Annual Research Review: Early intervention viewed through the lens of developmental neuroscience.

The overarching goal of this paper is to examine the efficacy of early intervention when viewed through the lens of developmental neuroscience. We begin by briefly summarizing neural development from conception through the first few postnatal years. We emphasize the role of experience during the postnatal period, and consistent with decades of research on critical periods, we argue that experience can represent both a period of opportunity and a period of vulnerability. Because plasticity is at the heart of early intervention, we next turn our attention to the efficacy of early intervention drawing from two distinct literatures: early intervention services for children growing up in disadvantaged environments, and children at elevated likelihood of developing a neurodevelopmental delay or disorder. In the case of the former, we single out interventions that target caregiving and in the case of the latter, we highlight recent work on autism. A consistent theme throughout our review is a discussion of how early intervention is embedded in the developing brain. We conclude our article by discussing the implications our review has for policy, and we then offer recommendations for future research.

Parental communicative input as a protective factor in Bangladeshi families living in poverty: A multi-dimensional perspective.

Studies from high-income populations have shown that stimulating, supportive communicative input from parents promote children's cognitive and language development. However, fewer studies have identified specific features of input supporting the healthy development of children growing up in low- or middle-income countries. The current study proposes and tests a multi-dimensional framework for understanding whether and how caregiver communicative input mediates the associations between socio-economic conditions and early development. We also examine how caregiver conceptual scaffolding and autonomy support uniquely and synergistically explain variation in child outcomes. Participants were 71 Bangladeshi families with five-year-olds who were exposed to a range of biological and psychosocial hazards from birth. Caregiver-child interactions during snack sharing and semi-structured play were coded for caregiver conceptual scaffolding, autonomy support, and child engagement. Findings indicate that the two dimensions of input were correlated, suggesting that caregivers who provided richer conceptual scaffolds were simultaneously more supportive of children's autonomy. Notably, conceptual scaffolding and autonomy support each mediated associations between maternal education and child verbal intelligence quotient (IQ) scores. Further, caregivers who supported greater autonomy in their children had children who participated in conversations more actively, and these children in turn had higher performance IQ scores. When considered simultaneously, conceptual scaffolding was associated with verbal IQ over and above autonomy support, whereas autonomy support related to child engagement, controlling for conceptual scaffolding. These findings shed new light on how environmental factors may support early development, contributing to the design of family-centered, culturally authentic interventions. A video abstract of this article can be viewed at https://youtu.be/9v_8sIv7ako RESEARCH HIGHLIGHTS: Studies from high-income countries have identified factors mitigating the impacts of socio-economic risks on development. Such research is scarce in low- and middle-income countries. The present study conceptualized and evaluated caregiver communicative input in Bangladeshi families along two interrelated yet distinct dimensions: conceptual scaffolding and autonomy support. Conceptual scaffolding and autonomy support individually mediated associations between maternal education and child verbal IQ, shedding light on protective factors in families living in poverty. Parents providing richer conceptual scaffolds were simultaneously more supportive of children's autonomy. However, the two dimensions each related to cognition and language through unique pathways.

Neural correlates of inhibitory control and associations with cognitive outcomes in Bangladeshi children exposed to early adversities.

There is strong support for the view that children growing up in low-income homes typically evince poorer performance on tests of inhibitory control compared to those growing up in higher income homes. Unfortunately, the vast majority of the work documenting this association has been conducted in high-income countries. It is not yet known whether the mechanisms found to mediate this association would generalize to children in low- and middle-income countries, where the risks of exposure to extreme poverty and a wide range of both biological and psychosocial hazards may be greater. We examined relations among early adversity, neural correlates of inhibitory control, and cognitive outcomes in 154 5-year-old children living in Dhaka, Bangladesh, an area with a high prevalence of poverty. Participants completed a go/no-go task assessing inhibitory control and their behavioral and event-related potential responses were assessed. Cortical source analysis was performed. We collected measures of poverty, malnutrition, maternal mental health, psychosocial adversity, and cognitive skills. Supporting studies in high-income countries, children in this sample exhibited a longer N2 latency and higher P3 amplitude to the no-go versus go condition. Unexpectedly, children had a more pronounced N2 amplitude during go trials than no-go trials. The N2 latency was related to their behavioral accuracy on the go/no-go task. The P3 mean amplitude, behavioral accuracy, and reaction time during the task were all associated with intelligence-quotient (IQ) scores. Children who experienced higher levels of psychosocial adversity had lower accuracy on the task and lower IQ scores.

