As the scale of cosmological surveys increases, so does the complexity in the analyses. This complexity can often make it difficult to derive the underlying principles, necessitating statistically rigorous testing to ensure the results of an analysis are consistent and reasonable. This is particularly important in multi-probe cosmological analyses like those used in the Dark Energy Survey (DES) and the upcoming Legacy Survey of Space and Time, where accurate uncertainties are vital. In this paper, we present a statistically rigorous method to test the consistency of contours produced in these analyses and apply this method to the Pippin cosmological pipeline used for type Ia supernova cosmology with the DES. We make use of the Neyman construction, a frequentist methodology that leverages extensive simulations to calculate confidence intervals, to perform this consistency check. A true Neyman construction is too computationally expensive for supernova cosmology, so we develop a method for approximating a Neyman construction with far fewer simulations. We find that for a simulated dataset, the 68% contour reported by the Pippin pipeline and the 68% confidence region produced by our approximate Neyman construction differ by less than a percent near the input cosmology; however, they show more significant differences far from the input cosmology, with a maximal difference of 0.05 in $\Omega_{M}$ and 0.07 in w. This divergence is most impactful for analyses of cosmological tensions, but its impact is mitigated when combining supernovae with other cross-cutting cosmological probes, such as the cosmic microwave background.

OBJECTIVES/GOALS: NSF often requires cross-disciplinary team composition to be competitive for funding. To what extent do research teams have multidisciplinary authorships after they win an award, given that awards are not contracts? We examined the quantity and quality of multidisciplinary collaboration of NSF-funded teams before and after receiving their award. METHODS/STUDY POPULATION: Our sample was 150 PIs and Co-PIs (67% male) from 58 NSF-funded EAGER (EArly-concept Grants for Exploratory Research) grants between 2013 and 2019. Using publicly available information, we collected the number of conference papers, publications, and grants PIs/co-PIs produced with each other (all PIs and co-PIs in a team or a partial subset). Based on Ph.D. fields, we also cataloged whether the combination of PIs/co-PI authors on outputs represented unidisciplinary or multidisciplinary collaboration after their NSF award. Multidisciplinary collaboration consisted of multidivisional (Ph.D. disciplines across NSF divisions, e.g., political science and cognitive psychology) or multidirectorate (Ph.D. disciplines across NSF directorates, e.g., psychology and engineering) authorship. RESULTS/ANTICIPATED RESULTS: Of the 74% of PI and co-PI teams who collaborated after their EAGER award, almost 9 out of 10 chose to work with a collaborator from a different discipline, and almost 8 out of 10 chose to work with a researcher from an extremely diverse discipline from their own (e.g., computer science and psychology). Research on interdisciplinary teams largely emphasizes the challenges and problems they face but the current research demonstrated that 90% of the sample chose to continue working together across disciplines after EAGER awards. Therefore, future research should dedicate more attention to the nontangible benefits members receive in interdisciplinary teams. Moreover, quality measures revealed higher H-indices for multidisciplinary than unidisciplinary journals and conferences. DISCUSSION/SIGNIFICANCE: Our archival results revealed that NSF EAGER grants are having their intended effect of being a catalyst for 1) continued multidisciplinary (and especially multidirectorate) collaboration) and 2) high-quality multidisciplinary publication and conference output. These results have contributed to NSF policy changes to reinstate the EAGER grant.

Research suggests that unsupportive parenting practices are consistent but modest risk factors for children’s behavioral and social problems, emphasizing the importance in identifying sources of variability in children’s vulnerability. To address this research direction, this study examined children’s callous-unemotional (CU) traits (i.e., affective indifference; lack of guilt or empathy), as a moderator of the associations among maternal and paternal unsupportive parenting and their externalizing symptoms. Participants included 240 mothers, partners, and their children (Mage = 4.6 years; 56% girls) from diverse backgrounds (48% Black; 16% Latinx) who took part in a longitudinal multi-method study with two measurement occasions spaced 2 years apart. Findings from structural equation modeling indicated the prospective association between observational assessments of unsupportive maternal (but not paternal) parenting and residualized changes in teacher reports children’s externalizing problems over 2 years was significantly moderated by maternal reports of children’s callous-unemotional traits (β = −.21, p < .05). Follow-up analyses of the interaction provided support for differential susceptibility. These findings highlight that children with elevated CU traits may experience diminished susceptibility to parenting, while children with lower levels of CU traits may exhibit plasticity in response to socialization environments.

