Evaluating implementation of LEAPS, a youth-led early childhood care and education intervention in rural Pakistan: protocol for a stepped wedge cluster-randomized trial.

BACKGROUND: The Sustainable Development Goals (SDGs) highlight the importance of investments in early childhood care and education (ECCE) and youth development. Given Pakistan's large young population, and gender and urban-rural inequalities in access to education, training, and employment, such investments offer opportunities. LEAPS is a youth-led ECCE program that trains female youth, 18-24 years, as Community Youth Leaders (CYLs) to deliver high-quality ECCE for children, 3.5-5.5 years, in rural Sindh, Pakistan. METHODS: We use a stepped wedge cluster-randomized trial to evaluate implementation of LEAPS. Ninety-nine clusters will be randomized to receive the intervention in one of three 7-month steps (33 clusters/step). The primary outcome is children's school readiness (indexed by the total score on the International Development and Early Learning Assessment (IDELA)). Secondary child outcomes are children's IDELA domain scores and executive functions. Data are collected in cross-sectional surveys of 1089 children (11 children/cluster from 99 clusters) aged 4.5-5.5 years at four timepoints (baseline and at the end of each step). Additionally, we will enroll three non-randomized youth participant open cohorts, one per step (33 CYLs: 66 comparison youth per cohort; 99:198 in total). Youth cohorts will be assessed at enrollment and every 7 months thereafter to measure secondary outcomes of youth personal and professional development, depressive symptoms, and executive functions. A non-randomized school cohort of 330 LEAPS students (10 students/cluster from 33 clusters) will also be enrolled and assessed during Step 1 after intervention rollout and at endline. The quality of the learning environment will be assessed in each LEAPS ECCE center and in a comparison center at two timepoints midway following rollout and at endline. A concurrent mixed-methods implementation evaluation will assess program fidelity and quality, and the extent to which a technical support strategy is successful in strengthening systems for program expansion. A cost evaluation will assess cost per beneficiary. Data collection for implementation and cost evaluations will occur in Step 3. DISCUSSION: Youth-led models for ECCE offer a promising approach to support young children and youth. This study will contribute to the evidence as a means to promote sustainable human development across multiple SDG targets. TRIAL REGISTRATION: ClinicalTrials.gov NCT03764436 . Registered on December 5, 2018.

Manifesto for new directions in developmental science.

Although developmental science has always been evolving, these times of fast-paced and profound social and scientific changes easily lead to disorienting fragmentation rather than coherent scientific advances. What directions should developmental science pursue to meaningfully address real-world problems that impact human development throughout the lifespan? What conceptual or policy shifts are needed to steer the field in these directions? The present manifesto is proposed by a group of scholars from various disciplines and perspectives within developmental science to spark conversations and action plans in response to these questions. After highlighting four critical content domains that merit concentrated and often urgent research efforts, two issues regarding "how" we do developmental science and "what for" are outlined. This manifesto concludes with five proposals, calling for integrative, inclusive, transdisciplinary, transparent, and actionable developmental science. Specific recommendations, prospects, pitfalls, and challenges to reach this goal are discussed.

Effects of the Mother-Child Education Program on Parenting Stress and Disciplinary Practices Among Refugee and Other Marginalized Communities in Lebanon: A Pilot Randomized Controlled Trial.

