Academic Research Organizations Research Articles

Blockchain in Engineering Education: The Teaching Factory Paradigm

The research work presented in this paper is related to the design and development of a framework based on the Blockchain technology for the upscaling of modern academic education. The goal is to securely and successfully connect the multiple stakeholders involved in the academic education, including students, universities, research organizations and industries as well. Based on the concept of the distributed ledger, each stakeholder maintains a copy of the Blockchain locally, ensuring valuable information, such as achievements, projects, intellectual property, and patents/inventions. By extension, the proposed framework can act as a reward system for the academic stakeholders, i.e. the universities and the students. On the one hand, students via the creation of a virtual wallet can gather reward points based on their performance, their achievements as well as their participation in Teaching Factories (TF). On the other hand, universities can benefit from this framework as regards their accreditation, in worldwide basis. Concretely, with the participation in TF, award points are provided to these organizations, which act as a proof of the educational quality they provide to the students. Similarly, industries and research foundations, are also rewarded for their participation in such TF. The TF in the proposed framework can be realized as Smart contracts created by the industries and undertaken by the academic or research organizations. Furthermore, with the proposed framework human resources managers are facilitated in selecting competent and adequately qualified professionals. The selection of the professionals is based on their academic portfolio, which is part of the distributed ledger. Therefore under the scope of this research work, a group of young engineers was formed. The students had the opportunity to get familiar with the concept of Blockchain and assisted in the conceptualization and development of a distributed Teaching Factory platform based on the Blockchain Technology.

Performance Index for Types of Clinical Research Support Service Providers for Academic Research Organizations in Japan: A Cross-Sectional Survey.

The purpose of this study was to conduct a factual survey to evaluate the type of clinical research support offered by service providers (supporters) in Japanese academic research organizations (AROs). From September to October 2018, we conducted an online questionnaire targeting researchers and supporters of AROs, including individuals supporting research and development (R&D) planning, as well as those involved in study management, biostatistics, coordination, data management, monitoring, and auditing. The number of responses was tabulated for each survey item. For items with written descriptions, we compiled summaries using the inductive regression method of qualitative research. Responses were obtained from 124 researchers, 258 supporters, and 40 AROs. None of the institutions responded that they had a performance index for all types of service providers, whereas 47% of institutions had an index for 1–3 types of service providers, and 40% of institutions had no index. Many institutions responded that they had a performance index for coordinators and data management, but few responded that there was a performance index for individuals engaged in R&D and study management. Furthermore, for all evaluations of AROs and researchers, the level of supporter satisfaction was low at only 20%. There was a discrepancy between the levels of researcher expectations and the actual contribution of R&D in the process of research planning. Our survey revealed that there is currently no performance index for services supporting clinical research. In future studies, we need to examine a performance index that accurately reflects the researcher attitudes revealed in this study.

Incidence of Pulmonary Embolus after Catheter Removal in Children with Central Venous Catheter Related Venous Thromboembolism: A Report from the CHAT Consortium

