bluuebunny/crossref_metadata_2025 huggingface dataset:
Is the NHS, as an employer, overburdened with regulations relating to its obligations to employees?
Authors: George Manoj , Joseph Renju
Published: August 2011

Purpose

The purpose of this paper is to provide an introduction to the existing regulations relating to the obligations of the NHS to its employees and to discuss whether the NHS is overburdened with these regulations.

Design/methodology/approach

Provides an overview of the current employment regulations and their impact on the NHS. The authors conducted a literature search in August 2009 on EMBASE, HMIC, MEDLINE, PsycINFO, HEALTH BUSINESS ELITE (1995‐2009) using the terms “NHS employee”, “NHS employer”, “Employment laws”. The reference sections of retrieved papers were hand‐searched for further relevant references.

Findings

The NHS seems to differ from other employers in several aspects. It has always remained high in political agenda, and has had to face high public expectations. The NHS has a huge workforce from a variety of disciplines regulated by different external agencies. There are several areas where it seems that the NHS is struggling with the obligations to its employees. The law regarding the employment contract, redundancy and termination of contract puts the NHS management, as revealed in many case laws, in several legal dilemmas. The working time directives, time off work provisions and the rapidly changing health and safety obligations do not give flexibility and thus create practical problems to the human resources department. The ever‐growing financial obligations seem to be challenging even the very existence of the NHS.

Originality/value

The value of this paper is in drawing attention to the fact that existing employment law is complex and consists of several complicated statutes. The NHS is also going through a period of rapid changes, in trying to set and meet stringent and unrealistic national targets and thereby putting enormous pressure on its management and workforce. The NHS is therefore struggling in several areas with the obligations to its employees.
Challenge of introducing evidence based medicine into clinical practice
Authors: Ogundele Michael
Published: August 2011

Purpose

This article aims to review the available literature on how clinicians meet the daily challenge of translating medical information into clinical EBM. It also seeks to describe the procedures involved in a local initiative in the UK to develop software applications for implementation of national clinical guidelines to enhance EBM in routine clinical practice.

Design/methodology/approach

It was hypothesised that improved access to these guidelines in routine clinical practice could be achieved through integrated local procedures, thereby enhancing the quality of care provided to children and adolescents with asthma or UTI. A literature search was performed using databases. To explore the preferences of the doctors and other healthcare professionals on how they accessed clinical guidelines, feedback was obtained. Stepwise implementation of the clinical guidelines was instituted over a period of three years in different primary care and hospital settings.

Findings

The professionals actively engaged with all the different stages in the implementation of the clinical guidelines. The majority preferred the interactive computerized system based on its ease of use, better aesthetic features, familiarity with the software and limited dependence on the technical skills of the users.

Research limitations/implications

The limitations of this study include lack of systematic data to assess the clinical effectiveness of the guidelines' implementation. Another apparent limitation of the study is the small size of participants within the paediatric unit of each organisation where the study was conducted.

Practical implications

There is a need for further comparative studies between the local intervention strategies described in this study and other implementation strategies, to identify the most effective implementation methods for electronic guideline‐based systems.

Social implications

Reliable high quality guidelines from reputable professional bodies could be successfully implemented at the primary or hospital‐based levels through a series of coordinated multidisciplinary interactive processes. This study has positive implications for improving the quality of care provided to children and adolescents, enhancing the role of clinical governance, provision of useful information to patients/carers and other healthcare providers.

Originality/value

This study highlights a potentially effective way of implementing and integrating an electronic guideline‐based computer system into local practice.
New governments: new policies
Authors: Spigelman Allan D.
Published: August 2011

Purpose

This article's aim is to report on the influence of changing of the political guard on health care and health care policy.

Design/methodology/approach

This is an observational piece.

Findings

Governments orchestrate change but whether change leads to improvement remains to be seen.

Originality/value

The article reports the effect of Government.
A voluntary safe table to help competitive organizations collaborate on improving quality
Authors: Marcus‐Smith Miriam
Published: August 2011

Purpose

Four Washington State associations came together to form a novel organization in response to rising healthcare sector costs, coupled with the need to ensure efficient provision of high quality care that improves health outcomes. This article seeks to explain the work and progress of that organization.

Design/methodology/approach

The article takes the form of a historical narrative.

Findings

The initiative has evolved from reliance on grants to becoming self‐funding, expanded the scope of its activities, and satisfied the needs of the stakeholders.

Practical implications

This organizational model is more efficient than going it alone on every effort, and may be a desirable solution for other communities.

Originality/value

This is the first published description of a unique, non‐profit organization founded in 1998, which can serve as a model for other regions that wish to promote collaborative benchmarking among competitive independent health care providers.
The structural fragility of financial systems
Authors: Gramlich Dieter , Oet Mikhail V.
Published: August 2011

Purpose

Lessons from the most recent financial crisis show specific vulnerabilities of financial markets due to weaknesses in the structure of the financial system (structural fragility). As the literature points out, the impact of systemic risk can be closely related to issues of concentration (“too big to fail”) and dependency (“too connected to fail”). However, different structural variables are emphasized in various ways, and most authors analyze each variable separately. This raises the questions of how structural fragility, as a cause of systemic distress, can be assessed more comprehensively and consistently, and what the implications are for modeling it within an integrated systemic risk framework. This paper seeks to address these issues.

