Surface modification of hydrophobic polymers for improvement of endothelial cell-surface interactions

The aim of this study is to improve the interaction of endothelial cells with polymers used in vascular prostheses. Polytetrafluoroethylene (PTFE; Teflon) films were treated by means of nitrogen and oxygen plasmas. Depending on the plasma exposure time, modified PTFE surfaces showed water-contact angles of 15¿58° versus 96° for unmodified PTFE. Electron spectroscopy in chemical analysis (ESCA) measurements revealed incorporation of both nitrogenand oxygen-containing groups into the PTFE surfaces, dependent on the plasma composition and exposure time. In-vitro biological evaluation of unmodified and modified PTFE surfaces showed that human endothelial cells, seeded from 20% human serum-containing culture medium, adhered well on to modified PTFE surfaces, but not on to unmodified films. Adhesion of endothelial cells on to expanded PTFE graft material (Gore-Tex) was also stimulated by plasma treatment of this substrate. On plasma-treated expanded PTFE, the adhering endothelial cells formed a monolayer, which covered the textured surface. The latter observation is important in view of the hemocompatibility of vascular grafts seeded with endothelial cells before implantation

Cochrane corner: PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease

In this synopsis we describe findings from a recent Cochrane review on PCSK9 inhibitors for cardiovascular disease prevention. Compared against placebo, PCSK9 inhibitors show a substantial reduction in atherogenic lipid particles (LDL-C, Apo-B and Lp(a)), and protective effects on: CVD, MI, stroke, and elevated creatinine. There is however only limited, and lower quality, evidence comparing PCSK9 inhibitors against active treatments such as statins or ezetimibe. Furthermore, the current evidence is limited by the relatively short follow-up (at most a median follow-up of 26 months) which likely also relates to the observed beneficial safety profile, showing no clear signals on adverse events such as influenza, myalgia, T2DM or cancers

PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease

Background Despite the availability of effective drug therapies that reduce low-density lipoprotein (LDL)-cholesterol (LDL-C), cardiovascular disease (CVD) remains an important cause of mortality and morbidity. Therefore, additional LDL-C reduction may be warranted, especially for patients who are unresponsive to, or unable to take, existing LDL-C-reducing therapies. By inhibiting the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme, monoclonal antibodies (PCSK9 inhibitors) may further reduce LDL-C, potentially reducing CVD risk as well. Objectives Primary To quantify short-term (24 weeks), medium-term (one year), and long-term (five years) effects of PCSK9 inhibitors on lipid parameters and on the incidence of CVD. Secondary To quantify the safety of PCSK9 inhibitors, with specific focus on the incidence of type 2 diabetes, cognitive function, and cancer. Additionally, to determine if specific patient subgroups were more or less likely to benefit from the use of PCSK9 inhibitors. Search methods We identified studies by systematically searching the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and Web of Science. We also searched Clinicaltrials.gov and the International Clinical Trials Registry Platform and screened the reference lists of included studies. We identified the studies included in this review through electronic literature searches conducted up to May 2016, and added three large trials published in March 2017. Selection criteria All parallel-group and factorial randomised controlled trials (RCTs) with a follow-up time of at least 24 weeks were eligible. Data collection and analysis Two review authors independently reviewed and extracted data. When data were available, we calculated pooled effect estimates. Main results We included 20 studies with data on 67,237 participants (median age 61 years; range 52 to 64 years). Twelve trials randomised participants to alirocumab, three trials to bococizumab, one to RG7652, and four to evolocumab. Owing to the small number of trials using agents other than alirocumab, we did not differentiate between types of PCSK9 inhibitors used. We compared PCSK9 inhibitors with placebo (thirteen RCTs), ezetimibe (two RCTs) or ezetimibe and statins (five RCTs). Compared with placebo, PCSK9 inhibitors decreased LDL-C by 53.86% (95% confidence interval (CI) 58.64 to 49.08; eight studies; 4782 participants; GRADE: moderate) at 24 weeks; compared with ezetimibe, PCSK9 inhibitors decreased LDL-C by 30.20% (95% CI 34.18 to 26.23; two studies; 823 participants; GRADE: moderate), and compared with ezetimibe and statins, PCSK9 inhibitors decreased LDL-C by 39.20% (95% CI 56.15 to 22.26; five studies; 5376 participants; GRADE: moderate). Compared with placebo, PCSK9 inhibitors decreased the risk of CVD events, with a risk difference (RD) of 0.91% (odds ratio (OR) of 0.86, 95% CI 0.80 to 0.92; eight studies; 59,294 participants; GRADE: moderate). Compared with ezetimibe and statins, PCSK9 inhibitors appeared to have a stronger protective effect on CVD risk, although with considerable uncertainty (RD 1.06%, OR 0.45, 95% CI 0.27 to 0.75; three studies; 4770 participants; GRADE: very low). No data were available for the ezetimibe only comparison. Compared with placebo, PCSK9 probably had little or no effect on mortality (RD 0.03%, OR 1.02, 95% CI 0.91 to 1.14; 12 studies; 60,684 participants; GRADE: moderate). Compared with placebo, PCSK9 inhibitors increased the risk of any adverse events (RD 1.54%, OR 1.08, 95% CI 1.04 to 1.12; 13 studies; 54,204 participants; GRADE: low). Similar effects were observed for the comparison of ezetimibe and statins: RD 3.70%, OR 1.18, 95% CI 1.05 to 1.34; four studies; 5376 participants; GRADE: low. Clinical event data were unavailable for the ezetimibe only comparison. Authors' conclusions Over short-term to medium-term follow-up, PCSK9 inhibitors reduced LDL-C. Studies with medium-term follow-up time (longest median follow-up recorded was 26 months) reported that PCSK9 inhibitors (compared with placebo) decreased CVD risk but may have increased the risk of any adverse events (driven by SPIRE-1 and -2 trials). Available evidence suggests that PCSK9 inhibitor use probably leads to little or no difference in mortality. Evidence on relative efficacy and safety when PCSK9 inhibitors were compared with active treatments was of low to very low quality (GRADE); follow-up times were short and events were few. Large trials with longer follow-up are needed to evaluate PCSK9 inhibitors versus active treatments as well as placebo. Owing to the predominant inclusion of high-risk patients in these studies, applicability of results to primary prevention is limited. Finally, estimated risk differences indicate that PCSK9 inhibitors only modestly change absolute risks (often to less than 1%)

Using fractional exhaled nitric oxide (FeNO) to diagnose steroid-responsive disease and guide asthma management in routine care

Acknowledgements We thank Robin Taylor for his informative thinking and publications on FeNO, which have helped to influence and direct the thinking of the authors. Funding Extraction of the real-life dataset was funded by Research in Real Life Limited, the analysis of the dataset and the writing of this manuscript were co-funded (50:50) by Research in Real Life Limited and Aerocrine.Peer reviewedPublisher PD

Wood Dust in Joineries and Furniture Manufacturing: An Exposure Determinant and Intervention Study.

