An update on the Cartwright (Yt) blood group system.

CONCLUSIONS: This update of the Cartwright blood group system (George MR. Cartwright blood group system review. Immunohematology 2012;28:49-54) reports the addition of three new antigens. From 1956 until 2017, the Cartwright (Yt) blood group system consisted of two antigens, Yta and Ytb. Yta is a high-prevalence antigen, and its antithetical antigen, Ytb, shows much lower prevalence. In 2017, YTEG was identified, and, in 2018, the International Society of Blood Transfusion added high-prevalence antigens YTLI and YTOT. Cartwright antigens result from point mutations in the acetylcholinesterase gene on chromosome 7q. Little is known about antibodies against YTEG, YTLI, and YTOT. Discovery of these new antigens required plasma inhibition studies and molecular analysis for further characterization. Based on experience with Yta and Ytb, Cartwright antibodies have rarely demonstrated clinical significance; nevertheless, cases of in vivo hemolysis have been reported, suggesting that clinical significance should be interpreted on a case-by-case basis.

Clinical approach after identification of a rare anti-Ena in a prenatal sample.

CONCLUSIONS: The antigens associated with the MNS blood group system (ISBT 002) are located on glycophorin A (GPA) and glycophorin B (GPB). The most frequently encountered antibodies to antigens in this system by a transfusion medicine service are those directed against M, N, S, and s. Individuals lacking GPA typically have red blood cells that lack M, N, and Ena, whereas those lacking both GPA and GPB lack M, N, and Ena as well as S, s, and U. Such individuals may develop a rare antibody, anti-Ena, directed against determinants on GPA. This antibody is capable of causing hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. This case report describes a pregnant woman found to have anti-Ena. Molecular testing supported an Mk phenotype that was found in several members of her immediate family.

Evaluation of different testing methods for identification of RhIG in red blood cell antibody detection.

BACKGROUND: RhIG has had great success in protecting fetuses from potential harm; however, little work has been done to demonstrate how long RhIG reactivity is detected in the mother after administration when using common red blood cell antibody detection methods. STUDY DESIGN AND METHODS: A retrospective investigation was performed examining positive antibody identification panels due to RhIG. These panels were run on solid-phase (SP) testing. The time to a positive result, length of detection, and positive strength of reactivity (PSR) were evaluated. Additionally, a comparative study was performed evaluating how sensitive SP, gel (GT), and tube testing (TT) were at detecting RhIG using serially diluted plasma samples spiked with different RhIG formulas. RESULTS: Retrospectively, most antibody identification panels by SP were positive 3.5 months after RhIG administration and demonstrated a strong PSR. The longest recorded positive panel was present at 4.5 months. RhIG administered intramuscularly could not be detected until several hours after injection. The comparative study showed that SP was the most sensitive method while GT and TT were comparable to one another in detecting RhIG. SP also recorded strong PSR at very low concentrations of RhIG. GT and TT recorded weak PSR even with higher concentrations of RhIG. CONCLUSION: SP is the most sensitive testing method and has the ability to detect RhIG 4 to 5 months after administration. TT and GT have the ability to detect RhIG up to 3 to 4 months after administration. Different RhIG formulas may show slightly different lengths of detection.

Evaluating differential effects using regression interactions and regression mixture models.

Research increasingly emphasizes understanding differential effects. This paper focuses on understanding regression mixture models, a relatively new statistical methods for assessing differential effects by comparing results to using an interactive term in linear regression. The research questions which each model answers, their formulation, and their assumptions are compared using Monte Carlo simulations and real data analysis. The capabilities of regression mixture models are described and specific issues to be addressed when conducting regression mixtures are proposed. The paper aims to clarify the role that regression mixtures can take in the estimation of differential effects and increase awareness of the benefits and potential pitfalls of this approach. Regression mixture models are shown to be a potentially effective exploratory method for finding differential effects when these effects can be defined by a small number of classes of respondents who share a typical relationship between a predictor and an outcome. It is also shown that the comparison between regression mixture models and interactions becomes substantially more complex as the number of classes increases. It is argued that regression interactions are well suited for direct tests of specific hypotheses about differential effects and regression mixtures provide a useful approach for exploring effect heterogeneity given adequate samples and study design.

