Development of the N400 for Word Learning in the First 2 Years of Life: A Systematic Review

The N400 ERP component is a direct neural index of word meaning. Studies show that the N400 component is already present in early infancy, albeit often delayed. Many researchers capitalize on this finding, using the N400 component to better understand how early language acquisition unfolds. However, variability in how researchers quantify the N400 makes it difficult to set clear predictions or build theory. Not much is known about how the N400 component develops in the first 2 years of life in terms of its latency and topographical distributions, nor do we know how task parameters affect its appearance. In the current paper we carry out a systematic review, comparing over 30 studies that report the N400 component as a proxy of semantic processing elicited in infants between 0 and 24 months old who listened to linguistic stimuli. Our main finding is that there is large heterogeneity across semantic-priming studies in reported characteristics of the N400, both with respect to latency and to distributions. With age, the onset of the N400 insignificantly decreases, while its offset slightly increases. We also examined whether the N400 appears different for recently-acquired novel words vs. existing words: both situations reveal heterogeneity across studies. Finally, we inspected whether the N400 was modulated differently with studies using a between-subject design. In infants with more proficient language skills the N400 was more often present or showed itself here with earlier latency, compared to their peers; but no consistent patterns were observed for distribution characteristics of the N400. One limitation of the current review is that we compared studies that widely differed in choice of EEG recordings, pre-processing steps and quantification of the N400, all of which could affect the characteristics of the infant N400. The field is still missing research that systematically tests development of the N400 using the same paradigm across infancy

Systematic assessment in an animal model of the angiogenic potential of different human cell sources for therapeutic revascularization

INTRODUCTION: Endothelial progenitor cells (EPC) capable of initiating or augmenting vascular growth were recently identified within the small population of CD34-expressing cells that circulate in human peripheral blood and which are considered hematopoietic progenitor cells (HPC). Soon thereafter human HPC began to be used in clinical trials as putative sources of EPC for therapeutic vascular regeneration, especially in myocardial and critical limb ischemias. However, unlike HPC where hematopoietic efficacy is related quantitatively to CD34(+ )cell numbers implanted, there has been no consensus on how to measure EPC or how to assess cellular graft potency for vascular regeneration. We employed an animal model of spontaneous neovascularization to simultaneously determine whether human cells incorporate into new vessels and to quantify the effect of different putative angiogenic cells on vascularization in terms of number of vessels generated. We systematically compared competence for therapeutic angiogenesis in different sources of human cells with putative angiogenic potential, to begin to provide some rationale for optimising cell procurement for this therapy. METHODS: Human cells employed were mononuclear cells from normal peripheral blood and HPC-rich cell sources (umbilical cord blood, mobilized peripheral blood, bone marrow), CD34(+ )enriched or depleted subsets of these, and outgrowth cell populations from these. An established sponge implant angiogenesis model was adapted to determine the effects of different human cells on vascularization of implants in immunodeficient mice. Angiogenesis was quantified by vessel density and species of origin by immunohistochemistry. RESULTS: CD34(+ )cells from mobilized peripheral blood or umbilical cord blood HPC were the only cells to promote new vessel growth, but did not incorporate into vessels. Only endothelial outgrowth cells (EOC) incorporated into vessels, but these did not promote vessel growth. CONCLUSIONS: These studies indicate that, since EPC are very rare, any benefit seen in clinical trials of HPC in therapeutic vascular regeneration is predominantly mediated by indirect proangiogenic effects rather than through direct incorporation of any rare EPC contained within these sources. It should be possible to produce autologous EOC for therapeutic use, and evaluate the effect of EPC distinct from, or in synergy with, the proangiogenic effects of HPC therapies

A missed opportunity: birth registration coverage is lagging behind Bacillus Calmette\u2013Gu\ue9rin (BCG) immunization coverage and maternal health services utilization in low- and lower middle-income countries

