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Abstract Objectives Serum protein abundance was assessed in adult and juvenile dermatomyositis (DM and JDM) patients to determine differentially regulated proteins, altered pathways, and candidate disease activity biomarkers. Methods Serum protein expression from 17 active adult DM and JDM patients each was compared to matched, healthy control subjects by a multiplex immunoassay. Pathway analysis and protein clustering of the differentially regulated proteins were examined to assess underlying mechanisms. Candidate disease activity biomarkers were identified by correlating protein expression with disease activity measures. Results Seventy-eight of 172 proteins were differentially expressed in the sera of DM and JDM patients compared to healthy controls. Forty-eight proteins were differentially expressed in DM, 32 proteins in JDM, and 14 proteins in both DM and JDM. Twelve additional differentially expressed proteins were identified after combining the DM and JDM cohorts. C-X-C motif chemokine ligand 10 (CXCL10) was the most strongly upregulated protein in both DM and JDM sera. Other highly upregulated proteins in DM included S100 calcium binding protein A12 (S100A12), CXCL9, and nicotinamide phosphoribosyltransferase (NAMPT), while highly upregulated proteins in JDM included matrix metallopeptidase 3 (MMP3), growth differentiation factor 15 (GDF15), and von Willebrand factor (vWF). Pathway analysis indicated that phosphoinositide 3-kinase (PI3K), p38 mitogen-activated protein kinase (MAPK), and toll-like receptor 7 (TLR7) signaling were activated in DM and JDM. Additional pathways specific to DM or JDM were identified. A protein cluster associated with neutrophils and mononuclear leukocytes and a cluster of interferon-associated proteins were observed in both DM and JDM. Twenty-two proteins in DM and 24 proteins in JDM sera correlated with global, muscle, and/or skin disease activity. Seven proteins correlated with disease activity measures in both DM and JDM sera. IL-1 receptor like 1 (IL1RL1) emerged as a candidate global disease activity biomarker in DM and JDM. Conclusion Coordinate analysis of protein expression in DM and JDM patient sera by a multiplex immunoassay validated previous gene expression studies and identified novel dysregulated proteins, altered signaling pathways, and candidate disease activity biomarkers. These findings may further inform the assessment of DM and JDM patients and aid in the identification of potential therapeutic targets.

Abstract This post hoc analysis of the randomized, placebo‐controlled N‐MOmentum study (NCT02200770) of inebilizumab in neuromyelitis optica spectrum disorder (NMOSD) evaluated relationships between circulating B‐cell subsets and aquaporin‐4 immunoglobulin G (AQP4‐lgG) titers and attacks. Among participants receiving placebo, CD20+ and CD27+ B‐cell counts were modestly increased from the pre‐attack visit to attack; plasmablast/plasma cell gene signature was increased from baseline to the pre‐attack visit (p = 0.016) and from baseline to attack (p = 0.009). With inebilizumab treatment, B‐cell subset counts decreased and did not increase with attacks. No difference in change of AQP4‐IgG titers from baseline to time of attack was observed.

Background: Little is known about the demographic and health correlates of secondhand cannabis smoke (SHCS) exposure, despite increased availability and use of cannabis across the U.S. This study examined the prevalence and correlates of SHCS exposure in a sample of N=5,410 adults living in Oklahoma and the association of SHCS exposure with self-reported respiratory problems. Methods: Data were from a repeated cross-sectional online survey of adults ages 18 and older who completed measurements of past 30-day SHCS exposure in the respondent’s home, in a vehicle, and/or in an indoor setting; harm perceptions of SHCS exposure; frequency of current respiratory symptoms; past 30-day use of cannabis, alcohol, and cigarettes Results: Almost half (42 %) reported past 30-day SHCS exposure. In bivariate tests, those exposed were male, younger, non-Hispanic (NH) black or Hispanic, reported lower educational and financial attainment, had lower harm perceptions of SHCS exposure, endorsed more respiratory symptoms, and reported past 30-day cannabis and cigarette use (all p’s

