A vintage model of technology diffusion: The effects of returns to disversity and learning by using

The diffusion of new technologies is a lengthy process and many firms continue to invest in relatively old technologies. This paper develops a vintage model of technology adoption and diffusion that aims at explaining these two phenomena. Our explanation for these phenomena emphasises the relevance of complementarity between different vintages (or, alternatively, returns to diversity) and learning-by- using. The model is characterised by simultaneous investments in vintages of different quality and endogenously determined scrapping of old technologies. We show that the stronger the complementarity between different vintages and the stronger the learning-by-using, the longer it takes before firms scrap (seemingly) inferior technologies

The Great North Sea Flood of 1953, The Deltaworks and the spatial distribution of people

Large shocks, such as natural disasters, are often found to have little or no effect on the equilibrium distribution of economic activity across space. Two apparently competing theoretical explanations for this phenomenon are the increasing returns theory and the locational fundamentals theory. This study investigates the population dynamics resulting from the flood that hit the Netherlands in 1953 and from the mitigation measures that followed it.A dynamic difference-in-differences analysis reveals that the flood had an immediate negative impact on population growth, but limited long term effects. The mitigation efforts, gathered under the Deltaworks Programme, are on the other hand found to have had positive effects that are persisting through time. Our results are consistent with both the theory of increasing returns and that of locational fundamentals. The results also suggest that the combined long term effect of the flood in 1953 and the mitigation measures that followed was an increased concentration of population in vulnerable areas

Wat is de meerwaarde van een canon voor het geschiedenisonderwijs? : Een didactische reflectie op het canondebat in Vlaanderen

Er zijn zowel tegen de Canon van Nederland als de onlangs gelanceerde Canon van Vlaanderen bezwaren geopperd. In dit artikel gaan we in op de plaats van een canon in het geschiedenisonderwijs. We laten zien dat critici, waaronder de auteurs van het standpunt van de Vlaamse Koninklijke Academie, de inhoud van de Canon verwarren met de didactische mogelijkheden van een canon. Aan de hand van drie belangrijke kritiekpunten bespreken we de mogelijke didactische functie van een canon. We gaan in op hoe een canon (1) de historische interesse van leerlingen kan stimuleren, (2) het uitbouwen van een historisch referentiekader kan ondersteunen en (3) leerlingen kan helpen om historisch te leren denken en redeneren. We plaatsen een canon tot slot in een breder perspectief van krachtige kennis en laten daarbij zien dat een canon in het onderwijs geen koesteren van het verleden hoeft te zijn, maar juist een impuls kan geven voor dialoog

Wat is de meerwaarde van een canon voor het geschiedenisonderwijs?:Een didactische reflectie op het canondebat in Vlaanderen

Er zijn zowel tegen de Canon van Nederland als de onlangs gelanceerde Canon van Vlaanderen bezwaren geopperd. In dit artikel gaan we in op de plaats van een canon in het geschiedenisonderwijs. We laten zien dat critici, waaronder de auteurs van het standpunt van de Vlaamse Koninklijke Academie, de inhoud van de Canon verwarren met de didactische mogelijkheden van een canon. Aan de hand van drie belangrijke kritiekpunten bespreken we de mogelijke didactische functie van een canon. We gaan in op hoe een canon (1) de historische interesse van leerlingen kan stimuleren, (2) het uitbouwen van een historisch referentiekader kan ondersteunen en (3) leerlingen kan helpen om historisch te leren denken en redeneren. We plaatsen een canon tot slot in een breder perspectief van krachtige kennis en laten daarbij zien dat een canon in het onderwijs geen koesteren van het verleden hoeft te zijn, maar juist een impuls kan geven voor dialoog

Initial results of secukinumab drug survival in patients with psoriasis: A multicentre daily practice cohort study

