The epidemiological impact of antiretroviral use predicted by mathematical models: a review

This review summarises theoretical studies attempting to assess the population impact of antiretroviral therapy (ART) use on mortality and HIV incidence. We describe the key parameters that determine the impact of therapy, and argue that mathematical models of disease transmission are the natural framework within which to explore the interaction between antiviral use and the dynamics of an HIV epidemic. Our review focuses on the potential effects of ART in resource-poor settings. We discuss choice of model type and structure, the potential for risk behaviour change following widespread introduction of ART, the importance of the stage of HIV infection at which treatment is initiated, and the potential for spread of drug resistance. These issues are illustrated with results from models of HIV transmission. We demonstrate that HIV transmission models predicting the impact of ART use should incorporate a realistic progression through stages of HIV infection in order to capture the effect of the timing of treatment initiation on disease spread. The realism of existing models falls short of properly reproducing patterns of diagnosis timing, incorporating heterogeneity in sexual behaviour, and describing the evolution and transmission of drug resistance. The uncertainty surrounding certain effects of ART, such as changes in sexual behaviour and transmission of ART-resistant HIV strains, demands exploration of best and worst case scenarios in modelling, but this must be complemented by surveillance and behavioural surveys to quantify such effects in settings where ART is implemented

Modelling the impact of antiretroviral use in resource-poor settings.

BACKGROUND: The anticipated scale-up of antiretroviral therapy (ART) in high-prevalence, resource-constrained settings requires operational research to guide policy on the design of treatment programmes. Mathematical models can explore the potential impacts of various treatment strategies, including timing of treatment initiation and provision of laboratory monitoring facilities, to complement evidence from pilot programmes. METHODS AND FINDINGS: A deterministic model of HIV transmission incorporating ART and stratifying infection progression into stages was constructed. The impact of ART was evaluated for various scenarios and treatment strategies, with different levels of coverage, patient eligibility, and other parameter values. These strategies included the provision of laboratory facilities that perform CD4 counts and viral load testing, and the timing of the stage of infection at which treatment is initiated. In our analysis, unlimited ART provision initiated at late-stage infection (AIDS) increased prevalence of HIV infection. The effect of additionally treating pre-AIDS patients depended on the behaviour change of treated patients. Different coverage levels for ART do not affect benefits such as life-years gained per person-year of treatment and have minimal effect on infections averted when treating AIDS patients only. Scaling up treatment of pre-AIDS patients resulted in more infections being averted per person-year of treatment, but the absolute number of infections averted remained small. As coverage increased in the models, the emergence and risk of spread of drug resistance increased. Withdrawal of failing treatment (clinical resurgence of symptoms), immunologic (CD4 count decline), or virologic failure (viral rebound) increased the number of infected individuals who could benefit from ART, but effectiveness per person is compromised. Only withdrawal at a very early stage of treatment failure, soon after viral rebound, would have a substantial impact on emergence of drug resistance. CONCLUSIONS: Our analysis found that ART cannot be seen as a direct transmission prevention measure, regardless of the degree of coverage. Counselling of patients to promote safe sexual practices is essential and must aim to effect long-term change. The chief aims of an ART programme, such as maximised number of patients treated or optimised treatment per patient, will determine which treatment strategy is most effective

Formulating MEDLINE queries for article retrieval based on PubMed exemplars

Bibliographic search engines allow endless possibilities for building queries based on specific words or phrases in article titles and abstracts, indexing terms, and other attributes. Unfortunately, deciding which attributes to use in a methodologically sound query is a non-trivial process. In this paper, we describe a system to help with this task, given an example set of PubMed articles to retrieve and a corresponding set of articles to exclude. The system provides the users with unigram and bigram features from the title, abstract, MeSH terms, and MeSH qualifier terms in decreasing order of precision, given a recall threshold. From this information and their knowledge of the domain, users can formulate a query and evaluate its performance. We apply the system to the task of distinguishing original research articles of functional magnetic resonance imaging (fMRI) of sensorimotor function from fMRI studies of higher cognitive functions

