Social Determinants of Premature Birth.

Social determinants of health have received increasing attention in public health, leading to increased understanding of how social factors-individual and contextual-shape the health of the mother and infant. However, racial differences in birth outcomes persist, with incomplete explanation for the widening disparity. Here, we highlight the social determinants of preterm birth, with special attention to the social experiences among African American women, which are likely attributed to structural racism and discrimination throughout life.

Lifetime Upward Economic Mobility and US-Born Latina Women's Preterm Birth Rates.

OBJECTIVES: To determine whether Latina women's upward economic mobility from early-life residence in impoverished urban neighborhoods is associated with preterm birth (< 37 weeks, PTB) . METHODS: Multivariate logistic regression analyses were performed on the Illinois transgenerational birth-file with appended US census income information for Hispanic infants (born 1989-1991) and their mothers (born 1956-1976). RESULTS: In Chicago, modestly impoverished-born Latina women (n = 1,674) who experienced upward economic mobility had a PTB rate of 8.5% versus 13.1% for those (n = 3,760) with a lifelong residence in modestly impoverished neighborhoods; the unadjusted and adjusted (controlling for age, marital status, adequacy of prenatal care, and cigarette smoking) RR equaled 0.65 (0.47, 0.90) and 0.66 (0.47, 0.93), respectively. Extremely impoverished-born Latina women (n = 2,507) who experienced upward economic mobility across their life-course had a PTB rate of 12.7% versus 15.9% for those (n = 3,849) who had a lifelong residence in extremely impoverished neighborhoods, the unadjusted and adjusted RR equaled 0.8 (0.63. 1.01) and 0.95 (0.75, 1.22), respectively. CONCLUSIONS FOR PRACTICE: Latina women's upward economic mobility from early-life residence in modestly impoverished urban neighborhoods is associated with a decreased risk of PTB. A similar trend is absent among their peers with an early-life residence in extremely impoverished areas.

Fetal Origins of Health Disparities: Transgenerational Consequences of Racism.

Despite advances in perinatal medicine, racial disparity in birth outcomes remains a public health problem in the USA. The underlying mechanisms for this long-standing racial disparity are incompletely understood. This review presents transgenerational risk factors for racial disparities in preterm birth, exploring the impact of interpersonal and structural racism, theoretical models of stress, and biological markers of racial disparities.

Women's Economic Mobility and Small for Gestational Age Rates: The Effect of Paternal Early-Life Socioeconomic Position.

OBJECTIVE: To determine whether paternal early-life socioeconomic position (defined by neighborhood income) modifies the association of maternal economic mobility and infant small for gestational age (weight for gestational age < 10th percentile, SGA) rates. METHODS: Stratified and multilevel binomial regression analyses were executed on the Illinois transgenerational dataset of parents (born 1956-1976) and their infants (born 1989-1991) with appended U.S. census income information. Only Chicago-born women with an early-life residence in impoverished or affluent neighborhoods were studied. RESULTS: The incidence of impoverished-born women's upward economic mobility among births (n = 3777) with early-life low socioeconomic position (SEP) fathers was less than that of those (n = 576) with early-life high SEP fathers: 56% vs 71%, respectively, p < 0.01. The incidence of affluent-born women's downward economic mobility among births (n = 2370) with early-life low SEP fathers exceeded that of those (n = 3822) with early-life high SEP fathers: 79% vs 66%, respectively, p < 0.01. The adjusted RR of infant SGA for maternal upward (compared to lifelong impoverishment) economic mobility among fathers with early-life low and high SEP equaled 0.68 (0.56, 0.82) and 0.81 (0.47, 1.42), respectively. The adjusted RR of infant SGA for maternal downward (compared to lifelong residence in affluent neighborhoods) economic mobility among fathers with early-life low and high SEP were 1.37 (0.91, 2.05) and 1.17 (0.86, 1.59), respectively. CONCLUSIONS: Paternal early-life SEP is associated with maternal economic mobility (both upward and downward); however, it does not modify the relationship between maternal economic mobility and infant SGA rates.

Assessing COVID-19 pandemic policies and behaviours and their economic and educational trade-offs across US states from Jan 1, 2020, to July 31, 2022: an observational analysis.

