Spatial cueing deficits in dyslexia reflect generalised difficulties with attentional selection

AbstractTraditionally, explanations of spatial cueing effects posit the operation of orienting mechanisms that act to reposition the spatial locus of attention. This process is often viewed to be analogous to the movement of an attentional ‘spotlight’ across the visual field to the cued region and is thought to occur either in an exogenous or endogenous manner, depending on the nature of the cue. In line with this view, anomalous findings in dyslexic groups using paradigms involving brief peripheral cues have been interpreted as evidence for a particular deficiency with stimulus-driven, exogenous orienting. Here, we demonstrate that an exogenous orienting deficit is an unfeasible explanation of recent findings in which dyslexic individuals fail to derive benefit from peripheral cues indicating the location of a target in a single fixation visual search task. In a series of experiments examining cueing effects in normal readers, we find no evidence to support the operation of an attentional orienting mechanism that is (i) fast but transient; (ii) automatic and involuntary; and (iii) preferentially driven by abrupt luminance transients. Rather, we find that the magnitude of obtained benefits is primarily determined by the informational value of the cue (irrespective of how information is conveyed) and the accessibility of the target representation once the cue had been delivered. In addition, we show that dyslexic individuals’ difficulties with cued search do not reflect problems with detecting and localising the cue, and generalise to different cue types. These results are consistent with a general weakness of attentional selection in dyslexia

Effects of a red background on magnocellular functioning in average and specifically disabled readers

AbstractTwo experiments were conducted using metacontrast masking to examine responses in the magno system of adults, average reading adolescents and adolescents with specific reading disability. In Experiment 1 the effects of a red background field on the metacontrast functions of adult subjects were investigated. Results showed that a red, compared to a photometrically matched white background field, significantly attenuated metacontrast magnitude, supporting the interpretation of metacontrast as due to magno system suppression of parvo system responses. The finding of a red background effect was replicated in Experiment 2 with the two adolescent groups. The metacontrast functions of the adolescent groups also differed significantly, with those with specific reading disability exhibiting weaker metacontrast than the average readers. This result is consistent with a deficit in the magno system of individuals with specific reading disability and indicates the continuation of the deficit beyond childhood

A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective study.

Funder: Victorian Cancer AgencyFunder: NIHR Manchester Biomedical Research CentreFunder: Cancer Research UKFunder: Cancer Council TasmaniaFunder: Instituto de Salud Carlos IIIFunder: Cancer AustraliaFunder: NIHR Oxford Biomedical Research CentreFunder: Fundación Científica de la Asociación Española Contra el CáncerFunder: Cancer Council South AustraliaFunder: Swedish Cancer SocietyFunder: NIHR Cambridge Biomedical Research CentreFunder: Institut Català de la SalutFunder: Cancer Council VictoriaFunder: Prostate Cancer Foundation of AustraliaFunder: National Institutes of HealthBACKGROUND: Lynch syndrome is a rare familial cancer syndrome caused by pathogenic variants in the mismatch repair genes MLH1, MSH2, MSH6, or PMS2, that cause predisposition to various cancers, predominantly colorectal and endometrial cancer. Data are emerging that pathogenic variants in mismatch repair genes increase the risk of early-onset aggressive prostate cancer. The IMPACT study is prospectively assessing prostate-specific antigen (PSA) screening in men with germline mismatch repair pathogenic variants. Here, we report the usefulness of PSA screening, prostate cancer incidence, and tumour characteristics after the first screening round in men with and without these germline pathogenic variants. METHODS: The IMPACT study is an international, prospective study. Men aged 40-69 years without a previous prostate cancer diagnosis and with a known germline pathogenic variant in the MLH1, MSH2, or MSH6 gene, and age-matched male controls who tested negative for a familial pathogenic variant in these genes were recruited from 34 genetic and urology clinics in eight countries, and underwent a baseline PSA screening. Men who had a PSA level higher than 3·0 ng/mL were offered a transrectal, ultrasound-guided, prostate biopsy and a histopathological analysis was done. All participants are undergoing a minimum of 5 years' annual screening. The primary endpoint was to determine the incidence, stage, and pathology of screening-detected prostate cancer in carriers of pathogenic variants compared with non-carrier controls. We used Fisher's exact test to compare the number of cases, cancer incidence, and positive predictive values of the PSA cutoff and biopsy between carriers and non-carriers and the differences between disease types (ie, cancer vs no cancer, clinically significant cancer vs no cancer). We assessed screening outcomes and tumour characteristics by pathogenic variant status. Here we present results from the first round of PSA screening in the IMPACT study. This study is registered with ClinicalTrials.gov, NCT00261456, and is now closed to accrual. FINDINGS: Between Sept 28, 2012, and March 1, 2020, 828 men were recruited (644 carriers of mismatch repair pathogenic variants [204 carriers of MLH1, 305 carriers of MSH2, and 135 carriers of MSH6] and 184 non-carrier controls [65 non-carriers of MLH1, 76 non-carriers of MSH2, and 43 non-carriers of MSH6]), and in order to boost the sample size for the non-carrier control groups, we randomly selected 134 non-carriers from the BRCA1 and BRCA2 cohort of the IMPACT study, who were included in all three non-carrier cohorts. Men were predominantly of European ancestry (899 [93%] of 953 with available data), with a mean age of 52·8 years (SD 8·3). Within the first screening round, 56 (6%) men had a PSA concentration of more than 3·0 ng/mL and 35 (4%) biopsies were done. The overall incidence of prostate cancer was 1·9% (18 of 962; 95% CI 1·1-2·9). The incidence among MSH2 carriers was 4·3% (13 of 305; 95% CI 2·3-7·2), MSH2 non-carrier controls was 0·5% (one of 210; 0·0-2·6), MSH6 carriers was 3·0% (four of 135; 0·8-7·4), and none were detected among the MLH1 carriers, MLH1 non-carrier controls, and MSH6 non-carrier controls. Prostate cancer incidence, using a PSA threshold of higher than 3·0 ng/mL, was higher in MSH2 carriers than in MSH2 non-carrier controls (4·3% vs 0·5%; p=0·011) and MSH6 carriers than MSH6 non-carrier controls (3·0% vs 0%; p=0·034). The overall positive predictive value of biopsy using a PSA threshold of 3·0 ng/mL was 51·4% (95% CI 34·0-68·6), and the overall positive predictive value of a PSA threshold of 3·0 ng/mL was 32·1% (20·3-46·0). INTERPRETATION: After the first screening round, carriers of MSH2 and MSH6 pathogenic variants had a higher incidence of prostate cancer compared with age-matched non-carrier controls. These findings support the use of targeted PSA screening in these men to identify those with clinically significant prostate cancer. Further annual screening rounds will need to confirm these findings. FUNDING: Cancer Research UK, The Ronald and Rita McAulay Foundation, the National Institute for Health Research support to Biomedical Research Centres (The Institute of Cancer Research and Royal Marsden NHS Foundation Trust; Oxford; Manchester and the Cambridge Clinical Research Centre), Mr and Mrs Jack Baker, the Cancer Council of Tasmania, Cancer Australia, Prostate Cancer Foundation of Australia, Cancer Council of Victoria, Cancer Council of South Australia, the Victorian Cancer Agency, Cancer Australia, Prostate Cancer Foundation of Australia, Asociación Española Contra el Cáncer (AECC), the Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional (FEDER), the Institut Català de la Salut, Autonomous Government of Catalonia, Fundação para a Ciência e a Tecnologia, National Institutes of Health National Cancer Institute, Swedish Cancer Society, General Hospital in Malmö Foundation for Combating Cancer

