Predicting the emergence of drug-resistant HSV-2: new predictions

BACKGROUND: Mathematical models can be used to predict the emergence and transmission of antiviral resistance. Previously it has been predicted that high usage of antivirals (in immunocompetent populations) to treat Herpes Simplex Virus type 2 (HSV-2) would only lead to fairly low levels of antiviral resistance. The HSV-2 predictions were based upon the assumption that drug-resistant strains of HSV-2 would be less infectious than drug-sensitive strains but that the drug-resistant strains would not be impaired in their ability to reactivate. Recent data suggest that some drug-resistant strains of HSV-2 are likely to be impaired in their ability to reactivate. Objectives: (1) To predict the effect of a high usage of antivirals on the prevalence of drug-resistant HSV-2 under the assumption that drug-resistant strains will be less infectious than drug-sensitive strains of HSV-2 and also have an impaired ability to reactivate. (2) To compare predictions with previous published predictions. METHODS: We generated theoretical drug-resistant HSV-2 strains that were attenuated (in comparison with drug-sensitive strains) in both infectivity and ability to reactivate. We then used a transmission model to predict the emergence and transmission of drug-resistant HSV-2 in the immunocompetent population assuming a high usage of antivirals. RESULTS: Our predictions are an order of magnitude lower than previous predictions; we predict that even after 25 years of high antiviral usage only 5 out of 10,000 immunocompetent individuals will be shedding drug-resistant virus. Furthermore, after 25 years, 52 cases of HSV-2 would have been prevented for each prevalent case of drug-resistant HSV-2. CONCLUSIONS: The predicted levels of drug-resistant HSV-2 for the immunocompetent population are so low that it seems unlikely that cases of drug-resistant HSV-2 will be detected

Inductive Reasoning Games as Influenza Vaccination Models: Mean Field Analysis

We define and analyze an inductive reasoning game of voluntary yearly vaccination in order to establish whether or not a population of individuals acting in their own self-interest would be able to prevent influenza epidemics. We find that epidemics are rarely prevented. We also find that severe epidemics may occur without the introduction of pandemic strains. We further address the situation where market incentives are introduced to help ameliorating epidemics. Surprisingly, we find that vaccinating families exacerbates epidemics. However, a public health program requesting prepayment of vaccinations may significantly ameliorate influenza epidemics.Comment: 20 pages, 7 figure

The importance of including dynamic social networks when modeling epidemics of airborne infections: does increasing complexity increase accuracy?

Mathematical models are useful tools for understanding and predicting epidemics. A recent innovative modeling study by Stehle and colleagues addressed the issue of how complex models need to be to ensure accuracy. The authors collected data on face-to-face contacts during a two-day conference. They then constructed a series of dynamic social contact networks, each of which was used to model an epidemic generated by a fast-spreading airborne pathogen. Intriguingly, Stehle and colleagues found that increasing model complexity did not always increase accuracy. Specifically, the most detailed contact network and a simplified version of this network generated very similar results. These results are extremely interesting and require further exploration to determine their generalizability

The parent programme implementation checklist (PPIC): the development and testing of an objective measure of skills and fidelity for the delivery of parent programmes

This is the author accepted manuscript. The final version is available from Taylor & Francis via the DOI in this recordBackground: Group-based parent programmes demonstrate positive benefits for adult and child mental health, and child behaviour outcomes. Greater fidelity to the programme delivery model equates to better outcomes for families attending, however, fidelity is typically self-monitored using programme specific checklists. Self-completed measures are open to bias, and it is difficult to know if positive outcomes found from research studies will be maintained when delivered in regular services. Currently, ongoing objective monitoring of quality is not conducted during usual service delivery. This is odd given that quality of other services is assessed objectively, for example by the Office for Standards in Education, Children's Services and Skills (OFSTED). Independent observations of programme delivery are needed to assess fidelity and quality of delivery to ensure positive outcomes, and therefore justify the expense of programme delivery. Methods: This paper outlines the initial development and reliability of a tool, the Parent Programme Implementation Checklist (PPIC), which was originally developed as a simple, brief and generic observational tool for independent assessment of implementation fidelity of group-based parent programmes. PPIC does not require intensive observer training before application/use. This paper presents initial data obtained during delivery of the Incredible Years BASIC programme across nine localities in England and Wales, United Kingdom (UK). Results: Reasonable levels of inter-rater reliability were achieved across each of the three subscales (Adherence, Quality and Participant Responsiveness) and the overall total score when applying percentage agreements (>70%) and intra-class correlations (ICC) (ICC range between 0.404 and 0.730). Intra-rater reliability (n = 6) was acceptable at the subscale level. Conclusions: We conclude that the PPIC has promise, and with further development could be utilised to assess fidelity of parent group delivery during research trials and standard service delivery. Further development would need to include data from other parent programmes, and testing by non-research staff. The objective assessment of quality of delivery would inform services where improvements could be made.This research was supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care – Yorkshire and Humber, and South West Peninsula

