A new mRNA structure prediction based approach to identifying improved signal peptides for bone morphogenetic protein 2.

BACKGROUND: Signal peptide (SP) engineering has proven able to improve production of many proteins yet is a laborious process that still relies on trial and error. mRNA structure around the translational start site is important in translation initiation and has rarely been considered in this context, with recent improvements in in silico mRNA structure potentially rendering it a useful predictive tool for SP selection. Here we attempt to create a method to systematically screen candidate signal peptide sequences in silico based on both their nucleotide and amino acid sequences. Several recently released computational tools were used to predict signal peptide activity (SignalP), localization target (DeepLoc) and predicted mRNA structure (MXFold2). The method was tested with Bone Morphogenetic Protein 2 (BMP2), an osteogenic growth factor used clinically for bone regeneration. It was hoped more effective BMP2 SPs could improve BMP2-based gene therapies and reduce the cost of recombinant BMP2 production. RESULTS: Amino acid sequence analysis indicated 2,611 SPs from the TGF-ß superfamily were predicted to function when attached to BMP2. mRNA structure prediction indicated structures at the translational start site were likely highly variable. The five sequences with the most accessible translational start sites, a codon optimized BMP2 SP variant and the well-established hIL2 SP sequence were taken forward to in vitro testing. The top five candidates showed non-significant improvements in BMP2 secretion in HEK293T cells. All showed reductions in secretion versus the native sequence in C2C12 cells, with several showing large and significant decreases. None of the tested sequences were able to increase alkaline phosphatase activity above background in C2C12s. The codon optimized control sequence and hIL2 SP showed reasonable activity in HEK293T but very poor activity in C2C12. CONCLUSIONS: These results support the use of peptide sequence based in silico tools for basic predictions around signal peptide activity in a synthetic biology context. However, mRNA structure prediction requires improvement before it can produce reliable predictions for this application. The poor activity of the codon optimized BMP2 SP variant in C2C12 emphasizes the importance of codon choice, mRNA structure, and cellular context for SP activity.

Characterisation of the Muscle Protein Synthetic Response to Resistance Exercise in Healthy Adults: A Systematic Review and Exploratory Meta-Analysis.

Methods: Five electronic databases (PubMed (Medline), Web of Science, Embase, Sport Discus, and Cochrane Library) were searched for controlled trials that assessed the MPS response to RE in healthy, adult humans, postabsorptive state. Individual study and random-effects meta-analysis arewere used to inform the effects of RE and covariates on MPS. Results from 79 controlled trials with 237 participants were analysed. Results: Analysis of the pooled effects revealed robust increases in MPS following RE (weighted mean difference (WMD): 0.032% h-1, 95% CI: [0.024, 0.041] % h-1, I2 = 92%, k = 37, P < 0.001). However, the magnitude of the increase in MPS was lower in older adults (>50 y: WMD: 0.015% h-1, 95% CI: [0.007, 0.022] % h-1, I2 = 76%, k = 12, P = 0.002) compared to younger adults (<35 y: WMD: 0.041% h-1, 95% CI: [0.030, 0.052] % h-1, I2 = 88%, k = 25, P < 0.001). Individual studies have reported that the temporal proximity of the RE, muscle group, muscle protein fraction, RE training experience, and the loading parameters of the RE (i.e., intensity, workload, and effort) appeared to affect the MPS response to RE, whereas sex or type of muscle contraction does not. Conclusion: A single bout of RE can sustain measurable increases in postabsorptive MPS soon after RE cessation and up to 48 h post-RE. However, there is substantial heterogeneity in the magnitude and time course of the MPS response between trials, which appears to be influenced by participants' age and/or the loading parameters of the RE itself.

Differences in 5'untranslated regions highlight the importance of translational regulation of dosage sensitive genes.