In the realm of biomedical advancement, extracellular vesicles (EVs) are revolutionizing our capacity to diagnose, monitor, and predict disease progression. However, the comprehensive exploration and clinical application of EVs face significant limitations due to the current isolation techniques. The size exclusion chromatography, commercial precipitation reagents, and ultracentrifugation are frequently employed, necessitating skilled operators and entailing challenges related to consistency, reproducibility, quality, and yields. Notably, the formidable challenge of extracellular vesicle isolation persists when dealing with clinical samples of limited availability. This study addresses these challenges by aiming to devise a rapid, user-friendly, and high-recovery EVs isolation technique tailored for blood samples. The NTI-EXO precipitation method demonstrated a 5-fold increase in the recovery of serum EVs compared to current methodologies. Importantly, we illustrate that a mere two drops of blood (∼100 µL) suffice for the recovery of enriched EVs. The integrity and quality of these isolated EVs were rigorously assessed for the size, purity, and contaminants. This method was validated through the successful isolation of EVs from organ transplant recipients to detect disease-specific exosomal markers, including LKB1, SARS-CoV-2 spike protein, and PD-L1. In conclusion, NTI-EXO method can be used for small clinical samples, thereby advancing discoveries in the EV-centric domain and propelling the frontiers of biomedical research and clinical applications.

ObjectiveTo determine the incidence, risk factors, and outcomes of pulmonary hypertension (PH) in the pediatric intensive care unit (PICU) after pediatric hematopoietic stem cell transplant (HCT).MethodsThis was a retrospective study of pediatric patients who underwent allogeneic HCT between January 2008-December 2014 at a center contributing to the Center for International Blood and Marrow Transplant Research data registry. Incidence of PH was assessed from PICU diagnostic codes from records merged from the Virtual Pediatric Systems database. Regression and survival analyses identified factors associated with post-HCT PH. Additional post-HCT morbidities and survival after PH were also assessed.ResultsAmong 6,995 HCT recipients, there were 29 cases of PH, a cumulative incidence of 0.42% (95% CI 0.27%-0.57%) at 60 months post-HCT. In the sub-cohort of 1,067 patients requiring intensive care after HCT, this accounted for a PH prevalence of 2.72% (95% CI 1.74–3.69%). There was an increased risk of developing PH associated with Black/African American race, metabolic disorders, partially HLA-matched or cord blood allografts, graft-versus-host prophylaxis regimen, and lower pre-HCT functional status. Patients who developed PH had significant PICU comorbidities including heart failure, pulmonary hemorrhage, respiratory failure, renal failure, and infections. Survival at 6 months after diagnosis of post-HCT PH was 51.7% (95% CI 32.5%-67.9%).ConclusionsPH is a rare but serious complication in the pediatric post-HCT population. A significant burden of additional comorbidities, procedural interventions, and risk of mortality is associated with its development. Close monitoring and prompt intervention for this severe complication are necessary in this vulnerable population.

Abstract Inebilizumab, a humanized, glycoengineered, IgG1 monoclonal antibody that depletes CD19+ B‐cells, is approved to treat aquaporin 4 (AQP4) IgG‐seropositive neuromyelitis optica spectrum disorder (NMOSD). Inebilizumab is afucosylated and engineered for enhanced affinity to Fc receptor III‐A (FCGR3A) receptors on natural killer cells to maximize antibody‐dependent cellular cytotoxicity. Previously, the F allele polymorphism at amino acid 158 of the FCGR3A gene (F158) was shown to decrease IgG‐binding affinity and reduce rituximab (anti‐CD20) efficacy for NMOSD attack prevention. In contrast, our current findings from inebilizumab‐treated NMOSD patients indicate similar clinical outcomes between those with F158 and V158 allele genotypes.

The objective of this study is to evaluate the uncertainties of the dosimetric modeling of active marrow (AM) exposure from bone-seeking 89,90Sr. The stochastic parametric skeletal dosimetry (SPSD) model was specifically developed to study the long-term effects resulting from chronic 89,90Sr exposure in populations of the radioactively contaminated territories of the Southern Urals region of the Russian Federation. The method permits the evaluation of the dose factors (DF(AM ← TBV) and DF(AM ← CBV)), which convert the radionuclide activity concentration in trabecular (TBV) and cortical (CBV) bone volumes into dose rate in the AM, and their uncertainties. The sources of uncertainty can be subdivided into inherent uncertainties related to the individual variability of the simulated objects and introduced uncertainties related to model simplifications. Inherent uncertainty components are the individual variability of bone chemical composition, bone density, bone micro- and macro-architecture as well as AM distribution within the skeleton. The introduced uncertainties may result from the stylization of bone segment geometry, assumption of uniform cortical thickness, restriction of bone geometry and the selection of the applied voxel resolution.The inherent uncertainty depends on a number of factors of influence. Foremost, it is the result of variability of AM distribution within the skeleton. Another important factor is the variability of bone micro- and macro-architecture. The inherent uncertainty of skeletal-average dose factors was found to be about 40–50%. The introduced uncertainty associated with the SPSD model approach does not exceed 16% and mainly depends on the error of bone-shape stylization. The overall inherent and introduced uncertainties of DF(AM ← TBV) and DF(AM ← CBV) are below 55% and 63%, respectively. The results obtained will be incorporated into the stochastic version of the Techa River Dosimetry System (TRDS-2016MC) that provides multiple realizations of the annual doses for each cohort member to obtain both a central estimate of the individual dose and information on the dose uncertainty.

