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Background Human epidermal growth factor receptor 2 (HER2) has emerged as an important prognostic and therapeutic target in advanced stage and recurrent uterine serous carcinoma (USC). The significance of tumoral HER2 expression in early-stage disease has not been established. Methods This multi-center cohort study included women with stage I USC treated from 2000 to 2019. Demographic, treatment, recurrence, and survival data were collected. Immunohistochemistry (IHC) was performed for HER2 and scored 0–3+. Equivocal IHC results (2+) were further tested with fluorescence in-situ hybridization (FISH). HER2 positivity was defined as 3+ IHC or FISH positive. Results One hundred sixty-nine patients with stage I USC were tested for HER2; 26% were HER2-positive. There were no significant differences in age, race, stage, adjuvant therapy, or follow-up duration between the HER2-positive and negative cohorts. Presence of lymph-vascular space invasion was correlated with HER2-positive tumors (p = .003). After a median follow-up of 50 months, there were 43 (25.4%) recurrences. There were significantly more recurrences in the HER2-positive cohort (50.0% vs 16.8%, p Conclusions Given its significant association with worse recurrence and survival outcomes, HER2 positivity appears to be a prognostic biomarker in women with stage I uterine serous carcinoma. These data provide support for clinical trials with anti-HER2-directed therapy in early-stage disease.

Objective To describe the characteristics and birth outcomes of women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as community spread in New York City was detected in March 2020. Methods We performed a prospective cohort study of pregnant women with laboratory-confirmed SARS-CoV-2 infection who gave birth from March 13 to April 12, 2020, identified at five New York City medical centers. Demographic and clinical data from delivery hospitalization records were collected, and follow-up was completed on April 20, 2020. Results Among this cohort (241 women), using evolving criteria for testing, 61.4% of women were asymptomatic for coronavirus disease 2019 (COVID-19) at the time of admission. Throughout the delivery hospitalization, 26.5% of women met World Health Organization criteria for mild COVID-19, 26.1% for severe, and 5% for critical. Cesarean birth was the mode of delivery for 52.4% of women with severe and 91.7% with critical COVID-19. The singleton preterm birth rate was 14.6%. Admission to the intensive care unit was reported for 17 women (7.1%), and nine (3.7%) were intubated during their delivery hospitalization. There were no maternal deaths. Body mass index (BMI) 30 or higher was associated with COVID-19 severity (P=.001). Nearly all newborns tested negative for SARS-CoV-2 infection immediately after birth (97.5%). Conclusion During the first month of the SARS-CoV-2 outbreak in New York City and with evolving testing criteria, most women with laboratory-confirmed infection admitted for delivery did not have symptoms of COVID-19. Almost one third of women who were asymptomatic on admission became symptomatic during their delivery hospitalization. Obesity was associated with COVID-19 severity. Disease severity was associated with higher rates of cesarean and preterm birth.

Aim Our aim was to explore the relationship of Low-Density Lipoprotein Cholesterol (LDL-C) with subclinical cardiovascular disease (CVD) in youth with T1D and T2D. We hypothesized the association of LDL-C with elevated arterial stiffness (AS) would be partially accounted by the co-occurrence of other CVD factors. Method We included 1376 youth with T1D and 157 with T2D from the SEARCH study. CVD risk factors including LDL-C, waist to height ratio (WHtR), mean arterial pressure (MAP), HbA1c, albumin to creatinine ratio (ACR), and insulin sensitivity (IS) score were measured at both visits. At follow up, elevated carotid-femoral AS was defined as levels above 6.8 m/s. Multivariable logistic regression evaluated the odds of elevated AS as a function of the average CVD risk factors. Results At follow up, age was 18.0 ± 4.1 and 21.6 ± 3.5 years and duration of diabetes was 7.8 ± 1.9 and 7.7 ± 1.9 years in T1D and T2D, respectively. Elevated AS was found in 8.4% of T1D and 49.0% of T2D participants. Each SD increase in LDL-C was associated with 1.28 increased odds (95% CI 1.05-1.54, P = .013) of elevated AS in youth with T1D. The association was similar but not statistically significant in T2D. WHtR, IS, and MAP were associated with elevated AS in both groups. Adjustment for WHtR or IS attenuated to non-significance the relationship between LDL-C and AS in T1D. Conclusions Obesity and insulin resistance attenuate the association of high LDL-C with AS suggesting they partially account for the adverse effects of LDL-C on cardiovascular health in youth with T1D.

Purpose Estimate effects of ranibizumab on diabetic retinopathy (DR) severity in US Hispanic and non-Hispanic white persons with center-involved diabetic macular edema (DME) causing vision impairment for whom ranibizumab treatment would be considered. Patients and methods This model simulated DR severity outcomes over 2 years in the better-seeing eye using US census, National Health and Nutrition Examination Survey, Wisconsin Epidemiologic Study of Diabetic Retinopathy, and Los Angeles Latino Eye Study data. Baseline DR severity estimated from Diabetic Retinopathy Clinical Research Network trial data. Changes in DR severity after 2 years, with/without monthly ranibizumab (0.3 or 0.5 mg), were estimated from Phase III clinical trial data (RIDE/RISE) using a 2-dimensional Monte Carlo simulation model. Number of patients over a 2-year period for whom 1) DR severity worsening was avoided, 2) DR severity improved, and 3) selected clinical events related to proliferative DR (PDR) occurred, was estimated. Results An estimated 37,274 US Hispanic and non-Hispanic white persons were projected to have DR with center-involved DME and be eligible for ranibizumab treatment. The number of persons with moderately severe non-proliferative DR (NPDR) or less severe DR at baseline who would worsen to PDR and experience a PDR complication over 2 years would be reduced from 437 with no ranibizumab to 19 with ranibizumab (95% reduction; 95% simulation interval [SI], 79-100%). The number of persons with severe NPDR or less severe DR at baseline who would be expected to improve by ≥2 DR severity levels over 2 years would increase from 1706 with no ranibizumab to 13,042 with ranibizumab (682% increase; 95% SI, 478-967%). Conclusion This model estimates that ranibizumab treatment in US Hispanic and non-Hispanic white patients with center-involved DME causing vision impairment would potentially reduce the number of patients with worsening DR and potentially increase the number with DR improvements.

