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Introduction:. The Accreditation Council for Graduate Medical Education Resident Case Log is one of the primary tools used to track surgical experience. Owing to the self-reported nature of case logging, there is uncertainty in the consistency and accuracy of case logging. The aims of this study are two-fold: to assess current resident case log Current Procedural Terminology (CPT) code selection and practices across orthopaedic surgery residencies and to understand current attitudes of both program directors (PD) and residents surrounding case logging. Methods:. Residents and PDs from 18 residency programs received standardized, consensus-built surveys distributed through the Collaborative Orthopaedic Educational Research Group. Resident surveys additionally contained clinical orthopaedic subspecialties vignettes on sports, trauma, and spine. Each subspecialty section contained 4 clinical vignettes with stepwise increases in complexity/CPT coding procedures. Results:. One hundred sixteen residents (response rate: 28.4%) and 16 PDs (response rate: 88.9%) participated. Formal case log training was reported by 53.0% of residents and 56.3% of PDs. A total of 7.8% of residents rated themselves “excellent” at applying CPT codes for the case log, while 0.0% PDs rated their residents' ability as “excellent.” In total, 40.9% of residents and 81.3% of PDs responded that it was “extremely important” or “very important” to code accurately (p = 0.006). Agreement between resident CPT code selection and number of cases and procedures logged for each clinical vignette was conducted using Fleiss' kappa. As the clinical vignettes increased in complexity, there was a decreasing trend in kappa values from the first (least complex) to the last (most complex) clinical vignette. Conclusions:. The inconsistent case logging practices, dubious outlook on case log accuracy and resident case logging ability and attitude, and lack of formal training signals a need for formal, standardized case log training. Enhanced case logging instruction and formalized educational training for PDs and residents would be a meaningful step toward capturing true operative experience, which would have a substantial impact on orthopaedic surgery resident education and assessment.

The paper studies bargaining games involving players with present-biased preferences. The paper shows that the relative timing of bargaining rewards and bargaining costs will determine whether the players’ present-bias will affect bargaining outcomes. In cases where players agree to a bargain in period 1 and experience all bargaining payoffs in period 2, the players will act in a time-consistent fashion. When time-inconsistent players incur immediate bargaining costs to produce delayed rewards, they will have an incentive to procrastinate. On the other hand, when players receive immediate bargaining rewards and incur delayed costs, they will have incentives to agree to bargains too soon and to agree to inefficient bargains. The paper shows that the players’ awareness of their own and the other player’s present-biased preferences will determine whether they engage in repeated time-inconsistent bargaining. A naïve player who engages in time-inconsistent bargaining will suffer welfare losses. We show that time-inconsistent bargaining can also create spillover welfare losses for other players. A time-consistent player who is counterparty-naïve about the other player can suffer spillover welfare losses that can be higher than those incurred by the time-inconsistent player. As a result, counterparty-sophisticated players will have an incentive to use cross-commitment devices to reduce the likelihood of spillover welfare losses. The paper also shows that cross commitment devices that target immediate payoffs dominate cross-commitments that target delayed payoffs. Finally, the paper shows that time-inconsistent bargaining can lead to inefficient delays in agreeing to bargains and in exiting bargaining relationships.

ABSTRACT Several severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have arisen that exhibit increased viral transmissibility and partial evasion of immunity induced by natural infection and vaccination. To address the specific antibody targets that were affected by recent viral variants, we generated 43 monoclonal antibodies (mAbs) from 10 convalescent donors that bound three distinct domains of the SARS-CoV-2 spike. Viral variants harboring mutations at K417, E484, and N501 could escape most of the highly potent antibodies against the receptor binding domain (RBD). Despite this, we identified 12 neutralizing mAbs against three distinct regions of the spike protein that neutralize SARS-CoV-2 and variants of concern (VOCs), including B.1.1.7 (alpha), P.1 (gamma), and B.1.617.2 (delta). Notably, antibodies targeting distinct epitopes could neutralize discrete variants, suggesting that different variants may have evolved to disrupt the binding of particular neutralizing antibody classes. These results underscore that humans exposed to the first pandemic wave of prototype SARS-CoV-2 possess neutralizing antibodies against current variants and that it is critical to induce antibodies targeting multiple distinct epitopes of the spike that can neutralize emerging variants of concern. IMPORTANCE We describe the binding and neutralization properties of a new set of human monoclonal antibodies derived from memory B cells of 10 coronavirus disease 2019 (COVID-19) convalescent donors in the first pandemic wave of prototype SARS-CoV-2. There were 12 antibodies targeting distinct epitopes on spike, including two sites on the RBD and one on the N-terminal domain (NTD), that displayed cross-neutralization of VOCs, for which distinct antibody targets could neutralize discrete variants. This work underlines that natural infection by SARS-CoV-2 induces effective cross-neutralization against only some VOCs and supports the need for COVID-19 vaccination for robust induction of neutralizing antibodies targeting multiple epitopes of the spike protein to combat the current SARS-CoV-2 VOCs and any others that might emerge in the future.