Abstract Research consistently demonstrates the over-representation of young people with speech, language and communication needs within the youth criminal justice system, with estimates suggesting this population accounts for up to 90% of young people who offend. Acknowledgement and understanding of these individual-based needs, along with identified service delivery adaptation(s) (where necessary) are required to ensure all young people, regardless of needs experienced, can effectively engage with, and have their voices heard, within the context of Youth Offending Services. By using a realist approach, qualitative interviews with stakeholders (n = 15) are used to explore service conditions required to incorporate speech, language and communication provision within a Youth Offending Service. Specifically, the research provides original and significant insights into the interconnections between understanding of speech, language and communication, service delivery models and engagement with young people. Seven themes pertaining to delivery requirements within youth offending settings were identified. From these themes, explanations in the form of programme theories are postulated detailing core service delivery conditions required in youth offending settings to address speech, language and communication need. These include, increased understanding of speech, language and communication; unpicking terminology and becoming communication friendly; staff cohesion prompting learning together; and co-construction approach to service delivery. The core approach underpinning these postulated programme theories was an increased awareness of speech, language and communication issues by youth offending staff. This increased awareness is evidenced to lead to an adaptation of behaviours and practices by staff which in turn increases engagement with young people.

Employability is core to our understanding of career sustainability, and at an individual level, identifying the personal resources that support employability in the achievement of career success is warranted. This study builds on the conservation of resources theory, examining the role of employability as a mediator in the relationship between psychological capital and objective career success. To test our hypotheses, we utilised a context-specific practitioner sample of 135 individuals with UK-accredited occupational psychology qualifications. Employability was conceptualised using the competence-based model, underpinned by occupational expertise. Psychological capital and employability were measured using self-report questionnaires, whilst career success was determined via gross annual salary and practitioner status, ensuring objective measures of this outcome variable. Structural equation modelling identified that the relationship between psychological capital and objective career success was fully mediated by employability. These novel findings have important theoretical and practical implications for the role of psychological capital as a personal resource in achieving career success via its influence on employability.

Summary: Background: Inebilizumab is an anti-CD19 antibody approved for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adults with aquaporin-4 autoantibodies. The relationship between B-cell, plasma-cell (PC), and immunoglobulin depletion with longitudinal reductions in NMOSD activity after inebilizumab treatment was characterised post hoc in an exploratory analysis from the N-MOmentum study (NCT02200770). Methods: Peripheral blood CD20+ B cells, PC gene signature, and immunoglobulin levels were assessed throughout N-MOmentum (follow-up ≥2.5 years); correlations with clinical metrics and magnetic resonance imaging (MRI) lesion activity were assessed. Findings: Inebilizumab induced durable B-cell and PC depletion within 1 week versus placebo. Although no association was observed between B-cell counts at time of attack and NMOSD activity, depth of B-cell depletion after the first dosing period correlated with clinical outcomes. All participants receiving inebilizumab demonstrated a robust long-term therapeutic response, and participants with ≤4 cells/μL after the first 6-month dosing interval had persistently deeper B-cell depletion, lower annualised attack rates (estimated rate [95% CI]: 0.034 [0.024–0.04] vs 0.086 [0.056–0.12]; p = 0.045), fewer new/enlarging T2 MRI lesions (0.49 [0.43–0.56] vs 1.36 [1.12–1.61]; p

Teachers are an occupational group particularly prone to suffering from burnout, a condition caused by chronic stress from work overload. Burnout is a risk factor for adverse psychological and physical health, thus it is important to test the efficacy of tools and techniques for alleviating burnout and enhancing job satisfaction. One potentially suitable technique is positive expressive writing. In the present study, we investigated the effects of a positive writing intervention on burnout, job satisfaction, anxiety, perceived stress and self-reported physical symptoms and compared these effects in teachers and other full-time workers.A group of teachers (n = 35) and a group of non-teachers (n = 31) who worked full-time in other professions were randomly allocated to complete either three consecutive days of positive expressive writing, or writing about a more neutral topic, online, 20 minutes per day, for three consecutive days State anxiety declined to a greater extent for participants in the positive writing condition compared to the neutral writing condition. Positive writing also conferred benefits on some aspects of job satisfaction, but not burnout. There were no specific benefits for teachers compared to non-teachers. The present study is the first to observe that positive expressive writing may be a useful technique for enhancing job satisfaction in full-time workers.