We analyze the sources of two politically relevant, yet opposing emotions: empathy and Schadenfreude. We propose that group and individual-level political factors affect empathy and Schadenfreude toward other groups. Using a survey experiment conducted in Lebanon we find that, when presented with a prompt about political repression, respondents are less likely to express empathy and more likely to express Schadenfreude when victims of political repression were from the out-group perceived as their group’s most recent antagonist. At the individual level, those more involved in their in-group’s community are generally more likely to feel Schadenfreude and less likely to express empathy.

Objective Incidence of youth-onset diabetes in India has not been well described. Comparison of incidence, across diabetes registries, has the potential to inform hypotheses for risk factors. We sought to compare the incidence of diabetes in the U.S.-based registry of youth onset diabetes (SEARCH) to the Registry of Diabetes with Young Age at Onset (YDR-Chennai and New Delhi regions) in India. Methods We harmonized data from both SEARCH and YDR to the Observational Medical Outcomes Partnership (OMOP) Common Data Model. Data were from youth registered with incident diabetes (2006-2012). Denominators were from census and membership data. We calculated diabetes incidence by averaging the total cases across the entire follow-up period and dividing this by the estimated census population corresponding to the source population for case ascertainment. Incidence was calculated for each of the registries and compared by type and within age and sex categories using a 2-sided, skew-corrected inverted score test. Results Incidence of type 1 was higher in SEARCH (21.2 cases/100 000 [95% CI: 19.9, 22.5]) than YDR (4.9 cases/100 000 [95% CI: 4.3, 5.6]). Incidence of type 2 diabetes was also higher in SEARCH (5.9 cases/100 000 [95% CI: 5.3, 6.6] in SEARCH vs 0.5/cases/100 000 [95% CI: 0.3, 0.7] in YDR). The age distribution of incident type 1 diabetes cases was similar across registries, whereas type 2 diabetes incidence was higher at an earlier age in SEARCH. Sex differences existed in SEARCH only, with a higher rate of type 2 diabetes among females. Conclusion The incidence of youth-onset type 1 and 2 diabetes was significantly different between registries. Additional data are needed to elucidate whether the differences observed represent diagnostic delay, differences in genetic susceptibility, or differences in distribution of risk factors.

BACKGROUND There is significant global variation in the prevalence of diabetic ketoacidosis (DKA) at diagnosis among youth with type 1 diabetes (T1D). However, data for youth with type 2 diabetes (T2D) are limited, even in developed countries. We compared the prevalence of DKA at diagnosis among individuals with T1D and T2D from the SEARCH for Diabetes in Youth (SEARCH) and the Registry of Youth Onset Diabetes in India (YDR) registries. METHODS We harmonized the SEARCH and YDR registries to the structure and terminology in the Observational Medical Outcome Partnership Common Data Model. Data used were from youth with T1D and T2D diagnosed before 20 years and newly diagnosed between 2006 and 2012 in YDR and 2009 and 2012 in SEARCH. RESULTS There were 5366 US youth (4078 with T1D, 1288 with T2D) and 2335 Indian youth (2108 with T1D, 227 with T2D). More than one third of T1D youth enrolled in SEARCH had DKA at diagnosis which was significantly higher than in YDR (35.3% vs 28.7%, P

An important goal of synthetic biology is to build biosensors and circuits with well-defined input-output relationships that operate at speeds found in natural biological systems. However, for molecular computation, most commonly used genetic circuit elements typically involve several steps from input detection to output signal production: transcription, translation, and post-translational modifications. These multiple steps together require up to several hours to respond to a single stimulus, and this limits the overall speed and complexity of genetic circuits. To address this gap, molecular frameworks that rely exclusively on post-translational steps to realize reaction networks that can process inputs at a time scale of seconds to minutes have been proposed. Here, we build mathematical models of fast biosensors capable of producing Boolean logic functionality. We employ protease-based chemical and light-induced switches, investigate their operation, and provide selection guidelines for their use as on-off switches. As a proof of concept, we implement a rapamycin-induced switch

Poly(aspartic acid) (PAA) is a biodegradable water-soluble anionic polymer that can potentially replace poly(acrylic acid) for industrial applications and has shown promise for regenerative medicine and drug delivery. This paper describes an efficient and sustainable route that uses protease catalysis to convert l-aspartate diethyl ester (Et2-Asp) to oligo(β-ethyl-α-aspartate), oligo(β-Et-α-Asp). Comparative studies of protease activity for oligo(β-Et-α-Asp) synthesis revealed α-chymotrypsin to be the most efficient. Papain, which is highly active for l-glutamic acid diethyl ester (Et2-Glu) oligomerization, is inactive for Et2-Asp oligomerization. The assignment of α-linkages between aspartate repeat units formed by α-chymotrypsin catalysis is based on nuclear magnetic resonance (NMR) trifluoacetic acid titration, circular dichroism, and NMR structural analysis. The influence of reaction conditions (pH, temperature, reaction time, and buffer/monomer/α-chymotrypsin concentrations) on oligopeptide yield and average degree of polymerization (DPavg) was determined. Under preferred reaction conditions (pH 8.5, 40 °C, 0.5 M Et2-Asp, 3 mg/mL α-chymotrypsin), Et2-Asp oligomerizations reached maximum oligo(β-Et-α-Asp) yields of ∼60% with a DPavg of ∼12 (Mn 1762) in just 5 min. Computational modeling using Rosetta software gave relative energies of substrate docking to papain and α-chymotrypsin active sites. The substrate preference calculated by Rosetta modeling of α-chymotrypsin and papain for Et2-Asp and Et2-Glu oligomerizations, respectively, is consistent with experimental results.

