Systematic analysis of variants escaping nonsense-mediated decay uncovers candidate Mendelian diseases.

Protein-truncating variants (PTVs) near the 3' end of genes may escape nonsense-mediated decay (NMD). PTVs in the NMD-escape region (PTVescs) can cause Mendelian disease but are difficult to interpret given their varying impact on protein function. Previously, PTVesc burden was assessed in an epilepsy cohort, but no large-scale analysis has systematically evaluated these variants in rare disease. We performed a retrospective analysis of 29,031 neurodevelopmental disorder (NDD) parent-offspring trios referred for clinical exome sequencing to identify PTVesc de novo mutations (DNMs). We identified 1,376 PTVesc DNMs and 133 genes that were significantly enriched (binomial p < 0.001). The PTVesc-enriched genes included those with PTVescs previously described to cause dominant Mendelian disease (e.g., SEMA6B, PPM1D, and DAGLA). We annotated ClinVar variants for PTVescs and identified 948 genes with at least one high-confidence pathogenic variant. Twenty-two known Mendelian PTVesc-enriched genes had no prior evidence of PTVesc-associated disease. We found 22 additional PTVesc-enriched genes that are not well established to be associated with Mendelian disease, several of which showed phenotypic similarity between individuals harboring PTVesc variants in the same gene. Four individuals with PTVesc mutations in RAB1A had similar phenotypes including NDD and spasticity. PTVesc mutations in IRF2BP1 were found in two individuals who each had severe immunodeficiency manifesting in NDD. Three individuals with PTVesc mutations in LDB1 all had NDD and multiple congenital anomalies. Using a large-scale, systematic analysis of DNMs, we extend the mutation spectrum for known Mendelian disease-associated genes and identify potentially novel disease-associated genes.

Anatomical and behavioural correlates of auditory perception in developmental dyslexia.

Developmental dyslexia is typically associated with difficulties in basic auditory processing and in manipulating speech sounds. However, the neuroanatomical correlates of auditory difficulties in developmental dyslexia (DD) and their contribution to individual clinical phenotypes are still unknown. Recent intracranial electrocorticography findings associated processing of sound amplitude rises and speech sounds with posterior and middle superior temporal gyrus (STG), respectively. We hypothesize that regional STG anatomy will relate to specific auditory abilities in DD, and that auditory processing abilities will relate to behavioral difficulties with speech and reading. One hundred and ten children (78 DD, 32 typically developing, age 7-15 years) completed amplitude rise time and speech in noise discrimination tasks. They also underwent a battery of cognitive tests. Anatomical MRI scans were used to identify regions in which local cortical gyrification complexity correlated with auditory behavior. Behaviorally, amplitude rise time but not speech in noise performance was impaired in DD. Neurally, amplitude rise time and speech in noise performance correlated with gyrification in posterior and middle STG, respectively. Furthermore, amplitude rise time significantly contributed to reading impairments in DD, while speech in noise only explained variance in phonological awareness. Finally, amplitude rise time and speech in noise performance were not correlated, and each task was correlated with distinct neuropsychological measures, emphasizing their unique contributions to DD. Overall, we provide a direct link between the neurodevelopment of the left STG and individual variability in auditory processing abilities in neurotypical and dyslexic populations.

Toward robust clinical genome interpretation: Developing a consistent terminology to characterize Mendelian disease-gene relationships-allelic requirement, inheritance modes, and disease mechanisms.

PURPOSE: The terminology used for gene-disease curation and variant annotation to describe inheritance, allelic requirement, and both sequence and functional consequences of a variant is currently not standardized. There is considerable discrepancy in the literature and across clinical variant reporting in the derivation and application of terms. Here, we standardize the terminology for the characterization of disease-gene relationships to facilitate harmonized global curation and to support variant classification within the ACMG/AMP framework. METHODS: Terminology for inheritance, allelic requirement, and both structural and functional consequences of a variant used by Gene Curation Coalition members and partner organizations was collated and reviewed. Harmonized terminology with definitions and use examples was created, reviewed, and validated. RESULTS: We present a standardized terminology to describe gene-disease relationships, and to support variant annotation. We demonstrate application of the terminology for classification of variation in the ACMG SF 2.0 genes recommended for reporting of secondary findings. Consensus terms were agreed and formalized in both Sequence Ontology (SO) and Human Phenotype Ontology (HPO) ontologies. Gene Curation Coalition member groups intend to use or map to these terms in their respective resources. CONCLUSION: The terminology standardization presented here will improve harmonization, facilitate the pooling of curation datasets across international curation efforts and, in turn, improve consistency in variant classification and genetic test interpretation.