Design/methodology/approach

On the basis of theoretical considerations and in the light of current transformations in financial markets, this paper explores elements of structural fragility and the requirements for modeling them.

Findings

The paper suggests an extended approach for conceptualizing structural fragility, evaluates directions for quantifying structural issues in early warning systems (EWSs) for systemic crises, and lays a theoretical groundwork for further empirical studies.

Originality/value

The need for supervisory actions to prevent crises is urgent, as is the need for integrating structural aspects into EWSs for systemic financial crises. Since a significant aspect of a financial firm's risk comes from outside the firm, individual institutions should understand and monitor the structural aspects of the various risk networks they are in.
Bet doubling in gambling and investing
Authors: Chapman Zaneta , Getzen Thomas
Published: August 2011

Purpose

The purpose of this paper is to analyze strategies for gamblers/investors to increase their chances of reaching certain monetary and/or survival goals while facing a losing proposition.

Design/methodology/approach

The paper investigates the use of credit by gamblers/investors as a means of increasing their expected survival time and thus their likelihood of winning. The paper considers a strategy in which a gambler/investor engages in bet doubling and uses credit to maximize the probability of winning a specified amount.

Findings

The model presented in this paper identifies the amount of credit that will make it possible for a gambler/investor to become a winner with an arbitrarily high degree of probability, even while facing a losing proposition. However, bet doubling can lead to large losses, and negative profits can be expected if the gambler/investor is faced with unfavorable odds. As an extension, the paper considers the impact of limited liability and finds that in that case, total losses are restricted and the gambler/investor can expect a positive net gain even while facing a losing proposition. It is also shown that the cost of obtaining credit is an important consideration and that it is ill‐advised for a gambler/investor to engage in such a strategy when the cost of credit is high relative to the probability of winning.

Originality/value

Although bet doubling is not new to the gambling literature, this paper considers the use of credit as a means of increasing survival time and expected net gain. Applications of the model are particularly useful to gamblers/investors when credit can be obtained at low costs.
A conditional CAPM: implications for systematic risk estimation
Authors: Milionis Alexandros
Published: August 2011

Purpose

The purpose of this paper is to examine, whether or not, the residuals of the market model (MM) are conditionally heteroscedastic; to examine, whether or not, there exists an intervalling effect in conditional heteroscedasticity in the residuals of the MM; to propose a simple data‐driven conditional capital asset pricing model (CAPM); and to examine the effect of conditional heteroscedasticity on the estimation of systematic risk.

Design/methodology/approach

Systematic risk coefficients (betas) are estimated at first using data of various frequencies from the Athens stock exchange without taking into account conditional heteroscedasticity. The same procedure is repeated, but this time taking into consideration conditional heteroscedasticity, which is found to exist. The results of the two approaches are compared.

Findings

Empirical evidence is provided for the existence of: conditional heteroscedasticity in MM residuals; a pronounced intervalling effect on autoregressive conditional heteroscedasticity (ARCH) in MM residuals; and generalized autoregressive conditional heteroscedasticity in mean type of conditional heteroscedasticity for the majority of cases where ARCH was present in MM residuals. These findings are conducive to a conditional CAPM, which takes into account the effect of conditional variance on expected returns, rather than the standard CAPM.

Practical implications

Better estimates of financial risk.

Originality/value

The intervalling effect in ARCH in the residuals of the MM is examined for the first time.
Hybrid forecasting models for S&P 500 index returns
Authors: Fukushima Akihiro
Published: August 2011

Purpose

The purpose of this paper is to propose two hybrid forecasting models which integrate available ones. A hybrid contaminated normal distribution (CND) model accurately reflects the non‐normal features of monthly S&P 500 index returns, and a hybrid GARCH model captures a serial correlation with respect to volatility. The hybrid GARCH model potentially enables financial institutions to evaluate long‐term investment risks in the S&P 500 index more accurately than current models.

Design/methodology/approach

The probability distribution of an expected investment outcome is generated with a Monte Carlo simulation. A taller peak and fatter tails (kurtosis), which the probability distribution of monthly S&P 500 index returns contains, is produced by integrating a CND model and a bootstrapping model. The serial correlation of volatilities is simulated by applying a GARCH model.

Findings

The hybrid CND model can simulate the non‐normality of monthly S&P 500 index returns, while avoiding the influence of discrete observations. The hybrid GARCH model, by contrast, can simulate the serial correlation of S&P 500 index volatilities, while generating fatter tails. Long‐term investment risks in the S&P 500 index are affected by the serial correlation of volatilities, not the non‐normality of returns.

Research limitations/implications

The hybrid models are applied only to the S&P 500 index. Cross‐sectional correlations among different asset groups are not examined.

