The recommended first-line treatment for insomnia is cognitive behavioral therapy for insomnia (CBTi), but access is limited. Telehealth- or internet-delivered CBTi are alternative ways to increase access. To date, these intervention modalities have never been compared within a single study. Further, few studies have examined (a) predictors of response to the different modalities, (b) whether successfully treating insomnia can result in improvement of health-related biomarkers, and (c) mechanisms of change in CBTi. This protocol was designed to compare the three CBTi modalities to each other and a waitlist control for adults aged 50–65 years (N = 100). Participants are randomly assigned to one of four study arms: in-person- (n = 30), telehealth- (n = 30) internet-delivered (n = 30) CBTi, or 12-week waitlist control (n = 10). Outcomes include self-reported insomnia symptom severity, polysomnography, circadian rhythms of activity and core body temperature, blood- and sweat-based biomarkers, cognitive functioning and magnetic resonance imaging.

From early on, infants show a preference for infant-directed speech (IDS) over adult-directed speech (ADS), and exposure to IDS has been correlated with language outcome measures such as vocabulary. The present multi-laboratory study explores this issue by investigating whether there is a link between early preference for IDS and later vocabulary size. Infants’ preference for IDS was tested as part of the ManyBabies 1 project, and follow-up CDI data were collected from a subsample of this dataset at 18 and 24 months. A total of 341 (18 months) and 327 (24 months) infants were tested across 21 laboratories. In neither preregistered analyses with North American and UK English, nor exploratory analyses with a larger sample did we find evidence for a relation between IDS preference and later vocabulary. We discuss implications of this finding in light of recent work suggesting that IDS preference measured in the laboratory has low test-retest reliability.

OBJECTIVES/GOALS: Uterine fibroids are benign tumors of the uterus with a high disease prevalence and burden, yet there are few multi-ancestry genetic studies. This is the largest and most diverse fibroid GWAS to-date. Our goal is to identify novel genetic variants and gene expression pathways associated with fibroids and characterize their biological relevance. METHODS/STUDY POPULATION: We performed a cross-ancestry meta-analysis of GWAS summary statistics from eight datasets. The total sample size was 74,294 cases and 465,810 controls with participants of European (80% of sample), African (4%), East Asian, and Central South Asian (16%) ancestry. We mapped variants to genes with OpenTarget Genetics and used Functional Mapping and Annotation to conduct tissue expression gene-set enrichment and identify lead variants. We used S-PrediXcan to estimate genetically predicted gene expression (GPGE) associated with fibroid risk. This was with models that predicted gene expression across 49 different tissue types. Ingenuity Pathway Analysis compiled significant GPGE genes and their weights with a scientific literature database to identify overlapping pathways. RESULTS/ANTICIPATED RESULTS: We identified 370 independent significant variants. Among these, we identified variants mapped to three novel genes (PAX2, VIP, FOXO3) and eight genes not previously validated (TEKT1, SLC16A11, RPEL1, RASL11B, ASGR1, SLC12A7, TTC28, POLR2A). Many loci have roles in cell cycle regulation or are associated with fibroid risk factors like blood pressure, BMI, and vitamin D levels. Loci were significantly enriched in DNA damage and cell cycle pathways. Of 588 significant predicted expression gene-tissue pairs, 173 unique genes were novel fibroid associations. These genes are also associated with cancers, estradiol, and endometriosis. Top enriched pathways included p53 signaling, HOTAIR, BRCA1DNA damage response, and pulmonary fibrosis signaling. In uterine tissue there were 15 novel GPGE associations. DISCUSSION/SIGNIFICANCE: Using this large and diverse data, we identified novel loci associated with fibroids that are enriched in hormone-response, DNA damage, and cell-cycle pathways. GPGE loci were in tumorigenesis and fibrosis pathways. These novel genetic loci and uterine gene expression findings may provide translational opportunities for novel fibroid treatments.

Background: Sex differences in treatment response to intravenous thrombolysis (IVT) are poorly characterized. We compared sex-disaggregated outcomes in patients receiving IVT for acute ischemic stroke in the Alteplase compared to Tenecteplase (AcT) trial, a Canadian multicentre, randomised trial. Methods: In this post-hoc analysis, the primary outcome was excellent functional outcome (modified Rankin Score [mRS] 0-1) at 90 days. Secondary and safety outcomes included return to baseline function, successful reperfusion (eTICI≥2b), death and symptomatic intracerebral hemorrhage. Results: Of 1577 patients, there were 755 women and 822 men (median age 77 [68-86]; 70 [59-79]). There were no differences in rates of mRS 0-1 (aRR 0.95 [0.86-1.06]), return to baseline function (aRR 0.94 [0.84-1.06]), reperfusion (aRR 0.98 [0.80-1.19]) and death (aRR 0.91 [0.79-1.18]). There was no effect modification by treatment type on the association between sex and outcomes. The probability of excellent functional outcome decreased with increasing onset-to-needle time. This relation did not vary by sex (pinteraction 0.42). Conclusions: The AcT trial demonstrated comparable functional, safety and angiographic outcomes by sex. This effect did not differ between alteplase and tenecteplase. The pragmatic enrolment and broad national participation in AcT provide reassurance that there do not appear to be sex differences in outcomes amongst Canadians receiving IVT.

