Mapping Lyman Continuum escape in Tololo 1247-232

Low redshift, spatially resolved Lyman continuum (LyC) emitters allow us to clarify the processes for LyC escape from these starburst galaxies. We use Hubble Space Telescope (HST) WFC3 and ACS imaging of the confirmed low-redshift LyC emitter Tol 1247-232 to study the ionization structure of the gas and its relation to the ionizing star clusters. We perform ionization parameter mapping (IPM) using [O III]4959, 5007 and [O II]3727 imaging as the high- and low-ionization tracers, revealing broad, large-scale, optically thin regions originating from the center, and reaching the outskirts of the galaxy, consistent with LyC escape. We carry out stellar population synthesis modeling of the 26 brightest clusters using our HST photometry. Combining these data with the nebular photometry, we find a global LyC escape fraction of f_esc = 0.12, with uncertainties also consistent with zero escape and with all measured f_esc values for this galaxy. Our analysis suggests that, similar to other candidate LyC emitters, a two-stage starburst has taken place in this galaxy, with a 12 Myr old, massive, central cluster likely having pre-cleared regions in and around the center, and the second generation of 2 - 4 Myr old clusters dominating the current ionization, including some escape from the galaxy.Comment: Accepted for publication in Ap

Differing calcification processes in cultured vascular smooth muscle cells and osteoblasts

© 2019 Published by Elsevier Inc.Arterial medial calcification (AMC) is the deposition of calcium phosphate mineral, often as hydroxyapatite, inthe medial layer of the arteries. AMC shares some similarities to skeletal mineralisation and has been associatedwith the transdifferentiation of vascular smooth muscle cells (VSMCs) towards an osteoblast-like phenotype. Thisstudy used primary mouse VSMCs and calvarial osteoblasts to directly compare the established and widely usedin vitromodels of AMC and bone formation. Significant differences were identified between osteoblasts andcalcifying VSMCs. First, osteoblasts formed large mineralised bone nodules that were associated with widespreaddeposition of an extracellular collagenous matrix. In contrast, VSMCs formed small discrete regions of calcifi-cation that were not associated with collagen deposition and did not resemble bone. Second, calcifying VSMCsdisplayed a progressive reduction in cell viability over time (≤7-fold), with a 50% increase in apoptosis,whereas osteoblast and control VSMCs viability remained unchanged. Third, osteoblasts expressed high levels ofalkaline phosphatase (TNAP) activity and TNAP inhibition reduced bone formation by to 90%. TNAP activity incalcifying VSMCs was∼100-fold lower than that of bone-forming osteoblasts and cultures treated withβ-gly-cerophosphate, a TNAP substrate, did not calcify. Furthermore, TNAP inhibition had no effect on VSMC calci-fication. Although, VSMC calcification was associated with increased mRNA expression of osteoblast-relatedgenes (e.g. Runx2, osterix, osteocalcin, osteopontin), the relative expression of these genes was up to 40-foldlower in calcifying VSMCs versus bone-forming osteoblasts. In summary, calcifying VSMCsin vitrodisplay somelimited osteoblast-like characteristics but also differ in several key respects: 1) their inability to form collagen-containing bone; 2) their lack of reliance on TNAP to promote mineral deposition; and, 3) the deleterious effectof calcification on their viability.Peer reviewedFinal Published versio

Outcome measures used in arthroplasty trials : systematic review of the 2008 and 2013 literature

Background/objective: Previously published literature assessing the reporting of outcome measures used in joint replacement randomised controlled trials (RCTs) has revealed disappointing results. It remains unknown as to whether international initiatives have led to any improvement in the quality of reporting and/or a reduction in the heterogeneity of outcome measures used. Our objective was to systematically assess and compare primary outcome measures and risk of bias of joint replacement RCTs published in 2008 and 2013. Methods: We searched MEDLINE, EMBASE and CENTRAL for RCTs investigating adult patients undergoing joint replacement surgery. Two authors independently identified eligible trials, extracted data and assessed risk of bias using the Cochrane tool. Results: Seventy RCTs (30 in 2008; 40 in 2013) met the eligibility criteria. There was no significant difference in the number of trials judged to be at low overall risk of bias (N=6, 20%) in 2008 compared with six (15%) in 2013 (χ2 =0.302, P=0.75). Significantly more trials published in 2008 did not specify a primary outcome measure (N=25, 83%) compared with 18 (45%) trials in 2013, χ2 = 10.6316, P=0.001). When specified, there was significant heterogeneity in the measures used to assess primary outcomes. Conclusion: While less than a quarter of trials published in both 2008 and 2013 were judged to be at low overall risk of bias, significantly more trials published in 2013 specified a primary outcome. Although this might represent a temporal trend towards improvement, the overall frequency of primary outcome reporting and the wide heterogeneity in primary outcomes reported remain suboptimal

