More comprehensive sex education reduced teen births: Quasi-experimental evidence.

Women in the United States are much more likely to become mothers as teens than those in other rich countries. Teen births are particularly likely to be reported as unintended, leading to debate over whether better information on sex and contraception might lead to reductions in teen births. We contribute to this debate by providing causal evidence at the population level. Our causal identification strategy exploits county-level variation in the timing and receipt of federal funding for more comprehensive sex education and data on age-specific teen birth rates at the county level constructed from birth certificate natality data covering all births in the United States. Our results show that federal funding for more comprehensive sex education reduced county-level teen birth rates by more than 3%. Our findings thus complement the mixed evidence to date from randomized control trials on teen pregnancies and births by providing population-level causal evidence that federal funding for more comprehensive sex education led to reductions in teen births.

Exposure to Crime and Racial Birth Outcome Disparities.

Urban communities in the United States were transformed at the end of the twentieth century by a rapid decline in neighborhood crime and violence. We leverage that sharp decline in violence to estimate the relationship between violent crime rates and racial disparities in birth outcomes. Combining birth certificate data from US counties with the FBI's Uniform Crime Reporting statistics from 1992 to 2002, we show that lower crime rates are associated with substantially smaller Black-White disparities in birth weight, low birth weight, and small for gestational age. These associations are stronger in more segregated counties, suggesting that the impacts of the crime decline may have been concentrated in places with larger disparities in exposure to crime. We also estimate birth outcome disparities under the counterfactual that the crime decline did not occur and show that reductions in crime statistically explain between one-fifth and one-half of the overall reduction in Black-White birth weight, LBW, and SGA disparities that occurred during the 1990s. Drawing on recent literature showing that exposure to violent crime has negative causal effects on birth outcomes, which in turn influence life-course outcomes, we argue that these results suggest that changes in national crime rates have implications for urban health inequality.

Racial/Ethnic Differences in Relationships Between Pregnancy Intentions and Maternal Outcomes.

Unplanned or unwanted pregnancies and births are linked to adverse maternal outcomes, but the extent to which such relationships hold for all racial/ethnic groups remains unknown. In this paper, I use large-scale data to estimate unadjusted and inverse propensity weighted associations between a five-level measure of pregnancy intention and six indicators of maternal well-being among separate samples of white, Black, and Hispanic mothers. I find substantial racial/ethnic variation. White and Hispanic mothers who reported that their pregnancies were mistimed, unwanted, or that they were unsure how they felt were significantly more likely to experience adverse outcomes than same-race/ethnicity mothers who reported that their pregnancy was intended, but the pattern was much more tenuous for Black mothers. After adjusting for potential confounding variables, relationships between pregnancy intentions and adverse outcomes remain substantial only for white and Hispanic mothers.

Do Pregnancy Intentions Matter? A Research Note Revisiting Relationships Among Pregnancy, Birth, and Maternal Outcomes.

The prevention of unplanned or unintended pregnancies continues to be a cornerstone of U.S. reproductive health policy, but the evidence that such pregnancies cause adverse maternal and child outcomes is limited. In this research note, we examine these relationships using recent large-scale data and inverse propensity weights estimated from generalized boosted models. We find that pregnancy timing is related to maternal experience during pregnancy, but not to infant outcomes at birth-both of which are consistent with prior research. In an addition to the literature, we show that pregnancy timing is relevant for a number of maternal outcomes, such as the onset of depression and intimate partner violence, changes in smoking behavior, and receipt of medical care. These findings suggest that policy intended to improve infant welfare by preventing unintended pregnancies has little empirical support, but that policy focused on increasing reproductive autonomy and maternal well-being has the potential to improve outcomes.

Chronic Obstructive Pulmonary Disease Alters Immune Cell Composition and Immune Checkpoint Inhibitor Efficacy in Non-Small Cell Lung Cancer.

