Dilatation of Lateral Ventricles with Brain Volumes in Infants with 3D Transfontanelle US

Ultrasound (US) can be used to assess brain development in newborns, as MRI is challenging due to immobilization issues, and may require sedation. Dilatation of the lateral ventricles in the brain is a risk factor for poorer neurodevelopment outcomes in infants. Hence, 3D US has the ability to assess the volume of the lateral ventricles similar to clinically standard MRI, but manual segmentation is time consuming. The objective of this study is to develop an approach quantifying the ratio of lateral ventricular dilatation with respect to total brain volume using 3D US, which can assess the severity of macrocephaly. Automatic segmentation of the lateral ventricles is achieved with a multi-atlas deformable registration approach using locally linear correlation metrics for US-MRI fusion, followed by a refinement step using deformable mesh models. Total brain volume is estimated using a 3D ellipsoid modeling approach. Validation was performed on a cohort of 12 infants, ranging from 2 to 8.5 months old, where 3D US and MRI were used to compare brain volumes and segmented lateral ventricles. Automatically extracted volumes from 3D US show a high correlation and no statistically significant difference when compared to ground truth measurements. Differences in volume ratios was 6.0 +/- 4.8% compared to MRI, while lateral ventricular segmentation yielded a mean Dice coefficient of 70.8 +/- 3.6% and a mean absolute distance (MAD) of 0.88 +/- 0.2mm, demonstrating the clinical benefit of this tool in paediatric ultrasound

The Transition to Middle School is Associated with Changes in the Developmental Trajectory of ADHD Symptomatology in Young Adolescents with ADHD

The attention deficit hyperactivity disorder (ADHD) symptom presentation of young adolescents with ADHD was examined in association with the transition to middle school. This study used data collected in the Multimodal Treatment Study of ADHD, which included children between 7 and 9 years of age with a diagnosis of ADHD (n=258) and grade- and sex-matched controls (n=112). The trajectory of ADHD symptoms before, during, and after the transition to middle school was modeled using hierarchical linear modeling. A clear developmental reduction in ADHD symptomatology was observed for all three ADHD symptom domains. For young adolescents with ADHD, the transition to middle school was associated with a disruption in the developmental decline of inattention, hyperactivity, and impulsivity symptoms as measured by parent ratings. This effect was also observed for teacher ratings of inattention and hyperactivity. These results support the assertion that the environmental changes associated with transitioning to middle school coincide with a transient reversal in ADHD symptom decline among children with ADHD

Can the Success of HIV Scale-Up Advance the Global Chronic NCD Agenda?