BACKGROUND: Untranslated regions (UTRs) are important mediators of post-transcriptional regulation. The length of UTRs and the composition of regulatory elements within them are known to vary substantially across genes, but little is known about the reasons for this variation in humans. Here, we set out to determine whether this variation, specifically in 5'UTRs, correlates with gene dosage sensitivity. RESULTS: We investigate 5'UTR length, the number of alternative transcription start sites, the potential for alternative splicing, the number and type of upstream open reading frames (uORFs) and the propensity of 5'UTRs to form secondary structures. We explore how these elements vary by gene tolerance to loss-of-function (LoF; using the LOEUF metric), and in genes where changes in dosage are known to cause disease. We show that LOEUF correlates with 5'UTR length and complexity. Genes that are most intolerant to LoF have longer 5'UTRs, greater TSS diversity, and more upstream regulatory elements than their LoF tolerant counterparts. We show that these differences are evident in disease gene-sets, but not in recessive developmental disorder genes where LoF of a single allele is tolerated. CONCLUSIONS: Our results confirm the importance of post-transcriptional regulation through 5'UTRs in tight regulation of mRNA and protein levels, particularly for genes where changes in dosage are deleterious and lead to disease. Finally, to support gene-based investigation we release a web-based browser tool, VuTR, that supports exploration of the composition of individual 5'UTRs and the impact of genetic variation within them.

Ecology: A few species dominate forest tree abundance pan-tropically.

An analysis of over 1 million old-growth tropical forest trees reveals that ∼2.2% of species comprise 50% of the individuals in Africa, Amazonia, and Southeast Asia, suggesting that the ecological mechanisms underpinning tree community assembly are ubiquitous across the tropics.

Bayesian evaluation of meat juice ELISA for detecting Salmonella in slaughtered pigs without specifying a cut-off.

BACKGROUND: Consumption of pork and pork products is a major source of human infection with Salmonella. Salmonella is typically subclinical in pigs, making it difficult to identify infected pigs. Therefore, effective surveillance of Salmonella in pigs critically relies on good knowledge on how well the diagnostic tests used perform. A test that has been used in several countries for Salmonella monitoring is serological testing of meat juice using an ELISA (MJ ELISA) to detect antibodies against Salmonella. This MJ ELISA data could be used to estimate infection prevalence and trends. However, as the MJ ELISA output is a sample-to-positive (S/P) ratio, which is a continuous outcome rather than a binary (positive/negative) result, the interpretation of this data depends upon a chosen cut-off. AIM: To apply Bayesian latent class models (BLCMs) to estimate diagnostic accuracy of the MJ ELISA test values in the absence of a gold standard without needing to apply a cut-off. METHODS AND RESULTS: BLCMs were fitted to data from a UK abattoir survey carried out in 2006 in order to estimate the diagnostic accuracy of MJ ELISA with respect to the prevalence of active Salmonella infection. This survey consisted of a MJ ELISA applied in parallel with the bacteriological testing of caecal contents, carcass swabs and lymph nodes (n = 625). A BLCM was also fitted to the same data but with dichotomisation of the MJ ELISA results, in order to compare with the model using continuous outcomes. Estimates were obtained for sensitivity and specificity of the ELISA over a range of S/P values and for the bacteriological tests and were found to be similar between the models using continuous and dichotomous ELISA outcomes. CONCLUSION: The Bayesian method without specifying a cut-off does allow prevalence to be inferred without specifying a cut-off for the ELISA. The study results will be useful for estimating infection prevalence from serological surveillance data.

ECHO "Bootcamp": An Innovative Training Model to Onboard Providers in the Care of Gender Diverse Patients.

Purpose: Extension for Community Health Outcomes (ECHO) is a model of continuing medical education meant to connect academic medical center-based specialists with community providers to increase capacity in managing complex health conditions. The purpose of this study was to evaluate the effectiveness of a shortened "bootcamp" ECHO model in increasing participant competence with topics related to transgender and gender diverse (TGD) health care and the impact of "bootcamp" participation on enrollment in an ongoing ECHO series. Methods: An ongoing monthly ECHO series was instituted on topics of TGD health. After 2 years, the team implemented a four-session "bootcamp" for four consecutive weeks during March 2022 to introduce foundational topics for new participants who had joined or were considering joining the ongoing series. Qualitative and quantitative results were collected from self-reported pre-/post-surveys as well as from in-session quizzes. Results: There were 71 participants in the "bootcamp" including health care providers and support staff. Attendees reported a 10.3% increase (p = 0.02) in self-reported comfort providing care to transgender patients. Pre-/post-knowledge improved in areas of health inequities (50% vs. 74% correct pre/post), surgical requirements (33% vs. 74%), and effects of masculinizing (55% vs. 70%) and feminizing (64% vs. 89%) hormone therapy. Prescribing providers reported a significant change across four areas of practice competency. Among 71 "bootcamp" participants, 15 registered for the ongoing program. Conclusion: Use of a "bootcamp" highlights ways to increase participant comfort and knowledge in providing TGD health care in a shortened timeframe and recruit new participants to an ongoing ECHO curriculum.

