Bottlebrush polymers are interesting topologies that have become increasingly relevant in various applications including rheology modifiers, super-soft elastomers, photonic crystals, anti-fouling coatings, the in vivo delivery of therapeutic agents, and as promising substrates in lithographic printing. These macromolecules are comprised of numerous polymeric side-chains densely grafted to a polymer backbone. The densely grafted nature of bottlebrush polymers results in steric repulsion between neighboring polymer chains, forcing these macromolecules to adopt a chain-extended conformation. Although these remarkable macromolecules have a many different applications, the transformative potential of the bottlebrush polymer topology has not been realized because the synthesis of high molecular weight bottlebrush polymers is challenging. This dissertation focusses on improving the synthesis of these large macromolecules using the grafting-through strategy in the first section and the transfer-to strategy in the second section. For the first time the effect of anchor group chemistry—the configuration of atoms linking the polymer to a polymerizable norbornene—was studied on the kinetics of ring-opening metathesis polymerization (ROMP) of macromonomers (MMs) initiated by Grubbs 3rd generation catalyst. A variance in the rate of propagation of >4-fold between similar MMs with different anchor groups was observed. This phenomenon was conserved across all MMs tested, regardless of solvent, molecular weight (MW), or repeat unit identity. Experimental and computational studies indicated that the rate differences likely resulted from a combination of varying steric demands and electronic structure among the different anchor groups. This new insight will allow others to achieve high MM conversion and prepare pure, high MW bottlebrush polymers by ROMP grafting-through. The second section of this dissertation deals with a little studied bottlebrush synthesis technique called the transfer-to method. This method is a hybrid of the grafting-from and grafting-to approaches in which the growing polymer side chains detach from the backbone, propagate freely in solution, and then reattach to the backbone in a chain transfer step. Several parameters were investigated to determine optimal conditions for this process. This study provides for the first time a guide to use the transfer-to method to produce high purity bottlebrush polymers with controllable backbone and side chain length. / Ph. D.

Randomised, controlled trials are widely regarded as the gold standard by which the clinical effectiveness of healthcare products should be evaluated. Debate continues as to the value of this method of product assessment in a complex area such as wound care. Any method that is employed to define a product’s clinical value is, however, useless unless its ongoing effectiveness in a clinical area or with an individual patient is effectively monitored.

Yes / Objectives To test whether an occupation based lifestyle intervention can sustain and improve the mental wellbeing of adults aged 65 years or over compared to usual care, using an individually randomised controlled trial. Participants 288 independently living adults aged 65 years or over, with normal cognition were recruited from two UK sites between December 2011 and November 2015. Interventions Lifestyle Matters is a NICE recommended multi-component preventive intervention designed to improve the mental wellbeing of community living older people at risk of decline. It involves weekly group sessions over four months and one to one sessions. Main outcome measures The primary outcome was mental wellbeing at 6 months (mental health dimension of the SF-36).Secondary outcomes included physical health dimensions of the SF-36, extent of depression (PHQ-9), quality of life (EQ-5D) and loneliness(de Jong Gierveld Loneliness Scale),assessed at 6 and 24 months. Results Data on 262 (intervention =136; usual care =126) participants were analysed using intention to treat analysis. Mean SF-36 mental health scores at six months differed by 2·3 points (95 CI -1·3 to 5·9; P=0·209) after adjustments. Conclusions Analysis shows little evidence of clinical or cost effectiveness in the recruited population with analysis of the primary outcome revealing that the study participants were mentally well at baseline. The results pose questions regarding how preventive interventions to promote wellbeing in older adults can be effectively targeted in the absence of proactive mechanisms to identify those who at risk of decline. / Primary Care Research Network (PCRN) funding was accessed to support recruitment activity in GP surgeries in Sheffield and NISCHR provided support in North Wales.

Yes / This article recounts our experience of eliciting, cataloguing and prioritizing conjectured Context-Mechanism-Outcome configurations at the outset of a realist evaluation, to provide new insight into how Context-Mechanism-Outcome configurations can be generated and theorized. Our construction of Context-Mechanism-Outcome configurations centred on how, why and in what circumstances teamwork was impacted by robotic surgery, rather than how and why this technology improved surgical outcomes as intended. We found that, as well as offering resources, robotic surgery took away resources from the theatre team, by physically reconfiguring the operating theatre and redistributing the surgical task load, essentially changing the context in which teamwork was performed. We constructed Context-Mechanism-Outcome configurations that explain how teamwork mechanisms were both constrained by the contextual changes, and triggered in the new context through the use of informal strategies. We conclude by reflecting on our application of realist evaluation to understand the potential impacts of robotic surgery on teamwork.

