This study offers a grounded theory of 'new ways of working' (NWW), an organizational design concept of Dutch origin with a global relevance. NWW concern business solutions for flexible workspaces enabled by digital network technologies. Theoretically, NWW are analysed with reference to Lefebvre's theory on the 'production of space' and are defined along three dimensions: the spatiotemporal 'flexibilization' of work practices, the 'virtualization' of the technologically pre-defined organization, and the 'interfacialization' of meaning making in the lifeworld of workers. Empirically, NWW are explored in a case study of an insurance company which in 2007 radically implemented NWW. The case study consists of a longitudinalbefore and after implementation research based on ethnographic fieldwork, conducted in 2007 and 2010. The article contributes with a conceptual framework for the analysis and management of NWW, and highlights contradictions and ambiguities in the implementation and appropriation of this innovative organizational design.

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Lactobacillus johnsonii (Ljo) N6.2 has been shown to mitigate the development of type 1 diabetes when administered to diabetes-prone rats. The specific mechanisms underlying this observed response remain under investigation. The objective of this study was to assess the effect of Ljo N6.2 on mucosal inflammatory response using differentiated Caco-2 monolayers. The mRNA expression levels of CCL20, CXCL8, and CXCL10 chemokines were determined by qRT-PCR. Ljo at 10(11) CFU/L induced a strong response in all chemokines examined. To assess the specific host-signaling pathways involved, we performed RT-PCR amplification of Toll-like receptors (TLR) and nucleotide-binding oligomerization domain-like receptors. TLR7 and TLR9 expression levels were induced 4.2- and 9-fold, respectively, whereas other TLR and nucleotide-binding oligomerization domain receptors were not modified. A similar effect was observed in Caco-2 monolayers treated with Ljo cell-free extract or purified nucleic acids (NA). Increased levels of IFN type 1 and IFN regulators Stat1 and IRF7 followed the upregulation of TLR9. Activation of TLR9 was also evidenced by increased Frizzled 5 expression in Ljo-treated Caco-2 cells and an increase in the number of Paneth cells in Ljo-fed, diabetes-prone rats. These results are in agreement with the polarizing-tolerizing mechanism recently described in which the apical stimulation of TLR9 in intestinal epithelial cells leads to a higher state of immunologic alertness. Furthermore, these results suggest that live probiotics could be, in the future, replaced with select cellular components.

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IntroductionMucopolysaccharidosis type I (MPS I) is a progressive multisystem lysosomal storage disease caused by deficiency of the enzyme α-L-iduronidase (IDUA). Patients present with a continuous spectrum of disease severity, and the most severely affected patients (Hurler phenotype; MPS I-H) develop progressive cognitive impairment. The treatment of choice for MPS I-H patients is haematopoietic stem cell transplantation, while patients with the more attenuated phenotypes benefit from enzyme replacement therapy.The potential of newborn screening (NBS) for MPS I is currently studied in many countries. NBS for MPS I, however, necessitates early assessment of the phenotype, in order to decide on the appropriate treatment. In this study, we developed an algorithm to predict phenotypic severity in newborn MPS I patients.MethodsThirty patients were included in this study. Genotypes were collected from all patients and all patients were phenotypically categorized at an age of > 18 months based on the clinical course of the disease. In 18 patients, IDUA activity in fibroblast cultures was measured using an optimized IDUA assay. Clinical characteristics from the first month of life were collected from 23 patients.ResultsHomozygosity or compound heterozygosity for specific mutations which are associated with MPS I-H, discriminated a subset of patients with MPS I-H from patients with more attenuated phenotypes (specificity 100%, sensitivity 82%). Next, we found that enzymatic analysis of IDUA activity in fibroblasts allowed identification of patients affected by MPS I-H. Therefore, residual IDUA activity in fibroblasts was introduced as second step in the algorithm. Patients with an IDUA activity of < 0.32 nmol x mg-1 × hr-1 invariably were MPS I-H patients, while an IDUA activity of > 0.66 nmol × mg-1 × hr-1 was only observed in more attenuated patients. Patients with an intermediate IDUA activity could be further classified by the presence of differentiating clinical characteristics, resulting in a model with 100% sensitivity and specificity for this cohort of patients.ConclusionUsing genetic, biochemical and clinical characteristics, all potentially available in the newborn period, an algorithm was developed to predict the MPS I phenotype, allowing timely initiation of the optimal treatment strategy after introduction of NBS.

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The constitution of 'third workspaces' in between the home and the corporate office Sytze F. Kingma This study analyses the constitution of commercially provided work spaces situated in between the home and the corporate office. These new workspaces are enabled by digital network technologies. Theoretically, this new category of contemporary business spaces is conceptualised as 'third workspaces', with reference to the work of Oldenburg (1989), Soja (1996) and Lefe-bvre (1991 [1974]). Empirically, these workspaces are explored in two ethnographic case studies dealing with recently founded and successful third workspace providers. The grounded theory resulting from these case studies addresses the role of the material settings, the technologies, the work ideologies as well as the user practices. Overall this study offers an analytical framework for studying and managing third workspaces, and highlights the ambiguities in the constitution of third work-spaces between the design and management on the one hand and the user practices on the other. is senior lecturer in organizational space and technology at the department of organization sciences of the VU University Amsterdam.