Rabies virus (RABV) is a deadly zoonosis that circulates in wild carnivore populations in North America. Intensive management within the USA and Canada has been conducted to control the spread of the raccoon (Procyon lotor) variant of RABV and work towards elimination. We examined RABV occurrence across the northeastern USA and southeastern Québec, Canada during 2008–2018 using a multi-method, dynamic occupancy model. Using a 10 km × 10 km grid overlaid on the landscape, we examined the probability that a grid cell was occupied with RABV and relationships with management activities (oral rabies vaccination (ORV) and trap-vaccinate-release efforts), habitat, neighbour effects and temporal trends. We compared raccoon RABV detection probabilities between different surveillance samples (e.g. animals that are strange acting, road-kill, public health samples). The management of RABV through ORV was found to be the greatest driver in reducing the occurrence of rabies on the landscape. Additionally, RABV occupancy declined further with increasing duration of ORV baiting programmes. Grid cells north of ORV management were at or near elimination ($\hat{\psi }_{{\rm north}}$ = 0.00, s.e. = 0.15), managed areas had low RABV occupancy ($\hat{\psi }_{{\rm managed}}$ = 0.20, s.e. = 0.29) and enzootic areas had the highest level of RABV occupancy ($\hat{\psi }_{{\rm south}}$ = 0.83, s.e. = 0.06). These results provide evidence that past management actions have been being successful at the goals of reducing and controlling the raccoon variant of RABV. At a finer scale we also found that vaccine bait type and bait density impacted RABV occupancy. Detection probabilities varied; samples from strange acting animals and public health had the highest detection rates. Our results support the movement of the ORV zone south within the USA due to high elimination probabilities along the US border with Québec. Additional enhanced rabies surveillance is still needed to ensure elimination is maintained.

This study examined children’s exposure to family adversity, hostile reactivity to parental conflict, and negative family representations as mediators of the prospective relation between their temperamental exuberance and externalizing symptoms. Participants included 243 preschool children (M age = 4.60 years; 56% girls) and parents (48% Black; 16% Latinx) in a multi-method and multi-informant study with three annual measurement occasions. Structural equation model results specifically supported children’s hostile reactivity to parental conflict and negative family representations as mediators. Exuberance predicted residualized increases in children’s hostile reactivity and negative family representations over a 1-year period. In turn, children’s hostile reactivity and negative family representations predicted their greater externalizing symptoms 1 year later after controlling for prior externalizing symptoms. Results are discussed in the context of their relation and refinement of temperamental models of developmental psychopathology.

We detected no correlation between standardized antimicrobial administration ratios (SAARs) and healthcare facility-onset Clostridioides difficile infection (HO-CDI) rates in 102 acute-care Veterans Affairs medical centers over 16 months. SAARs may be useful for investigating trends in local antimicrobial use, but no ratio threshold demarcated HO-CDI risk.

This study tested whether the associations between interparental conflict, children’s emotional reactivity, and school adjustment were moderated by children’s cortisol reactivity in a sample of young children (N = 243; mean age = 4.6 years at Wave 1; 56% female, 44% male) and their parents. Using a longitudinal, autoregressive design, observational assessments of children’s emotional reactivity at Wave 2 mediated the relationship between an observational measure of Wave 1 conflict between parents and teacher’s report of children’s school adjustment at Wave 3. However, children’s cortisol reactivity to parent conflict at Wave 1 moderated the first link, such that emotional reactivity operated as a mediator for children with heightened cortisol reactivity but not children with low cortisol reactivity. Moderation was expressed in a “for better” or “for worse” form hypothesized by biological sensitivity to context theory. Thus, children with high cortisol reactivity experienced greater emotional reactivity than their peers when faced with more destructive conflict but also lower emotional reactivity when exposed to more constructive interparental conflict. Results are discussed as to how they advance emotional security and biological sensitivity to context theories.

Decumulation Pathways are proposed to help achieve better retirement outcomes for those with Defined Contribution (DC) pensions. The DC fund is split into two parts, in proportions of the consumer’s choice. Most is allocated to the Pension Fund to provide a lifetime income, while the rest is placed in the Flexible Fund for flexible access and/or to leave as a legacy. The Flexible Fund is invested in flexi-access drawdown. The Pension Fund is invested in a guaranteed annuity, Collective Defined Contribution, or a Pooled Pension Fund which maintains individual DC funds but pools longevity risk between participants. An illustrative standard Decumulation Pathway is intended as a default solution, or can be tailored by the consumer. It uses the Pooled Pension Fund, an automated withdrawal strategy which ensures a lifetime income is provided and one that aims to increase in line with inflation, and a moderate risk investment strategy. The standard approach is evaluated using various metrics, indicating that it has as a strong chance of providing a higher income than could be obtained from an annuity or drawdown, with limited downside risk.

