The prognosis of allocentric and egocentric neglect : evidence from clinical scans

We contrasted the neuroanatomical substrates of sub-acute and chronic visuospatial deficits associated with different aspects of unilateral neglect using computed tomography scans acquired as part of routine clinical diagnosis. Voxel-wise statistical analyses were conducted on a group of 160 stroke patients scanned at a sub-acute stage. Lesion-deficit relationships were assessed across the whole brain, separately for grey and white matter. We assessed lesions that were associated with behavioural performance (i) at a sub-acute stage (within 3 months of the stroke) and (ii) at a chronic stage (after 9 months post stroke). Allocentric and egocentric neglect symptoms at the sub-acute stage were associated with lesions to dissociated regions within the frontal lobe, amongst other regions. However the frontal lesions were not associated with neglect at the chronic stage. On the other hand, lesions in the angular gyrus were associated with persistent allocentric neglect. In contrast, lesions within the superior temporal gyrus extending into the supramarginal gyrus, as well as lesions within the basal ganglia and insula, were associated with persistent egocentric neglect. Damage within the temporo-parietal junction was associated with both types of neglect at the sub-acute stage and 9 months later. Furthermore, white matter disconnections resulting from damage along the superior longitudinal fasciculus were associated with both types of neglect and critically related to both sub-acute and chronic deficits. Finally, there was a significant difference in the lesion volume between patients who recovered from neglect and patients with chronic deficits. The findings presented provide evidence that (i) the lesion location and lesion size can be used to successfully predict the outcome of neglect based on clinical CT scans, (ii) lesion location alone can serve as a critical predictor for persistent neglect symptoms, (iii) wide spread lesions are associated with neglect symptoms at the sub-acute stage but only some of these are critical for predicting whether neglect will become a chronic disorder and (iv) the severity of behavioural symptoms can be a useful predictor of recovery in the absence of neuroimaging findings on clinical scans. We discuss the implications for understanding the symptoms of the neglect syndrome, the recovery of function and the use of clinical scans to predict outcome

Phase II Trial of Concurrent Sunitinib and Image-Guided Radiotherapy for Oligometastases

BACKGROUND: Preclinical data suggest that sunitinib enhances the efficacy of radiotherapy. We tested the combination of sunitinib and hypofractionated image-guided radiotherapy (IGRT) in a cohort of patients with historically incurable distant metastases. METHODS: Twenty five patients with oligometastases, defined as 1-5 sites of active disease on whole body imaging, were enrolled in a phase II trial from 2/08 to 9/10. The most common tumor types treated were head and neck, liver, lung, kidney and prostate cancers. Patients were treated with the recommended phase II dose of 37.5 mg daily sunitinib (days 1-28) and IGRT 50 Gy (days 8-12 and 15-19). Maintenance sunitinib was used in 33% of patients. Median follow up was 17.5 months (range, 0.7 to 37.4 months). RESULTS: The 18-month local control, distant control, progression-free survival (PFS) and overall survival (OS) were 75%, 52%, 56% and 71%, respectively. At last follow-up, 11 (44%) patients were alive without evidence of disease, 7 (28%) were alive with distant metastases, 3 (12%) were dead from distant metastases, 3 (12%) were dead from comorbid illness, and 1 (4%) was dead from treatment-related toxicities. The incidence of acute grade ≥ 3 toxicities was 28%, most commonly myelosuppression, bleeding and abnormal liver function tests. CONCLUSIONS: Concurrent sunitinib and IGRT achieves major clinical responses in a subset of patients with oligometastases. TRIAL REGISTRATION: ClinicalTrials.gov NCT00463060

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations

Grey matter substrates of sub-acute allocentric vs. egocentric neglect (VBM: Analysis 1).

<p>Abbreviations: IFG, inferior frontal gyrus; IPL, inferior parietal lobule; ITG, inferior temporal gyrus; MFG, middle frontal gyrus; MTG, middle temporal gyrus; SFS, superior frontal sulcus; SMG, supramarginal gyrus; STG, superior temporal gyrus; STS, superior temporal sulcus; TPJ, temporo-parietal junction; VBM, voxel-based morphometry.</p>*<p>To further verify the observed dissociations between allocentric and egocentric neglect, we report here the results (F-tests) of the interaction analyses between allocentric and egocentric neglect, these analyses directly test whether brain-behaviour correlations observed for allocnetric neglect are significantly higher than those observed for egocentric neglect, and vice versa.</p

White matter substrates of chronic allocentric vs. egocentric neglect (VBM: Analysis 2).

