Quantitative Analysis of the Efficiency of Clonal Deletion in the Thymus

One of the major mechanisms for establishing self-tolerance is the clonal deletion of self-reactive T cells during their development in the thymus. Using a TCR transgenic mouse model, we have established a quantitative ex vivo assay for examining the sensitivity and specificity of negative selection. Thymic organ cultures established from mice of varying MHC haplotypes were incubated with antigen, and the efficiency of clonal deletion assessed. We show here that clonal deletion of CD4+8+ thymocytes is sensitive to both the gene dosage and the allelic variation of MHC class II molecules expressed on thymic antigen-presenting cells. We also find that when epithelial cells in the thymic cortex are the only antigen-presenting cells expressing the appropriate MHC class II molecules, negative selection of CD4+8+ cells is as efficient as when antigen is presented on all thymic antigen-presenting cells. These studies demonstrate that the induction of self-tolerance via clonal deletion in the thymus is a function not only of antigen concentration, but also of MHC class II cell-surface density. In addition, together with the reports of others, these results confirm that cortical epithelial cells can mediate negative selection, and demonstrate that they do so in the intact thymic microenvironment

Putting Differences in Context: Incorporating the Role of Status and Cooperation into Work Unit Ethnic Composition Research

Due to increasing diversity within organizations, understanding the impact of ethnic differences in work units has become a strategic imperative. Although the topic of much research, findings regarding the effect of work unit ethnic composition on work unit outcomes are inconsistent. I begin to address inconsistencies in the literature by incorporating the role of two moderators of intergroup contact, status and cooperation (Allport, 1954), into ethnic composition research. First, I introduce the construct of ethnic status, which reflects the degree of status ascribed to individuals based on ethnic group membership, and predict that work unit ethnic status separation (ESS) will negatively impact work unit processes (conflict, cohesion, trust) and performance (financial, manager-rated, citizenship behaviors). Second, I theorize that elements of the work unit (learning climate, performance climate) and community (ethnic composition, economics, political climate) context will moderate work unit ethnic composition effects, such that cooperative contexts ameliorate, but competitive contexts exacerbate, the negative relationship between work unit ESS and unit-level outcomes. In Study 1, I developed a measure of ethnic status and found support for the stability and validity of ethnic status in both student and adult samples. In Study 2, I used the status measure to calculate work unit composition (i.e., ESS). I then tested the interaction of work unit ESS with elements of the work unit and community context as a predictor of unit-level outcomes in a sample of 703 employees of a large bank, who were nested within 121 geographically dispersed work units (i.e., branches). To assess community contexts, I supplemented the bank sample with data from the United States Census. At the work unit level, I found that high ESS work units experienced less conflict and better financial performance in high learning climates than in low learning climates. At the community level, I found that the negative outcomes of work unit ESS, including high conflict, low cohesion and trust, and poor financial performance, were most severe in communities similarly characterized by high ESS. Results for the remaining work unit (performance climate) and community (economics, political climate) context factors were mixed. Theoretical and practical implications are discussed

Prevalence of atrial fibrillation in a regional Victoria setting, findings from the crossroads studies (2001–2003 and 2016–2018)

Objective: To estimate the prevalence of atrial fibrillation (AF) in regional Victoria at two time points (2001-2003 and 2016-2018), and to assess the use of electrocardiogram rhythm strips in a rural, community-based study for AF investigation. Design: Repeated cross-sectional design involving survey of residents of randomly selected households and a clinic. Predictors of AF were assessed using Firth penalised logistic regression, as appropriate for rare events. Setting: Goulburn Valley, Victoria. Participants: Household residents aged >= 16years. Non-pregnant participants aged 18+ were eligible for the clinic. Main outcome measures: Atrial fibrillation by 12 lead electrocardiogram (earlier study) or electrocardiogram rhythm strip (AliveCor (R) device) (recent study). Results: The age standardised prevalence of AF was similar between the two studies (1.6% in the 2001-2003 study and 1.8% in the 2016-2018 study, 95% confidence interval of difference -0.010, 0.014, p = 0.375). The prevalence in participants aged >= 65years was 3.4% (1.0% new cases) in the recent study. Predictors of AF in the earlier study were male sex, older age and previous stroke, while in the recent study they were previous stroke and self-reported diabetes. AliveCor (R) traces were successfully classified by the in-built algorithm (91%) vs physician (100%). Conclusion: The prevalence of AF among community-based participants in regional Victoria was similar to predominantly metropolitan-based studies, and was unchanged over time despite increased rates of risk factors. Electrocardiogram rhythm strip investigation was successfully utilised, and particularly benefited from physician overview