There is irrefutable evidence that routine physical activity or exercise can offer considerable health benefits to individuals living with various mental disorders. However, it is not clear what effect physical activity has on the symptoms of Tourette syndrome. Despite a paucity of evidence, physical activity or exercise has already been recommended by various health organizations for the management of tics. We provide a systematic review of the effects of physical activity or exercise on tic symptomology in individuals with Tourette syndrome. Major electronic databases were searched for all available publications before August 2017. Keywords and MeSH terms included “physical activity” or “exercise” or “exercise therapy” or “physical exertion” or “sports” and “tics” or “tic disorders” or “Tourette.” Eight studies were included, the majority of which were case reports. Despite a number of methodological limitations of the included studies, the review points to a trend that the effects of acute physical activity are intensity-dependent, where light intensity may alleviate and vigorous intensity may exacerbate tics. Chronic physical activity, however, appears to reduce the severity of tics even at higher intensity. Several physiological mechanisms may explain the differential effects of acute and chronic physical activity in Tourette syndrome. Future randomized controlled studies should better characterize the effects of different intensities and types of physical activity in Tourette syndrome.

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 describe the design and performance of the Engineering Development Array, which is a low-frequency radio telescope comprising 256 dual-polarisation dipole antennas working as a phased array. The Engineering Development Array was conceived of, developed, and deployed in just 18 months via re-use of Square Kilometre Array precursor technology and expertise, specifically from the Murchison Widefield Array radio telescope. Using drift scans and a model for the sky brightness temperature at low frequencies, we have derived the Engineering Development Array’s receiver temperature as a function of frequency. The Engineering Development Array is shown to be sky-noise limited over most of the frequency range measured between 60 and 240 MHz. By using the Engineering Development Array in interferometric mode with the Murchison Widefield Array, we used calibrated visibilities to measure the absolute sensitivity of the array. The measured array sensitivity matches very well with a model based on the array layout and measured receiver temperature. The results demonstrate the practicality and feasibility of using Murchison Widefield Array-style precursor technology for Square Kilometre Array-scale stations. The modular architecture of the Engineering Development Array allows upgrades to the array to be rolled out in a staged approach. Future improvements to the Engineering Development Array include replacing the second stage beamformer with a fully digital system, and to transition to using RF-over-fibre for the signal output from first stage beamformers.

Anomalous aortic origin of the coronary arteries is associated with exercise-induced ischaemia, leading some physicians to restrict exercise in patients with this condition. We sought to determine whether exercise restriction was associated with increasing body mass index over time. From 1998 to 2015, 440 patients ⩽30 years old were enrolled into an inception cohort. Exercise-restriction status was documented in 143 patients. Using linear mixed model repeated-measures regression, factors associated with increasing body mass index z-score over time, including exercise restriction and surgical intervention as time-varying covariates, were investigated. The 143 patients attended 558 clinic visits for which exercise-restriction status was recorded. The mean number of clinic visits per patient was 4, and the median duration of follow-up was 1.7 years (interquartile range (IQR) 0.5–4.4). The median age at first clinic visit was 10.3 years (IQR 7.1–13.9), and 71% (101/143) were males. All patients were alive at their most recent follow-up. At the first clinic visit, 54% (78/143) were exercise restricted, and restriction status changed in 34% (48/143) during follow-up. The median baseline body mass index z-score was 0.2 (IQR 0.3–0.9). In repeated-measures analysis, neither time-related exercise restriction nor its interaction with time was associated with increasing body mass index z-score. Surgical intervention and its interaction with time were associated with decreasing body mass index z-score. Although exercise restriction was not associated with increasing body mass index over time, surgical intervention was associated with decreasing body mass index z-score over time in patients with anomalous aortic origin of the coronary arteries.

After a protracted national discussion about racial mixture in the early 1990s, the Office of Management and Budget made the unprecedented decision in 1997 to allow Americans to “mark one or more” racial categories on the 2000 census. A small “multiracial movement” provoked this fundamental change in the way the government collects racial data. This case study shows that even very small and modest social movements can have profound effects on public policy through their unintended consequences. In winning a redefinition of how the U.S. government defines and counts by race, the multiracial movement of the 1990s set in motion a process that has both amplified and been amplified by broader structural and cultural changes in how Americans perceive race. The modest impact of a small social movement can ultimately produce very big consequences.

This study uses locally weighted regression to identify county-level characteristics that serve as drivers of creative employment throughout the southern United States. We found that higher per capita income, greater infrastructure investments, and the rural nature of a county tended to promote creative employment density, while higher scores on a natural amenity index had the opposite effect. We were also able to identify and map clusters of rural counties where the marginal effects of these variables on creative employment density were greatest. These findings should help rural communities to promote creative employment growth as a means of furthering rural economic development.

In 2010, the Alabama GOP took control of the state legislature for the first time since Reconstruction. The next year, in a sharply partisan vote, the legislature passed, and Governor Robert Bentley (R) signed into law, the Beason-Hammon Alabama Taxpayer and Citizen Protection Act, also known as House Bill 56, the harshest immigration law in the country. This punitive state law was the impetus for Black elites in Birmingham to frame the immigration debate as a matter of civil rights and thus to see the issue in a new light. When Alabama Republicans moved to the Right on immigration, Black leaders in Birmingham moved Left. In this study, backed up by an event analysis of local newspapers, an analysis of interviews with members of the Black elite in Birmingham in 2013, who were previously interviewed in 2007, helps to substantiate this claim. In the summer of 2007, against the backdrop of an immigration debate in Washington, our Black elite study participants largely told us they had no stake in immigration. By 2013, many were willing to fight for immigrant rights at the highest level.

Since its inception in 2010, the Network for Public Health Law (Network) has aligned with federal, state, tribal, and local public health practitioners to assess how law can promote and protect the public’s health. In 2013, Network authors illustrated major trends in public health laws and policies emanating from an internal assessment of thousands of requests for technical assistance nationally. More recently, the Robert Wood Johnson Foundation (RWJF) has invited the Network and other partners to consider new ideas and strategies toward building a “culture of health.” Per Figure 1, RWJF’s conception of a culture of health emphasizes key action areas essential to the promotion of health across all sectors and diverse populations.

A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.