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Children with prenatal alcohol exposure (PAE) may develop a range of neurological and behavioral deficits, including reading and language disorders. Studying the brain's structural connectivity and its relationship to pre-reading/reading skills in young children with PAE can help understand the roots of reading deficits associated with PAE. 363 diffusion MRI scans from 135 children (114 scans from 53 children with PAE) were collected between ages 3-7 years. Children completed NEPSY-II Phonological Processing and Speeded Naming to assess pre-reading skills at each scan. Structural brain network properties were assessed in 16 regions from both hemispheres using graph theory. Linear mixed models were used to account for repeated measures within participants. Children with PAE had significantly lower pre-reading scores than unexposed children, and significantly lower graph theory metrics across bilateral reading networks. Moreover, PAE significantly moderated the associations between Phonological Processing and global efficiency and nodal degree in the bilateral and left hemisphere reading networks, such that children with PAE had stronger associations than unexposed controls. No significant associations were found for Speeded Naming. Our results suggest that brain alterations may underlie early pre-reading difficulties in children with PAE., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Bisphenols and phthalates are two classes of endocrine-disrupting chemicals (EDCs) thought to influence weight and adiposity. Limited research has investigated their influence on maternal weight changes, and no prior work has examined maternal fat mass. We examined the associations between exposure to these chemicals during pregnancy and multiple maternal weight and fat mass outcomes., Methods: This study included a sample of 318 women enrolled in a Canadian prospective pregnancy cohort. Second trimester urinary concentrations of 2 bisphenols and 12 phthalate metabolites were quantified. Self-reported and measured maternal weights and measured skinfold thicknesses were used to calculate gestational weight gain, 3-months and 3- to 5-years postpartum weight retention, late pregnancy fat mass gain, total postpartum fat mass loss, and late postpartum fat mass retention. Adjusted robust regressions examined associations between chemicals and outcomes in the entire study population and sub-groups stratified by pre-pregnancy body mass index (BMI). Bayesian kernel machine regression examined chemical mixture effects., Results: Among women with underweight or normal pre-pregnancy BMIs, MBzP was negatively associated with weight retention at 3- to 5-years postpartum (B = -0.04, 95%CI: -0.07, -0.01). Among women with overweight or obese pre-pregnancy BMIs, MEHP and MMP were positively associated with weight retention at 3-months and 3- to 5-years postpartum, respectively (B's = 0.12 to 0.63, 95%CIs: 0.02, 1.07). DEHP metabolites and MCNP were positively associated with late pregnancy fat mass gain and late postpartum fat mass retention (B's = 0.04 to 0.18, 95%CIs: 0.001, 0.32). Further, the mixture of EDCs was positively associated with late pregnancy fat mass gain., Conclusion: In this cohort, pre-pregnancy BMI was a key determinant of the associations between second trimester exposure to bisphenols and phthalates and maternal weight changes and fat accumulation. Investigations of underlying physiological mechanisms, windows of susceptibility, and impacts on maternal and infant health are needed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The rates, yields, mechanisms and directionality of electron transfer (ET) are explored in twelve pairs of Rhodobacter (R.) sphaeroides and R. capsulatus mutant RCs designed to defeat ET from the excited primary donor (P*) to the A-side cofactors and re-direct ET to the normally inactive mirror-image B-side cofactors. In general, the R. sphaeroides variants have larger P + H B - yields (up to ∼90%) than their R. capsulatus analogs (up to ∼60%), where H B is the B-side bacteriopheophytin. Substitution of Tyr for Phe at L-polypeptide position L181 near B B primarily increases the contribution of fast P* → P + B B -  → P + H B - two-step ET, where B B is the "bridging" B-side bacteriochlorophyll. The second step (∼6-8 ps) is slower than the first (∼3-4 ps), unlike A-side two-step ET (P* → P + B A -  → P + H A - ) where the second step (∼1 ps) is faster than the first (∼3-4 ps) in the native RC. Substitutions near H B , at L185 (Leu, Trp or Arg) and at M-polypeptide site M133/131 (Thr, Val or Glu), strongly affect the contribution of slower (20-50 ps) P* → P + H B - one-step superexchange ET. Both ET mechanisms are effective in directing electrons "the wrong way" to H B and both compete with internal conversion of P* to the ground state (∼200 ps) and ET to the A-side cofactors. Collectively, the work demonstrates cooperative amino-acid control of rates, yields and mechanisms of ET in bacterial RCs and how A- vs. B-side charge separation can be tuned in both species., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Lymphatic filariasis (LF) has been targeted for elimination as a public health concern by 2030 with a goal to keep the prevalence of LF infections under the 1% threshold. While mass drug administration (MDA) is a primary strategy recommended by WHO, the use of insecticide treated nets (ITN) plays a crucial role as an alternative strategy when MDA cannot be used. In this paper, we use imitation dynamics to incorporate human behavior and voluntary use of ITN into the compartmental epidemiological model of LF transmission. We find the equilibrium states of the dynamics and the ITN usage as it depends on epidemiological parameters and the cost of ITNs. We investigate the conditions under which the voluntary use of ITNs can keep the LF prevalence under the 1% threshold. We found that when the cost of using the ITNs is about 10 5 smaller than the perceived cost of LF, then the voluntary use of ITNs will eliminate LF as a public health concern. Furthermore, when the ITNs are given away for free, our model predicts that over 80% of the population will use them which would eliminate LF completely in regions where Anopheles are the primary vectors., Competing Interests: Declaration of competing interest The authors declare no conflict of interest, (Copyright © 2024. Published by Elsevier Ltd.)

Early life antibiotic exposure may increase obesity risk. We investigated if prenatal, intrapartum, or childhood antibiotic use is associated with child zBMI score at 4 yrs of age. We included data from the Alberta Pregnancy Outcomes and Nutrition (APrON) study, a prospective cohort study, on maternal and child antibiotic exposure and clinic measures of height and weight at age 4 (n = 408). Prenatal and childhood antibiotic exposure was not associated with zBMI score. Maternal intrapartum antibiotic exposure was associated with a zBMI score increase of 0.12 (95 % CI; 0.04, 0.46) in children at 4 years of age compared to non-exposure intrapartum., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Raylene Reimer and Gerald Giesbrecht report financial support was provided by the Canadian Institutes of Health Research. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Competing interests The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Pre-reading abilities are predictive of later reading ability and can be assessed before reading begins. However, the neural correlates of pre-reading abilities in young children are not fully understood. To address this, we examined 246 datasets collected in an accelerated longitudinal design from 81 children aged 2-6 years (age = 4.6 ± 0.98 years, 47 males). Children completed pre-reading assessments (NEPSY-II Phonological Processing and Speeded Naming) and underwent a diffusion magnetic resonance imaging (MRI) scan to assess white matter connectivity. We defined a core neural network of reading and language regions based on prior literature, and structural connections within this network were assessed using graph theory analysis. Linear mixed models accounting for repeated measures were used to test associations between children's pre-reading performance and graph theory measures for the whole bilateral reading network and each hemisphere separately. Phonological Processing scores were positively associated with global efficiency, local efficiency, and clustering coefficient in the bilateral and right hemisphere networks, as well as local efficiency and clustering coefficient in the left hemisphere network. Our findings provide further evidence that structural neural correlates of Phonological Processing emerge in early childhood, before and during early reading instruction., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Schistosomiasis is a chronic and debilitating neglected tropical disease (NTD), second only to malaria as one of the most devastating parasitic diseases. Caused by a parasitic flatworm of the genus Schistosoma, infection occurs when skin comes in contact with contaminated freshwater that contains schistosome-hosting snails. The disease continues to be endemic in many regions of the Philippines, where it poses a significant public health challenge due to a lack of healthcare resources. In the Philippines, additional mammalian reservoirs for the S. japonicum parasite, especially bovines such as carabaos, also facilitate the spread