Cultural determinants of status: Implications for workplace evaluations and behaviors

Status is a valued workplace resource that facilitates career success, yet little is known regarding whether and how cultural orientation affects status attainment. We integrate status characteristics theory with the literature on individualism and collectivism and propose a cultural patterning in the determinants of status. Four studies (N = 379) demonstrate that cultural orientation influences the tendency to view high status individuals as competent versus warm (Study 1), uncover cultural differences in both individuals’ tendency to engage in competence and warmth behaviors to attain workplace status (Study 2) and evaluators’ tendency to ascribe status to individuals who demonstrate competence versus warmth (Study 3), and verify that cultural differences in the effects of competence and warmth on status perceptions, and in turn performance evaluations, generalize to real world interdependent groups (Study 4). Our findings advance theory on the cultural contingencies of status attainment and have implications for managing diversity at work

Architecture and Agency For Equity In Areas Beyond National Jurisdiction

The United Nations (UN) Sustainable Development Goals (SDGs) and the UN Decade of Ocean Science for Sustainable Development (Ocean Decade) bring increased attention to various aspects of ocean governance, including equity. One of the Ocean Decade\u27s identified challenges is to develop a sustainable and equitable ocean economy, but questions arise about how to conceptualize the multiple dimensions of equity in an ocean context. These questions become more complex as activities move away from coastal ecosystems and communities into off-shore Areas Beyond National Jurisdiction (ABNJ), where ocean resources are recognized simultaneously as unowned/open access and as common heritage. In this paper, we mobilize the Earth System Governance analytics of ‘architecture’ and ‘agency’, to reflect on the possibilities for equity in ABNJ. Motivated by the general attention to equity in UN initiatives like the SDGs and the Ocean Decade, we describe current UN architecture for ocean governance, including principles that might support equity. Existing UN architecture focuses on distributional equity among nation states, with less attention to recognitional or procedural equity. State actors have most agency, while non-state actors can exercise some via broad UN declarations and through mechanisms like ‘major groups.’ We use on-going negotiations in the International Seabed Authority on rules for mineral exploitation and in the Intergovernmental Conference on an international legally binding instrument under UNCLOS on the conservation and sustainable use of marine biological diversity of Areas Beyond National Jurisdiction to illustrate how existing architecture shapes possibilities for equity in ABNJ. As new governance possibilities are imagined, attending to existing architecture and agency can help avoid further entrenching existing power imbalances and unwittingly reproducing or exacerbating inequities

A Signal Detection Theoretic Analysis of the Carney Model of Auditory Processing

Abstract: Historically, signa[ detection theory (SDT) applied "outside" the ear has not provided valid estimates of the performance measured in psychophysical experiments. Our previous work, in which SDT wm applied at the output of each stage of the Auditory Image Model (AIM) (1), has indicated that this integrated approach affords theoretical performance predictions that are more closely matched to experimental data than previous approaches (2). In this paper, we describe the results obtained when a similar approach is applied to the output of the Camey model of auditory processing (3). Our results indicate that for a simultaneous masking task, when it is assumed that all parameters of the input signal are known, the performance predictions obtained from SDT integrated with AIM and the Carney model are similar at the neural firing stage, and both over-predict experimental measures. However, when it is assumed that the phase of the sinusoid is unknown, the integrated approach provides performance estimates that are fairly close to the performance levels observed experimentally

Design of a randomized superiority trial of a brief couple treatment for PTSD.

Interpersonal difficulties are common among veterans with posttraumatic stress disorder (PTSD) and are associated with poorer treatment response. Treatment outcomes for PTSD, including relationship functioning, improve when partners are included and engaged in the therapy process. Cognitive-behavioral conjoint therapy for PTSD (CBCT) is a manualized 15-session intervention designed for couples in which one partner has PTSD. CBCT was developed specifically to treat PTSD, engage a partner in treatment, and improve interpersonal functioning. However, recent research suggests that an abbreviated CBCT protocol may lead to sufficient gains in PTSD and relationship functioning, and yield lower dropout rates. Likewise, many veterans report a preference for receiving psychological treatments through clinical videoteleconferencing (CVT) rather than traditional face-to-face modalities that require travel to VA clinics. This manuscript describes the development and implementation of a novel randomized controlled trial (RCT) that examines the efficacy of an abbreviated 8-session version of CBCT ("brief CBCT," or B-CBCT), and compares the efficacy of this intervention delivered via CVT to traditional in-person platforms. Veterans and their partners were randomized to receive B-CBCT in a traditional Veterans Affairs office-based setting (B-CBCT-Office), CBCT through CVT with the veteran and partner at home (B-CBCT-Home), or an in office-delivered, couple-based psychoeducation control condition (PTSD Family Education). This study is the first RCT designed to investigate the delivery of B-CBCT specifically to veterans with PTSD and their partners, as well as to examine the delivery of B-CBCT over a CVT modality; findings could increase access to care to veterans with PTSD and their partners