Noncommunicable diseases (NCD) are the leading causes of death and disability worldwide but have received suboptimal attention and funding from the global health community. Although the first United Nations General Assembly Special Session (UNGASS) for NCD in 2011 aimed to stimulate donor funding and political action, only 1.3% of official development assistance for health was allocated to NCD in 2015, even less than in 2011. In stark contrast, the UNGASS on human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) in 2001 sparked billions of dollars in funding for HIV and enabled millions of HIV-infected individuals to access antiretroviral treatment. Using an existing analytic framework, we compare the global responses to the HIV and NCD epidemics and distill lessons from the HIV response that might be utilized to enhance the global NCD response. These include: 1) further educating and empowering communities and patients to increase demand for NCD services and to hold national governments accountable for establishing and achieving NCD targets; and 2) evidence to support the feasibility and effectiveness of large-scale NCD screening and treatment programs in low-resource settings. We conclude with a case study from Swaziland, a country that is making progress in confronting both HIV and NCD. In September 2011, the United Nations (UN) convened a UN General Assembly Special Session (UNGASS) on noncommunicable diseases (NCD). The event was the second UN High Level Meeting ever held for a health issue, following the successful UNGASS on human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) in 2001. Modeled after its predecessor, the 2011 meeting was intended to catalyze a response to what the World Health Organization (WHO) called an epidemic of “silent killers” that were the leading causes of death and disability worldwide, yet receive little attention from the global health community [1]. Looking back to the prior UNGASS on HIV/AIDS a decade earlier, the NCD meeting aspired to similar goals: rallying multisectoral and cross-national partnerships; stimulating robust donor funding; spurring ambitious targets and commitments on the part of national governments; and catalyzing rapid scale-up of NCD services in resource-limited settings [2]. Advocates highlighted similarities between chronic NCD and HIV/AIDS, including a stark mismatch between the burden of disease and available funding, and the need for programmatic innovation, continuity care, and health systems strengthening 3, 4 and 5. The UNGASS on NCD was successful at producing a Political Declaration to combat NCD [6], and many countries affirmed a commitment to ambitious NCD targets and to implementing evidence-based “best buys” 7 and 8. Yet 5 years later, the global NCD response has languished in what some have called an environment of “malignant neglect” [9]. Despite the fact that NCD account for 37% of disability-adjusted life years in low-income countries [10], only 1.3% of official development assistance for health was allocated to NCD in 2015 [11], a proportion that decreased between 2011 and 2015 [12]. Few resource-limited countries have operational national NCD strategies or adequate NCD services, awareness of and treatment-seeking rates for NCD have not improved [13], and the vast majority of people with cardiovascular disease, diabetes, cancer, and chronic respiratory disease remain undiagnosed and untreated 14 and 15. In contrast, in the years that followed the 2001 UNGASS, global spending on HIV increased by billions of dollars and the number of people initiating antiretroviral treatment (ART) in low- and middle-income countries soared from 400,000 in 2003 to nearly 17 million in 2015 [16]

Diffusion tensor imaging correlates with cytopathology in a rat model of neonatal hydrocephalus

<p>Abstract</p> <p>Background</p> <p>Diffusion tensor imaging (DTI) is a non-invasive MRI technique that has been used to quantify CNS abnormalities in various pathologic conditions. This study was designed to quantify the anisotropic diffusion properties in the brain of neonatal rats with hydrocephalus (HCP) and to investigate association between DTI measurements and cytopathology.</p> <p>Methods</p> <p>DTI data were acquired between postnatal day 7 (P7) and P12 in 12 rats with HCP induced at P2 and in 15 age-matched controls. Animals were euthanized at P11 or P22/P23 and brains were processed with immunohistochemistry for glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule (Iba-1), and luxol fast blue (LFB) to assess astrocytosis, microglial reactivity and degree of myelination, respectively.</p> <p>Results</p> <p>Hydrocephalic rats were consistently found to have an abnormally low (at corrected <it>p</it>-level of <0.05) fractional anisotropy (FA) value and an abnormally high mean diffusivity (MD) value in the cerebral cortex (CX), the corpus callosum (CC), and the internal capsule (IC). Immunohistochemical analysis demonstrated trends of increasing astrocyte and microglial reactivity in HCP rats at P11 that reached statistical significance at P22/P23. A trend toward reduced myelination in the HCP rats was also found at P22/P23. Correlation analysis at P11 for the CC demonstrated statistically significant correlations (or trends) between the DTI measurement (the decreased FA and increased MD values) and the GFAP or Iba-1 rankings. The immunohistochemical rankings in the IC at P22/P23 were also significantly correlated or demonstrated a trend with both FA and MD values.</p> <p>Conclusions</p> <p>This study demonstrates the feasibility of employing DTI on the brain in experimental hydrocephalus in neonatal rats and reveals impairments in multiple regions of interest in both grey and white matter. A strong correlation was found between the immunohistochemical results and the changes in anisotropic diffusion properties.</p

Parent-Reported Homework Problems in the MTA Study: Evidence for Sustained Improvement with Behavioral Treatment