of schistosomiasis. We extend existing compartment models to include human, snail, bovine, and free-living Schistosoma for a comprehensive look at the transmission dynamics of the disease. Sensitivity analysis of model parameters shows that the carabaos themselves can sustain the endemicity of schistosomiasis. Thus, we consider the control method of farming mechanization to avoid contaminated freshwater sources. We find that a reduction of contaminated water contacts by at least 77% will break the transmission cycle and eliminate the disease. However, reducing the contact by about 70% will still result in decrease of human schistosomiasis prevalence to under 1% in 15 years or less. Achieving such high reduction of contact rates could be a daunting task, especially in rural areas. Still, the potential to eliminate or at least reduce the schistosomiasis prevalence should be considered an additional benefit of mechanization efforts in the Philippines., Competing Interests: Declaration of Competing Interest The authors declare no competing interests, (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The maternal status of multiple micronutrients during pregnancy and postpartum and their potential associations with maternal health outcomes are largely undescribed., Objectives: This study aimed to examine associations between maternal iron and vitamin D status, individually and in combination, on depression symptoms in pregnant individuals., Methods: The Alberta Pregnancy Outcomes and Nutrition cohort study included pregnant participants and their children from Calgary and Edmonton, Canada. Iron biomarkers (serum ferritin [SF], soluble transferrin receptor, and hepcidin) were measured via immunoassays and vitamin D [25-hydroxyvitamin D3 (25(OH)D3) and 3-epi-25-hydoxyvitamin D3 (3-epi-25(OH)D3)] metabolites were quantifed using liquid chromatography with tandem mass spectroscopy. Four categories of maternal iron and vitamin D status during the second trimester were conceptualized using concentrations of SF and total 25-hydoxyvitamin D [25(OH)D], respectively. Maternal Edinburgh Postnatal Depression Scale (EPDS) scores during the third trimester (n = 1920) and 3 mo postpartum (n = 1822) were obtained., Results: Concentrations of maternal 25(OH)D3, 3-epi-25(OH)D3, and the ratio of both metabolites were significantly higher during the second trimester compared with their status at 3 mo postpartum. Higher second trimester maternal concentrations of SF (β: -0.8; 95% confidence interval [CI]: -1.5, -0.01), hepcidin (β: -0.5; 95% CI: -0.9, -0.2), and 25(OH)D3 (β: -0.01; 95% CI: -0.02, -0.004) predicted lower maternal EPDS scores during the third trimester. Pregnant individuals with a low iron (SF <15 μg/L) and replete vitamin D (25(OH)D ≥75 nmol/L) (β: 1.1; 95% CI: 0.03, 2.1) or low iron (SF <15 μg/L) and vitamin D (25(OH)D <75 nmol/L) (β: 2.2; 95% CI: 0.3, 4.2) status during midpregnancy had higher third trimester EPDS scores compared with those that were replete in both micronutrients., Conclusions: A higher midpregnancy maternal iron and vitamin D status, independently or in combination, predicted fewer maternal depression symptoms in the third trimester. Concentrations of maternal 25(OH)D3 and 3-epi-25(OH)D3 may be lower in the postpartum period compared with midpregnancy., Competing Interests: Conflict of interest The authors report no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Exposure to environmental chemicals has been linked to an increased risk of pregnancy-induced hypertension (PIH). This prospective cohort study examined the associations between PIH and maternal chemical exposure to four classes of chemicals (i.e., phthalates, bisphenols, perfluoroalkyl acids, non-essential metals and trace minerals). Participants included 420 pregnant women from the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort who had data available on diagnosed PIH and environmental chemical exposure. Twelve phthalate metabolites, two bisphenols, eight perfluoroalkyl acids and eleven non-essential metals or trace minerals were quantified in maternal urine or blood samples collected in the second trimester of pregnancy. Associations between the urinary and blood concentrations of these chemicals and PIH were assessed using multiple logistic and LASSO regression analyses in single- and multi-chemical exposure models, respectively. Thirty-five (8.3%) participants were diagnosed with PIH. In single chemical exposure models, two phthalate metabolites, mono-methyl phthalate (MMP) and monoethyl phthalate (MEP), three perfluoroalkyl acids, perfluoroheptanoic acid (PFHpA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA), and one metal, manganese, were associated with increased odds of PIH. The metabolites of di (2-ethylhexyl) phthalate (DEHP) and the molar sum of these metabolites, as well as antimony, displayed trend associations (p < 0.10). In multi-chemical exposure models using LASSO penalized regressions and double-LASSO regressions, MEP (AOR: 1.43, 95% CI: 1.09-1.88, p = 0.009) and PFNA (AOR: 2.03, 95% CI: 1.01-4.07, p = 0.04) were selected as the chemicals most highly associated with PIH. These findings suggest that maternal levels of phthalates and perfluoroalkyl acids may be associated with the diagnosis on PIH. Future research should consider both individual and multi-chemical exposures when examining predictors of PIH and other maternal cardiometabolic health disorders, such as preeclampsia, eclampsia, HELLP syndrome, and gestational diabetes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: On May 19, 2011, Calgary, Canada stopped fluoridating its drinking water. This prospective ecological study examined if maternal exposure to fluoride during pregnancy from drinking water that was fluoridated at the recommended level of 0.7 mg/L was associated with children's intelligence and executive function at 3-5 years of age., Methods: Participants were 616 maternal-child pairs enrolled in the Calgary cohort of the Alberta Pregnancy Outcomes and Nutrition (APrON) study between 2009 and 2012. Maternal-child pairs were classified as fully exposed to fluoridated drinking water throughout pregnancy (n = 295); exposed to fluoridated drinking water for at least part of the pregnancy plus an additional 90 days (n = 220); or not exposed to fluoridated drinking water during pregnancy plus the 90 days prior to pregnancy (n = 101). Children's Full Scale IQs were assessed using the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition: Canadian (WPPSI-IV CDN ). Children's executive functions were also assessed: working memory (WPPSI-IV CDN Working Memory Index), inhibitory control (Gift Delay, NEPSY-II Statue subtest), and cognitive flexibility (Boy-Girl Stroop, Dimensional Change Card Sort (DCCS))., Results: No associations were found between exposure group and Full Scale IQ. However, compared to no exposure, full exposure to fluoridated drinking water throughout pregnancy was associated with poorer performance on the Gift Delay (B = 0.53, 95 % CI = 0.31, 0.93). Sex-specific analyses revealed that girls in the fully exposed (AOR = 0.30, 95 % CI = 0.13, 0.74) and partially exposed groups (AOR = 0.42, 95 % CI = 0.17, 1.01) performed more poorly than girls in the not exposed group. Sex effects were also found on the DCCS; girls in the fully exposed (AOR = 0.34, 95 % CI = 0.14, 0.88) and partially exposed groups (AOR = 0.29, 95 % CI = 0.12, 0.73) performed more poorly., Conclusion: Maternal exposure to drinking water throughout pregnancy fluoridated at the level of 0.7 mg/L was associated with poorer inhibitory control and cognitive flexibility, particularly in girls, suggesting a possible need to reduce maternal fluoride exposure during pregnancy., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The coconut rhinoceros beetle (CRB), is one of the most damaging pests to coconut palms causing severe economic harm. Its expansion from Asia to the Pacific in the early 20th century has been stopped by virus control. However, a new haplotype CRB-Guam has recently escaped this control and invaded Guam, other Pacific islands, and has even established itself in the Western Hemisphere. In this paper, we present a compartmental ODE model of CRB population and control. We carefully consider CRB life stages and its interplay with coconut palms as well as "the green waste", the organic matters used by CRB for breeding sites. We calibrate and validate the model based on data count of CRBs trapped in Guam between 2008 and 2014. We derive the basic reproduction number determining the CRB population growth without any control measures. We also identify control levels required to eliminate CRBs. We show that, in the absence of viable virus control, the sanitation, i.e., the removal of the green waste is the most efficient way to control the population. Our model predicts that the sanitation efforts need to roughly double from the current levels to eliminate CRB from Guam. Furthermore, we demonstrate that a rare event like Typhoon Dolphin that hit Guam in 2015 can lead to a quick rise of the CRB population., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