Background: Civil registration and vital statistics (CRVS) systems lay the foundation for good governance by increasing the effectiveness and delivery of public services, providing vital statistics for the planning and monitoring of national development, and protecting fundamental human rights. Birth registration provides legal rights and facilitates access to essential public services such as health care and education. However, more than 110 low- and middle-income countries (LMICs) have deficient CRVS systems, and national birth registration rates continue to fall behind childhood immunization rates. Using Demographic and Health Survey (DHS) and Multiple Indicator Cluster Survey (MICS) data in 72 LMICs, the objectives are to (a) explore the status of birth registration, routine childhood immunization, and maternal health services utilization; (b) analyze indicators of birth registration, routine childhood immunization, and maternal health services utilization; and (c) identify missed opportunities for strengthening birth registration systems in countries with strong childhood immunization and maternal health services by measuring the absolute differences between the birth registration rates and these childhood and maternal health service indicators. Methods: We constructed a database using DHS and MICS data from 2000 to 2017, containing information on birth registration, immunization coverage, and maternal health service indicators. Seventy-three countries including 34 low-income countries and 38 lower middle-income countries were included in this exploratory analysis. Results: Among the 14 countries with disparity between birth registration and BCG vaccination of more than 50%, nine were from sub-Saharan Africa (Tanzania, Uganda, Gambia, Mozambique, Djibouti, Eswatini, Zambia, Democratic Republic of Congo, Ghana), two were from South Asia (Bangladesh, Nepal), one from East Asia and the Pacific (Vanuatu) one from Latin America and the Caribbean (Bolivia), and one from Europe and Central Asia (Moldova). Countries with a 50% or above absolute difference between birth registration and antenatal care coverage include Democratic Republic of Congo, Gambia, Mozambique, Nepal, Tanzania, and Uganda, in low-income countries. Among lower middle-income countries, this includes Eswatini, Ghana, Moldova, Timor-Leste, Vanuatu, and Zambia. Countries with a 50% or above absolute difference between birth registration and facility delivery care coverage include Democratic Republic of Congo, Djibouti, Moldova, and Zambia. Conclusion: The gap between birth registration and immunization coverage in low- and lower middle-income countries suggests the potential for leveraging immunization programs to increase birth registration rates. Engaging health providers during the antenatal, delivery, and postpartum periods to increase birth registration may be a useful strategy in countries with access to skilled providers

Toward Morphologically Relevant Extracellular Matrix in Vitro Models: 3D Fiber Reinforced Hydrogels

The extracellular matrix (ECM) is known to play an important role in the health of cells and tissues. Not only are chemical signals transmitted via bonds and tightly controlled diffusion, but the structure of the ECM also provides important physical signaling for the cells attached to it. The structure is composed of a mesh of fibrous proteins, such as collagen, embedded in a hydrated gel matrix of glycosaminoglycans. To study cell behavior with respect to the combined morphology and mechanics of such matrices is not currently possible with the types of 3D cell culture matrices available. Most of the cell culture matrices are single-phase bio- or polymeric hydrogels. Therefore, here we developed a continuous hybrid manufacturing process to make fiber-reinforced composite hydrogels. A far field electrospinning process was used to deposit the fibrous component with the aid of guiding electrodes; and a gravity-assisted, droplet-based system controlled the rate of addition of the cell-laden hydrogel component. The addition of the fibrous component slightly increased the elastic modulus of the pure hydrogel. The cells that were embedded into the fiber-reinforced hydrogels were viable for 8 days. The cells were randomly placed in the matrix such that some had no contact to the fibers and others were initially in proximity to fibers. The cells with no contact to fibers grew into spheroidal clusters within the hydrogel, and those in proximity to the fibers spread out and grew along the fibers showing that the fiber-reinforced hydrogels are able to control cell behavior with morphological cues

The financial cost of doctors emigrating from sub-Saharan Africa: human capital analysis

Objective To estimate the lost investment of domestically educated doctors migrating from sub-Saharan African countries to Australia, Canada, the United Kingdom, and the United States

Altered Cortico-Striatal–Thalamic Connectivity in Relation to Spatial Working Memory Capacity in Children with ADHD

Introduction: Attention deficit hyperactivity disorder (ADHD) captures a heterogeneous group of children, who are characterized by a range of cognitive and behavioral symptoms. Previous resting-state functional connectivity MRI (rs-fcMRI) studies have sought to understand the neural correlates of ADHD by comparing connectivity measurements between those with and without the disorder, focusing primarily on cortical–striatal circuits mediated by the thalamus. To integrate the multiple phenotypic features associated with ADHD and help resolve its heterogeneity, it is helpful to determine how specific circuits relate to unique cognitive domains of the ADHD syndrome. Spatial working memory has been proposed as a key mechanism in the pathophysiology of ADHD. Methods: We correlated the rs-fcMRI of five thalamic regions of interest (ROIs) with spatial span working memory scores in a sample of 67 children aged 7–11 years [ADHD and typically developing children (TDC)]. In an independent dataset, we then examined group differences in thalamo-striatal functional connectivity between 70 ADHD and 89 TDC (7–11 years) from the ADHD-200 dataset. Thalamic ROIs were created based on previous methods that utilize known thalamo-cortical loops and rs-fcMRI to identify functional boundaries in the thalamus. Results/Conclusion: Using these thalamic regions, we found atypical rs-fcMRI between specific thalamic groupings with the basal ganglia. To identify the thalamic connections that relate to spatial working memory in ADHD, only connections identified in both the correlational and comparative analyses were considered. Multiple connections between the thalamus and basal ganglia, particularly between medial and anterior dorsal thalamus and the putamen, were related to spatial working memory and also altered in ADHD. These thalamo-striatal disruptions may be one of multiple atypical neural and cognitive mechanisms that relate to the ADHD clinical phenotype

