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The following paper offers an in-depth, experiential analysis of the walking interview, applied within a participatory action research context. I share both reflection and critique, analyzing my experience conducting two walking interviews with stewards of urban green spaces in Vancouver, Canada and Medellín, Colombia that explored practices of care in urban nature as well as relationships to local urban ecologies. Discussion is oriented towards two essential methodological questions: (1) how does the use of walking interview advance research towards deeper understandings of stewardship practices and the relationships between stewards and urban nature; and (2) what is the lived and affective experience of conducting a walking interview as a researcher? I adopt a reflective and narrative style to emphasize the role of embodiment in community-engaged work and make explicit the discomfort and uncertainty inherent to qualitative and relationship-centered approaches to inquiry. My intention is to share lessons learned with scholars interested in pursuing similar research approaches. First, I introduce my work, myself, and my relationship and orientation to place-based qualitative inquiry. Next, I share accounts from two walking interviews held with urban green space stewards in Vancouver, CA and Medellín, CO. My experiences with walking interview illuminate its capacity to invite in-depth, sensory connection to place on the part of both the researcher and interviewee. I demystify the dynamics present between researcher and interviewee in the context of action research – commenting on how I navigated fluctuations from outsider to insider researcher (and back) and how negotiation of research relationships influenced my interview practice. I end with reflection on several limitations of the walking interview method, focusing on the challenge of navigating personal attachment and mutual obligation within the container of walking interview.

As cities attempt to ameliorate urban green inequities, a potential challenge has emerged in the form of green gentrification. Although practitioners are central to urban greening and associated gentrification, there has yet to be an exploration of practitioner perspectives on the phenomenon. We fill this gap with an online survey of 51 urban greening practitioners in Metro Vancouver and the Greater Toronto Area. Most respondents defined green gentrification as the displacement of vulnerable residents due to the installation or improvement of green space that attracts wealthy in-movers and increases property values. They were most likely to identify greening as driving green gentrification, with a minority identifying other systemic drivers with greening in a secondary role. Although 39 of 51 participants had some familiarity with green gentrification, most reported low confidence in their understanding of the concept, little evidence of using the concept in their work, and moderate concern that their work is implicated in green gentrification. The gentrification issues most encountered by practitioners were changes to neighbourhood character and uneven investment in public infrastructure, and those working in domains linked to planning, equity, and engagement were most likely to encounter gentrification issues. Practitioners experienced multiple barriers to addressing green gentrification, including limited institutional capacity, limited access to data and relevant information, policy/mandate restriction, and lack of engagement tools. Results indicate that practitioners have a moderate understanding of green gentrification but do not often use the concept in their work, despite their potential to contribute to or exacerbate it. This suggests some resistance to critiques of urban greening practice, a failure of scholarly critiques of urban greening to influence policy change, and the need for stronger research theory and research co-creation involving practitioners and academia.

Regeneration of myelin is mediated by oligodendrocyte progenitor cells—an abundant stem cell population in the central nervous system (CNS) and the principal source of new myelinating oligodendrocytes. Loss of myelin-producing oligodendrocytes in the CNS underlies a number of neurological diseases, including multiple sclerosis and diverse genetic diseases 1 – 3 . High-throughput chemical screening approaches have been used to identify small molecules that stimulate the formation of oligodendrocytes from oligodendrocyte progenitor cells and functionally enhance remyelination in vivo 4 – 10 . Here we show that a wide range of these pro-myelinating small molecules function not through their canonical targets but by directly inhibiting CYP51, TM7SF2, or EBP, a narrow range of enzymes within the cholesterol biosynthesis pathway. Subsequent accumulation of the 8,9-unsaturated sterol substrates of these enzymes is a key mechanistic node that promotes oligodendrocyte formation, as 8,9-unsaturated sterols are effective when supplied to oligodendrocyte progenitor cells in purified form whereas analogous sterols that lack this structural feature have no effect. Collectively, our results define a unifying sterol-based mechanism of action for most known small-molecule enhancers of oligodendrocyte formation and highlight specific targets to propel the development of optimal remyelinating therapeutics. Many small molecules that stimulate oligodendrocyte formation act not through their canonical pathways but by inhibiting enzymes within the cholesterol biosynthesis pathway and thereby inducing the accumulation of 8,9-unsaturated sterols.

