Re-imagining the data collection and analysis research process by proposing a rapid qualitative data collection and analytic roadmap applied to the dynamic context of precision medicine

Our implementation science study focuses on implementing a new way of practice and offers methodological specificity about how to rapidly investigate an individually tailored precision medicine intervention. A qualitative study advancing a new methodology for speedily identifying barriers and enablers to implementation in the context of childhood cancer. Data were collected through rapid ethnography, coded using the Consolidated Framework for Implementation Research, and analysed by Sentiment Analysis. Thirty-eight data collection events occurred during 14 multidisciplinary tumour board meetings, 14 curation meetings, and 10 informal conversations. Sentiment Analysis distilled Consolidated Framework for Implementation Research codes to reveal key barriers and enablers to implementation. A traffic light labelling system has been used to present levels of positivity and negativity (green for strong enablers and red for strong barriers), highlighting levels of concern regarding implementation. Within the intervention design characteristics, “Adaptability” was the strongest enabler and “Design quality and safety” the strongest barrier. Among the contextual factors: “Networks and communication” were the strongest enabler, and “Available resources” were the strongest barrier. Overall, there was a higher percentage of negative sentiment towards intervention design characteristics and contextual factors than positive sentiment, while more concerns were raised about intervention design factors than contextual factors. This study offers a rapid qualitative data collection and analytic methodological roadmap for establishing barriers and enablers to a paediatric precision medicine intervention

Identifying challenges to implementation of clinical practice guidelines for sentinel lymph node biopsy in patients with melanoma in Australia: Protocol paper for a mixed methods study

Introduction Sentinel lymph node biopsy (SLNB) is a diagnostic procedure developed in the 1990s. It is currently used to stage patients with primary cutaneous melanoma, provide prognostic information and guide management. The Australian Clinical Practice Guidelines state that SLNB should be considered for patients with cutaneous melanoma >1mm in thickness (or >0.8mm with high-risk pathology features). Until recently, sentinel lymph node (SLN) status was used to identify patients who might benefit from a completion lymph node dissection, a procedure that is no longer routinely recommended. SLN status is now also being used to identify patients who might benefit from systemic adjuvant therapies such as anti-programmed cell death 1 (PD1) checkpoint inhibitor immunotherapy or BRAFdirected molecular targeted therapy, treatments that have significantly improved relapse-free survival for patients with resected stage III melanoma and improved overall survival of patients with unresectable stage III and stage IV melanoma. Australian and international data indicate that approximately half of eligible patients receive an SLNB. Methods and analysis This mixed-methods study seeks to understand the structural, contextual and cultural factors affecting implementation of the SLNB guidelines. Data collection will include: (1) cross-sectional questionnaires and semistructured interviews with general practitioners and dermatologists; (2) semistructured interviews with other healthcare professionals involved in the diagnosis and early definitive care of melanoma patients and key stakeholders including researchers, representatives of professional colleges, training organisations and consumer melanoma groups; and (3) documentary analysis of documents from government, health services and non-government organisations. Descriptive analyses and multivariable regression models will be used to examine factors related to SLNB practices and attitudes. Qualitative data will be analysed using thematic analysis.This work was funded by the Melanoma Centre of Research Excellence grant (1135285) from the Australian National Health and Medical Research Council (NHMRC). RLM received funding from an NHMRC Translating Research into Practice Fellowship (1150989). AEC received an NHMRC Career Development Fellowship (1147843) and Cancer Institute NSW Career Development Fellowship (15/CDF/1-14)

“Beyond words”: a researcher’s guide to using photo elicitation in psychology

The use of photo elicitation is limited within the field of psychology despite its theoretical and practical potential. It offers significant benefits as a qualitative method that could present a new and interesting way of exploring previously understood topics within the discipline. Within our discussions, we present a Step-by-Step guide in which we outline the key practical stages, as well as ethical assurances involved in photo elicitation research, using our ongoing research as an illustrative example. It is intended that this could be used as a model of good practice for developing research paradigms beyond those typically used within the psychology discipline

Can Motivation Normalize Working Memory and Task Persistence in Children with Attention-Deficit/Hyperactivity Disorder? The Effects of Money and Computer-Gaming

Visual-spatial Working Memory (WM) is the most impaired executive function in children with Attention-Deficit/Hyperactivity Disorder (ADHD). Some suggest that deficits in executive functioning are caused by motivational deficits. However, there are no studies that investigate the effects of motivation on the visual-spatial WM of children with- and without ADHD. Studies examining this in executive functions other than WM, show inconsistent results. These inconsistencies may be related to differences in the reinforcement used. The effects of different reinforcers on WM performance were investigated in 30 children with ADHD and 31 non-ADHD controls. A visual-spatial WM task was administered in four reinforcement conditions: Feedback-only, 1 euro, 10 euros, and a computer-game version of the task. In the Feedback-only condition, children with ADHD performed worse on the WM measure than controls. Although incentives significantly improved the WM performance of children with ADHD, even the strongest incentives (10 euros and Gaming) were unable to normalize their performance. Feedback-only provided sufficient reinforcement for controls to reach optimal performance, while children with ADHD required extra reinforcement. Only children with ADHD showed a decrease in performance over time. Importantly, the strongest incentives (10 euros and Gaming) normalized persistence of performance in these children, whereas 1 euro had no such effect. Both executive and motivational deficits give rise to visual-spatial WM deficits in ADHD. Problems with task-persistence in ADHD result from motivational deficits. In ADHD-reinforcement studies and clinical practice (e.g., assessment), reinforcement intensity can be a confounding factor and should be taken into account. Gaming can be a cost-effective way to maximize performance in ADHD

