Dbp1 is a low performance paralog of RNA helicase Ded1 that drives impaired translation and heat stress response.

Ded1 and Dbp1 are paralogous conserved RNA helicases that enable translation initiation in yeast. Ded1 has been heavily studied but the role of Dbp1 is poorly understood. We find that the expression of these two helicases is controlled in an inverse and condition-specific manner. In meiosis and other long-term starvation states, Dbp1 expression is upregulated and Ded1 is downregulated, whereas in mitotic cells, Dbp1 expression is extremely low. Inserting the DBP1 ORF in place of the DED1 ORF cannot replace the function of Ded1 in supporting translation, partly due to inefficient mitotic translation of the DBP1 mRNA, dependent on features of its ORF sequence but independent of codon optimality. Global measurements of translation rates and 5' leader translation, activity of mRNA-tethered helicases, ribosome association, and low temperature growth assays show that-even at matched protein levels-Ded1 is more effective than Dbp1 at activating translation, especially for mRNAs with structured 5' leaders. Ded1 supports halting of translation and cell growth in response to heat stress, but Dbp1 lacks this function, as well. These functional differences in the ability to efficiently mediate translation activation and braking can be ascribed to the divergent, disordered N- and C-terminal regions of these two helicases. Altogether, our data show that Dbp1 is a "low performance" version of Ded1 that cells employ in place of Ded1 under long-term conditions of nutrient deficiency.

Race, Ethnicity, Language, and the Treatment of Low-Risk Febrile Infants.

Importance: Febrile infants at low risk of invasive bacterial infections are unlikely to benefit from lumbar puncture, antibiotics, or hospitalization, yet these are commonly performed. It is not known if there are differences in management by race, ethnicity, or language. Objective: To investigate associations between race, ethnicity, and language and additional interventions (lumbar puncture, empirical antibiotics, and hospitalization) in well-appearing febrile infants at low risk of invasive bacterial infection. Design, Setting, and Participants: This was a multicenter retrospective cross-sectional analysis of infants receiving emergency department care between January 1, 2018, and December 31, 2019. Data were analyzed from December 2022 to July 2023. Pediatric emergency departments were determined through the Pediatric Emergency Medicine Collaborative Research Committee. Well-appearing febrile infants aged 29 to 60 days at low risk of invasive bacterial infection based on blood and urine testing were included. Data were available for 9847 infants, and 4042 were included following exclusions for ill appearance, medical history, and diagnosis of a focal infectious source. Exposures: Infant race and ethnicity (non-Hispanic Black, Hispanic, non-Hispanic White, and other race or ethnicity) and language used for medical care (English and language other than English). Main Outcomes and Measures: The primary outcome was receipt of at least 1 of lumbar puncture, empirical antibiotics, or hospitalization. We performed bivariate and multivariable logistic regression with sum contrasts for comparisons. Individual components were assessed as secondary outcomes. Results: Across 34 sites, 4042 infants (median [IQR] age, 45 [38-53] days; 1561 [44.4% of the 3516 without missing sex] female; 612 [15.1%] non-Hispanic Black, 1054 [26.1%] Hispanic, 1741 [43.1%] non-Hispanic White, and 352 [9.1%] other race or ethnicity; 3555 [88.0%] English and 463 [12.0%] language other than English) met inclusion criteria. The primary outcome occurred in 969 infants (24%). Race and ethnicity were not associated with the primary composite outcome. Compared to the grand mean, infants of families that use a language other than English had higher odds of the primary outcome (adjusted odds ratio [aOR]; 1.16; 95% CI, 1.01-1.33). In secondary analyses, Hispanic infants, compared to the grand mean, had lower odds of hospital admission (aOR, 0.76; 95% CI, 0.63-0.93). Compared to the grand mean, infants of families that use a language other than English had higher odds of hospital admission (aOR, 1.08; 95% CI, 1.08-1.46). Conclusions and Relevance: Among low-risk febrile infants, language used for medical care was associated with the use of at least 1 nonindicated intervention, but race and ethnicity were not. Secondary analyses highlight the complex intersectionality of race, ethnicity, language, and health inequity. As inequitable care may be influenced by communication barriers, new guidelines that emphasize patient-centered communication may create disparities if not implemented with specific attention to equity.

