Partitioning variance in cortical morphometry into genetic, environmental, and subject-specific components.

The relative contributions of genetic variation and experience in shaping the morphology of the adolescent brain are not fully understood. Using longitudinal data from 11,665 subjects in the ABCD Study, we fit vertex-wise variance components including family effects, genetic effects, and subject-level effects using a computationally efficient framework. Variance in cortical thickness and surface area is largely attributable to genetic influence, whereas sulcal depth is primarily explained by subject-level effects. Our results identify areas with heterogeneous distributions of heritability estimates that have not been seen in previous work using data from cortical regions. We discuss the biological importance of subject-specific variance and its implications for environmental influences on cortical development and maturation.

Prospective transitions in hemoglobin A1c following gestational diabetes using Multistate Markov Models.

OBJECTIVE: We characterized the state-to-state transitions in postpartum A1c levels after gestational diabetes, including remaining in a state of normoglycemia or transitions between prediabetes or diabetes states of varying severity. METHODS: We used data from the APPLE Cohort, a postpartum population-based cohort of individuals with gestational diabetes between 2009-2011and linked HbA1c data with up to 9 years follow-up (N=34,171). We examined maternal sociodemographic and perinatal characteristics as predictors of transitions in A1c progression using Markov multistate models. RESULTS: In the first-year postpartum following gestational diabetes, 45.1% of people had no-diabetes, 43.1% had prediabetes, 4.6% had controlled diabetes and 7.2% had uncontrolled diabetes. Roughly two-thirds of individuals remained in same state in the next year. Black individuals were more likely to transition from pre-diabetes to uncontrolled diabetes (aHR: 2.32 95% CI: 1.21 ,4.47) than White persons. Perinatal risk factors were associated with disease progression and lower likelihood of improvement. For example, hypertensive disorders of pregnancy were associated with a stronger transition (aHR: 2.06 95% CI: 1.39, 3.05) from prediabetes to uncontrolled diabetes. CONCLUSIONS: We illustrate factors associated with adverse transitions in incremental A1c stages and describe patient profiles who may warrant enhanced postpartum monitoring.

The Chief Wellness Officer: A long overdue catalyst for systemic change in Emergency Medicine.

GOALS: The American healthcare system is amid a burnout epidemic, worsened by COVID, that must be addressed expeditiously and with high priority. The burden Emergency Physicians encountered before and during the pandemic is well known, with countless healthcare workers exiting the work force. A Chief Wellness Officer (CWO) is a senior leader who works primarily to cultivate organisational wellness and to foster and promote a culture of well-being throughout an institution. Specifically, the CWO assists the health system leadership promote clinician engagement and address clinician burnout. This paper explores the status of existing CWOs, and cites the benefits, impacts, and barriers to implementation of a CWO, with focus on the field of Emergency Medicine (EM). METHODS: A steering committee of wellness experts was formed from a national EM organisation. A purposive search and literature review using search terms relating to CWOs was completed. Publications were examined for relevance and recency. The committee created an online questionnaire surveying current US CWOs, conducted personal interviews, and met through regular focused meetings. A framework delineating the role of a CWO as an organisation evolves from instituting novice wellness interventions to expert organisational innovations was created. PRINCIPLE FINDINGS: Despite their title, CWOs are not regularly included in c-suite decisions. Barriers to instituting a CWO include perceived financial cost, the medical system itself, and physician resistance. Defining and measuring objective return on investment may be a solution to overcoming barriers. CWOs who create comprehensive institutional wellness innovations bring organisations to the highest proficient and expert levels of wellness practices, positively affecting physician engagement and deflecting burnout. CWOs instituting novice and beginner levels of wellness interventions, especially in EM, only modestly impact individual wellness practices. PRACTICAL APPLICATIONS: A CWO and team with an organisational voice and a C-suite stakeholder's seat are essential to centralising and leading effective wellness efforts and innovations in EM and other specialities. This team will improve the work environment and culture and begin to fix our broken healthcare system and providers.

Synthesis of High-Molecular-Weight and Strength Polyisobutylene-Based Polyurethane and Its Use for the Development of a Synthetic Heart Valve.