A double-blind randomized controlled trial of the effects of eicosapentaenoic acid supplementation on muscle inflammation and physical function in patients undergoing colorectal cancer resection

BackgroundResection of colorectal cancer (CRC) initiates inflammation, mediated at least partly by NFĸB (nuclear factor kappa-light-chain-enhancer of activated B-cells), leading to muscle catabolism and reduced physical performance. Eicosapentaenoic acid (EPA) has been shown to modulate NFĸB, but evidence for its benefit around the time of surgery is limited.ObjectiveTo assess the effect of EPA supplementation on muscle inflammation and physical function around the time of major surgery.DesignIn a double-blind randomized control trial, 61 patients (age: 68.3 ± 0.95 y; 42 male) scheduled for CRC resection, received 3 g per day of EPA (n = 32) or placebo (n = 29) for 5-days before and 21-days after operation. Lean muscle mass (LMM) (via dual energy X-ray absorptiometry (DXA)), anaerobic threshold (AT) (via cardiopulmonary exercise testing (CPET)) and hand-grip strength (HG) were assessed before and 4-weeks after surgery, with muscle biopsies (m. vastus lateralis) obtained for the assessment of NF-ĸB protein expression.ResultsThere were no differences in muscle NFĸB between EPA and placebo groups (mean difference (MD) −0.002; 95% confidence interval (CI) −0.19 to 0.19); p = 0.98). There was no difference in LMM (MD 704.77 g; 95% CI -1045.6 g–2455.13 g; p = 0.42) or AT (MD 1.11 mls/kg/min; 95% CI -0.52 mls/kg/min to 2.74 mls/kg/min; p = 0.18) between the groups. Similarly, there was no difference between the groups in HG at follow up (MD 0.1; 95% CI -1.88 to 2.08; p = 0.81). Results were similar when missing data was imputed.ConclusionEPA supplementation confers no benefit in terms of inflammatory status, as judged by NFĸB, or preservation of LMM, aerobic capacity or physical function following major colorectal surgery

Conus : First comprehensive conservation red list assessment of a marine gastropod mollusc genus

Marine molluscs represent an estimated 23% of all extant marine taxa, but research into their conservation status has so far failed to reflect this importance, with minimal inclusion on the authoritative Red List of the International Union for the Conservation of Nature (IUCN). We assessed the status of all 632 valid species of the tropical marine gastropod mollusc, Conus (cone snails), using Red List standards and procedures to lay the groundwork for future decadal monitoring, one of the first fully comprehensive global assessments of a marine taxon. Three-quarters (75.6%) of species were not currently considered at risk of extinction owing to their wide distribution and perceived abundance. However, 6.5% were considered threatened with extinction with a further 4.1% near threatened. Data deficiency prevented 13.8% of species from being categorised although they also possess characteristics that signal concern. Where hotspots of endemism occur, most notably in the Eastern Atlantic, 42.9% of the 98 species from that biogeographical region were classified as threatened or near threatened with extinction. All 14 species included in the highest categories of Critically Endangered and Endangered are endemic to either Cape Verde or Senegal, with each of the three Critically Endangered species restricted to single islands in Cape Verde. Threats to all these species are driven by habitat loss and anthropogenic disturbance, in particular from urban pollution, tourism and coastal development. Our findings show that levels of extinction risk to which cone snails are exposed are of a similar magnitude to those seen in many fully assessed terrestrial taxa. The widely held view that marine species are less at risk is not upheld

Do outcomes reported in randomised controlled trials of joint replacement surgery fulfil the OMERACT 2.0 Filter? A review of the 2008 and 2013 literature.

Background It is not known, whether outcome reporting in trials of total joint arthroplasty in the recent years is adequate or not. Our objective was to assess whether outcomes reported in total joint replacement (TJR) trials fulfil the Outcome Measures in Rheumatology (OMERACT) Filter 2.0. Methods We systematically reviewed all TJR trials in adults, published in English in 2008 or 2013. Searches were conducted in the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE. Two authors independently applied the inclusion criteria for the studies, and any disagreement was resolved with a third review author. All outcome measures were abstracted using a pre-piloted standardised data extraction form and assessed for whether they mapped to one of the three OMERACT Filter 2.0 core areas: pathophysiological, life impact, and death. Results From 1635 trials identified, we included 70 trials (30 in 2008 and 40 in 2013) meeting the eligibility criteria. Twenty-two (31%) trials reported the three essential OMERACT core areas. Among the 27 hip replacement surgery trials and 39 knee replacement surgery trials included, 11 hip (41%) and nine knee (23%) trials reported all three essential OMERACT core areas. The most common outcome domains/measures were pain (20/27, 74%) and function (23/27, 85%) in hip trials and pain (26/39, 67%) and function (27/39, 69%) in knee trials. Results were similar for shoulder and hand joint replacement trials. Conclusions We identified significant gaps in the measurement of OMERACT core outcome areas in TJR trials, despite the majority reporting outcome domains of pain and function. An international consensus of key stakeholders is needed to develop a core domain set for reporting of TJR trials

