Collaborative Research Agreement Research Articles

Epidemiology of Homebound Population Among Beneficiaries of a Large National Medicare Advantage Plan.

Interest in home-based care is increasing among Medicare Advantage (MA) plans. The epidemiology of homebound MA beneficiaries is unknown. To determine the prevalence, characteristics, predictors, health service use, and mortality outcomes of homebound beneficiaries of a large national MA plan. Cross-sectional. National MA plan. Humana MA beneficiaries in 2022 (n = 2 435 519). Homebound status was assessed via in-home assessment using previously defined categories: homebound (never or rarely left home in the past month), semihomebound (left home with assistance, had difficulty, or needed help leaving home), and not homebound. Demographic, clinical, health service use, and mortality outcomes were compared by homebound status. In 2022, the overall prevalence of homebound beneficiaries was 22.0% (8.4% of beneficiaries were homebound, and 13.6% were semihomebound). In adjusted models, female sex (odds ratio [OR], 1.36 [95% CI, 1.35 to 1.37), low-income status or dual eligibility for Medicare and Medicaid (OR, 1.56 [CI, 1.55 to 1.57]), dementia (OR, 2.36 [CI, 2.33 to 2.39]), and moderate to severe frailty (OR, 4.32 [CI, 4.19 to 4.45]) were predictive of homebound status. In multivariable logistic regression, homebound status was associated with increased odds of any emergency department visit (OR, 1.14 [ CI, 1.14 to 1.15]), any inpatient hospital admission (OR, 1.44 [CI, 1.42 to 1.46]), any skilled-nursing facility admission (OR, 2.18 [CI, 2.13 to 2.23]), and death (OR, 2.55 [CI, 2.52 to 2.58]). The study period overlapped the tail end of the COVID-19 pandemic, and data were derived from a single national MA plan, which limits generalizability. Overall homebound prevalence in a national MA plan was 22.0% and was independently associated with increased health service use and mortality. Study findings can inform strategic initiatives to identify and manage care for homebound beneficiaries. Humana, under a collaborative research agreement with Johns Hopkins University.

National dairy research programs: what is their role in animal health and sustainability research?

The US dairy industry has made great strides in improving animal health over many decades, which has driven substantial improvements in economic, social, and environmental sustainability. As consumer and corporate focus on climate continues to grow, the continued need to research and improve animal health and understand its connection with the environment is integral to the success of the dairy industry. Research to address these areas can be supported by national research programs and collaboration between them. The USDA and Dairy Management Inc established a collaborative research agreement in 2007; to date, this collaboration has not explicitly focused on animal health or its intersection with the environment. It is integral to the success of animal agriculture in an ever-changing sustainability landscape that animal health is addressed as a key piece of socioeconomic and environmental sustainability. An academic-industry stakeholder committee reached a consensus that supported this idea and identified that it is equally important to communicate these research findings with consumers in a way that resonates. The purpose of this Viewpoint article is to highlight that national research programs at the USDA Agricultural Research Service's National Animal Disease Center and Dairy Management Inc can and should play an important role in supporting and facilitating research at the intersection of animal health and sustainability broadly.

Respiratory Rate as a Factor in Lung Injury-Not Just What You Set, but How You Set.

Respiratory Rate as a Factor in Lung Injury-Not Just What You Set, but How You Set.

Strategies for the discovery of potential anticancer agents from plants collected from Southeast Asian tropical rainforests as a case study.

Covering up to early 2023The present review summarizes recent accomplishments made as part of a multidisciplinary, multi-institutional anticancer drug discovery project, wherein samples comprising higher plants were collected primarily from Southeast Asia, and also from Central America, and the West Indies. In the introductory paragraphs, a short perspective is provided on the current importance of plants in the discovery of cancer therapeutic agents, and the contributions of other groups working towards this objective are mentioned. For our own investigations, following their collection, tropical plants have been subjected to solvent extraction and biological evaluation for their antitumor potential. Several examples of purified plant lead bioactive compounds were obtained and characterized, and found to exhibit diverse structures, including those of the alkaloid, cardiac glycoside, coumarin, cucurbitacin, cyclobenzofuran (rocaglate), flavonoid, lignan, and terpenoid types. In order to maximize the efficiency of work on drug discovery from tropical plant species, strategies to optimize various research components have been developed, including those for the plant collections and taxonomic identification, in accordance with the requirements of contemporary international treaties and with a focus on species conservation. A major component of this aspect of the work is the development of collaborative research agreements with representatives of the source countries of tropical rainforest plants. The phytochemical aspects have included the preparation of plant extracts for initial screening and the selection of promising extracts for activity-guided fractionation. In an attempt to facilitate this process, a TOCSY-based NMR procedure has been applied for the determination of bioactive rocaglate derivatives in samples of Aglaia species (Meliaceae) collected for the project. Preliminary in vitro and in vivo mechanistic studies carried out by the authors are described for two tropical plant-derived bioactive lead compounds, corchorusoside C and (+)-betulin, including work conducted with a zebrafish (Danio rerio) model. In the concluding remarks, a number of lessons are summarized that our group has learned as a result of working on anticancer drug discovery using tropical plants, which we hope will be of interest to future workers.