What do health workers in Timor-Leste want, know and do? Findings from a national health labour market survey.

BACKGROUND: The objectives of this study were to understand the labour market dynamics among health workers, including their preferences and concerns, and to assess the skills, competence and performance (i.e. the 'know-do gap') of doctors working in Timor-Leste. METHODS: This cross-sectional survey was implemented in all 13 districts of Timor-Leste in 2014. We surveyed 443 health workers, including 175 doctors, 150 nurses and 118 midwives (about 20% of the health workers in the country). We also observed 632 clinical consultations with doctors, including 442 direct clinical observations, and tested 190 vignettes. RESULTS: The study highlights some positive findings, including the gender balance of health workers overall, the concentration of doctors in rural areas, the high overall reported satisfaction of staff with their work and high motivation, the positive intention to stay in the public sector, the feeling of being well prepared by training for work, the relatively frequent and satisfactory supervisions, and the good attitudes towards patients as identified in observations and vignettes. However, some areas require more investigations and investments. The overall clinical performance of the doctors was very good in terms of attitude and moderate in regard to history taking, health education and treatment. However, the average physical examination performance score was low. Doctors performed better with simulated cases than the real cases in general, which means they have better knowledge and skills than they actually demonstrated. The factors that were significantly associated with the clinical performance of doctors were location of the health facility (urban doctors were better) and consultation time (cases with more consultation time were better). Regression analysis suggests that lack of knowledge was significantly associated with lack of performance, while lack of motivation and equipment were not significant. CONCLUSIONS: The survey provides essential information for workforce planning and for developing training policies and terms and conditions that will attract and retain health workers in rural service. Improving the work environment and performance of doctors working in rural health facilities and ensuring compliance with clinical protocols are two priority areas needed to improve the performance of doctors in Timor-Leste.

Examining the relationship between psychosocial adversity and inhibitory control: an fMRI study of children growing up in extreme poverty.

Exposure to psychosocial adversity (PA) is associated with poor behavioral, physical, and mental health outcomes in adulthood. Growing evidence suggests that deficits in executive functions may in part moderate these outcomes, with inhibitory control as an example of such a putative moderator. However, much of the literature examining the development of inhibitory control has been based on children in higher resource environments, and little is known how growing up in a low resource setting might exacerbate the link between inhibitory control and health outcomes. In this context we collected fMRI data during a Go/No-Go inhibitory control task and PA variables for 68 children 5 to 7 years of age living in Dhaka, Bangladesh, an area with a high prevalence of PA. The children's mothers completed behavioral questionnaires to assess the child's PA and their own PA. Whole-brain activation underlying inhibitory control was examined using the No-Go versus Go contrast, and associations with PA variables were assessed using whole-brain regressions. Childhood neglect was associated with weaker activation in the right posterior cingulate, whereas greater family conflict, economic stress, and maternal PA factors were associated with greater activation in the left medial frontal gyrus, right superior and middle frontal gyrus, and left cingulate gyrus. These data suggest that neural networks supporting inhibitory control processes may vary as a function of exposure to different types of PA, particularly between those related to threat and deprivation. Furthermore, increased activation in children with greater PA may serve as a compensatory mechanism, allowing them to maintain similar behavioral task performance.

Exploration of auditory statistical learning, socioeconomic status, and language outcomes in Bangladeshi children: A functional near-infrared spectroscopy study.