ObjectiveTo assess prevalence and correlates of work presenteeism, absenteeism and work disability (WD) in patients with systemic lupus erythematous (SLE) and matched controls.MethodsPatients with SLE from six medical centres were recruited to complete a questionnaire consisting of several prevalidated survey instruments. The subject's rheumatologist completed medical history. Subjects recruited two non-SLE 'best friend' controls with matching demographics to complete a control survey. Analyses employed Student's t tests, χ(2) tests and logistic regression models.Results344 subjects with SLE and 322 controls submitted completed questionnaires. Mean pain, fatigue, Brief Cognitive Symptoms Index (BCSI) scores and depressive symptoms were worse in patients with SLE with WD (all p

Summary: Multimodal advances in single-cell sequencing have enabled the simultaneous quantification of cell surface protein expression alongside unbiased transcriptional profiling. Here, we present LinQ-View, a toolkit designed for multimodal single-cell data visualization and analysis. LinQ-View integrates transcriptional and cell surface protein expression profiling data to reveal more accurate cell heterogeneity and proposes a quantitative metric for cluster purity assessment. Through comparison with existing multimodal methods on multiple public CITE-seq datasets, we demonstrate that LinQ-View efficiently generates accurate cell clusters, especially in CITE-seq data with routine numbers of surface protein features, by preventing variations in a single surface protein feature from affecting results. Finally, we utilized this method to integrate single-cell transcriptional and protein expression data from SARS-CoV-2-infected patients, revealing antigen-specific B cell subsets after infection. Our results suggest LinQ-View could be helpful for multimodal analysis and purity assessment of CITE-seq datasets that target specific cell populations (e.g., B cells). Motivation: Multimodal single-cell sequencing enables multiple aspects for characterizing the dynamics of cell states and developmental processes. Properly integrating information from multiple modalities is a crucial step for interpreting cell heterogeneity. Here, we present LinQ-View, a computational workflow that provides an effective solution for integrating multiple modalities of CITE-seq data for downstream interpretation. LinQ-View balances information from multiple modalities to achieve accurate clustering results and is specialized in handling CITE-seq data with routine numbers of surface protein features.

Influenza viruses grown in eggs for the purposes of vaccine generation often acquire mutations during egg adaptation or possess different glycosylation patterns than viruses circulating among humans. Here, we report that seasonal influenza virus vaccines possess an egg-derived glycan that is an antigenic decoy, with egg-binding MAbs reacting with a sulfated N

With the ongoing pandemic, it is critical to understand how natural immunity against SARS-CoV-2 and COVID-19 develops. We have identified that subjects with more severe COVID-19 disease mount a more robust and neutralizing antibody response against SARS-CoV-2 spike protein.

Here we present a case of a 56 year old male with an Ewing-like bilateral retroperitoneal sarcoma with evidence of a EWSR1-POU5F1 fusion gene. Biopsy showed a high grade round cell sarcoma expressing strong membranous CD99 antigen. The tumor shrank considerably after extensive neoadjuvant chemo-radiation therapy. The resected specimens showed complete regression of the malignant component, with the residual tumor resembling ganglioglioma as well as of differentiated tumors of endoderm and mesoderm. While ganglioneuromatous differentiation of Ewing sarcoma has previously been reported, the other elements are a novel finding and may be attributed to the uncommon fusion transcript identified in this case and to the effect of therapy.