Weldability of irradiated Stainless Steel 304 materials harvested from the National Research Universal (NRU) reactor

The weldability of the neutron-irradiated Stainless Steel 304 (SS 304) materials containing estimated helium levels of 12 to 44 appm has been studied through a Collaborative Research and Development Agreement between the Canadian Nuclear Laboratories and Oak Ridge National Laboratory. The work utilizes a SS 304 component harvested from the National Research Universal reactor. Laser beam welding was used to explore suitable welding conditions and associated parameters, to determine helium concentration limits for successful welding of irradiated stainless-steels. The experimental results show that maximum fusion zone void sizes, fusion zone void quantity and total heat affected zone helium-induced crack length generally increased with increasing He levels and effective weld heat input. A proper combination of welding parameters with low effective heat input, such as, laser power, weld travel speed and wire feed speed, were shown to improve the welding quality, and potentially reduce the length and probability of the formation of grain boundary helium-induced cracking and voids of irradiated SS 304 even with He concentrations as high as about 44 appm.

0013 Psychomotor Vigilance Test Performance Declines Related to Illness Severity, not Sleep

Abstract Introduction While the Psychomotor Vigilance Test (PVT) has been used extensively to track vigilance degradation following sleep loss, there is evidence that it may also track vigilance degradation related to illness. However, it is unclear how much performance decline is driven by sleep loss related to an illness or the illness itself independent of sleep loss. Here we assessed how sleep and acute infectious diarrhea impact vigilance performance in a controlled human infection model (CHIM) with enterotoxigenic Escherichia coli (ETEC). Methods During a CHIM assessing the efficacy of an immunoprophylactic targeting ETEC, we measured sleep via actigraphy over an 8-day inpatient period. A 10-minute PVT was also administered up to three times each day in the morning, afternoon, and evening. Participants ingested an oral immunoprophylaxis 3 times/day on days -2 and -1, and ingested ETEC on day 0. Participants were categorized as to whether or not they experienced the primary endpoint of moderate-severe diarrhea (MSD). Results Among 56 participants (aged 34.7±8.5 years, 64% male), 54% reached the primary endpoint of moderate-severe diarrhea following ETEC infection. Total sleep times across the study did not differ between those with and without MSD. While PVT minor lapses (i.e., not responding within 500 milliseconds) did increase following ETEC infection for all subjects as revealed by a mixed linear model [effect of day: f(7,657)=3.35, p=0.002], there was also a significant main effect of group [f(1,657)=5.85, p=0.016], where those participants who experienced MSD following ETEC infection had more minor lapses across the study than those who did not experience MSD (6.28±0.43 vs 4.88±0.38). Conclusion While the negative impact of sleep loss on performance has been well demonstrated, these are the first data to suggest that illness severity[KT1] , independent of sleep loss, also negatively impacts performance. In operational populations such as the military, special care should be taken to prevent illness and remove ill operators from the field, just as this care should be taken to prevent sleep loss and remove sleepy operators. By preventing and monitoring sleep loss and illness, these operations can avoid potentially costly performance errors. Support (If Any) The clinical trial from which these data were obtained was funded by the Congressionally Directed Medical Research Program through the Joint Warfighter Medical Research Program under Award No. W81XWH-15-C-0083 to the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. The U.S. Army Medical Research Acquisition Activity was the awarding and administering acquisition office. The study was also funded by a Collaborative Research and Development Agreement with PATH Enteric Vaccine Solutions (NCRADA-NMRC-15-9589), as well as by the Military Operational Medicine Research Program (MOMRP).