Objectives: The size of one's support network is positively related to health and well-being. It is therefore important to understand this association in people with Type 1 diabetes, as this could inform interventions. Moreover, the type of support (emotional, instrumental, informational) offered likely varies by gender of both the person seeking support and offering support. We thus examine the relationship between the composition of (perceived) social support networks and well-being in a sample of 121 persons with Type 1 diabetes. Design: An egocentric social network survey, combined with survey measures. Main outcome(s): The size and composition of support networks and well-being. Measures: Participants indicated the type of support individuals in their contact network offered and their gender, alongside measures of perceived social support and well-being. They indicated which individuals offered which types of support (emotional, instrumental, informational). Results: Perceived support was associated with the actual size of the emotional support network. Further, the size of the emotional support network was associated with well-being. Using multilevel models we examined assortment by gender in social support networks. Compared to women, men were more inclined to list the opposite gender as support, especially for emotional and informational support. Conclusion: Mapping out an individual's multidimensional support network paints a more complete picture of support than single item measures of support. We therefore recommend relying on a social network methodology to gain a more complete understanding of support networks. The findings highlight that an association exists between emotional network size and wellbeing. Given the potential implications of this finding for the quality of life of diabetes patients, it is important to establish the causality of this relationship.

Little is known about the risks and benefits associated with medical cannabis legalization. The current study was an online panel survey of adult Oklahomans recruited between September and October 2020 (N = 1898). Respondents with and without a medical cannabis license were compared on sociodemographic, substance use and health characteristics, and sub-analyses focused on the characteristics of licensed and unlicensed past 30-day cannabis users. Among all participants, 19.34% (n = 367) reported that they had a medical cannabis license, and 35.73% (n = 676) reported past 30-day cannabis use. Licensees were more likely to be younger (i.e., 18–35 years of age; p = 0.001), identify as a sexual minority (p

Abstract Background Self-assembly of the amyloid-β (Aβ) peptide into aggregates, from small oligomers to amyloid fibrils, is fundamentally linked with Alzheimer’s disease (AD). However, it is clear that not all forms of Aβ are equally harmful and that linking a specific aggregate to toxicity also depends on the assays and model systems used (Haass et al., J Biol. Chem 269:17741–17748, 1994; Borchelt et al., Neuron 17:1005–1013, 1996). Though a central postulate of the amyloid cascade hypothesis, there remain many gaps in our understanding regarding the links between Aβ deposition and neurodegeneration. Methods In this study, we examined familial mutations of Aβ that increase aggregation and oligomerization, E22G and ΔE22, and induce cerebral amyloid angiopathy, E22Q and D23N. We also investigated synthetic mutations that stabilize dimerization, S26C, and a phospho-mimetic, S8E, and non-phospho-mimetic, S8A. To that end, we utilized BRI2-Aβ fusion technology and rAAV2/1-based somatic brain transgenesis in mice to selectively express individual mutant Aβ species in vivo. In parallel, we generated PhiC31-based transgenic Drosophila melanogaster expressing wild-type (WT) and Aβ40 and Aβ42 mutants, fused to the Argos signal peptide to assess the extent of Aβ42-induced toxicity as well as to interrogate the combined effect of different Aβ40 and Aβ42 species. Results When expressed in the mouse brain for 6 months, Aβ42 E22G, Aβ42 E22Q/D23N, and Aβ42WT formed amyloid aggregates consisting of some diffuse material as well as cored plaques, whereas other mutants formed predominantly diffuse amyloid deposits. Moreover, while Aβ40WT showed no distinctive phenotype, Aβ40 E22G and E22Q/D23N formed unique aggregates that accumulated in mouse brains. This is the first evidence that mutant Aβ40 overexpression leads to deposition under certain conditions. Interestingly, we found that mutant Aβ42 E22G, E22Q, and S26C, but not Aβ40, were toxic to the eye of Drosophila. In contrast, flies expressing a copy of Aβ40 (WT or mutants), in addition to Aβ42WT, showed improved phenotypes, suggesting possible protective qualities for Aβ40. Conclusions These studies suggest that while some Aβ40 mutants form unique amyloid aggregates in mouse brains, they do not exacerbate Aβ42 toxicity in Drosophila, which highlights the significance of using different systems for a better understanding of AD pathogenicity and more accurate screening for new potential therapies.

