Robust associations between the 20-item prosopagnosia index and the Cambridge face memory test in the general population

Developmental prosopagnosia (DP) is a neurodevelopmental condition, characterised by lifelong face recognition deficits. Leading research groups diagnose the condition using complementary computer-based tasks and self-report measures. In an attempt to standardise the reporting of self-report evidence, we recently developed the 20-Item Prosopagnosia Index (PI20), a short questionnaire measure of prosopagnosic traits suitable for screening adult samples for DP. Strong correlations between scores on the PI20 and performance on the Cambridge Face Memory Test (CFMT) appeared to confirm that individuals possess sufficient insight into their face recognition ability to complete a self-report measure of prosopagnosic traits. However, the extent to which people have insight into their face recognition abilities remains contentious. A lingering concern is that feedback from formal testing, received prior to administration of the PI20, may have augmented the self-insight of some respondents in the original validation study. To determine whether the significant correlation with the CFMT was an artefact of previously delivered feedback, we sought to replicate the validation study in individuals with no history of formal testing. We report highly significant correlations in two independent samples drawn from the general population, confirming i) that a significant relationship exists between PI20 scores and performance on the CFMT, and ii) that this is not dependent on the inclusion of individuals who have previously received feedback. These findings support the view that people have sufficient insight into their face recognition abilities to complete a self-report measure of prosopagnosic traits

Comparative analysis of potential broad-spectrum neuronal Cre drivers

Cre/Lox technology is a powerful tool in the mouse genetics tool-box as it enables tissue-specific and inducible mutagenesis of specific gene loci. Correct interpretation of phenotypes depends upon knowledge of the Cre expression pattern in the chosen mouse driver line to ensure that appropriate cell types are targeted. For studies of the brain and neurological disease a pan-neuronal promoter that reliably drives efficient neuron-specific transgene expression would be valuable. Here we compare a widely used “pan-neuronal” mouse Cre driver line, Syn1-cre, with a little-known alternative, Snap25-IRES2-cre. Our results show that the Syn1-cre line broadly expresses in the brain but is indetectable in more than half of all neurons and weakly active in testes. In contrast the Snap25-IRES2-cre line expressed Cre in a high proportion of neurons (~85%) and was indetectable in all non-brain tissues that were analysed, including testes. Our findings suggest that for many purposes Snap25-IRES2-cre is superior to Syn1-cre as a potential pan-neuronal cre driver

Native opportunities to stop hypertension: study protocol for a randomized controlled trial among urban American Indian and Alaska Native adults with hypertension

IntroductionAmerican Indian and Alaska Native (AI/AN) adults experience disproportionate cardiovascular disease (CVD) morbidity and mortality compared to other races, which may be partly attributable to higher burden of hypertension (HTN). Dietary Approaches to Stop Hypertension (DASH) is a high-impact therapeutic dietary intervention for primary and secondary prevention of CVD that can contribute to significant decreases in systolic blood pressure (BP). However, DASH-based interventions have not been tested with AI/AN adults, and unique social determinants of health warrant independent trials. This study will assess the effectiveness of a DASH-based intervention, called Native Opportunities to Stop Hypertension (NOSH), on systolic BP among AI/AN adults in three urban clinics.MethodsNOSH is a randomized controlled trial to test the effectiveness of an adapted DASH intervention compared to a control condition. Participants will be aged ≥18 years old, self-identify as AI/AN, have physician-diagnosed HTN, and have elevated systolic BP (≥ 130 mmHg). The intervention includes eight weekly, tailored telenutrition counseling sessions with a registered dietitian on DASH eating goals. Intervention participants will be provided $30 weekly and will be encouraged to purchase DASH-aligned foods. Participants in the control group will receive printed educational materials with general information about a low-sodium diet and eight weekly$30 grocery orders. All participants will complete assessments at baseline, after the 8-week intervention, and again 12 weeks post-baseline. A sub-sample of intervention participants will complete an extended support pilot study with assessments at 6- and 9-months post-baseline. The primary outcome is systolic BP. Secondary outcomes include modifiable CVD risk factors, heart disease and stroke risk scores, and dietary intake.DiscussionNOSH is among the first randomized controlled trials to test the impact of a diet-based intervention on HTN among urban AI/AN adults. If effective, NOSH has the potential to inform clinical strategies to reduce BP among AI/AN adults.Clinical trials registrationhttps://clinicaltrials.gov/ct2/show/NCT02796313, Identifier NCT02796313

POTs: Protective Optimization Technologies

Algorithmic fairness aims to address the economic, moral, social, and political impact that digital systems have on populations through solutions that can be applied by service providers. Fairness frameworks do so, in part, by mapping these problems to a narrow definition and assuming the service providers can be trusted to deploy countermeasures. Not surprisingly, these decisions limit fairness frameworks' ability to capture a variety of harms caused by systems. We characterize fairness limitations using concepts from requirements engineering and from social sciences. We show that the focus on algorithms' inputs and outputs misses harms that arise from systems interacting with the world; that the focus on bias and discrimination omits broader harms on populations and their environments; and that relying on service providers excludes scenarios where they are not cooperative or intentionally adversarial. We propose Protective Optimization Technologies (POTs). POTs provide means for affected parties to address the negative impacts of systems in the environment, expanding avenues for political contestation. POTs intervene from outside the system, do not require service providers to cooperate, and can serve to correct, shift, or expose harms that systems impose on populations and their environments. We illustrate the potential and limitations of POTs in two case studies: countering road congestion caused by traffic-beating applications, and recalibrating credit scoring for loan applicants.Comment: Appears in Conference on Fairness, Accountability, and Transparency (FAT* 2020). Bogdan Kulynych and Rebekah Overdorf contributed equally to this work. Version v1/v2 by Seda G\"urses, Rebekah Overdorf, and Ero Balsa was presented at HotPETS 2018 and at PiMLAI 201