Parent-report of child homework problems was examined as a treatment outcome variable in the MTA-Multimodal Treatment Study of Children with Attention-Deficit/ Hyperactivity Disorder (ADHD). Five hundred seventy-nine children ages 7.0 to 9.9 were randomly assigned to either medication management, behavioral treatment, combination treatment, or routine community care. Results showed that only participants who received behavioral treatment (behavioral and combined treatment) demonstrated sustained improvements in homework problems in comparison to routine community care. The magnitude of the sustained effect at the 10-month follow-up assessment was small to moderate for combined and behavioral treatment over routine community care (d=.37, .40, respectively). Parent ratings of initial ADHD symptom severity was the only variable found to moderate these effects

Decreased Brain Volume in Adults with Childhood Lead Exposure

Using magnetic resonance imaging to assess brain volumes, Kim Cecil and colleagues find that inner-city children with higher blood lead levels showed regions of decreased gray matter as adults

Infant Brain Atlases from Neonates to 1- and 2-Year-Olds

Background: Studies for infants are usually hindered by the insufficient image contrast, especially for neonates. Prior knowledge, in the form of atlas, can provide additional guidance for the data processing such as spatial normalization, label propagation, and tissue segmentation. Although it is highly desired, there is currently no such infant atlas which caters for all these applications. The reason may be largely due to the dramatic early brain development, image processing difficulties, and the need of a large sample size. Methodology: To this end, after several years of subject recruitment and data acquisition, we have collected a unique longitudinal dataset, involving 95 normal infants (56 males and 39 females) with MRI scanned at 3 ages, i.e., neonate, 1-yearold, and 2-year-old. State-of-the-art MR image segmentation and registration techniques were employed, to construct which include the templates (grayscale average images), tissue probability maps (TPMs), and brain parcellation maps (i.e., meaningful anatomical regions of interest) for each age group. In addition, the longitudinal correspondences between agespecific atlases were also obtained. Experiments of typical infant applications validated that the proposed atlas outperformed other atlases and is hence very useful for infant-related studies. Conclusions: We expect that the proposed infant 0–1–2 brain atlases would be significantly conducive to structural and functional studies of the infant brains. These atlases are publicly available in our website

Comparison of measures of marker informativeness for ancestry and admixture mapping

<p>Abstract</p> <p>Background</p> <p>Admixture mapping is a powerful gene mapping approach for an admixed population formed from ancestral populations with different allele frequencies. The power of this method relies on the ability of ancestry informative markers (AIMs) to infer ancestry along the chromosomes of admixed individuals. In this study, more than one million SNPs from HapMap databases and simulated data have been interrogated in admixed populations using various measures of ancestry informativeness: Fisher Information Content (FIC), Shannon Information Content (SIC), F statistics (F_ST), Informativeness for Assignment Measure (I_n), and the Absolute Allele Frequency Differences (delta, δ). The objectives are to compare these measures of informativeness to select SNP markers for ancestry inference, and to determine the accuracy of AIM panels selected by each measure in estimating the contributions of the ancestors to the admixed population.</p> <p>Results</p> <p>F_STand I_nhad the highest Spearman correlation and the best agreement as measured by Kappa statistics based on deciles. Although the different measures of marker informativeness performed comparably well, analyses based on the top 1 to 10% ranked informative markers of simulated data showed that I_nwas better in estimating ancestry for an admixed population.</p> <p>Conclusions</p> <p>Although millions of SNPs have been identified, only a small subset needs to be genotyped in order to accurately predict ancestry with a minimal error rate in a cost-effective manner. In this article, we compared various methods for selecting ancestry informative SNPs using simulations as well as SNP genotype data from samples of admixed populations and showed that the I_nmeasure estimates ancestry proportion (in an admixed population) with lower bias and mean square error.</p

Measuring universal health coverage based on an index of effective coverage of health services in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

