Characterizing developing executive functions in the first 1000 days in South Africa and Malawi: The Khula Study

Three important themes in neuroscience are parcellation, structure-function specificity, and neural plasticity. These themes relate to: 1. The ability to delineate brain regions, for example on the basis of their cellular composition, myeloarchitecture, microstructural architecture, and/or connectivity profiles; 2. Relate parcellations to specific cognitive functions or behaviors; and 3. The ability of the tissue microstructure and architecture to adaptively change in response to environmental influences, with concurrent functional consequences. Neural plasticity suggests that any regional delineation scheme is likely to change with age and functional development, which we can exploit to identify functionally relevant regions and their development with age. From a large longitudinal cohort of neurotypically-developing children, 0 to 13 years of age, we used a data-driven approach to subdivide the cortex based on cortical myelination patterns. Next, we quantified the relationships between rates of myelination across each region and rates of functional development (including motor, language, visuospatial, executive, and academic ability). Linking these evolving processes, we identified unique and overlapping cortical regions that underly diverse skill development, providing new insight into how the cortical myeloarchitecture develops throughout early childhood and its importance to developing cognitive functioning.

bioRxiv

Purpose Owing to the high cost of modern MRI systems, their use in clinical care and neurodevelopmental research is limited to hospitals and universities in high income countries. Ultra-low-field systems with significantly lower scanning costs bear the potential for global adoption, however their reduced SNR compared to 1.5 or 3T systems limits their applicability for research and clinical use. Methods In this paper, we describe a deep-learning based super-resolution approach to generate high-resolution isotropic T2-weighted scans from low-resolution inputs. We train a multi-orientation U-Net, which uses multiple low-resolution anisotropic images acquired in orthogonal orientations to construct a super-resolved output. Results Our approach exhibits improved quality of outputs compared to current state-of-the-art methods for super-resolution of ultra-low-field scans in paediatric populations. The average correlation value between volume estimates from high-field scans and super-resolved outputs rises to 0.77 using our method, compared to 0.71 using earlier techniques. Conclusion Our research serves as proof-of-principle of the viability of training deep-learning based super-resolution models for use in neurodevelopmental research and presents the first U-Net trained exclusively on paired ultra-low-field and high-field data from infants.

Developmental Psychology

A large body of research has established a relation between maternal education and children’s neurocognitive functions, such as executive function and language. However, most studies have focused on early childhood and relatively few studies have examined associations with changes in maternal education over time. Consequently, it remains unclear if early maternal education is longitudinally related to neurocognitive functions in children, adolescents, and young adults. In addition, the associations between changes in maternal education across development and more broadly defined neurocognitive outcomes remain relatively untested. The current study leveraged a large multicohort sample to examine the longitudinal relations between perinatal maternal education and changes in maternal education during development with children’s, adolescents’, and young adults’ neurocognitive functions (N= 2,688; M …

Magnetic Resonance in Medicine

Purpose This work reports for the first time on the implementation and application of cardiac diffusion‐weighted MRI on a Connectom MR scanner with a maximum gradient strength of 300 mT/m. It evaluates the benefits of the increased gradient performance for the investigation of the myocardial microstructure. Methods Cardiac diffusion‐weighted imaging (DWI) experiments were performed on 10 healthy volunteers using a spin‐echo sequence with up to second‐ and third‐order motion compensation (M2$$ {M}_2 $$ and M3$$ {M}_3 $$) and b=100, 450$$ b=100,450 $$, and 1000 s/mm2$$ \mathrm{s}/\mathrm{m}{\mathrm{m}}^2 $$ (twice the bmax$$ {b}_{\mathrm{max}} $$ commonly used on clinical scanners). Mean diffusivity (MD), fractional anisotropy (FA), helix angle (HA), and secondary eigenvector angle (E2A) were calculated for b = [100, 450] s/mm2$$ \mathrm{s}/\mathrm{m}{\mathrm{m}}^2 $$ and b …

Aim To review the epidemiology and outcomes of African children with cerebral palsy (CP) over a 21‐year period. Method The PubMed, Scopus, and Web of Science online databases were searched for original research on African children with CP aged 18 years and younger published from 2000 to 2021. Results A total of 1811 articles underwent review against explicit criteria; 93 articles were selected for inclusion in the scoping review. The reported prevalence of CP ranged from 0.8 to 10 per 1000 children. Almost half had perinatal risk factors, but up to 26% had no identifiable risk factor. At least one‐third of children with CP had one or more comorbidities, most commonly epilepsy, intellectual disability, and malnutrition. African children with CP demonstrated excess premature mortality approximately 25 times that of the general population, predominantly from infections. Hospital‐based and younger …

