirement of eukaryoticassimilation. Thorough ocean oxygenation in the Neoproterozoic led to Mo‐rich oceans, possibly contributing to the proliferation of eukaryotes and thus the Cambrian explosion of metazoan life. These ideas can be tested by more intensive study of the metal requirements in N assimilation and the biological strategies for metal uptake, regulation, and storage.
Acute and Chronic Ethanol Modulate Dopamine D2‐Subtype Receptor Responses in Ventral Tegmental Area GABA Neurons
Authors: Ludlow Kimberly H. , Bradley Katie D. , Allison David W. , Taylor Seth R. , Yorgason Jordan T. , Hansen David M. , Walton Christine H. , Sudweeks Sterling N. , Steffensen Scott C.
Published: March 2009

Background: Ventral tegmental area (VTA) γ‐aminobutyric acid (GABA) neurons appear to be critical substrates underlying the acute and chronic effects of ethanol on dopamine (DA) neurotransmission in the mesocorticolimbic system implicated in drug reward. VTA GABA neuron firing rate is reduced by acute ethanol and enhanced by DA via D2 receptor activation. The objective of this study was to evaluate the role of D2 receptors in acute ethanol inhibition of VTA GABA neuron activity, as well as the adaptation of D2 receptors by chronic ethanol consumption.

Methods: Using electrophysiological methods, we evaluated the effects of intraperitoneal ethanol on DA activation of VTA GABA neurons, the effects of DA antagonists on ethanol inhibition of their firing rate, as well as adaptations in firing rate following chronic ethanol consumption. Using single cell quantitative RT‐polymerase chain reaction (PCR), we evaluated the expression of VTA GABA neuron D2 receptors in rats consuming ethanol versus pair‐fed controls.

Results: In acute ethanol studies, microelectrophoretic activation of VTA GABA neurons by DA was inhibited by acute intraperitoneal ethanol, and intravenous administration of the D2 antagonist eticlopride blocked ethanol suppression of VTA GABA neuron firing rate. In chronic ethanol studies, while there were no signs of withdrawal at 24 hours, or significant adaptation in firing rate or response to acute ethanol, there was a significant down‐regulation in the expression of D2 receptors in ethanol‐consuming rats versus pair‐fed controls.

Conclusions: Inhibition of DA activation of VTA GABA neuron firing rate by ethanol, as well as eticlopride block of ethanol inhibition of VTA GABA neuron firing rate, suggests an interaction between ethanol and DA neurotransmission via D2 receptors, perhaps via enhanced DA release in the VTA subsequent to ethanol inhibition of GABA neurons. Down‐regulation of VTA GABA neuron D2 receptors by chronic ethanol might result from persistent DA release onto GABA neurons.
Ethyl Glucuronide in Hair Compared With Traditional Alcohol Biomarkers—A Pilot Study of Heavy Drinkers Referred to an Alcohol Detoxification Unit
Authors: Høiseth Gudrun , Morini Luca , Polettini Aldo , Christophersen Asbjørg , Mørland Jørg
Published: March 2009

Background:  Traditional biomarkers for heavy alcohol use include serum carbohydrate‐deficient transferrin (CDT), the enzymes aspartate aminotranserase (AST), and alanine aminotransferase (ALT) as well as gamma‐glutamyl transferase (GGT). Measurement of the nonoxidative ethanol metabolite, ethyl glucuronide (EtG) in hair, has been proposed as a new marker with superior qualities. The aim of this study was to investigate the sensitivity of EtG in hair to detect heavy alcohol use compared with CDT, AST, ALT, and GGT. We also wanted to study the quantitative relation between alcohol intake and the different biomarkers.

Methods:  Sixteen patients with a history of heavy alcohol use over the previous 3 months were recruited directly after admission to a withdrawal clinic. They were thoroughly interviewed about their drinking pattern as well as relevant diseases and use of medicines or drugs. Serum was sampled and analyzed for %CDT, AST, ALT, and GGT. Hair samples were collected and analyzed for EtG.

Results:  The mean estimated daily intake (EDI) over the previous 3 months was 206 ± 136 g pure alcohol. All patients fulfilled the criteria for heavy alcohol use. The sensitivity to detect heavy alcohol use was 64% for %CDT, 67% for AST, 67% for ALT, 93% for GGT, and 94% for EtG. There was no correlation between the quantitative values of EDI and %CDT, AST, ALT, and GGT. There was a positive, statistically significant correlation between EDI and the level of EtG in hair.