Under optimized synthesis conditions, for the first time, polyisobutylene-based polyurethane (PIB-PU) is prepared with 70% PIB soft segment (i.e., a bioinert and calcification-resistant PU) with Mn > 100 000 Da, 32 MPa ultimate strength, and 630% elongation. The key parameters for this achievement are a) the precise stoichiometry of the polyurethane forming reaction, specifically the use of highly purified di-isocyanate (4,4'-methylene-bis (phenyl isocyanate), MDI), and b) the increased solid content of the synthesis solution to the limit beyond which increased viscosity prevents stirring. The shape of the stress-strain trace of PIB-PU indicates a two-step failure starting with a reversible elastic (Hookean) region up to ≈50% yield, followed by a slower linearly increasing high-modulus-deformation region suggesting the strengthening of PIB soft segments by entanglement/catenation, and the hard segments by progressively ordering urethane domains. This PIB-PU is a candidate for a fully synthetic bioprosthetic heart valve since preliminary studies show that PIB-PU has impressive fatigue life.

Macromolecular Engineering and Additive Manufacturing of Polyisobutylene-Based Thermoplastic Elastomers. II. The Poly(styrene-b-isobutylene-b-styrene)/Poly(phenylene oxide) System.

This series of publications describes research rendering soft polyisobutylene (PIB)-based thermoplastic elastomers 3D printable by blending with rigid chemically compatible thermoplastics. The molecular structure, morphology, physical properties, and 3D printability of such blends have been systematically investigated. The authors' first report was concerned with the rendering of soft poly(styrene-b-isobutylene-b-styrene) (SIBS) 3D printable by blending with rigid polystyrene (PS). Here they report the macromolecular engineering of SIBS/polyphenylene oxide (PPO) blends for 3D printing. PPO, a rigid high-performance thermoplastic, is compatible with the hard PS block in SIBS; however, neither PPO nor SIBS can be directly 3D printed. The microphase-separated structures and physical properties of SIBS/PPO blends are systematically tuned by controlling blending ratios and molecular weights. Suitable composition ranges and desirable properties of SIBS/PPO blends for 3D printing are optimized. The morphology and properties of SIBS/PPO blends are characterized by an ensemble of techniques, including atomic force microscopy, small-angle X-ray scattering, and thermal and mechanical properties testing. The elucidation of processing-structure-property relationship of SIBS/PPO blends is essential for 3D printing and advanced manufacturing of high-performance polymer systems.

Predictors and Trends in First-Trimester Hemoglobin A1c Screening in New York City, 2009 to 2017.

Glycated hemoglobin is an adjunct tool in early pregnancy to assess glycemic control. We examined trends and maternal predictors for those who had A1c screening in early pregnancy using hospital discharge and vital registry data between 2009 and 2017 linked with the New York City A1C Registry (N = 798,312). First-trimester A1c screening increased from 2.3% in 2009 to 7.7% in 2017. The likelihood of screening became less targeted to high-risk patients over time, with a decrease in mean A1c values from 5.8% (95% confidence interval [CI]: 5.8, 5.9) to 5.3 (95% CI: 5.3, 5.4). The prevalence of gestational diabetes mellitus increased while testing became less discriminate for those with high-risk factors, including pregestational type 2 diabetes, chronic hypertension, obesity, age over 40 years, as well as Asian or Black non-Hispanic race/ethnicity. KEY POINTS: · First-trimester A1c screening increased from 2.3% in 2009 to 7.7% in 2017 in New York City.. · The likelihood of screening became less targeted to high-risk patients over time.. · The prevalence of gestational diabetes mellitus increased, while testing became less discriminate..

Excess Deaths in Mexico City and New York City During the COVID-19 Pandemic, March to August 2020.

Objectives. To estimate all-cause excess deaths in Mexico City (MXC) and New York City (NYC) during the COVID-19 pandemic. Methods. We estimated expected deaths among residents of both cities between March 1 and August 29, 2020, using log-linked negative binomial regression and compared these deaths with observed deaths during the same period. We calculated total and age-specific excess deaths and 95% prediction intervals (PIs). Results. There were 259 excess deaths per 100 000 (95% PI = 249, 269) in MXC and 311 (95% PI = 305, 318) in NYC during the study period. The number of excess deaths among individuals 25 to 44 years old was much higher in MXC (77 per 100 000; 95% PI = 69, 80) than in NYC (34 per 100 000; 95% PI = 30, 38). Corresponding estimates among adults 65 years or older were 1263 (95% PI = 1199, 1317) per 100 000 in MXC and 1581 (95% PI = 1549, 1621) per 100 000 in NYC. Conclusions. Overall, excess mortality was higher in NYC than in MXC; however, the excess mortality rate among young adults was higher in MXC. Public Health Implications. Excess all-cause mortality comparisons across populations and age groups may represent a more complete measure of pandemic effects and provide information on mitigation strategies and susceptibility factors. (Am J Public Health. 2021;111(10): 1847-1850. https://doi.org/10.2105/AJPH.2021.306430).

