Academic Seminar Research Articles

Large-Scale Manufacturing of CMV-CD19CAR T Cells and Characterization of Their Biologic and Immunologic Properties

We have successfully established a clinical platform for CD19 chimeric antigen receptor (CAR) T cells and evaluated its safety and efficacy in a series of pilot clinical trials following autologous hematopoietic cell transplantation (HCT) for treatment of high-risk non-Hodgkin lymphoma (NHL) and acute lymphoblastic leukemia (ALL). However, the full potential of this therapy has been limited by the lack of engraftment and persistence of CAR T cells in patients, most likely due to the inadequate antigen drive to stimulate robust expansion and long-term persistence of the infused CAR T cells. Additionally, CD19+ NHL seems less responsive to current CAR T cell technology than does CD19+ ALL that might be explained by lower engraftment and persistence of CAR T cells in NHL. To improve the efficacy and durability of CAR T cells in these disease settings, we sought to examine a novel approach based on properties of cytomegalovirus (CMV)-specific T cells. Specifically, we select CMV pp65-specific T cells for ex vivo modification with a CAR targeting CD19. After in vitro expansion, CMV-CD19 bi-specific T cells will be infused into the patient. A second round of expansion will be done in vivo, using a CMV vaccine (Triplex), developed and clinically evaluated multiple clinical sites including City of Hope. Triplex is a multi-antigen recombinant modified vaccinia Ankara (MVA) virus vaccine expressing pp65, IE1 and IE2, that has proven safe and immunogenic in Phase I trials in healthy volunteers and transplant patients and was highly tolerable and efficacious in a completed Phase II vaccine trial in allogeneic HCT recipients. We hypothesis that shorter ex vivo expansion time will prevent CAR T cell exhaustion that results in better in vivo expansion, especially after Triplex vaccination. Thus far, we have performed six large-scale manufacturing process development (PD) runs of CMV-CD19 CAR T cells using T cells from healthy donors. Briefly, peripheral blood mononuclear cells (PBMCs) were collected and processed in the CliniMACS Prodigy® system, in which PBMCs were first stimulated with a GMP-grade PepTivator® overlapping CMV pp65 peptide pool, then enriched for CMV-responsive IFNɣ+ T cells using the IFNγ Catchmatrix reagent (Miltenyi Biotec Inc.). CMV-responsive IFNɣ+ T cells were next transduced with a lentiviral vector encoding EGFRt/CAR, and finally expanded for approximately 15 days in vitro. As summarized in Table 1, we consistently recovered 4.8%+/-1.4 ×106 CMV specific T cells with 78.3%±2.9 purity from 1×109 PBMC input, which is the maximum input number suggested by the CCS program associated with the Prodigy system (Miltenyi Biotec Inc.). During the early stage PD runs, we noticed that red blood cell contamination in the PBMC layer after ficoll separation could negatively impact the yield of CMV-specific T cells. Thus, we optimized the separation process by performing a second ficoll whenever a red buffy coat was observed, and increased the yield of CMV-specific T cells from 2.8 ×106 to 9.25×106 (Table 1, HD 187.2 PBMCs underwent 2 subsequent ficolls). Phenotypic analysis demonstrated that freshly isolated CMV-specific T cells consisted of four different memory subsets (TEMRA, Tscm, Tcm and effector memory T cells). After in vitro expansion for 15 days, CMV-CAR bi-specific T cell expansion was significantly improved from 60×106 cells in the early stage runs to 200×106 in the late stage optimized runs (Figure 1). The CMV-CD19CAR T cells expressed CD62L, though not exhaustion markers such as PD1. Bispecific T cells exhibited bi-functionality upon stimulation with CD19+ tumor cells or CMVpp65 antigen, as indicated by secretion of IFNγ. Interestingly, we detected stronger effector function against CD19+ tumor cells from CMV-CD19CAR T cells compared to conventional CD19CAR T cells that were derived from the same donor (Figure 2). To validate our manufacturing process, we are currently conducting IND-enabling studies using patient-derived PBMC as the starting population and will initiate our first clinical trial in early 2020 for patients with intermediate/advanced-grade B cell NHL post lymphodepletion or autologous/allogeneic HCT followed by Triplex vaccination 28 days after T cell infusion for in vivo expansion of bi-specific CAR T cells. The primary objectives of these two trials are to examine safety and persistence/expansion of CMV-CD19CAR T cell before and after Triplex vaccine boost. Disclosures Nakamura: Merck: Membership on an entity's Board of Directors or advisory committees; Celgene: Other: support for an academic seminar in a university in Japan; Alexion: Other: support to a lecture at a Japan Society of Transfusion/Cellular Therapy meeting ; Kirin Kyowa: Other: support for an academic seminar in a university in Japan.