While findings show that throughout development, there are child- and age-specific patterns of brain functioning, there is also evidence for significantly greater inter-individual response variability in young children relative to adults. It is currently unclear whether this increase in functional "typicality" (i.e., inter-individual similarity) is a developmental process that occurs across early childhood, and what changes in BOLD response may be driving changes in typicality. We collected fMRI data from 81 typically developing 4-8-year-old children during passive viewing of age-appropriate television clips and asked whether there is increasing typicality of brain response across this age range. We found that the "increasing typicality" hypothesis was supported across many regions engaged by passive viewing. Post hoc analyses showed that in a priori ROIs related to language and face processing, the strength of the group-average shared component of activity increased with age, with no concomitant decline in residual signal or change in spatial extent or variability. Together, this suggests that increasing inter-individual similarity of functional responses to audiovisual stimuli is an important feature of early childhood functional brain development., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Reduced atmospheric acid deposition has given rise to recovery from acidification - defined as increasing pH, acid neutralization capacity (ANC), or alkalinity in surface waters. Strong evidence of recovery has been reported across North America and Europe, driving chemical responses. The primary chemical responses identified in this review were increasing concentration and changing character of natural organic matter (NOM) towards predominantly hydrophobic nature. The concentration of NOM also influenced trace metal cycling as many browning surface waters also reported increases in Fe and Al. Further, climate change and other factors (e.g., changing land use) act in concert with reductions in atmospheric deposition to contribute to widespread browning and will have a more pronounced effect as deposition stabilizes. The observed water quality trends have presented challenges for drinking water treatment (e.g., increased chemical dosing, poor filter operations, formation of disinfection by-products) and many facilities may be under designed as a result. This comprehensive review has identified key research areas to be addressed, including 1) a need for comprehensive monitoring programs (e.g., larger timescales; consistency in measurements) to assess climate change impacts on recovery responses and NOM dynamics, and 2) a better understanding of drinking water treatment vulnerabilities and the transition towards robust treatment technologies and solutions that can adapt to climate change and other drivers of changing water quality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Yaws is a chronic infection caused by the bacterium Treponema pallidum susp. pertenue (TPE) that was thought to be an exclusive human pathogen but was recently found and confirmed in nonhuman primates. In this paper, we develop the first compartmental ODE model for TPE infection with treatment of wild olive baboons. We solve for disease-free and endemic equilibria and give conditions on local and global stability of the disease-free equilibrium. We calibrate the model based on the data from Lake Manyara National Park in Tanzania. We use the model to help the park managers devise an effective strategy for treatment. We show that an increasing treatment rate yields a decrease in disease prevalence. This indicates that TPE can be eliminated through intense management in closed population. Specifically, we show that if the whole population is treated at least once every 5-6 years, a disease-free equilibrium can be reached. Furthermore, we demonstrate that to see a substantial decrease of TPE infection to near-elimination levels within 15 years, the whole population needs to be treated every 2-3 years., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Bisphenol A (BPA) is a synthetic chemical used for the manufacturing of plastics, epoxy resin, and many personal care products. This ubiquitous endocrine disruptor is detectable in the urine of over 80% of North Americans. Although adverse neurodevelopmental outcomes have been observed in children with high gestational exposure to BPA, the effects of prenatal BPA on brain structure remain unclear. Here, using magnetic resonance imaging (MRI), we studied the associations of maternal BPA exposure with children's brain structure, as well as the impact of comparable BPA levels in a mouse model. Our human data showed that most maternal BPA exposure effects on brain volumes were small, with the largest effects observed in the opercular region of the inferior frontal gyrus (ρ = -0.2754), superior occipital gyrus (ρ = -0.2556), and postcentral gyrus (ρ = 0.2384). In mice, gestational exposure to an equivalent level of BPA (2.25 μg BPA/kg bw/day) induced structural alterations in brain regions including the superior olivary complex (SOC) and bed nucleus of stria terminalis (BNST) with larger effect sizes (1.07≤ Cohens d ≤ 1.53). Human (n = 87) and rodent (n = 8 each group) sample sizes, while small, are considered adequate to perform the primary endpoint analysis. Combined, these human and mouse data suggest that gestational exposure to low levels of BPA may have some impacts on the developing brain at the resolution of MRI., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: DMK is co-founder of Path Therapeutics which is focused on epilepsy drug discovery., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Despite advances in deep learning, robust medical image segmentation in the presence of artifacts, pathology, and other imaging shortcomings has remained a challenge. In this paper, we demonstrate that by synergistically marrying the unmatched strengths of high-level human knowledge (i.e., natural intelligence (NI)) with the capabilities of deep learning (DL) networks (i.e., artificial intelligence (AI)) in garnering intricate details, these challenges can be significantly overcome. Focusing on the object recognition task, we formulate an anatomy-guided deep learning object recognition approach named AAR-DL which combines an advanced anatomy-modeling strategy, model-based non-deep-learning object recognition, and deep learning object detection networks to achieve expert human-like performance., Methods: The AAR-DL approach consists of 4 key modules wherein prior knowledge (NI) is made use of judiciously at every stage. In the first module AAR-R, objects are recognized based on a previously created fuzzy anatomy model of the body region with all its organs following the automatic anatomy recognition (AAR) approach wherein high-level human anatomic knowledge is precisely codified. This module is purely model-based with no DL involvement. Although the AAR-R operation lacks accuracy, it is robust to artifacts and deviations (much like NI), and provides the much-needed anatomic guidance in the form of rough regions-of-interest (ROIs) for the following DL modules. The 2nd module DL-R makes use of the ROI information to limit the search region to just where each object is most likely to reside and performs DL-based detection of the 2D bounding boxes (BBs) in slices. The 2D BBs hug the shape of the 3D object much better than 3D BBs and their detection is feasible only due to anatomy guidance from AAR-R. In the 3rd module, the AAR model is deformed via the found 2D BBs providing refined model information which now embodies both NI and AI decisions. The refined AAR model more actively guides the 4th refined DL-R module to perform final object detection via DL. Anatomy knowledge is made use of in designing the DL networks wherein spatially sparse objects and non-sparse objects are handled differently to provide the required level of attention for each., Results: Utilizing 150 thoracic and 225 head and neck (H&N) computed tomography (CT) data sets of cancer patients undergoing routine radiation therapy planning, the recognition performance of the AAR-DL approach is evaluated on 10 thoracic and 16 H&N organs in comparison to pure model-based approach (AAR-R) and pure DL approach without anatomy guidance. Recognition accuracy is assessed via location error/ centroid distance error, scale or size error, and wall distance error. The results demonstrate how the errors are gradually and systematically reduced from the 1st module to the 4th module as high-level knowledge is infused via NI at various stages into the processing pipeline. This improvement is especially dramatic for sparse and artifact-prone challenging objects, achieving a location error over all objects of 4.4 mm and 4.3 mm for the two body regions, respectively. The pure DL approach failed on several very challenging sparse objects while AAR-DL achieved accurate recognition, almost matching human performance, showing the importance of anatomy guidance for robust operation. Anatomy guidance also reduces the time required for training DL networks considerably., Conclusions: (i) High-level anatomy guidance improves recognition performance of DL methods. (ii) This improvement is especially noteworthy for spatially sparse, low-contrast, inconspicuous, and artifact-prone objects. (iii) Once anatomy guidance is provided, 3D objects can be detected much more accurately via 2D BBs than 3D BBs and the 2D BBs represent object containment with much more specificity. (iv) Anatomy guidance brings stability and robustness to DL approaches for object localization. (v) The training time can be greatly reduced by making use of anatomy guidance., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2022. Published by Elsevier B.V.)

