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Burkitt Lymphoma (BL) is a highly treatable cancer. However, delayed diagnosis of BL contributes to high mortality in BL endemic regions of Africa. Lack of enough pathologists in the region is a major reason for delayed diagnosis. The work described in this paper is a proof-of-concept study to develop a targeted, open access AI tool for screening of histopathology slides in suspected BL cases. Slides were obtained from a total of 90 BL patients. 70 Tonsillectomy samples were used as controls. We fine-tuned 6 pre-trained models and evaluated the performance of all 6 models across different configurations. An ensemble-based consensus approach ensured a balanced and robust classification. The tool applies novel features to BL diagnosis including use of multiple image magnifications, thus enabling use of different magnifications of images based on the microscope/scanner available in remote clinics, composite scoring of multiple models and utilizing MIL with weak labeling and image augmentation, enabling use of relatively low sample size to achieve good performance on the inference set. The open access model allows free access to the AI tool from anywhere with an internet connection. The ultimate aim of this work is making pathology services accessible, efficient and timely in remote clinics in regions where BL is endemic. New generation of low-cost slide scanners/microscopes is expected to make slide images available immediately for the AI tool for screening and thus accelerate diagnosis by pathologists available locally or online.

Objectives: To investigate the timeframe prior to symptom onset when cortico-basal ganglia white matter (white matter) loss begins in premanifest Huntington’s disease (preHD), and which striatal and thalamic sub-region white matter tracts are most vulnerable. Methods: We performed fixel-based analysis, which allows resolution of crossing white matter fibres at the voxel level, on diffusion tractography derived white matter tracts of striatal and thalamic sub-regions in two independent cohorts; TrackON-HD, which included 72 preHD (approx. 11 years before disease onset) and 85 controls imaged at three time points over two years; and the HD young adult study (HD-YAS), which included 54 preHD (approx. 25 years before disease onset) and 53 controls, imaged at one time point. Group differences in fibre density and cross section (FDC) were investigated. Results: We found no significant group differences in cortico-basal ganglia sub-region FDC in preHD gene carriers 25 years before onset. In gene carriers 11 years before onset, there were reductions in striatal (limbic and caudal motor) and thalamic (premotor, motor and sensory) FDC at baseline, with no significant change over 2 years. Caudal motor-striatal, pre-motor-thalamic, and primary motor-thalamic FDC at baseline, showed significant correlations with the Unified Huntington’s disease rating scale (UHDRS) total motor score (TMS). Limbic cortico-striatal FDC and apathy were also significantly correlated. Conclusions: Our findings suggest that limbic and motor white matter tracts to the striatum and thalamus are most susceptible to early degeneration in HD but that approximately 25 years from onset, these tracts appear preserved. These findings may have importance in determining the optimum time to initiate future disease modifying therapies in HD.

Background: Pathological processes in Huntington's disease (HD) begin many years prior to symptom onset. Recently we demonstrated that in a premanifest cohort approximately 24 years from predicted disease onset, despite intact function, there was evidence of subtle neurodegeneration. Here, we use novel imaging techniques to determine whether macro- and micro-structural changes can be detected across the whole-brain in the same cohort. Methods: 62 premanifest HD (PreHD) and 61 controls from the HD Young Adult Study (HD-YAS) were included. Grey and white matter volume, diffusion weighted imaging (DWI) measures of white matter microstructure, multiparametric maps (MPM) estimating myelin and iron content from magnetization transfer (MT), proton density (PD), longitudinal relaxation (R1) and effective transverse relaxation (R2*), and myelin g-ratio were examined. Group differences between PreHD and controls were assessed; associations between all imaging metrics and disease burden and CSF neurofilament light (NfL) were also performed. Volumetric and MPM results were corrected at a cluster-wise value of familywise error (FWE) 0.05. Diffusion and g-ratio results were corrected via threshold-free cluster enhancement at FWE 0.05. Findings: We showed significantly increased R1 and R2*, suggestive of increased iron, in the putamen, globus pallidum and external capsule of PreHD participants. There was also a significant association between lower cortical R2*, suggestive of reduced myelin or iron, and higher CSF NfL in the frontal lobe and the parieto-occipital cortices. No other results were significant at corrected levels. Interpretation: Increased iron in subcortical structures and the surrounding white matter is a feature of very early PreHD. Furthermore, increases in CSF NfL were linked to microstructural changes in the posterior parietal-occipital cortex, a region previously shown to undergo some of the earliest cortical changes in HD. These findings suggest that disease related process are occurring in both subcortical and cortical regions more than 20 years from predicted disease onset.

Psychological therapies, such as CBT, are an important part of the treatment of a range of psychiatric disorders such as depression and anxiety. There is a growing desire to understand the mechanisms by which such therapies effect change so as to improve treatment outcomes. Here we argue that adopting a computational framework may be one such approach. Computational psychiatry aims to provide a theoretical framework for moving between higher-level psychological states (like emotions, decisions and beliefs) to neural circuits, by modeling these constructs mathematically. These models are explicit hypotheses that contain quantifiable variables and parameters derived from each individual's behavior. This approach has two advantages. Firstly, some of the variables described by these models appears to reflect the neural activity of specific brain regions. Secondly, the parameters estimated by these models may offer a unique description of a patient's symptoms which can be used to both tailor therapy and track its effect. In doing so this approach may offer some additional granularity in understanding how psychological therapies, such as CBT, are working. Although this field shows significant promise, we also highlight several of the key hurdles that must first be overcome before clinical translation of computational insights can be realized.

Lightwand-guided intubation is a semi-blind technique that takes advantage of the anterior location of the trachea in relation to the oesophagus. Fibreoptic evaluation of lightwand-guided intubation has revealed a possibility of laryngeal interference and epiglottic distortion. Jaw lift, tongue traction or a combination of both have been used to assist in lightwand-guided intubation. This study fibreoptically evaluates lightwand-guided intubation using jaw lift and combined jaw and tongue traction. Eighty four patients with normal airway undergoing general anaesthesia were studied. This randomised, double blinded, cross over study was done in two phases. First phase - after achieving adequate depth of anaesthesia, a fibrescope was advanced nasally, and lightwand-guided intubation was carried out under direct fibreoptic visualisation with the aid of either jaw lift or combined jaw and tongue traction. Second phase - Extubation followed by reintubation using the other manoeuvre. Interference with laryngeal structures during intubation and position of the epiglottis at the end of intubation were noted. Epiglottic distortion (deviated to one side/infolded into trachea) was observed in 6 patients with jaw lift and 17 patients with combined jaw and tongue traction (P=0.003). Laryngeal interference was significantly higher (P=0.012) with combined manoeuvre (30/78) than with jaw lift alone (9/81). Although lightwand-guided intubation can be performed quickly and easily, interference with laryngeal structures and distortion of the epiglottis can occur. Jaw lift manoeuvre causes less laryngeal interference than combined jaw and tongue traction applied by a single operator.