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"Roth, Michael"
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Navigating financial toxicity in patients with cancer: A multidisciplinary management approach
Approximately one-half of individuals with cancer face personal economic burdens associated with the disease and its treatment, a problem known as financial toxicity (FT). FT more frequently affects socioeconomically vulnerable individuals and leads to subsequent adverse economic and health outcomes. Whereas multilevel systemic factors at the policy, payer, and provider levels drive FT, there are also accompanying intervenable patient-level factors that exacerbate FT in the setting of clinical care delivery. The primary strategy to intervene on FT at the patient level is financial navigation. Financial navigation uses comprehensive assessment of patients' risk factors for FT, guidance toward support resources, and referrals to assist patient financial needs during cancer care. Social workers or nurse navigators most frequently lead financial navigation. Oncologists and clinical provider teams are multidisciplinary partners who can support optimal FT management in the context of their clinical roles. Oncologists and clinical provider teams can proactively assess patient concerns about the financial hardship and employment effects of disease and treatment. They can respond by streamlining clinical treatment and care delivery planning and incorporating FT concerns into comprehensive goals of care discussions and coordinated symptom and psychosocial care. By understanding how age and life stage, socioeconomic, and cultural factors modify FT trajectory, oncologists and multidisciplinary health care teams can be engaged and informative in patient-centered, tailored FT management. The case presentations in this report provide a practical context to summarize authors' recommendations for patient-level FT management, supported by a review of key supporting evidence and a discussion of challenges to mitigating FT in oncology care.
Journal Article
Immune infiltration and PD-L1 expression in the tumor microenvironment are prognostic in osteosarcoma
Osteosarcoma patient survival has remained stagnant for 30 years. Novel therapeutic approaches are needed to improve outcomes. We examined the expression of Programmed Death Ligand 1 (PD-L1) and defined the tumor immune microenvironment to assess the prognostic utility in osteosarcoma. PD-L1 expression in osteosarcoma was examined in two patient cohorts using immunohistochemistry (IHC) (n = 48, n = 59) and expression was validated using quantitative real time PCR (n = 21) and western blotting (n = 9). IHC was used to determine the presence of tumor infiltrating lymphocytes and antigen-presenting cells (APCs) in the tumor. Expression of PD-L1 was correlated with immune cell infiltration and event-free-survival (EFS). The 25% of primary osteosarcoma tumors that express PD-L1 were more likely to contain cells that express PD-1 than PD-L1 negative tumors (91.7% vs 47.2%, p = 0.002). Expression of PD-L1 was significantly associated with the presence of T cells, dendritic cells, and natural killer cells. Although all immune cell types examined were present in osteosarcoma samples, only infiltration by dendritic cells (28.3%
vs.
83.9%, p = 0.001) and macrophages (45.5%
vs.
84.4%, p = 0.031) were associated with worse five-year-EFS. PD-L1 expression was significantly associated with poorer five-year-EFS (25.0%.
vs.
69.4%, p = 0.014). Further studies in osteosarcoma are needed to determine if targeting the PD-L1:PD-1 axis improves survival.
Journal Article
What more in/for science education : an ethnomethodological perspective
Annotation What more is there in and for science education to do in terms of researching science lessons? A lot, the author suggests, if research turns away from studying science education extracting social facts using special methods, which journal articles require to state, to studying the work and methods by means of which participants themselves create their structured world of science lessons. This book presents, with concrete materials from an inquiry-oriented physics course, a way of doing science education research that radically differs from existing approaches. This book articulates this approach for a science education audience, where this approach is by and large unknown, and where the primary literature is often experienced as impenetrable and as requiring years of work to gain entry. Consistent with this different approach, those materials are used that constitute the way in which the refl exive production of social order is observed by the actors (teachers, students) themselves.