: To assess wood dust exposures and determinants in joineries and furniture manufacturing and to evaluate the efficacy of specific interventions on dust emissions under laboratory conditions. Also, in a subsequent follow-up study in a small sample of joinery workshops, we aimed to develop, implement, and evaluate a cost-effective and practicable intervention to reduce dust exposures. : Personal inhalable dust (n = 201) was measured in 99 workers from 10 joineries and 3 furniture-making factories. To assess exposure determinants, full-shift video exposure monitoring (VEM) was conducted in 19 workers and task-based VEM in 32 workers (in 7 joineries and 3 furniture factories). We assessed the efficacy of vacuum extraction on hand tools and the use of vacuum cleaners instead of sweeping and dry wiping under laboratory conditions. These measures were subsequently implemented in three joinery workshops with 'high' (&gt;4 mg m-3) and one with 'low' (&lt;2 mg m-3) baseline exposures. We also included two control workshops (one 'low' and one 'high' exposure workshop) in which no interventions were implemented. Exposures were measured 4 months prior and 4 months following the intervention. : Average (geometric means) exposures in joinery and furniture making were 2.5 mg m-3 [geometric standard deviations (GSD) 2.5] and 0.6 mg m-3 (GSD 2.3), respectively. In joinery workers cleaning was associated with a 3.0-fold higher (P &lt; 0.001) dust concentration compared to low exposure tasks (e.g. gluing), while the use of hand tools showed 3.0- to 11.0-fold higher (P &lt; 0.001) exposures. In furniture makers, we found a 5.4-fold higher exposure (P &lt; 0.001) with using a table/circular saw. Laboratory efficiency experiments showed a 10-fold decrease in exposure (P &lt; 0.001) when using a vacuum cleaner. Vacuum extraction on hand tools combined with a downdraft table reduced exposures by 42.5% for routing (P &lt; 0.1) and 85.5% for orbital sanding (P &lt; 0.001). Following intervention measures in joineries, a borderline statistically significant (P &lt; 0.10) reduction in exposure of 30% was found in workshops with 'high' baseline exposures, but no reduction was shown in the workshop with 'low' baseline exposures. : Wood dust exposure is high in joinery workers and (to a lesser extent) furniture makers with frequent use of hand tools and cleaning being key drivers of exposure. Vacuum extraction on hand tools and alternative cleaning methods reduced workplace exposures substantially, but may be insufficient to achieve compliance with current occupational exposure limits.<br/

Mineral chemistry of igneous melanite garnets from analcite-bearing volcanic rocks, Alberta, Canada

The mineral chemistry of melanite garnets from the Crowsnest volcanic rocks of SW Alberta, Canada, has been investigated by using electron microprobe scans, quantitative analyses and multivariate statistical analysis. The garnets occur with aegirine-augite, sanidine, analcite and rare plagioclase as phenocrysts in trachyte and phonolite flows, agglomerates and tuffs. Wavelength dispersive microprobe scans reveal complex zonation patterns, both normal and oscillatory. The results of fifty quantitative analyses were subjected to R-mode factor analysis to delineate the chemical exchanges producing the zonation. The chemical zonation of the garnets may be attributed to four independent binary exchanges; Al-Fe3+, Si-Ti, Ca-Mn and Mg-Fe2+. The stoichiometry of these garnets, based on microprobe and wet chemical Fe analyses, combined with the strongly antithetic behavior of Si and Ti lead us to infer that the Ti in these garnets is dominantly tetravalent. It is clear from this study that quantitative modelling of the processes of crystal growth and zonation of melanite garnets in alkaline, undersaturated igneous rocks should be aimed at simulating the four chemical exchanges listed above

A synthetic study of acoustic full waveform inversion to improve seismic modelling of firn

The density structure of firn has implications for hydrological and climate modelling and for ice shelf stability. The firn structure can be evaluated from depth models of seismic velocity, widely obtained with Herglotz-Wiechert inversion (HWI), an approach that considers the slowness of refracted seismic arrivals. However, HWI is appropriate only for steady-state firn profiles and the inversion accuracy can be compromised where firn contains ice layers. In these cases, Full Waveform Inversion (FWI) can be more successful than HWI. FWI extends HWI capabilities by considering the full seismic waveform and incorporates reflected arrivals, thus offering a more accurate estimate of a velocity profile. We show the FWI characterisation of the velocity model has an error of only 1.7% for regions (vs. 4.2% with HWI) with an ice slab (20 m thick, 40 m deep) in an otherwise steady-state firn profile

Environmental DNA is effective in detecting the federally threatened Louisiana Pinesnake ( Pituophis ruthveni)

