Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years

Competition Between Auctions

Even though auctions are capturing an increasing share of commerce, they are typically treated in the theoretical economics literature as isolated. That is, an auction is typically treated as a single seller facing multiple buyers or as a single buyer facing multiple sellers. In this paper, we review the state of the art of competition between auctions. We consider three different types of competition: competition between auctions, competition between formats, and competition between auctioneers vying for auction traffic. We highlight the newest experimental, statistical and analytical methods in the analysis of competition between auctions.auctions, bidding, competition, auction formats, auction houses

User-centered visual analysis using a hybrid reasoning architecture for intensive care units

One problem pertaining to Intensive Care Unit information systems is that, in some cases, a very dense display of data can result. To ensure the overview and readability of the increasing volumes of data, some special features are required (e.g., data prioritization, clustering, and selection mechanisms) with the application of analytical methods (e.g., temporal data abstraction, principal component analysis, and detection of events). This paper addresses the problem of improving the integration of the visual and analytical methods applied to medical monitoring systems. We present a knowledge- and machine learning-based approach to support the knowledge discovery process with appropriate analytical and visual methods. Its potential benefit to the development of user interfaces for intelligent monitors that can assist with the detection and explanation of new, potentially threatening medical events. The proposed hybrid reasoning architecture provides an interactive graphical user interface to adjust the parameters of the analytical methods based on the users' task at hand. The action sequences performed on the graphical user interface by the user are consolidated in a dynamic knowledge base with specific hybrid reasoning that integrates symbolic and connectionist approaches. These sequences of expert knowledge acquisition can be very efficient for making easier knowledge emergence during a similar experience and positively impact the monitoring of critical situations. The provided graphical user interface incorporating a user-centered visual analysis is exploited to facilitate the natural and effective representation of clinical information for patient care

Training Competences in Industrial Risk Prevention with Lego® Serious Play®: A Case Study

This paper proposes the use of the Lego® Serious Play® (LSP) methodology as a facilitating tool for the introduction of competences for Industrial Risk Prevention by engineering students from the industrial branch (electrical, electronic, mechanical and technological engineering), presenting the results obtained in the Universities of Cadiz and Seville in the academic years 2017–2019. Current Spanish legislation does not reserve any special legal attribution, nor does it require specific competence in occupational risk prevention for the regulated profession of a technical industrial engineer (Order CIN 351:2009), and only does so in a generic way for that of an industrial engineer (Order CIN 311:2009). However, these universities consider the training in occupational health and safety for these future graduates as an essential objective in order to develop them for their careers in the industry. The approach is based on a series of challenges proposed (risk assessments, safety inspections, accident investigations and fire protection measures, among others), thanks to the use of “gamification” dynamics with Lego® Serious Play®. In order to carry the training out, a set of specific variables (industrial sector, legal and regulatory framework, business organization and production system), and transversal ones (leadership, teamwork, critical thinking and communication), are incorporated. Through group models, it is possible to identify dangerous situations, establish causes, share and discuss alternative proposals and analyze the economic, environmental and organizational impact of the technical solutions studied, as well as take the appropriate decisions, in a creative, stimulating, inclusive and innovative context. In this way, the theoretical knowledge which is acquired is applied to improve safety and health at work and foster the prevention of occupational risks, promoting the commitment, effort, motivation and proactive participation of the student teams.Spanish Ministry of Science, Innovation and Universities / European Social Fund: Ramón y Cajal contract (RYC-2017-22222

Training Competences in Industrial Risk Prevention with Lego (R) Serious Play (R): A Case Study

This paper proposes the use of the Lego (R) Serious Play (R) (LSP) methodology as a facilitating tool for the introduction of competences for Industrial Risk Prevention by engineering students from the industrial branch (electrical, electronic, mechanical and technological engineering), presenting the results obtained in the Universities of Cadiz and Seville in the academic years 2017-2019. Current Spanish legislation does not reserve any special legal attribution, nor does it require specific competence in occupational risk prevention for the regulated profession of a technical industrial engineer (Order CIN 351:2009), and only does so in a generic way for that of an industrial engineer (Order CIN 311:2009). However, these universities consider the training in occupational health and safety for these future graduates as an essential objective in order to develop them for their careers in the industry. The approach is based on a series of challenges proposed (risk assessments, safety inspections, accident investigations and fire protection measures, among others), thanks to the use of "gamification" dynamics with Lego (R) Serious Play (R). In order to carry the training out, a set of specific variables (industrial sector, legal and regulatory framework, business organization and production system), and transversal ones (leadership, teamwork, critical thinking and communication), are incorporated. Through group models, it is possible to identify dangerous situations, establish causes, share and discuss alternative proposals and analyze the economic, environmental and organizational impact of the technical solutions studied, as well as take the appropriate decisions, in a creative, stimulating, inclusive and innovative context. In this way, the theoretical knowledge which is acquired is applied to improve safety and health at work and foster the prevention of occupational risks, promoting the commitment, effort, motivation and proactive participation of the student teams

Shrinkage Estimators in Online Experiments

We develop and analyze empirical Bayes Stein-type estimators for use in the estimation of causal effects in large-scale online experiments. While online experiments are generally thought to be distinguished by their large sample size, we focus on the multiplicity of treatment groups. The typical analysis practice is to use simple differences-in-means (perhaps with covariate adjustment) as if all treatment arms were independent. In this work we develop consistent, small bias, shrinkage estimators for this setting. In addition to achieving lower mean squared error these estimators retain important frequentist properties such as coverage under most reasonable scenarios. Modern sequential methods of experimentation and optimization such as multi-armed bandit optimization (where treatment allocations adapt over time to prior responses) benefit from the use of our shrinkage estimators. Exploration under empirical Bayes focuses more efficiently on near-optimal arms, improving the resulting decisions made under uncertainty. We demonstrate these properties by examining seventeen large-scale experiments conducted on Facebook from April to June 2017

Games for a new climate: experiencing the complexity of future risks

This repository item contains a single issue of the Pardee Center Task Force Reports, a publication series that began publishing in 2009 by the Boston University Frederick S. Pardee Center for the Study of the Longer-Range Future.This report is a product of the Pardee Center Task Force on Games for a New Climate, which met at Pardee House at Boston University in March 2012. The 12-member Task Force was convened on behalf of the Pardee Center by Visiting Research Fellow Pablo Suarez in collaboration with the Red Cross/Red Crescent Climate Centre to “explore the potential of participatory, game-based processes for accelerating learning, fostering dialogue, and promoting action through real-world decisions affecting the longer-range future, with an emphasis on humanitarian and development work, particularly involving climate risk management.” Compiled and edited by Janot Mendler de Suarez, Pablo Suarez and Carina Bachofen, the report includes contributions from all of the Task Force members and provides a detailed exploration of the current and potential ways in which games can be used to help a variety of stakeholders – including subsistence farmers, humanitarian workers, scientists, policymakers, and donors – to both understand and experience the difficulty and risks involved related to decision-making in a complex and uncertain future. The dozen Task Force experts who contributed to the report represent academic institutions, humanitarian organization, other non-governmental organizations, and game design firms with backgrounds ranging from climate modeling and anthropology to community-level disaster management and national and global policymaking as well as game design.Red Cross/Red Crescent Climate Centr

Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care