Increasing Clinical Trial Participation of Black Women Diagnosed with Breast Cancer.

Despite racial disparities in breast cancer mortality, Black women remain underrepresented in clinical trials. In this mixed methods research, 48 Black women were engaged via focus group discussions and in-depth interviews to better understand the lived experience of women with breast cancer. The results of this qualitative study informed the development of a subsequent online survey to identify barriers, motivators, and other factors that influence decision-making by Black women diagnosed with breast cancer when considering clinical trial participation. Among the 257 Black survey participants, most (95%) were aware of clinical trials; of those, most viewed them as lifesaving (81%) and/or benefiting others (90%). Negative perceptions such as serious side effects (58%), not receiving real treatment (52%), or risk of potential harm (62%) were indicated. Barriers included financial expenses (49%), concerns that their condition could be made worse (29%), that they would receive a placebo (28%), or that treatment was unapproved (28%). Participants were more likely than their health care providers (HCPs) to initiate discussions of clinical trials (53% versus 33%), and 29% of participants indicated a need for more information about risks and benefits, even after having those conversations. The most trustworthy sources of information on clinical trials were HCPs (66%) and breast cancer support groups (64%). These results suggest that trusted communities are key for providing education on clinical trials. However, there is also a need for HCPs to proactively discuss clinical trials with patients to ensure that they are adequately informed about all aspects of participation.

Neutralizing Antibody Responses to Messenger RNA Coronavirus Disease 2019 Vaccines Versus Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Pregnant Women and Vaccine-Induced Antibody Transfer to Infants.

Background: Early coronavirus disease 2019 (COVID-19) vaccine trials excluded pregnant women, resulting in limited data about immunogenicity and maternal-fetal antibody transfer, particularly by gestational timing of vaccination. Methods: In this multicenter observational immunogenicity study, pregnant and nonpregnant women receiving COVID-19 vaccines were prospectively enrolled. Participants had sera collected before vaccination, at 14-28 days after each vaccine dose, at delivery (umbilical cord and peripheral), and from their infants at 3 and 6 months. Geometric mean titers (GMTs) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ID50 neutralizing antibody (nAb) against D614G-like viruses were compared by participant characteristics. Results: Overall, 23 nonpregnant and 85 pregnant participants (trimester of first vaccine dose: 10 first, 47 second, 28 third) were enrolled. Ninety-three percent (76/82 with blood samples) of pregnant participants had detectable SARS-CoV-2 nAb after 2 vaccine doses, but GMTs (95% confidence intervals) were lower in pregnant participants than nonpregnant participants (1722 [1136-2612] vs 4419 [2012-9703]; P = .04). By 3 and 6 months, 28% and 74% of infants, respectively, of vaccinated participants had no detectable nAb to D614G-like viruses. Among the 71 pregnant participants without detectable nAb before vaccination, cord blood GMTs at delivery were 5-fold higher among participants vaccinated during the third versus first trimester, and cord blood nAb titers appeared inversely correlated with weeks since first vaccine dose (R2 = 0.06, P = .06). Conclusions: Though most pregnant women develop nAb after 2 doses of mRNA COVID-19 vaccines, this analysis suggests that infant protection from maternal vaccination varies by gestational timing of vaccination and wanes. Additional prevention strategies such as caregiver vaccination may warrant consideration to optimize infant protection.

Bidirectional promoter activity from expression cassettes can drive off-target repression of neighboring gene translation.

