Lifespan benefits for the combination of rapamycin plus acarbose and for captopril in genetically heterogeneous mice

Mice bred in 2017 and entered into the C2017 cohort were tested for possible lifespan benefits of (R/S)-1,3-butanediol (BD), captopril (Capt), leucine (Leu), the Nrf2-activating botanical mixture PB125, sulindac, syringaresinol, or the combination of rapamycin and acarbose started at 9 or 16 months of age (RaAc9, RaAc16). In male mice, the combination of Rapa and Aca started at 9 months and led to a longer lifespan than in either of the two prior cohorts of mice treated with Rapa only, suggesting that this drug combination was more potent than either of its components used alone. In females, lifespan in mice receiving both drugs was neither higher nor lower than that seen previously in Rapa only, perhaps reflecting the limited survival benefits seen in prior cohorts of females receiving Aca alone. Capt led to a significant, though small (4% or 5%), increase in female lifespan. Capt also showed some possible benefits in male mice, but the interpretation was complicated by the unusually low survival of controls at one of the three test sites. BD seemed to produce a small (2%) increase in females, but only if the analysis included data from the site with unusually short-lived controls. None of the other 4 tested agents led to any lifespan benefit. The C2017 ITP dataset shows that combinations of anti-aging drugs may have effects that surpass the benefits produced by either drug used alone, and that additional studies of captopril, over a wider range of doses, are likely to be rewarding

Report on OTHER proposals for SSPEX

The only unifying factor among the experiments discussed is that they are all unique Opportunities and/or Techniques for High-caliber Experimental Research (OTHER). Thirteen of the experiments are briefly described

Lingual Squamous Cell Carcinoma Surrounded by Granular Cell Tumor

The granular cell tumor (GCT) is an uncommon, benign lesion with a preference for subcutaneous sites. In the head and neck, the tongue is the most common site, followed by the larynx. We experienced a case of a 27-year-old woman with lingual squamous cell carcinoma (SCC) surrounded by GCT. The pathological findings established that the lesion was SCC covered by GCT in the midline of the tongue. The size of the mass was very small, however, so we excised it in a diamond shape. There is an interesting association between GCTs and other malignant neoplasms. However, no causal relationship between GCT and these other carcinomas has been established. Here we report on an SCC coexisting with GCT at the same site as a median tongue lesion and review the literature

Mapping the integrated marketing communications research: A bibliometric analysis

Given the growing popularity of integrated marketing communications (IMC) among academicians and businessmen, this study examines the trends of theoretical development in IMC during 1991-2020 by using a comprehensive bibliometric analysis of 303 academic research papers. In addition to examining the citation and publication structures in terms of authors, institutions, countries, and sources, this study explores the publications and citations trends and identifies conceptual and intellectual structure of IMC literature. The results demonstrate that IMC literature follows a steady but slow growth rate, although average citations per document are high. Kitchen, PJ. (author), Northwestern University (institution), USA (country), and Journal of Marketing Communications (source) contributed the most to IMC literature. With 216 multi-authored documents, IMC can be recognized as a field of high research collaboration. About 84% of the keywords appeared only once in IMC literature. In addition, the foundation of IMC rests on a small number of articles by a few researchers published in handful number of journals. Finally, the keyword co-occurrence network analysis identifies different clusters of IMC research, of which clusters marked with the keywords (1) brand equity, (2) measurement, (3) IMC and consumer empowerment represent the highest research potential

Improved detection of RNA foci in C9orf72 amyotrophic lateral sclerosis post-mortem tissue using BaseScope™ shows a lack of association with cognitive dysfunction

