IRF7-Associated Immunophenotypes Have Dichotomous Responses to Virus/Allergen Coexposure and OM-85-Induced Reprogramming

High risk for virus-induced asthma exacerbations in children is associated with an IRF7lo immunophenotype, but the underlying mechanisms are unclear. Here, we applied a Systems Biology approach to an animal model comprising rat strains manifesting high (BN) versus low susceptibility (PVG) to experimental asthma, induced by virus/allergen coexposure, to elucidate the mechanism(s)-of-action of the high-risk asthma immunophenotype. We also investigated potential risk mitigation via pretreatment with the immune training agent OM-85. Virus/allergen coexposure in low-risk PVG rats resulted in rapid and transient airways inflammation alongside IRF7 gene network formation. In contrast, responses in high-risk BN rats were characterized by severe airways eosinophilia and exaggerated proinflammatory responses that failed to resolve, and complete absence of IRF7 gene networks. OM-85 had more profound effects in high-risk BN rats, inducing immune-related gene expression changes in lung at baseline and reducing exaggerated airway inflammatory responses to virus/allergen coexposure. In low-risk PVG rats, OM-85 boosted IRF7 gene networks in the lung but did not alter baseline gene expression or cellular influx. Distinct IRF7-associated asthma risk immunophenotypes have dichotomous responses to virus/allergen coexposure and respond differentially to OM-85 pretreatment. Extrapolating to humans, our findings suggest that the beneficial effects OM-85 pretreatment may preferentially target those in high-risk subgroups.

Fake News, False Beliefs, and the Fallible Art of Knowledge Maintenance

The term ‘fake news’, it is argued in this chapter, captures a novel kind of social-epistemic dysfunction that arises from systemic distortions of established processes of creating, disseminating, and consuming news-like content. Navigating informational environments populated by fake news requires the cultivation of epistemic routines that reduce our exposure to misleading and deceptive information, while at the same time continuing to allow us to partake in the collective growth of knowledge. Shifting the focus to epistemic routines steers a middle path between two frequently encountered dichotomous responses to the problem of fake news: viz., between emphasizing the individual’s responsibility to ‘think critically and check one’s sources’ and advocating technological tweaks (such as automated fact-checking). While epistemic agents ought to be held responsible for the epistemic routines they commit themselves to, there is also a collective need for making the predictable effects of such choices transparent to individuals, wherever technologically possible.

Pharmacists’ Perceptions, Barriers, and Potential Solutions to Implementing a Direct Pharmacy Access Policy in Indiana

This study assessed pharmacists’ perceptions, barriers, and potential solutions for implementing a policy allowing pharmacists to prescribe hormonal contraceptives in Indiana. A mixed-method survey ( n = 131, 22.3% response rate), using Likert-type scales, dichotomous responses (yes/no), and open-ended questions, was distributed to pharmacy preceptors in Indiana. Pharmacists felt prescribing contraceptives would be beneficial (79.1%) and were interested in providing this service (76.0%), but only 35.6% reported having the necessary resources. Participants with a PharmD were significantly more likely to feel the service would be beneficial (odds ratio [ OR] = 10.360, 95% confidence interval [CI: 1.679, 63.939]) and be interested in prescribing contraceptives ( OR = 9.069, 95% CI [1.456, 56.485]). Reimbursement (86.4%), training courses (84.7%), private counseling rooms (69.5%), and increasing technician responsibilities (52.5%) were identified as ways to ease implementation. Women had significantly greater odds of being more comfortable than men prescribing injections ( OR = 2.237, 95% CI [1.086, 4.605]), and intravaginal rings ( OR = 2.215, 95% CI [1.066, 4.604]), when controlling for age, degree, and setting. Qualitative findings reinforced quantitative findings.

