bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lack of Indinavir Effects on Methadone Disposition Despite Inhibition of Hepatic and Intestinal Cytochrome P4503A (CYP3A)
Authors: Kharasch Evan D. , Bedynek Pamela Sheffels , Hoffer Christine , Walker Alysa , Whittington Dale 
Published: January 2012

Background
Methadone disposition and pharmacodynamics are highly susceptible to interactions with antiretroviral drugs. Methadone clearance and drug interactions have been attributed to cytochrome P4503A4 (CYP3A4), but actual mechanisms are unknown. Drug interactions can be clinically and mechanistically informative. This investigation assessed effects of the protease inhibitor indinavir on methadone pharmacokinetics and pharmacodynamics, hepatic and intestinal CYP3A4/5 activity (using alfentanil), and intestinal transporter activity (using fexofenadine).

Methods
Twelve healthy volunteers underwent a sequential crossover. On three consecutive days they received oral alfentanil plus fexofenadine, intravenous alfentanil, and intravenous plus oral (deuterium-labeled) methadone. This was repeated after 2 weeks of indinavir. Plasma and urine analytes were measured by mass spectrometry. Opioid effects were measured by miosis.

Results
Indinavir significantly inhibited hepatic and first-pass CYP3A activity. Intravenous alfentanil systemic clearance and hepatic extraction were reduced to 40-50% of control, apparent oral clearance to 30% of control, and intestinal extraction decreased by half, indicating 50% and 70% inhibition of hepatic and first-pass CYP3A activity. Indinavir increased fexofenadine area under the plasma concentration-time curve 3-fold, suggesting significant P-glycoprotein inhibition. Indinavir had no significant effects on methadone plasma concentrations, methadone N-demethylation, systemic or apparent oral clearance, renal clearance, hepatic extraction or clearance, or bioavailability. Methadone plasma concentration-effect relationships were unaffected by indinavir.

Conclusions
Despite significant inhibition of hepatic and intestinal CYP3A activity, indinavir had no effect on methadone N-demethylation and clearance, suggesting little or no role for CYP3A in clinical disposition of single-dose methadone. Inhibition of gastrointestinal transporter activity had no influence of methadone bioavailability.
Impaired Nociception and Peripheral Opioid Antinociception in Mice Lacking Both Kinin B1 and B2 Receptors
Authors: Cayla Cecile , Labuz Dominika , Machelska Halina , Bader Michael , Schäfer Michael , Stein Christoph 
Published: January 2012

Background
Kinins (e.g., bradykinin) acting through the constitutively expressed B2 and the injury-induced B1 receptors are involved in pain and hyperalgesia, as previously shown by use of receptor-selective antagonists and single-receptor knockout models. Because the overall contribution of kinins to painful processes remains unclear, the aim of this study was to analyze pain-related behaviors of mice unable to respond to kinins because of a lack of both B1 and B2 receptors.

Methods
In knockout mice lacking both B1 and B2 receptors and in wild-type mice (n = 8-21 per group) the authors assessed nociceptive thresholds to mechanical and heat stimuli (von Frey and Hargreaves tests, respectively) in healthy animals and after induction of inflammatory and neuropathic pain, acid-induced visceral nociception, and modulation of nociceptive responses by peripherally administered opioid agonists.

Results
In knockout mice lacking both B1 and B2 receptors baseline nociceptive responses to heat were unaltered, nocifensive responses to bradykinin were abolished, acute acetic acid-induced visceral nociception was reduced by approximately 70% (mean difference: 19.5 writhes/30 min) and heat hypersensitivity in carrageenan-induced paw inflammation was decreased 48 h after injection (mean difference 2.88 s), hypersensitivities in chronic complete Freund's adjuvant-induced paw inflammation or after chronic constriction injury of the sciatic nerve were unchanged, and peripheral μ- and δ-opioid-induced analgesia after chronic constriction injury was reduced by 30-35% (mean differences: μ-agonist: 0.495 g, δ-agonist: 0.555 g).

Conclusions
These data suggest that kinins are important for nociception associated with acute short-lasting inflammation but are less essential in chronic stages of pain. The results also highlight a new protective function of kinins via interactions with the opioid system.
Arabidopsis ETR1 and ERS1 Differentially Repress the Ethylene Response in Combination with Other Ethylene Receptor Genes
Authors: Liu Qian , Wen Chi-Kuang 
Published: January 2012

