IMPACT: The Journal of the Center for Interdisciplinary Teaching and Learning. Volume 9, Issue 1, Winter 2020

Explicitly established to foreground interdisciplinary teaching and learning, Impact also welcomes evidence and discussion of experiential learning. Often the two – interdisciplinary teaching and experiential learning – co-exist. Yet even when they do not, both practices model how to think in myriad ways and to notice how knowledge is constructed. As our winter 2019 issue makes clear, interdisciplinary teaching and learning and experiential learning often begin with questions. Why does it matter that students grapple directly with archival material? What happens when undergraduates practice psychology by training dogs? Do students understand financial literacy? This issue also asks questions about students’ reading habits and faculty expectations of them as readers

Osteocyte dysfunction promotes osteoarthritis through MMP13-dependent suppression of subchondral bone homeostasis.

Osteoarthritis (OA), long considered a primary disorder of articular cartilage, is commonly associated with subchondral bone sclerosis. However, the cellular mechanisms responsible for changes to subchondral bone in OA, and the extent to which these changes are drivers of or a secondary reaction to cartilage degeneration, remain unclear. In knee joints from human patients with end-stage OA, we found evidence of profound defects in osteocyte function. Suppression of osteocyte perilacunar/canalicular remodeling (PLR) was most severe in the medial compartment of OA subchondral bone, with lower protease expression, diminished canalicular networks, and disorganized and hypermineralized extracellular matrix. As a step toward evaluating the causality of PLR suppression in OA, we ablated the PLR enzyme MMP13 in osteocytes while leaving chondrocytic MMP13 intact, using Cre recombinase driven by the 9.6-kb DMP1 promoter. Not only did osteocytic MMP13 deficiency suppress PLR in cortical and subchondral bone, but it also compromised cartilage. Even in the absence of injury, osteocytic MMP13 deficiency was sufficient to reduce cartilage proteoglycan content, change chondrocyte production of collagen II, aggrecan, and MMP13, and increase the incidence of cartilage lesions, consistent with early OA. Thus, in humans and mice, defects in PLR coincide with cartilage defects. Osteocyte-derived MMP13 emerges as a critical regulator of cartilage homeostasis, likely via its effects on PLR. Together, these findings implicate osteocytes in bone-cartilage crosstalk in the joint and suggest a causal role for suppressed perilacunar/canalicular remodeling in osteoarthritis

A novel approach to evaluate the effect of medicaments used in endodontic regeneration on root canal surface indentation

Bone Biology Laboratory http://www.iupui.edu/~bonelab/ Department of Anatomy and Cell Biology Indiana University School of Medicine Department of Biomedical Engineering IUPUIObjectives: To investigate the capability of a novel reference point indentation apparatus to test the indentation properties of root canal surface dentine treated with three intracanal medicaments used in endodontic regeneration. Materials and Methods: Immature human premolars were selected (n=22). Four specimens were obtained from each root and randomly assigned to three treatment groups and a control group. Each specimen was exposed to one of three treatment pastes (triple antibiotic (TAP), double antibiotic (DAP), or calcium hydroxide [Ca(OH)2] or neutral de-ionized water (control) for one or four weeks. After each time-interval, the indentation properties of the root canal dentine surfaces were measured using a BioDent reference point indenter. Two-way ANOVA and Fisher’s Protected Least Significant Differences were used for statistical analyses. Results: Significant differences in indentation parameters and estimated hardness between all groups at both time points were found. TAP treated dentine had the highest significant indentation parameters, followed by DAP treated dentine, untreated control dentine and Ca(OH)2 treated dentine, respectively. Furthermore, TAP treated dentine had the lowest significant estimated hardness, followed by DAP treated dentine, untreated control dentine and Ca(OH)2 treated dentine, respectively. Conclusion: BioDent reference point indenter was able to detect significant differences in indentation properties of root canal dentine treated with various medicaments. Clinical Relevance: The use of a reference point indenter is a promising approach to characterize the indentation properties of root canal surfaces without any surface modification. This might provide an in vitro mechanical measurement that is more representative of the actual clinical situation

Prospective Molecular Profiling of Canine Cancers Provides a Clinically Relevant Comparative Model for Evaluating Personalized Medicine (PMed) Trials.

Background Molecularly-guided trials (i.e. PMed) now seek to aid clinical decision-making by matching cancer targets with therapeutic options. Progress has been hampered by the lack of cancer models that account for individual-to-individual heterogeneity within and across cancer types. Naturally occurring cancers in pet animals are heterogeneous and thus provide an opportunity to answer questions about these PMed strategies and optimize translation to human patients. In order to realize this opportunity, it is now necessary to demonstrate the feasibility of conducting molecularly-guided analysis of tumors from dogs with naturally occurring cancer in a clinically relevant setting. Methodology A proof-of-concept study was conducted by the Comparative Oncology Trials Consortium (COTC) to determine if tumor collection, prospective molecular profiling, and PMed report generation within 1 week was feasible in dogs. Thirty-one dogs with cancers of varying histologies were enrolled. Twenty-four of 31 samples (77%) successfully met all predefined QA/QC criteria and were analyzed via Affymetrix gene expression profiling. A subsequent bioinformatics workflow transformed genomic data into a personalized drug report. Average turnaround from biopsy to report generation was 116 hours (4.8 days). Unsupervised clustering of canine tumor expression data clustered by cancer type, but supervised clustering of tumors based on the personalized drug report clustered by drug class rather than cancer type. Conclusions Collection and turnaround of high quality canine tumor samples, centralized pathology, analyte generation, array hybridization, and bioinformatic analyses matching gene expression to therapeutic options is achievable in a practical clinical window (\u3c1 \u3eweek). Clustering data show robust signatures by cancer type but also showed patient-to-patient heterogeneity in drug predictions. This lends further support to the inclusion of a heterogeneous population of dogs with cancer into the preclinical modeling of personalized medicine. Future comparative oncology studies optimizing the delivery of PMed strategies may aid cancer drug development