The Gap Between Subjective Return to Sports and Subjective Athletic Performance Intensity After Anterior Cruciate Ligament Reconstruction

Background: On a questionnaire administered to athletes who had undergone anterior cruciate ligament reconstruction (ACLR), some answered “yes” to a question regarding return to sports (RTS) at the preinjury level despite having lower postoperative subjective athletic performance (PoSAP) intensity compared with preoperative levels. Purpose: To investigate the agreement between responses regarding RTS and PoSAP intensity after ACLR. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: A total of 44 individuals, 24.8 ± 18.4 months after ACLR, participated in this study. They completed a questionnaire in which PoSAP was graded as a percentage of preoperative performance level. They also gave dichotomous responses (yes/no) to the question of whether they had been able to RTS at the same level as before their injury (RTS question). Participants were divided into 2 groups according to their PoSAP scores using different cutoff values (100%, 90%, 80%, and 70%), and an exploratory analysis was conducted of the cutoff value for dividing PoSAP scores that provided the greatest agreement with the response to the RTS question. Results: The mean PoSAP score was 87.5% ± 14.9%, and 33 participants (75%) answered “yes” to the RTS question. The agreement between the PoSAP score and the RTS question was lowest when the cutoff value was 100% (κ = 0.294) and highest when the cutoff value was 80% (κ = 0.676) and 90% (κ = 0.632). Conclusion: More athletes who had undergone ACLR answered “yes” to the RTS question even when their PoSAP score was around 80%. Asking only for dichotomous responses may result in overestimating the level to which these athletes’ performance has recovered after ACLR.

Analysing Standard Progressive Matrices (SPM-LS) with Bayesian Item Response Models

Raven’s Standard Progressive Matrices (SPM) test and related matrix-based tests are widely applied measures of cognitive ability. Using Bayesian Item Response Theory (IRT) models, I reanalyzed data of an SPM short form proposed by Myszkowski and Storme (2018) and, at the same time, illustrate the application of these models. Results indicate that a three-parameter logistic (3PL) model is sufficient to describe participants dichotomous responses (correct vs. incorrect) while persons’ ability parameters are quite robust across IRT models of varying complexity. These conclusions are in line with the original results of Myszkowski and Storme (2018). Using Bayesian as opposed to frequentist IRT models offered advantages in the estimation of more complex (i.e., 3–4PL) IRT models and provided more sensible and robust uncertainty estimates.

Analysing Standard Progressive Matrices (SPM-LS) with Bayesian Item Response Models

Raven’s Standard Progressive Matrices (SPM) test and related matrix-based tests are widely applied measures of cognitive ability. Using Bayesian Item Response Theory (IRT) models, I reanalyse data of an SPM short form proposed by Myszkowski & Storme (2018) and, at the same time, illustrate the application of these models. Results indicate that a 3-parameter logistic (3PL) model is sufficient to describe participants dichotomous responses (correct vs. incorrect) while persons' ability parameters are quite robust across IRT models of varying complexity. These conclusions are in line with the original results of Myszkowski & Storme (2018). Using Bayesian as opposed to frequentist IRT models offered advantages in the estimation of more complex (i.e., 3-4PL) IRT models and provided more sensible and robust uncertainty estimates.

Hemodynamic and functional effectiveness of the patient undergoing pulmonary thromboendarterectomy

Objective: to evaluate the hemodynamic and functional effectiveness of the patient undergoing thromboendarterectomy. Methods: a descriptive study of series of cases in postoperative patients of thromboendarterectomy from 2002 to 2016 with complete records was carried out. The data collection was done with an "ex profeso" sheet of 10 demographic items, 2 of somatometry, 6 hemodynamics, 1 functional, 6 gasometric and 9 of perfusion conduction, with open and dichotomous responses. For the data analysis, descriptive statistics, U Mann-Whitney tests and Kaplan-Meier survival analysis were applied; the significance was set at p <0.05. Results: 25 patients were studied, male prevalence (68%), age 43 ± 18 years. The cardiopulmonary bypass time was 222 ± 73 min. and the aortic clamp of 121 ± 71 min; in 80%total circulatory arrest was performed for periods of 20 min and reperfusion times of 10 min between each one. 20% of the patients were managed with selective cerebral perfusion. Thromboendarterectomy decreased pulmonary vascular resistance (p <0.0001) and mean pulmonary arterial pressure (p = 0.001) and increased cardiac output (p = 0.009), PaO2 (p = 0.035) and SaO2 (p = 0.015). 72% improved the functional class from III-IV to I-II. There was mortality of 20% associated to persistence of pulmonary arterial hypertension and the three-year survival was 80%. Two patients required ECMO A-V both successful. Conclusion: Thromboendarterectomy is the treatment of choice for patients with chronic pulmonary thromboembolism, significantly improving hemodynamic and functional parameters, reflected in their quality of life and survival.