OBJECTIVES/GOALS: Women and healthcare providers from underserved rural and urban communities participated in Community Engagement (CE) studios to offer perspectives for increasing research participation of women from diverse backgrounds prior to initiating recruitment for a randomized-controlled trial comparing treatments for urgency urinary incontinence. METHODS/STUDY POPULATION: CE studios are listening sessions to gather patient or community input on specific study areas of interest before implementation. Ten CE studios were held via Zoom at five study sites (Rhode Island, Washington DC, Alabama, New Mexico, and Southern California). Each site held two studios: 1) women living with urgency urinary incontinence, 2) clinicians providing care in their areas. Participants gave recommendations on ways to increase study participation of women from diverse racial and ethnic backgrounds with a focus on recruitment and retention, identification of barriers to participation, and suggested approaches to overcome those barriers. Summaries were compiled from each CE studio to identify similar and contrasting recommendations across sites. RESULTS/ANTICIPATED RESULTS: A total of 80 participants (47 community women experiencing urgency urinary incontinence, and 33 healthcare professionals) participated across all sites. Studio participants discussed anticipated barriers for participant recruitment and retention with a focus on solutions to those barriers. Based on these suggestions, we created recruitment materials using pictures, videos, and simple terminology. We created educational content to help providers with current best practices for urinary urgency incontinence. We have allowed most study visits to be conducted virtually, identified affiliated clinics in various locations to improve proximity to undeserved communities, and have earmarked additional funds to help offset travel costs including gas, public transportation, and childcare. DISCUSSION/SIGNIFICANCE: CE studios have provided pragmatic patient- and provider-centered recommendations that have been incorporated into functional strategies to improve research participation and diversity. CTSA CE core expertise can support successful CE studio planning and implementation.

It is under debate how preferential perfusion of the brain (brain-sparing) in fetal growth restriction (FGR) relates to long-term neurodevelopmental outcome. Epigenetic modification of neurotrophic genes by altered fetal oxygenation may be involved. To explore this theory, we performed a follow-up study of 21 FGR children, in whom we prospectively measured the prenatal cerebroplacental ratio (CPR) with Doppler sonography. At 4 years of age, we tested their neurodevelopmental outcome using the Wechsler Preschool and Primary Scale of Intelligence, the Child Behavior Checklist, and the Behavior Rating Inventory of Executive Function. In addition, we collected their buccal DNA to determine the methylation status at predefined genetic regions within the genes hypoxia-inducible factor-1 alpha (HIF1A), vascular endothelial growth factor A (VEGFA), erythropoietin (EPO), EPO-receptor (EPOR), brain-derived neurotrophic factor (BDNF), and neurotrophic tyrosine kinase, receptor, type 2 (NTRK2) by pyrosequencing. We found that FGR children with fetal brain-sparing (CPR <1, n = 8) demonstrated a trend (0.05 < p < 0.1) toward hypermethylation of HIF1A and VEGFA at their hypoxia-response element (HRE) compared with FGR children without fetal brain-sparing. Moreover, in cases with fetal brain-sparing, we observed statistically significant hypermethylation at a binding site for cyclic adenosine monophophate response element binding protein (CREB) of BDNF promoter exon 4 and hypomethylation at an HRE located within the NTRK2 promoter (both p <0.05). Hypermethylation of VEGFA was associated with a poorer Performance Intelligence Quotient, while hypermethylation of BDNF was associated with better inhibitory self-control (both p <0.05). These results led us to formulate the hypothesis that early oxygen-dependent epigenetic alterations due to hemodynamic alterations in FGR may be associated with altered neurodevelopmental outcome in later life. We recommend further studies to test this hypothesis.

Assessing the avalanche danger level requires snow stratigraphy and instability data. As such data are usually sparse, we investigated whether distributed snow cover modeling can be used to provide information on spatial instability patterns relevant for regional avalanche forecasting. Using Alpine3D, we performed spatially distributed simulations to evaluate snow instability for the winter season 2016–17 in the region of Davos, Switzerland. Meteorological data from automatic weather stations were interpolated to 100 m horizontal resolution and precipitation was scaled with snow depth measurements from airborne laser scanning. Modeled snow instability metrics assessed for two different weak layers suggested that the weak layer closer to the snow surface was more variable. Initially, it was less stable than the weak layer closer to the ground, yet it stabilized faster as the winter progressed. In spring, the simulated snowpack on south-facing slopes stabilized faster than on north-facing slopes, in line with the regional avalanche forecast. In the winter months January to March 2017, simulated instability metrics did not suggest that the snowpack on south-facing slopes was more stable, as reported in the regional avalanche forecast. Although a validation with field data is lacking, these model results still show the potential and challenges of distributed modeling for supporting operational avalanche forecasting.