Tissue-Resident PSGL1loCD4+ T Cells Interact with B Cells Via PD-1 and PD-L2 in Gvhd Target Tissues to Augment Autoimmune-like Chronic Gvhd

Chronic graft versus host disease (cGVHD) is a systemic autoimmune-like syndrome, and donor-type CD4+ T interaction with B cells plays an important role in its pathogenesis. Our recent publication has demonstrated that cGVHD pathogenesis does not require germinal center formation and is associated with expansion of extrafollicular CD44hiCD62LloPSGL1loCD4+ (PSGL1loCD4+) T cells in the spleen and GVHD target tissues. The causal role of PSGL1loCD4+ T cells in cGVHD pathogenesis remains unclear. With murine and humanized murine models, we show that both murine and human PSGL1loCD4+ T cells reside in tissues and do not circulate in the blood, and their high expression of PD-1 and ICOS and production of IL-21 suggest that they provide B cell help. In murine models, PSGL1loCD4+ T cells augment plasma cell expansion and autoantibody production via their PD-1 interaction with PD-L2 on B. In humanized mouse models, human PSGL1loCD4+ T cells from GVHD target tissues augment memory B cell differentiation into plasma cells and antibody production via their production of IL-21.These results indicate that tissue-resident PSGL1loCD4+ T cells augment autoantibody production and cGVHD pathogenesis. Targeting tissue-resident T cells may represent a novel approach for treating cGVHD. Disclosures Nakamura: Alexion: Other: support to a lecture at a Japan Society of Transfusion/Cellular Therapy meeting ; Kirin Kyowa: Other: support for an academic seminar in a university in Japan; Celgene: Other: support for an academic seminar in a university in Japan; Merck: Membership on an entity's Board of Directors or advisory committees. Martin:Abgenomics: Research Funding; Enlivex Therapeutics: Consultancy; Genentech: Consultancy, Other: One-time advisory board; Neovii: Other: One-time advisory board; Pfizer: Other: Data and Safety Monitoring Committee; Pharmacyclics LLC: Other: One-time advisory board; Procter and Gamble: Equity Ownership; Xenikos: Research Funding.

Equate, a Phase 1b/2 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of a Novel Targeted Anti-CD6 Therapy, Itolizumab, in Subjects with Newly Diagnosed Acute Graft Versus Host Disease

Equate, a Phase 1b/2 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of a Novel Targeted Anti-CD6 Therapy, Itolizumab, in Subjects with Newly Diagnosed Acute Graft Versus Host Disease

Allogeneic Transplantation for Myelodysplastic Syndrome in Adults over 50 Years Old Using Reduced Intensity/Non-Myeloablative Conditioning: Haploidentical Relative Versus Matched Unrelated Donor