Originality/value

The proposed hybrid models are unique because they combine available ones with a decision tree algorithm. In addition, the paper clearly explains the strengths and weaknesses of existing forecasting models.
From destination image building to identity‐based branding
Authors: Saraniemi Saila
Published: August 2011

Purpose

The purpose of this paper is to provide a detailed description of the various activities and processes undertaken by a particular national tourism organization (NTO) in carrying out its goal of developing a destination brand.

Design/methodology/approach

A single qualitative case study is primarily employed, though the study draws on data from multiple sources of information.

Findings

The study affirms the co‐creation and stakeholder viewpoints from having modeled the branding process and outlining the complex interaction of destination‐branding activities in the country‐level context. The study provides a critical discussion of the different approaches to branding, and the adoption of branding philosophies, in the destination context.

Research limitations/implications

Though this paper is based on a single country case study, it provides a strong and empirically grounded framework for identifying, in‐depth, several key destination branding processes and activities in great detail.

Originality/value

The co‐creation view of brands and branding is a neglected area in destination‐branding literature. Destination‐branding research, in particular, lacks grounded models that profoundly describe branding activities. This study contributes to the lack of empirically grounded knowledge of destination branding.
International tourists' image of Zhangjiajie, China: content analysis of travel blogs
Authors: Son Aram
Published: August 2011

Purpose

The purpose of this study is to identify Western travelers' image of Zhangjiajie, China as a tourist destination, drawing on data from contents of web travel blogs.

Design/methodology/approach

The study taps the rich content of travel blogs as an alternative research instrument to measure and understand negative and positive images of destinations formed by travelers. Analysis of content drawn from travel blog data followed qualitative methodology techniques and utilized NVivo software.

Findings

The study shows that travel blogs can form a good basis for measuring Western travelers' image of destination. This was the case for Zhangjiajie, where analysis of travelers' blogs indicated that they were impressed overall by the destination's beautiful natural scenery and were highly satisfied with nature‐based tourism attractions. The study also expounds on certain aspects of the destination that can be improved to satisfy Western travelers.

Originality/value

The majority of destination image studies rely on structured surveys developed from the researchers' point of view. This study attempts to explore tourists' own perspectives on the nature of a tourist destination by using travel blogs.
Cost reduction vs innovative search in R&D
Authors: Bromiley Philip , Washburn Mark
Published: August 2011

Purpose

This study aims to compare alternative search behaviors managers enact with regard to firm aspirations.

Design/methodology/approach

The behavioral theory of the firm predicts that poor performance relative to aspiration levels leads to search for ways to raise performance over aspirations. Most researchers have assumed search leads to risk‐taking or innovation. However, firms might search for ways to raise performance without incurring additional risk, such as reducing expenses. This paper compares the two models of search using data on research and development (R&D) spending.

Findings

The results generally support the cost cutting argument; R&D spending increases monotonically with performance relative to social aspirations.

Research limitations/implications

These results suggest researchers need to consider searches that emphasize cost reduction, as well as searches that emphasize innovation.

Originality/value

Overall, this paper extends behavioral work on risk‐taking and R&D to provide a more complex view of the interactions between kinds of aspiration levels and both innovation and search behavior.
Strategic reorientation and business turnaround: the case of global legacy airlines
Authors: Lawton Thomas , Rajwani Tazeeb , O'Kane Conor
Published: August 2011

Purpose

This paper aims to illustrate how legacy airlines can reorientate to achieve sharp recoveries in performance following prolonged periods of stagnation, decline and eroding competitiveness.

Design/methodology/approach

The authors use a qualitative analysis of five longitudinal case studies of legacy airlines that embarked on strategic change between 1997 and 2006. Data collection spanned ten years and included archival data, public documents, news clippings, accounts in specialist books and internal company documentation.

Findings

The paper identifies two distinct approaches for reorientation in the legacy airline industry. Companies that have fallen behind and are in risk of failure focus on regaining customer trust and loyalty, and restructuring route networks, business processes and costs in an “improvement and innovation” reorienting approach. Underperforming airlines, for whom growth has declined in traditional markets and who note that opportunities exist elsewhere, focus on product and service development and geographical growth in an “extension and expansion” reorienting approach.

Practical implications

The paper develops a framework for successful reorientation in the legacy airline industry. This framework encourages executives to focus on and leverage profit maximization, quality, leadership, alliance networks, regional consolidation and staff development during periods of strategy formulation and reorientation.

Originality/value

This research addresses the dearth of understanding and attention afforded to the concept of reorientation in the literature on strategic turnaround. The research also serves to emphasize the presence and importance of reorientation as a strategy of change within the legacy airline industry. Furthermore, in demonstrating how this strategy can be implemented in a sharp‐bending or performance improvement context, this study illustrates how reorientation is intertwined with the broader turnaround process.
Managing organizational capabilities: the Keystone step
Authors: Degravel Daniel
Published: August 2011

Purpose

This paper seeks to contribute to the RBV by focusing on a central construct, the “Keystone step”, within the firms' capability management field. It aims at providing a conceptual framework for top managers to understand the main related issues and steps, and to position their own organizational perspective.

