Explore the vast range of titles available.

[This corrects the article DOI: 10.1371/journal.pone.0220526.].

Previous work supports an age-specific impairment for recognition memory of pairs of words and other stimuli. The present study tested the generalization of an associative deficit across word, name, and nonword stimulus types in younger and older adults. Participants completed associative and item memory tests in one of three stimulus conditions and made metacognitive ratings of perceptions of self-efficacy, task success (\"postdictions\"), strategy success, task effort, difficulty, fatigue, and stamina. Surprisingly, no support was found for an age-related associative deficit on any of the stimulus types. We analyzed our data further using a multilayer perceptron artificial neural network. The network was trained to classify individuals as younger or older and its hidden unit activities were examined to identify data patterns that distinguished younger from older participants. Analysis of hidden unit activities revealed that the network was able to correctly classify by identifying three different clusters of participants, with two qualitatively different groups of older individuals. One cluster of older individuals found the tasks to be relatively easy, they believed they had performed well, and their beliefs were accurate. The other cluster of older individuals found the tasks to be difficult, believed they were performing relatively poorly, yet their beliefs did not map accurately onto their performance. Crucially, data from the associative task were more useful for neural networks to discriminate between younger and older adults than data from the item task. This work underscores the importance of considering both individual and age differences as well as metacognitive responses in the context of associative memory paradigms.

Cerebral palsy (CP) diagnosis is historically late, at between 12 and 24 months. We aimed to determine diagnosis age, fidelity to recommended tests and acceptability to parents and referrers of an early diagnosis clinic to implement a recent evidence-based clinical guideline for the early diagnosis of CP. A prospective observational case series of infants <12 months with detectable risks for CP attending our clinic was completed with data analysed cross-sectionally. Infants had a high risk of CP diagnosis at a mean age of 4.4 (standard deviation [SD] 2.3) months and CP diagnosis at 8.5 [4.1] months. Of the 109 infants seen, 57% had a diagnosis of CP or high risk of CP, showing high specificity to our inclusion criteria. Parent and referrer acceptability of the clinic was high. Paediatricians had the highest rate of referral (39%) followed by allied health (31%), primary carer (14%) and other health workers (16%). Fidelity to the guideline was also high. All infants referred <5 mths had the General Movements Assessment (GMA) and all except one had the Hammersmith Infant Neurological Examination (HINE) administered. N = 92 (84%) of infants seen had neuroimaging, including n = 53 (49%) who had magnetic resonance imaging (MRI), showing recommended tests are feasible. Referral to CP-specific interventions was at 4.7 [3.0] months, sometimes before referral to clinic. Clinicians can be confident CP can be diagnosed well under 12 months using recommended tools. This clinic model is acceptable to parents and referrers and supports access to CP-specific early interventions when they are likely to be most effective.

OBJECTIVES/GOALS: To examine i) how longstanding (≥6 years) community-based participatory research (CBPR) partnerships nationwide implemented a validated questionnaire to measure success and its contributing factors and ii) how the CBPR partnerships utilized and applied a feedback mechanism, or reports of findings from the questionnaire and a facilitation guide METHODS/STUDY POPULATION: This mixed methods study builds upon a larger NIH-funded project entitled ’Measurement Approaches to Partnership Success (MAPS). MAPS developed and validated the 109-item MAPS questionnaire to measure success in longstanding (≥6 years) CBPR partnerships. In 2020, 55 CBPR partnerships nationwide completed the MAPS Questionnaire and, a year later, received the MAPS Feedback Mechanism, consisting of questionnaire findings and a facilitation guide on how to present the findings. In this follow-up study, we administered multi-method surveys to each partnership contact person in 2022 to examine their experience with and utility of the MAPS Questionnaire and the MAPS Feedback mechanism. We performed descriptive analysis of quantitative responses using SAS and thematic analysis of qualitative responses. RESULTS/ANTICIPATED RESULTS: Survey responses have been presently collected from 14 partnerships. Preliminary findings suggest that the most frequently reported benefits of completing the MAPS Questionnaire included stimulating partnership reflections and ease of completion. Many partnerships shared results of the MAPS Questionnaire by e-mail or during partnership meetings. Nearly half of the partnerships rated components of the MAPS feedback mechanism as useful. Over one-third of the partnerships reported that the COVID pandemic limited their capacity to engage with the MAPS Feedback Mechanism. Key qualitative suggestions included making the MAPS Questionnaire shorter, providing it in a different format, and offering additional facilitation to support the implementation of the MAPS Feedback Mechanism. DISCUSSION/SIGNIFICANCE: This study examines how CBPR partnerships utilize an evaluation instrument and apply results on success. Current findings suggest potential utility of the MAPS Questionnaire and Feedback Mechanism for ongoing evaluation. Reducing the questionnaire length and providing facilitation resources may enhance implementation across diverse settings.