Interleukin 17-antagonist secukinumab demonstrated high efficacy for treatment of psoriasis in randomized controlled trials. However, performance in daily practice may differ from trials. Drug survival is a comprehensive outcome covering effectiveness and safety, suitable for analyses of daily practice. The aim of this study was to evaluate drug survival of secukinumab in a daily practice psoriasis cohort. Data were collected from 13 hospitals. Drug survival was analysed using Kaplan–Meier survival curves, split for reason of discontinuation. In total, 196 patients were included (83% biologic experienced). Overall, 12 and 18 months drug survival of secukinumab was 76% and 67%, respectively, and was mostly determined by ineffectiveness. There was a trend towards shorter drug survival in women and in biologic experienced patients. Thirteen percent of patients experienced at least one episode of fungal infection. This is one of the first studies of drug survival of secukinumab in patients with psoriasis treated in daily practice

Low relapse risk in poor risk AML after conditioning with 10-day decitabine, fludarabine and 2 Gray TBI prior to allogeneic hematopoietic cell transplantation.

Patients with poor risk acute myeloid leukemia (AML) have a dismal outcome. We hypothesized that combining decitabine with a standard non-myeloablative (NMA) conditioning regimen prior to allogeneic hematopoietic cell transplantation (allo HCT), might decrease the relapse incidence. We conducted a multicenter prospective phase II study (NCT02252107) with 10-day decitabine (20 mg/m(2)/day) integrated in a standard non-myeloablative conditioning regimen (3 days fludarabine 30 mg/m(2) with 2 Gray total body irradiation (TBI)). Patients with AML ≥ 18 years in 1st (in)complete remission (CR/CRi) with a poor or very poor risk profile, as defined by the HOVON-132 protocol, were eligible. Results: Forty-six patients (median age 60; range 23-74) were included. Median follow up time was 44 months (range 31-65 months). The cumulative 1-year incidence of relapse and NRM were respectively 23% and 11%. Incidence of grade III-IV acute graft-vs-host-disease (GVHD) and severe chronic GVHD were 13% and 20%, respectively. One-year OS was 70%. Application of ELN 2017 risk classification to the study cohort revealed a cumulative one-year relapse rate of respectively 31% and 13% for the adverse and intermediate risk patients. To conclude, the 10-day DEC/FLU/TBI conditioning regimen prior to allo HCT in poor risk AML patients is effective and feasible

Insight in modulation of inflammation in response to diclofenac intervention: a human intervention study

Background. Chronic systemic low-grade inflammation in obese subjects is associated with health complications including cardiovascular diseases, insulin resistance and diabetes. Reducing inflammatory responses may reduce these risks. However, available markers of inflammatory status inadequately describe the complexity of metabolic responses to mild anti-inflammatory therapy. Methods. To address this limitation, we used an integrative omics approach to characterize modulation of inflammation in overweight men during an intervention with the non-steroidal anti-inflammatory drug diclofenac. Measured parameters included 80 plasma proteins, >300 plasma metabolites (lipids, free fatty acids, oxylipids and polar compounds) and an array of peripheral blood mononuclear cells (PBMC) gene expression products. These measures were submitted to multivariate and correlation analysis and were used for construction of biological response networks. Results. A panel of genes, proteins and metabolites, including PGE2 and TNF-alpha, were identified that describe a diclofenac-response network (68 genes in PBMC, 1 plasma protein and 4 plasma metabolites). Novel candidate markers of inflammatory modulation included PBMC expression of annexin A1 and caspase 8, and the arachidonic acid metabolite 5,6-DHET. Conclusion. In this study the integrated analysis of a wide range of parameters allowed the development of a network of markers responding to inflammatory modulation, thereby providing insight into the complex process of inflammation and ways to assess changes in inflammatory status associated with obesity. Trial registration. The study is registered as NCT00221052 in clinicaltrials.gov database. © 2010 van Erk et al; licensee BioMed Central Ltd

Comparative Performance Information Plays No Role in the Referral Behaviour of GPs

