Informing the Need for a SARS-CoV-2 Booster Based Upon the Immune Responses among Young Healthy Adults to Variants Circulating in Late 2023.

BACKGROUND: COVID-19 remains a global public health challenge due to new immune-evasive SARS-CoV-2 variants and heterogeneous immunity. METHODS: In this cross-sectional study, we evaluated the adaptive immune responses in U.S. active-duty personnel who completed a COVID-19 primary vaccine series and with heterogenous SARS-CoV-2 vaccination and infection histories to 3 previously dominant variants (Ancestral, Delta, BA.5) and 3 circulating variants (XBB.1.5, EG.5, and BA.2.86) in late 2023. Analyses were performed based upon timing (within or beyond 12 months) and type (vaccine or infection) of the most recent exposure. RESULTS: Significant reduction was observed in binding antibodies, neutralization antibodies, memory B cells, and CD8+ T cells against circulating variants compared to previous variants. The reduction in antibody response was more pronounced in those whose most recent exposure was greater than 12 months from enrollment. In contrast, the CD4+ T cell response was largely consistent across all tested variants. The type of most recent exposure was not a significant factor in determining the magnitude of current immune responses. CONCLUSIONS: Administration of the XBB.1.5-based booster is likely to enhance cross-reactive humoral responses against SARS-CoV-2 circulating lineages. Ongoing surveillance of immune responses to emerging variants is needed for informing vaccine composition and timing.

Determining bifurcations to explosive synchronization for networks of coupled oscillators with higher-order interactions.

We determine bifurcations from gradual to explosive synchronization in coupled oscillator networks with higher-order coupling using self-consistency analysis. We obtain analytic bifurcation values for generic symmetric natural frequency distributions. We show that nonsynchronized, drifting, oscillators are non-negligible and play a crucial role in bifurcation. As such, the entire natural frequency distribution must be accounted for, rather than just the shape at the center. We verify our results for Lorentzian- and Gaussian-distributed natural frequencies.

Mechanisms of Near-Peer Learning in a Longitudinal Clerkship: A Grounded Theory Study.

PURPOSE: Many medical schools incorporate longitudinal clerkships, which promote continuity and may offer early clinical exposure during the preclinical curriculum. However, the mechanisms of near-peer learning and how it contributes to the development of clinical skills in longitudinal clinical experiences are less clear. The authors explored how peer-to-peer interactions among medical students influenced their developmental trajectories from nascent clinicians to more seasoned practitioners capable of juggling dual roles of clinical care and clinical supervision within longitudinal clerkships. METHOD: The Education-Centered Medical Home (ECMH) at Northwestern University Feinberg School of Medicine is a longitudinal clerkship that represents an ideal setting to explore peer learning. At ECMH continuity is established across all 4 years of medical school among small groups of students from each year, a preceptor, and a panel of outpatients. The authors conducted 6 focus groups and 9 individual interviews between March 2021 and February 2023 with medical students from all years. Using constructivist grounded theory, the authors collected and analyzed data iteratively using constant comparison to identify themes and explore their relationships. RESULTS: Within ECMH, peer relationships fostered an informal learning culture that enabled meaningful peer interactions while reinforcing the established culture. The authors identified 3 essential learning practices between senior and junior medical students: preparing for patient encounters, shifting roles dynamically during the joint encounter, and debriefing encounters afterwards. These practices strengthened learning relationships and supported students' developmental trajectories. CONCLUSIONS: Longitudinal peer learning relationships enabled meaningful peer interaction that influenced medical students' clinical development and capability for clinical supervision. Mutual trust, familiarity, and continuity facilitate targeted feedback practices and growth at the edge of junior students' capabilities. Optimizing this peer learning environment and seeking new opportunities to use longitudinal peer learning in clinical environments could promote psychological safety and professional identity formation for medical students.

Mathematical models of Plasmodium vivax transmission: A scoping review.