Utilization of allogeneic hematopoietic stem cell transplantation among patients with newly diagnosed acute myeloid leukemia in California: a population-based linked dataset study.

Acute myeloid leukemia (AML) often requires allogeneic hematopoietic cell transplantation (alloHCT) for cure, but historically alloHCT has been strikingly underutilized. Reasons for this remain uncertain at the population level. We examined alloHCT utilization over time and explored associations between demographic/healthcare factors and use of alloHCT by age group (AYA 15-39y, adult 40-64y, older adult 65-79y) using a linked dataset merging the Center for International Blood and Marrow Transplant Research, California Cancer Registry, and California Patient Discharge Database. Eligibility included patients newly diagnosed with AML in California between 2001-2016 who received induction therapy and had no prior HCT. Multivariable Fine-Gray regression analyses were fitted separately across age groups. Among 7,925 patients with AML, alloHCT utilization increased over time across all age groups; however, in the most recent time period studied (2011-2016), utilization within 2 years of diagnosis remained lowest in older adults (13%) relative to adults (41%) and AYAs (49%). Factors statistically significantly associated with lower alloHCT utilization: (1) AYAs: female sex, lower neighborhood socioeconomic status (nSES), uninsured or Indian Health Services (IHS) coverage; (2) adults: older age, male sex, non-Hispanic Black or Asian race and ethnicity, unmarried, lower nSES, uninsured or covered by Medicaid, Medicare, or IHS, higher comorbidity, and living 100+ miles from a transplant center; and (3) older adults: older age, Asian race, and unmarried. In conclusion, using a population-based linked dataset, we demonstrate that utilization of alloHCT among older patients newly diagnosed with AML remains low in California, and factors associated with utilization vary by age group.

The efficacy and safety of direct oral anticoagulants compared with low-molecular-weight heparin for venous thromboembolism prophylaxis after surgical resection of primary lower extremity bone or soft-tissue sarcoma.

INTRODUCTION: The incidence of postoperative venous thromboembolism (VTE) and wound complications is greater after sarcoma resection. We sought to identify differences in postoperative VTE and bleeding complications with direct oral anticoagulants (DOACs) versus low-molecular-weight heparin (LMWH) following resection of lower extremity primary bone or soft tissue sarcoma. METHODS: We retrospectively identified 2083 patients from the PearlDiver database who underwent resection of primary bone or soft tissue sarcoma of the lower extremity from January 2010 to October 2021 and prescribed LMWH or DOAC within 90-days postoperatively. The primary outcomes were comparison of postoperative incidence and odds of deep venous thrombosis (DVT), pulmonary embolism (PE), and bleeding complications within 90-days following resection. RESULTS: Patients prescribed DOACs had a greater odds of DVT (odds ratio [OR]: 1.60; 95% confidence interval [CI]: 1.06-2.41; p = 0.024) and PE (OR: 3.38; 95% CI: 1.96-5.86; p < 0.001) within 90-days following resection of bone sarcoma when compared with the LMWH cohort. Patients undergoing resection of soft tissue sarcomas also had greater odds DVT (OR: 1.65; 95% CI: 1.09-2.49; p = 0.016) and PE (OR: 2.62; 95% CI: 1.52-4.54; p < 0.001) in the DOAC cohort. There was no difference in the odds of bleeding complications. CONCLUSION: This study demonstrated an increased incidence and odds of VTE, but not bleeding complications, when using DOACs versus LMWH after primary bone or soft tissue sarcoma resection. LEVEL OF EVIDENCE: Level III.

