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Introduction: Pulse wave analysis provides an estimation of central (aortic) pressure and arterial wave reflections which relate to LV dysfunction and risk of CV events in adults. Recent adult studies suggest separation of the forward and backward waves may provide improved risk stratification for CV events. Data in youth are lacking. Hypothesis: We hypothesized that a significant difference in arterial wave reflections would be identified in young subjects with adverse CV risk factors. Methods: Vital signs, fasting lipids, glucose, insulin, HbA1c, and CRP were obtained in 551 patients aged 10-24 years in a study comparing vascular health among lean (L= 199), obese (O=173) and subjects with type 2 diabetes (T=179). Wave separation analyses were performed on pressure tracings obtained from radial artery tonometry. Group differences in CV risk factors and wave reflections were assessed using ANOVA. General linear models were constructed to elucidate independent predictors of wave reflections. Results: A more adverse CV risk profile was found in O and T subjects compared to L (higher BMI, SBP, DBP, LDL, TG, CRP, lower HDL in O and T vs L; all p≤0.0003). The T group had higher glucose, insulin, and HbA1c compared to the L and O groups (all p≤0.0001). The forward pulse wave amplitude (Pf) and the backward pulse wave amplitude (Pb) were significantly higher (P Conclusions: Adolescents and young adults with obesity and T2DM have altered forward and backward arterial wave reflections compared to lean controls related to adiposity, BP, and insulin levels. These new parameters may be useful in risk stratifying patients with adverse cardiovascular risk factors.

The Asian monsoon is a major component of the global climate system and can be divided into two subsystems, the Indian monsoon and the East Asian monsoon. Insights into monsoon behaviour and dynamics can be gained through studying past warm intervals in Earth's history. One such interval is the Pliocene epoch, specifically the mid-Piacenzian Warm Period (mPWP; 3.264–3.025 Ma). This time is characterised as a period of sustained warmth, with annual mean temperatures 2–3 °C higher than the pre-industrial era. Studies have examined the East Asian monsoon during the mPWP from both a geological data and climate modelling perspective. However, there has been little investigation into the behaviour of the Indian monsoon. Using a coupled atmosphere-ocean global climate model (HadCM3), the Indian summer monsoon response to orbital forcing during the mPWP is studied. Of the simulated interglacial events (Marine Isotope Stages KM5c, KM3, K1 and G17), MIS KM5c is the only one with a near-modern orbital forcing. This experiment is compared to a pre-industrial simulation to determine the nature of the mPWP Indian summer monsoon in the absence of a different pattern if insolation forcing. The monsoon at MIS KM5c, is simulated to be stronger than pre-industrial, with higher surface air temperatures and precipitation over land due to higher levels of CO2. MIS G17, K1, and KM3 represent interglacial events of similar magnitude with different insolation forcing than MIS KM5c. The Indian summer monsoon is simulated to be significantly stronger for the interglacials K1 and KM3, compared to KM5c. This is due to stronger precession forcing causing an increase in summer surface air temperature and precipitation. When combined with Pliocene geological boundary conditions, these results highlight the significant effect of orbital forcing on the strength of the Indian summer monsoon. The sensitivity of the Indian monsoon to orbital forcing has important implications for any parallels drawn between Pliocene and future monsoon behaviour.

This review describes the literature evaluating the potential adverse effects of youth-onset type 2 diabetes on the developing brain. A summary of recently published articles and the current state of knowledge are covered succinctly in this manuscript. Current literature suggests both cognitive and brain structural differences are found in youth with type 2 diabetes. Studies have shown poorer scores in a number of neurocognitive domains, particularly in areas of executive functioning and memory. Additionally, imaging studies have found differences in brain gray matter volume, white matter volume, and microstructural integrity. These findings are largely consistent with the adult literature. Youth with type 2 diabetes demonstrate lower cognitive scores and structural brain differences. Although causality has not yet been established, these findings are important because these individuals are still undergoing neurodevelopmental maturation.

Additional file 1: Figure S1. Detailed technical protocol. Figure S2. Data pre-processing. Figure S3. Distribution of changes in splice-junction scores. Figure S4. Average RBP binding score changes. Figure S5. Cumulative probability density of protein structural features. Figure S6. Quantile-quantile plot of PhyloP conservation scores. Figure S7. Model evaluation in terms of precision-recall curves. Figure S8. Performance of sub-models with features from each individual category. Figure S9. Distribution of minor allele frequencies of ExAC and GTEx iSNVs. Figure S10. Demonstration of PWM-derived matching score distribution.

BACKGROUND: To optimize treatment and prevent cardiovascular disease in subjects with type 1 diabetes, it is important to determine how cholesterol metabolism changes with type 1 diabetes. OBJECTIVE: To compare plasma levels of campesterol and β-sitosterol, markers of cholesterol absorption, as well as lathosterol, a marker of cholesterol synthesis, in youth with and without type 1 diabetes. METHODS: Serum samples were obtained from adolescent subjects with type 1 diabetes [n= 175, mean age 15.2 years, mean duration of diabetes 8.2 years] and without diabetes [n=74, mean age 15.4 years]. Campesterol, β-sitosterol, and lathosterol, were measured using targeted liquid chromatography tandem mass spectrometry, normalized to the control serum mean, and expressed in arbitrary units. The markers were then compared between groups and correlated with the available cardiometabolic variables. RESULTS: Campesterol and β-sitosterol levels were 30% higher in subjects with type 1 diabetes and positively correlated with hemoglobin A1c levels. In contrast, lathosterol levels were 20% lower in subjects with type 1 diabetes and positively correlated with triglycerides, body mass index, and systolic blood pressure. CONCLUSION: Plasma markers suggest that cholesterol absorption is increased whereas cholesterol synthesis is decreased in type 1 diabetes. Further studies to address the impact of these changes on the relative efficacy of cholesterol absorption and synthesis inhibitors in subjects with type 1 diabetes are urgently needed.

The Irish Skin Foundation (ISF) is a national charity dedicated to improving quality of life for people living with skin conditions. The ISF offers a unique 'Ask a Nurse' helpline service delivered by Dermatology Clinical Nurse Specialists, all of whom work in clinical practice, in hospital dermatology units in Ireland, and are up to date with best practice/current treatments. The ISF 'Ask a nurse' helpline has provided a valuable service (as evidenced by the 97% user satisfaction rating since the service was set up in 2016) in addressing the concerns of callers and supporting patients; and even more so during the Covid-19 pandemic.