Design/methodology/approach

The study explores the associated conceptual and empirical literature, borrowing from a strategic and a cognitive perspective, and defines and characterizes the central construct.

Findings

The author identifies a three‐step managerial process to handle capabilities: the Analytical step, the Action step, and the Keystone step. After briefly reviewing the resource‐based view, he suggests definitions and critical dimensions to design a conceptual frame articulated around the Keystone step, within which top managers can position and build their own approach. The critical founding rationale of capability management, rooted in underlying assumptions and beliefs, often implicit, hidden or neglected, increases the odds of blind managerial conceptual foundations. The author's claim focuses on the criticality of the Keystone step and the necessity of introspection to achieve sound strategic and capabilities‐related decisions.

Implications

Managers must recognize the importance of the Keystone step, devote resources to understand their own organizational “RBV position”, and acknowledge the mental flexibility to do so. The RBV should shift from an epistemology of “possession” to an epistemology of “embodiment”.

Originality/value

The paper offers an original vision of the capabilities management within the RBV, details out the issues of the current conceptual foundation of that managerial activity, and offers propositions for the Keystone step construct.
Guanxi, structural hole and closure
Authors: Lu Ren , Reve Torger
Published: August 2011

Purpose

Understanding China's economic success requires insights into its peculiarguanxi‐based market. Many scholars are confused about how to apply Western network theories to theguanxi‐based Chinese market. This paper aims to contribute to this comprehensive topic by theoretically exploring the differences among three fundamental network concepts:guanxi; structural hole; and closure.

Design/methodology/approach

Following Heide, the present paper categorises networks into three dimensions: network initiation, network maintenance and network termination, each based on different time phases. The three fundamental network concepts in every dimension are compared, laying out their similarities and dissimilarities in detail.

Findings

Although each of the three networks are initiated either naturally or artificially,guanxiis closely embedded in Chinese institutions. Unlike structural hole and closure, which can be applied at any level,guanxiis a special relation that only exists at the individual level. Structural hole and closure highlight the structures of the networks that bring them various benefits and constraints. Such merits are not evident inguanxi, in which favour exchange plays a crucial role in connecting entities. In addition,guanxihas special rules that affect the strength of ties.

Originality/value

The purpose of this paper is to articulate the differences amongguanxi, structural hole and closure. The systematic framework provides a platform to scholars interested in applying the Western network theory toguanxi‐based markets. The study work also provides new insights to non‐Chinese actors doing business in China.
Assessing the macroeconomic effects of fiscal policy in Colombia
Authors: Lozano Ignacio , Rodríguez Karen
Published: August 2011

Purpose

The purpose of this paper is to study the short‐term macroeconomic effects of the fiscal policy in Colombia for the 1980‐2007 period using a structural vector autoregression (SVAR) model.

Design/methodology/approach

The authors' benchmark is a five‐variable SVAR model which includes government spending, output, tax revenues, inflation and short‐term interest rates. In addition, the authors specified six‐variable VAR models, adding in turn private consumption, private investment, the unemployment rate and the real minimum wage to the last set of variables. Two alternative identification techniques are used in the VARs to check the robustness of the results.

Findings

The following effects of a positive government spending shock are found. First, the GDP responds positively and significantly during the first six quarters. The cumulative output multiplier fluctuates between 1.12 and 1.19. Second, both inflation and nominal interest rates respond positively and significantly. Third, the authors find a significant positive response by both private consumption and private investment. Finally, the unemployment rate reacts negatively and significantly.

Research limitations/implications

The most surprising result comes from the response of output to a positive shock in taxes. Nonetheless, the positive respond of the GDP is short lived and has little significance.

Practical implications

The authors' results support the smoothing role of fiscal policy on output fluctuations, which implies its capacity to restore real activity effectively in critical times like the ones currently being forecast.

Originality/value

The negligible results found previously for Colombia could be related to the fiscal data used, which are not keep coherence with national accounting. To solve these obstacles, a quarterly fiscal database is assembled on an approximately accrual basis for the general government.
An analysis of the effects of the severance payment reform on credit to Italian SMEs
Authors: Calcagno Riccardo , Kraeussl Roman , Monticone Chiara
Published: August 2011

Purpose

The purpose of this paper is to study the impact of the 2007 Italian severance payment reform on the cost and the access to credit for small‐ and medium‐sized enterprises (SMEs).

Design/methodology/approach

The authors study the implications of the reform adapting the theoretical credit‐rationing model of Holmstrom and Tirole, then estimate the capital outflows due to the reform and, using the theoretical prediction, assess its impact using mathematical simulations.

Findings

The authors predict that the reform may cause severe credit constraints to SMEs which cannot pledge enough collateral in order to obtain credit. The most direct consequences are to reduce in the long run the amount of liquid assets available to Italian firms, and to reduce their aggregate investment in a more than proportional way, due to access to credit restrictions. However, it will not increase the cost of intermediated finance, ceteris paribus.