Book
Pelargonium sidoides radix extract EPs 7630 reduces rhinovirus infection through modulation of viral binding proteins on human bronchial epithelial cells
Bronchial epithelial cells are the first target cell for rhinovirus infection. The course of viral infections in patients with acute bronchitis, asthma and COPD can be improved by oral application of Pelargonium sidoides radix extract; however, the mechanism is not well understood. This study investigated the in vitro effect of Pelargonium sidoides radix extract (EPs 7630) on the expression of virus binding cell membrane and host defence supporting proteins on primary human bronchial epithelial cells (hBEC). Cells were isolated from patients with severe asthma (n = 6), moderate COPD (n = 6) and non-diseased controls (n = 6). Protein expression was determined by Western-blot and immunofluorescence. Rhinovirus infection was determined by immunofluorescence as well as by polymerase chain reaction. Cell survival was determined by manual cell count after live/death immunofluorescence staining. All parameters were determined over a period of 3 days. The results show that EPs 7630 concentration-dependently and significantly increased hBEC survival after rhinovirus infection. This effect was paralleled by decreased expression of the inducible co-stimulator (ICOS), its ligand ICOSL and cell surface calreticulin (C1qR). In contrast, EPs 7630 up-regulated the expression of the host defence supporting proteins β-defensin-1 and SOCS-1, both in rhinovirus infected and un-infected hBEC. The expression of other virus interacting cell membrane proteins such as MyD88, TRL2/4 or ICAM-1 was not altered by EPs 7630. The results indicate that EPs 7630 may reduce rhinovirus infection of human primary BEC by down-regulating cell membrane docking proteins and up-regulating host defence proteins.
Journal Article
Immunologic and Non-Immunologic Mechanisms Leading to Airway Remodeling in Asthma
Asthma increases worldwide without any definite reason and patient numbers double every 10 years. Drugs used for asthma therapy relax the muscles and reduce inflammation, but none of them inhibited airway wall remodeling in clinical studies. Airway wall remodeling can either be induced through pro-inflammatory cytokines released by immune cells, or direct binding of IgE to smooth muscle cells, or non-immunological stimuli. Increasing evidence suggests that airway wall remodeling is initiated early in life by epigenetic events that lead to cell type specific pathologies, and modulate the interaction between epithelial and sub-epithelial cells. Animal models are only available for remodeling in allergic asthma, but none for non-allergic asthma. In human asthma, the mechanisms leading to airway wall remodeling are not well understood. In order to improve the understanding of this asthma pathology, the definition of “remodeling” needs to be better specified as it summarizes a wide range of tissue structural changes. Second, it needs to be assessed if specific remodeling patterns occur in specific asthma pheno- or endo-types. Third, the interaction of the immune cells with tissue forming cells needs to be assessed in both directions; e.g., do immune cells always stimulate tissue cells or are inflamed tissue cells calling immune cells to the rescue? This review aims to provide an overview on immunologic and non-immunologic mechanisms controlling airway wall remodeling in asthma.
Journal Article
On meaning and mental representation : a pragmatic approach
Annotation This book is about language in STEM research and about how it is thought about: as something that somehow refers to something else not directly accessible, often meaning, mental representation, or conception. Using the analyses of real data and analyses of the way certain concepts are used in the scientifi c literature, such as \"meaning,\" this book reframes the discussion about meaning, mental representation, and conceptions consistent with the pragmatic approaches that we have become familiar with through the works of K. Marx, L.S. Vygotsky, M.M. Bakhtin, V.N. Volo inov, L. Wittgenstein, F. Mikhailov, R. Rorty, and J. Derrida, to name but a few. All of these scholars, in one or another way, articulate a critique of a view of language that has been developed in a metaphysical approach from Plato through Kant and modern constructivism; this view of language, which already for Wittgenstein was an outmoded view in the middle of the last century, continuous to be alive today and dominating the way language is thought about and theorized.
Book
The Ensemble Kalman filter: a signal processing perspective
The ensemble Kalman filter (EnKF) is a Monte Carlo-based implementation of the Kalman filter (KF) for extremely high-dimensional, possibly nonlinear, and non-Gaussian state estimation problems. Its ability to handle state dimensions in the order of millions has made the EnKF a popular algorithm in different geoscientific disciplines. Despite a similarly vital need for scalable algorithms in signal processing, e.g., to make sense of the ever increasing amount of sensor data, the EnKF is hardly discussed in our field.
This self-contained review is aimed at signal processing researchers and provides all the knowledge to get started with the EnKF. The algorithm is derived in a KF framework, without the often encountered geoscientific terminology. Algorithmic challenges and required extensions of the EnKF are provided, as well as relations to sigma point KF and particle filters. The relevant EnKF literature is summarized in an extensive survey and unique simulation examples, including popular benchmark problems, complement the theory with practical insights. The signal processing perspective highlights new directions of research and facilitates the exchange of potentially beneficial ideas, both for the EnKF and high-dimensional nonlinear and non-Gaussian filtering in general.
Journal Article