Respiratory distress syndrome results from inadequate functional pulmonary surfactant and is a significant cause of mortality in preterm infants. Surfactant is essential for regulating alveolar interfacial surface tension, and its synthesis by Type II alveolar epithelial cells is stimulated by leptin produced by pulmonary lipofibroblasts upon activation by peroxisome proliferator-activated receptor γ (PPARγ). As it is unknown whether PPARγ stimulation or direct leptin administration can stimulate surfactant synthesis before birth, we examined the effect of continuous fetal administration of either the PPARγ agonist, rosiglitazone (RGZ; Study 1) or leptin (Study 2) on surfactant protein maturation in the late gestation fetal sheep lung. We measured mRNA expression of genes involved in surfactant maturation and showed that RGZ treatment reduced mRNA expression of LPCAT1 (surfactant phospholipid synthesis) and LAMP3 (marker for lamellar bodies), but did not alter mRNA expression of PPARγ, surfactant proteins (SFTP-A, -B, -C, and -D), PCYT1A (surfactant phospholipid synthesis), ABCA3 (phospholipid transportation), or the PPARγ target genes SPHK-1 and PAI-1. Leptin infusion significantly increased the expression of PPARγ and IGF2 and decreased the expression of SFTP-B. However, mRNA expression of the majority of genes involved in surfactant synthesis was not affected. These results suggest a potential decreased capacity for surfactant phospholipid and protein production in the fetal lung after RGZ and leptin administration, respectively. Therefore, targeting PPARγ may not be a feasible mechanistic approach to promote lung maturation.

Psychosocial stress in childhood and adolescence is linked to stress system dysregulation, although few studies have examined the relative impacts of parental harshness and parental disengagement. This study prospectively tested whether parental harshness and disengagement show differential associations with overall cortisol output in adolescence. Associations between overall cortisol output and adolescent mental health problems were tested concurrently. Adolescents from the Fragile Families and Child Wellbeing Study (FFCWS) provided hair samples for cortisol assay at 15 years (N = 171). Caregivers reported on parental harshness and disengagement experiences at 1, 3, 5, 9, and 15 years, and adolescents reported at 15 years. Both parent and adolescent reported depressive and anxiety symptoms and antisocial behaviors at 15. Greater parental harshness from 1–15 years, and harshness reported at 15 years in particular, was associated with higher overall cortisol output at 15. Greater parental disengagement from 1–15 years, and disengagement at 1 year specifically, was associated with lower cortisol output. There were no significant associations between cortisol output and depressive symptoms, anxiety symptoms, or antisocial behaviors. These results suggest that the unique variances of parental harshness and disengagement may have opposing associations with cortisol output at 15 years, with unclear implications for adolescent mental health.

In contrast to temperate regions, relationships between basin characteristics (e.g., type/size) and fossil pollen archives have received little attention in Amazonia. Here, we compare fossil pollen records of a small palm swamp (Cuatro Vientos; CV) and a nearby large lake (Laguna Chaplin, LCH) in Bolivian Amazonia, demonstrating that palm swamps can yield Quaternary pollen archives recording the history of terrestrial vegetation beyond the basin margin, rather than merely a history of localized swamp vegetation dynamics. The pollen assemblages from these two contrasting basins display remarkable agreement throughout their late Quaternary history, indicating past drier climates supported savanna landscape during the last glacial maximum (LGM; 24,000–18,000 cal yr BP) and savanna/semideciduous forest mosaic during the middle Holocene (7000-4750 cal yr BP) at both regional (inferred from LCH) and local (inferred from CV) spatial scales. Additionally, the local-scale catchment of CV and the basin's proximity to the riverine forests of the Río Paraguá enables exploration of the extent of gallery/riverine forests during the LGM and middle Holocene. We show that, between 24,000–4000 cal yr BP, riverine/gallery rainforests were substantially reduced compared with present, challenging the hypothesis that gallery rainforests were important refugia for rainforest species during the drier LGM and middle Holocene.

