Qualitative analysis of young adult ENDS users' expectations and experiences.

ObjectivesDespite extensive research into the determinants of electronic nicotine delivery system (ENDS) uptake, few studies have examined the psychosocial benefits ENDS users seek and experience. Using a consumer ritual framework, we explored how ENDS users recreated or replaced smoking practices, and considered implications for smoking cessation.DesignIn-depth interviews; data analysed using thematic analysis.SettingDunedin, New Zealand.Participants16 young adult ENDS users (age M=21.4, SD=1.9; 44% female).ResultsParticipants reported using different ENDS to achieve varying outcomes. Some used 'cigalikes' to recreate a physically and visually similar experience to smoking; they privileged device appearance over nicotine delivery. In contrast, others used personally crafted mods to develop new rituals that differentiated them from smokers and showcased their technical expertise. Irrespective of the device they used, several former smokers and dual users of cigarettes and ENDS experienced strong nostalgia for smoking attributes, particularly the elemental appeal of fire and the finiteness of a cigarette. Non-smoking participants used ENDS to maintain social connections with their peers.ConclusionsParticipants used ENDS to construct rituals that recreated or replaced smoking attributes, and that varied in the emphasis given to device appearance, nicotine delivery, and social performance. Identifying how ENDS users create new rituals and the components they privilege within these could help promote full transition from smoking to ENDS and identify those at greatest risk of dual use or relapse to cigarette smoking

DSpace How-To Guide: Tips and tricks for managing common DSpace chores

PDF fileThis short booklet is intended to introduce the commonest non-obvious customization related tasks for newcomers to DSpace administration. It has been written against the current stable version 1.3.2 of DSpace. We have tried to include instructions for different operating systems as required; most customizations, however, work identically cross-platform

Self-Censoring on Social Media Sites

Many users of social media sites self-censor by using character replacements or euphemisms to obscure the language they are using. The reasons for doing so vary from trying to avoid other users finding their posts in searches to evading censorship from site administration to adapting to site culture. This paper seeks to answer whether or not there is an association between reasons for self-censoring and tactics used for self-censoring. It also examines three sites where self-censoring is in different forms and amounts - Tumblr, Twitter, and TikTok - and how the tactics and reasons for self-censoring appear on those sites. To do so, I first investigated the rules and communities of the social media sites, taboos, terms and taxonomies for self-censoring practices, and the use of self-censoring in online communication and memes. Next, I conducted a survey and used that survey data to perform a chi-square test using reasons for self-censoring and tactics used for self-censoring as variables. I also conducted percentage observations on the data using the sites and tactics as variables, and then the sites and reasonings as variables. While my results for the chi-squared test were flawed, I found no correlation between self-censoring tactics and reasons for self-censoring. However, I did observe different patterns of tactics used and reasons for self-censoring on the different sites

Type I interferon-driven susceptibility to Mycobacterium tuberculosis is mediated by IL-1Ra.

The bacterium Mycobacterium tuberculosis (Mtb) causes tuberculosis and is responsible for more human mortality than any other single pathogen1. Progression to active disease occurs in only a fraction of infected individuals and is predicted by an elevated type I interferon (IFN) response2-7. Whether or how IFNs mediate susceptibility to Mtb has been difficult to study due to a lack of suitable mouse models6-11. Here, we examined B6.Sst1S congenic mice that carry the 'susceptible' allele of the Sst1 locus that results in exacerbated Mtb disease12-14. We found that enhanced production of type I IFNs was responsible for the susceptibility of B6.Sst1S mice to Mtb. Type I IFNs affect the expression of hundreds of genes, several of which have previously been implicated in susceptibility to bacterial infections6,7,15-18. Nevertheless, we found that heterozygous deficiency in just a single IFN target gene, Il1rn, which encodes interleukin-1 receptor antagonist (IL-1Ra), is sufficient to reverse IFN-driven susceptibility to Mtb in B6.Sst1S mice. In addition, antibody-mediated neutralization of IL-1Ra provided therapeutic benefit to Mtb-infected B6.Sst1S mice. Our results illustrate the value of the B6.Sst1S mouse to model IFN-driven susceptibility to Mtb, and demonstrate that IL-1Ra is an important mediator of type I IFN-driven susceptibility to Mtb infections in vivo