OBJECTIVE Genetic risk scores (GRS) aid classification of diabetes type in White European adult populations. We aimed to assess the utility of GRS in the classification of diabetes type among racially/ethnically diverse youth in the U.S. RESEARCH DESIGN AND METHODS We generated type 1 diabetes (T1D)- and type 2 diabetes (T2D)-specific GRS in 2,045 individuals from the SEARCH for Diabetes in Youth study. We assessed the distribution of genetic risk stratified by diabetes autoantibody positive or negative (DAA+/−) and insulin sensitivity (IS) or insulin resistance (IR) and self-reported race/ethnicity (White, Black, Hispanic, and other). RESULTS T1D and T2D GRS were strong independent predictors of etiologic type. The T1D GRS was highest in the DAA+/IS group and lowest in the DAA−/IR group, with the inverse relationship observed with the T2D GRS. Discrimination was similar across all racial/ethnic groups but showed differences in score distribution. Clustering by combined genetic risk showed DAA+/IR and DAA−/IS individuals had a greater probability of T1D than T2D. In DAA− individuals, genetic probability of T1D identified individuals most likely to progress to absolute insulin deficiency. CONCLUSIONS Diabetes type–specific GRS are consistent predictors of diabetes type across racial/ethnic groups in a U.S. youth cohort, but future work needs to account for differences in GRS distribution by ancestry. T1D and T2D GRS may have particular utility for classification of DAA− children.

Reconciling palaeodata with model simulations of the Pliocene climate is essential for understanding a world with atmospheric CO2 concentration near 400 parts per million by volume. Both models and data indicate an amplified warming of the high latitudes during the Pliocene, however terrestrial data suggests Pliocene high latitude temperatures were much higher than can be simulated by models. Here we show that understanding the Pliocene high latitude terrestrial temperatures is particularly difficult for the coldest months, where the temperatures obtained from models and different proxies can vary by more than 20 °C. We refer to this mismatch as the ‘warm winter paradox’. Analysis suggests the warm winter paradox could be due to a number of factors including: model structural uncertainty, proxy data not being strongly constrained by winter temperatures, uncertainties on data reconstruction methods and also that the Pliocene high latitude climate does not have a modern analogue. Refinements to model boundary conditions or proxy dating are unlikely to contribute significantly to the resolution of the warm winter paradox. For the Pliocene, high latitude, terrestrial, summer temperatures, models and different proxies are in good agreement. Those factors which cause uncertainty on winter temperatures are shown to be much less important for the summer. Until some of the uncertainties on winter, high latitude, Pliocene temperatures can be reduced, we suggest a data-model comparison should focus on the summer. This is expected to give more meaningful and accurate results than a data-model comparison which focuses on the annual mean.

Objective: Dysregulation of the immune system during pregnancy is associated with adverse pregnancy outcomes. Recent studies report cytokine changes during the acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We examine whether there is a lasting association between SARS-CoV-2 infection during pregnancy and peripheral blood cytokine levels. Study design: We conducted a case-control study at the Mount Sinai health system in NYC including 100 SARS-CoV-2 IgG antibody positive people matched to 100 SARS-CoV-2 IgG antibody negative people on age, race/ethnicity, parity, and insurance status. Blood samples were collected at a median gestational age of 34 weeks. Levels of 14 cytokines were measured. Results: Individual cytokine levels and cytokine cluster Eigenvalues did not differ significantly between groups, indicating no persisting maternal cytokine changes after SARS-CoV-2 infection during pregnancy. Conclusion: Our findings suggest that the acute inflammatory response after SARS-CoV-2 infection may be restored to normal values during pregnancy.

The Miocene to Pliocene (Neogene) occurred between 23.04 and 2.58 million years ago and includes intervals of peak global warmth where Earth’s average surface temperature was up to 8℃ warmer than present. Major cooling steps also occurred, across which Antarctica’s ice sheets advanced to the continental shelf for the first time and sea ice expanded across the Southern Ocean. Knowledge of Antarctic environmental change and ice sheet variability through this dynamic period in Earth history has advanced over the past 15 years. Major field and ship-based efforts to obtain new geological information have been completed and significant advances in numerical modelling approaches have occurred. Integration of ice proximal data and coupled climate-ice sheet model outputs with high-resolution reconstructions of ice volume and temperature variability from deep sea δ18O records now offer detailed insight into thresholds and tipping points in Earth’s climate system. Here we review paleoenvironmental data through key episodes in the evolution of Neogene climate to include the Miocene Climatic Optimum (MCO), Middle Miocene Climate Transition (MMCT), Tortonian Thermal Maximum (TTM), Late Miocene Cooling (LMC), and Pliocene Warm Period (PWP). This review shows that Antarctica’s climate and ice sheets remained dynamic throughout the Neogene. Given the analogous nature of warm episodes in the Miocene and Pliocene to future projections, the environmental reconstructions presented in this chapter offer a stark warning about the potential future of the AIS if warming continues at its current rate. If average global surface warming above pre-industrial values exceeds 2℃, a threshold will be crossed and AIS instabilities would likely be irreversible on multi-century timescales.

