bluuebunny/crossref_metadata_2025 huggingface dataset:
Recruiting high‐tech managerial talents in China: an institutional perspective
Authors: Rovai Serena
Published: June 2008

Purpose

The paper is part of the growing research on human resource management (HRM) in foreign multinational companies (MNCs) operating in the PRC. The purpose of this paper is to examine the critical role played by the host contextual factors on recruitment policies adoption for foreign high‐tech corporations operating in the PRC. In particular, the paper analyses the influence of institutional factors on “talent recruitment” and related policies and practices. In this perspective, the institutionalization theory was instrumental in explaining the degree to which recruitment policies and practices have been adapted, or not, to the host country environment or are more similar to those of multinational's headquarters and related standardised practices. The paper reviews the diverse studies related to people management in China and it stresses the lack of research for talents recruitment and selection in the PRC despite the critical situation in the local labour market.

Design/methodology/approach

This is an empirical paper based on a case‐study and field interviews.

Findings

This paper aims to provide an exploration of the main challenges and key issues for foreign high‐tech MNCs in recruiting managerial talents in the local labour market. It stresses the importance of the institutional context and its interaction with recruitment policies and practices. In particular, the study provides an overview of how the institutional environment has affected the transfer and adoption of specific recruitment policies in China and has resulted in an «adjustment» of their global HRM policies.

Research limitations/implications

As a result of opportunistic contacts and time‐constraints, this research is limited to western MNCs operating in China. However, it would be relevant to investigate the situation for talent recruitment and selection in local Chinese private companies in relation to the on‐going transformation and growing presence of those companies in the local labour market. Furthermore, the study only focuses on high‐tech MNCs without considering the situation and possible diverse variables and scenarios arising in diverse industrial companies.

Originality/value

The paper is of value in that it confirms that now‐a‐days, as in the past, despite the on‐going institutional transformation –, i.e. the approval of a new labour law – foreign high‐tech MNCs recruitment policies and practices in China are still affected by a coercive isomorphism despite the still limited influence of a mimetic and normative isomorphism through the dissemination of best practices by top business organisations and HRM consulting firms in the market. More specifically, the paper emphasises the negative role of the existing labour system – evolving from the system derived from previous China‐specific centrally planned economy – and the fact that it prevents transfer and complete implementation of globally standardised HRM policies in China for an effective recruitment of high‐tech managerial profiles in high‐tech MNCs.
Chinese foreign workers in Singapore's construction industry
Authors: Sui Pheng Low , Jun Ying Liu , Shan Shan Soh
Published: June 2008

Purpose

There is little understanding of the pressure, loneliness and homesickness, the workers from Mainland China faced when working overseas in a foreign land like Singapore. The families which the workers left behind in Mainland China when they work in Singapore were also neglected. The purpose of this paper is to examine the wider social aspects relating to Chinese foreign workers in the Singapore construction industry.

Design/methodology/approach

The research process was based on a questionnaire survey of Chinese construction workers in Singapore. A questionnaire with 45 questions was designed in which the information solicited included the socio‐demographic characteristics of the respondents, the reasons behind their trans‐national migration behaviour, the impact of this migratory behaviour on the workers and their families in Mainland China, and the workers' perceptions of and feelings towards working overseas. In total, 65 fully completed questionnaires were analyzed and reported in the study.

Findings

Supporting the family was the overarching reason for Chinese construction workers to work in Singapore. However, they were unhappy in Singapore owing to: feeling of homesickness, loneliness, long working hours, overtime work and a lack of understanding, empathy and appreciation from the locals.

Originality/value

This paper has taken the first step in exploring the neglected aspects of Chinese construction workers in Singapore. It provides a set of recommendations on how the relevant government authorities, employers and non‐governmental organizations can pay more attention to the emotional and psychological needs of these foreign workers. It also provides a better understanding of these workers to help raise public acceptance of them in society.
The effect of individual factors on the transfer of human resource management knowledge in Chinese subsidiaries
Authors: Wang‐Cowham Cindy
Published: June 2008

Purpose

The purpose of this paper is to examine the effect of individual factors on the transfer of human resource management (HRM) knowledge in Chinese subsidiaries of multinational corporations, and to explore the relationships between individual factors and introduce the concept of joint effect‐integrated capability.

Design/methodology/approach

Based on the notion that certain factors can affect knowledge transfer (KT), this paper examines the effect of four factors, i.e. cultural difference and adaptability, language and communication, working relationship, and motivation and willingness, on the transfer of HRM knowledge. The paper is based on an empirical study of 22 individual HR professionals from 21 Chinese subsidiaries. Data were collected through semi‐structured interviews conducted between January and April 2004 and an exploratory data analysis was carried out with the assistance of Nvivo software.

Findings

The study has found that Chinese HR managers have the ability of all four factors to facilitate the transfer of HRM knowledge. The findings further suggest that integrated capability‐joint effect could be generated from the four factors and affect the transfer process jointly. When the capability is positive, it facilitates the transfer. Conversely, when the capability is negative, it impedes the transfer.

Research limitations/implications

The findings not only extend the understanding of the effect of single factor on KT, but also the interrelationship between individual factors, their joint effect‐integrated capability and the transfer process.

