Financial control, blame avoidance and Radio Caroline: Talkin’ ‘bout my generation

This research examines the use of financial mechanisms that simultaneously impose controls and facilitate blame avoidance by public office-holders. A qualitative historical examination is used to examine legislation designed to prevent Radio Caroline, a pirate radio station, from broadcasting into Britain in the 1960s. Radio Caroline made a mockery of the British Government’s power to manage radio through a monopolist, the British Broadcasting Corporation. In addition, Radio Caroline played the type of rock music the British Government sought to suppress as representing the undesirable side of youth culture. This research examines the suppression of Radio Caroline through the Marine & Broadcasting (Offences) Act (UK) 1967 and the legislative scapegoating of Radio Caroline by targeting its revenue-earning potential. Inter-generational conflict underpinned the legislative scapegoating of Radio Caroline. This research demonstrates how financial controls can mask scapegoating and blame avoidance strategies by governments

The structure of EXTL3 helps to explain the different roles of bi-domain exostosins in heparan sulfate synthesis

Funder: University of Cambridge; doi: https://doi.org/10.13039/501100000735Funder: AstraZeneca; doi: https://doi.org/10.13039/100004325Funder: RCUK | Biotechnology and Biological Sciences Research Council (BBSRC); doi: https://doi.org/10.13039/501100000268Funder: RCUK | Engineering and Physical Sciences Research Council (EPSRC); doi: https://doi.org/10.13039/501100000266Funder: OpenPlant, BB/L014130/1Abstract: Heparan sulfate is a highly modified O-linked glycan that performs diverse physiological roles in animal tissues. Though quickly modified, it is initially synthesised as a polysaccharide of alternating β-d-glucuronosyl and N-acetyl-α-d-glucosaminyl residues by exostosins. These enzymes generally possess two glycosyltransferase domains (GT47 and GT64)—each thought to add one type of monosaccharide unit to the backbone. Although previous structures of murine exostosin-like 2 (EXTL2) provide insight into the GT64 domain, the rest of the bi-domain architecture is yet to be characterised; hence, how the two domains co-operate is unknown. Here, we report the structure of human exostosin-like 3 (EXTL3) in apo and UDP-bound forms. We explain the ineffectiveness of EXTL3’s GT47 domain to transfer β-d-glucuronosyl units, and we observe that, in general, the bi-domain architecture would preclude a processive mechanism of backbone extension. We therefore propose that heparan sulfate backbone polymerisation occurs by a simple dissociative mechanism

Rivaroxaban with or without aspirin in stable cardiovascular disease

BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months. RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=−4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group. CONCLUSIONS: Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events