Adverse environments are linked to elevated youth antisocial behavior. However, this relation is thought to depend, in part, on genetic susceptibility. The present study investigated whether polygenic risk for antisociality moderates relations between hostile environments and stable as well as dynamic antisocial behaviors across adolescence. We derived two antisocial-linked polygenic risk scores (PRS) (N = 721) based on previous genome-wide association studies. Forms of antisocial behavior (nonaggressive conduct problems, physical aggression, social aggression) and environmental hostility (harsh parenting and school violence) were assessed at age 13, 15, and 17 years. Relations to individual differences stable across adolescence (latent stability) vs. time-specific states (timepoint residual variance) of antisocial behavior were assessed via structural equation models. Higher antisocial PRS, harsh parenting, and school violence were linked to stable elevations in antisocial behaviors across adolescence. We identified a consistent polygenic-environment interaction suggestive of differential susceptibility in late adolescence. At age 17, harsher parenting was linked to higher social aggression in those with higher antisocial PRS, and lower social aggression in those with lower antisocial PRS. This suggests that genetics and environmental hostility relate to stable youth antisocial behaviors, and that genetic susceptibility moderates home environment-antisocial associations specifically in late adolescence.

OBJECTIVES/GOALS: Targeting the V-domain immunoglobulin suppressor of T cell activation (VISTA) signaling pathway has been suggested as a promising approach for overcoming resistance to current immune checkpoint therapies in advanced cancer. This review will synthesize the rapidly-expanding literature on VISTA protein expression on prognosis in various cancers. METHODS/STUDY POPULATION: To determine the prognostic significance of high VISTA expression across treatment-naïve malignant tumors, a systematic review and meta-analysis will be performed of published cohort studies which measured VISTA protein expression on solid tumors. Primary and secondary outcome endpoints of overall survival (OS) and disease-specific survival (DSS) will be compared across cohort studies using a random effects model to calculate pooled hazard ratios (HRs) for each time-to-event end point with 95% CIs. For articles that only provide Kaplan-Meier (KM) curves, the Engauge Digitizer software will be used to measure the time and survival probability coordinates on the KM curves to estimate the HRs. Correlations of VISTA expression and clinicopathological characteristics will be evaluated by pooled risk ratios. RESULTS/ANTICIPATED RESULTS: A search of 4 electronic databases including Pubmed, Embase, Web of Science and Cochrane resulted in 5578 publications of which 66 containing a broad spectrum of malignant solid tumors will undergo full-text review for study inclusion. Tumor types most represented with at least 3 articles include lung, pancreas, skin, head & neck, colorectal, mesothelioma, cervix, soft tissue, breast, liver and ovarian. Our working hypothesis is that the pooled HR for high VISTA expression on overall survival will be approaching 1.0 given conflicting reports across the cancer literature. Risk of bias will be assessed across studies. Quantifications of heterogeneity will be assessed by visual exploration of forest plots as well as by multiple statistical metrics including the Q statistic and the I²coefficient. DISCUSSION/SIGNIFICANCE: The results of this systematic review and meta-analysis will provide a more comprehensive understanding of VISTA’s prognostic role both across all malignant tumors and for subgroups of similar tumor types which may impact the types of tumors and tumor microenvironments selected for early trials of anti-VISTA therapy.

Theory and observation show that glacier-flow regimes characterized by high basal slip enhance the projection of topographic detail to the surface, motivating this investigation into the efficacy of using glacier surges to improve bed estimation. Here we adapt a Bayesian inversion scheme and apply it to real and synthetic data as a proof of concept. Synthetic tests show a reduction in mean RMSE between true and inferred beds by more than half, and an increase in the mean correlation coefficient of ~0.5, when data from slip- versus deformation-dominated regimes are used. Multi-epoch inversions, which partition slip- and deformation-dominated regimes, are shown to outperform inversions that average over these flow regimes thereby squandering information. Tests with real data from a surging glacier in Yukon, Canada, corroborate these results, while highlighting the challenges of limited or inconsistent data. With the growing torrent of satellite-based observations, fast-flow events such as glacier surges offer potential to improve bed estimation for some of the world's most dynamic glaciers.

We investigate the spatial distribution, spectral properties and temporal variability of primary producers (e.g. communities of microbial mats and mosses) throughout the Fryxell basin of Taylor Valley, Antarctica, using high-resolution multispectral remote-sensing data. Our results suggest that photosynthetic communities can be readily detected throughout the Fryxell basin based on their unique near-infrared spectral signatures. Observed intra- and inter-annual variability in spectral signatures are consistent with short-term variations in mat distribution, hydration and photosynthetic activity. Spectral unmixing is also implemented in order to estimate mat abundance, with the most densely vegetated regions observed from orbit correlating spatially with some of the most productive regions of the Fryxell basin. Our work establishes remote sensing as a valuable tool in the study of these ecological communities in the McMurdo Dry Valleys and demonstrates how future scientific investigations and the management of specially protected areas could benefit from these tools and techniques.

