Natural polymers as alternative consolidants for the preservation of waterlogged archaeological wood

In recent years there has been increased interest in examining alternative polymers for the conservation of archaeological artefacts, particularly waterlogged timbers, providing better, renewable, greener alternatives to poly(ethylene glycol) (PEG). The degradation of PEG consolidants in the timbers of the 16th century warship Mary Rose has been examined and the rheological and thermal properties of PEG has been compared to its monomethyl and dimethyl ethers and several polysaccharide consolidants (chitosan, guar and 2-hydroxyethyl cellulose) in order to evaluate their potential as alternative consolidants for the conservation of waterlogged wooden artefacts. Additionally, the effect of the polymers on the archaeological wood was characterised by thermogravimetric analysis and solid state NMR. The results suggest that the future of conservation technologies lies with polysaccharide consolidant materials, which show enhanced compatibility with wooden artefacts with no detectable side-effects while also being cheap, with extremely low toxicity, renewable and sustainably resourced.ZW and OAS acknowledge financial support from European Research Council Starting Investigators Grant (No. 240629, ASPiRe), the EPSRC and the Mary Rose Trust. ERJ thanks Dr. D. Reid for useful discussions on ssNMR techniques and the EPSRC for a doctoral training grant.This is the final version of the article. It first appeared from Maney via https://doi.org10.1179/2047058414Y.000000014

Synthesis and pinning properties of the infinite-layer superconductor Sr0.9La0.1CuO

We report the high-pressure synthesis of the electron-doped infinite-layer superconductor Sr0.9La0.1CuO2 and its superconducting properties. A Rietveld analysis of X-ray powder diffraction data showed that, within the resolution of the measurement, the sample had purely an infinite-layer structure without any discernible impurities. The superconducting volume fraction and the transition width were greatly improved compared to those in previous reports. The irreversibility field line and the intragranular critical current density were much higher than those of La1.85Sr0.15CuO4 and Nd1.85Ce0.15CuO4. The stronger pinning behaviors are consistent with the strong interlayer coupling due to the short distance between CuO2 planes.Comment: Physica C (in press) 5 pages, 4 figur

Utilization of Away-From-Home Food Establishments, Dietary Approaches to Stop Hypertension Diet Pattern, and Obesity

$\textbf{Introduction:}$ Eating meals away from home has been associated with the consumption of unhealthy foods and increased body weight. However, more rigorous assessment of the contribution of different types of away-from-home food establishments to overall diet quality and obesity is minimal. This study examined usage of these food establishments, accordance to the Dietary Approaches to Stop Hypertension (DASH) dietary pattern and obesity status in a nationally representative sample of adults in the United Kingdom. $\textbf{Methods:}$ A cross-sectional analysis of data from a national survey (N=2,083 aged ≥19 years, from 2008 to 2012) with dietary intake measured using a 4-day food diary, and height and weight measured objectively. Exposures included usage of (i.e., by proportion of energy) all away-from-home food establishments combined, and fast-food outlets, restaurants, and cafés separately. Outcomes included accordance with the DASH diet, and obesity status. Multivariable logistic regressions were conducted in 2016 to estimate associations between food establishments, diet quality, and obesity. $\textbf{Results:}$ People consuming a higher proportion of energy from any away-from-home food establishment had lower odds of DASH accordance (OR=0.45, 95% CI=0.31, 0.67) and increased odds of obesity (OR=1.48, 95% CI=1.10, 1.99). After adjustment, only use of fast-food outlets was significantly associated with lower odds of DASH accordance (OR=0.48, 95%=0.33, 0.69) and higher odds of obesity (OR=1.30, 95% CI=1.01, 1.69). $\textbf{Conclusions:}$ Although a greater reliance on eating away-from-home is associated with less-healthy diets and obesity, dietary public health interventions that target these food establishments may be most effective if they focus on modifying the use of fast-food outlets.The work was undertaken by the Centre for Diet and Activity Research, a UK Clinical Research Collaboration Public Health Research Centre of Excellence. Funding from the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, the National Institute for Health Research, and the Wellcome Trust, under the auspices of the UK Clinical Research Collaboration [RG72218], is gratefully acknowledged. In addition, Dr. Penney’s PhD studentship is generously supported by the Cambridge International Scholarship, a scheme funded by the Cambridge Commonwealth, European, and International Trust

