Quadruple Screening in the Age of Cell-Free DNA: What are We Losing?

Cell-free DNA has emerged as the most reliable, non-invasive prenatal screening tool for fetal aneuploidies. It has come to replace the previously widely used quadruple screen offered in the second trimester of pregnancy. This change comes with improved detection for aneuploidy but also presents potential gaps in prenatal diagnosis including detection of open fetal defects and emerging data on prediction of adverse pregnancy outcomes. This review article provides a historical summary of the quadruple marker screen and evaluates the intersection of this screen with cell-free DNA. Furthermore, it discusses points to consider as providers trend toward cell-free DNA testing alone and reviews potential options to remedy any disparities

Advanced Maternal Age and the Risk of Major Congenital Anomalies

Objective This study aims to determine if advanced maternal age (AMA) is a risk factor for major congenital anomalies, in the absence of aneuploidy. Study Design Retrospective cohort study of all patients with a singleton gestation presenting for second trimester anatomic survey over a 19-year study period. Aneuploid fetuses were excluded. Study groups were defined by maternal age ≤ 34 and ≥ 35 years. The primary outcome was the presence of one or more major anomalies diagnosed at the second trimester ultrasound. Univariable and multivariable logistic regression analyses were used to estimate the risk of major anomalies in AMA patients. Results Of 76,156 euploid fetuses, 2.4% (n = 1,804) were diagnosed with a major anomaly. There was a significant decrease in the incidence of major fetal anomalies with increasing maternal age until the threshold of age 35 (p < 0.001). Being AMA was significantly associated with an overall decreased risk for major fetal anomalies (adjusted odds ratio: 0.59, 95% confidence interval: 0.52–0.66). The subgroup analysis demonstrated similar results for women ≥ 40 years of age. Conclusion AMA is associated with an overall decreased risk for major anomalies. These findings may suggest that the “all or nothing” phenomenon plays a more robust role in embryonic development with advancing oocyte age, with anatomically normal fetuses being more likely to survive

Describing Self-confidence in Ultrasound Performance with Increased Exposure

Presented as a poster at 2020 IUSM Education Day

To Flip or Not to Flip: Learning Style Preferences among Millennial Physician Assistant Students

Introduction: Presenting material in a manner that is most palatable to students is important to improve the learning process. We evaluated the efficacy of different teaching styles including the flipped classroom and assessed the learning style preferences of a cohort of medical learners in a preclinical obstetrics and gynecology course. Methods: We conducted three teaching sessions with 35 physician assistant students. A different teaching style was implemented for each session including a traditional lecture with interactive learning technology augmentation, a flipped classroom, and a hybrid approach incorporating lecture and group work. Students were surveyed using a Likert scale regarding the efficacy of the format, clinical relevance of the material, and their learning preference for future sessions. Results: Students rated the traditional approach as the most effective, most relevant, and most preferred method. Students preferred the flipped classroom least, but they rated it as slightly more effective and relevant than the hybrid approach. Conclusion: The teaching style of various coursework including the preclinical obstetrics and gynecology curriculum may not need to be altered for millennial learners. This study showed the flipped classroom was the least favored teaching style and that there was a marked preference by students for a more traditional didactic lecture

The Velocity Function of Galaxies

We present a galaxy circular velocity function, Psi(log v), derived from existing luminosity functions and luminosity-velocity relations. Such a velocity function is desirable for several reasons. First, it enables an objective comparison of luminosity functions obtained in different bands and for different galaxy morphologies, with a statistical correction for dust extinction. In addition, the velocity function simplifies comparison of observations with predictions from high-resolution cosmological N-body simulations. We derive velocity functions from five different data sets and find rough agreement among them, but about a factor of 2 variation in amplitude. These velocity functions are then compared with N-body simulations of a LCDM model (corrected for baryonic infall) in order to demonstrate both the utility and current limitations of this approach. The number density of dark matter halos and the slope of the velocity function near v_*, the circular velocity corresponding to an ~L_* spiral galaxy, are found to be comparable to that of observed galaxies. The primary sources of uncertainty in construction of Psi(log v) from observations and N-body simulations are discussed and explanations are suggected to account for these discrepancies.Comment: Latex. 28 pages, 4 figures. Accepted by Ap

Breaking Bad News: A Randomized Trial Assessing Resident Performance After Novel Video Instruction