OBJECTIVE: Few randomized controlled trials (RCTs) have explored the implementation and impact of early childhood parenting education programs in very fragile contexts and humanitarian settings. We tested the effects of a group-based intervention, the Mother-Child Education Program (MOCEP), on parenting stress and practices among two refugee communities and one other marginalized community in Beirut, Lebanon. METHOD: A pilot wait-list RCT was conducted to assess the program's impact on maternal, child (average age: 4 years), and dyadic outcomes. A total of 106 mother-child dyads were randomly assigned to either the intervention group (n = 53) or the wait-list control group (n = 53). Analysis was conducted by modified intention-to-treat and supplemental analyses through multiple imputation of missing post-intervention data. RESULTS: Forty families (38%) withdrew early from the study. After completing the program, mothers in the intervention group showed a reduction in their harsh parenting practices, as indexed by the Disciplinary Style Questionnaire (Cohen's d = -0.76, 95% CI = -1.24, -0.27) and in their level of parenting stress, as indexed by the Parenting Stress Index-Short Form (PSI-SF; Cohen's d = -0.90, 95% CI = -1.39, -0.40). Exploratory but underpowered analyses of dyadic interactions revealed reductions in the PSI were associated with a reduction in harsh parenting after the intervention. However, we did not detect any positive impact on behavioral or emotional outcomes among the children. CONCLUSION: Our analyses suggest that MOCEP had a positive impact on disciplinary practices and parenting stress in a context of high fragility, but that broader effects on maternal and child outcomes may be dependent on program attendance and the availability of other services. We discuss implications of this pilot study for practice and research of a largely unexplored area of program evaluation. CLINICAL TRIAL REGISTRATION INFORMATION: Mother and Child Education Program in Palestinian Refugee Camps; https://clinicaltrials.gov; NCT02402556.

How do grandparents influence child health and development? A systematic review.

Grandparents are often a key source of care provision for their grandchildren, yet they are sidelined in caregiving research and policy decisions. We conducted a global, systematic review of the literature to examine the scope and quality of studies to date (PROSPERO database CRD42019133894). We screened 12,699 abstracts across 7 databases, and identified 206 studies that examined how grandparents influence child health and development. Indicators of grandparent involvement were contact, caregiving behaviors, and financial support. Our review focused on two research questions: how do grandparents influence child health and development outcomes, and what range of child outcomes is reported globally? We examined study design, sample characteristics, key findings, and outcomes pertaining to grandchildren's physical health, socio-emotional and behavioral health, and cognitive and educational development.  Our search captured studies featuring grandparent custodial care (n = 35), multigenerational care (n = 154), and both types of care (n = 17). We found substantial heterogeneity in the data provided on co-residence, caregiving roles, resources invested, outcomes, and mechanisms through which "grandparent effects" are manifested. We identified two important issues, related to operationalizing indicators of grandparent involvement and conceptualizing potential mechanisms, leading to gaps in the evidence base. Currently, our understanding of the pathways through which grandparents exert their influence is constrained by limited data on what grandparents actually do and insufficient attention given to interpersonal and structural contexts. We present a conceptual framework to explicitly measure and theorize pathways of care, with a view to inform research design and policy implementation. We underscore the need for more robust data on three indicators of caregiver involvement-contact, behavior, and support-and for careful description of structural and interpersonal contexts in caregiving research.

Effectiveness of a youth-led early childhood care and education programme in rural Pakistan: A cluster-randomised controlled trial.

BACKGROUND: The United Nation's Sustainable Development Goals encompass lifelong learning from birth to youth to adulthood (Goal 4) and economic opportunities for young people (Goal 8). The targets include improving access to quality early childhood care and education (ECCE) as well as learning and training opportunities for adolescents and youth. Cross-generational models for young children and youth may offer opportunities to address the interconnections between goals and targets for the next generation. We investigated whether an ECCE programme for young children (3.5-6.5 years) delivered by female youth (18-24 years) in rural Pakistan would be effective on children's school readiness. METHODS: In partnership with the National Commission for Human Development in Pakistan, we implemented the 'Youth Leaders for Early Childhood Assuring Children are Prepared for School' (LEAPS) programme to train female youth to deliver ECCE. The effectiveness of the LEAPS programme on children's school readiness was evaluated in a cluster-randomised controlled trial. We randomly allocated five clusters (villages) to receive the intervention (n = 170 children) and five clusters to control (n = 170 children). Children's school readiness was assessed after nine months of intervention exposure using the International Development and Early Learning Assessment tool. Analyses was by intention-to-treat. The trial is registered with ClinicalTrials.gov, number NCT02645162. FINDINGS: At endline, the intervention group had significantly higher school readiness scores (n = 166, mean percentage score 59.4, 95% CI 52.7 to 66.2) compared with the control group (n = 168, mean percentage score 45.5, 95% CI 38.8 to 52.3). The effect size (Cohen's d) was 0.3. CONCLUSION: Trained female youth delivered an ECCE programme that was effective in benefitting young children's school readiness. The cross-generational model is a promising approach to support early child development; however, further evaluation of the model is needed to assess the specific benefits to youth including their skills and economic development.