RATIONALE: Chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC) are interrelated diseases with substantial mortality, and the pathogenesis of both involves aberrant immune functioning. OBJECTIVES: To profile immune cell composition and function in patients with NSCLC and describe the effects of COPD on lung and tumor microenvironments. METHODS: We profiled resected lung and tumor tissue using flow cytometry and T-cell receptor sequencing in patients with and without COPD from a prospective cohort of patients undergoing resection of NSCLC. A murine cigarette smoke exposure model was used to evaluate the effect on pulmonary immune populations. A separate retrospective cohort of patients who received immune checkpoint inhibitors (ICIs) was analyzed, and their survival was quantified. MEASUREMENTS AND MAIN RESULTS: We observed an increased number of IFN-γ-producing CD8+ and CD4+ (T-helper cell type 1 [Th1]) lymphocytes in the lungs of patients with COPD. In both humans and mice, increased Th17 content was seen with smoke exposure, but was not associated with the development or severity of COPD. COPD-affected lung tissue displayed increased Th1 differentiation that was recapitulated in the matching tumor sample. PD-1 (programmed cell death protein 1) expression was increased in tumors of patients with COPD, and the presence of COPD was associated with progression-free survival in patients treated with ICIs. CONCLUSIONS: In patients with COPD, Th1 cell populations were expanded in both lung and tumor microenvironments, and the presence of COPD was associated with longer progression-free intervals in patients treated with ICIs. This has implications for understanding the immune mediators of COPD and developing novel therapies for NSCLC.

Pregnancy intentions' relationship with infant, pregnancy, maternal, and early childhood outcomes: Evidence from births in Alaska, Missouri, and Oklahoma.

OBJECTIVES: Much of reproductive health care policy in the United States focuses on enabling women to have intended pregnancies. Investigating whether the association between pregnancy intention and adverse outcomes for mothers and children in the immediate and longer term is due to intention or a mother's demographics provides valuable context for policy makers aiming to improve maternal and child outcomes. METHODS: We investigated relationships between pregnancy intention and pregnancy, infant, early childhood, and maternal outcomes using data from the Pregnancy Risk Assessment Monitoring System survey, conducted 2-8 months after the child's birth, and follow-up surveys from three states (Alaska, Missouri, and Oklahoma), administered at age 2-3 years old. We used logistic regressions with inverse propensity weights to measure associations, accounting for potential confounding factors. RESULTS: After inverse propensity weighting, pregnancy intention was associated with adverse maternal pregnancy behaviors but not most infant outcomes. Mothers who reported an unwanted pregnancy were associated with increased odds of the child receiving a developmental delay diagnosis. Among those who did not report depression prior to pregnancy, mothers with unwanted pregnancies were more likely to experience persistent depression, and mothers with pregnancies mistimed by two or more years had a higher likelihood of experiencing depression postpartum or in the follow up period. CONCLUSIONS: Our findings suggest that pregnancy intention is less consequential for maternal and child well-being than socio-economic disadvantage, suggesting that re-orienting policy toward social conditions and reproductive autonomy will serve better individual and population health.

Order Set Usage is Associated With Lower Hospital Mortality in Patients With Sepsis.

The Surviving Sepsis Campaign recommends standard operating procedures for patients with sepsis. Real-world evidence about sepsis order set implementation is limited. OBJECTIVES: To estimate the effect of sepsis order set usage on hospital mortality. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Fifty-four acute care hospitals in the United States from December 1, 2020 to November 30, 2022 involving 104,662 patients hospitalized for sepsis. MAIN OUTCOMES AND MEASURES: Hospital mortality. RESULTS: The sepsis order set was used in 58,091 (55.5%) patients with sepsis. Initial mean sequential organ failure assessment score was 0.3 lower in patients for whom the order set was used than in those for whom it was not used (2.9 sd [2.8] vs 3.2 [3.1], p < 0.01). In bivariate analysis, hospital mortality was 6.3% lower in patients for whom the sepsis order set was used (9.7% vs 16.0%, p < 0.01), median time from emergency department triage to antibiotics was 54 minutes less (125 interquartile range [IQR, 68-221] vs 179 [98-379], p < 0.01), and median total time hypotensive was 2.1 hours less (5.5 IQR [2.0-15.0] vs 7.6 [2.5-21.8], p < 0.01) and septic shock was 3.2% less common (22.0% vs 25.4%, p < 0.01). Order set use was associated with 1.1 fewer median days of hospitalization (4.9 [2.8-9.0] vs 6.0 [3.2-12.1], p < 0.01), and 6.6% more patients discharged to home (61.4% vs 54.8%, p < 0.01). In the multivariable model, sepsis order set use was independently associated with lower hospital mortality (odds ratio 0.70; 95% CI, 0.66-0.73). CONCLUSIONS AND RELEVANCE: In a cohort of patients hospitalized with sepsis, order set use was independently associated with lower hospital mortality. Order sets can impact large-scale quality improvement efforts.