Practical implications

The fact that the reform restricts access to credit, but does not increase the cost of debt, has important policy consequences, as public interventions subsidizing credit through a constant cost of debt may be ineffective.

Originality/value

While the topic has been analyzed in several respects (e.g. workers' participation to the reform, cost of an access to credit subsidy, etc.), no other study proposed an integrated view of these effects with a rigorous micro‐economic approach.
Ownership structure, corporate governance and corporate liquidity policy
Authors: Bokpin Godfred A. , Isshaq Zangina , Aboagye‐Otchere Francis
Published: August 2011

Purpose

The purpose of this paper is to examine the impact of ownership structure and corporate governance on corporate liquidity policy from a developing country perspective, Ghana Stock Exchange (GSE).

Design/methodology/approach

The authors adopt multiple regression analysis in estimating the relationship between ownership structure, corporate governance and corporate liquidity policy as well as the impact of corporate governance on insider ownership.

Findings

The authors find that foreign share ownership significantly predicts corporate cash holding on the GSE. The empirical result also portrays positive and statistically significant relationship between board size, financial leverage, firm size, profitability and corporate liquidity holding, and a negative and statistically significant relationship between board composition and corporate liquidity holding. The authors also document positive and statistically significant relationship between the various industry classifications namely manufacturing, distribution and the pharmaceutical industry and corporate cash holdings on the GSE but did not however find significant relationship between corporate governance and insider ownership on the GSE. The authors found positive relationship between Tobin's Q and inside ownership.

Originality/value

The main value of this paper is to analyze the relationship between ownership structure, corporate governance and corporate liquid policy from a developing country perspective.
Efficacy and safety of dalcetrapib in type 2 diabetes mellitus and/or metabolic syndrome patients, at high cardiovascular disease risk
Authors: Stalenhoef A. F. H. , Davidson M. H. , Robinson J. G. , Burgess T. , Duttlinger‐Maddux R. , Kallend D. , Goldberg A. C. , Bays H.
Published: August 2011

Aims: Mixed dyslipidaemia, characterized by low levels of high‐density lipoprotein cholesterol (HDL‐C) and high levels of triglycerides, is common in patients with type 2 diabetes mellitus (T2DM) and/or metabolic syndrome. Dalcetrapib effectively increases HDL‐C levels by modulating cholesteryl ester transfer protein (CETP) activity. The aim of this analysis was to investigate the lipid modifying efficacy and safety of dalcetrapib in patients with T2DM and/or metabolic syndrome.

Methods:
Post hoc analysis of dalcetrapib therapy in five placebo‐controlled, Phase II trials (4–48 weeks of duration) involving T2DM and/or metabolic syndrome, in dyslipidaemic patients with coronary heart disease (CHD) or CHD risk equivalent.

Results: Both in patients with and without T2DM and/or metabolic syndrome, dalcetrapib decreased CETP activity by 26–58% and increased HDL‐C levels by 23–34%, depending on dose and duration of treatment. Dalcetrapib did not significantly affect low‐density lipoprotein cholesterol (LDL‐C) or apolipoprotein B levels. Treatment with dalcetrapib was generally well tolerated with a similar number of adverse events reported between patient groups and between those receiving dalcetrapib compared with placebo.

Conclusions: Dalcetrapib similarly decreased CETP activity and increased HDL‐C levels in patients with and without T2DM or metabolic syndrome; the ongoing Phase III dal‐OUTCOMES study will help to determine if dalcetrapib's improvement in lipid levels also reduces cardiovascular morbidity and mortality.
Preference for dentist’s home visits among older people
Authors: Komulainen Kaija , Ylöstalo Pekka , Syrjälä Anna‐Maija , Ruoppi Piia , Knuuttila Matti , Sulkava Raimo , Hartikainen Sirpa
Published: August 2011

Komulainen K, Ylöstalo P, Syrjälä A‐M, Ruoppi P, Knuuttila M, Sulkava R, Hartikainen S. Preference for dentist’s home visits among older people. Community Dent Oral Epidemiol 2012; 40: 89–95. © 2011 John Wiley & Sons A/S

Abstract –  Objectives:  To investigate factors associated with older people’s preference for a dentist’s home visit. Methods: This is a report on 321 home‐dwelling participants (mean age 81.6) in the population‐based Geriatric Multidisciplinary Strategy for Good Care of the Elderly (GeMS) study, conducted in 2004–2005 in the city of Kuopio in eastern Finland. The information about sociodemographic and general health‐related factors and the use of social and health services was collected by two study nurses using a structured interview. Each study subject was given a clinical oral examination and an interview about oral health and the use of dental health care services by one of two dentists. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI). Results: Of the study subjects, 25.9% preferred a dentist’s home visit. The preference for choosing a dentist’s home visit was associated with a low score (≤24) in the Mini‐Mental State Examination, OR 6.1 (CI: 2.9–13.6), and a low score (<8) on the scale of Instrumental Activities of Daily Living, OR 8.0 (CI: 3.6–18.6). It was also associated with living alone, OR 5.9 (CI: 2.7–13.0), and high use of home care services, OR 9.3 (CI: 4.6–19.0). Conclusions: The findings of this study emphasize the need to organize dentists’ home visits in order to increase equality in the use of dental health care services among the older people with disabilities.
Evolutionary History and Functional Characterization of Three Large Genes Involved in Sporulation in Bacillus cereus Group Bacteria
Authors: Reiter Lillian , Tourasse Nicolas J. , Fouet Agnès , Loll Raphaël , Davison Sophie , Økstad Ole Andreas , Piehler Armin P. , Kolstø Anne-Brit
Published: August 2011