Originality/value

Existing research has concentrated on studying the effect of single factor on KT, knowledge management by and large. There is little research investigating the correlations between individual factors. This paper addresses this gap and introduces the concept of joint effect, integrated capability.
Multinational enterprises in China, East Asia, Latin America and Eastern Europe
Authors: Chantasasawat Busakorn , Fung K.C. , Iizaka Hitomi , Siu Alan
Published: June 2008

Purpose

The purpose of this paper is to examine whether multinational corporations moving into China have a negative impact on the extent of foreign firms moving into other developing countries in East Asia, Latin America and Eastern Europe.

Design/methodology/approach

The paper controls for a comprehensive set of determinants of why multinational enterprises enter the economies of East Asia, Latin America and Eastern Europe and then adds and examines the instrumented foreign direct investment flows into China to proxy the impact of China on these other economies.

Findings

It was found that the multinational enterprises entering into China stimulate investment in east Asia, but have no significant effects on multinational enterprises entering into Eastern Europe and Latin America.

Research limitations/implications

Owing to data constraints, it was not possible to examine if these conclusions hold for different sectors such as the automobile and electronics sectors.

Practical implications

Governments in developing countries should focus on increasing their attractiveness to multinational enterprises. Policies such as lowering of the corporate tax rates should help.

Originality/value

The paper includes a very comprehensive set of factors and then uses foreign direct investment flows into China as a proxy for the impact of China on other economies.
Interdependence of income between China and ASEAN‐5 countries
Authors: Lau Evan , Po Lee Koon
Published: June 2008

Purpose

The purpose of the paper is to empirically examine the interdependence of income between China and ASEAN‐5 countries by using the real gross domestic product (GDP). Besides answering this important policy question, the paper is also concerned with ascertaining the causal direction between China and the ASEAN‐5 income.

Design/methodology/approach

The paper resorts to the standard time series econometrics analysis. These includes the unit root, cointegration and the Granger causality tests in order to test the causal interplay and interdependence of income between ASEAN‐5 and China for the estimation period from 1960 to 2003 obtained from the Penn World Table (PWT) 6.2.

Findings

Empirical results are found to support the strong interdependence of income between China and ASEAN‐5 countries. Further, the causality experiment suggests that China is the key factor in connecting (equilibrium point) the ASEAN‐5 region, where China in one‐way or another marks the resemblance of the income amongst these economies.

Originality/value

The paper is of value in that it highlights the issue of interdependence of income especially in developing countries. With the increasing interest of economic integration around the globe especially the China‐ASEAN Free Trade Area (CAFTA), the interdependence and synchronization movements of income between member countries is an important characteristic for suitability towards the regional common currency goal.
Modeling the impact of coal‐to‐liquids technologies on China's energy markets
Authors: Huang Haixiao , Fletcher Jerald J. , Sun Qingyun
Published: June 2008

Purpose

The purpose of the study is to evaluate the impact of China's current coal‐to‐liquids (CTL) activities on its coal and oil markets from 2005 to 2025.

Design/methodology/approach

A partial equilibrium multi‐equation model of China's oil and coal markets is developed based on data obtained from the existing literature. The impact of CTL technologies on China's oil and coal markets is evaluated using computer simulations by solving the model under scenarios with and without CTL production.

Findings

The simulation results show that on average, the planned CTL activities will decrease crude oil prices by 5.73 percent and China's oil imports by 6.09 percent and increase China's domestic oil supply by 9.26 percent over the 20 year period. Also, China's demand for oil will increase by 0.35 percent on average, suggesting that CTL production will slightly stimulate China's demand for oil because of the drop in oil prices. China's demand for coal will also increase by 1.02 percent because of the additional demand for coal created by CTL production. Surprisingly, both coal prices and China's coal supply will decline by 0.51 percent while the demand for coal and coal supply of the rest of the world will be reduced by 1.63 percent and 0.28 percent, respectively.

Originality/value

The paper is the first study on the implication of CTL conversion from an economist's point of view. It applies an economic model to quantify the impacts of such technology on overall energy prices and supplies.
Economic growth and resource allocation: the case of China
Authors: Wong Kar‐yiu
Published: June 2008

Purpose

This paper aims to examine the factors of growth of a developing country such as China. Because of the existence of domestic distortions, the traditional approach of using the growth of gross domestic product (GDP) to represent economic growth of the economy is not appropriate. This paper seeks to estimate how a change in resource misallocation may affect the measured growth rate of GDP.

Design/methodology/approach

Using provincial data for four southern provinces of China for the years from 2000 to 2004, the paper considers two hypothetical cases, one in which labor allocation is fixed, and one in which labor allocation is assumed to be optimal both before and after growth. The growth factors for GDP in these two hypothetical cases are compared with the observed growth factors.

Findings

This paper argues that the growth rate of GDP has overestimated the growth rate of the economy in this period. It can thus be said that the degree of the distortion caused labor misallocation decreases over time in this period.

Research limitations/implications

Because of limitations of data, this study treats each province as one sector, producing one homogeneous product, although the same methodology can be applied to more than one sector in each province. Furthermore, the present work assumes constant external prices.