BACKGROUND: The USA struggled in responding to the COVID-19 pandemic, but not all states struggled equally. Identifying the factors associated with cross-state variation in infection and mortality rates could help to improve responses to this and future pandemics. We sought to answer five key policy-relevant questions regarding the following: 1) what roles social, economic, and racial inequities had in interstate variation in COVID-19 outcomes; 2) whether states with greater health-care and public health capacity had better outcomes; 3) how politics influenced the results; 4) whether states that imposed more policy mandates and sustained them longer had better outcomes; and 5) whether there were trade-offs between a state having fewer cumulative SARS-CoV-2 infections and total COVID-19 deaths and its economic and educational outcomes. METHODS: Data disaggregated by US state were extracted from public databases, including COVID-19 infection and mortality estimates from the Institute for Health Metrics and Evaluation's (IHME) COVID-19 database; Bureau of Economic Analysis data on state gross domestic product (GDP); Federal Reserve economic data on employment rates; National Center for Education Statistics data on student standardised test scores; and US Census Bureau data on race and ethnicity by state. We standardised infection rates for population density and death rates for age and the prevalence of major comorbidities to facilitate comparison of states' successes in mitigating the effects of COVID-19. We regressed these health outcomes on prepandemic state characteristics (such as educational attainment and health spending per capita), policies adopted by states during the pandemic (such as mask mandates and business closures), and population-level behavioural responses (such as vaccine coverage and mobility). We explored potential mechanisms connecting state-level factors to individual-level behaviours using linear regression. We quantified reductions in state GDP, employment, and student test scores during the pandemic to identify policy and behavioural responses associated with these outcomes and to assess trade-offs between these outcomes and COVID-19 outcomes. Significance was defined as p<0·05. FINDINGS: Standardised cumulative COVID-19 death rates for the period from Jan 1, 2020, to July 31, 2022 varied across the USA (national rate 372 deaths per 100 000 population [95% uncertainty interval [UI] 364-379]), with the lowest standardised rates in Hawaii (147 deaths per 100 000 [127-196]) and New Hampshire (215 per 100 000 [183-271]) and the highest in Arizona (581 per 100 000 [509-672]) and Washington, DC (526 per 100 000 [425-631]). A lower poverty rate, higher mean number of years of education, and a greater proportion of people expressing interpersonal trust were statistically associated with lower infection and death rates, and states where larger percentages of the population identify as Black (non-Hispanic) or Hispanic were associated with higher cumulative death rates. Access to quality health care (measured by the IHME's Healthcare Access and Quality Index) was associated with fewer total COVID-19 deaths and SARS-CoV-2 infections, but higher public health spending and more public health personnel per capita were not, at the state level. The political affiliation of the state governor was not associated with lower SARS-CoV-2 infection or COVID-19 death rates, but worse COVID-19 outcomes were associated with the proportion of a state's voters who voted for the 2020 Republican presidential candidate. State governments' uses of protective mandates were associated with lower infection rates, as were mask use, lower mobility, and higher vaccination rate, while vaccination rates were associated with lower death rates. State GDP and student reading test scores were not associated with state COVD-19 policy responses, infection rates, or death rates. Employment, however, had a statistically significant relationship with restaurant closures and greater infections and deaths: on average, 1574 (95% UI 884-7107) additional infections per 10 000 population were associated in states with a one percentage point increase in employment rate. Several policy mandates and protective behaviours were associated with lower fourth-grade mathematics test scores, but our study results did not find a link to state-level estimates of school closures. INTERPRETATION: COVID-19 magnified the polarisation and persistent social, economic, and racial inequities that already existed across US society, but the next pandemic threat need not do the same. US states that mitigated those structural inequalities, deployed science-based interventions such as vaccination and targeted vaccine mandates, and promoted their adoption across society were able to match the best-performing nations in minimising COVID-19 death rates. These findings could contribute to the design and targeting of clinical and policy interventions to facilitate better health outcomes in future crises. FUNDING: Bill & Melinda Gates Foundation, J Stanton, T Gillespie, J and E Nordstrom, and Bloomberg Philanthropies.

Cost-effectiveness of Vitamin A supplementation among children in three sub-Saharan African countries: An individual-based simulation model using estimates from Global Burden of Disease 2019.

