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Investigating the effects of handedness on the consistency of lateralisation for speech production and semantic processing tasks using functional transcranial Doppler sonography
<p>The left hemisphere is dominant for language in most people, but lateralisation strength varies between different tasks and individuals. A large body of literature has shown that handedness is associated with lateralisation: left handers have weaker language lateralisation on average, and a greater incidence of atypical (right hemisphere) lateralisation; but typically these studies have relied on a single measure of language lateralisation. Here we consider the relationships between lateralisation for two different language tasks. We investigated the influence of handedness on lateralisation using functional transcranial Doppler sonography (fTCD), using an existing dataset (N=151 adults, 21 left handed). We compared a speech production task (word generation) and a semantic association task. We demonstrated stronger left-lateralisation for word generation than semantic association; and a moderate correlation between laterality indices for the two tasks (r=0.59). Laterality indices were stronger for right than left handers, and left handers were more likely than right handers to have atypical (right hemisphere) lateralisation or inconsistent lateralisation between the two tasks. These results add to our knowledge of individual differences in lateralisation, and support the view that language lateralisation is multifactorial rather than unitary.</p>
Detecting Progression of Melanocytic Choroidal Tumors by Sequential Imaging: Is Ultrasonography Necessary?
Purpose: To determine if ultrasonography is necessary to detect progression of choroidal melanocytic tumors undergoing sequential multi-modal imaging with color photography, autofluorescence (AF) and optical coherence tomography (OCT). Methods: All patients with choroidal melanoma undergoing treatment at Moorfields Eye Hospital between January 2016 and March 2020 were reviewed to identify those with treatment deferred by ≥2 months. Tumors that showed progression prior to treatment, defined as an increase in (a) basal dimensions (b) thickness (c) orange pigment and/or (d) sub-retinal fluid, were included. Mushroom shape, Orange pigment, Large size, Enlargement and Sub-retinal fluid (MOLES) scores were assigned to all tumors at earliest date and date of treatment. Results: A total of 99 patients with a mean age of 66 years (range: 26-90) were included. The initial MOLES score was 1 in 2 cases, 2 in 23 cases, and ≥3 in 74 cases. Progression was detected with sequential color photography alone in 100% of MOLES 1/2 and 97% of lesions with a MOLES score of ≥3. When findings on AF and OCT were included, sensitivity for detecting subtle change without ultrasonography improved to 100% for MOLES 3 and 97% for MOLES 4/5. Only one patient included in this study had an isolated increase in thickness that may have been missed had sequential ultrasonography not been performed. Overall, the sensitivity for detecting progression with color photographs alone was 97% (95% CI 93-100%) and increased to 99% (95% CI 97-100%) by including autofluorescence and OCT. Conclusions: Monitoring of choroidal nevi, particularly those classified as MOLES 1 or 2 (i.e., low-risk or high-risk naevi), can be accomplished safely without the need for ultrasonography. The findings of this study may remove barriers to the implementation of tele-oncology clinics for the monitoring of choroidal melanocytic tumors.
© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ. Background: Conjunctival melanoma is the second most common conjunctival malignant tumour after squamous cell carcinoma, usually arising from primary acquired melanosis and less commonly from a conjunctival naevus or de novo. We report four cases of conjunctival melanoma masquerading as ocular surface squamous neoplasia. Methods: Four patients (2 females and 2 males; mean age 60.7 years; range 41-72 years) were referred for suspicious conjunctival lesions. In all cases, the lesions had a perilimbal location, were non-pigmented (cases 1 and 3) or mildly pigmented (cases 2 and 4), had a fleshy (cases 1, 2 and 4) or papillomatous (case 3) appearance and involved the corneal surface. In each case, our main clinical differential diagnosis included conjunctival intraepithelial neoplasia and squamous cell carcinoma. All four patients underwent an excisional biopsy with double freeze-thaw cryotherapy and alcohol keratoepitheliectomy. Results: In all four cases, the histopathological diagnosis was of invasive conjunctival melanoma with extension to the deep surgical margins. Adjuvant therapy consisting of strontium-90 β radiotherapy (all 4 patients) and topical Mitomicyn C (patient 2) was administered. Conclusion: Conjunctival melanoma can clinically resemble ocular surface squamous neoplasia. Clinical impressions therefore need to be confirmed histopathologically.
A blood-based metabolomics test to distinguish relapsing-remitting and secondary progressive multiple sclerosis: addressing practical considerations for clinical application.
The transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive MS (SPMS) represents a huge clinical challenge. We previously demonstrated that serum metabolomics could distinguish RRMS from SPMS with high diagnostic accuracy. As differing sample-handling protocols can affect the blood metabolite profile, it is vital to understand which factors may influence the accuracy of this metabolomics-based test in a clinical setting. Herein, we aim to further validate the high accuracy of this metabolomics test and to determine if this is maintained in a 'real-life' clinical environment. Blood from 31 RRMS and 28 SPMS patients was subjected to different sample-handling protocols representing variations encountered in clinics. The effect of freeze-thaw cycles (0 or 1) and time to erythrocyte removal (30, 120, or 240 min) on the accuracy of the test was investigated. For test development, samples from the optimised protocol (30 min standing time, 0 freeze-thaw) were used, resulting in high diagnostic accuracy (mean ± SD, 91.0 ± 3.0%). This test remained able to discriminate RRMS and SPMS samples that had experienced additional freeze-thaw, and increased standing times of 120 and 240 min with accuracies ranging from 85.5 to 88.0%, because the top discriminatory metabolite biomarkers from the optimised protocol remained discriminatory between RRMS and SPMS despite these sample-handling variations. In conclusion, while strict sample-handling is essential for the development of metabolomics-based blood tests, the results confirmed that the RRMS vs. SPMS test is resistant to sample-handling variations and can distinguish these two MS stages in the clinics.
The role of pontine lesion location in differentiating multiple sclerosis from vascular risk factor-related small vessel disease.
BACKGROUND: Differentiating multiple sclerosis (MS) from vascular risk factor (VRF)-small vessel disease (SVD) can be challenging. OBJECTIVE AND METHODS: In order to determine whether or not pontine lesion location is a useful discriminator of MS and VRF-SVD, we classified pontine lesions on brain magnetic resonance imaging (MRI) as central or peripheral in 93 MS cases without VRF, 108 MS patients with VRF and 43 non-MS cases with VRF. RESULTS: MS without VRF were more likely to have peripheral pons lesions (31.2%, 29/93) than non-MS with VRF (0%, 0/43) (Exp(B) = 29.8; 95% confidence interval (CI) = (1.98, 448.3); p = 0.014) but there were no significant differences regarding central pons lesions between MS without VRF (5.4%, 5/93) and non-MS with VRF patients (16.3%, 7/43) (Exp(B) = 0.89; 95% CI = (0.2, 3.94); p = 0.87). The presence of peripheral pons lesions discriminated between MS and VRF-SVD with 100% (95% CI = (91.8, 100)) specificity. The proportion of peripheral pons lesions in MS with VRF (30.5%, 33/108) was similar to that seen in MS without VRF (31.2%, 29/93, p = 0.99). Central lesions occurred in similar frequency in MS with VRF (8.3%, 9/108) and non-MS with VRF (16.3%, 7/43, p = 0.15). CONCLUSION: Peripheral pons lesion location is a good discriminator of MS from vascular lesions.
Estimates of the prevalence of low back pain (LBP) vary considerably, depending on the data source and the definitions used. The lifetime prevalence for LBP ranges from 49% up to 84% , making it one of the most common medical complaints . The cumulative lifetime prevalence of LBP lasting at least 2 weeks was 16% for individuals aged between 25 and 74 years . Fifty percent of adults have reported experiencing LBP at some point in their life . Approximately 10% of individuals report having had back pain within the previous year, and 6.8% report having LBP at any one point in time [5,28]. The incidence of LBP ranges from 28 to 30 episodes/1000 persons per year , being highest in male patients and in patients between 25 and 64 years of age. © 2008 Springer-Verlag Berlin Heidelberg.
The epidemiology of postoperative rehabilitation after spinal surgery is not well explored. This lack of evidence includes not only the epidemiology but also the efficacy of postoperative rehabilitation after spinal surgery. So far, no comprehensive guidelines about this topic have been published. There is some evidence for the efficacy of postoperative rehabilitation after disc surgery [4, 6, 8, 10, 17, 21, 25]. © 2008 Springer-Verlag Berlin Heidelberg.