Background: Allogeneic hematopoietic cell transplantation (HCT) has been a successful strategy to treat myelodysplastic syndrome (MDS). With only approximately one-third of patients having an HLA matched sibling, most transplants use mismatched relative (haploidentical) or unrelated donors. In the current analysis we sought to study outcomes after haploidentical related compared to HLA-matched unrelated donor HCT for MDS (de novo or therapy-related). Methods: We retrospectively studied 176 recipients of haploidentical related donor and 427 recipients of 8/8 HLA-matched unrelated donor HCT in the United States between 2012 and 2017. The primary outcome was overall survival. The effect of donor type on survival and other transplant outcomes were studied using a Cox regression model. Results: Patient and disease characteristics are presented in Table 1. Most transplants (85%) were for de novo MDS in both donor groups. Although all patients received reduced intensity regimens, the predominant conditioning regimens were confounded by donor type. Total body irradiation (TBI) 200 cGy/cyclophosphamide/fludarabine (TBI/Cy/Flu; 82%) was the predominant regimen for haploidentical HCT and fludarabine with busulfan or melphalan (Flu/Bu or Flu/Mel; 79%) without in vivo T-cell depletion was the predominant regimen for unrelated donor HCT. Similarly, graft-versus-host disease (GVHD) prophylaxis was also confounded by donor type. Posttransplant cyclophosphamide/calcineurin inhibitor/mycophenolate (PT-Cy/CNI/MMF) was the prophylaxis regimen for all haploidentical transplants. CNI/MMF (31%) or CNI/methotrexate (69%) was used for unrelated donor transplants. Peripheral blood was the predominant graft for both donor types. The median follow-up was 24 months (range 3-77) after haploidentical and 36 months (range 3-74) after unrelated donor HCT. Results of multivariate analysis, adjusted for HCT-CI, prior treatment with hypomethylating agents (HMAs), and IPPS-R did not show differences in survival by donor type (HR 0.98, p=0.85; 40% vs. 37%), Figure 1. However, the relapse rate (adjusted for prior HMAs, IPSS-R, and recipient sex) was higher after haploidentical compared to unrelated donor HCT (HR 1.60, p=0.002, 53% vs. 34%), which led to lower disease-free survival after haploidentical HCT (HR 1.30, p=0.03; 21% vs. 32%), Figure 1. To further test the effect of regimen intensity, low dose TBI regimens were compared to Flu/Bu and Flu/Mel; we did not observe a difference in relapse risk (HR 0.95, p=0.76). Non-relapse mortality did not differ by donor type (HR 0.88, p=0.46). Interval between diagnosis and transplant was also not associated with outcomes. Acute grade II-IV acute GVHD (HR 0.46, p<0.001) and chronic GVHD (HR 0.34, p<0.001) was less common after haploidentical HCT. The 1-year graft failure rate was higher after haploidentical compared to unrelated donor HCT (15% and 8%, respectively, p=0.02). Conclusion: Although the current analysis did not show differences in survival between haploidentical related and matched unrelated donor HCT, the higher relapse and consequently lower disease-free survival associated with the haploidentical HCT approach in this analysis (primarily TBI/Cy/Flu with PT-Cy/CNI/MMF) warrants caution. A more definitive comparison of the two donor types can be accomplished only if more haploidentical transplants were to use Flu/Bu or Flu/Mel conditioning. Figure 1 Disclosures Grunwald: Celgene: Consultancy; Pfizer: Consultancy; Agios: Consultancy; Merck: Consultancy; Abbvie: Consultancy; Medtronic: Equity Ownership; Incyte: Consultancy, Research Funding; Daiichi Sankyo: Consultancy; Amgen: Consultancy; Trovagene: Consultancy; Cardinal Health: Consultancy; Janssen: Research Funding; Genentech/Roche: Research Funding; Novartis: Research Funding; Forma Therapeutics: Research Funding. Bolanos-Meade:Incyte Corporation: Other: DSMB fees. Bredeson:Otsuka: Research Funding. Gupta:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sierra Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Research Funding. Mussetti:Takeda: Honoraria; BMS: Honoraria; Novartis: Honoraria; Italfarmaco: Honoraria. Nakamura:Merck: Membership on an entity's Board of Directors or advisory committees; Celgene: Other: support for an academic seminar in a university in Japan; Alexion: Other: support to a lecture at a Japan Society of Transfusion/Cellular Therapy meeting ; Kirin Kyowa: Other: support for an academic seminar in a university in Japan. Nishihori:Novartis: Research Funding; Karyopharm: Research Funding. Solh:Celgene: Speakers Bureau; Amgen: Speakers Bureau; ADC Therapeutics: Research Funding. Weisdorf:Fate Therapeutics: Consultancy; Pharmacyclics: Consultancy; Incyte: Research Funding.

Optimization of Tacrolimus Serum Levels When Combined with Post-Transplant Cyclophosphamide As Graft-Versus-Host Disease Prophylaxis after Hematopoietic Cell Transplantation: Outcome Data Analysis