© 2020 Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: Achieving universal health coverage (UHC) involves all people receiving the health services they need, of high quality, without experiencing financial hardship. Making progress towards UHC is a policy priority for both countries and global institutions, as highlighted by the agenda of the UN Sustainable Development Goals (SDGs) and WHO's Thirteenth General Programme of Work (GPW13). Measuring effective coverage at the health-system level is important for understanding whether health services are aligned with countries' health profiles and are of sufficient quality to produce health gains for populations of all ages. Methods: Based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we assessed UHC effective coverage for 204 countries and territories from 1990 to 2019. Drawing from a measurement framework developed through WHO's GPW13 consultation, we mapped 23 effective coverage indicators to a matrix representing health service types (eg, promotion, prevention, and treatment) and five population-age groups spanning from reproductive and newborn to older adults (≥65 years). Effective coverage indicators were based on intervention coverage or outcome-based measures such as mortality-to-incidence ratios to approximate access to quality care; outcome-based measures were transformed to values on a scale of 0–100 based on the 2·5th and 97·5th percentile of location-year values. We constructed the UHC effective coverage index by weighting each effective coverage indicator relative to its associated potential health gains, as measured by disability-adjusted life-years for each location-year and population-age group. For three tests of validity (content, known-groups, and convergent), UHC effective coverage index performance was generally better than that of other UHC service coverage indices from WHO (ie, the current metric for SDG indicator 3.8.1 on UHC service coverage), the World Bank, and GBD 2017. We quantified frontiers of UHC effective coverage performance on the basis of pooled health spending per capita, representing UHC effective coverage index levels achieved in 2019 relative to country-level government health spending, prepaid private expenditures, and development assistance for health. To assess current trajectories towards the GPW13 UHC billion target—1 billion more people benefiting from UHC by 2023—we estimated additional population equivalents with UHC effective coverage from 2018 to 2023. Findings: Globally, performance on the UHC effective coverage index improved from 45·8 (95% uncertainty interval 44·2–47·5) in 1990 to 60·3 (58·7–61·9) in 2019, yet country-level UHC effective coverage in 2019 still spanned from 95 or higher in Japan and Iceland to lower than 25 in Somalia and the Central African Republic. Since 2010, sub-Saharan Africa showed accelerated gains on the UHC effective coverage index (at an average increase of 2·6% [1·9–3·3] per year up to 2019); by contrast, most other GBD super-regions had slowed rates of progress in 2010–2019 relative to 1990–2010. Many countries showed lagging performance on effective coverage indicators for non-communicable diseases relative to those for communicable diseases and maternal and child health, despite non-communicable diseases accounting for a greater proportion of potential health gains in 2019, suggesting that many health systems are not keeping pace with the rising non-communicable disease burden and associated population health needs. In 2019, the UHC effective coverage index was associated with pooled health spending per capita (r=0·79), although countries across the development spectrum had much lower UHC effective coverage than is potentially achievable relative to their health spending. Under maximum efficiency of translating health spending into UHC effective coverage performance, countries would need to reach $1398 pooled health spending per capita (US$ adjusted for purchasing power parity) in order to achieve 80 on the UHC effective coverage index. From 2018 to 2023, an estimated 388·9 million (358·6–421·3) more population equivalents would have UHC effective coverage, falling well short of the GPW13 target of 1 billion more people benefiting from UHC during this time. Current projections point to an estimated 3·1 billion (3·0–3·2) population equivalents still lacking UHC effective coverage in 2023, with nearly a third (968·1 million [903·5–1040·3]) residing in south Asia. Interpretation: The present study demonstrates the utility of measuring effective coverage and its role in supporting improved health outcomes for all people—the ultimate goal of UHC and its achievement. Global ambitions to accelerate progress on UHC service coverage are increasingly unlikely unless concerted action on non-communicable diseases occurs and countries can better translate health spending into improved performance. Focusing on effective coverage and accounting for the world's evolving health needs lays the groundwork for better understanding how close—or how far—all populations are in benefiting from UHC. Funding: Bill & Melinda Gates Foundation