Acknowledgements The authors would like to thank: (i) the Medical Research Council Edinburgh Brain Bank (ethics approval from East of Scotland Research Ethics Service, 16/ES/0084)) for supplying all post-mortem brain material and the Scottish Motor Neurone Disease Register (SMNDR)/Care Audit Research and Evaluation for Motor Neurone Disease (CARE-MND) consortium for all clinical and demographic data (ethical approval from Scotland A Research Ethics Committee 10/MRE00/78 and 15/SS/0216); (ii) The Scottish MND Clinical Specialist team for obtaining consent from patients with MND for inclusion in these studies; (iii) MND Scotland and the Sylvia Aitken Charitable Trust for funding CS to help to establish the MND Tissue Bank. The authors would also like to thank Advanced Cell Diagnostics for gifting the C9orf72 probe (BaseScopeTM Probe - BA-GGGGCCn-3zz-st, Cat Code: 704181), prior to it being made commercially available. Funding A.R.M. is a Lady Edith Wolfson Clinical Fellow and is jointly funded by the Medical Research Council and the Motor Neurone Disease Association (MR/R001162/1). He also acknowledges support from the Rowling Scholars scheme, administered by the Anne Rowling Regenerative Neurology Clinic, University of Edinburgh, Edinburgh, UK. The Chandran laboratory is supported by the Euan MacDonald Centre and the UK Dementia Research Institute, which receives its funding from UK DRI Ltd, funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. J.M.G. is funded by a starter grant for clinical lecturers from the Academy of Medical Sciences (AMS: 210JMG 3102 R45620) and C.S. is supported by a Medical Research Council grant (MR/L016400/1).Peer reviewe

Photonic-plasmonic hybrid single-molecule nanosensor measures the effect of fluorescent labels on DNA-protein dynamics

Current methods to study molecular interactions require labeling the subject molecules with fluorescent reporters. However, the effect of the fluorescent reporters on molecular dynamics has not been quantified because of a lack of alternative methods. We develop a hybrid photonic-plasmonic antenna-in-a-nanocavity single-molecule biosensor to study DNA-protein dynamics without using fluorescent labels. Our results indicate that the fluorescein and fluorescent protein labels decrease the interaction between a single DNA and a protein due to weakened electrostatic interaction. Although the study is performed on the DNA-XPA system, the conclusion has a general implication that the traditional fluorescent labeling methods might be misestimating the molecular interactions

Effectiveness and cost effectiveness of pharmacist input at the ward level: a systematic review and meta-analysis

Background Pharmacists play important role in ensuring timely care delivery at the ward level. The optimal level of pharmacist input, however, is not clearly defined. Objective To systematically review the evidence that assessed the outcomes of ward pharmacist input for people admitted with acute or emergent illness. Methods The protocol and search strategies were developed with input from clinicians. Medline, EMBASE, Centre for Reviews and Dissemination, The Cochrane Library, NHS Economic Evaluations, Health Technology Assessment and Health Economic Evaluations databases were searched. Inclusion criteria specified the population as adults and young people (age >16 years) who are admitted to hospital with suspected or confirmed acute or emergent illness. Only randomised controlled trials (RCTs) published in English were eligible for inclusion in the effectiveness review. Economic studies were limited to full economic evaluations and comparative cost analysis. Included studies were quality-assessed. Data were extracted, summarised. and meta-analysed, where appropriate. Results Eighteen RCTs and 7 economic studies were included. The RCTs were from USA (n=3), Sweden (n=2), Belgium (n=2), China (n=2), Australia (n=2), Denmark (n=2), Northern Ireland, Norway, Canada, UK and Netherlands. The economic studies were from UK (n=2), Sweden (n=2), Belgium and Netherlands. The results showed that regular pharmacist input was most cost effective. It reduced length-of-stay (mean= -1.74 days [95% CI: -2.76, -0.72], and increased patient and/or carer satisfaction (Relative Risk (RR) =1.49 [1.09, 2.03] at discharge). At £20,000 per quality-adjusted life-year (QALY)-gained cost-effectiveness threshold, it was either cost-saving or cost-effective (Incremental Cost Effectiveness Ratio (ICER) =£632/ QALY-gained). No evidence was found for 7-day pharmacist presence. Conclusions Pharmacist inclusion in the ward multidisciplinary team improves patient safety and satisfaction and is cost-effective when regularly provided throughout the ward stay. Research is needed to determine whether the provision of 7-day service is cost-effective.Peer reviewe

