Technologies that can record neural activity at cellular resolution at multiple spatial and temporal scales are typically much larger than the animals that are being recorded from and are thus limited to recording from head-fixed subjects. Here we have engineered robotic neural recording devices-'cranial exoskeletons'-that assist mice in maneuvering recording headstages that are orders of magnitude larger and heavier than the mice, while they navigate physical behavioral environments. We discovered optimal controller parameters that enable mice to locomote at physiologically realistic velocities while maintaining natural walking gaits.
View Article and Find Full Text PDFPurpose: The etiopathogenesis of coronal nonsyndromic craniosynostosis (cNCS), a congenital condition defined by premature fusion of 1 or both coronal sutures, remains largely unknown.
Methods: We conducted the largest genome-wide association study of cNCS followed by replication, fine mapping, and functional validation of the most significant region using zebrafish animal model.
Results: Genome-wide association study identified 6 independent genome-wide-significant risk alleles, 4 on chromosome 7q21.
Background: Gastroschisis is a birth defect with the greatest risk among women <20 years of age.
Methods: Pregnant women attending the University of Utah's Maternal-Fetal Medicine Diagnostic Center between 2011 and 2017 for either their routine diagnostic ultrasound or referral were recruited (cases: pregnant women with fetal gastroschisis, n = 53 participated/57, 93%; controls: pregnant women without fetal abnormalities, n = 102 participated/120, 85%). A clinic coordinator consented and interviewed women and obtained a blood sample and prenatal medical records.
Background: The use of chlorine to treat drinking water produces disinfection by-products (DBPs), which have been associated with congenital heart defects (CHDs) in some studies.
Methods: Using National Birth Defects Prevention Study data, we linked geocoded residential addresses to public water supply measurement data for DBPs. Self-reported water consumption and filtration methods were used to estimate maternal ingestion of DBPs.
Understanding how circuits in the brain simultaneously coordinate their activity to mediate complex ethnologically relevant behaviors requires recording neural activities from distributed populations of neurons in freely behaving animals. Current miniaturized imaging microscopes are typically limited to imaging a relatively small field of view, precluding the measurement of neural activities across multiple brain regions. Here we present a miniaturized micro-camera array microscope (mini-MCAM) that consists of four fluorescence imaging micro-cameras, each capable of capturing neural activity across a 4.
View Article and Find Full Text PDFBackground: Socioeconomic factors may lead to a disproportionate impact on health care usage and death among individuals with congenital heart defects (CHD) by race, ethnicity, and socioeconomic factors. How neighborhood poverty affects racial and ethnic disparities in health care usage and death among individuals with CHD across the life span is not well described.
Methods And Results: Individuals aged 1 to 64 years, with at least 1 CHD-related () code were identified from health care encounters between January 1, 2011, and December 31, 2013, from 4 US sites.
Background: Gastroschisis is a serious birth defect with midgut prolapse into the amniotic cavity. The objectives of this study were to evaluate the prevalence and time trends of gastroschisis among programs in the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR), focusing on regional variations and maternal age changes in the population.
Methods: We analyzed data on births from 1980 to 2017 from 27 ICBDSR member programs, representing 24 countries and three regions (Europe , Latin America, North America).
Complex behaviors are mediated by neural computations occurring throughout the brain. In recent years, tremendous progress has been made in developing technologies that can record neural activity at cellular resolution at multiple spatial and temporal scales. However, these technologies are primarily designed for studying the mammalian brain during head fixation - wherein the behavior of the animal is highly constrained.
View Article and Find Full Text PDFBackground: Gastroschisis prevalence more than doubled between 1995 and 2012. While there are individual-level risk factors (e.g.
View Article and Find Full Text PDFBackground: Individual measures of socioeconomic status (SES) have been associated with an increased risk of neural tube defects (NTDs); however, the association between neighborhood SES and NTD risk is unknown. Using data from the National Birth Defects Prevention Study (NBDPS) from 1997 to 2011, we investigated the association between measures of census tract SES and NTD risk.
Methods: The study population included 10,028 controls and 1829 NTD cases.