The
Bacillus cereus
group of bacteria is a group of closely related species that are of medical and economic relevance, including
B. anthracis
,
B. cereus
, and
B. thuringiensis
. Bacteria from the
Bacillus cereus
group encode three large, highly conserved genes of unknown function (named
crdA
,
crdB
, and
crdC
) that are composed of 16 to 35 copies of a repeated domain of 132 amino acids at the protein level. Bioinformatic analysis revealed that there is a phylogenetic bias in the genomic distribution of these genes and that strains harboring all three large genes mainly belong to cluster III of the
B. cereus
group phylogenetic tree. The evolutionary history of the three large genes implicates gain, loss, duplication, internal deletion, and lateral transfer. Furthermore, we show that the transcription of previously identified antisense open reading frames in
crdB
is simultaneously regulated with its host gene throughout the life cycle
in vitro
, with the highest expression being at the onset of sporulation. In
B. anthracis
, different combinations of double- and triple-knockout mutants of the three large genes displayed slower and less efficient sporulation processes than the parental strain. Altogether, the functional studies suggest an involvement of these three large genes in the sporulation process.
Role of Phase Variation in the Resistance of Myxococcus xanthus Fruiting Bodies to Caenorhabditis elegans Predation
Authors: Dahl John L. , Ulrich Christina H. , Kroft Tim L.
Published: August 2011

The phenomenon of phase variation between yellow and tan forms ofMyxococcus xanthushas been recognized for several decades, but it is not known what role this variation may play in the ecology of myxobacteria. We confirm an earlier report that tan variants are disproportionately more numerous in the resulting spore population of aM. xanthusfruiting body than the tan vegetative cells that contributed to fruiting body formation. However, we found that tan cells may not require yellow cells for fruiting body formation or starvation-induced sporulation of tan cells. Here we report three differences between the yellow and tan variants that may play important roles in the soil ecology ofM. xanthus. Specifically, the yellow variant is more capable of forming biofilms, is more sensitive to lysozyme, and is more resistant to ingestion by bacteriophagous nematodes. We also show that the myxobacterial fruiting body is more resistant to predation by worms than are dispersedM. xanthuscells.
Allometric scaling of peak power output accurately predicts time trial performance and maximal oxygen consumption in trained cyclists
Authors: Lamberts Robert P , Lambert Michael I , Swart Jeroen , Noakes Timothy D
Published: August 2011

Objective

The purpose of this study was to determine if peak power output (PPO) adjusted for body mass0.32is able to accurately predict 40-km time trial (40-km TT) performance.

Methods

45 trained male cyclists completed after familiarisation, a PPO test including respiratory gas analysis, and a 40-km TT. PPO, maximal oxygen consumption (VO2max) and 40-km TT time were measured. Relationships between 40-km TT performance and (I) absolute PPO (W) and VO2max(l/min), (II) relative PPO (W/kg) and VO2max(ml/min/kg) and (III) PPO and VO2maxadjusted for body mass (W/kg0.32and ml/min/kg0.32, respectively) were studied.

Results

The continuous ramp protocol resulted in a similar relationship between PPO and VO2max(r=0.96, p<0.0001) compared with a stepwise testing protocol but was associated with a lower standard error of the estimated when predicting VO2max. PPO adjusted for body mass (W/kg0.32) had the strongest relationship with 40-km TT performance (s) (r=−0.96, p<0.0001). Although significant relationships were also found between absolute (W) and/or relative PPO (W/kg) and 40-km TT performance (s), these relationships were significantly weaker than the relationship between 40-km TT performance and PPO adjusted for body mass (W/kg0.32) (p<0.0001).

Conclusions

VO2maxcan be accurately predicted from PPO when using a continuous ramp protocol, possibly even more accurately than when using a stepwise testing protocol. 40-km TT performance (s) in trained cyclists can be predicted most accurately by PPO adjusted for body mass (W/kg0.32). As both VO2maxand 40-km TT performance can be accurately predicted from a PPO test, this suggests that (well)-trained cyclists can possibly be monitored more frequently and with fewer tests.
Safety and cost effectiveness of step-down unit admission following elective neurointerventional procedures
Authors: Richards Boyd F , Fleming J Brett , Shannon Chevis N , Walters Beverly C , Harrigan Mark R
Published: August 2011

Objective

Post-procedure monitoring in a neurointensive care unit (NICU) after neurointerventional procedures is conventional at most centers. However, NICU resources are scarce and costly. The purpose of this study was to determine whether an intermediate care step-down unit could be a safe and cost-effective alternative to the NICU for patients after uncomplicated neurointerventional procedures.