Conclusions:  In this study, EtG in hair and GGT showed the best sensitivity to detect heavy alcohol use and there was a positive correlation between EDI and the concentrations of EtG in hair. Before giving recommendations for clinical practice, further studies should be carried out on larger materials and populations with a wider range of alcohol intake.
Collateral Reports in the College Setting: A Meta‐Analytic Integration
Authors: Borsari Brian , Muellerleile Paige
Published: March 2009

Background:  The majority of research examining college drinking utilizes self‐report data, and collateral reports have been used to verify participants’ self‐reported alcohol use.

Methods:  This meta‐analytic integration examined the correspondence of over 970 collateral and participant dyads in the college setting.

Results and Conclusions:  Results indicated that there is little bias (mean difference) between collateral estimates of participant drinking and participant’s self‐report. A cumulative meta‐analysis revealed that this (null) effect was stable and unlikely to be altered by subsequent research or the existence of unpublished studies. Analysis of the agreement between collaterals and participant estimates (measured by intraclass correlation coefficients; ICCs) revealed moderate levels of agreement (mean ICC = 0.501). Examination of predictors of both bias and agreement in collateral and participant reports indicates a possible intentional and protective underreporting on the part of the collaterals. Ways to reduce this bias are discussed along with the value of using collaterals to verify participant self‐report in the college setting.
How Technology–Based New Firms Leverage Newness and Smallness to Commercialize Disruptive Technologies
Authors: Carayannopoulos Sofy
Published: March 2009

Although the survival of young firms is challenged by the liabilities of newness, there are numerous instances where these firms have been successful at commercializing disruptive technologies at the expense of much larger and stronger incumbents. This paper explores this phenomenon and argues that the characteristics that challenge young technology–venture survival are also potential sources of advantage when commercializing disruptive technologies. The propositions developed also identify the boundary conditions for the advantages by examining the context of commercialization that is created by four types of disruptive technologies. The contributions of this paper are relevant to the enhanced understanding of the liabilities of newness, as well as the commercialization of disruptive technologies.
Predictors of Hospital Admission for Chronic Obstructive Pulmonary Disease Exacerbations in Canadian Emergency Departments
Authors: Rowe Brian H. , Villa‐Roel Cristina , Guttman Alex , Ross Scott , Mackey Duncan , Sivilotti Marco L. A. , Worster Andrew , Stiell Ian G. , Willis Virginia , Borgundvaag Bjug
Published: March 2009

Objectives:  The objective was to examine predictors of hospital admission among adults presenting to Canadian emergency departments (EDs) for acute exacerbations of chronic obstructive pulmonary disease (COPD). Current acute treatment approaches and outcomes 2 weeks after the ED visit are also described.

Methods:  Subjects, aged ≥35 years presenting with COPD exacerbations to 16 EDs across Canada, underwent a structured in‐ED interview and a telephone interview 2 weeks later.

Results:  Of 501 study patients, 247 (49.3%; 95% confidence interval [CI] = 44.9% to 53.6%) were admitted. Admitted patients were older, were more often former smokers, and had more admissions for COPD during the past 2 years. They also reported more days of activity limitation and use of inhaled beta2‐agonists in the previous 24 hours. Canadian Triage and Acuity Scale (CTAS), respiratory rate (RR), and airflow obstruction were more severe in the hospitalized group. Most of the patients received inhaled beta2‐agonists, anticholinergics, oral corticosteroids (CS), and antibiotics; hospitalized patients received more aggressive treatments. The median ED length of stay (LOS) of admitted patients was 13.1 hours (interquartile range [IQR] = 7.4‐23.0) compared to 5.6 hours (IQR = 4.2‐8.4) in discharged patients. Admission was associated with at least two COPD admissions in the past 2 years (odds ratio [OR] = 2.10; 95% CI = 1.24 to 3.56), receiving oral CS for COPD (OR = 1.72; 95% CI = 1.08 to 2.74), having a CTAS score of 1–2 (OR = 2.04; 95% CI = 1.33 to 3.12), and receiving adjunct ED treatments (OR = 3.95; 95% CI = 2.45 to 6.35). Use of EDs for usual COPD care was associated with a reduced risk of admission (OR = 0.43; 95% CI = 0.28 to 0.66).