Clinical implementation of a knowledge based planning tool for prostate VMAT

Abstract Background A knowledge based planning tool has been developed and implemented for prostate VMAT radiotherapy plans providing a target average rectum dose value based on previously achievable values for similar rectum/PTV overlap. The purpose of this planning tool is to highlight sub-optimal clinical plans and to improve plan quality and consistency. Methods A historical cohort of 97 VMAT prostate plans was interrogated using a RayStation script and used to develop a local model for predicting optimum average rectum dose based on individual anatomy. A preliminary validation study was performed whereby historical plans identified as “optimal” and “sub-optimal” by the local model were replanned in a blinded study by four experienced planners and compared to the original clinical plan to assess whether any improvement in rectum dose was observed. The predictive model was then incorporated into a RayStation script and used as part of the clinical planning process. Planners were asked to use the script during planning to provide a patient specific prediction for optimum average rectum dose and to optimise the plan accordingly. Results Plans identified as “sub-optimal” in the validation study observed a statistically significant improvement in average rectum dose compared to the clinical plan when replanned whereas plans that were identified as “optimal” observed no improvement when replanned. This provided confidence that the local model can identify plans that were suboptimal in terms of rectal sparing. Clinical implementation of the knowledge based planning tool reduced the population-averaged mean rectum dose by 5.6Gy. There was a small but statistically significant increase in total MU and femoral head dose and a reduction in conformity index. These did not affect the clinical acceptability of the plans and no significant changes to other plan quality metrics were observed. Conclusions The knowledge-based planning tool has enabled substantial reductions in population-averaged mean rectum dose for prostate VMAT patients. This suggests plans are improved when planners receive quantitative feedback on plan quality against historical data

Conversations on grief and hope: A collaborative autoethnographic account exploring the lifeworlds of international youth engaged with climate action

This paper explores the lifeworlds of international youth involved in climate and/or environmental social action, narratives that have been largely absent from a literature that has tended to focus on ‘traditional’ youth activists located in the urban Global North. Written as a novel collaborative autoethnography involving youth as co-authors, the paper a) collectively reflects on the stories of youth from different countries and cultures on their journeys towards climate action, and b) foregrounds an emotional framing to examine these experiences. The youth co-authors, whose experiences are the focus of this paper, form part of innovative international Youth Advisory Board, set up to provide peer support to youth new to climate and environmental social action, as part of our British Academy Youth Futures-funded participatory action research project. We examine the youth’s narratives exploring opportunities and barriers they have navigated, their inspirations and the intersections with a range of other socio-cultural factors

MMASS: an optimized array-based method for assessing CpG island methylation

We describe an optimized microarray method for identifying genome-wide CpG island methylation called microarray-based methylation assessment of single samples (MMASS) which directly compares methylated to unmethylated sequences within a single sample. To improve previous methods we used bioinformatic analysis to predict an optimized combination of methylation-sensitive enzymes that had the highest utility for CpG-island probes and different methods to produce unmethylated representations of test DNA for more sensitive detection of differential methylation by hybridization. Subtraction or methylation-dependent digestion with McrBC was used with optimized (MMASS-v2) or previously described (MMASS-v1, MMASS-sub) methylation-sensitive enzyme combinations and compared with a published McrBC method. Comparison was performed using DNA from the cell line HCT116. We show that the distribution of methylation microarray data is inherently skewed and requires exogenous spiked controls for normalization and that analysis of digestion of methylated and unmethylated control sequences together with linear fit models of replicate data showed superior statistical power for the MMASS-v2 method. Comparison with previous methylation data for HCT116 and validation of CpG islands from PXMP4, SFRP2, DCC, RARB and TSEN2 confirmed the accuracy of MMASS-v2 results. The MMASS-v2 method offers improved sensitivity and statistical power for high-throughput microarray identification of differential methylation

Methylation of class II transactivator gene promoter IV is not associated with susceptibility to Multiple Sclerosis

<p>Abstract</p> <p>Background</p> <p>Multiple sclerosis (MS) is a complex trait in which alleles at or near the class II loci <it>HLA-DRB1 </it>and <it>HLA-DQB1 </it>contribute significantly to genetic risk. The MHC class II transactivator (<it>MHC2TA</it>) is the master controller of expression of class II genes, and methylation of the promoter of this gene has been previously been shown to alter its function. In this study we sought to assess whether or not methylation of the <it>MHC2TA </it>promoter pIV could contribute to MS disease aetiology.</p> <p>Methods</p> <p>In DNA from peripheral blood mononuclear cells from a sample of 50 monozygotic disease discordant MS twins the <it>MHC2TA </it>promoter IV was sequenced and analysed by methylation specific PCR.</p> <p>Results</p> <p>No methylation or sequence variation of the <it>MHC2TA </it>promoter pIV was found.</p> <p>Conclusion</p> <p>The results of this study cannot support the notion that methylation of the pIV promoter of <it>MHC2TA </it>contributes to MS disease risk, although tissue and timing specific epigenetic modifications cannot be ruled out.</p

Clinical Assessment of a Recombinant Simian Adenovirus ChAd63: A Potent New Vaccine Vector

Background. Vaccine development in human Plasmodium falciparum malaria has been hampered by the exceptionally high levels of CD8+ T cells required for efficacy. Use of potently immunogenic human adenoviruses as vaccine vectors could overcome this problem, but these are limited by preexisting immunity to human adenoviruses