Accounting as capital and doxa: exploring power and Resistance in world bank projects in Tonga

Purpose: The purpose of this paper is to explore the role of accounting both as a resource and an element of the social context in the relationship between the World Bank and the Island Kingdom of Tonga. Design/methodology/approaches We implemented a qualitative field study design collecting data through 13 semi-structured interviews and rich consultation with 10 informants. We also did in depth reviews of various World Bank lending agreements to Tonga. Such an approach is necessary for collecting the rich data required to address our research purpose. Bourdieu’s concepts of doxa and capital provided the framework for problematizing our research purpose and for making sense of our collected data. Findings The role of accounting in dominating and controlling of Indigenous people is mediated by the doxic rules and existing capital arrangements in several contextual levels ranging from the National level to the village level. Research limitations/ implications While we deployed the understanding of the doxic rules and capital arrangements of various fields to better understand the roles of accounting in the relationship between Tonga and the World Bank, we really did not explore the grey area where fields (and by extension the overlapping of doxic rules and capital arrangements) overlap each other. We suspect that an enhanced understanding of the role of accounting will be arrived at if this area is better articulated. Practical implications This study shows that accounting as an accountability tool is deployed in various social contexts each with its own doxic rule complications and capital arrangements. Accordingly, this study provides policy makers and foreign donors to Tonga and other Pacific Islands information on the struggles to implement accounting at local level. And similarly, it provides evidence on local level enablers for the implementation of accounting as an accountability tool. Originality/ value This study contributes to the growing accounting body of work that seeks to better understand accounting in Indigenous settings by proposing that role of accounting as a tool for domination is mediated in various social settings by the doxic value and the existing capital arrangements in those settings

Predictive performance of parent-metabolite population pharmacokinetic models of (S)-ketamine in healthy volunteers

Purpose The recent repurposing of ketamine as treatment for pain and depression has increased the need for accurate population pharmacokinetic (PK) models to inform the design of new clinical trials. Therefore, the objectives of this study were to externally validate available PK models on (S)-(nor)ketamine concentrations with in-house data and to improve the best performing model when necessary. Methods Based on predefined criteria, five models were selected from literature. Data of two previously performed clinical trials on (S)-ketamine administration in healthy volunteers were available for validation. The predictive performances of the selected models were compared through visual predictive checks (VPCs) and calculation of the (root) mean (square) prediction errors (ME and RMSE). The available data was used to adapt the best performing model through alterations to the model structure and re-estimation of inter-individual variability (IIV). Results The model developed by Fanta et al. (Eur J Clin Pharmacol 71:441-447, 2015) performed best at predicting the (S)-ketamine concentration over time, but failed to capture the (S)-norketamine C-max correctly. Other models with similar population demographics and study designs had estimated relatively small distribution volumes of (S)-ketamine and thus overpredicted concentrations after start of infusion, most likely due to the influence of circulatory dynamics and sampling methodology. Model predictions were improved through a reduction in complexity of the (S)-(nor)ketamine model and re-estimation of IIV. Conclusion The modified model resulted in accurate predictions of both (S)-ketamine and (S)-norketamine and thereby provides a solid foundation for future simulation studies of (S)-(nor)ketamine PK in healthy volunteers after (S)-ketamine infusion.Stress-related psychiatric disorders across the life spa

Item response theory in early phase clinical trials: utilization of a reference model to analyze the Montgomery-Asberg Depression Rating Scale

In clinical trials, Montgomery-Åsberg Depression Rating Scale (MADRS) questionnaire data are added up to total scores before analysis, assuming equal contribution of each separate question. Item Response Theory (IRT)-based analysis avoids this by using individual question responses to determine the latent variable (ψ), which represents a measure of depression severity. However, utilization of IRT in early phase trials remains difficult, because large datasets are needed to develop IRT models. Therefore, we aimed to evaluate the application and assumptions of a reference IRT model for analysis of an early phase trial. A cross-over, placebo-controlled study investigating the effect of intravenous racemic ketamine on MADRS scores in patients with treatment-resistant major depressive disorder was used as a case study. One hundred forty-seven MADRS responses were measured in 17 patients at five timepoints (predose to 2 weeks after dosing). Two reference IRT models based on different patient populations were selected from literature and used to determine ψ, while testing multiple approaches regarding assumed data distribution. Use of ψ versus total score to determine treatment effect was compared through linear mixed model analysis. Results showed that determined ψ values did not differ significantly between assumed distributions, but were significantly different when changing reference IRT model. Estimated treatment effect size was not significantly affected by chosen approach nor reference population. Finally, increased precision to determine treatment effect was achieved by using IRT versus total scores. This demonstrates the usefulness of reference IRT model application for analysis of questionnaire data in early phase clinical trials. Prevention, Population and Disease management (PrePoD)Public Health and primary car