We study an eco-evolutionary dynamics in finite populations of two haploid asexually reproducing allelic types. We focus on the quasi-neutral case when individual types differ only in their intrinsic birth and death rates but have the same expected lifetime reproductive output. We assume that the population size can fluctuate stochastically. We solve the Kolmogorov forward equation in the population whose size fluctuates only minimally and show that the fixation probability is decreasing with the increasing turnover rate. We also show that when the mutant's turnover is small enough, selection favors the mutant replacing residents. Similarly, when the turnover is high enough, selection opposes the replacement. This basic result has previously been demonstrated numerically for the contact process and shown analytically for the Moran process; the current paper extends this analysis to provide an analytical proof for the contact process. We also demonstrate numerically that our results extend for general fluctuating populations and beyond the quasi-neutral case., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Preprocessing choices present a particular challenge for researchers working with functional magnetic resonance imaging (fMRI) data from young children. Steps which have been shown to be important for mitigating head motion, such as censoring and global signal regression (GSR), remain controversial, and benchmarking studies comparing preprocessing pipelines have been conducted using resting data from older participants who tend to move less than young children. Here, we conducted benchmarking of fMRI preprocessing steps in a population with high head-motion, children aged 4-8 years, leveraging a unique longitudinal, passive viewing fMRI dataset. We systematically investigated combinations of global signal regression (GSR), volume censoring, and ICA-AROMA. Pipelines were compared using previously established metrics of noise removal as well as metrics sensitive to recovery of individual differences (i.e., connectome fingerprinting), and stimulus-evoked responses (i.e., intersubject correlations; ISC). We found that: 1) the most efficacious pipeline for both noise removal and information recovery included censoring, GSR, bandpass filtering, and head motion parameter (HMP) regression, 2) ICA-AROMA performed similarly to HMP regression and did not obviate the need for censoring, 3) GSR had a minimal impact on connectome fingerprinting but improved ISC, and 4) the strictest censoring approaches reduced motion correlated edges but negatively impacted identifiability., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Guinea-worm disease (GWD) was thought to be almost eliminated in Chad when it reemerged in 2010. The disease now shows a peculiar pattern of spreading along Chari River and its tributaries, rather than clustering around a particular drinking water source. We create a mathematical model of GWD that includes the population dynamics of the parasite as well as the dynamics of its hosts (copepods, fish, humans, and domestic dogs). We calibrate our model based on data from the literature and validate it on the recent GWD annual incidence data from Chad. The effective reproduction number predicted by our model agrees well with the empirical value of roughly 1.25 derived directly from the data. Our model thus supports the hypothesis that the parasite now uses fish as intermediate transport hosts. We predict that GWD transmission can be most easily interrupted by avoiding eating uncooked fish and by burying the fish entrails to prevent transmission through dogs. Increasing the mortality of copepods and even partially containing infected dogs to limit their access to water sources is another important factor for GWD eradication., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Early childhood is an important period of sensory, motor, cognitive and socio-emotional maturation, yet relatively little is known about the brain changes specific to this period. Voxel-based morphometry (VBM) is a technique to estimate regional brain volumes from magnetic resonance (MR) images. The default VBM processing pipeline can be customized to increase accuracy of segmentation and normalization, yet the impact of customizations on analyses in young children are not clear. Here, we assessed the impact of different preprocessing steps on T1-weighted MR images from typically developing children in two separate cohorts. Data were processed with the Computational Anatomy Toolbox (CAT12), using seven different VBM pipelines with distinct combinations of tissue probability maps (TPMs) and DARTEL templates created using the Template-O-Matic, and CerebroMatic. The first cohort comprised female children aged 3.9-7.9 years (N = 62) and the second included boys and girls aged 2.7-8 years (N = 74). We found that pipelines differed significantly in their tendency to classify voxels as grey or white matter and the conclusions about some age effects were pipeline-dependent. Our study helps to both understand age-associations in grey and white matter volume across early childhood and elucidate the impact of VBM customization on brain volumes in this age range., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Poliomyelitis is a worldwide disease that has nearly been eradicated thanks to the Global Polio Eradication Initiative. Nevertheless, the disease is currently still endemic in three countries. In this paper, we incorporate the vaccination in a two age-class model of polio dynamics. Our main objective is to see whether mandatory vaccination policy is needed or if polio could be almost eradicated by a voluntary vaccination. We perform game theoretical analysis and compare the herd immunity vaccination levels with the Nash equilibrium vaccination levels. We show that the gap between two vaccination levels is too large. We conclude that the mandatory vaccination policy is therefore needed to achieve a complete eradication., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Previous research reports associations between prenatal exposure to phthalates and childhood behavior problems; however, the neural mechanisms that may underlie these associations are relatively unexplored., Objective: This study examined microstructural white matter as a possible mediator of the associations between prenatal phthalate exposure and behavior problems in preschool-aged children., Methods: Data are from a subsample of a prospective pregnancy cohort, the Alberta Pregnancy Outcomes and Nutrition (APrON) study (n = 76). Mother-child pairs were included if mothers provided a second trimester urine sample, if the child completed a successful magnetic resonance imaging (MRI) scan at age 3-5 years, and if the Child Behavior Checklist was completed within 6 months of the MRI scan. Molar sums of high (HMWP) and low molecular weight phthalates (LMWP) were calculated from levels in urine samples. Associations between prenatal phthalate concentrations, fractional anisotropy (FA) and mean diffusivity (MD) in 10 major white matter tracts, and preschool behavior problems were investigated., Results: Maternal prenatal phthalate concentrations were associated with MD of the right inferior fronto-occipital fasciculus (IFO), right pyramidal fibers, left and right uncinate fasciculus (UF), and FA of the left inferior longitudinal fasciculus (ILF). Mediation analyses showed that prenatal exposure to HMWP was indirectly associated with Internalizing (path ab = 0.09, CI .95  = 0.02, 0.20) and Externalizing Problems (path ab = 0.09, CI .95  = 0.01, 0.19) through MD of the right IFO, and to Internalizing Problems (path ab = 0.11, CI .95  = 0.01, 0.23) through MD of the right pyramidal fibers., Discussion: This study provides the first evidence of childhood neural correlates of prenatal phthalate exposure. Results suggest that prenatal phthalate exposure may be related to microstructural white matter in the IFO, pyramidal fibers, UF, and ILF. Further, MD of the right IFO and pyramidal fibers may transmit childhood risk for behavioral problems., Competing Interests: Declaration of competing interest CL's spouse is an employee of GE Healthcare. All other authors declare no actual or potential competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Structural and functional neuroimaging studies show language and reading processes are left-lateralized, and associated with a dispersed group of left brain regions. However, it is unclear when and how asymmetry of these regions emerges. We characterized the development of structural and functional asymmetry of the language network in 386 datasets from 117 healthy children (58 male) across early childhood (2-7.5 years). Structural asymmetry was investigated using diffusion tensor imaging (DTI) and manual delineation of the arcuate fasciculus. Functional connectivity asymmetry was calculated from seed regions in the inferior frontal gyrus (IFG) and middle temporal gyrus (MTG). We show that macrostructural asymmetry of the arcuate fasciculus is present by age 2 years, while leftward asymmetry of microstructure and functional connectivity with the IFG increases across the age range. This emerging microstructural and functional asymmetry likely underlie the development of language and reading skills during this time., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Recent work has suggested atypical neural reward responses in individuals with Autism Spectrum Disorder (ASD), particularly for social reinforcers. Less is known about neural responses to restricted interests and few studies have investigated response to rewards in a learning context. We investigated neurophysiological differences in reinforcement learning between adolescents with ASD and typically developing (TD) adolescents (27 ASD, 31 TD). FMRI was acquired during a learning task in which participants chose one of two doors to reveal an image outcome. Doors differed in their probability of showing liked and not-liked images, which were individualized for each participant. Participants chose the door paired with liked images, but not the door paired with not-liked images, significantly above chance and choice allocation did not differ between groups. Interestingly, participants with ASD made choices less consistent with their initial door preferences. We found a neural prediction-error response at the time of outcome in the ventromedial prefrontal and posterior cingulate cortices that did not differ between groups. Together, behavioural and neural findings suggest that learning with individual interest outcomes is not different between individuals with and without ASD, adding to our understanding of motivational aspects of ASD., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Artisanal and small-scale gold