The consent process for research studies can be burdensome for potential participants due to complex information and lengthy consent forms. This pragmatic study aimed to improve the consent experience and evaluate its impact on participant decision making, study knowledge, and satisfaction with the In Our DNA SC program, a population-based genomic screening initiative. We compared two consent procedures: standard consent (SC) involving a PDF document and enhanced consent (EC) incorporating a pictograph and true or false questions. Decision-making control, study knowledge, satisfaction, and time to consent were assessed. We analyzed data for 109 individuals who completed the SC and 96 who completed the EC. Results indicated strong decision-making control and high levels of knowledge and satisfaction in both groups. While no significant differences were found between the two groups, the EC experience took longer for participants to complete. Future modifications include incorporating video modules and launching a Spanish version of the consent experience. Overall, this study contributes to the growing literature on consent improvements and highlights the need to assess salient components and explore participant preferences for receiving consent information.

We recently reported on the radio-frequency attenuation length of cold polar ice at Summit Station, Greenland, based on bi-static radar measurements of radio-frequency bedrock echo strengths taken during the summer of 2021. Those data also allow studies of (a) the relative contributions of coherent (such as discrete internal conducting layers with sub-centimeter transverse scale) vs incoherent (e.g. bulk volumetric) scattering, (b) the magnitude of internal layer reflection coefficients, (c) limits on signal propagation velocity asymmetries (‘birefringence’) and (d) limits on signal dispersion in-ice over a bandwidth of ~100 MHz. We find that (1) attenuation lengths approach 1 km in our band, (2) after averaging 10 000 echo triggers, reflected signals observable over the thermal floor (to depths of ~1500 m) are consistent with being entirely coherent, (3) internal layer reflectivities are ≈–60$\to$–70 dB, (4) birefringent effects for vertically propagating signals are smaller by an order of magnitude relative to South Pole and (5) within our experimental limits, glacial ice is non-dispersive over the frequency band relevant for neutrino detection experiments.

OBJECTIVES/GOALS: Glioblastomas (GBMs) are heterogeneous, treatment-resistant tumors that are driven by populations of cancer stem cells (CSCs). In this study, we perform an epigenetic-focused functional genomics screen in GBM organoids and identify WDR5 as an essential epigenetic regulator in the SOX2-enriched, therapy resistant cancer stem cell niche. METHODS/STUDY POPULATION: Despite their importance for tumor growth, few molecular mechanisms critical for CSC population maintenance have been exploited for therapeutic development. We developed a spatially resolved loss-of-function screen in GBM patient-derived organoids to identify essential epigenetic regulators in the SOX2-enriched, therapy resistant niche. Our niche-specific screens identified WDR5, an H3K4 histone methyltransferase responsible for activating specific gene expression, as indispensable for GBM CSC growth and survival. RESULTS/ANTICIPATED RESULTS: In GBM CSC models, WDR5 inhibitors blocked WRAD complex assembly and reduced H3K4 trimethylation and expression of genes involved in CSC-relevant oncogenic pathways. H3K4me3 peaks lost with WDR5 inhibitor treatment occurred disproportionally on POU transcription factor motifs, required for stem cell maintenance and including the POU5F1(OCT4)::SOX2 motif. We incorporated a SOX2/OCT4 motif driven GFP reporter system into our CSC cell models and found that WDR5 inhibitor treatment resulted in dose-dependent silencing of stem cell reporter activity. Further, WDR5 inhibitor treatment altered the stem cell state, disrupting CSC in vitro growth and self-renewal as well as in vivo tumor growth. DISCUSSION/SIGNIFICANCE: Our results unveiled the role of WDR5 in maintaining the CSC state in GBM and provide a rationale for therapeutic development of WDR5 inhibitors for GBM and other advanced cancers. This conceptual and experimental framework can be applied to many cancers, and can unmask unique microenvironmental biology and rationally designed combination therapies.

