Screening for Meares–Irlen sensitivity in adults: can assessment methods predict changes in reading speed?

Two methods of assessing candidates for coloured overlays were compared with the aim of determining which method had the most practical utility. A total of 58 adults were assessed as potential candidates for coloured overlays, using two methods; a questionnaire, which identified self-reported previous symptoms, and a measure of perceptual distortions immediately prior to testing. Participants were classified as normal, Meares-Irlen sensitive, and borderline sensitive. Reading speed was measured with and without coloured overlays, using the Wilkins Rate of Reading Test and the change in speed was calculated. Participants classified as normal did not show any significant benefit from reading with an overlay. In contrast, a significant reading advantage was found for the borderline and Meares-Irlen participants. Current symptom rating was found to be a significant predictor of the change in reading speed, however the previous symptom rating was not found to be a reliable predictor. These data indicate that the assessment of perceptual distortions immediately prior to measuring colour preference and reading speed is the most meaningful method of assessing pattern glare and determining the utility of coloured overlays.     

Identification of the pre-proliferative diabetic eye

The rationale for early identification of the stage of diabetic retinopathy immediately preceding development of fibrovascular proliferation is that early diagnosis affords the opportunity to treat by photocoagulation or other methods at the appropriate stage of retinal disease. Aids to identification include: venous abnormalities, intraretinal microvascular abnormalities, "cotton-wool" spots and fluorescein angiographic evidence of capillary non-perfusion. Although no one of these fundus changes is specific for the pre-proliferative stage of diabetic retinopathy, the presence of more than one of these findings increases the risk of subsequent fibrovascular proliferation. The development of frank proliferation frequently occurs within two years of first appearance of the preproliferative stage.     

Spread of bovine herpesvirus type 5 (BHV-5) in the rabbit brain after intranasal inoculation

Following intranasal inoculation of wild-type BHV-5 in rabbits, we studied the sequential transneuronal passage of the virus in the CNS by immunocytochemistry, histopathology, and virus isolation. At 4 and 6 days postinfection (d.p.i.), rabbits had no or mild neurological signs, and virus was isolated only from the olfactory bulbs. At 8 and 9 d.p.i., infected rabbits had severe neurological signs, and virus could be isolated from multiple regions of the brain segments. In these rabbits, high titers of virus were consistently present in the anterior and posterior cortices, including frontal, piriform/entorhinal, temporal, parietal, and occipital cortices, the hippocampus and the amygdala. Virus was isolated occasionally from the midbrain/diencephalon and pons/medulla. Virus was not isolated from the cerebellum and trigeminal ganglion of rabbits examined from 2-12 d.p.i. Immunocytochemistry revealed virus-specific antigens at 4 d.p.i. within the glomerular layer, external plexiform layer, and mitral cell layer of the main olfactory bulb. At 6 d.p.i., virus-specific antigens were also present within the inner granular layer of the main olfactory bulb. At 8 and 9 d.p.i., widespread BHV-5-specific staining occurred in the areas of the brain connected to the main olfactory bulb, including the frontal/cingulate cortex, anterior olfactory nucleus, lateral olfactory tubercle, piriform/entorhinal cortex, hippocampus, amygdala, dorsal raphe, and locus coeruleus. In the trigeminal ganglion, specific staining was detected within a few neurons at 2,4, 6, 8 d.p.i. However, further spread of the virus along the trigeminal pathway was not evident. These data indicate that BHV-5 replicates and spreads preferentially in the olfactory pathway following intranasal instillation and that this viral spread correlated with the severity of neurological symptoms and histopathological lesions.     

Prospective technical validation and assessment of intra-tumour heterogeneity of a low density array hypoxia gene profile in head and neck squamous cell carcinoma

Background and purposeTumour hypoxia is associated with a poor prognosis in head and neck squamous cell carcinoma (HNSCC), however there is no accepted method for assessing hypoxia clinically. We aimed to conduct a technical validation of a hypoxia gene expression signature using the TaqMan Low Density Array (TLDA) platform to investigate if this approach reliably identified hypoxic tumours.Materials and methodsTumour samples (n = 201) from 80 HNSCC patients were collected prospectively from two centres. Fifty-three patients received pimonidazole prior to surgery. TaqMan Low Density Array-Hypoxia Scores (TLDA-HS) were obtained by quantitative real-time PCR (qPCR) using a 25-gene signature and customised TLDA cards. Assay performance was assessed as coefficient of variation (CoV).ResultsThe assay was sensitive with linear reaction efficiencies across a 4log₁₀ range of inputted cDNA (0.001–10 ng/μl). Intra- (CoV = 6.9%) and inter- (CoV = 2.0%) assay reproducibility were excellent. Intra-tumour heterogeneity was lower for TLDA-HS (23.2%) than for pimonidazole (67.2%) or single gene measurements of CA9 (62.2%), VEGFA (45.0%) or HIG2 (39.4%). TLDA-HS in HNSCC cell lines increased with decreasing pO₂. TLDA-HS correlated with Affymetrix U133 Plus 2.0 microarray HS (p < 0.01) and positive pimonidazole scores (p = 0.005).ConclusionsGene expression measurements of hypoxia using a 25-gene signature and TLDA cards are sensitive, reproducible and associated with lower intra-tumour heterogeneity than assaying individual genes or pimonidazole binding. The approach is suitable for further assessment of prognostic and predictive capability in clinical trial material.     

Working memory as a moderator of impulsivity and alcohol involvement: Testing the cognitive-motivational theory of alcohol use with prospective and working memory updating data

Research consistently shows that individuals high in impulsivity are at increased risk for excessive alcohol use and alcohol-related problems including alcohol use disorders (AUDs). Recent theorizing posits that working memory (WM) ability might moderate this association, but extant studies have suffered from methodological shortcomings, particularly mischaracterizing WM as a single, unitary construct and using only cross-sectional designs. This paper reports two studies that attempted to replicate and extend previous investigations of the relationship between WM, impulsivity, and alcohol involvement using two independent samples. Study 1 used a large (N = 489 at baseline), prospective cohort of college students at high and low risk for AUD to investigate interactions between WM capacity and impulsivity on cross-sectional and prospective alcohol involvement. Study 2 used a large (N = 420), cross-sectional sample of participants in an alcohol challenge study to investigate similar interactions between WM updating and impulsivity on recent alcohol involvement. Whereas Study 1 found that WM capacity moderates the relationship between some measures of impulsivity and alcohol involvement, with effects prospectively predicting alcohol involvement for up to three years, Study 2 did not find similar moderation effects when using measures of WM updating. These findings highlight the multifaceted nature of WM, which is often overlooked in the alcohol and impulsivity literature.