Differentiating normal and problem gambling: a grounded theory approach.

A previous study (Ricketts &amp; Macaskill, 2003) delineated a theory of problem gambling based on the experiences of treatment seeking male gamblers and allowed predictions to be made regarding the processes that differentiate between normal and problem gamblers. These predictions are the focus of the present study, which also utilised a grounded theory approach, but with a sample of male high frequency normal gamblers. The findings suggest that there are common aspects of gambling associated with arousal and a sense of achievement. The use of gambling to manage negative emotional states differentiated normal and problem gambling. Perceived self-efficacy , emotion management skills and perceived likelihood of winning money back were intervening variables differentiating problem and normal gamblers.</p

Systemic perturbations of the kynurenine pathway precede progression to dementia independently of amyloid-β

Increasing evidence suggests that kynurenine pathway (KP) dyshomeostasis may promote disease progression in dementia. Studies in Alzheimer's disease (AD) patients confirm KP dyshomeostasis in plasma and cerebrospinal fluid (CSF) which correlates with amyloid-β and tau pathology. Herein, we performed the first comprehensive study assessing baseline levels of KP metabolites in participants enrolling in the Australian Imaging Biomarkers Flagship Study of Aging. Our purpose was to test the hypothesis that changes in KP metabolites may be biomarkers of dementia processes that are largely silent. We used a cross-sectional analytical approach to assess non-progressors (N = 73); cognitively normal (CN) or mild cognitive impairment (MCI) participants at baseline and throughout the study, and progressors (N = 166); CN or MCI at baseline but progressing to either MCI or AD during the study. Significant KP changes in progressors included increased 3-hydroxyanthranilic acid (3-HAA) and 3-hydroxyanthranilic acid/anthranilic acid (3-HAA/AA) ratio, the latter having the largest effect on the odds of an individual being a progressor (OR 35.3; 95% CI between 14 and 104). 3-HAA levels were hence surprisingly bi-phasic, high in progressors but low in non-progressors or participants who had already transitioned to MCI or dementia. This is a new, unexpected and interesting result, as most studies of the KP in neurodegenerative disease show reduced 3-HAA/AA ratio after diagnosis. The neuroprotective metabolite picolinic acid was also significantly decreased while the neurotoxic metabolite 3-hydroxykynurenine increased in progressors. These results were significant even after adjustment for confounders. Considering the magnitude of the OR to predict change in cognition, it is important that these findings are replicated in other populations. Independent validation of our findings may confirm the utility of 3-HAA/AA ratio to predict change in cognition leading to dementia in clinical settings

The International Cancer Expert Corps: A Unique Approach for Sustainable Cancer Care in Low and Lower-Middle Income Countries

The growing burden of non-communicable diseases including cancer in low- and lower-middle income countries (LMICs) and in geographic-access limited settings within resource-rich countries requires effective and sustainable solutions. The International Cancer Expert Corps (ICEC) is pioneering a novel global mentorship–partnership model to address workforce capability and capacity within cancer disparities regions built on the requirement for local investment in personnel and infrastructure. Radiation oncology will be a key component given its efficacy for cure even for the advanced stages of disease often encountered and for palliation. The goal for an ICEC Center within these health disparities settings is to develop and retain a high-quality sustainable workforce who can provide the best possible cancer care, conduct research, and become a regional center of excellence. The ICEC Center can also serve as a focal point for economic, social, and healthcare system improvement. ICEC is establishing teams of Experts with expertise to mentor in the broad range of subjects required to establish and sustain cancer care programs. The Hubs are cancer centers or other groups and professional societies in resource-rich settings that will comprise the global infrastructure coordinated by ICEC Central. A transformational tenet of ICEC is that altruistic, human-service activity should be an integral part of a healthcare career. To achieve a critical mass of mentors ICEC is working with three groups: academia, private practice, and senior mentors/retirees. While in-kind support will be important, ICEC seeks support for the career time dedicated to this activity through grants, government support, industry, and philanthropy. Providing care for people with cancer in LMICs has been a recalcitrant problem. The alarming increase in the global burden of cancer in LMICs underscores the urgency and makes this an opportune time fornovel and sustainable solutions to transform cancer care globally