Social Support, Simpatía, and Hypertension Prevalence in Hispanics/Latinos: Findings from the HCHS/SOL Sociocultural Ancillary Study.

There is a significant burden of hypertension in the United States, which extends to the large and growing Hispanic/Latino population. Previous literature suggests that psychosocial factors are related to hypertension in Hispanics/Latinos. However, cultural factors unique to this population have been largely understudied in this context. The purpose of the current investigation was to examine the association of hypertension prevalence with social support and simpatía, a Hispanic/Latino cultural value emphasizing social harmony. Cross-sectional data from 5,313 adult Hispanics/Latinos, age 18 to 75 years, representing multiple heritage groups were collected as part of the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study. Contrary to predictions, higher social support was related to higher odds of hypertension prevalence across models (OR = 1.11, 95% CI: 1.02, 1.22). In the final main effects logistic regression model, higher simpatía was related to lower odds of hypertension (OR = .83, 95% CI: .77, .90). Sex modified the link between simpatía and hypertension, with significant effects for men but not women. A 1 SD increase in simpatía was associated with 36% lower odds of hypertension in Hispanic/Latino men. The findings suggest that social support was inversely related with hypertension prevalence and that simpatía may be a protective cultural characteristic in relation to hypertension in the Hispanic/Latino population, but only in men. These results contribute to a growing discourse about the role of Hispanic/Latino cultural values in cardiovascular health.

Validation of interpersonal support evaluation list-12 (ISEL-12) scores among English- and Spanish-speaking Hispanics/Latinos from the HCHS/SOL Sociocultural Ancillary Study.

The Interpersonal Support Evaluation List-12 (ISEL-12; Cohen, Mermelstein, Kamarck, & Hoberman, 1985) is broadly employed as a short-form measure of the traditional ISEL, which measures functional (i.e., perceived) social support. The ISEL-12 can be scored by summing the items to create an overall social support score; three subscale scores representing appraisal, belonging, and tangible social support have also been proposed. Despite extensive use, studies of the psychometric properties of ISEL-12 scores have been limited, particularly among Hispanics/Latinos, the largest and fastest growing ethnic group in the United States. The current study investigated the reliability and structural and convergent validity of ISEL-12 scores using data from 5,313 Hispanics/Latinos who participated in the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study. Participants completed measures in English or Spanish and identified their ancestry as Dominican, Central American, Cuban, Mexican, Puerto Rican, or South American. Cronbach's alphas suggested adequate internal consistency for the total score for all languages and ancestry groups; coefficients for the subscale scores were not acceptable. Confirmatory factor analyses revealed that the one-factor and three-factor models fit the data equally well. Results from multigroup confirmatory factor analyses supported a similar one-factor structure with equivalent response patterns and variances between language groups and ancestry groups. Convergent validity analyses suggested that the total social support score related to scores of social network integration, life engagement, perceived stress, and negative affect (depression, anxiety) in the expected directions.

Site-specific androgen receptor serine phosphorylation linked to epidermal growth factor-dependent growth of castration-recurrent prostate cancer.

