Summary
Background
The nonstructural 3 serine protease inhibitors (PIs), boceprevir and telaprevir, represent the first in a new generation of directly acting antivirals against genotype 1 hepatitis ...C (HCV) infection. When used in combination with pegylated interferon and ribavirin, these drugs greatly improve sustained virological response rates in both treatment‐naïve patients and patients who have had previous virological failure on treatment. However, the addition of these new agents will increase the complexity of therapeutic regimens, the rates of side‐effects and costs.
Aims
To review concisely the current evidence and to suggest current best practice, for the use of telaprevir and boceprevir in the management of chronic genotype 1 HCV infection.
Methods
These guidelines for the use of boceprevir and telaprevir have been formulated following extensive review of the current literature, are based on the consensus opinion of a panel of national experts, and have been openly discussed and debated at a national meeting of HCV care providers.
Results
We have made recommendations on a number of the key practical issues facing HCV care providers: (i) Which patients to treat?; (ii) Standards for the provision of care; (iii) Pre‐treatment considerations; (iv) Which treatment regimens to use?; (v) Stopping rules; and (vi) Management of adverse effects. Finally, we have produced suggested algorithms for the assessment and treatment of these patients.
Conclusions
These UK Consensus guidelines indicate the current best practice for the use of boceprevir and telaprevir in the management of genotype 1 chronic HCV infection.
Many young, massive stars are found in close binaries. Using population synthesis simulations we predict the likelihood of a companion star being present when these massive stars end their lives as ...core-collapse supernovae (SNe). We focus on stripped-envelope SNe, whose progenitors have lost their outer hydrogen and possibly helium layers before explosion. We use these results to interpret new Hubble Space Telescope observations of the site of the broad-lined Type Ic SN 2002ap, 14 years post-explosion. For a subsolar metallicity consistent with SN 2002ap, we expect a main-sequence (MS) companion present in about two thirds of all stripped-envelope SNe and a compact companion (likely a stripped helium star or a white dwarf/neutron star/black hole) in about 5% of cases. About a quarter of progenitors are single at explosion (originating from initially single stars, mergers, or disrupted systems). All of the latter scenarios require a massive progenitor, inconsistent with earlier studies of SN 2002ap. Our new, deeper upper limits exclude the presence of an MS companion star >8-10 M , ruling out about 40% of all stripped-envelope SN channels. The most likely scenario for SN 2002ap includes nonconservative binary interaction of a primary star initially 23 M . Although unlikely (<1% of the scenarios), we also discuss the possibility of an exotic reverse merger channel for broad-lined Type Ic events. Finally, we explore how our results depend on the metallicity and the model assumptions and discuss how additional searches for companions can constrain the physics that govern the evolution of SN progenitors.
Summary
Background
Therapeutic options for the management of hepatitis C virus (HCV) infection have evolved rapidly over the past two decades, with a consequent improvement in cure rates. Novel ...therapeutic agents are an area of great interest in the research community, with a number of these agents showing promise in the clinical setting.
Aims
To assess and present the available evidence for the use of novel therapeutic agents for the treatment of HCV, updating previous guidelines.
Methods
All Phase 2 and 3 studies, as well as presentations from international Hepatology meetings were identified and reviewed for suitable inclusion, based on studies of new therapies in HCV. Treatment‐naïve and experienced individuals, as well as cirrhotic and co‐infected individuals were included.
Results
Sofosbuvir, simeprevir and faldaprevir, along with pegylated interferon and ribavirin, have a role in the treatment of chronic HCV infection. The precise regimens are largely dependent on the patient characteristics, patient and physician preferences, and cost implication.
Conclusions
Therapies for chronic HCV have evolved dramatically in recent years. Interferon‐free regimens are now possible without compromise in the rate of sustained viral response. The decision as to which regimen is most appropriate is multifactorial, and based on efficacy, safety and cost.
Only five species of the once-diverse Rhinocerotidae remain, making the reconstruction of their evolutionary history a challenge to biologists since Darwin. We sequenced genomes from five rhinoceros ...species (three extinct and two living), which we compared to existing data from the remaining three living species and a range of outgroups. We identify an early divergence between extant African and Eurasian lineages, resolving a key debate regarding the phylogeny of extant rhinoceroses. This early Miocene (∼16 million years ago mya) split post-dates the land bridge formation between the Afro-Arabian and Eurasian landmasses. Our analyses also show that while rhinoceros genomes in general exhibit low levels of genome-wide diversity, heterozygosity is lowest and inbreeding is highest in the modern species. These results suggest that while low genetic diversity is a long-term feature of the family, it has been particularly exacerbated recently, likely reflecting recent anthropogenic-driven population declines.
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•Analysis of genomes from all five extant and three extinct rhinoceros species•Strong phylogenomic support for the geographical hypothesis of rhinoceros evolution•Basal split between African and Eurasian lineages in the early Miocene (∼16 mya)•While all rhinoceroses have low genome diversity, it is lowest in modern-day ones
The comparison of de novo genomes from the white, black, Sumatran, and greater one-horned rhinoceroses with the genomes of a historic Javan rhinoceros and three extinct Pleistocene species resolves the evolutionary relationships within the Rhinocerotidae family and reveals that low genetic diversity is a long-term feature of rhinoceroses.
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•A novel paramyxid parasite, Marteilia cocosarum n. sp. infecting common cockles is described.•Phylogenetic analyses of 18S, ITS-1, and ITS-2 rDNA were performed.•A detailed ...description of the morphology and pathology based on histology, ISH, and TEM is presented.
