Setting the STAGES:Introduction to the Special Issue

For now, this Special Issue is one of a kind. Each piece grows directly out of the cross-institutional network between the University of St Andrews (STA), the University of Glasgow (G), and the University of Edinburgh (E)’s Security studies (S) programmes. Together, we have created the acronym STAGES to capture these ongoing collaborations. In August 2018, we, as a small group of colleagues working at each contributing university started to discuss how our master students can learn more about security beyond the confines of their separate classrooms. As Jorge M. Lasma writes, ‘In many cases, classrooms have slowly come to be seen as the only domains for learning. Other forms and channels of learning and knowledge are viewed with suspicion and sometimes even discouraged for fear of higher costs’ (2013, p. 369). Challenging this idea, we set out to create a collective project to allow different students, with their own unique opinions and viewpoints on security, to meet one another to share their ideas in open, honest and lived ways

Effects of Very Low Nicotine Content Cigarettes on Smoking Behavior and Biomarkers of Exposure in Menthol and Non-menthol Smokers.

IntroductionBecause 30% of cigarettes sold in the United States are characterized as menthol cigarettes, it is important to understand how menthol preference may affect the impact of a nicotine reduction policy.MethodsIn a recent trial, non-treatment-seeking smokers were randomly assigned to receive very low nicotine cigarettes (VLNC; 0.4 mg nicotine/g tobacco) or normal nicotine cigarettes (NNC; 15.5 mg/g) for 20 weeks. On the basis of preference, participants received menthol or non-menthol cigarettes. We conducted multivariable regression analyses to examine whether menthol preference moderated the effects of nicotine content on cigarettes per day (CPD), breath carbon monoxide (CO), urinary total nicotine equivalents (TNE), urinary 2-cyanoethylmercapturic acid (CEMA), and abstinence.ResultsAt baseline, menthol smokers (n = 346) reported smoking fewer CPD (14.9 vs. 19.2) and had lower TNE (52.8 vs. 71.6 nmol/mg) and CO (17.7 vs. 20.5 ppm) levels than non-menthol smokers (n = 406; ps < .05). At week 20, significant interactions indicated that menthol smokers had smaller treatment effects than non-menthol smokers for CPD (-6.4 vs. -9.3), TNE (ratio of geometric means, 0.22 vs. 0.10) and CEMA (ratio, 0.56 vs. 0.37; ps < .05), and trended toward a smaller treatment effect for CO (-4.5 vs. -7.3 ppm; p = .06). Odds ratios for abstinence at week 20 were 1.88 (95% confidence interval [CI] = 0.8 to 4.4) for menthol and 9.11 (95% CI = 3.3 to 25.2) for non-menthol VLNC smokers (p = .02) relative to the NNC condition.ConclusionsAlthough menthol smokers experienced reductions in smoking, toxicant exposure, and increases in quitting when using VLNC cigarettes, the magnitude of change was smaller than that observed for non-menthol smokers.ImplicationsResults of this analysis suggest that smokers of menthol cigarettes may respond to a nicotine reduction policy with smaller reductions in smoking rates and toxicant exposure than would smokers of non-menthol cigarettes

Preliminary results of a feasibility study of the use of information technology for identification of suspected colorectal cancer in primary care: the CREDIBLE study

This is the final version of the article. Available from Cancer Research UK/Nature Publishing Group via the DOI in this record.BACKGROUND: We report the findings of a feasibility study using information technology to search electronic primary care records and to identify patients with possible colorectal cancer. METHODS: An algorithm to flag up patients meeting National Institute for Health and Care Excellence (NICE) urgent referral criteria for suspected colorectal cancer was developed and incorporated into clinical audit software. This periodically flagged up such patients aged 60 to 79 years. General practitioners (GPs) reviewed flagged-up patients and decided on further clinical management. We report the numbers of patients identified and the numbers that GPs judged to need further review, investigations or referral to secondary care and the final diagnoses. RESULTS: Between January 2012 and March 2014, 19,580 records of patients aged 60 to 79 years were searched in 20 UK general practices, flagging up 809 patients who met urgent referral criteria. The majority of the patients had microcytic anaemia (236 (29%)) or rectal bleeding (205 (25%)). A total of 274 (34%) patients needed further clinical review of their records; 199 (73%) of these were invited for GP consultation, and 116 attended, of whom 42 were referred to secondary care. Colon cancer was diagnosed in 10 out of 809 (1.2%) flagged-up patients and polyps in a further 28 out of 809 (3.5%). CONCLUSIONS: It is technically possible to identify patients with colorectal cancer by searching electronic patient records.We acknowledge the General Practitioners, practice nurses, practice managers and administrative staff who supported this study, our trial co-ordinator Marie Crook, Anthony Ingold who was one of our patient representatives and MSDi for their support in developing the software algorithm. We also acknowledge the support of the National Institute for Health Research Clinical Research Network. This study was funded by the National Awareness and Early Diagnosis Initiative (NAEDI). TM is partly funded by the National Institute for Health Research (NIHR) through the Collaborations for Leadership in Applied Health Research and Care for the West Midlands (CLAHRC-WM) programme

