This article refines a foundational tenet of rational choice theory known as the principle of description invariance. Attempts to apply this principle to human agents with imperfect knowledge have paid insufficient attention to two aspects: first, agents’ epistemic situations, i.e. whether and when they recognize alternative descriptions of an object to be equivalent; and second, the individuation of objects of description, i.e. whether and when objects count as the same or different. An important consequence is that many apparent ‘framing effects’ may not violate the principle of description invariance, and the subjects of these effects may not be irrational.

Exclusion of special populations (older adults; pregnant women, children, and adolescents; individuals of lower socioeconomic status and/or who live in rural communities; people from racial and ethnic minority groups; individuals from sexual or gender minority groups; and individuals with disabilities) in research is a pervasive problem, despite efforts and policy changes by the National Institutes of Health and other organizations. These populations are adversely impacted by social determinants of health (SDOH) that reduce access and ability to participate in biomedical research. In March 2020, the Northwestern University Clinical and Translational Sciences Institute hosted the “Lifespan and Life Course Research: integrating strategies” “Un-Meeting” to discuss barriers and solutions to underrepresentation of special populations in biomedical research. The COVID-19 pandemic highlighted how exclusion of representative populations in research can increase health inequities. We applied findings of this meeting to perform a literature review of barriers and solutions to recruitment and retention of representative populations in research and to discuss how findings are important to research conducted during the ongoing COVID-19 pandemic. We highlight the role of SDOH, review barriers and solutions to underrepresentation, and discuss the importance of a structural competency framework to improve research participation and retention among special populations.

Bermúdez claims that agents think about framed outcomes, not outcomes themselves; and that seemingly incoherent preferences can be rational, once defined over framed outcomes. However, the agents in his examples know that alternative frames describe the same outcome, neutrally understood. This undermines the restriction of their preferences to framed outcomes and, in turn, the argument for rational framing effects.

As, Pb and Hg are common environmental contaminants in low- and middle-income countries. We investigated the association between child toxicant exposure and growth and development and determined if this association was mitigated by Se concentration. Toxicant concentrations in fingernail samples, anthropometry and Bayley’s Scales of Infant Development, 3rd edition domains were assessed in 36-month-old children whose mothers had been part of a randomised controlled trial in rural Vietnam. Multivariable regression analyses were performed to estimate the effect of toxicant exposure on clinical outcomes with adjustments for potential confounders and interaction with fingernail Se concentration. We analysed 658 children who had data for at least one physical or developmental outcome, and at least one toxicant measurement, and each of the covariates. Fingernail As concentration was negatively associated with language (estimate per 10 % increase in As: −0·19, 95 % CI: (–0·32, −0·05)). Pb was negatively associated with cognition (estimate per 10 % increase in Pb: −0·08 (–0·15, −0·02)), language (estimate per 10 % increase in Pb: −0·18 (–0·28, −0·10)) and motor skills (estimate per 10 % increase in Pb: −0·12 (–0·24, 0·00)). Hg was negatively associated with cognition (estimate per 10 % increase in Hg: −0·48, (–0·72, −0·23)) and language (estimate per 10 % increase in Hg −0·51, (–0·88, −0·13)) when Se concentration was set at zero in the model. As Se concentration increased, the negative associations between Hg and both cognition and language scores were attenuated. There was no association between toxicant concentration and growth. As, Pb and Hg concentrations in fingernails of 3-year-old children were associated with lower child development scores. The negative association between Hg and neurological development was reduced in magnitude with increasing Se concentration. Se status should be considered when assessing heavy metal toxicants in children and their impact on neurodevelopmental outcomes.

OBJECTIVES/GOALS: The Colorado Community Engagement Alliance Against COVID-19 Disparities (CO-CEAL) Team has worked with 5 racial/ethnic communities in Colorado to understand COVID-19 vaccine hesitancy and develop messages, materials and dissemination strategies to impact vaccine hesitancy. Relationships have been key facilitators of this work. METHODS/STUDY POPULATION: CO-CEAL was funded for one year as a part of the national CEAL Teams effort. CO-CEAL engaged urban Hispanic/LatinX, rural Hispanic/LatinX, urban African/American, rural African Immigrant and urban American Indian/Alaska Native communities through Community Connectors in each community. Our Community Connectors led recruitment of community members for our community survey data collection (goal of 200 surveys from each community) and participation in our 5 Community (Boot Camp) Translations. Where possible we worked with Community Connectors and leveraged community relationships with whom we had worked over multiple years and projects. In two communities we worked to quickly build and establish new relationships with Community Connectors and their communities. RESULTS/ANTICIPATED RESULTS: The rapid nature of the CO-CEAL project, its timeline and the unusual nature of the funding mechanism required adaptations to usual ways of working on both the academic and community side.In our CO-CEAL partner communities where there was a history of working together, concerns, possible barriers and other issues tended to be rapidly addressed. The prior existing, long-standing relationships fostered trust that enabled open airing of concerns and an ability to address issues as they arose. In CO-CEAL partner communities where new relationships were being forged, trust needed to be build from the ground up. This made adaptations more challenging and the ability to address concerns and issues as they arose more problematic. Although the work has moved forward in all communities, extra care has been required in some. DISCUSSION/SIGNIFICANCE: When crises necessitate rapid action in communities, the depth of prior investments in building and maintaining relationships makes a difference in how rapidly and successfully partners can work together to address a crisis like the COVID-19 pandemic. Funders and Academic researchers should invest broadly in communities to enable rapid responses.