Plasmodium vivax is one of the most geographically widespread malaria parasites in the world, primarily found across South-East Asia, Latin America, and parts of Africa. One of the significant characteristics of the P. vivax parasite is its ability to remain dormant in the human liver as hypnozoites and subsequently reactivate after the initial infection (i.e. relapse infections). Mathematical modelling approaches have been widely applied to understand P. vivax dynamics and predict the impact of intervention outcomes. Models that capture P. vivax dynamics differ from those that capture P. falciparum dynamics, as they must account for relapses caused by the activation of hypnozoites. In this article, we provide a scoping review of mathematical models that capture P. vivax transmission dynamics published between January 1988 and May 2023. The primary objective of this work is to provide a comprehensive summary of the mathematical models and techniques used to model P. vivax dynamics. In doing so, we aim to assist researchers working on mathematical epidemiology, disease transmission, and other aspects of P. vivax malaria by highlighting best practices in currently published models and highlighting where further model development is required. We categorise P. vivax models according to whether a deterministic or agent-based approach was used. We provide an overview of the different strategies used to incorporate the parasite's biology, use of multiple scales (within-host and population-level), superinfection, immunity, and treatment interventions. In most of the published literature, the rationale for different modelling approaches was driven by the research question at hand. Some models focus on the parasites' complicated biology, while others incorporate simplified assumptions to avoid model complexity. Overall, the existing literature on mathematical models for P. vivax encompasses various aspects of the parasite's dynamics. We recommend that future research should focus on refining how key aspects of P. vivax dynamics are modelled, including spatial heterogeneity in exposure risk and heterogeneity in susceptibility to infection, the accumulation of hypnozoite variation, the interaction between P. falciparum and P. vivax, acquisition of immunity, and recovery under superinfection.

Diverse array of neutralizing antibodies elicited upon Spike Ferritin Nanoparticle vaccination in rhesus macaques.

The repeat emergence of SARS-CoV-2 variants of concern (VoC) with decreased susceptibility to vaccine-elicited antibodies highlights the need to develop next-generation vaccine candidates that confer broad protection. Here we describe the antibody response induced by the SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine candidate adjuvanted with the Army Liposomal Formulation including QS21 (ALFQ) in non-human primates. By isolating and characterizing several monoclonal antibodies directed against the Spike Receptor Binding Domain (RBD), N-Terminal Domain (NTD), or the S2 Domain, we define the molecular recognition of vaccine-elicited cross-reactive monoclonal antibodies (mAbs) elicited by SpFN. We identify six neutralizing antibodies with broad sarbecovirus cross-reactivity that recapitulate serum polyclonal antibody responses. In particular, RBD mAb WRAIR-5001 binds to the conserved cryptic region with high affinity to sarbecovirus clades 1 and 2, including Omicron variants, while mAb WRAIR-5021 offers complete protection from B.1.617.2 (Delta) in a murine challenge study. Our data further highlight the ability of SpFN vaccination to stimulate cross-reactive B cells targeting conserved regions of the Spike with activity against SARS CoV-1 and SARS-CoV-2 variants.

Can Asymmetry in Total Knee Arthroplasty Design Lead to More Normal-Like Postoperative Kinematics? A Multi-Implant Evaluation.

BACKGROUND: Few studies have evaluated the effects of symmetrical versus asymmetrical implant designs, more specifically the femoral condyles, trochlear groove, joint line, and bearing surfaces. The objective of this study was to investigate multiple posterior cruciate-retaining (PCR) total knee arthroplasty (TKA) designs influencing factors related to TKA asymmetry, and to investigate whether asymmetry can improve postoperative knee kinematics. METHODS: In vivo tibio-femoral kinematics for 99 subjects was evaluated in this retrospective study. Overall, 10 subjects had a nonimplanted, normal knee, and 89 subjects had 1 of 3 PCR TKAs with varying degrees of asymmetry within their femoral and tibial components (PCR #1 = 30, PCR #2 = 29, PCR #3 = 30). All TKAs were implanted by the same surgeon and were analyzed using fluoroscopy during a deep knee bend. RESULTS: At full extension, all 3 PCR TKAs experienced a more posteriorized position of the femoral condyles compared to the normal knee, with the 2 asymmetrical PCR TKAs experiencing more anteriorization compared to the third, symmetrical PCR TKA. Both the normal knee and the PCR TKA with greatest amount of asymmetry experienced statistically more posterior femoral rollback of the lateral condyle than the other 2 PCR TKAs. The PCR TKA with greater asymmetry also experienced statistically greater range of motion than the other 2 PCR TKAs. CONCLUSIONS: With increasing flexion, the design with the most asymmetry also experienced the most posterior femoral rollback, axial rotation, and greatest range of motion. The results in this study seem to suggest that the inclusion of asymmetry in a TKA could be beneficial for achieving more normal-like kinematics and greater weight-bearing knee flexion.