Towards the prediction of protein interaction partners using physical docking.

Deciphering the whole network of protein interactions for a given proteome ('interactome') is the goal of many experimental and computational efforts in Systems Biology. Separately the prediction of the structure of protein complexes by docking methods is a well-established scientific area. To date, docking programs have not been used to predict interaction partners. We provide a proof of principle for such an approach. Using a set of protein complexes representing known interactors in their unbound form, we show that a standard docking program can distinguish the true interactors from a background of 922 non-redundant potential interactors. We additionally show that true interactions can be distinguished from non-likely interacting proteins within the same structural family. Our approach may be put in the context of the proposed 'funnel-energy model'; the docking algorithm may not find the native complex, but it distinguishes binding partners because of the higher probability of favourable models compared with a collection of non-binders. The potential exists to develop this proof of principle into new approaches for predicting interaction partners and reconstructing biological networks.

Declining violence and improving birth outcomes in the US: Evidence from birth certificate data.

The decline in crime that occurred in the last decade of the 20th century was one of the most important societal changes in recent US history. In this paper, we leverage the sharp decline in violence that began in the 1990s to estimate the relationship between county-level murder rates and individual-level birth outcomes for Black, Hispanic, and White mothers. Using the FBI's Uniform Crime Reporting data from 1992 to 2002 and individual-level data from more than 30,000,000 US birth certificates, we employ two-way fixed effects models with a rich set of controls to compare births to similar women in the same county who experienced different crime rates during their pregnancies. Elevated murder rates are associated with substantially higher risks of low birth weight for White mothers, low birth weight and small for gestational age among Black mothers, and small for gestational age among Hispanic mothers. Sensitivity analyses show that the existence of confounders that would invalidate these inferences is highly unlikely, suggesting that we have identified causal relationships, even if some uncertainty about the precision of our estimates remains. These findings have potential implications for prenatal and postpartum care, and they add to a growing body of evidence showing that the "Great American Crime Decline" was strongly linked to improved outcomes among groups that experienced the steepest declines in violence.

Activation of p53 enhances apoptosis and insulin resistance in a rat model of alcoholic liver disease.

BACKGROUND & AIMS: Chronic ethanol consumption in the Long-Evans (LE) rat has been associated with hepatic p53 activation, and inhibition of the insulin/PI3K/AKT signal transduction cascade due to increased expression of PTEN. We hypothesize that p53 activation and altered insulin signaling may influence the susceptibility of rats to ethanol-induced liver damage. Furthermore, p53 not only activates programmed cell death pathways and suppresses hepatocellular survival signals, but also promotes gluconeogenesis to increase systemic insulin resistance due to a novel metabolic function. METHODS: Fischer (F), Sprague-Dawley (SD) and LE rats were fed ethanol-containing or control liquid diet for 8 weeks. Histopathological and biochemical changes were assessed. RESULTS: Here, we demonstrate that chronic ethanol feeding in rats promotes p53 activation, hepatic steatosis, oxidative stress, PUMA, and PTEN expression, which contribute to hepatocellular death and diminished insulin signaling in the liver. Such changes are pronounced in the LE, less prominent in SD, and virtually absent in the F rat strain. More importantly, there is activation of Tp53-induced glycolysis and apoptosis regulator (TIGAR) in the ethanol-fed LE rat. This event generates low hepatic fructose-2,6-bisphosphate (Fru-2,6-P2) levels, reduced lactate/pyruvate ratio and may contribute to increased basal glucose turnover and high residual hepatic glucose production during euglycemic hyperinsulinemic clamp. CONCLUSIONS: p53 activation correlates with the susceptibility to ethanol-induced liver damage in different rat strains. p53 not only orchestrates apoptosis and suppresses cell survival, but by activating TIGAR and decreasing hepatic Fru-2,6-P2) levels it promotes insulin resistance and therefore, contributes to the metabolic abnormalities associated with hepatic steatosis.

