Making Materials Matter—A Contribution to a Sociomaterial Perspective on Work Environment

This paper aims to discuss the implications of adopting an STS (science and technology studies)- based conceptualization of the psychosocial work environment. We problematize how work environment research presently divides elements of working conditions into separate physical and psychosocial dimensions. Based on actor network theory, a currently dominant perspective in the field of STS, we discuss the concept of sociomaterial work environment. An ANT perspective on work environment is relevant and timely, we argue, first and foremost because more entities are embraced in the analyses. We argue that the ANT perspective leads to a more nuanced understanding of the work environment where it is not a set of predefined categories that is the focus of interest, but rather the work environment as multiple locally performed aspects of agency, translation, and collectively constructed reality. This perspective on work environment, we argue, addresses pivotal issues raised in the work environment debate during the last ten years, for instance of how the work environment as a concept saliently belongs to a social democratic Scandinavian agenda in which the singular employee in a work environment context is predominantly seen as a victim. This trope, which was peaking in the 1970s, is increasingly becoming obsolete in a changing economy with still more flexible jobs. The contribution of this paper is to provide a presentation and a discussion of the potentials and pitfalls provided by a shift toward a sociomaterial work environment perspective, as well as an empirical exemplification of a sociomaterial approach to work environment assessment

No influence of the polymorphisms CYP2C19 and CYP2D6 on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma

BACKGROUND: The response to treatment varies among patients with multiple myeloma and markers for prediction of treatment outcome are highly needed. Bioactivation of cyclophosphamide and thalidomide, and biodegradation of bortezomib, is dependent on cytochrome P450 metabolism. We explored the potential influence of different polymorphisms in the CYP enzymes on the outcome of treatment. METHODS: Data was analyzed from 348 patients undergoing high-dose treatment and stem cell support in Denmark in 1994 to 2004. Clinical information on relapse treatment in 243 individual patients was collected. The patients were genotyped for the non-functional alleles CYP2C19*2 and CYP2D6*3, *4, *5 (gene deletion), *6, and CYP2D6 gene duplication. RESULTS: In patients who were treated with bortezomib and were carriers of one or two defective CYP2D6 alleles there was a trend towards a better time-to-next treatment. We found no association between the number of functional CYP2C19 and CYP2D6 alleles and outcome of treatment with cyclophosphamide or thalidomide. Neither was the number of functional CYP2C19 and CYP2D6 alleles associated with neurological adverse reactions to thalidomide and bortezomib. CONCLUSION: There was no association between functional CYP2C19 and CYP2D6 alleles and treatment outcome in multiple myeloma patients treated with cyclophosphamide, thalidomide or bortezomib. A larger number of patients treated with bortezomib are needed to determine the role of CYP2D6 alleles in treatment outcome

A randomized placebo-controlled phase II study of clarithromycin or placebo combined with VCD induction therapy prior to high-dose melphalan with stem cell support in patients with newly diagnosed multiple myeloma

Abstract Background The objective of this randomized placebo-controlled study was to investigate the efficacy and safety of clarithromycin in combination with bortezomib–cyclophosphamide–dexamethasone (VCD) in patients with newly diagnosed multiple myeloma eligible for high-dose therapy. Methods Patients were randomized to receive tablet clarithromycin 500 mg or matching placebo tablet twice daily during the first 3 cycles of VCD induction therapy. Primary endpoint was to compare the rate of very good partial response (VGPR) or better response after three cycles of VCD combined with clarithromycin or placebo. Results The study was prematurely stopped for safety reasons after the inclusion of 58 patients (36% of the planned study population). The patients were randomly assigned to clarithromycin (n = 27) or placebo (n = 31). VGPR or better response after the VCD induction therapy was obtained in 12 patients (44.4%, 95% CI 25.5–64.7) and in 16 patients (51.6%, 33.1–69.8) (p = 0.59) in the clarithromycin group and the placebo group, respectively. Seven patients (25.9%) in the clarithromycin group developed severe gastrointestinal complications (≥ grade 3) comprising pain, neutropenic enterocolitis, paralytic ileus or peptic ulcer. These complications occurred in only one patient in the placebo group. Septicemia with Gram negative bacteria was observed in 5 patients in the clarithromycin group in contrast to one case of pneumococcal septicemia in the placebo group. Patient-reported QoL were negatively affected in the clarithromycin group compared to the placebo group. Conclusion The study was prematurely stopped due to serious adverse events, in particular serious gastrointestinal complications and septicemia. The response data do not suggest any effect of clarithromycin when added to the VCD regimen. The combination of clarithromycin and bortezomib containing regimens is toxic and do not seem to offer extra anti-myeloma efficacy. Trial registration EudraCT (no. 2014-002187-32, registered 7 October 2014, https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-002187-32/DK) and ClinicalTrials.gov (no NCT02573935, retrospectively registered 12 October 2015, https://www.clinicaltrials.gov/ct2/show/NCT02573935?term=Gregersen&cntry=DK&rank=9