Adults' Understandings and Experiences of the Capacity to Consent to Substance-Involved Sexual Activity.

Most research on capacity to consent to substance-involved sex has focused exclusively on the implications of alcohol with little attention given to other or additional psychoactive drugs. This study aimed to explore people's understanding and experiences of the capacity to consent to alcohol- and/or drug-involved sexual activity. UK adults (N = 354) completed an online mixed-methods survey on sexual consent during sober, alcohol- and/or drug-involved sex. Qualitative data were analyzed using thematic analysis. Themes for capacity to consent were: (1) "There is no normative understanding of substance-involved sexual consent," (2) "Moving beyond the binary of consciousness versus incapacitation" and (3) "Substance-involved sexual decisions are viewed as irresponsible." The findings illustrated that capacity to consent is nuanced and multidimensional, and that people's understandings and experiences of capacity to consent to substance-involved sex are not solely individual, but rather, they are also shaped by their environment. We call for a multidimensional view of capacity to consent, where a standard of "unimpaired," rather than sober, is used and modeled by academics, legislators, and educators.

Exploring the Advantages and Challenges of MR-Guided Radiotherapy in Non-Small-Cell Lung Cancer: Who are the Optimal Candidates?

The landscape of lung radiotherapy (RT) has rapidly evolved over the past decade with modern RT and surgical techniques, systemic therapies, and expanding indications for RT. To date, 2 MRI-guided RT (MRgRT) units, 1 using a 0.35T magnet and 1 using a 1.5T magnet, are available for commercial use with more systems in the pipeline. MRgRT offers distinct advantages such as real-time target tracking, margin reduction, and on-table treatment adaptation, which may help overcome many of the common challenges associated with thoracic RT. Nonetheless, the use of MRI for image guidance and the current MRgRT units also have intrinsic limitations. In this review article, we will discuss clinical experiences to date, advantages, challenges, and future directions of MRgRT to the lung.

Multimodal pathways to joint attention in infants with a familial history of autism.

Joint attention (JA) is an early-developing behavior that allows caregivers and infants to share focus on an object. Deficits in JA, as measured through face-following pathways, are a defining feature of autism spectrum disorder (ASD) and are observable as early as 12 months of age in infants later diagnosed with ASD. However, recent evidence suggests that JA may be achieved through hand-following pathways by children with and without ASD. Development of JA through multimodal pathways has yet to be studied in infants with an increased likelihood of developing ASD. The current study investigated how 6-, 9- and 12-month-old infants with (FH+) and without (FH-) a family history of ASD engaged in JA. Parent-infant dyads played at home while we recorded the interaction over Zoom and later offline coded for hand movements and gaze. FH+ and FH- infants spent similar amounts of time in JA with their parents, but the cues available before JA were different. Parents of FH+ infants did more work to establish JA and used more face-following than hand-following pathways compared to parents of FH- infants, likely reflecting differences in infant motor or social behavior. These results suggest that early motor differences between FH+ and FH- infants may cascade into differences in social coordination.

Risk perception or hazard perception? Examining misperceptions of miners' personal exposures to noise.

