Analysis of the judgement bias test for welfare assessment in rats

The identification of cognitive biases has become an important measure of animal affective (emotional) state, and therefore, animal welfare. Negative cognitive biases can be evidenced by animals preferentially processing novel information pessimistically and judgement-bias testing is the commonplace methodology to detect such biases. As the use of judgement-biases has increased in the scientific community, concerns regarding the efficacy and repeatability of these methods has been questioned. This body of work began with the aim of identifying the effects that a common housing procedure would have on judgement bias expression in rats. However, after analysis of data multiple confounding factors were identified that were argued to have seriously impacted on validity of methods employed. Therefore, investigations in this thesis focussed on a commonly employed, active choice judgement bias test as used in rats. Confounding factors that have received limited attention in the literature have been applied to these studies. These factors include phase of oestrous, social status, housing density and space allocation. It was aimed to investigate if the judgement bias test employed can find practical utility in welfare assessment of the laboratory rat. In addition to investigating the effects of external factors on animal expression to the judgement bias test, investigations into the mechanistic nature of the test were also undertaken. Extinction of learning, which results in the animals failing to perform the test parameters, is a commonly reported limitation of these methods, as are significantly long training times often associated with their use. These two factors were also identified and studied in this thesis, with the aim of improving practicality of the judgement bias discrimination task (JBT) to allow its employment in applied animal husbandry situations. This thesis has identified many potentially confounding concerns of judgement bias testing in rats. Whilst evidence suggests that the JBT may never find practical use as a welfare assessment technique, it remains an extremely important indicator of animal affect. Improved understanding of these confounding factors will increase validity of the JBT as a tool for detection of affective state.Thesis (Ph.D.) -- University of Adelaide, School of Animal and Veterinary Sciences, 201

Attention deficits after incident stroke in the acute period: Frequency across types of attention and relationships to patient characteristics and functional outcomes

Background: Attention deficits are common post stroke and result in poorer functional outcomes. This study examined the frequency of attention deficits after incident stroke and their correlates. Method: Attention of 94 stroke survivors was assessed using the Bells test, Trails Making Test A/B, 2.4- and 2.0-second trials of the Paced Auditory Serial Addition Test (PASAT), and Integrated Auditory Visual Continuous Performance Test (IVA-CPT) within 3 weeks post stroke. Wider functioning was assessed using the Medical Short Form-36 (SF-36) Physical and Mental Component Summary scores (PCS and MCS), London Handicap Scale, Modified Rankin Scale, General Health Questionnaire-28, and Cognitive Failures Questionnaire (CFQ). Results: Most participants were impaired or very impaired on the IVA-CPT (z scores > 3 SDs below normative mean) but not other attention measures. Functional independence and cognitive screening test (Mini-Mental State Examination) performance were significantly related to IVA-CPT, Trails A/B, and Bells tests but not PASAT. Better performance across the Bells test was related to better SF-36 PCS, whereas Trails A and the PASAT were related to SF-36 MCS. Better CFQ naming was related to Trails B, whereas worse CFQ memory was related to better PASAT performance. Conclusion: Attention deficits are common post stroke, though frequency varies widely across the forms of attention assessed, with tests of neglect and speeded attention tasks being linked to quality of life. This variability of performance and linking to wider outcomes suggests the need for comprehensive assessment of attention and that attention is a viable target for rehabilitative efforts

The empirical replicability of task-based fMRI as a function of sample size

Replicating results (i.e. obtaining consistent results using a new independent dataset) is an essential part of good science. As replicability has consequences for theories derived from empirical studies, it is of utmost importance to better understand the underlying mechanisms influencing it. A popular tool for non-invasive neuroimaging studies is functional magnetic resonance imaging (fMRI). While the effect of underpowered studies is well documented, the empirical assessment of the interplay between sample size and replicability of results for task-based fMRI studies remains limited. In this work, we extend existing work on this assessment in two ways. Firstly, we use a large database of 1400 subjects performing four types of tasks from the IMAGEN project to subsample a series of independent samples of increasing size. Secondly, replicability is evaluated using a multi-dimensional framework consisting of 3 different measures: (un)conditional test-retest reliability, coherence and stability. We demonstrate not only a positive effect of sample size, but also a trade-off between spatial resolution and replicability. When replicability is assessed voxelwise or when observing small areas of activation, a larger sample size than typically used in fMRI is required to replicate results. On the other hand, when focussing on clusters of voxels, we observe a higher replicability. In addition, we observe variability in the size of clusters of activation between experimental paradigms or contrasts of parameter estimates within these

Predatory journals and their practices present a conundrum for systematic reviewers and evidence synthesisers of health research: A qualitative descriptive study