Introduction; Delivering bad news to patients is an essential skill for physicians, which is often developed through patient encounters. Residents in our program participate in objective structured clinical examinations (OSCEs) on an annual basis to evaluate their skills in these scenarios. Our objectives were to develop an educational video and determine if an educational video provided to residents prior to OSCEs would improve performance. Methods: Previous OSCEs were reviewed to identify best practices and to create a four-minute video highlighting the "do's and don'ts" of delivering bad news. Residents in two post-graduate year (PGY) classes were randomized to watch the video prior to or after a standardized patient encounter. Three masked reviewers assessed resident empathy, attention, and understanding on 10 five-point Likert scales and assigned a total score (scale: 0-50). Hedges' g was used to assess mean scores and effect size. Results: A total of 17 residents participated in the evaluation: nine in the pre-OSCE video group and eight in the control group. Residents randomized to the video prior to the patient encounter had a mean score of 37.01 (SD=3.6). Residents randomized to the control group had a mean score of 35.38 (SD=4.85). Hedges' g was 0.37 (95% CI: -0.59 to 1.33). Conclusion: Residents randomized to the video group had a small increase in OSCE performance, which was not statistically significant. The novel video was helpful and addresses the need for a quick pre-assessment educational tool, though interns and graduating medical students may be a more appropriate target audience for instruction

A dual role for prediction error in associative learning

Confronted with a rich sensory environment, the brain must learn statistical regularities across sensory domains to construct causal models of the world. Here, we used functional magnetic resonance imaging and dynamic causal modeling (DCM) to furnish neurophysiological evidence that statistical associations are learnt, even when task-irrelevant. Subjects performed an audio-visual target-detection task while being exposed to distractor stimuli. Unknown to them, auditory distractors predicted the presence or absence of subsequent visual distractors. We modeled incidental learning of these associations using a Rescorla--Wagner (RW) model. Activity in primary visual cortex and putamen reflected learning-dependent surprise: these areas responded progressively more to unpredicted, and progressively less to predicted visual stimuli. Critically, this prediction-error response was observed even when the absence of a visual stimulus was surprising. We investigated the underlying mechanism by embedding the RW model into a DCM to show that auditory to visual connectivity changed significantly over time as a function of prediction error. Thus, consistent with predictive coding models of perception, associative learning is mediated by prediction-error dependent changes in connectivity. These results posit a dual role for prediction-error in encoding surprise and driving associative plasticity

Association of blood lead level with neurological features in 972 children affected by an acute severe lead poisoning outbreak in Zamfara State, northern Nigeria.

BACKGROUND: In 2010, Médecins Sans Frontières (MSF) investigated reports of high mortality in young children in Zamfara State, Nigeria, leading to confirmation of villages with widespread acute severe lead poisoning. In a retrospective analysis, we aimed to determine venous blood lead level (VBLL) thresholds and risk factors for encephalopathy using MSF programmatic data from the first year of the outbreak response. METHODS AND FINDINGS: We included children aged ≤5 years with VBLL ≥45 µg/dL before any chelation and recorded neurological status. Odds ratios (OR) for neurological features were estimated; the final model was adjusted for age and baseline VBLL, using random effects for village of residence. 972 children met inclusion criteria: 885 (91%) had no neurological features; 34 (4%) had severe features; 47 (5%) had reported recent seizures; and six (1%) had other neurological abnormalities. The geometric mean VBLLs for all groups with neurological features were >100 µg/dL vs 65.9 µg/dL for those without neurological features. The adjusted OR for neurological features increased with increasing VBLL: from 2.75, 95%CI 1.27-5.98 (80-99.9 µg/dL) to 22.95, 95%CI 10.54-49.96 (≥120 µg/dL). Neurological features were associated with younger age (OR 4.77 [95% CI 2.50-9.11] for 1-<2 years and 2.69 [95%CI 1.15-6.26] for 2-<3 years, both vs 3-5 years). Severe neurological features were seen at VBLL <105 µg/dL only in those with malaria. INTERPRETATION: Increasing VBLL (from ≥80 µg/dL) and age 1-<3 years were strongly associated with neurological features; in those tested for malaria, a positive test was also strongly associated. These factors will help clinicians managing children with lead poisoning in prioritising therapy and developing chelation protocols