mining (ASGM) in Tanzania results in occupational exposures and environmental contamination to toxic chemical elements such as arsenic and mercury. Populations living in such areas may be exposed by various routes, and prenatal exposure to arsenic and mercury has been associated with adverse birth outcomes and developmental delays. The aim of this study was to determine if levels of arsenic and mercury differed among pregnant women living in areas with and without ASGM activities in Northern Tanzania. This cross-sectional study is part of the ongoing Mining and Health prospective longitudinal study. Spot urine samples and dried blood spots were collected at the antenatal health clinics from pregnant women (n = 1056) at 16-27 weeks gestation. Urine samples were analyzed for total arsenic (T-As) and dried blood spots were analyzed for total mercury (T-Hg). Women in the ASGM cohort had median T-As levels (9.4 μg/L; IQR: 4.9-15.1) and T-Hg levels (1.2 μg/L; IQR: 0.8-1.86) that were significantly higher than the median T-As levels (6.28 μg/L; IQR: 3.7-14.1) and T-Hg levels (0.66 μg/L; IQR: 0.3-1.2) of women in the non-ASGM cohort (Mann-Whitney U test, T-As: z = -9.881, p = 0.0005; T-Hg: z = -3.502, p < 0.0001). Among pregnant women from ASGM areas, 25% had urinary T-As and 75% had blood T-Hg above the established human biomonitoring reference values of 15 and 0.80 μg/L. In the ASGM cohort, lower maternal education and low socioeconomic status increased the odds of higher T-As levels by 20% (p < 0.05) and 10% (p < 0.05), respectively. Women involved in mining activities and those of low socioeconomic status had increased odds of higher T-Hg by 70% (p < 0.001) and 10% (p < 0.05), respectively. Arsenic and mercury concentrations among women in non-ASGM areas suggest exposure sources beyond ASGM activities that need to be identified. Arsenic and mercury levels in women in Tanzania are of public health concern and their association with adverse birth and child developmental outcomes will be examined in future studies on this cohort., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Contouring (segmentation) of Organs at Risk (OARs) in medical images is required for accurate radiation therapy (RT) planning. In current clinical practice, OAR contouring is performed with low levels of automation. Although several approaches have been proposed in the literature for improving automation, it is difficult to gain an understanding of how well these methods would perform in a realistic clinical setting. This is chiefly due to three key factors - small number of patient studies used for evaluation, lack of performance evaluation as a function of input image quality, and lack of precise anatomic definitions of OARs. In this paper, extending our previous body-wide Automatic Anatomy Recognition (AAR) framework to RT planning of OARs in the head and neck (H&N) and thoracic body regions, we present a methodology called AAR-RT to overcome some of these hurdles. AAR-RT follows AAR's 3-stage paradigm of model-building, object-recognition, and object-delineation. Model-building: Three key advances were made over AAR. (i) AAR-RT (like AAR) starts off with a computationally precise definition of the two body regions and all of their OARs. Ground truth delineations of OARs are then generated following these definitions strictly. We retrospectively gathered patient data sets and the associated contour data sets that have been created previously in routine clinical RT planning from our Radiation Oncology department and mended the contours to conform to these definitions. We then derived an Object Quality Score (OQS) for each OAR sample and an Image Quality Score (IQS) for each study, both on a 1-to-10 scale, based on quality grades assigned to each OAR sample following 9 key quality criteria. Only studies with high IQS and high OQS for all of their OARs were selected for model building. IQS and OQS were employed for evaluating AAR-RT's performance as a function of image/object quality. (ii) In place of the previous hand-crafted hierarchy for organizing OARs in AAR, we devised a method to find an optimal hierarchy for each body region. Optimality was based on minimizing object recognition error. (iii) In addition to the parent-to-child relationship encoded in the hierarchy in previous AAR, we developed a directed probability graph technique to further improve recognition accuracy by learning and encoding in the model "steady" relationships that may exist among OAR boundaries in the three orthogonal planes. Object-recognition: The two key improvements over the previous approach are (i) use of the optimal hierarchy for actual recognition of OARs in a given image, and (ii) refined recognition by making use of the trained probability graph. Object-delineation: We use a kNN classifier confined to the fuzzy object mask localized by the recognition step and then fit optimally the fuzzy mask to the kNN-derived voxel cluster to bring back shape constraint on the object. We evaluated AAR-RT on 205 thoracic and 298 H&N (total 503) studies, involving both planning and re-planning scans and a total of 21 organs (9 - thorax, 12 - H&N). The studies were gathered from two patient age groups for each gender - 40-59 years and 60-79 years. The number of 3D OAR samples analyzed from the two body regions was 4301. IQS and OQS tended to cluster at the two ends of the score scale. Accordingly, we considered two quality groups for each gender - good and poor. Good quality data sets typically had OQS ≥ 6 and had distortions, artifacts, pathology etc. in not more than 3 slices through the object. The number of model-worthy data sets used for training were 38 for thorax and 36 for H&N, and the remaining 479 studies were used for testing AAR-RT. Accordingly, we created 4 anatomy models, one each for: Thorax male (20 model-worthy data sets), Thorax female (18 model-worthy data sets), H&N male (20 model-worthy data sets), and H&N female (16 model-worthy data sets). On "good" cases, AAR-RT's recognition accuracy was within 2 voxels and delineation boundary distance was within ∼1 voxel. This was similar to the variability observed between two dosimetrists in manually contouring 5-6 OARs in each of 169 studies. On "poor" cases, AAR-RT's errors hovered around 5 voxels for recognition and 2 voxels for boundary distance. The performance was similar on planning and replanning cases, and there was no gender difference in performance. AAR-RT's recognition operation is much more robust than delineation. Understanding object and image quality and how they influence performance is crucial for devising effective object recognition and delineation algorithms. OQS seems to be more important than IQS in determining accuracy. Streak artifacts arising from dental implants and fillings and beam hardening from bone pose the greatest challenge to auto-contouring methods., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The light-harvesting 2 complex (LH2) of the purple phototrophic bacterium Rhodobacter sphaeroides is a highly efficient, light-harvesting antenna that allows growth under a wide-range of light intensities. In order to expand the spectral range of this antenna complex, we first used a series of competition assays to measure the capacity of the non-native pigments 3-acetyl chlorophyll (Chl) a, Chl d, Chl f or bacteriochlorophyll (BChl) b to replace native BChl a in the B800 binding site of LH2. We then adjusted the B800 site and systematically assessed the binding of non-native pigments. We find that Arg -10 of the LH2 β polypeptide plays a crucial role in binding specificity, by providing a hydrogen-bond to the 3-acetyl group of native and non-native pigments. Reconstituted LH2 complexes harbouring the series of (B)Chls were examined by transient absorption and steady-state fluorescence spectroscopies. Although slowed 10-fold to ~6 ps, energy transfer from Chl a to B850 BChl a remained highly efficient. We measured faster energy-transfer time constants for Chl d (3.5 ps) and Chl f (2.7 ps), which have red-shifted absorption maxima compared to Chl a. BChl b, red-shifted from the native BChl a, gave extremely rapid (≤0.1 ps) transfer. These results show that modified LH2 complexes, combined with engineered (B)Chl biosynthesis pathways in vivo, have potential for retaining high efficiency whilst acquiring increased spectral range., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: The derivation of quantitative information from images in a clinically practical way continues to face a major hurdle because of image segmentation challenges. This paper presents a novel approach, called automatic anatomy recognition-disease quantification (AAR-DQ), for disease quantification (DQ) on positron emission tomography/computed tomography (PET/CT) images. This approach explores how to decouple DQ methods from explicit dependence on object (e.g., organ) delineation through the use of only object recognition results from our recently developed automatic anatomy recognition (AAR) method to quantify disease burden., Method: The AAR-DQ process starts off with the AAR approach for modeling anatomy and automatically recognizing objects on low-dose CT images of PET/CT acquisitions. It incorporates novel aspects of model building that relate to finding an optimal disease map for each organ. The parameters of the disease map are estimated from a set of training image data sets including normal subjects and patients with metastatic cancer. The result of recognition for an object on a patient image is the location of a fuzzy model for the object which is optimally adjusted for the image. The model is used as a fuzzy mask on the PET image for estimating a fuzzy disease map for the specific patient and subsequently for quantifying disease based on this map. This process handles blur arising in PET images from partial volume effect entirely through accurate fuzzy mapping to account for heterogeneity and gradation of disease content at the voxel level without explicitly performing correction for the partial volume effect. Disease quantification is performed from the fuzzy disease map in terms of total lesion glycolysis (TLG) and standardized uptake value (SUV) statistics. We also demonstrate that the method of disease quantification is applicable even when the "object" of interest is recognized manually with a simple and quick action such as interactively specifying a 3D box ROI. Depending on the degree of automaticity for object and lesion recognition on PET/CT, DQ can be performed at the object level either semi-automatically (DQ-MO) or automatically (DQ-AO), or at the lesion level either semi-automatically (DQ-ML) or automatically., Results: We utilized 67 data sets in total: 16 normal data sets used for model building, and 20 phantom data sets plus 31 patient data sets (with various types of metastatic cancer) used for testing the three methods DQ-AO, DQ-MO, and DQ-ML. The parameters of the disease map were estimated using the leave-one-out strategy. The organs of focus were left and right lungs and liver, and the disease quantities measured were TLG, SUV Mean , and SUV Max . On phantom data sets, overall error for the three parameters were approximately 6%, 3%, and 0%, respectively, with TLG error varying from 2% for large "lesions" (37 mm diameter) to 37% for small "lesions" (10 mm diameter). On patient data sets, for non-conspicuous lesions, those overall errors were approximately 19%, 14% and 0%; for conspicuous lesions, these overall errors were approximately 9%, 7%, 0%, respectively, with errors in estimation being generally smaller for liver than for lungs, although without statistical significance., Conclusions: Accurate disease quantification on PET/CT images without performing explicit delineation of lesions is feasible following object recognition. Method DQ-MO generally yields more accurate results than DQ-AO although the difference is statistically not significant. Compared to current methods from the literature, almost all of which focus only on lesion-level DQ and not organ-level DQ, our results were comparable for large lesions and were superior for smaller lesions, with less demand on training data and computational resources. DQ-AO and even DQ-MO seem to have the potential for quantifying disease burden body-wide routinely via the AAR-DQ approach., (Copyright © 2018. Published by Elsevier B.V.)

