Usage of link-level performance indicators for HSDPA network-level simulations in E-UMTS

The paper describes integration of HSDPA (high-speed downlink packet access) link-level simulation results into network-level simulations for enhanced UMTS. The link-level simulations model all physical layer features depicted in the 3GPP standards. These include: generation of transport blocks; turbo coding; rate matching; spreading; scrambling; modulation. At the receiver side, all complementary blocks are designed, with soft-decision demodulation, and a turbo decoder using the MAP (maximum a posteriori) algorithm with 8 iterations. An analytical formula is defined that fits the CQI (channel quality indicator) dependent BLER (block error rate) versus E/sub b//N/sub 0/ results in an AWGN channel. This formula models the physical layer in the network-level simulator. A further extension for frequency selective fading channels has been defined. The network-level simulator includes propagation models that provide SNR values. Based on these SNR values and the simplified physical layer model, an algorithm selects the CQI, and determines the actual BLER at time of reception. The rounding down and delaying of the CQI reporting, which corresponds to the W-CDMA standard, has a significant impact on throughput and transfer delay of the HS-DSCH. Some compensation can be found in a modified transmission. The integration of the link-level and network-level simulators gives accurate and realistic results that can be used in more studies that focus on network layer aspects of packet based services over HSDP

Fair channel-dependent scheduling in CDMA systems

In this study a scheduling algorithm for CDMA systems is presented which is a trade-off between two extreme ways of scheduling: C/I based and Round-Robin scheduling. The simulation results indeed display that the advantages of both these extremes have been combined in the new algorithm: a good fairness, comparable to that of the Round-Robin scheduling, together with almost the same power gain as reached in the C/I based scheduling

Data management and data analysis techniques in pharmacoepidemiological studies using a pre-planned multi-database approach : a systematic literature review

PurposeTo identify pharmacoepidemiological multi-database studies and to describe data management and data analysis techniques used for combining data. MethodsSystematic literature searches were conducted in PubMed and Embase complemented by a manual literature search. We included pharmacoepidemiological multi-database studies published from 2007 onwards that combined data for a pre-planned common analysis or quantitative synthesis. Information was retrieved about study characteristics, methods used for individual-level analyses and meta-analyses, data management and motivations for performing the study. ResultsWe found 3083 articles by the systematic searches and an additional 176 by the manual search. After full-text screening of 75 articles, 22 were selected for final inclusion. The number of databases used per study ranged from 2 to 17 (median=4.0). Most studies used a cohort design (82%) instead of a case-control design (18%). Logistic regression was most often used for individual-level analyses (41%), followed by Cox regression (23%) and Poisson regression (14%). As meta-analysis method, a majority of the studies combined individual patient data (73%). Six studies performed an aggregate meta-analysis (27%), while a semi-aggregate approach was applied in three studies (14%). Information on central programming or heterogeneity assessment was missing in approximately half of the publications. Most studies were motivated by improving power (86%). ConclusionsPharmacoepidemiological multi-database studies are a well-powered strategy to address safety issues and have increased in popularity. To be able to correctly interpret the results of these studies, it is important to systematically report on database management and analysis techniques, including central programming and heterogeneity testing. (c) 2015 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.Peer reviewe

Effectiveness of a COVID-19 contact tracing app in a simulation model with indirect and informal contact tracing

During the COVID-19 pandemic, contact tracing was used to identify individuals who had been in contact with a confirmed case so that these contacted individuals could be tested and quarantined to prevent further spread of the SARS-CoV-2 virus. Many countries developed mobile apps to find these contacted individuals faster. We evaluate the epidemiological effectiveness of the Dutch app CoronaMelder, where we measure effectiveness as the reduction of the reproduction number R. To this end, we use a simulation model of SARS-CoV-2 spread and contact tracing, informed by data collected during the study period (December 2020 - March 2021) in the Netherlands. We show that the tracing app caused a clear but small reduction of the reproduction number, and the magnitude of the effect was found to be robust in sensitivity analyses. The app could have been more effective if more people had used it, and if notification of contacts could have been done directly by the user and thus reducing the time intervals between symptom onset and reporting of contacts. The model has two innovative aspects: i) it accounts for the clustered nature of social networks and ii) cases can alert their contacts informally without involvement of health authorities or the tracing app.</p

Viral mimic poly-(I:C) attenuates airway epithelial T cell suppressive capacity; implications for asthma

