Feasibility and Informative Value of Environmental Sample Collection in the National Children\u27s Vanguard Study

Background: Birth cohort studies provide the opportunity to advance understanding of the impact of environmental factors on childhood health and development through prospective collection of environmental samples. Methods: We evaluated the feasibility and informative value of the environmental sample collection methodology in the initial pilot phase of the National Children\u27s Study, a planned U.S. environmental birth cohort study. Environmental samples were collected from January 2009–September 2010 at up to three home visits: pre-pregnancy (n¼306), pregnancy (n¼807), and 6-months postnatal (n¼117). Collections included air for particulate matter r2.5 mm (PM2.5), nitrogen dioxide, ozone, volatile organic compounds (VOCs), and carbonyls; vacuum dust for allergens/endotoxin; water for VOCs, trihalomethanes (THMs), and haloacetic acids (HAAs); and wipe samples for pesticides, semi-volatile organics, and metals. We characterized feasibility using sample collection rates and times and informative value using analyte detection frequencies (DF). Results: Among the 1230 home visits, environmental sample collection rates were high across all sample types (mean¼89%); all samples except the air PM2.5 samples had collection times o30 min. Informative value was low for water VOCs (median DF¼0%) and pesticide floor wipes (median DF¼5%). Informative value was moderate for air samples (median DF¼35%) and high for water THMs and HAAs (median DF¼91% and 75%, respectively). Conclusions: Though collection of environmental samples was feasible, some samples (e.g., wipe pesticides and water VOCs) yielded limited information. These results can be used in conjunction with other study design considerations, such as target population size and hypotheses of interest, to inform the method selection of future environmental health birth cohort studies

Effects of memory load and distraction on performance and event-related slow potentials in a visuospatial working memory task

Brain electrical activity related to working memory was recorded at 15 scalp electrodes during a visuospatial delayed response task. Participants (N = 18) touched the remembered position of a target on a computer screen after either a 1 or 8 sec delay. These memory trials were compared to sensory trials in which the target remained present throughout the delay and response periods. Distracter stimuli identical to the target were briefly presented during the delay on 30% of trials. Responses were less accurate in memory than sensory trials, especially after the long delay. During the delay slow potentials developed that were significantly more negative in memory than sensory trials. The difference between memory and sensory trials was greater at anterior than posterior electrodes. On trials with distracters, the slow potentials generated by memory trials showed further enhancement of negativity whereas there were minimal effects on accuracy of performance. The results provide evidence that engagement of visuospatial working memory generates slow wave negativity with a timing and distribution consistent with frontal activation. Enhanced brain activity associated with working memory is required to maintain performance in the presence of distraction. © 1997 by the Massachusetts Institute of Technolog

Epigenetic modification of cytosines fine tunes the stability of i-motif DNA

i-Motifs are widely used in nanotechnology, play a part in gene regulation and have been detected in human nuclei. As these structures are composed of cytosine, they are potential sites for epigenetic modification. In addition to 5-methyl- and 5-hydroxymethylcytosine modifications, recent evidence has suggested biological roles for 5-formylcytosine and 5-carboxylcytosine. Herein the human telomeric i-motif sequence was used to examine how these four epigenetic modifications alter the thermal and pH stability of i-motifs. Changes in melting temperature and transitional pH depended on both the type of modification and its position within the i-motif forming sequence. The cytosines most sensitive to modification were next to the first and third loops within the structure. Using previously described i-motif forming sequences, we screened the MCF-7 and MCF-10A methylomes to map 5-methylcytosine and found the majority of sequences were differentially methylated in MCF7 (cancerous) and MCF10A (non-cancerous) cell lines. Furthermore, i-motif forming sequences stable at neutral pH were significantly more likely to be epigenetically modified than traditional acidic i-motif forming sequences. This work has implications not only in the epigenetic regulation of DNA, but also allows discreet tunability of i-motif stability for nanotechnological applications

Scoping Review: Physical Activity and Social Functioning in Young People With Autism Spectrum Disorder