The androgen receptor (AR) is required for prostate cancer development and contributes to tumor progression after remission in response to androgen deprivation therapy. Epidermal growth factor (EGF) increases AR transcriptional activity at low levels of androgen in the CWR-R1 prostate cancer cell line derived from the castration-recurrent CWR22 prostate cancer xenograft. Here we report that knockdown of AR decreases EGF stimulation of prostate cancer cell growth and demonstrate a mechanistic link between EGF and AR signaling. The EGF-induced increase in AR transcriptional activity is dependent on phosphorylation at mitogen-activated protein kinase consensus site Ser-515 in the AR NH(2)-terminal region and at protein kinase C consensus site Ser-578 in the AR DNA binding domain. Phosphorylation at these sites alters the nuclear-cytoplasmic shuttling of AR and AR interaction with the Ku-70/80 regulatory subunits of DNA-dependent protein kinase. Abolishing AR Ser-578 phosphorylation by introducing an S578A mutation eliminates the AR transcriptional response to EGF and increases both AR binding of Ku-70/80 and nuclear retention of AR in association with hyperphosphorylation of AR Ser-515. The results support a model in which AR transcriptional activity increases castration-recurrent prostate cancer cell growth in response to EGF by site-specific serine phosphorylation that regulates nuclear-cytoplasmic shuttling through interactions with the Ku-70/80 regulatory complex.

Heregulin-induced activation of HER2 and HER3 increases androgen receptor transactivation and CWR-R1 human recurrent prostate cancer cell growth.

PURPOSE: The androgen receptor (AR) is a ligand-dependent transcription factor that mediates gene expression and growth of normal and malignant prostate cells. In prostate tumors that recur after androgen withdrawal, the AR is highly expressed and transcriptionally active in the absence of testicular androgens. In these "androgen-independent" tumors, alternative means of AR activation have been invoked, including regulation by growth factors and their receptors in prostate cancer recurrence. EXPERIMENTAL DESIGN AND RESULTS: In this report, we show that HER receptor tyrosine kinases 1 through 4 are expressed in the CWR-R1 recurrent prostate cancer cell line; their stimulation by epidermal growth factor (EGF) and heregulin activates downstream signaling, including mitogen-activated protein kinase and phosphatidylinositol-3 kinase and Akt pathways. We show that heregulin activates HER2 and HER3 and increases androgen-dependent AR transactivation of reporter genes in CWR-R1 cells. Tyrosine phosphorylation of HER2 and HER3, AR transactivation, and cell proliferation induced by heregulin were more potently inhibited by the EGFR/HER2 dual tyrosine kinase inhibitor GW572016 (lapatinib) than the EGFR-specific inhibitor ZD1839 (gefitinib). Basal proliferation in the absence of growth factors was also inhibited by GW572016 to a greater extent than ZD1839, suggesting that low level HER2/HER3 activation perhaps by an autocrine pathway contributes to the proliferation signal. CONCLUSIONS: These data indicate that heregulin signaling through HER2 and HER3 increases AR transactivation and alters growth in a recurrent prostate cancer cell line. Therefore, inhibition of low-level HER2 signaling may be a potential novel therapeutic strategy in prostate cancer.

Epidermal growth factor increases coactivation of the androgen receptor in recurrent prostate cancer.

Growth of normal and neoplastic prostate is mediated by the androgen receptor (AR), a ligand-dependent transcription factor activated by high affinity androgen binding. The AR is highly expressed in recurrent prostate cancer cells that proliferate despite reduced circulating androgen. In this report, we show that epidermal growth factor (EGF) increases androgen-dependent AR transactivation in the recurrent prostate cancer cell line CWR-R1 through a mechanism that involves a post-transcriptional increase in the p160 coactivator transcriptional intermediary factor 2/glucocorticoid receptor interacting protein 1 (TIF2/GRIP1). Site-specific mutagenesis and selective MAPK inhibitors linked the EGF-induced increase in AR transactivation to phosphorylation of TIF2/GRIP1. EGF signaling increased the coimmunoprecipitation of TIF2 and AR. AR transactivation and its stimulation by EGF were reduced by small interfering RNA inhibition of TIF2/GRIP1 expression. The data indicate that EGF signaling through MAPK increases TIF2/GRIP1 coactivation of AR transactivation in recurrent prostate cancer.