The unique environment of space is characterized by several stress factors, including intense radiation, microgravity, high vacuum and extreme temperatures, among others. These stress conditions individually or in-combination influence genetics and gene regulation and bring potential evolutionary changes in organisms that would not occur under the Earth's gravity regime (1 × g). Thus, space can be explored to support the emergence of new varieties of microbes and plants, that when selected for, can exhibit increased growth and yield, improved resistance to pathogens, enhanced tolerance to drought, low nutrient and disease, produce new metabolites and others. These properties may be more difficult to achieve using other approaches under 1 × g. This review provides an overview of the space microgravity and ionizing radiation conditions that significantly influence organisms. Changes in the genomics, physiology, phenotype, growth and metabolites of organisms in real and simulated microgravity and radiation conditions are illustrated. Results of space biological experiments show that the space environment has significant scientific, technological and commercial potential. Combined these potentials can help address the future of life on Earth, part of goal e of astrobiology.

Winter ice dynamics plays an important role in the energy budget of the air-ice-ocean system, through the formation of leads and ridges. In summer, thermodynamic processes cause a transition in the ice pack from a mechanical continuum to an ensemble of floes that move in a state of free drift, with little floe-floe interaction. Results from the recent Surface Heat Budget of the Arctic Ocean (SHEBA) experiment have demonstrated that even under summer conditions, ice dynamics can still cause dramatic changes in the characteristics of the ice-ocean matrix that affect the energy budget. To illustrate this, we present observations taken before and after a period of sustained, moderate winds in late July 1998, which was preceded by an extended period of low winds. These conditions resulted in significant differential motion of ice floes in the vicinity of SHEBA. The measurements include the mass balance of the ice cover, the distribution of ice and open water, and salinity and temperature profiles in leads. The data show that after the storm there was a significant change in the amount and distribution of open-water areas, that there was an increase in the rate of bottom ablation, and that a stratified layer of warm fresh water that had formed at the top of leads during melt had become mixed.

Dormant states of organisms are easier to store than the living state because they tolerate larger variations in temperature, light, storage space etc., making them attractive for laboratory culture stocks and also for experiments under special circumstances, especially space flight experiments. Like several other organisms, Euglena gracilis is capable of forming desiccation tolerant resting states in order to survive periods of unfavourable environmental conditions. In earlier experiments it was found that dormant Euglena cells must not become completely desiccated. Some residual moisture is required to ensure recovery of the resting states. To analyse the water demand in recovery of Euglena resting states, cells were transferred to a defined amount of cotton wool (0.5 g). Subsequently different volumes of medium (1, 2, 3, 4, 5, 8, 10 and 20 ml) were added in order to supply humidity; a control was set up without additional liquid. Samples were sealed in transparent 50 ml falcon tubes and stored for 9 months under three different conditions:

• • Constant low light conditions in a culture chamber at 20°C,

• • In a black box, illuminated with short light emitting diode-light pulses provided by joule thieves and

• • In darkness in a black box.

After 9 months, cells were transferred to fresh medium and cell number, photosynthetic efficiency and movement behavior was monitored over 3 weeks. It was found that cells recovered under all conditions except in the control, where no medium was supplied. Transcription levels of 21 genes were analysed with a Multiplex-polymerase chain reaction. One hour after rehydration five of these genes were found to be up-regulated: ubiquitin, heat shock proteins HSP70, HSP90, the calcium-sensor protein frequenin and a distinct protein kinase, which is involved in gravitaxis. The results indicate a transient general stress response of the cells.

Stunting is a measure of overall nutritional status and is a major public health concern because of its association with child mortality and morbidity and later adult performance. This study examined the effects of pregnancy events, birth characteristics and infant risk exposure on stunting at age 2 years. The study, established in 1990 in Soweto, an urban South African township, included 1098 mother–infant pairs enroled in the Birth to Twenty Plus longitudinal birth cohort study. In total, 22% of children were stunted at age 2 years, with males at greater risk than females [24.8 v. 19.4%, odds ratio (OR)=1.38; 95% confidence interval (CI): 1.03, 1.83]. In unadjusted analysis, male sex, household socio-economic status (SES), overcrowding, maternal age, maternal education, single motherhood, ethnicity, birth weight, gestational age and duration of infant breastfeeding were all significantly associated with stunting. In multivariable analysis, higher birth weight was protective against stunting for both sexes. Higher maternal education was protective for females only (adjusted odds ratio (AOR)=0.35; 95% CI: 0.14, 0.87), whereas wealthier household SES protected males (AOR for richest SES group=0.39; 95% CI: 0.16, 0.92). In this and other similar settings, current stunting prevention efforts focussing on primarily providing targeted proximal interventions, such as food supplements, risk undermining the critical importance of addressing key distal determinants of stunting such as SES and maternal education.