Conclusions:  Exacerbations of COPD in Canadian EDs result in prolonged ED stays and approximately 50% hospitalization despite aggressive acute treatment approaches. Historical, severity, and treatment‐related factors were strongly associated with hospital admission. Validation of these results should be completed prior to widespread use.
Caveolin‐1 regulation of dynamin‐dependent, raft‐mediated endocytosis of cholera toxin–B sub‐unit occurs independently of caveolae
Authors: Lajoie Patrick , Kojic Liliana D. , Nim Satra , Li Lei , Dennis James W. , Nabi Ivan R.
Published: March 2009

Ganglioside GM1‐bound cholera toxin–B sub‐unit (CT‐b) enters the cell via clathrin‐coated pits and dynamin‐independent non‐caveolar raft‐dependent endocytosis. Caveolin‐1 (Cav1), associated with caveolae formation, is a negative regulator of non‐caveolar raft‐dependent endocytosis. In mammary epithelial tumour cells deficient for Mgat5, Cav1 is stably expressed at levels below the threshold for caveolae formation, forming stable oligomerized Cav1 microdomains or scaffolds that were shown to suppress EGFR signalling and reduce the plasma membrane diffusion rate of both EGFR and CT‐b. Below threshold levels of Cav1 also inhibit the dynamin‐dependent raft‐mediated endocytosis of CT‐b to the Golgi indicating that Cav1‐negative regulation of raft‐dependent endocytosis is caveolae independent. Inhibition of CT‐b internalization does not require Cav1 phosphorylation but does require an intact Cav1 scaffolding domain. By flow cytometry, both over‐expression of Cav1 and the dynamin K44A mutant block CT‐b internalization from the plasma membrane defining a dynamin‐dependent raft pathway for CT‐b endocytosis in these cells. However, only minimal co‐localization between CT‐b and Cav1 is observed. These results suggest that Cav1 regulates raft‐dependent internalization of CT‐b indirectly via a mechanism that requires the Cav1 scaffolding domain and the formation of oligomerized Cav1 microdomains but not caveolae.
Endothelial glycocalyx dimensions are reduced in growing collateral arteries and modulate leucocyte adhesion in arteriogenesis
Authors: Grundmann Sebastian , Schirmer Stephan H. , Hekking Liesbeth H. P. , Post Jan Andries , Ionita Mihaela G. , Groot Daphne de , Royen Niels van , Berg Bernard van den , Vink Hans , Moser Martin , Bode Christoph , Kleijn Dominique de , Pasterkamp Gerard , Piek Jan J. , Hoefer Imo E.
Published: March 2009

During collateral artery growth, monocytes adhere to the endothelium and secrete cytokines from the perivascular space promoting arteriogenesis. Recently, the endothelial glycocalyx has been shown to modulate leucocyte infiltration in atherogenic regions. The role of this endothelial surface coating in arteriogenesis, however, has not been investigated so far. We now report that local plasma levels of hyaluronic acid are specifically increased in collateral arterial blood of coronary artery disease patients and hypothesized that components of the endothelial glycocalyx are shed during arteriogenesis, resulting in decreased glycocalyx dimensions and an increased leucocyte extravasation. In a rabbit model of femoral artery ligation, electron microscopy revealed a decrease in glycocalyx dimensions in collateral arteries compared with quiescent anastomoses (67.5 ± 47.2 nm versus 101.0 ± 11.3 nm; P < 0.001). This decrease was correlated with a higher number of perivascular macrophages around collateral arteries. The additional glycocalyx perturbation by local hyaluronidase infusion almost completely removed the endothelial surface layer and temporarily stimulated leucocyte accumulation in the perivascular space. However, complete perturbation of the glycocalyx by hyaluronidase infusion resulted in a significant attenuation of collateral artery growth assessed by microsphere‐based perfusion measurements (ml/min/100 mmHg: hyaluronidase: 27.5 ± 3.5; Controls: 47.1 ± 3.83; P < 0.001) and a lower percentage of actively proliferating vascular smooth muscle cells. A decreased expression of the shear‐stress regulated pro‐arteriogenic genes eNOS and TGF‐β1 suggests an impaired mechanotransduction as the underlying mechanisms. For the first time, we describe the role of the endothelial glycocalyx in collateral artery growth. Although complete abrogation led to attenuated arteriogenesis, shedding of glycocalyx components is observed during collateral artery growth.
Embryonic stem cell‐derived cardiomyocytes as a model to study fetal arrhythmia related to maternal disease
Authors: Kadir Siti H. Sheikh Abdul , Ali Nadire N. , Mioulane Maxime , Brito‐Martins Marta , Abu‐Hayyeh Shadi , Foldes Gabor , Moshkov Alexey V. , Williamson Catherine , Harding Sian E. , Gorelik Julia
Published: March 2009

