The Role of Multiple Birth and Birth Complications in the Association Between Assisted Reproductive Technology Conception and Autism Diagnosis.

In recent decades, the use of assisted reproductive technology (ART) has increased rapidly. To assess the relationship between ART and autism diagnosis, we linked California birth records from 2000 through 2016 with contemporaneous records from the National ART Surveillance System (NASS) and autism caseload records from California's Department of Developmental Services from 2000 through November 2019. All 95,149 birth records that were successfully linked to a NASS record, indicating an ART birth, were matched 1:1 using propensity scores to non-ART births. We calculated the hazard risk ratio (HRR) for autism diagnosis and the proportions of the relationship between ART conception and autism diagnosis mediated by multiple birth pregnancy and related birth complications. The HRR for autism diagnosis following ART compared with non-ART conception is 1.26 (95% CI, 1.17-1.35). Multiple birth, preterm birth, and Cesarean delivery jointly mediate 77.9% of the relationship between ART conception and autism diagnosis. Thus, increased use of single embryo transfer in the United States to reduce multiple births and related birth complications may be a strategy to address the risk of autism diagnosis among ART-conceived children.

Representational Similarity Analysis for Tracking Neural Correlates of Haptic Learning on a Multimodal Device.

A goal of wearable haptic devices has been to enable haptic communication, where individuals learn to map information typically processed visually or aurally to haptic cues via a process of cross-modal associative learning. Neural correlates have been used to evaluate haptic perception and may provide a more objective approach to assess association performance than more commonly used behavioral measures of performance. In this article, we examine Representational Similarity Analysis (RSA) of electroencephalography (EEG) as a framework to evaluate how the neural representation of multifeatured haptic cues changes with association training. We focus on the first phase of cross-modal associative learning, perception of multimodal cues. A participant learned to map phonemes to multimodal haptic cues, and EEG data were acquired before and after training to create neural representational spaces that were compared to theoretical models. Our perceptual model showed better correlations to the neural representational space before training, while the feature-based model showed better correlations with the post-training data. These results suggest that training may lead to a sharpening of the sensory response to haptic cues. Our results show promise that an EEG-RSA approach can capture a shift in the representational space of cues, as a means to track haptic learning.

Developmental Trajectories of Autism.

OBJECTIVES: The goal of this study was to describe the typical, longitudinal, developmental trajectories of communication and social functioning in individuals with autism spectrum disorder from childhood through adulthood and to determine the correlates of these trajectories. METHODS: Children with autism spectrum disorder who were born in California from 1992 through 2016 and enrolled with the California Department of Developmental Services were identified. Subjects with <4 evaluations in the database were excluded, resulting in a sample of 71 285 individuals. Score sequences were constructed based on evaluative items for communication and social functioning. Typical trajectories were identified using group-based latent trajectory modeling, and logistic regression was used to determine the odds of classification into a social adolescent decline trajectory by individual-, family-, and zip code-level factors. RESULTS: Six typical patterns of communication functioning and 7 typical patterns of social functioning were identified. Whereas the majority of autistic individuals exhibit improved communication functioning as they age, the majority of individuals exhibit steady social functioning. A small group of individuals (5.0%) exhibits high social functioning in childhood that declines in adolescence. Membership in this adolescent decline group is associated with maternal non-Hispanic white race and ethnicity, female sex, moderate levels of maternal education, lower zip code-level median home values and population density, and higher zip code-level inequality. CONCLUSIONS: Most autistic individuals show improved communication and social functioning as they age, but not all do. Trajectory group membership is correlated with socioeconomic status. Future research should investigate what drives these correlations.

A flexible design framework to design graded porous bone scaffolds with adjustable anisotropic properties.

Since the success of bone regenerative medicine depends on scaffold morphological and mechanical properties, numerous scaffolds designs have been proposed in the last decade, including graded structures that are suited to enhance tissue ingrowth. Most of these structures are based either on foams with a random pore definition, or on the periodic repetition of a unit cell (UC). These approaches are limited by the range of target porosities and obtained effective mechanical properties, and do not permit to easily generate a pore size gradient from the core to the periphery of the scaffold. In opposition, the objective of the present contribution is to propose a flexible design framework to generate various three-dimensional (3D) scaffolds structures including cylindrical graded scaffolds from the definition of a UC by making use of a non-periodic mapping. Conformal mappings are firstly used to generate graded circular cross-sections, while 3D structures are then obtained by stacking the cross-sections with or without a twist between different scaffold layers. The effective mechanical properties of different scaffold configurations are presented and compared using an energy-based efficient numerical method, pointing out the versatility of the design procedure to separately govern longitudinal and transverse anisotropic scaffold properties. Among these configurations, a helical structure exhibiting couplings between transverse and longitudinal properties is proposed and permits to extend the adaptability of the proposed framework. In order to investigate the capacity of common additive manufacturing techniques to fabricate the proposed structures, a subset of these configurations is elaborated using a standard SLA setup, and subjected to experimental mechanical testing. Despite observed geometric differences between the initial design and the actual obtained structures, the effective properties are satisfyingly predicted by the proposed computational method. Promising perspectives are offered concerning the design of self-fitting scaffolds with on-demand properties depending on the clinical application.