Introduction: Appropriate timing of central venous Catheter (CVC) removal in children after the diagnosis of a CVC-related thrombosis (CRT) is poorly characterized. Due to the risk of embolization, ASH guidelines recommend initiating anticoagulation before CVC removal, but without a specified treatment period before CVC removal. An abstract from the 2019 ASH meeting did not find an increase in embolization rates when comparing anticoagulation treatment < or >48 hours prior to removal (Houghton et al, Blood 2019) in adult cancer patients with upper extremity CRT. This current study aimed to use data within the multi-institutional Children's Hospital-Acquired Thrombosis (CHAT) Consortium Registry to evaluate the incidence of symptomatic pulmonary embolism (PE) after CVC removal. Methods: The CHAT Registry is a retrospective cohort study which consists of detailed data from children aged 0-21 years with a hospital-acquired venous thromboembolism (HA-VTE) from eight U.S. centers. Eligible participants were those with a CRT. Participants were excluded if the diagnosis of thrombosis was >/= 3 days after CVC removal or if the CRT was due to a failed attempt at inserting a CVC. CHAT included details on demographics, medical history, CVC insertion and removal dates, anticoagulation start and stop dates and secondary outcomes, such as PE were extracted for analysis. Participants were divided into three groups, those in which (1) CVC removal occurred without anticoagulation initiation, (2) CVC removal occurred <48 hours after starting anticoagulation, and (3) CVC removal occurred ≥48 hours after starting anticoagulation (Figure 1). Results: A total of 687 CRT events from 663 participants were included. The median age at hospital admission was 1.4 years (IQR 0.1, 11.3) The majority of participants were male, 57% (378), 54% were non-Hispanic (359) and 46% were White (307). The most common past medical history for all participants with a CRT was congenital heart disease (22%, n=148) followed by cancer (11%, n=71), metabolic or mitochondrial disorder (3%, n=22) and inflammatory bowel disease (3%, n=21). For 76 CRT events the CVC was not removed during the participant's hospitalization or the removal date was unknown, therefore these events were excluded from further analysis. Anticoagulation was not initiated for 72 CRT events and for these events the median time from VTE diagnosis to CVC removal was one day (range 0-5.5). For the events that received anticoagulation there were 311 with CVC removal <48 hours and 228 events with CVC removal ≥48 hours (Table 1). Most of the CRT events with CVC removal <48 hours were in the lower extremity (52%, n=161) compared to CRT events with CVC removal ≥48 hours, which were mostly in the upper extremity (56%, n=127). A peripherally inserted central catheter was the most common CVC type regardless of group, followed by a temporary femoral line (Table 1). For all 611 CRT events in which the CVC was removed, there was only one case of PE (0.16%), which occurred <48 hours after CVC removal and initiation of anticoagulation (Figure 1). Conclusions: While current guidelines suggest anticoagulation before removal of CVCs in the setting of CRT to prevent embolization and PE, removal appears safe regardless of duration of anticoagulation before CVC removal in this pediatric cohort. These findings support need to substantiate the findings our CHAT consortium's ongoing prospective cohort study, but while waiting for these results, potential PEs should not weigh heavily in providers clinical decision making on timing of CVC removal. Disclosures Jaffray: CSL Behring: Research Funding; Octapharma: Other: Unrestricted funds for physician education. Baumann Kreuziger:CSL Behring: Consultancy; Quercegen pharmaceuticals: Consultancy. Mahajerin:Spark Therapeutics, Alexion, Genentech, Inc.: Speakers Bureau. Croteau:Hemophilia Federation of America: Honoraria; National Hemophilia Foundation: Honoraria; Sigilon Therapeutics: Consultancy; ATHN: Research Funding; Spark Therapeutics: Research Funding; CSL-Behring: Consultancy; Novo Nordisk: Research Funding; Pfizer: Consultancy; Genentech: Consultancy; Bayer: Consultancy. Young:BioMarin, Freeline, Genentech/Roche, Grifols, Kedrion, Novo Nordisk, Sanofi Genzyme, Spark, Takeda, and UniQure: Honoraria; Bayer, CSL Behring, Freeline, UniQure: Consultancy; Genentech/Roche, Grifols, and Takeda: Research Funding. Goldenberg:Academic Research Organization CPC Clinical Research: Consultancy; Daiici Sankyo: Consultancy; Novartis: Consultancy; Chiesi: Consultancy; Roshan Pharmaceuticals: Consultancy.

Relative and Absolute Risk Reductions in Cardiovascular and Kidney Outcomes With Canagliflozin Across KDIGO Risk Categories: Findings From the CANVAS Program

Canagliflozin reduces the risk for cardiovascular and kidney outcomes in type 2 diabetes. This study aimed to assess the relative and absolute effects of canagliflozin on clinical outcomes across different KDIGO (Kidney Disease: Improving Global Outcomes) risk categories based on estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio. Post hoc analysis of the CANagliflozin cardioVascular Assessment Study (CANVAS) Program. The CANVAS Program randomly assigned 10,142 participants with type 2 diabetes at high cardiovascular risk and with eGFR≥30mL/min/1.73m2 to treatment with canagliflozin or placebo. Canagliflozin or matching placebo. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, with a set of other cardiovascular and kidney prespecified outcomes. Of 10,142 participants, 10,031 (98.9%) had available baseline eGFR and urinary albumin-creatinine ratio data. The proportion of participants in low-, moderate-, high-, and very high-risk KDIGO categories was 58.6%, 25.8%, 10.6%, and 5.0%, respectively. The relative effect of canagliflozin on the primary outcome (HR, 0.86; 95% CI, 0.75-0.97) was consistent across KDIGO risk categories (Ptrend=0.2), with similar results for other cardiovascular and kidney outcomes. Absolute reductions in the primary outcome were greaterwithin higher KDIGO risk categories (Ptrend=0.03) with a similar pattern of effect for the composite of cardiovascular death or hospitalization for heart failure (P trend=0.06) and for chronic eGFR slope (Ptrend= 0.04). Predominantly a low kidney risk population, relatively few participants in higher KDIGO risk categories, and exclusion of individuals with eGFR<30mL/min/1.73m2. Although the relative effects of canagliflozin are similar across KDIGO risk categories, absolute risk reductions are likely greater for individuals at higher KDIGO risk. The KDIGO classification system may be able to identify individuals who might derive greater benefits for end-organ protection from treatment with canagliflozin. This post hoc analysis was not specifically funded. The original CANVAS Program trials were funded by Janssen Research & Development, LLC and were conducted as a collaboration between the funder, an academic steering committee, and an academic research organization, George Clinical. The original trials of the CANVAS Program were registered at ClinicalTrials.gov with study numbers NCT01032629 and NCT01989754.