Tenofovir disoproxil fumarate can cause renal and bone toxic effects related to high plasma tenofovir concentrations. Tenofovir alafenamide is a novel tenofovir prodrug with a 90% reduction in plasma tenofovir concentrations. Tenofovir alafenamide-containing regimens can have improved renal and bone safety compared with tenofovir disoproxil fumarate-containing regimens. In these two controlled, double-blind phase 3 studies, we recruited treatment-naive HIV-infected patients with an estimated creatinine clearance of 50 mL per min or higher from 178 outpatient centres in 16 countries. Patients were randomly assigned (1:1) to receive once-daily oral tablets containing 150 mg elvitegravir, 150 mg cobicistat, 200 mg emtricitabine, and 10 mg tenofovir alafenamide (E/C/F/tenofovir alafenamide) or 300 mg tenofovir disoproxil fumarate (E/C/F/tenofovir disoproxil fumarate) with matching placebo. Randomisation was done by a computer-generated allocation sequence (block size 4) and was stratified by HIV-1 RNA, CD4 count, and region (USA or ex-USA). Investigators, patients, study staff, and those assessing outcomes were masked to treatment group. All participants who received one dose of study drug were included in the primary intention-to-treat efficacy and safety analyses. The main outcomes were the proportion of patients with plasma HIV-1 RNA less than 50 copies per mL at week 48 as defined by the the US Food and Drug Adminstration (FDA) snapshot algorithm (pre-specified non-inferiority margin of 12%) and pre-specified renal and bone endpoints at 48 weeks. These studies are registered with ClinicalTrials.gov, numbers NCT01780506 and NCT01797445. We recruited patients from Jan 22, 2013, to Nov 4, 2013 (2175 screened and 1744 randomly assigned), and gave treatment to 1733 patients (866 given E/C/F/tenofovir alafenamide and 867 given E/C/F/tenofovir disoproxil fumarate). E/C/F/tenofovir alafenamide was non-inferior to E/C/F/tenofovir disoproxil fumarate, with 800 (92%) of 866 patients in the tenofovir alafenamide group and 784 (90%) of 867 patients in the tenofovir disoproxil fumarate group having plasma HIV-1 RNA less than 50 copies per mL (adjusted difference 2·0%, 95% CI −0·7 to 4·7). Patients given E/C/F/tenofovir alafenamide had significantly smaller mean serum creatinine increases than those given E/C/F/tenofovir disoproxil fumarate (0·08 vs 0·12 mg/dL; p<0·0001), significantly less proteinuria (median % change −3 vs 20; p<0·0001), and a significantly smaller decrease in bone mineral density at spine (mean % change −1·30 vs –2·86; p<0·0001) and hip (−0·66 vs –2·95; p<0·0001) at 48 weeks. Through 48 weeks, more than 90% of patients given E/C/F/tenofovir alafenamide or E/C/F/tenofovir disoproxil fumarate had virological success. Renal and bone effects were significantly reduced in patients given E/C/F/tenofovir alafenamide. Although these studies do not have the power to assess clinical safety events such as renal failure and fractures, our data suggest that E/C/F/tenofovir alafenamide will have a favourable long-term renal and bone safety profile. Gilead Sciences.

Ecologists have traditionally studied intraspecific variation by sampling species across their geographic ranges. However, whether this classic approach produces samples that accurately represent species' climatic niches is largely unknown. Alternative niche‐based study designs using species' climatic niches to inform sampling locations should more efficiently and completely capture the breadth of the niche, but the magnitude of this difference and how it may vary is unclear. Here we use conifers as a model system to explore these issues and reach specific recommendations for future sampling designs. Using an independent data set of high‐quality species' occurrences, we first show that recent publications examining variation across geographic space do a poor job of capturing the full breadth of species' niches, such that on average, only 22% of species' niche space was sampled. This was also true of a large compiled database, the International Tree‐Ring Data Bank (ITRDB), which yielded average niche coverage of only 45%. Finally, we simulated common sampling designs (i.e. random points, grids and transects) in both geographic and niche‐based sampling frameworks. Using two sampling metrics, niche coverage and niche undersampling, we measured how completely and evenly these simulated studies characterized the niches of 64 North American conifers. Niche‐based sampling better represented species' niches than geographic sampling, with the magnitude of this difference depending on study design and sample size. Niche‐based gridded study designs achieved the most complete sampling at all but the smallest sample sizes, covering ~15–25% more of a species' niche than similar designs implemented geographically. With fewer than 10 samples, however, all study designs performed poorly, and niche‐based transects achieved slightly higher niche coverage. Consequently, when more than a handful of samples are collected, we recommend that studies seeking to characterize variation across a species' niche consider using a gridded study design implemented in a niche‐based sampling framework.

Aim The assumption that the native distributions of species are in equilibrium with climate has been shown to be frequently violated, despite its centrality to many niche model applications. We currently lack a framework that predicts these violations. Here, we examine whether variation in climatic disequilibrium is structured by properties of species’ native distributions and climatic niches. Location Global. Methods We built climatic niche models for 106 pine (Pinus L.) species, including 25 that have naturalized outside their native range. We measured the extent of climate space occupied exclusively by naturalized populations and considered what fraction of this space was available within the native continent and near the native range. We examined the consequences of disequilibrium for estimates of potential range filling and sister species niche conservatism. Results Most species (23 of 25) have naturalized in climate conditions outside the native niche, leading to increases in the total known suitable climate space. Increases in niche size were negatively related to native niche size. Increases were often large; one species expanded its niche by almost 10% of the global climate space. These increases were associated primarily with cooler, wetter and less seasonal climates. Increases in known niche size lowered potential range filling estimates within species’ native continent and ecoregion. Naturalized data did not strengthen support for niche conservatism among sister species. Main conclusions Among pines, climatic disequilibrium is the norm and not the exception. The magnitude of this disequilibrium can be vast, such that the native range greatly under‐represents the true climatic tolerances of some species. Fortunately, this disequilibrium can be predicted largely by the size of a species’ native niche. Accounting for this disequilibrium can improve our ability to characterize ecological phenomena, including potential range filling. This is an essential step towards improving the conservation value of ecological niche models.

