Minimum target prices for production of direct acting antivirals and associated diagnostics to combat Hepatitis C Virus

Combinations of direct-acting antivirals (DAAs) can cure hepatitis C virus (HCV) in the majority of treatment-naïve patients. Mass treatment programs to cure HCV in developing countries are only feasible if the costs of treatment and laboratory diagnostics are very low. This analysis aimed to estimate minimum costs of DAA treatment and associated diagnostic monitoring. Clinical trials of HCV DAAs were reviewed to identify combinations with consistently high rates of sustained virological response across hepatitis C genotypes. For each DAA, molecular structures, doses, treatment duration, and components of retrosynthesis were used to estimate costs of large-scale, generic production. Manufacturing costs per gram of DAA were based upon treating at least 5 million patients per year and a 40% margin for formulation. Costs of diagnostic support were estimated based on published minimum prices of genotyping, HCV antigen tests plus full blood count/clinical chemistry tests. Predicted minimum costs for 12-week courses of combination DAAs with the most consistent efficacy results were: US$122 per person for sofosbuvir+daclatasvir; US$152 for sofosbuvir+ribavirin; US$192 for sofosbuvir+ledipasvir; and US$115 for MK-8742+MK-5172. Diagnostic testing costs were estimated at US$90 for genotyping US$34 for two HCV antigen tests and US$22 for two full blood count/clinical chemistry tests. Conclusions: Minimum costs of treatment and diagnostics to cure hepatitis C virus infection were estimated at US$171-360 per person without genotyping or US$261-450 per person with genotyping. These cost estimates assume that existing large-scale treatment programs can be established. (Hepatology 2015;61:1174–1182

The role of social networks and trusted peers in promoting biodiverse carbon plantings

Social capital has the potential to influence the success of biodiverse carbon plantings in the face of uncertainty amongst rural landholders about the need or efficacy of efforts to address climate change through tree planting. We conducted 17 face-to-face semi-structured interviews with landholders in Victoria, Australia who voluntarily participate in biodiverse carbon plantings on their land, focussing in particular on the role of social capital for understanding how 'early adopters' can advocate for programs locally. Interviews revealed the importance of social networks and the profound impact of trusted peers on the diffusion of carbon planting schemes. Social capital dimensions are especially important for shaping ongoing participation and the ways that participants become active agents in trusted relationships that influence participation of others. Our results suggest that positive impacts of social networks can counteract doubts about the validity of climate adaptation responses such as carbon planting, and enable landholders to connect the program with existing stewardship motivations. The ability for early adopters of the program to demonstrate the physical materialisation of their plantings to others was vital to this process. We propose that targeting champions and trusted peers in local communities could accelerate the proliferation of biodiverse carbon planting schemes

Highly conductive Sb-doped layers in strained Si

The ability to create stable, highly conductive ultrashallow doped regions is a key requirement for future silicon-based devices. It is shown that biaxial tensile strain reduces the sheet resistance of highly doped n-type layers created by Sb or As implantation. The improvement is stronger with Sb, leading to a reversal in the relative doping efficiency of these n-type impurities. For Sb, the primary effect is a strong enhancement of activation as a function of tensile strain. At low processing temperatures, 0.7% strain more than doubles Sb activation, while enabling the formation of stable, ~10-nm-deep junctions. This makes Sb an interesting alternative to As for ultrashallow junctions in strain-engineered complementary metal-oxide-semiconductor device

Re-evaluation of cosmic ray cutoff terminology

The study of cosmic ray access to locations inside the geomagnetic field has evolved in a manner that has led to some misunderstanding and misapplication of the terminology originally developed to describe particle access. This paper presents what is believed to be a useful set of definitions for cosmic ray cutoff terminology for use in theoretical and experimental cosmic ray studies