Variants within the MMP3 gene are associated with achilles tendinopathy: possible interaction with the COL5A1 gene

Objectives: Sequence variation within the COL5A1 and TNC genes are known to associate with Achilles tendinopathy. The primary aim of this case-control genetic association study was to investigate whether variants within the matrix metalloproteinase 3 (MMP3) gene also contributed to both Achilles tendinopathy and Achilles tendon rupture in a Caucasian population. A secondary aim was to establish whether variants within the MMP3 gene interacted with the COL5A1 rs12722 variant to raise risk of these pathologies. Methods: 114 subjects with symptoms of Achilles tendon pathology and 98 healthy controls were genotyped for MMP3 variants rs679620, rs591058 and rs650108. Results: As single markers, significant associations were found between the GG genotype of rs679620 (OR = 2.5, 95% CI 1.2 to 4.90, p = 0.010), the CC genotype of rs591058 (OR = 2.3, 95% CI 1.1 to 4.50, p = 0.023) and the AA genotype of rs650108 (OR = 4.9, 95% CI 1.0 to 24.1, p = 0.043) and risk of Achilles tendinopathy. The ATG haplotype (rs679620, rs591058, and rs650108) was under-represented in the tendinopathy group when compared to the control group (41% vs 53%, p = 0.038). Finally, the G allele of rs679620 and the T allele of COL5A1 rs12722 significantly interacted to raise risk of AT (p = 0.006). No associations were found between any of the MMP3 markers and Achilles tendon rupture. Conclusion: Variants within the MMP3 gene are associated with Achilles tendinopathy. Furthermore, the MMP3 gene variant rs679620 and the COL5A1 marker rs12722 interact to modify the risk of tendinopathy. These data further support a genetic contribution to a common sports related injur

The β-blocker Nebivolol Is a GRK/β-arrestin Biased Agonist

Nebivolol, a third generation β-adrenoceptor (β-AR) antagonist (β-blocker), causes vasodilation by inducing nitric oxide (NO) production. The mechanism via which nebivolol induces NO production remains unknown, resulting in the genesis of much of the controversy regarding the pharmacological action of nebivolol. Carvedilol is another β-blocker that induces NO production. A prominent pharmacological mechanism of carvedilol is biased agonism that is independent of Gαs and involves G protein-coupled receptor kinase (GRK)/β-arrestin signaling with downstream activation of the epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase (ERK). Due to the pharmacological similarities between nebivolol and carvedilol, we hypothesized that nebivolol is also a GRK/β-arrestin biased agonist. We tested this hypothesis utilizing mouse embryonic fibroblasts (MEFs) that solely express β2-ARs, and HL-1 cardiac myocytes that express β1- and β2-ARs and no detectable β3-ARs. We confirmed previous reports that nebivolol does not significantly alter cAMP levels and thus is not a classical agonist. Moreover, in both cell types, nebivolol induced rapid internalization of β-ARs indicating that nebivolol is also not a classical β-blocker. Furthermore, nebivolol treatment resulted in a time-dependent phosphorylation of ERK that was indistinguishable from carvedilol and similar in duration, but not amplitude, to isoproterenol. Nebivolol-mediated phosphorylation of ERK was sensitive to propranolol (non-selective β-AR-blocker), AG1478 (EGFR inhibitor), indicating that the signaling emanates from β-ARs and involves the EGFR. Furthermore, in MEFs, nebivolol-mediated phosphorylation of ERK was sensitive to pharmacological inhibition of GRK2 as well as siRNA knockdown of β-arrestin 1/2. Additionally, nebivolol induced redistribution of β-arrestin 2 from a diffuse staining pattern into more intense punctate spots. We conclude that nebivolol is a β2-AR, and likely β1-AR, GRK/β-arrestin biased agonist, which suggests that some of the unique clinically beneficial effects of nebivolol may be due to biased agonism at β1- and/or β2-ARs. © 2013 Erickson et al