Children acquire attention skills rapidly during early childhood as their brains undergo vast neural development. Attention is well studied in the adult brain, yet due to the challenges associated with scanning young children, investigations in early childhood are sparse. Here, we examined the relationship between age, attention and functional connectivity (FC) during passive viewing in multiple intrinsic connectivity networks (ICNs) in 60 typically developing girls between 4 and 7 years whose sustained, selective and executive attention skills were assessed. Visual, auditory, sensorimotor, default mode (DMN), dorsal attention (DAN), ventral attention (VAN), salience, and frontoparietal ICNs were identified via Independent Component Analysis and subjected to a dual regression. Individual spatial maps were regressed against age and attention skills, controlling for age. All ICNs except the VAN showed regions of increasing FC with age. Attention skills were associated with FC in distinct networks after controlling for age: selective attention positively related to FC in the DAN; sustained attention positively related to FC in visual and auditory ICNs; and executive attention positively related to FC in the DMN and visual ICN. These findings suggest distributed network integration across this age range and highlight how multiple ICNs contribute to attention skills in early childhood., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Brain alterations are associated with reading and language difficulties in older children, but little research has investigated relationships between early language skills and brain white matter structure during the preschool period. We studied 68 children aged 3.0-5.6 years who underwent diffusion tensor imaging and participated in assessments of Phonological Processing and Speeded Naming. Tract-based spatial statistics and tractography revealed relationships between Phonological Processing and diffusion parameters in bilateral ventral white matter pathways and the corpus callosum. Phonological Processing was positively correlated with fractional anisotropy and negatively correlated with mean diffusivity. The relationships observed in left ventral pathways are consistent with studies in older children, and demonstrate that structural markers for language performance are apparent as young as 3 years of age. Our findings in right hemisphere areas that are not as commonly found in adult studies suggest that young children rely on a widespread network for language processing that becomes more specialized with age., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Vitamin D is important in promoting healthy pregnancy and fetal development. We undertook this study to measure 25-hydroxyvitamin D in maternal and cord blood and to identify maternal factors related to vitamin D status in Calgary., Methods: Blood samples collected at the time of delivery from the Alberta Pregnancy Outcomes and Nutrition study cohort (ApronStudy.ca) participants were processed for plasma and assayed using liquid chromatography mass spectrometry methodology for 25(OH)D 3 ., Results: Ninety-two pairs of maternal and cord blood samples were obtained. The prevalence of 25(OH)D 3 insufficiency-25(OH)D 3 <75 nmol/L-was 38% and 80% in women and neonates, respectively. Vitamin D supplementation was the only clinical factor associated with 25(OH)D 3 sufficiency, and the odds of sufficiency were 3.75 (95% CI 1.00 to 14.07) higher for women and 5.27 (95% CI 1.37 to 20.27) when over 2000 IU/day were used., Conclusion: Using liquid chromatography mass spectrometry, we demonstrated a very high prevalence of vitamin D insufficiency in cord blood and that the use of high dose vitamin D was associated with greater odds of sufficiency in pregnant women and cord blood in Alberta., (Copyright © 2017 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Background: Perinatal maternal depression is a serious health concern with potential lasting negative consequences for children. Prenatal depression is associated with altered brain gray matter in children, though relations between postpartum depression and children's brains and the role of white matter are unclear., Methods: We studied 52 women who provided Edinburgh Postnatal Depression Scale (EPDS) scores during each trimester of pregnancy and at 3 months postpartum and their children who underwent magnetic resonance imaging at age 2.6 to 5.1 years. Associations between maternal depressive symptoms and magnetic resonance imaging measures of cortical thickness and white matter structure in the children were investigated., Results: Women's second trimester EPDS scores negatively correlated with children's cortical thickness in right inferior frontal and middle temporal regions and with radial and mean diffusivity in white matter emanating from the inferior frontal area. Cortical thickness, but not diffusivity, correlations survived correction for postpartum EPDS. Postpartum EPDS scores negatively correlated with children's right superior frontal cortical thickness and with diffusivity in white matter originating from that region, even after correcting for prenatal EPDS., Conclusions: Higher maternal depressive symptoms prenatally and postpartum are associated with altered gray matter structure in children; the observed white matter correlations appear to be uniquely related to the postpartum period. The reduced thickness and diffusivity suggest premature brain development in children exposed to higher maternal perinatal depressive symptoms. These results highlight the importance of ensuring optimal women's mental health throughout the perinatal period, because maternal depressive symptoms appear to increase children's vulnerability to nonoptimal brain development., (Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Bisphenol A (BPA) is associated with dysregulation of hypothalamic-pituitary-adrenal (HPA) axis activity in rodents, but evidence in humans is lacking., Objective: To determine whether BPA exposure during pregnancy is associated with dysregulation of the HPA-axis, we examined the association between urinary BPA concentrations and diurnal salivary cortisol in pregnant women. Secondary analyses investigated whether the association between BPA and cortisol was dependent on fetal sex., Methods: Diurnal salivary cortisol and urinary BPA were collected during pregnancy from 174 women in a longitudinal cohort study, the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Associations between BPA and daytime cortisol and the cortisol awakening response (CAR) were estimated using mixed models after adjusting for covariates., Results: Higher concentrations of total BPA uncorrected for urinary creatinine were associated with dysregulation of the daytime cortisol pattern, including reduced cortisol at waking, β=-.055, 95% CI (-.100, -.010) and a flatter daytime pattern, β=.014, 95% CI (.006, .022) and β=-.0007 95% CI (-.001, -.0002) for the linear and quadratic slopes, respectively. Effect sizes in creatinine corrected BPA models were slightly smaller. None of the interactions between fetal sex and BPA were significant (all 95% CI's include zero)., Conclusions: These findings provide the first human evidence suggesting that BPA exposure is associated with dysregulation of HPA-axis function during pregnancy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Developmental coordination disorder (DCD) and attention-deficit hyperactivity disorder (ADHD) are highly comorbid neurodevelopmental disorders; however, the neural mechanisms of this comorbidity are poorly understood. Previous research has demonstrated that children with DCD and ADHD have altered brain region communication, particularly within the motor network. The structure and function of the motor network in a typically developing brain exhibits hemispheric dominance. It is plausible that functional deficits observed in children with DCD and ADHD are associated with neurodevelopmental alterations in within- and between-hemisphere motor network functional connection strength that disrupt this hemispheric dominance. We used resting-state functional magnetic resonance imaging to examine functional connections of the left and right primary and sensory motor (SM1) cortices in children with DCD, ADHD and DCD + ADHD, relative to typically developing children. Our findings revealed that children with DCD, ADHD and DCD + ADHD exhibit atypical within- and between-hemisphere functional connection strength between SM1 and regions of the basal ganglia, as well as the cerebellum. Our findings further support the assertion that development of atypical motor network connections represents common and distinct neural mechanisms underlying DCD and ADHD. In children with DCD and DCD + ADHD (but not ADHD), a significant correlation was observed between clinical assessment of motor function and the strength of functional connections between right SM1 and anterior cingulate cortex, supplementary motor area, and regions involved in visuospatial processing. This latter finding suggests that behavioral phenotypes associated with atypical motor network development differ between individuals with DCD and those with ADHD.