Post-transplant cyclophosphamide (PTCy) in combination with tacrolimus and mycophenolate mofetil (MMF) has been used increasingly in recent years to prevent graft-versus-host disease (GvHD) in patients undergoing hematopoietic cell transplantation (HCT), and has been proven safe and effective regardless of HLA matching criteria. Historically, the therapeutic dose level recommended for tacrolimus has ranged from 10 to 15 ng/mL, when combined with methotrexate, and between 5-10 ng/mL when combined with sirolimus. However, data on the optimal starting dose and serum level of tacrolimus when combined with PTCy does not exist. Given tacrolimus's broad inhibition on T-cells activation and the PTCy's selective inhibition on alloreactive T-cells, we hypothesized that lower serum levels of tacrolimus could suffice to achieve optimal transplant outcomes. We retrospectively identified a consecutive case series of 219 patients who received HCT with PTCy (50 mg/kg on days +3 and +4) in combination with tacrolimus and MMF (day +5) as GvHD prophylaxis at City of Hope from January 2011 to June 2018. Tacrolimus was delivered with continuous intravenous infusion until engraftment, then switched to equivalent oral dose. Tacrolimus dosing was weight-based (WBD) in 80 patients and fixed dose (FD) of 1 mg in 139 patients. We captured Tacrolimus levels at two different time points: 1. the initial steady state (ISS) and 2. at engraftment level (EL) to identify which time point will correlate with better HCT outcomes. At each time point, transplant outcomes were compared between patients with serum levels ≥10 ng/mL and <10 ng/mL. We analyzed and compared the overall survival (OS), progression-free survival (PFS), relapse rate, non-relapse mortality (NRM), cumulative incidence of Grade 2-4 acute GVHD and chronic GVHD between the two groups by univariate and multivariate analysis. P values were 2 sided at a significance level of 0.05. Correlation between method of administration and serum level of tacrolimus was examined by chi-square test. Patients received HCT either from a haploidentical (n=175), matched (n=6), or mismatched donor (n= 38). Tacrolimus levels at the ISS (median: day +9 of HCT, range 8-16) was <10 ng/mL in 181 patients with median age of 52 years (interquartile range: 30-62) and ≥ 10 ng/mL in 38 patients with median age of 39 years (interquartile range: 18-55), (P = 0.004). Regardless of the conditioning regimen, tacrolimus level at ISS was <10 ng/ml in majority of patients (81% in myeloablative conditioning and 84 in reduced intensity conditioning). Majority of patients (91%) who received peripheral blood stem cells as graft source were more likely to have tacrolimus levels <10 ng/ml, whereas 56% of patients who received bone marrow as graft source had tacrolimus levels <10 ng/ml. Lastly, majority of patients (89%) who received tacrolimus at the FD had a serum level of <10 ng/mL at ISS as compared to 73% of patients who received the drug at WBD of the drug (P=0.003) At ISS, 18 months OS, PFS, relapse rate were 64%, 58% and 19%, respectively, in patients with tacrolimus level <10 ng/mL, which compared favorably to 48%, 45%, and 35%, respectively, in patients with Tacrolimus level ≥10 ng/mL (Figure 1). In multivariable analysis, patients with tacrolimus level <10 ng/mL had lower relapse rate (HR= 0.53; 95% CI: 0.26-1.05 p=0.067) and better PFS (HR=0.50; 95% CI: 0.31-0.82, P= 0.006). While no difference was seen in OS (p= 0.76), cumulative incidence of NRM (P=0.59), acute GVHD grade II-IV (P=0.23), grade III-IV (P=0.46) or chronic GVHD (p=0.38) between the two groups at the ISS. In the multivariable analysis and after adjusting for all baseline and clinically relevant variables, EL did not correlate with any outcome In conclusion, tacrolimus dosing at a FD was more likely resulting in ISS of 4-10 ng/mL (86% of patients in <10 ng/mL group). ISS tacrolimus levels of less than 10 ng/mL was correlated with lower relapse rate and better PFS, without a significant increase in GVHD or NRM. Figure 1 Disclosures Salhotra: Celgene: Other: Research Support; Kadmon Corporation: Other: Non paid consultant. Aldoss:Helocyte: Consultancy, Honoraria, Other: travel/accommodation/expenses; Jazz Pharmaceuticals: Honoraria, Other: travel/accommodation/expenses, Speakers Bureau; Agios: Consultancy, Honoraria; AUTO1: Consultancy. Stein:Amgen: Consultancy, Speakers Bureau; Celgene: Speakers Bureau; Stemline: Speakers Bureau. Nakamura:Alexion: Other: support to a lecture at a Japan Society of Transfusion/Cellular Therapy meeting ; Merck: Membership on an entity's Board of Directors or advisory committees; Celgene: Other: support for an academic seminar in a university in Japan; Kirin Kyowa: Other: support for an academic seminar in a university in Japan.

Incidence and Risk Factors of De Novo Skin Cancer in a Contemporary Cohort of Hematopoietic Cell Transplantation Survivors