Asymmetry in children's salivary cortisol and alpha-amylase in the context of marital conflict: links to children's emotional security and adjustment.

Recent research supports the promise of examining interactive models of physiological processes on children's adjustment. The present study investigates interactions between children's autonomic nervous system activity and adrenocortical functioning in the context of marital discord; specifically, testing models of concurrent responses proposed by Bauer et al. ([2002] Developmental and Behavioral Pediatrics 23:102-113) in the prediction of children's behavioral responses to conflict and adjustment. Asymmetry and symmetry in children's salivary alpha-amylase and cortisol were examined in 195 children (M age = 8 years) in response to viewing conflict vignettes. Results were partially consistent with an interactive model in the context of high marital discord; asymmetry among higher alpha-amylase and lower cortisol related to higher emotional insecurity and concurrent and subsequent maladjustment. In contrast, patterns of symmetrical responses were related to greater maladjustment for children exposed to lower levels of marital discord, supporting an additive model. Findings support the importance of a multisystem approach to investigating the adaptiveness of children's physiological stress responses, while also highlighting the value of considering physiological responses in the context of family risk.

Continued Positive Job Search Experience for New Pathologists Seeking First Employment During the COVID-19 Pandemic (2020-2022).

CONTEXT.­: As pathologists retire and leave the field, it is critical to accurately capture employment trends for new-in-practice pathologists. There is always interest in the job market for newly graduated pathology trainees and prospective pathology trainees, but it is unclear how the COVID-19 pandemic may have affected the job search experience. OBJECTIVE.­: To provide an update on trends gleaned from a survey of pathology graduates' job search experiences during the COVID-19 pandemic. DESIGN.­: We analyzed data from an annual job search survey sent by the College of American Pathologists Graduate Medical Education Committee between 2020 and 2022 to College of American Pathologists junior members and fellows in practice 3 years or less actively looking for a nonfellowship position. Various indicators of the job search experience were compared year to year and with the data previously published 2017 to 2019 and 2012 to 2016. RESULTS.­: Analysis revealed continued positive trends between the 2020 to 2022 data and the data from 2017 to 2019 and 2012 to 2016. This includes continued ease in finding positions, continued availability of jobs in the subspecialty of choice, continued satisfaction with the positions accepted, and, notably, higher starting salaries. CONCLUSIONS.­: Despite the many challenges of the COVID-19 pandemic, job market trends for newly graduated pathology trainees continue to be favorable with respect to multiple indicators compared with 2 prior periods, 2017 to 2019 and 2012 to 2016.

Leadership perspectives on osteopathic medical school applicants to pathology residency training.

The number of graduating allopathic (MD) medical students matching into pathology has declined in recent years, while the number of osteopathic (DO) medical students has increased modestly, given the rapid expansion of osteopathic medical schools. Nonscholarly publications and materials on the internet often perpetuate negative perceptions of osteopathic physicians. Anecdotally, perspectives exist that some pathology residency programs are not DO-friendly; however, the reasons and how widespread an effect this might be are unclear. Our survey queried pathology chairs and residency program directors about their perceptions of osteopathic applicants and their knowledge of osteopathic medical school/training in general. This study utilized two similar, parallel surveys of pathology chairs and residency program directors with general questions structured around the perceptions and knowledge of both allopathic and osteopathic physicians, their medical training, and the consideration of osteopathic applicants to pathology residency. Pathology residency leaders acknowledge some negative perceptions of osteopathic physicians in the medical profession, the news, and social media. They also have some knowledge and perception gaps regarding osteopathic training and applicants, although experience with training osteopathic physicians as residents has been equivalent to that with allopathic physicians, and consideration appears to be fairly equal for osteopathic applicants. Even though negative perceptions of osteopathic physicians persist in news and social media, our surveys demonstrate that the leadership of pathology residency programs does not hold the same degree of bias and that DOs perform well in allopathic pathology residency programs without evidence of inferior outcomes.

Finite Mixtures for Simultaneously Modelling Differential Effects and Non-Normal Distributions.