Diet has a major influence on the composition and metabolic output of the gut microbiome. Higher-protein diets are often recommended for older consumers; however, the effect of high-protein diets on the gut microbiota and faecal volatile organic compounds (VOC) of elderly participants is unknown. The purpose of the study was to establish if the faecal microbiota composition and VOC in older men are different after a diet containing the recommended dietary intake (RDA) of protein compared with a diet containing twice the RDA (2RDA). Healthy males (74⋅2 (sd 3⋅6) years; n 28) were randomised to consume the RDA of protein (0⋅8 g protein/kg body weight per d) or 2RDA, for 10 weeks. Dietary protein was provided via whole foods rather than supplementation or fortification. The diets were matched for dietary fibre from fruit and vegetables. Faecal samples were collected pre- and post-intervention for microbiota profiling by 16S ribosomal RNA amplicon sequencing and VOC analysis by head space/solid-phase microextraction/GC-MS. After correcting for multiple comparisons, no significant differences in the abundance of faecal microbiota or VOC associated with protein fermentation were evident between the RDA and 2RDA diets. Therefore, in the present study, a twofold difference in dietary protein intake did not alter gut microbiota or VOC indicative of altered protein fermentation.

OBJECTIVES/GOALS: We compared the validity of an International Classification of Diseases, Clinical Modification (ICD) algorithm for identifying high-grade cervical intraepithelial neoplasia and adenocarcinoma in situ (together referred to as CIN2+) from ICD 9th revision (ICD-9) and 10th revision (ICD-10) codes. METHODS/STUDY POPULATION: Using Tennessee Medicaid data, we identified cervical diagnostic procedures in 2008-2017 among females aged 18-39 years in Davidson County, TN. Gold-standard cases were pathology-confirmed CIN2+ diagnoses validated by HPV-IMPACT, a population-based surveillance project in catchment areas of five US states. Procedures in the ICD transition year (2015) were excluded to account for implementation lag. We pre-grouped diagnosis and procedure codes by theme. We performed feature selection using least absolute shrinkage and selection operator (LASSO) logistic regression with 10-fold cross validation and validated models by ICD-9 era (2008-2014, N = 6594) and ICD-10 era (2016-2017, N = 1270). RESULTS/ANTICIPATED RESULTS: Of 7864 cervical diagnostic procedures, 880 (11%) were true CIN2+ cases. LASSO logistic regression selected the strongest features of case status: Having codes for a CIN2+ tissue diagnosis, non-specific CIN tissue diagnosis, high-grade squamous intraepithelial lesion, receiving a cervical treatment procedure, and receiving a cervical/vaginal biopsy. Features of non-case status were codes for a CIN1 tissue diagnosis, Pap test, and HPV DNA test. The ICD-9 vs ICD-10 algorithms predicted case status with 68% vs 63% sensitivity, 95% vs 94% specificity, 63% vs 64% positive predictive value, 96% vs 94% negative predictive value, 92% vs 89% accuracy, and C-indices of 0.95 vs 0.92, respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Overall, the algorithm’s validity for identifying CIN2+ case status was similar between coding versions. ICD-9 had slightly better discriminative ability. Results support a prior study concluding that ICD-10 implementation has not substantially improved the quality of administrative data from ICD-9.

This project will work closely with existing service partners involved in street level services and focus on testing and evaluating three approaches for street level interventions for youth who are homeless and who have severe or moderate mentally illness. Youth will be asked to choose their preferred service approach:

Housing First related initiatives focused on interventions designed to move youth to appropriate and available housing and ongoing housing supports.

Treatment First initiatives to provide Mental Health/Addiction supports and treatment solutions, and; Simultaneous attention to both Housing and Treatment Together

Our primary objective is to understand the service delivery preferences of homeless youth and understand the outcomes of these choices. Our research questions include:

1. 1. Which approaches to service are chosen by youth?

2. 2. What are the differences and similarities between groups choosing each approach?

3. 3. What are the critical ingredients needed to effectively implement services for homeless youth from the perspectives of youth, families and service providers?