In vitro permeation and biological activity of punicalagin and zinc (II) across skin and mucous membranes prone to Herpes simplex virus infection

Coadministration of pomegranate rind extract (PRE) and zinc (II) ions has recently been reported as a potential new topical treatment for Herpes simplex virus (HSV) infections. In the current work we examined the in vitro topical delivery of punicalagin (major phytochemical of PRE) and zinc from hydrogels across epithelial membranes that can become infected with HSV. Porcine epidermal, buccal and vaginal mucous membranes were excised and mounted in Franz diffusion cells and dosed with a simple hydrogel containing PRE and zinc sulphate (ZnSO4). The permeation of punicalagin and zinc were determined by HPLC and ICPMS respectively; punicalagin was also determined in the basal layers by reverse tape stripping. Receptor phases from the epidermal membrane experiment were also used to challenge HSV-1 in Vero host cells, and ex vivo porcine skin was used to probe COX-2 modulation. Punicalagin and zinc permeated each of the three test membranes, with significantly greater amounts of both delivered across the epidermal membrane. The amounts of punicalagin permeating the buccal and vaginal membranes were similar, although the amount of zinc permeating the vaginal membrane was comparatively very large – it is known that zinc interacts with vaginal mucosa. The punicalagin recovered by reverse tape stripping of the epidermal, buccal and vaginal membranes gave 0.47 ± 0.016, 0.45 ± 0.052 and 0.51 ± 0.048 nM cm− 2 respectively, and were statistically the same (p < 0.05). A 2.5 log reduction was achieved against HSV-1 using diffusion cell receptor phase, and COX-2 expression was reduced by 64% in ex vivo skin after 6 h. Overall, a hydrogel containing 1.25 mg mL− 1 PRE and 0.25 M ZnSO4 was able to topically deliver both the major bioactive compound within PRE and Zn (II) across all membranes and into the site specific region of Herpes simplex vesicular clusters, while maintaining potentiated virucidal and anti-inflammatory properties. This novel therapeutic system therefore has potential for the topical treatment of HSV infections

Social gaze in preterm infants may act as an early indicator of atypical lateralization

Rachael Davis - ORCID: 0000-0002-3887-6003 https://orcid.org/0000-0002-3887-6003VoR deposited and AM unrestricted on 2022-02-10.Visual field biases have been identified as markers of atypical lateralisation in children with developmental conditions, but this is the first investigation to consider early lateralised gaze behaviours for social stimuli in preterm infants. Eyetracking methods with 51 preterm (33 male, 92.1% White) and 61 term-born (31 male, 90.1% White) infants aged 8-10 months from Edinburgh, UK, captured the development of visual field biases, comparing gaze behaviour to social and non-social stimuli on the left versus right of the screen. Preterm infants showed a significantly reduced interest to social stimuli on the left versus right compared to term children (d =.58). Preterm children exhibit early differential orienting preferences that may be an early indicator of atypical lateralised function.This work is a secondary analysis of data collected from Theirworld Edinburgh Birth Cohort, which is supported by Theirworld (www.theirworld.org) and is carried out in the MRC Centre for Reproductive Health at the University of Edinburgh (MRC G1002033).https://doi.org/10.1111/cdev.13734aheadofprintaheadofprin

Scaling Laws for Mitotic Chromosomes

During mitosis in higher eukaryotes, each chromosome condenses into a pair of rod-shaped chromatids. This process is co-regulated by the activity of several gene families, and the underlying biophysics remains poorly understood. To better understand the factors regulating chromosome condensation, we compiled a database of mitotic chromosome size and DNA content from the tables and figures of &gt;200 published papers. A comparison across vertebrate species shows that chromosome width, length and volume scale with DNA content to the powers ∼1/4, ∼1/2, and ∼1, respectively. Angiosperms (flowering plants) show a similar length scaling, so this result is not specific to vertebrates. Chromosome shape and size thus satisfy two conditions: (1) DNA content per unit volume is approximately constant and (2) the cross-sectional area increases proportionately with chromosome length. Since viscous drag forces during chromosome movement are expected to scale with length, we hypothesize that the cross-section increase is necessary to limit the occurrence of large chromosome elongations that could slow or stall mitosis. Lastly, we note that individual vertebrate karyotypes typically exhibit a wider range of chromosome lengths as compared with angiosperms