Biomedical Data Annotation: An OCT Imaging Case Study.

In ophthalmology, optical coherence tomography (OCT) is a widely used imaging modality, allowing visualisation of the structures of the eye with objective and quantitative cross-sectional three-dimensional (3D) volumetric scans. Due to the quantity of data generated from OCT scans and the time taken for an ophthalmologist to inspect for various disease pathology features, automated image analysis in the form of deep neural networks has seen success for the classification and segmentation of OCT layers and quantification of features. However, existing high-performance deep learning approaches rely on huge training datasets with high-quality annotations, which are challenging to obtain in many clinical applications. The collection of annotations from less experienced clinicians has the potential to alleviate time constraints from more senior clinicians, allowing faster data collection of medical image annotations; however, with less experience, there is the possibility of reduced annotation quality. In this study, we evaluate the quality of diabetic macular edema (DME) intraretinal fluid (IRF) biomarker image annotations on OCT B-scans from five clinicians with a range of experience. We also assess the effectiveness of annotating across multiple sessions following a training session led by an expert clinician. Our investigation shows a notable variance in annotation performance, with a correlation that depends on the clinician's experience with OCT image interpretation of DME, and that having multiple annotation sessions has a limited effect on the annotation quality.

Clinical outcomes and safety of Diphoterine® irrigation for chemical eye injury: A single-centre experience in the United Kingdom.

PURPOSE: Diphoterine® is an amphoteric irrigating solution armed with rapid pH-neutralising action. It serves as an effective first-aid treatment for managing chemical burns, including chemical eye injury (CEI). However, its use is not widely adopted in current clinical practice, primarily attributed to limited clinical evidence. This study aims to highlight the experience in using Diphoterine for managing CEI in a UK tertiary referral centre. METHODS: This retrospective case series included all patients who presented with CEI and treated with Diphoterine at the James Cook University Hospital, UK, between April 2018 and February 2020. RESULTS: Seven patients (10 eyes) were included; the mean age was 28.2 ± 17.0 years (ranged, 3-70 years) and 85.7% were male. All patients presented with an alkaline injury with a mean presenting pH of 8.7 ± 0.7 and a median (±interquartile range [IQR]) corrected-distance visual acuity (CDVA) of 0.10 ± 0.28 logMAR. Based on Roper-Hall classification, 90% and 10% of the eyes were of grade-I and -IV CEI, respectively. All eyes received normal saline/water as the first irrigation fluid and Diphoterine as second irrigation fluid. The mean pH improved slightly after first irrigation (8.4 ± 0.7; p = 0.13) and significantly after second irrigation (7.6 ± 0.4; p = 0.001). The volume of irrigation used was significantly less for Diphoterine (520 ± 193 mL) than for normal saline/water (2700 ± 2451 mL; p = 0.016). At final follow-up (median = 5 days), the median CDVA remained stable at 0.10 ± 0.28 logMAR (p = 0.60). One patient developed near-total limbal stem cell deficiency as a complication of grade-IV injury and was awaiting limbal stem cell transplantation at last follow-up. CONCLUSION: This study represents the first case series in the United Kingdom, reporting the use of Diphoterine in managing CEI. The rapid pH-neutralising action of Diphoterine, with less volume required, makes it an ideal initial treatment for efficiently managing adult and paediatric patients with CEI in clinics.

Retention in clinical trials after prison release: results from a clinical trial with incarcerated men with HIV and opioid dependence in Malaysia.

Background: Study retention is a major challenge in HIV clinical trials conducted with persons recruited from correctional facilities. Objective: To examine study retention in a trial of within-prison methadone initiation and a behavioral intervention among incarcerated men with HIV and opioid dependence in Malaysia. Methods: In this 2x2 factorial trial, 296 incarcerated men with HIV and opioid dependence were allocated to (1) an HIV risk reduction intervention, the Holistic Health Recovery Program for Malaysia (HHRP-M), (2) pre-release methadone initiation, (3) both interventions, or (4) standard care (NCT02396979). Here we estimate effects of these interventions on linkage to the study after prison release and completion of post-release study visits. Results: Most participants (68.9%) completed at least one post-release study visit but few (18.6%) completed all 12. HHRP-M was associated with a 13.5% (95% confidence interval (CI): 3.8%, 23.2%) increased probability of completing at least one post-release study visit. Although not associated with initial linkage, methadone treatment was associated with an 11% (95% CI: 2.0%, 20.6%) increased probability of completing all twelve post-release study visits. Being subject to forced relocation outside Kuala Lumpur after prison release decreased retention by 43.3% (95% CI: -51.9%, -34.8%). Conclusion: Retaining study participants in HIV clinical trials following prison release is challenging and potentially related to the broader challenges that participants experience during community reentry. Researchers conducting clinical trials with this population may want to consider methadone and HHRP as means to improve post-release retention, even in clinical trials where these interventions are not being directly evaluated.

Effects of rising amyloidß levels on hippocampal synaptic transmission, microglial response and cognition in APPSwe/PSEN1M146V transgenic mice.

BACKGROUND: Progression of Alzheimer's disease is thought initially to depend on rising amyloidß and its synaptic interactions. Transgenic mice (TASTPM; APPSwe/PSEN1M146V) show altered synaptic transmission, compatible with increased physiological function of amyloidß, before plaques are detected. Recently, the importance of microglia has become apparent in the human disease. Similarly, TASTPM show a close association of plaque load with upregulated microglial genes. METHODS: CA1 synaptic transmission and plasticity were investigated using in vitro electrophysiology. Microglial relationship to plaques was examined with immunohistochemistry. Behaviour was assessed with a forced-alternation T-maze, open field, light/dark box and elevated plus maze. FINDINGS: The most striking finding is the increase in microglial numbers in TASTPM, which, like synaptic changes, begins before plaques are detected. Further increases and a reactive phenotype occur later, concurrent with development of larger plaques. Long-term potentiation is initially enhanced at pre-plaque stages but decrements with the initial appearance of plaques. Finally, despite altered plasticity, TASTPM have little cognitive deficit, even with a heavy plaque load, although they show altered non-cognitive behaviours. INTERPRETATION: The pre-plaque synaptic changes and microglial proliferation are presumably related to low, non-toxic amyloidß levels in the general neuropil and not directly associated with plaques. However, as plaques grow, microglia proliferate further, clustering around plaques and becoming phagocytic. Like in humans, even when plaque load is heavy, without development of neurofibrillary tangles and neurodegeneration, these alterations do not result in cognitive deficits. Behaviours are seen that could be consistent with pre-diagnosis changes in the human condition. FUNDING: GlaxoSmithKline; BBSRC; UCL; ARUK; MRC.

A genome-wide gene-expression analysis and database in transgenic mice during development of amyloid or tau pathology.

We provide microarray data comparing genome-wide differential expression and pathology throughout life in four lines of "amyloid" transgenic mice (mutant human APP, PSEN1, or APP/PSEN1) and "TAU" transgenic mice (mutant human MAPT gene). Microarray data were validated by qPCR and by comparison to human studies, including genome-wide association study (GWAS) hits. Immune gene expression correlated tightly with plaques whereas synaptic genes correlated negatively with neurofibrillary tangles. Network analysis of immune gene modules revealed six hub genes in hippocampus of amyloid mice, four in common with cortex. The hippocampal network in TAU mice was similar except that Trem2 had hub status only in amyloid mice. The cortical network of TAU mice was entirely different with more hub genes and few in common with the other networks, suggesting reasons for specificity of cortical dysfunction in FTDP17. This Resource opens up many areas for investigation. All data are available and searchable at http://www.mouseac.org.