Use of azacitidine and its safety and efficacy in daily clinical practice in The Netherlands:the OCEAN study

Contains fulltext : 229349.pdf (Publisher’s version ) (Closed access

A 'Performative' Social Movement: The Emergence of Collective Contentions within Collaborative Governance

The enmeshment of urban movements in networks of collaborative governance has been characterised as a process of co-option in which previously disruptive contentions are absorbed by regimes and reproduced in ways that do not threaten the stability of power relations. Applying a theoretical framework drawn from feminist philosopher Judith Butler this paper directs attention to the development of collective oppositional identities that remain embedded in conventional political processes. In a case study of the English tenants' movement, it investigates the potential of regulatory discourses that draw on market theories of performative voice to offer the collectivising narratives and belief in change that can generate the emotional identification of a social movement. The paper originates the concept of the ‘performative social movement’ to denote the contentious claims that continue to emerge from urban movements that otherwise appear quiescent

Teams between Neo-Taylorism and Anti-Taylorism

The concept of teamworking is the product of two distinct developments. One: a neo- Tayloristic form of organization of work, of which Toyota has shown that it can be very profitable, was packaged and reframed to make it acceptable to the Western public. Two: anti-Tayloristic ways of organizing work, inspired by ideals of organizational democracy, were relabeled to make these acceptable to profit-oriented managers. Drawing on empirical research in Scandinavia, Germany, The Netherlands and the UK, as well as on published case studies of Japanese companies, the paper develops a neo-Tayloristic and an anti-Tayloristic model of teamworking. Key concerns in the teamworking literature are intensification of work and the use of shop floor autonomy as a cosmetic or manipulative device. Indeed, all the features of neo-Tayloristic teamworking are geared towards the intensification of work. However, one of the intensification mechanisms, the removal of Tayloristic rigidities in the division of labor, applies to anti-Tayloristic teamworking as well. This poses a dilemma for employee representatives. In terms of autonomy, on the other hand, the difference between neo-Tayloristic and anti-Tayloristic teamworking is real. In anti-Tayloristic teamworking, there is no supervisor inside the team. The function of spokesperson rotates. All team members can participate in decision-making. Standardization is not relentlessly pursued; management accepts some measure of worker control. There is a tendency to alleviate technical discipline, e.g. to find alternatives for the assembly line. Buffers are used. Remuneration is based on proven skill level; there are no group bonuses. In contrast, in neo-Tayloristic teamworking, a permanent supervisor is present in the team as team leader. At most, only the team leader can participate in decision-making. Standardization is relentlessly pursued. Management prerogatives are nearly unlimited. Job designers treat technical discipline, e.g. short-cycled work on the assembly line, as unproblematic. There are no buffers. A substantial part of wages consists of individual bonuses based on assessments by supervisors on how deeply workers cooperate in the system. Group bonuses are also given. The instability and vulnerability of anti-Tayloristic teamworking imply that it can only develop and flourish when managers and employee representatives put determined effort into it. The opportunity structure for this contains both economic and political elements. In mass production, the economic success of Toyota, through skillful mediation by management gurus, makes the opportunity structure for anti-Tayloristic teamworking relatively unfavorable

Radiofrequency ablation and chemotherapy versus chemotherapy alone for locally advanced pancreatic cancer (PELICAN):study protocol for a randomized controlled trial

Contains fulltext : 239066.pdf (Publisher’s version ) (Open Access)BACKGROUND: Approximately 80% of patients with locally advanced pancreatic cancer (LAPC) are treated with chemotherapy, of whom approximately 10% undergo a resection. Cohort studies investigating local tumor ablation with radiofrequency ablation (RFA) have reported a promising overall survival of 26-34 months when given in a multimodal setting. However, randomized controlled trials (RCTs) investigating the effect of RFA in combination with chemotherapy in patients with LAPC are lacking. METHODS: The "Pancreatic Locally Advanced Unresectable Cancer Ablation" (PELICAN) trial is an international multicenter superiority RCT, initiated by the Dutch Pancreatic Cancer Group (DPCG). All patients with LAPC according to DPCG criteria, who start with FOLFIRINOX or (nab-paclitaxel/)gemcitabine, are screened for eligibility. Restaging is performed after completion of four cycles of FOLFIRINOX or two cycles of (nab-paclitaxel/)gemcitabine (i.e., 2 months of treatment), and the results are assessed within a nationwide online expert panel. Eligible patients with RECIST stable disease or objective response, in whom resection is not feasible, are randomized to RFA followed by chemotherapy or chemotherapy alone. In total, 228 patients will be included in 16 centers in The Netherlands and four other European centers. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, RECIST response, CA 19.9 and CEA response, toxicity, quality of life, pain, costs, and immunomodulatory effects of RFA. DISCUSSION: The PELICAN RCT aims to assess whether the combination of chemotherapy and RFA improves the overall survival when compared to chemotherapy alone, in patients with LAPC with no progression of disease following 2 months of systemic treatment. TRIAL REGISTRATION: Dutch Trial Registry NL4997 . Registered on December 29, 2015. ClinicalTrials.gov NCT03690323 . Retrospectively registered on October 1, 2018

Urban interventionism as a challenge to aesthetic order::Towards an aesthetic criminology