OBJECTIVE: We investigated the effects of chronic exposures to particulate and traffic-related air pollution on allostatic load (AL) score, a marker of cumulative biological risk, among youth with type 1 diabetes. RESEARCH DESIGN AND METHODS: Participants were drawn from five clinical sites of the SEARCH for Diabetes in Youth (SEARCH) study (n=2,338). Baseline questionnaires, anthropometric measures, and a fasting blood test were taken at a clinic visit between 2001 and 2005. AL was operationalized using 10 biomarkers reflecting cardiovascular, metabolic, and inflammatory risk. Annual residential exposures to PM(2.5) and proximity to heavily-trafficked major roadways were estimated for each participant. Poisson regression models adjusted for sociodemographic and lifestyle factors were conducted for each exposure. RESULTS: No significant associations were observed between exposures to PM(2.5) or proximity to traffic and AL score, however analyses were suggestive of effect modification by race for residential distance to heavily-trafficked major roadways (p=0.02). In stratified analyses, residing

Summary: Genetic counselors are trained to deliver complicated genomic test results to parents of pediatric patients. However, there is limited knowledge on how parents perceive this information and what they understand about the results. This research aims to qualitatively explore parents’ experiences receiving genomic test results for their children. As part of formative research for the NYCKidSeq Study, we recruited a purposive sample of parents of 22 children stratified by child race/ethnicity and test result classification (positive, uncertain, or negative) and conducted in-depth interviews using a semi-structured guide. Analysis was conducted using grounded theory’s constant comparative method across cases and themes. Parents described different elements of understanding: genetics knowledge; significance and meaning of positive, uncertain, or negative results; and implications for the health of their child and family. Parents reported challenges understanding technical details and significance of their child’s results but gladly allowed their providers to be custodians of this information. However, of the different elements of understanding described, parents cared most deeply about being able to understand implications for their child’s and family’s health. These findings suggest that a counseling approach that primarily addresses parents’ desire to understand how to best care for their child and family may be more appropriate than an information-heavy approach focused on technical details. Further research is warranted to confirm these findings in larger parent cohorts and to explore ways genetic counseling can support parents’ preferences without sacrificing important components of parent understanding and overall satisfaction with their experiences with genomic medicine.

Aims We sought to characterize the direction and associated factors of eGFR change following diagnosis of youth-onset type 1 and type 2 diabetes. Methods We assessed the direction of eGFR change at two visits (mean 6.6 years apart) in SEARCH, a longitudinal cohort study of youth-onset type 1 and type 2 diabetes. We used the CKiDCr-CysC equation to estimate GFR and categorized ‘rising’ and ‘declining’ eGFR as an annual change of ≥3 ml/min/1.73 m2 in either direction. Multivariable logistic regression evaluated factors associated with directional change in eGFR. Results Estimated GFR declined in 23.8% and rose in 2.8% of participants with type 1 diabetes (N = 1225; baseline age 11.4 years), and declined in 18.1% and rose in 15.6% of participants with type 2 diabetes (N = 160; baseline age 15.0 years). Factors associated with rising and declining eGFR (versus stable) in both type 1 and type 2 diabetes included sex, age at diagnosis, baseline eGFR and difference in fasting glucose between study visits. Additional factors in type 1 diabetes included time from baseline visit, HbA1c and body mass index. Conclusions Over the first decade of diabetes, eGFR decline is more common in type 1 diabetes whereas eGFR rise is more common in type 2 diabetes.

Scholars often find that highlands and rural areas foster insurgencies. However, others have argued that cities can also be centers of insurgent activity and that nonterritorial insurgencies are different from territorial guerilla wars. We expect that in a nonterritorial insurgency, the high quality of local knowledge makes populated rural areas inhospitable to nonterritorial insurgent activity. Using data from a random sample of about 750 Medaille de la Resistance Francaise recipients, we find that departments with more residents in cities and large towns had more medal recipients than rural departments. Analyses of repression patterns (finding that insurgent arrests are less likely in cities than rural areas) and the historical record provide further evidence for the information mechanism.

Information about the loads of total and soluble reactive phosphorus entering Lake Erie is required in order to support commitments made under Annex 4 of the Great Lakes Water Quality Agreement. For these purposes, annual (water year) total phosphorus loads to Lake Erie are updated (2003–2013) and soluble reactive loads are reported on a lakewide basis for the first time (2009–2013). Complete documentation including input data and error estimates are provided. The results confirm previously documented long-term declining TP loads and show how these are driven by early and recent improvements in point source discharges, but are confounded by recent increases in nonpoint source loads that may in turn be due to increasing trends in precipitation and river discharge. The record since 2009 for SRP indicates high interannual variability and no discernible change in loadings over time. Recent TP loads are dominated by nonpoint sources (71%), with lower contributions from point sources (19%) and the balance comprising atmospheric deposition and loads from the upstream Great Lakes. Approximately one-half (49%) of the load of SRP is contributed from nonpoint sources, approximately 39% comprises point sources, and atmospheric deposition and upstream loads comprise 6% each. Loads are highest to the western basin for TP and highest to the Huron–Erie corridor for SRP. U.S. sources account for a majority (> 80%) of the phosphorus loads entering the lake. Recommendations for improvements to the study approach are made including the identification of monitoring gaps and the testing of assumptions that require independent verification.

Myelodysplastic syndrome (MDS) is a heterogeneous group of hematological malignancies with considerably variable prognoses and curable only with hematopoietic cell transplantation (HCT). Few studies comparing MDS HCT outcomes between sibling and umbilical cord blood (UCB) donors exist. Using the University of Minnesota Blood and Marrow Transplant (BMT) database, we retrospectively analyzed HCT outcomes among 89 MDS patients undergoing either sibling or double UCB HCT in 2000-2013. We observed similar survival, relapse and non-relapse mortality between sibling and UCB donor sources. Relapse was increased in those with monosomal karyotype (P=0.04) and with reduced intensity conditioning (P

A mass balance model is used to simulate total phosphorus (TP) concentrations for the lower Great Lakes based on measured and estimated historical TP loading time series. Although Lake Erie is the primary focus, Lake Ontario is included in order to provide information about its potential response to proposed Lake Erie TP load reductions. The results demonstrate that Lake Erie loading controls would have a measurable effect on both Lake Erie and Lake Ontario's offshore phosphorus concentrations.

Background Gestational age estimation by last menstrual period (LMP) vs. ultrasound (or best obstetric estimate in the US) may result in discrepant classification of preterm vs. term birth. We investigated whether such discrepancies are associated with adverse infant outcomes. Methods We studied singleton livebirths in the Medical Birth Registries of Norway, Sweden and Finland and US live birth certificates from 1999 to the most recent year available. Risk ratios (RR) with 95% confidence intervals (CI) by discordant and concordant gestational age estimation for infant, neonatal and post-neonatal mortality, Apgar score

The mid-Piacenzian is known as a period of relative warmth when compared to the present day. A comprehensive understanding of conditions during the Piacenzian serves as both a conceptual model and a source for boundary conditions as well as means of verification of global climate model experiments. In this paper we present the PRISM4 reconstruction, a paleoenvironmental reconstruction of the mid-Piacenzian ( ∼ 3 Ma) containing data for paleogeography, land and sea ice, sea-surface temperature, vegetation, soils, and lakes. Our retrodicted paleogeography takes into account glacial isostatic adjustments and changes in dynamic topography. Soils and lakes, both significant as land surface features, are introduced to the PRISM reconstruction for the first time. Sea-surface temperature and vegetation reconstructions are unchanged but now have confidence assessments. The PRISM4 reconstruction is being used as boundary condition data for the Pliocene Model Intercomparison Project Phase 2 (PlioMIP2) experiments.