Informed by the National Institute of Mental Health's Research Domain Criteria (RDoC) and developmental psychopathology frameworks, the current study used cortisol area under the curve with respect to ground (AUCg) as an index of differential sensitivity to context, which was expected to predispose young children with elevated vulnerability to adverse caregiving experiences and adaptive sensitivity to intervention effects. Particularly, the study aimed to determine whether improving caregivers’ responsive parenting through the Filming Interactions to Nurture Development (FIND) intervention would buffer children's biologically embedded vulnerability to caregivers’ depressive symptoms. Data were derived from a randomized controlled trial using pretest–posttest design with low-income families of children aged 4 to 36 months (N = 91). Young children's differential sensitivity was measured using cortisol AUCg during a structured stress paradigm. As hypothesized, children whose cortisol AUCg indicated greater sensitivity to social context exhibited more internalizing and externalizing behaviors in relation to caregivers’ elevated depressive symptoms. Critically, the intervention program was effective in attenuating psychopathology symptoms among the more biologically sensitive children. As proven by rigorous statistical tests, the findings of this study partially supported the differential susceptibility hypotheses, indicating both greater vulnerability to adverse conditions and responsiveness to intervention among children with high levels of cortisol AUCg.

The aim of this study was to explore associations between internet/email use in a large sample of older English adults with their social isolation and loneliness. Data from the English Longitudinal Study of Ageing Wave 8 were used, with complete data available for 4,492 men and women aged ⩾ 50 years (mean age = 64.3, standard deviation = 13.3; 51.7% males). Binomial logistic regression was used to analyse cross-sectional associations between internet/email use and social isolation and loneliness. The majority of older adults reported using the internet/email every day (69.3%), fewer participants reported once a week (8.5%), once a month (2.6%), once every three months (0.7%), less than every three months (1.5%) and never (17.4%). No significant associations were found between internet/email use and loneliness, however, non-linear associations were found for social isolation. Older adults using the internet/email either once a week (odds ratio (OR) = 0.60, 95% confidence interval (CI) = 0.49–0.72) or once a month (OR = 0.60, 95% CI = 0.45–0.80) were significantly less likely to be socially isolated than every day users; those using internet/email less than once every three months were significantly more likely to be socially isolated than every day users (OR = 2.87, 95% CI = 1.28–6.40). Once every three months and never users showed no difference in social isolation compared with every day users. Weak associations were found between different online activities and loneliness, and strong associations were found with social isolation. The study updated knowledge of older adults’ internet/email habits, devices used and activities engaged in online. Findings may be important for the design of digital behaviour change interventions in older adults, particularly in groups at risk of or interventions targeting loneliness and/or social isolation.

BACKGROUND: IGTS is a rare phenomenon of paradoxical germ cell tumor (GCT) growth during or following treatment despite normalization of tumor markers. We sought to evaluate the frequency, clinical characteristics and outcome of IGTS in patients in 21 North-American and Australian institutions. METHODS: Patients with IGTS diagnosed from 2000-2017 were retrospectively evaluated. RESULTS: Out of 739 GCT diagnoses, IGTS was identified in 33 patients (4.5%). IGTS occurred in 9/191 (4.7%) mixed-malignant GCTs, 4/22 (18.2%) immature teratomas (ITs), 3/472 (0.6%) germinomas/germinomas with mature teratoma, and in 17 secreting non-biopsied tumours. Median age at GCT diagnosis was 10.9 years (range 1.8-19.4). Male gender (84%) and pineal location (88%) predominated. Of 27 patients with elevated markers, median serum AFP and Beta-HCG were 70 ng/mL (range 9.2-932) and 44 IU/L (range 4.2-493), respectively. IGTS occurred at a median time of 2 months (range 0.5-32) from diagnosis, during chemotherapy in 85%, radiation in 3%, and after treatment completion in 12%. Surgical resection was attempted in all, leading to gross total resection in 76%. Most patients (79%) resumed GCT chemotherapy/radiation after surgery. At a median follow-up of 5.3 years (range 0.3-12), all but 2 patients are alive (1 succumbed to progressive disease, 1 to malignant transformation of GCT). CONCLUSION: IGTS occurred in less than 5% of patients with GCT and most commonly after initiation of chemotherapy. IGTS was more common in patients with IT-only on biopsy than with mixed-malignant GCT. Surgical resection is a principal treatment modality. Survival outcomes for patients who developed IGTS are favourable.

Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.

We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.