Small Change: Economics and the British coin-tree

This is the accepted manuscript for the following article: Ceri Houlbrook, “Small Change: Economics and the British coin-tree”, Post Medieval Archaeology, Vol. 49(1), June 2015. The final published version can be found at: http://www.tandfonline.com/doi/full/10.1179/0079423615Z.00000000074 © Society for Post-Medieval Archaeology 2015Throughout the c.2000 year period coins have been circulated in Britain, they have also been ritually employed, most notably as votive deposits. Focusing specifically on the understudied custom of the British coin-tree, whereby coins are ritually embedded into the barks of trees, this paper considers the coin’s role and applicability as a deposit. It aims to demonstrate that our understanding of the coin’s past, present, and future ritual employment is not only aided by a consideration of economics and the coin’s secular function; it would be utterly incomplete without it.Peer reviewedFinal Accepted Versio

Cardiac Glycosides Ouabain and Digoxin Interfere with the Regulation of Glutamate Transporter GLAST in Astrocytes Cultured from Neonatal Rat Brain

Glutamate transport (GluT) in brain is mediated chiefly by two transporters GLT and GLAST, both driven by ionic gradients generated by (Na+, K+)-dependent ATPase (Na+/K+-ATPase). GLAST is located in astrocytes and its function is regulated by translocations from cytoplasm to plasma membrane in the presence of GluT substrates. The phenomenon is blocked by a naturally occurring toxin rottlerin. We have recently suggested that rottlerin acts by inhibiting Na+/K+-ATPase. We now report that Na+/K+-ATPase inhibitors digoxin and ouabain also blocked the redistribution of GLAST in cultured astrocytes, however, neither of the compounds caused detectable inhibition of ATPase activity in cell-free astrocyte homogenates (rottlerin inhibited app. 80% of Pi production from ATP in the astrocyte homogenates, IC50 = 25 μM). Therefore, while we may not have established a direct link between GLAST regulation and Na+/K+-ATPase activity we have shown that both ouabain and digoxin can interfere with GluT transport and therefore should be considered potentially neurotoxic

Testing assumptions for endophenotype studies in ADHD: Reliability and validity of tasks in a general population sample

BACKGROUND: Advances in both genetic and cognitive-experimental studies on attention deficit hyperactivity disorder (ADHD) have opened new opportunities for cognitive endophenotype research. In such genetic designs the focus is on individual differences in characteristics, associated with ADHD, that can be measured reliably over time. Genetic studies that take a 'quantitative trait loci' approach hypothesise that multiple susceptibility genes contribute to a continuous dimension of ADHD symptoms. As an important initial step, we aimed to investigate the underlying assumptions that (1) key cognitive-experimental tasks indicate adequate test-retest reliability and (2) ADHD symptom scores in a general population sample are associated with performance on these tasks. METHODS: Forty-nine children were assessed on a go/no-go task and a reaction time task (the 'fast task') that included manipulations with event rate and incentives. The children were assessed twice, with a test-retest interval of two weeks. RESULTS: The majority of the task variables demonstrated moderate-to-good test-retest reliability. The correlations between teacher ratings of ADHD symptoms and key task variables were .4–.6: ADHD symptoms were associated with poor performance (especially high reaction time variability) in a slow baseline condition, whereas there was low or no association in conditions with a faster event rate or incentives. In contrast, no clear pattern of findings emerged based on parent ratings of ADHD symptoms. CONCLUSION: The data support the usefulness of the go/no-go and fast tasks for genetic studies, which require reliable and valid indices of individual differences. The overall pattern of associations between teacher ratings of ADHD symptoms and task variables is consistent with effects of event rate and incentives on performance, as predicted by the model of activation and arousal regulation. The lack of a clear pattern of findings with parent ratings of ADHD symptoms warrants further study

Functional gait rehabilitation in elderly people following a fall-related hip fracture using a treadmill with visual context: design of a randomized controlled trial

Background: Walking requires gait adjustments in order to walk safely in continually changing environments. Gait adaptability is reduced in older adults, and (near) falls, fall-related hip fractures and fear of falling are common in this population. Most falls occur due to inaccurate foot placement relative to environmental hazards, such as obstacles. The C-Mill is an innovative, instrumented treadmill on which visual context (e. g., obstacles) is projected. The C-Mill is well suited to train foot positioning relative to environmental properties while concurrently utilizing the high-intensity practice benefits associated with conventional treadmill training. The present protocol was designed to examine the efficacy of C-Mill gait adaptability treadmill training for improving walking ability and reducing fall incidence and fear of falling relative to conventional treadmill training and usual care. We hypothesize that C-Mill gait adaptability treadmill training and conventional treadmill training result in better walking ability than usual care due to the enhanced training intensity, with superior effects for C-Mill gait adaptability treadmill training on gait adaptability aspects of walking given the concurrent focus on practicing step adjustments. Methods/design: The protocol describes a parallel group, single-blind, superiority randomized controlled trial with pre-tests, post-tests, retention-tests and follow-up. Hundred-twenty-six older adults with a recent fall-related hip fracture will be recruited from inpatient rehabilitation care and allocated to six weeks of C-Mill gait adaptability treadmill training (high-intensity, adaptive stepping), conventional treadmill training (high-intensity, repetitive stepping) or usual care physical therapy using block randomization, with allocation concealment by opaque sequentially numbered envelopes. Only data collectors are blind to group allocation. Study parameters related to walking ability will be assessed as primary outcome pre-training, post-training, after 4 weeks retention and 12 months follow-up. Secondary study parameters are measures related to fall incidence, fear of falling and general health. Discussion: The study will shed light on the relative importance of adaptive versus repetitive stepping and practice intensity for effective intervention programs directed at improving walking ability and reducing fall risk and fear of falling in older adults with a recent fall-related hip fracture, which may help reduce future fall-related health-care costs