The nuclear magnetic resonance (NMR) lipoprotein profile provides additional cardiovascular risk information beyond traditional lipids in high-risk adults. Similar studies have not been conducted in youth.To evaluate the relationship between the NMR profile and preclinical vascular measures in youth.We studied 96 obese youth with prediabetes (mean age = 18.1 ± 3.6 years, 63% female, 78% African American) and 118 obese normoglycemic controls (mean age = 18.0 ± 3.1 years, 75% female, 62% African American) cross sectionally. Traditional lipids (triglycerides, total, high-density lipoprotein [HDL], and low-density lipoprotein [LDL] cholesterol), NMR particle size (particle concentration [P] and size) and vascular thickness (carotid IMT) and stiffness (pulse wave velocity [PWV]) were measured. Independent associations between lipoproteins with carotid IMT and PWV after adjustment for group, age, race, sex, BMI z score, blood pressure, HOMA-IR, and A1c were studied.NMR analysis revealed youth with prediabetes exhibited a more atherogenic profile with higher levels of small LDL-P and HDL-P and lower levels of intermediate and large HDL-P (P .03). In addition, lower intermediate HDL-P was associated with a higher carotid IMT, whereas higher small HDL-P was associated with a higher PWV (P .01). Traditional lipids were not significantly different between groups and were not associated with either vascular outcome.NMR lipoprotein subclasses have improved sensitivity compared to traditional lipids to detect lipoprotein abnormalities in normoglycemic and prediabetic obese youth and are independently associated with preclinical vascular thickness and stiffness. NMR lipids may enhance cardiovascular risk assessment in youth.

Chromosomal microarray analysis (CMA) is a diagnostic tool used in the evaluation of pediatric patients with congenital anomalies or developmental and intellectual disability. In both the pediatric and prenatal patient population, CMA has been shown to have a higher detection rate of chromosomal abnormalities than conventional karyotype alone. Currently, the diagnostic yield of prenatal CMA is highest when applied to the evaluation of a fetus with multiple ultrasound anomalies. Challenges arise when CMA yields isolated findings not associated with a phenotype on ultrasound or variants of uncertain significance, which warrants evaluation of the risks, benefits, limitations and optimal incorporation of CMA into prenatal care. The clinical cases presented here will be used to illustrate these issues.

Stringent complete remission (CR) in acute myeloid leukemia (AML) requires the absence of both morphologic and flow cytometric evidence of disease. We have previously shown that persistent AML detected by flow cytometry (FC+) before reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT) was associated with significantly increased relapse, shorter disease-free survival (DFS) and poorer overall survival (OS), independent of morphologic blast count. We evaluated the effect of FC status on outcomes of alloHCT for AML after either myeloablative conditioning (MAC) or RIC regimens. In 203 patients (MAC, n=80 and RIC, n=123) with no morphologic evidence of persistent AML pre-transplant on marrow biopsy. The allografts included 130 umbilical cord blood (UCB) and 73 sibling donors. We performed central review of pre-transplant standard sensitivity flow cytometry to identify detectable FC+. Twenty-five patients were FC+, including 15 (18.7%) receiving MAC and 10 (8.1%) RIC alloHCT. Among RIC patients FC+ was associated with significantly inferior relapse, disease-free survival (DFS), and overall survival (OS) [multiple regression hazard ratio (HR) 3.8, (95% confidence interval (95% CI) 1.7–8.7), p

Background Children with type 1 diabetes demonstrate worse cognitive performance compared with their peers. Little is known regarding the cognitive and behavioral performance in obese adolescents with type 2 diabetes. Methods Cross sectional evaluation of 20 obese adolescents with type 2 diabetes and 20 healthy adolescents was performed in Cincinnati, Ohio. Cognitive tests that included measures of processing speed, working memory, verbal and semantic fluency and parent reports of executive function and problem behavior were compared. Academic achievement and the relationship between cognitive/behavioral scores and diabetes duration and diabetes control (hemoglobin A1c) were assessed in the type 2 diabetes group only. Results The type 2 diabetes group had mean duration of diabetes of 2.8 ± 2.2 yr and hemoglobin A1c of 7.9 ± 2.2%. Adolescents with type 2 diabetes scored lower than controls on tests of working and verbal memory and processing speed (all p

Military successes present war leaders with a choice between maintaining their existing aims and strategy and changing one or the other to extend their gains or make the war cheaper. “Staying the course” minimizes the risk of failure but also foregoes possible gains. Making a change increases the risk of failure but leaves nothing on the table. I argue that emotional responses—particularly contentment and joy—account for leaders’ preferences for changing or maintaining their approach to war. Joy, elicited by novel good news, makes change more likely because it leads to the derogation of risks and obstacles. Contentment, elicited by expected good news, tends to produce resistance to change. I substantiate my claims through World War II-era case studies from Japan and the United States.

Background: Contemporary therapies for metastatic castration-resistant prostate cancer (mCRPC) have shown survival improvements, which do not account for patient experience and health-related quality of life (HRQoL). Methods: This literature review included a search of MEDLINE for randomized clinical trials enrolling ⩾50 patients with mCRPC and reporting on patient-reported outcomes (PROs) since 2010. Results: Nineteen of 25 publications describing seven treatment regimens (10 clinical trials and nine associated secondary analyses) met the inclusion criteria and were critically appraised. The most commonly used measures were the Functional Assessment of Cancer Therapy-Prostate (n=5 trials) and Brief Pain Inventory Short Form (n=4 trials) questionnaires. The published data indicated that HRQoL and pain status augmented the clinical efficacy data by providing a better understanding of treatment impact in mCRPC. Abiraterone acetate and prednisone, enzalutamide, radium-223 dichloride and sipuleucel-T offered varying levels of HRQoL benefit and/or pain mitigation versus their respective comparators, whereas three treatments (mitoxantrone, estramustine phosphate and docetaxel, and cabazitaxel) had no meaningful impact on HRQoL or pain. The main limitation of the data were that the PROs utilized were not developed for use in mCRPC patients and hence may not have comprehensively captured symptoms important to this population. Conclusions: Recently published randomized clinical trials of new agents for mCRPC have captured elements of the patient experience while on treatment. Further research is required to standardize methods for measuring, quantifying and reporting on HRQoL and pain in patients with mCRPC in the clinical practice setting.

