46 research outputs found
Persistence and dispersal in a Southern Hemisphere glaciated landscape: the phylogeography of the spotted snow skink (Niveoscincus ocellatus) in Tasmania
BACKGROUND: The aim of this research was to identify the effects of Pleistocene climate change on the distribution of fauna in Tasmania, and contrast this with biotic responses in other temperate regions in the Northern and Southern Hemisphere that experienced glacial activity during this epoch. This was achieved by examining the phylogeographic patterns in a widely distributed Tasmanian endemic reptile, Niveoscincus ocellatus. 204 individuals from 29 populations across the distributional range of N. ocellatus were surveyed for variation at two mitochondrial genes (ND2, ND4), and two nuclear genes (β-globin, RPS8). Phylogenetic relationships were reconstructed using a range of methods (maximum parsimony, Bayesian inference and haplotype networks), and the demographic histories of populations were assessed (AMOVA, Tajima’s D, Fu’s Fs, mismatch distributions, extended Bayesian skyline plots, and relaxed random walk analyses). RESULTS: There was a high degree of mitochondrial haplotype diversity (96 unique haplotypes) and phylogeographic structure, where spatially distinct groups were associated with Tasmania’s Northeast and a large area covering Southeast and Central Tasmania. Phylogeographic structure was also present within each major group, but the degree varied regionally, being highest in the Northeast. Only the Southeastern group had a signature of demographic expansion, occurring during the Pleistocene but post-dating the Last Glacial Maximum. In contrast, nuclear DNA had low levels of variation and a lack of phylogeographic structure, and further loci should be surveyed to corroborate the mitochondrial inferences. CONCLUSIONS: The phylogeographic patterns of N. ocellatus indicate Pleistocene range and demographic expansion in N. ocellatus, particularly in the Southeast and Central areas of Tasmania. Expansion in Central and Southeastern areas appears to have been more recent in both demographic and spatial contexts, than in Northeast Tasmania, which is consistent with inferences for other taxa of greater stability and persistence in Northeast Tasmania during the Last Glacial Maximum. These phylogeographic patterns indicate contrasting demographic histories of populations in close proximity to areas directly affected by glaciers in the Southern Hemisphere during the LGM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12862-015-0397-y) contains supplementary material, which is available to authorized users
The impact of currently licensed therapies on viral and immune responses in Chronic Hepatitis B: considerations for future novel therapeutics.
Despite the availability of a preventative vaccine, chronic hepatitis B (CHB) remains a global healthcare challenge with the risk of disease progression due to cirrhosis and hepatocellular carcinoma. Although current treatment strategies, interferon and nucleos(t)ide analogues have contributed to reducing morbidity and mortality related to CHB, these therapies are limited in providing functional cure. The treatment paradigm in CHB is rapidly evolving with a number of new agents in the developmental pipeline. However, until novel agents with functional cure capability are available in the clinical setting, there is a pressing need to optimize currently licensed therapies. Here, we discuss current agents used alone and/or in combination strategies along with the impact of these therapies on viral and immune responses. Novel treatment strategies are outlined, and the potential role of current therapies in the employment of pipeline agents is discussedWellcome Trust Clinical Research Training Fellowship (107389/Z/15/Z)NIHR Academic Clinical LectureshipBarts Charity Project Grants (723/1795 and MGU/0406NIHR Research for patient benefit award (PB‐PG‐0614‐34087) to PTF
Why, who and when to start treatment for chronic hepatitis B infection.
Chronic hepatitis B remains a major global health challenge due to morbidity and mortality from hepatocellular carcinoma and complications of liver cirrhosis. Current treatment regimens are non-curative and, once initiated, treatment is of indefinite duration for the majority. The decision to initiate treatment decisions is based on risk stratification.
Advances in our understanding of the natural history of chronic hepatitis B have led to a paradigm shift in recommendations for treatment. Emerging non-invasive biomarkers of disease activity will further enhance disease stratification.
In this review, we summarise the guidance from major international societies on treatment for chronic hepatitis B and explore some of the novel approaches to disease assessment
Immune Tolerant Chronic Hepatitis B: The Unrecognized Risks
The authors were supported by a Barts and The London Charity Large Project grant (723/1795
to P.T.F.K.) and an NIHR Research for patient benefit award (Grant No. PB-PG-0614-34087 to PTFK); a Singapore
Translational Research Investigator Award (NMRC/STaR/013/2012 to A.B.); institutional funding from the Fox
Chase Cancer Center (W.S.M.); and a Fox Chase Cancer Center Core Grant (CA006927) (S.L.)