BackgroundThe study aim was to determine whether associations of antenatal maternal anaemia with smaller corpus callosum, putamen, and caudate nucleus volumes previously described in children at age 2–3 years persist to age 6-7 years in the Drakenstein Child Health Study (DCHS).MethodsThis neuroimaging sub-study was nested within the DCHS, a South African population-based birth cohort. Pregnant women were enrolled (2012-2015) and mother-child dyads were followed prospectively. A sub-group of children had magnetic resonance imaging at 6-7 years of age (2018-2022). Mothers had haemoglobin measurements during pregnancy and a proportion of children were tested postnatally. Maternal anaemia (haemoglobin< 11g/dL) and child anaemia were classified using WHO and local guidelines. Linear modeling was used to investigate associations between antenatal maternal anaemia status, maternal haemoglobin concentrations, and regional child brain volumes. Models included potential confounders and were conducted with and without child anaemia to assess the relative roles of antenatal versus postnatal anaemia.ResultsOverall, 157 children (Mean [SD] age of 75.54 [4.77] months; 84 [53.50%] male) were born to mothers with antenatal haemoglobin data. The prevalence of maternal anaemia during pregnancy was 31.85%(50/157). In adjusted models, maternal anaemia status was associated with smaller volumes of the total corpus callosum (adjusted percentage difference,-6.77%; p= 0.003), left caudate nucleus (adjusted percentage difference,-5.98%, p= 0.005), and right caudate nucleus (adjusted percentage …

JAMA Network Open

ImportancePrenatal alcohol exposure (PAE) and prenatal tobacco exposure (PTE) are risk factors associated with adverse neurobehavioral and cognitive outcomes.ObjectiveTo quantify long-term associations of PAE and PTE with brain activity in early and middle childhood via electroencephalography (EEG).Design, Setting, and ParticipantsThis cohort study included participants enrolled in the Safe Passage Study (August 2007 to January 2015), from which a subset of 649 participants were followed up in the Environmental Influences on Child Health Outcomes Program. From September 2018 through November 2022, EEG recordings were obtained at ages 4, 5, 7, 9, or 11 years. Data were analyzed from November 2022 to November 2023.ExposuresMaternal self-reported consumptions of alcohol and tobacco during pregnancy were captured at the recruitment interview and at up to 3 visits during pregnancy (20 …

Aim To identify cerebral palsy (CP) variables collected in CP registries from high‐income countries (HICs) and low‐ and middle‐income countries (LMICs) to assist with the development of a regional CP registry relevant to the African region. Method A systematic search of online databases to identify peer‐reviewed publications and grey literature about CP risk‐factor variables, using Ovid MEDLINE, Embase Ovid, CINAHL, and Google Scholar. Results A total of 197 studies published from global CP registries between 1990 and 2023 were identified. CP registries both from HICs and from LMICs included variables on prenatal CP risk factors. LMIC registries focused more on socioeconomic factors (the physical structure of the family home [21.1%, n = 8, in LMICs vs 1.7%, n = 2, in HICs]). Prenatal modifiable and non‐modifiable risk factors were emphasized in HICs. LMIC registries included more postnatal CP …

Biological psychiatry

BackgroundAutism is a heterogeneous neurodevelopmental condition accompanied by differences in brain connectivity. Structural connectivity in autism has mainly been investigated within the white matter. However, many genetic variants associated with autism highlight genes related to synaptogenesis and axonal guidance, thus also implicating differences in intrinsic (i.e., gray matter) connections in autism. Intrinsic connections may be assessed in vivo via so-called intrinsic global and local wiring costs.MethodsHere, we examined intrinsic global and local wiring costs in the brain of 359 individuals with autism and 279 healthy control participants ages 6 to 30 years from the EU-AIMS LEAP (Longitudinal European Autism Project). FreeSurfer was used to derive surface mesh representations to compute the estimated length of connections required to wire the brain within the gray matter. Vertexwise between-group …

