Phylodynamic Reconstruction Reveals Norovirus GII.4 Epidemic Expansions and their Molecular Determinants

Noroviruses are the most common cause of viral gastroenteritis. An increase in the number of globally reported norovirus outbreaks was seen the past decade, especially for outbreaks caused by successive genogroup II genotype 4 (GII.4) variants. Whether this observed increase was due to an upswing in the number of infections, or to a surveillance artifact caused by heightened awareness and concomitant improved reporting, remained unclear. Therefore, we set out to study the population structure and changes thereof of GII.4 strains detected through systematic outbreak surveillance since the early 1990s. We collected 1383 partial polymerase and 194 full capsid GII.4 sequences. A Bayesian MCMC coalescent analysis revealed an increase in the number of GII.4 infections during the last decade. The GII.4 strains included in our analyses evolved at a rate of 4.3–9.0×10−3 mutations per site per year, and share a most recent common ancestor in the early 1980s. Determinants of adaptation in the capsid protein were studied using different maximum likelihood approaches to identify sites subject to diversifying or directional selection and sites that co-evolved. While a number of the computationally determined adaptively evolving sites were on the surface of the capsid and possible subject to immune selection, we also detected sites that were subject to constrained or compensatory evolution due to secondary RNA structures, relevant in virus-replication. We highlight codons that may prove useful in identifying emerging novel variants, and, using these, indicate that the novel 2008 variant is more likely to cause a future epidemic than the 2007 variant. While norovirus infections are generally mild and self-limiting, more severe outcomes of infection frequently occur in elderly and immunocompromized people, and no treatment is available. The observed pattern of continually emerging novel variants of GII.4, causing elevated numbers of infections, is therefore a cause for concern

Medicinal cannabis users downplaying and shifting stigma: Articulations of the ‘natural’, of what is/is not a ‘drug’ and oppositions with ‘chemical’ substances

Whilst sympathy exists among the general public for chronically ill and/or disabled people who use cannabis medicinally, cannabis remains a prohibited substance in the UK. How do medicinal cannabis users negotiate this potential stigma when talking about their use of this substance? I reflect on the spoken discourses of 10 medicinal cannabis users (from a sample of 32), obtained by way of qualitative interviews, adopting a critical discourse analysis approach to the data. Specifically, I focus on their articulations around three related themes: cannabis as a ‘natural’ substance, discursive oppositions between cannabis and other substances and articulations about what is/is not a ‘drug’. I examine how participants articulated these themes in ways that attempted to negotiate the potential for stigma that talking about their substance use involved. I found they used rhetorical strategies that downplay their own deviance, attempt to shift the application of stigma to users of other substances or both. I argue that the more powerful the discursive resources that are articulated, the less rhetorical work an individual has to do to negotiate positive moral standing in an encounter. I also consider to what degree these articulations involved constructions emphasising individual self-control. I argue that in asserting that cannabis is a ‘natural’ substance (and therefore is less inherently risky to use than manufactured substances) the participants do emphasise their individual self-control