Practical implications

The present study shows the importance of removing distortions in the economy, and how an improvement in the efficiency may raise the GDP of the economy.

Originality/value

The methodology and approach introduced here are quite new and are useful in assessing the implications of distortions on production and welfare.
Classification confidence weighted majority voting using decision tree classifiers
Authors: Tóth Norbert , Pataki Béla
Published: June 2008

Purpose

The purpose of this paper is to provide classification confidence value to every individual sample classified by decision trees and use this value to combine the classifiers.

Design/methodology/approach

The proposed system is first theoretically explained, and then the use and effectiveness of the proposed system is demonstrated on sample datasets.

Findings

In this paper, a novel method is proposed to combine decision tree classifiers using calculated classification confidence values. This confidence in the classification is based on distance calculation to the relevant decision boundary (distance conditional), probability density estimation and (distance conditional) classification confidence estimation. It is shown that these values – provided by individual classification trees – can be integrated to derive a consensus decision.

Research limitations/implications

The proposed method is not limited to axis‐parallel trees, it is applicable not only to oblique trees, but also to any kind of classifier system that uses hyperplanes to cluster the input space.

Originality/value

A novel method is presented to extend decision tree like classifiers with confidence calculation and a voting system is proposed that uses this confidence information. The proposed system possesses several novelties (e.g. it not only gives class probabilities, but also classification confidences) and advantages over previous (traditional) approaches. The voting system does not require an auxiliary combiner or gating network, as in the mixture of experts structure and the method is not limited to decision trees with axis‐parallel splits; it is applicable to any kind of classifiers that use hyperplanes to cluster the input space.
Intelligent water drops algorithm
Authors: Shah‐Hosseini Hamed
Published: June 2008

Purpose

The purpose of this paper is to test the capability of a new population‐based optimization algorithm for solving an NP‐hard problem, called “Multiple Knapsack Problem”, or MKP.

Design/methodology/approach

Here, the intelligent water drops (IWD) algorithm, which is a population‐based optimization algorithm, is modified to include a suitable local heuristic for the MKP. Then, the proposed algorithm is used to solve the MKP.

Findings

The proposed IWD algorithm for the MKP is tested by standard problems and the results demonstrate that the proposed IWD‐MKP algorithm is trustable and promising in finding the optimal or near‐optimal solutions. It is proved that the IWD algorithm has the property of the convergence in value.

Originality/value

This paper introduces the new optimization algorithm, IWD, to be used for the first time for the MKP and shows that the IWD is applicable for this NP‐hard problem. This research paves the way to modify the IWD for other optimization problems. Moreover, it opens the way to get possibly better results by modifying the proposed IWD‐MKP algorithm.
Design of optimal spacecraft‐asteroid formations through a hybrid global optimization approach
Authors: Alisa Maddock Christie , Vasile Massimiliano
Published: June 2008

Purpose

The purpose of this paper is to present a methodology and experimental results on using global optimization algorithms to determine the optimal orbit, based on the mission requirements, for a set of spacecraft flying in formation with an asteroid.

Design/methodology/approach

A behavioral‐based hybrid global optimization approach is used to first characterize the solution space and find families of orbits that are a fixed distance away from the asteroid. The same optimization approach is then used to find the set of Pareto optimal solutions that minimize both the distance from the asteroid and the variation of the Sun‐spacecraft‐asteroid angle. Two sample missions to asteroids, representing constrained single and multi‐objective problems, were selected to test the applicability of using an in‐house hybrid stochastic‐deterministic global optimization algorithm (Evolutionary Programming and Interval Computation (EPIC)) to find optimal orbits for a spacecraft flying in formation with an orbit. The Near Earth Asteroid 99942 Apophis (2004 MN4) is used as the case study due to a fly‐by of Earth in 2029 leading to two potential impacts in 2036 or 2037. Two black‐box optimization problems that model the orbital dynamics of the spacecraft were developed.

Findings

It was found for the two missions under test, that the optimized orbits fall into various distinct families, which can be used to design multi‐spacecraft missions with similar orbital characteristics.

Research limitations/implications

The global optimization software, EPIC, was very effective at finding sets of orbits which met the required mission objectives and constraints for a formation of spacecraft in proximity of an asteroid. The hybridization of the stochastic search with the deterministic domain decomposition can greatly improve the intrinsic stochastic nature of the multi‐agent search process without the excessive computational cost of a full grid search. The stability of the discovered families of formation orbit is subject to the gravity perturbation of the asteroid and to the solar pressure. Their control, therefore, requires further investigation.