Adolescent caffeine use and problematic school behavior: A longitudinal analysis of student survey data and teacher observations.

INTRODUCTION: Caffeine is a psychostimulant possessing arousal, motor activation, and reinforcing properties, which is consumed daily by most adolescents aged 12-19 years. Although current understanding of the implications of adolescent caffeine consumption for school behaviors remains incomplete, studies have shown that in addition to acute effects of the drug, in common with other habit-forming psychoactive substances, regular use leads to physical dependence, evidenced by recurring negative withdrawal symptoms. METHODS: Employing two waves of longitudinal data, we tested the prospective association between daily caffeine use and homeroom teacher-observed self-control and problem behavior in a sample of middle-school students in 20 schools in West Virginia in the United States. Caffeine was operationalized with two dichotomized variables, daily consumption of <100 mg, and daily consumption of >100 mg, versus no daily use. Gender, mother's education, family financial status, social support by primary caregiver and adults in school, and school climate, were applied as covariates in linear mixed models. RESULTS: Daily caffeine use of >100 mg was robustly and inversely associated with self-control and positively associated with problem behavior. CONCLUSIONS: Caffeine consumption and associated withdrawal symptoms may be an important factor in problematic school behavior among adolescents. Recent advent of highly concentrated caffeine products (e.g., caffeine "shots") commonly marketed directly at youth, should give rise to concerns including consideration about limiting caffeine consumption among children and youth.

Safe Listening at Venues and Events with Amplified Music - United States, 2022.

Nearly one in four (24.4%) U.S. adults aged 20-69 years show evidence of noise-induced hearing loss (1). Among those reporting exposure to noise outside of work, 19.9% showed possible noise-induced hearing loss. Exposure to non-job-related noise can be substantial (2). Loud music from personal listening devices and entertainment venues might place more than 1 billion teenagers and young adults at risk for hearing loss worldwide (3). Early noise exposure might increase the risk for age-related hearing loss later in life (4). CDC analyzed data from the 2022 FallStyles survey (conducted by Porter Novelli via the Ipsos' KnowledgePanel) on U.S. adult perceptions regarding preventing hearing loss from amplified music at venues or events. More than one half of U.S. adults agreed with one or more of the following protective actions: limiting sound levels, posting warning signs, and using hearing protection when music at such events reaches potentially hazardous levels. Hearing and other health professionals can make use of existing materials available from the World Health Organization (WHO), CDC, and other professional organizations to raise awareness about noise risks and promote protective behaviors.

Metastatic sarcomatoid carcinoma to bone.

BACKGROUND AND OBJECTIVES: Distinguishing sarcomatoid carcinoma from primary sarcoma is clinically important. We sought to characterize metastatic sarcomatoid bone disease and its management. METHODS: We analyzed the characteristics of all cases of sarcomatoid carcinoma to bone at a single institution from 2001 to 2021, excluding patients with nonosseous metastases. Survival was evaluated using the Kaplan-Meier method. RESULTS: We identified 15 cases of metastatic sarcomatoid carcinoma to bone. In seven cases the primary cancer was unknown at presentation. Renal cell carcinoma was suspected or confirmed in nine cases. Nine patients presented with pathologic fracture and two with concomitant visceral metastases. All patients underwent image-guided core needle or open biopsy. Ten required surgery for discrete osseous metastases; in four cases definitive surgery was delayed (median delay, 19 days) due to inability to rule out sarcoma with frozen section. No patients required reoperation or had construct failure. Thirteen died of disease; median survival was 17.5 months (interquartile range, 6.2-25.1). CONCLUSIONS: Metastatic sarcomatoid carcinoma is a clinically challenging entity. Multidisciplinary input and communication are key to identifying the primary carcinoma, locating osseous metastases, and defining an operative fixation that will survive the remainder of the patient's life.

Factors affecting adherence to a high-risk surveillance protocol among patients with Li-Fraumeni syndrome.