Methods

A retrospective review was undertaken of 127 consecutive patients over a 3-year period undergoing elective neurointerventional procedures including treatment of intracranial aneurysms, tumors, arteriovenous malformations and dural arteriovenous fistulas. Seventy-one patients were admitted to a step-down unit and 56 patients were admitted to the NICU. Endpoints were post-procedural complications, hospital costs and length of stay. Patients admitted to the step-down unit were compared with patients admitted to the NICU.

Results

Patients admitted to the step-down unit did not have more complications than patients admitted to the NICU. Two patients admitted to the step-down unit had neurological complications after the procedure which were immediately recognized by nursing staff and adequately managed. The mean (SD) total cost per patient was $19 299 ($6955) for patients admitted to the step-down unit and $22 716 ($8052) for patients admitted to the NICU, resulting in a statistically significant cost saving for patients admitted to the step-down unit of $3417 (p=0.012). The mean (SD) total cost less procedural costs per patient was $8442 ($4062) for patients in the step-down unit and $10 631 ($4727) for those admitted to the NICU, which was also statistically significant (p=0.005). Length of stay averaged 21.7 h for patients admitted to the step-down unit and 24.9 h for those admitted to the NICU (p=0.016).

Conclusions

A step-down unit is a safe and cost-effective alternative to the NICU for patients undergoing elective neurointerventional procedures.
Mechanisms of atrial-selective block of Na+ channels by ranolazine: I. Experimental analysis of the use-dependent block
Authors: Zygmunt Andrew C. , Nesterenko Vladislav V. , Rajamani Sridharan , Hu Dan , Barajas-Martinez Hector , Belardinelli Luiz , Antzelevitch Charles
Published: August 2011

Atrial-selective inhibition of cardiac Na+ channel current ( INa) and INa-dependent parameters has been shown to contribute to the safe and effective management of atrial fibrillation. The present study examined the basis for the atrial-selective actions of ranolazine. Whole cell INa was recorded at 15°C in canine atrial and ventricular myocytes and in human embryonic kidney (HEK)-293 cells expressing SCN5A. Tonic block was negligible at holding potentials from −140 to −100 mV, suggesting minimal drug interactions with the closed state. Trains of 40 pulses were elicited over a range of holding potentials to determine use-dependent block. Guarded receptor formalism was used to analyze the development of block during pulse trains. Use-dependent block by ranolazine increased at more depolarized holding potentials, consistent with an interaction of the drug with either preopen or inactivated states, but was unaffected by longer pulse durations between 5 and 200 ms, suggesting a weak interaction with the inactivated state. Block was significantly increased at shorter diastolic intervals between 20 and 200 ms. Responses in atrial and ventricular myocytes and in HEK-293 cells displayed a similar pattern. Ranolazine is an open state blocker that unbinds from closed Na+ channels unusually fast but is trapped in the inactivated state. Kinetic rates of ranolazine interactions with different states of atrial and ventricular Na+ channels were similar. Our data suggest that the atrial selectivity of ranolazine is due to a more negative steady-state inactivation curve, less negative resting membrane potential, and shorter diastolic intervals in atrial cells compared with ventricular cells at rapid rates.
Intermittent hypobaric hypoxia improves postischemic recovery of myocardial contractile function via redox signaling during early reperfusion
Authors: Wang Zhi-Hua , Chen Yi-Xiong , Zhang Cai-Mei , Wu Lan , Yu Zhuo , Cai Xiao-Long , Guan Yi , Zhou Zhao-Nian , Yang Huang-Tian
Published: August 2011

Intermittent hypobaric hypoxia (IHH) protects hearts against ischemia-reperfusion (I/R) injury, but the underlying mechanisms are far from clear. ROS are paradoxically regarded as a major cause of myocardial I/R injury and a trigger of cardioprotection. In the present study, we investigated whether the ROS generated during early reperfusion contribute to IHH-induced cardioprotection. Using isolated perfused rat hearts, we found that IHH significantly improved the postischemic recovery of left ventricular (LV) contractile function with a concurrent reduction of lactate dehydrogenase release and myocardial infarct size (20.5 ± 5.3% in IHH vs. 42.1 ± 3.8% in the normoxic control, P < 0.01) after I/R. Meanwhile, IHH enhanced the production of protein carbonyls and malondialdehyde, respective products of protein oxidation and lipid peroxidation, in the reperfused myocardium and ROS generation in reperfused cardiomyocytes. Such effects were blocked by the mitochondrial ATP-sensitive K+channel inhibitor 5-hydroxydecanoate. Moreover, the IHH-improved postischemic LV performance, enhanced phosphorylation of PKB (Akt), PKC-ε, and glycogen synthase kinase-3β, as well as translocation of PKC-ε were not affected by applying H2O2(20 μmol/l) during early reperfusion but were abolished by the ROS scavengers N-(2-mercaptopropionyl)glycine (MPG) and manganese (III) tetrakis (1-methyl-4-pyridyl)porphyrin. Furthermore, IHH-reduced lactate dehydrogenase release and infarct size were reversed by MPG. Consistently, inhibition of Akt with wortmannin and PKC-ε with εV1-2 abrogated the IHH-improved postischemic LV performance. These findings suggest that IHH-induced cardioprotection depends on elevated ROS production during early reperfusion.
Curcumin augments lung maturation, preventing neonatal lung injury by inhibiting TGF-β signaling
Authors: Sakurai Reiko , Li Yishi , Torday John S. , Rehan Virender K.
Published: August 2011