Auditory statistical learning, or the ability to detect statistical regularities in continuously presented stimuli, is thought to be one element that underlies language acquisition. Prior studies have uncovered behavioral and neural correlates of statistical learning, yet additional work is needed from low- and middle-income countries to explore whether statistical learning varies across cultures or underlies associations often found between socioeconomic status (SES) and language outcomes. In the present study, we explored the feasibility of using functional near-infrared spectroscopy (fNIRS) to explore auditory statistical learning in Bangladesh, a lower-middle-income country. Participants were 102 2-year-old (M = 25.72 months, SD = 2.07 months) and 125 5-year-old children (M = 62.35 months, SD = 2.46 months) living in a low-income urban neighborhood of Dhaka (average family income of 28,145.13 Bangladeshi Takas or 260.06 U.S. dollars per month). We also collected measures of SES and language outcomes. Brain responses during the statistical learning paradigm could be detected with fNIRS in both two- and 5-year-olds, with 2-year-olds exhibiting a higher response to predictable sequences and 5-year-olds exhibiting higher responses to unpredictable sequences. fNIRS correlates of statistical learning were not related to language outcomes but were associated with SES in the 5-year-old cohort. This study demonstrates the utility of employing fNIRS to study the neural correlates of statistical learning in low- and middle-income countries and the feasibility of expanding the representativeness of the existing literature. These findings also highlight potential areas for inquiry into how SES may relate to individual differences in statistical learning responses. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Effectiveness of father-inclusive interventions on maternal, paternal, couples, and early child outcomes in low- and middle-income countries: A systematic review.

Most caregiving interventions for young children are directed to female caregivers. Relatively few have included male caregivers as program participants especially in low- and middle-income countries (LMICs). The range of potential benefits that can be achieved through the engagement of fathers and male caregivers has not been adequately explored from a family systems perspective. We reviewed interventions that engaged male caregivers to support young children in LMICs and summarized impacts on maternal, paternal, couples, and child outcomes. We searched MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, and Global Health Library for quantitative evaluation studies of social and behavioral interventions that included fathers or other male caregivers to improve nurturing care for young children under 5 years of age in LMICs. Three authors independently extracted data using a structured form. Forty-four articles, representing 33 intervention evaluations, were included. The most common type of intervention targeted fathers along with their female partners and primarily to address child nutrition and health. Across interventions, maternal outcomes were the most evaluated outcomes (82%), followed by paternal (58%), couple's relationship (48%) and child-level outcomes (45%). Overall, father-inclusive interventions had positive impacts on maternal, paternal and couples' relationship outcomes. Although there was greater variation in the degree of supportive evidence for child outcomes compared to maternal, paternal, and couples outcomes, findings suggested mostly positive effects across all outcomes. Limitations included relatively weak study designs and heterogeneity across interventions, outcome types, and measurement tools. Interventions that include fathers and other male caregivers have potential to improve maternal and paternal caregiving, couple's relationships dynamics, and early child outcomes in LMICs. More evaluation studies, using rigorous methods and robust measurement frameworks, is needed to bolster this evidence-base about the effect of fathers' engagement for young children, caregivers, and families in LMICs.

Comparison of effectiveness and safety of sodium polystyrene sulfonate and sodium zirconium cyclosilicate for treatment of hyperkalemia in hospitalized patients.

PURPOSE: Potassium binders are frequently utilized for the treatment of hyperkalemia in hospitalized patients; however, there is limited data directly comparing individual agents. The purpose of this study was to compare the effectiveness and safety of sodium polystyrene sulfonate (SPS) and sodium zirconium cyclosilicate (SZC) for hyperkalemia treatment in hospitalized patients. METHODS: This retrospective cohort study evaluated adult patients who were admitted within a 7-hospital health system and received SPS or SZC for a serum potassium level greater than 5.0 mEq/L. Patients receiving dialysis prior to SPS/SZC administration, those receiving other potassium-lowering medications within 6 hours prior to blood sampling for a repeat potassium level, and those started on kidney replacement therapy prior to sampling for a repeat potassium level were excluded. RESULTS: Following evaluation of 3,903 patients, the mean reduction in serum potassium 4 to 24 hours after binder administration was 0.96 mEq/L with SPS and 0.78 mEq/L with SZC (P < 0.0001). The median dose of SPS was 30 g (interquartile range [IQR], 15-30 g) while the median (IQR) dose of SZC was 10 g (10-10 g). Resolution of hyperkalemia within 24 hours was achieved in a higher percentage of patients with use of SPS (74.9%) versus SZC (68.8%) (P < 0.001). CONCLUSION: One of the largest comparisons of SPS and SZC conducted to date, this study demonstrated the effectiveness and safety of both agents. While a statistically greater reduction in serum potassium was observed with use of SPS, there was significant dosing variability among agents that limited the ability to directly compare specific doses. Further investigation is needed to determine the optimal dose of each agent for acute hyperkalemia management. This data will inform clinical decisions about the choice of potassium binder for acute hyperkalemia.

