IMPACT: The Journal of the Center for Interdisciplinary Teaching and Learning. Volume 8, Issue 1, Winter 2019

IMPACT: The Journal of the Center for Interdisciplinary Teaching & Learning is a peer-reviewed, biannual online journal that publishes scholarly and creative non-fiction essays about the theory, practice and assessment of interdisciplinary education. Impact is produced by the Center for Interdisciplinary Teaching & Learning at the College of General Studies, Boston University (www.bu.edu/cgs/citl).In this issue of Impact you will find a humanities scholar deeply engaged with the arcing out of a new territory: the interdisciplinary study of the Grateful Dead. Impact’s own Christopher Coffman’s review essay should be required reading for scholars of popular music, performance studies and history. His review also serves as an important reference for those who aspire to teach a course on the Grateful Dead, as well as for those who wish to write review essays. In this issue we also hear from those who are engaged in teaching people who are incarcerated. Importantly, Stephanie Cage’s essay looks to incarcerated people themselves to find out what they think about prison education. Peter Wakefield encourages us to see The Great Gatsby anew, in particular in the context of American racism and White supremacy. Wakefield’s essay is important too because it had its genesis in Writing, the State, and the Rise of Neo-Nationalism: Historical Contexts and Contemporary Concerns, a conference sponsored by the Center for Interdisciplinary Teaching & Learning

Investigating the Potential Causal Relationship Between Parental Knowledge and Youth Risky Behavior: a Propensity Score Analysis

This longitudinal study aims to explore the potential causal relationship between parental knowledge and youth risky behavior among a sample of rural, early adolescents (84% White, 47% male). Using Inverse Propensity Weighting, the sample was adjusted by controlling for 33 potential confounding variables. Confounding variables include other aspects of the parent-child relationship, parental monitoring, demographic variables and earlier levels of problem behavior. The effect of parental knowledge was significant for youth substance and polysubstance use initiation, alcohol and cigarette use, attitudes towards substance use, and delinquency. Our results suggest that parental knowledge may be causally related to substance use during middle school, as the relationship between knowledge and youth outcomes remained after controlling for 33 different confounding variables. The discussion focuses on understanding issues of causality in parenting and intervention implications

Active-duty military service members’ visual representations of PTSD and TBI in masks

Active-dutymilitary service members have a significant risk of sustaining physical and psychological trauma resulting in traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD). Within an interdisciplinary treatment approach at the National Intrepid Center of Excellence, servicemembers participated in mask making during art therapy sessions. This study presents an analysis of the mask-making experiences of service members (n = 370) with persistent symptoms from combatand mission-related TBI, PTSD, and other concurrent mood issues. Data sources included mask images and therapist notes collected over a five-year period. The data were coded and analyzed using grounded theory methods. Findings indicated that mask making offered visual representations of the self related to individual personhood, relationships, community, and society. Imagery themes referenced the injury, relational supports/losses, identity transitions/questions, cultural metaphors, existential reflections, and conflicted sense of self. These visual insights provided an increased understanding of the experiences of service members, facilitating their recovery

Oral Iron Replacement Normalizes Fibroblast Growth Factor 23 in Iron Deficient Patients with Autosomal Dominant Hypophosphatemic Rickets

Autosomal dominant hypophosphatemic rickets (ADHR) is caused by mutations impairing cleavage of fibroblast growth factor 23 (FGF23). FGF23 gene expression increases during iron deficiency. In humans and mice with the ADHR mutation, iron deficiency results in increased intact FGF23 concentrations and hypophosphatemia. We conducted a prospective open label pilot clinical trial of oral iron replacement over 12 months in ADHR patients to test the hypothesis that oral iron administration would normalize FGF23 concentrations. Eligibility criteria included: FGF23 mutation; and either serum iron 30 pg/mL at screening. Key exclusion criteria were kidney disease and pregnancy. Oral iron supplementation started at 65 mg daily and was titrated based on fasting serum iron concentration. The primary outcome was decrease in fasting intact FGF23 by ≥20% from baseline. Six adults (three male, three female) having the FGF23-R176Q mutation were enrolled; five completed the 12-month protocol. At baseline three of five subjects had severely symptomatic hypophosphatemia (phosphorus <2.5 mg/dL) and received calcitriol with or without phosphate concurrent with oral iron during the trial. The primary outcome was met by 4 of 5 (80%) subjects all by month 4, and 5 of 5 had normal intact FGF23 at month 12. Median (minimum, maximum) intact FGF23 concentration decreased from 172 (20, 192) pg/mL at baseline to 47 (17, 78) pg/mL at month 4 and 42 (19, 63) pg/mL at month 12. Median ferritin increased from 18.6 (7.7, 82.5) ng/mL at baseline to 78.0 (49.6, 261.0) ng/mL at month 12. During iron treatment, all three subjects with baseline hypophosphatemia normalized serum phosphorus, had markedly improved symptoms, and were able to discontinue calcitriol and phosphate. Oral iron repletion normalized FGF23 and phosphorus in symptomatic, iron-deficient ADHR subjects. Thus, the standard approach to ADHR should include recognition, treatment, and prevention of iron deficiency

Interferon Gamma-1b Does Not Increase Markers of Bone Resorption in Autosomal Dominant Osteopetrosis

In autosomal dominant osteopetrosis type 2 (ADO2) CLCN7 mutations cause impaired osteoclast function. Severe consequences include skeletal fragility despite high bone mass, osteomyelitis, osteonecrosis, bone marrow failure, and severe cranial nerve impingement. There is no effective medical treatment for ADO2. We recruited subjects with ADO2 into a 14-week, open-label, pilot clinical trial of interferon gamma-1b. Doses were titrated based on tolerability and if fasting serum C-telopeptide (CTX) was <25% above baseline at week 8, targeting doses of 100 mcg/m2 three times a week. The primary outcomes were change from baseline in CTX and N-telopeptide/creatinine ratio (NTX/Cr) at week 14. Secondary outcomes included changes in urine calcium/creatinine ratio, bone formation markers and tolerability. Nine adults and 3 children were recruited. Severe manifestations of ADO2 included histories of fractures (100%), osteomyelitis (16.7%), vision loss (50%), and anemia (58.3%). Baseline CTX and NTX/Cr were generally low-normal. Procollagen type I N-terminal propeptide was elevated or in the upper-normal range in 11/12 (91.6%) subjects. Elevations of AST and LDH were common. One subject withdrew due to rash. Five subjects achieved doses of 50 ug/m2 three days a week, while 6 reached the full dose of 100 ug/m2 three days a week. Only 3/11 (27.3%) completing subjects achieved the primary outcome of increasing CTX ≥25% above baseline at week 14. The mean change from baseline in CTX at week 14 was +2.2% (SD 43.2%, p=0.86). Likewise, there was no significant change in NTX/Cr (mean change −2.1%, p=0.81). Interferon gamma-1b was poorly tolerated. Most subjects had adverse events, and the Mental Health and Mental Component Scales of the SF-36v2 declined slightly (p<0.05). Over 14 weeks, interferon gamma-1b failed to significantly increase bone turnover markers in ADO2 and was poorly tolerated. Consequently, interferon gamma-1b is unlikely to be effective for decreasing bone mass in ADO2

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Teaching In Your PJs: Hybrid Learning in PA Education

This focused discussion introduced the concepts, challenges of hybrid learning. It included a presentation of student’s perceptions on hybrid learning both before and after participating in a hybrid course. The participants the broke into small groups to discuss transitioning common courses into a hybrid format