There is no effective intervention to prevent or treat bronchopulmonary dysplasia (BPD). Curcumin has potent antioxidant and anti-inflammatory properties, and it modulates signaling of peroxisome proliferator-activated receptor-γ (PPARγ), an important molecule in the pathobiology of BPD. However, its role in the prevention of BPD is not known. We determined 1) if curcumin enhances neonatal lung maturation, 2) if curcumin protects against hyperoxia-induced neonatal lung injury, and 3) if this protection is mediated by blocking TGF-β. Embryonic day 19 fetal rat lung fibroblasts were exposed to 21% or 95% O2 for 24 h following 1 h of treatment with curcumin. Curcumin dose dependently accelerated e19 fibroblast differentiation [increased parathyroid hormone-related protein (PTHrP) receptor, PPARγ, and adipocyte differentiation-related protein (ADRP) levels and triolein uptake] and proliferation (increased thymidine incorporation). Pretreatment with curcumin blocked the hyperoxia-induced decrease (PPARγ and ADRP) and increase (α-smooth muscle actin and fibronectin) in markers of lung injury/repair, as well as the activation of TGF-β signaling. In a separate set of experiments, neonatal Sprague-Dawley rat pups were exposed to 21% or 95% O2 for 7 days with or without intraperitoneal administration of curcumin. Analysis for markers of lung injury/repair [PTHrP receptor, PPARγ, ADRP, fibronectin, TGF-β receptor (activin receptor-like kinase 5), and Smad3] and lung morphology (radial alveolar count) demonstrated that curcumin effectively blocks TGF-β activation and hyperoxia-induced lung injury. Therefore, curcumin accelerates lung maturation by stimulating key alveolar epithelial-mesenchymal interactions and prevents hyperoxia-induced neonatal lung injury, possibly by blocking TGF-β activation, suggesting that it is a potential intervention against BPD.
Combining EGFR and mTOR Blockade for the Treatment of Epithelioid Sarcoma
Authors: Xie Xianbiao , Ghadimi Markus P.H. , Young Eric D. , Belousov Roman , Zhu Quan-sheng , Liu Juehui , Lopez Gonzalo , Colombo Chiara , Peng Tingsheng , Reynoso David , Hornick Jason L. , Lazar Alexander J. , Lev Dina
Published: August 2011

Purpose: Molecular deregulations underlying epithelioid sarcoma (ES) progression are poorly understood yet critically needed to develop new therapies. Epidermal growth factor receptor (EGFR) is overexpressed in ES; using preclinical models, we examined the ES EGFR role and assessed anti-ES EGFR blockade effects, alone and with mTOR inhibition.

Experimental Design: EGFR and mTOR expression/activation was examined via tissue microarray (n = 27 human ES specimens; immunohistochemistry) and in human ES cell lines (Western blot and quantitative reverse transcriptase PCR). Cell proliferation, survival, migration, and invasion effects of EGFR and mTOR activation treated with erlotinib (anti-EGFR small-molecule inhibitor) alone and combined with rapamycin were assessed in cell culture assays. In vivo growth effects of erlotinib alone or with rapamycin were evaluated using severe combined immunodeficient mouse ES xenograft models.

Results: EGFR was expressed and activated in ES specimens and cell lines. EGFR activation increased ES cell proliferation, motility, and invasion and induced cyclin D1, matrix metalloproteinase (MMP) 2, and MMP9 expression. EGFR blockade inhibited these processes and caused significant cytostatic ES growth inhibition in vivo. mTOR pathway activation at varying levels was identified in all tissue microarray–evaluable ES tissues; 88% of samples had no or reduced PTEN expression. Similarly, both ES cell lines showed enhanced mTOR activity; VAESBJ cells exhibited constitutive mTOR activation uncoupled from EGFR signaling. Most importantly, combined erlotinib/rapamycin resulted in synergistic anti-ES effects in vitro and induced superior tumor growth inhibition in vivo versus single agent administration.

Conclusions: EGFR and mTOR signaling pathways are deregulated in ES. Preclinical ES model–derived insights suggest that combined inhibition of these targets might be beneficial, supporting evaluations in clinical trials. Clin Cancer Res; 17(18); 5901–12. ©2011 AACR.