1,506 research outputs found

    Cost-Volume-Profit Analysis

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    The Ethical Dimension of Personal Knowledge

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    Letters

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    Seabed corrugations beneath an Antarctic ice shelf revealed by autonomous underwater vehicle survey: Origin and implications for the history of Pine Island Glacier

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    Ice shelves are critical features in the debate about West Antarctic ice sheet change and sea level rise, both because they limit ice discharge and because they are sensitive to change in the surrounding ocean. The Pine Island Glacier ice shelf has been thinning rapidly since at least the early 1990s, which has caused its trunk to accelerate and retreat. Although the ice shelf front has remained stable for the past six decades, past periods of ice shelf collapse have been inferred from relict seabed "corrugations" (corrugated ridges), preserved 340 km from the glacier in Pine Island Trough. Here we present high-resolution bathymetry gathered by an autonomous underwater vehicle operating beneath an Antarctic ice shelf, which provides evidence of long-term change in Pine Island Glacier. Corrugations and ploughmarks on a sub-ice shelf ridge that was a former grounding line closely resemble those observed offshore, interpreted previously as the result of iceberg grounding. The same interpretation here would indicate a significantly reduced ice shelf extent within the last 11 kyr, implying Holocene glacier retreat beyond present limits, or a past tidewater glacier regime different from today. The alternative, that corrugations were not formed in open water, would question ice shelf collapse events interpreted from the geological record, revealing detail of another bed-shaping process occurring at glacier margins. We assess hypotheses for corrugation formation and suggest periodic grounding of ice shelf keels during glacier unpinning as a viable origin. This interpretation requires neither loss of the ice shelf nor glacier retreat and is consistent with a "stable" grounding-line configuration throughout the Holocene

    Making sense of IL-6 signalling cues in pathophysiology

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    Unravelling the molecular mechanisms that account for functional pleiotropy is a major challenge for researchers in cytokine biology. Cytokine–receptor cross-reactivity and shared signalling pathways are considered primary drivers of cytokine pleiotropy. However, reports epitomized by studies of Jak-STAT cytokine signalling identify interesting biochemical and epigenetic determinants of transcription factor regulation that affect the delivery of signal-dependent cytokine responses. Here, a regulatory interplay between STAT transcription factors and their convergence to specific genomic enhancers support the fine-tuning of cytokine responses controlling host immunity, functional identity, and tissue homeostasis and repair. In this review, we provide an overview of the signalling networks that shape the way cells sense and interpret cytokine cues. With an emphasis on the biology of interleukin-6, we highlight the importance of these mechanisms to both physiological processes and pathophysiological outcomes

    Survey of self-assessed preparedness for clinical practice in one Croatian medical school

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    <p>Abstract</p> <p>Background</p> <p>The Croatian higher education system is in the process of reforming its medical curricula to comply with European Union standards. We conducted a survey of students enrolled at the University of Zagreb (Croatia) asking them to rate their perception of preparedness for clinical practice prior to initiation of the reform process. The purpose of the survey was to identify self-perceived deficiencies in education and to establish a reference point for the later assessment of ongoing educational reform.</p> <p>Findings</p> <p>One-hundred and forty seven (N = 147) graduates reported the levels of perceived preparedness on 30 items grouped into 8 educational domains. Main domains were: understanding science, practical skills/patient management, holistic care, prevention, interpersonal skills, confidence/coping skills, collaboration, and self-directed learning. For each item, graduates self assessed their preparedness on a scale ranging from 1 to 4, with 1 = "Very inadequate", 2 = "Somewhat inadequate", 3 = "Somewhat adequate", and 4 = "Very adequate". In 7 out of 8 domains the achieved median score was ≥ 3. Students expressed low confidence (defined when ≥ 25% of respondents supplied a rating for the survey question as: "very inadequate" or "somewhat inadequate") with interpersonal skills (discussing terminal disease, counseling distraught patients, balancing professional and personal life), and in performing certain basic semi-invasive or invasive procedures.</p> <p>Conclusion</p> <p>Zagreb medical graduates identified several deficiencies within educational domains required for standard clinical practice. Ongoing educational efforts need to be directed towards the correction of these deficiencies in order to achieve standards required by the European Union.</p