Introduction: Hematopoietic cell transplantation (HCT)-related factors, such as total body irradiation (TBI) used for conditioning, graft-versus-host disease (GvHD), and prolonged exposure to calcineurin-inhibitors, can result in high risk for subsequent skin cancers in long-term survivors. Previous studies examining skin cancers after HCT have largely focused on patients transplanted in earlier eras (<2000), which may not be as informative for providers caring for survivors treated with contemporary conditioning (e.g. less myeloablative) approaches or GvHD treatment regimens, and do not account for newer stem cell sources (e.g. cord, haploidentical) with their evolving immunosuppression risk. Additionally, due to registry reporting, past studies have largely focused on melanoma, which underestimates the burden due to more common skin cancers such as squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). The current study describes the incidence and risk factors of melanoma and non-melanoma skin cancer in a large contemporary cohort of HCT survivors. Methods: 2338 consecutive patients who underwent a first HCT between 2005 and 2014 at City of Hope (COH) and survived ≥1 year, were included in the study. Patients with a history of skin cancer prior to HCT were excluded from the cohort. All skin cancers were validated using pathology reports, and physician notes (20%) whenever the former was not available. Skin cancers included SCC, BCC, melanoma, atypical fibroxanthoma, and merkel cell carcinoma. Patients were followed from HCT to death, second HCT, last known alive date, or December 31, 2018, whichever occurred first. Cumulative incidence of skin cancer was estimated taking into consideration competing risk of death. Fine-Gray sub-distributional hazard regression was used to calculate hazard ratio (HR) estimates, adjusted for relevant covariates. Results: Median age at HCT was 51.8y (range: 0.7-78.7); 57.6% were male; 56.5% were non-Hispanic white (NHW); 4.4% had a history of Pre-HCT cancer (antecedent to primary diagnosis); 47.7% underwent allogeneic HCT; 22.0% received myeloablative TBI (≥1200 cGy)-based conditioning. Among survivors of allogeneic HCT, 57.2% developed ≥moderate chronic GvHD (84% involving the skin); the most common immunosuppressive agents used for the management of ≥moderate chronic GvHD were tacrolimus (84.6%), followed by sirolimus (76.5%), and cyclosporine (28.4%). Burden of skin cancer over time: 179 survivors developed a total of 450 skin cancers after HCT; median time from HCT to first skin cancer was 2.8 years (range: 0.2-13.6). SCC was the most common subtype (59.1%), followed by BCC (31.3%), melanoma (5.1%), and other (4.4%); 43.4% of patients with SCC had invasive or high grade disease at presentation. The cumulative incidence of de novo skin cancer after HCT was 8.3% at 5 years, and 14.8% at 10 years (figure). Eighty-nine patients with skin cancer had a second skin cancer at a median of 0.5 years (range: 0.2 to 7.2) from the first; 55.1% were of a different histology. The cumulative incidence of a second skin cancer was 41.9% at 5-years (figure). Risk factors: Multivariate analysis revealed male sex (HR=1.7, p=0.0008), NHW race/ethnicity (HR=9.0, p<0.0001), older age HCT (≥50years at HCT, HR=2.4, p<0.0001), allogeneic HCT (HR=2.2, p<0.0001), and a history non-skin cancer prior to HCT (HR=1.7, p=0.04) to be significant and independent predictors of post-HCT skin cancer risk. Among allogeneic HCT patients, neither severity of chronic GvHD, location (e.g. skin), nor duration of post-HCT immunosuppression were associated with risk of de novo skin cancer, irrespective of skin cancer histology. Conclusions: This study confirms the higher risk of skin cancer by sex, race/ethnicity, and age at HCT, and highlights the greater than two-fold risk of skin cancer among allogeneic HCT survivors compared to autologous patients, a finding that is not entirely explained by GvHD and its treatment. Further, we identified a previously unreported association between pre-HCT (non-skin) cancer and post-HCT cancer risk, and describe the very high burden of multiple histologically distinct skin cancers over time. Taken together, these data set form the basis for implementation of updated risk-based screening and prevention practices in survivors at highest risk of skin cancer after HCT. Disclosures Abdulla: Johnson & Johnson: Research Funding; Elorac: Research Funding; Trillium: Research Funding; Stemline: Research Funding; MiRagen: Research Funding; Bionz: Research Funding; Mallinckrodt: Research Funding; Mallinckrodt: Consultancy; Mallinckrodt: Speakers Bureau. Nakamura:Merck: Membership on an entity's Board of Directors or advisory committees; Celgene: Other: support for an academic seminar in a university in Japan; Alexion: Other: support to a lecture at a Japan Society of Transfusion/Cellular Therapy meeting ; Kirin Kyowa: Other: support for an academic seminar in a university in Japan.

Pre-service Teachers' Beliefs About Inclusive Education Before and After Multi-Compared to Mono-professional Co-teaching: An Exploratory Study