This paper is a revised and updated edition of a previous description of the Quebec Newborn Twin Study (QNTS), an ongoing prospective longitudinal follow-up of a birth cohort of twins born between 1995 and 1998 in the greater Montreal area, Québec, Canada. The goal of QNTS is to document individual differences in the cognitive, behavioral, and social-emotional aspects of developmental health across childhood, their early genetic and environmental determinants, as well as their putative role in later social-emotional adjustment, school, health, and occupational outcomes. A total of 662 families of twins were initially assessed when the twins were aged 6 months. These twins and their family were then followed regularly. QNTS now has 16 waves of data collected or planned, including 5 in preschool. Over the last 24 years, a broad range of physiological, cognitive, behavioral, school, and health phenotypes were documented longitudinally through multi-informant and multimethod measurements. QNTS also entails extended and detailed multilevel assessments of proximal (e.g., parenting behaviors, peer relationships) and distal (e.g., family income) features of the child’s environment. QNTS children and a subset of their parents have been genotyped, allowing for the computation of a variety of polygenic scores. This detailed longitudinal information makes QNTS uniquely suited for the study of the role of the early years and gene–environment transactions in development.

Introduction: While negative consequences of incident delirium on functional and cognitive decline have been widely studied, very limited data is available regarding functional and cognitive outcomes in Emergency Department (ED) patients. The aim of this study was therefore to evaluate the impact of ED stay-associated delirium on older patient's functional and cognitive status at 60 days post-ED visit. Methods: This study is a planned sub-analysis of a large multicentre prospective cohort study (the INDEED study). This project took place between March and July of the years 2015 and 2016 within 5 participating EDs across the province of Quebec. Independent non-delirious patients aged □65, with an ED stay at least 8hrs were monitored until 24hrs post-ward admission. A 60-day follow-up phone assessment was also conducted. Participants were screened for delirium using the validated Confusion Assessment Method (CAM) and the severity of its symptoms was measured using the Delirium Index. Functional and cognitive status were assessed at baseline as well as at the 60-day follow-up using the validated OARS and TICS-m. Results: A total of 608 patients were recruited, 393 of which completed the 60-day follow-up. Sixty-nine patients obtained a positive CAM during ED-stay or within the first 24 hours following ward admission. At 60-days, those patients experienced a loss of 3.1 (S.D. 4.0) points on the OARS scale compared to non-delirious patients who lost 1.6 (S.D. 3.0) (p = 0.03). A significant difference in cognitive function was also noted at 60-days, as delirious patients’ TICS-m score decreased by 2.1 (S.D. 6.2) compared to non-delirious patients, who showed a minor improvement of 0.5 (S.D. 5.8) (p = 0.01). Conclusion: People who developed ED stay-associated delirium have lower baseline functional and cognitive status than non-delirious patients and they will experience a more significant decline at 60 days post-ED visit.

Introduction: Delirium is a frequent pathology in the elderly presenting to the emergency department (ED) and is seldom recognised. This condition is associated with many medical complications and has been shown to increase the hospital length-of-stay. The objective of this study was to identify the predictor factors of developing delirium in this high-risk population. Methods: Design: This study was part of the multicenter prospective cohort INDEED study. Participants: Patients aged 65 and older, initially free of delirium and with an ED stay of 8h or longer, were followed up to 24h after ward admission. Measures: Clinical and demographic variables were collected by interview and chart review. A research professional assessed their delirium status twice daily using the Confusion Assessment Method (CAM). Analyses: A classification tree was used to select predictors and cut-points that minimized classification error of patients with incident delirium. After literature review, nineteen predictors were considered for inclusion in the model (eight non-modifiable and eleven modifiable factors). Results: Among the 605 patients included in this study, incident delirium was detected by the CAM in 69 patients (11.4%). In total, fourteen variables were included in a preliminary model, of which six were intrinsic to the patient and eight were modifiable in the ED. Variables with the greatest impact in the prediction of delirium includes age, cognitive status, ED length of stay, autonomy in daily activities, fragility and mobility during their hospital stay. The diagnostic performance of the model applied to the study sample gave a sensitivity of 78.3% (95% CI: 66.7 to 87.3), a specificity of 100.0% (95% CI: 99.3 to 100.0), a PPV of 100.0% (95% CI: 93.4 to 100.0) and a NPV of 97.3% (95% CI: 95.6 to 98.5). Conclusion: The delirium risk model developed in this study shows promising results with elevated sensitivity and specificity values. Considering the limited ability to predict and detect delirium among physicians, the potential increase in sensitivity provided by this tool could be beneficial to patients. This model will ultimately serve to identify high-risk patients with the goal of developing strategies to alter modifiable risk factors and subsequently decrease the incidence of delirium in this population.