Diseases of bivalve molluscs caused by paramyxid parasites of the genus Marteilia have been linked to mass mortalities and the collapse of commercially important shellfish populations. Until recently, no Marteilia spp. have been detected in common cockle (Cerastoderma edule) populations in the British Isles. Molecular screening of cockles from ten sites on the Welsh coast indicates that a Marteilia parasite is widespread in Welsh C. edule populations, including major fisheries. Phylogenetic analysis of ribosomal DNA (rDNA) gene sequences from this parasite indicates that it is a closely related but different species to Marteilia cochillia, a parasite linked to mass mortality of C. edule fisheries in Spain, and that both are related to Marteilia octospora, for which we provide new rDNA sequence data. Preliminary light and transmission electron microscope (TEM) observations support this conclusion, indicating that the parasite from Wales is located primarily within areas of inflammation in the gills and the connective tissue of the digestive gland, whereas M. cochillia is found mainly within the epithelium of the digestive gland. The impact of infection by the new species, here described as Marteilia cocosarum n. sp., upon Welsh fisheries is currently unknown.
Summary
Hepatitis C virus (HCV) antiviral treatment for people who inject drugs (PWID) could prevent onwards transmission and reduce chronic prevalence. We assessed current PWID treatment rates in ...seven UK settings and projected the potential impact of current and scaled‐up treatment on HCV chronic prevalence. Data on number of PWID treated and sustained viral response rates (SVR) were collected from seven UK settings: Bristol (37–48% HCV chronic prevalence among PWID), East London (37–48%), Manchester (48–56%), Nottingham (37–44%), Plymouth (30–37%), Dundee (20–27%) and North Wales (27–33%). A model of HCV transmission among PWID projected the 10‐year impact of (i) current treatment rates and SVR (ii) scale‐up with interferon‐free direct acting antivirals (IFN‐free DAAs) with 90% SVR. Treatment rates varied from <5 to over 25 per 1000 PWID. Pooled intention‐to‐treat SVR for PWID were 45% genotypes 1/4 95%CI 33–57% and 61% genotypes 2/3 95%CI 47–76%. Projections of chronic HCV prevalence among PWID after 10 years of current levels of treatment overlapped substantially with current HCV prevalence estimates. Scaling‐up treatment to 26/1000 PWID annually (achieved already in two sites) with IFN‐free DAAs could achieve an observable absolute reduction in HCV chronic prevalence of at least 15% among PWID in all sites and greater than a halving in chronic HCV in Plymouth, Dundee and North Wales within a decade. Current treatment rates among PWID are unlikely to achieve observable reductions in HCV chronic prevalence over the next 10 years. Achievable scale‐up, however, could lead to substantial reductions in HCV chronic prevalence.
We report new near-IR integral field spectroscopy of the central starburst region of the barred spiral galaxy M83 obtained with Cambridge Infra-Red Panoramic Survey Spectrograph (CIRPASS) on ...Gemini-South, which we analyse in conjunction with GHαFaS Fabry–Perot data, an Anglo-Australian Telescope (AAT) IRIS2 Ks-band image, and near- and mid-IR imaging from the Hubble and Spitzer space telescopes. The bulk of the current star formation activity is hidden from optical view by dust extinction, but is seen in the near- and mid-IR to the north of the nucleus. This region is being fed by inflow of gas through the bar of M83, traced by the prominent dust lane entering into the circumnuclear region from the north. An analysis of stellar ages confirms that the youngest stars are indeed in the north-west. A gradual age gradient, with older stars further to the south, characterizes the well-known star-forming arc in the central region of M83, and is consistent with a stable scenario where gas inflow into the central regions is facilitated by the galactic bar. Detailed analyses of the Paβ ionized gas kinematics and near-IR imaging confirm that the kinematic centre coincides with the photometric centre of M83, and that these are offset significantly, by about 3 arcsec or 60 pc, from the visible nucleus of the galaxy. We discuss two possible options, the first of which postulates that the kinematic and photometric centre traces a galaxy nucleus hidden by a substantial amount of dust extinction, in the range AV= 3–10 mag. By combining this information with kinematic results and using arguments from the literature, we conclude that such a scenario is, however, unlikely, as is the existence of other ‘hidden’ nuclei in M83. We thus concur with recent authors and favour a second option, in which the nucleus of the galaxy is offset from its kinematic and photometric centre. This is presumably a result of some past interaction, possibly related to the event which lies at the origin of the disturbance of the outer disc of the galaxy. We find some indications for a disturbance in the Hα velocity field which would confirm the influence of the m= 1 perturbation in the gravitational potential, but note that further high-quality stellar kinematic data are needed to confirm this scenario.
Background & Aims Patients with genotype 3 hepatitis C virus (HCV) infection and cirrhosis have poor response rates after 24 weeks treatment with pegylated interferon and ribavirin. Treatment for 48 ...weeks is therefore recommended, although the benefits of this are untested. We examined extended therapy in patients with genotype 3 HCV and advanced fibrosis. Methods Multicentre, open labelled randomized trial comparing therapy with 24 weeks pegylated interferon and ribavirin to 48 weeks of the same therapy. Results 136 patients completed the study. 67 received 24 weeks therapy and the SVR rate (48%) did not differ from that seen in the 69 patients who received 48 weeks therapy (42%). The response rates in patients with biopsy proven cirrhosis (13 patients treated for 24 weeks, 18 patients treated for 48 weeks) or cirrhosis proven on imaging (28 patients treated for 24 weeks and 25 patients treated for 48 weeks) were 46% in those treated for 24 weeks and 40% in those treated for 48 weeks. The differences were not significantly different. Treatment failure was due to relapse in the majority of patients. Conclusions Patients with genotype 3 HCV and advanced fibrosis do not benefit from extended therapy with pegylated interferon and ribavirin.
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