BACKGROUND: Vitamin A Supplementation (VAS) is a cost-effective intervention to decrease mortality associated with measles and diarrheal diseases among children aged 6-59 months in low-income countries. Recently, experts have suggested that other interventions like large-scale food fortification and increasing the coverage of measles vaccination might provide greater impact than VAS. In this study, we conducted a cost-effectiveness analysis of a VAS scale-up in three sub-Saharan African countries. METHODS: We developed an individual-based microsimulation using the Vivarium simulation framework to estimate the cost and effect of scaling up VAS from 2019 to 2023 in Nigeria, Kenya, and Burkina Faso, three countries with different levels of baseline coverage. We calibrated the model with disease and risk factor estimates from the Global Burden of Disease 2019 (GBD 2019). We obtained baseline coverage, intervention effects, and costs from a systematic review. After the model was validated against GBD inputs, we modeled an alternative scenario where we scaled-up VAS coverage from 2019 to a level that halved the exposure to lack of VAS in 2023. Based on the simulation outputs for DALYs averted and intervention cost, we determined estimates for the incremental cost-effectiveness ratio (ICER) in USD/DALY. FINDINGS: Our estimates for ICER are as follows: $860/DALY [95% UI; 320, 3530] in Nigeria, $550/DALY [240, 2230] in Kenya, and $220/DALY [80, 2470] in Burkina Faso. Examining the data for DALYs averted for the three countries over the time span, we found that the scale-up led to 21 [5, 56] DALYs averted per 100,000 person-years in Nigeria, 21 [5, 47] DALYs averted per 100,000 person-years in Kenya, and 14 [0, 37] DALYs averted per 100,000 person-years in Burkina Faso. CONCLUSIONS: VAS may no longer be as cost-effective in low-income regions as it has been previously. Updated estimates in GBD 2019 for the effect of Vitamin A Deficiency on causes of death are an additional driver of this lower estimate of cost-effectiveness.

Quantifying the effects of the COVID-19 pandemic on gender equality on health, social, and economic indicators: a comprehensive review of data from March, 2020, to September, 2021.

BACKGROUND: Gender is emerging as a significant factor in the social, economic, and health effects of COVID-19. However, most existing studies have focused on its direct impact on health. Here, we aimed to explore the indirect effects of COVID-19 on gender disparities globally. METHODS: We reviewed publicly available datasets with information on indicators related to vaccine hesitancy and uptake, health care services, economic and work-related concerns, education, and safety at home and in the community. We used mixed effects regression, Gaussian process regression, and bootstrapping to synthesise all data sources. We accounted for uncertainty in the underlying data and modelling process. We then used mixed effects logistic regression to explore gender gaps globally and by region. FINDINGS: Between March, 2020, and September, 2021, women were more likely to report employment loss (26·0% [95% uncertainty interval 23·8-28·8, by September, 2021) than men (20·4% [18·2-22·9], by September, 2021), as well as forgoing work to care for others (ratio of women to men: 1·8 by March, 2020, and 2·4 by September, 2021). Women and girls were 1·21 times (1·20-1·21) more likely than men and boys to report dropping out of school for reasons other than school closures. Women were also 1·23 (1·22-1·23) times more likely than men to report that gender-based violence had increased during the pandemic. By September 2021, women and men did not differ significantly in vaccine hesitancy or uptake. INTERPRETATION: The most significant gender gaps identified in our study show intensified levels of pre-existing widespread inequalities between women and men during the COVID-19 pandemic. Political and social leaders should prioritise policies that enable and encourage women to participate in the labour force and continue their education, thereby equipping and enabling them with greater ability to overcome the barriers they face. FUNDING: The Bill & Melinda Gates Foundation.

Rapid, Efficient, and Cost-Effective Gene Editing of Enterococcus faecium with CRISPR-Cas12a.

Considered a serious threat by the Centers for Disease Control and Prevention, multidrug-resistant Enterococcus faecium is an increasing cause of hospital-acquired infection. Here, we provide details on a single-plasmid CRISPR-Cas12a system for generating clean deletions and insertions. Single manipulations were carried out in under 2 weeks, with successful deletions/insertions present in >80% of the clones tested. Using this method, we generated three individual clean deletion mutations in the acpH, treA, and lacL genes and inserted codon-optimized unaG, enabling green fluorescent protein (GFP)-like fluorescence under the control of the trehalase operon. The use of in vivo recombination for plasmid construction kept costs to a minimum. IMPORTANCE Enterococcus faecium is increasingly associated with hard-to-treat antibiotic-resistant infections. The ability to generate clean genomic alterations is the first step in generating a complete mechanistic understanding of how E. faecium acquires pathogenic traits and causes disease. Here, we show that CRISPR-Cas12a can be used to quickly (under 2 weeks) and cheaply delete or insert genes into the E. faecium genome. This substantial improvement over current methods should speed up research on this important opportunistic pathogen.