Exercise capacity following SARS-CoV-2 infection is related to changes in cardiovascular and lung function in military personnel.

BACKGROUND: Since the COVID-19 pandemic, post-COVID syndrome (persistent symptoms/complications lasting >12 weeks) continues to pose medical and economic challenges. In military personnel, where optimal fitness is crucial, prolonged limitations affecting their ability to perform duties has occupational and psychological implications, impacting deployability and retention. Research investigating post-COVID syndrome exercise capacity and cardiopulmonary effects in military personnel is limited. METHODS: UK military personnel were recruited from the Defence Medical Services COVID-19 Recovery Service. Participants were separated into healthy controls without prior SARS-CoV-2 infection (group one), and participants with prolonged symptoms (>12 weeks) after mild-moderate (community-treated) and severe (hospitalised) COVID-19 illness (group 2 and 3, respectively). Participants underwent cardiac magnetic resonance imaging (CMR) and spectroscopy, echocardiography, pulmonary function testing and cardiopulmonary exercise testing (CPET). RESULTS: 113 participants were recruited. When compared in ordered groups (one to three), CPET showed stepwise decreases in peak work, work at VT1 and VO2 max (all p < 0.01). There were stepwise decreases in FVC (p = 0.002), FEV1 (p = 0.005), TLC (p = 0.002), VA (p < 0.001), and DLCO (p < 0.002), and a stepwise increase in A-a gradient (p < 0.001). CMR showed stepwise decreases in LV/RV volumes, stroke volumes and LV mass (LVEDVi/RVEDVi p < 0.001; LVSV p = 0.003; RVSV p = 0.001; LV mass index p = 0.049). CONCLUSION: In an active military population, post-COVID syndrome is linked to subclinical changes in maximal exercise capacity. Alongside disease specific changes, many of these findings share the phenotype of deconditioning following prolonged illness or bedrest. Partitioning of the relative contribution of pathological changes from COVID-19 and deconditioning is challenging in post-COVID syndrome recovery.

The Association Between Sexual Identity, Depression, and Adolescent Substance Use.

Sexual minority youth (SMY) represent a population vulnerable to several adverse health consequences. Specifically, SMY experience depression and substance use at substantially higher rates than heterosexual peers. Better understanding the relationship between depression and substance use among SMY may help reduce morbidity and mortality. We hypothesize that depression will moderate increased substance use rates seen in SMY. Weighted logistical analyses of covariance, adjusted for race/ethnicity, sex, and age, compared the relationship between sexual identity, depression, and substance use (14 outcomes), using data from the 2019 Youth Risk Behavior Survey (n = 13,677) of high school students. SMY reported depression at rates nearly double than heterosexual peers (63.9% vs 33.0%). Except for vaping and alcohol, SMY had significantly higher odds of all SU (aORs 1.41-2.45, p < 0.001-0.0011). After adjusting for depression, odds of all SMY substance use decreased; most relationships remained significant (aORs 0.73-1.89), though the relationship between SMY and lifetime cannabis use became non-significant. The relationship between SMY and current vaping became significant and the relationship between SMY and alcohol and binge-drinking remained non-significant. SMY are at higher risk for use of most substances and depression compared to heterosexual youth. As depression consistently plays a role in the relationship between sexual minority status and adolescent substance use across a wide variety of substances, it may be a modifiable risk factor for substance use among sexual minority youth that should be screened for and treated. This study additionally provides important information for future studies examining nuances of SMY substance use patterns.