Background. Pre–lung transplant (LTx) gastroesophageal reflux (GER) and circulating antibodies against the lung self-antigens (SAbs) collagen V and K-alpha-1 tubulin may predispose recipients to chronic lung allograft dysfunction (CLAD). We aimed to study the association of pre-LTx GER or pre-LTx SAbs with CLAD. Methods. In this retrospective analysis of patients who underwent LTx between 2015 and 2019, pre-LTx GER and SAbs were dichotomously defined as present or absent. The study group comprised recipients with either GER‚ SAbs, or both, and the control group comprised recipients without GER or SAbs. Endpoints included CLAD and survival. Results. Ninety-five LTx recipients were divided into a study group (n = 71; 75%) and a control group (n = 24; 25%). Pretransplant GER was associated with pre-LTx SAbs (odds ratio [95% confidence intervals], 5.022 [1.419-17.770]; P = 0.012). In addition, the study group (either GER‚ SAbs, or both) had a higher risk of CLAD (hazard ratio [95% confidence intervals], 8.787 [1.694-45.567]; P = 0.010) and lower CLAD-free survival after LTx than the control group (P = 0.007); however, overall survival was similar between the 2 groups (P = 0.618). Conclusions. GER was associated with elevated SAbs in LTx candidates, and either GER, SAbs, or both were associated with CLAD in LTx recipients. This association suggests that GER may cause an immune response to normally sequestered lung-associated self-antigens that drives ongoing lung injury.

Background. Persistent orthostatic hypotension (OH) is a lesser-known complication of lung transplantation (LTx). In this retrospective case series, we describe the clinical manifestations, complications, and treatment of persistent OH in 13 LTx recipients. Methods. We identified LTx recipients who underwent transplantation between March 1, 2018, and March 31, 2020, with persistent symptomatic OH and retrospectively queried the records for clinical information. Results. Thirteen patients were included in the analysis, 9 (69%) had underlying pulmonary fibrosis, and 12 (92%) were male. The median age, height, and body mass index at LTx were 68 years, 70 inches, and 27 kg/m2, respectively. Six (46%) patients were deceased at the time of chart abstraction with a median (IQR) posttransplant survival of 12.6 months (6, 21); the 7 remaining living patients were a median of 19.6 months (18, 32) posttransplant. Signs and symptoms of OH developed a median of 60 (7, 75) days after transplant. Patients were treated with pharmacological agents and underwent extensive physical therapy. Most patients required inpatient rehabilitation (n = 10, 77%), and patients commonly developed comorbid conditions including weight loss, renal insufficiency with eGFR

Previous work suggests that relative increases in socially evaluative threat modulate the psychobiological stress response. However, few studies have compared stressors which manipulate the level of socially evaluative threat to which the participant is exposed. Here we present two studies. In the first, we assessed the integrity of an ecologically valid, laboratory stressor (direct socially evaluated multitasking) and its effects on acute psychobiological reactivity and ability to evoke an anticipatory response prior to participation. Specifically, we assessed whether the expectation and experience of direct social evaluation (multitasking while standing and facing an evaluator) evokes greater reactivity than indirect evaluation (over-the-shoulder evaluation). In the second study, we sought to replicate the findings regarding acute stress reactivity whilst extending the assessment window to assess the extent to which the stressor evokes anticipatory responses. As hypothesized, greater reactivity was observed following direct social evaluation compared with indirect observation. Increases in anxiety, heart rate and blood pressure were demonstrated across both studies and the paradigm therefore provides an ecologically valid technique for the activation of psychological and cardiovascular stress responding. Additionally, anticipation of experiencing socially evaluated multitasking led to increases in anxiety, tension, and worry prior to the event itself, supporting previous suggestions that threat anticipation may prolong the activation of stress mechanisms. In the present studies we assessed whether the expectation and experience of direct social evaluation evokes greater reactivity than indirect evaluation. The findings have demonstrated that direct social evaluation of multitasking is a more potent stressor than multitasking with indirect evaluation. Furthermore, our findings indicate that the period of anticipation of stressful events may be critical to understanding the process of stress regulation, and as such we recommend extending the sampling window to allow for the investigation of these processes.

Long-term survival after lung transplant remains severely limited by chronic lung allograft dysfunction. Antibody-mediated rejection of lung transplant allografts is usually caused by donor-specific antibodies (DSAs) directed toward donor human leukocyte antigens (HLAs). Typically, patients with antibody-mediated rejection have significantly higher circulating DSAs and increased mean fluorescence intensity than those without antibody-mediated rejection. However, some patients with antibody-mediated rejection have low mean fluorescence intensities, partly due to the “sponge effect” related to DSAs binding to HLA molecules within the lung. Herein, we report the case of an 18-year-old, female lung transplant recipient who required retransplantation and developed circulating DSAs directed toward the first allograft but detected in circulation only after retransplantation. The present case draws attention to a rare finding of sponge effect in a patient with antibody-mediated rejection leading to allograft failure.