BACKGROUND: High-risk surveillance for patients with Li-Fraumeni syndrome (LFS) has shown a stage shift and improved overall survival, but is demanding. Our objective was to evaluate surveillance adherence in a population of patients with LFS presenting for high-risk care. METHODS: A retrospective analysis of surveillance adherence of adult patients with LFS at a single institution was performed. Adherence was defined by the duration from initial University of Virginia (UVA) LFS clinic visit to the time of first missed surveillance test. Two-sample t-tests and ANOVA tests were used to identify factors associated with duration of adherence. RESULTS: A total of 42 patients were evaluated in the UVA LFS clinic between 2017 and 2021. Of these, 21 patients met inclusion criteria. At the time of review, 6 patients (29%) were up to date with high-risk surveillance recommendations. The mean duration of adherence was 17 months. Female sex was found to be associated with longer duration of adherence (mean 21 mo vs. 3.5 mo for males, p = 0.02). A personal history or active diagnosis of cancer was also associated with increased adherence (p = 0.02). However, neither age (p = 0.89), geography (p = 0.84), or known family history of LFS (p = 0.08) were associated with duration of adherence. CONCLUSION: Female sex as well as a personal history of cancer were associated with longer duration of adherence to recommended high-risk surveillance among patients with LFS. Identification of barriers to surveillance will be essential moving forward to increase adherence and promote early detection of cancer, thereby reducing the morbidity and mortality of LFS.

Identifying Gender-Related Differences in Graduate Medical Education with the Use of a Web-Based Professionalism Monitoring Tool.

OBJECTIVES: Medical education is required to ensure a healthy training and learning environment for resident physicians. Trainees are expected to demonstrate professionalism with patients, faculty, and staff. West Virginia University Graduate Medical Education (GME) initiated a Web-based professionalism and mistreatment form ("button") on our Web site for reporting professionalism breaches, mistreatment, and exemplary behavior events. The purpose of this study was to identify characteristics in resident trainees who had a "button push" activation about their behavior to better understand ways to improve professionalism in GME. METHODS: This West Virginia University institutional review board-approved quality improvement study is a descriptive analysis of GME button push activations from July 2013 through June 2021. We compared characteristics of all of those trainees who had specific button activation(s) about their behavior. Data are reported as frequency and percentage. Nominal data and interval data were analyzed using the χ2 and the t test, respectively. P < 0.05 was significant. Logistic regression was used to analyze those differences that were significant. RESULTS: In the 8-year study period, there were 598 button activations, and 54% (n = 324) of the activations were anonymous. Nearly all of the button reports (n = 586, 98%) were constructively resolved within 14 days. Of the 598 button activations, 95% (n = 569) were identified as involving one sex, with 66.3% (n = 377) identified as men and 33.7% (n = 192) as women. Of the 598 activations, 83.7% (n = 500) involved residents and 16.3% (n = 98) involved attendings. One-time offenders comprised 90% (n = 538), and 10% (n = 60) involved individuals who had previous button pushes about their behavior. CONCLUSIONS: Implementation of a professionalism-monitoring tool, such as our Web-based button push, identified gender differences in the reporting of professionalism breaches, because twice as many men as women were identified as the instigator of a professionalism breech. The tool also facilitated timely interventions and exemplary behavior recognition.

"It is more isolating to patients if you aren't familiar with the resources": a pilot test of a clinician sensitivity training on eating disorders in pregnancy.

It is more isolating to patients if you aren't familiar with the resources: A pilot test of a clinician sensitivity training on eating disorders in pregnancy.(IRB Number: 1909705198).Background Pregnant women with a history of eating disorders (EDs) or active EDs have greater maternal and child health complications. They are also unlikely to disclose their history with an ED to their clinician, few of which are confident in their knowledge to provide appropriate care for patients who present with EDs. This study's goal was to evaluate changes to knowledge, behavior, and attitudes for health professionals who were part of a sensitivity training (to provide information of and awareness, address potential clinician biases, and offer strategies for more patient-centered care with de-stigmatizing language) about eating disorders and pregnancy compared with those who received a reference document.Methods Our pilot study compared responses of health professionals before and after this sensitivity training (N = 54) with a group who were provided a clinician reference document about the same topic (N = 61).Results Mann-Whitney Wilcoxon tests showed significant differences between the sensitivity training and reference document groups, with the sensitivity training resulting in increases to participants' perception of ED's relevance to overall treatment (p = 0.018), comfort in providing resources (p < 0.0001), frequency of ability to introduce strategies (p = 0.001), and interest in additional strategies/recommendations in treating patients with eating disorders (p = 0.009). Thematic analysis of the open-ended responses indicated four major themes: Resources and support, Treatment, Additional training, and Clinician Strategies. Discussion Results indicated that the sensitivity training improved training outcomes compared to the reference document group. Qualitative responses from both groups indicated four themes that can help inform ED-centered care. This study provides context for future directions for continuing education courses as well as clinical training recommendations for treating pregnant patients with EDs.