Comparative performance information (CPI) about the quality of hospital care is information used to identify high-quality hospitals and providers. As the gatekeeper to secondary care, the general practitioner (GP) can use CPI to reflect on the pros and cons of the available options with the patient and choose a provider best fitted to the patient’s needs. We investigated how GPs view their role in using CPI to choose providers and support patients. Method: We used a mixed-method, sequential, exploratory design to conduct explorative interviews with 15 GPs about their referral routines, methods of referral consideration, patient involvement, and the role of CPI. Then we quantified the qualitative results by sending a survey questionnaire to 81 GPs affiliated with a representative national research network. Results: Seventy GPs (86% response rate) filled out the questionnaire. Most GPs did not know where to find CPI (87%) and had never searched for it (94%). The GPs reported that they were not motivated to use CPI due to doubts about its role as support information, uncertainty about the effect of using CPI, lack of faith in better outcomes, and uncertainty about CPI content and validity. Nonetheless, most GPs believed that patients would like to be informed about quality-of- care differences (62%), and about half the GPs discussed quality-of-care differences with their patients (46%), though these discussions were not based on CPI. Conclusion: Decisions about referrals to hospital care are not based on CPI exchanges during GP consultations. As a gatekeeper, the GP is in a good position to guide patients through the enormous amount of quality information that is available. Nevertheless, it is unclear how and whether the GP’s role in using information about quality of care in the referral process can grow, as patients hardly ever initiate a discussion based on CPI, though they seem to be increasingly more critical about differences in quality of care. Future research should address the conditions needed to support GPs’ ability and willingness to use CPI to guide their patients in the referral process

Initial Results of Secukinumab Drug Survival in Patients with Psoriasis:A Multicentre Daily Practice Cohort Study

Interleukin 17-antagonist secukinumab demonstrated high efficacy for treatment of psoriasis in randomized controlled trials (RCTs). However, performance in daily practice may differ from trials. Drug survival is a comprehensive outcome covering effectiveness and safety, suitable for analyses of daily practice. The aim of this study was to evaluate drug survival of secukinumab in a daily practice psoriasis cohort. Data were collected from 13 hospitals. Drug survival was analysed using Kaplan-Meier survival curves, split for reason of discontinuation. In total, 196 patients were included (83% biologic experienced). Overall, 12 and 18 months drug survival of secukinumab was 76% and 67%, respectively, and was mostly determined by ineffectiveness. There was a trend towards shorter drug survival in women and in biologic experienced patients. Thirteen percent of patients experienced at least 1 episode of fungal infection. This is one of the first studies of drug survival of secukinumab in patients with psoriasis treated in daily practic

Expression of the chemokine receptor CCR5 in psoriasis and results of a randomized placebo controlled trial with a CCR5 inhibitor

Several reports have indicated that the chemokine receptor CCR5 and its ligands, especially CCL5 (formerly known as RANTES), may play a role in the pathogenesis of psoriasis. The purpose of this investigation was to examine the expression of CCR5 and its ligands in chronic plaque psoriasis and to evaluate the clinical and immunohistochemical effect of a CCR5 receptor inhibitor. Immunohistochemical analysis showed low but significant increased total numbers of CCR5 positive cells in epidermis and dermis of lesional skin in comparison to non-lesional skin. However, relative expression of CCR5 proportional to the cells observed revealed that the difference between lesional and non-lesional skin was only statistically significant in the epidermis for CD3 positive cells and in the dermis for CD68 positive cells. Quantification of mRNA by reverse transcriptase-polymerase chain reaction only showed an increased expression of CCL5 (RANTES) in lesional skin. A randomized placebo-controlled clinical trial in 32 psoriasis patients revealed no significant clinical effect and no changes at the immunohistochemical level comparing patients treated with placebo or a CCR5 inhibitor SCH351125. We conclude that although CCR5 expression is increased in psoriatic lesions, this receptor does not play a crucial role in the pathogenesis of psoriasis