The use of hybrid analytics to establish effective strategies for household energy conservation

Taiwan highly relies on foreign countries' supply in various types of energy because of the shortage of energy resources. Taiwanese government encourages industrial and academic research organizations to invest research in energy conservation that could be applicable to countries with similar settings. This research analyzed energy conservation and demographic data of households in Taiwan and developed a novel method for best setting household energy conservation strategies. Through the analysis of high volume and high dimensional data, it showed a hybrid analytical method is required, to predict and identify target households and refine their energy conservation strategies. The hybrid method includes a Logistic Regression based predictive model and a Rough Set Theory-based decision-making model. A hybrid analytical approach is used to identify target households and the critical energy conservation factors by households, such as the use of air conditioning in terms of time length and time of the day, age of the house, energy conservation of the electrical appliances, and price promotion. References show that no study was conducted with such a hybrid approach that can refine strategies for the households that were false-positive in achieving the conservation goal. Besides the above-mentioned purpose, this novel method intended to lower the promotion cost, as promotion is a part of the strategy refinement. In overall, the following problems were considered for decision-making: 1. how to identify the target households that require strategy refinement, 2. how to identify key variables and determine the change of these variables to increase the likelihood of achieving conservation goal, 3. what options can be provided to the decision-makers for feasible strategy refinements. Some studies with qualitative approaches and judgmental decision-making methods were found in this area. However, with the available large dataset, the proposed quantitative method achieved better decision-making efficiency and result optimality.

Abstract 6494: Personalize My Treatment (PMT): A pan-Canadian initiative integrating precision oncology across Canada - PMT-001 pilot project

Abstract More than 90% of cancer therapeutics in development are targeted therapies. Although the number of patients who can benefit from targeted therapies is increasing, many of the biomarkers are identified in only a small fraction of patients. Identifying and enrolling these rare cancer patient sub-populations into clinical trials presents an enormous challenge to both pharmaceutical companies and clinicians. Furthermore, in Canada, the lack of harmonized standard of care molecular testing for cancer patients results in a discordance in the number of genes tested across Hospital sites. Identifying patients with biomarkers of interest across Canada is essential to attract precision oncology clinical trials to Canada and to offer cancer patients better therapeutic options and improved outcomes. Founded in 2014, Exactis Innovation is a non-profit Academic Research Organization which aims to integrate precision oncology across Canada. Exactis has consolidated a pan-Canadian network of 13 cancer care centre sites and 4 federated laboratories. Network sites host an REB-approved molecular cancer patient registry (PMT), through which patients can be profiled, identified as carrying a biomarker, followed throughout their disease trajectory and be re-contacted if their molecular profile matches a clinical trial or an approved therapy. Here we report the results of Exactis' first profiling initiative (PMT-001), performed across 8 Exactis Network sites within 3 Canadian provinces in a four months' time period. In summary, 447 individual tumors specimens were collected from breast, colorectal, lung and ovary cancer patients and 382 were profiled using the Oncomine comprehensive assay v3 (OCAv3) panel DNA (n=365) and OCAv3 DNA/RNA (n=151). At least one aberration was identified in 346 participants. As expected, the top mutated genes across the 4 cohorts were TP53 (50%), PIK3CA(15%), KRAS (12.5%) and BRCA1/2 (12%/11%). At the fusion level, we identified EML4-ALK (5.2%), KIF5B-RET(1.7%) and MET exon 14 skipping (3.4%) in NSCLC participants and we identified RSPO3 (3%) and RSPO2 (2%) fusion in colorectal cancer participants. The profiling pilot of the PMT initiative shows how strong foundations within the Exactis pan-Canadian network is resulting in fast, high quality and meaningful molecular data for Canadian cancer patients. Citation Format: Maud Marques, Karen Gambaro, Mathilde Couetoux de Tertre, Suzan McNamara, Cyrla Hoffer, The Exactis Network, Richard Fajzel, Gerald Batist. Personalize My Treatment (PMT): A pan-Canadian initiative integrating precision oncology across Canada - PMT-001 pilot project [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6494.

CD26 as a Prognostic Marker in Allogeneic Hematopoietic Stem Cell Transplantation

Background: The success of hematopoietic stem cell transplantation (HSCT) depends upon donor stem cell harvest. Conventionally CD34 has been considered as marker of hematopoietic stem cells; however, the association of CD34+ cells with post-transplant outcomes has not been consistent. Current efforts are focused on identification of new markers that serve as potential predictors of post-transplant clinical outcome. Methods: This study includes donor harvests collected from twenty-three allogeneic donors during period 2008-2009 and respective transplant recipients followed for clinical outcomes till March 2019. Percent CD26+ and CD34+ cells in PBSC harvest were analyzed using flow cytometry. Infused dose of CD26+ and CD34+ cells was evaluated for its association with various clinical outcomes. Findings: Median donor and patient age was 28 and 24 years, respectively; 13 and 17 were males, respectively. Median CD34br CD45lo HSC expression was 0·57% (IQR 0·24-1·03) while median CD26 expression was 19·64% (IQR 8·96-33·56) of all nucleated cells. Lower CD26 expression correlated with lower risk of developing aGvHD (p=0·056). Higher infused CD26+ cell dose was associated with early WBC engraftment (p=0·004), higher risk of CMV reactivation (p=0·020) and a tendency to lower overall survival (p=0·066). There was no correlation between infused CD26+ and CD34+ cell dose. Interpretation: This forms the first study suggesting CD26 expression on donor harvest and CD26+ cell dose may serve as potential markers for transplant outcomes. If validated further in larger studies, it may be helpful in management of GvHD prophylaxis and improving survival with risk-based tailored therapeutics. Funding Statement: This study was funded by Indian Co-operative Oncology Network- Academic Research Organization, Mumbai, India. Declaration of Interests: Authors declare no potential financial conflicts of interest. Ethics Approval Statement: The study was approved by the institutional ethics committee. All patients and donors provided consent for study participation.