Divergent semantic integration (DSI): Extracting creativity from narratives with distributional semantic modeling.

We developed a novel conceptualization of one component of creativity in narratives by integrating creativity theory and distributional semantics theory. We termed the new construct divergent semantic integration (DSI), defined as the extent to which a narrative connects divergent ideas. Across nine studies, 27 different narrative prompts, and over 3500 short narratives, we compared six models of DSI that varied in their computational architecture. The best-performing model employed Bidirectional Encoder Representations from Transformers (BERT), which generates context-dependent numerical representations of words (i.e., embeddings). BERT DSI scores demonstrated impressive predictive power, explaining up to 72% of the variance in human creativity ratings, even approaching human inter-rater reliability for some tasks. BERT DSI scores showed equivalently high predictive power for expert and nonexpert human ratings of creativity in narratives. Critically, DSI scores generalized across ethnicity and English language proficiency, including individuals identifying as Hispanic and L2 English speakers. The integration of creativity and distributional semantics theory has substantial potential to generate novel hypotheses about creativity and novel operationalizations of its underlying processes and components. To facilitate new discoveries across diverse disciplines, we provide a tutorial with code (osf.io/ath2s) on how to compute DSI and a web app ( osf.io/ath2s ) to freely retrieve DSI scores.

Accuracy of Digital Impressions at Varying Implant Depths: An In Vitro Study.

PURPOSE: Implants placed at variable depths may vary the amount of visible scannable surface of a scan body. Intraoral scanner technology uses advanced optical principles to record the surface of the scan body to accurately capture the implant position. The purpose of this study is to investigate the effect implant placement depth has on the accuracy of digital implant impressions using an intraoral scanner. MATERIALS AND METHODS: A partially edentulous gypsum master model was fabricated to allow the positioning of a single implant analog at different depths. Four groups were created based on the planned implant depths of 7, 6, 3, and 0 mm and corresponding visibility of the scan body at 2, 3, 6, and 9 mm. The model was digitized with a laboratory scanner for the reference scan and with an intraoral scanner to generate 15 test scans per group, with a total of 60 scans. The test scans were superimposed onto the reference scan using the best fit algorithm to analyze and measure the positional (dXYZ) and angular deviation (d⍬) of the scan body using three-dimensional metrology software. Statistical analysis was performed using a one-way ANOVA and pairwise comparison was done with a Tukey-Kramer HSD test (α = 0.05). RESULTS: The one-way ANOVA of the groups for the dXYZ and dθ parameters was statistically significant (F3,56 = 11.45, p < 0.001, F3,56 = 24.04, p < 0.001). Group D (9 mm) showed the least positional deviation at 38.41 µm (95% CI 30.26; 46.56) and the least angular deviation of 0.17° (95% CI 0.12; 0.21). Group A (2 mm) showed the greatest positional deviation of 77.17 µm (95% CI 65.23; 89.11) and greatest angular deviation of 0.84° (95% CI 0.65; 1.03). The positional and angular deviation increased with increased implant depth. CONCLUSIONS: The accuracy of digital impressions is influenced by the implant depth and the amount of visibility of the scan body. The trueness and precision are highest when the implant is placed at 0 mm depth with complete visibility of the scan body and decreases with subgingival implant placement.

The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources.