While perceptions of risk have been examined in the workplace to understand safety behavior, hazard perception has been overlooked, particularly for chemical, physical, and biological agents. This study sought to establish the prevalence of one type of mismatch in hazard perception, - noise misperception - among miners, to examine whether different types of noisy environments (e.g., continuous, highly variable, etc.) alter workers' misperception of their noise exposures, and to evaluate whether noise misperception is associated with hearing protection device (HPD) use behavior. In this cross-sectional study across 10 surface mines in the USA, 135 normal-hearing participants were surveyed on their perceptions of exposure to noise at work and were monitored for three shifts, each with personal noise dosimetry, to examine which workers had a mismatch in perceived versus true noise exposure by 8-hr, time-weighted average, NIOSH exposure limits (TWANIOSH). Mixed effects logistic regression and probit Bayesian Kernel Machine Regression (BKMR) models examining on the odds of noise misperception associated with four different noise metrics (kurtosis, crest factor, variability, and number of peaks >135 dB) were used to determine which types of noisy environments may influence noise misperception. The relationship between noise misperception and odds of not wearing HPDs during a work shift was further examined. Our findings showed that nearly 1 in 3 workers underestimated their exposure to noise when their true exposure was in fact hazardous (TWANIOSH≥85 dBA) for at least one shift, and 6% misperceived hazardous exposures for all shifts. Work shifts with highly kurtotic noise distributions (>3) had 3.1 (95% CI: 1.1 to 8.4) times significantly higher odds of resulting in misperceived noise; no other noise metric was significantly associated with noise misperception. BKMR modeling provided further evidence that kurtosis dominates this relationship, with an IQR increase in kurtosis significantly associated with 1.68 (95% CI: 1.13 to 2.50) higher odds of noise misperception. Although not statistically significant, misperception of hazardous noise exposure was associated with 3.2 (95% CI: 0.8 to 12.5) times higher odds of not using earplugs during a work shift. Misperception of noise occurs in the workplace, and likely occurs for other physical, chemical, and biological exposures. This hazard misperception may influence risk perceptions and worker behavior and reduce the effectiveness of behavior-related training. Elimination, substitution, or engineering controls of exposures is the best way to prevent hazard misperceptions and exposure-related diseases.

Syphilis in Hematopathology Practice: A Diagnostic Challenge.

CONTEXT.­: Syphilis, a reemerging disease caused by spirochete Treponema pallidum, is becoming more frequent in surgical pathology and hematopathology practices. Hematopathologists typically receive lymph node biopsies from patients with syphilis who have localized or diffuse lymphadenopathy. Occasionally, syphilis infection in the aerodigestive tract can show a prominent lymphoplasmacytic infiltrate and mimic lymphoma. Besides the varying and occasional atypical morphology, the fact that clinical suspicion tends to be low or absent when histologic evaluation is requested adds to the importance of making this diagnosis. OBJECTIVE.­: To summarize histologic features of syphilitic lymphadenitis and syphilis lesions in the aerodigestive tract, and to review differential diagnosis and potential diagnostic pitfalls. DATA SOURCES.­: Literature review via PubMed search. CONCLUSIONS.­: Characteristic histologic findings in syphilitic lymphadenitis include thickened capsule with plasma cell-rich inflammatory infiltrate, reactive follicular and paracortical hyperplasia with prominent lymphoplasmacytic infiltrate, and vasculitis. Lymph nodes, however, can show a number of other nonspecific histologic features, which frequently makes the diagnosis quite challenging. In the aerodigestive tract, syphilis is characterized by plasma cell-rich infiltrates. Immunohistochemistry for T pallidum is the preferred method for detecting spirochetes; however, this immunohistochemical stain shows cross-reactivity with other treponemal and commensal spirochetes. Differential diagnosis of syphilis in lymph nodes and the aerodigestive tract is broad and includes reactive, infectious, and neoplastic entities. Pathologists should be aware of the histologic features of syphilis and keep this challenging entity in the differential diagnosis.

Maternal Health Experiences of Black Deaf and Hard of Hearing Women in the United States.

INTRODUCTION: Deaf and hard of hearing (DHH) women are faced with numerous health inequities, including adverse pregnancy and birth outcomes. These outcomes are likely exacerbated for Black DHH women because of the intersection of disability and race. This study aimed to explore the pregnancy and birth experiences of Black DHH women to identify factors that influence their pregnancy outcomes. METHODS: Semistructured interviews were conducted between 2018 and 2019 with 67 DHH women who gave birth in the past five years. The present study represents a subgroup analysis of eight of the 67 women who self-identified as Black. Interviews were recorded, transcribed, and analyzed for emerging themes. RESULTS: Primary themes centered on unmet needs, barriers, and facilitators. Barriers included limited access to health information owing to communication difficulties and challenges obtaining accommodations. Key facilitators included the availability of sign language interpreters, familial support, and cultural understanding from providers. Participants emphasized these facilitators in their recommendations to providers and DHH women. Findings also underscored the critical role of recognizing cultural identity in perinatal health care delivery. CONCLUSIONS: This study outlines themes that affect pregnancy and birthing experiences among Black DHH women in the United States. Study implications include a call to action for providers to prioritize communication accommodations, accessible information, and compassionate care for all Black DHH women. Furthermore, future work should explore the impact of cultural and racial concordance between patients and their health care providers and staff. Understanding how intersectional identities affect perinatal health care access is crucial for reducing disparities among Black DHH women.