Interstellar medium disruption in the Centaurus A group

We present the results of a 21 cm neutral hydrogen (HI) line detection experiment in the direction of 18 low luminosity dwarf galaxies of the Centaurus A group, using the Australia Telescope National Facility 64m Parkes Radio Telescope and the Australia Telescope Compact Array. Five dwarfs have HI masses between M_HI=4x10^5 to M_HI=2.1x10^7 Msol and 0.04<M_HI/L_B<1.81 Msol L_{sol, B}^-1. The other 13 have upper-limits between M_HI<5x10^5 and M_HI<4x10^6 Msol (M_HI}/L_B<0.24 Msol L_{sol, B}^-1). Two of the mixed-morphology dwarfs remain undetected in HI, a situation that is in contrast to that of similar Local Group and Sculptor group objects where all contain significant amounts of neutral gas. There is a discontinuity in the HI properties of Centaurus A group low luminosity dwarfs that is unobserved amongst Sculptor group dwarfs. All objects fainter than M_B=-13 have either M_HI>10^7 Msol or M_HI<10^6 Msol. This gap may be explained by the ram pressure stripping mechanism at work in this dense environment where all galaxies with M_HI<10^7 Msol have been stripped of their gas. The required intergalactic medium density to achieve this is ~10^-3 cm^-3.Comment: 7 figures, 2 table

Revision of basal macropodids from the Riversleigh World Heritage Area with descriptions of new material of Ganguroo bilamina Cooke, 1997 and a new species

The relationship of basal macropodids (Marsupialia: Macropodoidea) from the Oligo-Miocene of Australia have been unclear. Here, we describe a new species from the Bitesantennary Site within the Riversleigh's World Heritage Area (WHA), Ganguroo bites n. sp., new cranial and dental material of G. bilamina, and reassess material previously described as Bulungamaya delicata and 'Nowidgee matrix'. We performed a metric analysis of dental measurements on species of Thylogale which we then used, in combination with morphological features, to determine species boundaries in the fossils. We also performed a phylogenetic analysis to clarify the relationships of basal macropodid species within Macropodoidea. Our results support the distinction of G. bilamina, G. bites and B. delicata, but 'Nowidgee matrix' appears to be a synonym of B. delicata. The results of our phylogenetic analysis are inconclusive, but dental and cranial features suggest a close affinity between G. bilamina and macropodids. Finally, we revise the current understanding of basal macropodid diversity in Oligocene and Miocene sites at Riversleigh WHA

Far-Ultraviolet to Near-Infrared Spectroscopy of A Nearby Hydrogen Poor Superluminous Supernova Gaia16apd

We report the first maximum-light far-Ultraviolet to near-infrared spectra (1000A - 1.62um, rest) of a H-poor superluminous supernova, Gaia16apd. At z=0.1018, it is one of the closest and the UV brightest such events, with 17.4 (AB) magnitude in Swift UV band (1928A) at -11days pre-maximum. Assuming an exponential form, we derived the rise time of 33days and the peak bolometric luminosity of 3x10^{44}ergs^-1. At maximum light, the estimated photospheric temperature and velocity are 17,000K and 14,000kms^-1 respectively. The inferred radiative and kinetic energy are roughly 1x10^{51} and 2x10^{52}erg. Gaia16apd is extremely UV luminous, emitting 50% of its total luminosity at 1000 - 2500A. Compared to the UV spectra (normalized at 3100A) of well studied SN1992A (Ia), SN2011fe(Ia), SN1999em (IIP) and SN1993J (IIb), it has orders of magnitude more far-UV emission. This excess is interpreted primarily as a result of weaker metal line blanketing due to much lower abundance of iron-group elements in the outer ejecta. Because these elements originate either from the natal metallicity of the star, or have been newly produced, our observation provides direct evidence that little of these freshly synthesized material, including 56Ni, was mixed into the outer ejecta, and the progenitor metallicity is likely sub-solar. This disfavors Pair-Instability Supernova (PISN) models with Helium core masses >=90Msun, where substantial 56Ni material is produced. Higher photospheric temperature of Gaia16apd than that of normal SNe may also contribute to the observed far-UV excess. We find some indication that UV luminous SLSNe-I like Gaia16apd could be common. Using the UV spectra, we show that WFIRST could detect SLSNe-I out to redshift of 8.Comment: 19 pages. Match with the version accepted in Ap