Originality/value

This paper contributes to both the field of space mission design for close‐proximity orbits and to the field of global optimization. In particular, suggests a common formulation for single and multi‐objective problems and a robust and effective hybrid search method based on behaviorism. This approach provides an effective way to identify families of optimal formation orbits.
Structural studies of Saccharomyces cerevesiae mitochondrial NADP‐dependent isocitrate dehydrogenase in different enzymatic states reveal substantial conformational changes during the catalytic reaction
Authors: Peng Yingjie , Zhong Chen , Huang Wei , Ding Jianping
Published: June 2008

Isocitrate dehydrogenases (IDHs) catalyze oxidative decarboxylation of isocitrate (ICT) into α‐ketoglutarate (AKG). We report here the crystal structures of Saccharomyces cerevesiae mitochondrial NADP‐IDH Idp1p in binary complexes with coenzyme NADP, or substrate ICT, or product AKG, and in a quaternary complex with NADPH, AKG, and Ca2+, which represent different enzymatic states during the catalytic reaction. Analyses of these structures identify key residues involved in the binding of these ligands. Comparisons among these structures and with the previously reported structures of other NADP‐IDHs reveal that eukaryotic NADP‐IDHs undergo substantial conformational changes during the catalytic reaction. Binding or release of the ligands can cause significant conformational changes of the structural elements composing the active site, leading to rotation of the large domain relative to the small and clasp domains along two hinge regions (residues 118–124 and residues 284–287) while maintaining the integrity of its secondary structural elements, and thus, formation of at least three distinct overall conformations. Specifically, the enzyme adopts an open conformation when bound to NADP, a quasi‐closed conformation when bound to ICT or AKG, and a fully closed conformation when bound to NADP, ICT, and Ca2+ in the pseudo‐Michaelis complex or with NADPH, AKG, and Ca2+ in the product state. The conformational changes of eukaryotic NADP‐IDHs are quite different from those of Escherichia coli NADP‐IDH, for which significant conformational changes are observed only between two forms of the apo enzyme, suggesting that the catalytic mechanism of eukaryotic NADP‐IDHs is more complex than that of EcIDH, and involves more fine‐tuned conformational changes.
The structure of “defective in induced resistance” protein of Arabidopsis thaliana, DIR1, reveals a new type of lipid transfer protein
Authors: Lascombe Marie‐Bernard , Bakan Bénédicte , Buhot Nathalie , Marion Didier , Blein Jean‐Pierre , Larue Valéry , Lamb Chris , Prangé Thierry
Published: June 2008

Screening of transfer DNA (tDNA) tagged lines of Arabidopsis thaliana for mutants defective in systemic acquired resistance led to the characterization of dir1‐1 (defective in induced resistance [systemic acquired resistance, SAR]) mutant. It has been suggested that the protein encoded by the dir1 gene, i.e., DIR1, is involved in the long distance signaling associated with SAR. DIR1 displays the cysteine signature of lipid transfer proteins, suggesting that the systemic signal could be lipid molecules. However, previous studies have shown that this signature is not sufficient to define a lipid transfer protein, i.e., a protein capable of binding lipids. In this context, the lipid binding properties and the structure of a DIR1–lipid complex were both determined by fluorescence and X‐ray diffraction. DIR1 is able to bind with high affinity two monoacylated phospholipids (dissociation constant in the nanomolar range), mainly lysophosphatidyl cholines, side‐by‐side in a large internal tunnel. Although DIR1 shares some structural and lipid binding properties with plant LTP2, it displays some specific features that define DIR1 as a new type of plant lipid transfer protein. The signaling function associated with DIR1 may be related to a specific lipid transport that needs to be characterized and to an additional mechanism of recognition by a putative receptor, as the structure displays on the surface the characteristic PxxP structural motif reminiscent of SH3 domain signaling pathways.
The structure of a fibril‐forming sequence, NNQQNY, in the context of a globular fold
Authors: Guo Zhefeng , Eisenberg David
Published: June 2008

Numerous human disorders are associated with the formation of protein fibrils. The fibril‐forming capacity of a protein has been found in recent studies to be determined by a short segment of residues that forms a dual β‐sheet, called a steric zipper, in the spine of the fibril. The question arises as to whether a fibril‐forming segment, when inserted within the sequence of a globular protein, will invariably cause the protein to form fibrils. Here we investigate this question by inserting the known fibril‐forming segment NNQQNY into the globular enzyme, T7 endonuclease I. From earlier studies, we know that in its fibril form, NNQQNY is in an extended conformation. We first found that the inserted NNQQNY stimulates fibril formation of T7 endonuclease I in solution. Thus NNQQNY within T7 endonuclease I can exist in an extended conformation, capable of forming the steric zipper in the core of a fibril. We also found that T7 endonuclease I folds into a decamer that does not form fibrils. We determined the structure of the decamer by X‐ray crystallography, finding an unusual oligomer without point group symmetry, and finding that the NNQQNY segments within the decamer adopt two twisted conformations, neither is apparently able to fibrillize. We conclude that twisting of fibril forming sequences from the fully extended conformation, imposed by the context of their placement in proteins, can interfere with fibril formation.
Association of BLV infection profiles with alleles of the BoLA‐DRB3.2 gene
Authors: Juliarena M. A. , Poli M. , Sala L. , Ceriani C. , Gutierrez S. , Dolcini G. , Rodríguez E. M. , Mariño B. , Rodríguez‐Dubra C. , Esteban E. N.
Published: June 2008

