I wanted to feel the way they did: Mimesis as a situational dynamic of peer mentoring by ex-offenders

This is an Accepted Manuscript of an article published by Taylor & Francis in Deviant Behavior on 10/10/2016, available online: http://www.tandfonline.com/doi/full/10.1080/01639625.2016.1237829Despite growing enthusiasm for peer mentoring as a criminal justice intervention, very little is known about what actually happens within these relationships. Drawing on an ethnographic study of peer mentoring in the North of England this article will foreground the concept of inspiration” in these settings. It will argue that Rene Girard’s theory of mimesis offers a framework with which to analyze role modeling in mentoring relationships and that a Girardian reading also offers interesting insights into the unresolved problem of the origins of personal change

Averting biodiversity collapse in tropical forest protected areas

The rapid disruption of tropical forests probably imperils global biodiversity more than any other contemporary phenomenon¹⁻³. With deforestation advancing quickly, protected areas are increasingly becoming final refuges for threatened species and natural ecosystem processes. However, many protected areas in the tropics are themselves vulnerable to human encroachment and other environmental stresses⁴⁻⁹. As pressures mount, it is vital to know whether existing reserves can sustain their biodiversity. A critical constraint in addressing this question has been that data describing a broad array of biodiversity groups have been unavailable for a sufficiently large and representative sample of reserves. Here we present a uniquely comprehensive data set on changes over the past 20 to 30 years in 31 functional groups of species and 21 potential drivers of environmental change, for 60 protected areas stratified across the world’s major tropical regions. Our analysis reveals great variation in reserve ‘health’: about half of all reserves have been effective or performed passably, but the rest are experiencing an erosion of biodiversity that is often alarmingly widespread taxonomically and functionally. Habitat disruption, hunting and forest-product exploitation were the strongest predictors of declining reserve health. Crucially, environmental changes immediately outside reserves seemed nearly as important as those inside in determining their ecological fate, with changes inside reserves strongly mirroring those occurring around them. These findings suggest that tropical protected areas are often intimately linked ecologically to their surrounding habitats, and that a failure to stem broad-scale loss and degradation of such habitats could sharply increase the likelihood of serious biodiversity declines.Keywords: Ecology, Environmental scienc

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Reductions in HeV titre via treatment with lower RNAi concentrations.

<p>HeLa cells were transfected with 1 µg/ml Poly IC, 1 nM of control or HeV targeting siRNAs. Transfection media was replaced after 4 hours and cells were infected with HeV clinical isolate at an MOI of 0.1. Infected cells were incubated for 24 hours before supernatant removed and processed for TCID₅₀ assay. Cells infected with supernatant were incubated for 3 days before TCID₅₀ calculation and are shown as the mean ± S.E.M. of three biological replicates.</p

Reductions in HeV titre via pre-treatment with RNAi and Poly IC.

<p>HeLa cells were transfected with 40 µg/ml Poly IC, 40 nM control (black bars), HeV targeting siRNA, or combined Poly IC/siN15. Transfection media was replaced after 4 hours and cells were infected with HeV clinical isolate at an MOI of 0.1. <b>A)</b> Infected cells were incubated for 24 hours before RNA extraction. Gene expression levels of N were quantified by qRT-PCR as relative expression to B-actin housekeeping gene. Results are the mean ± SEM of six biological replicates from two independent experiments. Significant differences between Oligofectamine control and siRNAs are indicated (*p = <0.05; two-sided t-test). <b>B)</b> Infected cells were incubated for 24 hours before supernatant removed and processed for TCID₅₀ assay. Cells infected with supernatant were incubated for 3 days before TCID₅₀ calculation and are shown as the mean ± S.E.M. of six biological replicates from two independent experiments.</p

Reductions in HeV titre via pre-treatment with combined RNAi.

<p>HeLa cells were transfected with 40 nM combined HeV targeting (white bars) or control (black bars) siRNAs. Transfection media was replaced after 4 hours and cells were infected with HeV clinical isolate at an MOI of 0.1. Infected cells were incubated for 24 hours before supernatant removed and processed for TCID₅₀ assay. Cells infected with supernatant were incubated for 3 days before TCID₅₀ calculation and are shown as the mean ± S.E.M. of six biological replicates from two independent experiments. Differences between the combination treatments and expected values based on the average of singular siRNA treatments (grey bars) are shown.</p

Reductions in HeV via pre-treatment with RNAi.

<p>HeLa cells were transfected with 40 µg/ml Poly IC, 40 nM control or HeV targeting siRNAs. Transfection media was replaced after 4 hours and cells were infected with HeV clinical isolate at an MOI of 0.1. Infected cells were incubated for 24 hours before <b>A)</b> Infected cells were fixed and labelled for HeV N, P or M protein and DAPI stain. Cells were imaged with a Leica confocal microscope. Indicative images are shown. Scale bar = 50 µM. <b>B)</b> Supernatant was removed and titrated for TCID₅₀ assay. Cells infected with supernatant were incubated for 3 days before TCID₅₀ was calculated and shown as the mean ± S.E.M. of six biological replicates from two independent experiments. Significant differences between Oligofectamine control and siRNAs are indicated (***p = <0.001, two-sided t-test).</p

Ability of siRNAs to knockdown recombinant HeV-luciferase and cause immune stimulation.

<p>HeLa cells were transfected with 40 µg/ml Poly IC, 40 nM control or HeV targeting siRNAs. siLuciferase was a positive control (grey bar), while scrambled (ScrM7) siRNA and Oligofectamine were negative controls (black bars). <b>A)</b> Transfection media was replaced after 4 hours and cells were infected with recombinant HeV-luciferase at an MOI of 0.5. Infected cells were incubated for 24 hours before luciferase activity was measured. Levels of luciferase luminescence were normalized to Oligofectamine control levels and are the mean ± S.D. of six biological replicates from two independent experiments. <b>B)</b> Cells were incubated for 12 hours before RNA extraction. Gene expression levels of IL-6 were quantified by qRT-PCR as relative expression to B-actin housekeeping gene. Results are the mean ± S.D. of six biological replicates from two independent experiments. Significant differences between Oligofectamine control and siRNAs are indicated (**p = <0.01, ***p = <0.001, ****p = <0.0001; two-sided t-test).</p

Sequence characterisation of HeV siRNAs and D-siRNAs targeting N, P and M genes.

<p>Nucleocapsid siRNAs are conventional 21 bp siRNAs. All M, P and ScrM7 are D-siRNAs that are 25+27 bp long, with a two RNA nucleotide overhang only on the antisense strand and two DNA nucleotides on the sense strand depicted in lowercase letters.</p

Reductions in HeV gene expression and protein caused by RNAi targeting HeV.

<p>HeLa cells were transfected with 40 µg/ml Poly IC, 40 nM control or HeV targeting siRNAs. Transfection media was replaced after 4 hours and cells were infected with HeV clinical isolate at an MOI of 0.1. <b>A)</b> Infected cells were incubated for 24 hours before RNA extraction. Gene expression levels of N were quantified by qRT-PCR as relative expression to B-actin housekeeping gene. Results are the mean ± SEM of six biological replicates from two independent experiments. Significant differences between Oligofectamine control and siRNAs are indicated (*p = <0.05; two-sided t-test). <b>B)</b> Infected cells were incubated for 24 hours and were subsequently fixed and labelled for HeV N protein and DAPI nuclear stain. Cells were imaged with an EVOS Microscope at 10x objective and analysed for the presence or absence of GFP indicating N protein. Indicative images are shown.</p