Epidemiology and integrated control of Potato Late Blight in Europe

Phytophthora infestans, the causal agent of late blight, is a major threat to potato production in northwestern Europe. Before 1980, the worldwide population of P. infestans outside Mexico appeared to be asexual and to consist of a single clonal lineage of A1 mating type characterized by a single genotype. It is widely believed that new strains migrated into Europe in 1976 and that this led to subsequent population changes including the introduction of the A2 mating type. The population characteristics of recently collected isolates in NW Europe show a diverse population including both mating types, sexual reproduction and oospores, although differences are observed between regions. Although it is difficult to find direct evidence that new strains are more aggressive, there are several indications from experiments and field epidemics that the aggressiveness of P. infestans has increased in the past 20 years. The relative importance of the different primary inoculum sources and specific measures for reducing their role, such as covering dumps with plastic and preventing seed tubers from becoming infected, is described for the different regions. In NW Europe, varieties with greater resistance tend not to be grown on a large scale. From the grower’s perspective, the savings in fungicide input that can be achieved with these varieties are not compensated by the higher (perceived) risk of blight. Fungicides play a crucial role in the integrated control of late blight. The spray strategies in NW Europe and a table of the specific attributes of the most important fungicides in Europe are presented. The development and use of decision support systems (DSSs) in NW Europe are described. In The Netherlands, it is estimated that almost 40% of potato growers use recommendations based on commercially available DSS. In the Nordic countries, a new DSS concept with a fixed 7-day spray interval and a variable dose rate is being tested. In the UK, commercially available DSSs are used for c. 8% of the area. The validity of Smith Periods for the new population of P. infestans in the UK is currently being evaluated

Locating financial incentives among diverse motivations for long-term private land conservation

A variety of policy instruments are used to promote the conservation of biodiversity on private land. These instruments are often employed in unison to encourage land stewardship beneficial for biodiversity across a broad range of program types, but questions remain about which instruments are the appropriate tools when seeking long-term change to land-management practice. Drawing on three case studies, two in Australia and one in South Africa, spanning various program types-a biodiverse carbon planting scheme, a covenanting program, and a voluntary stewardship program-we investigate the importance of financial incentives and other mechanisms from the landholder&#039;s perspective. From participant interviews we find that landholders have preconceived notions of stewardship ethics. Motivations to enroll into a private land conservation program are not necessarily what drives ongoing participation, and continued delivery of multiple mechanisms will likely ensure long-term landholder engagement. Financial incentives are beneficial in lowering uptake costs to landholders but building landholder capacity, management assistance, linking participants to a network of conservation landholders, and recognition of conservation efforts may be more successful in fostering long-term biodiversity stewardship. Furthermore, we argue that diverse, multiple instrument approaches are needed to provide the flexibility required for dynamic, adaptive policy responses. We raise a number of key considerations for conservation organizations regarding the appropriate mix of financial and nonfinancial components of their programs to address long-term conservation objectives

Star Formation, Radio Sources, Cooling X-ray Gas, and Galaxy Interactions in the Brightest Cluster Galaxy in 2A0335+096

We present deep emission-line imaging taken with the SOAR Optical Imaging Camera of the brightest cluster galaxy (BCG) in the nearby (z=0.035) X-ray cluster 2A0335+096. We analyze long-slit optical spectroscopy, archival VLA, Chandra X-ray, and XMM UV data. 2A0335+096 is a bright, cool-core X-ray cluster, once known as a cooling flow. Within the highly disturbed core revealed by Chandra X-ray observations, 2A0335+096 hosts a highly structured optical emission-line system. The redshift of the companion is within 100 km/s of the BCG and has certainly interacted with the BCG, and is likely bound to it. The comparison of optical and radio images shows curved filaments in H-alpha emission surrounding the resolved radio source. The velocity structure of the emission-line bar between the BCG nucleus and the companion galaxy provides strong evidence for an interaction between the two in the last ~50 Myrs. The age of the radio source is similar to the interaction time, so this interaction may have provoked an episode of radio activity. We estimate a star formation rate of >7 solar mass/yr based on the Halpha and archival UV data, a rate similar to, but somewhat lower than, the revised X-ray cooling rate of 10-30 solar masses/year estimated from XMM spectra by Peterson & workers. The Halpha nebula is limited to a region of high X-ray surface brightness and cool X-ray temperature. The detailed structures of H-alpha and X-ray gas differ. The peak of the X-ray emission is not the peak of H-alpha emission, nor does it lie in the BCG. The estimated age of the radio lobes and their interaction with the optical emission-line gas, the estimated timescale for depletion and accumulation of cold gas, and the dynamical time in the system are all similar, suggesting a common trigger mechanism.Comment: Accepted AJ, July 2007 publication. Vol 134, p. 14-2