Generic protease detection technology for monitoring periodontal disease

Periodontal diseases are inflammatory conditions that affect the supporting tissues of teeth and can lead to destruction of the bone support and ultimately tooth loss if untreated. Progression of periodontitis is usually site specific but not uniform, and currently there are no accurate clinical methods for distinguishing sites where there is active disease progression from sites that are quiescent. Consequently, unnecessary and costly treatment of periodontal sites that are not progressing may occur. Three proteases have been identified as suitable markers for distinguishing sites with active disease progression and quiescent sites: human neutrophil elastase, cathepsin G and MMP8. Generic sensor materials for the detection of these three proteases have been developed based on thin dextran hydrogel films cross-linked with peptides. Degradation of the hydrogel films was monitored using impedance measurements. The target proteases were detected in the clinically relevant range within a time frame of 3 min. Good specificity for different proteases was achieved by choosing appropriate peptide cross-linkers.<br/

Endoplasmic reticulum targeting fluorescent probes to image mobile Zn2+

Zn2+ plays an important role in the normal function of the endoplasmic reticulum (ER) and its deficiency can cause ER stress, which is related to a wide range of diseases. In order to provide tools to better understand the role of mobile Zn2+ in ER processes, the first custom designed ER-localised fluorescent Zn2+ probes have been developed through the introduction of a cyclohexyl sulfonylurea as an ER-targeting unit with different Zn2+ receptors. Experiments in vitro and in cellulo show that both probes have a good fluorescence switch on response to Zn2+, high selectivity over other cations, low toxicity, ER-specific targeting ability and are efficacious imaging agents for mobile Zn2+ in four different cell lines. Probe 9 has been used to detect mobile Zn2+ changes under ER stress induced by both tunicamycin or thapsigargin, which indicates that the new probes should allow a better understanding of the mechanisms cells use to respond to dysfunction of zinc homeostasis in the ER and its role in the initiation and progression of diseases to be developed

Effect of trimetazidine dihydrochloride therapy on exercise capacity in patients with nonobstructive hypertrophic cardiomyopathy: A randomized clinical trial

Importance: Hypertrophic cardiomyopathy causes limiting symptoms in patients, mediated partly through inefficient myocardial energy use. There is conflicting evidence for therapy with inhibitors of myocardial fatty acid metabolism in patients with nonobstructive hypertrophic cardiomyopathy. Objective: To determine the effect of oral therapy with trimetazidine, a direct inhibitor of fatty acid β-oxidation, on exercise capacity in patients with symptomatic nonobstructive hypertrophic cardiomyopathy. Design, Setting, and Participants: This randomized, placebo-controlled, double-blind clinical trial at The Heart Hospital, University College London Hospitals, London, United Kingdom was performed between May 31, 2012, and September 8, 2014. The trial included 51 drug-refractory symptomatic (New York Heart Association class ≥2) patients aged 24 to 74 years with a maximum left ventricular outflow tract gradient 50 mm Hg or lower and a peak oxygen consumption during exercise of 80% or less predicted value for age and sex. Statistical analysis was performed from March 1, 2016 through July 4, 2018. Interventions: Participants were randomly assigned to trimetazidine, 20 mg, 3 times daily (n = 27) or placebo (n = 24) for 3 months. Main Outcomes and Measures: The primary end point was peak oxygen consumption during upright bicycle ergometry. Secondary end points were 6-minute walk distance, quality of life (Minnesota Living with Heart Failure questionnaire), frequency of ventricular ectopic beats, diastolic function, serum N-terminal pro-brain natriuretic peptide level, and troponin T level. Results: Of 49 participants who received trimetazidine (n = 26) or placebo (n = 23) and completed the study, 34 (70%) were male; the mean (SD) age was 50 (13) years. Trimetazidine therapy did not improve exercise capacity, with patients in the trimetazidine group walking 38.4 m (95% CI, 5.13 to 71.70 m) less than patients in the placebo group at 3 months after adjustment for their baseline walking distance measurements. After adjustment for baseline values, peak oxygen consumption was 1.35 mL/kg per minute lower (95% CI, -2.58 to -0.11 mL/kg per minute; P = .03) in the intervention group after 3 months. Conclusions and Relevance: In symptomatic patients with nonobstructive hypertrophic cardiomyopathy, trimetazidine therapy does not improve exercise capacity. Pharmacologic therapy for this disease remains limited. Trial Registration: ClinicalTrials.gov identifier: NCT01696370