Successful conservation of rare, threatened, or endangered (RTE) species is dependent upon rapid and accurate assessment of their distribution and abundance. However, assessments are challenging as RTE species typically exist as numerically small populations in often fragmented habitats and can possess complex natural histories. Environmental DNA (eDNA) analysis may provide a rapid, cost‐effective means of assessing RTE species presence/absence in viable habitat patches. We evaluated the efficacy of eDNA surveillance for the Louisiana Pinesnake (Pituophis ruthveni), an elusive, semi‐fossorial, nonvenomous colubroid snake endemic to Louisiana and Texas, USA, that has dramatically declined in both distribution and abundance. We developed two quantitative polymerase chain reaction (qPCR) assays that target the mitochondrial cytochrome c oxidase subunit I (COI) and mitochondrially encoded ATP synthase membrane subunit 6 (ATP6) genes. We validated each assay in silico, in vitro, and in situ, and investigated the influence of eDNA extraction method and genetic marker on assay performance. Both assays were highly sensitive and successfully detected the Louisiana Pinesnake under artificial and field conditions, including bedding samples collected from captive snake enclosures (100%), soil samples from Louisiana Pinesnake release sites (100%), and soil samples from sites where Louisiana Pinesnakes were documented via radio telemetry (45%). Although differences between genetic markers were negligible, assay performance was strongly influenced by eDNA extraction method. Informed by our results, we discuss methodological and environmental factors influencing Louisiana Pinesnake eDNA detection and quantification, broader implications for management and conservation of the Louisiana Pinesnake and other terrestrial reptiles and provide recommendations for future research. We suggest that eDNA surveys can more effectively assess Louisiana Pinesnake occupancy than conventional sampling, highlighting the need for comprehensive eDNA monitoring initiatives to better identify suitable habitat that will promote persistence of this imperiled species going forward

Hot and bothered: using trait-based approaches to assess climate change vulnerability in reptiles

One-fifth of the world’s reptiles are currently estimated as threatened with extinction, primarily due to the immediate threats of habitat loss and overexploitation. Climate change presents an emerging slow-acting threat. However, few IUCN Red List assessments for reptiles explicitly consider the potential role of climate change as a threat. Thus, climate change vulnerability assessments can complement existing Red List assessments and highlight further, emerging priorities for conservation action. Here we present the first trait-based global climate change vulnerability assessment for reptiles to estimate the climate change vulnerability of a random representative sample of 1498 species of reptiles. We collected species-specific traits relating to three dimensions of climate change, sensitivity, low adaptability, and exposure which we combined to assess overall vulnerability. We found 80.5% of species highly sensitive to climate change, primarily due to habitat specialisation, while 48% had low adaptability and 58% had high exposure. Overall, 22% of species assessed were highly vulnerable to climate change. Hotspots of climate vulnerability did not always overlap with hotspots of threatened species richness, with most of the vulnerable species found in northwestern South America, southwestern USA, Sri Lanka, the Himalayan Arc and southern India. Most families were found to be significantly more vulnerable to climate change than expected by chance. Our findings build on previous work on reptile extinction risk to provide an overview of the risk posed to reptiles by climate change. Despite significant data gaps for a number of traits, we recommend that these findings are integrated into reassessments of species’ extinction risk, to monitor both immediate and slow-acting threats to reptiles

Deconstructing the lesbian, gay, bisexual, transgender victim of sex trafficking: Harm, exceptionality and religion–sexuality tensions

Contrary to widespread belief, sex trafficking also targets lesbian, gay, bisexual, transgender (LGBT) communities. Contemporary social and political constructions of victimhood lie at the heart of regulatory policies on sex trafficking. Led by the US Department of State, knowledge about LGBT victims of trafficking constitutes the newest frontier in the expansion of criminalization measures. These measures represent a crucial shift. From a burgeoning range of preemptive measures enacted to protect an amorphous class of ‘all potential victims’, now policies are heavily premised on the risk posed by traffickers to ‘victims of special interest’. These constructed identities, however, are at odds with established structures. Drawing on a range of literatures, the core task of this article is to confront some of the complexities and tensions surrounding constructions of LGBT trafficking victims. Specifically, the article argues that discourses of ‘exceptional vulnerability’ and the polarized notions of ‘innocence’ and ‘guilt’ inform hierarchies of victimhood. Based on these insights, the article argues for the need to move beyond monolithic understandings of victims, by reframing the politics of harm accordingly