Ultrasound-facilitated, catheter-directed thrombolysis vs anticoagulation alone for acute intermediate-high-risk pulmonary embolism: Rationale and design of the HI-PEITHO study

BackgroundDue to the bleeding risk of full-dose systemic thrombolysis and the lack of major trials focusing on the clinical benefits of catheter-directed treatment, heparin antiocoagulation remains the standard of care for patients with intermediate-high-risk pulmonary embolism (PE). Methods and resultsThe Higher-Risk Pulmonary Embolism Thrombolysis (HI-PEITHO) study (ClinicalTrials.gov Identifier: NCT04790370) is a multinational multicenter randomized controlled parallel-group comparison trial. Patients with: (1) confirmed acute PE; (2) evidence of right ventricular (RV) dysfunction on imaging; (3) a positive cardiac troponin test; and (4) clinical criteria indicating an elevated risk of early death or imminent hemodynamic collapse, will be randomized 1:1 to treatment with a standardized protocol of ultrasound-facilitated catheter-directed thrombolysis plus anticoagulation, vs anticoagulation alone. The primary outcome is a composite of PE-related mortality, cardiorespiratory decompensation or collapse, or non-fatal symptomatic and objectively confirmed PE recurrence, within 7 days of randomization. Further assessments cover, apart from bleeding complications, a broad spectrum of functional and patient-reported outcomes including quality of life indicators, functional status and the utilization of health care resources over a 12-month follow-up period. The trial plans to include 406 patients, but the adaptive design permits a sample size increase depending on the results of the predefined interim analysis. As of May 11, 2022, 27 subjects have been enrolled. The trial is funded by Boston Scientific Corporation and through collaborative research agreements with University of Mainz and The PERT Consortium. ConclusionsRegardless of the outcome, HI-PEITHO will establish the first-line treatment in intermediate-high risk PE patients with imminent hemodynamic collapse. The trial is expected to inform international guidelines and set the standard for evaluation of catheter-directed reperfusion options in the future.

VEDOLIZUMAB REDUCES DENDRITIC CELLS AND NAÏVE LYMPHOCYTES IN THE COLON MUCOSA

Abstract Vedolizumab blocks integrin alpha4/beta7 interaction with MAdCAM-1 on intestinal vascular endothelial cells. It is believed to treat inflammatory bowel disease (IBD) by preventing alpha4/beta7+ cells in blood from entering the intestinal mucosa. By CyTOF and flow cytometry, we found high expression of alph4/beta7 on nearly all myeloid dendritic cells in the blood. Flow cytometry was also performed on colon biopsies from 71 IBD patients on vedolizumab matched 1:1 with similar biopsies from 71 matched IBD patients not on vedolizumab. In the colon, vedolizumab use was associated with significantly fewer intramucosal myeloid dendritic cells (CD1c+, CD14−, CD11c+, HLA-DR+, Wilcoxon p=0.000001) in patients responsive to vedolizumab, but not in non-responders, relative to their respective controls. Fewer intramucosal naïve B (IgD+, Wilcoxon p=0.0001) and CD4 T cells (CD45RA+, Wilcoxon p=0.001) were also observed, regardless of treatment efficacy. No differences were observed in the frequency of other T or B cell subsets, including CD8 T cells, effector T cells, plasma cells and memory B cells expressing different immunoglobin isotypes, suggesting that they have an alternative means of recruitment not present among naïve lymphocytes, such as integrin alpha4/beta1, which binds VCAM-1. Thus we find no evidence that that vedolizumab functions by preventing effector lymphocytes from entering the intestinal mucosa. We instead associated vedolizumab use with fewer colonic naïve lymphocyte and myeloid dendritic cells. The latter is of particular interest, as it alone correlates with clinical response to this therapy. Supported by a collaborative research agreement with Takeda Pharmaceuticals

Protocol for a systematic review of the in vivo studies on radiofrequency (100\u2009kHz\u2013300\u2009GHz) electromagnetic field exposure and cancer