Deployment of autonomous IoT drones for precision farming in an automated manner

Precision farming (PF), as described by European Commission, is a management approach that focuses on (near real-time) observation, measurement, and responses to variability in crops, fields and animals; it can help increase crop yields and animal performance, reduce costs, including labour costs, and optimise process inputs; all of these can help increase profitability; at the same time, PF can increase work safety and reduce the environmental impacts of agriculture and farming practices, thus contributing to the sustainability of agricultural production. Vehicles are becoming increasingly automated by taking on more and more tasks under improving intelligent control systems equipped with enhancing low-power monitoring sensor technologies and Artificial Intelligence (AI) techniques. Autonomous Unmanned Aerial Vehicles (UAVs) (A-UAVs), as flying autonomous robots, with self-learning and self-decision-making abilities by executing non-trivial sequences of events with decimetre-level accuracy based on a set of rules, control loops and constraints using dynamic flight plans involving autonomous take-off and landing are taking their indispensable parts with little or no human in the loop to accomplish various automated tasks. PF is one of the most promising applications showing the benefits of using drones where a lack of human element in the farming industry is becoming evident. For instance, remote monitoring using Internet of Things (IoT) UAVs is safe, cost-effective and could be easily and frequently repeated, providing prompt information about livestock's population size and their instant location and health-related issues. The University of Central Lancashire (UCLan) has been developing intelligent IoT drones to execute numerous tasks in various disciplines (https://www.uclan.ac.uk/business/archive/lidz) for a decade within the concept of Automation of Everything (AoE) and Internet of Everything (IoE) using several supervised and unsupervised AI techniques. This research demonstrates how highly integrated technologies with drones can help the farming industry overcome challenging issues. Intelligent UAVs can overtake some of the labour-intensive tasks to execute PF. The integration of UAVs embedded with IoT and sensor-driven technologies into farming can improve productivity with substantial cost savings. IoT technologies instilled with AI techniques can lead to automated ways of performing daily routines in large farms. Within this perspective, in this event, several examples of PF-based IoT drones and their equipment, developed by UCLan, are demonstrated

SelfPub 2.0

The self-publishing revolution has created a drastic increase in the number or works being published in the social sciences and humanities. This windfall of content has created an abundance that can be overwhelming, but it ultimately presents an opportunity for libraries to develop deeper and more unique collections. The preconference at the 2013 Charleston Conference focused on several interrelated topics in the self-publishing world: navigating the abundance of self-published material, libraries’ adoption of the role of publisher, vendor perspectives on self-published content and plans for the future, issues in humanities and social science acquisitions of self-published works, and an agent’s perspective on how self-publishing fits into the traditional publishing world. Speakers include librarians, publishers, vendors, and academics involved with a number of projects and efforts to pioneer this emerging field

Beyond heritage science: A review

Heritage science is an established and thriving field of enquiry. Initially considered as inherently cross-disciplinary, encompassing both the needs of conservators and practitioners and the high-quality evidence produced by scientists, heritage science has, through its expansion in recent years, formed a discipline in its own right. Here, we examine how heritage science can, and to an extent has, moved beyond the straightforward scientific analysis of historical materials and artefacts through an exploration of heritage science’s interactions with four key themes: (i) historical and archival research, (ii) conservation practice, (iii) policy at governmental, organisational and institutional levels, and (iv) a view to how new technologies, such as machine learning and artificial intelligence, can shape the future of heritage science. Much of the review narrative is framed via the analysis of UK-based case studies; however, they deal with issues that are international in nature (universal) and therefore transcend the UK context. Taken together, we demonstrate that heritage science as a discipline is capable of directly instigating or (re-)framing new areas or avenues of research, as well as enhancing and feeding into existing research questions, and has adapted and evolved along with emerging technologies and funding opportunities

Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study.