Abstract Background Systemic lupus erythematosus (SLE) is an autoimmune disease with genetic, hormonal, and environmental influences. In Western Europe and North America, individuals of West African descent have a 3–4 fold greater incidence of SLE than Caucasians. Paradoxically, West Africans in sub-Saharan Africa appear to have a low incidence of SLE, and some studies suggest a milder disease with less nephritis. In this study, we analyzed sera from African American female SLE patients and four other cohorts, one with SLE and others with varying degrees of risk for SLE in order to identify serologic factors that might correlate with risk of or protection against SLE. Methods Our cohorts included West African women with previous malaria infection assumed to be protected from development of SLE, clinically unaffected sisters of SLE patients with high risk of developing SLE, healthy African American women with intermediate risk, healthy Caucasian women with low risk of developing SLE, and women with a diagnosis of SLE. We developed a lupus risk index (LRI) based on titers of IgM and IgG anti-double stranded DNA antibodies and levels of C1q. Results The risk index was highest in SLE patients; second highest in unaffected sisters of SLE patients; third highest in healthy African-American women and lowest in healthy Caucasian women and malaria-exposed West African women. Conclusion This risk index may be useful in early interventions to prevent SLE. In addition, it suggests new therapeutic approaches for the treatment of SLE.

The generation of high affinity antibodies is a crucial aspect of immunity induced by vaccination or infection. Investigation into the B cells that produce these antibodies grants key insights into the effectiveness of novel immunogens to induce a lasting protective response against endemic or pandemic pathogens, such as influenza viruses, human immunodeficiency virus, or severe acute respiratory syndrome coronavirus-2. However, humoral immunity has largely been studied at the serological level, limiting our knowledge on the specificity and function of B cells recruited to respond to pathogens. In this review, we cover a number of recent innovations in the field that have increased our ability to connect B cell function to the B cell repertoire and antigen specificity. Moreover, we will highlight recent advances in the development of both ex vivo and in vivo models to study human B cell responses. Together, the technologies highlighted in this review can be used to help design and validate new vaccine designs and platforms.

A descriptive and exploratory study was carried out at the University of Medical Sciences of Guantanamo during 2014-2015, with the objective of elaborating educational software containing a compendium of exercises related to the different specialties of the technology, with the aim of the developing oral communication and writing in the practical classes of the English language, developing in the students hearing, linguistic, grammatical and reading skills in correspondence with their professional sphere, reinforcing also the instructive and educational work of the teacher and the cognitive and strategic independence of the student, which implies a higher professional level. The completion of these courses is an option to achieve the preparation of human resources in less time. The implementation of didactic exercises in the software that was proposed was the pattern to develop communication in the English language practice and contributed to a greater motivation in the classes.

Antibodies are critical for providing protection against influenza virus infections. However, protective humoral immunity against influenza viruses is limited by the antigenic drift and shift of the major surface glycoproteins, hemagglutinin and neuraminidase. Importantly, people are exposed to influenza viruses throughout their life and tend to reuse memory B cells from prior exposure to generate antibodies against new variants. Despite this, people tend to recall memory B cells against constantly evolving variable epitopes or non-protective antigens, as opposed to recalling them against broadly neutralizing epitopes of hemagglutinin. In this review, we discuss the factors that impact the generation and recall of memory B cells against distinct viral antigens, as well as the immunological limitations preventing broadly neutralizing antibody responses. Lastly, we discuss how next-generation vaccine platforms can potentially overcome these obstacles to generate robust and long-lived protection against influenza A viruses.

The paper studies bargaining games involving players with present-biased preferences. The paper shows that the relative timing of bargaining rewards and bargaining costs will determine whether the players' present-bias will affect bargaining outcomes. In cases where players agree to a bargain in period 1 and experience all bargaining payoffs in period 2, the players will act in a time-consistent fashion. When time-inconsistent players incur immediate bargaining costs to produce delayed rewards, they will have an incentive to procrastinate. On the other hand, when players receive immediate bargaining rewards and incur delayed costs, they will have incentives to agree to bargains too soon and to agree to inefficient bargains. The paper shows that the players' awareness of their own and the other player's present-biased preferences will determine whether they engage in repeated time-inconsistent bargaining. A naïve player who engages in time-inconsistent bargaining will suffer welfare losses. We show that time-inconsistent bargaining can also create spillover welfare losses for other players. A time-consistent player who is counterparty-naïve about the other player can suffer spillover welfare losses that can be higher than those incurred by the time-inconsistent player. As a result, counterparty-sophisticated players will have an incentive to use cross-commitment devices to reduce the likelihood of spillover welfare losses. The paper also shows that cross commitment devices that target immediate payoffs dominate cross-commitments that target delayed payoffs. Finally, the paper shows that time-inconsistent bargaining can lead to inefficient delays in agreeing to bargains and in exiting bargaining relationships. [ABSTRACT FROM AUTHOR]