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

Poor auditory task scores in children with specific reading and language difficulties : some poor scores are more equal than others

Children with specific reading disability (SRD) or specific language impairment (SLI), who scored poorly on an auditory discrimination task, did up to 140 runs on the failed task. Forty-one percent of the children produced widely fluctuating scores that did not improve across runs (untrainable errant performance), 23% produced widely fluctuating scores in early runs that did improve across runs (trainable errant performance), 26% produced stable poor scores that did not improve across runs (untrainable nonerrant poor performance), and 23% produced stable poor scores that did improve across runs (trainable nonerrant performance). In most cases, trainable and untrainable errant performance, and nonerrant poor performance, could be predicted from a child's first two auditory task scores. These results illustrate that poor auditory task scores produced by children with SRD and SLI do not reflect a unitary deficit, do not necessarily reflect poor perception, and do not always respond to training.27 page(s

Blindsight in subjects with homonymous visual ªeld defects.

Abstract s Brain damage in the visual system can lead to apparently blind visual areas. However, more elaborate testing indicates that some visual ability may still exist for speciªc stimuli in the otherwise blind regions. This phenomenon is called "blindsight" if subjects report no conscious awareness of visual stimuli but when forced to guess, nevertheless perform better than chance. It has mainly been suggested that secondary visual pathways are responsible for this phenomenon. However, no published study has clearly shown the neural mechanism responsible for blindsight. Furthermore, experimental artifacts may have been responsible for the appearance of the phenomenon in some subjects. In the present study, the visual ªelds of nine subjects were mapped and residual visual performance was examined in many areas using three different experimental procedures. Artifacts such as stray light or eye movements were well controlled. In addition, conªdence ratings were required after each trial in the forced-choice tests. The results show that only one subject with a lesion in the optic radiation had blindsight in two discrete areas of the affected visual ªeld. Spared optic radiation ªbers of the main (primary) geniculo-striate visual pathway were most likely to account for this ªnding.

Dyslexia and practice in the attentional blink : evidence of slower task learning in dyslexia

In this paper we provide an extension to our previous investigation into dyslexia and the attentional blink (AB) (Badcock et al., 2008). The AB is a phenomenon of temporal attention whereby there is a performance cost in reporting a second target when it appears within 500 msec of a first target. We examined performance differences between the first and second 90 trials in a single AB session in a group of adult readers as well as in 6 blocks of 30 trials for T1 only. Overall, there was a significant improvement across the session but most critically, this improvement was greater in magnitude and slower in the phonological dyslexic observers than in control observers. Therefore, group differences were related to rate of improvement. In line with a recent review of the literature, it is suggested that the overall performance difference between the groups relates to general performance factors and not the AB per se. Whether extended practice would entirely attenuate the group difference remains to be seen but it is suggested that the general performance difference relates to development of successful coordination of visual and temporal uncertainties in the distracter and target stimuli.7 page(s

No differential attentional blink in dyslexia after controlling for baseline sensitivity

Previous research has associated a prolonged attentional blink (AB) with adult dyslexia [Hari, R., Valta, M., & Uutela, K. (1999). Prolonged attentional dwell time in dyslexic adults. Neuroscience Letters, 271, 202-204]. The AB represents a limitation in temporal information processing, estimated as the time interval between two targets necessary for accurate recall (e.g., [Raymond, J. E., Shapiro, K. L., & Arnell, K. M. (1992). Temporary suppression of visual processing in an RSVP task: An attentional blink? Journal of Experimental Psychology: Human Perception and Performance, 18, 849-860]). Utilizing single- and dual-target procedures, this investigation extended upon previous research. When controlling for baseline sensitivity as estimated in the dual-target condition, there was no significant difference between dyslexic and control performance. Finding no evidence of a single-target task difference or prolonged AB effect in dyslexia, it is suggested that baseline sensitivity differences relate to difficulties with task demands in dyslexic readers.6 page(s