BackgroundThe study aim was to determine whether associations of antenatal maternal anaemia with smaller corpus callosum, putamen, and caudate nucleus volumes previously described in children at age 2–3 years persist to age 6-7 years in the Drakenstein Child Health Study (DCHS).MethodsThis neuroimaging sub-study was nested within the DCHS, a South African population-based birth cohort. Pregnant women were enrolled (2012-2015) and mother-child dyads were followed prospectively. A sub-group of children had magnetic resonance imaging at 6-7 years of age (2018-2022). Mothers had haemoglobin measurements during pregnancy and a proportion of children were tested postnatally. Maternal anaemia (haemoglobin< 11g/dL) and child anaemia were classified using WHO and local guidelines. Linear modeling was used to investigate associations between antenatal maternal anaemia status, maternal haemoglobin concentrations, and regional child brain volumes. Models included potential confounders and were conducted with and without child anaemia to assess the relative roles of antenatal versus postnatal anaemia.ResultsOverall, 157 children (Mean [SD] age of 75.54 [4.77] months; 84 [53.50%] male) were born to mothers with antenatal haemoglobin data. The prevalence of maternal anaemia during pregnancy was 31.85%(50/157). In adjusted models, maternal anaemia status was associated with smaller volumes of the total corpus callosum (adjusted percentage difference,-6.77%; p= 0.003), left caudate nucleus (adjusted percentage difference,-5.98%, p= 0.005), and right caudate nucleus (adjusted percentage …

Journal of Cognition and Development

Understanding executive functions (EFs) development is of high value to global developmental science. Recent calls for a more inclusive and equitable developmental science argue that tasks and questionnaires that are developed using only a subset of the population are not likely to be appropriate for EFs measurement in global contexts unless explicitly tested . Here, we examined a task commonly used to assess EFs in Western populations in a non-Western sample of Jordanian children. We used the Hearts and Flowers (HF) task to examine (a) its value for assessing EFs development in Jordanian children, and (b) whether task performance was associated with socioeconomic variables and parent report of academic achievement, internalizing, and externalizing behaviors measured with the Arabic Child Behavior Checklist. We report data from N = 93 5.5–8.5 year-old Jordanian children. We found the task …

Inpainting has recently emerged as a valuable and interesting technology to employ in the analysis of medical imaging data, in particular brain MRI. A wide variety of methodologies for inpainting MRI have been proposed and demonstrated on tasks including anomaly detection.In this work we investigate the statistical relationship between inpainted brain structures and the amount of subject-specific conditioning information, i.e. the other areas of the image that are masked. In particular, we analyse the distribution of inpainting results when masking additional regions of the image, specifically the contra-lateral structure. This allows us to elucidate where in the brain the model is drawing information from, and in particular, what is the importance of hemispherical symmetry? Our experiments interrogate a diffusion inpainting model through analysing the inpainting of subcortical brain structures based on intensity and estimated area change. We demonstrate that some structures show a strong influence of symmetry in the conditioning of the inpainting process.

Imaging Neuroscience

Biophysical models of diffusion tailored to quantify gray matter microstructure are gathering increasing interest. The two-compartment Neurite EXchange Imaging (NEXI) model has been proposed recently to account for neurites, extra-cellular space, and exchange across the cell membrane. NEXI parameter estimation requires multi-shell multi-diffusion time data and has so far only been implemented experimentally on animal data collected on a preclinical magnetic resonance imaging (MRI) set-up. In this work, the translation of NEXI to the human cortex in vivo was achieved using a 3 T Connectom MRI system with 300 mT/m gradients, that enables the acquisition of a broad range of b-values (0 – 7.5 ms/µm²) with a window covering short to intermediate diffusion times (20 – 49 ms) suitable for the characteristic exchange times (10 – 50 ms). Microstructure estimates of four model variants: NEXI, NEXIdot (its …

Nature neuroscience

The human brain grows quickly during infancy and early childhood, but factors influencing brain maturation in this period remain poorly understood. To address this gap, we harmonized data from eight diverse cohorts, creating one of the largest pediatric neuroimaging datasets to date focused on birth to 6 years of age. We mapped the developmental trajectory of intracranial and subcortical volumes in ∼2,000 children and studied how sociodemographic factors and adverse birth outcomes influence brain structure and cognition. The amygdala was the first subcortical volume to mature, whereas the thalamus exhibited protracted development. Males had larger brain volumes than females, and children born preterm or with low birthweight showed catch-up growth with age. Socioeconomic factors exerted region- and time-specific effects. Regarding cognition, males scored lower than females; preterm birth affected all …

