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BPTF depleted 4T1 tumors are flat compared to controls and BPTF does not affect MDSC amplification or metastasis to the lung.

Microarray data analysis of significant genes in 4T1 tumors harvested from NSG mice. List of primer sequences used in this study.

Genetic studies in fruit flies have implicated the chromatin remodeling complex nucleosome remodeling factor (NURF) in immunity, but it has yet to be studied in mammals. Here we show that its targeting in mice enhances antitumor immunity in two syngeneic models of cancer. NURF was disabled by silencing of bromodomain PHD-finger containing transcription factor (BPTF), the largest and essential subunit of NURF. We found that both CD8+ and CD4+ T cells were necessary for enhanced antitumor activity, with elevated numbers of activated CD8+ T cells observed in BPTF-deficient tumors. Enhanced cytolytic activity was observed for CD8+ T cells cocultured with BPTF-silenced cells. Similar effects were not produced with T-cell receptor transgenic CD8+ T cells, implicating the involvement of novel antigens. Accordingly, enhanced activity was observed for individual CD8+ T-cell clones from mice bearing BPTF-silenced tumors. Mechanistic investigations revealed that NURF directly regulated the expression of genes encoding immunoproteasome subunits Psmb8 and Psmb9 and the antigen transporter genes Tap1 and Tap2. The PSMB8 inhibitor ONX-0914 reversed the effects of BPTF ablation, consistent with a critical role for the immunoproteasome in improving tumor immunogenicity. Thus, NURF normally suppresses tumor antigenicity and its depletion improves antigen processing, CD8 T-cell cytotoxicity, and antitumor immunity, identifying NURF as a candidate therapeutic target to enhance antitumor immunity. Cancer Res; 76(21); 6183–92. ©2016 AACR.

Supplemental figure legends for Mayes et al.

Gene Ontology of microarray data by DAVID analysis.

Objective: Chemotherapy-induced nausea and vomiting (CINV) are common with doxorubicin-cyclophosphamide (AC) chemotherapy. Recommended antiemetic regimens incorporate neurokinin-1 receptor antagonist (NK1RA), 5-hydroxytryptamine type-3 receptor antagonist (5HT3RA), corticosteroid, and dopamine antagonists. This post-hoc analysis compared results of 3 prospective antiemetic studies conducted among Chinese breast cancer patients who received (neo)adjuvant AC, in order to identify optimal antiemetic prophylaxis. Methods: A total of 304 patients were included: Group 1, ondansetron/dexamethasone (D1); Group 2, aprepitant/ondansetron/dexamethasone (D1); Group 3, aprepitant/ondansetron/dexamethasone (D1–3); Group 4, aprepitant/ondansetron/dexamethasone (D1–3)/olanzapine; and Group 5, netupitant/palonosetron/dexamethasone (D1–3). Antiemetic efficacies of Groups 3, 4, and 5 during cycle 1 of AC were individually compared with Group 1. In addition, emesis outcomes of patients in Groups 3 and 5, and those of Groups 2 and 3, were compared. Results: When comparing efficacies of a historical doublet (5HT3RA/dexamethasone) with triplet antiemetic regimens (NK1RA/5HT3RA/dexamethasone) with/without olanzapine, complete response (CR) percentages and quality of life (QOL) in overall phase of cycle 1 AC were compared between Group 1 and the other groups: Group 1 vs. 3, 41.9% vs. 38.3% (P = 0.6849); Group 1 vs. 4, 41.9% vs. 65.0% (P = 0.0107); and Group 1 vs. 5, 41.9% vs. 60.0% (P = 0.0460). Groups 4 and 5 achieved a better QOL. When comparing netupitant-based (Group 3) with aprepitant-based (Group 5) triplet antiemetics, CR percentages were 38.3% vs. 60.0%, respectively (P = 0.0176); Group 5 achieved a better QOL. When comparing 1 day (Group 2) vs. 3 day (Group 3) dexamethasone, CR percentages were 46.8% and 38.3%, respectively (P = 0.3459); Group 3 had a worse QOL. Conclusions: Aprepitant-containing triplets were non-superior to doublet antiemetics. Netupitant-containing triplets and adding olanzapine to aprepitant-containing triplets were superior to doublets. Netupitant/palonosetron/dexamethasone was superior to aprepitant/ondansetron/dexamethasone. Protracted administration of dexamethasone provided limited additional benefit.

As the Knowledge Translation (KT) field advances, there is an increasing need to identify priorities to help shape future directions for research. An important source of KT priorities is ‘experts’ who are well-established researchers and practitioners. Another potential source for identifying priorities is trainees. Given that many KT trainees are developing their programs of research, understanding their main concerns and priorities for KT research and practice is critical to supporting the development and advancement of KT as a field. The purpose of this study was to identify priorities for research and practice in the KT field from the perspectives of KT researcher and practitioner trainees.

Medical education is constantly evolving, especially as students were forced to study from home during the coronavirus disease 2019 (COVID-19) pandemic, and new technologies have driven the rapid development of supplemental online educational resources. In this study, we examine if 360° videos can promote increased engagement over standard two-dimensional (2D) videos among medical students learning anatomy. We enrolled 39 fourth-year medical students to watch two four-minute videos of anatomy lab exercises in a 360° three-dimensional format using an immersive headset or in a 2D format on a laptop computer. Every two minutes, students were asked to rate their engagement from 0-100. Following the videos, they reported their degree of agreement with 14 statements related to engagement, practicality, and interest in the technology. While watching the videos, the average engagement reported by the 360° video group was higher at each time point than the engagement reported by the two-dimensional group. Further, the engagement remained high in the 360° group through the six- and eight-minute timepoints. In the post-video survey, the 360° group reported a statistically significantly higher average engagement in seven of eight measures on the assessment. A 360° video was rated as more practical and interesting than a two-dimensional video. No significant difference existed in the perceived ease of learning. Overall, the use of 360° video may improve engagement for short videos used in medical education. However, developing a better understanding of its impact on learning outcomes will be critical for determining the overall value and effectiveness of this tool.