Managed relocation (MR) has rapidly emerged as a potential intervention strategy in the toolbox of biodiversity management under climate change. Previous authors have suggested that MR (also referred to as assisted colonization, assisted migration, or assisted translocation) could be a last-alternative option after interrogating a linear decision tree. We argue that numerous interacting and value-laden considerations demand a more inclusive strategy for evaluating MR. The pace of modern climate change demands decision making with imperfect information, and tools that elucidate this uncertainty and integrate scientific information and social values are urgently needed. We present a heuristic tool that incorporates both ecological and social criteria in a multidimensional decision-making framework. For visualization purposes, we collapse these criteria into 4 classes that can be depicted in graphical 2-D space. This framework offers a pragmatic approach for summarizing key dimensions of MR: capturing uncertainty in the evaluation criteria, creating transparency in the evaluation process, and recognizing the inherent tradeoffs that different stakeholders bring to evaluation of MR and its alternatives.

Bilirubin acts as a potent endogenous antioxidant, with higher concentrations associated with lower rates of CVD; the antiretroviral drug atazanavir (ATV) increases bilirubin levels but may also increase von Willebrand factor levels. We tested the hypothesis that increasing endogenous bilirubin using ATV would improve cardiometabolic risk factors and vascular function in older patients with HIV. Ninety participants were enrolled in two study protocols. In protocol 1, we evaluated markers of inflammation, thrombosis, and conduit artery endothelial function in subjects on non-ATV containing regimens. Participants were randomly assigned to continue baseline treatment or switch to an ATV-based regimen. Measurements were made at baseline and 28 days. In the protocol 2, we enrolled 30 subjects who received atazanavir for more than one year and were compared to the aim 1 protocol subjects at baseline. 60 subjects were enrolled in the first protocol (mean age 53, +/- 6 years), with 31 randomized to ATV and 29 continuing baseline treatment. Atazanavir significantly increased serum total bilirubin levels (p<0.001) and acutely but not chronically plasma total antioxidant capacity (p<0.001). An increase in von Willebrand Factor (p<0.001) and reduction in hs-CRP (p = 0.034) were noted. No changes were seen in either flow-mediated endothelium-dependent or vasodilation. In cross-sectional analysis (second protocol), similar findings were seen in the baseline attributes of non-atazanavir-based and long-term atazanavir users. Increasing serum bilirubin levels with atazanavir in subjects with HIV reduces hs-CRP, temporarily reduces oxidative stress, but increases von Willebrand Factor. Atazanavir does not improve endothelial function of conduit arteries. ClinicalTrials.gov NCT03019783.

Anthropogenic climate change is predicted to cause many extinctions worldwide1. Although species endemic to islands or archipelagos have high conservation value and are vulnerable to human impacts2,3, there has been no global analysis of climate-driven extinction risk focused on island endemics. Here, we use conifers as a model system to assess extinction risk among island endemics under climate projections for 2070. We employ the emerging technique of combining native and non-native occurrence data to model climatic conditions under which each species can sustain a population4–7 and also incorporate horticultural data to model the broader range of conditions that allow short-term survival. Our projections indicate that some species will retain suitable climatic conditions, some will experience conditions completely precluding survival and others will experience intermediate-risk conditions that lead to population decline and eventual extinction. Based on different climate change models, we report island size thresholds of 400 to 20,000 km2, below which extinction risks increase. These patterns are driven by correlations among island area and the breadth of species’ realized, fundamental and tolerance niches. Notably, realized and fundamental niche breadth are positively correlated. Our results highlight management interventions needed to protect species from climate-driven extinction across islands of different sizes.

Surgeons are often unfamiliar with the costs of surgical instrumentation and supplies. We hypothesized that surgeon cost feedback would be associated with a reduction in cost. A multidisciplinary team evaluated surgical supply costs for laparoscopic appendectomies of 7 surgeons (surgeons A-G) at a single-center academic institution. In the intervention, each surgeon was debriefed with their average supply cost per case, their partner’s average supply cost per case, the cost of each surgical instrument/supply, and the cost of alternatives. In addition, the laparoscopic appendectomy tray was standardized to remove extraneous instruments. Pre-intervention (March 2017-February 2018) and post-intervention (March 2018-October 2018) costs were compared. Pre-intervention, the surgeons’ average supply cost per case ranged from $754-$1189; when ranked from most to least expensive, surgeon A > B > C > D > E > F > G. Post-intervention, the surgeons’ average supply cost per case ranged from $676 to $846, and ranked from surgeon G > D > F > C > E > B > A. Overall, the average cost per case was lower in the post-intervention group ($854.35 vs. $731.11, P < .001). This resulted in savings per case of $123.24 (14.4%), to a total annualized savings of $29 151.