Targeted selection-based genome-editing approaches have enabled many fundamental discoveries and are used routinely with high precision. We found, however, that replacement of DBP1 with a common selection cassette in budding yeast led to reduced expression and function for the adjacent gene, MRP51, despite all MRP51 coding and regulatory sequences remaining intact. Cassette-induced repression of MRP51 drove all mutant phenotypes detected in cells deleted for DBP1. This behavior resembled the 'neighboring gene effect' (NGE), a phenomenon of unknown mechanism whereby cassette insertion at one locus reduces the expression of a neighboring gene. Here, we leveraged strong off-target mutant phenotypes resulting from cassette replacement of DBP1 to provide mechanistic insight into the NGE. We found that the inherent bidirectionality of promoters, including those in expression cassettes, drives a divergent transcript that represses MRP51 through combined transcriptional interference and translational repression mediated by production of a long undecoded transcript isoform (LUTI). Divergent transcript production driving this off-target effect is general to yeast expression cassettes and occurs ubiquitously with insertion. Despite this, off-target effects are often naturally prevented by local sequence features, such as those that terminate divergent transcripts between the site of cassette insertion and the neighboring gene. Thus, cassette-induced off-target effects can be eliminated by the insertion of transcription terminator sequences into the cassette, flanking the promoter. Because the driving features of this off-target effect are broadly conserved, our study suggests it should be considered in the design and interpretation of experiments using integrated expression cassettes in other eukaryotic systems, including human cells.

Agreement Between Pregnant Individuals' Self-Report of Coronavirus Disease 2019 (COVID-19) Vaccination and Medical Record Documentation.

For public health research such as vaccine uptake or effectiveness assessments, self-reported coronavirus disease 2019 (COVID-19) vaccination status may be a more efficient measure than verifying vaccination status from medical records if agreement between sources is high. We assessed agreement between self-reported and medical record-documented COVID-19 vaccination status among pregnant individuals followed in a cohort during August 2020-October 2021. At end of pregnancy, participants completed questionnaires about COVID-19 vaccine receipt during pregnancy; staff verified vaccination status using medical records. Agreement was assessed between self-reported and medical record vaccination status using Cohen's kappa. There was high agreement between self-reported and medical record vaccination status (Kappa coefficient=0.94, 95% CI 0.91-0.98), suggesting that self-report may be acceptable for ascertaining COVID-19 vaccination status during pregnancy.

A Workplace Procedure Training Cart to Augment Pediatric Resident Procedural Learning.

OBJECTIVE: Our primary aim was to describe pediatric residents' use of a workplace procedural training cart. An exploratory aim was to examine if the cart associated with increased resident procedural experiences with real patients. METHODS: Guided by the procedural training construct of "Learn, See, Practice, Prove, Do, Maintain," we created a novel workplace procedural training cart with videos (learn and see) and simulation equipment (practice and prove). An electronic logbook recorded resident use data, and a brief survey solicited residents' perceptions of the cart's educational impact. We queried our electronic medical record to compare the proportion of real procedures completed by residents before and after the intervention. RESULTS: From August 1 to December 31, 2019, 24 pediatric residents (10 interns and 14 seniors) rotated in the pediatric emergency department. Twenty-one cart encounters were logged, mostly by interns (67% [14/21]). The 21 cart encounters yielded 32 learning activities (8 videos watched and 24 procedures practiced), reflecting the residents' interest in laceration repair (50% [4/8], 54% [13/24]) and lumbar puncture (38% [3/8], 33% [8/24]). All users agreed (29% [6/21]) or strongly agreed (71% [15/21]) the cart encouraged practice and improved confidence in independently performing procedures. No changes were observed in the proportion of actual procedures completed by residents. CONCLUSIONS: A workplace procedural training cart was used mostly by pediatric interns. The cart cultivated residents' perceived confidence in real procedures but was not used by all residents or influenced residents' procedural behaviors in the pediatric emergency department.

Respiratory Viral Infections and Infection Prevention Practices Among Women With Acute Respiratory Illness During Delivery Hospitalizations During the 2019-2020 Influenza Season.

BACKGROUND: We conducted a cross-sectional study of pregnant women with acute respiratory illness during delivery hospitalizations during influenza season to describe clinical testing for respiratory viruses and infection prevention practices. METHODS: Women had nasal swabs tested for influenza and other respiratory viruses. Among 91 enrolled women, 22 (24%) had clinical testing for influenza. RESULTS: Based on clinical and study testing combined, 41 of 91 (45%) women had samples positive for respiratory viruses. The most common virus was influenza (17 of 91, 19%); 53% (9 of 17) of influenza virus infections were identified through study testing alone. Only 16% of women were on droplet precautions. CONCLUSIONS: Peripartum respiratory infections may be underrecognized.

