Liver Enzyme Abnormalities and Associated Risk Factors in HIV Patients on Efavirenz-Based HAART with or without Tuberculosis Co-Infection in Tanzania.

To investigate the timing, incidence, clinical presentation, pharmacokinetics and pharmacogenetic predictors for antiretroviral and anti-tuberculosis drug induced liver injury (DILI) in HIV patients with or without TB co-infection. A total of 473 treatment naïve HIV patients (253 HIV only and 220 with HIV-TB co-infection) were enrolled prospectively. Plasma efavirenz concentration and CYP2B6*6, CYP3A5*3, *6 and *7, ABCB1 3435C/T and SLCO1B1 genotypes were determined. Demographic, clinical and laboratory data were collected at baseline and up to 48 weeks of antiretroviral therapy. DILI case definition was according to Council for International Organizations of Medical Sciences (CIOMS). Incidence of DILI and identification of predictors was evaluated using Cox Proportional Hazards Model. The overall incidence of DILI was 7.8% (8.3 per 1000 person-week), being non-significantly higher among patients receiving concomitant anti-TB and HAART (10.0%, 10.7 per 1000 person-week) than those receiving HAART alone (5.9%, 6.3 per 1000 person-week). Frequency of CYP2B6*6 allele (p = 0.03) and CYP2B6*6/*6 genotype (p = 0.06) was significantly higher in patients with DILI than those without. Multivariate cox regression model indicated that CYP2B6*6/*6 genotype and anti-HCV IgG antibody positive as significant predictors of DILI. Median time to DILI was 2 weeks after HAART initiation and no DILI onset was observed after 12 weeks. No severe DILI was seen and the gain in CD4 was similar in patients with or without DILI. Antiretroviral and anti-tuberculosis DILI does occur in our setting, presenting early following HAART initiation. DILI seen is mild, transient and may not require treatment interruption. There is good tolerance to HAART and anti-TB with similar immunological outcomes. Genetic make-up mainly CYP2B6 genotype influences the development of efavirenz based HAART liver injury in Tanzanians

Proposing new variables for the identification of strategic groups in franchising

The identification of strategic groups in the Spanish franchising area is the main aim of this study. The authors have added some new strategic variables (not used before) to the study and have classified franchisors between sectors and distribution strategy. The results reveal the existence of four perfectly differentiated strategic groups (types of franchisors). One of the major implications of this study is that the variables that build a strategic group vary depending on the respective sector the network operates in and its distribution strategy. This fact indicates that including sector and distribution strategy is absolutely necessary to achieve good classifications of franchisor type

Giving risk management culture a role in strategic planning

WOS: 000413939000023Strategically planned and implemented risk management paves the way for competitive advantage and a decisive edge for global financial institutions. The importance of risk management becomes more evident in financial instability periods. The failure of global financial institutions in the recent financial crisis revealed that firms with strong risk management and culture were more prepared and economically less damaged. As financial institutions have been criticized severely about risk management practices, it also becomes clear that most financial institutions have difficulties in developing a risk management culture. To have a clear understanding of risk management culture, the chapter aims to highlight a need to extend our understanding of risk management culture and how it can find a voice in the strategic planning of global financial institutions

The state of HRM in the Middle East:Challenges and future research agenda

Based on a robust structured literature analysis, this paper highlights the key developments in the field of human resource management (HRM) in the Middle East. Utilizing the institutional perspective, the analysis contributes to the literature on HRM in the Middle East by focusing on four key themes. First, it highlights the topical need to analyze the context-specific nature of HRM in the region. Second, via the adoption of a systematic review, it highlights state of development in HRM in the research analysis set-up. Third, the analysis also helps to reveal the challenges facing the HRM function in the Middle East. Fourth, it presents an agenda for future research in the form of research directions. While doing the above, it revisits the notions of “universalistic” and “best practice” HRM (convergence) versus “best-fit” or context distinctive (divergence) and also alternate models/diffusion of HRM (crossvergence) in the Middle Eastern context. The analysis, based on the framework of cross-national HRM comparisons, helps to make both theoretical and practical implications

Prospect theory, mitigation and adaptation to climate change

Climate change is one of the most pressing challenges in current environmental policy. Appropriate policies intended to stimulate efficient adaptation and mitigation should not exclusively rely on the assumption of the homo oeconomicus, but take advantage of well-researched alternative behavioural patterns. Prospect theory provides a number of climate-relevant insights, such as the notion that evaluations of outcomes are reference dependent, and the relevance of perceived certainty of outcomes. This paper systematically reviews what prospect theory can offer to analyse mitigation and adaptation. It is shown that accounting for reference dependence and certainty effects contributes to a better understanding of some well-known puzzles in the climate debate, including (but not limited to) the different uptake of mitigation and adaptation amongst individuals and nations, the role of technical vs. financial adaptation, and the apparent preference for hard protection measures in coastal adaptation. Finally, concrete possibilities for empirical research on these effects are proposed

Harvesting Candidate Genes Responsible for Serious Adverse Drug Reactions from a Chemical-Protein Interactome

Identifying genetic factors responsible for serious adverse drug reaction (SADR) is of critical importance to personalized medicine. However, genome-wide association studies are hampered due to the lack of case-control samples, and the selection of candidate genes is limited by the lack of understanding of the underlying mechanisms of SADRs. We hypothesize that drugs causing the same type of SADR might share a common mechanism by targeting unexpectedly the same SADR-mediating protein. Hence we propose an approach of identifying the common SADR-targets through constructing and mining an in silico chemical-protein interactome (CPI), a matrix of binding strengths among 162 drug molecules known to cause at least one type of SADR and 845 proteins. Drugs sharing the same SADR outcome were also found to possess similarities in their CPI profiles towards this 845 protein set. This methodology identified the candidate gene of sulfonamide-induced toxic epidermal necrolysis (TEN): all nine sulfonamides that cause TEN were found to bind strongly to MHC I (Cw*4), whereas none of the 17 control drugs that do not cause TEN were found to bind to it. Through an insight into the CPI, we found the Y116S substitution of MHC I (B*5703) enhances the unexpected binding of abacavir to its antigen presentation groove, which explains why B*5701, not B*5703, is the risk allele of abacavir-induced hypersensitivity. In conclusion, SADR targets and the patient-specific off-targets could be identified through a systematic investigation of the CPI, generating important hypotheses for prospective experimental validation of the candidate genes