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Abstract Background Severe eosinophilic asthma (SEA) is characterised by elevated blood/sputum eosinophil counts and airway inflammation, which can lead to mucus plug-mediated airway obstruction, increased exacerbation frequency, declines in lung function, and death. Benralizumab targets the alpha-subunit of the interleukin-5 receptor found on eosinophils, leading to rapid and near complete eosinophil depletion. This is expected to result in reduced eosinophilic inflammation, reduced mucus plugging and improved airway patency and airflow distribution. Methods BURAN is an interventional, single-arm, open-label, uncontrolled, prospective, multicentre study during which participants will receive three 30 mg subcutaneous doses of benralizumab at 4-week intervals. This study will use functional respiratory imaging (FRI), a novel, quantitative method of assessing patients’ lung structure and function based on detailed, three-dimensional models of the airways, with direct comparison of images taken at Weeks 0 and 13. Patients aged ≥ 18 years with established SEA who may be receiving oral corticosteroids and/or other asthma controller medications, who are inadequately controlled on inhaled corticosteroid-long-acting β2-agonist therapies and who have had ≥ 2 asthma exacerbations in the previous 12 months will be included. The objectives of BURAN are to describe changes in airway geometry and dynamics, measured by specific image-based airway volume and other FRI endpoints, following benralizumab therapy. Outcomes will be evaluated using descriptive statistics. Changes in FRI parameters, mucus plugging scores and central/peripheral ratio will be quantified as mean percent change from baseline (Week 0) to Week 13 (± 5 days) and statistical significance will be evaluated using paired t-tests. Relationships between FRI parameters/mucus plugging scores and conventional lung function measurements at baseline will be assessed with linear regression analyses for associations between outcomes, scatterplots to visualise the relationship, and correlation coefficients (Spearman’s rank and Pearson’s) to quantify the strength of these associations. Conclusions The BURAN study will represent one of the first applications of FRI—a novel, non-invasive, highly sensitive method of assessing lung structure, function and health—in the field of biologic respiratory therapies. Findings from this study will increase understanding of cellular-level eosinophil depletion mechanisms and improvements in lung function and asthma control following benralizumab treatment. Trial registration EudraCT: 2022-000152-11 and NCT05552508

Case Presentation: A 35-year-old woman presented to the emergency department with severe right inguinal pain. Her medical history was non-contributory and there was no known trauma or injury to the region. Amid concern for an incarcerated inguinal hernia, a computed tomography was obtained revealing a linear foreign body (FB) lateral to the femoral vessels. The FB was removed without complication at bedside and found to be a beading needle likely occultly lodged three days prior. Discussion: Occult inguinal FBs are rare but can lead to deep venous thrombosis or pulmonary embolism if in or near vessels. By nature of being occult, an absence of ingestion, insertion, or penetrative history should not preclude consideration of a FB etiology. Computed tomography imaging is crucial in determining the urgency of, and approach to, inguinal foreign body removal.

Abstract To determine whether quantitative computed tomography (qCT)‐derived metrics of pulmonary vascular volume distribution could distinguish chronic obstructive pulmonary disease (COPD) subjects with associated pulmonary hypertension (PH) from those without and to characterize associations of these measurements with clinical and physiological characteristics and outcomes. We collected retrospective CT, pulmonary hemodynamic, clinical, and outcomes data from subjects with COPD and right‐heart catheterization‐confirmed PH (PH‐COPD) and control subjects with COPD but without PH. We measured the volumes of pulmonary vessels 10 mm2 in cross‐sectional area as a percentage of total pulmonary vascular volume (qCT‐derived volume of pulmonary vessels 10 mm2 in cross‐sectional area [BV10] as a volume fraction of total pulmonary blood volume [BV10%], respectively) using Functional Respiratory Imaging (FRI), an automated qCT platform, and compared them between PH and control arms and between subjects with mild‐moderate PH and those with severe disease. Correlations of hemodynamics with pulmonary function and associations with survival were tested. Forty‐five PH‐COPD and 42 control subjects were studied. BV5% was lower in PH subjects (32.2% vs. 37.7%, p = 0.003), and BV10% was higher (50.2% vs. 43.5, p = 0.001). Subjects with severe PH did not differ from those with mild‐moderate PH in qCT. Pulmonary vascular volumes were not associated with pulmonary function. BV10 was associated with mean pulmonary artery pressure (r = 0.3, p = 0.05). Associations with survival were observed for BV5% (hazard ratio 0.63, p = 0.02) and BV10% (hazard ratio 1.43, p = 0.03) in the PH‐COPD arm, but not for controls. qCT‐derived measures of pulmonary vascular volume may have diagnostic and prognostic significance in PH‐COPD and should be investigated further as screening and risk stratification tools