Implementation characteristics of father-inclusive interventions in low- and middle-income countries: A systematic review.

Although prior reviews have documented the effectiveness of engaging male caregivers in early childhood interventions, little is known about how these interventions have been designed and implemented to reach, engage, and support male caregivers in low-resource global settings. We searched five bibliographic databases for intervention studies that engaged male caregivers to improve nurturing care for children under 5 years of age in low- and middle-income countries. Forty-four articles met the inclusion criteria, which represented 33 interventions. Fathers specifically were the most common type of male caregivers targeted in these interventions. The majority of interventions invited fathers to participate alongside their female partners. Community-based peer-groups were the most common delivery model. Most interventions used the same program structure for fathers as applied to mothers, with few considering whether implementation adaptations were needed for men. Intervention curricula were multicomponent and largely targeted child nutrition, health, and couples' relationships. A minority of programs addressed parenting, psychosocial wellbeing, violence prevention, gender attitudes, or economic support. Behavior change techniques were limited to interactive counseling and peer learning. Male caregivers remain missing from caregiving interventions for young children. A greater focus on implementation research can inform better inclusion, engagement, and support for male caregivers in nurturing care interventions.

Correction: Measurement tools and indicators for assessing nurturing care for early childhood development: A scoping review.

[This corrects the article DOI: 10.1371/journal.pgph.0000373.].

Shedding light on functional near-infrared spectroscopy and open science practices.

Open science practices work to increase methodological rigor, transparency, and replicability of published findings. We aim to reflect on what the functional near-infrared spectroscopy (fNIRS) community has done to promote open science practices in fNIRS research and set goals to accomplish over the next 10 years.

Measurement tools and indicators for assessing nurturing care for early childhood development: A scoping review.

Nurturing care encompasses five components that are crucial for supporting early childhood development: good health, adequate nutrition, opportunities for early learning, responsive caregiving, and safety and security. While there has been increasing attention in global public health towards designing and delivering programs, services, and policies to promote nurturing care, measurement has focused more on the components of health and nutrition, with less attention to early learning, responsive caregiving, and safety and security. We conducted a scoping review to identify articles that measured at least one nurturing care outcome in a sample of caregivers and/or children under-5 years of age in low- and middle-income countries (LMICs). We systematically searched five electronic bibliographic databases for peer-reviewed articles published from database inception until November 30, 2020. We first classified outcomes to their respective nurturing care component, and then applied an inductive approach to organize key constructs within each nurturing care component and the specific measures and indicators used across studies. We identified 239 total articles representing more than 50 LMICs for inclusion in the review. The majority of included studies reported a measure of nutrition (N = 166), early learning (N = 140), and health (N = 102), followed by responsive caregiving (N = 78) and lastly safety and security (N = 45). For each nurturing care component, we uncovered multiple constructs relevant to children under-5: nutrition (e.g., anthropometry, complementary feeding), early learning (e.g., stimulation practices, early childhood education), health (e.g., birth outcomes, morbidity), responsive caregiving (e.g., parental responsivity, parent-child interactions), and safety and security (e.g., discipline, inadequate supervision). Particularly for outcomes of early learning and responsive caregiving, there was greater variability with regards to the measures used, reported indicators, and analytic construction of variables than the other three nurturing care components. This study provides a comprehensive review of the current state of measurement of nurturing care. Additional research is needed in order to establish the most optimal measures and indicators for assessing nurturing care, especially for early learning and responsive caregiving.

Association of psychosocial adversity and social information processing in children raised in a low-resource setting: an fNIRS study.

Social cognition skills and socioemotional development are compromised in children growing up in low SES contexts, however, the mechanisms underlying this association remain unknown. Exposure to psychosocial risk factors early in life alters the child's social milieu and in turn, could lead to atypical processing of social stimuli. In this study, we used functional Near Infrared Spectroscopy (fNIRS) to measure cortical responses to a social discrimination task in children raised in a low-resource setting at 6, 24, and 36 months. In addition, we assessed the relation between cortical responses to social and non-social information with psychosocial risk factors assessed using the Childhood Psychosocial Adversity Scale (CPAS). In line with previous findings, we observed specialization to social stimuli in cortical regions in all age groups. In addition, we found that risk factors were associated with social discrimination at 24 months (intimate partner violence and verbal abuse and family conflict) and 36 months (verbal abuse and family conflict and maternal depression) but not at 6 months. Overall, the results show that exposure to psychosocial adversity has more impact on social information processing in toddlerhood than earlier in infancy.

