435 research outputs found

    Computational modeling of ovarian cancer dynamics suggests optimal strategies for therapy and screening

    Get PDF
    High-grade serous tubo-ovarian carcinoma (HGSC) is a major cause of cancer-related death. Treatment is not uniform, with some patients undergoing primary debulking surgery followed by chemotherapy (PDS) and others being treated directly with chemotherapy and only having surgery after three to four cycles (NACT). Which strategy is optimal remains controversial. We developed a mathematical framework that simulates hierarchical or stochastic models of tumor initiation and reproduces the clinical course of HGSC. After estimating parameter values, we infer that most patients harbor chemoresistant HGSC cells at diagnosis and that, if the tumor burden is not too large and complete debulking can be achieved, PDS is superior to NACT due to better depletion of resistant cells. We further predict that earlier diagnosis of primary HGSC, followed by complete debulking, could improve survival, but its benefit in relapsed patients is likely to be limited. These predictions are supported by primary clinical data from multiple cohorts. Our results have clear implications for these key issues in HGSC management

    Do teashirt family genes specify trunk identity? Insights from the single tiptop/teashirt homolog of Tribolium castaneum

    Get PDF
    The Drosophila teashirt gene acts in concert with the homeotic selector (Hox) genes to specify trunk (thorax and abdomen) identity. There has been speculation that this trunk-specifying function might be very ancient, dating back to the common ancestor of insects and vertebrates. However, other evidence suggests that the role of teashirt in trunk identity is not well conserved even within the Insecta. To address this issue, we have analyzed the function of Tc-tiotsh, the lone teashirt family member in the red flour beetle, Tribolium castaneum. Although Tc-tiotsh is important for aspects of both embryonic and imaginal development including some trunk features, we find no evidence that it acts as a trunk identity gene. We discuss this finding in the context of recent insights into the evolution and function of the Drosophila teashirt family genes

    Patients' views on responsibility for the management of musculoskeletal disorders – A qualitative study

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Musculoskeletal disorders are very common and almost inevitable in an individual's lifetime. Enabling self-management and allowing the individual to take responsibility for care is stated as desired in the management of these disorders, but this may be asking more than people can generally manage. A willingness among people to take responsibility for musculoskeletal disorders and not place responsibility out of their hands or on employers but to be shared with medical professionals has been shown. The aim of the present study was to describe how people with musculoskeletal disorders think and reason regarding responsibility for prevention, treatment and management of the disorder.</p> <p>Methods</p> <p>Individual interviews with a strategic sample of 20 individuals with musculoskeletal disorders were performed. The interviews were tape-recorded, transcribed verbatim and analysed according to qualitative content analysis.</p> <p>Results</p> <p>From the interviews an overarching theme was identified: own responsibility needs to be met. The analysis revealed six interrelated categories: Taking on responsibility, Ambiguity about responsibility, Collaborating responsibility, Complying with recommendations, Disclaiming responsibility, and Responsibility irrelevant. These categories described different thoughts and reasoning regarding the responsibility for managing musculoskeletal disorders. Generally the responsibility for prevention of musculoskeletal disorders was described to lie primarily on society/authorities as they have knowledge of what to prevent and how to prevent it. When musculoskeletal disorders have occurred, health care should provide fast accessibility, diagnosis, prognosis and support for recovery. For long-term management, the individuals themselves are responsible for making the most out of life despite disorders.</p> <p>Conclusion</p> <p>No matter what the expressions of responsibility for musculoskeletal disorders are, own responsibility needs to be met by society, health care, employers and family in an appropriate way, with as much or as little of the "right type" of support needed, based on the individual's expectations.</p

    Knowledge systems, health care teams, and clinical practice: a study of successful change

    Get PDF
    Clinical teams are of growing importance to healthcare delivery, but little is known about how teams learn and change their clinical practice. We examined how teams in three US hospitals succeeded in making significant practice improvements in the area of antimicrobial resistance. This was a qualitative cross-case study employing Soft Knowledge Systems as a conceptual framework. The purpose was to describe how teams produced, obtained, and used knowledge and information to bring about successful change. A purposeful sampling strategy was used to maximize variation between cases. Data were collected through interviews, archival document review, and direct observation. Individual case data were analyzed through a two-phase coding process followed by the cross-case analysis. Project teams varied in size and were multidisciplinary. Each project had more than one champion, only some of whom were physicians. Team members obtained relevant knowledge and information from multiple sources including the scientific literature, experts, external organizations, and their own experience. The success of these projects hinged on the teams' ability to blend scientific evidence, practical knowledge, and clinical data. Practice change was a longitudinal, iterative learning process during which teams continued to acquire, produce, and synthesize relevant knowledge and information and test different strategies until they found a workable solution to their problem. This study adds to our understanding of how teams learn and change, showing that innovation can take the form of an iterative, ongoing process in which bits of K&I are assembled from multiple sources into potential solutions that are then tested. It suggests that existing approaches to assessing the impact of continuing education activities may overlook significant contributions and more attention should be given to the role that practical knowledge plays in the change process in addition to scientific knowledge