Some internal medicine residency program directors have expressed concerns that their third-year residents may have been subjected to inappropriate communication during the 2016 fellowship recruitment season. The authors sought to study applicants' interpersonal communication experiences with fellowship programs. Many respondents indicated that they had been asked questions that would constitute violations of the National Residency Matching Program (NRMP) Communications Code of Conduct agreement, including how they plan to rank specific programs. Moreover, female respondents were more likely to have been asked questions during interview experiences about other programs to which they applied, and about their family plans. Post-interview communication policies were not made clear to most applicants. These results suggest ongoing challenges for the internal medicine community to improve communication with applicants and uniform compliance with the NRMP communications code of conduct during the fellowship recruitment process.

Background Standardized letters of recommendation (SLOR) have become common features of the medical school to residency transition. Research has shown many advantages over the narrative letter of recommendation including improved letter-writing efficiency, ease of interpretation, and improved reliability as performance predictors. Currently, at least four specialties require fellowship SLORs. Internal medicine adopted its SLOR in 2017. Previous research showed fellowship program directors’ satisfaction with the 2017 guidelines. Little is known about residency program directors’ acceptance and adherence to the guidelines. Objectives The study sought to assess the adoption rate of each component, barriers to adoption, time commitment, and alignment with intended goals of the guidelines. Methods Anonymous survey links were posted to an internal medicine discussion forum prior to the guidelines in spring 2017 and twice following the guidelines in fall 2018 and winter 2019. Two-sample tests of proportions were used to compare respondent characteristics with known survey population data. Pre- and post-survey comparisons were assessed for statistical significance with Pearson chi-squared statistic. Results The response rate varied from 30% to 35% for each survey period. Medical knowledge, patient care, interpersonal and communication skills, professionalism, and scholarly activity were reported frequently (>96%) at baseline. Inclusion of residency program characteristics, systems-based practice, practice-based learning and improvement, and skills sought to master increased over the study period. Conclusions The new guidelines improved uniform reporting of all core competency data. Overall, the gains were modest, as many pre-survey respondents reported high rates of including components within the guidelines.

Teachers appear as characters in a wide range of literary writing. To date, few scholars have systematically studied the teachers who appear in works of literature. Much of the existing work has focused on relatively small numbers of teachers and has been presented in the form of brief essays rather than formal research (e.g., Booth, 2006; Crume, 1989; Shockley, 1971). Other scholars have written longer pieces exploring issues ranging from an exploration of tensions among gender, authority, and desire (Keroes, 1999), to an analysis of teachers who appear as characters in novels written for young adults (Burnaford, 2001; Smedman, 1989), to an examination of race, class, gender, and control in fictional depictions of teachers (Brunner, 1994). However, no one has ever attempted to classify the range of teacher identities that appear in a large and diverse sampling of literary works. In fact, no one has even compiled a relatively well-rounded list of literary teachers--one which spans multiple genres, multiple historical periods, and multiple audience levels. The purpose of this study is therefore to systemically categorize the types of teachers that appear in a broad range of literature, and to define the various identities that are depicted. It is hoped that this important preliminary work will spawn a wide range of future studies into the lives, careers, and identities of literary teachers.

This article describes a long-term effort to improve student achievement in an urban school district through a unique school-university partnership. The Oak Park School District in Oak Park, Michigan, collaborated with Western Michigan University (WMU) to design and administer special master's and doctoral degree programs for nearly half the district teachers. Several features distinguish the program from other school-university partnerships. First, the partnership idea, including all early planning, originated with the school district and not the university. Second, the academic content of the degree programs transcended the university's set curriculum to address teachers' needs. Third, the focus of the degree programs changed from pedagogy to educational leadership. Finally, there was a practical factor: the school district and the university are separated by 150 miles. This article describes the history and evolution of the partnership and provides a brief overview of its successes and shortcomings.

Case Presentation: A 35-year-old woman presented to the emergency department with severe right inguinal pain. Her medical history was non-contributory and there was no known trauma or injury to the region. Amid concern for an incarcerated inguinal hernia, a computed tomography was obtained revealing a linear foreign body (FB) lateral to the femoral vessels. The FB was removed without complication at bedside and found to be a beading needle likely occultly lodged three days prior. Discussion: Occult inguinal FBs are rare but can lead to deep venous thrombosis or pulmonary embolism if in or near vessels. By nature of being occult, an absence of ingestion, insertion, or penetrative history should not preclude consideration of a FB etiology. Computed tomography imaging is crucial in determining the urgency of, and approach to, inguinal foreign body removal.