Incidence and Clinical Characteristics of and Risk Factors for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Among Pregnant Individuals in the United States.

BACKGROUND: Data about the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among pregnant individuals are needed to inform infection-prevention guidance and counseling for this population. METHODS: We prospectively followed a cohort of pregnant individuals during August 2020-March 2021 at 3 US sites. The 3 primary outcomes were incidence rates of any SARS-CoV-2 infection, symptomatic infection, and asymptomatic infection, during pregnancy during periods of SARS-CoV-2 circulation. Participants self-collected weekly midturbinate nasal swabs for SARS-CoV-2 reverse transcription-polymerase chain reaction testing, completed weekly illness symptom questionnaires, and submitted additional swabs with coronavirus disease 2019 (COVID-19)-like symptoms. An overall SARS-CoV-2 infection incidence rate weighted by population counts of women of reproductive age in each state was calculated. RESULTS: Among 1098 pregnant individuals followed for a mean of 10 weeks, 9% (99/1098) had SARS-CoV-2 infections during the study. Population-weighted incidence rates of SARS-CoV-2 infection were 10.0 per 1000 (95% confidence interval, 5.7-14.3) person-weeks for any infection, 5.7 per 1000 (1.7-9.7) for symptomatic infections, and 3.5 per 1000 (0-7.1) for asymptomatic infections. Among 96 participants with SARS-CoV-2 infections and symptom data, the most common symptoms were nasal congestion (72%), cough (64%), headache (59%), and change in taste or smell (54%); 28% had measured or subjective fever. Median symptom duration was 10 (interquartile range, 6-16) days. CONCLUSIONS: Pregnant individuals in this study had a 1% risk of SARS-CoV-2 infection per week, underscoring the importance of COVID-19 vaccination and other prevention measures during pregnancy while SARS-CoV-2 is circulating in the community.

Attitudes Toward COVID-19 Illness and COVID-19 Vaccination among Pregnant Women: A Cross-Sectional Multicenter Study during August-December 2020.

OBJECTIVE: The aim of the study was to evaluate pregnant women's attitudes toward COVID-19 illness and vaccination and identify factors associated with vaccine acceptability. STUDY DESIGN: This was a cross-sectional survey among pregnant women enrolled in a prospective COVID-19 cohort study in Salt Lake City, UT, Birmingham, AL, and New York, NY, from August 9 to December 10, 2020. Women were eligible if they were 18 to 50 years old and <28 weeks of gestation. Upon enrollment, women completed surveys regarding concerns about COVID-19 illness and likelihood of getting COVID-19 vaccine if one were available during pregnancy. Vaccine acceptability was defined as a response of "very likely" or "somewhat likely" on a 4-point Likert scale. Factors associated with vaccine acceptability were assessed with multivariable logistic regression. RESULTS: Of 939 pregnant women eligible for the main cohort study, 915 (97%) consented to participate. Among these 915 women, 39% self-identified as White, 23% Black, 33% Hispanic, and 4% Other. Sixty-two percent received an influenza vaccine last season. Seventy-two percent worried about getting sick with COVID-19. If they were to get sick, 92% worried about harm to their pregnancy and 80% about harm to themselves. Only 41% reported they would get a vaccine. Of women who were unlikely to get vaccinated, the most frequently cited concern was vaccine safety for their pregnancy (82%). Non-Hispanic Black and Hispanic women had lower odds of accepting a vaccine compared with non-Hispanic White women (adjusted odds ratios [aOR] 0.4, 95% CI 0.2-0.6 for both). Receipt of influenza vaccine during the previous season was associated with higher odds of vaccine acceptability (aOR 2.1, 95% CI 1.5-3.0). CONCLUSION: Although most pregnant women worried about COVID-19 illness, <50% were willing to get vaccinated during pregnancy. Racial and ethnic disparities in plans to accept COVID-19 vaccine highlight the need to prioritize strategies to address perceived barriers among groups at high risk for COVID-19. KEY POINTS: · Less than half of pregnant patients stated they would get a COVID-19 vaccine.. · Protecting their baby was the most common reason for acceptance and refusal of the COVID-19 vaccine.. · Patients of minority race/ethnicity and those without prior influenza vaccination were less likely to accept the COVID-19 vaccine..

