The PL calibration for Milky Way Cepheids and its implications for the distance scale

The rationale behind recent calibrations of the Cepheid PL relation using the Wesenheit formulation is reviewed and reanalyzed, and it is shown that recent conclusions regarding a possible change in slope of the PL relation for short-period and long-period Cepheids are tied to a pathological distribution of HST calibrators within the instability strip. A recalibration of the period-luminosity relation is obtained using Galactic Cepheids in open clusters and groups, the resulting relationship, described by log L/L_sun = 2.415(+-0.035) + 1.148(+-0.044)log P, exhibiting only the moderate scatter expected from color spread within the instability strip. The relationship is confirmed by Cepheids with HST parallaxes, although without the need for Lutz-Kelker corrections, and in general by Cepheids with revised Hipparcos parallaxes, albeit with concerns about the cited precisions of the latter. A Wesenheit formulation of Wv = -2.259(+-0.083) - 4.185(+-0.103)log P for Galactic Cepheids is tested successfully using Cepheids in the inner regions of the galaxy NGC 4258, confirming the independent geometrical distance established for the galaxy from OH masers. Differences between the extinction properties of interstellar and extragalactic dust may yet play an important role in the further calibration of the Cepheid PL relation and its application to the extragalactic distance scale.Comment: Accepted for Publication (Astrophysics & Space Science

Australia’s Resource Use Trajectories

Australia’s export oriented large natural resources sectors of agriculture and mining, the ways in which large scale services such as nutrition, water, housing, transport and mobility, and energy are organized, as well as the consumption patterns of Australia’s wealthy urban households, create a unique pattern of overall resource use in Australia. In an attempt to contribute to a new environmental information system compatible with economic accounts, we represent Australia’s resource use by employing standard biophysical indicators for resource use developed within the OECD context. We are looking at the last three decades of resource use and the economic, social and environmental implications. We also discuss scenarios of future resource use patterns based on a stocks and flows model of the Australian economy. We argue that current extractive economic patterns have contributed to the recent economic boom in Australia but will eventually lead to negative social and environmental outcomes. While there is currently little evidence of political support for changing the economic focus on export-oriented agriculture and mining industries, there is significant potential for improvements in socio-technological systems, and room for more sustainable household consumption.natural resources, resource use patterns and dynamics, physical accounting, resource productivity, social and environmental impacts of resource use, Australia

Modelling the impact of ivermectin on River Blindness and its burden of morbidity and mortality in African Savannah: EpiOncho projections

BACKGROUND: The African Programme for Onchocerciasis Control (APOC) has refocused its goals on the elimination of infection where possible, seemingly achievable by 15–17 years of annual mass distribution of ivermectin in some African foci. Previously, APOC had focused on the elimination of onchocerciasis as a public health problem. Timeframes have been set by the World Health Organization, the London Declaration on Neglected Tropical Diseases and the World Bank to achieve these goals by 2020–2025. METHODS: A novel mathematical model of the dynamics of onchocercal disease is presented which links documented associations between Onchocerca volvulus infection and the prevalence and incidence of morbidity and mortality to model outputs from our host age- and sex-structured onchocerciasis transmission framework (EpiOncho). The model is calibrated for African savannah settings, and used to assess the impact of long-term annual mass administration of ivermectin on infection and ocular and skin disease and to explore how this depends on epidemiological and programmatic variables. RESULTS: Current onchocerciasis disease projections, which do not account for excess mortality of sighted individuals with heavy microfilarial loads, underestimate disease burden. Long-term annual ivermectin treatment is highly effective at reducing both the morbidity and mortality associated with onchocerciasis, and this result is not greatly influenced by treatment coverage and compliance. By contrast, impact on microfilarial prevalence and intensity is highly dependent on baseline endemicity, treatment coverage and systematic non-compliance. CONCLUSIONS: The goals of eliminating morbidity and infection with ivermectin alone are distinctly influenced by epidemiological and programmatic factors. Whilst the former goal is most certainly achievable, reaching the latter will strongly depend on initial endemicity (the higher the endemicity, the greater the magnitude of inter-treatment transmission), advising caution when generalising the applicability of successful elimination outcomes to other areas. The proportion of systematic non-compliers will become far more influential in terms of overall success in achieving elimination goals

Uncertainty Surrounding Projections of the Long-Term Impact of Ivermectin Treatment on Human Onchocerciasis