A timeline of pediatric bone healing using fracture healing characteristics that can be assessed solely using radiographs would be practical for forensic casework, where the fracture event may precede death by days, months, or years. However, the dating of fractures from radiographs is difficult, imprecise, and lacks consensus, as only a few aspects of the healing process are visible on radiographs. Multiple studies in both the clinical and forensic literature have attempted to develop a usable scale to assess pediatric bone healing on radiographs using various healing characteristics. In contrast to the orthopedic definition, a fracture in forensic casework is only considered to be healed when the area around the fracture has been remodeled to the point that the fracture is difficult to detect on a radiograph or on the surface of the bone itself, a process that can take several years. We subjectively assessed visible characteristics of healing in radiograms of fractures occurring in 942 living children and adolescents. By dividing these assessments into learning and test (validation) sets, the accuracy of a newly proposed fracture healing scale was compared to a previous study. Two machine learning models were used to test predictions of the new scale. All three models produced similar estimates with substantial imprecision. Results corroborate the Malone model with an independent dataset and support the efficacy of using less complex models to estimate fracture age in children.

The revelation in May 2015 of the shipment of γ irradiation–inactivated wild-type Bacillus anthracis spore preparations containing a small number of live spores raised concern about the safety and security of these materials. The finding also raised doubts about the validity of the protocols and procedures used to prepare them. Such inactivated reference materials were used as positive controls in assays to detect suspected B. anthracis in samples because live agent cannot be shipped for use in field settings, in improvement of currently deployed detection methods or development of new methods, or for quality assurance and training activities. Hence, risk-mitigated B. anthracis strains are needed to fulfill these requirements. We constructed a genetically inactivated or attenuated strain containing relevant molecular assay targets and tested to compare assay performance using this strain to the historical data obtained using irradiation-inactivated virulent spores.

In order to understand psychobiological responses to stress it is necessary to observe how people react to controlled stressors. A range of stressors exist for this purpose; however, laboratory stressors that are representative of real life situations provide more ecologically valid opportunities for assessing stress responding. The current study assessed psychobiological responses to an ecologically valid laboratory stressor involving multitasking and critical evaluation. The stressor elicited significant increases in psychological and cardiovascular stress reactivity; however, no cortisol reactivity was observed. Other socially evaluative laboratory stressors that lead to cortisol reactivity typically require a participant to perform tasks that involve verbal responses, whilst standing in front of evaluative others. The current protocol contained critical evaluation of cognitive performance; however, this was delivered from behind a seated participant. The salience of social evaluation may therefore be related to the response format of the task and the method of evaluation. That is, the current protocol did not involve the additional vulnerability associated with in person, face-to-face contact, and verbal delivery. Critical evaluation of multitasking provides an ecologically valid technique for inducing laboratory stress and provides an alternative tool for assessing psychological and cardiovascular reactivity. Future studies could additionally use this paradigm to investigate those components of social evaluation necessary for eliciting a cortisol response. Keywords: Multitasking, Critical social evaluation, Stress reactivity, Ecological validity

Abstract Collagen fibers, one of the key load-bearing components of the extracellular matrix, contribute significantly to tissue integrity through their mechanical properties of strain-dependent stiffening. This study investigated the effects of bacterial collagenase on the mechanical behavior of individual bovine lung collagen fibers in the presence or absence of mechanical forces, with a focus on potential implications for emphysema, a condition associated with collagen degradation and alveolar wall rupture. Tensile tests were conducted on individual collagen fibers isolated from bovine lung tissue. The rate of degradation was characterized by the change in fiber Young’s modulus during 60 min of digestion under various mechanical conditions mimicking the mechanical stresses on the fibers during breathing. Compared to digestion without mechanical forces, a significantly larger drop of fiber modulus was observed in the presence of static or intermittent mechanical forces. Fiber yield stress was also reduced after digestion indicating compromised fiber failure. By incorporating fibril waviness obtained by scanning electron microscopic images, an analytic model allowed estimation of fibril modulus. A computational model that incorporated waviness and the results of tensile tests was also developed to simulate and interpret the data. The simulation results provided insights into the mechanical consequences of bacterial collagenase and mechanical forces on collagen fibers, revealing both fibril softening and rupture during digestion. These findings shed light on the microscale changes in collagen fiber structure and mechanics under enzymatic digestion and breathing-like mechanical stresses with implications for diseases that are impacted by collagen degradation such as emphysema.

