Inclusion Not Exclusion: Comparative Educational Perspectives at the Heart of Sustainable Development in the Gulf States

Welcome to this special edition of FIRE: Forum for International Research in Education. This issue celebrates the rich variety of research brought together at the 6th Annual Gulf Comparative Education Society (GCES) Symposium in April 2015. Hosted by Middlesex University at their Dubai campus, the symposium was an opportunity to share and critically discuss matters related to comparative and educational research in a region where opportunities for such activities can be challenging to access. Speakers from Kuwait to Oman came together, and in the form of the conference found both a voice and a support network. The richness of this meeting of minds has been captured in part though this special edition. Building on the quality of research that FIRE has become recognized for, we hope you will find the content of this issue interesting, thought provoking, and even controversial, as all good research should be. Above all, we hope it inspires even more academics from within this region to come forward and participate in the debate at future GCES conferences

Influence of pharmacogenetic variability on the pharmacokinetics and toxicity of the aurora kinase inhibitor danusertib

Objectives Danusertib is a serine/threonine kinase inhibitor of multiple kinases, including aurora-A, B, and C. This explorative study aims to identify possible relationships between single nucleotide polymorphisms in genes coding for drug metabolizing enzymes and transporter proteins and clearance of danusertib, to clarify the interpatient variability in exposure. In addition, this study explores the relationship between target receptor polymorphisms and toxicity of danusertib. Methods For associations with clearance, 48 cancer patients treated in a phase I study were analyzed for ABCB1, ABCG2 and FMO3 polymorphisms. Association analyses between neutropenia and drug target receptors, including KDR, RET, FLT3, FLT4, AURKB and AURKA, were performed in 30 patients treated at recommended phase II dose-levels in three danusertib phase I or phase II trials. Results No relationships between danusertib clearance and drug metabolizing enzymes and transporter protein polymorphisms were found. Only, for the one patient with FMO3 18281AA polymorphism, a significantly higher clearance was noticed, compared to patients carrying at least 1 wild type allele. No effect of target receptor genotypes or haplotypes on neutropenia was observed. Conclusions As we did not find any major correlations between pharmacogenetic variability in the studied enzymes and transporters and pharmacokinetics nor toxicity, it is unlikely that danusertib is highly susceptible for pharmacogenetic variation. Therefore, no dosing alterations of danusertib are expected in the future, based on the polymorphisms studied. However, the relationship between FMO3 polymorphisms and clearance of danusertib warrants further research, as we could study only a small group of patients

CT-guided iodine-125 seed permanent implantation for recurrent head and neck cancers

<p>Abstract</p> <p>Background</p> <p>To investigate the feasibility, and safety of ¹²⁵I seed permanent implantation for recurrent head and neck carcinoma under CT-guidance.</p> <p>Results</p> <p>A retrospective study on 14 patients with recurrent head and neck cancers undergone ¹²⁵I seed implantation with different seed activities. The post-plan showed that the actuarial D90 of ¹²⁵I seeds ranged from 90 to 218 Gy (median, 157.5 Gy). The follow-up was 3 to 60 months (median, 13 months). The median local control was 18 months (95% CI, 6.1-29.9 months), and the 1-, 2-, 3-, and 5- year local controls were 52%, 39%, 39%, and 39%, respectively. The 1-, 2-, 3-, and 5- survival rates were 65%, 39%, 39% and 39%, respectively, with a median survival time of 20 months (95% CI, 8.7-31.3 months). Of all patients, 28.6% (4/14) died of local recurrence, 7.1% (1/14) died of metastases, one patient died of hepatocirrhosis, and 8 patients are still alive to the date of data analysis.</p> <p>Conclusion</p> <p>CT-guided ¹²⁵I seed implantation is feasible and safe as a salvage or palliative treatment for patients with recurrent head and neck cancers.</p

CD4+ T Cell-Derived IL-2 Signals during Early Priming Advances Primary CD8+ T Cell Responses