On the role of the upper part of words in lexical access : evidence with masked priming

More than 100 years ago, Huey (1908) indicated that the upper part of words was more relevant for perception than the lower part. Here we examined whether mutilated words, in their upper/lower portions (e.g., , , , ), can automatically access their word units in the mental lexicon. To that end, we conducted four masked repetition priming experiments with the lexical decision task. Results showed that mutilated primes produced a sizeable masked repetition priming effect. Furthermore, the magnitude of the masked repetition priming effect was greater when the upper part of the primes was preserved than when the lower portion was preserved –this was the case not only when the mutilated words were presented in lowercase but also when the mutilated words were presented in uppercase. Taken together, these findings suggest that the front-end of computational models of visual-word recognition should be modified to provide a more realistic account at the level of letter features.The research reported in this article has been partially supported by Grant PSI2008-04069/PSIC and CONSOLIDER-INGENIO2010 CSD2008-00048 from the Spanish Ministry of Science and Innovation and by Grant PTDC/PSI-PCO/104671/2008 from the Portuguese Foundation for Science and Technology

Dysregulation of kynurenine metabolism is related to proinflammatory cytokines, attention, and prefrontal cortex volume in schizophrenia

The kynurenine pathway (KP) of tryptophan (TRP) catabolism links immune system activation with neurotransmitter signaling. The KP metabolite kynurenic acid (KYNA) is increased in the brains of people with schizophrenia. We tested the extent to which: (1) brain KP enzyme mRNAs, (2) brain KP metabolites, and (3) plasma KP metabolites differed on the basis of elevated cytokines in schizophrenia vs. control groups and the extent to which plasma KP metabolites were associated with cognition and brain volume in patients displaying elevated peripheral cytokines. KP enzyme mRNAs and metabolites were assayed in two independent postmortem brain samples from a total of 71 patients with schizophrenia and 72 controls. Plasma KP metabolites, cognition, and brain volumes were measured in an independent cohort of 96 patients with schizophrenia and 81 healthy controls. Groups were stratified based on elevated vs. normal proinflammatory cytokine mRNA levels. In the prefrontal cortex (PFC), kynurenine (KYN)/TRP ratio, KYNA levels, and mRNA for enzymes, tryptophan dioxygenase (TDO) and kynurenine aminotransferases (KATI/II), were significantly increased in the high cytokine schizophrenia subgroup. KAT mRNAs significantly correlated with mRNA for glial fibrillary acidic protein in patients. In plasma, the high cytokine schizophrenia subgroup displayed an elevated KYN/TRP ratio, which correlated inversely with attention and dorsolateral prefrontal cortex (DLPFC) volume. This study provides further evidence for the role of inflammation in a subgroup of patients with schizophrenia and suggests a molecular mechanism through which inflammation could lead to schizophrenia. Proinflammatory cytokines may elicit conversion of TRP to KYN in the periphery and increase the N-methyl-D-aspartate receptor antagonist KYNA via increased KAT mRNA and possibly more enzyme synthesis activity in brain astrocytes,  leading to DLPFC volume loss, and attention impairment in schizophrenia.Jochen Kindler, Chai K. Lim, Cynthia Shannon Weickert, Danny Boerrigter, Cherrie Galletly, Dennis Liu, Kelly R. Jacobs, Ryan Balzan, Jason Bruggemann, Maryanne O’Donnell, Rhoshel Lenroot, Gilles J. Guillemin and Thomas W. Weicker