SUMMARYChronic infection with hepatitis C virus (HCV) is a common cause of liver cirrhosis and cancer. We performed RNA-sequencing in primary human hepatocytes activated with synthetic dsRNA to mimic HCV infection. Upstream of IFNL3 (IL28B) on chromosome 19q13.13, we discovered a novel, transiently induced region that harbors dinucleotide variant ss469415590 (TT/ΔG), which is in high linkage disequilibrium with rs12979860, a genetic marker strongly associated with HCV clearance. ss469415590-ΔG is a frame-shift variant that creates a novel primate-specific gene, designated interferon lambda 4 (IFNL4), which encodes a protein of moderate similarity with IFNL3. Compared to rs12979860, ss469415590 is more strongly associated with HCV clearance in individuals of African ancestry, whereas it provides comparable information in Europeans and Asians. Transient over-expression of IFNL4 in a hepatoma cell line induced STAT1/STAT2 phosphorylation and expression of interferon-stimulated genes. Our findings provide new insights into the genetic regulation of HCV clearance and its clinical management.

Abstract Exhaled nitric oxide (FeNO) is an established respiratory biomarker with clinical applications in the diagnosis and management of asthma. Because FeNO depends strongly on the flow (exhalation) rate, early protocols specified that measurements should be taken when subjects exhaled at a fixed rate of 50 ml/s. Subsequently, multiple flow (or “extended”) protocols were introduced which measure FeNO across a range of fixed flow rates, allowing estimation of parameters including CawNO and CANO which partition the physiological sources of NO into proximal airway wall tissue and distal alveolar regions (respectively). A recently developed dynamic model of FeNO uses flow‐concentration data from the entire exhalation maneuver rather than plateau means, permitting estimation of CawNO and CANO from a wide variety of protocols. In this paper, we use a simulation study to compare CawNO and CANO estimation from a variety of fixed flow protocols, including: single maneuvers (30, 50,100, or 300 ml/s) and three established multiple maneuver protocols. We quantify the improved precision with multiple maneuvers and the importance of low flow maneuvers in estimating CawNO. We conclude by applying the dynamic model to FeNO data from 100 participants of the Southern California Children's Health Study, establishing the feasibility of using the dynamic method to reanalyze archived online FeNO data and extract new information on CawNO and CANO in situations where these estimates would have been impossible to obtain using traditional steady‐state two compartment model estimation methods.

Background: In May 2017, the Alliance for Academic Internal Medicine (AAIM) published guidelines intending to standardize and improve internal medicine residency program director (PD) letters of recommendation (LORs) for fellowship applicants. Objectives: This study aimed to examine fellowship PDs impressions of the new guidelines, letter writers’ adherence to the guidelines, and the impact of LORs that conformed to guidelines compared to non-standardized letters. Methods: The authors anonymously surveyed fellowship PDs from January to March 2018 to gather input about LORs submitted to their programs during the 2017 fellowship application cycle. Results: A total of 78% of survey respondents were satisfied with letters that followed the AAIM guidelines, whereas 48% of respondents were satisfied with letters that did not. Fellowship PDs felt that letters that followed the AAIM guidelines were more helpful than letters that did not, especially for differentiating between applicants from the same institution and for understanding residents’ performance across the six core competency domains. Fellowship PDs provided several suggestions for residency PDs to make the LORs even more helpful. Conclusion: Fellowship PD respondents indicated that LORs that followed the new AAIM guidelines were more helpful than letters that did not.

Some internal medicine residency program directors have expressed concerns that their third-year residents may have been subjected to inappropriate communication during the 2016 fellowship recruitment season. The authors sought to study applicants’ interpersonal communication experiences with fellowship programs. Many respondents indicated that they had been asked questions that would constitute violations of the National Residency Matching Program (NRMP) Communications Code of Conduct agreement, including how they plan to rank specific programs. Moreover, female respondents were more likely to have been asked questions during interview experiences about other programs to which they applied, and about their family plans. Post-interview communication policies were not made clear to most applicants. These results suggest ongoing challenges for the internal medicine community to improve communication with applicants and uniform compliance with the NRMP communications code of conduct during the fellowship recruitment process.