Pediatric functional magnetic resonance neuroimaging: tactics for encouraging task compliance

<p>Abstract</p> <p>Background</p> <p>Neuroimaging technology has afforded advances in our understanding of normal and pathological brain function and development in children and adolescents. However, noncompliance involving the inability to remain in the magnetic resonance imaging (MRI) scanner to complete tasks is one common and significant problem. Task noncompliance is an especially significant problem in pediatric functional magnetic resonance imaging (fMRI) research because increases in noncompliance produces a greater risk that a study sample will not be representative of the study population.</p> <p>Method</p> <p>In this preliminary investigation, we describe the development and application of an approach for increasing the number of fMRI tasks children complete during neuroimaging. Twenty-eight healthy children ages 9-13 years participated. Generalization of the approach was examined in additional fMRI and event-related potential investigations with children at risk for depression, children with anxiety and children with depression (N = 120). Essential features of the approach include a preference assessment for identifying multiple individualized rewards, increasing reinforcement rates during imaging by pairing tasks with chosen rewards and presenting a visual 'road map' listing tasks, rewards and current progress.</p> <p>Results</p> <p>Our results showing a higher percentage of fMRI task completion by healthy children provides proof of concept data for the recommended tactics. Additional support was provided by results showing our approach generalized to several additional fMRI and event-related potential investigations and clinical populations.</p> <p>Discussion</p> <p>We proposed that some forms of task noncompliance may emerge from less than optimal reward protocols. While our findings may not directly support the effectiveness of the multiple reward compliance protocol, increased attention to how rewards are selected and delivered may aid cooperation with completing fMRI tasks</p> <p>Conclusion</p> <p>The proposed approach contributes to the pediatric neuroimaging literature by providing a useful way to conceptualize and measure task noncompliance and by providing simple cost effective tactics for improving the effectiveness of common reward-based protocols.</p

Early Science with the Large Millimeter Telescope: COOL BUDHIES I - a pilot study of molecular and atomic gas at z~0.2

An understanding of the mass build-up in galaxies over time necessitates tracing the evolution of cold gas (molecular and atomic) in galaxies. To that end, we have conducted a pilot study called CO Observations with the LMT of the Blind Ultra-Deep H I Environment Survey (COOL BUDHIES). We have observed 23 galaxies in and around the two clusters Abell 2192 (z = 0.188) and Abell 963 (z = 0.206), where 12 are cluster members and 11 are slightly in the foreground or background, using about 28 total hours on the Redshift Search Receiver (RSR) on the Large Millimeter Telescope (LMT) to measure the $^{12}$CO J = 1 --> 0 emission line and obtain molecular gas masses. These new observations provide a unique opportunity to probe both the molecular and atomic components of galaxies as a function of environment beyond the local Universe. For our sample of 23 galaxies, nine have reliable detections (S/N$\geq$3.6) of the $^{12}$CO line, and another six have marginal detections (2.0 < S/N < 3.6). For the remaining eight targets we can place upper limits on molecular gas masses roughly between $10^9$ and $10^{10} M_\odot$. Comparing our results to other studies of molecular gas, we find that our sample is significantly more abundant in molecular gas overall, when compared to the stellar and the atomic gas component, and our median molecular gas fraction lies about $1\sigma$ above the upper limits of proposed redshift evolution in earlier studies. We discuss possible reasons for this discrepancy, with the most likely conclusion being target selection and Eddington bias.Comment: MNRAS, submitte

Development and geometry of isotropic and directional shrinkage crack patterns

We have studied shrinkage crack patterns which form when a thin layer of an alumina/water slurry dries. Both isotropic and directional drying were studied. The dynamics of the pattern formation process and the geometric properties of the isotropic crack patterns are similar to what is expected from recent models, assuming weak disorder. There is some evidence for a gradual increase in disorder as the drying layer become thinner, but no sudden transition, in contrast to what has been seen in previous experiments. The morphology of the crack patterns is influenced by drying gradients and front propagation effects, with sharp gradients having a strong orienting and ordering effect.Comment: 8 pages, 11 figures, 8 in jpg format, 3 in postscript. See also http://mobydick.physics.utoronto.ca/mud.htm

Endothelin‐1 response to whole‐body vibration in obese and normal weight individuals