Human Metapneumovirus Induces IRF1 via TANK-Binding Kinase 1 and Type I IFN.

The innate immune and host-protective responses to viruses, such as the airway pathogen human metapneumovirus (HMPV), depend on interferons (IFNs) that is induced through TANK-binding kinase 1 (TBK1) and IFN regulatory factors (IRFs). The transcription factor IRF1 is important for host resistance against several viruses and has a key role in induction of IFN-λ at mucosal surfaces. In most cell types IRF1 is expressed at very low levels, but its mRNA is rapidly induced when the demand for IRF1 activity arises. Despite general recognition of the importance of IRF1 to antiviral responses, the molecular mechanisms by which IRF1 is regulated during viral infections are not well understood. Here we identify the serine/threonine kinase TBK1 and IFN-ß as critical regulators of IRF1 mRNA and protein levels in human monocyte-derived macrophages. We find that inhibition of TBK1 activity either by the semi-selective TBK1/IKKε inhibitor BX795 or by siRNA-mediated knockdown abrogates HMPV-induced expression of IRF1. Moreover, we show that canonical NF-κB signaling is involved in IRF1 induction and that the TBK1/IKKε inhibitor BX795, but not siTBK1 treatment, impairs HMPV-induced phosphorylation of the NF-κB subunit p65. At later time-points of the infection, IRF1 expression depended heavily on IFN-ß-mediated signaling via the IFNAR-STAT1 pathway. Hence, our results suggest that TBK1 activation and TBK1/IKKε-mediated phosphorylation of the NF-κB subunit p65 control transcription of IRF1. Our study identifies a novel mechanism for IRF1 induction in response to viral infection of human macrophages that could be relevant not only to defense against HMPV, but also to other viral, bacterial and fungal pathogens.

The social patterning of autism diagnoses reversed in California between 1992 and 2018.

As rates of autism diagnosis increased dramatically over the past number of decades, prevalence rates were generally highest among Whites and among those of higher socioeconomic status (SES). Using a unique, population-level dataset, we find that rates of autism diagnosis continued to be on the rise in recent years, but who is diagnosed changed during the study period. Our data consist of birth records of all 13,272,573 children born in the state of California in 1992 through 2016 linked to autism caseload records for January 1992 through November 2019 from California's Department of Developmental Services. California's diagnosed autism incidence rate rose from 0.49 per 1,000 3-6 y olds in 1998 to 3.49 per 1,000 3-6 y olds in 2018, a 612% increase. However, diagnosed incidence rates did not rise uniformly across sociodemographic groups. By 2018, children of Black and Asian mothers were diagnosed at higher rates than children of non-Hispanic White mothers. Furthermore, among children of non-Hispanic White and Asian mothers, children of lower SES were diagnosed at higher rates than children of higher SES. These changes align with sociological theories of health disparities and contain important clues for more fully understanding the autism epidemic.

From Lead Exposure in Early Childhood to Adolescent Health: A Chicago Birth Cohort.

OBJECTIVES: To assess the relationships between childhood lead exposure and 3 domains of later adolescent health: mental, physical, and behavioral. METHODS: We followed a random sample of birth cohort members from the Project on Human Development in Chicago Neighborhoods, recruited in 1995 to 1997, to age 17 years and matched to childhood blood test results from the Department of Public Health. We used ordinary least squares regression, coarsened exact matching, and instrumental variables to assess the relationship between average blood lead levels in childhood and impulsivity, anxiety or depression, and body mass index in adolescence. All models adjusted for relevant individual, household, and neighborhood characteristics. RESULTS: After adjustment, a 1 microgram per deciliter increase in average childhood blood lead level significantly predicts 0.06 (95% confidence interval [CI] = 0.01, 0.12) and 0.09 (95% CI = 0.03, 0.16) SD increases and a 0.37 (95% CI = 0.11, 0.64) point increase in adolescent impulsivity, anxiety or depression, and body mass index, respectively, following ordinary least squares regression. Results following matching and instrumental variable strategies are very similar. CONCLUSIONS: Childhood lead exposure undermines adolescent well-being, with implications for the persistence of racial and class inequalities, considering structural patterns of initial exposure.

Directional acuity of whole-body perturbations during standing balance.