Regression mixture models have been increasingly applied in the social and behavioral sciences as a method for identifying differential effects of predictors on outcomes. While the typical specification of this approach is sensitive to violations of distributional assumptions, alternative methods for capturing the number of differential effects have been shown to be robust. Yet, there is still a need to better describe differential effects that exist when using regression mixture models. The current study tests a new approach that uses sets of classes (called differential effects sets) to simultaneously model differential effects and account for non-normal error distributions. Monte Carlo simulations are used to examine the performance of the approach. The number of classes needed to represent departures from normality is shown to be dependent on the degree of skew. The use of differential effects sets reduced bias in parameter estimates. Applied analyses demonstrated the implementation of the approach for describing differential effects of parental health problems on adolescent body mass index using differential effects sets approach. Findings support the usefulness of the approach which overcomes the limitations of previous approaches for handling non-normal errors.

Using regression mixture models with non-normal data: Examining an ordered polytomous approach.

Mild to moderate skew in errors can substantially impact regression mixture model results; one approach for overcoming this includes transforming the outcome into an ordered categorical variable and using a polytomous regression mixture model. This is effective for retaining differential effects in the population; however, bias in parameter estimates and model fit warrant further examination of this approach at higher levels of skew. The current study used Monte Carlo simulations; three thousand observations were drawn from each of two subpopulations differing in the effect of X on Y. Five hundred simulations were performed in each of the ten scenarios varying in levels of skew in one or both classes. Model comparison criteria supported the accurate two class model, preserving the differential effects, while parameter estimates were notably biased. The appropriate number of effects can be captured with this approach but we suggest caution when interpreting the magnitude of the effects.

The phenotype of pathology residency program directors.

Pathology residency programs vary greatly across the United States. To the authors' knowledge, little is formally known about the "phenotype" or career pathways of pathology residency program directors (PDs). PDs, former PDs (FPDs), and associate PDs (APDs) were surveyed, aiming to address whether or not dominant phenotypes or pathways to graduate medical education leadership exist. Several trends emerged including: 76% Whites, 70% females, 15% MD/PhDs, and more junior faculty (33% being <5 years in practice, another 24% being in practice <10 years, and 41% assistant professors at time of first PD/APD appointment). Anatomic and clinical pathology-certified individuals represented 79%. Sixty-two percent of respondents were on a nontenure employment track, with only 18% indicating tenure track. For subspecialty focus, cytopathology (25%), transfusion medicine (16%), and hematopathology (14%) represented the most common subspecialties practiced. A majority (65%) had served as a chief resident during residency, and most (61%) of PDs had served as APDs first. Most (60%) had not served as fellowship director. Most (65%) had not participated in any education leadership training, with 27% having participated in certificate programs or other educational professional development. Thematic analysis of perceived key criterion in selection for the role was passion for education, demeanor, emotional intelligence, and willingness to serve the department. This information may influence training or experience pursued by individuals aspiring to pathology graduate medical education leadership, inform chairs on qualities to look for, and supplement future educational sessions of the Association of Pathology Chairs Program Directors Council.

The phenotype of academic pathology chairs.

Academic pathology departments across the United States vary greatly in terms of size, clinical workloads and research activity. It is therefore not surprising that their chairs may be an equally diverse group. However, to our knowledge, little is formally known about the "phenotype" (academic credentials, leadership background, and subspecialty focus) or career pathways of these individuals. Using a survey tool, this study sought to determine whether or not dominant phenotypes or trends. Several predominant findings emerged including: race (80% Whites), gender (68% males), dual degrees (41% MD/PhDs), years in practice (56% being in practice >15 years at time of first chair appointment), rank upon appointment (88% holding the rank of professor), and funded research (67% holding research funding). While Anatomic and Clinical Pathology (AP/CP) certified chairs represented 46% of the cohort, 30% were AP-only and another 10% were Anatomic Pathology and Neuropathology (AP/NP) certified. For subspecialty focus, neuropathology (13%) and molecular pathology (15%) were disproportionately represented compared to the general population of pathologists. Previous leadership roles on the path to chairmanship included vice chair (41%), division chief (39%), residency program director (29%), or fellowship director (27%). Many (41%) had not participated in any formal business or leadership training. This information may influence training or experience pursued by individuals aspiring to academic pathology leadership. It also highlights the challenges of suboptimal diversity in race and gender, as well as the professional backgrounds of academic pathology chairs and may suggest consideration of alternate pathways to leadership.