Development and Validation of a Natural Language Processing Tool to Identify Injuries in Infants Associated With Abuse.

OBJECTIVES: Medically minor but clinically important findings associated with physical child abuse, such as bruises in pre-mobile infants, may be identified by frontline clinicians yet the association of these injuries with child abuse is often not recognized, potentially allowing the abuse to continue and even to escalate. An accurate natural language processing (NLP) algorithm to identify high-risk injuries in electronic health record notes could improve detection and awareness of abuse. The objectives were to: 1) develop an NLP algorithm that accurately identifies injuries in infants associated with abuse and 2) determine the accuracy of this algorithm. METHODS: An NLP algorithm was designed to identify ten specific injuries known to be associated with physical abuse in infants. Iterative cycles of review identified inaccurate triggers, and coding of the algorithm was adjusted. The optimized NLP algorithm was applied to emergency department (ED) providers' notes on 1344 consecutive sample of infants seen in 9 EDs over 3.5 months. Results were compared with review of the same notes conducted by a trained reviewer blind to the NLP results with discrepancies adjudicated by a child abuse expert. RESULTS: Among the 1344 encounters, 41 (3.1%) had one of the high-risk injuries. The NLP algorithm had a sensitivity and specificity of 92.7% (95% confidence interval [CI]: 79.0%-98.1%) and 98.1% (95% CI: 97.1%-98.7%), respectively, and positive and negative predictive values were 60.3% and 99.8%, respectively, for identifying high-risk injuries. CONCLUSIONS: An NLP algorithm to identify infants with high-risk injuries in EDs has good accuracy and may be useful to aid clinicians in the identification of infants with injuries associated with child abuse.

The impact of a child abuse guideline on differences between pediatric and community emergency departments in the evaluation of injuries.

BACKGROUND: Although child physical abuse is missed more frequently in community (CEDs) vs. pediatric emergency departments (PEDs), little information exists describing how evaluations of high-risk injuries differ between these settings. OBJECTIVES: To determine differences in evaluations of infants for abuse between a PED and CEDs and whether a child abuse guideline reduced these differences. PARTICIPANTS AND SETTING: Infants presenting to one PED (n = 162) and three CEDs (n = 159) with 3 injury categories: 1) Injuries for which the American Academy of Pediatrics recommends skeletal survey (SS) testing (infants <5-months with an oral injury or bruising, <9-months with a non-skull fracture, and < 12-months with an intracranial hemorrhage); 2) an oral injury or high-risk bruising in older infants; and 3) multiple types of high-risk injuries. METHODS: We assessed differences in SS testing and child protective services (CPS) reporting between the PED and CEDs before and after implementation of a child abuse guideline. RESULTS: The median (IQR) age was 4 months (2-7). Before guideline implementation, infants with injuries in categories 1 and 2 had an increased odds of SS testing in the PED vs. the CEDs (Category 1: aOR 2.83, 95% CI: 1.01-8.10; Category 2: aOR 10.1, CI: 1.2-88.0) and CPS reporting (Category 1: aOR 7.96, CI: 2.3-26.7; Category 2: aOR 12.0, CI: 1.4-103.5). After guideline implementation, there were no statistically significant differences in testing and reporting for any injury category. CONCLUSIONS: Implementation of a child abuse guideline minimized differences between a PED and CEDs in the evaluation of infants with injuries concerning for abuse.

Disparities in Accessing and Reading Open Notes in the Emergency Department Upon Implementation of the 21st Century CURES Act.