<p>Abbreviations: IFOF, inferior fronto-occipital fasciculus; ILF, inferior longitudinal fasciculus; post, posterior; SLF, superior longitudinal fasciculus; TR, thalamic radiation; UNC, uncinate fasciculus; VBM, voxel-based morphometry.</p>*<p>To further verify the observed dissociations between allocentric and egocentric neglect, we report here the results (F-tests) of the interaction analyses between allocentric and egocentric neglect, these analyses directly test whether brain-behaviour correlations observed for allocentric neglect are significantly higher than those observed for egocentric neglect, and vice versa.</p

Voxel-wise statistical analysis of grey matter damage: allocentric vs. egocentric neglect at the chronic phase following stroke.

<p>VBM results showing voxels corresponding to grey matter damage in (<b>A</b>) left allocentric, (<b>B</b>) left egocentric and (<b>C</b>) both forms of neglect (conjunction analysis). Please note that in <b>A</b>, <b>B</b> and <b>C</b> the lesioned areas are coloured according to their significance level in the VBM analysis, where a brighter colour indicates a higher t-value. The numbers in brackets indicate the peak MNI coordinates. (<b>D</b>) To further illustrate the relationship between grey matter loss and any associated allocentric or egocentric symptoms at the chronic phase, all clusters identified by VBM as described above are plotted on a rendered brain. AG, angular gyrus; BG, basal ganglia; INS, insula; SMG, supramarginal gyrus; TPJ, temporal-parietal junction.</p

Patient details: clinical and demographic data.

*<p>Overall lesion size (volume) in the neglect group was not significantly larger than in the group without neglect symptoms (t(158) = 1.7, p>0.5);</p>**<p>For the acute/subacute phase the number of days indicate stroke to test (initial BUCS) interval and at the chronic phase number of days indicate the interval between initial BUCS test and follow up BUCS;</p>***<p>Patient who at sub-acute phase following stroke showed any type of neglect symptoms including egocentric and allocentric neglect for either left or right side of space; ACT, Apple Cancellation task; the maximum achievable score in the Apple Cancellation task is 50 (ACT accuracy). The cut-off for total numbers of target (full apples) omissions i.e. accuracy score is 40/50. Egocentric neglect is determined by whether patients miss targets (complete apples) on the left or right side of the page (asymmetry score calculated based on left- vs. right-side errors, ACT/AFA asymmetry score for full apples indicating either left or right deficits). Allocentric neglect is determined by whether patients make false positive responses by cancelling incomplete apples (distractors) where the gap is on either the right or left side of each apple, irrespective of the position of the (incomplete) apple on the page (asymmetry score calculated based on left- vs. right-side errors, AIncA asymmetry score for incomplete apples); BL, bleed/hemorrhagic stroke; F, female; ISCH, ischemic stroke L, left; M, male; max/range, maximum achievable score and range of scores within the group of patients; Orient1, orientation measure assessing personal information; Orient2, orientation measure assessing time and space awareness; R, right; SD; standard deviation; VE, visual extinction test, the task consists of 4 unilateral left, 4 unilateral right and 8 bilateral trials, asymmetry score calculated based on left- vs. right-side misses.</p

Example of the Apples cancellation task (A) used to simultaneously test for allocentric and egocentric symptoms.

<p>In this test patients are asked to cross out all the full apples. Egocentric neglect is measured by whether patients miss targets (full apples) predominantly on one side of the page and allocentric neglect is measured by whether patients make false positive responses by cancelling predominantly left or right distracters (according to the position of the gap defining a distracter; for full details and scoring see the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0047821#s2" target="_blank">Methods</a> section). (<b>B</b>) and (<b>C</b>) present scatterplots of egocentric neglect errors against allocentric neglect errors at the sub-acute (<b>B</b>) and chronic (<b>C</b>) phases following stroke. There was significant correlation between allocentric and egocentric neglect scores at either phase. Please note that the middle grey dot corresponds to results for non-impaired patients. (<b>D</b>) Behavioural results – the number of patients with egocentric and allocentric neglect symptoms at the sub-acute and chronic phase following stroke.</p

Voxel-wise statistical analysis of white matter damage: allocentric vs. egocentric neglect at the chronic phase following stroke.

<p>VBM results showing voxels corresponding to white matter damage in (<b>A</b>) left allocentric, (<b>B</b>) left egocentric neglect and (<b>C</b>) both forms of neglect (conjunction analysis). Please note that in <b>A, B</b> and <b>C</b> the lesioned areas are coloured according to their significance level in the VBM analysis, where a brighter colour indicates a higher t-value. The numbers in brackets indicate the peak MNI coordinates.</p