Experiential exposure as the key to recruiting medical students into pathology.

Medical student interest and pursuit of a career in pathology have been steadily declining since 2015. We conducted three separate surveys of medical students to better understand these trends. In our first survey, we focused on assessing U.S. allopathic medical students understanding and perceptions of pathology. We later surveyed U.S. osteopathic medical students as a companion to the allopathic medical student survey, in which many similarities were discovered with some key differences. In our final survey, we specifically looked at curriculum differences between the U.S. allopathic medical schools that graduate the most students who enter pathology training programs (Group 1) versus those schools that graduate the fewest future pathologists (Group 2) to determine if the curriculum had an impact on medical student matriculation into pathology. Together, through these surveys, we were able to identify several remarkable recurring trends, presenting areas of targetable action. Here, we summarize themes from the three studies as well as a review of pertinent literature to offer best practices for exposing and engaging medical students to pathology and possibly recruiting students to consider pathology as a career.

How influential are medical school curriculum and other medical school characteristics in students' selecting pathology as a specialty?

There has been a significant decline in the number of United States allopathic medical students matching to pathology residency programs. Data acquired from the American Association of Medical Colleges (AAMC) show sustained variation in the medical school production of students who go on to pathology residency. When divided into groups based on the medical school's historical volume of graduates entering pathology, the schools in groups labeled Group 1 and Group 2 produced significantly higher and lower proportions of pathology residents, respectively. This study aimed to identify what medical school curriculum elements and other medical school characteristics might explain the differences observed in the AAMC data. The Dean or another undergraduate medical education contact from the Group 1 and Group 2 schools was invited to participate in an interview. Pathology Program Directors and Pathology Department Chairs were also included in communications. Thirty interviews were completed with equal numbers from each group. Interview questions probed pathology experiences, existence, and structure of a pathology interest group, options for post-sophomore fellowships, recent curriculum changes, and the extent of mentoring programs. Surprisingly, the curriculum does not appear to be a predictor of a medical school's production of students who enter pathology residency. A significantly greater percentage of Group 1 schools are public institutions compared to Group 2 schools. Other factors that may increase the number of students who go into pathology include mentoring, active learning versus observation, and post-sophomore fellowships or other opportunities to work in the capacity of a new pathology resident.

Interparental conflict in kindergarten and adolescent adjustment: prospective investigation of emotional security as an explanatory mechanism.

Advancing the long-term prospective study of explanations for the effects of marital conflict on children's functioning, relations were examined between interparental conflict in kindergarten, children's emotional insecurity in the early school years, and subsequent adolescent internalizing and externalizing problems. Based on a community sample of 235 mothers, fathers, and children (Ms=6.00, 8.02, 12.62years), and multimethod and multireporter assessments, structural equation model tests provided support for emotional insecurity in early childhood as an intervening process related to adolescent internalizing and externalizing problems, even with stringent autoregressive controls over prior levels of functioning for both mediating and outcome variables. Discussion considers implications for understanding pathways between interparental conflict, emotional insecurity, and adjustment in childhood and adolescence.

Factors influencing US osteopathic medical students to choose pathology as a specialty.

The decline in the number of US allopathic (Medical Doctor or M.D.) medical students matching to pathology residency has been a topic of much discussion at national pathology professional society meetings and in recent publications. A recent survey of fourth-year allopathic medicals students was conducted to better understand the rationale behind students' interest or lack thereof in pathology as a specialty. This study utilizes a similar survey tool gauging osteopathic (Doctor of Osteopathy or D.O.) student knowledge and interest in pathology, and offers insight into a possible growth market for the specialty. Similar to allopathic students, osteopathic students noted that clinical or research opportunities in pathology during medical school, autopsy observation/participation, and participation in pathology interest groups correlated with a greater likelihood of selecting pathology as a specialty. However, some key differences in osteopathic medical school curricular elements including microscope use, gross pathology specimen demonstrations, case-based learning by pathologists, exposure to pathology during other rotations, awareness of a pathology interest group, as well as an overall understanding of the everyday work of a pathologist were noted. Experiential exposure to pathology, and direct mentorship from pathologists may present an opportunity for pathology professional organizations, and pathology residency programs to partner with osteopathic medical schools to increase interest in the field, and aid in pipeline development.