We examined age differences in metacognitive monitoring of emotionally-valenced stimuli. If older adults (OAs) are more focused on emotionally meaningful goals in late life (Carstensen, 2006), then they should demonstrate attentional and memory biases for positive stimuli over neutral and negative stimuli and, arguably, these cognitive biases should be reflected in their metacognitive judgments of learning. Judgments of learning (JOLs) for memory of positive, negative, and neutral words were collected. Younger adults (YAs) aged 18-23 years and OAs aged 65-90 years (N = 85) studied words in each valence category and made immediate JOLs, followed by a two-alternative forced choice (2AFC) recognition memory task. Analyses of JOLs revealed evidence for a positivity effect (Mather & Carstensen, 2005) in metacognitive confidence for OAs and an emotional salience effect in YAs (Tauber & Dunlosky, 2012; Zimmerman & Kelley, 2010). Predictably, YAs recognized more words than OAs, but valence did not affect number of words recognized and valence did not moderate age differences in recognition memory (p = .055). Memory monitoring as measured by resolution accuracy was equivalent in YAs and OAs (Hertzog & Dunlosky, 2011). Positive affect was higher and negative affect was lower in OAs relative to YAs (Gallant, Spaniol, & Yang, 2019), lending additional evidence to an orientation toward the positive in older adulthood. These results are novel in that they demonstrate an age-related positivity effect that extends beyond the domains of memory and emotion to the domain of metacognitive aging. Discussion will focus on theoretical, methodological, and applied implications.

Drug repurposing could provide novel treatment options for Duchenne muscular dystrophy. Because tamoxifen—an oestrogen receptor regulator—reduced signs of muscular pathology in a Duchenne muscular dystrophy mouse model, we aimed to assess the safety and efficacy of tamoxifen in humans as an adjunct to corticosteroid therapy over a period of 48 weeks. We did a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 12 study centres in seven European countries. We enrolled ambulant boys aged 6·5–12·0 years with a genetically confirmed diagnosis of Duchenne muscular dystrophy and who were on stable corticosteroid treatment for more than 6 months. Exclusion criteria included ophthalmological disorders, including cataracts, and haematological disorders. We randomly assigned (1:1) participants using an online randomisation tool to either 20 mg tamoxifen orally per day or matched placebo, stratified by centre and corticosteroid intake. Participants, caregivers, and clinical investigators were masked to treatment assignments. Tamoxifen was taken in addition to standard care with corticosteroids, and participants attended study visits for examinations every 12 weeks. The primary efficacy outcome was the change from baseline to week 48 in scores on the D1 domain of the Motor Function Measure in the intention-to-treat population (defined as all patients who fulfilled the inclusion criteria and began treatment). This study is registered with ClinicalTrials.gov (NCT03354039) and is completed. Between May 24, 2018, and Oct 14, 2020, 95 boys were screened for inclusion, and 82 met inclusion criteria and were initially enrolled into the study. Three boys were excluded after initial screening due to cataract diagnosis or revoked consent directly after screening, but before randomisation. A further boy assigned to the placebo group did not begin treatment. Therefore, 40 individuals assigned tamoxifen and 38 allocated placebo were included in the intention-to-treat population. The primary efficacy outcome did not differ significantly between tamoxifen (–3·05%, 95% CI –7·02 to 0·91) and placebo (–6·15%, –9·19 to –3·11; 2·90% difference, –3·02 to 8·82, p=0·33). Severe adverse events occurred in two participants: one participant who received tamoxifen had a fall, and one who received placebo suffered a panic attack. No deaths or life-threatening serious adverse events occurred. Viral infections were the most common adverse events. Tamoxifen was safe and well tolerated, but no difference between groups was reported for the primary efficacy endpoint. Slower disease progression, defined by loss of motor function over time, was indicated in the tamoxifen group compared with the placebo group, but differences in outcome measures were neither clinically nor statistically significant. Currently, we cannot recommend the use of tamoxifen in daily clinical practice as a treatment option for boys with Duchenne muscular dystrophy due to insufficient clinical evidence. Thomi Hopf Foundation, ERA-Net, Swiss National Science Foundation, Duchenne UK, Joining Jack, Duchenne Parent Project, Duchenne Parent Project Spain, Fondation Suisse de Recherche sur les Maladies Musculaires, Association Monegasque contre les Myopathies.

IntroductionOral rehydration salts (ORS) and zinc comprise the globally recommended treatment for diarrhoea in children aged <5 years. However, limited access contributes to low uptake of this treatment and subsequently high rates of morbidity and mortality among this age group in low-income and middle-income countries. We adopted approaches used for private-sector value-chains of fast-moving consumer-goods, involving the simultaneous stimulation of supply and demand. These approaches were applied to the introduction of an innovative co-packaged diarrhoea-treatment kit (ORSZ co-pack) to increase ORS and zinc coverage at the community level in Zambia.MethodsWe tested our approach using an observational pre–post test study design in two intervention districts in rural Zambia (Kalomo and Katete), each with a matched comparator (Monze and Petauke, respectively). We assessed the effect on coverage, of ORS and zinc as well as ORS alone, by conducting household surveys of a total of 2458 and 2477 caregivers of children aged <5 years at baseline and endline, respectively, across the four districts. We also assessed whether the source of ORS (public or private sector) changed following the intervention.ResultsBoth intervention districts experienced significant increases in coverage of ORS and zinc from <1% at baseline to 46.9% and 46.3% in Kalomo and Katete, respectively. Uptake in the comparator districts remained low at 1.7% and 0.6% in Monze and Petauke, respectively. For the secondary outcome examining ORS coverage (with or without zinc), the intervention was associated with a significant increase in Kalomo versus Monze, but not in Katete versus Petauke. There was a clear shift from the public to the private sector, and specifically to the use of the ORSZ co-pack.ConclusionImplementation of a value-chain creation approach for an innovative, over-the-counter, co-packaged diarrhoea-treatment kit can significantly improve the coverage of ORS and zinc.

Pragmatic partnerships with industry can work argue Simon Berry and colleagues, but Nick Spencer thinks the conflicts of interest are too great