Unlabelled: Although recent efforts have led to the development of highly effective androgen receptor (AR)-directed therapies for the treatment of advanced prostate cancer, a significant subset of patients will progress with resistant disease including AR-negative tumors that display neuroendocrine features [neuroendocrine prostate cancer (NEPC)]. On the basis of RNA sequencing (RNA-seq) data from a clinical cohort of tissue from benign prostate, locally advanced prostate cancer, metastatic castration-resistant prostate cancer and NEPC, we developed a multi-step bioinformatics pipeline to identify NEPC-specific, overexpressed gene transcripts that encode cell surface proteins. This included the identification of known NEPC surface protein CEACAM5 as well as other potentially targetable proteins (e.
View Article and Find Full Text PDFBackground: Two strong risk factors for gastroschisis are young maternal age (<20 years) and low/normal pre-pregnancy body mass index (BMI), yet the reasons remain unknown. We explored whether neighborhood-level socioeconomic position (nSEP) during pregnancy modified these associations.
Methods: We analyzed data from 1269 gastroschisis cases and 10,217 controls in the National Birth Defects Prevention Study (1997-2011).
Complex behaviors are mediated by neural computations occurring throughout the brain. In recent years, tremendous progress has been made in developing technologies that can record neural activity at cellular resolution at multiple spatial and temporal scales. However, these technologies are primarily designed for studying the mammalian brain during head fixation - wherein the behavior of the animal is highly constrained.
View Article and Find Full Text PDFSingle-chain fragment variable (scFv) domains play an important role in antibody-based therapeutic modalities, such as bispecifics, multispecifics and chimeric antigen receptor T cells or natural killer cells. However, scFv domains exhibit lower stability and increased risk of aggregation due to transient dissociation ("breathing") and inter-molecular reassociation of the two domains (VL and VH). We designed a novel strategy, referred to as stapling, that introduces two disulfide bonds between the scFv linker and the two variable domains to minimize scFv breathing.
View Article and Find Full Text PDFBackground: Neighborhood-level socioeconomic position has been shown to influence birth outcomes, including selected birth defects. This study examines the un derstudied association between neighborhood-level socioeconomic position during early pregnancy and the risk of gastroschisis, an abdominal birth defect of increasing prevalence.
Methods: We conducted a case-control study of 1,269 gastroschisis cases and 10,217 controls using data from the National Birth Defects Prevention Study (1997-2011).
The etiology of biliary atresia (BA) is unknown, but recent studies suggest a role for rare protein-altering variants (PAVs). Exome sequencing data from the National Birth Defects Prevention Study on 54 child-parent trios, one child-mother duo, and 1513 parents of children with other birth defects were analyzed. Most (91%) cases were isolated BA.
View Article and Find Full Text PDFBackground: The sixth Strategic Planning Session of the Society for Birth Defects Research and Prevention (BDRP) was held on April 24-25, 2022, in Alexandria, VA.
Methods: This effort built upon previous strategic planning sessions, conducted every 5 years.
Results: The overall process was designed to identify BDRP's vision, purpose, culture, and potential, as well as to communicate the value that BDRP brings to its members, volunteers, partners, and the greater community.
Purpose: This study aimed to describe health care use by type of health providers and care settings visited by children with spina bifida (SB) and to compare this use between children with and without a shunt.
Methods: Health care use data were extracted from a larger study on the health and functioning of children with SB aged 3-6 years. The present study focused on the medical information subsection of a parent-reported survey related to SB care, general care, specialty care (e.
Introduction: Arsenic crosses the placenta and accumulates in fetal tissues. In the United States, diet is the predominant route of arsenic exposure, but epidemiologic data are sparse regarding this exposure and development of birth defects. Using data from a large case-control study, we explored associations between maternal dietary arsenic exposure and congenital heart defects (CHDs), the most prevalent birth defects.
View Article and Find Full Text PDFBackground We sought to characterize health care usage for adolescents with congenital heart defects (CHDs) using population-based multisite surveillance data. Methods and Results Adolescents aged 11 to 18 years with ≥1 CHD-related diagnosis code and residing in 5 US sites were identified in clinical and administrative data sources for the years 2011 to 2013. Sites linked data on all inpatient, emergency department (ED), and outpatient visits.
View Article and Find Full Text PDFBackground: Maternal exposure to weather-related extreme heat events (EHEs) has been associated with congenital heart defects (CHDs) in offspring. Certain medications may affect an individual's physiologic responses to EHEs. We evaluated whether thermoregulation-related medications modified associations between maternal EHE exposure and CHDs.
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