PURPOSE: Several groups and resources provide information that pertains to the validity of gene-disease relationships used in genomic medicine and research; however, universal standards and terminologies to define the evidence base for the role of a gene in disease and a single harmonized resource were lacking. To tackle this issue, the Gene Curation Coalition (GenCC) was formed. METHODS: The GenCC drafted harmonized definitions for differing levels of gene-disease validity on the basis of existing resources, and performed a modified Delphi survey with 3 rounds to narrow the list of terms. The GenCC also developed a unified database to display curated gene-disease validity assertions from its members. RESULTS: On the basis of 241 survey responses from the genetics community, a consensus term set was chosen for grading gene-disease validity and database submissions. As of December 2021, the database contained 15,241 gene-disease assertions on 4569 unique genes from 12 submitters. When comparing submissions to the database from distinct sources, conflicts in assertions of gene-disease validity ranged from 5.3% to 13.4%. CONCLUSION: Terminology standardization, sharing of gene-disease validity classifications, and resolution of curation conflicts will facilitate collaborations across international curation efforts and in turn, improve consistency in genetic testing and variant interpretation.

Interobserver agreement in the diagnosis of anal dysplasia: comparison between gastrointestinal and gynaecological pathologists and utility of consensus conferences.

AIMS: Management of anal dysplasia relies upon the accurate diagnosis of anal biopsy specimens. As institutions move towards subspecialty signout (SSSO), decisions must be made regarding whether to assign anal biopsies to the gastrointestinal (GI) or gynaecological (GYN) pathology service. MATERIALS AND RESULTS: We identified 200 archival tissue biopsies of anal mucosa and circulated them among three GI pathologists and three GYN pathologists. Each pathologist separately scored each biopsy as normal, atypical, low-grade squamous intra-epithelial lesion (LSIL) or high-grade squamous intra-epithelial lesion (HSIL). Every case that was called HSIL by at least one pathologist was stained with p16 immunostain and a 'gold standard' interpretation of whether or not a case represented HSIL was made. The GI pathologists agreed on 97 (49%) cases prior to consensus; the GYN pathologists agreed on 33 (17%). The sensitivities of the three GI pathologists in detecting HSIL against the 'gold standard' were 47, 100 and 21% and for the GYN pathologists the sensitivities were 74, 89 and 84%; the sensitivities of the GI and GYN consensus diagnoses were 74% each. The specificities of the three GI pathologists in detecting HSIL were 99, 90 and 100% and for the GYN pathologists the specificities were 99, 92 and 91%; the specificities of both the GI and GYN consensus diagnoses were 100%. CONCLUSIONS: A mild to moderate degree of interobserver variability exists in the diagnosis of anal dysplasia among pathologists. Our study indicates the utility of some form of consensus conference, as overall agreement among GI pathologists and among GYN pathologists improved following in-person consensus.

Ten simple rules for training yourself in an emerging field.

The opportunity to participate in and contribute to emerging fields is increasingly prevalent in science. However, simply thinking about stepping outside of your academic silo can leave many students reeling from the uncertainty. Here, we describe 10 simple rules to successfully train yourself in an emerging field, based on our experience as students in the emerging field of ecological forecasting. Our advice begins with setting and revisiting specific goals to achieve your academic and career objectives and includes several useful rules for engaging with and contributing to an emerging field.

Caffeine consumption and onset of alcohol use among early adolescents.

Preventing or delaying the onset of alcohol use among children and youth is an important public health goal. One possible factor in alcohol use onset among early adolescents is caffeine. The aim of this study was to assess the possible contribution of caffeine to the onset of alcohol use during early adolescence. We used data from the Young Mountaineer Health Study Cohort. Survey data were collected from 1349 (response rate: 80.7%) 6th grade students (mean age at baseline 11.5 years) in 20 middle schools in West Virginia during the fall of 2020, and again approximately 6 months later in spring of 2021. We limited our analyses to students reporting never having used any form of alcohol at baseline. Logistic regression was employed in multivariable analyses and both Odds Ratios and Relative Risks reported. At follow-up, almost 14% of participants reported having consumed alcohol at least once and 57% used caffeine of 100 mg + daily. In multivariable analyses we controlled for social and behavioral variables known to impact tobacco use. Caffeine use was operationalized as a three-level factor: no use, <100 mg per day, and 100 + mg per day, with the latter being the approximate equivalent of the minimum of a typical cup of coffee or can of energy drink. Caffeine use of 100 mg + per day was significantly related to alcohol use at 6-months follow-up (OR: 1.79, RR: 1.56, p = .037). We conclude that caffeine consumption among 11-12-year-old adolescents may be a factor in early onset of alcohol use.

