An Open-Label, Multicenter Observational Study for Patients with Alzheimer's Disease Treated with Memantine in the Clinical Practice

Background/Aims: In this post-marketing observational study, the safety and effectiveness of memantine were evaluated in patients with Alzheimer’s disease (AD). Methods: In a 6-month, observational, open-label study at 202 specialist sites in Greece, the effectiveness of memantine was evaluated using the Mini-Mental State Examination (MMSE) and the Instrumental Activities of Daily Living (IADL) scale at baseline, and after 3 and 6 months. Discontinuation rates and adverse drug reactions (ADRs) were also recorded to evaluate the safety profile of memantine. Results: 2,570 patients participated in the study. Three and 6 months after baseline, MMSE and IADL scores were significantly improved compared to baseline. At the end of the study, 67% of the patients had improved their MMSE score; 7.1% of the patients reported ≧1 ADRs, and treatment was discontinued due to ADR in 0.7%. Conclusion: Memantine was well tolerated and had a positive effect on the patient’s cognitive and functional ability in real-life clinical practice, in agreement with randomized, controlled trials

Scalable Impairment-Aware Anycast Routing in Multi-Domain Optical Grid Networks

ABSTRACT In optical Grid networks, the main challenge is to account for not only network parameters, but also for resource availability. Anycast routing has previously been proposed as an effective solution to provide job scheduling services in optical Grids, offering a generic interface to access Grid resources and services. The main weakness of this approach is its limited scalability, especially in a multi-domain scenario. This paper proposes a novel anycast proxy architecture, which extends the anycast principle to a multi-domain scenario. The main purpose of the architecture is to perform aggregation of resource and network states, and as such improve computational scalability and reduce control plane traffic. Furthermore, the architecture has the desirable properties of allowing Grid domains to maintain their autonomy and hide internal configuration details from other domains. Finally, we propose an impairment-aware anycast routing algorithm that incorporates the main physical layer characteristics of large-scale optical networks into its path computation process. By integrating the proposed routing scheme into the introduced architecture we demonstrate significant network performance improvements. Keywords: Grid computing, routing algorithms, optical networks, physical impairments, anycast routing. INTRODUCTION Today, the need for network systems to support storage and computing services for science and business, is often satisfied by relatively isolated computing infrastructure (clusters). Migration to truly distributed and integrated applications requires optimization and (re)design of the underlying network technology to create a Grid platform for the cost and resource efficient delivery of network services with substantial data transfer, processing power and/or data storage requirements. Optical networks offer an undeniable potential for the Grid, given their proven track-record in the context of high-speed, long-haul, networking. Not only eScience applications dealing with large experimental data sets (e.g. particle physics) but also business/consumer oriented applications can benefit from optical Grid infrastructure [1]: both the high data rates typical of eScience applications and the low latency requirements of consumer/business applications (cf. interactivity) can effectively be addressed. When using transparent WDM as such network technology, signals are transported end-to-end optically without being converted to the electrical domain in between. Connection provisioning of all-optical connections (lightpaths) between source and destination nodes is based on specific routing and wavelength assignment algorithms (RWA). Traditional RWA schemes only account for network conditions such as connectivity and available capacity, without considering physical layer details. However, in transparent optical networks covering large geographical areas, the optical signal experiences the accumulation of physical impairments through transmission and switching, possibly resulting in unacceptable signal quality Another emerging and challenging task in distributed and heterogeneous computing environments, is job scheduling: when and where to execute a given Grid job, based on the requirements of the job (for instance a deadline and minimal computational power) and the current state of the network and resources. Traditionally, a local scheduler optimizes utilization and performance of a single Grid site, while a meta-scheduler is distributes workload across different sites. Current implementations of these (meta-)schedulers only account for Grid resource availability In this paper we propose a novel architecture to support impairment-aware anycast routing for large-scale optical Grid networks. Section 2 discusses general approaches to support multi-domain networks. We then proceed to introduce a novel architecture, which can provide anycast Grid services in a multi-domain scenario (Section 3). Simulation analysis is used to demonstrate the improved scalability without incurring significant performance loss. Furthermore, Section 4 shows how to incorporate physical layer impairments, to further improve the performance of optical Grid networks. Conclusions are presented in Section 5

Energy efficiency considerations in integrated IT and optical network resilient infrastructures

