Wireless internet architecture and testbed for wineglass

One of the most challenging issues in the area of mobile communication is the deployment of IPbased wireless multimedia networks in public and business environments. The public branch may involve public mobile networks, like UMTS as 3G system, while the business branch introduces local radio access networks by means of W-LANs. Conventional mobile networks realise mobile specific functionality, e.g. mobility management or authentication and accounting, by implementing appropriate mechanisms in specific switching nodes (e.g. SGSN in GPRS). In order to exploit the full potential of IP networking solutions a replacement of these mechanisms by IP-based solutions might be appropriate. In addition current and innovative future services in mobile environments require at least soft-guaranteed, differentiated QoS. Therefore the WINE GLASS project investigates and implements enhanced IP-based techniques supporting mobility and QoS in a wireless Internet architecture. As a means to verify the applicability of the implemented solutions, location-aware services deploying both IP-mobility and QoS mechanisms will be implemented and demonstratedPeer ReviewedPostprint (published version

Analysis of symmetries in models of multi-strain infections

In mathematical studies of the dynamics of multi-strain diseases caused by antigenically diverse pathogens, there is a substantial interest in analytical insights. Using the example of a generic model of multi-strain diseases with cross-immunity between strains, we show that a significant understanding of the stability of steady states and possible dynamical behaviours can be achieved when the symmetry of interactions between strains is taken into account. Techniques of equivariant bifurcation theory allow one to identify the type of possible symmetry-breaking Hopf bifurcation, as well as to classify different periodic solutions in terms of their spatial and temporal symmetries. The approach is also illustrated on other models of multi-strain diseases, where the same methodology provides a systematic understanding of bifurcation scenarios and periodic behaviours. The results of the analysis are quite generic, and have wider implications for understanding the dynamics of a large class of models of multi-strain diseases

The effects of symmetry on the dynamics of antigenic variation

In the studies of dynamics of pathogens and their interactions with a host immune system, an important role is played by the structure of antigenic variants associated with a pathogen. Using the example of a model of antigenic variation in malaria, we show how many of the observed dynamical regimes can be explained in terms of the symmetry of interactions between different antigenic variants. The results of this analysis are quite generic, and have wider implications for understanding the dynamics of immune escape of other parasites, as well as for the dynamics of multi-strain diseases.Comment: 21 pages, 4 figures; J. Math. Biol. (2012), Online Firs

Impact of generic alendronate cost on the cost-effectiveness of osteoporosis screening and treatment

Introduction: Since alendronate became available in generic form in the Unites States in 2008, its price has been decreasing. The objective of this study was to investigate the impact of alendronate cost on the cost-effectiveness of osteoporosis screening and treatment in postmenopausal women. Methods: Microsimulation cost-effectiveness model of osteoporosis screening and treatment for U.S. women age 65 and older. We assumed screening initiation at age 65 with central dual-energy x-ray absorptiometry (DXA), and alendronate treatment for individuals with osteoporosis; with a comparator of "no screening" and treatment only after fracture occurrence. We evaluated annual alendronate costs of $20 through$800; outcome measures included fractures; nursing home admission; medication adverse events; death; costs; quality-adjusted life-years (QALYs); and incremental cost-effectiveness ratios (ICERs) in 2010 U.S. dollars per QALY gained. A lifetime time horizon was used, and direct costs were included. Base-case and sensitivity analyses were performed. Results: Base-case analysis results showed that at annual alendronate costs of $200 or less, osteoporosis screening followed by treatment was cost-saving, resulting in lower total costs than no screening as well as more QALYs (10.6 additional quality-adjusted life-days). When assuming alendronate costs of$400 through $800, screening and treatment resulted in greater lifetime costs than no screening but was highly cost-effective, with ICERs ranging from$714 per QALY gained through $13,902 per QALY gained. Probabilistic sensitivity analyses revealed that the cost-effectiveness of osteoporosis screening followed by alendronate treatment was robust to joint input parameter estimate variation at a willingness-to-pay threshold of$50,000/QALY at all alendronate costs evaluated. Conclusions: Osteoporosis screening followed by alendronate treatment is effective and highly cost-effective for postmenopausal women across a range of alendronate costs, and may be cost-saving at annual alendronate costs of $200 or less. © 2012 Nayak et al

Faster growth with shorter antigens can explain a VSG hierarchy during African trypanosome infections:a feint attack by parasites

The parasitic African trypanosome, Trypanosoma brucei, evades the adaptive host immune response by a process of antigenic variation that involves the clonal switching of variant surface glycoproteins (VSGs). The VSGs that come to dominate in vivo during an infection are not entirely random, but display a hierarchical order. How this arises is not fully understood. Combining available genetic data with mathematical modelling, we report a VSG-length-dependent hierarchical timing of clonal VSG dominance in a mouse model, consistent with an inverse correlation between VSG length and trypanosome growth-rate. Our analyses indicate that, among parasites switching to new VSGs, those expressing shorter VSGs preferentially accumulate to a detectable level that is sufficient to trigger a targeted immune response. This may be due to the increased metabolic cost of producing longer VSGs. Subsequent elimination of faster-growing parasites then allows slower-growing parasites with longer VSGs to accumulate. This interaction between the host and parasite is able to explain the temporal distribution of VSGs observed in vivo. Thus, our findings reveal a length-dependent hierarchy that operates during T. brucei infection. This represents a ‘feint attack’ diversion tactic utilised by these persistent parasites to out-maneuver the host adaptive immune system