Stent-Related Adverse Events >1 Year After Percutaneous Coronary Intervention

BackgroundThe majority of stent-related major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) are believed to occur within the first year. Very-late (>1-year) stent-related MACE have not been well described. ObjectivesThe purpose of this study was to assess the frequency and predictors of very-late stent-related events or MACE by stent type. MethodsIndividual patient data from 19 prospective, randomized metallic stent trials maintained at a leading academic research organization were pooled. Very-late MACE (a composite of cardiac death, myocardial infarction [MI], or ischemia-driven target lesion revascularization [ID-TLR]), and target lesion failure (cardiac death, target-vessel MI, or ID-TLR) were assessed within year 1 and between 1 and 5 years after PCI with bare-metal stents (BMS), first-generation drug-eluting stents (DES1) and second-generation drug-eluting stents (DES2). A network meta-analysis was performed to evaluate direct and indirect comparisons. ResultsAmong 25,032 total patients, 3,718, 7,934, and 13,380 were treated with BMS, DES1, and DES2, respectively. MACE rates within 1 year after PCI were progressively lower after treatment with BMS versus DES1 versus DES2 (17.9% vs. 8.2% vs. 5.1%, respectively, p < 0.0001). Between years 1 and 5, very-late MACE occurred in 9.4% of patients (including 2.9% cardiac death, 3.1% MI, and 5.1% ID-TLR). Very-late MACE occurred in 9.7%, 11.0%, and 8.3% of patients treated with BMS, DES1, and DES2, respectively (p < 0.0001), linearly increasing between 1 and 5 years. Similar findings were observed for target lesion failure in 19,578 patients from 12 trials. Findings were confirmed in the network meta-analysis. ConclusionsIn this large-scale, individual patient data pooled study, very-late stent-related events occurred between 1 and 5 years after PCI at a rate of ∼2%/year with all stent types, with no plateau evident. New approaches are required to improve long-term outcomes after PCI.

Academic entrepreneurship and public research organisations: a conceptual study of the drivers and obstacles of research spin-off creation

Academic entrepreneurship and public research organisations: a conceptual study of the drivers and obstacles of research spin-off creation

Academic entrepreneurship and public research organisations: a conceptual study of the drivers and obstacles of research spin-off creation

In the modern society, universities and research centres are directly involved in the process of country economic growth by spurring product development, by creating new industries, and by contributing to employment and wealth creation. Research based spin offs are often the best way to reach these goals. For this reason, the number of research based firms spurred by Public Research Organisations is remarkably increased in the last years both in United States and in European Countries. On the other hand, this growth is not homogeneously distributed among different countries. According to these considerations, the aim of this paper is to understand which characteristics of public research institutions can influence positively or negatively the rise of research spin offs and which policies the research organisations can adopt to favour the generation of research-based spin-offs.

ACT-15 AD-SGE-REIC GENE THERAPY FOR MALIGNANT GLIOMA

INTRODUCTIONMalignant gliomas are one of the most common and aggressive intracranial neoplasms in humans. Expression of the gene encoding reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) is reduced in a variety of human cancer cells. We previously showed the antitumor effect of an adenoviral vector carrying REIC/Dkk-3 gene (Ad-CAG-REIC). Recently, we have also developed a novel adenoviral vector expressing REIC/Dkk-3 (Ad-SGE-REIC). We assessed the anti-glioma effect of the Ad-SGE-REIC and planned a clinical trial of Ad-SGE-REIC for malignant glioma.MATERIALS AND METHODSWe evaluated a cytotoxicity assay to treatments with Ad-SGE-REIC, Ad-CAG-REIC, or Ad-LacZ (control) using malignant glioma cells. The survival of mice in each group was analyzed by the Kaplan-Meier method. We also performed Good Laboratory Practice (GLP) toxicology tests and prepared a protocol for this clinical trial.RESULTSThe treatment with Ad-SGE-REIC showed the number of malignant glioma cells attached to the bottom of culture wells was significantly reduced in a time-dependent manner. Mice treated with Ad-SGE-REIC significantly prolonged survival time more than those treated with other vectors. A cGMP product of Ad-SGE-REIC was developed and supplied by a startup biotech company, Momotaro-Gene Inc. We conducted GLP toxicology tests using the intracranial injection of higher doses of Ad-SGE-REIC at Shin Nippon Biomedical Laboratories (SNBL Japan). After finishing the consultation with Pharmaceuticals and Medical Devices Agency (PMDA), we prepared a protocol for a phase I/IIa clinical trial of Ad-SGE-REIC for the treatment of recurrent malignant glioma with our academic research organization (ARO), supported by Japan Agency for Medical Research and Development (AMED). This protocol was reviewed by our institution review board in March 2019. We submitted a notification of this trial in April 2019.CONCLUSIONSWe demonstrated the anti-glioma effect of Ad-SGE-REIC. We start a phase I/IIa clinical trial of Ad-SGE-REIC for the treatment of recurrent malignant glioma (https://jrct.niph.go.jp/en-latest-detail/jRCT2063190013).