How long is Long-COVID? Symptomatic improvement between 12 and 18 months in a prospective cohort study.

INTRODUCTION: COVID-19 infection can precede, in a proportion of patients, a prolonged syndrome including fatigue, exercise intolerance, mood and cognitive problems. This study aimed to describe the profile of fatigue-related, exercise-related, mood-related and cognitive-related outcomes in a COVID-19-exposed group compared with controls. METHODS: 113 serving UK Armed Forces participants were followed up at 5, 12 (n=88) and 18 months (n=70) following COVID-19. At 18 months, 56 were in the COVID-19-exposed group with 14 matched controls. Exposed participants included hospitalised (n=25) and community (n=31) managed participants. 43 described at least one of the six most frequent symptoms at 5 months: fatigue, shortness of breath, chest pain, joint pain, exercise intolerance and anosmia. Participants completed a symptom checklist, patient-reported outcome measures (PROMs), the National Institute for Health cognitive battery and a 6-minute walk test (6MWT). PROMs included the Fatigue Assessment Scale (FAS), Generalised Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9) and Patient Checklist-5 (PCL-5) for post-traumatic stress. RESULTS: At 5 and 12 months, exposed participants presented with higher PHQ-9, PCL-5 and FAS scores than controls (ES (effect size) ≥0.25, p≤0.04). By 12 months, GAD-7 was not significantly different to controls (ES <0.13, p=0.292). Remaining PROMs lost significant difference by 18 months (ES ≤0.11, p≥0.28). No significant differences in the cognitive scales were observed at any time point (F=1.96, p=0.167). At 5 and 12 months, exposed participants recorded significantly lower distances on the 6MWT (ηp 2≥0.126, p<0.01). 6MWT distance lost significant difference by 18 months (ηp 2<0.039, p>0.15). CONCLUSIONS: This prospective cohort-controlled study observed adverse outcomes in depression, post-traumatic stress, fatigue and submaximal exercise performance up to 12 months but improved by 18-month follow-up, in participants exposed to COVID-19 compared with a matched control group.

An Investigation of the Protein Quality and Temporal Pattern of Peripheral Blood Aminoacidemia following Ingestion of 0.33 g·kg-1 Body Mass Protein Isolates of Whey, Pea, and Fava Bean in Healthy, Young Adult Men.

An increase in the intake of legumes is recommended in the promotion of plant-sourced (PSP) rather than animal-sourced (ASP) protein intake to produce a more sustainable diet. This study evaluated the quality of novel PSP isolates from pea (PEA) and fava bean (FAVA) and an ASP isolate of whey (WHEY) and compared the magnitude and temporal pattern of peripheral arterial aminoacidemia following ingestion of 0.33 g·kg-1 body mass of protein isolate in healthy young adult men (n = 9). Total indispensable amino acids (IAA) comprised 58% (WHEY), 46% (PEA), and 42% (FAVA) of the total amino acid (AA) composition, with the ingested protein providing 108% (WHEY), 77% (PEA), and 67% (FAVA) of the recommended per diem requirement of IAA. Reflecting the AA composition, the area under the curve (∆AUC0-180), post-ingestion increase in total IAA for WHEY was 41% (p < 0.001) and 57% (p < 0.001) greater than PEA and FAVA, respectively, with PEA exceeding FAVA by 28% (p = 0.003). As a sole-source, single-dose meal-size serving, the lower total IAA for PEA and FAVA would likely evoke a reduced post-prandial anabolic capacity compared to WHEY. Incorporated into a food matrix, the promotion of PSP isolates contributes to a more sustainable diet.

Posting patterns in peer online support forums and their associations with emotions and mood in bipolar disorder: Exploratory analysis.