Focus groups with staff and family members will occur to assist in understanding the nature of each of service approach, changes that evolve within services, & facilitators and barriers to service delivery. This work will be important in determining which approach is chosen by youth and why. Evaluating the outcomes with each choice will provide valuable information about outcomes for the service options chosen by youth. This assist in better identifying weaknesses in the services offered and inform further development of treatment options that youth will accept.

Dietary patterns describe the combination of foods and beverages in a diet and the frequency of habitual consumption. Better understanding of childhood dietary patterns and antenatal influences could inform intervention strategies to prevent childhood obesity. We derived empirical dietary patterns in 1142 children (average age 6·0 (sd 0·2) years) in New Zealand, whose mothers had participated in the Screening for Pregnancy Endpoints (SCOPE) cohort study and explored associations with measures of body composition. Participants (Children of SCOPE) had their diet assessed by FFQ, and dietary patterns were extracted using factor analysis. Three distinct dietary patterns were identified: ‘Healthy’, ‘Traditional’ and ‘Junk’. Associations between dietary patterns and measures of childhood body composition (waist, hip, arm circumferences, BMI, bioelectrical impedance analysis-derived body fat % and sum of skinfold thicknesses (SST)) were assessed by linear regression, with adjustment for maternal influences. Children who had higher ‘Junk’ dietary pattern scores had 0·24 (sd 0·08; 95 % CI 0·04, 0·13) cm greater arm and 0·44 (sd 0·05; 95 % CI 0·01, 0·10) cm greater hip circumferences and 1·13 (sd 0·07; 95 % CI 0·03, 0·12) cm greater SST and were more likely to be obese (OR 1·74; 95 % CI 1·07, 2·82); those with higher ‘Healthy’ pattern scores were less likely to be obese (OR 0·62; 95 % CI 0·39, 1·00). In a large mother–child cohort, a dietary pattern characterised by high-sugar and -fat foods was associated with greater adiposity and obesity risk in children aged 6 years, while a ‘Healthy’ dietary pattern offered some protection against obesity. Targeting unhealthy dietary patterns could inform public health strategies to reduce the prevalence of childhood obesity.

Healthcare personnel who perform invasive procedures and are living with HIV or hepatitis B have been required to self-notify the NC state health department since 1992. State coordinated review of HCP utilizes a panel of experts to evaluate transmission risk and recommend infection prevention measures. We describe how this practice balances HCP privacy and patient safety and health.

We have designed and implemented an experimental module in the 2014 Health and Retirement Study to measure older persons' willingness to defer claiming of Social Security benefits. Under the current system’ status quo where delaying claiming boosts eventual benefits, we show that 46% of the respondents would delay claiming and work longer. If respondents were instead offered an actuarially fair lump sum payment instead of higher lifelong benefits, about 56% indicate they would delay claiming. Without a work requirement, the average amount needed to induce delayed claiming is only $60,400, while when part-time work is stipulated, the amount is slightly higher, $66,700. This small difference implies a low utility value of leisure foregone, of under 20% of average household income.

The Murchison Widefield Array is a low-frequency Square Kilometre Array precursor located at the Murchison Radio-astronomy Observatory in Western Australia. Primarily designed as an imaging telescope, but with a flexible signal path, the capabilities of this telescope have recently been extended to include off-line incoherent and tied-array beam formation using recorded antenna voltages. This has provided the capability for high-time and frequency resolution observations, including a pulsar science program. This paper describes the algorithms and pipeline that we have developed to form the tied-array beam products from the summation of calibrated signals of the antenna elements, and presents example polarimetric profiles for PSRs J0437-4715 and J1900-2600 at 185 MHz.

