Ecorys (Netherlands)

Abstract We estimate the effect of nonemployment experienced by Italian youth after secondary school exit on subsequent labor market outcomes. We focus on the impact on earnings and labor market participation both in the short term and in the long term. By estimating a factor-analytic model that controls for time-varying unobserved heterogeneity, we find that the negative effect of nonemployment on earnings is persistent, being sizeable and statistically significant up to 25 years after school completion. Penalties in terms of participation last instead shorter. Hence, early nonemployment operates by persistently locking the youth who get off to a bad start into low-wage jobs.

Abstract European policy supports cutting-edge research on Industry 4.0, aiming to promote excellence and ensure a balanced distribution of regional Industry 4.0 capacities. We analyse Industry 4.0 research projects financed by the European Union’s framework programmes over a 14-year period, investigating whether less developed regions benefit from interaction with more advanced regions that have a stronger capacity to diversify their Industry 4.0 technologies. We find a strong path-dependency in technological diversification between programming periods. Moreover, while national Industry 4.0 programmes negatively affect the capacity of regions to diversify technologies, possibly generating a substitution effect, we find that regional networking does not support less diversified regions in mastering multiple technologies.

This manual provides key information and instructions on the application and use of the SHERPA Characterisation Tool for rural areas. The tool was developed to examine the characteristics of rural areas in the EU. It consists of an excel file providing information on a set of indicators related to different key topics (e.g. climate, infrastructure, demography) based on data obtained from European databases (i.e. Eurostat, JRC).

Tumor molecular profiling upon disease progression enables investigations of the tumor evolution. Next-generation sequencing (NGS) of liquid biopsies constitutes a noninvasive readily available source of tumor molecular information. In this study, 124 plasma samples from advanced EGFR-positive NSCLC patients, treated with a first-line EGFR tyrosine kinase inhibitor (EGFR-TKI) were collected upon disease progression. The circulating cell-free DNA (cfDNA) was sequenced using the Oncomine Pan-Cancer Cell-Free Assay™. Excluding EGFR mutations, the most frequently mutated gene was TP53 (57.3%), followed by APC (11.3%), FGFR3 (7.3%), and KRAS (5.6%). Different molecular alterations were observed upon disease progression depending on the location of the original EGFR-sensitizing mutation. Specifically, the detection of the p.T790M mutation was significantly associated with the presence of exon 19 mutations in EGFR (Fisher p-value: 0.028). All KRAS activating mutations (n = 8) were detected in tumors with EGFR mutations in exons 18 and 21 (Fisher p-value < 0.001). Similarly, mutations in NRAS and HRAS were more frequently detected in samples from tumors harboring mutations in exons 18 or 21 (Fisher p-value: 0.050 and Fisher p-value: 0.099, respectively). In conclusion, our data suggest that the mechanisms underlying EGFR-TKI resistance could be dependent on the exon location of the original EGFR-sensitizing mutation.

Glioblastoma (GBM) is the most aggressive and frequent primary brain tumor in adults with a median overall survival of 15 months. Tumor recurrence and poor prognosis are related to cancer stem cells (CSCs), which drive resistance to therapies. A common characteristic in GBM is CDKN2A gene loss, located close to the cluster of type I IFN genes at Ch9p21. Newcastle disease virus (NDV) is an avian paramyxovirus with oncolytic and immunostimulatory properties that has been proposed for the treatment of GBM. We have analyzed the CDKN2A-IFN I gene cluster in 1018 glioma tumors and evaluated the NDV oncolytic effect in six GBM CSCs ex vivo and in a mouse model. Our results indicate that more than 50% of GBM patients have some IFN deletion. Moreover, GBM susceptibility to NDV is dependent on the loss of the type I IFN. Infection of GBM with an NDV-expressing influenza virus NS1 protein can overcome the resistance to oncolysis by NDV of type I-competent cells. These results highlight the potential of using NDV vectors in antitumor therapies.