Cost-effectiveness of antenatal multiple micronutrients and balanced energy protein supplementation compared to iron and folic acid supplementation in India, Pakistan, Mali, and Tanzania: A dynamic microsimulation study.

BACKGROUND: Malnutrition among women of childbearing age is especially prevalent in Asia and sub-Saharan Africa and can be harmful to the fetus during pregnancy. In the most recently available Demographic and Health Survey (DHS), approximately 10% to 20% of pregnant women in India, Pakistan, Mali, and Tanzania were undernourished (body mass index [BMI] <18.5 kg/m2), and according to the Global Burden of Disease (GBD) 2017 study, approximately 20% of babies were born with low birth weight (LBW; <2,500 g) in India, Pakistan, and Mali and 8% in Tanzania. Supplementing pregnant women with micro and macronutrients during the antenatal period can improve birth outcomes. Recently, the World Health Organization (WHO) recommended antenatal multiple micronutrient supplementation (MMS) that includes iron and folic acid (IFA) in the context of rigorous research. Additionally, WHO recommends balanced energy protein (BEP) for undernourished populations. However, few studies have compared the cost-effectiveness of different supplementation regimens. We compared the cost-effectiveness of MMS and BEP with IFA to quantify their benefits in 4 countries with considerable prevalence of maternal undernutrition. METHODS AND FINDINGS: Using nationally representative estimates from the 2017 GBD study, we conducted an individual-based dynamic microsimulation of population cohorts from birth to 2 years of age in India, Pakistan, Mali, and Tanzania. We modeled the effect of maternal nutritional supplementation on infant birth weight, stunting and wasting using effect sizes from Cochrane systematic reviews and published literature. We used a payer's perspective and obtained costs of supplementation per pregnancy from the published literature. We compared disability-adjusted life years (DALYs) and incremental cost-effectiveness ratios (ICERs) in a baseline scenario with existing antenatal IFA coverage with scenarios where 90% of antenatal care (ANC) attendees receive either universal MMS, universal BEP, or MMS + targeted BEP (women with prepregnancy BMI <18.5 kg/m2 receive BEP containing MMS while women with BMI ≥18.5 kg/m2 receive MMS). We obtained 95% uncertainty intervals (UIs) for all outputs to represent parameter and stochastic uncertainty across 100 iterations of model runs. ICERs for all scenarios were lowest in Pakistan and greatest in Tanzania, in line with the baseline trend in prevalence of and attributable burden to LBW. MMS + targeted BEP averts more DALYs than universal MMS alone while remaining cost-effective. ICERs for universal MMS compared to baseline IFA were $52 (95% UI: $28 to $78) for Pakistan, $72 (95% UI: $37 to $118) for Mali, $70 (95% UI: $43 to $104) for India, and $253 (95% UI: $112 to $481) for Tanzania. ICERs for MMS + targeted BEP compared to baseline IFA were $54 (95% UI: $32 to $77) for Pakistan, $73 (95% UI: $40 to $104) for Mali, $83 (95% UI: $58 to $111) for India, and $245 (95% UI: $127 to $405) for Tanzania. Study limitations include generalizing experimental findings from the literature to our populations of interest and using population-level input parameters that may not reflect the heterogeneity of subpopulations. Additionally, our microsimulation fuses multiple sources of data and may be limited by data quality and availability. CONCLUSIONS: In this study, we observed that MMS + targeted BEP averts more DALYs and remains cost-effective compared to universal MMS. As countries consider using MMS in alignment with recent WHO guidelines, offering targeted BEP is a cost-effective strategy that can be considered concurrently to maximize benefits and synergize program implementation.

Impact of fenbendazole resistance in Ascaridia dissimilis on the economics of production in turkeys.