BackgroundAn Italian project aims to review the scientific literature on the possible carcinogenicity of radiofrequency (100 kHz–300 GHz) electromagnetic field (RF-EMF) exposure. The ENEA team has to carry out a systematic review of the in vivo studies on this topic.ObjectivesDevelopment of a protocol for a systematic review (meta-analysis included) to investigate the potential carcinogenic risk following RF-EMF in vivo exposure to doses above or within legal limits. The aims of this review are (1) to provide a descriptive and, if possible, a quantitative summary of the results of the examined RF-EMF in vivo studies, together with an assessment of the consistency of observations and of the causes of heterogeneity, and (2) to assess the weight of evidence to support or refute the hypothesis of carcinogenic effects caused by RF-EMF exposure and to draw conclusions about the potential for carcinogenicity of RF-EMF exposure.MethodsWe will search for relevant studies in electronic academic databases and in the reference list of selected papers and reviews on the topic, including the descriptive reviews on RF-EMF carcinogenic effect carried out by international panels of experts since 2011. The following elements of the PECO question were defined: experimental studies on rodents of both sexes, all ages and species, all genetic backgrounds (Population) exposed to RF-EMF alone, or in combination with other physical or chemical agents (Exposure); only studies reporting outcome data in exposed and sham control groups (Comparison); and all types of cancer with all tumor-related outcome measures (Outcome) will be included.Only peer-reviewed articles written in English will be considered without limit in the publication date.Eligibility criteria were defined for papers to be included. A risk of bias assessment will be performed using a tool specifically developed for animal studies. A meta-analysis will be performed, if feasible, for all outcome measures; for subgroup analysis, a minimum of 3 studies per subgroup will be required. If meta-analysis will not be possible, a narrative synthesis of the results will be reported.Systematic review registrationPROSPERO CRD42020191105HighlightsAn Italian collaborative research agreement aims to review the scientific literature on the possible carcinogenicity of RF-EMF (100 kHz – 300 GHz).The ENEA team will systematically review and, if possible, meta-analyse estimates the effects of in vivo exposure to RF-EMF exposure on cancer.The ENEA group is a multidisciplinary team of researchers with a consolidated experience both in carcinogenicity experiments and radiofrequency dosimetric assessment.The proposed protocol uses the NTP OHAT Approach for Systematic Review as an organizing framework.The proposed protocol aims to lead to the first systematic review providing a strength of evidence assessment on this topic.

Monopoly Spotting: The Management of Openness in University-Industry Research Collaborations

Industry and universities engage in collaborative research often without a clear understanding of how open the research results should be. The contractual terms of the research project document agreed on openness. The terms also decide if access through licensing will be exclusive to a few, or available for the many in open innovation. However, collaborative research agreements are complicated with entangled terms. We applied a novel method for analysing such agreements on 484 publicly sponsored projects in different industries. Placing the projects in the method’s two-by-two matrix, we found that around 20 per cent of the projects, across all industries, have agreements that allow knowledge monopolies to form. We find a positive association between the openness of the research results and the projects that are climate and transport-related. For organisations, research managers and policymakers, the method can be used on a single project or a portfolio of collaborative projects to better align with research policy.

Abstract B29: The importance of epitope spreading in the generation of effective antitumor immunity in mice treated with combination immunotherapy

Abstract Recent clinical successes of PD-1/L1 and CTLA-4 blockade have demonstrated the potential of immunotherapies for the treatment of cancer. Research suggests the clinical efficacy of these checkpoint blockade therapies requires the presence of tumor-reactive T cells prior to therapy. It is thought that these tumor-reactive T cells primarily recognize nonsynonymous mutations (neoepitopes) uniquely expressed by a patient’s tumor. Unfortunately, at present the majority of patients fail to respond to checkpoint blockade, and it is hypothesized that one can improve their efficacy by combining them with vaccines targeting neoepitopes. Using the MC38 murine colon cancer model, we previously showed that an effective antitumor immunity could be generated when combining either a peptide or recombinant adenoviral-based vaccine targeting neoepitopes with three rationally selected immune-oncology agents. We utilized an IL-15 superagonist (N-803) to promote the generation and expansion of T cells and a tumor-targeted IL12 (NHS-IL12) and PD-L1 blockade to facilitate T-cell expansion and function within the tumor microenvironment. This multifaceted treatment regimen was effective at inducing tumor clearance in the majority of animals treated. In the present study, we examine the immune response in animals that fail to respond to our treatment regimen. By analyzing the spread of immunity to neoepitopes expressed by the MC38 tumor, but not contained within the vaccine, we were able to correlate treatment failures to less diversity in the antitumor immune response. To examine this observation more closely, tumor-bearing mice were treated with different combinations of neoepitope vaccine, N-803, PD-L1 blockade, and NHS-IL12, to ascertain which components of the combination therapy facilitated epitope spreading. We also examined which cell populations were able to cooperate with tumor-reactive CD8+ T cells to promote and/or inhibit epitope spread. Our observations demonstrate the importance of a diverse antitumor immune response and offers insights on how one might increase the diversity of the antitumor immune response following treatment with immune-oncology agents. These studies were performed in collaboration with NantOmics, NantBio and ImmunityBio, and EMD Serono as a part of Collaborative Research and Development Agreements (CRADA) with the NCI. Citation Format: Karin L. Lee, Claudia Palena, Jeffrey Schlom, Duane H. Hamilton. The importance of epitope spreading in the generation of effective antitumor immunity in mice treated with combination immunotherapy [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr B29.