This article is concerned with ideas of urban order and considers the scope for playing with people’s expectations of order. In particular, drawing on criminological, philosophical and urban studies literatures, the article explores the notion of aesthetic order. The power to dictate aesthetic order is highlighted. The example of urban interventionism is used to consider those that challenge an approved aesthetic order. Here the article draws on cultural criminology and visual criminology, with illustrations coming from research in Toronto, Canada. Influenced by Alison Young’s (2014a) conceptualisation of ‘cities within the city’, the article considers how different people using the same space have different or overlapping ways of understanding aesthetic order. Of relevance to criminology, it is contended that people or things that contravene an approved aesthetic order may face banishment and criminalisation. It is concluded that respect for such difference is required. An aesthetic criminology is suggested

Single Nucleotide Polymorphism (SNP)-Based Loss of Heterozygosity (LOH) Testing by Real Time PCR in Patients Suspect of Myeloproliferative Disease

During tumor development, loss of heterozygosity (LOH) often occurs. When LOH is preceded by an oncogene activating mutation, the mutant allele may be further potentiated if the wild-type allele is lost or inactivated. In myeloproliferative neoplasms (MPN) somatic acquisition of JAK2V617F may be followed by LOH resulting in loss of the wild type allele. The occurrence of LOH in MPN and other proliferative diseases may lead to a further potentiating the mutant allele and thereby increasing morbidity. A real time PCR based SNP profiling assay was developed and validated for LOH detection of the JAK2 region (JAK2LOH). Blood of a cohort of 12 JAK2V617F-positive patients (n = 6 25–50% and n = 6>50% JAK2V617F) and a cohort of 81 patients suspected of MPN was stored with EDTA and subsequently used for validation. To generate germ-line profiles, non-neoplastic formalin-fixed paraffin-embedded tissue from each patient was analyzed. Results of the SNP assay were compared to those of an established Short Tandem Repeat (STR) assay. Both assays revealed JAK2LOH in 1/6 patients with 25–50% JAK2V617F. In patients with >50% JAK2V617F, JAK2LOH was detected in 6/6 by the SNP assay and 5/6 patients by the STR assay. Of the 81 patients suspected of MPN, 18 patients carried JAK2V617F. Both the SNP and STR assay demonstrated the occurrence of JAK2LOH in 5 of them. In the 63 JAK2V617F-negative patients, no JAK2LOH was observed by SNP and STR analyses. The presented SNP assay reliably detects JAK2LOH and is a fast and easy to perform alternative for STR analyses. We therefore anticipate the SNP approach as a proof of principle for the development of LOH SNP-assays for other clinically relevant LOH loci

Rapid Immunomagnetic Negative Enrichment of Neutrophil Granulocytes from Murine Bone Marrow for Functional Studies In Vitro and In Vivo

Polymorphonuclear neutrophils (PMN) mediate early immunity to infection but can also cause host damage if their effector functions are not controlled. Their lack or dysfunction is associated with severe health problems and thus the analysis of PMN physiology is a central issue. One prerequisite for PMN analysis is the availability of purified cells from primary organs. While human PMN are easily isolated from peripheral blood, this approach is less suitable for mice due to limited availability of blood. Instead, bone marrow (BM) is an easily available reservoir of murine PMN, but methods to obtain pure cells from BM are limited. We have developed a novel protocol allowing the isolation of highly pure untouched PMN from murine BM by negative immunomagnetic isolation using a complex antibody cocktail. The protocol is simple and fast (∼1 h), has a high yield (5–10*106 PMN per animal) and provides a purity of cells equivalent to positive selection (>80%). Most importantly, cells obtained by this method are non-activated and remain fully functional in vitro or after adoptive transfer into recipient animals. This method should thus greatly facilitate the study of primary murine PMN in vitro and in vivo

Evidence That a Lipolytic Enzyme—Hematopoietic-Specific Phospholipase C-β2—Promotes Mobilization of Hematopoietic Stem Cells by Decreasing Their Lipid Raft-Mediated Bone Marrow Retention and Increasing the Promobilizing Effects of Granulocytes

Hematopoietic stem/progenitor cells (HSPCs) reside in the bone marrow (BM) microenvironment and are retained there by the interaction of membrane lipid raft-associated receptors, such as the α-chemokine receptor CXCR4 and the α4β1-integrin (VLA-4, very late antigen 4 receptor) receptor, with their respective specific ligands, stromal-derived factor 1 and vascular cell adhesion molecule 1, expressed in BM stem cell niches. The integrity of the lipid rafts containing these receptors is maintained by the glycolipid glycosylphosphatidylinositol anchor (GPI-A). It has been reported that a cleavage fragment of the fifth component of the activated complement cascade, C5a, has an important role in mobilizing HSPCs into the peripheral blood (PB) by (i) inducing degranulation of BM-residing granulocytes and (ii) promoting their egress from the BM into the PB so that they permeabilize the endothelial barrier for subsequent egress of HSPCs. We report here that hematopoietic cell-specific phospholipase C-β2 (PLC-β2) has a crucial role in pharmacological mobilization of HSPCs. On the one hand, when released during degranulation of granulocytes, it digests GPI-A, thereby disrupting membrane lipid rafts and impairing retention of HSPCs in BM niches. On the other hand, it is an intracellular enzyme required for degranulation of granulocytes and their egress from BM. In support of this dual role, we demonstrate that PLC-β2-knockout mice are poor mobilizers and provide, for the first time, evidence for the involvement of this lipolytic enzyme in the mobilization of HSPCs