Feed conversion efficiency is among the most important factors affecting profitable production of poultry.Infections with parasitic nematodes can decrease efficiency of production, making parasite control through the use of anthelmintics an important component of health management. In ruminants and horses, anthelmintic resistance is highly prevalent in many of the most important nematode species, which greatly impacts their control. Recently, we identified resistance to fenbendazole in an isolate of Ascaridia dissimilis, the most common intestinal helminth of turkeys. Using this drug-resistant isolate, we investigated the impact that failure to control infections has on weight gain and feed conversion in growing turkeys. Birds were infected on D 0 with either a fenbendazole-susceptible or -resistant isolate, and then half were treated with fenbendazole (SafeGuard Aquasol) at 4- and 8-wk postinfection. Feed intake and bird weight were measured for each pen weekly throughout the study, and feed conversion rate was calculated. Necropsy was performed on birds from each treatment group to assess worm burdens at wk 7 and 9 postinfection. In the birds infected with the susceptible isolate, fenbendazole-treated groups had significantly better feed conversion as compared to untreated groups. In contrast, there were no significant differences in feed conversion between the fenbendazole-treated and untreated groups in the birds infected with the resistant isolate. At both wk 7 and 9, worm burdens were significantly different between the treated and untreated birds infected with the drug-susceptible isolate, but not in the birds infected with the drug-resistant isolate. These significant effects on feed conversion were seen despite having a rather low worm establishment in the birds. Overall, these data indicate that A. dissimilis can produce significant reductions in feed conversion, and that failure of treatment due to the presence of fenbendazole-resistant worms can have a significant economic impact on turkey production. Furthermore, given the low worm burdens and an abbreviated grow out period of this study, the levels of production loss we measured may be an underestimate of the true impact that fenbendazole-resistant worms may have on a commercial operation.

CRISPR-based diagnostics.

The accurate and timely diagnosis of disease is a prerequisite for efficient therapeutic intervention and epidemiological surveillance. Diagnostics based on the detection of nucleic acids are among the most sensitive and specific, yet most such assays require costly equipment and trained personnel. Recent developments in diagnostic technologies, in particular those leveraging clustered regularly interspaced short palindromic repeats (CRISPR), aim to enable accurate testing at home, at the point of care and in the field. In this Review, we provide a rundown of the rapidly expanding toolbox for CRISPR-based diagnostics, in particular the various assays, preamplification strategies and readouts, and highlight their main applications in the sensing of a wide range of molecular targets relevant to human health.

Using deep learning for dermatologist-level detection of suspicious pigmented skin lesions from wide-field images.

A reported 96,480 people were diagnosed with melanoma in the United States in 2019, leading to 7230 reported deaths. Early-stage identification of suspicious pigmented lesions (SPLs) in primary care settings can lead to improved melanoma prognosis and a possible 20-fold reduction in treatment cost. Despite this clinical and economic value, efficient tools for SPL detection are mostly absent. To bridge this gap, we developed an SPL analysis system for wide-field images using deep convolutional neural networks (DCNNs) and applied it to a 38,283 dermatological dataset collected from 133 patients and publicly available images. These images were obtained from a variety of consumer-grade cameras (15,244 nondermoscopy) and classified by three board-certified dermatologists. Our system achieved more than 90.3% sensitivity (95% confidence interval, 90 to 90.6) and 89.9% specificity (89.6 to 90.2%) in distinguishing SPLs from nonsuspicious lesions, skin, and complex backgrounds, avoiding the need for cumbersome individual lesion imaging. We also present a new method to extract intrapatient lesion saliency (ugly duckling criteria) on the basis of DCNN features from detected lesions. This saliency ranking was validated against three board-certified dermatologists using a set of 135 individual wide-field images from 68 dermatological patients not included in the DCNN training set, exhibiting 82.96% (67.88 to 88.26%) agreement with at least one of the top three lesions in the dermatological consensus ranking. This method could allow for rapid and accurate assessments of pigmented lesion suspiciousness within a primary care visit and could enable improved patient triaging, utilization of resources, and earlier treatment of melanoma.

Explaining the Black-White Disparity in Preterm Birth: A Consensus Statement From a Multi-Disciplinary Scientific Work Group Convened by the March of Dimes.

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.

Why does racial inequity in health persist?

Attempts over decades have failed to eliminate the glaring inequity in birth outcomes between Americans of different races. We propose broadening the approach to dealing with racial health inequity by considering the interplay of race and class in the politics of the United States. This approach, combined with a grasp of the historical roots of race relations in North America, could hold the promise of improving our country's abysmal showing in international comparisons of population health indicators, including birth outcomes.

Online biology degree program broadens access for women, first-generation to college, and low-income students, but grade disparities remain.