Abstract
The ethylene response is negatively regulated by a family of five ethylene receptor genes in Arabidopsis (Arabidopsis thaliana). The five members of the ethylene receptor family can physically interact and form complexes, which implies that cooperativity for signaling may exist among the receptors. The ethylene receptor gene mutations etr1-1 ( C65Y )(for ethylene response1-1), ers1-1 ( I62P ) (for ethylene response sensor1-1), and ers1C65Y are dominant, and each confers ethylene insensitivity. In this study, the repression of the ethylene response by these dominant mutant receptor genes was examined in receptor-defective mutants to investigate the functional significance of receptor cooperativity in ethylene signaling. We showed that etr1-1 ( C65Y ), but not ers1-1 ( I62P ), substantially repressed various ethylene responses independent of other receptor genes. In contrast, wild-type receptor genes differentially supported the repression of ethylene responses by ers1-1 ( I62P ); ETR1 and ETHYLENE INSENSITIVE4 (EIN4) supported ers1-1 ( I62P ) functions to a greater extent than did ERS2, ETR2, and ERS1. The lack of both ETR1 and EIN4 almost abolished the repression of ethylene responses by ers1C65Y, which implied that ETR1 and EIN4 have synergistic effects on ers1C65Y functions. Our data indicated that a dominant ethylene-insensitive receptor differentially repressed ethylene responses when coupled with a wild-type ethylene receptor, which supported the hypothesis that the formation of a variety of receptor complexes may facilitate differential receptor signal output, by which ethylene responses can be repressed to different extents. We hypothesize that plants can respond to a broad ethylene concentration range and exhibit tissue-specific ethylene responsiveness with differential cooperation of the multiple ethylene receptors.
Pericentromeric Effects Shape the Patterns of Divergence, Retention, and Expression of Duplicated Genes in the Paleopolyploid Soybean
Authors: Du Jianchang , Tian Zhixi , Sui Yi , Zhao Meixia , Song Qijian , Cannon Steven B. , Cregan Perry , Ma Jianxin 
Published: January 2012

AbstractThe evolutionary forces that govern the divergence and retention of duplicated genes in polyploids are poorly understood. In this study, we first investigated the rates of nonsynonymous substitution (Ka) and the rates of synonymous substitution (Ks) for a nearly complete set of genes in the paleopolyploid soybean (Glycine max) by comparing the orthologs between soybean and its progenitor species Glycine soja and then compared the patterns of gene divergence and expression between pericentromeric regions and chromosomal arms in different gene categories. Our results reveal strong associations between duplication status and Ka and gene expression levels and overall low Ks and low levels of gene expression in pericentromeric regions. It is theorized that deleterious mutations can easily accumulate in recombination-suppressed regions, because of Hill-Robertson effects. Intriguingly, the genes in pericentromeric regions—the cold spots for meiotic recombination in soybean—showed significantly lower Ka and higher levels of expression than their homoeologs in chromosomal arms. This asymmetric evolution of two members of individual whole genome duplication (WGD)-derived gene pairs, echoing the biased accumulation of singletons in pericentromeric regions, suggests that distinct genomic features between the two distinct chromatin types are important determinants shaping the patterns of divergence and retention of WGD-derived genes.
Valproate in acute mania: is our practice evidence based?
Authors: Vasudev Kamini , Mead Anna , Macritchie Karine , Young Allan H. 
Published: January 2012

PurposeThis audit was conducted on acute psychiatric in‐patient wards with the aim of establishing if valproate prescribing in acute mania followed evidence‐based guidelines with particular emphasis on formulations used and whether accelerated valproate dosing was employed.Design/methodology/approachCase notes from 43 (42 percent male) patients admitted with mania and subsequently discharged on valproate were reviewed. Valproate formulation, weight measurement (necessary for dose‐calculation in accelerated dosing), initial valproate dose and increments, serum valproate monitoring and other prescribed psychotropic agents were noted.FindingsMost (95 percent) patients received sodium valproate (epilim chrono/generic), the remaining received valproate semi‐sodium (depakote). All but one patient received antipsychotic medication in combination. Weight was recorded in only four (9 percent) patients. The mean valproate daily dose after the first week was 1,027 mg (sd=408). It took 29 (sd=42) days to reach the maximum daily dose (1,426 mg sd=467) from valproate initiation. Serum levels were monitored in 34 (79 percent) cases, but the mean period between valproate initiation to the first serum level test was 38 (sd=47) days. A significant positive correlation was found between days taken to reach maximum dose and hospital stay (Spearman's rho=0.41, n=43, p=0.006, two‐tailed).Practical implicationsAccelerated valproate dosing was not common practice, which may have resulted in suboptimal efficacy, probably leading to combination treatment.Originality/valueThis study highlights the need for adequate initial dosing and dose increments when treating manic patients and suggests current practice is not evidence‐based. Local prescribing policy and national guidelines' influence on practice are discussed.
The two‐week rule for suspected colorectal cancer
Authors: Ndukwe Nenna , Borowski David W. , Lee Angela , Orr Anne , Dexter‐Smith Sarah , Agarwal Anil K. 
Published: January 2012