TianQin project and international collaboration

The proposed TianQin gravitational wave observatory is aiming to detect gravitational wave signals in the millihertz frequency band, through the method of space-borne laser interferometry. In total, three satellites will be launched, each following a geocentric orbit, with an orbital altitude of about one hundred thousand kilometers. They form into an equilateral triangle formation, with an orbital period of <sc>3.6 d.</sc> The orbital plane of TianQin is fixed almost constant, towards one specific gravitational wave source, RXJ0806.3+1527, so that TianQins response to this source is maximized, and this source can be used to calibrate and assess the facilities performance. It is widely anticipated that in the millihertz frequency band, there lurks a wide variety of gravitational wave sources, ranging from massive black hole binary mergers, extreme mass ratio inspirals, Galactic binary white dwarves, stellar mass binary compact objects inspirals, as well as stochastic gravitational wave background. Meanwhile, the expected source number in such frequency band would also be huge. The successful implementation of the TianQin project would pave the way towards exciting prospects of future gravitational wave research. By successfully performing gravitational wave observation, the TianQin gravitational wave observatory can open a new window for the study of gravitational wave astronomy, gravitational wave cosmology as well as gravitational wave physics. The science prospect of TianQin gravitational wave observation can be further enhanced through a combination with multi-band gravitational wave detection and multi-messenger astronomical observations, by collaboration with gravitational wave detectors operating in different frequency bands as well as with other probes focusing on different messengers like electro-magnetic signals, neutrinos or cosmic rays. The TianQin project will also greatly promote the construction of a high-precision space-time reference system, ultra-long-range laser interferometry, high-precision satellite platform, etc. The development of cutting-edge space technologies has important applications in the national economy as well as the national strategic needs. Currently, the TianQin project has made important progress in the precision gravity measurement facility, the payload research base, the laser ranging station, the simulation facility for space-borne gravitation wave detection on ground, and the series test satellite for the TianQin project. Based on the long-term accumulation of relevant technology, the TianQin project team proposed the goal of achieving gravitational wave detection in the 2030s, and a 0123 plan roadmap is formulated, aiming to perform, step by step, lunar or relay satellite laser ranging, testing key technology like space-borne laser interferometry and drag-free control, verifying high precision space-borne laser interferometry technology, and ultimately detecting gravitational wave. By the 2030s, the scientific cooperation between scientists from all over the world and the use of various means to jointly conduct exploration and research on the Universe will face great development. So far, the TianQin project has held many international seminars and received extensive international attention and active participation. Currently, the TianQin Collaboration Group has been formally established, with a collaboration group advisory committee also established, consisting of scientists with significant influence in the field of gravitational wave detection all over the world. The TianQin project will establish a collaborative research or comprehensive cooperation agreement with foreign universities or research organizations, and vigorously promote the China-led space-borne gravitational wave detection business. Through extensive international cooperation, the TianQin project will unite domestic and foreign strengths and strive to take the lead in realizing the gravitational wave detection in the window of millihertz band.

Knowledge Co-production in Contested Spaces: An Evaluation of the North Slope Borough – Shell Baseline Studies Program

Supporting the development of trusted and usable science remains a key challenge in contested spaces. This paper evaluates a collaborative research agreement between the North Slope Borough of Alaska and Shell Exploration and Production Company—an agreement that was designed to improve collection of information and management of issues associated with the potential impacts of oil and gas development in the Arctic. The evaluation is based on six categories of knowledge co-production indicators: external factors, inputs, processes, outputs, outcomes, and impacts. Two sources of data were used to assess the indicators: interviews with steering committee members and external science managers (n = 16) and a review of steering committee minutes. Interpretation of the output and outcome indicators suggests that the Baseline Studies Program supported a broad range of research, though there were differences in how groups perceived the relevance and legitimacy of project outcomes. Several input, process, and external variables enabled the co-production of trusted science in an emergent boundary organization and contested space; these variables included governance arrangements, leveraged capacities, and the inclusion of traditional knowledge. Challenges to knowledge co-production on the North Slope include logistics, differences in cultures and decision contexts, and balancing trade-offs among perceived credibility, legitimacy, and relevance. Reinforced lessons learned included providing time to foster trust, developing adaptive governance approaches, and building capacity among scientists to translate community concerns into research questions.