Water, salt water, and alkaline solution uptake in epoxy thin films

As a means of characterizing the diffusion parameters of fiber reinforced polymer (FRP) composites within a relatively short time frame, the potential use of short term tests on epoxy films to predict the long-term behavior is investigated. Reference is made to the literature to assess the effectiveness of Fickian and anomalous diffusion models to describe solution uptake in epoxies. The influence of differing exposure conditions on the diffusion in epoxies, in particular the effect of solution type and temperature, are explored. Experimental results, where the solution uptake in desiccated (D) or undesiccated (U) thin films of a commercially available epoxy matrix subjected to water (W), salt water (SW), or alkali concrete pore solution (CPS) at either 20 or 60°C, are also presented. It was found that the type of solution did not significantly influence the diffusion behavior at 20°C and that the mass uptake profile was anomalous. Exposure to 60°C accelerated the initial diffusion behavior and appeared to raise the level of saturation. In spite of the accelerated approach, conclusive values of uptake at saturation remained elusive even at an exposure period of 5 years. This finding questions the viability of using short-term thin film results to predict the long-term mechanical performance of FRP materialsThe first author was funded through an Engingeering and Physical Science Research Council Doctoral Training Award.This is the peer reviewed version of Scott, P. and Lees, J.M. (2013) Water, salt water and alkaline solution uptake in epoxy thin films, Journal of Applied Polymer Science, v. 130 (3) pp. 1898-1908 which has been published on: http://dx.doi.org/10.1002/app.39331. © 2013 Wiley Periodicals, Inc

A systematic review and meta-synthesis of the impact of low back pain on people's lives

Copyright @ 2014 Froud et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background - Low back pain (LBP) is a common and costly problem that many interpret within a biopsychosocial model. There is renewed concern that core-sets of outcome measures do not capture what is important. To inform debate about the coverage of back pain outcome measure core-sets, and to suggest areas worthy of exploration within healthcare consultations, we have synthesised the qualitative literature on the impact of low back pain on people’s lives. Methods - Two reviewers searched CINAHL, Embase, PsycINFO, PEDro, and Medline, identifying qualitative studies of people’s experiences of non-specific LBP. Abstracted data were thematic coded and synthesised using a meta-ethnographic, and a meta-narrative approach. Results - We included 49 papers describing 42 studies. Patients are concerned with engagement in meaningful activities; but they also want to be believed and have their experiences and identity, as someone ‘doing battle’ with pain, validated. Patients seek diagnosis, treatment, and cure, but also reassurance of the absence of pathology. Some struggle to meet social expectations and obligations. When these are achieved, the credibility of their pain/disability claims can be jeopardised. Others withdraw, fearful of disapproval, or unable or unwilling to accommodate social demands. Patients generally seek to regain their pre-pain levels of health, and physical and emotional stability. After time, this can be perceived to become unrealistic and some adjust their expectations accordingly. Conclusions - The social component of the biopsychosocial model is not well represented in current core-sets of outcome measures. Clinicians should appreciate that the broader impact of low back pain includes social factors; this may be crucial to improving patients’ experiences of health care. Researchers should consider social factors to help develop a portfolio of more relevant outcome measures.Arthritis Research U

Stimulus-dependent maximum entropy models of neural population codes

Neural populations encode information about their stimulus in a collective fashion, by joint activity patterns of spiking and silence. A full account of this mapping from stimulus to neural activity is given by the conditional probability distribution over neural codewords given the sensory input. To be able to infer a model for this distribution from large-scale neural recordings, we introduce a stimulus-dependent maximum entropy (SDME) model---a minimal extension of the canonical linear-nonlinear model of a single neuron, to a pairwise-coupled neural population. The model is able to capture the single-cell response properties as well as the correlations in neural spiking due to shared stimulus and due to effective neuron-to-neuron connections. Here we show that in a population of 100 retinal ganglion cells in the salamander retina responding to temporal white-noise stimuli, dependencies between cells play an important encoding role. As a result, the SDME model gives a more accurate account of single cell responses and in particular outperforms uncoupled models in reproducing the distributions of codewords emitted in response to a stimulus. We show how the SDME model, in conjunction with static maximum entropy models of population vocabulary, can be used to estimate information-theoretic quantities like surprise and information transmission in a neural population.Comment: 11 pages, 7 figure