The mid-Pliocene Warm Period (mPWP), analogous to future climate conditions, is considered a test-bed for the predictive capability of climate models. Here, Dowsett et al. review our understanding of the mPWP and discuss recent and future advances in the context of proxy data/model integration., The mid-Pliocene Warm Period (mPWP) offers an opportunity to understand a warmer-than-present world and assess the predictive ability of numerical climate models. Environmental reconstruction and climate modelling are crucial for understanding the mPWP, and the synergy of these two, often disparate, fields has proven essential in confirming features of the past and in turn building confidence in projections of the future. The continual development of methodologies to better facilitate environmental synthesis and data/model comparison is essential, with recent work demonstrating that time-specific (time-slice) syntheses represent the next logical step in exploring climate change during the mPWP and realizing its potential as a test bed for understanding future climate change.

Insulin resistance is associated with microalbuminuria among youth with diabetes mellitus. We sought to determine the dose–response effect of insulin sensitivity (IS) on the magnitude of albuminuria and whether there is a threshold below which urine albumin excretion increases. These analyses included participants from the SEARCH for Diabetes in Youth Study with incident diabetes who completed a baseline study visit (n = 2988). We estimated IS using a validated equation incorporating waist circumference, HbA1C, and fasting serum triglycerides. Multivariate regression analyses were performed to assess the effect of IS on urine albumin creatinine ratio (UACR), stratified by diabetes type. The IS threshold was then determined using segmented regressions within each diabetes type and incorporated into the multivariate model. There was an association between IS and UACR in type 2 diabetes only (beta = −0.39; p

Background/Aims: The goal of this study was to determine the effect of dietary genistein (naturally occurring phytoestrogen) on jejunal secretory function in a clinically relevant model of diabetes and obesity, the leptin-defIcient ob/ob mouse. Methods: We measured transepithelial short circuit current (Isc), across freshly isolated segments of jejunum from 12-week old male and female ob/ob and lean C57Bl/6J mice fed a genistein diet (600 mg genistein/kg diet) for 4-weeks. Separate segments of jejunum were frozen for western blot determination of key proteins involved in secretory transport. Results: Basal Isc was signifIcantly decreased (by 33%, P

Examining association between serial participation in youth organized sports (OS) and concurrent cardiometabolic risk factors, with long-term health status, will aid understanding the role of OS participation. Combining data from a prospective study and a follow-up survey, we aimed to determine association between youth OS participation and cardiometabolic risk factors with health and physical activity (PA) in young adulthood. Cardiometabolic risk factors were monitored yearly, and OS involvement through middle school, high school, and college, together with current status was recorded 12 years after the initial study began; 462 participants completed follow-up. Cardiometabolic risk factors included: body mass index (BMI), waist circumference, blood pressure, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) cholesterol and triglycerides, fasting glucose and insulin. Participants continuing OS participation from middle to high school and/or college had significantly lower BMI/BMI z-scores [24.7 vs 27.4 (p

OBJECTIVES: Examine the relationship between household food insecurity (HFS; i.e., access to nutritionally adequate and safe food) and disordered eating behaviors (i.e., restriction, bingeing, insulin manipulation, etc.) among a sample of young adults with youth-onset type 1 (T1D) or type 2 diabetes (T2D). METHODS: We used cross-sectional data from the SEARCH for Diabetes in Youth Study. Individuals (n = 792) ages ≥18 years completed the U.S. Household Food Security Survey Module and the Diabetes Eating Problem Survey-Revised (DEPS-R) between 2016 and 2019. We converted HFS scores to a 10-point scale and dichotomized scores into food secure (HFS ≤ 2.2) vs. food insecure (HFS > 2.2). Multivariable linear regression was used to evaluate the association of HFS with continuous DEPS-R score (i.e., 0–80, with a greater score indicating greater symptoms of disordered eating), adjusting for potential confounders (i.e., sex, age, race/ethnicity, education, household income, insurance, depressive symptoms, and duration of diabetes). We further stratified analyses by diabetes type. RESULTS: Participants were on average 23.8 ± 3.7 years, 59.6% female, 49.6% non-Latino white, and had a mean diabetes duration of 11.5 ± 3.1 years. The overall mean DEPS-R score was 17.3 ± 10.0 points. Mean DEPS-R scores in individuals living in food secure households (n = 709) and food insecure households (n = 83) were 16.6 ± 9.45 and 23.4 ± 12.4, respectively. The adjusted DEPS-R scores were 3.6 points (95% CI = 1.5, 5.7; P 0.05). CONCLUSIONS: Lower household food security in young adults with T1D, but not T2D, is associated with increased disordered eating scores. These results may allow clinicians and other public health professionals to target individuals with low household food security as being at higher risk for potential disordered eating, particularly those with T1D. FUNDING SOURCES: NIDDK & CDC.

6084 Background: Uterine serous carcinoma (USC) is a rare and aggressive malignancy, accounting for 40% of all endometrial cancer deaths. Human Epidermal Growth Factor Receptor 2 (HER2) has emerged as an important prognostic and therapeutic target in USC. Given recent randomized trial results, HER2-directed therapy is now recommended in advanced-stage or recurrent, HER2-positive disease. The significance of tumoral HER2 expression in early-stage disease has not yet been established. Methods: In this IRB-approved, retrospective, multi-institutional cohort, women diagnosed with stage I USC from 2000-2018 were identified. Patient demographic, treatment, and survival data were collected. Immunohistochemistry (IHC) was performed for HER2 and scored 0-3+. Equivocal IHC results (2+) were further tested with in-situ hybridization (ISH) per the 2007 ASCO-CAP HER2 breast cancer guidelines. HER2 overexpression (“positive”) was defined as 3+ IHC or ISH positive. Kaplan-Meier analyses and Cox-proportional hazards were used to compare survival between the cohorts. Results: In total, 173 patients with stage I USC were tested for HER2; 25% were HER2-positive, 77.4% had stage IA and 22.6% had stage IB disease. Adequate clinical follow up was available for 168 patients. There were no significant differences in age, race/ethnicity, body mass index, surgical management, sub-stage, tumor size, adjuvant therapy, or follow-up duration between the HER2-positive and negative cohorts. On univarite analysis, presence of lymph-vascular space invasion was correlated with HER2-positive tumors (p=0.003). After a median follow-up of 50 months, there were 41 (24.4%) recurrences. Significantly more recurrences were observed in the HER2-positive cohort (47.6% vs. 16.7%, p

