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- Gonzalez-Ericsson, Paula, et al.
(författare)
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The path to a better biomarker: application of a risk management framework for the implementation of PD‐L1 and TILs as immuno‐oncology biomarkers into breast cancer clinical trials and daily practice
- 2020
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Ingår i: Journal of Pathology. - : Wiley. - 1096-9896 .- 0022-3417. ; 250:5, s. 667-684
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Forskningsöversikt (refereegranskat)abstract
- Immune checkpoint inhibitor therapies targeting PD‐1/PD‐L1 are now the standard of care in oncology across several hematologic and solid tumor types, including triple negative breast cancer (TNBC). Patients with metastatic or locally advanced TNBC with PD‐L1 expression on immune cells occupying ≥1% of tumor area demonstrated survival benefit with the addition of atezolizumab to nab‐paclitaxel. However, concerns regarding variability between immunohistochemical PD‐L1 assay performance and inter‐reader reproducibility have been raised. High tumor‐infiltrating lymphocytes (TILs) have also been associated with response to PD‐1/PD‐L1 inhibitors in patients with breast cancer (BC). TILs can be easily assessed on hematoxylin and eosin–stained slides and have shown reliable inter‐reader reproducibility. As an established prognostic factor in early stage TNBC, TILs are soon anticipated to be reported in daily practice in many pathology laboratories worldwide. Because TILs and PD‐L1 are parts of an immunological spectrum in BC, we propose the systematic implementation of combined PD‐L1 and TIL analyses as a more comprehensive immuno‐oncological biomarker for patient selection for PD‐1/PD‐L1 inhibition‐based therapy in patients with BC. Although practical and regulatory considerations differ by jurisdiction, the pathology community has the responsibility to patients to implement assays that lead to optimal patient selection. We propose herewith a risk‐management framework that may help mitigate the risks of suboptimal patient selection for immuno‐therapeutic approaches in clinical trials and daily practice based on combined TILs/PD‐L1 assessment in BC.
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- Abel, I, et al.
(författare)
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Overview of the JET results with the ITER-like wall
- 2013
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10, s. 104002-
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Tidskriftsartikel (refereegranskat)abstract
- Following the completion in May 2011 of the shutdown for the installation of the beryllium wall and the tungsten divertor, the first set of JET campaigns have addressed the investigation of the retention properties and the development of operational scenarios with the new plasma-facing materials. The large reduction in the carbon content (more than a factor ten) led to a much lower Z(eff) (1.2-1.4) during L- and H-mode plasmas, and radiation during the burn-through phase of the plasma initiation with the consequence that breakdown failures are almost absent. Gas balance experiments have shown that the fuel retention rate with the new wall is substantially reduced with respect to the C wall. The re-establishment of the baseline H-mode and hybrid scenarios compatible with the new wall has required an optimization of the control of metallic impurity sources and heat loads. Stable type-I ELMy H-mode regimes with H-98,H-y2 close to 1 and beta(N) similar to 1.6 have been achieved using gas injection. ELM frequency is a key factor for the control of the metallic impurity accumulation. Pedestal temperatures tend to be lower with the new wall, leading to reduced confinement, but nitrogen seeding restores high pedestal temperatures and confinement. Compared with the carbon wall, major disruptions with the new wall show a lower radiated power and a slower current quench. The higher heat loads on Be wall plasma-facing components due to lower radiation made the routine use of massive gas injection for disruption mitigation essential.