Psychoneuroendocrinology

BackgroundGestational diabetes mellitus (GDM) affects around 10% of pregnancies in the US and has been linked to neurodevelopmental sequalae in children. However, there is a paucity of studies investigating early life neural markers in GDM-exposed infants.MethodsThis study examined the association of GDM on relative EEG power among infants approximately 30.16 hours postnatal age among a diverse cohort of mother-infant dyads (45% Multiracial, 25% Black, 69% Hispanic or Latina). The final sample consisted of 101 healthy term-age infants (gestational age at birth Mage= 39.0 ± 0.95, 46.5% female), 44 with exposure to GDM.ResultsWe did not observe a main effect of GDM on infant relative EEG power. Our post-hoc analyses revealed a significant interaction effect between GDM and infant birth weight on relative EEG power in AS in fifteen frequency bands-electrode regions. In stratified analyses, we …

Network Neuroscience

In response to a growing interest in refining brain connectivity assessments, this study focuses on integrating white matter fibre-specific microstructural properties into structural connectomes. Spanning ages 8-19 years in a developmental sample, it explores age-related patterns of microstructure-informed network properties at both local and global scales. First the diffusion-weighted signal fraction associated with each tractography-reconstructed streamline was constructed. Subsequently, the Convex Optimization Modelling for Microstructure-Informed Tractography (COMMIT) approach was employed to generate microstructure-informed connectomes from diffusion MRI data. To complete the investigation, network characteristics within eight functionally defined networks (visual, somatomotor, dorsal attention, ventral attention, limbic, frontoparietal, default mode, and subcortical networks) were evaluated …

Wellcome Open Research

The term ‘executive functions’ (EFs) refers to a set of skills that support flexible control over thought and action. Classic EFs (working memory, inhibitory control, and cognitive flexibility) do not show measurable stable function until after the third year of life and continue to develop into early adulthood. However, even at the earliest ages, these EFs are shown to have value for predicting school readiness and academic achievement. They continue to have predictive value for success, mental health, and general well-being across the lifespan including in ageing populations. As such, understanding the developing brain and cognitive developmental dynamics that set the stage for the development of EFs, in the first three years of life, is crucial for developing programming that supports healthy EFs development. The goal of this manuscript is to describe the goals, hypotheses, participant populations, and methodology of the Khula Study. Khula is a multi-modal multi-site longitudinal birth cohort study designed to characterise emerging EFs in the first 1000 days of life in global majority settings. Most research to date has been conducted in highincome countries rather than low- and middle-income countries that comprise most of the world’s child population. We assert that understanding and supporting EF development has global importance, but this must be done with the understanding that EFs are skills that develop within the context of adaptation to one’s environment. As such, the Khula Study aims to understand which EF influences are common across cultures but also which are culture specific. We will address these questions by incorporating data …

Wellcome Open Research

Background In the UK, mortality incidence of residents in long-term care facilities (LTCFs) was high during the first two waves of the COVID-19 pandemic. Prior to the pandemic, mortality risk was greater amongst new LTCFs admissions compared to longer term residents. Following the re-opening of these facilities to new residents after the second wave of the pandemic, we hypothesised that this difference would be more pronounced. We aimed to establish whether this occurred by comparing mortality risk in new admissions with existing residents. Methods Data were accessed from the VIVALDI study, a prospective cohort study set up to investigate COVID-19 in English LTCFs. Residents aged over 65 were included and analysis performed over the Delta (16 th May 2021-19 th December 2021) and Omicron (19 th December 2021-31 st March 2022) waves of the pandemic. Classification into new and existing residents was based on presence in the LTCF before or after 24 th April 2021. Mixed effects Cox regression models were used, with separate hazard ratios associated for existing vs new residents estimated for each calendar month. Results 11,532 residents were observed during the Delta wave and 9,801 during the Omicron wave. Mortality hazard ratios for existing care home residents compared to new care home residents stabilised after September 2021, following a period of reduced risk between May (HR: 0.23 95% CI: 0.11-0.47) and August (HR: 0.37, CI:0.29-0.47 …

Wellcome Open Research

We present the genome assembly of the pennate diatom Epithemia pelagica strain UHM3201 (Ochrophyta; Bacillariophyceae; Rhopalodiales; Rhopalodiaceae) and that of its cyanobacterial endosymbiont (Chroococcales: Aphanothecaceae). The genome sequence of the diatom is 60.3 megabases in span, and the cyanobacterial genome has a length of 2.48 megabases. Most of the diatom nuclear genome assembly is scaffolded into 15 chromosomal pseudomolecules. The organelle genomes have also been assembled, with the mitochondrial genome 40.08 kilobases and the plastid genome 130.75 kilobases in length. A number of other prokaryote MAGs were also assembled.

Wellcome Open Research

We present a genome assembly from an individual Fragum whitleyi (a heart cockle; Mollusca; Bivalvia; Veneroida; Cardiidae). The genome sequence is 1224.6 megabases in span. Most of the assembly is scaffolded into 18 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 30.34 kilobases in length.

