Health Self-Management Applications in the Workplace:Multidisciplinary studies on worker behaviour and autonomy

Health Self-Management Applications (HSMAs) have become popular tools to self-regulate behaviour in the workplace. HSMAs give users feedback on their bodily functioning, and thereby aim to stimulate the improvement of worker behaviour. HSMA feedback can vary from delayed to real-time messaging, can be focused on past performance or on future development, and it can increasingly be adjusted to the user’s preferences. The use of technologies such as HSMAs raises questions about effectiveness and the potential effects on worker autonomy. This thesis aims to examine how HSMAs can responsibly and effectively be developed and used to stimulate workers to show more healthy behaviours. This involves two experimental field studies, and a case study of SPRINT@work, the multidisciplinary research project this thesis is a part of. This thesis shows that workers are unlikely to alter behaviour that they can identify themselves, such as prolonged sitting behaviour, but do alter behaviour that they were unaware of, such as fatigue during typing. The use of HSMAs is shown to affect the autonomy of workers, especially for those workers with higher BMI. We find that such ethical issues can be prevented by using a context-specific ethics, and that explicating the privacy and autonomy of workers in the work environment can improve the responsible use of HSMAs. This research combined qualitative and quantitative data from both experimental and case study research into a multidisciplinary view on the responsible and effective development of HSMAs for the work environment

Cancer systems biology: exploring cancer-associated genes on cellular networks

Genomic alterations lead to cancer complexity and form a major hurdle for a comprehensive understanding of the molecular mechanisms underlying oncogenesis. In this review, we describe the recent advances in studying cancer-associated genes from a systems biological point of view. The integration of known cancer genes onto protein and signaling networks reveals the characteristics of cancer genes within networks. This approach shows that cancer genes often function as network hub proteins which are involved in many cellular processes and form focal nodes in the information exchange between many signaling pathways. Literature mining allows constructing gene-gene networks, in which new cancer genes can be identified. The gene expression profiles of cancer cells are used for reconstructing gene regulatory networks. By doing so, the genes, which are involved in the regulation of cancer progression, can be picked up from these networks after which their functions can be further confirmed in the laboratory.Comment: More similar papers at http://www.bri.nrc.ca/wan

Glycoproteomic analysis of two mouse mammary cell lines during transforming growth factor (TGF)-β induced epithelial to mesenchymal transition

<p>Abstract</p> <p>Background</p> <p>TGF-β acts as an antiproliferative factor in normal epithelial cells and at early stages of oncogenesis. However, later in tumor development TGF-β can become tumor promoting through mechanisms including the induction of epithelial-to-mesenchymal transition (EMT), a process that is thought to contribute to tumor progression, invasion and metastasis. To identify EMT-related breast cancer therapeutic targets and biomarkers, we have used two proteomic approaches to find proteins that change in abundance upon the induction of EMT by TGF-β in two mouse mammary epithelial cell lines, NMuMG and BRI-JM01.</p> <p>Results</p> <p>Preliminary experiments based on two-dimensional electrophoresis of a hydrophobic cell fraction identified only 5 differentially expressed proteins from BRI-JM01 cells. Since 3 of these proteins were glycoproteins, we next used the lectin, wheat germ agglutinin (WGA), to enrich for glycoproteins, followed by relative quantification of tryptic peptides using a label-free LC-MS based method. Using these approaches, we identified several proteins that are modulated during the EMT process, including cell adhesion molecules (several members of the Integrin family, Fibronectin, Activated leukocyte cell adhesion molecule, and Neural cell adhesion molecule 1) and regulators of cellular signaling (Tumor-associated calcium signal transducer 2, Basigin).</p> <p>Conclusion</p> <p>Interestingly, despite the fact that TGF-β induces similar EMT phenotypes in NMuMG and BRI-JM01 cells, the proteomic results for the two cell lines showed only minimal overlap. These differences likely result in part from the conservative cut-off values used to define differentially-expressed proteins in these experiments. Alternatively, it is possible that the two cell lines may use different mechanisms to achieve an EMT transition.</p

Identification of high-quality cancer prognostic markers and metastasis network modules

There has been great interest in attempting to identify gene expression signatures that predict cancer survival. In this study a new algorithm is developed to analyse gene expression datasets that accurately classify both ER+ and ER− breast cancers into low- and high-risk groups

PO-033 Identification and functional evaluation of monoclonal antibodies specifically targeting human carbonic anhydrase IX