Background: Mental disorders are one of the leading contributors to the global burden of disease. The Alberta Pregnancy Outcomes and Nutrition (APrON) study was initiated in 2008 to better understand perinatal environmental impacts on maternal mental health and child development., Aims: This pregnancy cohort was established to investigate the relationship between the maternal environment (e.g. nutritional status), maternal mental health status, birth outcomes, and child development. The purpose of this paper is to describe the creation of this longitudinal cohort, the data collection tools and procedures, and the background characteristics of the participants., Subjects: Participants were pregnant women age 16 or older, their infants and the biological fathers., Outcome Measures: For the women, data were collected during each trimester of pregnancy and at 3, 6, 12, 24, and 36months after the birth of their infant. Maternal measures included diet, stress, current mental and physical health, health history, and lifestyle. In addition, maternal biological samples (DNA, blood, urine, and spot breast milk samples) were banked. Paternal data included current mental and physical health, health history, lifestyle, and banked DNA samples. For infants, DNA and blood were collected as well as information on health, development and feeding behavior., Results: At the end of recruitment in 2012, the APrON cohort included 2140 women, 2172 infants, and 1417 biological fathers. Descriptive statistics of the cohort, and comparison of women who stayed in the study and those who dropped out are discussed., Conclusion: Findings from the longitudinal cohort may have important implications for health policy and clinical practice., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Vitamin D is critical for healthy pregnancies and normal fetal development. It is important to accurately ascertain vitamin D status in mothers and their newborns to establish the optimal vitamin D concentration during pregnancy. There are many different metabolites and epimers of vitamin D in peripheral blood and controversy as to the importance of epimers in estimating vitamin D status in maternal and infant health., Objectives: We undertook this study to measure 25-hydroxyvitamin D metabolites and epimers and their relations in maternal and cord blood and to evaluate the impact of the inclusion of epimers on assessing vitamin D status., Methods: We performed a substudy in a longitudinal cohort of pregnant women and their infants in Alberta, Canada [APrON (Alberta Pregnancy Outcomes and Nutrition) Study]. Maternal and cord blood plasma collected at the time of newborn delivery was stored at -70°C until testing and assayed for 25-hydroxyergocalciferol [25(OH)D2], 25-hydroxycholecalciferol [25(OH)D3], and 3-epi-25-hydroxycholecalciferol [3-epi-25(OH)D3] by using LC-tandem mass spectrometry. The effect of 3-epi-25(OH)D3 on estimates of vitamin D adequacy was explored by using McNemar's chi-square test at both recommended thresholds of 50 and 75 nmol/L., Results: Ninety-two pairs of maternal and cord blood samples were obtained. 3-Epi-25(OH)D3 was detected in all samples, comprising 6.0% and 7.8% of 25(OH)D3 in maternal and cord blood, respectively. Positive correlations were found between 25(OH)D3 and 3-epi-25(OH)D3 for both maternal and cord blood (maternal blood: r = 0.34, P = 0.01; cord blood: r = 0.44, P = 0.01). In addition, regression analysis showed a significant association between vitamin D supplementation and 3-epi-25(OH)D3 in maternal and cord blood (β: 0.423; 95% CI: 0.173, 0.672). When 3-epi-25(OH)D3 was not included in plasma vitamin D estimations, 38% of women and 80% of neonates were classified as having an insufficient concentration (<75 nmol/L); however, with 3-epi-25(OH)D3 included, the estimates of insufficiency were significantly lower: 33% and 73% for women and neonates, respectively., Conclusions: Using LC-MS/MS we showed the presence of 3-epi-25(OH)D3 in all samples of pregnant women and their cord blood, and when the 3-epimer was included in the estimation of status the prevalence of vitamin D insufficiency (<75 nmol/L) was significantly lower. Our data suggest that the high use of dietary supplements in this group of women contributes to 3-epi-25(OH)D3 concentrations in both maternal and cord blood. Further research on the role of the epimers in characterizing vitamin D status in pregnancy and infancy is imperative., (© 2016 American Society for Nutrition.)