Wellcome Open Research

Background For more than a century, scientists have tried to find the key to causation of mental ill health in heredity and genetics. The difficulty of finding clear and actionable answers in our genes has not stopped them looking. This history offers important context to understanding mental health science today. Methods This article explores the main themes in research on genetics and inheritance in psychiatry from the second half of the nineteenth century to the present day, to address the question: what is the history of genetics as a causative explanation in mental health science? We take a critical historical approach to the literature, interrogating primary and secondary material for the light it brings to the research question, while considering the social and historical context. Results We begin with the statistics gathered in asylums and used to ‘prove’ the importance of heredity in mental ill health. We then move through early twentieth century Mendelian models of mental inheritance, the eugenics movement, the influence of social psychiatry, new classifications and techniques of the postwar era, the Human Genome Project and Genome Wide Association Studies (GWAS) and epigenetics. Setting these themes in historical context shows that this research was often popular because of wider social, political and cultural issues, which impacted the views of scientists just as they did those of policymakers, journalists and the general public. Conclusions We argue that attempting to unpick this complex history …

Wellcome Open Research

Background The Behaviour Change Intervention Ontology (BCIO) aims to improve the clarity, completeness and consistency of reporting within intervention descriptions and evidence synthesis. However, a recommended method for transparently annotating intervention evaluation reports using the BCIO does not currently exist. This study aimed to develop a data extraction template for annotating using the BCIO. Methods The BCIO data extraction template was developed in four stages: i) scoping review of papers citing component ontologies within the BCIO, ii) development of a draft template, iii) piloting and revising the template, and iv) dissemination and maintenance of the template. Results A prototype data extraction template using Microsoft Excel was developed based on BCIO annotations from 14 papers. The ‘BCIO data extraction template v1’ was produced following piloting and revision, incorporating a facility for user feedback. Discussion This data extraction template provides a single, accessible resource to extract all necessary characteristics of behaviour change intervention scenarios. It can be used to annotate the presence of BCIO entities for evidence synthesis, including systematic reviews. In the future, we will update this template based on feedback from the community, additions of newly published ontologies within the BCIO, and revisions to existing ontologies.

Wellcome Open Research

Background When studying the development of children through the preteen years into adolescence, it is often important to link features of their physical and mental health to the stage of puberty at the time. This is complex since individuals vary substantially in the ages at which they reach different pubertal milestones. Methods The Avon Longitudinal Study of Parents and Children (ALSPAC) is an ongoing longitudinal cohort study based in southwest England that recruited over 14000 women in pregnancy, with expected dates of delivery between April 1991 and December 1992. From 1999, information on puberty was collected using a number of different methods : (a) A series of annual questionnaires were administered when the index children were aged between eight and 17 years; these were mainly concerned with the physical changes associated with puberty; (b) identification of the age at peak height growth using the SITAR methodology; and (c) retrospective information from the girls on their age at onset of menstruation (menarche). Results The advantages and disadvantages of each method are discussed. Conclusions The data are available for analysis by interested researchers.

Wellcome Open Research

Background Health-focused research funders increasingly support multi-country research partnerships that study health, urban development and equity in global settings. To develop new knowledge that benefits society, these grants require researchers to integrate diverse knowledges and data, and to manage research-related aspects of coloniality, such as power imbalances and epistemic injustices. We conducted research to develop a transdisciplinary study proposal with partners in multiple middle and high income countries, aiming to embed equity into the methodology and funding model. Methods Parallel to literature review, we used participatory and social research methods to identify case study cities for our primary study and to inform our study design. We conducted semi-structured interviews with informed and consented sustainable urban development experts in the USA (n=23). We co-developed our research approach with our global advisory group (n=14) and conducted a participatory workshop (n=30) to identify case study sites, also informed by conversations with international academic experts in sustainable development (n=27). Results Through literature review we found that there is a need to study the contextual pre-conditions of urban transformation, the influence of coloniality on understandings of how cities can change and the failure of standard development practices to meet the needs of all residents and the planet. Through expert input and literature we found that decolonial and storytelling methods may help us show …