Bovine leukaemia virus (BLV) causes lymphosarcoma and persistent lymphocytosis (PL). Some MHC class II gene polymorphisms have been associated with resistance and susceptibility to the development of lymphosarcoma and PL, as well as with a reduced number of circulating BLV‐infected lymphocytes. Previously, 230 BLV‐infected Holstein cattle were classified into two infection profiles characterized by low and high proviral loads (LPL and HPL respectively). Here, the influence of the polymorphism at the BoLA‐DRB3.2* gene of these animals was examined. After genotyping, the association between the BoLA‐DRB3.2* alleles and the BLV infection profile was determined as the odds ratio (OR). Two subtypes of allele *11 were identified (ISAG*0901 and *0902). Allele ISAG*0902 showed a stronger association with the LPL profile (OR = 8.24; P < 0.0001) than allele *11 itself (OR = 5.82; P < 0.0001). Allele ISAG*1701 (*12) also showed significant association with the LPL profile (OR = 3.46; P < 0.0055). Only one allele, ISAG*1501 or 03 (*16), showed significant association with HPL (OR = 0.36; P < 0.0005). The DRB3.2* alleles were assigned to three categories: resistant (R), susceptible (S) and neutral (N). Based on their DRB3 genotypes, cattle were classified as homozygous or heterozygous. The RR and RN genotypes were associated with the LPL profile, while the SS and NS genotypes were associated with the HPL profile. The RS genotype could not be associated with any particular profile. Our results show that allele ISAG*0902 appears to be the best BLV resistance marker in Holstein cattle.
Development of a sufficient design for estimation of fluconazole pharmacokinetics in people with HIV infection
Authors: Roos Juliana F. , Kirkpatrick Carl M. J. , Tett Susan E. , McLachlan Andrew J. , Duffull Stephen B.
Published: June 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Optimal design is being employed more frequently to help reduce the number of samples taken per patient, the number of patients and number of doses to be given within a study.

• In doing this the economic and patient resources required to conduct a population pharmacokinetic or pharmacokinetic–pharmacodynamic study are reduced.

WHAT THIS STUDY ADDS

• This is the first time that healthy volunteer data (e.g. from Phase I) have been used to develop an optimal design that is to be conducted in a population with different characteristics due to disease (e.g. Phase II).

AIMS To assess an optimal design that is sufficient to gain precise estimates of the pharmacokinetic (PK) parameters for fluconazole in people with HIV infection.

METHODS Two studies were identified, the first in healthy volunteers and the second in HIV patients. The investigators (J.F.R. and S.B.D.) were blinded to the second study results. The healthy volunteer study was modelled and a design was found to estimate the PK parameters. The design was evaluated by comparison of the standard errors of the parameters and the predictive performance of the optimal design. The predictive performance was assessed by comparing model predictions against observed concentrations for two models. The first model, termed ‘sufficient design’, was developed from data extracted from the HIV study that corresponded to the optimal design. The second model, termed ‘HIV outcome model’, by modelling all the data from the HIV study.

RESULTS An optimal design HIV study was developed which had considerably fewer blood samples and dosing arms compared with the actual HIV study. The optimized design performed as well as the actual HIV study in terms of parameter precision. The performance of the design, described as the precision (mg l−1)2 (95% confidence interval) of the predicted concentrations to the actual concentrations for the ‘sufficient design’ and ‘HIV outcome model’ models were: 0.63 (0.40, 0.87) and 0.56 (0.32, 0.79), respectively.

CONCLUSION This study demonstrates how data from healthy volunteers can be utilized via optimal design methodology to design a successful study in the target population.
A limited sampling strategy for tacrolimus in renal transplant patients
Authors: Mathew Binu S. , Fleming Denise H. , Jeyaseelan Visalakshi , Chandy Sujith J. , Annapandian V. M. , Subbanna P. K. , John George T.
Published: June 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Tacrolimus trough concentration is being currently used for dose individualization.

• Limited sampling strategies (LSS) have been developed and validated for renal transplant patients.

• Earlier literature has suggested that measurement of tacrolimus AUC is more reliable than trough with respect to both rejection and nephrotoxicity.

WHAT THIS STUDY ADDS

• Four thousand renal transplants take place annually in India, with many patients prescribed tacrolimus in combination with mycophenolate and steroid.

• In this study a LSS with two points, i.e. trough and 1.5 h postdose was developed and validated to estimate AUC0–12.

• The added benefit of only a single additional sample with completion of blood collection in 1.5 h and minimum additional cost makes this a viable LSS algorithm in renal transplant patients.

• In patients having tacrolimus trough concentrations outside the recommended range (<3 and >10 ng ml−1 in the treatment protocol in our institution) or having side‐effects in spite of trough concentrations in the desired range, we can estimate AUC using this LSS for a better prediction of exposure.

AIMS

To develop and validate limited sampling strategy (LSS) equations to estimate area under the curve (AUC0–12) in renal transplant patients.

METHODS

Twenty‐nine renal transplant patients (3–6 months post transplant) who were at steady state with respect to tacrolimus kinetics were included in this study. The blood samples starting with the predose (trough) and collected at fixed time points for 12 h were analysed by microparticle enzyme immunoassay. Linear regression analysis estimated the correlations of tacrolimus concentrations at different sampling time points with the total measured AUC0–12. By applying multiple stepwise linear regression analysis, LSS equations with acceptable correlation coefficients (R2), bias and precision were identified. The predictive performance of these models was validated by the jackknife technique.