IL-17 contributes to CD4-mediated graft-versus-host disease.

CD4(+) interleukin-17 (IL-17)(+) T cells (Th17 cells) have been implicated in allograft rejection of solid organs and several autoimmune diseases. However, the functional role of Th17 cells in the development of acute graft-versus-host disease (GVHD) has not been well-characterized. We detected significant numbers of alloreactive CD4(+) donor T cells expressing IL-17, IL-17F, or IL-22 in the lymphoid organs of recipients of an allogeneic bone marrow transplant. We found no differences in GVHD mortality or graft-versus-tumor (GVT) activity between wild type (WT) and IL-17(-/-) T-cell recipients. However, upon transfer of murine IL-17(-/-) CD4(+) T cells in an allogeneic BMT model, GVHD development was significantly delayed behind recipients of WT CD4(+) T cells, yet overall GVHD mortality was unaffected. Moreover, recipients of IL-17(-/-) CD4(+) T cells had significantly fewer Th1 cells during the early stages of GVHD. Furthermore, we observed a decrease in the number of IFN-gamma-secreting macrophages and granulocytes and decreased production of proinflammatory cytokines (interferon [IFN]-gamma, IL-4, and IL-6) in recipients of IL-17(-/-) CD4(+) T cells. We conclude that IL-17 is dispensable for GVHD and GVT activity by whole T cells, but contributes to the early development of CD4-mediated GVHD by promoting production of proinflammatory cytokines.

Whither weathering? The variable significance of age in Black-White low birth weight disparities.

This paper uses birth certificate data to provide novel estimates of the age-specific risk of a low birth weight birth (LBW, an infant born weighting <2500 g) for U.S.-born non-Hispanic Black and White mothers, and finds that patterns vary markedly over space and time. Notably, risk of an LBW birth for Black mothers increased much more steeply with age in 1991-94 than in 2014-17. This decline in LBW risks among older Black mothers led to a decline in the Black-White LBW gap of more than half a percentage point. Both patterns and changes were regional; while age gradients on the Black-White LBW gap were lowest in the South in 1991-94, by 2014-17 they had increased in the South and declined in the rest of the country. These descriptive data allow a new examination of hypotheses regarding the causes of age-specific racial LBW gaps. Research has found that racial disparities in a number of health outcomes, including LBW, increase with age, leading some to speculate that this increase is due to the cumulative effects of exposure to disadvantage. The large degree of variability in Black-White LBW disparities suggests that age-specific causes may also play a role. A series of counterfactual trend analyses explore the roles of two specific mechanisms, smoking and hypertension, and compares these to a more fundamental indicator of socioeconomic status: education.

Towards the Development of Digital Twins for the Bio-manufacturing Industry.

The bio-manufacturing industry, along with other process industries, now has the opportunity to be engaged in the latest industrial revolution, also known as Industry 4.0. To successfully accomplish this, a physical-to-digital-to-physical information loop should be carefully developed. One way to achieve this is, for example, through the implementation of digital twins (DTs), which are virtual copies of the processes. Therefore, in this paper, the focus is on understanding the needs and challenges faced by the bio-manufacturing industry when dealing with this digitalized paradigm. To do so, two major building blocks of a DT, data and models, are highlighted and discussed. Hence, firstly, data and their characteristics and collection strategies are examined as well as new methods and tools for data processing. Secondly, modelling approaches and their potential of being used in DTs are reviewed. Finally, we share our vision with regard to the use of DTs in the bio-manufacturing industry aiming at bringing the DT a step closer to its full potential and realization.

Academics in Absentia: An Opportunity to Rethink Conferences in the Age of Coronavirus Cancellations.