Wellcome Open Research

Background We have previously demonstrated that older residents of long-term care facilities (LTCF) in the UK show levels of anti-spike antibodies that are comparable to the general population following primary series and booster vaccination for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, data on the humoral response to other SARS-CoV-2 proteins associated with natural infection are scarce in this vulnerable population. Methods We measured quantitative levels of anti-nucleocapsid antibodies in blood samples taken from LTCF residents and staff after initial and repeat SARS-CoV-2 infections, between December 2020 and March 2023. Data on SARS-CoV-2 infection and vaccination were obtained through linkage to national datasets. Linear mixed effects models were used to investigate anti-nucleocapsid antibody levels, using log10 scale, in relation to time from most recent infection. This included evaluation of associations between repeat infection, staff/resident status, age, sex, Omicron infection and vaccination history and peak antibody level and slope of decline with time. Results We analysed 405 antibody observations from 220 residents and 396 observations from 215 staff. Repeat infection was associated with 8.5-fold (95%CI 4.9-14.8-fold) higher initial (peak) median anti-nucleocapsid antibody level, with steeper subsequent slope of decline. There were no significant differences in antibody level associated with resident (vs. staff) status or age, but Omicron infection was associated with 3.6-fold (95 …

Wellcome Open Research

Background Collecting and storing large number of sputum samples with a view to culturing these in the future requires an efficient initial handling method. We devised a modified sputum digestion and decontamination method that maximised storage capacity and Mycobacterium tuberculosis (M.tb) recovery from culture while minimising laboratory workload and risk of contamination. Methods We collected smear microscopy positive sputum samples from patients with pulmonary tuberculosis (TB). The sputum samples were split and processed using both the standard N-Acetyl-L-cysteine and sodium hydroxide (NALC-NaOH) method and our modified method before freezing and later culturing in BD BACTEC 960 Mycobacterium Growth Indicator Tubes (MGIT) system. We assessed the Time to Positivity (TPP) and Growth Unit (GU) data. Results We selected 22 sputum samples to compare two digestion and decontamination methods. The samples that underwent the modified method had longer TTP (p < 0.05) but similar GU in comparison to standard method. Overall, 1/22 samples failed to grow in MGIT after being processed by the modified method. We then applied the modified method to 348 sputum samples with Rifampicin resistance detected by GeneXpert MTB/RIF assay, which were frozen for between 1-25 months. The overall MGIT positive, negative, and contamination rate was 90.5%, 7.8%, and 1.7%, respectively. There was no significant difference in MGIT result when samples were grouped by duration of storage or positive smear grade. Conclusions Our modified method yielded acceptable M.tb recovery rate and low …

Wellcome Open Research

The term ‘executive functions’ (EFs) refers to a set of skills that support flexible control over thought and action. Classic EFs (working memory, inhibitory control, and cognitive flexibility) do not show measurable stable function until after the third year of life and continue to develop into early adulthood. However, even at the earliest ages, these EFs are shown to have value for predicting school readiness and academic achievement. They continue to have predictive value for success, mental health, and general well-being across the lifespan including in ageing populations. As such, understanding the developing brain and cognitive developmental dynamics that set the stage for the development of EFs, in the first three years of life, is crucial for developing programming that supports healthy EFs development. The goal of this manuscript is to describe the goals, hypotheses, participant populations, and methodology of the Khula Study. Khula is a multi-modal multi-site longitudinal birth cohort study designed to characterise emerging EFs in the first 1000 days of life in global majority settings. Most research to date has been conducted in highincome countries rather than low- and middle-income countries that comprise most of the world’s child population. We assert that understanding and supporting EF development has global importance, but this must be done with the understanding that EFs are skills that develop within the context of adaptation to one’s environment. As such, the Khula Study aims to understand which EF influences are common across cultures but also which are culture specific. We will address these questions by incorporating data …

Wellcome Open Research

Background When the Avon Longitudinal Study of Parents and Children (ALSPAC) was planned, it was assumed that the clinical obstetric data would be easily accessible from the newly developed National Health Service computerised ‘STORK’ system. Pilot studies, however, showed that, although fairly accurate in regard to aspects of labour and delivery, it was, at the time (1990-2), inadequate for identifying the full antenatal and postnatal details of clinical complications and treatments of the women in the Study. Methods A scheme was therefore developed to train research staff to find and abstract relevant details from clinical records onto proformas designed for the purpose. Extracting such data proved very time consuming (up to six hours for complicated pregnancies) and consequently expensive. Funding for the enterprise was obtained piecemeal using specific focussed grants to extract data for subsamples of the Study, including a random sample to serve as controls. Results To date, detailed records have been completed for 8369 pregnancies, and a further 5336 (13,705 in total) have complete details on specific prenatal areas, including serial measures of maternal blood pressure, proteinuria and weight. In this Data Note we describe the information abstracted from the obstetric medical records concerning the mother during pregnancy, labour, delivery and the first two weeks of the puerperium. Information abstracted relating to the fetus (including fetal monitoring, presentation, method of delivery) and neonate (signs of asphyxia, resuscitation, treatment and well-being) have been described in a further Data Note …

