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Neurocognitive and functional neuroimaging studies point to frontal lobe abnormalities in schizophrenia. Molecular and behavioural genetic studies suggest that the frontal lobe is under significant genetic influence. We carried out structural magnetic resonance imaging (MRI) of the frontal lobe in monozygotic (MZ) twins concordant or discordant for schizophrenia and healthy MZ control twins.
The sample comprised 21 concordant pairs, 17 discordant affected and 18 discordant unaffected twins from 19 discordant pairs, and 27 control pairs. Groups were matched on sociodemographic variables. Patient groups (concordant, discordant affected) did not differ on clinical variables. Volumes of superior, middle, inferior and orbital frontal gyri were calculated using the Cavalieri principle on the basis of manual tracing of anatomic boundaries. Group differences were investigated covarying for whole-brain volume, gender and age.
Results for superior frontal gyrus showed that twins with schizophrenia (i.e. concordant twins and discordant affected twins) had reduced volume compared to twins without schizophrenia (i.e. discordant unaffected and control twins), indicating an effect of illness. For middle and orbital frontal gyrus, concordant (but not discordant affected) twins differed from non-schizophrenic twins. There were no group differences in inferior frontal gyrus volume.
These findings suggest that volume reductions in the superior frontal gyrus are associated with a diagnosis of schizophrenia (in the presence or absence of a co-twin with schizophrenia). On the other hand, volume reductions in middle and orbital frontal gyri are seen only in concordant pairs, perhaps reflecting the increased genetic vulnerability in this group.
OBJECTIVES/SPECIFIC AIMS: The objective of this study is to use machine Learning techniques to generate maps of epithelium and lumen density in MRI space. METHODS/STUDY POPULATION: Methods: We prospectively recruited 39 patients undergoing prostatectomy for this institutional review board (IRB) approved study. Patients underwent MP-MRI before prostatectomy on a 3T field strength MRI scanner (General Electric, Waukesha, WI, USA) using an endorectal coil. MP-MRI included field-of-view optimized and constrained undistorted single shot (FOCUS) diffusion weighted imaging with 10 b-values (b=0, 10, 25, 50, 80, 100, 200, 500, 1000, and 2000), dynamic contrast enhanced imaging, and T2-weighted imaging. T2 weighted images were intensity normalized and apparent diffusion coefficient maps were calculated. The dynamic contrast enhanced data was used to calculate the percent change in signal intensity before and after contrast injection. All images were aligned to the T2 weighted image. Robotic prostatectomy was performed 2 weeks after image acquisition. Prostate samples were sliced using a 3D printed slicing jig matching the slice profile of the T2 weighted image. Whole mount samples at 10 μm thickness were taken, hematoxylin and eosin stained, digitized, and annotated by a board certified pathologist. A total of 210 slides were included in this study. Lumen and epithelium were automatically segmented using a custom algorithm written in MATLAB. The algorithm was validated by comparing manual to automatic segmentation on 18 samples. Slides were aligned with the T2 weighted image using a nonlinear control point warping technique. Lumen and epithelium density and the expert annotation were subsequently transformed into MRI space. Co-registration was validated by applying a known warp to tumor masks noted by the pathologist and control point warping the whole mount slide to match the transform. Overlap was measured using a DICE coefficient. A learning curve was generated to determine the optimal number of patients to train the algorithm on. A PLS algorithm was trained on 150 random permutations of patients incrementing from 1 to 29 patients. Slides were stratified such that all slides from a single patient were in the same cohort. Three cohorts were generated, with tumor burden balanced across all cohort. A PLS algorithm was trained on 2 independent training sets (cohorts 1 and 2) and applied to cohort 3. The input vector consisted of MRI values and the target variable was lumen and epithelium density. The algorithm was trained lesion-wise. Trained PiCT models were applied to the test cohort voxel-wise to generate 2 new image contrasts. Mean lesion values were compared between high grade, low grade, and healthy tissue using an ANOVA. An ROC analysis was performed lesion-wise on the test set. RESULTS/ANTICIPATED RESULTS: Results: The segmentation accuracy validation revealed R=0.99 and R=0.72 (p<0.001) for lumen and epithelium, respectively. The co-registration accuracy revealed a 94.5% overlap. The learning curve stabilized at 10 patients with a root mean square error of 0.14, thus the size of the 2 independent training cohorts was set to 10, leaving 19 for the test cohort. DISCUSSION/SIGNIFICANCE OF IMPACT: We present a technique for combining radiology and pathology with machine learning for generating predictive cytological topography (PiCT) maps of cellularity and lumen density prostate. The voxel-wise approach to mapping cellular features generates 2 new interpretable image contrasts, which can potentially increase confidence in diagnosis or guide biopsy and radiation treatment.
