In our own backyard: urban health inequities and Aboriginal experiences of neighbourhood life, social capital and racism.

This report is about Aboriginal and Torres Strait Islander people who live in urban areas. Thus it contributes to filling the gap in literature and knowledge about the health and everyday life experience of urban Indigenous peoples.This study, the Adelaide Aboriginal and Torres Strait Islander Health (AATSIH) project, was funded by the National Health and Medical Research Council (NHMRC) and focused on neighbourhood life, social capital, experiences of racism and health. This was a ‘companion’ project to another NHMRC project (the General Location and Health project (the General L&H project) – see Baum, Ziersch, Zhang et al, 2007) that explored neighbourhood life and social capital for the general population in four contrasting socio-economic areas in Adelaide

Switching the Interpenetration of Confined Asymmetric Polymer Brushes

The interpenetration of two polymer brushes on approaching flat surfaces has been investigated. When compacting polymer brushes with an asymmetric charge on each surface, one neutral and the other weakly charged, we find that the brush interpenetration becomes a parameter that can be controlled by the pH of the hydrating solution. The switching between high and low degrees of brush interpenetration was investigated with numerical self-consistent field theory (nSCF) and experimentally using a sample environment which combines neutron reflectometry with a surface force type apparatus. Initially, a pair of uncharged poly(ethylene oxide), PEO, brushes are examined, where one of the brushes is deuterated to distinguish it from a hydrogenous counterpart. We find in both nSCF and these experiments that there is no significant overlap between the brushes as both compact into polymer blocks with little hydration. However, when a weak polyelectrolyte poly(2-(dimethylamino)ethyl methacrylate), PDMAEMA, brush is confined against a deuterated neutral PEO brush and the pH of the hydrating solution is below the polycation’s pKa of 7.5, then the presence of charged groups on the PDMAEMA allows significant interpenetration to occur between the two polymer brushes on contact. This interpenetration remains once the polymer brushes dehydrate due to the confining pressure that is applied. Raising the pH to a value above the pKa, removes the charges from the polyelectrolyte brush resulting in little to no interpenetration between the two brushes. Therefore, by simply adjusting the pH of the hydrating solution the interpenetration state between polymer brush pairs can be switched when one brush is a weak polyelectrolyte. Since polymer brushes are widely investigated and used to reduce friction between solid surfaces, this effect may have significant implications in the design and operation of polymer brushes with controllable friction properties

Malleability of the cortical hand map following a finger nerve block

Electrophysiological studies in monkeys show that finger amputation triggers local remapping within the deprived primary somatosensory cortex (S1). Human neuroimaging research, however, shows persistent S1 representation of the missing hand\u27s fingers, even decades after amputation. Here, we explore whether this apparent contradiction stems from underestimating the distributed peripheral and central representation of fingers in the hand map. Using pharmacological single-finger nerve block and 7-tesla neuroimaging, we first replicated previous accounts (electrophysiological and other) of local S1 remapping. Local blocking also triggered activity changes to nonblocked fingers across the entire hand area. Using methods exploiting interfinger representational overlap, however, we also show that the blocked finger representation remained persistent despite input loss. Computational modeling suggests that both local stability and global reorganization are driven by distributed processing underlying the topographic map, combined with homeostatic mechanisms. Our findings reveal complex interfinger representational features that play a key role in brain (re)organization, beyond (re)mapping

Malleability of the cortical hand map following a finger nerve block

Electrophysiological studies in monkeys show that finger amputation triggers local remapping within the deprived primary somatosensory cortex (S1). Human neuroimaging research, however, shows persistent S1 representation of the missing hand's fingers, even decades after amputation. Here, we explore whether this apparent contradiction stems from underestimating the distributed peripheral and central representation of fingers in the hand map. Using pharmacological single-finger nerve block and 7-tesla neuroimaging, we first replicated previous accounts (electrophysiological and other) of local S1 remapping. Local blocking also triggered activity changes to nonblocked fingers across the entire hand area. Using methods exploiting interfinger representational overlap, however, we also show that the blocked finger representation remained persistent despite input loss. Computational modeling suggests that both local stability and global reorganization are driven by distributed processing underlying the topographic map, combined with homeostatic mechanisms. Our findings reveal complex interfinger representational features that play a key role in brain (re)organization, beyond (re)mapping

Homogeneous Subgroups of Young Children with Autism Improve Phenotypic Characterization in the Study to Explore Early Development