Serving GODAE Data and Products to the Ocean Community

The Global Ocean Data Assimilation Experiment (GODAE [http:// www.godae.org]) has spanned a decade of rapid technological development. The ever-increasing volume and diversity of oceanographic data produced by in situ instruments, remote-sensing platforms, and computer simulations have driven the development of a number of innovative technologies that are essential for connecting scientists with the data that they need. This paper gives an overview of the technologies that have been developed and applied in the course of GODAE, which now provide users of oceanographic data with the capability to discover, evaluate, visualize, download, and analyze data from all over the world. The key to this capability is the ability to reduce the inherent complexity of oceanographic data by providing a consistent, harmonized view of the various data products. The challenges of data serving have been addressed over the last 10 years through the cooperative skills and energies of many individuals

The Emergence of HIV Transmitted Resistance in Botswana: “When Will the WHO Detection Threshold Be Exceeded?”

BACKGROUND: The Botswana antiretroviral program began in 2002 and currently treats 42,000 patients, with a goal of treating 85,000 by 2009. The World Health Organization (WHO) has begun to implement a surveillance system for detecting transmitted resistance that exceeds a threshold of 5%. However, the WHO has not determined when this threshold will be reached. Here we model the Botswana government's treatment plan and predict, to 2009, the likely stochastic evolution of transmitted resistance. METHODS: We developed a model of the stochastic evolution of drug-resistant strains and formulated a birth-death Master equation. We analyzed this equation to obtain an analytical solution of the probabilistic evolutionary trajectory for transmitted resistance, and used treatment and demographic data from Botswana. We determined the temporal dynamics of transmitted resistance as a function of: (i) the transmissibility (i.e., fitness) of the drug-resistant strains that may evolve and (ii) the rate of acquired resistance. RESULTS: Transmitted resistance in Botswana will be unlikely to exceed the WHO's threshold by 2009 even if the rate of acquired resistance is high and the strains that evolve are half as fit as the wild-type strains. However, we also found that transmission of drug-resistant strains in Botswana could increase to ∼15% by 2009 if the drug-resistant strains that evolve are as fit as the wild-type strains. CONCLUSIONS: Transmitted resistance will only be detected by the WHO (by 2009) if the strains that evolve are extremely fit and acquired resistance is high. Initially after a treatment program is begun a threshold lower than 5% should be used; and we advise that predictions should be made before setting a threshold. Our results indicate that it may be several years before the WHO's surveillance system is likely to detect transmitted resistance in other resource-poor countries that have significantly less ambitious treatment programs than Botswana

HIV Drug-resistant Strains as Epidemiologic Sentinels

The decrease in the proportion of drug resistance among newly infected HIV-1 patients may signal a worsening of the epidemic

The calcium-dependent ribonuclease XendoU promotes ER network formation through local RNA degradation

How cells shape and remodel organelles in response to cellular signals is a poorly understood process. Using Xenopus laevis egg extract, we found that increases in cytosolic calcium lead to the activation of an endogenous ribonuclease, XendoU. A fraction of XendoU localizes to the endoplasmic reticulum (ER) and is required for nuclear envelope assembly and ER network formation in a catalysis-dependent manner. Using a purified vesicle fusion assay, we show that XendoU functions on the surface of ER membranes to promote RNA cleavage and ribonucleoprotein (RNP) removal. Additionally, RNA removal from the surface of vesicles by RNase treatment leads to increased ER network formation. Using human tissue culture cells, we found that hEndoU localizes to the ER, where it promotes the formation of ER tubules in a catalysis-dependent manner. Together, these results demonstrate that calcium-activated removal of RNA from membranes by XendoU promotes and refines ER remodeling and the formation of tubular ER

Real estate investment and urban density: Exploring the polycentric urban region using a topological lens

Focusing on commercial office real estate as both a manifestation of and a conduit of cross-border capital flows, this paper refers to the concepts of topology and topography in a theoretical and empirical exploration of contemporary ‘network economy’ spatial implications for the ‘polycentric urban region’ (PUR). A body of research has cast doubt on the normative European representation of the multi-centre PUR as a balanced, sustainable spatial development model. Yet, the model has continued to be propagated in European territorial strategy and has been influential internationally. Academic perspectives and qualitative evidence reviewed in the paper shed a light on mutual dependencies and recursive relations between network economy global structural processes, international office real estate investment practices mediated by city governments, and the spatial configuration of density. Commercial investment and city planning actor practices chime with urban agglomeration, spatial concentration and density. Quantitative evidence of associations between urban density and office real estate investment returns and capital flows is found. It is concluded that network economy topology, politics and the city are in a dialectical relationship with the PUR territorial governance agenda for spatially balanced regional development