Staff training in positive behaviour support (PBS) is a widespread treatment approach for challenging behaviour in adults with intellectual disability.
To evaluate whether such training is clinically effective in reducing challenging behaviour during routine care (trial registration: NCT01680276).
We carried out a multicentre, cluster randomised controlled trial involving 23 community intellectual disability services in England, randomly allocated to manual-assisted staff training in PBS (n = 11) or treatment as usual (TAU, n = 12). Data were collected from 246 adult participants.
No treatment effects were found for the primary outcome (challenging behaviour over 12 months, adjusted mean difference = −2.14, 95% CI: −8.79, 4.51) or secondary outcomes.
Staff training in PBS, as applied in this study, did not reduce challenging behaviour. Further research should tackle implementation issues and endeavour to identify other interventions that can reduce challenging behaviour.
In the context of an austere financial climate, local health care budget holders are increasingly expected to make and enact decisions to decommission (reduce or stop providing) services. However, little is currently known about the experiences of those seeking to decommission. This paper presents the first national study of decommissioning in the English National Health Service drawing on multiple methods, including: an interview-based review of the contemporary policy landscape of health care decommissioning; a national online survey of commissioners of health care services responsible for managing and enacting budget allocation decisions locally; and illustrative vignettes provided by those who have led decommissioning activities. Findings are presented and discussed in relation to four themes: national-local relationships; organisational capacity and resources for decommissioning; the extent and nature of decommissioning; and intended outcomes of decommissioning. Whilst it is unlikely that local commissioners will be able to ‘successfully’ implement decommissioning decisions unless aspects of engagement, local context and outcomes are addressed, it remains unclear what ‘success’ looks like in terms of a decommissioning process.
We describe the design and performance of the Engineering Development Array, which is a low-frequency radio telescope comprising 256 dual-polarisation dipole antennas working as a phased array. The Engineering Development Array was conceived of, developed, and deployed in just 18 months via re-use of Square Kilometre Array precursor technology and expertise, specifically from the Murchison Widefield Array radio telescope. Using drift scans and a model for the sky brightness temperature at low frequencies, we have derived the Engineering Development Array’s receiver temperature as a function of frequency. The Engineering Development Array is shown to be sky-noise limited over most of the frequency range measured between 60 and 240 MHz. By using the Engineering Development Array in interferometric mode with the Murchison Widefield Array, we used calibrated visibilities to measure the absolute sensitivity of the array. The measured array sensitivity matches very well with a model based on the array layout and measured receiver temperature. The results demonstrate the practicality and feasibility of using Murchison Widefield Array-style precursor technology for Square Kilometre Array-scale stations. The modular architecture of the Engineering Development Array allows upgrades to the array to be rolled out in a staged approach. Future improvements to the Engineering Development Array include replacing the second stage beamformer with a fully digital system, and to transition to using RF-over-fibre for the signal output from first stage beamformers.
To investigate the feasibility of a national audit of epistaxis management led and delivered by a multi-region trainee collaborative using a web-based interface to capture patient data.
Six trainee collaboratives across England nominated one site each and worked together to carry out this pilot. An encrypted data capture tool was adapted and installed within the infrastructure of a university secure server. Site-lead feedback was assessed through questionnaires.
Sixty-three patients with epistaxis were admitted over a two-week period. Site leads reported an average of 5 minutes to complete questionnaires and described the tool as easy to use. Data quality was high, with little missing data. Site-lead feedback showed high satisfaction ratings for the project (mean, 4.83 out of 5).
This pilot showed that trainee collaboratives can work together to deliver an audit using an encrypted data capture tool cost-effectively, whilst maintaining the highest levels of data quality.