RESULTS

Three models were identified, all with R2 ≥ 0.907. Two point models included one with trough (C0) and 1.5 h postdose (C1.5), another with trough and 4 h postdose. Increasing the number of sampling time points to more than two increased R2 marginally (0.951 to 0.990). After jackknife validation, the two sampling time point (trough and 1.5 h postdose) model accurately predicted AUC0–12. Regression coefficient R2 = 0.951, intraclass correlation = 0.976, bias [95% confidence interval (CI)] 0.53% (−2.63, 3.69) and precision (95% CI) 6.35% (4.36, 8.35).

CONCLUSION

The two‐point LSS equation [AUC0–12 = 19.16 + (6.75.C0) + (3.33.C1.5)] can be used as a predictable and accurate measure of AUC0–12 in stable renal transplant patients prescribed prednisolone and mycophenolate.
Pathogenic ATM mutations occur rarely in a subset of multiple myeloma patients
Authors: Austen Belinda , Barone Giancarlo , Reiman Anne , Byrd Philip J. , Baker Claire , Starczynski Jane , Nobbs Michael C. , Murphy Raymond P. , Enright Helen , Chaila Elijah , Quinn John , Stankovic Tatjana , Pratt Guy , Taylor A. Malcolm R.
Published: June 2008

Ataxia Telangiectasia (A‐T) patients have biallelic inactivation of the ATM gene and exhibit a 200‐fold‐increased frequency of lymphoid tumours. ATM mutations have been found in a number of adult lymphoid malignancies but there is no data on the occurrence of ATM mutations in multiple myeloma tumours. The purpose of our work was to investigate the occurrence of ATM mutations in multiple myeloma and to this end we screened 45 sporadic cases for ATM mutations using denaturing high‐performance liquid chromatography analysis and DNA sequencing. Pathogenic ATM mutations were identified in 2/45 of the myelomas compared with a published estimate of ATM mutant allele frequency in the UK population of 2/521 (P = 0·033). One was the missense mutation 7181C>T which was then modelled in an expression system and the S2394L protein shown to have no ATM kinase activity. The second myeloma had the pathogenic ATM splice site mutation IVS40‐1G>C leading to loss of exon 41. We also report a 48‐year‐old ataxia telangiectasia patient who developed multiple myeloma. Taken together our study suggests that ATM mutation may play a role in the pathogenesis of a subset of multiple myelomas.
The small glycine‐rich RNA binding protein AtGRP7 promotes floral transition in Arabidopsis thaliana
Authors: Streitner Corinna , Danisman Selahattin , Wehrle Franziska , Schöning Jan C. , Alfano James R. , Staiger Dorothee
Published: June 2008

The RNA binding protein AtGRP7 is part of a circadian slave oscillator in Arabidopsis thaliana that negatively autoregulates its own mRNA, and affects the levels of other transcripts. Here, we identify a novel role for AtGRP7 as a flowering‐time gene. An atgrp7‐1 T‐DNA mutant flowers later than wild‐type plants under both long and short days, and independent RNA interference lines with reduced levels of AtGRP7, and the closely related AtGRP8 protein, are also late flowering, particularly in short photoperiods. Consistent with the retention of a photoperiodic response, the transcript encoding the key photoperiodic regulator CONSTANS oscillates with a similar pattern in atgrp7‐1 and wild‐type plants. In both the RNAi lines and in the atgrp7‐1 mutant transcript levels for the floral repressor FLC are elevated. Conversely, in transgenic plants ectopically overexpressing AtGRP7, the transition to flowering is accelerated mainly in short days, with a concomitant reduction in FLC abundance. The late‐flowering phenotype of the RNAi lines is suppressed by introducing the flc‐3 loss‐of‐function mutation, suggesting that AtGRP7 promotes floral transition, at least partly by downregulating FLC. Furthermore, vernalization overrides the late‐flowering phenotype. Retention of both the photoperiodic response and vernalization response are features of autonomous pathway mutants, suggesting that AtGRP7 is a novel member of the autonomous pathway.
Cutaneous rhinosporidiosis presents with recurrent nasal philtrum mass in southern Turkey
Authors: Ağırdır Bülent V. , Derin Alper T. , Özbilim Gülay , Akman Ayse
Published: June 2008

We report a case of cutaneous rhinosporidiosis localized in the nasal philtrum. The patient's complaints started 3 months prior to being seen in our clinics. Ear, nose, and throat examination showed the presence of a polypoid lesion filling the right nostril. Complete surgical resection of the polypoid lesion provided a temporary relief as the patient developed the same lesion atin 6 weeks post‐operation. The appearance and the recurrence pattern have led us to determine whether this lesion was rhinosporidiosis. Histopathological examination confirmed rhinosporidiosis. Finally, we performed complete resection followed by cauterization of the base of the mass. The infection has been reported in hot, tropical climates, and endemic zones of India and Sri Lanka. To our knowledge there is no reported case of rhinosporidiosis from southern Turkey within the subtropical Mediterranean climatic area.
Body mass index is a stronger predictor of alanine aminotransaminase levels than alcohol consumption
Authors: Adams Leon A , Knuiman Matthew W , Divitini Mark L , Olynyk John K
Published: June 2008

Background and Aims:  The relative effects of obesity compared to alcohol on liver injury are uncertain. We examined their effects on alanine aminotransferase (ALT) and gamma glutamyltransferase (GGT) levels in a population‐based cohort.