Among nursing home outbreaks of coronavirus disease 2019 (COVID-19) with ≥3 breakthrough infections when the predominant severe acute respiratory coronavirus virus 2 (SARS-CoV-2) variant circulating was the SARS-CoV-2 δ (delta) variant, fully vaccinated residents were 28% less likely to be infected than were unvaccinated residents. Once infected, they had approximately half the risk for all-cause hospitalization and all-cause death compared with unvaccinated infected residents.

In the US Southwest and Northwest Mexico, people and turkeys (Meleagris gallopavo) have had a reciprocal relationship for millennia; turkeys supplied feathers, meat, and other resources, whereas people provided food, shelter, and care. To investigate how turkeys fit within subsistence, economic production, sociopolitical organization, and religious and ritual practice in the Mimbres Valley of southwestern New Mexico, we report on genetic (mtDNA) and stable isotope (δ13C, δ15N) data from turkeys recovered from Mimbres Classic period (AD 1000–1130) sites. Results indicate that Mimbres aviculturists had haplogroup H1 and H2 turkeys, and most ate maize-based diets similar to humans, but some ate nonmaize and mixed diets. We contextualize these data to other turkey studies from the northern Southwest and discuss how the human-turkey relationship began, the evidence for pens and restricting turkey movement, and the socioecological factors related to turkey management during the Classic period, particularly the challenges associated with providing maize to turkeys during times of environmental stress. This study has broad relevance to places where people managed wild, tame, and domestic animals, and we offer new insights into how prehispanic, small-scale, middle-range agricultural societies managed turkeys for ritual and utilitarian purposes.

By many measures, the public knows little about politics. But just how little people seem to know depends on the questions that are put to them. In particular, knowledge levels seem higher when people are asked closed- rather than open-ended questions. In turn, differences between estimated knowledge levels are sometimes attributed to fundamental differences between these types of questions. Building on this previous research, the present study uses a pre-registered experiment conducted with a representative national sample to shed new light on the relationship between question form and knowledge measurement. The authors find that inferences about political knowledge depend less on fundamental differences between open- and closed-ended questions than on two little-appreciated aspects of survey design: the number and difficulty of the response options that accompany closed-ended questions. These aspects of survey design have large effects. Scholars who use the same questions with different response options may reach substantively different conclusions about the public's levels of knowledge.

Patients with single-ventricle CHD undergo a series of palliative surgeries that culminate in the Fontan procedure. While the Fontan procedure allows most patients to survive to adulthood, the Fontan circulation can eventually lead to multiple cardiac complications and multi-organ dysfunction. Care for adolescents and adults with a Fontan circulation has begun to transition from a primarily cardiac-focused model to care models, which are designed to monitor multiple organ systems, and using clues from this screening, identify patients who are at risk for adverse outcomes. The complexity of care required for these patients led our centre to develop a multidisciplinary Fontan Management Programme with the primary goals of earlier detection and treatment of complications through the development of a cohesive network of diverse medical subspecialists with Fontan expertise.

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.

In western Canada, more money is spent on wild oat herbicides than on any other weed species, and wild oat resistance to herbicides is the most widespread resistance issue. A direct-seeded field experiment was conducted from 2010 to 2014 at eight Canadian sites to determine crop life cycle, crop species, crop seeding rate, crop usage, and herbicide rate combination effects on wild oat management and canola yield. Combining 2× seeding rates of early-cut barley silage with 2× seeding rates of winter cereals and excluding wild oat herbicides for 3 of 5 yr (2011 to 2013) often led to similar wild oat density, aboveground wild oat biomass, wild oat seed density in the soil, and canola yield as a repeated canola–wheat rotation under a full wild oat herbicide rate regime. Wild oat was similarly well managed after 3 yr of perennial alfalfa without wild oat herbicides. Forgoing wild oat herbicides in only 2 of 5 yr from exclusively summer annual crop rotations resulted in higher wild oat density, biomass, and seed banks. Management systems that effectively combine diverse and optimal cultural practices against weeds, and limit herbicide use, reduce selection pressure for weed resistance to herbicides and prolong the utility of threatened herbicide tools.

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.