Classification of amyloidosis by model‐assisted mass spectrometry‐based proteomics

Funding Information: Funding: This research was partly funded by a “Center of Clinical Excellence” research grant from the Health Region of Southern Denmark to Odense Amyloidosis Center (AmyC). Publisher Copyright: © 2021 by the authors. Li-censee MDPI, Basel, Switzerland.Amyloidosis is a rare disease caused by the misfolding and extracellular aggregation of proteins as insoluble fibrillary deposits localized either in specific organs or systemically through-out the body. The organ targeted and the disease progression and outcome is highly dependent on the specific fibril‐forming protein, and its accurate identification is essential to the choice of treat-ment. Mass spectrometry‐based proteomics has become the method of choice for the identification of the amyloidogenic protein. Regrettably, this identification relies on manual and subjective inter-pretation of mass spectrometry data by an expert, which is undesirable and may bias diagnosis. To circumvent this, we developed a statistical model‐assisted method for the unbiased identification of amyloid‐containing biopsies and amyloidosis subtyping. Based on data from mass spectrometric analysis of amyloid‐containing biopsies and corresponding controls. A Boruta method applied on a random forest classifier was applied to proteomics data obtained from the mass spectrometric analysis of 75 laser dissected Congo Red positive amyloid‐containing biopsies and 78 Congo Red negative biopsies to identify novel “amyloid signature” proteins that included clusterin, fibulin‐1, vitronectin complement component C9 and also three collagen proteins, as well as the well‐known amyloid signature proteins apolipoprotein E, apolipoprotein A4, and serum amyloid P. A SVM learning algorithm were trained on the mass spectrometry data from the analysis of the 75 amyloid-containing biopsies and 78 amyloid‐negative control biopsies. The trained algorithm performed su-perior in the discrimination of amyloid‐containing biopsies from controls, with an accuracy of 1.0 when applied to a blinded mass spectrometry validation data set of 103 prospectively collected am-yloid‐containing biopsies. Moreover, our method successfully classified amyloidosis patients ac-cording to the subtype in 102 out of 103 blinded cases. Collectively, our model‐assisted approach identified novel amyloid‐associated proteins and demonstrated the use of mass spectrometry‐based data in clinical diagnostics of disease by the unbiased and reliable model‐assisted classification of amyloid deposits and of the specific amyloid subtype.publishersversionpublishe

Abnormal IGF-Binding Protein Profile in the Bone Marrow of Multiple Myeloma Patients

Insulin-like growth factor (IGF) signalling plays a key role in homing, progression, and treatment resistance in multiple myeloma (MM). In the extracellular environment, the majority of IGF molecules are bound to one of six IGF-binding proteins (IGFBP1-6), leaving a minor fraction of total IGF free and accessible for receptor activation. In MM, high IGF-receptor type 1 expression levels correlate with a poor prognosis, but the status and role of IGF and IGFBPs in the pathobiology of MM is unknown. Here we measured total IGF1, IGF2, and intact IGFBP levels in blood and bone marrow samples from MM (n = 17), monoclonal gammopathy of undetermined significance (MGUS) (n = 37), and control individuals (n = 15), using ELISA (IGFs) and 125I-IGF1 Western Ligand Blotting (IGFBPs). MGUS and MM patients displayed a significant increase in intact IGFBP-2 (2.5-3.8 fold) and decrease in intact IGFBP-3 (0.6-0.5 fold) in the circulation compared to control individuals. Further, IGFBP-2 as well as total IGFBP levels were significantly lower in bone marrow compared to circulation in MM and MGUS only, whereas IGF1, IGF2, and IGFBP-3 were equally distributed between the two compartments. In conclusion, the profound change in IGFBP profile strongly suggests an increased IGF bioavailability in the bone marrow microenvironment in MGUS and MM, despite no change in growth factor concentration

Pomalidomide-based treatment in relapsed refractory mulitiple myeloma: Analysis of baseline characteristics and safety profile of patients who died in the European post approval safety study: PS1418

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