Wellcome Open Research

Background Research about anxiety, depression and psychosis and their treatments is often reported using inconsistent language, and different aspects of the overall research may be conducted in separate silos. This leads to challenges in evidence synthesis and slows down the development of more effective interventions to prevent and treat these conditions. To address these challenges, the Global Alliance for Living Evidence on aNxiety, depressiOn and pSychosis (GALENOS) Project is conducting a series of living systematic reviews about anxiety, depression and psychosis. An ontology (a classification and specification framework) for the domain of mental health is being created to organise and synthesise evidence within these reviews. It will also be an aid to synthesising evidence in the wider mental health field. Aim The aim of the study is to develop a Mental Health Ontology that includes entities with clear and unique labels and definitions to describe and synthesise evidence about mental health. Methods We will develop the Mental Health Ontology through six steps: (1) defining the ontology’s scope; (2) identifying, labelling and defining the ontology’s entities for the GALENOS living systematic reviews; (3) identifying and refining entities and their structure by drawing on existing classification frameworks; (4) refining entities via iterative stakeholder consultations regarding the ontology’s clarity and comprehensiveness; (5) formally specifying the relationships between entities in the Mental Health Ontology; and (6) making the ontology …

Wellcome Open Research

A strong and effective COVID-19 and future pandemic responses rely on global efforts to carry out surveillance of infections and emerging SARS-CoV-2 variants and to act accordingly in real time. Many countries in Southeast Asia lack capacity to determine the potential threat of new variants, or other emerging infections. Funded by Wellcome, the Southeast Asia initiative to combat SARS-CoV-2 variants (SEACOVARIANTS) consortium aims to develop and apply a multidisciplinary research platform in Southeast Asia (SEA) for rapid assessment of the biological significance of SARS-CoV-2 variants, thereby informing coordinated local, regional and global responses to the COVID-19 pandemic. Our proposal is delivered by the Vietnam and Thailand Wellcome Africa Asia Programmes, bringing together a multidisciplinary team in Indonesia, Thailand and Vietnam with partners in Singapore, the UK and the USA. Herein we outline five work packages to deliver strengthened regional scientific capacity that can be rapidly deployed for future outbreak responses.

Wellcome Open Research

Many people with bipolar disorder have disrupted circadian rhythms. This means that the timing of sleep and wake activities becomes out-of-sync with the standard 24-hour cycle. Circadian rhythms are strongly influenced by light levels and previous research suggests that people with bipolar disorder might have a heightened sensitivity to light, causing more circadian rhythm disruption, increasing the potential for triggering a mood switch into mania or depression. Lithium has been in clinical use for over 70 years and is acknowledged to be the most effective long-term treatment for bipolar disorder. Lithium has many reported actions in the body but the precise mechanism of action in bipolar disorder remains an active area of research. Central to this project is recent evidence that lithium may work by stabilising circadian rhythms of mood, cognition and rest/activity. Our primary hypothesis is that people with bipolar disorder have some pathophysiological change at the level of the retina which makes them hypersensitive to the visual and non-visual effects of light, and therefore more susceptible to circadian rhythm dysfunction. We additionally hypothesise that the mood-stabilising medication lithium is effective in bipolar disorder because it reduces this hypersensitivity, making individuals less vulnerable to light-induced circadian disruption. We will recruit 180 participants into the HELIOS-BD study. Over an 18-month period, we will assess visual and non-visual responses to light, as well as retinal microstructure, in people with bipolar disorder compared to healthy controls. Further, we will assess whether individuals with bipolar …