The availability of analytical methods that utilize the very intense and bright X-rays from synchrotron radiation sources has fundamentally changed the way in which geoscientists, environmental scientists and soil scientists study complex environmental samples and decipher the chemical and biological processes that impact the speciation, transport and potential bioavailability of environmental toxins (Brown et al., 2006). Such samples are often mixtures of crystalline and amorphous phases in particle-sizes ranging from cm to nm, adsorbed metal ions and organic molecules, natural organic matter, microbial organisms, algae, plant materials and aqueous solutions. The processes that affect the chemical forms and environmental fate of contaminants in such mixtures range from surface adsorption, desorption, precipitation and dissolution reactions, often involving a combination of hydrolysis, ligand exchange and electron transfer, to biological interactions in which microbial organisms, algae or plants interact with mineral surfaces and environmental contaminants.

The Sahara was wetter and greener during multiple interglacial periods of the Quaternary, when some have suggested it featured very large (mega) lakes, ranging in surface area from 30,000 to 350,000 km2. In this paper, we review the physical and biological evidence for these large lakes, especially during the African Humid Period (AHP) 11–5 ka. Megalake systems from around the world provide a checklist of diagnostic features, such as multiple well-defined shoreline benches, wave-rounded beach gravels where coarse material is present, landscape smoothing by lacustrine sediment, large-scale deltaic deposits, and in places, tufas encrusting shorelines. Our survey reveals no clear evidence of these features in the Sahara, except in the Chad basin. Hydrologic modeling of the proposed megalakes requires mean annual rainfall ≥1.2 m/yr and a northward displacement of tropical rainfall belts by ≥1000 km. Such a profound displacement is not supported by other paleo-climate proxies and comprehensive climate models, challenging the existence of megalakes in the Sahara. Rather than megalakes, isolated wetlands and small lakes are more consistent with the Sahelo-Sudanian paleoenvironment that prevailed in the Sahara during the AHP. A pale-green and discontinuously wet Sahara is the likelier context for human migrations out of Africa during the late Quaternary.

Introduction: Prevalence and incidence of delirium in older patients admitted to acute and long-term care facilities ranges between 9.6% and 89% but little is known in the context of emergency department (ED) incident delirium. Literature regarding the incidence of delirium in the ED and its potential impacts on hospital length of stay (LOS), functional status and unplanned ED readmissions is scant, its consequences have yet to be clearly identified in order to orient modern acute medical care. Methods: This study is part of the multicenter prospective cohort INDEED study. Three Canadian EDs completed the two years prospective study (March-July 2015 and Feb-May 2016). Patients aged 65 years old, initially free of delirium with an ED stay 8hours were followed up to 24h after ward admission. Patients were assessed 2x/day during their entire ED stay and up to 24 hours on hospital ward by research assistants (RA). The primary outcome of this study was incident delirium in the ED or within 24 h of ward admission. Functional and cognitive status were assessed using validated Older Americans’ Resources and Services and the Telephone Interview for Cognitive Status- modified tools. The Confusion Assessment Method (CAM) was used to detect incident delirium. ED and hospital administrative data were collected. Inter-observer agreement was realized among RA. Results: Incident delirium was not different between sites, nor between phases, nor between times from one site to another. All phases confounded, there is between 7 to 11% of ED related incident delirious episodes. Differences were seen in ED LOS between sites in non-delirious patients, but also between some sites for delirious participants (p<0.05). Only one site had a difference in ED LOS between their delirious and non-delirious patients, respectively of 52.1 and 40.1 hours (p<0.05). There is also a difference between sites in the time between arrival to the ED and the incidence of delirium (p=0.003). Kappa statistics were computed to measure inter-rater reliability of the CAM. Based on an alpha of 5%, 138 patients would allow 80% power for an estimated overall incidence proportion of 15 % with 5% precision.. Other predictive delirium variables, such as cognitive status, environmental factors, functional status, comorbidities, physiological status, and ED and hospital length of stay were similar between sites and phases. Conclusion: The fact that incidence of delirium was the same for all sites, despite the differences of ED LOS and different time periods suggest that many other modifiable and non-modifiable factors along LOS influenced the incidence of ED induced delirium. Emergency physician should concentrate on improving senior-friendly environment for the ED.