In allergen-sensitised asthmatic individuals, allergen-specific type-2 T-helper cells proliferate and secrete type-2 cytokines (e.g. interleukin (IL)-4, -5 and -13), driving the airway inflammatory response that gives rise to the clinical symptoms of asthma. Both early-life sensitisation to aeroallergens and lower respiratory viral infections are important environmental risk factors for developing asthma. Additionally, respiratory viral infections are the most common trigger for asthma exacerbations. Of interest, many asthma susceptibility genes are expressed in the airway epithelium [1], which forms the first continuous line of defence against inhaled environmental insults, including viruses and aeroallergens. Impaired immune regulation and failure to maintain tolerance to allergens is thought to contribute to allergic sensitisation. Asthma epithelium may be deficient in its innate immune defence against viral infections, resulting in increased viral replication upon rhinovirus infection compared to nonasthma-derived epithelial cultures [2]. Furthermore, there is evidence for loss of the mucosal immune barrier in asthma, with disruption of epithelial integrity [1, 3]. This may lead not only to increased permeability, but also to the release of pro-inflammatory mediators, specifically of cytokines that drive type-2 responses [3, 4]. We recently observed that the ability of allergens to disrupt epithelial barrier function is related to the development of type-2-mediated inflammation in asthma [5, 6]. Furthermore, we demonstrated that healthy murine lung epithelium is a potent inhibitor of T-cell proliferation and that this inhibition is lost upon viral infection [7]. It is unknown if this immune regulatory effect is displayed by human epithelium and is dysregulated in asthma. We hypothesise that changes in this regulatory effect translate into aberrant regulation of T-cell responses in asthma. We studied the epithelial regulation of T-cell proliferation and cytokine responses upon epithelial stimulation with a viral mimic, using co-culture of human T-cells and primary bronchial epithelial cells (PBECs) from healthy controls and asthma patients

Easy Wireless: broadband ad-hoc networking for emergency services

Wireless ad-hoc networks will enable emergency services to continuously overview and act upon the actual status of the situation by retrieving and exchanging detailed up-to-date information between the rescue workers. Deployment of high-bandwidth, robust, self-organising ad-hoc networks will enable quicker response to typical what/where/when questions, than the more vulnerable low-bandwidth communication networks currently in use. This paper addresses a number of results of the Easy Wireless project that enable high bandwidth robust ad-hoc networking. Most of the concepts presented here have been experimentally verified and/or prototyped

Protease-Activated Receptor-2 Activation Contributes to House Dust Mite-Induced IgE Responses in Mice

Aeroallergens such as house dust mite (HDM), cockroach, and grass or tree pollen are innocuous substances that can induce allergic sensitization upon inhalation. The serine proteases present in these allergens are thought to activate the protease-activated receptor (PAR)-2, on the airway epithelium, thereby potentially inducing allergic sensitization at the expense of inhalation tolerance. We hypothesized that the proteolytic activity of allergens may play an important factor in the allergenicity to house dust mite and is essential to overcome airway tolerance. Here, we aimed to investigate the role of PAR-2 activation in allergic sensitization and HDM-induced allergic airway inflammation. In our study, Par-2 deficient mice were treated with two different HDM extracts containing high and low serine protease activities twice a week for a period of 5 weeks. We determined airway inflammation through quantification of percentages of mononuclear cells, eosinophils and neutrophils in the bronchial alveolar lavage fluid and measured total IgE and HDM-specific IgE and IgG1 levels in serum. Furthermore, Th2 and pro-inflammatory cytokines including IL-5, IL-13, Eotaxin-1, IL-17, KC, Chemokine (C-C motif) ligand 17 (CCL17) and thymic stromal lymphopoietin (TSLP), were measured in lung tissue homogenates. We observed that independent of the serine protease content, HDM was able to induce elevated levels of eosinophils and neutrophils in the airways of both wild-type (WT) and Par-2 deficient mice. Furthermore, we show that induction of pro-inflammatory cytokines by HDM exposure is independent of Par-2 activation. In contrast, serine protease activity of HDM does contribute to enhanced levels of total IgE, but not HDM-specific IgE. We conclude that, while Par-2 activation contributes to the development of IgE responses, it is largely dispensable for the HDM-induced induction of pro-inflammatory cytokines and airway inflammation in an experimental mouse model of HDM-driven allergic airway disease

Paracrine Regulation of Alveolar Epithelial Damage and Repair Responses by Human Lung-Resident Mesenchymal Stromal Cells

COPD is characterized by irreversible lung tissue damage. We hypothesized that lung-derived mesenchymal stromal cells (LMSCs) reduce alveolar epithelial damage via paracrine processes, and may thus be suitable for cell-based strategies in COPD. We aimed to assess whether COPD-derived LMSCs display abnormalities. LMSCs were isolated from lung tissue of severe COPD patients and non-COPD controls. Effects of LMSC conditioned-medium (CM) on H(2)O(2)-induced, electric field- and scratch-injury were studied in A549 and NCI-H441 epithelial cells. In organoid models, LMSCs were co-cultured with NCI-H441 or primary lung cells. Organoid number, size and expression of alveolar type II markers were assessed. Pre-treatment with LMSC-CM significantly attenuated oxidative stress-induced necrosis and accelerated wound repair in A549. Co-culture with LMSCs supported organoid formation in NCI-H441 and primary epithelial cells, resulting in significantly larger organoids with lower type II-marker positivity in the presence of COPD-derived versus control LMSCs. Similar abnormalities developed in organoids from COPD compared to control-derived lung cells, with significantly larger organoids. Collectively, this indicates that LMSCs’ secretome attenuates alveolar epithelial injury and supports epithelial repair. Additionally, LMSCs promote generation of alveolar organoids, with abnormalities in the supportive effects of COPD-derived LMCS, reflective of impaired regenerative responses of COPD distal lung cells