Background There is limited work on the impact of chemotherapy‐induced nausea and vomiting (CINV) on quality of life (QoL) in adriamycin‐cyclophosphamide (AC)–treated patients with breast cancer. The objectives of the study were the following: (a) to confirm if symptoms of CINV led to lower QoL during AC; (b) to evaluate the pattern of changes in patients’ QoL during multiple cycles of AC; and (c) to assess if the QoL in an earlier cycle affected the QoL in subsequent cycles of AC. Materials and Methods This is a secondary pooled data analysis that included 303 Chinese patients with breast cancer who received 1,177 cycles of adjuvant AC in three prospective antiemetic studies. QoL data were based on Functional Living Index–emesis (FLIE) scored over three to four AC cycles. CINV symptoms assessed included “no significant nausea” (NSN), “significant nausea” (SN), “no vomiting” (NoV), “vomiting” (V), and complete response (CR). Results Across all AC cycles, the mean scores for the FLIE nausea domain for patients who experienced NSN versus SN were 10.92 versus 53.92, respectively (p, This article focuses on chemotherapy‐induced nausea and vomiting and quality of life of breast cancer patients through multiple cycles of treatment.

© 2017 Deborah D. Blecic, Stephen E. Wiberley Jr., Sandra L. De Groote, John Cullars, Mary Shultz, and Vivian Chan. This study investigated contributions to the peer-reviewed library and information science (LIS) journal literature by U.S. academic librarian (USAL) authors over a ten-year period (2003-2012). The results were compared to those of two previous five-year studies that covered the time periods of 1993-1997 and 1998-2002 to examine longitudinal trends. For USAL authors as a group, publication productivity, the proportion of peer-reviewed articles contributed to the LIS literature, and sole-authorship declined. Among USALs who did publish, productivity patterns remained similar over twenty years, with a slight increase in the percentage of USAL authors who published three or more articles in five years. The top twenty high-publication libraries from 2003 to 2012 were from public research universities, unlike two earlier studies that found private university libraries among the top twenty.

Introduction: Large Granular Lymphocyte (LGL) leukemia is a rare lymphoproliferative disorder usually manifested in elderly individuals, with mean age of onset at 65. However, LGL leukemia cases in pediatric and young adult (age 50) cohort. Methods: We retrospectively collected clinical data from 23 young adult (age 50) LGL leukemia patients. All participants signed informed consent to provide biospecimens and clinical records to the LGL Leukemia Registry. Whole exome (PBMC and saliva) and RNA sequencing (PBMC) was conducted on 115 patients. Sanger sequencing was utilized to determine STAT3 mutational status in the remaining 102 patients. Results: STAT3 is the most frequently mutated gene in LGL leukemia, and the mutation is associated with lower absolute neutrophil counts (ANC). We observed no differences in the frequency of STAT3 somatic mutations in young adult, adult, and older adult LGL leukemia (p=0.143). However, we detected a significant positive linear relationship between age of the patient and ANC values (p=0.002) for STAT3 mutant patients (Figure 1A). STAT3 wild-type (WT) patients did not display this relationship (p=0.756). No age associated trends were detected for hemoglobin values, although we detected decreasing red blood cell (RBC) values with increasing age for both STAT3 mutated and WT patients (p= 0.031, 0.010, respectively). No difference in sex (male vs female) balance was found within the young adult cohort (p=0.190). As rheumatoid arthritis (RA) is observed in ~30% of LGL leukemia patients, we asked if this prevalence also holds in the younger cohort. RA was observed in similar proportion in all young, adult, and older adult groups (p=1). To compare the severity of disease manifestation between the age groups, we first asked how many patients ever initiated LGL-related treatments in each age group. We found that patients under 50 are more likely to be on LGL related treatments compared to patients over the age of 50 (p=0.016) (Figure 1B). Next, we examined length of survival between age groups. Despite increased initiation of LGL related treatments, no statistically significant difference in overall survival (OS) was observed between patients under 50 and patients over the age of 50 (p=0.33) (Figure 1C). Therefore, we asked if the treatment response in younger patients is better compared to older patients. We observed no statistically significant differences in the routine LGL treatment responses between patients under 50 and patients over the age of 50 (p=0.732). Interestingly, epigenetic and chromatin modifier mutations are equally common in patients 50 years old and under relative to older adult patients (p= 0.271) (Figure 1D). Transcriptomic analysis of the PBMC data revealed enrichment of TNFα signaling in patients older than 50, while IFNα and IFNγ signaling was enriched in patients 50 years old and younger. Conclusions: We report the clinical and molecular analysis of LGL leukemia in pediatric/young adult and adult patients compared to the older adult patients that comprise the majority of LGL cases. We show that while STAT3 mutation frequency is similar across all age groups, younger patients with STAT3 mutation show lower ANC values compared to older patients. Importantly, we show that younger patients exhibit a more severe disease, as indicated by increased initiation of LGL treatment. However, overall survival in younger groups compared to older patients is not impacted. Finally, we show that younger patients display similar proportions of epigenetic and chromatin modifying mutations that are a prominent feature of older patients, and feature enrichment of IFNα and IFNγ signaling distinct from older patients. Figure 1 Figure 1. Disclosures Feith: Kymera Therapeutics: Membership on an entity's Board of Directors or advisory committees. Loughran: Dren Bio: Membership on an entity's Board of Directors or advisory committees; Keystone Nano: Membership on an entity's Board of Directors or advisory committees; Bioniz Therapeutics: Membership on an entity's Board of Directors or advisory committees; Kymera Therapeutics: Membership on an entity's Board of Directors or advisory committees.