STUDY OBJECTIVE: There is a continued movement toward health data transparency, accelerated by the 21st Century CURES Act, which mandated the automatic and immediate release of clinical notes, often termed "open notes." Differences in utilization among different patient demographics and disproportionately affected populations within the emergency department (ED) are not yet known. METHODS: This was an observational study of 10 EDs and 3 urgent care centers across a single health system over a 13-week period from February 1, 2021 to May 2, 2021. Primary outcomes included the proportion of patients with patient portal access to open notes at the time of encounter, the proportion of patients with access who opened the clinical note, and time from clinical note signing to patient read. RESULTS: Among 98,725 patient visits, less than half (48.9%) had patient portal access, of which 13.7% read an open note. Access was less likely in patients who were under age 18 (odds ratio 0.10, 95% confidence interval 0.08 to 0.11), older than 65 (0.82, 0.73 to 0.93), Black non-Hispanic (0.66, 0.61 to 0.73), non-English speakers, and on public insurance. Patients were less likely to read open notes if they identified as Black non-Hispanic (0.61, 0.57 to 0.66), spoke Spanish (0.70, 0.60 to 0.81), or were on public insurance. CONCLUSION: We identified substantial differences in digital access to clinical notes as well as patient utilization of open notes in a large, diverse sample. Health transparency initiatives must address not only technology adoption broadly but also the unique barriers faced by populations experiencing disadvantage to facilitate equitable access to and awareness about digital health tools without the unintended consequence of expanding disparities.

Performing Ribosome Profiling to Assess Translation in Vegetative and Meiotic Yeast Cells.

Ribosome profiling, first developed in 2009, is the gold standard for quantifying and qualifying changes to translation genome-wide (Ingolia et al., Science, 2009). Though first designed and optimized in vegetative budding yeast, it has since been modified and specialized for use in diverse cellular states in yeast, as well as in bacteria, plants, human cells, and many other organisms (Ingolia et al. Science, 2009, reviewed in (Ingolia et al., Cold Spring Harb Perspect Biol, 2019; Brar and Weissman, Nat Rev Mol Cell Biol, 2015)). Here we report the current ribosome profiling protocol used in our lab to study genome-wide changes to translation in budding yeast undergoing the developmental process of meiosis (Brar et al., Science, 2012; Cheng et al., Cell, 2018). We describe this protocol in detail, including the following steps: collection and flash freezing samples, cell lysis and extract preparation, sucrose gradient centrifugation and monosome collection, RNA extraction, library preparation, and library quality control. Almost every step presented here should be directly applicable to performing ribosome profiling in other eukaryotic cell types or cell states.

Small Rare Earth Magnets Adhered to Pharyngeal Tissue in a Pediatric Emergency Department Patient.

BACKGROUND: Small rare earth magnets pose a known health risk to children and many cases of ingestion and aspiration with associated complications have been described. More unusual, but also seen in children, are retained foreign bodies in the oropharynx that require extraction. CASE REPORT: We present the case of a 3-year-old boy with persistent left-sided sore throat 1 h after ingestion of several 3-mm spherical rare earth magnets. No foreign bodies were visible in the oropharynx on examination; however, a chest radiograph revealed two adjacent magnets within the lower pharyngeal space, as well as four magnets linearly clumped within the small intestine. The patient was taken to the operating room, where visual inspection under general anesthesia revealed two magnets adhered to the pharyngoepiglottic folds (one on the laryngeal surface and one on the glottic surface). They were removed in full without issue, preventing aspiration. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Given the recent increase in incidence of rare earth magnet ingestion, emergency providers ought to be aware of the risks and complications associated with magnetic foreign body ingestion in children and the workup and considerations involved in their removal. Providers should also advocate for improved safety controls of these products, which have been found to be effective in the past.

Global mapping of translation initiation sites by TIS profiling in budding yeast.

Translation initiation site (TIS) profiling allows for the genome-wide identification of TISs in vivo by exclusively capturing mRNA fragments within ribosomes that have just completed translation initiation. It leverages translation inhibitors, such as harringtonine and lactimidomycin (LTM), that preferentially capture ribosomes at start codon positions, protecting TIS-derived mRNA fragments from nuclease digestion. Here, we describe a step-by-step protocol for TIS profiling in LTM-treated budding yeast that we developed to identify TISs and open reading frames in vegetative and meiotic cells. For complete details on the use and execution of this protocol, please refer to Eisenberg et al. (2020).

Aurora B-dependent Ndc80 degradation regulates kinetochore composition in meiosis.