Scaffold-based [Fe]-hydrogenase model: H2 activation initiates Fe(0)-hydride extrusion and non-biomimetic hydride transfer.

We report the synthesis and reactivity of a model of [Fe]-hydrogenase derived from an anthracene-based scaffold that includes the endogenous, organometallic acyl(methylene) donor. In comparison to other non-scaffolded acyl-containing complexes, the complex described herein retains molecularly well-defined chemistry upon addition of multiple equivalents of exogenous base. Clean deprotonation of the acyl(methylene) C-H bond with a phenolate base results in the formation of a dimeric motif that contains a new Fe-C(methine) bond resulting from coordination of the deprotonated methylene unit to an adjacent iron center. This effective second carbanion in the ligand framework was demonstrated to drive heterolytic H2 activation across the Fe(ii) center. However, this process results in reductive elimination and liberation of the ligand to extrude a lower-valent Fe-carbonyl complex. Through a series of isotopic labelling experiments, structural characterization (XRD, XAS), and spectroscopic characterization (IR, NMR, EXAFS), a mechanistic pathway is presented for H2/hydride-induced loss of the organometallic acyl unit (i.e. pyCH2-C[double bond, length as m-dash]O → pyCH3+C[triple bond, length as m-dash]O). The known reduced hydride species [HFe(CO)4]- and [HFe3(CO)11]- have been observed as products by 1H/2H NMR and IR spectroscopies, as well as independent syntheses of PNP[HFe(CO)4]. The former species (i.e. [HFe(CO)4]-) is deduced to be the actual hydride transfer agent in the hydride transfer reaction (nominally catalyzed by the title compound) to a biomimetic substrate ([TolIm](BArF) = fluorinated imidazolium as hydride acceptor). This work provides mechanistic insight into the reasons for lack of functional biomimetic behavior (hydride transfer) in acyl(methylene)pyridine based mimics of [Fe]-hydrogenase.

Individual, social-normative, and policy predictors of smoking cessation: a multilevel longitudinal analysis.

OBJECTIVES: We assessed the prospective impact of individual, social-normative, and policy predictors of quit attempts and smoking cessation among Massachusetts adults. METHODS: We interviewed a representative sample of current and recent smokers in Massachusetts by telephone in 2001 through 2002 and then again twice at 2-year intervals. The unit of analysis was the 2-year transition from wave 1 to wave 2 and from wave 2 to wave 3. Predictors of quit attempts and abstinence of longer than 3 months were analyzed using multilevel analysis. Predictors included individual, social-normative, and policy factors. RESULTS: Multivariate analyses of 2-year transitions showed that perceptions of strong antismoking town norms were predictive of abstinence (odds ratio = 2.06; P < .01). Household smoking bans were the only policy associated with abstinence, but smoking bans at one's worksite were significant predictors of quit attempts. CONCLUSIONS: Although previous research showed a strong relation between local policy and norms, we found no observable, prospective impact of local policy on smoking cessation over 2 years. Our findings provide clear support for the importance of strong antismoking social norms as a facilitator of smoking cessation.

The impact of Massachusetts' smoke-free workplace laws on acute myocardial infarction deaths.

OBJECTIVES: We examined the rate of acute myocardial infarction (AMI) deaths in Massachusetts before and after the implementation of a comprehensive smoke-free workplace law in July 2004. METHODS: We used Poisson regression models to examine the impact of the state law in cities and towns with and without previous local smoking bans and the effect of the local laws for the period of 1999 through 2006. RESULTS: The AMI mortality rate decreased by 7.4% (95% confidence interval [CI] = 3.3%, 11.4%) after implementation of the state law. The state ban had an impact in cities and towns with no prior local smoking ban (9.2% decrease; P < .001) but not cities and towns with a prior local smoking ban. However, there was a nonsignificant 4.9% (95% CI = -5.0%, 13.9%) decrease associated with the local smoking ban that preceded the effect of the state ban. The effect of the state ban was modest (-1.6%) in the first 12 months after implementation but much larger after the first 12 months (-18.6%; P < .001). CONCLUSIONS: Comprehensive statewide smoke-free workplace laws in Massachusetts were associated with an estimated 270 fewer AMI deaths per year. These results add to the evidence suggesting that smoke-free air laws are associated with lower rates of AMI.