Monitoring one heart to help two: heart rate variability and resting heart rate using wearable technology in active women across the perinatal period.

BACKGROUND: Characterizing normal heart rate variability (HRV) and resting heart rate (RHR) in healthy women over the course of a pregnancy allows for further investigation into disease states, as pregnancy is the ideal time period for these explorations due to known decreases in cardiovascular health. To our knowledge, this is the first study to continuously monitor HRV and RHR using wearable technology in healthy pregnant women. METHODS: A total of 18 healthy women participated in a prospective cohort study of HRV and RHR while wearing a WHOOP® strap prior to conception, throughout pregnancy, and into postpartum. The study lasted from March 2019 to July 2021; data were analyzed using linear mixed models with splines for non-linear trends. RESULTS: Eighteen women were followed for an average of 405.8 days (SD = 153). Minutes of logged daily activity decreased from 28 minutes pre-pregnancy to 14 minutes by third trimester. A steady decrease in daily HRV and increase in daily RHR were generally seen during pregnancy (HRV Est. = - 0.10, P < 0.0001; RHR Est. = 0.05, P < 0.0001). The effect was moderated by activity minutes for both HRV and RHR. However, at 49 days prior to birth there was a reversal of these indices with a steady increase in daily HRV (Est. = 0.38, P < 0.0001) and decrease in daily RHR (Est. = - 0.23, P < 0.0001), regardless of activity level, that continued into the postpartum period. CONCLUSIONS: In healthy women, there were significant changes to HRV and RHR throughout pregnancy, including a rapid improvement in cardiovascular health prior to birth that was not otherwise known. Physical activity minutes of any type moderated the known negative consequences of pregnancy on cardiovascular health. By establishing normal changes using daily data, future research can now evaluate disease states as well as physical activity interventions during pregnancy and their impact on cardiovascular fitness.

Development and validation across trimester of the Prenatal Eating Behaviors Screening tool.

Rapid screening tools are useful for identifying at-risk patients and referring them for further assessment and treatment, but none exist that consider the unique medical needs of pregnant women with eating disorders (EDs). There is a need for a rapid, sensitive, and specific screening tool that can be used to identify a potential ED in pregnancy. We started with a set of 25 questions, developed from our qualitative work along with other ED screening tools, and tested on a development (n = 190) and validation sample (n = 167). Statistical analysis included factor analysis and logistic regressions with ROC curves. Development and validation samples were combined for trimester analysis (n = 357). Refining the tool to 12 items demonstrated strong internal reliability (development alpha = 0.95, validation alpha = 0.91). With correlated errors, questions demonstrated acceptable CFA fit (development: GFI: 0.91, RMSEA: 0.10, NNFI: 0.95; validation: GFI: 0.85, RMSEA: 0.14, NNFI: 0.86). Similar fits were seen by trimester: first trimester n = 127, GFI: 0.89, RMSEA: 0.12, NNFI: 0.94; second trimester n = 150, GFI: 0.83, RMSEA: 0.14, NNFI: 0.88; third trimester n = 80, GFI: 0.99, NNFI: 0.99. Validation against current ED diagnosis demonstrated acceptable sensitivity and specificity using a cutoff of 39 (development sensitivity = 80.7%, specificity = 79.7%, OR = 16.42, 95% CI: 7.51, 35.88; validation sensitivity = 69.2%, specificity = 86.5%, OR: 17.43, 95% CI: 6.46, 47.01). Findings suggest the PEBS tool can reliably and sensitively detect EDs across pregnancy trimesters with 12 questions. A further implication of this work is to reduce health and mental health treatment disparities through this standard and rapid screening measure to ensure early identification and treatment.