Creating an academic research organization to efficiently design, conduct, coordinate, and analyze clinical trials: The Center for Clinical Trials & Data Coordination

When properly executed, the randomized controlled trial is one of the best vehicles for assessing the effectiveness of one or more interventions. However, numerous challenges may emerge in the areas of study startup, recruitment, data quality, cost, and reporting of results. The use of well-run coordinating centers could help prevent these issues, but very little exists in the literature describing their creation or the guiding principles behind their inception.The Center for Clinical Trials & Data Coordination (CCDC) was established in 2015 through institutional funds with the intent of 1) providing relevant expertise in clinical trial design, conduct, coordination, and analysis; 2) advancing the careers of clinical investigators and CCDC-affiliated faculty; and 3) obtaining large data coordinating center (DCC) grants. We describe the organizational structure of the CCDC as well as the homegrown clinical trial management system integrating nine crucial elements: electronic data capture, eligibility and randomization, drug and external data tracking, safety reporting, outcome adjudication, data and safety monitoring, statistical analysis and reporting, data sharing, and regulatory compliance.Lastly, we share numerous lessons that can be taken from our experience. Specifically, we focus on 1) funding for DCCs, 2) the importance of DCCs to clinical researchers, 3) the expertise of DCC personnel, and 4) continually striving to improve.In conclusion, the CCDC strives to provide high-quality support for the design, conduct, coordination, and analyses of clinical trials, and we hope this paper will serve as a blueprint for future clinical trialists involved in DCCs.

Obinutuzumab combined with lenalidomide for relapsed or refractory follicular B-cell lymphoma (GALEN): a multicentre, single-arm, phase 2 study

Lenalidomide plus rituximab is approved to treat patients with relapsed or refractory follicular lymphoma. Obinutuzumab has been shown to enhance antibody-dependent cellular cytotoxicity, phagocytosis, and direct B-cell killing better than rituximab. Our aim was to determine the activity and safety of lenalidomide plus obinutuzumab in previously treated patients with relapsed or refractory follicular lymphoma. In this multicentre, single-arm, phase 2 study, patients were enrolled from 24 Lymphoma Academic Research Organisation centres in France. Eligible patients (age ≥18 years) had histologically confirmed CD20-positive relapsed or refractory follicular lymphoma of WHO grade 1, 2, or 3a; an ECOG performance status of 0-2; and received at least one previous rituximab-containing therapy. Patients received oral lenalidomide (20 mg) plus intravenously infused obinutuzumab as induction therapy (1000 mg; six 28-day cycles), 1-year maintenance with lenalidomide (10 mg; 12 28-day cycles; days 2-22) plus obinutuzumab (1000 mg; alternate cycles), and 1-year maintenance with obinutuzumab (1000 mg; six 56-day cycles; day 1). The primary endpoint was the proportion of patients who achieved an overall response at induction end as per investigator assessment using the 1999 international working group criteria. The secondary endpoints were event-free survival, progression-free survival, overall survival, and safety. Analyses were per-protocol; the efficacy population included all patients who received at least one dose of both obinutuzumab and lenalidomide, and the safety population included all patients who received one dose of either investigational drug. The study is registered with ClinicalTrials.gov, number NCT01582776, and is ongoing but closed to accrual. Between June 11, 2014, and Dec 18, 2015, 89 patients were recruited and 86 patients were evaluable for efficacy and 88 for safety. Median follow-up was 2·6 years (IQR 2·2-2·8). 68 (79%) of 86 evaluable patients (95% CI 69-87) achieved an overall response at induction end, meeting the prespecified primary endpoint. At 2 years, event-free survival was 62% (95% CI 51-72), progression-free survival 65% (95% CI 54-74), duration of response 70% (95% CI 57-79), and overall survival 87% (95% CI 78-93). Complete response was achieved by 33 (38%, 95% CI 28-50) of 86 patients at induction end, and the proportion of patients achieving a best overall response was 70 (81%, 95% CI 72-89) and 72 (84%, 74-91) of 86 patients during induction and treatment, respectively. The most common adverse events were asthenia (n=54, 61%), neutropenia (n=38, 43%), bronchitis (n=36, 41%), diarrhoea (n=35, 40%), and muscle spasms (n=34, 39%). Neutropenia was the most common toxicity of grade 3 or more; four (5%) patients had febrile neutropenia. 57 serious adverse events were reported in 30 (34%) of 88 patients. The most common serious adverse events were basal cell carcinoma (n=5, 6%), febrile neutropenia (n=4, 5%), and infusion-related reaction (n=3, 3%). One patient died due to treatment-related febrile neutropenia. Our data shows that lenalidomide plus obinutuzumab is active in previously treated patients with relapsed or refractory follicular lymphoma, including those with early relapse, and has a manageable safety profile. Randomised trials of new immunomodulatory regimens, such as GALEN or using GALEN as a backbone, versus lenalidomide plus rituximab, are warranted. Lymphoma Academic Research Organisation, and Celgene and Roche.