Context Large granular lymphocyte (LGL) leukemia is a rare lymphoproliferative disorder of primarily CD8+ T or natural killer (NK) cell lineage whose molecular landscape is poorly characterized. Objective In this study, we defined the landscape of non-synonymous somatic variants in LGL leukemia exomes, asked whether these mutational profiles differed across LGL leukemia subtypes, and tested whether mutational groups were associated with clinical features. Design We leveraged paired whole-exome and transcriptome sequencing in the largest LGL leukemia study to date, which included 116 patients (93 TCRαβ T-LGL, 11 NK-LGL, and 12 TCRγδ T-LGL). Patients The study was conducted under IRB-approved protocols for the LGL Leukemia Registry at the University of Virginia School of Medicine. 116 LGL patients meeting diagnosis criteria by the World Health Organization (evidence of clonality, persistence of chronic expansion >6 months) were recruited for this study. Results The mutational landscape of LGL leukemia identified ARHGAP25, CCL22, CDH8, DNMT3A, FAS, KDM6A, KMT2D, PIK3R1, STAT3, STAT5B, TET2, and TNFAIP3 as recurrently mutated putative drivers using IntOGen bioinformatic driver analysis. The majority of gene mutations spanned all LGL subtypes, with the notable exception of CCL22, which was mutated exclusively within NK-LGL (4/11; 36.4%; p=0.0008). Moreover, there was a predilection for co-occurrence of STAT3 mutations with epigenetic modifier KMT2D (p Conclusions These findings highlight the clinical and molecular heterogeneity of this rare disorder. LGL leukemia research is supported by NCI R01CA178393, P30CA044579, T32LM012416, T32GM007267, F30CA225046. Additional support is provided by Bess Family Charitable Fund, LGL Leukemia Foundation, Dr. Charles and Katharine Hutton Tweedy, William J. Branch, Dr. Szabolcs Szentpetery, and a generous anonymous donor.

Purpose To determine whether point-of-care clinical decision support can effectively reduce inappropriate medical imaging of patients who present to the emergency department (ED) with low-back pain (LBP). Materials and Methods This was a prospective, single-center study of lumbar imaging referrals made by 43 emergency physicians at a major acute care center. Each physician saw at least 10 LBP cases in both pre- and post-intervention periods. A point-of-care checklist of accepted red flags for LBP was designed by a working group of physicians and embedded in the computerized order entry form for lumbar imaging. We compared imaging rates of LBP and physician variation in imaging ordering before and after the implementation of the checklist. We then measured the potential harms of reduced imaging. Results After intervention, the proportion of LBP patients with an imaging order fell significantly (median: 22% to 17%; mean: 23% to 18%; P = .0002) compared with pre-intervention baseline. The percentage of patients without imaging who were later imaged at a hospital outpatient clinic within 30 days was 2.3% before intervention and 2.2% after ( P = .974). In addition, the proportion of patients discharged from the ED without imaging who returned to the ED within 30 days was 8.2% before intervention and 6.9% after ( P = .170). One minor thoracic spine compression fracture was missed, but management was not impacted. No serious diagnoses were missed. Conclusion Clinical decision support integrated in electronic order entry forms can safely and effectively reduce imaging orders for LBP patients in the ED.

// Kimberly Mayes 1 , Zeinab Elsayed 1 , Aiman Alhazmi 1 , Michael Waters 2 , Suehyb G. Alkhatib 1 , Mark Roberts 1 , Carolyn Song 1 , Kristen Peterson 1 , Vivian Chan 1 , Nikhil Ailaney 1 , Pumoli Malapati 1 , Tana Blevins 3 , Berislav Lisnic 4 , Catherine I. Dumur 3 and Joseph W. Landry 1 1 The Department of Human and Molecular Genetics, Virginia Institute of Molecular Medicine, Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia 23298, USA 2 The Department of Biochemistry, Virginia Commonwealth University, Richmond, Virginia 23298, USA 3 The Department of Pathology, Virginia Commonwealth University, Richmond, Virginia 23298, USA 4 The Center for Proteomics and Department for Histology and Embryology, University of Rijeka, Faculty of Medicine, 51000 Rijeka, Croatia Correspondence to: Joseph W. Landry, email: joseph.landry@vcuhealth.org Keywords: BPTF, chromatin remodeling, antitumor immunity, NK cell, heparanase Received: January 31, 2017 Accepted: April 26, 2017 Published: May 12, 2017 ABSTRACT Using syngeneic BALB/c mouse breast cancer models, we show that the chromatin remodeling subunit bromodomain PHD finger transcription factor (BPTF) suppresses natural killer (NK) cell antitumor activity in the tumor microenvironment (TME). In culture, BPTF suppresses direct natural cytotoxicity receptor (NCR) mediated NK cell cytolytic activity to mouse and human cancer cell lines, demonstrating conserved functions. Blocking mouse NCR1 in vivo rescues BPTF KD tumor weights, demonstrating its importance for the control of tumor growth. We discovered that BPTF occupies heparanase ( Hpse ) regulatory elements, activating its expression. Increased heparanase activity results in reduced cell surface abundance of the NCR co-ligands: heparan sulfate proteoglycans (HSPGs). Using gain and loss of function approaches we show that elevated heparanase levels suppress NK cell cytolytic activity to tumor cells in culture. These results suggest that BPTF activates heparanase expression, which in turn reduces cell surface HSPGs and NCR co-ligands, inhibiting NK cell activity. Furthermore, gene expression data from human breast cancer tumors shows that elevated BPTF expression correlates with reduced antitumor immune cell signatures, supporting conserved roles for BPTF in suppressing antitumor immunity. Conditional BPTF depletion in established mouse breast tumors enhances antitumor immunity, suggesting that inhibiting BPTF could provide a novel immunotherapy.