The European Integrated Project GEYSERS - Generalised Architecture for Dynamic Infrastructure Services - is concentrating on infrastructures incorporating integrated optical network and IT resources in support of the Future Internet with special emphasis on cloud computing. More specifically GEYSERS proposes the concept of Virtual Infrastructures over one or more interconnected Physical Infrastructures comprising both network and IT resources. Taking into consideration the energy consumption levels associated with the ICT today and the expansion of the Internet in size and complexity, that incurring increased energy consumption of both IT and network resources, energy efficient infrastructure design becomes critical. To address this need, in the framework of GEYSERS, we propose energy efficient design of infrastructures incorporating integrated optical network and IT resources, supporting resilient end-to-end services. Our modeling results quantify significant energy savings of the proposed solution by jointly optimizing the allocation of both network and IT resources

Streptococcus pneumoniae Serotype-2 Childhood Meningitis in Bangladesh: A Newly Recognized Pneumococcal Infection Threat

BACKGROUND: Streptococcus pneumoniae is a leading cause of meningitis in countries where pneumococcal conjugate vaccines (PCV) targeting commonly occurring serotypes are not routinely used. However, effectiveness of PCV would be jeopardized by emergence of invasive pneumococcal diseases (IPD) caused by serotypes which are not included in PCV. Systematic hospital based surveillance in Bangladesh was established and progressively improved to determine the pathogens causing childhood sepsis and meningitis. This also provided the foundation for determining the spectrum of serotypes causing IPD. This article reports an unprecedented upsurge of serotype 2, an uncommon pneumococcal serotype, without any known intervention. METHODS AND FINDINGS: Cases with suspected IPD had blood or cerebrospinal fluid (CSF) collected from the beginning of 2001 till 2009. Pneumococcal serotypes were determined by capsular swelling of isolates or PCR of culture-negative CSF specimens. Multicenter national surveillance, expanded from 2004, identified 45,437 patients with suspected bacteremia who were blood cultured and 10,618 suspected meningitis cases who had a lumber puncture. Pneumococcus accounted for 230 culture positive cases of meningitis in children <5 years. Serotype-2 was the leading cause of pneumococcal meningitis, accounting for 20.4% (45/221; 95% CI 15%-26%) of cases. Ninety eight percent (45/46) of these serotype-2 strains were isolated from meningitis cases, yielding the highest serotype-specific odds ratio for meningitis (29.6; 95% CI 3.4-256.3). The serotype-2 strains had three closely related pulsed field gel electrophoresis types. CONCLUSIONS: S. pneumoniae serotype-2 was found to possess an unusually high potential for causing meningitis and was the leading serotype-specific cause of childhood meningitis in Bangladesh over the past decade. Persisting disease occurrence or progressive spread would represent a major potential infection threat since serotype-2 is not included in PCVs currently licensed or under development

Risk factors for death from invasive pneumococcal disease, europe, 2010

We studied the possible association between patient age and sex, clinical presentation, Streptococcus pneumoniae serotype, antimicrobial resistance, and death in invasive pneumococcal disease cases reported by 17 European countries during 2010. The study sample comprised 2,921 patients, of whom 56.8% were men and 38.2% were >65 years of age. Meningitis occurred in 18.5% of cases. Death was reported in 264 (9.0%) cases. Older age, meningitis, and nonsusceptibility to penicillin were signifcantly asso ciated with death. Non-pneumococcal conjugate vaccine (PCV) serotypes among children 65 years of age, risk did not differ by serotype. These fndings highlight differences in case-fatality rates between sero types and age; thus, continued epidemiologic surveillance across all ages is crucial to monitor the long-term effects of PCVs

Trends in invasive bacterial diseases during the first 2 years of the COVID-19 pandemic: analyses of prospective surveillance data from 30 countries and territories in the IRIS Consortium.

BACKGROUND The Invasive Respiratory Infection Surveillance (IRIS) Consortium was established to assess the impact of the COVID-19 pandemic on invasive diseases caused by Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, and Streptococcus agalactiae. We aimed to analyse the incidence and distribution of these diseases during the first 2 years of the COVID-19 pandemic compared to the 2 years preceding the pandemic. METHODS For this prospective analysis, laboratories in 30 countries and territories representing five continents submitted surveillance data from Jan 1, 2018, to Jan 2, 2022, to private projects within databases in PubMLST. The impact of COVID-19 containment measures on the overall number of cases was analysed, and changes in disease distributions by patient age and serotype or group were examined. Interrupted time-series analyses were done to quantify the impact of pandemic response measures and their relaxation on disease rates, and autoregressive integrated moving average models were used to estimate effect sizes and forecast counterfactual trends by hemisphere. FINDINGS Overall, 116 841 cases were analysed: 76 481 in 2018-19, before the pandemic, and 40 360 in 2020-21, during the pandemic. During the pandemic there was a significant reduction in the risk of disease caused by S pneumoniae (risk ratio 0·47; 95% CI 0·40-0·55), H influenzae (0·51; 0·40-0·66) and N meningitidis (0·26; 0·21-0·31), while no significant changes were observed for S agalactiae (1·02; 0·75-1·40), which is not transmitted via the respiratory route. No major changes in the distribution of cases were observed when stratified by patient age or serotype or group. An estimated 36 289 (95% prediction interval 17 145-55 434) cases of invasive bacterial disease were averted during the first 2 years of the pandemic among IRIS-participating countries and territories. INTERPRETATION COVID-19 containment measures were associated with a sustained decrease in the incidence of invasive disease caused by S pneumoniae, H influenzae, and N meningitidis during the first 2 years of the pandemic, but cases began to increase in some countries towards the end of 2021 as pandemic restrictions were lifted. These IRIS data provide a better understanding of microbial transmission, will inform vaccine development and implementation, and can contribute to health-care service planning and provision of policies. FUNDING Wellcome Trust, NIHR Oxford Biomedical Research Centre, Spanish Ministry of Science and Innovation, Korea Disease Control and Prevention Agency, Torsten Söderberg Foundation, Stockholm County Council, Swedish Research Council, German Federal Ministry of Health, Robert Koch Institute, Pfizer, Merck, and the Greek National Public Health Organization