Transcatheter arterial chemoembolization (TACE) offers a survival benefit to patients with intermediate hepatocellular carcinoma (HCC). A widely accepted TACE regimen includes administration of doxorubicin-oil emulsion followed by gelatine sponge-conventional TACE. Recently, a drug-eluting bead (DC Bead) has been developed to enhance tumor drug delivery and reduce systemic availability. This randomized trial compares conventional TACE (cTACE) with TACE with DC Bead for the treatment of cirrhotic patients with HCC. Two hundred twelve patients with Child-Pugh A/B cirrhosis and large and/or multinodular, unresectable, N0, M0 HCCs were randomized to receive TACE with DC Bead loaded with doxorubicin or cTACE with doxorubicin. Randomization was stratified according to Child-Pugh status (A/B), performance status (ECOG 0/1), bilobar disease (yes/no), and prior curative treatment (yes/no). The primary endpoint was tumor response (EASL) at 6 months following independent, blinded review of MRI studies. The drug-eluting bead group showed higher rates of complete response, objective response, and disease control compared with the cTACE group (27% vs. 22%, 52% vs. 44%, and 63% vs. 52%, respectively). The hypothesis of superiority was not met (one-sided P = 0.11). However, patients with Child-Pugh B, ECOG 1, bilobar disease, and recurrent disease showed a significant increase in objective response (P = 0.038) compared to cTACE. DC Bead was associated with improved tolerability, with a significant reduction in serious liver toxicity (P &lt; 0.001) and a significantly lower rate of doxorubicin-related side effects (P = 0.0001). TACE with DC Bead and doxorubicin is safe and effective in the treatment of HCC and offers a benefit to patients with more advanced disease

Beyond Heritage Science: A Review

Heritage science is an established and thriving field of enquiry. Initially considered as inherently cross-disciplinary, encompassing both the needs of conservators and practitioners and the high-quality evidence produced by scientists, heritage science has, through its expansion in recent years, formed a discipline in its own right. Here, we examine how heritage science can, and to an extent has, moved beyond the straightforward scientific analysis of historical materials and artefacts through an exploration of heritage science’s interactions with four key themes: (i) historical and archival research, (ii) conservation practice, (iii) policy at governmental, organisational and institutional levels, and (iv) a view to how new technologies, such as machine learning and artificial intelligence, can shape the future of heritage science. Much of the review narrative is framed via the analysis of UK-based case studies; however, they deal with issues that are international in nature (universal) and therefore transcend the UK context. Taken together, we demonstrate that heritage science as a discipline is capable of directly instigating or (re-)framing new areas or avenues of research, as well as enhancing and feeding into existing research questions, and has adapted and evolved along with emerging technologies and funding opportunities

Beta Cell Hubs Dictate Pancreatic Islet Responses to Glucose

N.R.J. was supported by a Diabetes UK RW and JM Collins Studentship (12/0004601). J.B. was supported by a European Foundation for the Study of Diabetes (EFSD) Albert Renold Young Scientist Fellowship and a Studienstiftung des deutschen Volkes PhD Studentship. D.T. was supported by an Advanced Grant from the European Research Commission (268795). G.A.R. was supported by Wellcome Trust Senior Investigator (WT098424AIA) and Royal Society Wolfson Research Merit Awards, and by MRC Programme (MR/J0003042/1), Biological and Biotechnology Research Council (BB/J015873/1), and Diabetes UK Project (11/0004210) grants. G.A.R. and M.W. acknowledge COST Action TD1304 Zinc-Net. D.J.H. was supported by Diabetes UK R.D. Lawrence (12/0004431), EFSD/Novo Nordisk Rising Star and Birmingham Fellowships, a Wellcome Trust Institutional Support Award, and an MRC Project Grant (MR/N00275X/1) with G.A.R. D.J.H and G.A.R. were supported by Imperial Confidence in Concept (ICiC) Grants. J.F. was supported by an MRC Programme grant (MR/L02036X/1). L.P. provided human islets through collaboration with the Diabetes Research Institute, IRCCS San Raffaele Scientific Institute (Milan), within the European islet distribution program for basic research supported by JDRF (1-RSC-2014-90-I-X). P.M. and M.B. were supported by the Innovative Medicine Initiative Joint Undertaking under grant agreement no. 155005 (IMIDIA), resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution, and by the Italian Ministry of University and Research (PRIN 2010-2012). D.B. and E.B. provided human islets through the European Consortium for Islet Transplantation sponsored by JDRF (1-RSC-2014-100-I-X)