    Improved glycemic control and vascular function in overweight and obese subjects by glyoxalase 1 inducer formulation

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    Risk of insulin resistance, impaired glycemic control and cardiovascular disease is excessive in overweight and obese populations. We hypothesised that increasing expression of glyoxalase 1 (Glo1) – an enzyme that catalyses the metabolism of reactive metabolite and glycating agent, methylglyoxal – may improve metabolic and vascular health. Dietary bioactive compounds were screened for Glo1 inducer activity in a functional reporter assay, hits confirmed in cell culture and an optimised Glo1 inducer formulation evaluated in a randomised, placebo-controlled crossover clinical trial in 29 overweight and obese subjects. We found trans-resveratrol (tRES) and hesperetin (HESP), at concentrations achieved clinically, synergised to increase Glo1 expression. In highly overweight subjects (BMI >27.5 kg/m2), tRES-HESP co-formulation increased expression and activity of Glo1 (+ 27%. P<0.05), decreased plasma methylglyoxal (-37%, P<0.05) and total body methylglyoxal-protein glycation (-14%, P<0.01). It decreased fasting and postprandial plasma glucose (-5%, P<0.01 and – 6%, P<0.03, respectively), increased Oral Glucose Insulin Sensitivity index (+42 mlmin-1m-2, P<0.02) and improved arterial dilatation ΔFMD/ΔGTND (95%CI 0.13–2.11). In all subjects, it decreased vascular inflammation marker sICAM-1 (-10%, P<0.01). In previous clinical evaluations, tRES and HESP individually were ineffective. tRES-HESP co-formulation could be a suitable treatment for improved metabolic and vascular health in overweight and obese populations

    Development of an in vitro periodontal biofilm model for assessing antimicrobial and host modulatory effects of bioactive molecules

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    Background: Inflammation within the oral cavity occurs due to dysregulation between microbial biofilms and the host response. Understanding how different oral hygiene products influence inflammatory properties is important for the development of new products. Therefore, creation of a robust host-pathogen biofilm platform capable of evaluating novel oral healthcare compounds is an attractive option. We therefore devised a multi-species biofilm co-culture model to evaluate the naturally derived polyphenol resveratrol (RSV) and gold standard chlorhexidine (CHX) with respect to anti-biofilm and anti-inflammatory properties.&lt;p&gt;&lt;/p&gt; Methods: An in vitro multi-species biofilm containing &lt;i&gt;S. mitis, F. nucleatum, P. Gingivalis&lt;/i&gt; and &lt;i&gt;A. Actinomycetemcomitans&lt;/i&gt; was created to represent a disease-associated biofilm and the oral epithelial cell in OKF6-TERT2. Cytotoxicity studies were performed using RSV and CHX. Multi-species biofilms were either treated with either molecule, or alternatively epithelial cells were treated with these prior to biofilm co-culture. Biofilm composition was evaluated and inflammatory responses quantified at a transcriptional and protein level.&lt;p&gt;&lt;/p&gt; Results: CHX was toxic to epithelial cells and multi-species biofilms at concentrations ranging from 0.01-0.2%. RSV did not effect multi-species biofilm composition, but was toxic to epithelial cells at concentrations greater than 0.01%. In co-culture, CHX-treated biofilms resulted in down regulation of the inflammatory chemokine IL-8 at both mRNA and protein level. RSV-treated epithelial cells in co-culture were down-regulated in the release of IL-8 protein, but not mRNA.&lt;p&gt;&lt;/p&gt; Conclusions: CHX possesses potent bactericidal properties, which may impact downstream inflammatory mediators. RSV does not appear to have bactericidal properties against multi-species biofilms, however it did appear to supress epithelial cells from releasing inflammatory mediators. This study demonstrates the potential to understand the mechanisms by which different oral hygiene products may influence gingival inflammation, thereby validating the use of a biofilm co-culture model.&lt;p&gt;&lt;/p&gt
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