Purpose The psychological and social factors associated with smoking initiation and continuation are different for young and adult smokers. Before 2005, there were no population-based smoking cessation interventions targeting young smokers in Hong Kong, China. This study describes the processes and outcomes of an individualized "Youth Quitline" service for young Hong Kong Chinese smokers over a 10-year period. Methods A retrospective population-based study was conducted to evaluate the effectiveness of the Quitline and identify the predictors of quitting. Telephone records were used to obtain information of each call. Young smokers of the Quitline completed a questionnaire at baseline and 6-month follow-up. Data were collected between August 2005 and August 2015. Results Over the 10-year period, the Youth Quitline received 7,720 telephone inquiries and provided smoking cessation counseling to 1,684 young smokers. At the 6-month follow-up, 16.9% had reduced cigarette consumption by more than 50%, 33.8% had tried quitting, and 23.6% had successfully quit smoking. Logistic regression analyses indicated that 7 factors, including (1) age; (2) daily cigarette consumption; (3) level of nicotine dependence; (4) intention to quit; (5) having made at least one quit attempt; (6) level of self-efficacy; and (7) adherence to telephone counseling, significantly predicted smoking cessation at 6 months. Conclusions During the first 10 years of the Youth Quitline, we trained many youths to become smoking cessation peer counselors. The Youth Quitline successfully increased youths' awareness of the risks of smoking and smoking cessation services and provided individualized smoking cessation counseling services to young smokers.

Background Ultrasound as an educational tool in preclinical medical education needs to be examined because of its broad and increasing use in medicine and its potential in enhancing students' anatomical knowledge and diagnostic skills. This study examines the role of ultrasound and preparation in first-year medical students' learning to identify and palpate lumbar spine landmarks. Methods Surveys were collected from first-year medical students who attended the lumbar spine workshop. Students were randomly stratified into two groups: using ultrasound and not using ultrasound. Student-diagnosed lumbar spine somatic dysfunctions were assessed by two blinded physicians. Results Three hundred and eighteen first-year students completed the survey. Sixty six percent (n = 104) of the students in the ultrasound group stated that ultrasound improved their physical examination skills. No significant difference existed between the ultrasound and non-ultrasound groups in confidence level in palpation, engagement level in workshop, nor accurately diagnosing lumbar somatic dysfunction. A significantly greater proportion of prepared students, compared to unprepared students, responded that the workshop helped with diagnosing and was engaging, and that ultrasound did or would improve physical examination skills (all p Conclusion The study results can assist in the design of future studies and workshops on ultrasound in preclinical education. Our study suggests the need for further research exploring ultrasound's role in helping preclinical medical students acquire basic and advanced palpatory and diagnostic skills.

ObjectivesThis is a prospective study evaluating NEPA in patients with breast cancer (the NEPA group), who received (neo)adjuvant AC chemotherapy (consisting of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2). The primary objectives were to assess the efficacy and safety of NEPA in controlling chemotherapy-induced nausea and vomiting (CINV). The secondary objectives were to compare CINV between the NEPA group and historical controls (the APR group) who received aprepitant in an earlier prospective randomised study.Patients and methods60 patients participated in the NEPA group; 62 were in the APR group. Eligibility criteria of both groups were similar, that is, Chinese patients with breast cancer who were treated with (neo)adjuvant AC. NEPA group received NEPA and dexamethasone; APR group received aprepitant, ondansetron and dexamethasone. Individuals filled in self-reported diary, visual analogue scale for nausea and Functional Living Index-Emesis questionnaire.ResultsWithin the NEPA group, 70.0%, 85.7% and 60.0%, respectively reported complete response in the acute, delayed and overall phases in cycle 1 AC. When compared with the historical APR group during cycle 1 AC, NEPA group achieved significantly higher rates of complete response, complete protection, total control, ‘no significant nausea’ and ‘no nausea’ in the delayed phase; similar findings were noted in the overall phase with significantly better quality of life. Superior efficacy of NEPA was maintained over multiple cycles. Both antiemetic regimens were well tolerated.ConclusionIn this study on Chinese patients with breast cancer who were uniformly receiving AC, NEPA was effective in controlling CINV.Trial registration numberNCT03386617.