The ability to perceive the direction of whole-body motion during standing may be critical to maintaining balance and preventing a fall. Our first goal was to quantify kinesthetic perception of whole-body motion by estimating directional acuity thresholds of support-surface perturbations during standing. The directional acuity threshold to lateral deviations in backward support-surface motion in healthy, young adults was quantified as 9.5±2.4° using the psychometric method (n=25 subjects). However, inherent limitations in the psychometric method, such as a large number of required trials and the predetermined stimulus set, may preclude wider use of this method in clinical populations. Our second goal was to validate an adaptive algorithm known as parameter estimation by sequential testing (PEST) as an alternative threshold estimation technique to minimize the required trial count without predetermined knowledge of the relevant stimulus space. The directional acuity threshold was estimated at 11.7±3.8° from the PEST method (n=11 of 25 subjects, psychometric threshold=10.1±3.1°) using only one-third the number of trials compared to the psychometric method. Furthermore, PEST estimates of the direction acuity threshold were highly correlated with the psychometric estimates across subjects (r=0.93) suggesting that both methods provide comparable estimates of the perceptual threshold. Computational modeling of both techniques revealed similar variance in the estimated thresholds across simulations of about 1°. Our results suggest that the PEST algorithm can be used to more quickly quantify whole-body directional acuity during standing in individuals with balance impairments.

Short and long interpregnancy intervals: correlates and variations by pregnancy timing among U.S. women.

CONTEXT: Short and long interpregnancy intervals are associated with adverse health outcomes. Little is known about the correlates of short and long interpregnancy intervals in the general population, and whether correlates vary by pregnancy intention. METHODS: Data on 10,236 pregnancies following a live birth were drawn from the 1995, 2002 and 2006-2010 waves of the National Survey of Family Growth. Logistic regression was used to assess characteristics associated with women's reporting short interpregnancy intervals (less than 12 months) and long intervals (greater than 60 months). Analyses were stratified by whether women considered their pregnancies well timed or mistimed. RESULTS: Thirty-one percent of pregnancies following short intervals and 47% following long intervals were well timed. Among well-timed pregnancies only, the odds of short intervals were elevated if women had been 35 or older, rather than aged 20-29, at last pregnancy (odds ratio, 2.3); if their prior infant had died (10.6); or if they had wanted their prior pregnancy sooner than it had occurred (2.2). Overall, the odds of long intervals were higher among minority groups than among whites (1.4-1.6) and were lower among women who had been 30 or older at prior pregnancy than among those who had been in their 20s (0.1-0.5); they increased with level of family income. Correlates of long intervals generally varied little by intention. CONCLUSIONS: Although the majority of pregnancies at short intervals are unintended, specific subsets of women have elevated odds of intending short interpregnancy intervals.

Deformation mechanisms of plasticized starch materials.

The aim of this paper is to understand the influence of plasticizer and plasticizer amount on the mechanical and deformation behaviors of plasticized starch. Glycerol, sorbitol and mannitol have been used as plasticizers. After extrusion of the various samples, dynamic mechanical analyses and video-controlled tensile tests have been performed. It was found that the nature of plasticizer, its amount as well as the aging of the material has an impact on the involved deformation mechanism. The variations of volume deformation could be explained by an antiplasticization effect (low plasticizer amount), a phase-separation phenomenon (excess of plasticizer) and/or by the retrogradation of starch.

Pressure impact of autoclave treatment on water sorption and pectin composition of flax cellulosic-fibres.

The tensile properties of flax fibres might permit them to be used in composites as reinforcement in organic resin, as long as their mechanical properties are reproducible and their water sorption are reduced. In this study, to minimise the variability of mechanical properties, several samples of flax fibres were blended as a non-woven fabric. In order to reduce the water absorption of this non-woven technical fibres, an autoclave treatment was performed which was expected to remove the pectins and then to reduce the water sorption on their negative charges. The impact of autoclave pressure (0.5, 1 and 2 bars) on water sorption was investigated by using a gravimetric static equilibrium method. The Park model based on the three sorption modes: Langmuir, Henry's law and clustering, was successfully used to simulate the experimental sorption data. The lowest pressure treatments impacted only the Langmuir contribution while the 2 bar autoclave-treatment positively impacted the water resistance in the core of fibres by reducing Henry's absorption rate. This was shown to be related to the chemical modifications at the surface and in the core of fibres. A schematic model is presented relating the water sorption and the pectic composition of the fabric.

Six developmental trajectories characterize children with autism.