We apply two methods to estimate the 21-cm bispectrum from data taken within the Epoch of Reionisation (EoR) project of the Murchison Widefield Array (MWA). Using data acquired with the Phase II compact array allows a direct bispectrum estimate to be undertaken on the multiple redundantly spaced triangles of antenna tiles, as well as an estimate based on data gridded to the uv-plane. The direct and gridded bispectrum estimators are applied to 21 h of high-band (167–197 MHz; z = 6.2–7.5) data from the 2016 and 2017 observing seasons. Analytic predictions for the bispectrum bias and variance for point-source foregrounds are derived. We compare the output of these approaches, the foreground contribution to the signal, and future prospects for measuring the bispectra with redundant and non-redundant arrays. We find that some triangle configurations yield bispectrum estimates that are consistent with the expected noise level after 10 h, while equilateral configurations are strongly foreground-dominated. Careful choice of triangle configurations may be made to reduce foreground bias that hinders power spectrum estimators, and the 21-cm bispectrum may be accessible in less time than the 21-cm power spectrum for some wave modes, with detections in hundreds of hours.

After five positive randomized controlled trials showed benefit of mechanical thrombectomy in the management of acute ischemic stroke with emergent large-vessel occlusion, a multi-society meeting was organized during the 17th Congress of the World Federation of Interventional and Therapeutic Neuroradiology in October 2017 in Budapest, Hungary. This multi-society meeting was dedicated to establish standards of practice in acute ischemic stroke intervention aiming for a consensus on the minimum requirements for centers providing such treatment. In an ideal situation, all patients would be treated at a center offering a full spectrum of neuroendovascular care (a level 1 center). However, for geographical reasons, some patients are unable to reach such a center in a reasonable period of time. With this in mind, the group paid special attention to define recommendations on the prerequisites of organizing stroke centers providing medical thrombectomy for acute ischemic stroke, but not for other neurovascular diseases (level 2 centers). Finally, some centers will have a stroke unit and offer intravenous thrombolysis, but not any endovascular stroke therapy (level 3 centers). Together, these level 1, 2, and 3 centers form a complete stroke system of care. The multi-society group provides recommendations and a framework for the development of medical thrombectomy services worldwide.

Essential variables to consider for an efficient control strategy for invasive plants include dispersion pattern (i.e., satellite or invasion front) and patch expansion rate. These variables were demonstrated for buffelgrass [Pennisetum ciliare (L.) Link], a C4 perennial grass introduced from Africa, which has invaded broadly around the world. The study site was along a roadway in southern Arizona (USA). The P. ciliare plant distributions show the pattern of clumping associated with the satellite (nascent foci) colonization pattern (average nearest neighbor test, z-score −47.2, P<0.01). The distance between patches ranged from 0.743 to 12.8 km, with an average distance between patches of 5.6 km. Median patch expansion rate was 271% over the 3-yr monitoring period versus 136% found in other studies of established P. ciliare patches. Targeting P. ciliare satellite patches as a control strategy may exponentially reduce the areal doubling time, while targeting the largest patches may have less effect on the invasion speed.

Many believe that global capital markets will generate lower returns in the future versus the past. We examine how persistently lower real returns will reshape work, retirement, saving, and investment behavior of older persons using a calibrated dynamic life cycle model. In a low return regime, workers build up less wealth in their tax-qualified 401(k) accounts versus the past, claim social security benefits later, and work more. Moreover, the better-educated are more sensitive to real interest rate changes, while the least-educated alter their behavior less. Interestingly, the distribution of wealth is more uniform in periods of persistent low expected returns.

Two competing explanations for why consumers have trouble with financial decisions are gaining momentum. One is that people are financially illiterate since they lack understanding of simple economic concepts and cannot carry out computations such as computing compound interest, which could cause them to make suboptimal financial decisions. A second is that impatience or present-bias might explain suboptimal financial decisions. That is, some people persistently choose immediate gratification instead of taking advantage of larger long-term payoffs. We use experimental evidence from Chile to explore how these factors appear related to poor financial decisions. Our results show that our measure of impatience is a strong predictor of wealth and investment in health. Financial literacy is also correlated with wealth though it appears to be a weaker predictor of sensitivity to framing in investment decisions. Policymakers interested in enhancing retirement well-being would do well to consider the importance of both factors.