Autism Spectrum Disorder (ASD) affects ~1 in 59 people in North America and diagnoses continue to rise (Center for Disease Control and Prevention, 2018). Unfortunately, the exact cause of ASD is unknown and therapy remains the primary means of intervention. People with ASD experience social and behavioral deficits associated with the disorder, which affect all aspects of life such as academics, relationships, and physical activity. Research has shown a relationship between physical activity and social skills in typically developing individuals; however, this relationship is less understood in people with ASD. The purpose of this scoping review was to uncover what is known about ASD, physical activity, and social functioning. The authors searched four databases and included 40 primary research articles in the review, most of which demonstrated a relationship between physical activity and social functioning for people with ASD. The relationship appears bidirectional: social functioning influences physical activity (to a lesser extent) and physical activity influences social functioning (to a greater extent). Regrettably, there were many limitations in these articles, such as small sample sizes and the under-representation of females and adults. Therefore, the review highlights several directions for future research

The Precision Array for Probing the Epoch of Reionization: 8 Station Results

We are developing the Precision Array for Probing the Epoch of Reionization (PAPER) to detect 21cm emission from the early Universe, when the first stars and galaxies were forming. We describe the overall experiment strategy and architecture and summarize two PAPER deployments: a 4-antenna array in the low-RFI environment of Western Australia and an 8-antenna array at our prototyping site in Green Bank, WV. From these activities we report on system performance, including primary beam model verification, dependence of system gain on ambient temperature, measurements of receiver and overall system temperatures, and characterization of the RFI environment at each deployment site. We present an all-sky map synthesized between 139 MHz and 174 MHz using data from both arrays that reaches down to 80 mJy (4.9 K, for a beam size of 2.15e-5 steradians at 154 MHz), with a 10 mJy (620 mK) thermal noise level that indicates what would be achievable with better foreground subtraction. We calculate angular power spectra ($C_\ell$) in a cold patch and determine them to be dominated by point sources, but with contributions from galactic synchrotron emission at lower radio frequencies and angular wavemodes. Although the cosmic variance of foregrounds dominates errors in these power spectra, we measure a thermal noise level of 310 mK at $\ell=100$ for a 1.46-MHz band centered at 164.5 MHz. This sensitivity level is approximately three orders of magnitude in temperature above the level of the fluctuations in 21cm emission associated with reionization.Comment: 13 pages, 14 figures, submitted to AJ. Revision 2 corrects a scaling error in the x axis of Fig. 12 that lowers the calculated power spectrum temperatur

A computational atlas of the hippocampal formation using ex vivo, ultra-high resolution MRI: Application to adaptive segmentation of in vivo MRI.

AbstractAutomated analysis of MRI data of the subregions of the hippocampus requires computational atlases built at a higher resolution than those that are typically used in current neuroimaging studies. Here we describe the construction of a statistical atlas of the hippocampal formation at the subregion level using ultra-high resolution, ex vivo MRI. Fifteen autopsy samples were scanned at 0.13mm isotropic resolution (on average) using customized hardware. The images were manually segmented into 13 different hippocampal substructures using a protocol specifically designed for this study; precise delineations were made possible by the extraordinary resolution of the scans. In addition to the subregions, manual annotations for neighboring structures (e.g., amygdala, cortex) were obtained from a separate dataset of in vivo, T1-weighted MRI scans of the whole brain (1mm resolution). The manual labels from the in vivo and ex vivo data were combined into a single computational atlas of the hippocampal formation with a novel atlas building algorithm based on Bayesian inference. The resulting atlas can be used to automatically segment the hippocampal subregions in structural MRI images, using an algorithm that can analyze multimodal data and adapt to variations in MRI contrast due to differences in acquisition hardware or pulse sequences. The applicability of the atlas, which we are releasing as part of FreeSurfer (version 6.0), is demonstrated with experiments on three different publicly available datasets with different types of MRI contrast. The results show that the atlas and companion segmentation method: 1) can segment T1 and T2 images, as well as their combination, 2) replicate findings on mild cognitive impairment based on high-resolution T2 data, and 3) can discriminate between Alzheimer's disease subjects and elderly controls with 88% accuracy in standard resolution (1mm) T1 data, significantly outperforming the atlas in FreeSurfer version 5.3 (86% accuracy) and classification based on whole hippocampal volume (82% accuracy)

Temporal Trends and Factors Associated with Bisphosphonate Discontinuation and Restart