Stimulating naïve CD8+ T cells with specific antigens and costimulatory signals is insufficient to induce optimal clonal expansion and effector functions. In this study, we show that the activation and differentiation of CD8+ T cells require IL-2 provided by activated CD4+ T cells at the initial priming stage within 0–2.5 hours after stimulation. This critical IL-2 signal from CD4+ cells is mediated through the IL-2Rβγ of CD8+ cells, which is independent of IL-2Rα. The activation of IL-2 signaling advances the restriction point of the cell cycle, and thereby expedites the entry of antigen-stimulated CD8+ T-cell into the S phase. Besides promoting cell proliferation, IL-2 stimulation increases the amount of IFNγ and granzyme B produced by CD8+ T cells. Furthermore, IL-2 at priming enhances the ability of P14 effector cells generated by antigen activation to eradicate B16.gp33 tumors in vivo. Therefore, our studies demonstrate that a full CD8+ T-cell response is elicited by a critical temporal function of IL-2 released from CD4+ T cells, providing mechanistic insights into the regulation of CD8+ T cell activation and differentiation

REACH: a mixed-methods study to investigate the measurement, prediction and improvement of retention and engagement in outpatient HIV care

BACKGROUND Antiretroviral therapy (ART) benefits individuals living with human immunodeficiency virus (HIV) through reduced morbidity and mortality, and brings public health gains through a reduction in HIV transmission. People living with human immunodeficiency virus (PLWH) need to know their HIV status and engage in HIV care in order for these individual and public health benefits to be realised. OBJECTIVE To explore, describe and understand HIV outpatient attendance in PLWH, in order to develop cost-effective interventions to optimise engagement in care. DESIGN A mixed-methods study incorporating secondary analysis of data from the UK Collaborative HIV Cohort (UK CHIC) study and primary data collection. METHODS Phase 1 – an engagement-in-care (EIC) algorithm was developed to categorise patients as in care or out of care for each month of follow-up. The algorithm was used in group-based trajectory analysis to examine patterns of attendance over time and of the association between the proportion of months in care before ART initiation and post-ART mortality and laboratory test costs. Phase 2 – a cross-sectional survey was conducted among patients attending seven London HIV clinics. Regular attenders (all appointments attended in past year), irregular attenders (one or more appointments missed in past year) and non-attenders (recent absence of ≥ 1 year) were recruited. A ‘retention risk tool’ was developed to identify those at risk of disengaging from care. Individual in-depth interviews and focus groups were conducted with PLWH. Phase 3 – key informant interviews were conducted with HIV service providers. Interventions were developed from the findings of phases 2 and 3. RESULTS Plots from group-based trajectory analysis indicated that four trajectories best fitted the data. Higher EIC is associated with reduced mortality but the association between EIC before starting ART, and post-ART mortality [relative hazard (RH) per 10% increase in EIC 0.29, 95% confidence interval (CI) 0.18 to 0.47] was attenuated after adjustment for fixed covariates and post-ART cluster of differentiation 4 counts and viral loads (RH 0.74, 95% CI 0.42 to 1.30). Small differences were found in pre-ART EIC and the costs of post-ART lab tests. The final model for the retention risk tool included age at diagnosis, having children, recreational drug use, drug/alcohol dependency, insufficient money for basic needs and use of public transport to get to the clinic. Quantitative and qualitative data showed that a range of psychological, social and economic issues were associated with disengagement from care. The negative impact of stigma on attendance was highlighted. Interventions were proposed that support a holistic approach to care including peer support, address stigma by holding clinics in alternative locations and involve training staff to encourage attendance. CONCLUSIONS The study shows the adverse health impacts of disengaging from HIV care and demonstrates the importance of the wider health and social context in managing HIV effectively. Although phase 1 analysis was based on UK data, phases 2 and 3 were limited to London. The interventions proposed are supported by the data but their cost-effectiveness requires testing. Future research is needed to evaluate the interventions, to validate our retention risk tool across populations and settings, and to fully analyse the economic costs of disengaging from HIV care

