Complexity Theory for a New Managerial Paradigm: A Research Framework

In this work, we supply a theoretical framework of how organizations can embed complexity management and sustainable development into their policies and actions. The proposed framework may lead to a new management paradigm, attempting to link the main concepts of complexity theory, change management, knowledge management, sustainable development, and cybernetics. We highlight how the processes of organizational change have occurred as a result of the move to adapt to the changes in the various global and international business environments and how this transformation has led to the shift toward the present innovation economy. We also point how organizational change needs to deal with sustainability, so that the change may be consistent with present needs, without compromising the future

Managing multimorbidity in primary care in patients with chronic respiratory conditions

The term multimorbidity is usually defined as the coexistence of two or more chronic conditions within an individual, whereas the term comorbidity traditionally describes patients with an index condition and one or more additional conditions. Multimorbidity of chronic conditions markedly worsens outcomes in patients, increases treatment burden and increases health service costs. Although patients with chronic respiratory disease often have physical comorbidities, they also commonly experience psychological problems such as depression and anxiety. Multimorbidity is associated with increased health-care utilisation and specifically with an increased number of prescription drugs in individuals with multiple chronic conditions such as chronic obstructive pulmonary disease. This npj Primary Care Respiratory Medicine Education Section case study involves a patient in a primary care consultation presenting several common diseases prevalent in people of this age. The patient takes nine different drugs at this moment, one or more pills for each condition, which amounts to polypharmacy. The problems related with polypharmacy recommend that a routine medication review by primary care physicians be performed to reduce the risk of adverse effects of polypharmacy among those with multiple chronic conditions. The primary care physician has the challenging role of integrating all of the clinical problems affecting the patient and reviewing all medicaments (including over-the-counter medications) taken by the patient at any point in time, and has the has the key to prevent the unwanted consequences of polypharmacy. Multimorbid chronic disease management can be achieved with the use of care planning, unified disease templates, use of information technology with appointment reminders and with the help of the wider primary care and community teams

Click and drive Consumer attitude to product development: Towards future transformations of the driving experience

Purpose – The purpose of this paper is to supply indications that may be useful in the process of development of new products that fully exploit the value potential of Internet of Things (IoT) technologies in the automotive industry. To this aim, the authors investigate how applications of the IoT to smart vehicles are perceived by consumers and describe different ways to increase their satisfaction. Design/methodology/approach – After a literature review focused on IoT and consumer behaviour in the automotive industry, the authors apply the Kano model to find the drivers for achieving customer satisfaction with new product developments in smartcars. Findings – Automotive companies need to consider what is attractive to drivers and what consumers consider to be “driver-friendly”. Using an empirical analysis, the authors highlight the motivations for developing a smartcar to fits the expectation of Italian drivers. Research limitations/implications – While the global framework given by this paper can be useful in all contexts, the empirical part is based on the Italian consumer. Further research may extend the application of the model to other countries to improve the generalizability of the results. Practical implications – This study supplies an analysis of qualitative data that may prove useful to researchers and managers in planning their strategic and operative activities with the aim of improving the development of IoT-related products in the automotive industry. Originality/value – This paper fulfils the need for an original research framework that sheds light on relevant insights and gives useful hints on the development of IoT technologies in the automotive sector. Paper type Research pape

Monocyte induction of e-selectin-mediated endothelial activation releases VE-Cadherin junctions to promote tumor cell extravasation in the metastasis cascade

Tumor cells interact with blood constituents and these interactions promote metastasis. Selectins are vascular receptors facilitating interactions of tumor cells with platelets, leukocytes, and endothelium, but the role of endothelial E-selectin remains unclear. Here we show that E-selectin is a major receptor for monocyte recruitment to tumor cell-activated endothelium. Experimental and spontaneous lung metastasis using murine tumor cells, without E-selectin ligands, were attenuated in E-selectin-deficient mice. Tumor cell-derived CCL2 promoted endothelial activation, resulting in enhanced endothelial E-selectin expression. The recruitment of inflammatory monocytes to metastasizing tumor cells was dependent on the local endothelial activation and the presence of E-selectin. Monocytes promoted transendothelial migration of tumor cells through the induction of E-selectin-dependent endothelial retractions and a subsequent modulation of tight junctions through dephosphorylation of VE-cadherin. Thus, endothelial E-selectin shapes the tumor microenvironment through the recruitment, adhesion, and activation of monocytes that facilitate tumor cell extravasation and thereby metastasis. These findings provide evidence that endothelial E-selectin is a novel factor contributing to endothelial retraction required for efficient lung metastasis. Cancer Res; 76(18); 5302-12. ©2016 AACR

Nuclear heparanase-1 activity suppresses melanoma progression via its DNA-binding affinity

Heparanase-1 (HPSE) plays a pivotal role in structural remodeling of the ECM and glycocalyx thus conferring protumorigenic, proangiogenic and prometastatic properties to many cancer entities. In addition to its extracellular function, recent studies suggest an intracellular activity of HPSE with a largely unknown significance during tumor progression. Therefore, we investigated the relevance of HPSE duality in malignant melanoma in vitro as well as in mouse melanoma models basing on the intradermal injection of transfected melanoma cells. In line with its extracellular action, HPSE-deficiency led to a reduced shedding of the glycocalyx accompanied by a reduced availability of VEGF affecting tumor growth and vascularization. In contrast, we measured an elevated expression of the protumorigenic factors pentraxin-3, tissue factor, TNF-and most prominently MMP-9 upon HPSE knockdown. In vivo, HPSE-deficiency was related to increased lymph node metastasis. While inhibition of its extracellular function heparin was unable to block the gene regulatory impact of HPSE we proposed an intracellular mechanism. Immunostainings revealed a counter-staining of HPSE and NF-B in the nucleus suggesting a close relationship between both proteins. This finding was further supported by the discovery of a direct charge-driven molecular interaction between HPSE and DNA by using atomic force microscopy and a co-precipitation approach. Our findings are novel and point towards a dual identity of HPSE in malignant melanoma with a protumorigenic extracellular activity and a tumor suppressive nuclear action. Identification of molecular strategies to shuttle extracellular HPSE into the nuclei of cancer cells envisions new therapeutic options

Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa‐Porthos axis in Drosophila

Cellular metabolism must adapt to changing demands to enable homeostasis. During immune responses or cancer metastasis, cells leading migration into challenging environments require an energy boost, but what controls this capacity is unclear. Here, we study a previously uncharacterized nuclear protein, Atossa (encoded by CG9005), which supports macrophage invasion into the germband of Drosophila by controlling cellular metabolism. First, nuclear Atossa increases mRNA levels of Porthos, a DEAD-box protein, and of two metabolic enzymes, lysine-α-ketoglutarate reductase (LKR/SDH) and NADPH glyoxylate reductase (GR/HPR), thus enhancing mitochondrial bioenergetics. Then Porthos supports ribosome assembly and thereby raises the translational efficiency of a subset of mRNAs, including those affecting mitochondrial functions, the electron transport chain, and metabolism. Mitochondrial respiration measurements, metabolomics, and live imaging indicate that Atossa and Porthos power up OxPhos and energy production to promote the forging of a path into tissues by leading macrophages. Since many crucial physiological responses require increases in mitochondrial energy output, this previously undescribed genetic program may modulate a wide range of cellular behaviors