Introduction Poor vascularisation of solid tumours leads to inadequate nutrient and oxygen supplies which forces tumour cells to reprogram their metabolism. As a consequence the tumour cell's environment becomes acidic and hypoxic. This, in turn, triggers signalling cascades involving for example heterodimeric hypoxia-inducible factor (HIF). Activation of this hypoxia-induced transcriptional program is crucial for the survival of tumour cells in their hostile microenvironment but also their ability to metastasize. One of the genes upregulated through the HIF pathway is carbonic anhydrase (CA)-IX (CAIX, gene G250/MN-encoded transmembrane protein). CA-IX catalyses carbon dioxide (CO2) thereby generating a proton (H+) and bicarbonate (HCO3-), the latter of which is transported back into the cell and utilised to help safeguard intracellular pH (pHi) stability. Except for the stomach and the gallbladder, CA-IX expression is negligible in normal tissues. In contrast, a broad range of tumours express high levels of CA-IX, where the protein can serve as a biomarker for the early stages of tumour development but also as tumour marker of hypoxia associated with resistance to chemotherapy and radiotherapy. Material and methods Preclinical and clinical studies have shown that CA-IX is a promising therapeutic target for detection and therapy for several cancer types. To date only a limited number of ant-CAIX monoclonal antibodies (mAbs) have been available for clinical testing as therapeutic and imaging agents. In the current study, we generated and functionally categorised a panel of 51 mouse mAbs that specifically bind to human CA-IX. Results and discussions Characterisation of the mAbs revealed that of the mAbs with the best biophysical characteristics, three3 mAbs are suitable as an antibody-drug conjugate (ADC), two2 mAbs inhibit the CA-IX enzyme activity, and one1 mAb that is suitable for CA-IX imaging purposes. Conclusion These preliminary data presented here could thus form the basis for the development of novel CA-IX targeted immunotherapies and diagnostic tools for the treatment of cancer

Cancer systems biology: exploring cancer-associated genes on cellular networks

Genomic alterations lead to cancer complexity and form a major hurdle for comprehensive understanding of the molecular mechanisms underlying oncogenesis. In this review, we describe recent advances in studying cancer-associated genes from a systems biology point of view. The integration of known cancer genes onto protein and signaling networks reveals the characteristics of cancer genes within networks. This approach shows that cancer genes often function as network hub proteins which are involved in many cellular processes and form focal nodes in information exchange between many signaling pathways. Literature mining allows constructing gene-gene networks, in which new cancer genes can be identified. The gene expression profiles of cancer cells are used for reconstructing gene regulatory networks. By doing so, genes which are involved in the regulation of cancer progression can be picked up from these networks, after which their functions can be further confirmed in the laboratoryNRC publication: Ye

Ethics in Design and Implementation of Technologies for Workplace Health Promotion: A Call for Discussion

Aim: This study aims to initiate discussion on the ethical issues surrounding the development and implementation of technologies for workplace health promotion. We believe this is a neglected topic and such a complex field of study that we cannot come up with solutions easily or quickly. Therefore, this study is the starting point of a discussion about the ethics of and the need for policies around technologies for workplace health promotion. Method: Based on a literature review, the present study outlines current knowledge of ethical issues in research, development, and implementation of technologies in the workplace. Specifically, the focus is on two ethical issues that play an important role in the worker–employer relation: privacy and autonomy. Application: Two cases indicative for a multidisciplinary project aimed at developing and evaluating sensor and intervention technologies that contribute to keeping ageing workers healthy and effectively employable are explored. A context-specific approach of ethics is used to investigate ethical issues during the development and implementation of sensor and intervention technologies. It is a holistic approach toward the diverse field of participants and stakeholders, and the diversity in perceptions of relevant values, depending on their respective professional languages. Discussion: The results show how protecting the privacy and autonomy of workers cannot be seen as stand-alone issues, but, rather, there is interplay between these values, the work context, and the responsibilities of workers and employers. Consequently, technologies in this research project are designed to improve worker conscientious autonomy, while concurrently creating balance between privacy and health, and assigning responsibilities to appropriate stakeholders. Conclusion: Focusing on a contextual conceptualisation of the ethical principles in the design and implementation of digital health technologies helps to avoid compartmentalization, out-of-context generalisation, and neglect of identifying responsibilities. Although it is a long reiterative process in which all stakeholders need to be included in order to assess all ethical issues sufficiently, this process is crucial to achieving the intended goal of a technology. Having laid out the landscape and problems of ethics around technologies for workplace health promotion, we believe policies and standards, and a very overdue discussion about these, are needed

Expression of TGF-beta type II receptor antisense RNA impairs TGF-beta signaling in vitro and promotes mammary gland differentiation in vivo

NRC publication: Ye