Background: Low-level, chronic viral infections have been suspect in the development of select autoimmune diseases, including primary Sjögren’s syndrome (pSS). Multiple studies have shown stimulation of antiviral response pathways in pSS tissues suggestive of a viral infection. Yet, with this data in hand, a causal link between a viral infection and development of pSS had not been identified. Therefore, a study was designed to further define the viral landscape within pSS-affected salivary gland tissue to identify potential viral-mediated triggers in the pathogenesis of this autoimmune disease. Methods: A viral microarray was utilized to measure viral transcripts present in salivary gland tissue from patients diagnosed with pSS compared to healthy controls. Murine models of salivary gland localized HDV antigen expression were developed to evaluate the capacity of a chronic HDV signature to trigger the development of a pSS-like phenotype. Results: Through this analysis, two distinct viral profiles were identified, including the increased presence of hepatitis delta virus (HDV) in 50% of pSS patients evaluated. Presence of HDV antigen and sequence were confirmed in minor salivary gland tissue. Patients with elevated HDV levels in salivary gland tissue were negative for detectible hepatitis B virus (HBV) surface antigen and antibodies to HBV or HDV. Expression of HDV antigens in vivo resulted in reduced stimulated saliva flow, increase in focal lymphocytic infiltrates, and development of autoantibodies. Conclusion: Identification of HDV in pSS patients and induction of a complete pSS-like phenotype in vivo provides further support of a viral-mediated etiopathology in the development of pSS.

This conceptual study examines the neoliberal knowledge economy as a dimension of globalisation policy within East Asian higher education. In exploring the practice of linguistic instrumentalisation, this inquiry aims to demonstrate the influence of English on the hereditary reproduction of social class. Calling on the theories of Pierre Bourdieu and Michel Foucault, this inquiry explores the interplay between one's hereditary and ultimate class membership and how proficiency in English mediates this hierarchy. Reinforced by a doxic knowledge of the 'entrepreneurial' credential ladder, aptitude in English represents a 'weapon' of empowerment (symbolic capital), used to certify and signal global readiness. Nevertheless, the meritocratic 'freedom of choice' leitmotiv supporting neoliberal governmentality fails to rationalise not only the class-conscious capitals that enable foreign language education but the ideological agendas that inhibit agency in such a manner as choosing English remains contingent rather than free. Given the economic benefits associated with EFL proficiency, this inquiry foregrounds inherited social class within its analysis, moving towards a deeper engagement with the socio-economic dimensions of foreign language education and the processes by which education is (further) reduced to strengthening pre-existing power relations.

Objective: To describe the use of a continuous quality improvement process for strengthening our simulated patient (SP) program and the initial steps that have been implemented. Innovation: A workgroup that included five clinical faculty with significant experience working with SPs and a strong interest in improving the SP program was developed. The Plan-Do-Study-Act model was used as it allowed for incremental quality improvement changes, in order to ensure a high-quality SP program designed to optimize student learning. Data were gathered from students, SPs, and faculty. Opportunities for improvement were prioritized based on anticipated benefits and available resources. Changes related to planning, implementation, and evaluation and feedback have been executed. Critical Analysis: Changes related to planning that were implemented included developing handbooks for SPs, faculty, and graduate student instructors, as well as material for students in order to better describe the program. SPs are now referred to as “simulated” as opposed to “standardized” as part of a broader effort to clarify the purpose of SP interactions to students. Streamlined rubrics have been piloted, including electronic rubrics for first year students. SPs are being trained on fewer cases, in order to improve the training program. When possible, activities now take place in one large classroom instead of many small classrooms to improve oversight. Finally, additional feedback has been obtained from SPs via a retreat. These changes have been well received by students, SPs, and faculty. Next Steps: The collection of this data and initial quality improvement changes provided a basis for hiring a full-time employee who will: dedicate 50% of their time to programmatic assessment of the SP program, support faculty with logistics and training, and be the face of our program to the students and SPs. Further, formal quantitative and qualitative assessment of the SP program has begun. Type: Note

Genome sequence analyses of the 2014 Ebola Virus (EBOV) isolates revealed a potential problem with the diagnostic assays currently in use; i.e., drifting genomic profiles of the virus may affect the sensitivity or even produce false-negative results. We evaluated signature erosion in ebolavirus molecular assays using an in silico approach and found frequent potential false-negative and false-positive results. We further empirically evaluated many EBOV assays, under real time PCR conditions using EBOV Kikwit (1995) and Makona (2014) RNA templates. These results revealed differences in performance between assays but were comparable between the old and new EBOV templates. Using a whole genome approach and a novel algorithm, termed BioVelocity, we identified new signatures that are unique to each of EBOV, Sudan virus (SUDV), and Reston virus (RESTV). Interestingly, many of the current assay signatures do not fall within these regions, indicating a potential drawback in the past assay design strategies. The new signatures identified in this study may be evaluated with real-time reverse transcription PCR (rRT-PCR) assay development and validation. In addition, we discuss regulatory implications and timely availability to impact a rapidly evolving outbreak using existing but perhaps less than optimal assays versus redesign these assays for addressing genomic changes.