BACKGROUND: Mental health (MH) peer online forums offer robust support where internet access is common, but healthcare is not, e.g., in countries with under-resourced MH support, rural areas, and during pandemics. Despite their widespread use, little is known about who posts in such forums, and in what mood states. The discussion platform Reddit is ideally suited to study this as it hosts forums (subreddits) for MH and non-MH topics. In bipolar disorder (BD), where extreme mood states are core defining features, mood influences are particularly relevant. OBJECTIVES: This exploratory study investigated posting patterns of Reddit users with a self-reported BD diagnosis and the associations between posting and emotions, specifically: 1) What proportion of the identified users posts in MH versus non-MH subreddits? 2) What differences exist in the emotions that they express in MH or non-MH subreddit posts? 3) How does mood differ between those users who post in MH subreddits compared to those who only post in non-MH subreddits? METHODS: Reddit users were automatically identified via self-reported BD diagnosis statements and all their 2005-2019 posts were downloaded. First, the percentages of users who posted only in MH (non-MH) subreddits were calculated. Second, affective vocabulary use was compared in MH versus non-MH subreddits by measuring the frequency of words associated with positive emotions, anxiety, sadness, anger, and first-person singular pronouns via the LIWC text analysis tool. Third, a logistic regression distinguished users who did versus did not post in MH subreddits, using the same LIWC variables (measured from users' non-MH subreddit posts) as predictors, controlling for age, gender, active days, and mean posts/day. RESULTS: 1) Two thirds of the identified 19,685 users with a self-reported BD diagnosis posted in both MH and non-MH subreddits. 2) Users who posted in both MH and non-MH subreddits exhibited less positive emotion but more anxiety and sadness and used more first-person singular pronouns in their MH subreddit posts. 3) Feminine gender, higher positive emotion, anxiety, and sadness were significantly associated with posting in MH subreddits. CONCLUSIONS: Many Reddit users who disclose a BD diagnosis use a single account to discuss MH and other concerns. Future work should determine whether users exhibit more anxiety and sadness in their MH subreddit posts because they more readily post in MH subreddits when experiencing lower mood or because they feel more able to express negative emotions in these spaces. MH forums may reflect the views of people who experience more extreme mood (outside of MH subreddits) compared to people who do not post in MH subreddits. These findings can be useful for MH professionals to discuss online forums with their clients. For example, they may caution them that forums may underrepresent people living well with BD.

The Impact of Age and Psychosocial Factors on Cognitive and Auditory Outcomes During the COVID-19 Pandemic.

PURPOSE: In March 2020, the U.K. government announced that people should isolate to reduce the spread of the virus that causes COVID-19. Outside a pandemic, psychosocial factors, such as socialization and mental health, may impact the relationship between hearing loss and increased dementia risk. We aim to report the impact of psychosocial factors, including social isolation, depression, and engagement in activities, on hearing and cognitive function in younger and older adults during the COVID-19 pandemic. METHOD: An online survey and experiment assessed self-reported psychosocial factors, self-reported hearing ability and speech-in-noise perception, and cognition. Data were collected between June 2020 and February 2021. Older (n = 112, Mage = 70.08) and younger (n = 121, Mage = 20.52) monolingual speakers of English, without any language or neurological disorders participated. Multiple linear regression models were employed to investigate hypothesized associations between psychosocial factors, and hearing and cognition, in older and younger adults. RESULTS: Multiple regression analyses indicated that older adults displayed poorer speech-in-noise perception and poorer performance on one of four cognitive tasks, compared with younger adults; increased depression was associated with poorer subjective hearing. Other psychosocial factors did not significantly predict hearing or cognitive function. CONCLUSIONS: Data suggest that self-reported hearing and depression are related. This conclusion is important for understanding the associations between hearing loss and cognitive decline in the long term, as both hearing loss and depression are risk factors for dementia. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.23810838.

Mindfulness-Based Stress Reduction for Our Time: A Curriculum that is up to the Task.