Abstract P5-13-05: Overcoming barriers to achieve a successful breast cancer patient recruitment: Professionals' views

Abstract Accurate recruitment in performing clinical trials is crucial to avoid delays in the availability of potential beneficial treatments for patients. However, optimal strategies to improve it remain elusive and highly variable. The aim of this study was to identify the factors affecting recruitment from a multi-professional approach. Methods: A convergent mixed method study was used, including key informant in-depth interviews (n=13), 5 focus groups (n=40) and a 209-item Likert-scale survey for the measurement of a whole array of variables of interest (i.e. job attitudes, job satisfaction, job stressors and social status). A purposive sample of professionals from thirty-three clinical trial sites in Spain were targeted. Qualitative data were analyzed alongside quantitative data to document patterns and modifiers of recruitment performance. Audio material was recorded, transcribed verbatim and analyzed using the framework method. Findings: Pattern observed in qualitative data was confirmed in quantitative analysis. A total of 32 key barriers to successful patient recruitment were identified and clustered in three categories. The most commonly reported barriers and facilitators regarding a multifactorial approach were: System/organization: Counting on experienced recruiters and having a strong team-workforce awareness (92,3%); automated recruitment software, scientific culture, recruiting philosophy, adequate workload demands (88%); high stimuli and interprofessional trust (84%). However, lack of time devoted to clinical research in favor of assistance demands, excessive workload and bureaucratic tasks were the most salient stressors to fulfill professional research and recruitment responsibilities (54%). Working team conditions: Insufficient workforce support as well as high employee turnover contributed to emotional exhaustion and depersonalization and to a lower personal accomplishment (15%). Interpersonal relations affected not only motivation and performance but professionalism satisfaction with outcomes. Professional recruiter characteristics: Professionals with a high level of expertise and academic specialization (&amp;gt;5 years), greater active involvement in relevant clinical trials just as interprofessional prestige and recognition showed a greater satisfaction. Consequently, they were prompted to intensify their efforts to fulfill recruitment. The more effective clinical research settings were those better aligned with attributes for becoming high recruiters and with better multi-professional articulation. Suggestions to improve recruitment included providing professionals with devoted time for research, setting up collaborative research agreements, building a clinical research network, collaborative tumor registries, clinical trials data sharing resources, multidisciplinary functional units and committees, flexible staffing models and empowering oncologists/managers leadership. Conclusions: This study provided useful understanding of how to maximize patient recruitment at clinical research sites. Strong team-workforce and adequate workload were the most important identified factors for achieving it. Results will be used to inform professionals and stakeholders of the next steps needed and to engage them to fulfill accurate recruitment. Citation Format: Casas A, Gonzàlez X, Capelán M, Morales J, Fabián M, Ciruelos E, Gabriele G. Overcoming barriers to achieve a successful breast cancer patient recruitment: Professionals' views [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-13-05.

Trade Secrets in Collaborative Research Agreements Between Universities and Industry

Trade Secrets in Collaborative Research Agreements Between Universities and Industry

Strengthening African Population-Based Cancer Registration Through Regional Mentorship: UICC Fellowship Experience at Zimbabwe National Cancer Registry