Paternal Jail Incarceration and Birth Outcomes: Evidence from New York City, 2010-2016.

OBJECTIVES: To examine population-level associations between paternal jail incarceration during pregnancy and infant birth outcomes using objective measures of health and incarceration. METHODS: We use multivariate logistic regression models and linked records on all births and jail incarcerations in New York City between 2010 and 2016. RESULTS: 0.8% of live births were exposed to paternal incarceration during pregnancy or at the time of birth. After accounting for parental sociodemographic characteristics, maternal health behaviors, and maternal health care access, paternal incarceration during pregnancy remains associated with late preterm birth (OR = 1.34, 95% CI = 1.21, 1.48), low birthweight (OR = 1.39, 95% CI = 1.27, 1.53), small size for gestational age (OR = 1.35, 95% CI = 1.17, 1.57), and NICU admission (OR = 1.14, 95% CI = 1.05, 1.24). CONCLUSIONS: We found strong positive baseline associations (p < 0.001) between paternal jail incarceration during pregnancy with probabilities of all adverse outcomes examined. These associations did not appear to be driven purely by duration or frequency of paternal incarceration. These associations were partially explained by parental characteristics, maternal health behavior, and health care. These results indicate the need to consider paternal incarceration as a potential stressor and source of trauma for pregnant women and infants.

A comparison between telehealth and face-to-face delivery of a brief alcohol intervention for college students.

BACKGROUND: Problematic alcohol use is a common occurrence among college students. While empirically supported interventions exist, their access is typically limited to those with greater resources. There has been an expansion of services provided via telehealth to increase client access to treatment in the health care field. However, the evidence is mixed regarding the effectiveness of face-to-face versus telehealth interventions and there is a gap in the literature regarding brief alcohol interventions delivered via telehealth. As such, the purpose of this study was to test the effectiveness of a well-validated brief alcohol screening and intervention for college students (BASICS) when conducted face-to-face or through a videoconferencing system. Method: Participants included 51 college students who engaged in heavy episodic drinking (5+ drinks for males and 4+ drinks for females over a two hour period) over the last two weeks. They were randomly assigned to receive the face-to-face or telehealth intervention and completed a variety of questionnaires throughout. Follow up data on the participant's alcohol use and alcohol-related problems was collected at 1-, 2-, and 3-months. Multilevel modeling in SAS was utilized for analyses, which included the modeling of treatment outcome trajectories and the influence of predictors on the trajectory of change for each outcome. Results: Results indicated that the intervention significantly reduced alcohol consumption and related problems regardless of condition. Both conditions saw an increase in treatment satisfaction and therapeutic alliance between the two sessions. Increased therapeutic alliance resulted in greater decreases in alcohol use and related harm across both conditions. Additionally, those with a mental health diagnosis showed greater improvement related to risk reduction for both treatment modalities. Conclusion: In sum, the results of this study suggest that telehealth services should be further implemented and the BASICS intervention can be effectively delivered via telehealth for college students.

Apoptosis signal-regulating kinase-1 promotes inflammasome priming in macrophages.

We previously showed that mice deficient in apoptosis signal-regulating kinase-1 (ASK1) were partially protected against ventilator-induced lung injury. Because ASK1 can promote both cell death and inflammation, we hypothesized that ASK1 activation regulates inflammasome-mediated inflammation. Mice deficient in ASK1 expression (ASK1-/-) exhibited significantly less inflammation and lung injury (as measured by neutrophil infiltration, IL-6, and IL-1ß) in response to treatment with inhaled lipopolysaccharide (LPS) compared with wild-type (WT) mice. To determine whether this proinflammatory response was mediated by ASK1, we investigated inflammasome-mediated responses to LPS in primary macrophages and bone marrow-derived macrophages (BMDMs) from WT and ASK1-/- mice, as well as the mouse alveolar macrophage cell line MH-S. Cells were treated with LPS alone for priming or LPS followed by ATP for activation. When macrophages were stimulated with LPS followed by ATP to activate the inflammasome, we found a significant increase in secreted IL-1ß from WT cells compared with ASK1-deficient cells. LPS priming stimulated an increase in NOD-like receptor 3 (NLRP3) and pro-IL-1ß in WT BMDMs, but expression of NLRP3 was significantly decreased in ASK1-/- BMDMs. Subsequent ATP treatment stimulated an increase in cleaved caspase-1 and IL-1ß in WT BMDMs compared with ASK1-/- BMDMs. Similarly, treatment of MH-S cells with LPS + ATP caused an increase in both cleaved caspase-1 and IL-1ß that was diminished by the ASK-1 inhibitor NQDI1. These results demonstrate, for the first time, that ASK1 promotes inflammasome priming.