Adverse events related to long-term use of bisphosphonates have raised interest in temporary drug discontinuation. Trends in bisphosphonate discontinuation and restart, as well factors associated with these decisions, are not fully understood at a population level. We investigated temporal trends of bisphosphonate discontinuation from 2010 to 2015 and identified factors associated with discontinuation and restart of osteoporosis therapy. Our cohort consisted of long-term bisphosphonate users identified from 2010 to 2015 Medicare data. We defined discontinuation as 6512\u2009months without bisphosphonate prescription claims. We used conditional logistic regression to compare factors associated with alendronate discontinuation or osteoporosis therapy restart in the 120-day period preceding discontinuation or restart referent to the 120-day preceding control periods. Among 73,800 long-term bisphosphonate users, 59,251 (80.3%) used alendronate, 6806 (9.2%) risedronate, and 7743 (10.5%) zoledronic acid, exclusively. Overall, 26,281 (35.6%) discontinued bisphosphonates for at least 12\u2009months. Discontinuation of bisphosphonates increased from 1.7% in 2010, reaching a peak of 14% in 2012 with levels plateauing through 2015. The factors most strongly associated with discontinuation of alendronate were: benzodiazepine prescription (adjusted odds ratio [aOR] = 2.5; 95% confidence interval [CI] 2.1, 3.0), having a dual-energy X-ray absorptiometry (DXA) scan (aOR = 1.8; 95% CI 1.7, 2.0), and skilled nursing facility care utilization (aOR = 1.8; 95% CI 1.6, 2.1). The factors most strongly associated with restart of osteoporosis therapy were: having a DXA scan (aOR = 9.9; 95% CI 7.7, 12.6), sustaining a fragility fracture (aOR = 2.8; 95% CI 1.8, 4.5), and an osteoporosis or osteopenia diagnosis (aOR = 2.5; 95% CI 2.0, 3.1). Our national evaluation of bisphosphonate discontinuation showed that an increasing proportion of patients on long-term bisphosphonate therapy discontinue medications. The factors associated with discontinuation of alendronate were primarily related to worsening of overall health status, whereas traditional factors associated with worsening bone health were associated with restarting osteoporosis medication. \ua9 2019 American Society for Bone and Mineral Research

Relationship of Auditory Electrophysiological Responses to Magnetic Resonance Spectroscopy Metabolites in Early Phase Psychosis

Both auditory evoked responses and metabolites measured by magnetic resonance spectroscopy (MRS) are altered in schizophrenia and other psychotic disorders, but the relationship between electrophysiological and metabolic changes are not well characterized. We examined the relation of MRS metabolites to cognitive and electrophysiological measures in individuals during the early phase of psychosis (EPP) and in healthy control subjects. The mismatch negativity (MMN) of the auditory event-related potential to duration deviant tones and the auditory steady response (ASSR) to 40 Hz stimulation were assessed. MRS was used to quantify glutamate+glutamine (Glx), N-Acetylasparate (NAA), creatine (Cre), myo-inositol (Ins) and choline (Cho) at a voxel placed medially in the frontal cortex. MMN amplitude and ASSR power did not differ between groups. The MRS metabolites Glx, Cre and Cho were elevated in the psychosis group. Partial least squares analysis in the patient group indicated that elevated levels of MRS metabolites were associated with reduced MMN amplitude and increased 40 Hz ASSR power. There were no correlations between the neurobiological measures and clinical measures. These data suggest that elevated neurometabolites early in psychosis are accompanied by altered auditory neurotransmission, possibly indicative of a neuroinflammatory or excitotoxic disturbance which disrupts a wide range of metabolic processes in the cortex

Temporospatial shifts in Sandhill Crane staging in the Central Platte River Valley in response to climatic variation and habitat change