The biomechanical and functional outcomes of autologous chondrocyte implantation for articular cartilage defects of the knee: A systematic review.

PURPOSE: Autologous chondrocyte implantation (ACI) is primarily performed in active, young patients to treat knee pain and functional limitations resulting from articular cartilage injury. Nevertheless, the functional outcomes of ACI remain poorly understood. This systematic review aimed to evaluate the biomechanical and functional outcomes of ACI. METHODS: Ovid MEDLINE, Embase, and Web of Science were systematically searched using the terms 'Knee OR Knee joint AND Autologous chondrocyte implantation OR ACI'. Inclusion and exclusion criteria were used to screen publications by title, abstract, and full text. Study quality and bias were assessed by two reviewers. Means and standard deviations of all collected variables were calculated and presented in the review. PROSPERO ID: CRD42021238768. RESULTS: Nineteen articles including 20 ACI cohorts were included. In general, the average range of motion (ROM) improved with clinical (>5°) and statistical significance (p < 0.05) postoperatively: 130.5 ± 14.8° to 136.1 ± 10.2°. Knee strength significantly improved within the first two postoperative years but remained poorer than control groups at final follow-up. No statistical differences were found between ACI and control groups in their ability to perform functional activities like the 6-minute walk test. CONCLUSION: Knee range of motion generally improved following ACI. Although, some studies reported that knee strengths remained significantly poorer than healthy controls, particularly >2-years postoperatively, implying that longer-term strength training may benefit patients.However, the volume of research and current level of evidence remain low, thus further research is required to better understand the impact of ACI on knee function and guide future rehabilitative protocols.

PRELIMINARY EVALUATION OF SYMMETRIC DIMETHYLARGININE AS A BIOMARKER OF RENAL INSUFFICIENCY IN WILD AND REHABILITATED FLORIDA MANATEES (TRICHECHUS MANATUS LATIROSTRIS).

Currently, there are limited antemortem tests available to evaluate renal function in Florida manatees (Trichechus manatus latirostris). Although few reports of renal pathology in manatees exist in the veterinary literature, debilitated animals that present to rehabilitation centers are frequently dehydrated, may have sustained renal trauma secondary to watercraft injury, and may experience ischemic events related to coagulation disorders leading to renal compromise. Clinicians remain limited to the analysis of blood urea nitrogen, creatinine levels, and urinalysis (if urine is obtained) to determine the extent of renal insufficiency, which may not accurately reflect renal function. This poses a diagnostic challenge for clinicians in discerning how critical renal compromise is to the animal's overall health and prognosis. For the first phase of this study, retrospective symmetric dimethylarginine (SDMA) values were determined from banked serum or plasma samples from 14 wild Florida manatees that had been collected while the animals were under rehabilitation in zoological institutions prior to their deaths. Values of SDMA for nine samples from eight manatees with known renal disease, as determined by histopathology, were compared to SDMA values for seven samples from six manatees with no reported renal lesions on histopathology. Values of SDMA from wild Florida manatees with known renal disease (mean 33.56 µg/dl ± 13.15, P= 0.017) were statistically significantly elevated when compared to SDMA values from manatees with no reported renal lesions (mean = 18.71 µg/dl ± 6.9) on histopathology. For the second phase of the study, serum or plasma samples were obtained from wild manatee populations from two geographically separate presumed-healthy wild manatee populations (n = 57). Although the upper limit was higher, serum SDMA concentrations from presumed-healthy wild manatees were comparable to those reported in small animal and equine medicine at 5.88-16.97 µg/dl.