Wellcome Open Research

Background Schizophrenia is one of the most burdensome psychiatric disorders. Novel neuromodulatory techniques including cathodal transcranial direct current stimulation (c-tDCS) and continuous theta burst stimulation (cTBS) using repetitive transcranial magnetic stimulation (rTMS) are increasingly being used in alleviating the auditory verbal hallucinations that are persisting despite adequate antipsychotic treatment. Brain connectivity modulation by stimulating the left temporoparietal junction is thought to mediate these effects. The differential neurobiological mechanisms and efficacy of these two neuromodulation techniques are not known. We are unaware of any systematic studies that can guide clinicians in choosing between the two techniques. This protocol describes a parallel-arm, double-blind, randomized cross-over study to identify resting brain functional connectivity markers of response to cTBS and c-tDCS persistent auditory hallucinations to improve the efficacy of interventions. Methods Two hundred and ten consenting patients with schizophrenia with persistent auditory hallucinations will be randomly assigned to receive 15 days (30 sessions) of c-tDCS+sham-TBS or sham-tDCS+cTBS over the left temporoparietal region at three study centres. After a gap of 2-4 weeks, non-responders to the intervention will cross-over to the other arm. Clinical assessments, neurocognitive assessments, and multimodal investigations (magnetic resonance imaging, electroencephalography, heart rate variability, investigative transcranial magnetic stimulation-transcranial direct current stimulation, gene polymorphisms) will be conducted at …

Wellcome Open Research

Background Health-focused research funders increasingly support multi-country research partnerships that study health, urban development and equity in global settings. To develop new knowledge that benefits society, these grants require researchers to integrate diverse knowledges and data, and to manage research-related aspects of coloniality, such as power imbalances and epistemic injustices. We conducted research to develop a transdisciplinary study proposal with partners in multiple middle and high income countries, aiming to embed equity into the methodology and funding model. Methods Parallel to literature review, we used participatory and social research methods to identify case study cities for our primary study and to inform our study design. We conducted semi-structured interviews with informed and consented sustainable urban development experts in the USA (n=23). We co-developed our research approach with our global advisory group (n=14) and conducted a participatory workshop (n=30) to identify case study sites, also informed by conversations with international academic experts in sustainable development (n=27). Results Through literature review we found that there is a need to study the contextual pre-conditions of urban transformation, the influence of coloniality on understandings of how cities can change and the failure of standard development practices to meet the needs of all residents and the planet. Through expert input and literature we found that decolonial and storytelling methods may help us show …

Wellcome Open Research

Background Health-focused research funders increasingly support multi-country research partnerships that study health, urban development and equity in global settings. To develop new knowledge that benefits society, these grants require researchers to integrate diverse knowledges and data, and to manage research-related aspects of coloniality, such as power imbalances and epistemic injustices. We conducted research to develop a transdisciplinary study proposal with partners in multiple middle and high income countries, aiming to embed equity into the methodology and funding model. Methods Parallel to literature review, we used participatory and social research methods to identify case study cities for our primary study and to inform our study design. We conducted semi-structured interviews with informed and consented sustainable urban development experts in the USA (n=23). We co-developed our research approach with our global advisory group (n=14) and conducted a participatory workshop (n=30) to identify case study sites, also informed by conversations with international academic experts in sustainable development (n=27). Results Through literature review we found that there is a need to study the contextual pre-conditions of urban transformation, the influence of coloniality on understandings of how cities can change and the failure of standard development practices to meet the needs of all residents and the planet. Through expert input and literature we found that decolonial and storytelling methods may help us show …

Wellcome Open Research

Background When the Avon Longitudinal Study of Parents and Children (ALSPAC) was planned, it was assumed that the clinical obstetric data would be easily accessible from the newly developed National Health Service computerised ‘STORK’ system. Pilot studies, however, showed that, although fairly accurate in regard to aspects of labour and delivery, it was, at the time (1990-2), inadequate for identifying the full antenatal and postnatal details of clinical complications and treatments of the women in the Study. Methods A scheme was therefore developed to train research staff to find and abstract relevant details from clinical records onto proformas designed for the purpose. Extracting such data proved very time consuming (up to six hours for complicated pregnancies) and consequently expensive. Funding for the enterprise was obtained piecemeal using specific focussed grants to extract data for subsamples of the Study, including a random sample to serve as controls. Results To date, detailed records have been completed for 8369 pregnancies, and a further 5336 (13,705 in total) have complete details on specific prenatal areas, including serial measures of maternal blood pressure, proteinuria and weight. In this Data Note we describe the information abstracted from the obstetric medical records concerning the mother during pregnancy, labour, delivery and the first two weeks of the puerperium. Information abstracted relating to the fetus (including fetal monitoring, presentation, method of delivery) and neonate (signs of asphyxia, resuscitation, treatment and well-being) have been described in a further Data Note …

Wellcome Open Research

We present a genome assembly from an individual male Gadus morhua (the Atlantic cod; Chordata; Actinopteri; Gadiformes; Gadidae). The genome sequence is 669.9 megabases in span. Most of the assembly is scaffolded into 23 chromosomal pseudomolecules. Gene annotation of this assembly on Ensembl identified 23,515 protein coding genes.