The kinetochore complex is a conserved machinery that connects chromosomes to spindle microtubules. During meiosis, the kinetochore is restructured to accommodate a specialized chromosome segregation pattern. In budding yeast, meiotic kinetochore remodeling is mediated by the temporal changes in the abundance of a single subunit called Ndc80. We previously described the regulatory events that control the timely synthesis of Ndc80. Here, we report that Ndc80 turnover is also tightly regulated in meiosis: Ndc80 degradation is active in meiotic prophase, but not in metaphase I. Ndc80 degradation depends on the ubiquitin ligase APCAma1 and is mediated by the proteasome. Importantly, Aurora B-dependent Ndc80 phosphorylation, a mark that has been previously implicated in correcting erroneous microtubule-kinetochore attachments, is essential for Ndc80 degradation in a microtubule-independent manner. The N terminus of Ndc80, including a 27-residue sequence and Aurora B phosphorylation sites, is both necessary and sufficient for kinetochore protein degradation. Finally, defects in Ndc80 turnover predispose meiotic cells to chromosome mis-segregation. Our study elucidates the mechanism by which meiotic cells modulate their kinetochore composition through regulated Ndc80 degradation, and demonstrates that Aurora B-dependent regulation of kinetochores extends beyond altering microtubule attachments.

Differences in Frequency of Visits to Pediatric Primary Care Practices and Emergency Departments by Body Mass Index.

OBJECTIVES: To examine differences in utilization across health care settings among children by body mass index (BMI) categories to help identify opportunities for interventions. METHODS: A retrospective study was conducted using 1 year of electronic health records following an index primary care visit for children 3 to 17 years old in 2016. Index visits occurred at >40 pediatric practices affiliated with a Northeastern health system. Using normal BMI as a reference group, we examined the extent to which children's BMI percentile categories were associated with primary care visits, emergency department (ED) visits, hospitalizations, and ED visit acuity. Age, sex, race/ethnicity, and insurance status were used as covariates. RESULTS: Of those with biologically plausible values for height and weight (n = 30,352), the prevalences of overweight, obesity, and severe obesity were 16.3%, 12.4%, and 5.7%, respectively. Children outside of the normal BMI range made more primary care visits; however, relative patterns of ED utilization were not consistent. Children with obesity versus normal BMI were less likely to have ED visits of high acuity. Risk of hospitalization was higher among children with overweight or severe obesity. CONCLUSIONS: Children's BMI categories were associated with health care utilization, specifically primary care visits, ED visits, and hospitalizations. Further investigation is needed to explore the drivers of these differences in utilization, such as the impact of stigma and perceived weight bias on care-seeking patterns, and to examine the role of settings outside of primary care in pediatric weight management.

X + Y Scheduling in Pediatric Residency: Continuity, Handoffs, and Trainee Experience.

BACKGROUND: Many internal medicine residency programs have transitioned to an X + Y clinic schedule, in which weekly continuity clinics are removed and clinic experience is instead condensed into 2-week blocks interspersed throughout the year, but few pediatric training programs have adopted this approach. We initiated X + Y scheduling in the 2015 academic year, with the hypothesis that outpatient continuity could be maintained or improved while inpatient handoffs would be reduced. We also hypothesized that learner experience with X + Y scheduling would be positive. METHODS: Continuity and handoffs were compared over a 7-month period in 2013 to 2014 and 2015 to 2016. Outpatient continuity was calculated as the proportion of visits in which the patient was seen by the designated primary care provider (PCP). Handoffs were calculated through analysis of the online resident schedule with comparison of weekly totals for all inpatient teams. Resident perceptions were obtained in an online survey of residents who experienced both systems. RESULTS: With X + Y scheduling, overall outpatient continuity improved from 2914 of 9882 (29.5%) of visits seen by a patient's PCP to 3066 of 9769 (31.4%) (P = .004), but preventive visit continuity decreased from 2170 of 4687 (46.2%) to 2025 of 4709 (43%) (P = .001). Inpatient handoffs decreased with X + Y scheduling from 30 to 20 weekly handoffs (P < .001). In total, 85% of residents reported a positive experience with X + Y scheduling. CONCLUSIONS: An X + Y scheduling approach in pediatrics is a viable alternative to weekly clinics, resulting in improved learner experience, reductions in inpatient handoffs, and small mixed effects on outpatient continuity.