BackgroundRecent studies in Mali, Nigeria, and Senegal have indicated that annual (or biannual) ivermectin distribution may lead to local elimination of human onchocerciasis in certain African foci. Modelling-based projections have been used to estimate the required duration of ivermectin distribution to reach elimination. A crucial assumption has been that microfilarial production by Onchocerca volvulus is reduced irreversibly by 30-35% with each (annual) ivermectin round. However, other modelling-based analyses suggest that ivermectin may not have such a cumulative effect. Uncertainty in this (biological) and other (programmatic) assumptions would affect projected outcomes of long-term ivermectin treatment.Methodology/principal findingsWe modify a deterministic age- and sex-structured onchocerciasis transmission model, parameterised for savannah O. volvulus-Simulium damnosum, to explore the impact of assumptions regarding the effect of ivermectin on worm fertility and the patterns of treatment coverage compliance, and frequency on projections of parasitological outcomes due to long-term, mass ivermectin administration in hyperendemic areas. The projected impact of ivermectin distribution on onchocerciasis and the benefits of switching from annual to biannual distribution are strongly dependent on assumptions regarding the drug's effect on worm fertility and on treatment compliance. If ivermectin does not have a cumulative impact on microfilarial production, elimination of onchocerciasis in hyperendemic areas may not be feasible with annual ivermectin distribution.Conclusions/significanceThere is substantial (biological and programmatic) uncertainty surrounding modelling projections of onchocerciasis elimination. These uncertainties need to be acknowledged for mathematical models to inform control policy reliably. Further research is needed to elucidate the effect of ivermectin on O. volvulus reproductive biology and quantify the patterns of coverage and compliance in treated communities

The potential impact of moxidectin on onchocerciasis elimination in Africa: an economic evaluation based on the Phase II clinical trial data

BACKGROUND: Spurred by success in several foci, onchocerciasis control policy in Africa has shifted from morbidity control to elimination of infection. Clinical trials have demonstrated that moxidectin is substantially more efficacious than ivermectin in effecting sustained reductions in skin microfilarial load and, therefore, may accelerate progress towards elimination. We compare the potential cost-effectiveness of annual moxidectin with annual and biannual ivermectin treatment. METHODS: Data from the first clinical study of moxidectin were used to parameterise the onchocerciasis transmission model EPIONCHO to investigate, for different epidemiological and programmatic scenarios in African savannah settings, the number of years and in-country costs necessary to reach the operational thresholds for cessation of treatment, comparing annual and biannual ivermectin with annual moxidectin treatment. RESULTS: Annual moxidectin and biannual ivermectin treatment would achieve similar reductions in programme duration relative to annual ivermectin treatment. Unlike biannual ivermectin treatment, annual moxidectin treatment would not incur a considerable increase in programmatic costs and, therefore, would generate sizeable in-country cost savings (assuming the drug is donated). Furthermore, the impact of moxidectin, unlike ivermectin, was not substantively influenced by the timing of treatment relative to seasonal patterns of transmission. CONCLUSIONS: Moxidectin is a promising new drug for the control and elimination of onchocerciasis. It has high programmatic value particularly when resource limitation prevents a biannual treatment strategy, or optimal timing of treatment relative to peak transmission season is not feasible. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-015-0779-4) contains supplementary material, which is available to authorized users

How can onchocerciasis elimination in Africa be accelerated? Modelling the impact of increased ivermectin treatment frequency and complementary vector control

Background: Great strides have been made toward onchocerciasis elimination by mass drug administration (MDA) of ivermectin. Focusing on MDA-eligible areas, we investigated where the elimination goal can be achieved by 2025 by continuation of current practice (annual MDA with ivermectin) and where intensification or additional vector control is required. We did not consider areas hypoendemic for onchocerciasis with loiasis coendemicity where MDA is contraindicated. Methods: We used 2 previously published mathematical models, ONCHOSIM and EPIONCHO, to simulate future trends in microfilarial prevalence for 80 different settings (defined by precontrol endemicity and past MDA frequency and coverage) under different future treatment scenarios (annual, biannual, or quarterly MDA with different treatment coverage through 2025, with or without vector control strategies), assessing for each strategy whether it eventually leads to elimination. Results: Areas with 40%–50% precontrol microfilarial prevalence and ≥10 years of annual MDA may achieve elimination with a further 7 years of annual MDA, if not achieved already, according to both models. For most areas with 70%–80% precontrol prevalence, ONCHOSIM predicts that either annual or biannual MDA is sufficient to achieve elimination by 2025, whereas EPIONCHO predicts that elimination will not be achieved even with complementary vector control. Conclusions: Whether elimination will be reached by 2025 depends on precontrol endemicity, control history, and strategies chosen from now until 2025. Biannual or quarterly MDA will accelerate progress toward elimination but cannot guarantee it by 2025 in high-endemicity areas. Long-term concomitant MDA and vector control for high-endemicity areas might be useful