Aims. To explore how changes in insulin regimen are associated with estimated adiposity over time among youths and young adults with type 1 diabetes and whether any associations differ according to sex. Materials and Methods. Longitudinal data were analyzed from youths and young adults with type 1 diabetes in the SEARCH for Diabetes in Youth study. Participants were classified according to insulin regimen categorized as exclusive pump (“pump only”), exclusive injections (“injections only”), injection-pump transition (“injections-pump”), or pump-injection transition (“pump-injections”) for each follow-up visit completed. Estimated body fat percentage (eBFP) was calculated using validated equations. Sex-specific, linear mixed effects models examined the relationship between the insulin regimen group and change in eBFP during follow-up, adjusted for baseline eBFP, baseline insulin regimen, time-varying insulin dose, sociodemographic factors, and baseline HbA1c (≥9.0% vs. 12.7 ± 2.4 years. In fully adjusted models for females, exclusive pump use over the study duration was associated with significantly greater increases in eBFP compared to exclusive use of injections ( difference in rate of change = 0.023 % increase per month, 95 % CI = 0.01 , 0.04). Injection-to-pump transitions and pump-to-injection transitions were also associated with greater increases in eBFP compared to exclusive use of injections ( difference in rate of change = 0.02 % , 95 % CI = 0.004 , 0.03, and 0.02%; 95 % CI = 0.0001 , 0.04, respectively). There was no relationship between the insulin regimen and eBFP among males. Conclusions. Among females with type 1 diabetes, exclusive and partial pump use may have the unintended consequence of increasing adiposity over time compared to exclusive use of injections, independent of insulin dose.

Quality Improvement Success Stories are published by the American Diabetes Association in collaboration with the American College of Physicians and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes. The following article describes an effort to reduce iatrogenic insulin-associated hypoglycemia at the University of Chicago Medical Center in Chicago, IL.

Research suggest prenatal vaccination against coronavirus disease-19 (COVID-19) is safe. However, previous studies utilized retrospectively collected data or examined late pregnancy vaccinations. We investigated the associations of COVID-19 vaccination throughout pregnancy with delivery and neonatal outcomes. We included 1,794 mother-neonate dyads enrolled in the Generation C Study with known prenatal COVID-19 vaccination status and complete covariate and outcome data. We used multivariable quantile regressions to estimate the effect of prenatal COVID-19 vaccination on birthweight, delivery gestational age, and blood loss at delivery; and Poisson generalized linear models for Caesarean delivery (CD) and Neonatal Intensive Care Unit (NICU) admission. Using the above methods, we estimated effects of trimester of vaccine initiation on these outcomes. In our sample, 13.7% (n = 250) received at least one prenatal dose of any COVID-19 vaccine. Vaccination was not associated with birthweight (β = 12.42 g [-90.5, 114.8]), gestational age (β = 0.2 days [-1.1, 1.5]), blood loss (β = -50.6 ml [-107.0, 5.8]), the risks of CD (RR = 0.8; [0.6, 1.1]) or NICU admission (RR = 0.9 [0.5, 1.7]). Trimester of vaccine initiation was also not associated with these outcomes. Our findings suggest that there is no associated risk between prenatal COVID-19 vaccination and adverse delivery and neonatal outcomes in a cohort sample from NYC.

Objective To examine the associations between five major adverse pregnancy outcomes and long term risks of ischemic heart disease in mothers. Design National cohort study. Setting Sweden. Participants All 2 195 266 women with a first singleton delivery in Sweden during 1973-2015. Main outcome measures The main outcome measure was incidence of ischemic heart disease from delivery to 2018, identified from nationwide inpatient and outpatient diagnoses. Cox regression was used to calculate hazard ratios for ischemic heart disease associated with preterm delivery, small for gestational age, pre-eclampsia, other hypertensive disorders of pregnancy, and gestational diabetes, adjusting for other adverse pregnancy outcomes and maternal factors. Co-sibling analyses assessed for confounding by shared familial (genetic and environmental) factors. Results During 53.6 million person years of follow-up, ischemic heart disease was diagnosed in 83 881 (3.8%) women. All five adverse pregnancy outcomes were independently associated with increased risk of ischemic heart disease. In the 10 years after delivery, adjusted hazard ratios for ischemic heart disease associated with specific adverse pregnancy outcomes were 2.09 (95% confidence interval 1.77 to 2.46) for other hypertensive disorders of pregnancy, 1.72 (1.55 to 1.90) for preterm delivery, 1.54 (1.37 to 1.72) for pre-eclampsia, 1.30 (1.09 to 1.56) for gestational diabetes, and 1.10 (1.00 to 1.21) for small for gestational age. The hazard ratios remained significantly increased even 30-46 years after delivery: 1.47 (1.30 to 1.66) for other hypertensive disorders of pregnancy, 1.40 (1.29 to 1.51) for gestational diabetes, 1.32 (1.28 to 1.36) for pre-eclampsia, 1.23 (1.19 to 1.27) for preterm delivery, and 1.16 (1.13 to 1.19) for small for gestational age. These findings were only partially ( Conclusions In this large national cohort, women who experienced any of five major adverse pregnancy outcomes showed an increased risk for ischemic heart disease up to 46 years after delivery. Women with adverse pregnancy outcomes should be considered for early preventive evaluation and long term risk reduction to help prevent the development of ischemic heart disease.

ObjectiveThe objective of this study was to understand how women perceive the role of their Obstetrician and Gynecologist (OBGYN) in screening for and providing preexposure prophylaxis (PrEP) for HIV prevention.MethodsWe recruited women ages 18–45 years receiving obstetric or gynecological care at an academic medical center in the Bronx, NY. Thirty participants were enrolled: 10 seeking care for family planning, 10 seeking prenatal care, and 10 seeking care for a sexually transmitted infection. We screened participants for HIV acquisition risk using a PrEP screening tool. We conducted face-to-face, semi-structured interviews, which were audio-recorded, transcribed, and entered into Dedoose for analysis of themes using a grounded theory approach.ResultsSixty percent of the participants were Latinx and 33% African American. Seventy percent had one or more risk factors for HIV acquisition based on the PrEP screening tool, indicating they would benefit from a PrEP discussion. Three main themes emerged from the analysis of interview data. Participants viewed OBGYNs as experts in sexual and reproductive healthcare and believed they were experts in PrEP. Participants were concerned about “PrEP stigma”, being judged by their clinicians as being sexually promiscuous if they expressed a need for PrEP. Lastly, when participants trusted their OBGYN, that trust became a facilitator for women to consider PrEP and offset stigma as a barrier to identifying patients who are candidates for PrEP.ConclusionWomen established in care with an OBGYN are enthusiastic about having access to PrEP services incorporated into their sexual and reproductive healthcare. A universal approach to HIV prevention would avert stigma surrounding HIV care and prevention.