There is current heightened public consciousness of the intersecting challenges of social and racial injustice, other forms of inequity, and the climate and biodiversity crisis. We examine how these current realities influence how we engage as Mindfulness-Based Stress Reduction (MBSR) and Mindfulness-Based Program (MBP) teachers and researchers. Although Kabat-Zinn developed MBSR as a vehicle to enable engagement with both the individual and the collective drivers of distress and flourishing, predominant research and practice trends within the MBP field have prioritised individual wellbeing, and have not been accessible to the full societal demographic. Furthermore, there is increasing recognition that the systemic social inequities that influence access to public services have not been addressed in the MBP field. In response, there is now an increasing trend exploring how MBP participation can influence 'bigger than self' concerns, with research, practice and theory suggesting that the inner personal transformation that mindfulness practice enables, supports individuals to compassionately reconnect to self, other and the natural world in ways that foster prosocial behaviour change, and enables awareness building of personal bias and conditioning. In this paper we present perspectives on ways of both retaining fidelity to the existing MBSR program, and simultaneously embracing anti-oppression teaching methods and content, and an inclusive recognition of the micro, meso and macro causes and conditions that drive distress and flourishing. We are a group of racially diverse MBP teachers and trainers from both sides of the Atlantic, who are engaged in training initiatives with people from Black, Latinex, Indigenous, Asian, and People of Color communities.

Gender-affirming hormone therapy, mental health, and surgical considerations for aging transgender and gender diverse adults.

As the transgender and gender diverse (TGD) population ages, more transfeminine and transmasculine individuals present to clinic to initiate or continue their gender-affirming care at older ages. Currently available guidelines on gender-affirming care are excellent resources for the provision of gender-affirming hormone therapy (GAHT), primary care, surgery, and mental health care but are limited in their scope as to whether recommendations require tailoring to older TGD adults. Data that inform guideline-recommended management considerations, while informative and increasingly evidence-based, mainly come from studies of younger TGD populations. Whether results from these studies, and therefore recommendations, can or should be extrapolated to aging TGD adults remains to be determined. In this perspective review, we acknowledge the lack of data in older TGD adults and discuss considerations for evaluating cardiovascular disease, hormone-sensitive cancers, bone health and cognitive health, gender-affirming surgery, and mental health in the older TGD population on GAHT.

The Impact of the COVID-19 Pandemic on a Dedicated Vascular Emergency Clinic.

BACKGROUND: Vascular Emergency Clinics (VEC) improve patient outcomes in chronic limb-threatening ischemia (CLTI). They provide a "1 stop" open access policy, whereby "suspicion of CLTI" by a healthcare professional or patient leads to a direct review. We assessed the resilience of the outpatient VEC model to the first year of the coronavirus disease (COVID-19) pandemic. METHODS: A retrospective review of a prospectively maintained database of all patients assessed in our VEC for lower limb pathologies between March 2020 and April 2021 was performed. This was cross-referenced to national and loco-regional Governmental COVID-19 data. Individuals with CLTI were further analysed to determine Peripheral Arterial Disease-Quality Improvement Framework compliance. RESULTS: Seven hundred and ninety one patients attended for 1,084 assessments (Male n = 484, 61%; Age 72.5 ± standard deviation 12.2 years; White British n = 645, 81.7%). In total, 322 patients were diagnosed with CLTI (40.7%). A total of 188 individuals (58.6%) underwent a first revascularization strategy (Endovascular n = 128, 39.8%; Hybrid n = 41, 12.7%; Open surgery n = 19, 5.9%; Conservative n = 134, 41.6%). Major lower limb amputation rate was 10.9% (n = 35) and mortality rate was 25.8% (n = 83) at 12 months of follow-up. Median referral to assessment time was 3 days (interquartile range: 1-5). For the nonadmitted patient with CLTI, the median assessment to intervention was 8 days (interquartile range: 6-15) and median referral to intervention time of 11 days (11-18). CONCLUSIONS: The VEC model has demonstrated strong resilience to the COVID-19 pandemic with rapid treatment timelines maintained for patients with CLTI.

Monitoring of chronic wasting disease (CWD) (IV).