Thalassemias and hemophilias are the most important inherited hematological diseases in Hong Kong and China. Prenatal diagnosis has significantly decreased the burden of these diseases. For thalassemia major, adequate transfusion and iron chelation therapy have dramatically improved patient outlook. Hematopoietic stem cell transplantation is curative for thalassemia major and is increasingly adopted. The efficacy of arsenic trioxide in acute promyelocytic leukemia (APL) was discovered in China. An oral formulation of arsenic trioxide was developed in Hong Kong for newly diagnosed and relapsed APL patients. With combination chemotherapy containing non-P-glycoprotein-dependent drugs and L-asparaginase, durable remission can be achieved in the most patients.

Objectives There is limited literature describing the effect exercise may have on depression and an individual’s health-related quality of life (HRQoL) in Parkinson’s Disease (PD). We aim to quantify this effect. Methods A cross-sectional questionnaire was administered to 60 PD subjects. The Parkinson’s Disease Questionnaire-39 (PDQ-39) summary index and the Geriatric Depression Scale-30 were used to quantify HRQoL and depression, respectively. Data were obtained on exercise habits. ANOVA and multivariate linear regression analysis were used to calculate mean differences in HRQoL. Results Depression was consistently related to HRQoL ( p Discussion Exercising and depression may interact to affect HRQoL. Thus, coordination of mental health evaluation and exercise regimens in persons with PD may improve HRQoL.

AIMS AND OBJECTIVES To explore the relationship between smoking and other risk behaviours among Chinese young people in Hong Kong. BACKGROUND There is growing concern about coexisting risk behaviours in young smokers. Information about smoking and other risk behaviours is crucial for developing interventions to promote smoking abstinence and adoption of healthy lifestyles. The relationship between smoking and other risk behaviours among Chinese young people in Hong Kong has not been explored. DESIGN This is a mixed-method retrospective population-based study. METHODS A retrospective population-based study was conducted with 1,147 young smokers through Youth Quitline between November 2011-July 2016. Attitudes, behaviours and experiences related to smoking and risk behaviours among Chinese young smokers were examined in semi-structured qualitative interviews with 30 participants randomly selected from the retrospective population-based study. RESULTS In total, 45.5% participants reported engaging in at least one other risk behaviour. The interviews revealed that drinking alcohol may have a significant impact on quitting smoking. In addition, smoking may be a gateway for more serious risk behaviours during adolescence. Low health awareness may explain the unhealthy lifestyles among young smokers. CONCLUSIONS This study bridges a gap in existing literature by exploring relationships between smoking and other risk behaviours among young people in Hong Kong. RELEVANCE TO CLINICAL PRACTICE Given the interrelationships between smoking and other risk behaviours, a holistic approach should be used to promote smoking cessation and healthy lifestyles among young smokers. If young smokers improve their health and quit smoking at the same time, their physical and mental development will benefit as a secondary outcome.

The Ontario Ministry of Education and Training’s Task Force on University Accountability first proposed key performance indicators (KPIs) for colleges and universities in Ontario in the early 1990s. The three main KPIs for Ontario universities are the rates of (1) graduation, (2) employment, and (3) Ontario Student Assistance Program loan default. This exploratory and descriptive study examined the perceptions of 12 key informants from 11 participating universities about the efficacy and effectiveness of these KPIs. The results of this study demonstrate that a clear majority of participants believe these KPIs are not having the intended impact. This paper analyzes the evidence and makes recommendations designed to foster efficient collaboration between stakeholders; it also asks all parties to clarify their goals, agreed expectations, and requirements, in order to develop effective measures of institutional performance and accountability and address the political needs of the government, the universities, and the public. Resume Au debut des annees 90, le Groupe de travail sur la responsabilisation des universites du ministere de l’Education et de la Formation de l’Ontario a d’abord propose des indicateurs de performance pour les colleges et les universites de l’Ontario. Ces trois principaux indicateurs cles de performance (ICP) pour les universites ontariennes sont (1) les taux d’obtention des diplomes, (2) les taux d’embauche et (3) les taux de defaut de remboursement des prets du Regime d’aide financiere aux etudiantes et etudiants de l’Ontario (RAFEO). Cette etude exploratoire et descriptive a examine la perception de 12 repondants cles (provenant de 11 universites participantes) envers l’efficacite de ces ICP. Les resultats de cette etude demontrent qu’en majorite absolue, les participants croient que ces ICP n’ont pas l’effet envisage. Ce rapport analyse les preuves et emet des recommandations ayant pour but de favoriser une collaboration efficace entre les intervenants. Il demande aussi a chaque partie de clarifier les objectifs, les attentes convenues et les exigences etablies dans le but d’elaborer des mesures efficaces de la performance et de la responsabilisation des etablissements, ainsi que d’adresser les besoins politiques du gouvernement, des universites et du public.

Background Knowledge translation (KT) refers to the process of moving evidence into healthcare policy and practice. Understanding the experiences and perspectives of individuals who develop careers in KT is important for designing training programs and opportunities to enhance capacity in KT research and practice. To date, however, limited research has explored the challenges that trainees encounter as they develop their careers in KT. Aims The purpose of this study is to identify the challenges that KT trainees face in their KT research or practice. Methods An online survey was conducted with a sample of trainees associated with the Knowledge Translation Trainee Collaborative or the KT Canada Summer Institutes, with written responses thematically analyzed. Findings A total of 35 individual responses were analyzed, resulting in the identification of six interrelated themes, listed in descending order of prevalence: limited availability of KT-specific resources (54%), difficulty inherent in investigating KT (34%), KT not recognized as a distinct field (23%), colleagues’ limited knowledge and understanding of KT (20%), competing priorities and limited time (20%), and difficulties in relation to collaboration (14%). Discussion KT trainees experience specific challenges in their work: limited understanding of KT in other stakeholder groups; limited structures or infrastructure to support those who do KT; the inherently interdisciplinary and applied nature of KT; and the resultant complexities of scientific inquiry in this field, such as designing and testing multifaceted, multilevel implementation strategies and accounting for contextual factors. Linking Evidence to Action KT training and capacity-building efforts are needed to better position health systems to routinely adopt knowledge into healthcare policy and practice.