I have chronic eczema since I was 3 months old; eczema covers my entire body & scalp. I spent a lot of my childhood & young adult life in "Hume Street" hospital, each admission would last 2 - 3 weeks at a time in a bid to get my eczema under control again. My entire life.

Objective: To estimate difference in population-level glycemic control and the emergence of diabetes complications given a theoretical scenario whereby non-White youth and young adults (YYA) with type 1 diabetes (T1D) receive and follow an equivalent distribution of diabetes treatment regimens as non-Hispanic White YYA. Research Design and Methods: Longitudinal data from YYA diagnosed 2002-2005 in the SEARCH for Diabetes in Youth Study were analyzed. Based on self-reported race/ethnicity, YYA were classified as non-White race or Hispanic ethnicity (non-White subgroup) versus non-Hispanic White race (White subgroup). In the White versus non-White subgroups, propensity scores model estimated treatment regimens, including patterns of insulin modality, self-monitored glucose frequency, and continuous glucose monitoring use. An analysis based on policy evaluation technique in reinforcement learning estimated the effect of each treatment regimen on hemoglobin A1c (HbA1c) and diabetes complications for non-White YYA. Results: The study included n=978 YYA. The sample was 47.5% female and77.5% non-Hispanic White, with mean age 12.8±2.4 years at diagnosis. The estimated population mean of longitudinal average HbA1c over visits was 9.2% and 8.2% for the non-White and White subgroup, respectively (difference=0.9%). Within the non-White subgroup, mean HbA1c across visits was estimated to decrease by 0.33% (95%CI: -0.45%, -0.21%) if these YYA received the distribution of diabetes treatment regimens of the White subgroup, explaining approximately 35% of the estimated difference between the two subgroups. The non-White subgroup was also estimated to have a lower risk of developing diabetic retinopathy, diabetic kidney disease, and peripheral neuropathy with the White youth treatment regimen distribution (p Conclusions: Mathematically modeling an equalized distribution of T1D self-management tools and technology accounted for part but not all disparities in glycemic control between non-White and White YYA, underscoring the complexity of race/ethnicity-based health inequity.

Background The objective of the study was to understand how pregnant women learned about Zika infection and to identify what sources of information were likely to influence them during their pregnancy. Methods We conducted 13 semi-structed interviews in English and Spanish with women receiving prenatal care who were tested for Zika virus infection. We analyzed the qualitative data using descriptive approach. Results Pregnant women in the Bronx learned about Zika from family, television, the internet and their doctor. Informational sources played different roles. Television, specifically Spanish language networks, was often the initial source of information. Women searched the internet for additional information about Zika. Later, they engaged in further discussions with their healthcare providers. Conclusions Television played an important role in providing awareness about Zika to pregnant women in the Bronx, but that information was incomplete. The internet and healthcare providers were sources of more complete information and are likely the most influential. Efforts to educate pregnant women about emerging infectious diseases will benefit from using a variety of approaches including television messages that promote public awareness followed up by reliable information via the internet and healthcare providers.

Objective Exclusive breastmilk feeding during the delivery hospitalization, a Joint Commission indicator of perinatal care quality, is associated with longer-term breastfeeding success. Marked racial and ethnic disparities in breastfeeding exclusivity and duration existed prior to COVID-19. The pandemic, accompanied by uncertainty regarding intrapartum and postpartum safety practices, may have influenced disparities in infant feeding practices. Our objective was to examine whether the first wave of the COVID-19 pandemic in New York City was associated with a change in racial and ethnic disparities in exclusive breastmilk feeding during the delivery stay. Methods We conducted a cross-sectional study of electronic medical records from 14,964 births in two New York City hospitals. We conducted a difference-in-differences (DID) analysis to compare Black-white, Latina-white, and Asian-white disparities in exclusive breastmilk feeding in a pandemic cohort (April 1-July 31, 2020, n=3122 deliveries) to disparities in a pre-pandemic cohort (January 1, 2019-February 28, 2020, n=11,842). We defined exclusive breastmilk feeding as receipt of only breastmilk during delivery hospitalization, regardless of route of administration. We ascertained severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection status from reverse transcription-polymerase chain reaction tests from nasopharyngeal swab at admission. For each DID model (e.g. Black-white disparity), we used covariate-adjusted log binomial regression models to estimate racial and ethnic risk differences, pandemic versus pre-pandemic cohort risk differences, and an interaction term representing the DID estimator. Results Exclusive breastmilk feeding increased from pre-pandemic to pandemic among white (40.8% to 46.6%, pp=0.004) women, but not Black (22.6% to 25.3%, p=0.275) or Latina (20.1% to 21.4%, p=0.515) women overall. There was an increase in the Latina-white exclusive breastmilk feeding disparity associated with the pandemic (DID estimator=6.3 fewer cases per 100 births (95% CI=-10.8, -1.9)). We found decreased breastmilk feeding specifically among SARS-CoV-2 positive Latina women (20.1% pre-pandemic vs. 9.1% pandemic p=0.013), and no change in Black-white or Asian-white disparities. Conclusions We observed a pandemic-related increase in the Latina-white disparity in exclusive breastmilk feeding, urging hospital policies and programs to increase equity in breastmilk feeding and perinatal care quality during and beyond this health emergency.