Embryonic stem cell‐derived cardiomyocytes (ESC‐CM) have many of the phenotypic properties of authentic cardiomyocytes, and great interest has been shown in their possibilities for modelling human disease. Obstetric cholestasis affects 1 in 200 pregnant women in the United Kingdom. It is characterized by raised serum bile acids and complicated by premature delivery and unexplained fetal death at late gestation. It has been suggested that the fetal death is caused by the enhanced arrhythmogenic effect of bile acids in the fetal heart, and shown that neonatal susceptibility to bile acid‐induced arrhythmia is lost in the adult rat cardiomyocyte. However, the mechanisms of the observed bile acid effects are not fully understood and their in vivo study in human beings is difficult. Here we use ESC‐CM from both human and mouse ESCs to test our proposal that immature cardiomyocytes are more susceptible to the effect of raised bile acids than mature ones. We show that early ESC‐CM exhibit bile acid‐induced disruption of rhythm, depression of contraction and desynchronization of cell coupling. In both species the ESC‐CM become resistant to these arrhythmias as the cells mature, and this develops in line with the respective gestational periods of mouse and human. This represents the first demonstration of the use of ESC‐CM as a model system for human cardiac pathology, and opens the way for both investigation of mechanisms and a high throughput screen for drug discovery.
Myxoid atypical fibroxanthoma: a previously undescribed variant
Authors: Patton A. , Page R. , Googe P. B. , King R.
Published: March 2009

Background: Atypical fibroxanthomas (AFX) are dermal‐based cutaneous tumors typically found in sun‐damaged skin of the elderly. Histologic variants include spindle cell, clear cell, osteoid, osteoclastic, chondroid, pigmented, and granular cell. To date, myxoid change in AFX, has not been described.

Methods: Four cases were retrieved from the consultation and surgical pathology files of Knoxville Dermatopathology Laboratory, Knoxville, Tennessee during a 4‐year period. The clinical and histologic findings were reviewed and Alcian blue/periodic acid‐Schiff (PAS) stain and panel of immunohistochemical stains was obtained.

Results: All 4 lesions occurred as solitary lesions in elderly males on the head and neck (2 cases) and upper extremity (2 cases). Histologically all tumors demonstrated a well‐circumscribed, cellular lesion centered in the dermis and composed of a mix of atypical pleomorphic and spindle cells in a prominent myxomatous background. A junctional component was absent and the tumors did not arise from the epidermis or adnexal structures. Subcutaneous involvement was absent in all cases. Tumor cells were negative for melanocytic and epithelial markers. Positive staining was noted with CD10 (3/4 cases) and vimentin (4/4 cases).

Conclusion: Myxoid change in AFX is rare and previously undescribed in the English literature. Myxoid change may be a prominent finding in benign and malignant cutaneous tumors and awareness of this variant of AFX will avoid misdiagnosis.
Ex vivo expanded haematopoietic progenitor cells improve dermal wound healing by paracrine mechanisms
Authors: Templin Christian , Grote Karsten , Schledzewski Kai , Ghadri Jelena‐Rima , Schnabel Sabine , Napp Lars Christian , Schieffer Bernhard , Kurzen Hjalmar , Goerdt Sergij , Landmesser Ulf , Koenen Wolfgang , Faulhaber Jörg
Published: March 2009

Background:  Although dermal wounds are common, treatment remains limited and largely ineffective. Recent studies suggest that therapeutic application of progenitor cells is useful for tissue regeneration.

Objective:  We here investigated the effects exerted by the recently characterized immortalized haematopoietic progenitor cell line DKmix and their conditioned medium in a murine wound healing model.