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Goals, Tasks, and Bonds: Toward the Computational Assessment of Therapist Versus Client Perception of Working Alliance

Early client dropout is one of the most significant challenges facing psychotherapy: recent studies suggest that at least one in five clients will leave treatment prematurely. Clients may terminate therapy for various reasons, but one of the most common causes is the lack of a strong working alliance. The concept of working alliance captures the collaborative relationship between a client and their therapist when working toward the progress and recovery of the client seeking treatment. Unfortunately, clients are often unwilling to directly express dissatisfaction in care until they have already decided to terminate therapy. On the other side, therapists may miss subtle signs of client discontent during treatment before it is too late. In this work, we demonstrate that nonverbal behavior analysis may aid in bridging this gap. The present study focuses primarily on the head gestures of both the client and therapist, contextualized within conversational turn-taking actions between the pair during psychotherapy sessions. We identify multiple behavior patterns suggestive of an individual’s perspective on the working alliance; interestingly, these patterns also differ between the client and the therapist. These patterns inform the development of predictive models for self-reported ratings of working alliance, which demonstrate significant predictive power for both client and therapist ratings. Future applications of such models may stimulate preemptive intervention to strengthen a weak working alliance, whether explicitly attempting to repair the existing alliance or establishing a more suitable client-therapist pairing, to ensure that clients encounter fewer barriers to receiving the treatment they need

Association of air quality during forest fire season with respiratory emergency department visits in Vancouver, British Columbia

Background: Climate change has been deemed the biggest global health threat of the 21st century. One consequence of climate change is the increasing frequency and severity of forest fires. Smoke from wildfires has the ability to negatively impact air quality over large distances. The aim of this study was to examine the association that air quality had on emergency department visits for cardiac, respiratory and psychiatric/behavioral health chief complaints during forest fire season in Vancouver, British Columbia. Methods: The study period was January 1, 2009 – December 31, 2019. Forest fire season was defined as April 1- September 30. Air quality (measured by PM2.5 in ug/m3) was obtained from the Vancouver International Airport (YVR) Air Quality station. Emergency department visit data (CEDIS triage complaint) was acquired from a regional emergency department database. A generalized linear mixed model with Poisson link function was used to determine the relative risk (as a percentage) for respiratory, cardiac and psychiatric/behavioral health CEDIS triage complaints associated with a 10 unit increase in PM2.5. Results: PM2.5 during forest fire season was significantly associated with emergency department visits for respiratory chief complaints. For every 10 ug/m3 increase in PM2.5, there was a 4.61% (95% CI: 3.07, 6.17) increase in relative risk of respiratory chief complaints presenting to emergency departments. No association was found between PM2.5 and cardiac or psychiatric/behavioral health chief complaints during forest fire season or non-forest fire season. During non-forest fire season, PM2.5 was found to be negatively associated with respiratory (-3.57, 95% CI: -5.44, -1.66) and cardiac chief complaints (-2.77, 95% CI: -4.16, -1.47). Conclusion: Our results indicate a probable association between air quality during forest fire season and emergency department visits for respiratory chief complaints. This provides further illustration of the widespread impact of climate change, and underscores the importance of efforts to address it

Point-of-care motion capture and biomechanical assessment improve clinical utility of dynamic balance testing for lower extremity osteoarthritis.

Musculoskeletal conditions impede patient biomechanical function. However, clinicians rely on subjective functional assessments with poor test characteristics for biomechanical outcomes because more advanced assessments are impractical in the ambulatory care setting. Using markerless motion capture (MMC) in clinic to record time-series joint position data, we implemented a spatiotemporal assessment of patient kinematics during lower extremity functional testing to evaluate whether kinematic models could identify disease states beyond conventional clinical scoring. 213 trials of the star excursion balance test (SEBT) were recorded by 36 subjects during routine ambulatory clinic visits using both MMC technology and conventional clinician scoring. Conventional clinical scoring failed to distinguish patients with symptomatic lower extremity osteoarthritis (OA) from healthy controls in each component of the assessment. However, principal component analysis of shape models generated from MMC recordings revealed significant differences in subject posture between the OA and control cohorts for six of the eight components. Additionally, time-series models of subject posture change over time revealed distinct movement patterns and reduced overall postural change in the OA cohort compared to the controls. Finally, a novel metric quantifying postural control was derived from subject specific kinematic models and was shown to distinguish OA (1.69), asymptomatic postoperative (1.27), and control (1.23) cohorts (p = 0.0025) and to correlate with patient-reported OA symptom severity (R = -0.72, p = 0.018). Time series motion data have superior discriminative validity and clinical utility than conventional functional assessments in the case of the SEBT. Novel spatiotemporal assessment approaches can enable routine in-clinic collection of objective patient-specific biomechanical data for clinical decision-making and monitoring recovery