Intermediate filament–membrane attachments function synergistically with actin-dependent contacts to regulate intercellular adhesive strength

By tethering intermediate filaments (IFs) to sites of intercellular adhesion, desmosomes facilitate formation of a supercellular scaffold that imparts mechanical strength to a tissue. However, the role IF–membrane attachments play in strengthening adhesion has not been directly examined. To address this question, we generated Tet-On A431 cells inducibly expressing a desmoplakin (DP) mutant lacking the rod and IF-binding domains (DPNTP). DPNTP localized to the plasma membrane and led to dissociation of IFs from the junctional plaque, without altering total or cell surface distribution of adherens junction or desmosomal proteins. However, a specific decrease in the detergent-insoluble pool of desmoglein suggested a reduced association with the IF cytoskeleton. DPNTP-expressing cell aggregates in suspension or substrate-released cell sheets readily dissociated when subjected to mechanical stress whereas controls remained largely intact. Dissociation occurred without lactate dehydrogenase release, suggesting that loss of tissue integrity was due to reduced adhesion rather than increased cytolysis. JD-1 cells from a patient with a DP COOH-terminal truncation were also more weakly adherent compared with normal keratinocytes. When used in combination with DPNTP, latrunculin A, which disassembles actin filaments and disrupts adherens junctions, led to dissociation up to an order of magnitude greater than either treatment alone. These data provide direct in vitro evidence that IF–membrane attachments regulate adhesive strength and suggest furthermore that actin- and IF-based junctions act synergistically to strengthen adhesion

Doctor recommendations are related to patient interest and use of behavioral treatment for chronic pain and addiction

The opioid crisis has highlighted the importance of improving patients’ access to behavioral treatments for chronic pain and addiction. What is not known is if patients are interested in receiving these treatments. In this cross-sectional study, over 1000 participants with chronic pain were surveyed using an anonymous online questionnaire on Amazon Mechanical Turk (Mturk) to investigate participants’ use of and interest in pharmacological and behavioral treatments for chronic pain and addiction. Participants also indicated whether their doctor had recommended these treatments. The majority of participants reported using medication for their pain (83.19%) and that their doctor recommended medication (85.05%), whereas fewer participants reported using (67.45%) and being recommended to (62.82%) behavioral treatments. We found 63.67% of participants screened positive for possible opioid misuse; those who screened positive were more interested in receiving behavioral treatments than those who did not screen positive. Participants who received treatment recommendations were more likely to be interested in receiving those treatments as compared to participants who did not. The results suggest that recommendations for behavioral treatments and interest in those treatments are related. Results also suggest that patients endorsing behaviors consistent with opioid misuse are interested in behavioral treatments

Self-Study In Patient Safety And Quality Improvement To Enhance Student Experience In Interprofessional Case Competition

Objective: The Interprofessional Student Advisory Team (IPSAT) at the University of New England (UNE) organized its 2nd interprofessional student case competition, modeled after the CLARION competition from the University of Minnesota. Completion of an online certificate in patient safety and quality improvement from the Institute for Healthcare Improvement (IHI) Open School was added as a pre-requisite to participation in the 2014 competition. Completion of this program was predicted to improve student preparedness and confidence and facilitate interprofessional teamwork during their case preparation. Conclusions: Survey results indicate an increase in student confidence and preparedness for interprofessional teamwork during the 2014 UNE IPSAT case competition. Survey research was limited by a small number of completed surveys, a delay in IRB approval and unfamiliarity with the IRB suggested survey software. IPSAT student leaders at UNE will continue to require completion of the IHI Open School Basic Certificate as a prerequisite for enrollment in future IPSAT case competitions.https://dune.une.edu/minigrant_ipsat2014/1000/thumbnail.jp