The response of the Antarctic ice sheets to future warming is uncertain. The IPCC are predicting minimal melt from Antarctica while others suggest increased meltwater contributions are possible. The Pliocene period (5.333 Ma to 2.58 Ma) may provide insights into future ice sheet response, because atmospheric CO2 concentrations were similar to today (350-450 ppmv) and the earth surface was between 2 °C and 4 °C warmer than the preindustrial conditions. Geological records indicate that Antarctica's ice sheets were smaller and more dynamic at this time and many sea-level estimates require meltwater input from the Greenland, West (WAIS) and East Antarctic Ice sheets (EAIS). However, only a few records exist proximal to the Antarctic ice sheet which allow for reconstruction of the Pliocene climate state. We present a multiproxy climate reconstruction from a sedimentary succession that was deposited in an ancient fjord within the Transantarctic Mountains, covering discrete intervals between the early Pliocene and the late Pleistocene. In contrast to modern frigid conditions, our records indicate sea surface temperatures of about 5.6 °C at c. 4.1 Ma, the presence of a plant community at the fjord margins and evidence of soil formation. Simulations of potential vegetation cover in the Pliocene indicate our reconstruction is most compatible with a complete collapse of the WAIS and a large scale retreat of the EAIS from the subglacial basins with atmospheric CO2 levels of less than 450 ppmv. Our study indicates that under present day atmospheric CO2 conditions, in the early Pliocene, the Antarctic ice sheets retreated significantly. Understanding the mechanisms driving this large-scale ice sheet retreat would enable us to assess whether current atmospheric CO2 concentrations will lead to the same ice sheet configuration once the Earth system has come to a new equilibrium state.

Background Cardiovascular disease (CVD) is the leading cause of death among individuals with diabetes, but little is known about the role of exposures to environmental chemicals such as pesticides in the early development of CVD risk in this population. Objectives To describe changes over time in concentrations of pesticide biomarkers among youth with diabetes in the United States and to estimate the longitudinal association between these concentrations and established risk factors for CVD. Methods Pesticide biomarkers were quantified in urine and serum samples from 87 youth with diabetes participating in the multi-center SEARCH cohort study. Samples were obtained around the time of diagnosis (baseline visit, between 2006 and 2010) and, on average, 5.4 years later (follow-up visit, between 2012 and 2015). We calculated geometric mean (95% CI) pesticide biomarker concentrations. Eight CVD risk factors were measured at these two time points: body mass index (BMI) z-score, HbA1c, insulin sensitivity, fasting C-peptide (FCP), LDL cholesterol, HDL cholesterol, total cholesterol, and triglycerides. Linear regression models were used to estimate the associations between each pesticide biomarker at baseline and each CVD risk factor at follow-up, adjusting for baseline health outcome, elapsed time between baseline and follow up, sex, age, race/ethnicity, and diabetes type. Results Participants were, on average, 14.2 years old at their baseline visit, and most were diagnosed with type 1 diabetes (57.5%). 4-nitrophenol, 3-phenoxybenzoic acid, 2,4-dichlorophenoxyacetic acid (2,4-D), 3,5,6-trichloro-2-pyridinol, 2,2-bis(4-chlorophenyl)-1,1-dichloroethene, and hexachlorobenzene were detected in a majority of participants at both time points. Participants in the highest quartile of 2,4-D and 4-nitrophenol at baseline had HbA1c levels at follow-up that were 1.05 percentage points (95% CI: −0.40, 2.51) and 1.27 percentage points (0.22, 2.75) higher, respectively, than participants in the lowest quartile of these pesticide biomarkers at baseline. These participants also had lower log FCP levels (indicating reduced beta-cell function) compared to participants in the lowest quartile at baseline: beta (95% CI) for log FCP of −0.64 (−1.17, −0.11) for 2,4-D and −0.39 (−0.96, 0.18) for 4-nitrophenol. In other words, participants in the highest quartile of 2,4-D had a 47.3% lower FCP level compared to participants in the lowest quartile, and those in the highest quartile of 4-nitrophenol had a 32.3% lower FCP level than those in the lowest quartile. Participants with trans-nonachlor concentrations in the highest quartile at baseline had HbA1c levels that were 1.45 percentage points (−0.11, 3.01) higher and log FCP levels that were −0.28 (−0.84, 0.28) lower than participants in the lowest quartile at baseline, that is to say, participants in the highest quartile of trans-nonachlor had a 24.4% lower FCP level than those in the lowest quartile. While not all of these results were statistically significant, potentially due to the small same size, clinically, there appears to be quantitative differences. No associations were observed between any pesticide biomarker at baseline with BMI z-score or insulin sensitivity at follow-up. Conclusions Exposure to select pesticides may be associated with impaired beta-cell function and poorer glycemic control among youth with diabetes.

It has been clearly established that the climate of Asia is significantly affected by high-elevation orogens such as the Tibetan Plateau, Mongolian Plateau and Tian-Shan. The East Asian Monsoon (EAM), one of the most prominent features of Asian climate, has been well studied in a modern context and its dynamics are generally well understood. However, specific features of the EAM are less studied and understood in a palaeoclimate context, largely because of associated uncertainties in palaeotopography for the Cenozoic era. Here, we investigate changes in the individual stages of the EAM in response to increasing topography over Central Asia. We perform a series of sensitivity experiments with different palaeogeographic elevations using a coupled ocean-atmosphere General Circulation Model (HadCM3), to investigate seasonal variability of the EAM, and investigate the emergent critical threshold in elevation where the patterns of atmospheric circulation and climate over Asia attains the characteristics observed in the modern climate system. Our results indicate that above an elevation threshold of 3000 m, EAM circulation follows the modern pattern, but below that threshold, EAM circulation and precipitation follow a distinctly different pattern, where the westerly jet does not propagate into the higher latitudes and monsoonal precipitation is limited to June and July. This shift in circulation pattern has important implications for the successful interpretation of proxy-based palaeoclimate and environmental reconstructions. In addition, our results emphasize the importance of the latitudinal position of high-elevation on the EAM circulation, by showing that low-elevation can produce modern-like EAM conditions, if located at different latitudes than modern.