Benefit of woodland and other natural environments for adolescents’ cognition and mental health

Epidemiological studies have established positive associations of urban nature with cognitive development and mental health. However, why specifically these health benefits are received remains unclear, especially in adolescents. We used longitudinal data in a cohort of 3,568 adolescents aged 9 to 15 years at 31 schools across London, UK, to examine the associations between natural-environment types and adolescents’ cognitive development, mental health and overall well-being. We characterized natural-environment types in three tiers, where natural space was distinguished into green and blue space, and green space was further distinguished into woodland and grassland. We showed that, after adjusting for other confounding variables, higher daily exposure to woodland, but not grassland, was associated with higher scores for cognitive development and a lower risk of emotional and behavioural problems for adolescents. A similar but smaller effect was seen for green space, but not blue space, with higher scores for cognitive development. Our results suggest that urban planning decisions to optimize ecosystem benefits linked to cognitive development and mental health should carefully consider the type of natural environment included

Hepatocyte cholesterol content modulates glucagon receptor signalling

Objective To determine whether glucagon receptor (GCGR) actions are modulated by cellular cholesterol levels. Methods We determined the effects of experimental cholesterol depletion and loading on glucagon-mediated cAMP production, ligand internalisation and glucose production in human hepatoma cells, mouse and human hepatocytes. GCGR interactions with lipid bilayers were explored using coarse-grained molecular dynamic simulations. Glucagon responsiveness was measured in mice fed a high cholesterol diet with or without simvastatin to modulate hepatocyte cholesterol content. Results GCGR cAMP signalling was reduced by higher cholesterol levels across different cellular models. Ex vivo glucagon-induced glucose output from mouse hepatocytes was enhanced by simvastatin treatment. Mice fed a high cholesterol diet had increased hepatic cholesterol and a blunted hyperglycaemic response to glucagon, both of which were partially reversed by simvastatin. Simulations identified likely membrane-exposed cholesterol binding sites on the GCGR, including a site where cholesterol is a putative negative allosteric modulator. Conclusions Our results indicate that cellular cholesterol content influences glucagon sensitivity and indicate a potential molecular basis for this phenomenon. This could be relevant to the pathogenesis of non-alcoholic fatty liver disease, which is associated with both hepatic cholesterol accumulation and glucagon resistance

What to do with diabetes therapies when HbA1c lowering is inadequate:add, switch, or continue? A MASTERMIND study

This is the author accepted manuscript. The final version is available from BioMed Central via the DOI in this record.Background: It is unclear what to do when people with type 2 diabetes have had no or a limited glycemic response to a recently introduced medication. Intra-individual HbA1c variability can obscure true response. Some guidelines suggest stopping apparently ineffective therapy, but no studies have addressed this issue. Methods: In a retrospective cohort analysis using the UK Clinical Practice Research Datalink (CPRD), we assessed the outcome of 55,530 patients with type 2 diabetes starting their second or third non-insulin glucose lowering medication, with a baseline HbA1c >58mmol/mol (7.5%). For those with no HbA1c improvement or a limited response at 6 months (HbA1c fall <5.5mmol/mol [0.5%]) we compared HbA1c 12 months later in those who continued their treatment unchanged, switched to new treatment, or added new treatment. Results: An increase or a limited reduction in HbA1c was common, occurring in 21.9% (12,168/55,230), who had a mean HbA1c increase of 2.5mmol/mol (0.2%). After this limited response, continuing therapy was more frequent (n=9,308; 74%) than switching (n=1,177; 9%) or adding (n=2,163; 17%). Twelve months later, in those who switched medication HbA1c fell (-6.8mmol/mol [-0.6%], 95%CI -7.7, -6.0) only slightly more than those who continued unchanged (-5.1 mmol/mol [-0.5%], 95%CI -5.5, -4.8). Adding another new therapy was associated with a substantially better reduction (-12.4mmol/mol [-1.1%], 95%CI -13.1, -11.7). Propensity score matched subgroups demonstrated similar results. Conclusions: Where glucose lowering therapy does not appear effective on initial HbA1c testing, changing agents does not improve glycemic control. The initial agent should be continued with another therapy added.Medical Research Council (MRC)National Institute for Health Research (NIHR

Are the new drugs better? Changing UK prescribing of Type 2 diabetes medications and effects on HbA1c and weight, 2010 to 2016