We propose a novel LiDAR extrinsic calibration method that does not require external calibration settings or human intervention. Instead of using fixed calibration targets, our algorithm automatically detects valid geometry-level features in random surrounding scenes. As an assumption-free approach, we introduce an initial state estimation algorithm to aid the global optimization process. This is achieved by extending the Rotation-Invariant Feature (RIF) to tolerate noise and uncertainty from LiDAR and environments, which results in robust point correspondence matching. In order to improve efficiency, the translation and rotation offsets are optimized separately through Branch-and-Bound (BnB) optimization. The proposed algorithm shows promising results on an outdoor calibration dataset and outperforms previous calibration methods. It also demonstrates comparable robustness to offline calibration approaches, but with fewer constraints and assumptions.

Planning safe trajectories under uncertain and dynamic conditions makes the autonomous driving problem significantly complex. Current sampling-based methods such as Rapidly Exploring Random Trees (RRTs) are not ideal for this problem because of the high computational cost. Supervised learning methods such as Imitation Learning lack generalization and safety guarantees. To address these problems and in order to ensure a robust framework, we propose a Hierarchical Reinforcement Learning (HRL) structure combined with a Proportional-Integral-Derivative (PID) controller for trajectory planning. HRL helps divide the task of autonomous vehicle driving into sub-goals and supports the network to learn policies for both high-level options and low-level trajectory planner choices. The introduction of sub-goals decreases convergence time and enables the policies learned to be reused for other scenarios. In addition, the proposed planner is made robust by guaranteeing smooth trajectories and by handling the noisy perception system of the ego-car. The PID controller is used for tracking the waypoints, which ensures smooth trajectories and reduces jerk. The problem of incomplete observations is handled by using a Long-Short-Term-Memory (LSTM) layer in the network. Results from the high-fidelity CARLA simulator indicate that the proposed method reduces convergence time, generates smoother trajectories, and is able to handle dynamic surroundings and noisy observations., 7 pages, 5 figures

Labeled data are paramount for modern, deep learning object detection models. However, such data are not always available, either due to time and financial constraints or due to the rarity of certain objects. In this paper, we show that the CARLA simulator can be used effectively to provide automatic annotations for custom street-view objects, boosting datasets for objects with few labels. We evaluate our models on real world images and show that low-shot training data expanded by synthetic images rendered in CARLA can provide better performance than training models with low-shot examples alone. To overcome the sim-to-real domain gap, we perform domain randomization by taking advantage of CARLA's diverse simulations of weather conditions, actors, and maps. We train detectors on CARLA-generated images of two different object classes and evaluate them on publicly available datasets. We provide access to our synthetic fire hydrant33https://www.kaggle.com/xinhez/synthetic-fire-hydrants and crosswalk44https://www.kaggle.com/buvision/synthetic-crosswalks datasets as well as provide step-by-step instructions55https://www.github.com/xinhez/simulation-for-detection to generate custom datasets in CARLA.

In 2017–2019, the March of Dimes convened a workgroup with biomedical, clinical, and epidemiologic expertise to review knowledge of the causes of the persistent Black-White disparity in preterm birth (PTB). Multiple databases were searched to identify hypothesized causes examined in peer-reviewed literature, 33 hypothesized causes were reviewed for whether they plausibly affect PTB and either occur more/less frequently and/or have a larger/smaller effect size among Black women vs. White women. While definitive proof is lacking for most potential causes, most are biologically plausible. No single downstream or midstream factor explains the disparity or its social patterning, however, many likely play limited roles, e.g., while genetic factors likely contribute to PTB, they explain at most a small fraction of the disparity. Research links most hypothesized midstream causes, including socioeconomic factors and stress, with the disparity through their influence on the hypothesized downstream factors. Socioeconomic factors alone cannot explain the disparity's social patterning. Chronic stress could affect PTB through neuroendocrine and immune mechanisms leading to inflammation and immune dysfunction, stress could alter a woman's microbiota, immune response to infection, chronic disease risks, and behaviors, and trigger epigenetic changes influencing PTB risk. As an upstream factor, racism in multiple forms has repeatedly been linked with the plausible midstream/downstream factors, including socioeconomic disadvantage, stress, and toxic exposures. Racism is the only factor identified that directly or indirectly could explain the racial disparities in the plausible midstream/downstream causes and the observed social patterning. Historical and contemporary systemic racism can explain the racial disparities in socioeconomic opportunities that differentially expose African Americans to lifelong financial stress and associated health-harming conditions. Segregation places Black women in stressful surroundings and exposes them to environmental hazards. Race-based discriminatory treatment is a pervasive stressor for Black women of all socioeconomic levels, considering both incidents and the constant vigilance needed to prepare oneself for potential incidents. Racism is a highly plausible, major upstream contributor to the Black-White disparity in PTB through multiple pathways and biological mechanisms. While much is unknown, existing knowledge and core values (equity, justice) support addressing racism in efforts to eliminate the racial disparity in PTB.