Background and Objective Certain patients with heart failure (HF) are unable to tolerate spironolactone therapy due to hyperkalemia. Patiromer is a novel agent used to treat hyperkalemia and has been shown to be efficacious, safe, and well-tolerated. The potential clinical outcomes and economic value of using patiromer and spironolactone in patients with HF unable to otherwise tolerate spironolactone due to hyperkalemia are unclear. The objective of this analysis was to model the potential pharmacoeconomic value of using patiromer and spironolactone in patients with a history of hyperkalemia that prevents them from utilizing spironolactone. Methods We performed a cost-effectiveness analysis of treatment with patiromer, spironolactone, and an angiotensin-converting enzyme inhibitor (ACEI) in patients with New York Heart Association (NYHA) class III–IV HF compared with ACEI alone. A Markov model was constructed to simulate a cohort of 65-year-old patients diagnosed with HF from the payer perspective across the lifetime horizon. Clinical inputs were derived from the RALES and OPAL-HK randomized trials of spironolactone and patiromer, respectively. Utility estimates and costs were derived from the literature and list prices. Outcomes assessed included hospitalization, life expectancy, and quality-adjusted life-years (QALYs), costs, and the incremental cost-effectiveness ratio (ICER). One-way and probability sensitivity analyses were performed to test the robustness of the model findings. Results Treatment with patiromer–spironolactone–ACEI was projected to increase longevity compared with ACEI alone (5.29 vs. 4.62 life-years gained, respectively), greater QALYs (2.79 vs. 2.60), and costs (US$28,200 vs. US$18,200), giving an ICER of US$52,700 per QALY gained. The ICERs ranged from US$40,000 to US$85,800 per QALY gained in 1-way sensitivity analyses. Conclusion Our results suggest that the use of spironolactone–patiromer–ACEI may provide clinical benefit and good economic value in patients with NYHA class III–IV HF unable to tolerate spironolactone due to hyperkalemia. Electronic supplementary material The online version of this article (10.1007/s40273-018-0709-3) contains supplementary material, which is available to authorized users.

High-resolution, easily accessible paleoclimate data are essential for environmental, evolutionary, and ecological studies. The availability of bioclimatic layers derived from climatic simulations representing conditions of the Late Pleistocene and Holocene has revolutionized the study of species responses to Late Quaternary climate change. Yet, integrative studies of the impacts of climate change in the Early Pleistocene and Pliocene – periods in which recent speciation events are known to concentrate – have been hindered by the limited availability of downloadable, user-friendly climatic descriptors. Here we present PaleoClim, a free database of downscaled paleoclimate outputs at 2.5-minute resolution (~5 km at equator) that includes surface temperature and precipitation estimates from snapshot-style climate model simulations using HadCM3, a version of the UK Met Office Hadley Centre General Circulation Model. As of now, the database contains climatic data for three key time periods spanning from 3.3 to 0.787 million years ago: the Marine Isotope Stage 19 (MIS19) in the Pleistocene (~787 ka), the mid-Pliocene Warm Period (~3.264–3.025 Ma), and MIS M2 in the Late Pliocene (~3.3 Ma). Machine-accessible metadata file describing the reported data (ISA-Tab format)

Purpose Geographic atrophy (GA) is an advanced form of age-related macular degeneration. GA often initially spares the center of the fovea, leading to a functional disconnect between reading speed and distance visual acuity. This study was designed to determine the correlation between baseline GA lesion size, change in lesion size, and maximum reading speed (MRS) over 18 months. Methods Post hoc analysis included US patients from the phase 2 Mahalo study of intravitreal lampalizumab with Minnesota low-vision reading (MNREAD) assessments at baseline and 6, 12, and 18 months. Binocular MRS was assessed using MNREAD Acuity Charts and GA lesion size by fundus autofluorescence. Correlations were estimated using Spearman's rank correlation coefficient. Results Seventy-seven patients were included in the analysis. Baseline MRS correlated with baseline GA lesion size (correlation coefficient, -0.47; 95% confidence interval, -0.63 to -0.28; P < 0.0001). In patients with lesions ≥10 mm2 (four disc areas), the proportion reading below a nonfluent level (MRS

When applying autonomous driving technology to real-world scenarios, environmental uncertainties make the development of decision-making algorithms difficult. Modeling the problem as a Partially Observable Markov Decision Process (POMDP) [1] allows the algorithm to consider these uncertainties in the decision process, which makes it more robust to real sensor characteristics. However, solving the POMDP with reinforcement learning (RL) [2] often requires storing a large number of observations. Furthermore, for continuous action spaces, the system is computationally inefficient. This paper addresses these problems by proposing to model the problem as an MDP and learn a policy with RL using hierarchical options (HOMDP). The suggested algorithm can store the state-action pairs and only uses current observations to solve a POMDP problem. We compare the results of to the time-to-collision method [3] and the proposed POMDP-with-LSTM method. Our results show that the HOMDP approach is able to improve the performance of the agent for a four-way intersection task with two-way stop signs. The HOMDP method can generate both higher-level discrete options and lower-level continuous actions with only the observations of the current step.

Vehicle segmentation is an important step in perception for autonomous driving vehicles, providing object-level environmental understanding. Its performance directly affects other functions in the autonomous driving car, including Decision-Making and Trajectory Planning. However, this task is challenging for planar LIDAR due to its limited vertical field of view (FOV) and quality of points. In addition, directly estimating 3D location, dimensions and heading of vehicles from an image is difficult due to the limited depth information of a monocular camera. We propose a method that fuses a vision-based instance segmentation algorithm and LIDAR-based segmentation algorithm to achieve an accurate 2D bird's-eye view object segmentation. This method combines the advantages of both camera and LIDAR sensor: the camera helps to prevent over-segmentation in LIDAR, and LIDAR segmentation removes false positive areas in the interest regions in the vision results. A modified T-linkage RANSAC is applied to further remove outliers. A better segmentation also results in a better orientation estimation. We achieved a promising improvement in average absolute heading error and 2D IOU on both a reduced-resolution KITTI dataset and our Cadillac SRX planar LIDAR dataset.

It is essential for autonomous driving cars to understand and predict other surrounding cars' behaviors, especially in urban environments, due to the high traffic volumes and complex interactions. Modeling the interaction among cars and their behaviors is challenging. The behavior estimation of a surrounding car serves as prior knowledge which helps the trajectory planner generate a path to perform properly with the other vehicles. It closes the gap between the high-level decision making and path planning. A new data-driven method is proposed to extend our previous behavior estimation. The new method predicts the continuous lane-change trajectory of a target car by modeling the interaction of all its surrounding vehicles' trajectories, without over-the-air communication between vehicles. The advantages of this approach are: 1. Learning the interactive model from real data; 2. Giving long-horizon estimation of the continuous trajectory of a target vehicle. The method is trained and evaluated on a public dataset. The experimental results show that the proposed method successfully predicts trajectories considering mutual interactions among cars, with low error based on the ground-truth.