The impact of the H-1B cap exemption on Ph.D. labor markets

The American Competitiveness in the Twenty-First Century Act of 2000 (AC21) eliminated the H-1B cap for foreign employees of academic, nonprofit and government research organizations. This act potentially affects the job preferences of newly graduated foreign Ph.D. students. Choosing a career in an uncapped H-1B-qualified entity means circumventing the risk of facing the fiercely competitive H-1B application process and possibly avoiding potential losses due to a visa rejection. We use data from the census of Ph.D. graduates to examine the causal effect of this policy change on academic and industry labor markets in the USA. We find that as a result of this policy, Ph.D. graduates with temporary visas are 5 percentage points more likely to pursue a job in academia, and 3–4 percentage points less likely to choose a job in industry. A series of robustness checks exclude other external factors around the same time period driving the results.

PB1893 NON‐INTERVENTIONAL RETROSPECTIVE MULTICENTER STUDY EVALUATING REAL WORD IDELALISIB USE IN CLL AND INHL PATIENTS ENROLLED IN THE FRENCH EARLY ACCESS PROGRAM (EAP)

Please indicate where the abstract has been published before: ASH Abstract‐Blood 2018 132:5924.Background:Idelalisib (IDELA), a PI3K‐delta inhibitor, is indicated for the treatment of adult patients (pts) with chronic lymphocytic leukemia (CLL) and for pts with follicular lymphoma refractory to two prior lines of treatment. Its clinical efficacy and safety profile have been established in clinical trials, however, there is a paucity of real‐word data regarding its use. This study was initiated to describe pts who started IDELA treatment during the French EAP.Aims:The aims of this retrospective multicenter study were to describe the effectiveness, adverse events (AE), adverse drug reaction (ADR), serious ADR (SADR), AE of special interest (AESI: diarrhea/colitis, pneumonitis, liver enzyme elevation, neutropenia, infection, and rash), and IDELA use in adult pts previously enrolled in the EAP between June and October 2014 for CLL or iNHL.Methods:Physicians who enrolled at least one patient in the EAP were contacted to participate in this study. For each patient, 12 months follow up data were collected and monitored by the Lymphoma Academic Research Organization (LYSARC). The primary endpoint was the overall response rate (ORR) at 6 months. Statistical analysis was descriptiveResults:Seventy‐five pts were included, 41 in CLL group (39 in third‐line or later line and 2 in first‐line with del(17p)/TP53m unsuitable for chemo‐immunotherapy and 34 in iNHL group, all refractory after two prior lines of treatment (table 1). In CLL/iNHL groups respectively, median IDELA treatment duration was 25.1 weeks/18.9 weeks, ORR was 82.8%/56.5% at 6 months (data reported in 29 pts/23 pts), median PFS was not reached (NR)/ 6.7 months, median time to next treatment (TTNT) defined as the time between the date of the last IDELA intake and the start of next treatment after progression of disease (PD) was NR/11.6 months, median OS was NR in both groups and OS estimate at 12 months was 69.9%/67.6% (table 2). In CLL/iNHL groups respectively, at least one ADR related to IDELA was reported during the study in 35 pts (85.4%)/26 pts (76.5%) and SADR related to IDELA in 23 pts (56.1%)/15 pts (44.1%), most frequently reported AEs were: infections and infestations 61.0%/50.0% [Pneumocystis jirovecii pneumonia (PJP) 2.4%/5.9%], gastrointestinal disorders 56.1%/35.3% (diarrhea 41.5%/29.4%), blood and lymphatic system disorders 41.5%/41.2% (neutropenia 17.1%/23.5%) and lab investigation 43.9%/47.1% (hepatic enzyme increase 19.5%/14.7%). 24 pts (58.5%)/15 pts (44.1%) interrupted IDELA temporarily for AE, 6 pts (14.6%)/8 pts (23.5%) discontinued permanently for AE, 38 pts (92.7%)/25 pts (73.5%) had at least one AESI and 3 pts (7.3%)/6 pts (17.6%) permanently discontinued IDELA for AESI. Deaths were reported during the study in 13 pts (31.7%)/11 pts (32.4%), due to PD (46.2%/72.7%).Summary/Conclusion:The results of this study of heavily pretreated CLL and iNHL population indicate that IDELA is an effective treatment in routine clinical practice with an acceptable safety profile. ORR at 6 months was 83%/56.5% in CLL/iNHL mirroring those of clinical trials (Furman NEJM 2014, Gopal NEJM 2014). The pattern of AEs corresponds to that reported in previous clinical studies and might be improved by specific management of AESI.image

Grupos temáticos de la Red Internacional de Historiógrafos de la Comunicación. Fortalecer la investigación desde el enfoque interdisciplinario

En el presente trabajo se describen los criterios que guiaron la conformación de los grupos temáticos de la Red Internacional de Historiógrafos de la Comunicación, una organización académica de investigación constituida en 2016, en línea con la estrategia seguida en los últimos años por múltiples organizaciones profesionales y académicas para impulsar los diálogos inter y transdisciplinares.