Detecting relic gravitational radiation from string cosmology with LIGO

A characteristic spectrum of relic gravitational radiation is produced by a period of ``stringy inflation" in the early universe. This spectrum is unusual, because the energy-density rises rapidly with frequency. We show that correlation experiments with the two gravitational wave detectors being built for the Laser Interferometric Gravitational Observatory (LIGO) could detect this relic radiation, for certain ranges of the parameters that characterize the underlying string cosmology model.Comment: 6 pages, 5 eps figures, Revte

The Cost of Annual versus Biannual Community-Directed Treatment of Onchocerciasis with Ivermectin: Ghana as a Case Study

BACKGROUND: It has been proposed that switching from annual to biannual (twice yearly) mass community-directed treatment with ivermectin (CDTI) might improve the chances of onchocerciasis elimination in some African foci. However, historically, relatively few communities have received biannual treatments in Africa, and there are no cost data associated with increasing ivermectin treatment frequency at a large scale. Collecting cost data is essential for conducting economic evaluations of control programmes. Some countries, such as Ghana, have adopted a biannual treatment strategy in selected districts. We undertook a study to estimate the costs associated with annual and biannual CDTI in Ghana. METHODOLOGY: The study was conducted in the Brong-Ahafo and Northern regions of Ghana. Data collection was organized at the national, regional, district, sub-district and community levels, and involved interviewing key personnel and scrutinizing national records. Data were collected in four districts; one in which treatment is delivered annually, two in which it is delivered biannually, and one where treatment takes place biannually in some communities and annually in others. Both financial and economic costs were collected from the health care provider's perspective. PRINCIPAL FINDINGS: The estimated cost of treating annually was US Dollars (USD) 0.45 per person including the value of time donated by the community drug distributors (which was estimated at USD 0.05 per person per treatment round). The cost of CDTI was approximately 50–60% higher in those districts where treatment was biannual than in those where it was annual. Large-scale mass biannual treatment was reported as being well received and considered sustainable. CONCLUSIONS/SIGNIFICANCE: This study provides rigorous evidence of the different costs associated with annual and biannual CDTI in Ghana which can be used to inform an economic evaluation of the debate on the optimal treatment frequency required to control (or eliminate) onchocerciasis in Africa

Assessing potential cluster Cepheids from a new distance and reddening parameterization and 2MASS photometry

A framework is outlined to assess Cepheids as potential cluster members from readily available photometric observations. A relationship is derived to estimate colour excess and distance for individual Cepheids through a calibration involving recently published HST parallaxes and a cleaned sample of established cluster Cepheids. Photometric (V-J) colour is found to be a viable parameter for approximating a Cepheid's reddening. The non-universal nature of the slope of the Cepheid PL relation for BV photometry is confirmed. By comparison, the slopes of the VJ and VI relations seem relatively unaffected by metallicity. A new Galactic Cepheid confirmed here, GSC 03729-01127 (F6-G1 Ib), is sufficiently coincident with the coronal regions of Tombaugh 5 to warrant follow-up radial velocity measures to assess membership. CCD photometry and O--C diagrams are presented for GSC 03729-01127 and the suspected cluster Cepheids AB Cam and BD Cas. Fourier analysis of the photometry for BD Cas and recent estimates of its metallicity constrain it to be a Population I overtone pulsator rather than a Type II s-Cepheid. AB Cam and BD Cas are not physically associated with the spatially-adjacent open clusters Tombaugh 5 and King 13, respectively, the latter being much older (log t ~ 9) than believed previously. Rates of period change are determined for the three Cepheids from archival and published data. GSC 03729-01127 and AB Cam exhibit period increases, implying fifth and third crossings of the instability strip, respectively, while BD Cas exhibits a period decrease, indicating a second crossing, with possible superposed trends unrelated to binarity. More importantly, the observed rates of period change confirm theoretical predictions. The challenges and prospects for future work in this area of research are discussed.Comment: accepted for publication (MNRAS