Methods and Results:  Injection of both DKmix cells and their conditioned medium accelerated wound repair between days 3 and 10 compared with PBS‐injected control mice (n = 8, P < 0.01 DKmix cells vs control, P < 0.01 conditioned medium vs control at day 6). The treated groups exhibited more CD31+‐capillaries at day 6 after injury compared with the control group (n = 4, P < 0.01 DKmix cells vs control, P < 0.001 conditioned medium vs control), whereas there was no change in infiltrated CD68+ macrophages. Conditioned medium of DKmix cells induced tube formation of human endothelial cells in Matrigel assays (n = 4–6, P < 0.05 conditioned medium vs control) as well as migration (n = 4, P < 0.01 conditioned medium vs control) and proliferation of murine 3T3 fibroblasts (n = 5, P < 0.05 conditioned medium vs control). Abundant levels of matrix metalloproteinase −2 and −9 in the supernatants were detected. Protein arrays of the supernatants revealed a strong secretion of cytokines and growth factors, such as monocyte chemoatractant protein‐1 and GM‐CSF from DKmix cells.

Conclusion:  DKmix cells improve skin‐substitute wound healing by promoting angiogenesis as well as migration and proliferation of fibroblasts. These data suggest that immortalized haematopoietic progenitor cells significantly improve dermal wound healing by paracrine effects.
Low to high Ca2+‐switch causes phosphorylation and association of desmocollin 3 with plakoglobin and desmoglein 3 in cultured keratinocytes
Authors: Aoyama Yumi , Yamamoto Yukari , Yamaguchi Fumiko , Kitajima Yasuo
Published: March 2009

Abstract:  Although desmocollins (Dscs) and desmogleins (Dsgs) are known to be bound to each other to form desmosomes, neither their interactions nor regulations that occur in human keratinocytes grown in low and high Ca2+medium has been determined. In this study, we investigated whether Dsc3 interacts with Dsg3 in a cell line of human squamous cell carcinoma keratinocytes (DJM‐1) grown in low (0.05 mm) or high (1.27 mm) Ca2+medium. Anti‐Dsc3 monoclonal antibody did not co‐immunoprecipitate Dsg3 nor plakoglobin with Dsc3 in low Ca2+culture, whereas it co‐immunoprecipitated plakoglobin already at 10 min and Dsg3 at 60 min after Ca2+‐switch in association with Dsc3 phosphorylation at serine residues. These results suggest that both the binding of Dsc3 to plakoglobin and Dsc3 phosphorylation are involved in Dsc3 binding to Dsg3 during Ca2+‐induced desmosome assembly.
Endogenous survivin modulates survival and proliferation in UVB‐treated human keratinocytes
Authors: Dallaglio Katiuscia , Palazzo Elisabetta , Marconi Alessandra , Dumas Marc , Truzzi Francesca , Lotti Roberta , Bontè Frederic , Pincelli Carlo
Published: March 2009

Abstract:  Survivin is a bi‐functional member of inhibitor of apoptosis protein family, as it is able to both inhibit apoptosis and to regulate cell cycle. We investigated the role of survivin in human keratinocytes under normal conditions and during UVB irradiation. Survivin siRNA decreases proliferation and induces apoptosis in human keratinocytes, in a mode consistent with the mitotic catastrophe. Low doses UVB increase survivin expression at earlier times, while high doses down‐regulate survivin level. Low doses UVB induce cell cycle arrest in G2/M, while high doses UVB cause apoptosis. Moreover, overexpression of survivin protects keratinocytes from UVB‐induced apoptosis, and silencing of survivin renders keratinocytes more susceptible to UVB‐induced cell death. Finally, survivin siRNA increases UVB‐induced reduction of cell proliferation. Taken together, these results indicate that survivin plays a critical role in epidermal homeostasis in normal conditions and during UVB exposure, with possible implication in skin carcinogenesis.
Frontiers and controversies in the pathobiology of vitiligo: separating the wheat from the chaff
Authors: Boissy Raymond E. , Spritz Richard A.
Published: March 2009