Teacher beliefs are action guiding in the classrooms. Teacher beliefs about inclusive education are thus a crucial pre-requisite for its success. Therefore, those beliefs have to be addressed during the first phase of teacher training. Generally accepted concepts or operationalized definitions would be valuable guidelines for pre-service teachers and their educators. However, neither the ones nor the others are available at present. Therefore, pre-service teachers have to fall back on their own beliefs, a rather unexplored notion so far. Within the present study, pre-service teachers’ beliefs about inclusive education were assessed before and after an academic seminar. During this academic seminar, participants co-taught in either multi-professional (i.e. one pre-service teacher for special educational needs and one for general education) or mono-professional (i.e. both pre-service teachers for special educational needs or both for general education) teams in inclusive classes of secondary schools. Pre-service teachers’ beliefs were assessed with the help of concept-maps, which were created by the participants at two testing times. The concept-maps were analyzed employing graph-theoretical approaches as well as qualitative, summarizing content analysis methods. Results show that pre-service teachers who worked in multi-professional teams expanded their conceptualization of inclusive education to include facets like individualization and differentiation, while pre-service teachers who worked in mono-professional teams displayed no such expansion. Also, the conceptualization of pre-service teachers who worked in mono-professional teams contained a larger percentage of propositions addressing disadvantages and negative consequences of inclusive education. Therefore, it is concluded that multi-professional co-teaching during teacher training helps prepare teachers for successful inclusive education.

Language immersion in the multi-system education in Andorra

<p>Celem artykułu jest ukazanie wielosystemowości szkolnictwa w Andorze oraz związanej z nim immersji językowej. Poczynione obserwacje podczas uczestnictwa w seminarium naukowym w Andorze oraz pozyskanie odpowiedniej literatury umożliwiło zgłębienie oryginalności tamtejszego systemu oświaty, polegającego na wolności wyboru jednego z trzech systemów szkolnictwa: szkoły andorskiej, francuskiej lub hiszpańskiej, a co za tym idzie immersji językowej. Decydując się na wybór szkoły, rodzice i uczniowie kierują się takimi kryteriami jak, odległość szkoły od miejsca zamieszkania, język wykładowy, możliwość kontynuowania nauki za granicą. Różnorodność systemów edukacji wynika z historii księstwa Andory. Pierwsze szkoły założyli Francuzi i Hiszpanie, aby rywalizować o wpływy na danym terenie. Nowatorska szkoła andorska powstała dopiero w 1983 roku, od tego czasu rozwija się najprężniej i ma największą liczbę uczniów. Autorka zadaje pytanie o związek między systemem szkolnictwa i tożsamość narodową Andorczyków oraz możliwość współpracy tych systemów.</p>

Vivre le pèlerinage (médieval). Une expérience corporelle

The project Migrating Art Historians, conducted during the spring semester 2017, consisted of an experimental academic seminar that took the form of a pilgrimage, on foot, from Lausanne in Switzerland to Mont-Saint-Michel in France. The aim was to understand, to the extent possible, how the experience of a twenty-first-century viewer can transform her or his perception of medieval objects and, indispensably, of faith during the Middle Ages. The project also prompted reflection on the transformation of the pilgrim's gaze through bodily rhythm. Long, often arduous, cross-country walks, on one hand, activate the imagination of pilgrims' expectations; on the other hand, the physical effort enables the creation of space in which the memory of sacred places and objects recently experienced plays an essential role. And of course, several days of walking leads eventually to fatigue, with the result that the perception of images and figures depicted is also affected by the natural bodily production of endorphins. For a today's viewers, this can mean a heightened aesthetic sensibility; for medieval pilgrims, it may have offered a way to stimulate the devotional relationship with images.

Women's visibility in academic seminars: Women ask fewer questions than men.

The attrition of women in academic careers is a major concern, particularly in Science, Technology, Engineering, and Mathematics subjects. One factor that can contribute to the attrition is the lack of visible role models for women in academia. At early career stages, the behaviour of the local community may play a formative role in identifying ingroup role models, shaping women’s impressions of whether or not they can be successful in academia. One common and formative setting to observe role models is the local departmental academic seminar, talk, or presentation. We thus quantified women’s visibility through the question-asking behaviour of academics at seminars using observations and an online survey. From the survey responses of over 600 academics in 20 countries, we found that women reported asking fewer questions after seminars compared to men. This impression was supported by observational data from almost 250 seminars in 10 countries: women audience members asked absolutely and proportionally fewer questions than male audience members. When asked why they did not ask questions when they wanted to, women, more than men, endorsed internal factors (e.g., not working up the nerve). However, our observations suggest that structural factors might also play a role; when a man was the first to ask a question, or there were fewer questions, women asked proportionally fewer questions. Attempts to counteract the latter effect by manipulating the time for questions (in an effort to provoke more questions) in two departments were unsuccessful. We propose alternative recommendations for creating an environment that makes everyone feel more comfortable to ask questions, thus promoting equal visibility for women and members of other less visible groups.