AIMS: To determine among adolescents and young adults with youth-onset type 1 diabetes and type 2 diabetes the rates and risk factors for albuminuria regression and progression. The research hypothesis was that youth with type 2 diabetes would be more likely to show progression of albuminuria. METHODS: Data from SEARCH, a longitudinal observational study of youth-onset type 1 diabetes (N=1316) and type 2 diabetes (N=143) were analyzed. Urine albumin:creatinine ratio (UACR) was measured from random urine specimens at baseline and follow-up visits (mean 7 years later). Albuminuria regression was defined as halving of baseline UACR when baseline UACR was ≥30μg/mg; progression was defined as doubling of baseline UACR when follow-up UACR was ≥30μg/mg, respectively. Multivariable regression assessed risk factors associated with low-risk albuminuria category (combined persistently-low albuminuria and regression) versus moderate-risk albuminuria category (combined persistently-high albuminuria and progression). RESULTS: Albuminuria progression was more common in type 2 diabetes versus type 1 diabetes (15.4% versus 6.0%, p

Based on simulations with 15 climate models in the Pliocene Model Intercomparison Project (PlioMIP), the regional climate of East Asia (focusing on China) during the mid-Pliocene is investigated in this study. Compared to the pre-industrial, the multi-model ensemble mean (MMM) of all models shows the East Asian summer winds (EASWs) largely strengthen in monsoon China, and the East Asian winter winds (EAWWs) strengthen in south monsoon China but slightly weaken in north monsoon China in the mid-Pliocene. The MMM of all models also illustrates a warmer and wetter mid-Pliocene climate in China. The simulated weakened mid-Pliocene EAWWs in north monsoon China and intensified EASWs in monsoon China agree well with geological reconstructions. However, there is a large model–model discrepancy in simulating mid-Pliocene EAWW, which should be further addressed in the future work of PlioMIP.

Author(s): Ustun, Celalettin; Morgan, Elizabeth; Moodie, Erica EM; Pullarkat, Sheeja; Yeung, Cecilia; Broesby-Olsen, Sigurd; Ohgami, Robert; Kim, Young; Sperr, Wolfgang; Vestergaard, Hanne; Chen, Dong; Kluin, Philip M; Dolan, Michelle; Mrozek, Krzysztof; Czuchlewski, David; Horny, Hans-Peter; George, Tracy I; Kristensen, Thomas Kielsgaard; Ku, Nam K; Yi, Cecilia Arana; Moller, Michael Boe; Marcucci, Guido; Baughn, Linda; Schiefer, Ana-Iris; Hilberink, JR; Pullarkat, Vinod; Shanley, Ryan; Kohlschmidt, Jessica; Coulombe, Janie; Salhotra, Amandeep; Soma, Lori; Cho, Christina; Linden, Michael A; Akin, Cem; Gotlib, Jason; Hoermann, Gregor; Hornick, Jason; Nakamura, Ryo; Deeg, Joachim; Bloomfield, Clara D; Weisdorf, Daniel; Litzow, Mark R; Valent, Peter; Huls, Gerwin; Perales, Miguel-Angel; Borthakur, Gautam | Abstract: BackgroundAlthough the prognosis of core-binding factor (CBF) acute myeloid leukemia (AML) is better than other subtypes of AML, 30% of patients still relapse and may require allogeneic hematopoietic cell transplantation (alloHCT). However, there is no validated widely accepted scoring system to predict patient subsets with higher risk of relapse.MethodsEleven centers in the US and Europe evaluated 247 patients with t(8;21)(q22;q22).ResultsComplete remission (CR) rate was high (92.7%), yet relapse occurred in 27.1% of patients. A total of 24.7% of patients received alloHCT. The median disease-free (DFS) and overall (OS) survival were 20.8 and 31.2 months, respectively. Age, KIT D816V mutated (11.3%) or nontested (36.4%) compared with KIT D816V wild type (52.5%), high white blood cell counts (WBC), and pseudodiploidy compared with hyper- or hypodiploidy were included in a scoring system (named I-CBFit). DFS rate at 2 years was 76% for patients with a low-risk I-CBFit score compared with 36% for those with a high-risk I-CBFit score (P l 0.0001). Low- vs high-risk OS at 2 years was 89% vs 51% (P l 0.0001).ConclusionsI-CBFit composed of readily available risk factors can be useful to tailor the therapy of patients, especially for whom alloHCT is not need in CR1 (ie, patients with a low-risk I-CBFit score).

BACKGROUND AND OBJECTIVES: New pediatric hypertension definitions were recently published in a clinical practice guideline (CPG). We evaluated the impact of the CPG, compared with the previous guideline ("Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents"), on the prevalence of hypertension and associations with target organ damage (TOD) in high-risk youth. METHODS: Participants (10–18 years old) undergoing an evaluation of the cardiovascular effects of obesity and type 2 diabetes mellitus in youth were studied. Blood pressure was categorized according to the 2 guidelines as normal, elevated, and hypertension (stages 1 and 2). Measures of TOD (carotid artery intima-media thickness, pulse wave velocity, left ventricular mass, and diastolic function) were obtained. Associations between blood pressure categories and TOD and the sensitivity of hypertension classification in identifying TOD were evaluated. RESULTS: Data were available for 364 participants (65% female sex; 15.1 ± 2.1 years of age). Hypertension was identified in 8% and 13% as defined in the Fourth Report and CPG, respectively (P = .007). The 2 guidelines revealed similar associations with TOD; however, the CPG demonstrated improved sensitivity of TOD detection in hypertensive participants. For example, the proportion of participants with an abnormal left ventricular mass categorized as hypertensive increased from 20% to 31% as defined in the Fourth Report and CPG, respectively (P < .001). CONCLUSIONS: Incorporation of the CPG increased the prevalence of pediatric hypertension in a population of high-risk youth and improved the sensitivity of TOD identification in hypertensive participants.

Protein-coding genetic variants that strongly affect disease risk can provide important clues into disease pathogenesis. Here we report an exome sequence analysis of 20,791 type 2 diabetes (T2D) cases and 24,440 controls from five ancestries. We identify rare (minor allele frequency30 SLC30A8 alleles, and (b) within 12 gene sets, including those corresponding to T2D drug targets (p=6.1×10−3) and candidate genes from knockout mice (p=5.2×10−3). Within our study, the strongest T2D rare variant gene-level signals explain at most 25% of the heritability of the strongest common single-variant signals, and the rare variant gene-level effect sizes we observe in established T2D drug targets will require 110K-180K sequenced cases to exceed exome-wide significance. To help prioritize genes using associations from current smaller sample sizes, we present a Bayesian framework to recalibrate association p-values as posterior probabilities of association, estimating that reaching ppwww.type2diabetesgenetics.org.