‘Like the stranger at a funeral who cries more than the bereaved’: ethical dilemmas in ethnographic research with children

This article contributes to debates on the practicality and utility of prior ethical review in ethnography and qualitative research using an ethnography of children’s involvement in artisanal gold mining work in Ghana as a case study. Reflecting on dilemmas and obstacles encountered in attempts to employ prescribed institutional ethical guidance modelled for childhood research in the UK during the fieldwork, the discussion brings to attention some of the problems that can arise when ethical guidance is not anchored in the lived realities or value systems of the setting in which fieldwork is conducted. The article seeks to rejuvenate calls for more flexible and socio-culturally responsive ethical review and practice as an alternative to the prescriptive ethical regimes

Using emergency department-based inception cohorts to determine genetic characteristics associated with long term patient outcomes after motor vehicle collision: Methodology of the CRASH study

<p>Abstract</p> <p>Background</p> <p>Persistent musculoskeletal pain and psychological sequelae following minor motor vehicle collision (MVC) are common problems with a large economic cost. Prospective studies of pain following MVC have demonstrated that demographic characteristics, including female gender and low education level, and psychological characteristics, including high pre-collision anxiety, are independent predictors of persistent pain. These results have contributed to the psychological and social components of a biopsychosocial model of post-MVC pain pathogenesis, but the biological contributors to the model remain poorly defined. Recent experimental studies indicate that genetic variations in adrenergic system function influence the vulnerability to post-traumatic pain, but no studies have examined the contribution of genetic factors to existing predictive models of vulnerability to persistent pain.</p> <p>Methods/Design</p> <p>The Project CRASH study is a federally supported, multicenter, prospective study designed to determine whether variations in genes affecting synaptic catecholamine levels and alpha and beta adrenergic receptor function augment social and psychological factors in a predictive model of persistent musculoskeletal pain and posttraumatic stress disorder (PTSD) following minor MVC. The Project CRASH study will assess pain, pain interference and PTSD symptoms at 6 weeks, 6 months, and 1 year in approximately 1,000 patients enrolled from 8 Emergency Departments in four states with no-fault accident laws.</p> <p>Discussion</p> <p>The results from this study will provide insights into the pathophysiology of persistent pain and PTSD following MVC and may serve to improve the ability of clinicians and researchers to identify individuals at high risk for adverse outcomes following minor MVC.</p

Nitrogen Limitation of the Summer Phytoplankton and Heterotrophic Prokaryote Communities in the Chukchi Sea

Major changes to Arctic marine ecosystems have resulted in longer growing seasons with increased phytoplankton production over larger areas. In the Chukchi Sea, the high productivity fuels intense benthic denitrification creating a nitrogen (N) deficit that is transported through the Arctic to the Atlantic Ocean, where it likely fuels N fixation. Given the rapid pace of environmental change and the potentially globally significant N deficit, we conducted experiments aimed at understanding phytoplankton and microbial N utilization in the Chukchi Sea. Ship-board experiments tested the effect of nitrate (NO3-) additions on both phytoplankton and heterotrophic prokaryote abundance, community composition, photophysiology, carbon fixation and NO3- uptake rates. Results support the critical role of NO3- in limiting summer phytoplankton communities to small cells with low production rates. NO3- additions increased particulate concentrations, abundance of large diatoms, and rates of carbon fixation and NO3- uptake by cells &gt;1 μm. Increases in the quantum yield and electron turnover rate of photosystem II in +NO3- treatments suggested that phytoplankton in the ambient dissolved N environment were N starved and unable to build new, or repair damaged, reaction centers. While some increases in heterotrophic prokaryote abundance and production were noted with NO3- amendments, phytoplankton competition or grazers likely dampened these responses. Trends toward a warmer more stratified Chukchi Sea will likely enhance summer oligotrophic conditions and further N starve Chukchi Sea phytoplankton communities