Community-Based Settings and Sampling Strategies: Implications for Reducing Racial Health Disparities Among Black Men, New York City, 2010–2013

Introduction Rates of screening colonoscopies, an effective method of preventing colorectal cancer, have increased in New York City over the past decade, and racial disparities in screening have declined. However, vulnerable subsets of the population may not be reached by traditional surveillance and intervention efforts to improve colorectal cancer screening rates. Methods We compared rates of screening colonoscopies among black men aged 50 or older from a citywide random-digit–dial sample and a location-based sample focused on hard-to-reach populations to evaluate the representativeness of the random-digit–dial sample. The location-based sample (N = 5,568) was recruited from 2010 through 2013 from community-based organizations in New York City. Descriptive statistics were used to compare these data with data for all black men aged 50 or older from the 2011 cohort of the Community Health Survey (weighted, N = 334) and to compare rates by community-based setting. Results Significant differences in screening colonoscopy history were observed between the location-based and random-digit–dial samples (49.1% vs 62.8%, P \u3c .001). We observed significant differences between participants with and without a working telephone among the location-based sample and between community-based settings. Conclusions Vulnerable subsets of the population such as those with inconsistent telephone access are excluded from random-digit–dial samples. Practitioners and researchers should consider the target population of proposed interventions to address disparities, and whether the type of setting reaches those most in need of services

Selective improvement of pulmonary arterial hypertension with a dual ETA/ETB receptors antagonist in the apolipoprotein E−/− model of PAH and atherosclerosis

Idiopathic pulmonary arterial hypertension (IPAH) is increasingly diagnosed in elderly patients who also have an increased risk of comorbid atherosclerosis. Apolipoprotein E deficient (ApoE-/-) mice develop atherosclerosis with severe PAH when fed a high-fat diet (HFD), and have increased levels of endothelin (ET)-1. ET-1 receptor antagonists (ERAs) are used for the treatment of PAH but less is known about whether ERAs are beneficial in atherosclerosis. We therefore examined whether treatment of HFD-ApoE-/- mice with macitentan, a dual ETA/ETB receptor antagonist, would have any effect on both atherosclerosis and PAH. ApoE-/- mice were fed chow or HFD for 8 weeks. After 4 weeks of HFD, mice were randomised to a 4-week treatment of macitentan by food (30mg/kg/day dual ETA/ETB antagonist), or placebo groups. Echocardiography and closed-chest right heart catheterisation were used to determine PAH phenotype and serum samples were collected for cytokine analysis. Thoracic aortas were harvested to assess vascular reactivity using wire myography, and histological analyses were performed on the brachiocephalic artery and aortic root to assess atherosclerotic burden. Macitentan treatment of HFD-fed ApoE-/- mice was associated with a beneficial effect on the PAH phenotype and led to an increase in endothelial-dependent relaxation in thoracic aortae. Macitentan treatment was also associated with a significant reduction in interleukin 6 (IL-6) concentration but there was no significant effect on atherosclerotic burden. Dual blockade of ETA/ETB receptors improves endothelial function and improves experimental PAH but had no significant effect on atherosclerosis

Breast may not always be best: Moderation of effects of postnatal depression by breastfeeding and infant sex

Background: There is good evidence that female infants are particularly vulnerable to poor emotional outcomes following in utero glucocorticoid exposure. It is currently unclear whether such efects might persist into the postnatal period for breastfed infants, as maternal cortisol is expressed in breastmilk and is infuenced by maternal psychological distress. We pre-registered hypotheses that maternal postnatal depression would be associated with infant negative emotionality, and that this efect would be moderated by breastfeeding status and infant sex. Methods: We analysed data from the Wirral Child Health and Development Study (WCHADS), a prospective epidemiological study starting in pregnancy. Nine weeks after birth mothers self-reported depressive symptoms and breastfeeding status, and reported infant negative emotionality using the distress to limits subscale of the infant behaviour questionnaire (IBQ-R) when their infant was aged 9 weeks and 14 months. Maximum likelihood estimations made use of data from 857 mother-infant pairs. Results: At 9 weeks of age, maternal postnatal depressive symptoms were positively associated with infant distress to limits; however, this efect was not moderated by infant sex or breastfeeding. At age 14 months, the association between postnatal depression symptoms and distress to limits was greatest in the breastfed females, whereas the association was smaller, but still signifcant, in the non-breastfed females. For males, the association was non-signifcant in both the breastfed and non-breastfed groups. A test of sex diference between breastfed males and females was signifcant. Conclusions: We provide evidence that efects of maternal postnatal depression on child emotional outcomes are moderated by breastfeeding status and difer by infant sex. Female vulnerability to elevated maternal breastmilk glucocorticoids may, at least in part, explain these efects