Importance Changes in the prevalence of youth-onset diabetes have previously been observed. Objective To estimate changes in prevalence of type 1 and type 2 diabetes in youths in the US from 2001 to 2017. Design, setting, and participants In this cross-sectional observational study, individuals younger than 20 years with physician-diagnosed diabetes were enumerated from 6 areas in the US (4 geographic areas, 1 health plan, and select American Indian reservations) for 2001, 2009, and 2017. Exposures Calendar year. Main outcomes and measures Estimated prevalence of physician-diagnosed type 1 and type 2 diabetes overall and by race and ethnicity, age, and sex. Results Among youths 19 years or younger, 4958 of 3.35 million had type 1 diabetes in 2001, 6672 of 3.46 million had type 1 diabetes in 2009, and 7759 of 3.61 million had type 1 diabetes in 2017; among those aged 10 to 19 years, 588 of 1.73 million had type 2 diabetes in 2001, 814 of 1.85 million had type 2 diabetes in 2009, and 1230 of 1.85 million had type 2 diabetes in 2017. The estimated type 1 diabetes prevalence per 1000 youths for those 19 years or younger increased significantly from 1.48 (95% CI, 1.44-1.52) in 2001 to 1.93 (95% CI, 1.88-1.98) in 2009 to 2.15 (95% CI, 2.10-2.20) in 2017, an absolute increase of 0.67 per 1000 youths (95%, CI, 0.64-0.70) and a 45.1% (95% CI, 40.0%-50.4%) relative increase over 16 years. The greatest absolute increases were observed among non-Hispanic White (0.93 per 1000 youths [95% CI, 0.88-0.98]) and non-Hispanic Black (0.89 per 1000 youths [95% CI, 0.88-0.98]) youths. The estimated type 2 diabetes prevalence per 1000 youths aged 10 to 19 years increased significantly from 0.34 (95% CI, 0.31-0.37) in 2001 to 0.46 (95% CI, 0.43-0.49) in 2009 to 0.67 (95% CI, 0.63-0.70) in 2017, an absolute increase of 0.32 per 1000 youths (95% CI, 0.30-0.35) and a 95.3% (95% CI, 77.0%-115.4%) relative increase over 16 years. The greatest absolute increases were observed among non-Hispanic Black (0.85 per 1000 youths [95% CI, 0.74-0.97]) and Hispanic (0.57 per 1000 youths [95% CI, 0.51-0.64]) youths. Conclusions and relevance In 6 areas of the US from 2001 to 2017, the estimated prevalence of diabetes among children and adolescents increased for both type 1 and type 2 diabetes.

BACKGROUND Dyslipidemia has been documented in youth with type 2 diabetes. There is a paucity of studies examining dyslipidemia over time in youth with type 2 diabetes and associated risk factors. OBJECTIVE To evaluate lipids at baseline and follow-up and associated risk factors in youth with type 2 diabetes. METHODS We studied 212 youth with type 2 diabetes at baseline and after an average of 7 years of follow-up in the SEARCH for Diabetes in Youth Study. Abnormal lipids were defined as high-density lipoprotein cholesterol (HDL-C) 100, or triglycerides >150 (all mg/dl). We evaluated participants for progression to abnormal lipids (normal lipids at baseline and abnormal at follow-up), regression (abnormal lipids at baseline and normal at follow-up), stable normal, and stable abnormal lipids over time for HDL-C, LDL-C, and triglycerides. Associations between hemoglobin A1c (HbA1c) and adiposity over time (area under the curve [AUC]) with progression and stable abnormal lipids were evaluated. RESULTS HDL-C progressed, regressed, was stable normal, and stable abnormal in 12.3%, 11.3%, 62.3%, and 14.2% of participants, respectively. Corresponding LDL-C percentages were 15.6%, 12.7%, 42.9%, and 28.8% and triglycerides were 17.5%, 10.8%, 55.7%, and 16.0%. Each 1% increase in HbA1c AUC was associated with a 13% higher risk of progression and stable abnormal triglycerides and a 20% higher risk of progression and stable abnormal LDL-C. Higher adiposity AUC was marginally (p = 0.049) associated with abnormal HDL-C. CONCLUSIONS Progression and stable abnormal LDL-C and triglycerides occur in youth with type 2 diabetes and are associated with higher HbA1c.

Background The COVID-19 pandemic is an ongoing global health threat, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Questions remain about how SARS-CoV-2 impacts pregnant individuals and their children. Objective To expand our understanding of the effects of SARS-CoV-2 infection during pregnancy on pregnancy outcomes, regardless of symptomatology, by using serological tests to measure IgG antibody levels. Methods The Generation C Study is an ongoing prospective cohort study conducted at the Mount Sinai Health System. All pregnant individuals receiving obstetrical care at the Mount Sinai Healthcare System from 20 April 2020 onwards are eligible for participation. For the current analysis, we included participants who had given birth to a liveborn singleton infant on or before 22 September 2020. For each woman, we tested the latest prenatal blood sample available to establish seropositivity using a SARS-CoV-2 serologic enzyme-linked immunosorbent assay. Additionally, RT-PCR testing was performed on a nasopharyngeal swab taken during labour. Pregnancy outcomes of interest (i.e., gestational age at delivery, preterm birth, small for gestational age, Apgar scores, maternal and neonatal intensive care unit admission, and length of neonatal hospital stay) and covariates were extracted from medical records. Excluding individuals who tested RT-PCR positive at delivery, we conducted crude and adjusted regression models to compare antibody positive with antibody negative individuals at delivery. We stratified analyses by race/ethnicity to examine potential effect modification. Results The SARS-CoV-2 seroprevalence based on IgG measurement was 16.4% (95% confidence interval 13.7, 19.3; n=116). Twelve individuals (1.7%) were SARS-CoV-2 RT-PCR positive at delivery. Seropositive individuals were generally younger, more often Black or Hispanic, and more often had public insurance and higher pre-pregnancy BMI compared with seronegative individuals. None of the examined pregnancy outcomes differed by seropositivity, overall or stratified by race/ethnicity. Conclusion Seropositivity for SARS-CoV-2 without RT-PCR positivity at delivery (suggesting that infection occurred earlier during pregnancy) was not associated with selected adverse maternal or neonatal outcomes among live births in a cohort sample from New York City.