The objective of this study was to identify homogenous classes of young children with autism spectrum disorder (ASD) to improve phenotypic characterization. Children were enrolled in the Study to Explore Early Development between 2 and 5 years of age. 707 children were classified with ASD after a comprehensive evaluation with strict diagnostic algorithms. Four classes of children with ASD were identified from latent class analysis: mild language delay with cognitive rigidity, mild language and motor delay with dysregulation, general developmental delay, and significant developmental delay with repetitive motor behaviors. We conclude that a four-class phenotypic model of children with ASD best describes our data and improves phenotypic characterization of young children with ASD. Implications for screening, diagnosis, and research are discussed

Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science

Abstract Background Many interventions found to be effective in health services research studies fail to translate into meaningful patient care outcomes across multiple contexts. Health services researchers recognize the need to evaluate not only summative outcomes but also formative outcomes to assess the extent to which implementation is effective in a specific setting, prolongs sustainability, and promotes dissemination into other settings. Many implementation theories have been published to help promote effective implementation. However, they overlap considerably in the constructs included in individual theories, and a comparison of theories reveals that each is missing important constructs included in other theories. In addition, terminology and definitions are not consistent across theories. We describe the Consolidated Framework For Implementation Research (CFIR) that offers an overarching typology to promote implementation theory development and verification about what works where and why across multiple contexts. Methods We used a snowball sampling approach to identify published theories that were evaluated to identify constructs based on strength of conceptual or empirical support for influence on implementation, consistency in definitions, alignment with our own findings, and potential for measurement. We combined constructs across published theories that had different labels but were redundant or overlapping in definition, and we parsed apart constructs that conflated underlying concepts. Results The CFIR is composed of five major domains: intervention characteristics, outer setting, inner setting, characteristics of the individuals involved, and the process of implementation. Eight constructs were identified related to the intervention (e.g., evidence strength and quality), four constructs were identified related to outer setting (e.g., patient needs and resources), 12 constructs were identified related to inner setting (e.g., culture, leadership engagement), five constructs were identified related to individual characteristics, and eight constructs were identified related to process (e.g., plan, evaluate, and reflect). We present explicit definitions for each construct. Conclusion The CFIR provides a pragmatic structure for approaching complex, interacting, multi-level, and transient states of constructs in the real world by embracing, consolidating, and unifying key constructs from published implementation theories. It can be used to guide formative evaluations and build the implementation knowledge base across multiple studies and settings.http://deepblue.lib.umich.edu/bitstream/2027.42/78272/1/1748-5908-4-50.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/2/1748-5908-4-50-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/3/1748-5908-4-50-S3.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/4/1748-5908-4-50-S4.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/5/1748-5908-4-50.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/6/1748-5908-4-50-S2.PDFPeer Reviewe

HNF1α inhibition triggers epithelial-mesenchymal transition in human liver cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Hepatocyte Nuclear Factor 1α (HNF1α) is an atypical homeodomain-containing transcription factor that transactivates liver-specific genes including albumin, α-1-antitrypsin and α- and β-fibrinogen. Biallelic inactivating mutations of <it>HNF1A </it>have been frequently identified in hepatocellular adenomas (HCA), rare benign liver tumors usually developed in women under oral contraceptives, and in rare cases of hepatocellular carcinomas developed in non-cirrhotic liver. HNF1α-mutated HCA (H-HCA) are characterized by a marked steatosis and show activation of glycolysis, lipogenesis, translational machinery and mTOR pathway. We studied the consequences of HNF1α silencing in hepatic cell lines, HepG2 and Hep3B and we reproduced most of the deregulations identified in H-HCA.</p> <p>Methods</p> <p>We transfected hepatoma cell lines HepG2 and Hep3B with siRNA targeting HNF1α and obtained a strong inhibition of HNF1α expression. We then looked at the phenotypic changes by microscopy and studied changes in gene expression using qRT-PCR and Western Blot.</p> <p>Results</p> <p>Hepatocytes transfected with HNF1α siRNA underwent severe phenotypic changes with loss of cell-cell contacts and development of migration structures. In HNF1α-inhibited cells, hepatocyte and epithelial markers were diminished and mesenchymal markers were over-expressed. This epithelial-mesenchymal transition (EMT) was related to the up regulation of several EMT transcription factors, in particular <it>SNAIL </it>and <it>SLUG</it>. We also found an overexpression of TGFβ1, an EMT initiator, in both cells transfected with HNF1α siRNA and H-HCA. Moreover, TGFβ1 expression is strongly correlated to HNF1α expression in cell models, suggesting regulation of TGFβ1 expression by HNF1α.</p> <p>Conclusion</p> <p>Our results suggest that HNF1α is not only important for hepatocyte differentiation, but has also a role in the maintenance of epithelial phenotype in hepatocytes.</p