Methods:  Adult residents (2610: 1326 males, 1284 females) from Busselton, Australia, participated in a cross‐sectional survey determining alcohol intake as determined by a validated questionnaire, anthropometric measurements and serum analysis. Alcohol consumption was classified as never, light (<140 g/week), moderate (140–420 g/week) or heavy (>420 g/week).

Results:  The majority of subjects were either overweight (41%) or obese (17%). A minority of subjects were moderate (25%) or heavy drinkers (4%). Body mass index (BMI) and waist circumference were strongly associated with ALT and GGT (P < 0.0001 for all tests). Alcohol consumption was modestly associated with ALT in females (P = 0.01) but not in males (P = 0.9). In contrast, GGT was significantly associated with alcohol in both genders (P < 0.0005). The risk of an elevated ALT was seven‐fold higher with obesity but only two‐fold higher with moderate or heavy alcohol use. Obesity accounted for half of all elevated ALT levels in the cohort, whereas alcohol excess was responsible for less than 10%. No synergistic effect was observed between BMI or waist circumference and alcohol on ALT or GGT (P > 0.2 for all tests).

Conclusions:  Excess weight is more common than excessive alcohol consumption in the community and confers a greater risk of elevated aminotransaminase levels.
Liver disease and the renin–angiotensin system: Recent discoveries and clinical implications
Authors: Lubel John S , Herath Chandana B , Burrell Louise M , Angus Peter W
Published: June 2008

The renin–angiotensin system (RAS) is a key regulator of vascular resistance, sodium and water homeostasis and the response to tissue injury. Historically, angiotensin II (Ang II) was thought to be the primary effector peptide of this system. Ang II is produced predominantly by the effect of angiotensin converting enzyme (ACE) on angiotensin I (Ang I). Ang II acts mainly through the angiotensin II type‐1 receptor (AT1) and, together with ACE, these components represent the ‘classical’ axis of the RAS. Drug therapies targeting the RAS by inhibiting Ang II formation (ACE inhibitors) or binding to its receptor (angiotensin receptor blockers) are now in widespread clinical use and have been shown to reduce tissue injury and fibrosis in cardiac and renal disease independently of their effects on blood pressure. In 2000, two groups using different methodologies identified a homolog of ACE, called ACE2, which cleaves Ang II to form the biologically active heptapeptide, Ang‐(1–7). Conceptually, ACE2, Ang‐(1–7), and its putative receptor, themasreceptor represent an ‘alternative’ axis of the RAS capable of opposing the often deleterious actions of Ang II. Interestingly, ACE inhibitors and angiotensin receptor blockers increase Ang‐(1–7) production and it has been proposed that some of the beneficial effects of these drugs are mediated through upregulation of Ang‐(1–7) rather than inhibition of Ang II production or receptor binding. The present review focuses on the novel components and pathways of the RAS with particular reference to their potential contribution towards the pathophysiology of liver disease.
Chromoscopic endomicroscopy: In vivo cellular resolution imaging of the colorectum
Authors: Smith Lesley‐Ann , Tiffin Nick , Thomson Mike , Cross Simon S , Hurlstone David P
Published: June 2008

Advances in imaging technology and engineering have now permitted functional integration of a confocal endomicroscope into the distal tip of a conventional video colonoscope enabling imaging of the surface epithelium and the underlying lamina propria during ongoing video endoscopy. For the first time, the endoscopist is now able to resolve the surface and subsurface mucosa at cellular resolution in vivo and in real time. A new era in endoscopic imaging has therefore begun – histoendoscopy. In addition to providing a high‐accuracy in vivo optical biopsy tool for the differentiation between benign hyperplasia, intra‐epithelial neoplasia and carcinoma in sporadic cohorts, endomicroscopy with targeted biopsies has now been shown to increase the yield of intra‐epithelial neoplasia complicating ulcerative colitis. Furthermore, recent data examining endomicroscopic molecular ex vivo imaging using anti‐CD44v6 antibody has identified aberrant crypt foci based on their surface molecular expression. Receptor overexpression in vivo in humans may, in the near future, be exploited for the diagnosis of inflammation, neoplasia and in predicting targeted molecular therapy. Endomicroscopy will be key to this immuno‐imaging interface. Within the present review, we discuss the current clinical evidence in support of confocal endomicroscopy and explore the new diagnostic possibilities for this technology.
V4 Total laparoscopic restorative proctocolectomy for ulcerative colitis
Authors: Sagar P. M. , Gonsalves S. J. , Brayshaw I. , Williams G.
Published: June 2008

Introduction:  Laparoscopic ileal pouch‐anal anastomosis (IPAA) has been shown to be a safe and feasible technique for patients with ulcerative colitis refractory to medical management and familial polyposis. We aim to demonstrate our technique of total laparoscopic proctocolectomy with intracorporeal pouch‐anal anastomosis with specific reference to intaroperative tricks of the trade.