Online education has grown rapidly in recent years with many universities now offering fully online degree programs even in STEM disciplines. These programs have the potential to broaden access to STEM degrees for people with social identities currently underrepresented in STEM. Here, we ask to what extent is that potential realized in terms of student enrollment and grades for a fully online degree program. Our analysis of data from more than 10,000 course-enrollments compares student demographics and course grades in a fully online biology degree program to demographics and grades in an equivalent in-person biology degree program at the same university. We find that women, first-generation to college students and students eligible for federal Pell grants constitute a larger proportion of students in the online program compared to the in-person mode. However, the online mode of instruction is associated with lower course grades relative to the in-person mode. Moreover, African American/Black, Hispanic/Latinx, Native American, and Pacific Islander students as well as federal Pell grant eligible students earned lower grades than white students and non-Pell grant eligible students, respectively, but the grade disparities were similar among both in-person and online student groups. Finally, we find that grade disparities between men and women are larger online compared to in-person, but that for first-generation to college women, the online mode of instruction is associated with little to no grade gap compared to continuing generation women. Our findings indicate that although this online degree program broadens access for some student populations, inequities in the experience remain and need to be addressed in order for online education to achieve its inclusive mission.

Proportional multistate lifetable modelling of preventive interventions: concepts, code and worked examples.

Burden of Disease studies-such as the Global Burden of Disease (GBD) Study-quantify health loss in disability-adjusted life-years. However, these studies stop short of quantifying the future impact of interventions that shift risk factor distributions, allowing for trends and time lags. This methodology paper explains how proportional multistate lifetable (PMSLT) modelling quantifies intervention impacts, using comparisons between three tobacco control case studies [eradication of tobacco, tobacco-free generation i.e. the age at which tobacco can be legally purchased is lifted by 1 year of age for each calendar year) and tobacco tax]. We also illustrate the importance of epidemiological specification of business-as-usual in the comparator arm that the intervention acts on, by demonstrating variations in simulated health gains when incorrectly: (i) assuming no decreasing trend in tobacco prevalence; and (ii) not including time lags from quitting tobacco to changing disease incidence. In conjunction with increasing availability of baseline and forecast demographic and epidemiological data, PMSLT modelling is well suited to future multiple country comparisons to better inform national, regional and global prioritization of preventive interventions. To facilitate use of PMSLT, we introduce a Python-based modelling framework and associated tools that facilitate the construction, calibration and analysis of PMSLT models.

Assessment of faithful interleukin-3 production by novel bicistronic interleukin-3 reporter mice.

Interleukin-3 (IL-3) is an important hematopoietic growth factor and immunregulatory cytokine. Although activated T helper cells represent a main source of IL-3, other cell types have been reported to express this cytokine. However, precise identification and quantification of the cells that produce IL-3 in vivo have not been performed. Therefore, we used a CRISPR/Cas approach to engineer mice containing a bicistronic mRNA linking a readily identifiable reporter, enhanced green fluorescent protein (ZsGreen1), to IL-3 expression. To characterize these novel reporter mice, we first examined ZsGreen1 expression by CD4 T cells subsets primed and activated in vitro. We found that activated Th1 cells expressed ∼4-fold higher levels of ZsGreen1 as compared to Th0 and Th2 cells. Endogenous IL-3 expression remained intact although reporter Th1 cells secreted ∼33 % less IL-3 than similarly activated wild-type cells. To characterize the ability of reporter mice to accurately mark IL-3-producing cells in vivo, we infected mice with Nippostrongylus brasiliensis. Low but significant numbers of ZsGreen1+ CD4 T cells were detected in the mesenteric lymph nodes and lung following both primary and secondary infection. No difference in basophil and intestinal mast cell numbers were observed between infected reporter and wild-type mice indicating that reporter mice secreted IL-3 levels in vivo that results in IL-3-driven biological activities which are indistinguishable from those observed in corresponding wild-type mice. These IL-3 reporter mice will be a valuable resource to investigate IL-3-dependent immune responses in vivo.

Excess Early (< 34 weeks) Preterm Rates Among Non-acknowledged and Acknowledged Low Socioeconomic Position Fathers: The Role of Women's Selected Pregnancy-Related Risk Factors.