Abstract:  The pathogenesis of vitiligo is complex and not well understood. Genes play a role in all aspects of vitiligo pathogenesis, and studies are ongoing to identify these genes and understand their biology. There is a body of interlocking, compelling evidence supporting an autoimmune basis for most or all cases of generalized vitiligo. The development of an autoimmune disease generally involves three components; the immune system, environmental triggers and other exogenous precipitating factors, and the target tissue. In vitiligo, precipitating factors could induce melanocyte damage in genetically susceptible individuals and consequent cell death, loss of tolerance, and induction of melanocyte‐directed autoimmunity. Future research will more precisely define the multiple biological events that regulate development of vitiligo.
Protective effect of pomegranate‐derived products on UVB‐mediated damage in human reconstituted skin
Authors: Afaq Farrukh , Zaid Mohammad Abu , Khan Naghma , Dreher Mark , Mukhtar Hasan
Published: March 2009

Abstract:  Solar ultraviolet (UV) radiation, particularly its UVB (290–320 nm) component, is the primary cause of many adverse biological effects including photoageing and skin cancer. UVB radiation causes DNA damage, protein oxidation and induces matrix metalloproteinases (MMPs). Photochemoprevention via the use of botanical antioxidants in affording protection to human skin against UVB damage is receiving increasing attention. Pomegranate, from the tree Punica granatum, contains anthocyanins and hydrolysable tannins and possesses strong antioxidant and anti‐tumor‐promoting properties. In this study, we determined the effect of pomegranate‐derived products – POMx juice, POMx extract and pomegranate oil (POMo) – against UVB‐mediated damage using reconstituted human skin (EpiDermTM FT‐200). EpiDerm was treated with POMx juice (1–2 μl/0.1 ml/well), POMx extract (5–10 μg/0.1 ml/well) and POMo (1–2 μl/0.1 ml/well) for 1 h prior to UVB (60 mJ/cm2) irradiation and was harvested 12 h post‐UVB to assess protein oxidation, markers of DNA damage and photoageing by Western blot analysis and immunohistochemistry. Pretreatment of Epiderm with pomegranate‐derived products resulted in inhibition of UVB‐induced (i) cyclobutane pyrimidine dimers (CPD), (ii) 8‐dihydro‐2′‐deoxyguanosine (8‐OHdG), (iii) protein oxidation and (iv) proliferating cell nuclear antigen (PCNA) protein expression. We also found that pretreatment of Epiderm with pomegranate‐derived products resulted in inhibition of UVB‐induced (i) collagenase (MMP‐1), (ii) gelatinase (MMP‐2, MMP‐9), (iii) stromelysin (MMP‐3), (iv) marilysin (MMP‐7), (v) elastase (MMP‐12) and (vi) tropoelastin. Gelatin zymography revealed that pomegranate‐derived products inhibited UVB‐induced MMP‐2 and MMP‐9 activities. Pomegranate‐derived products also caused a decrease in UVB‐induced protein expression of c‐Fos and phosphorylation of c‐Jun. Collectively, these results suggest that all three pomegranate‐derived products may be useful against UVB‐induced damage to human skin.
Gpnmb is a melanosome‐associated glycoprotein that contributes to melanocyte/keratinocyte adhesion in a RGD‐dependent fashion
Authors: Tomihari Mizuki , Hwang Sun‐Hee , Chung Jin‐Sung , Cruz Jr. Ponciano D. , Ariizumi Kiyoshi
Published: March 2009

Abstract:  Gpnmb is a glycosylated transmembrane protein implicated in the development of glaucoma in mice and melanoma in humans. It shares significant amino acid sequence homology with the melanosome protein Pmel‐17. Its extracellular domain contains a RGD motif for binding to integrin and its intracellular domain has a putative endosomal and/or melanosomal‐sorting motif. These features led us to posit that Gpnmb is associated with melanosomes and involved in cell adhesion. We showed that human Gpnmb is expressed constitutively by melanoma cell lines, primary‐cultured melanocytes and epidermal melanocytes in situ, with most of it found intracellularly within melanosomes and to a lesser degree in lysosomes. Our newly developed monoclonal antibody revealed surface expression of Gpnmb on these pigment cells, albeit to a lesser degree than the intracellular fraction. Gpnmb expression was upregulated by UVA (but not UVB) irradiation and by α‐melanocyte‐stimulating hormone (MSH) (but not β‐MSH); its cell surface expression on melanocytes (but not on melanoma cells) was increased markedly by IFN‐γ and TNF‐α. PAM212 keratinocytes adhered to immobilized Gpnmb in a RGD‐dependent manner. These results indicate that Gpnmb is a melanosome‐associated glycoprotein that contributes to the adhesion of melanocytes with keratinocytes.