Background: Exosomes, a type of extracellular vesicle, are a novel mode of tissue-to-tissue communication. Recent work suggests a role of exosomes in the development of obesity-related metabolic disease, such as insulin resistance or type 2 diabetes. With bariatric surgery, individuals undergo significant weight reduction and dramatic metabolic improvements. We hypothesize that exosomes mediate the metabolic improvements following bariatric surgery. Methods: We performed comprehensive exosome analyses, including measuring size and serum concentration of exosomes, and evaluating exosomal microRNAs expression pattern in 30 teenagers who underwent sleeve gastrectomy (age=16.7± 0.4 years; gender=26 females, 4 males; race= 19 Caucasians, 11 African Americans). Individuals who had ever been diagnosed with diabetes were excluded from the study. Results: We observed a significant reduction in serum exosome concentration (pre-op= 4.47x108± 6.28X107particles/mL; post-op=2.56x108± 2.44X107particles/mL, p=0.01), and a drastic shift of exosomal RNA expression pattern 1 month after bariatric surgery in obese adolescents, in concurrent with a modest initial weight loss (Pre-op weight=138.6± 5.3kg, Post-op weight=123.3± 5.0kg). Conclusion: Drastic changes in exosome profile were observed 1 month after bariatric surgery in severely obese adolescents. It is interesting that the most significant change happens in the first month after the surgery with a modest initial weight reduction, indicating the presence of molecular processes responsible for the improvements in metabolic condition following bariatric surgery, independent of weight loss. These findings suggest that the exosomes play a key role in the profound metabolic improvements following bariatric surgery, and serve as a novel biomarker or a therapeutic target for metabolic diseases. Disclosure A. Kim: None. K. Murakami: None. V.J. Borra: None. L.M. Dolan: None. A. Shah: None. T. Nakamura: None.

Urinary (U) neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) are markers of renal tubular injury. Whether NGAL and KIM-1 are elevated in early diabetic kidney disease (DKD) is not known. We performed a pilot study to compare the U concentrations (C) of NGAL and KIM-1 in YA with T1D or T2D from the SEARCH registry and healthy controls (n 45 in each group). The YA with diabetes were selected based on age at dx > 10 years and duration >8 years and were randomly selected across the quartiles of eGFR with similar age, gender and ethnicity. T1D (age 21 ± 2 years; duration 9.6 ± 1.0 years; HbA1c 9.3 ± 2.1% eGFR 126 ± 19 mL/min/1.73m2, UACR 11 ± 16 µg/mg), T2D (age 24 ± 3 years, duration 9.8 ± 1.2 years, HbA1c 8.5 ± 3.0%, eGFR 128 ± 21 mL/min/1.73m2, UACR 38 ± 71 µg/mg), controls (age 23 ± 3 years). In each group 50% were female, 41% white, 43% AA, and 16% Hisp. NGAL and KIM-1 were significantly elevated in T1D and T2D compared with controls (p < 0.001, p< 0.007). Although there was a trend for a greater UC of NGAL in T2D than T1D and a greater UC of KIM-1 in T1D than T2D, these differences were not statistically significant. Elevated UC of NGAL and KIM-1 are present in YA with T1D and T2D suggesting the presence of tubular damage early in the course of diabetes. Further investigation will determine if these markers can be used to assess the natural history of tubular injury or monitor therapeutic intervention in DKD. Disclosure N.M. Sheanon: None. A.K. Mottl: None. R. Dagostino: Consultant; Self; Teva Pharmaceutical Industries Ltd., Acelity, RedHill Biopharma, Edwards Lifesciences. C. Suerken: None. M. Afkarian: None. D. Dabelea: None. G. Imperatore: None. S.M. Marcovina: None. D.J. Pettitt: None. S. Saydah: None. L.M. Dolan: None.

We address the problem of learning autonomous driving behaviors in urban intersections using deep reinforcement learning (DRL). DRL has become a popular choice for creating autonomous agents due to its success in various tasks. However, as the problems tackled become more complex, the number of training iterations necessary increase drastically. Curriculum learning has been shown to reduce the required training time and improve the performance of the agent, but creating an optimal curriculum often requires human handcrafting. In this work, we learn a policy for urban intersection crossing using DRL and introduce a method to automatically generate the curriculum for the training process from a candidate set of tasks. We compare the performance of the automatically generated curriculum (AGC) training to those of randomly generated sequences and show that AGC can significantly reduce the training time while achieving similar or better performance.

Predicting lane-changing intentions has long been a very active area of research in the autonomous driving community. However, most of the literature has focused on individual vehicles and did not consider both the neighbor information and the accumulated effects of vehicle history trajectories when making the predictions. We propose to apply a surrounding-aware LSTM algorithm for predicting the intention of a vehicle to perform a lane change that takes advantage of both vehicle past trajectories and their neighbor’s current states. We trained the model on real-world lane changing data and were able to show in simulation that these two components can lead not only to higher accuracy, but also to earlier lane-changing prediction time, which plays an important role in potentially improving the autonomous vehicle’s overall performance.

Cooperative driving behavior is essential for driv- ing in traffic, especially for ramp merging, lane changing or navigating intersections. Autonomous vehicles should also man- age these situations by behaving cooperatively and naturally. In this paper, we enhance our previous learning-based method to efficiently estimate other vehicles’ intentions and interact with them in ramp merging scenarios, without over-the-air commu- nication between vehicles. The proposed approach inherits our previous Probabilistic grahpical Model (PGM) and distance- keeping framework. Real driving trajectories are used to learn transition models in the PGM. Thus, besides the structure of the PGM, our method does not require human-designed reward or cost functions. The PGM-based intention estimation is followed by an off-the-shelf distance-keeping model to generate proper acceleration/deceleration controls. The PGM plays a plug-in role in our self-driving framework. The new model eliminates two assumptions in the previous model: 1) a fixed merging point for all merging agents, which is hard to determine before the merging vehicles make the merge; 2) Perfect velocity mea- surement, which requires sophisticated perception systems. We validate the performance of our method both on real merging data and using a designed merging strategy in simulation, and show significant improvements compared with previous methods. Parameter design is also discussed by experiments. The new method is computationally efficient, and exhibits better robustness against sensing uncertainty.

Increasingly, scholars are recognizing the influences of emotion on foreign policy decision-making processes. Not merely feelings, emotions are sets of sentimental, physiological, and cognitive processes that typically arise in response to situational stimuli. They play a central role in psychological and social processes that shape foreign policy decision-making and behavior. In recent years, three important areas of research on emotion in foreign policy have developed: one examining the effects of emotion on how foreign policy decision makers understand and think-through problems, another focused on the role of emotion in diplomacy, and a third that investigates how mass emotion develops and shapes the context in which foreign policy decisions are made. These literatures have benefitted greatly from developments in the study of emotion by psychologists, neuroscientists, and others. Effectively using emotion to study foreign policy, however, requires some understanding of how these scholars approach the study of emotion and other affective phenomena. In addition to surveying the literatures in foreign policy analysis that use emotion, then, this article also addresses definitional issues and the different theories of emotion common among psychologists and neuroscientists. Some of the challenges scholars of emotion in foreign policy face: the interplay of the psychological and the social in modelling collective emotions, the issues involved in observing emotions in the foreign policy context, the theoretical challenge of emotion regulation, and the challenge of winning broader acceptance of the importance of emotion in foreign policy by the broader scholarly community.