Background: South Africa (SA) recently established an urban population-based cancer registry in Ekurhuleni metropolitan district in Gauteng Province. The Ekurhuleni Population-Based Cancer Registry (EPBCR) aims to inform cancer policy and comprehensive cancer control programs. The registry covers 3.5 million residents including public/private, rural/urban patients and a mix of the multiethnic SA population. The first complete year's data will be published in April 2018. It is crucial that high-quality data collected by newly established registries are comparable regionally and globally. The Union for International Cancer Control (UICC) fellowship provides a practical opportunity for South African National Cancer Registry staff to learn from the Zimbabwe National Cancer Registry (ZNCR), a well-established population-based registry in the region. Aim: To enhance the SA EPBCR through observation and application of methods for population-based cancer registration used at the ZNCR. Methods: A desktop review of published and unpublished articles/reports of the ZNCR was conducted. Semi-structured informal interviews were conducted with registry staff to understand data processes from case finding to reporting. Representative data sources were visited to understand case-finding processes. Results: The ZNCR was established in 1985 through a collaborative research agreement between the Ministry of Health (MoH) and International Agency for Research on Cancer (IARC). Its activities are overseen by a 17-member constituted multidisciplinary advisory committee. The registry staff comprise one registrar, one executive assistant (EA) and four health information assistants (HIA). The process of ensuring quality data are guided by the African Cancer Registry Network and the International Association of Cancer Registries standards for population-based cancer registries. The ZNCR uses a combination of active and passive case-finding methods where HIAs have unrestricted access to patient information in private and public sectors such as hospitals, pathology laboratories, radiotherapy centers and death registries. HIAs conduct patient interviews for accurate demographics and to complete missing information. Cases are coded according to International Classification of Diseases for Oncology-V3 and Canreg software is used for data entry, quality control and analysis. The hard copies are stored in locked cabinets in offices with restricted access. The data are then used for reporting and research. Conclusion: The support of government, commitment of advisory committee volunteers, highly trained and experienced staff are key elements behind the success of ZNCR. Strict adherence to international practices for population-based cancer registration has enabled ZNCR to produce high-quality data for research and cancer programs. The processes used by ZNCR will be customised and implemented at EPBCR.

Randomized Trial Of Amino Acid Mixture Combined With Physical Activity Promotion In Overweight Adults

PURPOSE: The purpose of this study was to test the efficacy of arginine, alanine, and phenylalanine mixture (A-mix) ingestion at 1,500 mg/day in combination with the promotion of physical activity for abdominal fat reduction in overweight adults. METHODS: A placebo-controlled, double-blind, parallel-group, randomized trial for 12 weeks combined with a 4-week follow-up period was conducted at a single center in Minato-ku, Tokyo, Japan, between December 2016 and May 2017. The data were examined between June and August 2017. The study participants were 200 overweight adults within the age of 20-64 years old. The participants were randomly assigned to the A-mix or a placebo group, and were administered 500-mL test beverage containing 1,500 mg or 0 mg of A-mix, respectively, for 12 weeks. All participants endeavored to maintain a physically active lifestyle between week 0 and week 12 through monthly sessions of physical activity. The primary endpoints were the 12-week changes in the abdominal total, subcutaneous, and visceral fat areas, as assessed by computed tomography. RESULTS: Of the 200 enrolled participants, 199 (99%) accomplished the 12-week intervention and 4-week follow-up period. The per-protocol-based analysis for 194 participants demonstrated that the abdominal total fat area decreased significantly in the A-mix group compared with that of the placebo group (difference, 10.0 cm2; 95% confidence interval, 0.4-19.6 cm2; P = 0.041). Comparable outcomes were acquired for the abdominal subcutaneous fat area (difference, 7.4 cm2; 95% confidence interval, 0.1-14.7 cm2; P = 0.047). No study-related unfavorable events occurred. CONCLUSIONS: A-mix supplementation in combination with physical activity promotion facilitated abdominal fat reduction in overweight adults. This trial was based on a collaborative research agreement between the University of Tsukuba Faculty of Medicine and Meiji Co., Ltd. K.U., C.S., and S.I. are employees of Meiji Co., Ltd.

Collaborative Research and Development, and Collaborative Research and Development Agreements in view of American Contract Law: Focused on Ownership of the Results, such as Intellectual Property Right, of Collaborative Research Between Large - sized company and Small - sized company

Collaborative Research and Development, and Collaborative Research and Development Agreements in view of American Contract Law: Focused on Ownership of the Results, such as Intellectual Property Right, of Collaborative Research Between Large - sized company and Small - sized company

MO-FG-BRA-06: Electromagnetic Beacon Insertion in Lung Cancer Patients and Resultant Surrogacy Errors for Dynamic MLC Tumour Tracking