Since 1998, the Ministry of Training, Colleges and Universities in Ontario, Canada, has required that data on specific key performance indicators (KPIs) be made public by its publicly funded universities. The information is intended to be used by universities to demonstrate their achievements, to improve their programmes and services, and to provide a basis for informed decision-making by potential students and their parents in the selection of institutions and programmes. An exploratory and descriptive study on the perception of major informants of participating universities regarding the efficacy and effectiveness of existing KPIs uncovered a number of underlying issues: KPIs are not seen as appropriate measures of performance and accountability at institutional or programme levels; awarding performance funding through aggregation at institutional and system levels is far removed from programme improvement at the decision-making level; and, Ontario Student Assistance Programme Default Rates are driven b...

The National Comprehensive Cancer Network (NCCN) guidelines are the gold standard in hereditary cancer risk assessment, screening, and treatment. A minority of physicians follow NCCN guidelines for BRCA1 or BRCA2 mutations. This study assesses the impact of an interventional educational program on HBOC in terms of knowledge. Physicians were sent an invite to join either an intervention survey (web-training offered prior to the knowledge survey) or control survey (web-training offered after the knowledge survey). Sixty-nine physicians in the intervention arm and 67 physicians in the control arm completed the survey. The interventional group regularly answered items correctly at a higher frequency than the control group. For example, 64.71% (n = 44) of physicians in the intervention group knew that multi-gene testing does not have to include only highly penetrant genes compared to 32.84% (n = 22) of the control group (p

Purpose The Knowledge Exchange–Decision Support (KE-DS) Model provides a framework outlining essential components of knowledge generation and exchange. The purpose of this research was to illustrate how the Model makes explicit the different contextual aspects implicit in the planning and implementation of two cancer navigation programs in Canada. Methods The KE-DS Model guided the collection and analysis of interviews with program personnel and narrative data. A qualitative thematic analysis was conducted wherein we compared and contrasted the planning and implementation of these two navigation programs. Results The planning and implementation of these two programs was conceptualized differently and adapted to meet local contingencies. The KE-DS Model highlighted three factors that influenced program delivery. First, the structure of health services was shaped by the interaction of professionals and services operating in the region, and the existing health services influenced the program’s approach to navigation. Second, while there were similarities in the professional roles and responsibilities of the navigators, these roles and responsibilities also reflected local context in their approaches to patient assessment, referral, education, coordination of services, and advocacy. Third, these two distinct approaches to navigation have responded to the needs of diverse populations being served by improving access to care. Conclusions Evidence generated using the KE-DS Model could ensure a more robust and structured approach to the planning and implementation of future navigation programs. The Model prompts users to make explicit the different types of evidence utilized during program planning and implementation. The systematic collection of new information on program implementation using the KE-DS Model in future initiatives will contribute to an improved understanding of the science of knowledge exchange.

Genetic studies in fruit flies have implicated the chromatin remodeling complex nucleosome remodeling factor (NURF) in immunity, but it has yet to be studied in mammals. Here we show that its targeting in mice enhances antitumor immunity in two syngeneic models of cancer. NURF was disabled by silencing of bromodomain PHD-finger containing transcription factor (BPTF), the largest and essential subunit of NURF. We found that both CD8+ and CD4+ T cells were necessary for enhanced antitumor activity, with elevated numbers of activated CD8+ T cells observed in BPTF-deficient tumors. Enhanced cytolytic activity was observed for CD8+ T cells cocultured with BPTF-silenced cells. Similar effects were not produced with T-cell receptor transgenic CD8+ T cells, implicating the involvement of novel antigens. Accordingly, enhanced activity was observed for individual CD8+ T-cell clones from mice bearing BPTF-silenced tumors. Mechanistic investigations revealed that NURF directly regulated the expression of genes encoding immunoproteasome subunits Psmb8 and Psmb9 and the antigen transporter genes Tap1 and Tap2. The PSMB8 inhibitor ONX-0914 reversed the effects of BPTF ablation, consistent with a critical role for the immunoproteasome in improving tumor immunogenicity. Thus, NURF normally suppresses tumor antigenicity and its depletion improves antigen processing, CD8 T-cell cytotoxicity, and antitumor immunity, identifying NURF as a candidate therapeutic target to enhance antitumor immunity. Cancer Res; 76(21); 6183–92. ©2016 AACR.