Patient and Methods:  The patient is a 16‐year‐old male with ulcerative colitis. The video demonstrates a total laparoscopic proctocolectomy and formation of a (J) ileal pouch anal anastomosis. A standard colonic mobilisation of the colon was performed with the use of the Goldfinger retractor to aid vessel division and the use of the harmonic scalpel for mesenteric division apart from the transverse mesocolon where the ligasure was employed. The right colon was only mobilised after complete mesenteric division of the left & transverse colon to prevent looping. The rectum, once mobilised to the pelvic floor, was divided in the AP direction with the endoGIA. Techniques to prevent twisting of the pouch and inadvertent twisting of the proximal small bowel are demonstrated. The video also highlights the importance of positioning the patient and use of 0 and 30 degree scopes. A technique to tackle a defect in the anal stump is also described.

Conclusion:  The technique of laparoscopic IPAA adheres to the principles of open pouch surgery but we await the development of more suitable laparoscopic staplers to aid the clinician in division of the anorectal junction.
V6 The feasibility of laparoscopic rectal resection for cancer
Authors: Khan J. , Qureshi T. , Parvaiz A.
Published: June 2008

Introduction:  Total mesorectal excision (TME) has offered the lowest recurrence rates and best survival in rectal cancer patients. Recently several multi‐centre trials have demonstrated the feasibility of laparoscopic colonic resections for cancer. However the technical difficulties and lack of supporting data has prevented surgeons from attempting laparoscopic TME for operable rectal cancer. We present a video demonstration of lap TME technique performed at our unit for rectal cancer resections.

Methods:  The surgical technique involves using two 10 mm and two 5 mm ports to perform rectal resections. Adherence to advanced oncological principles like high tie of IMA and IMV is the rule. Splenic flexure is routinely mobilised for mid to low rectal cancers. Total mesorectal excision is performed using diathermy hook. Rectal washout is performed before transection of the rectum using lap stapler device.

Results:  Between October 2006–December 2007, 30 rectal cancers have been operated laparoscopically at our institution using this technique. There were four APER and 26 anterior resections. The median age was 72 years with a median BMI of 25. Median operative time was 235 min with a median hospital stay of 7 days. There were no leaks.

Conclusions:  With proper training and experience, laparoscopic rectal cancer resection is technically feasible and safe to perform with good oncological outcomes.
EXTRA‐FIRM NETWORKS AND KOREAN INVESTMENT IN THE UNITED STATES
Authors: GRESS DOUGLAS R. , POON JESSIE
Published: June 2008

This paper focuses on Korean firms’ relationships with extra‐firm institutional actors through an investigation of their international investment in the United States. The study draws from two surveys that were conducted in 2004. The first survey was conducted on US State Offices of Trade and Investment (SOTI) in Seoul, and the second survey on Korean subsidiaries that are located in the United States. The results indicate that extra‐firm relationships are perceived to be much more important by US SOTIs. Several offices correlate the presence of Korean investment in their home states to the offices’ activities with Korean parent companies in Seoul arising from synergies created with other Korean institutional actors. Korean subsidiaries in the United States do not evaluate competition between places to be as important in their locational decision; however, regular intra‐firm discussions of country‐specific policies are found to correlate with perceived firm‐level benefits from locational choices. The results further suggest a shift in traditional control of extra‐firm interactions from the headquarters in Seoul to the subsidiary in the United States.
Regulation of neural progenitor cell development in the nervous system
Authors: Corbin Joshua G. , Gaiano Nicholas , Juliano Sharon L. , Poluch Sylvie , Stancik Elizabeth , Haydar Tarik F.
Published: June 2008

The mammalian telencephalon, which comprises the cerebral cortex, olfactory bulb, hippocampus, basal ganglia, and amygdala, is the most complex and intricate region of the CNS. It is the seat of all higher brain functions including the storage and retrieval of memories, the integration and processing of sensory and motor information, and the regulation of emotion and drive states. In higher mammals such as humans, the telencephalon also governs our creative impulses, ability to make rational decisions, and plan for the future. Despite its massive complexity, exciting work from a number of groups has begun to unravel the developmental mechanisms for the generation of the diverse neural cell types that form the circuitry of the mature telencephalon. Here, we review our current understanding of four aspects of neural development. We first begin by providing a general overview of the broad developmental mechanisms underlying the generation of neuronal and glial cell diversity in the telencephalon during embryonic development. We then focus on development of the cerebral cortex, the most complex and evolved region of the brain. We review the current state of understanding of progenitor cell diversity within the cortical ventricular zone and then describe how lateral signaling via the Notch‐Delta pathway generates specific aspects of neural cell diversity in cortical progenitor pools. Finally, we review the signaling mechanisms required for development, and response to injury, of a specialized group of cortical stem cells, the radial glia, which act both as precursors and as migratory scaffolds for newly generated neurons.