Platelet refractoriness in acquired hemophagocytic syndrome.

BACKGROUND: Acquired hemophagocytic syndrome (AHPS) is a severe inflammatory disorder often caused by Epstein-Barr virus (EBV). Proliferation of activated macrophages produces uncontrolled cytokine production. Thrombocytopenia is common in AHPS, previously attributed to inadequate or ineffective marrow platelet (PLT) production. PLT transfusion response is not well reported. Two patients with fatal AHPS developed unexplained PLT transfusion refractoriness before definitive diagnosis. CASE REPORTS: PLT refractoriness was noted during the care of two patients. The refractoriness was determined to be nonimmune and both demonstrated various clinical signs and laboratory findings consistent with AHPS. The first patient's AHPS was attributable to EBV infection. In the other patient, no underlying cause could be found. Both patients had an aggressive clinical course and succumbed to this relatively rare syndrome. The PLT refractoriness was evident before the AHPS diagnosis was made. DISCUSSION: AHPS is not generally a consideration in the evaluation of nonimmune PLT refractoriness. However, these illustrative cases make an argument for its consideration in the differential diagnosis of PLT refractoriness in severely ill patients. Once present, it is unclear if the refractoriness can be reversed by AHPS-targeted therapy.

Understanding children's emotional processes and behavioral strategies in the context of marital conflict.

Marital conflict is a distressing context in which children must regulate their emotion and behavior; however, the associations between the multidimensionality of conflict and children's regulatory processes need to be examined. The current study examined differences in children's (N = 207, mean age = 8.02 years) emotions (mad, sad, scared, and happy) and behavioral strategies to regulate conflict exposure during resolved, unresolved, escalating, and child-rearing marital conflict vignettes. Children's cortisol levels were assessed in relation to child-rearing and resolved conflict vignettes. Anger and sadness were associated with escalating and child-rearing conflicts, fearfulness was related to escalating and unresolved conflicts, and happiness was associated with resolution. Anger was associated with children's strategies to stop conflict, whereas sadness was associated with monitoring and avoidant strategies. Cortisol recovery moderated the link between fearfulness and behavioral regulation. These results highlight the importance of children's emotions and regulatory processes in understanding the impact of marital conflict.

Positive Job Search Experience for New Pathologists Seeking First Employment Between 2017 and 2019.

CONTEXT.­: An aging population calls for an adequate response in the workforce of medical professionals. The field of pathology has seen a downward trend in numbers of graduating US allopathic medical students choosing the specialty. Concerns about the job market after residency and fellowship graduation may be a contributing factor. OBJECTIVE.­: To provide an update on the trends emerging from a survey of pathology graduates' job search experience for their first nonfellowship position. DESIGN.­: Data from an annual job search survey sent by the College of American Pathologists Graduate Medical Education Committee between 2017 and 2019 to College of American Pathologists junior members and fellows in practice 3 years or less actively looking for a nonfellowship position was analyzed. Various indicators of the job search experience were compared year to year and with the previously published 2012 to 2016 benchmark data. RESULTS.­: Analysis revealed positive trends between the 2017 to 2019 data and the 2012 to 2016 benchmark data, including participants' perceiving more ease in finding a position, improved availability of jobs in their subspecialty choice, and higher ratings of satisfaction with the position accepted, as well as a greater proportion of respondents finding a position within 6 months of initiating their job search. CONCLUSIONS.­: The job market for pathology residents and fellows looking for their first nonfellowship position has improved with respect to multiple indicators, such as ease of finding a position, length of job search, and satisfaction with the position accepted when comparing 2017 to 2019 data with the 2012 to 2016 benchmark data.