Upregulation of endothelin‐1 (ET‐1) is the hallmark of various cardiovascular diseases (CVD). The purpose of the present study was to assess the ET‐1 response to an acute bout of whole‐body vibration (WBV) in humans and to determine the role of adiposity. Twenty‐two participants volunteered for the study; they were grouped into overweight/obese [(OW/OB): n = 11, Age: 33 ± 4 years, Body mass index (BMI): 35 ± 10 kg/m(2)] or normal weight [(NW): n = 11, Age: 28 ± 7 years, BMI: 21 ± 2 kg/m(2)]. Participants engaged in 10 cycles of WBV exercise (1 cycle = 1 min WBV followed by 30 s of rest). Blood samples were analyzed for ET‐1 pre‐WBV (PRE), immediately post (POST), 1 h (1H), 3 h (3H), and 24 h (24H) post‐WBV. There was a significant time main effect of WBV on circulating ET‐1 (F = 12.5, p < 0.001); however, the ET‐1 response was similar (F = 0.180, p = 0.677) between groups. Specifically, compared to PRE, a significant increase in ET‐1 was observed at 1H (p = 0.017) and 3H (p = 0.025). In addition, concentrations of ET‐1 were significantly lower at 24H compared to PRE (p = 0.019), 1H (p < 0.001), and 3H (p < 0.001). Maximal oxygen uptake during WBV was similar between the two groups. Acute WBV resulted in an initial rise in ET‐1, followed by a significantly lower ET‐1 at 24H in both groups. Findings support the utility of routine WBV exercise to elicit a decrease in ET‐1 and improve CVD risk, similar to what has been reported with traditional modes of exercise

Combination of eribulin and aurora a inhibitor MLN8237 prevents metastatic colonization and induces cytotoxic autophagy in breast cancer

© 2016 American Association for Cancer Research.Recent findings suggest that the inhibition of Aurora A (AURKA) kinase may offer a novel treatment strategy against metastatic cancers. In the current study, we determined the effects of AURKA inhibition by the small molecule inhibitor MLN8237 both as a monotherapy and in combination with the microtubuletargeting drug eribulin on different stages of metastasis in triplenegative breast cancer (TNBC) and defined the potential mechanism of its action. MLN8237 as a single agent and in combination with eribulin affected multiple steps in the metastatic process, including migration, attachment, and proliferation in distant organs, resulting in suppression of metastatic colonization and recurrence of cancer. Eribulin application induces accumulation of active AURKA in TNBC cells, providing foundation for the combination therapy. Mechanistically, AURKA inhibition induces cytotoxic autophagy via activation of the LC3B/p62 axis and inhibition of pAKT, leading to eradication of metastases, but has no effect on growth of mammary tumor. Combination of MLN8237 with eribulin leads to a synergistic increase in apoptosis in mammary tumors, as well as cytotoxic autophagy in metastases. These preclinical data provide a new understanding of the mechanisms by which MLN8237 mediates its antimetastatic effects and advocates for its combination with eribulin in future clinical trials for metastatic breast cancer and early-stage solid tumors

Validation of Cadherin HAV6 Peptide in the Transient Modulation of the Blood-Brain Barrier for the Treatment of Brain Tumors

This work is licensed under a Creative Commons Attribution 4.0 International License.The blood-brain barrier (BBB) poses a major obstacle by preventing potential therapeutic agents from reaching their intended brain targets at sufficient concentrations. While transient disruption of the BBB has been used to enhance chemotherapeutic efficacy in treating brain tumors, limitations in terms of magnitude and duration of BBB disruption exist. In the present study, the preliminary safety and efficacy profile of HAV6, a peptide that binds to the external domains of cadherin, to transiently open the BBB and improve the delivery of a therapeutic agent, was evaluated in a murine brain tumor model. Transient opening of the BBB in response to HAV6 peptide administration was quantitatively characterized using both a gadolinium magnetic resonance imaging (MRI) contrast agent and adenanthin (Ade), the intended therapeutic agent. The effects of HAV6 peptide on BBB integrity and the efficacy of concurrent administration of HAV6 peptide and the small molecule inhibitor, Ade, in the growth and progression of an orthotopic medulloblastoma mouse model using human D425 tumor cells was examined. Systemic administration of HAV6 peptide caused transient, reversible disruption of BBB in mice. Increases in BBB permeability produced by HAV6 were rapid in onset and observed in all regions of the brain examined. Concurrent administration of HAV6 peptide with Ade, a BBB impermeable inhibitor of Peroxiredoxin-1, caused reduced tumor growth and increased survival in mice bearing medulloblastoma. The rapid onset and transient nature of the BBB modulation produced with the HAV6 peptide along with its uniform disruption and biocompatibility is well-suited for CNS drug delivery applications, especially in the treatment of brain tumors