Nuclear astrophysics is an interdisciplinary field focused on exploring the impact of nuclear physics on the evolution and explosions of stars and the cosmic creation of the elements. While researchers in astrophysics and in nuclear physics are separately using machine learning approaches to advance studies in their fields, there is currently little use of machine learning in nuclear astrophysics. We briefly describe the most common types of machine learning algorithms, and then detail their numerous possible uses to advance nuclear astrophysics, with a focus on simulation-based nucleosynthesis studies. We show that machine learning offers novel, complementary, creative approaches to address many important nucleosynthesis puzzles, with the potential to initiate a new frontier in nuclear astrophysics research.

ABSTRACT Biological invasions pose significant threats to ecological and economic stability, with invasive pests like the Asian longhorned beetle (Anoplophora glabripennis Motschulsky, ALB) causing substantial damage to forest ecosystems. Effective pest management relies on comprehensive knowledge of the insect's biology and invasion history. This study uses genomics to address these knowledge gaps and inform existing biosurveillance frameworks. We used 2768 genome‐wide single nucleotide polymorphisms to compare invasive A. glabripennis populations in North America, using genomic variation to trace their sources of invasion and spread patterns, thereby refining our understanding of this species' invasion history. We found that most North American A. glabripennis infestations were distinct, resulting from multiple independent introductions from the native range. Following their introduction, all invasive populations experienced a genetic bottleneck which was followed by a population expansion, with a few also showing secondary spread to satellite infestations. Our study provides a foundation for a genome‐based biosurveillance tool that can be used to clarify the origin of intercepted individuals, allowing regulatory agencies to strengthen biosecurity measures against this invasive beetle.

Purpose: The /[voiced alveolar approximant]/ productions of young children acquiring American English are highly variable and often inaccurate, with [w] as the most common substitution error. One acoustic indicator of the goodness of children's /[voiced alveolar approximant]/ productions is the difference between the frequency of the second formant (F2) and the third formant (F3), with a smaller F3-F2 difference being associated with a perceptually more adultlike /[voiced alveolar approximant]/. This study analyzed the effectiveness of automatically extracted F3-F2 differences in characterizing young children's productions of /[voiced alveolar approximant]/-/w/ in comparison with manually coded measurements. Method: Automated F3-F2 differences were extracted from productions of a variety of different /[voiced alveolar approximant]/- and /w/-initial words spoken by 3- to 4-year-old monolingual preschoolers (N = 117; 2,278 tokens in total). These automated measures were compared to ratings of the phoneme goodness of children's productions as rated by untrained adult listeners (n = 132) on a visual analog scale, as well as to narrow transcriptions of the production into four categories: [[voiced alveolar approximant]], [w], and two intermediate categories. Results: Data visualizations show a weak relationship between automated F3-F2 differences with listener ratings and narrow transcriptions. Mixed-effects models suggest the automated F3-F2 difference only modestly predicts listener ratings (R2 = 0.37) and narrow transcriptions (R2 = 0.32). Conclusion: The weak relationship between automated F3-F2 difference and both listener ratings and narrow transcriptions suggests that these automated acoustic measures are of questionable reliability and utility in assessing preschool children's mastery of the /[voiced alveolar approximant]/-/w/ contrast.

This is a case of a 36-year-old gentleman with haemophilia A who was presented with an acute atraumatic soft tissue swelling in the right thigh. Open biopsy was performed with the resultant diagnosis of a synovial cell sarcoma. Although the clinical findings were nonspecific they could easily have been found in a bleeding haemophilic pseudotumour. The findings reported on MRI scan initially were highly consistent with those present in patients with mild haemophilia. An important part of orthopaedic management in haemophilia is concerned with intraarticular and intramuscular bleeding. Haematomas are common and sarcomas are rare. However the absence of trauma should alert the clinician to the possibility that the abnormality may represent haemorrhage into a tumour and not just haematoma, even in a haemophilic patient.