Independent impacts of aging on mitochondrial DNA quantity and quality in humans

Background The accumulation of mitochondrial DNA (mtDNA) mutations, and the reduction of mtDNA copy number, both disrupt mitochondrial energetics, and may contribute to aging and age-associated phenotypes. However, there are few genetic and epidemiological studies on the spectra of blood mtDNA heteroplasmies, and the distribution of mtDNA copy numbers in different age groups and their impact on age-related phenotypes. In this work, we used whole-genome sequencing data of isolated peripheral blood mononuclear cells (PBMCs) from the UK10K project to investigate in parallel mtDNA heteroplasmy and copy number in 1511 women, between 17 and 85 years old, recruited in the TwinsUK cohorts. Results We report a high prevalence of pathogenic mtDNA heteroplasmies in this population. We also find an increase in mtDNA heteroplasmies with age (β = 0.011, P = 5.77e-6), and showed that, on average, individuals aged 70-years or older had 58.5% more mtDNA heteroplasmies than those under 40-years old. Conversely, mtDNA copy number decreased by an average of 0.4 copies per year (β = −0.395, P = 0.0097). Multiple regression analyses also showed that age had independent effects on mtDNA copy number decrease and heteroplasmy accumulation. Finally, mtDNA copy number was positively associated with serum bicarbonate level (P = 4.46e-5), and inversely correlated with white blood cell count (P = 0.0006). Moreover, the aggregated heteroplasmy load was associated with blood apolipoprotein B level (P = 1.33e-5), linking the accumulation of mtDNA mutations to age-related physiological markers. Conclusions Our population-based study indicates that both mtDNA quality and quantity are influenced by age. An open question for the future is whether interventions that would contribute to maintain optimal mtDNA copy number and prevent the expansion of heteroplasmy could promote healthy aging

Language in international business: a review and agenda for future research

A fast growing number of studies demonstrates that language diversity influences almost all management decisions in modern multinational corporations. Whereas no doubt remains about the practical importance of language, the empirical investigation and theoretical conceptualization of its complex and multifaceted effects still presents a substantial challenge. To summarize and evaluate the current state of the literature in a coherent picture informing future research, we systematically review 264 articles on language in international business. We scrutinize the geographic distributions of data, evaluate the field’s achievements to date in terms of theories and methodologies, and summarize core findings by individual, group, firm, and country levels of analysis. For each of these dimensions, we then put forward a future research agenda. We encourage scholars to transcend disciplinary boundaries and to draw on, integrate, and test a variety of theories from disciplines such as psychology, linguistics, and neuroscience to gain a more profound understanding of language in international business. We advocate more multi-level studies and cross-national research collaborations and suggest greater attention to potential new data sources and means of analysis

Mechanism of cellular rejection in transplantation

The explosion of new discoveries in the field of immunology has provided new insights into mechanisms that promote an immune response directed against a transplanted organ. Central to the allograft response are T lymphocytes. This review summarizes the current literature on allorecognition, costimulation, memory T cells, T cell migration, and their role in both acute and chronic graft destruction. An in depth understanding of the cellular mechanisms that result in both acute and chronic allograft rejection will provide new strategies and targeted therapeutics capable of inducing long-lasting, allograft-specific tolerance

Housing: An Under-Explored Influence on Children’s Well-Being and Becoming

Research on housing has tended to focus on adult outcomes, establishing relationships between housing and a number of aspects of health and well-being. Research exploring the influence of housing on children has been more limited, and has tended to focus on adult concerns around risk behaviours, behavioural problems and educational attainment. While these outcomes are important, they neglect the impact of housing on children’s lives beyond these concerns. There are a number of reasons to believe that housing would play an important role in children’s well-being more broadly. Family stress and strain models highlight how housing difficulties experienced by adults may have knock on effects for children, while Bronfenbrenner’s ecological approach to human development emphasises the importance of children’s experiences of their environments, of which the home is among the most important. This paper summaries the existing evidence around housing and child outcomes, predominantly educational and behavioural outcomes, and argues for the extension of this work to consider the impact of housing on children’s lives more broadly, especially their subjective well-being