Nuclear power plant flooding can cause extensive damage. A more robust understanding of nuclear power plant performance in flooding scenarios can help identify weaknesses and opportunities for improvement. However, the performance of various components under flooding conditions is not well characterized. Limited component flooding performance characterizations interfere with comprehensive risk analysis and understanding potential economic impacts. To help address this shortcoming, doorways, common components found in nuclear power plants, were tested to determine their behavior under flooding conditions. Door flooding fragility experiments were performed in the Portal Evaluation Tank, a semi-cylindrical, 7,500-L (2,000-gal) capacity tank. The tank contains a 5.8 ​m2 (62.4 ​ft2) square opening for the installation of testable components. The first sets of experiments were conducted using hollow core doors subjected to a water rise scenario. Tank modifications expanded testing capabilities and further testing was conducted, including industrial steel doors. From six hollow core door experiments, the lowest failure water depth was 0.71 ​m (28 in.) and the highest failure water depth was 0.99 ​m (39 in.). From thirteen outward swinging steel door experiments, the average failure depth was 0.9 ​m (35.4 in.) while the highest failure depth for steel doors occurred at 1.07 ​m (42.1 in.). An inward swinging steel door test resulted in a failure depth of 2.05 ​m (80.5 in.). Data collected is being analyzed using Bayesian regression methods to determine parameters of influence, inform future experiments, and generate door fragility curves, which can be integrated into comprehensive risk analysis.

Objectives: This study, developed within the Innovative Medicines Initiative Joint Undertaking project PRECISESADS framework, aimed at functionally characterize the monocyte subsets in RA patients, and analyze their involvement in the increased CV risk associated with RA.Methods: The frequencies of monocyte subpopulations in the peripheral blood of 140 RA patients and 145 healthy donors (HDs) included in the PRECISESADS study were determined by flow cytometry. A second cohort of 50 RA patients and 30 HDs was included, of which CD14+ and CD16+ monocyte subpopulations were isolated using immuno-magnetic selection. Their transcriptomic profiles (mRNA and microRNA), proinflammatory patterns and activated pathways were evaluated and related to clinical features and CV risk. Mechanistic in vitro analyses were further performed.Results: CD14++CD16+ intermediate monocytes were extended in both cohorts of RA patients. Their increased frequency was associated with the positivity for autoantibodies, disease duration, inflammation, endothelial dysfunction and the presence of atheroma plaques, as well as with the CV risk score. CD14+ and CD16+ monocyte subsets showed distinctive and specific mRNA and microRNA profiles, along with specific intracellular signaling activation, indicating different functionalities. Moreover, that specific molecular profiles were interrelated and associated to atherosclerosis development and increased CV risk in RA patients. In vitro, RA serum promoted differentiation of CD14+CD16− to CD14++CD16+ monocytes. Co-culture with RA-isolated monocyte subsets induced differential activation of endothelial cells.Conclusions: Our overall data suggest that the generation of inflammatory monocytes is associated to the autoimmune/inflammatory response that mediates RA. These monocyte subsets, -which display specific and distinctive molecular signatures- might promote endothelial dysfunction and in turn, the progression of atherosclerosis through a finely regulated process driving CVD development in RA.

The articles collected in this journal are devoted to the topic of teaching speech and theater in community colleges and junior colleges. "Here's Looking at Us," a report of the Association for Communication Administrators' (ACA) 1975 Denver conference on speech communication at the community college and junior college levels, details suggestions concerning curricula, staffing and administration, instruction, research, and professional issues. An afterword provides discussions of the role of the Speech Communication Association (SCA), teacher preparation, future conferences, and other issues not specifically covered in the conference itself. Additional contents include "Speech Communication in the Community-Junior College: A Bibliography"; "Teaching the Community College Student: Methods and Procedures for a Developmental Course in Speech Communication"; "Readers Theatre and Evening School: A Perfect Match"; "The Community College and Career Communications: An Unlimited Opportunity"; and "For Your Information," a profile of Ph.D. degrees conferred during 1973-1974 in the speech communication arts and sciences. (KS)

Bernard L Silverman1, Christopher J Barnes2, Barbara N Campaigne3, Douglas B Muchmore31Alkermes, Inc, Cambridge, MA, USA; 2i3 Statprobe, Ann Arbor, MI; 3Eli Lilly and Company, Indianapolis, IN, USAAbstract: Diabetes mellitus is a significant worldwide health problem, with the incidence of type 2 diabetes increasing at alarming rates. Insulin resistance and dysregulated blood glucose control are established risk factors for microvascular complications and cardiovascular disease. Despite the recognition of diabetes as a major health issue and the availability of a growing number of medications designed to counteract its detrimental effects, real and perceived barriers remain that prevent patients from achieving optimal blood glucose control. The development and utilization of inhaled insulin as a novel insulin delivery system may positively influence patient treatment adherence and optimal glycemic control, potentially leading to a reduction in cardiovascular complications in patients with diabetes.Keywords: diabetes, inhaled insulin, cardiovascular disease, blood glucose

This study examined beliefs and practices of Kentucky's Chapter 1 reading teachers (n=1,279) in light of requirements of the Hawkins-Stafford Amendments requiring instruction in advanced skills in Chapter 1 programs. Most teachers' practices did not match their beliefs; those whose beliefs and practices were consistent with an advanced skills orientation were more professionally involved. (Author/DB)