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

Siciak-Zahariuta extremal functions, analytic discs and polynomial hulls

We prove two disc formulas for the Siciak-Zahariuta extremal function of an arbitrary open subset of complex affine space. We use these formulas to characterize the polynomial hull of an arbitrary compact subset of complex affine space in terms of analytic discs. Similar results in previous work of ours required the subsets to be connected

A Room of One\u27s Own? Accessory Dwelling Unit Reforms and Local Parochialism

Over the past decade, a number of state and local governments have amended land use regulations to permit the accessory dwelling units (“ADUs”) on single-family lots. Measured by raw numbers of reforms, the campaign to secure legal reforms permitting ADUs appears to be a tremendous success. The question remains, however, whether these reforms overcome the well-documented land-use parochialism that has, for decades, represented a primary obstacle to increasing the supply of affordable housing. In order to understand more about their actual effects, this Article examines ADU reforms in a context which ought to predict a minimal level of local parochialism. In 2002, California enacted state-wide legislation mandating that local governments either amend their zoning laws to permit ADUs in single-family zones or accept the imposition of a state-dictated regulatory regime. We carefully examined the zoning law of all California cities with populations over 50,000 people (150 total cities) to determine how local governments actually implemented ADU reforms “on the ground” after the state legislation was enacted. Our analysis suggests that the seeming success story masks hidden local regulatory barriers. Local governments have responded to local political pressures by delaying the enactment of ADU legislation (and, in a few cases, simply refusing to do so despite the state mandate), imposing burdensome procedural requirements that are contrary to the spirit, if not the letter, of the state-law requirement that ADUs be permitted “as of right,” requiring multiple off-street parking spaces, and imposing substantive and procedural design requirements. Taken together, these details likely dramatically suppress the value of ADUs as a means of increasing affordable housing

Catholic Schools, Charter Schools, and Urban Neighborhoods

This paper addresses implications for urban neighborhoods of two dramatic shifts in the American educational landscape: (1) the rapid disappearance of Catholic schools from urban neighborhoods, and (2) the rise of charter schools. In previous studies, we linked Catholic school closures to increased disorder and crime, and decreased social cohesion, in Chicago neighborhoods. This paper turns to two questions unanswered in our previous investigations. First, because we focused exclusively on school closures in our previous studies, we were uncertain whether our results reflected the work that open Catholic schools do as neighborhood institutions or whether we were finding a “loss effect.” Second, since we have thus far focused on one type of educational institution, we could not say whether we were finding “school effects” generally, or “Catholic school effects” in particular. In this paper, we begin to answer both questions by comparing the effects of open Catholic and charter schools on neighborhood crime rates. Relying on police-beat-level data, we find that that police beats with open Catholic schools have lower rates of serious crime than those without one. Usually, a charter appears to have no statistically significant effect on crime rates. Our findings are important for a number of related reasons discussed in the paper

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

Tunneling mechanism of light transmission through metallic films

A mechanism of light transmission through metallic films is proposed, assisted by tunnelling between resonating buried dielectric inclusions. This is illustrated by arrays of Si spheres embedded in Ag. Strong transmission peaks are observed near the Mie resonances of the spheres. The interaction among various planes of spheres and interference effects between these resonances and the surface plasmons of Ag lead to mixing and splitting of the resonances. Transmission is proved to be limited only by absorption. For small spheres, the effective dielectric constant can be tuned to values close to unity and a method is proposed to turn the resulting materials invisible.Comment: 4 papges, 5 figure

Incorporation of random alloy GaBix_{x}As1−x_{1-x} barriers in InAs quantum dot molecules: alloy strain and orbital effects towards enhanced tunneling

Self-assembled InAs quantum dots (QDs), which have long hole-spin coherence times and are amenable to optical control schemes, have long been explored as building blocks for qubit architectures. One such design consists of vertically stacking two QDs to create a quantum dot molecule (QDM). The two dots can be resonantly tuned to form "molecule-like" coupled hole states from the hybridization of hole states otherwise localized in each respective dot. Furthermore, spin-mixing of the hybridized states in dots offset along their stacking direction enables qubit rotation to be driven optically, allowing for an all-optical qubit control scheme. Increasing the magnitude of this spin mixing is important for optical quantum control protocols. To enhance the tunnel coupling and spin-mixing across the dots, we introduce Bi in the GaAs inter-dot barrier. Previously, we showed how to model InAs/GaBiAs in an atomistic tight-binding formalism, and how the dot energy levels are affected by the alloy. In this paper, we discuss the lowering of the tunnel barrier, which results in a three fold increase of hole tunnel coupling strength in the presence of a 7% alloy. Additionally, we show how an asymmetric strain between the two dots caused by the alloy shifts the resonance. Finally, we discuss device geometries for which the introduction of Bi is most advantageous.Comment: RevTex 4-2, 11 pages, 9 figure

Radiocarbon dating of methane and carbon dioxide evaded from a temperate peatland stream

Streams draining peatlands export large quantities of carbon in different chemical forms and are an important part of the carbon cycle. Radiocarbon (14C) analysis/dating provides unique information on the source and rate that carbon is cycled through ecosystems, as has recently been demonstrated at the air-water interface through analysis of carbon dioxide (CO2) lost from peatland streams by evasion (degassing). Peatland streams also have the potential to release large amounts of methane (CH4) and, though 14C analysis of CH4 emitted by ebullition (bubbling) has been previously reported, diffusive emissions have not. We describe methods that enable the 14C analysis of CH4 evaded from peatland streams. Using these methods, we investigated the 14C age and stable carbon isotope composition of both CH4 and CO2 evaded from a small peatland stream draining a temperate raised mire. Methane was aged between 1617-1987 years BP, and was much older than CO2 which had an age range of 303-521 years BP. Isotope mass balance modelling of the results indicated that the CO2 and CH4 evaded from the stream were derived from different source areas, with most evaded CO2 originating from younger layers located nearer the peat surface compared to CH4. The study demonstrates the insight that can be gained into peatland carbon cycling from a methodological development which enables dual isotope (14C and 13C) analysis of both CH4 and CO2 collected at the same time and in the same way