Over 80% of the Mid-Continent Sandhill Crane (Antigone canadensis) Population (MCP), estimated at over 660,000 individuals, stops in the Central Platte River Valley (CPRV) during spring migration from mid-February through mid-April. Research suggests that the MCP may be shifting its distribution spatially and temporally within the CPRV. From 2002 to 2017, we conducted weekly aerial surveys of Sandhill Cranes staging in the CPRV to examine temporal and spatial trends in their abundance and distribution. Then, we used winter temperature and drought severity measures from key wintering and early migratory stopover locations to assess the impacts of weather patterns on annual migration chronology in the CPRV. We also evaluated channel width and land cover characteristics using aerial imagery from 1938, 1998, and 2016 to assess the relationship between habitat change and the spatial distribution of the MCP in the CPRV. We used generalized linear models, cumulative link models, and Akaike’s information criterion corrected for small sample sizes (AICc) to compare temporal and spatial models. Temperatures and drought conditions at wintering and migration locations that are heavily used by Greater Sandhill Cranes (A. c. tabida) best predicted migration chronology of the MCP to the CPRV. The spatial distribution of roosting Sandhill Cranes from 2015 to 2017 was best predicted by the proportion of width reduction in the main channel since 1938 (rather than its width in 2016) and the proportion of land cover as prairie-meadow habitat within 800 m of the Platte River. Our data suggest that Sandhill Cranes advanced their migration by an average of just over 1 day per year from 2002 to 2017, and that they continued to shift eastward, concentrating at eastern reaches of the CPRV. Climate change, land use change, and habitat loss have all likely contributed to Sandhill Cranes coming earlier and staying longer in fewer reaches of the CPRV, increasing their site use intensity. These historically unprecedented densities may present a disease risk to Sandhill Cranes and other waterbirds, including Whooping Cranes (Grus americana). Our models suggest that conservation actions may be maintaining Sandhill Crane densities in areas that would otherwise be declining in use. We suggest that management actions intended to mitigate trends in the distribution of Sandhill Cranes, including wet meadow restoration, may similarly benefit prairie- and braided river–endemic species of concern. Más del 80% de la población de grullas canadienses (Antigone canadensis), de la zona central del continente (MCP por sus siglas en inglés), estimada en más de 660,000, descansa en el valle central del Río Platte (CPRV por sus siglas en inglés) durante su migración de primavera, desde mediados de febrero hasta mediados de abril. Diversos estudios indican que su distribución espacial y temporal podría estar cambiando dentro del CPRV. Desde el año 2002 hasta el 2017 realizamos sondeos aéreos semanales de grullas canadienses en el CPRV para estudiar las tendencias temporales y espaciales relacionadas a su abundancia y distribución. Usamos mediciones de temperatura durante el invierno y de la severidad de la sequía de lugares claves de invernada y de sitios de descanso durante su migración temprana para evaluar el impacto de los patrones climáticos en la cronología migratoria anual del CPRV. También analizamos la amplitud del canal y las características de la cubierta terrestre usando imágenes aéreas de 1938, 1998 y 2016 con el fin de evaluar la relación entre el cambio de hábitat y la distribución espacial de la MCP en el CPRV. Utilizamos modelos lineales generalizados, modelos de enlace acumulativo y el criterio de información de Akaike adecuados a muestras pequeñas (AICc), para comparar modelos temporales y espaciales. Las condiciones climáticas y de sequía en los sitios de invernada y migración más usados por la grulla canadiense mayor (A. c. tabida) predijeron mejor la cronología migratoria de la MCP en el CPRV. La reducción de la amplitud del canal principal desde 1938, junto con el porcentaje de cubierta terrestre como hábitat de pradera dentro de los 800 m del río Platte, fue el mejor predictor de la distribución espacial de la grulla canadiense desde el año 2015 hasta el 2017. Nuestros estudios indican que las grullas canadienses adelantaron su migración en un promedio poco más de un día por año entre el 2002 y el 2017 y que continuaron desplazándose hacia el este, concentrándose en los extremos orientales del CPRV. El cambio climático, el cambio de uso del suelo y la pérdida del hábitat probablemente contribuyeron a la migración temprana de esta especie y a su permanencia más prolongada en algunos sectores del CPRV, aumentando la intensidad del uso del sitio. Estas densidades sin precedentes podrían presentar un riesgo de enfermedad para la grulla canadiense y otras aves acuáticas, incluidas las grullas trompeteras (Grus americana). Nuestros modelos indican que las medidas actuales de conservación podrían ser la causa de preservación de la densidad poblacional de la grulla canadiense en áreas en las que, de otra forma, su presencia estaría disminuyendo. Sugerimos que las medidas de control destinadas a mitigar la tendencia de distribución de la grulla canadiense, incluyendo la restauración de los prados húmedos, pueden beneficiar de igual manera a las especies endémicas, praderas y ríos trenzados de nuestro interés