The parasite intraerythrocytic cycle and human circadian cycle are coupled during malaria infection.

During infections with the malaria parasites Plasmodium vivax, patients exhibit rhythmic fevers every 48 h. These fever cycles correspond with the time the parasites take to traverse the intraerythrocytic cycle (IEC). In other Plasmodium species that infect either humans or mice, the IEC is likely guided by a parasite-intrinsic clock [Rijo-Ferreiraet al., Science 368, 746-753 (2020); Smith et al., Science 368, 754-759 (2020)], suggesting that intrinsic clock mechanisms may be a fundamental feature of malaria parasites. Moreover, because Plasmodium cycle times are multiples of 24 h, the IECs may be coordinated with the host circadian clock(s). Such coordination could explain the synchronization of the parasite population in the host and enable alignment of IEC and circadian cycle phases. We utilized an ex vivo culture of whole blood from patients infected with P. vivax to examine the dynamics of the host circadian transcriptome and the parasite IEC transcriptome. Transcriptome dynamics revealed that the phases of the host circadian cycle and the parasite IEC are correlated across multiple patients, showing that the cycles are phase coupled. In mouse model systems, host-parasite cycle coupling appears to provide a selective advantage for the parasite. Thus, understanding how host and parasite cycles are coupled in humans could enable antimalarial therapies that disrupt this coupling.

Recognizing and Reducing Delirium in the Intensive Care Unit.

This article discusses a quality improvement study conducted on intensive care unit (ICU) staff nurses that assessed their ability to utilize the CAM-ICU tool for delirium detection properly. Staff members' expertise in identifying and managing delirious patients directly correlates with reducing the long-term sequelae associated with ICU delirium. The cohort of ICU nurses participating in this research study took a questionnaire on 4 separate occasions. The survey ascertained quantitative and qualitative data, reflecting personal knowledge about the CAM-ICU tool and delirium. After each round of assessment, group and one-on-one educational sessions were provided by the researchers. The study culminated with providing each staff member a delirium reference card (badge buddy) containing relevant and easily accessible clinical information that supported the ICU staff nurses in correctly implementing the CAM-ICU tool.

Trimodality Therapy Improves Disease Control in Radiation-Associated Angiosarcoma of the Breast.

PURPOSE: To evaluate the impact of trimodality treatment versus monotherapy or dual therapy for radiation-associated angiosarcoma of the breast (RAASB) after prior breast cancer treatment. EXPERIMENTAL DESIGN: With Institutional Review Board approval, we identified patients diagnosed with RAASB and abstracted data on disease presentation, treatment, and oncologic outcomes. Trimodality therapy included (i) taxane induction, (ii) concurrent taxane/radiation, and then (iii) surgical resection with wide margins. RESULTS: A total of 38 patients (median age 69 years) met inclusion criteria. Sixteen received trimodality therapy and 22 monotherapy/dual therapy. Skin involvement and disease extent were similar in both groups. All trimodality patients required reconstructive procedures for wound closure/coverage, compared with 48% of monotherapy/dual therapy patients (P < 0.001). Twelve of 16 (75%) patients receiving trimodality therapy had a pathologic complete response (pCR). With median follow-up of 5.6 years, none had local recurrence, 1 patient (6%) had distant recurrence, and no patients died. Among 22 patients in the monotherapy/dual therapy group, 10 (45%) had local recurrence, 8 (36%) had distant recurrence, and 7 (32%) died of disease. Trimodality therapy demonstrated significantly better 5-year recurrence-free survival [RFS; 93.8% vs. 42.9%; P = 0.004; HR, 7.6 (95% confidence interval, CI: 1.3-44.2)]. Combining all patients with RAASB regardless of treatment, local recurrence was associated with subsequent distant recurrence (HR, 9.0; P = 0.002); distant recurrence developed in 3 of 28 (11%) patients without local recurrence compared with 6 of 10 (60%) with local recurrence. The trimodality group had more surgical complications that required reoperation or prolonged healing. CONCLUSIONS: Trimodality therapy for RAASB was more toxic but is promising, with a high rate of pCR, durable local control, and improved RFS.