This multi-method longitudinal study evaluated how changes in maternal sensitive parenting may operate as an indirect factor linking family instability and the development of child externalizing problems over time. This study also investigated how mothers’ stress reactivity within the sympathetic nervous system (SNS) may moderate the association between family instability and the development of maternal sensitivity. Participants were 235 families with a young child (Mage = 2.97 years at the first measurement occasion) and these families were followed for two annual measurement occasions. Maternal sensitivity was observed during two discipline tasks (i.e., forbidden toy, discipline discussion tasks), and maternal SNS stress reactivity was indicated by their salivary alpha-amylase (sAA) reactivity to an interpersonal stressor. Findings revealed significant direct effects of family instability and family instability-x-sAA reactivity interaction in association with the change in maternal sensitivity over time. For both tasks, mothers with greater sAA reactivity exhibited stronger associations between family instability and the growth of their sensitivity. Tests of indirect effects indicated that change in maternal sensitivity operated as an indirect factor between family instability-x-sAA reactivity interaction and the change in child externalizing problems. The present findings have important implications for understanding parental and child sequelae associated with unstable family contexts.

A growing body of research connects Christian nationalism—a preference for a religiously conservative political regime—to social and political beliefs. This paper raises questions about the validity of a popular scale used to measure those attitudes. I begin by exploring the factor structure of the six-item Christian nationalism index. I then show how semi-supervised machine learning can be used to illustrate classification problems within that scale. Finally, I demonstrate that this index performs poorly at the interval level, a combination of measurement error and the sorting out of religious and political preferences. These attitudes have become so bound up in conventional politics that they often exhibit a threshold rather than a linear relationship to political preferences. I conclude with an appeal for care in matching theory to empirics: Christian nationalism is a prominent political theology, but research must grapple with the limitations of prevailing measurement tools when operationalizing it.

According to differential susceptibility theory (DST), some children may be more sensitive to both positive and negative features of the environment. However, research has generated a list of widely disparate temperamental traits that may reflect differential susceptibility to the environment. In addition, findings have implicated these temperament × environment interactions in predicting a wide variety of child outcomes. This study uses a novel evolutionary model of temperament to examine whether differential susceptibility operates in a domain-general or domain-specific manner. Using a racially and socioeconomically diverse sample of 243 preschoolers and their parents (56% female; 48% African American), we examined the interactions between maternal and paternal parenting quality and two evolutionary informed temperament profiles (i.e., Hawks and Doves) in predicting changes in teacher-reported conduct problems and depressive symptoms from preschool to first grade. Results suggest that differential susceptibility operates in a domain-specific fashion. Specifically, the “Hawk” temperament was differentially susceptible to maternal parenting in predicting externalizing problems. In contrast, the “Dove” temperament was susceptible to both paternal and maternal parenting quality in predicting changes in depressive symptoms. Findings provide support for an integrative framework that synthesizes DST with an evolutionary, function-based approach to temperament.

OBJECTIVES/GOALS: Immunomodulatory drugs (IMiDs) are critical to multiple myeloma (MM) disease control. IMiDs act by inducing Cereblon-dependent degradation of IKZF1 and IKZF3, which leads to IRF4 and MYC downregulation (collectively termed the “Ikaros axis”). We therefore hypothesized that IMiD treatment fails to downregulate the Ikaros axis in IMiD resistant MM. METHODS/STUDY POPULATION: To measure IMiD-induced Ikaros axis downregulation, we designed an intracellular flow cytometry assay that measured relative protein levels of IKZF1, IKZF3, IRF4 and MYC in MM cells following ex vivo treatment with the IMiD Pomalidomide (Pom). We established this assay using Pom-sensitive parental and dose-escalated Pom-resistant MM cell lines before assessing Ikaros axis downregulation in CD38+CD138+ MM cells in patient samples (bone marrow aspirates). To assess the Ikaros axis in the context of MM intratumoral heterogeneity, we used a 35-marker mass cytometry panel to simultaneously characterize MM subpopulations in patient samples. Lastly, we determined ex vivo drug sensitivity in patient samples via flow cytometry. RESULTS/ANTICIPATED RESULTS: Our hypothesis was supported in MM cell lines, as resistant lines showed no IMiD-induced decrease in any Ikaros axis proteins. However, when assessed in patient samples, Pom treatment caused a significant decrease in IKZF1, IKZF3 and IRF4 regardless of IMiD sensitivity. Mass cytometry in patient samples revealed that individual Ikaros axis proteins were differentially expressed between subpopulations. When correlating this with ex vivo Pom sensitivity of MM subpopulations, we observed that low IKZF1 and IKZF3 corresponded to Pom resistance. Interestingly, most of these resistant populations still expressed MYC. We therefore assessed whether IMiD resistant MM was MYC dependent by treating with MYCi975. In 88% (7/8) of patient samples tested, IMiD resistant MM cells were sensitive to MYC inhibition. DISCUSSION/SIGNIFICANCE: While our findings did not support our initial hypothesis, our data suggest a mechanism where MYC expression becomes Ikaros axis independent to drive IMiD resistance, and resistant MM is still dependent on MYC. This suggests targeting MYC directly or indirectly via a mechanism to be determined may be an effective strategy to eradicate IMiD resistant MM.