BackgroundUnder a constrained health care budget, cost-increasing technologies may displace funds from existing health services. However, it is unknown what services are displaced and how such displacement takes place in practice. The aim of our study was to investigate how the Dutch hospital sector has dealt with the introduction of cost-increasing health technologies, and to present evidence of the relative importance of three main options to deal with cost-increases in health care: increased spending, increased efficiency, or displacement of other services.MethodsWe conducted six case-studies and interviewed 84 professionals with various roles and responsibilities (practitioners, heads of clinical department, board of directors, insurers, and others) to investigate how they experienced decision making in response to the cost pressure of cost-increasing health technologies. Transcripts were analyzed thematically in Atlas.ti on the basis of an item list.ResultsDirect displacement of high-value care due to the introduction of new technologies was not observed; respondents primarily pointed to increased spending and efficiency measures to accommodate the introduction of the cost-increasing technologies. Respondents found it difficult to identify the opportunity costs; partly due to limited transparency in the internal allocation of funds within a hospital. Furthermore, respondents experienced the entry of new technologies and cost-containment as two parallel processes that are generally not causally linked: cost containment was experienced as a permanent issue to level costs and revenues, independent from entry of new technologies. Furthermore, the way of financing was found important in displacement in the Netherlands, especially as there is a separate budget for expensive drugs. This budget pressure was found to be reallocated horizontally across departments, whereas the budget pressure of other services is primarily reallocated vertically within departments or divisions. Respondents noted that hospitals have reacted to budget pressures primarily through a narrowing in the portfolio of their services, and a range of (other) efficiency measures. The board of directors is central in these processes, insurers are involved only to a limited extent.ConclusionsOur findings indicate that new technologies were generally accommodated by greater efficiency and increased spending, and that hospitals sought savings or efficiency measures in response to cumulative cost pressures rather than in response to single cost-increasing technologies.

to establish the clinical and economic consequences (resource utilization and healthcare costs) of non-alcoholic fatty liver in the setting of the usual clinical practice in Spain. an observational, retrospective study was performed based on a review of the medical records of adult patients ≥ 18 years of age who sought medical care from 2017 to 2018. Patients were categorized into two groups according to fibrosis stage (estimation method: FIB-4): a) F0-F2; and b) F3-F4 (advanced fibrosis). Follow-up lasted one year. Primary endpoints included comorbidity, concomitant medication, resource utilization and costs. Results were analyzed using a multivariate approach with p < 0.05. a total of 8,151 patients were recruited with a mean age of 61.1 years and 51.5 % were male. By group: a) mild fibrosis n = 7,127, 87.4 %; and b) advanced fibrosis n = 1,024, 12.6 % (6.8 % with liver cirrhosis). The most common comorbidities included 63 % dyslipidemia, 52 % obesity, 52 % hypertension and 35 % diabetes. The average number of drugs used was 2.1 per patient. Patients with advanced fibrosis (F3-F4) had a higher average number of concomitant medications (2.5 vs 2.1; p < 0.001) and a higher AST/ALT ratio (1.1 vs 0.8; p < 0.001). The average cost (patient-year) for subjects with advanced fibrosis, corrected for covariates, was higher (€1,812 vs €1,128, p < 0.001). Age, morbidity, concomitant medication, fibrosis stage and total costs were higher in patients with diabetes. patients with advanced fibrosis were associated with more comorbidity and concomitant medications, which resulted in higher healthcare costs for the National Health System.

The NeXOS project — Next Generation Ocean Sensors — aims to improve the temporal and spatial coverage, resolution and quality of marine observations through the development of cost-efficient innovative and interoperable in-situ sensors deployable from multiple platforms, and Web Services for key domains and applications. This typically involves innovation activities undertaken by scientists in cooperation with suppliers and users. ECORYS, as the leader of the Work Package responsible for economic viability and industrialization, designed and applied a framework, suitable for guiding the innovation development process from conceptualization to market penetration, in a complex multi-actor environment.