The COVID-19 pandemic has caused major disruptions to the academic medicine community, including the cancellation of most medical and health professions conferences. In this Perspective, the authors examine both the short- and longer-term implications of these cancellations, including the effects on the professional development and advancement of junior faculty and learners. While the COVID-19 pandemic is new in 2020, impediments to conference attendance and participation are not. Cost, personal responsibilities at home, and clinical duties have always restricted attendance. The authors argue that the unprecedented hardships of this pandemic present a unique opportunity to reimagine how conferences can be conducted and to rethink what it means to be part of an academic community. While there are challenges with this digital transformation of academia, there are also undeniable opportunities: online abstracts and recorded presentations enable wider viewership, virtual sessions permit wider participation and greater interactivity, and the elimination of travel facilitates more diverse expert panel participation. The authors conclude with proposals for how conference organizers and participants can expand access by leveraging available distance learning technology and other virtual tools, both during the COVID-19 pandemic and beyond.

Successful Treatment of Cannabinoid Hyperemesis Syndrome with Topical Capsaicin.

Cannabinoid hyperemesis syndrome (CHS) is a clinical entity in which marijuana users develop nausea, vomiting, and abdominal pain that improves with hot water bathing or cannabis cessation. Previous models suggest that CHS arises solely from the derangement of cannabinoid receptor type 1 signaling. However, involvement of transient receptor potential vanilloid subtype 1 (TRPV1) receptor, which is activated by marijuana, capsaicin, and heat, could fill gaps in existing models, including the enigmatic role of hot water bathing. We propose that chronic cannabis use decreases TRPV1 signaling and alters gastric motility, and we report the case of a CHS patient whose symptoms improved after topical capsaicin.

Crowning achievement: a case of dental aspiration.

Aspiration of foreign bodies during dental procedures is a rare but potentially serious complication. We present a case of a 75-year-old man who aspirated a dental crown requiring flexible bronchoscopic retrieval. We discuss the risk factors for aspiration, the radiographic features of diagnosis, and the techniques for management and retrieval.

Neuroendocrine Morbidity After Pediatric Optic Gliomas: A Longitudinal Analysis of 166 Children Over 30 Years.

CONTEXT: Fifty percent of pediatric low-grade gliomas affect the optic pathway, hypothalamus, and suprasellar areas (OP/HSGs), resulting in significant long-term neuroendocrinopathy. OBJECTIVE: This study aimed to dissect tumor- from treatment-related risk factors for OP/HSG-associated neuroendocrinopathy. DESIGN: This was a retrospective case notes analysis of 166 children with newly diagnosed OP/HSGs at our quaternary center between 1980 and 2010 by multivariate Cox, linear, and logistic regression. RESULTS: Patients were of median (range) age 4.9 (0.2-15.4) years at diagnosis and followed up for 8.3 (0.04-26.8) years. Despite high 20-year overall survival (81.0%), progression-free and endocrine event-free survival (EEFS) were 47.2 and 20.8%, respectively. EEFS declined up to 15 years post-diagnosis, with hypothalamic involvement (P < .001) being implicated more than radiotherapy (P = .008) in earlier endocrinopathy; the reverse being true of its density (radiotherapy P < .001; hypothalamic involvement P = .006). GH deficiency (GHD) was most common (40.3%), followed by central precocious puberty (CPP, 26.0%), gonadotropin (GnD; 20.4%), TSH (13.3%), and ACTH (13.3%) deficiencies. GHD increased with later treatment eras (P < .01), but replacement did not increase progression. CPP was associated with future GnD (P < .05). Posterior pituitary dysfunction (PPD; 7.2%) occurred in 57.9% after only biopsies or shunt procedures, and was associated with 6/13 deaths; 50.2% became obese. Tumor extent, surgery, and increased endocrinopathy, rather than radiotherapy, predicted visuocognitive morbidity. CONCLUSIONS: This first longitudinal OP/HSG-specific study demonstrates that hypothalamo-pituitary dysfunction evolves hierarchically over decades. Tumor location predicts its speed of onset and radiotherapy its density. GnD can evolve from previous CPP, whereas life-threatening PPD can occur after any surgery. Our data suggest that recent radiation-avoiding chemotherapeutic strategies have increased GHD without improving survival.