Background: Emerging evidence from observational studies suggests that prenatal exposure to phthalates affects neurodevelopment in children., Objective: To conduct a systematic review of the existing literature on the association between urinary phthalate concentrations and children's neurodevelopment., Methods: We searched electronic bibliographic databases (MEDLINE, PubMed, EMBASE, PsycINFO, CINAHL, Global Health, CAB abstracts, and ERIC) (1910 to February 21st, 2014); reference lists of included articles, and conference abstracts (American Psychiatric Association, American Academy of Neurology, and Pediatric Academic Societies). Two independent reviewers screened abstracts and extracted data. We included original studies reporting on the association between prenatal or childhood urinary phthalate metabolites, and cognitive and behavioral outcomes (e.g., IQ scores, BASC-2 scores or equivalent) in children 0-12 years of age., Results: Of 2804 abstracts screened, 11 original articles met our criteria for inclusion., Conclusions: A systematic review of the literature supports the contention that prenatal exposure phthalates is associated with adverse cognitive and behavioral outcomes in children, including lower IQ, and problems with attention, hyperactivity, and poorer social communication. Further research characterizing the associations between specific phthalate metabolites and children's neurodevelopmental outcomes is needed to support the development of mitigation strategies and enhance the development of appropriate health policy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To assess the suitability of instrumented gait and balance measures for diagnosis and estimation of disease severity in PD., Methods: Each subject performed iTUG (instrumented Timed-Up-and-Go) and iSway (instrumented Sway) using the APDM(®) Mobility Lab. MDS-UPDRS parts II and III, a postural instability and gait disorder (PIGD) score, the mobility subscale of the PDQ-39, and Hoehn & Yahr stage were measured in the PD cohort. Two sets of gait and balance variables were defined by high correlation with diagnosis or disease severity and were evaluated using multiple linear and logistic regressions, ROC analyses, and t-tests., Results: 135 PD subjects and 66 age-matched controls were evaluated in this prospective cohort study. We found that both iTUG and iSway variables differentiated PD subjects from controls (area under the ROC curve was 0.82 and 0.75 respectively) and correlated with all PD severity measures (R(2) ranging from 0.18 to 0.61). Objective exam-based scores correlated more strongly with iTUG than iSway. The chosen set of iTUG variables was abnormal in very mild disease. Age and gender influenced gait and balance parameters and were therefore controlled in all analyses., Interpretation: Our study identified sets of iTUG and iSway variables which correlate with PD severity measures and differentiate PD subjects from controls. These gait and balance measures could potentially serve as markers of PD progression and are under evaluation for this purpose in the ongoing NIH Parkinson Disease Biomarker Program., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: The Infant Behavior Questionnaire-Revised (IBQ-R) is a widely used parent report measure of infant temperament. Items marked 'does not apply' (NA) are treated as missing data when calculating scale scores, but the effect of this practice on assessment of infant temperament has not been reported., Aims: To determine the effect of NA responses on assessment of infant temperament and to evaluate the remedy offered by several missing data strategies., Study Design: A prospective, community-based longitudinal cohort study., Subjects: 401 infants who were born>37 weeks of gestation., Outcome Measures: Mothers completed the short form of the IBQ-R when infants were 3-months and 6-months of age., Results: The rate of NA responses at the 3-month assessment was three times as high (22%) as the rate at six months (7%). Internal consistency was appreciably reduced and scale means were inflated in the presence of NA responses, especially at 3-months. The total number of NA items endorsed by individual parents was associated with infant age and parity. None of the missing data strategies completely eliminated problems related to NA responses but the Expectation Maximization algorithm greatly reduced these problems., Conclusions: The findings suggest that researchers should exercise caution when interpreting results obtained from infants at 3 months of age. Careful selection of scales, selecting a full length version of the IBQ-R, and use of a modern missing data technique may help to maintain the quality of data obtained from very young infants., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

To make Quantitative Radiology (QR) a reality in radiological practice, computerized body-wide Automatic Anatomy Recognition (AAR) becomes essential. With the goal of building a general AAR system that is not tied to any specific organ system, body region, or image modality, this paper presents an AAR methodology for localizing and delineating all major organs in different body regions based on fuzzy modeling ideas and a tight integration of fuzzy models with an Iterative Relative Fuzzy Connectedness (IRFC) delineation algorithm. The methodology consists of five main steps: (a) gathering image data for both building models and testing the AAR algorithms from patient image sets existing in our health system; (b) formulating precise definitions of each body region and organ and delineating them following these definitions; (c) building hierarchical fuzzy anatomy models of organs for each body region; (d) recognizing and locating organs in given images by employing the hierarchical models; and (e) delineating the organs following the hierarchy. In Step (c), we explicitly encode object size and positional relationships into the hierarchy and subsequently exploit this information in object recognition in Step (d) and delineation in Step (e). Modality-independent and dependent aspects are carefully separated in model encoding. At the model building stage, a learning process is carried out for rehearsing an optimal threshold-based object recognition method. The recognition process in Step (d) starts from large, well-defined objects and proceeds down the hierarchy in a global to local manner. A fuzzy model-based version of the IRFC algorithm is created by naturally integrating the fuzzy model constraints into the delineation algorithm. The AAR system is tested on three body regions - thorax (on CT), abdomen (on CT and MRI), and neck (on MRI and CT) - involving a total of over 35 organs and 130 data sets (the total used for model building and testing). The training and testing data sets are divided into equal size in all cases except for the neck. Overall the AAR method achieves a mean accuracy of about 2 voxels in localizing non-sparse blob-like objects and most sparse tubular objects. The delineation accuracy in terms of mean false positive and negative volume fractions is 2% and 8%, respectively, for non-sparse objects, and 5% and 15%, respectively, for sparse objects. The two object groups achieve mean boundary distance relative to ground truth of 0.9 and 1.5 voxels, respectively. Some sparse objects - venous system (in the thorax on CT), inferior vena cava (in the abdomen on CT), and mandible and naso-pharynx (in neck on MRI, but not on CT) - pose challenges at all levels, leading to poor recognition and/or delineation results. The AAR method fares quite favorably when compared with methods from the recent literature for liver, kidneys, and spleen on CT images. We conclude that separation of modality-independent from dependent aspects, organization of objects in a hierarchy, encoding of object relationship information explicitly into the hierarchy, optimal threshold-based recognition learning, and fuzzy model-based IRFC are effective concepts which allowed us to demonstrate the feasibility of a general AAR system that works in different body regions on a variety of organs and on different modalities., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Developmental coordination disorder (DCD) and attention deficit/hyperactivity disorder (ADHD) are prevalent childhood disorders that frequently co-occur. Evidence from neuroimaging research suggests that children with these disorders exhibit disruptions in motor circuitry, which could account for the high rate of co-occurrence. The primary objective of this study was to investigate the functional connections of the motor network in children with DCD and/or ADHD compared to typically developing controls, with the aim of identifying common neurophysiological substrates. Resting-state fMRI was performed on seven children with DCD, 21 with ADHD, 18 with DCD + ADHD and 23 controls. Resting-state connectivity of the primary motor cortex was compared between each group and controls, using age as a co-factor. Relative to controls, children with DCD and/or ADHD exhibited similar reductions in functional connectivity between the primary motor cortex and the bilateral inferior frontal gyri, right supramarginal gyrus, angular gyri, insular cortices, amygdala, putamen, and pallidum. In addition, children with DCD and/or ADHD exhibited different age-related patterns of connectivity, compared to controls. These findings suggest that children with DCD and/or ADHD exhibit disruptions in motor circuitry, which may contribute to problems with motor functioning and attention. Our results support the existence of common neurophysiological substrates underlying both motor and attention problems.

Purpose: Previous research suggests that having diabetes may complicate the passage from adolescence to adulthood. The aim of this study was to establish if young adults with Type 1 diabetes (T1DM) had delays in aspects of their psychosocial maturation compared with healthy controls (HC)., Methods: A cross-sectional study compared psychosocial maturation in individuals aged 18-25 years with T1DM to age-matched healthy controls. After obtaining consent, participants completed the following measures: Responsibility and Independence Scale for Adolescents (RISA; psychosocial maturity); Social Maturation Index (SMI, social maturity); Levenson's Locus of Control Scales (LOC, internal versus external locus of control) and the Social Density Grid (SDG, social network)., Results: In total, 160 subjects completed the study (97 T1DM, 63 HC). Participants included 101 females. No group differences were found on the RISA total score or the Responsibility or Independence Subscales of this measure. On the SMI, the proportion of subjects within each category (good, moderate or poor) was similar for each group. The overall number of social contacts identified on the SDG was similar for all groups; however, individuals with diabetes identified fewer friends within their social network that knew each other (F (2,160) = 3.28, p < .05). No significant group differences were found for LOC., Conclusions: Young adults with Type 1 diabetes did not show delayed psychosocial maturation when compared with healthy young adult controls.

Genes can be mutated by altering DNA content (base changes) or DNA length (insertions or deletions). Most in vitro directed evolution processes utilize nucleotide content changes to produce DNA libraries. We tested whether gain of function mutations could be identified using a mutagenic process that produced only nucleotide deletions. Short nucleotide stretches were deleted in a plasmid encoding lacZ, and screened for increased beta-galactosidase activity. Several mutations were found in the origin of replication that quantitatively and qualitatively altered plasmid behavior in vivo. Some mutations allowed co-residence of ColE1 plasmids in Escherichia coli, and implicate hairpin structures II and III of the ColE1 RNA primer as determinants of plasmid compatibility. Thus, useful and unexpected mutations can be found from libraries containing only deletions.

High-throughput phenotype screening and target identification have been combined in an effort to isolate antimicrobial, small-molecule therapeutics. This approach, developed by Brown and colleagues and reported in this issue, is a major technological advance for antimicrobial drug discovery.