Genome-Wide Association Study of Exercise Behavior in Dutch and American Adults

The objective of this study was to identify genetic variants that are associated with adult leisure-time exercise behavior using genome-wide association in two independent samples

Vitamin D supplementation and breast cancer prevention : a systematic review and meta-analysis of randomized clinical trials

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the “Related Article” feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I2 test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74–1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23–1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54–1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L

Global circulation patterns of seasonal influenza viruses vary with antigenic drift.

Understanding the spatiotemporal patterns of emergence and circulation of new human seasonal influenza virus variants is a key scientific and public health challenge. The global circulation patterns of influenza A/H3N2 viruses are well characterized, but the patterns of A/H1N1 and B viruses have remained largely unexplored. Here we show that the global circulation patterns of A/H1N1 (up to 2009), B/Victoria, and B/Yamagata viruses differ substantially from those of A/H3N2 viruses, on the basis of analyses of 9,604 haemagglutinin sequences of human seasonal influenza viruses from 2000 to 2012. Whereas genetic variants of A/H3N2 viruses did not persist locally between epidemics and were reseeded from East and Southeast Asia, genetic variants of A/H1N1 and B viruses persisted across several seasons and exhibited complex global dynamics with East and Southeast Asia playing a limited role in disseminating new variants. The less frequent global movement of influenza A/H1N1 and B viruses coincided with slower rates of antigenic evolution, lower ages of infection, and smaller, less frequent epidemics compared to A/H3N2 viruses. Detailed epidemic models support differences in age of infection, combined with the less frequent travel of children, as probable drivers of the differences in the patterns of global circulation, suggesting a complex interaction between virus evolution, epidemiology, and human behaviour.T.B. was supported by a Newton International Fellowship from the Royal Society and through NIH U54 GM111274. S.R. was supported by MRC (UK, Project MR/J008761/1), Wellcome Trust (UK, Project 093488/Z/10/Z), Fogarty International Centre (USA, R01 TW008246‐01), DHS (USA, RAPIDD program), NIGMS (USA, MIDAS U01 GM110721‐01) and NIHR (UK, Health Protection Research Unit funding). The Melbourne WHO Collaborating Centre for Reference and Research on Influenza was supported by the Australian Government Department of Health and thanks N. Komadina and Y.‐M. Deng. The Atlanta WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza was supported by the U.S. Department of 13 Health and Human Services. NIV thanks A.C. Mishra, M. Chawla‐Sarkar, A.M. Abraham, D. Biswas, S. Shrikhande, AnuKumar B, and A. Jain. Influenza surveillance in India was expanded, in part, through US Cooperative Agreements (5U50C1024407 and U51IP000333) and by the Indian Council of Medical Research. M.A.S. was supported through NSF DMS 1264153 and NIH R01 AI 107034. Work of the WHO Collaborating Centre for Reference and Research on Influenza at the MRC National Institute for Medical Research was supported by U117512723. P.L., A.R. & M.A.S were supported by EU Seventh Framework Programme [FP7/2007‐2013] under Grant Agreement no. 278433-­‐PREDEMICS and ERC Grant agreement no. 260864. C.A.R. was supported by a University Research Fellowship from the Royal Society.This is the author accepted manuscript. It is currently under infinite embargo pending publication of the final version

Estimating Dengue Transmission Intensity from Sero-Prevalence Surveys in Multiple Countries

BACKGROUND:Estimates of dengue transmission intensity remain ambiguous. Since the majority of infections are asymptomatic, surveillance systems substantially underestimate true rates of infection. With advances in the development of novel control measures, obtaining robust estimates of average dengue transmission intensity is key for assessing both the burden of disease from dengue and the likely impact of interventions. METHODOLOGY/PRINCIPAL FINDINGS:The force of infection (λ) and corresponding basic reproduction numbers (R0) for dengue were estimated from non-serotype (IgG) and serotype-specific (PRNT) age-stratified seroprevalence surveys identified from the literature. The majority of R0 estimates ranged from 1-4. Assuming that two heterologous infections result in complete immunity produced up to two-fold higher estimates of R0 than when tertiary and quaternary infections were included. λ estimated from IgG data were comparable to the sum of serotype-specific forces of infection derived from PRNT data, particularly when inter-serotype interactions were allowed for. CONCLUSIONS/SIGNIFICANCE:Our analysis highlights the highly heterogeneous nature of dengue transmission. How underlying assumptions about serotype interactions and immunity affect the relationship between the force of infection and R0 will have implications for control planning. While PRNT data provides the maximum information, our study shows that even the much cheaper ELISA-based assays would provide comparable baseline estimates of overall transmission intensity which will be an important consideration in resource-constrained settings