OBJECTIVE: The goal of this study was to describe the typical longitudinal developmental trajectories of social and communication functioning in children with autism and to determine the correlates of these trajectories. METHODS: Children with autism who were born in California from 1992 through 2001 and enrolled with the California Department of Developmental Services were identified. Subjects with <4 evaluations present in the database were excluded, resulting in a sample of 6975 children aged 2 to 14 years. Score sequences were constructed based on 9 evaluative items for social, communication, and repetitive behavior functioning. Typical trajectories were identified by using group-based latent trajectory modeling, and multinomial logistic regression models were used to determine the odds of classification within each trajectory varied by individual and family-level factors. RESULTS: Six typical patterns of social, communication, and repetitive behavior functioning were identified. These trajectories displayed significant heterogeneity in developmental pathways, and children whose symptoms were least severe at first diagnosis tended to improve more rapidly than those severely affected. One group of ∼10% of children experienced rapid gains, moving from severely affected to high functioning. Socioeconomic factors were correlated with trajectory outcomes; children with non-Hispanic, white, well-educated mothers were more likely to be high functioning, and minority children with less-educated mothers or intellectual disabilities were very unlikely to experience rapid gains. CONCLUSIONS: Children with autism have heterogeneous developmental pathways. One group of children evidenced remarkable developmental change over time. Understanding what drives these outcomes is thus critical.

Pectinase treatments on technical fibres of flax: Effects on water sorption and mechanical properties.

This study is focused on enzymatically upgrading the functional properties of flax fibres. Green flax fibres were treated with a polygalacturonase and a pectate lyase (PaL) and their properties were compared with dew-retted fibres. Morphological observations, vapour-sorption analyses and mechanical measurements showed that PaL-treatment was able not only to mime retting in terms of bundle division, but also to improve the mechanical properties of technical fibres. Conversely, these properties were shifted down after the polygalacturonase treatment, mainly due to the presence of contaminating glycanases. At the level of the elementary fibres, nanoindentation data indicated the highest stiffness of the secondary wall for PaL-treated fibres. The tensile properties exhibited equal, but moderate values of the Young's modulus (∼37±14GPa) and breaking strength (∼650±300MPa) for retted and PaL-treated fibres; we hypothesize an impact of the growth conditions on the fibre chemical structure with an excess of matrix pectins compared to the amount of glucomannan coating the cellulose microfibrils.

Effect of chemical treatments on water sorption and mechanical properties of flax fibres.

In this work, in order to improve the adhesion between a polyester matrix (unsaturated polyester resin) and flax fibres (Linum usitatissimum L.) and to increase their moisture resistance, chemical surface treatments have been used. These different treatments were performed with maleic anhydride (MA), acetic anhydride (Ac), silane (Si) and styrene (S). The modified flax fibres were characterized by means of infrared spectroscopy and surface energy analysis. The effect of these treatments on water sorption was investigated by using a gravimetric static equilibrium method. Water sorption isotherms were derived from kinetic data. The Park model based on the three sorption modes: Langmuir, Henry's law and clustering, was successfully used to simulate the experimental sorption data. It was found that the (Ac) and particularly (S) treatments reduced overall water uptake of flax fibres. We show that tensile modulus, breaking strength and breaking strain depend on the chemical treatment used.

Phospholipase A2 action on planar lipid bilayers generates a small, transitory current that is voltage independent.

Addition of either bee venom or Trimeresurus flavoviridis phospholipase A2 (PLA2) to the solution bathing the front side of a voltage-clamped, planar lipid bilayer consistently produced a transitory current lasting approximately 100 s. This current is consistent with anions moving through the membrane to the rear side. The peak current is independent of holding potential. PLA2 activity on phospholipid membranes not only produced a current but also led to membrane rupture within 300 s. The current depends on Ca2+ and lipid type. Addition of PLA2 in the absence of Ca2+ or to membranes made of nonsubstrate lipids (e.g., glycerol monooleate or lysophosphatidylcholine) produced no current and did not break the bilayer. Peak current height, signal decay time, and time to membrane rupture all depended on PLA2 dose, whereas total charge produced was constant. This current does not flow through ion channels because there are no channels present and the current is not voltage dependent. The evidence is consistent with the hypothesis that the current is generated by the movement of ionized fatty acid produced by PLA2 action. These results demonstrate a simple method to measure enzyme activity in the presence of different substrates and varied environmental conditions.

Phospholipase A2-evoked destabilization of planar lipid membranes.

The ability of phospholipase A2 (PLA2) to enhance the flux of charged molecules across a planar lipid bilayer was examined. Within 300 s of adding PLA2, the membrane destabilized, with transient currents and eventual failure of membrane integrity. This effect was blocked by removal of free Ca2+ (with EGTA) or by substitution of normal phospholipids with non-substrate lipids, indicating specificity of PLA2 activity. PLA2 may similarly destabilize plasma membranes, allowing for the movement of molecules down their concentration gradients. PLA2, which is activated by cerebral ischemia, could thus contribute to the extracellular accumulation of neurotoxic excitatory amino acids.