Predatory journals are a blemish on scholarly publishing and academia and the studies published within them are more likely to contain data that is false. The inclusion of studies from predatory journals in evidence syntheses is potentially problematic due to this propensity for false data to be included. To date, there has been little exploration of the opinions and experiences of evidence synthesisers when dealing with predatory journals in the conduct of their evidence synthesis. In this paper, the thoughts, opinions, and attitudes of evidence synthesisers towards predatory journals and the inclusion of studies published within these journals in evidence syntheses were sought. Focus groups were held with participants who were experienced evidence synthesisers from JBI (previously the Joanna Briggs Institute) collaboration. Utilising qualitative content analysis, two generic categories were identified: predatory journals within evidence synthesis, and predatory journals within academia. Our findings suggest that evidence synthesisers believe predatory journals are hard to identify and that there is no current consensus on the management of these studies if they have been included in an evidence synthesis. There is a critical need for further research, education, guidance, and development of clear processes to assist evidence synthesisers in the management of studies from predatory journals.</p

Assessing the risk of bias of quantitative analytical studies: introducing the vision for critical appraisal within JBI systematic reviews

A key step in the systematic review process is the assessment of the methodological quality (or risk of bias) of the included studies. At JBI, we have developed several tools to assist with this evaluation. As evidence synthesis methods continue to evolve, it has been necessary to revise and reflect on JBI’s current approach to critical appraisal and to plan a strategy for the future. In this first paper of a series focusing on risk of bias assessment, we introduce our vision for risk of bias assessment for JBI. In future papers in this series, the methodological approach taken for this revision process will be discussed, along with the revised tools and guidance for using these tools

Ground motion prediction at gravitational wave observatories using archival seismic data

Gravitational wave observatories have always been affected by tele-seismic earthquakes leading to a decrease in duty cycle and coincident observation time. In this analysis, we leverage the power of machine learning algorithms and archival seismic data to predict the ground motion and the state of the gravitational wave interferometer during the event of an earthquake. We demonstrate improvement from a factor of 5 to a factor of 2.5 in scatter of the error in the predicted ground velocity over a previous model fitting based approach. The level of accuracy achieved with this scheme makes it possible to switch control configuration during periods of excessive ground motion thus preventing the interferometer from losing lock. To further assess the accuracy and utility of our approach, we use IRIS seismic network data and obtain similar levels of agreement between the estimates and the measured amplitudes. The performance indicates that such an archival or prediction scheme can be extended beyond the realm of gravitational wave detector sites for hazard-based early warning alerts.Comment: 10 pages, 7 figures; matches published versio

Identification of Lineage-Uncommitted, Long-Lived, Label-Retaining Cells in Healthy Human Esophagus and Stomach, and in Metaplastic Esophagus

Background & Aims The existence of slowly cycling, adult stem cells has been challenged by the identification of actively cycling cells. We investigated the existence of uncommitted, slowly cycling cells by tracking 5-iodo-2'-deoxyuridine (IdU) label-retaining cells (LRCs) in normal esophagus, Barrett's esophagus (BE), esophageal dysplasia, adenocarcinoma, and healthy stomach tissues from patients. Methods Four patients (3 undergoing esophagectomy, 1 undergoing esophageal endoscopic mucosal resection for dysplasia and an esophagectomy for esophageal adenocarcinoma) received intravenous infusion of IdU (200 mg/m2 body surface area; maximum dose, 400 mg) over a 30-minute period; the IdU had a circulation half-life of 8 hours. Tissues were collected at 7, 11, 29, and 67 days after infusion, from regions of healthy esophagus, BE, dysplasia, adenocarcinoma, and healthy stomach; they were analyzed by in situ hybridization, flow cytometry, and immunohistochemical analyses. Results No LRCs were found in dysplasias or adenocarcinomas, but there were significant numbers of LRCs in the base of glands from BE tissue, in the papillae of the basal layer of the esophageal squamous epithelium, and in the neck/isthmus region of healthy stomach. These cells cycled slowly because IdU was retained for at least 67 days and co-labeling with Ki-67 was infrequent. In glands from BE tissues, most cells did not express defensin-5, Muc-2, or chromogranin A, indicating that they were not lineage committed. Some cells labeled for endocrine markers and IdU at 67 days; these cells represented a small population (<0.1%) of epithelial cells at this time point. The epithelial turnover time of the healthy esophageal mucosa was approximately 11 days (twice that of the intestine). Conclusions LRCs of human esophagus and stomach have many features of stem cells (long lived, slow cycling, uncommitted, and multipotent), and can be found in a recognized stem cell niche. Further analyses of these cells, in healthy and metaplastic epithelia, is required