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- Calås, David, 1992-
(författare)
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Entrepreneurship as Organizing Desire
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Desire has been recognized as a crucial driver of entrepreneurial behavior and economic development for over a century, but despite its central position in the theorization of entrepreneurship, its underlying philosophical assumptions are rarely questioned. Seeking to pave the way for an understanding of desire as a quality of entrepreneurial practices, in this dissertation I uncover and problematize the prevailing understanding of desire in entrepreneurship research, which frequently entails viewing desire as a motivational force situated within the entrepreneurial subject.In the literature review I identify four different ways in which desire has previously been linked to entrepreneurship and used to understand entrepreneurial phenomena: (a) desire as a dispositional quality of the entrepreneur, (b) entrepreneurship as a means of producing desirable outcomes, (c) entrepreneurship as a desirable category in itself, and (d) entrepreneurship as a capacity to produce desiring. Against this backdrop, I suggest a framework of desire by looking to the theory of Pierre Bourdieu, drawing on his relational ontology and praxeology to understand desire as socially distributed and culturally constituted. I then use this Bourdieusian framework in a qualitative case study about the creation of a contemporary art exhibition venue, using the framework to explore entrepreneurial practices and to address the research inquiry into how desire is organized in the area of culture.The case study illustrates how desiring is deeply intertwined with entrepreneurial practices and demonstrates how a Bourdieusian perspective can be used to provide a more nuanced picture of the role desire plays in processes of organizational emergence. The dissertation ultimately brings forth a way of understanding desire through the metaphor of organizing desire, which I summarize in ten tenets. The study makes several contributions: Theoretically, it brings forth an understanding of organizing desire that can enrich entrepreneurship theory and give greater insight into entrepreneurial phenomena. Empirically, the study presents and analyzes a case of entrepreneurship situated within the area of arts and culture. Methodologically, the study offers a reflection on the challenges of studying organizations in emergence and adopts a Bourdieusian framework to arrive at an understanding of desire as a force that both organizes entrepreneurial practices and is organized by them. Finally, in practical terms this dissertation implies that desire need not be viewed as a quality exclusively belonging to individual entrepreneurs but can also be seen as part of the social world—an insight that comes with an ethical responsibility for other desiring beings.
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- Calås, David, et al.
(författare)
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Inter-ethnography : from individual beings to collective becoming
- 2021
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Ingår i: Organizational ethnography. - Cheltenham : Edward Elgar Publishing. - 9781786438096 - 9781786438102 ; , s. 91-109
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Bokkapitel (refereegranskat)abstract
- To highlight the ‘in-between’ aspects of organizational ethnography an alternative approach to traditional organizational ethnography is explored: inter-ethnography. This approach serves to destabilize the traditional notion of organizational ethnography as an individual and subjectivist project, as well as to escape the notion of a static field position from which the researcher – as observer or participant – learns about an organization’s culture. Inter-ethnography speaks in favour of a dynamic field presence in which the researchers’ cultural positions and understandings alter as they interact with different actors related to the studied organization. Inter-ethnography in this sense denotes a fundamental shift in epistemology: from individual beings to collective becoming. To illustrate the approach, we report from a doctoral course in qualitative methods that turned out to be a study of academic culture. The report progresses in a transparent manner from a realist account of the organizational setting via our confessions about our own learning processes to an impressionistic dialogue between us to inculcate that the ethnographic knowledge making process resides not only between writers of the text, but also between the writers and the readers. In this sense, our report represents an invitation to the reader to partake in the joint production of intersubjectivity.
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- Engblom, David, 1975-, et al.
(författare)
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Activation of prostanoid EP3 and EP4 receptor mRNA-expressing neurons in the rat parabrachial nucleus by intravenous injection of bacterial wall lipopolysaccharide
- 2001
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Ingår i: Journal of Comparative Neurology. - : Wiley. - 0021-9967 .- 1096-9861. ; 440:4, s. 378-386
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Tidskriftsartikel (refereegranskat)abstract
- Systemic inflammation activates central autonomic circuits, such as neurons in the pontine parabrachial nucleus. This activation may be the result of afferent signaling through the vagus nerve, but it may also depend on central prostaglandin-mediated mechanisms. Recently, we have shown that neurons in the parts of the parabrachial nucleus that are activated by immune challenge express prostaglandin receptors of the EP3 and EP4 subtypes, but it remains to be determined if the prostaglandin receptor-expressing neurons are identical to those that respond to immune stimuli. In the present study, bacterial wall lipopolysaccharide was injected intravenously in adult male rats and the expression of c-fos mRNA and of EP3 and EP4 receptor mRNA was examined with complementary RNA probes labeled with digoxigenin and radioisotopes, respectively. Large numbers of neurons in the external lateral parabrachial subnucleus, a major target of vagal-solitary tract efferents, expressed c-fos mRNA. Quantitative analysis showed that about 60% (range 40%–79%) of these neurons also expressed EP3 receptor mRNA. Conversely, slightly more than 50% (range 48%–63%) of the EP3 receptor-expressing neurons in the same subnucleus coexpressed c-fos mRNA. In contrast, few EP4 receptor-expressing neurons were c-fos positive, with the exception of a small population located in the superior lateral and dorsal lateral subnuclei. These findings show that immune challenge activates central autonomic neurons that could be the target of centrally produced prostaglandin E2, suggesting that synaptic signaling and paracrine mechanisms may interact on these neurons. J. Comp. Neurol. 440:378–386, 2001. © 2001 Wiley-Liss, Inc.
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