Persistent tobacco use and excessive alcohol consumption are major public health concerns worldwide. Both alcohol and nicotine dependence (AD, ND) are genetically influenced complex disorders that exhibit a high degree of comorbidity. To identify gene variants contributing to one or both of these addictions, we first conducted a pooling-based genomewide association study (GWAS) in an Australian population, using Illumina Infinium 1M arrays. Allele frequency differences were compared between pooled DNA from case and control groups for: (1) AD, 1224 cases and 1162 controls; (2) ND, 1273 cases and 1113 controls; and (3) comorbid AD and ND, 599 cases and 488 controls. Secondly, we carried out a GWAS in independent samples from the Netherlands for AD and for ND. Thirdly, we performed a meta-analysis of the 10, 000 most significant AD- and ND-related SNPs from the Australian and Dutch samples. In the Australian GWAS, one SNP achieved genomewide significance (p < 5 x 10-8) for ND (rs964170 in ARHGAPlOon chromosome 4, p = 4.43 x 10”8) and three others for comorbid AD/ND (rs7530302 near MARK1 on chromosome 1 (p = 1.90 x 10-9), rs1784300 near DDX6 on chromosome 11 (p = 2.60 x 10-9) and rs12882384 in KIAA1409 on chromosome 14 (p = 4.86 x 10-8)). None of the SNPs achieved genomewide significance in the Australian/Dutch meta-analysis, but a gene network diagram based on the top-results revealed overrepre-sentation of genes coding for ion-channels and cell adhesion molecules. Further studies will be requirec before the detailed causes of comorbidity between AC and ND are understood.

The identification of multipotent adipose-derived stromal cells (ASC) has raised hope that tissue regeneration approaches established with bone-marrow-derived stromal cells (BMSC) can be reproduced with a cell-type that is far more accessible in large quantities. Recent detailed comparisons, however, revealed subtle functional differences between ASC and BMSC, stressing the concept of a common mesenchymal progenitor existing in a perivascular niche across all tissues. Focussing on bone and cartilage repair, this review summarises recent in vitro and in vivo studies aiming towards tissue regeneration with ASC. Advantages of good accessibility, high yield and superior growth properties are counterbalanced by an inferiority of ASC to form ectopic bone and stimulate long-bone healing along with their less pronounced osteogenic and angiogenic gene expression signature. Hence, particular emphasis is placed on establishing whether stem cell activity of ASC is so far proven and relevant for successful osteochondral regeneration, or whether trophic activity may largely determine therapeutic outcome.

We describe the geometry and kinematics of a Jurassic to Early Cretaceous transpressive sinistral strike-slip system within a metamorphic basement inlier of the Mesozoic magmatic arc near Bahia Agua Dulce at latitudes 31–32°S in north-central Chile and discuss possible relations with the Atacama Fault System further north. Sinistral transpression overprints structures of an accretionary system that is represented by the metamorphic basement. Sub-vertical semi-ductile NNW-striking strike-slip shear zones are the most conspicuous structures. Chlorite and sericite grew, and white mica and quartz dynamically recrystallized, suggesting low-grade metamorphic conditions during semi-ductile deformation. Folds at the 10–100 metre scale developed before and during strike-slip shearing. The folds are deforming a former sub-horizontal transposition foliation that originated during prior accretion processes. The folds have axes sub-parallel to the strike-slip shear zones and sub-vertical axial surfaces indicating a component of shortening parallel to the shear-zone boundaries, suggesting an overall transpressive deformation regime. Transpressive strike-slip deformation also affects Middle Triassic (Anisian) basal breccias of the El Quereo Formation. 40Ar–39Ar laser ablation ages of synkinematically recrystallized white mica in one of the shear zones provide an age of 174–165 Ma for the waning stages of semi-ductile strike-slip shearing. The semi-ductile shear zones are cut by mafic and rhyolite dykes. Two rhyolite dykes yield 40Ar–39Ar ages of 160.5 ± 1.7 Ma and 131.9 ± 1.7 Ma, respectively. The latter dyke has been affected by brittle faulting. Fault-slip analysis shows that the kinematics of the faulting event is similar to the one of the semi-ductile shearing event, suggesting that sinistral transpression continued after ~130 Ma. Timing, kinematics and geographic position suggest that the shear zones at Bahia Agua Dulce represent a southern continuation of the prominent Atacama Fault System that affected the Jurassic/Early Cretaceous arc over its ~1400 km length.

The inner composition, defect content and morphology of AlGaAs nanowires (NWs) grown on (111)B-GaAs by Au-catalyzed MOVPE is reported. The NWs grow tapered with their [111] axis normal to the substrate. The Raman spectra of single AlGaAs NWs were measured in non-resonant conditions with sub-μ-meter spatial resolution, allowing determination of the Al content. NWs consist of GaAs for TG<475°C, but show a two-fold compositional structure for TG >475°C, namely an AlxGa1-xAs core surrounded by an AlyGa1-yAs (y<x) shell, ascribed to the combination of Au-catalyzed (axial) and conventional (sidewall) growth. The cross-sectional shape of AlGaAs NWs changes from triangular (for TG=500÷525°C) to almost hexagonal (for TG=550°C), due to an exchange between and {110} planes as the slowest to grow. The NWs have free-electron concentrations ∼1018 cm-3, due to Si contamination of the Al source.