Motivation? The Effects of High-Impact Experiential Learning Activities on Political Science Students

This research examines whether high-impact experiential learning activities in politics motivate students positively in learning, personal development and establishing career goals? Using participant observations and student journals recorded during their participation in the Osgood Center for International Studies 2017 Presidential Inauguration Seminar and the Washington Center for Internships and Academic Seminar’s 2016 Democratic and Republican Convention seminars, this research identifies specific outcomes related to the impact of such experiential learning opportunities on students of political science.

Effect of Seminar on Compassion on student self-compassion, mindfulness and well-being: A randomized controlled trial

ABSTRACTObjective: Mindfulness-based interventions have been shown to have psychological benefits in college students. We explored the effects of an academic Seminar on Compassion on student psychological health. Participants: Forty-one participants (14 male, 27 female, mean age 19.8 ± 1.4 years) were assessed pre- and post- spring semesters 2013 and 2014. Methods: Students were randomized to the Seminar on Compassion or a wait-list control group. Participants completed self-report measures on anxiety, depression, perceived stress, self-compassion, compassion and mindfulness. Salivary alpha-amylase was also assessed. Results: At baseline, self-compassion and mindfulness were negatively correlated with depression, anxiety, and perceived stress. There were significant changes between the intervention and control group from Time 1 to Time 2 in mindfulness, self-compassion, compassion, and salivary alpha-amylase; however, there were no significant changes in depression, anxiety, and perceived stress. Conclusions: The course was effective in increasing mindfulness, self-compassion and compassion, and decreasing a salivary marker of stress.

How to Reckon with Past Evils? Rethinking Transitional Justice Strategies in Post-Authoritarian and Post-Conflict Environments

The Łódź PPSY International Seminar Transitional Justice: Between Redemption and Retribution was the first scientific event co-organized by the Chair of International Law and International Relations (Faculty of Law and Administration, University of Łódź), Research Centre of University of Łódź "The Balkans at the Turn of the 20th and the 21st Century", Professor Czesław Mojsiewicz International Cooperation Fund, Adam Marszałek Publishing House and the Editorial Board of the Polish Political Science Yearbook. The idea that stood behind the organization of the academic seminar was to analyse the current scientific and practical trends witnessed in a global discourse on transitional justice. Deliberations on post-violence efforts and all closely related topics, especially the issue of politics of memory, gathered in the Polish city of Łódź 20 researchers, coming from 7 Polish universities and 8 foreign academic centres. It is worth mentioning that participants of the seminar represented 9 different countries, such as Germany, the Netherlands, Poland, Romania, Slovakia, South Sudan, Ukraine, the United Kingdom and the United States.

Playful Furniture

Are shaggy seats which make cute noises playful or disruptive in a conference setting? This article pushes the limits of game scholars’ lusory attitude by breaching an academic seminar with a playful experiment. Five MurMur Moderator seats, interactive and interruptive furniture prototypes, were set up at a game research seminar where they were used as ambient elements during the presentations. The experience was evaluated by observation, accompanied with seminar tweets, and by conducting a small survey after the seminar. The experiences of the participants varied from enthusiastically positive to strong negative feelings. Through this experiment, we were able to explore the important issue of polarized attitudes of adults toward play and provide some food for thought for the future design of adult play.

The Academic Seminar of “Ecological Aesthetics: Literature Foundation and Theoretical Development” and the Review of the Conference on Thesis Proposal of “Literature Review and Research on Ecological Aesthetics”

The Academic Seminar of “Ecological Aesthetics: Literature Foundation and Theoretical Development” and the Review of the Conference on Thesis Proposal of “Literature Review and Research on Ecological Aesthetics”

WhatsApp Messaging: Achievements and Success in Academia

In recent years, there has been a significant rise in the use of technological means in general and in academic teaching in particular. Many programs have been developed that include computer-assisted teaching, as well as online courses at educational institutions. The current study focuses on WhatsApp messaging and its use in academia. Studies have found that class WhatsApp groups serve for communicating with students, nurturing a social atmosphere in the classroom, forming dialogue and collaborations between students, and as a means of learning. The current study explored students' level of achievements and satisfaction as part of a WhatsApp group in a case study of a seminar course, with the aim of investigating whether use of a WhatsApp group as part of guiding an academic seminar will improve achievements in writing the seminar paper. The findings show a significant positive relationship between the achievements of WhatsApp users and their satisfaction, such that the higher the achievements of WhatsApp users the higher their satisfaction. This tool was found to have a strong effect on students' achievements. The current findings illuminate the possibilities offered by technological tools for teaching practice.