Purpose: To assess endo-bronchial electromagnetic beacon insertion and to quantify the geometric accuracy of using beacons as a surrogate for tumour motion in real-time multileaf collimator (MLC) tracking of lung tumours. Methods: The LIGHT SABR trial is a world-first clinical trial in which the MLC leaves move with lung tumours in real time on a standard linear accelerator. Tracking is performed based on implanted electromagnetic beacons (CalypsoTM, Varian Medical Systems, USA) as a surrogate for tumour motion. Five patients have been treated and have each had three beacons implanted endo-bronchially under fluoroscopic guidance. The centre of mass (C.O.M) has been used to adapt the MLC in real-time. The geometric error in using the beacon C.O.M as a surrogate for tumour motion was measured by measuring the tumour and beacon C.O.M in all phases of the respiratory cycle of a 4DCT. The surrogacy error was defined as the difference in beacon and tumour C.O.M relative to the reference phase (maximum exhale). Results: All five patients have had three beacons successfully implanted with no migration between simulation and end of treatment. Beacon placement relative to tumour C.O.M varied from 14 to 74 mm and in one patient spanned two lobes. Surrogacy error was measured in each patient on the simulation 4DCT and ranged from 0 to 3 mm. Surrogacy error as measured on 4DCT was subject to artefacts in mid-ventilation phases. Surrogacy error was a function of breathing phase and was typically larger at maximum inhale. Conclusion: Beacon placement and thus surrogacy error is a major component of geometric uncertainty in MLC tracking of lung tumours. Surrogacy error must be measured on each patient and incorporated into margin calculation. Reduction of surrogacy error is limited by airway anatomy, however should be taken into consideration when performing beacon insertion and planning. This research is funded by Varian Medical Systems via a collaborative research agreement.

Allogeneic Stem Cell Transplantation in a Pediatric Patient with Whim Syndrome

WHIM syndrome (warts, hypogammaglobulinemia, infections, and myelokathexis) is a rare autosomal dominant immunodeficiency disorder that is caused by a gain in function in cysteine-X-cysteine chemokine receptor 4 ( CXCR4 ) gene. Affected individuals have recurrent infections of the respiratory tract and soft tissues, and marked susceptibility to warts caused by human papilloma viruses (HPV). Patients have an increased risk of malignancy (lymphoma) and HPV-associated cancers. The optimal therapy for WHIM syndrome has not been defined and treatment has been with supportive care using intravenous immunoglobulin (IVIG) and granulocyte colony stimulating factor (G-CSF). New CXCR4 antagonist therapies are still in either phase I trials (plerixafor) or considered experimental (Chlacone-4). A successful umbilical cord blood transplant has been reported by Kriven et al . Here we describe a successful matched unrelated allogeneic stem cell transplant (SCT) in a girl with WHIM syndrome caused by a known mutation in the CXCR4 gene. This patient was diagnosed at birth with familial congenital neutropenia as findings were similar to those for the patient9s mother and maternal grandmother. A complete blood count showed pancytopenia (WBC= 1.03 x10 3 /µL, hemoglobin= 9.2 g/dL, platelet count= 74,000/µL, ANC= 70). Despite G-CSF and IVIG therapy, the patient had recurrent infections with sinusitis and pneumonia, along with progressive organomegaly with progressive pancytopenia. At the age of 4, the patient underwent matched unrelated SCT with a fully ablative regimen [busulfan 0.8 mg/kg/dose for 16 doses (days -9, -8, -7, and -6), cyclophosphamide 50 mg/kg/dose for 4 doses (days -5, -4, -3, and -2) and alemtuzumab 5 mg/day (weight-based dosage) for 3 doses (days -5, -4, and -3)]. Tacrolimus and mini methotrexate (on days +1, +3, +6 and +11) were given for GVHD prophylaxis. Neutrophil and platelet engraftment occurred on days + 21 and + 45, respectively. The patient is 100% donor chimeric. Post-transplant course has been complicated by grade II skin GVHD treated successfully with oral and topical steroids. The patient also developed adenovirus, BK virus and HHV-6 viral reactivations but without disease. The patient is now approximately 2 years post SCT with durable engraftment, normal humoral immune reconstitution and no chronic GVHD. Thus, stem cell transplant following myeloablative conditioning can be accomplished for patients with WHIM syndrome. Furthermore, transplantation performed at the patient9s young age likely prevented complications of recurrent infections and warts. Disclosures Allen: NovImmune: Consultancy, Other: unpaid; Roche: Consultancy, Other: unpaid. Heslop: Cell Medica: Other: Licensing Agreement; Celgene: Other: Collaborative research agreement.