PurposeThere has been considerable interest in the “two‐week rule” referral pathway efficacy for patients with suspected colorectal cancer. This study aims to explore the psychological impact on these patients.Design/methodology/approachConsecutive patients referred for urgent investigations under the “two‐week rule” were invited to take part in semi‐structured interviews using interpretative phenomenological analysis (IPA). Interviews were audio‐taped, transcribed verbatim and analysed using investigator triangulation to enhance data trustworthiness.FindingsTen out of 23 (43.5 per cent) patients consented to interviews; none were diagnosed with cancer. Four super‐ordinate themes were explored, referring to the “making sense of the threat to health”, impact on self, impact on others, reflections on the “two‐week rule” referral, and its investigative process. Participants reported their anxiety, fear, vulnerability and coping mechanisms, but also raised concerns about the communication received during the “two‐week rule” referral process. Female participants preferred a female endoscopist.Originality/valueThis study is the first of its kind exploring the psychological effects of the “two‐week rule” process for colorectal cancer, highlighting potential areas for improvement in patient information, and satisfaction with the referral process.
The effect of bidding success in construction bidding
Authors: Lan Oo Bee , Lo Hing‐Po , Teck‐Heng Lim Benson 
Published: January 2012

PurposeWinning a bid will carry implications for capacity level of a construction firm. This paper aims to examine the impact of a winning bid on contractors' bid pricing strategies.Design/methodology/approachIn identifying the specific types of bidding trends before and after a winning bid, the variations in bids are expressed as a function of time relative to winning bid – the “event” of interest in this study – using a piecewise mixed effects model. The bids analysed comprised series of bids with a winning bid in between, recorded from Hong Kong building contractors.FindingsThe results show that there is a relationship between bid price and bidding success. The bidders in general bid low for time periods before a winning bid and they are less competitive in time periods after a winning bid. However, by considering the individual bidders' characteristics that relate to differences in bidding competitiveness, it is shown that there is remarkable heterogeneity among the bidders in bid pricing decision for pre‐ and post‐winning periods. Nevertheless, the statistically significant bidding trends before and after a winning bid strengthen the notion that systematic changes in bidding behaviour over time do occur in reality in response to changes in firm capacity level.Originality/valueThis empirical investigation provides strong evidence on the systematic changes in bidding behaviour over time in response to changes in firm capacity level, supporting the need to incorporate firm capacity level in the future development of a suitable theoretical framework on construction bidding.
Capacity building of construction industries in Sub‐Saharan developing countries
Authors: Kululanga Grant 
Published: January 2012

PurposeThe need for capacity building of construction industries in developing countries cannot be over‐emphasised in order to ensure quality of services and products as well as the application of innovative ways for delivering construction services. Accordingly, using systems institutional paradigm approach as a conceptual premise, this paper aims to make the case for a fundamental turnaround for construction developmental approach in developing countries, that identify levels which should be considered as instrumental for capacity building of the construction industry in the Sub‐Saharan region, for example Malawi.Design/methodology/approachTo ascertain a quad‐level framework which should be considered essential for capacity building of the construction industry, a questionnaire survey was employed. Data were elicited from prominent heads of sections from five stakeholders of the construction industry that operated in Malawi on the constructs for capacity building of a construction industry. Sixty completed questionnaires were received with a response rate of 90 per cent to the designed sample size.FindingsThe quad‐level framework for capacity development of a construction industry for developing countries was validated by an overall level of 77 per cent of agreement from key and prominent heads of sections of the five stakeholders of the construction industry. The rankings of the variables for capacity building for each level of the framework have provided the key foci and orientations of the industry for one of the Southern African countries of the Sub‐Saharan region.Research limitations/implicationsThe study forms the basis for further research; future research could be directed towards other developing countries to further enrich the industry on the dynamics of capacity building of construction industries in developing countries.Originality/valueThis paper is the first to critically examine the antecedents and invoke a quad‐level framework for capacity development of construction industries.
Human resource practices of contractors that lead to job satisfaction of professional staff
Authors: Lim Lewis J.W. , Ling Florence Y.Y. 
Published: January 2012