It has been almost 5 years since I coauthored a commentary on the timing of planned delivery in which I argued that data on improved outcomes continued to strengthen the case for delivery at 39 weeks’ gestation.1,2 At the time, 37 weeks was considered term, and waiting until 39 weeks for planned deliveries had been gaining momentum on the basis of improved outcome data, quality improvement initiatives, and advocacy efforts.3–5 Previously, “term” was an umbrella that encompassed anywhere from 3 weeks before to 2 weeks after the estimated due date. But given the difference in neonatal outcomes, especially in respiratory morbidity, the American College of Obstetricians and Gynecologists added further classifications and defined 37 + 0/7 to 38 + 6/7 weeks’ gestation as early term, 39 + 0/7 to 40 + 6/7 weeks’ gestation as full term, 41 + 0/7 to 41 + 6/7 weeks’ gestation as late term, and 42 + 0/7 weeks’ gestation and beyond as postterm.6 Today, most obstetricians follow guidelines and rather than act at 37 weeks, … Address correspondence to Siobhan M. Dolan, MD, MPH, Mount Sinai Hospital Klingenstein Pavilion, 1176 5th Ave, 9th Floor, Box 1170, New York, NY 10029. E-mail: siobhan.dolan{at}mssm.edu

OBJECTIVE Increased carotid intima-media thickness (cIMT) is associated with cardiovascular (CV) events in adults and with elevated CV risk factors in youth. The aim of this study was to determine whether obesity has an direct or indirect association with cIMT. METHODS Structural equation modeling was used to elucidate pathways for obesity to change cIMT. Complete data were collected twice on 294 participants (mean age 17.5 years, 16% with type 2 diabetes). Latent baseline and follow-up cIMT, BMI, and CV risk factors were analyzed with SAS 9.4. Model fit was assessed. RESULTS There were increases in BMI, mean arterial pressure (MAP), low-density lipoprotein cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, C-reactive protein, and glucose and a decrease in insulin and glycosylated hemoglobin over 5 years (all p < 0.05). Only bulb (0.031 mm) and internal (0.027 mm) cIMT increased (all p < 0.001). Significant direct effects on cIMT change were baseline MAP (β 0.23), BMI z score (β 0.16), change in glucose (β 0.37), and age (β 0.37; all p < 0.05). Change in MAP showed a trend (β 0.14, p = 0.10). BMI also had a significant indirect effect (β 0.17), whereas non-HDL demonstrated no significant effect. CONCLUSIONS Baseline adiposity drives increasing blood pressure and glucose in high-risk youth leading to accelerated accumulation of carotid arterial injury. Prevention of acquisition of obesity in youth is critical in slowing development of CV disease.

Aims Women who deliver pre-term have higher future risks of hypertension and ischaemic heart disease, but long-term risks of heart failure (HF) are unknown. We examined these risks in a large national cohort. Methods and results All 2 201 284 women with a singleton delivery in Sweden during 1973–2015 were followed up for inpatient or outpatient HF diagnoses through 2015. Cox regression was used to compute hazard ratios (HRs) for HF associated with pregnancy duration, adjusting for other maternal factors. Co-sibling analyses assessed for confounding by shared familial (genetic and/or environmental) factors. In 48.2 million person-years of follow-up, 19 922 women were diagnosed with HF (median age: 60.7 years). Within 10 years after delivery, the adjusted HR was 2.96 [95% confidence interval (CI): 2.48–3.53] for HF associated with pre-term (gestational age: Conclusion Pre-term and early term delivery were associated with markedly increased future hazards for HF, which persisted after adjusting for other maternal and familial factors and remained elevated 40 years later. Pre-term and early-term delivery should be recognized as risk factors for HF across the life course. Key Question What are the long-term hazards for heart failure (HF) across the life course in women who deliver preterm? Key Finding Preterm and early term delivery were associated with ∼3- and 1.7-fold adjusted hazards for HF in the next 10 years vs. full-term delivery. These hazards declined but remained elevated 40 years later, and were not explained by shared familial factors. Take Home Message Preterm and early term delivery were associated with increased future hazards for HF, which persisted for 40 years after adjusting for other maternal and familial factors. Preterm and early term delivery should be recognized as lifelong risk factors for HF.

This work proposes a novel framework for motion planning using trajectory optimization for autonomous driving. First, a two-phase behavioral policy maker (BPM) is proposed as a high-level decision maker to mimic human-like driving style by avoiding unnecessary tasks and early lane changes. Second, a comprehensive study on iterative adaptive weight tuning functions has been done to limit manual weight tuning in the Constrained Iterative Linear Quadratic Regulator (CILQR) motion planner. Third, a jerk-minimized CILQR is presented to ensure the comfort and safety of passengers by generating smooth trajectories. The simulation results show efficiency, safety, and comfort of generated trajectories.

AimsTo compare left ventricular structure (LV) and diastolic function in young adults with youth- onset diabetes by type, determine the prevalence of abnormal diastolic function by diabetes type using published values from age similar healthy controls, and examine the risk factors associated with diastolic function.MethodsIn a cross sectional analysis we compared LV structure and diastolic function from two dimensional echocardiogram in participants with type 1 (T1D) and type 2 diabetes (T2D) who participated in the SEARCH for Diabetes in Youth Study. Linear models were used to examine the risk factors associated with worse diastolic function.ResultsOf 479 participants studied, 258 had T1D (mean age 21.2 ± 5.2 years, 60.5% non-Hispanic white, 53.9% female) and 221 had T2D (mean age 24.8 ± 4.3 years, 24.4% non-Hispanic white, 73.8% female). Median diabetes duration was 11.6 years. Participants with T2D had greater LV mass index and worse diastolic function that persisted after adjustment for differences in risk factors compared with participants with T1D (all p ConclusionsLV structure and diastolic function is worse in individuals with T2D compared to T1D. However, abnormal diastolic function in seen in both groups compared to published values from age similar healthy controls.