Sex differences in foetal origins of child emotional symptoms: a test of evolutionary hypotheses in a large, general population cohort

Background Based on previous findings from the Wirral Child Health and Development Study (WCHADS), and on evolutionary hypotheses, we preregistered analyses of data from a large epidemiological sample (https://osf.io/fn5g9/register/564d31db8c5e4a7c9694b2be), to test for sex‐dependent moderation by prenatal maternal depressive symptoms of the association between postnatal maternal depressive symptoms and child emotional problems. Methods A total of 8,354 mothers and children were followed from pregnancy to 3.5 years in the Avon Longitudinal Study of Parents and Children (ALSPAC). Self‐report measures of prenatal and postnatal maternal depressive symptoms, and maternal report of child emotional symptoms were administered. Results There was a three‐way interaction between maternal prenatal and postnatal depression, and child sex (Coeff .042 95% CI 0.015 to 0.068, p = .002). This arose from moderation by prenatal depression, in opposite directions in boys and in girls. In boys, the association between postnatal depression and child emotional symptoms was weaker following lower prenatal depressive symptoms (interaction term coeff = .030, p = .001), and in girls, to a lesser extent, the association was stronger following lower prenatal depressive symptoms (interaction term coeff = −.012, p = .221). Conclusions We replicated the finding from the WCHADS that prenatal depression modifies the association between postnatal depression and children's emotional problems in a sex‐dependent fashion. In ALSPAC, the sex difference was explained mainly by a protective effect of low prenatal depression in boys, while in WCHADS, it arose from greater vulnerability of girls to postnatal depression following low prenatal depression. In the light of these findings, in evaluating and implementing early interventions, there is need to consider that risks associated with postnatal depression may vary depending on maternal mood during pregnancy and may differ between boys and girls

Engaging Opportunities: Connecting young people with contemporary research and researchers

This is the final report for ‘Engaging Opportunities’, an RCUK-funded School-University Partnership between the Open University and the Denbigh Teaching School Alliance. Informed by action research, this four-year project was designed to create structured, strategic, sustainable and equitable mechanisms for effective school-university engagement with research. The report describes an evidence-based strategy designed to embed school-university engagement with research within the University’s strategic planning for research and the operational practices of researchers. Through the early stages of our partnership we noted a lack of suitable planning tools that work for researchers, teachers and students. We therefore introduced a flexible and adaptable framework of four types of activity—open lectures, open dialogues, open inquiry and open creativity—combined with an upstream approach to planning based on a set of six principles. A sub-set of these activities were evaluated through a combination of surveys, interviews and interventions. In conclusion, we argue that institutional and professional cultures can be resistant to the prospect of fully embedding school-university engagement with research in a structured, strategic and sustainable manner, and offer suggestions for how this context could and should be changed

Sex-dependent associations between maternal prenatal cortisol and child callous-unemotional traits: findings from the Wirral Child Health and Development Study