Characteristics of Mothers and Infants Living in Homeless Shelters and Public Housing in New York City.

Introduction Homelessness can result in poor health. The number of families with children living in NYC homeless shelters increased 55% from 2008 to 2014. Half of children living in shelter in 2014 were younger than 6 years old. We compared demographics and health outcomes of mothers and infants residing in NYC homeless shelters to those residing in public housing in this cross-sectional study. Methods Addresses of NYC Department of Homeless Services shelters and NYC Housing Authority (NYCHA) developments were matched to NYC Department of Health birth certificate data for the years 2008-2013. Sociodemographic and health characteristics of newborns residing in shelters were compared to newborns in NYCHA housing using Chi square tests. Results Mothers residing in shelters were younger, more likely to be black and less likely to be Hispanic, more likely to have been born outside NYC and reside in the Bronx. Babies born to mothers living in shelter were more likely to have low birth weight (< 2500 g), be born preterm (< 37 gestational weeks), require assisted ventilation immediately following delivery, have a NICU admission, and use Medicaid. They were less likely to breastfeed within 5 days of delivery and be discharged to their residence. Discussion Homeless mothers and infants had poorer health outcomes compared with those living in public housing. Understanding the health disparities of homeless infants can provide guidance for developing future policies and research initiatives, which may be used to inform the development of new policies to improve health outcomes of homeless infants and their mothers.

Sex Difference in Meningococcal Disease Mortality, New York City, 2008-2016.

Background: The case fatality rate (CFR) from invasive meningococcal disease (IMD) in New York City (NYC) is greater than national figures, with higher rates among females than males across all age groups. Methods: We conducted a retrospective cohort study among 151 persons aged ≥15 years diagnosed with IMD in NYC during 2008-2016 identified through communicable disease surveillance. We examined demographic, clinical, and community-level associations with death to confirm the elevated risk of mortality among female IMD patients after adjusting for confounders and to determine factors associated with female IMD mortality. Relative risks of death were estimated using multivariable log-linear Poisson regression with a robust error variance. Results: Females had a higher CFR (n = 23/62; 37%) following IMD than males (n = 17/89; 19%) (adjusted relative risk [aRR], 2.1; 95% confidence interval [CI], 1.2-3.8). Controlling for demographic and clinical factors, there was a significant interaction between sex and fatal outcomes related to meningitis: the relative risk of death for females with meningitis was 13.7 (95% CI, 3.2-58.1) compared with males. In the model restricted to females, altered mental status (aRR, 7.5; 95% CI, 2.9-19.6) was significantly associated with an increased risk of death. Conclusions: Female mortality from IMD was significantly increased compared with males, controlling for other predictors of mortality. Sex-based differences in recognition and treatment need to be evaluated in cases of meningococcal disease. Our study highlights the importance of analyzing routine surveillance data to identify and address disparities in disease incidence and outcomes.

Rapid analysis of fentanyls and other novel psychoactive substances in substance use disorder patient urine using paper spray mass spectrometry.

RATIONALE: Drug overdose deaths due to fentanyls and other novel psychoactive substances (NPS) are on the rise. The higher potencies of fentanyl analogs compared with morphine require new technologies to identify and quantitate NPS. METHODS: Paper spray tandem mass spectrometry (MS/MS) and high-resolution mass spectrometry were used to identify and measure fentanyl analogs as well as common drugs of abuse in urine samples from substance use disorder clinics. Ten-microliter urine samples were deposited directly on paper spray cartridges previously loaded with internal standards, dried, and analyzed with no other sample treatment. Quantitative results were obtained using MS/MS. Individual drugs were identified using high-resolution accurate mass spectrometry, and confirmed by data-dependent MS/MS. RESULTS: Calibration curves in urine were linear over a range of 0.5-50 ng/mL with R2 of 0.99 or better for eight representative fentanyl analogs. Cartridges preloaded with internal standards demonstrated satisfactory quantitative results compared with LC/MS. Direct identification and confirmation of fentanyl analogs and other common drugs of abuse in urine using high-resolution accurate mass and MS/MS fragmentation were demonstrated at low picogram levels. CONCLUSIONS: Paper spray mass spectrometry can reliably identify and quantitate fentanyl analogs and other drugs of abuse in urine. Using paper spray cartridges as collection devices reduces exposure and transportation risks associated with biological fluids. Cartridges preloaded with labeled internal standards can be effective for targeted screening of fentanyl analogs and other drugs of abuse.