    At work and play; business events as entrepreneurial spaces

    Get PDF
    There is inadequate literature examining, and illustrating, the integration of play and business events and how this facilitates entrepreneurial opportunities. Business events are distinct from the patterns of ordinary life and increasingly offer participants an ‘invitation to play’, encouraging socialization and trust. This article examines the role of play in the design of business events and how this can enable entrepreneurial outcomes. Through examination of diverse, but related, literature and three contrasting, empirically based, case studies, this article illustrates how event creators take an increasingly entrepreneurial approach. These cases range from a charity event with participants sleeping with the homeless on a city’s streets, a major flooring manufacturer designing events to outsource innovation and an imaginative event activity termed ‘coffee and papers’. Designing events that fuse, rather than polarize, play and work enables business event settings, and activities, which trigger entrepreneurial outcomes. This article adds to the embryonic literature and concludes by identifying four principles that underlie the effectual facilitation of play in a business event setting

    Explicit hypoxia targeting with tumor suppression by creating an “obligate” anaerobic Salmonella Typhimurium strain

    Get PDF
    Using bacteria as therapeutic agents against solid tumors is emerging as an area of great potential in the treatment of cancer. Obligate and facultative anaerobic bacteria have been shown to infiltrate the hypoxic regions of solid tumors, thereby reducing their growth rate or causing regression. However, a major challenge for bacterial therapy of cancer with facultative anaerobes is avoiding damage to normal tissues. Consequently the virulence of bacteria must be adequately attenuated for therapeutic use. By placing an essential gene under a hypoxia conditioned promoter, Salmonella Typhimurium strain SL7207 was engineered to survive only in anaerobic conditions (strain YB1) without otherwise affecting its functions. In breast tumor bearing nude mice, YB1 grew within the tumor, retarding its growth, while being rapidly eliminated from normal tissues. YB1 provides a safe bacterial vector for anti-tumor therapies without compromising the other functions or tumor fitness of the bacterium as attenuation methods normally do

    Toward optimal implementation of cancer prevention and control programs in public health: A study protocol on mis-implementation

    Get PDF
    Abstract Background Much of the cancer burden in the USA is preventable, through application of existing knowledge. State-level funders and public health practitioners are in ideal positions to affect programs and policies related to cancer control. Mis-implementation refers to ending effective programs and policies prematurely or continuing ineffective ones. Greater attention to mis-implementation should lead to use of effective interventions and more efficient expenditure of resources, which in the long term, will lead to more positive cancer outcomes. Methods This is a three-phase study that takes a comprehensive approach, leading to the elucidation of tactics for addressing mis-implementation. Phase 1: We assess the extent to which mis-implementation is occurring among state cancer control programs in public health. This initial phase will involve a survey of 800 practitioners representing all states. The programs represented will span the full continuum of cancer control, from primary prevention to survivorship. Phase 2: Using data from phase 1 to identify organizations in which mis-implementation is particularly high or low, the team will conduct eight comparative case studies to get a richer understanding of mis-implementation and to understand contextual differences. These case studies will highlight lessons learned about mis-implementation and identify hypothesized drivers. Phase 3: Agent-based modeling will be used to identify dynamic interactions between individual capacity, organizational capacity, use of evidence, funding, and external factors driving mis-implementation. The team will then translate and disseminate findings from phases 1 to 3 to practitioners and practice-related stakeholders to support the reduction of mis-implementation. Discussion This study is innovative and significant because it will (1) be the first to refine and further develop reliable and valid measures of mis-implementation of public health programs; (2) bring together a strong, transdisciplinary team with significant expertise in practice-based research; (3) use agent-based modeling to address cancer control implementation; and (4) use a participatory, evidence-based, stakeholder-driven approach that will identify key leverage points for addressing mis-implementation among state public health programs. This research is expected to provide replicable computational simulation models that can identify leverage points and public health system dynamics to reduce mis-implementation in cancer control and may be of interest to other health areas
    • 

    corecore