The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S) plays critical roles in host cell entry. Non-synonymous substitutions affecting S are not uncommon and have become fixed in a number of SARS-CoV-2 lineages. A subset of such mutations enable escape from neutralizing antibodies or are thought to enhance transmission through mechanisms such as increased affinity for the cell entry receptor, angiotensin-converting enzyme 2 (ACE2). Independent genomic surveillance programs based in New Mexico and Louisiana contemporaneously detected the rapid rise of numerous clade 20G (lineage B.1.2) infections carrying a Q677P substitution in S. The variant was first detected in the US on October 23, yet between 01 Dec 2020 and 19 Jan 2021 it rose to represent 27.8% and 11.3% of all SARS-CoV-2 genomes sequenced from Louisiana and New Mexico, respectively. Q677P cases have been detected predominantly in the south central and southwest United States; as of 03 Feb 2021, GISAID data show 499 viral sequences of this variant from the USA. Phylogenetic analyses revealed the independent evolution and spread of at least six distinct Q677H sub-lineages, with first collection dates ranging from mid-August to late November 2020. Four 677H clades from clade 20G (B.1.2), 20A (B.1.234), and 20B (B.1.1.220, and B.1.1.222) each contain roughly 100 or fewer sequenced cases, while a distinct pair of clade 20G clusters are represented by 754 and 298 cases, respectively. Although sampling bias and founder effects may have contributed to the rise of S:677 polymorphic variants, the proximity of this position to the polybasic cleavage site at the S1/S2 boundary are consistent with its potential functional relevance during cell entry, suggesting parallel evolution of a trait that may confer an advantage in spread or transmission. Taken together, our findings demonstrate simultaneous convergent evolution, thus providing an impetus to further evaluate S:677 polymorphisms for effects on proteolytic processing, cell tropism, and transmissibility.
The value added by better urban design has for some time been contested. Nevertheless, the bene ts of identifying a linkage between better urban design and enhanced economic value, as well as social and environmental value, are potentially signi cant. This article reports on one part of a recent research study that attempted to explore this linkage. It examines a review of stakeholder views on value and urban design on the basis of six case studies of varying urban design quality. The research method and case studies are brie y outlined, before the detailed views of key stakeholders-investors, developers, designers, occupiers, local authorities and everyday users-are presented and conclusions drawn. A key nding is that the bene ts of better urban design are increasingly acknowledged across all key stakeholder groups, albeit in different ways and forms.
Gaps in hepatitis C virus (HCV) testing, diagnosis, liver disease assessment and treatment uptake among people who inject drugs (PWID) persist. We aimed to describe the cascade of HCV care among PWID in Australia, prior to and following unrestricted access to direct‐acting antiviral (DAA) treatment. Participants enrolled in an observational cohort study between 2014 and 2018 provided fingerstick whole‐blood samples for dried blood spot, Xpert HCV Viral Load and venepuncture samples. Participants underwent transient elastography and clinical assessment by a nurse or general practitioner. Among 839 participants (mean age 43 years), 66% were male (n = 550), 64% (n = 537) injected drugs in the previous month, and 67% (n = 560) reported currently receiving opioid substitution therapy. Overall, 45% (n = 380) had detectable HCV RNA, of whom 23% (n = 86) received HCV treatment within 12 months of enrolment. HCV treatment uptake increased from 2% in the pre‐DAA era to 38% in the DAA era. Significant liver fibrosis (F2‐F4) was more common in participants with HCV infection (38%) than those without (19%). Age 50 years or older (aOR, 2.88; 95% CI, 1.18‐7.04) and attending a clinical follow‐up with nurse (aOR, 3.19; 95% CI, 1.61‐6.32) or physician (aOR, 11.83; 95% CI, 4.89‐28.59) were associated with HCV treatment uptake. Recent injection drug use and unstable housing were not associated with HCV treatment uptake. HCV treatment uptake among PWID has increased markedly in the DAA era. Evaluation of innovative and simplified models of care is required to further enhance treatment uptake.
This article explores the role of drug use‐related stigma in constraining access to healthcare services. Drawing on interviews with 20 people conducted shortly after leaving an Australian alcohol and other drug withdrawal management unit, the article explores their willingness and ability to access primary care, hospital and further services. It finds repeated descriptions of feeling ignored and shamed during efforts to access care, with some descriptions relating to subtle signs of disapproval or condemnation, and others to being ignored or dismissed. Some accounts additionally emphasise unwelcoming atmospheres, and exclusion by omission of signals of welcome and encouragement. The article goes on to consider, for the first time in this field, contemporary notions of welcome and hospitality as outlined within the cosmopolitanism tradition, asking whether they offer insights into how healthcare may become more accessible for people who regularly experience stigmatisation. In concluding, the article considers the need to think further about forms of exclusion that occur when social and individual histories of stigma are not institutionally recognised, and measures to counter these histories are not actively adopted.
Since the advent of direct‐acting antiviral hepatitis C treatments, widespread enthusiasm about disease elimination has emerged. This article examines experiences of hepatitis C treatment and cure in this period. Mobilising Fraser and Seear's (Making disease, making citizens: The politics of hepatitis C, Ashgate, 2011) approach to hepatitis C as a ‘gathering’, we analyse cure not as a biomedical phenomenon but as a social and material event. To do so, we take a Science and Technology Studies‐inspired approach to analyse three complementary cases drawn from an Australian project on experiences of hepatitis C, treatment and cure. First, we analyse the ways a friendship between two women combines with adjustments to treatment access to produce a gathering that makes cure possible. Second, we analyse the forces that gather and distribute responsibility when a cure does not occur in a context shaped by oversimplified treatment logics. Third, we analyse a gathering of relations in which hepatitis C lingers, thereby limiting the cure's possible transformative effects. We argue that, even in an era defined by highly effective medicines, the hepatitis C cure is not necessarily straightforward, but an unpredictable gathering constituted by a fragile coalescing of social and material forces.
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