Reportable Bacterial Infections among New York City-Born Infants, 2001-2009.

OBJECTIVE: To determine rates of reportable bacterial infections among infants in New York City and identify populations at risk and preventable causes of morbidity. STUDY DESIGN: This retrospective cohort study matched live births in New York City from 2001-2009 to reported cases of bacterial infections among infants less than 1 year of age. Characteristics recorded on birth certificates were compared between infants with bacterial enteric infection, bacterial nonenteric infection, and no reportable bacterial infection. Multinomial logistic regression and multivariable logistic regression were used to identify risk factors for infection. RESULTS: Bacterial infection was reported in 4.6 cases per 1000 live births. Of 4524 infants with a reportable infection, the majority (2880, 63%) had an enteric infection. Asian/Pacific Islanders in Brooklyn were the borough-level race/ethnic group with the highest enteric infection rate (8.5 per 1000 live births). Citywide, infants with enteric infections were disproportionately male, from higher poverty neighborhoods, born to foreign-born mothers, and enrolled in Special Supplemental Food Program for Women, Infants, and Children or Medicaid. In contrast, infants with nonenteric infections were more likely to have low birthweight and mothers characterized by US birth and black race or white Hispanic race/ethnicity. CONCLUSIONS: Distinct patterns of risk factors for enteric and nonenteric bacterial infections among infants were identified. The results suggest that infants born to Asian/Pacific Islander mothers residing in Brooklyn should be a focus of enteric disease prevention. More research is necessary to better understand what behaviors increase the risk of enteric disease in this population.

Real-Time Monitoring of Chemical and Topological Rearrangements in Solidifying Amphiphilic Polymer Co-Networks: Understanding Surface Demixing.

Amphiphilic polymer co-networks provide a unique route to integrating contrasting attributes of otherwise immiscible components within a bicontinuous percolating morphology and are anticipated to be valuable for applications such as biocatalysis, sensing of metabolites, and dual dialysis membranes. These co-networks are in essence chemically forced blends and have been shown to selectively phase-separate at surfaces during film formation. Here, we demonstrate that surface demixing at the air-film interface in solidifying polymer co-networks is not a unidirectional process; instead, a combination of kinetic and thermodynamic interactions leads to dynamic molecular rearrangement during solidification. Time-resolved gravimetry, low contact angles, and negative out-of-plane birefringence provided strong experimental evidence of the transitory trapping of thermodynamically unfavorable hydrophilic moieties at the air-film interface due to fast asymmetric solvent depletion. We also find that slow-drying hydrophobic elements progressively substitute hydrophilic domains at the surface as the surface energy is minimized. These findings are broadly applicable to common-solvent bicontinuous systems and open the door for process-controlled performance improvements in diverse applications. Similar observations could potentially be coupled with controlled polymerization rates to maximize the intermingling of bicontinuous phases at surfaces, thus generating true three-dimensional, bicontinuous, and undisturbed percolation pathways throughout the material.

Mortality of New York children with sickle cell disease identified through newborn screening.

PURPOSE: Long-term follow-up of newborn screening for conditions such as sickle cell disease can be conducted using linkages to population-based data. We sought to estimate childhood sickle cell disease mortality and risk factors among a statewide birth cohort with sickle cell disease identified through newborn screening. METHODS: Children with sickle cell disease identified by newborn screening and born to New York residents in 2000-2008 were matched to birth and death certificates. Mortality rates were calculated (using numbers of deaths and observed person-years at risk) and compared with mortality rates for all New York children by maternal race/ethnicity. Stratified analyses were conducted to examine associations between selected factors and mortality. RESULTS: Among 1,911 infants with sickle cell disease matched to birth certificates, 21 deaths were identified. All-cause mortality following diagnosis was 3.8 per 1,000 person-years in the first 2 years of life and 1.0 per 1,000 person-years at ages 2-9 years. The mortality rate was significantly lower among children of foreign-born mothers and was significantly higher among preterm infants with low birth weight. The mortality rates were not significantly higher for infants after 28 days with sickle cell disease than for all New York births, but they were 2.7-8.4 times higher for children 1 through 9 years old with homozygous sickle cell disease than for those of all non-Hispanic black or Hispanic children born to New York residents. CONCLUSION: Estimated mortality risk in children with homozygous sickle cell disease remains elevated even after adjustment for maternal race/ethnicity. These results provide evidence regarding the current burden of child mortality among children with sickle cell disease despite newborn screening.Genet Med 17 6, 452-459.