Introduction: It is documented that physicians and nurses fail to detect delirium in more than half of cases from various clinical settings, which could have serious consequences for seniors and for our health care system. The present study aimed to describe the rate of documented incident delirium in 5 Canadian Emergency departments (ED) by health professionals (HP). Methods: This study is part of the multicenter prospective cohort INDEED study. Patients aged 65 years old, initially free of delirium with an ED stay 8hours were followed up to 24h after ward admission. Delirium status was assessed twice daily using the Confusion Assessment Method (CAM) by trained research assistants (RA). HP reviewed patient charts to assess detection of delirium. HP had no specific routine detection of delirious ED patients. Inter-observer agreement was realized among RA. Comparison of detection between RA and HP was realized with univariate analyses. Results: Among the 652 included patients, 66 developed a delirium as evaluated with the CAM by the RA. Among those 66 patients, only 10 deliriums (15.2%) were documented in the patients medical file by the HP. 54 (81.8%) patients with a CAM positive for delirium by the RA were not recorded by the HP, 2 had incomplete charts. The delirium index was significantly higher in the HP reported group compared to the HP not reported, respectively 7.1 and 4.5 (p<0.05). Other predictive delirium variables, such as cognitive status, functional status, comorbidities, physiological status, and ED and hospital length of stay were similar between groups. Conclusion: It seems that health professionals missed 81.8% of the potential delirious ED patients in comparison to routine structured screening of delirium. HP could identify patients with a greater severity of symptoms. Our study points out the need to better identify elders at risk to develop delirium and the need for fast and reliable tools to improve the screening of this disorder.

The acoustic televiewer is a geophysical logging instrument that is deployed in a water-filled borehole and operated while trolling. It generates a digital, magnetically oriented image of the borehole wall that is developed from the amplitudes and transit times of acoustic waves emitted from the tool and reflected at the water–wall interface. The transit-time data are also converted to radial distances, from which cross-sectional views of the borehole shape can be constructed. Because the televiewer is equipped with both a three-component magnetometer and a two-component inclinometer, the borehole’s trajectory in space is continuously recorded as well. This instrument is routinely used in mining and hydrogeologic applications, but in this investigation it was deployed in two boreholes drilled into Upper Fremont Glacier, Wyoming, U.S.A. The acoustic images recorded in this glacial setting are not as clear as those typically obtained in rocks, due to a lower reflection coefficient for water and ice than for water and rock. Results indicate that the depth and orientation of features intersecting the boreholes can be determined, but that interpreting their physical nature is problematic and requires corroborating information from inspection of cores. Nevertheless, these data can provide some insight into englacial structural characteristics. Additional information derived from the cross-sectional geometry of the borehole, as well as from its trajectory, may also be useful in studies concerned with stress patterns and deformation processes.

The American public's beliefs about the causes of social inequality vary greatly, with debates over the causes of racial inequality tending to be the most salient and divisive. Among whites in particular, liberals tend to see inequality as rooted in society's ills, whereas conservatives tend to see inequality as rooted in individuals’ shortcomings. Given this, many infer that white conservatives are more likely than white liberals to adopt the controversial view that racial inequality is “natural,” i.e., due to genetically inherited characteristics. We argue that genetic explanations for racial inequality, in and of themselves, offer little appeal to white conservatives. However, when white citizens are exposed to media messages that emphasize the egalitarian implications of genetic similarity between racial groups, those on the left and right engage in biased assimilation, resulting in a “nature” (conservative) versus “nurture” (liberal) divide. Data from two studies of white Americans—one representative survey and one experiment—support this theoretical framework.

Among the solar proxies, κ1 Cet, stands out as potentially having a mass very close to solar and a young age. We report magnetic field measurements and planetary habitability consequences around this star, a proxy of the young Sun when life arose on Earth. Magnetic strength was determined from spectropolarimetric observations and we reconstruct the large-scale surface magnetic field to derive the magnetic environment, stellar winds, and particle flux permeating the interplanetary medium around κ1 Cet. Our results show a closer magnetosphere and mass-loss rate 50 times larger than the current solar wind mass-loss rate when Life arose on Earth, resulting in a larger interaction via space weather disturbances between the stellar wind and a hypothetical young-Earth analogue, potentially affecting the habitability. Interaction of the wind from the young Sun with the planetary ancient magnetic field may have affected the young Earth and its life conditions.