Evaluation Capacity Building

Purpose: Growing emphasis on program and practice evaluation in social work education coalesces with a growing interest in evaluation capacity building (ECB) within the interdisciplinary field of evaluation. However, the literature on ECB, while recognizing the importance of imparting knowledge and skills to individuals, largely ignores the potential contribution of courses that are offered as part of academic degree-granting programs. Methods: This article describes a seminar on program evaluation within a postgraduate course leading to a master of social work degree attended by currently employed social workers. The students were required to plan the evaluation of a program conducted by their respective agencies and carry out the evaluation, if possible. A survey was conducted among the graduates. Results: Almost all respondents reported that the seminar had improved their own evaluation capacity, and about a third reported enhanced evaluation capacity of their respective agencies. The ECB effect was strongest when stakeholders were involved in the evaluation. Discussion: An academic seminar can contribute to ECB, this contribution could be enhanced by designing the seminar with this purpose in mind.

AIRING ETHNIC AND LINGUISTIC IDENTITIES THROUGH PUBLIC MEDIA COMIC PERFORMANCES: CHALLENGING AND REINSCRIBING NORMATIVE IDEOLOGIES

This essay discusses double voicings in heteroglossic public media comic performances of ethnic and linguistic identities. The objective is to show an example of how airing ethnic-linguistic identities through media comic performances brings to the open previously silenced, sensitive issues for necessary public debate, also providing a rich field for research on contemporary sociolinguistic questions. The example explored here is a comparative illustration, presented at an academic seminar, between the data analyzed by Jaffe (2000), featuring comic bilingual performances in Corsica, and comic radio and television performances featuring a German-Brazilian character. First, the multi-site, multimedia academic seminar course is introduced. Next, four illustrative videos, shown during the seminar presentation as a counterpoint to Jaffe’s data, are described, two of which spotlight D. Heda, a fictional German-Brazilian comic character. Further material is examined here – an interview with the radio journalist who created and performs D. Heda, in which he presents his radio program as validating German-Brazilian identities. This is briefly contrasted with comments by a course participant arguing such humor is disparaging of German-Brazilians. Finally, in light of recent studies of similar heteroglossic public media comic performances, the tensions these performances may create between challenging and reinscribing normative ideologies are discussed. This work is licensed under a Creative Commons Attribution 3.0 License.

Letter to the Editor Reply to commentary by G. Sikri and S. Dua on the article "Correlation between single nucleotide polymorphisms in hypoxia-related genes and susceptibility to acute high-altitude pulmonary edema" published in Genetics and Molecular Research 14 (3): 11562-11572 to the letter published in Genet. Mol. Res. 14 (4): 15904-15905.

The object in this study was a Han Chinese population in Lhasa, with 3658 m in altitude from Chengdu, which has 505 m in altitude by air. Within 24 to 48 h before the subjects arrived in the plateau, they completed a basic situation questionnaire, under the guidance of medical staff. Within 24 to 48 h after they reached the plateau, the subjects completed an acute plateau disease questionnaire. The diagnostic standard of HAPE and the diagnosis of acute plateau disease were adopted by the Lake Louise diagnostic standards in 1991 and the Chinese Medical Association promulgated the domestic diagnostic criteria on the Third National Plateau Medical Academic Seminar. Other diseases that cause acute symptoms of altitude sickness, such as plateau pulmonary edema, plateau cerebral edema, acute respiratory infections and neurosis, were excluded. According to the Lake Louise standard, questionnaire and symptom score values >3 points were diagnosed as HAPE. According to the national standard, the questionnaire and symptom score values >5 points were diagnosed as HAPE. At the present, morbidity of HAPE remains relatively high in China. The research shows that usually in the case of not taking preventive measures, according to the factors such as altitude, speed, and time of arrival, the incidence of HAPE is 30% to 90%. Epidemiological survey shows that HAPE happens at an altitude of 2500 m above the plateau. And an altitude of 3000 m above the plateau of China is occupied 1/6 of the total land area, the population of permanent residents is more than sixty million. We detected the 200 cases who adapted to plateau and the 106 cases of patients with HAPE susceptibility genes SNP locus, and got the key SNP loci of HAPE susceptibility genes. We maked the corresponding gene chip diagnostic kits.

Knowledge and Community: The Effect of a First-Year Seminar on Student Persistence

Abstract This study explores the effects of an academic seminar on the persistence of first-year college students, including effects on students most at risk of dropping out. A secondary interest was demonstrating the utility of using classification and regression tree analysis to identify relevant predictors of student persistence. The results of the study showed that persistence rates improved for all students who took the seminar and, most importantly, that the persistence rate for higher-risk students showed double the improvement of that of lower-risk students. Results also suggest that changes in student perception of the value of a college education and engagement in classroom discussion are factors for improving the persistence of higher-risk students.