OBJECTIVE: To determine the proportion of the excess early preterm birth (< 34 weeks, PTB) rates among non-acknowledged and acknowledged low socioeconomic position (SEP) fathers attributable to White and African-American women's selected pregnancy-related risk factors for PTB. METHODS: Oaxaca-Blinder decomposition methods were performed on the Illinois transgenerational birth-file of infants (1989-1991) and their parents (1956-1976) with appended U.S. census income information. The neighborhood income of father's place of residence at the time of his birth and at the time of his infant's birth were used to measure lifetime SEP. RESULTS: Among non-Latina White women, the early PTB rate for non-acknowledged (n = 3260), acknowledged low SEP (n = 1430), and acknowledged high SEP (n = 9141) fathers equaled 4.02%, 1.82%, and 1.19, respectively; p < 0.001. White women's selected pregnancy-related risk factors for PTB (inadequate prenatal usage, suboptimal weight gain, and/or cigarette smoking) were responsible for 19.3% and 41.2% of the explained disparities in early PTB rates for non-acknowledged and acknowledged low (compared to acknowledged high) SEP fathers, respectively. Among African-American women, the early PTB rate for non-acknowledged (n = 22,727), acknowledged low SEP (n = 4426), and acknowledged high SEP (n = 365) fathers equaled 6.72%, 4.34%, and 3.29%, respectively; p < 0.001. African-American women's selected pregnancy-related risk factors for PTB were responsible for 21.4% and 20.2% of the explained disparities in early PTB rates for non-acknowledged and acknowledged low SEP fathers, respectively. CONCLUSIONS: Non-Latina White and African-American women's selected pregnancy-related risk factors for PTB explain a significant percentage of excess early PTB rates among non-acknowledged and acknowledged low (compared to acknowledged high) SEP fathers.

The promise and pitfalls of precision medicine to resolve black-white racial disparities in preterm birth.

Differences in preterm birth rates between black and white women are the largest contributor to racial disparities in infant mortality. In today's age of precision medicine, analysis of the genome, epigenome, metabolome, and microbiome has generated interest in determining whether these biomarkers can help explain racial disparities. We propose that there are pitfalls as well as opportunities when using precision medicine analyses to interrogate disparities in health. To conclude that racial disparities in complex conditions are genetic in origin ignores robust evidence that social and environmental factors that track with race are major contributors to disparities. Biomarkers measured in omic assays that may be more environmentally responsive than genomics, such as the epigenome or metabolome, may be on the causal pathway of race and preterm birth, but omic observational studies suffer from the same limitations as traditional cohort studies. Confounding can lead to false conclusions about the causal relationship between omics and preterm birth. Methodological strategies (including stratification and causal mediation analyses) may help to ensure that associations between biomarkers and exposures, as well as between biomarkers and outcomes, are valid signals. These epidemiologic strategies present opportunities to assess whether precision medicine biomarkers can uncover biology underlying perinatal health disparities.

Early and Late Preterm Birth Rates Among US-Born Urban Women: The Effect of Men's Lifelong Class Status.

OBJECTIVE: To ascertain the relation of men's lifelong class status (as measured by neighborhood income) to the rates of early (< 34 weeks) and late (34-36 weeks) preterm birth (PTB). METHODS: Stratified and multilevel, multivariable binomial regression analyses were computed on the Illinois transgenerational birth-file of infants (born 1989-1991) and their parents (born 1956-1976) with appended U.S. census income information. The median family income of men's census tract residence at two-time periods were utilized to assess lifelong class status (defined by residence in either the lower or upper half of neighborhood income distribution). RESULTS: In Cook County Illinois, the preterm rate for births (n = 8115) to men with a lifelong lower class status was twice that of births (n = 10,330) to men with a lifelong upper class status: 13% versus 6.0%, RR = 2.2 (2.0, 2.4). This differential was greatest in early PTB rates: 3.9% versus 1.4%, RR = 3.0 (2.5, 3.7). The relation of men's lifelong class status to both PTB components persisted among non-teens, married, college-educated, and non-Latina White women, respectively. The adjusted (controlling for maternal demographic characteristics) RR of early and late PTB for men with a lifelong lower (versus upper) class status were 1.4 (1.1, 1.9) and 1.2 (1.0, 1.4), respectively. The population attributable risk of early PTB for men's lifelong lower class status equaled 16%. CONCLUSIONS: Men's lifelong lower (versus upper) class status is a novel risk factor for early preterm birth regardless of maternal demographic characteristics. This intriguing finding has public health relevance.