Integrating large-scale neuroimaging research datasets: harmonisation of white matter hyperintensity measurements across Whitehall and UK Biobank datasets
<jats:title>ABSTRACT</jats:title><jats:p>Large scale neuroimaging datasets present the possibility of providing normative distributions for a wide variety of neuroimaging markers, which would vastly improve the clinical utility of these measures. However, a major challenge is our current poor ability to integrate measures across different large-scale datasets, due to inconsistencies in imaging and non-imaging measures across the different protocols and populations. Here we explore the harmonisation of white matter hyperintensity (WMH) measures across two major studies of healthy elderly populations, the Whitehall II imaging sub-study and the UK Biobank. We identify pre-processing strategies that maximise the consistency across datasets and utilise multivariate regression to characterise sample differences contributing to study-level differences in WMH variations. We also present a parser to harmonise WMH-relevant non-imaging variables across the two datasets. We show that we can provide highly calibrated WMH measures from these datasets with: (1) the inclusion of a number of specific standardised processing steps; and (2) appropriate modelling of sample differences through the alignment of demographic, cognitive and physiological variables. These results open up a wide range of applications for the study of WMHs and other neuroimaging markers across extensive databases of clinical data.</jats:p><jats:sec><jats:title>HIGHLIGHTS</jats:title><jats:list list-type="bullet"><jats:list-item><jats:p>We harmonised measures of WMHs across two studies on healthy ageing</jats:p></jats:list-item><jats:list-item><jats:p>Specific pre-processing strategies can increase comparability across studies</jats:p></jats:list-item><jats:list-item><jats:p>Modelling of biological differences is crucial to provide calibrated measures</jats:p></jats:list-item></jats:list></jats:sec>
Optogenetic strategies to restore vision in patients blind from end-stage retinal degenerations aim to render remaining retinal neurons light-sensitive. We present an innovative combination of multi-electrode array recordings together with complex pattern-generating light source as a toolset to determine the extent to which neural retinal responses to complex light stimuli can be restored following viral delivery of red-shifted channelrhodopsin in the retinally-degenerate mouse. Our data indicate that retinal output level spatiotemporal response characteristics achieved by optogenetic gene therapy closely parallel those observed for normal mice but equally reveal important limitations, some of which could be mitigated by using bipolar-cell targeted gene-delivery approaches. As clinical trials are commencing, these data provide important new information on the capacity and limitations of channelrhodopsin-based gene therapies. The toolset we established enables comparing optogenetic constructs and stem-cell-based techniques, thereby providing an efficient and sensitive starting point to identify future approaches for vision restoration.
Determinants of Quality of Life in Geographic Atrophy Secondary to Age-Related Macular Degeneration.
Purpose: To longitudinally evaluate vision-related quality of life (VRQoL) in geographic atrophy (GA) secondary to age-related macular degeneration (AMD) and define its relation to visual function and structural biomarkers. Methods: Patients with GA secondary to AMD were recruited in the context of the prospective, non-interventional, natural-history Directional Spread in Geographic-Atrophy study (NCT02051998). Fundus autofluorescence and infrared reflectance images were semi-automatically annotated for GA. Linear mixed-effects models were applied to investigate the association of putative determinants with the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) VRQoL. Results: A total of 87 patients with a mean age ± SD of 77.07 ± 7.49 years were included in the analysis. At baseline, median (IQR) best-corrected visual acuity (BCVA) was 0.3 (0.51) for the better eye and 0.89 (0.76) for the worse eye; 46% of the patients showed binocular and 25.3% monocular non-central GA. The VRQoL composite score was impaired: 69.96 (24.03). Sixty-six patients with a median of 2 (2) follow-up visits after 1.08 (0.78) years were examined longitudinally. Conclusions: Vision-related quality of life is significantly impaired in patients with GA secondary to AMD. The cross-sectional and longitudinal association of VRQoL with visual functional and structural biomarkers supports the validity of the NEI VFQ-25 VRQoL.
Purpose:To describe foveal sparing (FS) in central retinal dystrophies (RD). Methods:Participants for this retrospective study were identified from the retinal dystrophy database of the Department of Ophthalmology at Radboud University Medical Center. FS was defined as an intact foveal structure surrounded by at least 180° of chorioretinal atrophy, and a best-corrected visual acuity (BCVA) of <1.0 logMAR (>20/200 Snellen). Eligible eyes were identified using fundus autofluorescence (FAF) images, and FS was confirmed using near-infrared reflectance (NIR) imaging and spectral-domain optical coherence tomography when available. Clinical and demographic data were extracted from medical records. We performed quantification of FS and chorioretinal atrophic areas using semiautomated software on fundus autofluorescence and NIR images. We calculated the chronologic change using eye-wise linear regression. Results:We identified 36 patients (56 eyes) with FS. RDs included: Stargardt disease (STGD1;20 patients), central areolar choroidal dystrophy (CACD; 7 patients), mitochondrial retinal dystrophy (MRD; 6 patients), pseudo-Stargardt pattern dystrophy (PSPD; 3 patients). Median age at first presentation was 60 (interquartile range [IQR] 54-63) years. Median BCVA at first presentation ranged from 20/25 Snellen in STGD1, to 20/38 Snellen in MRD. Progression of the chorioretinal atrophic area ranged from 0.26 (0.25-0.28) mm/year in PSPD, to 0.14 (0.11-0.22) in CACD. Change in FS area over time was similar between the different dystrophies. Conclusions:The presence of FS in different RDs suggests a disease-independent mechanism that prolongs the survival of the fovea. The associated preservation of BCVA is important for the individual prognosis and has implications for the design of therapeutic trials for RDs.