IL2RG, identified as overexpressed by RNA-seq profiling of pancreatic intraepithelial neoplasia, mediates pancreatic cancer growth.

Pancreatic ductal adenocarcinoma evolves from precursor lesions, the most common of which is pancreatic intraepithelial neoplasia (PanIN). We performed RNA-sequencing analysis of laser capture microdissected PanINs and normal pancreatic duct cells to identify differentially expressed genes between PanINs and normal pancreatic duct, and between low-grade and high-grade PanINs. One of the most highly overexpressed transcripts identified in PanIN is interleukin-2 receptor subunit gamma (IL2RG) encoding the common gamma chain, IL2Rγ. CRISPR-mediated knockout of IL2RG in orthotopically implanted pancreatic cancer cells resulted in attenuated tumor growth in mice and reduced JAK3 expression in orthotopic tumors. These results indicate that IL2Rγ/JAK3 signaling contributes to pancreatic cancer cell growth in vivo.

Associations between age or sex and prevalence of gastric ulceration in Standardbred racehorses in training.

OBJECTIVE: To determine associations between age, sex, or medical treatment and prevalence and severity of gastric ulceration in Standardbred racehorses in training. DESIGN: Cross-sectional study. ANIMALS: 224 Standardbred racehorses in training. PROCEDURE: Gastroscopy was performed on each horse, and mucosal ulceration was graded from 0 (normal mucosa, no lesions) to 3 (extensive, often coalescing, lesions with areas of deep ulceration). Associations between age, sex, or treatment and prevalence and severity of ulcers were evaluated. RESULTS: Prevalence of gastric ulceration was 87%. Although there was little association between age and prevalence of ulcers, there was an association between age and severity of ulcers. Most 2-year-old horses (57.7%) had an ulcer score of 0 or 1. In all other age groups, most (58% to 82.61%) of horses had an ulcer score of 2 or 3. Although overall prevalence of ulceration was comparable among sex groups, the relative risk for gastric ulceration increased with age in castrated males, whereas it decreased in females and sexually intact males. CONCLUSIONS AND CLINICAL RELEVANCE: Gastric ulceration is common in Standardbred horses in race training. Severity is higher in horses > or = 3 years of age than in 2-year-old horses. Relative risk for ulceration increases with age in castrated males.

Odds of moderate or severe gastric ulceration in racehorses receiving antiulcer medications.

OBJECTIVE: To determine the odds of moderate or severe gastric ulceration in racehorses treated with various antiulcer medications. DESIGN: Unmatched case-control study. ANIMALS: 798 horses in active race training (252 Thoroughbreds and 546 Standardbreds). Only horses that had been receiving a single antiulcer medication or no antiulcer medication for at least 2 weeks prior to examination were included. PROCEDURE: Gastroscopy was performed on each horse by a single individual who was not aware of the horses' antiulcer treatments, and severity of gastric ulceration was scored. Signalment and medication history were recorded. Logistic regression was used to determine whether identification of moderate or severe ulceration was associated with treatment, age, breed, or sex. Treatments were grouped as no treatment, buffer, sucralfate, histamine type 2 receptor antagonist, compounded omeprazole, proprietary omeprazole at a low dosage, and proprietary omeprazole at a high dosage. RESULTS: Only proprietary omeprazole was associated with significantly lower odds of moderate or severe ulceration, compared with no treatment. Risks of moderate or severe gastric ulceration in horses receiving a buffer, sucralfate, a histamine type 2 receptor antagonist, or compounded omeprazole were not significantly different from risks in horses receiving no antiulcer medication. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that the proprietary formulation of omeprazole was associated with a significantly lower risk of moderate or severe gastric ulceration, compared with no treatment, in racehorses in active race training, whereas other antiulcer medications were not.