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We then discuss potential molecular mechanisms underlying timing enhancer function. Finally, we explore recent evidence drawing connections between timing enhancers and genetic risk for immunopathology. We argue that the timing enhancer model is a useful framework for understanding how cis-regulatory elements control the central dimension of timing in lymphocyte biology.
Identifying distinctive features of the vocal fold (VF) during development could have significant clinical implications for treating voice disorders. This study investigates the structural organization of the VF microanatomy across gender and age groups using optical coherence tomography (OCT).

Prospective clinical trial.

In vivo OCT images were acquired from 97 patients (58 males and 39 females) aged between 6 weeks and 27 years. All patients showed no signs of vocal fold pathology on endoscopy. Morphological features were extracted from OCT images and statistically compared between age groups. This study was performed at Massachusetts Eye and Ear between 2017 and 2019.

All OCT acquisitions show a stratified microanatomy across age groups, even in newborns suggesting the presence of a superficial lamina propria (SLP) at birth. Linderalactone Furthermore, the optical scattering in the VF lamina propria changes according to age, suggesting subepithelial maturation. Although the epithelium thickness was relatively constant across age groups, the SLP showed a significant linear relationship between age and thickness (P = .016). Furthermore, a significant difference (P = .002) in SLP thickness was found between young adult males and females. The overall thickness of the entire mucosa did not change significantly with age.

OCT is a noninvasive imaging modality capable of providing quantitative morphological features to describe the VF development. A stratified structure can be observed in OCT from newborns to young adults. Further investigations could combine OCT, acoustic measurements, and molecular sensitive techniques to provide a complete interpretation of the VF development.

NA Laryngoscope, 2021.
NA Laryngoscope, 2021.The unraveling of the pathophysiology of acute myeloid leukemia (AML) has resulted in rapid translation of the information into clinical practice. After more than 40 years of slow progress in AML research, the US Food and Drug Administration has approved nine agents for different AML treatment indications since 2017. In this review, we detail the progress that has been made in the research and treatment of AML, citing key publications related to AML research and therapy in the English literature since 2000. The notable subsets of AML include acute promyelocytic leukemia (APL), core-binding factor AML (CBF-AML), AML in younger patients fit for intensive chemotherapy, and AML in older/unfit patients (usually at the age cutoff of 60-70 years). We also consider within each subset whether the AML is primary or secondary (therapy-related, evolving from untreated or treated myelodysplastic syndrome or myeloproliferative neoplasm). In APL, therapy with all-trans retinoic acid and arsenic trioxide results in estimatedon, AML therapy is evolving rapidly and treatment results are improving in all AML subsets as novel agents and strategies are incorporated into traditional AML chemotherapy. LAY SUMMARY Ongoing research in acute myeloid leukemia (AML) is progressing rapidly. Since 2017, the US Food and Drug Administration has approved 10 drugs for different AML indications. This review updates the research and treatment pathways for AML.
While many students participate in research years or fellowships prior to entering the otolaryngology-head and neck surgery (OHNS) match, the effects of these fellowships on match outcomes remains unclear. This study aimed to assess the impact of research fellowships on odds of matching into OHNS.

Cross-sectional analysis.

Applications from first-time, US allopathic seniors between the 2014-2015 and the 2019-2020 application cycles were reviewed. Data were abstracted from Electronic Residency Application Service applications and match results determined using the National Residency Matching Program database and online public sources. The relationship between research fellowships and matching was analyzed using multivariate logistic regression.

Of the 1775 applicants included, nearly 16% (n = 275) participated in research fellowships and 84.1% matched (n = 1492). Research fellows were no more likely to match into OHNS than non-research fellows (86.9% vs. 83.5%, unadjusted odds ratio [OR] 1.31, P = .161), even when adjusting for applicant characteristics (predicted probability [PP] 88.8% vs. 85.8%, adjusted OR 1.31, P = .210). For applicants from top 25 medical schools, however, research fellowships were associated with higher odds of matching (PP 96.5% vs. 90.0%, adjusted OR 3.07, P = .017). In addition, completing a fellowship was associated with significantly greater odds of matching into a top 25 OHNS residency program (PP 58.6% vs. 30.5%, adjusted OR 3.24, P < .001).

Fellowships may be beneficial for select applicants, though for most, they are not associated with improved odds of matching. These findings provide context for OHNS residency candidates considering research fellowships and should be carefully weighed against other potential advantages and disadvantages of fellowships.

N/A Laryngoscope, 2021.
N/A Laryngoscope, 2021.The three-parameter logistic model is widely used to model the responses to a proficiency test when the examinees can guess the correct response, as is the case for multiple-choice items. However, the weak identifiability of the parameters of the model results in large variability of the estimates and in convergence difficulties in the numerical maximization of the likelihood function. To overcome these issues, in this paper we explore various shrinkage estimation methods, following two main approaches. First, a ridge-type penalty on the guessing parameters is introduced in the likelihood function. The tuning parameter is then selected through various approaches cross-validation, information criteria or using an empirical Bayes method. The second approach explored is based on the methodology developed to reduce the bias of the maximum likelihood estimator through an adjusted score equation. The performance of the methods is investigated through simulation studies and a real data example.
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