Objectives To determine haematological parameters in fetuses affected by homozygous α0-thalassemia. Methods This was a cross-sectional retrospective study reviewing 546 blood samples (268 fetal and 278 neonatal cord) being collected between 1993 and 2006, from 12 weeks' gestation onwards for any indication, including the prenatal diagnosis of homozygous α0-thalassemia, other haematological disorders, hydrops or aneuploidy. The proportion of haemoglobin (Hb) fractions was determined by electrophoresis of haemolysate on cellulose acetate in all samples. Results There were significant differences in the haematological parameters between homozygous α0-thalassemia (n = 183) and control (n = 363) which were either heterozygous α0-thalassemia (alpha thalassemia trait) or normal. In homozygous α0-thalassemia, the median Hb level, proportion of Hb Bart's (γ4) and Hb Portland 1(ζ2γ2) were 6.4 g/dL, 77.5% and 22.5%, respectively. While the Hb level and the proportion of Hb Bart's increased significantly with gestation, the proportion of Hb Portland 1 decreased. The Hb level contributed by Hb Portland 1 remained around 1.4 g/dL throughout gestation. The proportion of mild, moderate and severe anaemia in the affected fetuses was 27.5, 32.7 and 39.8%, respectively. There was no significant difference in these proportions across different gestation (P = 0.231). There were no differences in the haematological parameters between hydropic and non-hydropic fetuses. Conclusion Although the degree of anaemia is mild in around one-quarter of the affected fetuses, the contribution by Hb Portland 1 (ζ2γ2) to the Hb level was very low throughout gestation, and the affected fetuses may therefore be at risk for hypoxia. Copyright © 2010 John Wiley & Sons, Ltd.

Using syngeneic BALB/c mouse breast cancer models, we show that the chromatin remodeling subunit bromodomain PHD finger transcription factor (BPTF) suppresses natural killer (NK) cell antitumor activity in the tumor microenvironment (TME). In culture, BPTF suppresses direct natural cytotoxicity receptor (NCR) mediated NK cell cytolytic activity to mouse and human cancer cell lines, demonstrating conserved functions. Blocking mouse NCR1 in vivo rescues BPTF KD tumor weights, demonstrating its importance for the control of tumor growth. We discovered that BPTF occupies heparanase (Hpse) regulatory elements, activating its expression. Increased heparanase activity results in reduced cell surface abundance of the NCR co-ligands: heparan sulfate proteoglycans (HSPGs). Using gain and loss of function approaches we show that elevated heparanase levels suppress NK cell cytolytic activity to tumor cells in culture. These results suggest that BPTF activates heparanase expression, which in turn reduces cell surface HSPGs and NCR co-ligands, inhibiting NK cell activity. Furthermore, gene expression data from human breast cancer tumors shows that elevated BPTF expression correlates with reduced antitumor immune cell signatures, supporting conserved roles for BPTF in suppressing antitumor immunity. Conditional BPTF depletion in established mouse breast tumors enhances antitumor immunity, suggesting that inhibiting BPTF could provide a novel immunotherapy. Citation Format: Kimberly Mayes, Zeinab Elsayed, Aiman Alhazmi, Michael Waters, Suehyb Alkhatib, Mark Roberts, Carolyn Song, Kristen Peterson, Vivian Chan, Nikhil Ailaney, Pumoli Malapati, Tana Blevins, Berislav Lisnic, Catherine Dumur, Joseph Landry. Tumor cell intrinsic BPTF inhibits NK cell activity and the abundance of natural cytotoxicity receptor co-ligands [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr A28.

Objective To evaluate in maternal plasma, the efficacy of detecting the paternal β-gene mutation and informative single nucleotide polymorphisms (SNPs) linked to the paternal-mutant or -normal allele in non-invasive prenatal diagnosis (NIPND). Study design In 20 at-risk pregnancies, using the allele-specific arrayed primer extension (AS-APEX) technology of the previously published “Thalassemia” array, cyanine-5-deoxycytosine triphosphate (Cy5-dCTP) was incorporated into the extended strands to matched PCR-amplified maternal plasma DNA templates, to detect both the paternal β-gene mutation and informative paternal SNPs. Results Sensitivity experiment showed that 5 pg DNA as starting template gave detectable signals on the array. In 13 cases (65%), the paternal-derived β-gene mutation and/or informative mutant-associated SNP were detected. A subsequent invasive procedure was required to determine if the fetus had a β-thalassemia (thal) major or minor genotype. In 3 cases (15%), absence of the paternal mutant or mutant-associated SNP excluded a β-thal major fetus; while in 4 cases (20%), this approach was non-discriminative as both parents carry the same mutation without any informative SNP. Conclusion This approach was useful in 16 out of 20 (80%) pregnancies at risk for β-thal in southern Chinese.

The birth of babies with homozygous α0-thalassemia can be prevented by prenatal screening and diagnosis. Serial ultrasound examination of fetal cardio–thoracic ratio and placental thickness can exclude an affected pregnancy and, thus, reduce the need for an invasive test. Whether middle cerebral artery Doppler is useful in the prediction is not clear. 3D ultrasound examination, maternal blood-smear screening for fetal hemoglobin Bart’s cells and maternal serum markers for Down syndrome have also been investigated. In view of the recent data on the survival of affected fetuses after in utero transfusion, it is arguable whether the latter should be offered as an alternative to termination of pregnancy after prenatal diagnosis. Preimplantation genetic diagnosis is possible, particularly for couples with repeatedly affected pregnancies.