Microenvironmental Modulation of Decorin and Lumican in Temozolomide-Resistant Glioblastoma and Neuroblastoma Cancer Stem-Like Cells

The presence of cancer stem cells (CSCs) or tumor-initiating cells can lead to cancer recurrence in a permissive cell–microenvironment interplay, promoting invasion in glioblastoma (GBM) and neuroblastoma (NB). Extracellular matrix (ECM) small leucine-rich proteoglycans (SLRPs) play multiple roles in tissue homeostasis by remodeling the extracellular matrix (ECM) components and modulating intracellular signaling pathways. Due to their pan-inhibitory properties against receptor tyrosine kinases (RTKs), SLRPs are reported to exert anticancer effects in vitro and in vivo. However, their roles seem to be tissue-specific and they are also involved in cancer cell migration and drug resistance, paving the way to complex different scenarios. The aim of this study was to determine whether the SLRPs decorin (DCN) and lumican (LUM) are recruited in cell plasticity and microenvironmental adaptation of differentiated cancer cells induced towards stem-like phenotype. Floating neurospheres were generated by applying CSC enrichment medium (neural stem cell serum-free medium, NSC SFM) to the established SF-268 and SK-N-SH cancer cell lines, cellular models of GBM and NB, respectively. In both models, the time-dependent synergistic activation of DCN and LUM was observed. The highest DCN and LUM mRNA/protein expression was detected after cell exposure to NSC SFM for 8/12 days, considering these cells as SLRP-expressing (SLRP+) CSC-like. Ultrastructural imaging showed the cellular heterogeneity of both the GBM and NB neurospheres and identified the inner living cells. Parental cell lines of both GBM and NB grew only in soft agar + NSC SFM, whereas the secondary neurospheres (originated from SLRP+ t8 CSC-like) showed lower proliferation rates than primary neurospheres. Interestingly, the SLRP+ CSC-like from the GBM and NB neurospheres were resistant to temozolomide (TMZ) at concentrations >750 μM. Our results suggest that GBM and NB CSC-like promote the activation of huge quantities of SLRP in response to CSC enrichment, simultaneously acquiring TMZ resistance, cellular heterogeneity, and a quiescent phenotype, suggesting a novel pivotal role for SLRP in drug resistance and cell plasticity of CSC-like, allowing cell survival and ECM/niche modulation potential.This study was supported by Fundació la Marató TV3, Project n° 111431

METIS research advances towards the 5G mobile and wireless system definition

[EN] The Mobile and wireless communications Enablers for the Twenty-twenty Information Society (METIS) project is laying the foundations of Fifth Generation (5G) mobile and wireless communication system putting together the point of view of vendors, operators, vertical players, and academia. METIS envisions a 5G system concept that efficiently integrates new applications developed in the METIS horizontal topics and evolved versions of existing services and systems. This article provides a first view on the METIS system concept, highlights the main features including architecture, and addresses the challenges while discussing perspectives for the further research work.Part of this work has been performed in the framework of the FP7 project ICT-317669 METIS, which is partly funded by the European Commission. The authors would like to acknowledge the contributions of their colleagues in METIS with special thanks to Petar Popovski, Peter Fertl, David Gozalvez-Serrano, Andreas Hoglund, Zexian Li, and Krystian Pawlak. Also thanks to Josef Eichinger and Malte Schellmann for the fruitful discussions during the revision of this article.Monserrat Del Río, JF.; Mange, G.; Braun, V.; Tullberg, H.; Zimmermann, G.; Bulakci, O. (2015). METIS research advances towards the 5G mobile and wireless system definition. 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