PurposeThe aim of this research is to investigate the effect of contractors' human resource (HR) practices on job satisfaction of their professional staff. The specific objectives are to: determine the effectiveness of contractors' HR practices; find out the level of job satisfaction that professional staff who work for contractors have; and study the relationship between HR practices and job satisfaction.Design/methodology/approachThe research method was based on survey and a structured questionnaire, which was specially designed for the study, was the data collection instrument. Data were collected via e‐mail surveys and face to face interviews. The sampling frame comprised randomly chosen professionals who work for building contractors in Singapore.FindingsResults showed that contractors' professionals are significantly satisfied with many of their firms' HR practices. The study found that these professionals have significant job satisfaction in terms of career opportunities, nature of their jobs and overall working environment. The results also show that many of the HR practices are significantly correlated with job satisfaction.Research limitations/implicationsThe main limitation of the research is the relatively small sample size and low response rate. In addition, respondents' indication of their satisfaction level is contextualized to professional staff working in Singapore in a specific market condition, thereby limiting generalization of the results. The implication is that the findings would be more relevant to construction firms in Singapore at the time when the industry is just emerging from a recession.Practical implicationsIt is recommended that contractors make an effort to understand what their professional staff want in HRM so as to efficiently channel their resources to create job satisfaction through appropriate HR practices. The study uncovered HR practices that employees are unsatisfied with. These include dissatisfaction with quantum of rewards, and firms' methods of dealing with employees' feedback and resolving conflicts. The practical implication of the findings is that contractors should improve on these practices so that their employees would not be more dissatisfied.Originality/valueThe originality of the study is that some HR practices that lead to job satisfaction of construction companies' professionals have been uncovered. The results could inform construction firms on what HR practices they may adopt to engender higher job satisfaction among their professional employees.
Grand theories as barriers to using IC concepts
Authors: Dumay John C. 
Published: January 2012

PurposeThe purpose of this paper is to answer the question “What are the barriers to the use of IC concepts?” by discussing and critiquing two contemporary grand theories about IC, being market‐to‐book ratios as a representation of IC and that disclosing IC leads to greater profitability.Design/methodology/approachThe paper reviews contemporary IC literature and explores reasons why these grand theories of IC hinder its adoption.FindingsThe research finds that these grand theories mislead because they cannot be proven empirically. Therefore, managers should attempt to better understand the possible causal relationships between their people, processes and stakeholders (human, structural and relational capital) rather than adopting someone else's mousetrap.Practical implicationsIn order to improve the use of IC concepts they should be examined as differentiation theories of practice that take into account the agent (people) as a unit of analysis, the actual practice of IC and the resultant changes within an organisation, rather than trying to achieve the impossible generalisations of IC grand theories. Researchers need to conduct more critical and performative research into IC rather than ostensive research.Originality/valueAllows academics and practitioners to understand the barriers to implementing IC in organisations, potentially allowing for the development of better engineered IC practices rather than the development of additional IC models.
Linking knowledge processes with firm performance: organizational culture
Authors: Nold Herbert A. 
Published: January 2012

PurposeThe purpose of this paper is to report the results of a matched sample comparison group study of elements of organizational culture that enable knowledge processes to drive superior firm performance.Design/methodology/approachA matched sample comparison group approach was used to compare firm performance among matched pairs of public companies. Companies demonstrating high levels of trust (benchmark group) were matched with firms of similar size in the same industries demonstrating lower levels of trust (control group).FindingsThe benchmark group generated significantly superior value, operating performance, and had higher average annual growth rates than matching firms in the control group. Firms with higher relative levels of trust embedded in the organizational culture are more likely to outperform similar firms with lower levels of trust.Research limitations/implicationsThe findings are based on surveys and financial performance of companies with securities traded on stock exchanges in the USA and may not represent other organizational forms, other geographic, economic, or cultural environments.Practical implicationsThis study begins to identify a link between knowledge management, organizational learning, and knowledge creation (collectively knowledge processes) with firm performance.Social implicationsIdentifying elements of organizational culture that link knowledge processes with firm performance is essential to developing a leadership model that reinforces enabling cultural attributes.Originality/valueMany researchers have identified a lack of empirical research linking knowledge processes with firm performance. This study begins to fill the research gap with evidence that elements of organizational culture, specifically trust, enable firms to convert knowledge and learning initiatives into tangible performance recognized by financial markets.
Intellectual capital disclosure commitment: myth or reality?
Authors: Branswijck Deborah , Everaert Patricia 
Published: January 2012

PurposeThe purpose of this paper is to compare intellectual capital disclosure in the prospectus of an initial public offering (IPO) with the intellectual capital disclosure in the subsequent annual report. The first objective was to investigate whether companies make a commitment toward intellectual capital disclosure. The second objective was to investigate whether companies report more on intellectual capital in the prospectus.Design/methodology/approachThis study investigated the prospectus and annual report using a sample of 55 firms that applied for an initial listing in Belgium and The Netherlands from 2005‐2009. A coding framework of 86 items was used to perform the content analysis.FindingsThe existence of intellectual capital disclosure commitment was confirmed. Moreover, the results demonstrated that companies report more extensively on intellectual capital in their prospectus in comparison to their annual reports.Originality/valueThis paper documents the first study to provide empirical evidence on the existence of intellectual capital disclosure commitment. Therefore, it offers a new path for future intellectual capital disclosure research.