Context Definition and Query Language: Conceptual Specification, Implementation, and Evaluation.

As IoT grows at a staggering pace, the need for contextual intelligence is a fundamental and critical factor for IoT intelligence, efficiency, effectiveness, performance, and sustainability. As the standardisation efforts for IoT are fast progressing, efforts in standardising context management platforms led by the European Telecommunications Standards Institute (ETSI) are gaining more attention from both academic and industrial research organizations. These standardisation endeavours will enable intelligent interactions between ‘things’, where things could be devices, software components, web-services, or sensing/actuating systems. Therefore, having a generic platform to describe and query context is crucial for the future of IoT applications. In this paper, we propose Context Definition and Query Language (CDQL), an advanced approach that enables things to exchange, reuse and share context between each other. CDQL consists of two main parts, namely: context definition model, which is designed to describe situations and high-level context; and Context Query Language (CQL), which is a powerful and flexible query language to express contextual information requirements without considering details of the underlying data structures. An important feature of the proposed query language is its ability to query entities in IoT environments based on their situation in a fully dynamic manner where users can define situations and context entities as part of the query. We exemplify the usage of CDQL on three different smart city use cases to highlight how CDQL can be utilised to deliver contextual information to IoT applications. Performance evaluation has demonstrated scalability and efficiency of CDQL in handling a fairly large number of concurrent context queries.

Організація наукових досліджень в університетах: стан і розвиток

The article is devoted to the analysis of one of the main factors of the modern development of Ukraine – the scientific provision of the innovative character of the socio-economic development of Ukraine. The main attention is paid to the analysis of scientific activity in the field of higher education..The system of higher education, along with the provision of a staffing component of the innovative economy, serves as a connecting link that combines education, science and production into a single whole..Organization of scientific work at the universities differs from the one at the academic and industry research organizations because the use and implementation of research results at universities takes place directly in the process of education and improvement of personnel training. This determines the specific problems of management and organization of research work in the higher education institutions. The article reveals the negative changes that have taken place in the scientific sector over the past 20 years. Analysis of development of the scientific sphere data, their comparison with the data of developed countries indicate that the main reason for reducing the amount of scientific research, the number of scientific institutions, the number of scientists was a decrease in the funding of science. The main attention is paid to the analysis of scientific activity in the field of higher education, which concentrates most of the country’s scientific potential. The organization of scientific work in institutions of higher education and the effectiveness of its management structures are researched. The main modern problems of the university science development are formulated, their content is disclosed and ways of overcoming the crisis phenomena in the scientific sector of higher education are formulated.

The Global academic research organization network: Data sharing to cure diseases and enable learning health systems.

IntroductionGlobal data sharing is essential. This is the premise of the Academic Research Organization (ARO) Council, which was initiated in Japan in 2013 and has since been expanding throughout Asia and into Europe and the United States. The volume of data is growing exponentially, providing not only challenges but also the clear opportunity to understand and treat diseases in ways not previously considered. Harnessing the knowledge within the data in a successful way can provide researchers and clinicians with new ideas for therapies while avoiding repeats of failed experiments. This knowledge transfer from research into clinical care is at the heart of a learning health system.MethodsThe ARO Council wishes to form a worldwide complementary system for the benefit of all patients and investigators, catalyzing more efficient and innovative medical research processes. Thus, they have organized Global ARO Network Workshops to bring interested parties together, focusing on the aspects necessary to make such a global effort successful. One such workshop was held in Austin, Texas, in November 2017. Representatives from Japan, Taiwan, Singapore, Europe, and the United States reported on their efforts to encourage data sharing and to use research to inform care through learning health systems.ResultsThis experience report summarizes presentations and discussions at the Global ARO Network Workshop held in November 2017 in Austin, TX, with representatives from Japan, Korea, Singapore, Taiwan, Europe, and the United States. Themes and recommendations to progress their efforts are explored. Standardization and harmonization are at the heart of these discussions to enable data sharing. In addition, the transformation of clinical research processes through disruptive innovation, while ensuring integrity and ethics, will be key to achieving the ARO Council goal to overcome diseases such that people not only live longer but also are healthier and happier as they age.ConclusionsThe achievement of global learning health systems will require further exploration, consensus‐building, funding aligned with incentives for data sharing, standardization, harmonization, and actions that support global interests for the benefit of patients.