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.Aim: The availability of new glucose‐lowering drugs has changed UK National Institute of Clinical Excellence Type 2 diabetes guidelines, but there has been little evaluation of real‐world use of these drugs, or of the population‐level impact of their use. We examined changes in UK prescribing for patients starting second‐ and third‐line medications, and population‐level trends in glycaemic response and weight change. Methods: We extracted incident second‐ and third‐line oral prescription records for patients with Type 2 diabetes in the UK‐representative Clinical Practice Research Datalink, 2010 to 2016 (n = 68,902). Each year we calculated the proportion of each drug prescribed as the percentage of the total prescribed. We estimated annual mean six‐month HbA1c response and weight change using linear regression, standardised for clinical characteristics. Results: Use of Dipeptidyl peptidase‐4 (DPP4) inhibitors has increased markedly to overtake sulfonylureas as the most commonly prescribed second‐line drug in 2016 (43% vs 34% of total prescriptions compared with 18% v 59% in 2010). Use of sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors has increased rapidly to 14% of second‐line and 27% of third‐line prescriptions in 2016. Mean HbA1c response at six months was stable over time (2016: 13.5 (95% confidence interval 12.8, 14.1) mmol/mol vs 2010: 13.9 (13.6;14.2) mmol/mol, p = 0.21). We found mean weight loss at six months in 2016, in contrast to 2010 where there was mean weight gain (2016: −1.2 (−0.9; −1.5) kg vs 2010: +0.4 (+0.3; +0.5) kg, p < 0.001). Conclusion: The pattern of drug prescribing to manage patients with Type 2 diabetes has changed rapidly in the United Kingdom. Increasing use of DPP4 inhibitors and SGLT2 inhibitors has not resulted in improved glycaemic control but has improved the body weight of patients starting second‐ and third‐line therapy. Acknowledgement: This abstract is submitted on behalf of the MASTERMIND consortium

Experiences of acquired brain injury survivors participating in online and hybrid performance arts programmes: an ethnographic study

Background: Performance arts can benefit people with acquired brain injury (ABI). This study explored the online delivery during COVID-19 restrictions, of a performance art intervention through the experiences of participants, artists and facilitators. Methods: Two community-based programmes were delivered. Online ethnographic observations and semi-structured interviews with participants, artists and facilitators were completed. Results: The programmes benefited participants by addressing loneliness and isolation; building confidence through peer support; improving physical limitations through movement; improving communication through music and vocal work; and using poetry, visual arts, metaphor and performance to make sense of participants’ experiences. Participants had mixed experiences of participation, but it was an acceptable alternative to in-person arts interventions for those who overcame digital challenges. Conclusions: ABI survivors can engage in online performance art programmes and find participation valuable for their health, well-being, and recovery. More work is needed to explore the generalisability of these findings, especially given digital poverty

RAMP2 influences glucagon receptor pharmacology via trafficking and signaling

Endogenous satiety hormones provide an attractive target for obesity drugs. Glucagon causes weight loss by reducing food intake and increasing energy expenditure. To further understand the cellular mechanisms by which glucagon and related ligands activate the glucagon receptor (GCGR), we investigated the interaction of the GCGR with receptor activity modifying protein (RAMP)2, a member of the family of receptor activity modifying proteins. We used a combination of competition binding experiments, cell surface enzyme-linked immunosorbent assay, functional assays assessing the Gαs and Gαq pathways and β-arrestin recruitment, and small interfering RNA knockdown to examine the effect of RAMP2 on the GCGR. Ligands tested were glucagon; glucagonlike peptide-1 (GLP-1); oxyntomodulin; and analog G(X), a GLP-1/glucagon coagonist developed in-house. Confocal microscopy was used to assess whether RAMP2 affects the subcellular distribution of GCGR. Here we demonstrate that coexpression of RAMP2 and the GCGR results in reduced cell surface expression of the GCGR. This was confirmed by confocal microscopy, which demonstrated that RAMP2 colocalizes with the GCGR and causes significant GCGR cellular redistribution. Furthermore, the presence of RAMP2 influences signaling through the Gαs and Gαq pathways, as well as recruitment of β-arrestin. This work suggests that RAMP2 may modify the agonist activity and trafficking of the GCGR, with potential relevance to production of new peptide analogs with selective agonist activities