The politics and aesthetics of commemoration: national days in southern Africa

The contributions to the special section in this issue study recent independence celebrations and other national days in South Africa, Namibia, Zimbabwe, Madagascar and the Democratic Republic of Congo. They explore the role of national days in state-making and nation-building, and examine the performativity of nationalism and the role of performances in national festivities. Placing the case studies in a broader, comparative perspective, the introduction first discusses the role of the state in national celebrations, highlighting three themes: firstly, the political power-play and contested politics of memory involved in the creation of a country’s festive calendar; secondly, the relationship between state control of national days and civic or popular participation or contestation; and thirdly, the complex relationship between regional and ethnic loyalties and national identifications. It then turns to the role of performance and aesthetics in the making of nations in general, and in national celebrations in particular. Finally, we look at the different formats and meanings of national days in the region and address the question whether there is anything specific about national days in southern Africa as compared to other parts of the continent or national celebrations world-wide.Web of Scienc

Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease A Randomized Clinical Trial

Importance Deutetrabenazine is a novel molecule containing deuterium, which attenuates CYP2D6 metabolism and increases active metabolite half-lives and may therefore lead to stable systemic exposure while preserving key pharmacological activity. Objective To evaluate efficacy and safety of deutetrabenazine treatment to control chorea associated with Huntington disease. Design, Setting, and Participants Ninety ambulatory adults diagnosed with manifest Huntington disease and a baseline total maximal chorea score of 8 or higher (range, 0-28; lower score indicates less chorea) were enrolled from August 2013 to August 2014 and randomized to receive deutetrabenazine (n = 45) or placebo (n = 45) in a double-blind fashion at 34 Huntington Study Group sites. Interventions Deutetrabenazine or placebo was titrated to optimal dose level over 8 weeks and maintained for 4 weeks, followed by a 1-week washout. Main Outcomes and Measures Primary end point was the total maximal chorea score change from baseline (the average of values from the screening and day-0 visits) to maintenance therapy (the average of values from the week 9 and 12 visits) obtained by in-person visits. This study was designed to detect a 2.7-unit treatment difference in scores. The secondary end points, assessed hierarchically, were the proportion of patients who achieved treatment success on the Patient Global Impression of Change (PGIC) and on the Clinical Global Impression of Change (CGIC), the change in 36-Item Short Form– physical functioning subscale score (SF-36), and the change in the Berg Balance Test. Results Ninety patients with Huntington disease (mean age, 53.7 years; 40 women [44.4%]) were enrolled. In the deutetrabenazine group, the mean total maximal chorea scores improved from 12.1 (95% CI, 11.2-12.9) to 7.7 (95% CI, 6.5-8.9), whereas in the placebo group, scores improved from 13.2 (95% CI, 12.2-14.3) to 11.3 (95% CI, 10.0-12.5); the mean between-group difference was –2.5 units (95% CI, –3.7 to –1.3) (P < .001). Treatment success, as measured by the PGIC, occurred in 23 patients (51%) in the deutetrabenazine group vs 9 (20%) in the placebo group (P = .002). As measured by the CGIC, treatment success occurred in 19 patients (42%) in the deutetrabenazine group vs 6 (13%) in the placebo group (P = .002). In the deutetrabenazine group, the mean SF-36 physical functioning subscale scores decreased from 47.5 (95% CI, 44.3-50.8) to 47.4 (44.3-50.5), whereas in the placebo group, scores decreased from 43.2 (95% CI, 40.2-46.3) to 39.9 (95% CI, 36.2-43.6), for a treatment benefit of 4.3 (95% CI, 0.4 to 8.3) (P = .03). There was no difference between groups (mean difference of 1.0 unit; 95% CI, –0.3 to 2.3; P = .14), for improvement in the Berg Balance Test, which improved by 2.2 units (95% CI, 1.3-3.1) in the deutetrabenazine group and by 1.3 units (95% CI, 0.4-2.2) in the placebo group. Adverse event rates were similar for deutetrabenazine and placebo, including depression, anxiety, and akathisia. Conclusions and Relevance Among patients with chorea associated with Huntington disease, the use of deutetrabenazine compared with placebo resulted in improved motor signs at 12 weeks. Further research is needed to assess the clinical importance of the effect size and to determine longer-term efficacy and safety