Non-Interventional Retrospective Multicenter Study Evaluating Real Word Idelalisib Use in Chronic Lymphocytic Leukemia and Indolent Non-Hodgkin Lymphoma Patients Enrolled in the French Early Access Program

INTRODUCTIONIdelalisib (IDELA), the first-in-class PI3K-delta inhibitor, is indicated in Europe in combination with rituximab (R) or ofatumumab for the treatment (tt) of adult patients (pts) with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy, or as first-line tt of pts with 17p deletion (del(17p)) or TP53 mutation (TP53m), not eligibles for any other therapies and as monotherapy for pts with follicular lymphoma (FL) refractory to two prior lines of tt. IDELA has significant clinical activity with a manageable safety profile. However, there is a paucity of real word data regarding its effectiveness and safety. The REALIST study was initiated to better describe pts who started IDELA treatment during the French Early Access Program (EAP).AIMSThe aim of this retrospective multicenter study was to describe efficacy, adverse events (AEs), serious AEs (SAEs), AEs of special interest (AESIs, defined as diarrhea/colitis, pneumonitis, liver enzyme elevation, neutropenia, infection, and rash) and IDELA use in adult pts previously enrolled in the French EAP for CLL or iNHL.METHODSAll Investigators who enrolled at least one pt in the EAP were contacted by email inviting them to participate in this study. Only pts who initiated IDELA tt between June and October 2014 have been included in this study. For each pt, 12 months (m) follow up data were collected via an electronic Case Report Form and monitored by the Lymphoma Academic Research Organization (LYSARC). The Primary endpoint was the overall response rate (ORR) at 6 m and its 95% confidence interval (95% CI). Statistical analysis was descriptive.RESULTSSeventy-five pts were included, 41 in CLL group (39 in third-line or late and 2 in first-line with del(17p)/TP53m unsuitable for chemo-immunotherapy (CIT)) and 34 in iNHL group, all refractory after two prior lines of tt. Table 1 lists key pt characteristics at the time of initiation of IDELA. In CLL/iNHL groups respectively, median IDELA tt duration was 25.1 weeks/18.9 weeks, ORR, was 82.8%/56.5% at 6 m (data reported in 29 pts/23 pts) and 100%/57.1% at 12 m (data reported in 12 pts/14 pts), median PFS was not reached (NR)/ 6.7 m, median time to next tt (TTNT) defined as the time between the date of the last IDELA intake and the start of next tt after progression of disease (PD) was NR/11.6 m, median OS was NR in both groups and OS estimate at M12 was 69.9%/67.6%. Additional efficacy data are presented in Table 2, Fig 1 and Fig 2. In CLL/iNHL groups respectively, at least one AE was reported during the study in 35 pts (85.4%)/26 pts (76.5%), most frequently reported AEs by SOC/PT were: infections and infestations 61.0%/50.0% (pneumocystis jirovecii pneumonia (PJP) 2.4%/5.9%), gastrointestinal disorders 56.1%/35.3% (diarrhea 41.5%/29.4%), blood and lymphatic system disorders 41.5%/41.2% (neutropenia 17.1%/23.5%) and investigation 43.9%/47.1% (hepatic enzyme increase 19.5%/14.7%). 24 pts (58.5%)/15 pts (44.1%) discontinued temporary IDELA, 6 pts (14.6%)/8 pts (23.5%) discontinued permanently for AE, 38 pts (92.7%)/25 pts (73.5%) had at least one AESI, 10 pts (24.4%)/11 pts (32.4%) had at least one serious AESI, 3 pts (7.3%)/6 pts (17.6%) permanently discontinued IDELA for AESI and deaths were reported during the study in 13 pts (31.7%)/11 pts (32.4%), mainly due to PD (46.2%/72.7%).CONCLUSIONThe results of this non-Interventional study of heavily pretreated CLL and iNHL population treated by IDELA monotherapy or in combination with rituximab indicate that IDELA is an effective treatment in routine clinical practice with an acceptable safety profile. ORR at 6 months was 83% in CLL full analysis set and 79% in del(17p)/TP53m sub-group and 55% in FL sub group. These results mirror those of clinical trials. No unexpected IDELA safety information was identified in this study and the pattern of AEs corresponds to that reported in previous clinical studies and might be improved by specific management of AESI including PJP prophylaxis to be administered to all patients throughout IDELA treatment. DisclosuresYsebaert:Roche: Consultancy, Research Funding; Gilead Sciences, Inc.: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Feugier:Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Salles:Novartis: Consultancy, Honoraria; Roche: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Abbvie: Honoraria; Acerta: Honoraria; Amgen: Honoraria; Epizyme: Honoraria; Gilead Sciences: Honoraria; Janssen: Honoraria; Merck: Honoraria; Morphosys: Honoraria; Pfizer: Honoraria; Servier: Honoraria; Takeda: Honoraria. Sylvain:Gilead: Other: scientific advisor board. Glorian Kergaravat:Gilead Sciences: Employment. Simpson:Gilead Sciences: Employment. Ramroth:Gilead Sciences: Employment. Abdelhadi:Gilead Sciences: Employment. Haioun:Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Gilead Sciences: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Sciences: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Roche: Consultancy, Honoraria. Troussard:Gilead: Other: scientific advisory board.