Bone mineral density (BMD) is one of the major determinants of risk for osteoporotic fracture. Multiple studies reveal that peak bone mass is under strong genetic influence. One of the major susceptibility loci for peak spine BMD has been mapped to chromosome 1q21-q23 in the Caucasian population. We have previously replicated this finding in Southern Chinese pedigrees and detected a maximum multipoint log of odds (LOD) score of 2.36 in this region. To further fine-map this region, 380 single-nucleotide polymorphic (SNP) markers were genotyped in 610 sibpairs from 231 families. Several markers were identified in the association analysis as important candidates underlying BMD variation. Among them, successful replication was demonstrated for SNPs in pre-B-cell leukemia homeobox 1 (PBX1) gene in two other unrelated case-control cohorts. The functional role of PBX1 in bone metabolism was examined in vitro using human bone-derived cells (HBDC) and murine MC3T3-E1 pre-osteoblasts. PBX1 mRNA was constitutively expressed in both HBDC and MC3T3-E1 cells. Immunostaining revealed that PBX1 is localized in the nucleus compartment. Silencing of PBX1 by RNAi in MC3T3-E1 cells decreased the expression of Runx2 and Osterix, the critical transcription factors for osteogenesis, but accelerated cell proliferation and bone nodule formation. Overall, our data suggest a genetic and functional association of PBX1 with BMD.

Low bone mineral density (BMD) is a major risk factor for osteoporotic fracture. Chromosome 14q has previously been linked to BMD variation in several genome-wide linkage scans in Caucasian populations.Our objective was to replicate and identify the novel candidate genes in the quantitative trait loci (QTL) at chromosome 14q QTL.Eighteen microsatellite markers were genotyped for a 117-cM interval in 306 Southern Chinese pedigrees with 1459 subjects. Successful replication of the QTL was confirmed within this region for trochanter and total hip BMD. Using a gene prioritization approach as implemented in the Endeavour program, we genotyped 65 single-nucleotide polymorphisms in the top five ranking candidate genes within the linkage peak in 706 and 760 case-control subject pairs with extremely high and low trochanter and total hip BMD, respectively.Single-marker and haplotype analyses revealed that ESR2 and latent TGF-beta binding protein 2 (LTBP2) had significant associations with trochanter and total hip BMD. Multiple logistic regression revealed a strong genetic association between LTBP2 gene locus and total hip BMD variation (P=0.0004) and prevalent fracture (P=0.01). Preliminary in vitro study showed differential expression of LTBP2 gene in MC3T3-E1 mouse preosteoblastic cells in culture.Apart from ESR2, LTBP2 is a novel positional candidate gene in chromosome 14q QTL for BMD variation and fracture.

Background The need to identify priorities to help shape future directions for research and practice increases as the knowledge translation (KT) field advances. Since many KT trainees are developing their research programs, understanding their concerns and KT research and practice priorities is important to supporting the development and advancement of KT as a field. Our purpose was to identify research and practice priorities in the KT field from the perspectives of KT researcher/practitioner trainees. Findings Survey response rate was 62 % (44/71). Participants were mostly Canadian graduate students, post-doctoral fellows, residents, and learners from various disciplines; the majority was from Ontario (44 %) and Quebec (20 %). Seven percent (5/71) were from other countries including USA, UK, and Switzerland. Seven main KT priority themes were identified: determining the effectiveness of KT strategies, technology use, increased key stakeholder involvement, context, theory, expand ways of inquiry, and sustainability. Conclusions Overall, the priorities identified by the trainees correspond with KT literature and with KT experts’ views. The trainees appeared to push the boundaries of current KT literature with respect to creative use of communication technologies research. Electronic supplementary material The online version of this article (doi:10.1186/s13012-015-0282-5) contains supplementary material, which is available to authorized users.

Background: Quit attempters often have episodes of smoking relapse before they eventually quit. Interactive text messaging through mobile phones has been shown to increase abstinence. This service can be potentially applied on the platform of a social networking service to help quitters maintain abstinence. Objective: Our aim was to determine if the group discussion and reminders via the WhatsApp or Facebook social group were effective to prevent smoking relapse in quitters who had stopped smoking recently. Methods: This was a single-blinded, parallel, 3-arm pilot cluster randomized controlled trial allocating recent quitters, who had completed an 8-week treatment and reported abstinence for at least 7 days, to WhatsApp (n=42), Facebook (n=40), and a control group (n=54). The 2 intervention groups participated in a 2-month online group discussion with either WhatsApp or Facebook moderated by a trained smoking cessation counselor and received a self-help booklet on smoking cessation. The control group only received the booklet. The primary outcome was the 2- and 6-month relapse rates, defined as the proportion of participants who smoked at least 5 cigarettes in 3 consecutive days. Results: Fewer participants in the WhatsApp group (17%, 7/42) reported relapse than the control group (42.6%, 23/54) at 2-month (OR 0.27, 95% CI 0.10-0.71) and 6-month (40.5%, 17/42 vs 61.1%, 33/54; OR 0.43, 95% CI 0.19-0.99) follow-ups. The Facebook group (30.0%, 12/40) had an insignificantly lower relapse rate than the control group (42.6%, 23/54) at 2-month (OR 0.58, 95% CI 0.24-1.37) and 6-month (52.5%, 13/40 vs 61.1%, 33/54; OR 0.70, 95% CI 0.31-1.61) follow-ups. The WhatsApp social groups had more moderators’ posts (median 60, IQR 25 vs median 32, IQR 7; P =.05) and participants’ posts (median 35, IQR 50 vs median 6, IQR 9; P =.07) than their Facebook counterparts, but the difference was insignificant. Conclusions: The intervention via the WhatsApp social group was effective in reducing relapse probably because of enhanced discussion and social support. Inactive discussion in the Facebook social group might have attributed to the lower effectiveness. ClinicalTrial: Clinicaltrials.gov NCT02007369; https://clinicaltrials.gov/show/NCT02007369 (Archived by WebCite® at http://www.webcitation.org/6c3RbltQG) [J Med Internet Res 2015;17(10):e238]