This thesis describes the implementation of a Controlled English Commenting (CEC) system that aids a VHDL modeler in entering controlled English comments. The CEC system developed includes a graphical user interface (GUI). The interface permits a modeler to submit comments for insertion at user selected points in a text file containing the model. A submitted comment is analyzed for vocabulary and syntax, and is then inserted if it is controlled English. If it is not, the CEC system extracts all possible controlled English comments that can be formed from the original comment and presents them to the user for selection and entry into the model. The interface then queries the user to complete any residual portions of the original comment until the user is satisfied. Until the user becomes familiar with the constraints of the controlled language, significant interaction is needed, particularly on complex comments. Preliminary experiments indicate that users rapidly learn the language's constraints and the need for interactive help declines. / Master of Science

A general purpose computer model for the SCR is developed. The model, consisting of both a circuit analog and parameter estimation procedure, is uniformly applicable to popular computer aided design and analysis programs such as SPICE2 and SCEPTRE. The circuit analog is based on the intrinsic three PN junction structure of the SCR and is similar to Nienhus' model. The parameter estimation procedure requires only manufacturer's specification sheet quantities as a database. It employs some of the concepts developed by Hu for a SPICE2 SCR model. This uniform model, denoted the J³ SCR model, is shown to be a useful design aid through computer simulation of fault transients which may occur in a"Schwarz" converter. The transients simulated would not be observable without use of a highly accurate continuous topology non-linear SCR model such as is developed here. / Ph. D.

Yes / Biomaterials capable of precisely controlling the delivery of agrochemicals/biologics/drugs/fragrances have significant markets in the agriscience/healthcare industries. Here, we report the development of degradable electroactive polymers and their application for the controlled delivery of a clinically relevant drug (the anti-inflammatory dexamethasone phosphate, DMP). Electroactive copolymers composed of blocks of polycaprolactone (PCL) and naturally occurring electroactive pyrrole oligomers (e.g., bilirubin, biliverdin, and hemin) were prepared and solution-processed to produce films (optionally doped with DMP). A combination of in silico/in vitro/in vivo studies demonstrated the cytocompatibility of the polymers. The release of DMP in response to the application of an electrical stimulus was observed to be enhanced by ca. 10-30% relative to the passive release from nonstimulated samples in vitro. Such stimuli-responsive biomaterials have the potential for integration devices capable of delivering a variety of molecules for technical/medical applications. / This research was funded by a variety of sources, and the authors acknowledge the UK Engineering and Physical Sciences Research Council (EPSRC) National Productivity Investment Fund (NPIF) for a PhD Studentship for M.D.A. (Grant references: EP/R512564/1, 2065445), in support of the EPSRC First Grant for J.G.H. (Grant reference: EP/ R003823/1); the UK Royal Society for support of J.G.H. (Grant reference: RG160449); and the UK Royal Society and CONICET (Argentina) for supporting M.D.A., S.M., M.F.D., and J.G.H. (Grant Reference: A103355).

The purpose of this project was to fabricate biodegradable ophthalmic inserts for controlled delivery of pilocarpine and evaluate them by both in-vitro and in-vivo studies. Emphasis was placed on the use of an inexpensive material as a drug carrier and on the ease of fabrication of the device. Based on these criteria, absorbable gelatin was selected to fabricate a matrix system. Absorbable gelatin can be obtained by either thermal treatment or chemical crosslinking of gelatin. In the first part of this project, we fabricated an insert using Gelfoamᴿ, an absorbable gelatin sponge obtained by thermal treatment. A prolonged in-vitro release of pilocarpine from the device was achieved through pharmaceutical modification by embedding a retardant in the pores. The devices impregnated with polyethylene glycol monostearate (PMS) and cetyl esters wax (CEW) were found to be most effective. The in-vivo evaluation of the devices indicated that pharmaceutical modification of Gelfoamᴿ is an effective means of improving the biological activity of pilocarpine without altering the biodegradability of the biopolymer backbone. The CEW device produces a substantial improvement in drug bioavailability and an increase in the duration of biological effect over that from the two commercial formulations, the eyedrop and the gel. In the second part of the project, we fabricated absorbable gelatin inserts through chemical crosslinking of gelatin. The effect of selected fabrication variables on profiles of the in-vitro release of pilocarpine and the dynamic water uptake by the crosslinked gelatin devices was investigated. These results were further substantiated by the measurement of the degree of crosslinking of gelatin. The in-vivo study indicated that the modification of the structure of gelatin by crosslinking is another simple and effective way of improving bioavailability and extending the duration of effect of pilocarpine incorporated in the biopolymeric device. In addition, altering the degree of crosslinking of gelatin allows a variation of the biodegradation time of the polymer.

This thesis presents algorithms and tools for the automated design of RF LC CMOS voltage controlled oscillators (VCOs) with low phase noise given a set of specifications. The electromagnetic solver, ASITIC, combined with the circuit simulator, SpectreRF, allows optimization of the VCO circuit parameters and inductor layout. This approach gives a phase noise improvement of up to 20 dBc/Hz in the flicker noise region and up to 5 dBc/Hz in the thermal noise region. An optimization program for the computer-aided design of on-chip spiral inductors has also been developed. This program allows the designer to obtain the layout of an inductor with a required inductance value and maximal quality factor, thus enabling a reduction in the phase noise of the VCO being designed. The circuit simulator SPICE3 has been extended to handle phase noise analysis based on a non-linear perturbation analysis for oscillators. The implemented technique allows for an accurate simulation of phase noise due to devices described either by analytical or numerical models. With this extension, the automated design of RF LC oscillators can be performed within the SPICE3 framework. Furthermore, the technique is available in a public domain software and can be extended to other application domains. / Graduation date: 2004

Graduation date: 2003