Elevated maternal glucocorticoids during pregnancy may impact on fetal development in a sex-dependent way, leading to increased amygdala activation and increased risk for internalising disorders in females. Based on evidence implicating reduced amygdala activation in callous-unemotional (CU) traits, we predicted that elevated maternal cortisol in pregnancy would be associated with lower CU traits and elevated anxious-depressed symptoms, only in girls. Participants were 225 members of a stratified subsample within an epidemiological longitudinal cohort (WCHADS). Salivary cortisol was measured over two days at 32 weeks gestation (on waking, 30-min post-waking and during the evening) and the log of the area under the curve (LogAUC) was calculated as an index of diurnal cortisol. Mothers reported on child CU traits and anxious-depressed symptoms at 2.5, 3.5 and 5.0 years of age. As predicted there was a sex of child by cortisol interaction (p < .001) whereby elevated maternal cortisol was associated with lower child CU traits, explaining 25% of the variance, in girls, but not in boys. This effect remained when controlling for relevant confounders and anxious-depressed symptoms. By contrast, elevated maternal cortisol did not predict higher anxious-depressed symptoms in girls. The study adds to growing evidence for sex-dependent effects of elevated maternal cortisol during pregnancy on early child psychopathology, consistent with mediation by elevated amygdala activation. The conditions under which, in girls, this is associated with heightened responsiveness to others' distress characteristic of low CU traits, or with increased affective symptoms, require further study

Maternal prenatal cortisol predicts infant negative emotionality in a sex-dependent manner

Objective Prenatal stress influences fetal developmental trajectories, which may implicate glucocorticoid mechanisms. There is also emerging evidence that effects of prenatal stress on offspring development are sex-dependent. However, little is known about the prospective relationship between maternal prenatal cortisol levels and infant behaviour, and whether it may be different in male and female infants. We sought to address this question using data from a prospective longitudinal cohort, stratified by risk. Method The Wirral Child Health and Development Study (WCHADS) cohort (n = 1233) included a stratified random sub-sample (n = 216) who provided maternal saliva samples, assayed for cortisol, at home over two days at 32 weeks of pregnancy (on waking, 30-min post-waking and during the evening) and a measure of infant negative emotionality from the Neonatal Behavioural Assessment Scale (NBAS) at five weeks-of-age. General population estimates of associations among measures were obtained using inverse probability weights. Results Maternal prenatal cortisol sampled on waking predicted infant negative emotionality in a sex-dependent manner (interaction term, p = 0.005); female infants exposed to high levels of prenatal cortisol were more negative (Beta = 0.440, p = 0.042), whereas male infants were less negative (Beta = − 0.407, p = 0.045). There was no effect of the 30-min post-waking measure or evening cortisol. Discussion Our findings add to an emerging body of work that has highlighted sex differences in fetal programming, whereby females become more reactive following prenatal stress, and males less reactive. A more complete understanding of sex-specific developmental trajectories in the context of prenatal stress is essential for the development of targeted prevention strategies

Sentinel Node Identification Rate and Nodal Involvement in the EORTC 10981-22023 AMAROS Trial

Background The randomized EORTC 10981-22023 AMAROS trial investigates whether breast cancer patients with a tumor-positive sentinel node biopsy (SNB) are best treated with an axillary lymph node dissection (ALND) or axillary radiotherapy (ART). The aim of the current substudy was to evaluate the identification rate and the nodal involvement. Methods The first 2,000 patients participating in the AMAROS trial were evaluated. Associations between the identification rate and technical, patient-, and tumor-related factors were evaluated. The outcome of the SNB procedure and potential further nodal involvement was assessed. Results In 65 patients, the sentinel node could not be identified. As a result, the sentinel node identification rate was 97% (1,888 of 1,953). Variables affecting the success rate were age, pathological tumor size, histology, year of accrual, and method of detection. The SNB results of 65% of the patients (n = 1,220) were negative and the patients underwent no further axillary treatment. The SNB results were positive in 34% of the patients (n = 647), including macrometastases (n = 409, 63%), micrometastases (n = 161, 25%), and isolated tumor cells (n = 77, 12%). Further nodal involvement in patients with macrometastases, micrometastases, and isolated tumor cells undergoing an ALND was 41, 18, and 18%, respectively. Conclusions With a 97% detection rate in this prospective international multicenter study, the SNB procedure is highly effective, especially when the combined method is used. Further nodal involvement in patients with micrometastases and isolated tumor cells in the sentinel node was similar—both were 18%