MODELING THE DEMAND FOR DURABLE INPUTS: DISTRIBUTED LAGS AND CAUSALITY

Vector-autoregressive-moving-average (VARMA) modeling was used to identify distributed lag relationships among farm tractor derived demand variables and to provide a basis for formally testing the hypothesis that the price of new tractor horsepower is exogeneous to its quantity demanded. Similar causality tests were used for a number of other explanatory variables, including the interest rate, price of diesel fuel, and price of used tractors. Results indicate that several lagged variables are significant causal factors and that the dynamic nature of the demand structure cannot be ignored when explaining tractor demand.Demand and Price Analysis,

Controlling the layer localization of gapless states in bilayer graphene with a gate voltage

Experiments in gated bilayer graphene with stacking domain walls present topological gapless states protected by no-valley mixing. Here we research these states under gate voltages using atomistic models, which allow us to elucidate their origin. We find that the gate potential controls the layer localization of the two states, which switches non-trivially between layers depending on the applied gate voltage magnitude. We also show how these bilayer gapless states arise from bands of single-layer graphene by analyzing the formation of carbon bonds between layers. Based on this analysis we provide a model Hamiltonian with analytical solutions, which explains the layer localization as a function of the ratio between the applied potential and interlayer hopping. Our results open a route for the manipulation of gapless states in electronic devices, analogous to the proposed writing and reading memories in topological insulators

Chemical abundances in spiral and irregular galaxies. O and N abundances derived from global emission--line spectra

The validity of oxygen and nitrogen abundances derived from the global emission-line spectra of galaxies via the P-method has been investigated using a collection of published spectra of individual HII regions in irregular and spiral galaxies. The conclusions of Kobulnicky, Kennicutt & Pizagno (1999) that global emission-line spectra can reliably indicate the chemical properties of galaxies has been confirmed. It has been shown that the comparison of the global spectrum of a galaxy with a collection of spectra of individual HII regions can be used to distinguish high and low metallicity objects and to estimate accurate chemical abundances in a galaxy. The oxygen and nitrogen abundances in samples of UV-selected and normal nearby galaxies have been determined. It has been found that the UV-selected galaxies occupy the same area in the N/O -- O/H diagram as individual HII regions in nearby galaxies. Finally, we show that intermediate-redshift galaxies systematically deviate from the metallicity -- luminosity trend of local galaxies.Comment: 15 pages, 17 figures, accepted for publication in Astronomy and Astrophysic

Discovery of low mass objects in Taurus

In infrared (2.2 micron, K-band) search of small regions (25 in square) near 26 members of the Taurus star-forming association has revealed 20 dim (K = 13-16 mag) stellar objects near 13 of them. Of these 20 objects, 9 are exceptionally red. It is argued that these 9 are probably also Taurus members. From the luminosities (0.4 to 4 times 10 the -3 power luminosity) and ages (estimated at 10(exp 6) years), masses can be determined by reference to theoretical low-mass cooling curves. The masses are in the range 0.005 to 0.015 solar mass, i.e., low-mass brown dwarfs. Proper motion studies of 7 of the objects visible on the POSS plates conducted by Burton Jones establish that 4 are highly probable Taurus members while 1 is a possible member

How Governance Regimes Shape the Implementation of Water Reuse Schemes

The governance dimensions of water reuse scheme development and operation, such as policies and regulatory frameworks, and public involvement and stakeholder collaboration, can serve to both facilitate and constrain wider adoption of water reuse practices. This paper explores the significance and underlying structure of the key governance challenges facing the water reuse sector in Europe. It presents empirical evidence from interviews and focus group sessions conducted at four water reuse schemes: an indirect potable reuse scheme at Torreele (Belgium), the urban reuse of treated municipal wastewater at the London Olympic Park (United Kingdom) and at Sabadell (Spain), and the reuse of agro-industrial effluent for irrigation at Capitanata (Italy). The findings underscore the importance of clarity in policy arrangements around water reuse, as well as of the financial competitiveness of reuse projects compared to alternative water supply options. Operators of water reuse schemes expressed a preference for water quality standards, which focus on appropriateness for use rather than over-emphasise the waters’ origin so that unnecessary treatment and costs can be avoided. Positive public support was widely acknowledged as an important factor in the success or failure of water reuse schemes. We conclude that constructive institutional relationships underpin many of the challenges faced by reuse scheme operators and that greater emphasis should be given to building confidence and gaining trust in water service providers through early identification of how governance regimes shape the viability of new scheme