The European Commission requested an analysis of the Chronic Wasting Disease (CWD) monitoring programme in Norway, Sweden, Finland, Iceland, Estonia, Latvia, Lithuania and Poland (9 January 2017-28 February 2022). Thirteen cases were detected in reindeer, 15 in moose and 3 in red deer. They showed two phenotypes, distinguished by the presence or absence of detectable disease-associated normal cellular prion protein (PrP) in lymphoreticular tissues. CWD was detected for the first time in Finland, Sweden and in other areas of Norway. In countries where the disease was not detected, the evidence was insufficient to rule out its presence altogether. Where cases were detected, the prevalence was below 1%. The data also suggest that the high-risk target groups for surveillance should be revised, and 'road kill' removed. Data show that, in addition to differences in age and sex, there are differences in the prion protein gene (PRNP) genotypes between positive and negative wild reindeer. A stepwise framework has been proposed with expanded minimum background surveillance to be implemented in European countries with relevant cervid species. Additional surveillance may include ad hoc surveys for four different objectives, specific to countries with/without cases, focusing on parallel testing of obex and lymph nodes from adult cervids in high-risk target groups, sustained over time, using sampling units and a data-driven design prevalence. Criteria for assessing the probability of CWD presence have been outlined, based on the definition of the geographical area, an annual assessment of risk of introduction, sustained minimum background surveillance, training and engagement of stakeholders and a surveillance programme based on data-driven parameters. All positive cases should be genotyped. Sample sizes for negative samples have been proposed to detect and estimate the frequency of PRNP polymorphisms. Double-strand sequencing of the entire PRNP open reading frame should be undertaken for all selected samples, with data collated in a centralised collection system at EU level.

Mindfulness-based programmes and 'bigger than self' issues: protocol for a scoping review.

INTRODUCTION: Mindfulness-based programmes (MBPs) have an established, growing evidence base as interventions to optimise health, well-being and performance of individual participants. Emerging evidence suggests that MBPs also enhance prosociality, encouraging individuals to contribute to positive social change. This study focuses on the potential of MBPs to facilitate development of participants' inner resources that support prosocial shifts. The review seeks to detect shifts in MBP benefit from individual toward 'bigger than self', informing and empowering individual and collective responses to complex societal and global issues. The review aims to map current literature on MBPs and social change, into a descriptive overview with commentary on quality, trends, theoretical models and gaps, and on how training in MBPs potentially enables individual and collective responses to societal and global issues. Recommendations for future directions for researchers seeking to advance this evidence base, and practitioners developing innovative MBPs for this purpose will be provided. METHODS AND ANALYSIS: A scoping review of peer-reviewed literature will be undertaken and reported on according to the Joanna Briggs Institute (JBI) Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidance. Systematic searches of four scientific databases will be undertaken to identify potentially eligible articles published from all time to current date. Data will be extracted using an extraction template and analysed descriptively using narrative synthesis. ETHICS AND DISSEMINATION: This scoping review involves no human participants, so ethics is not required. Findings will be shared through professional networks, conference presentations and journal publication.

The contributions of decoding skill and lexical knowledge to the development of irregular word reading.

Two recent computational models of reading development propose that irregular words are read using a combination of decoding and lexical knowledge but differ in assumptions about how these sources of information interact and about the relative importance of different aspects of lexical knowledge. We report developmental data that help to adjudicate these differences. Study 1 adopted a correlational approach to investigate the item-level relations between the ability to read a word aloud, general decoding ability, and knowledge of the word's phonological form (lexical phonology) or meaning (lexical semantics). We found that the latter three factors all influenced accuracy of oral reading. We observed trends indicating that the impact of differences in decoding skill and lexical knowledge were more prominent for irregular words. Study 2 comprised two experiments in which novel irregular words were taught; in Experiment 1 we compared phonological to no pretraining, whereas in Experiment 2 we compared phonological to phonological plus semantics pretraining. Exposure to the phonological form of the word had a substantial impact in the early stages of learning, whereas the impact of adding semantics was more modest and emerged later. Our findings provide strong evidence that irregular words are read using a combination of decoding and lexical knowledge, with a greater contribution from lexical phonology than lexical semantics. Computational models of learning to read are currently unable to fully account for our data, therefore we propose some modifications. We advocate an instructional approach whereby phonics and vocabulary teaching are combined to support irregular word reading. (PsycInfo Database Record (c) 2023 APA, all rights reserved).