The Fabrication and Evaluation of Silicon MOSFETs With 0.5 to 0.1 Micron Gate Lengths

This Thesis describes the application of high resolution electron beam lithography and dry etching techniques to the fabrication of experimental silicon MOSFETs with sub 0.5 micron gate lengths. HRN, a negative electron beam resist is investigated and demonstrated to have a resolution of 0.1 microns. Two alternative dry etching processes are reported for patterning 0.1 micron polysilicon gate electrodes using HRN masking. The first process uses chlorine plasma etching whilst the second process uses silicon tetrachloride reactive ion etching. MOSFET scaling theory is introduced and then used as a guide for designing the experimental sub 0.5 micron devices. A full processing sequence is developed for fabricating the experimental devices. This process includes self-aligned ion implantation and rapid thermal annealing steps, to form the shallow source and drain drift regions. Devices with gate oxide thicknesses of 150 angstroms and channel doping levels in the range from 3x10e16 to 1.2x10e18 atoms/cm3 have been implemented. Electrical measurements are reported for the range of devices which have been fabricated. Results are included for MOSFETs with gate lengths of only 0.11 microns. At a channel doping level of 1.2x10e18 atoms/cm3 the 0.11 micron devices exhibit a transconductance of 70 mS/mm. A slightly modified process is described which has been used to implement a second set of sub 0.5 micron devices together with 19 stage unloaded n-MOS ring oscillator circuits. Preliminary high speed measurements are reported for these circuits which have gate lengths of 0.23 microns. Minimum stage delays of 80 psec have been achieved with a corresponding power-delay product of 210 fJ

Increasing Innovation-driven Entrepreneurship in Scotland through Collective Impact

In Scotland we have an opportunity to redefine ourselves as a nation of dynamic and high achieving entrepreneurs, targeting global market opportunities, using innovation as a key driver of sales growth, making a significant contribution to the creation of employment and wealt

Minocycline 200 mg or 400 mg versus placebo for mild Alzheimer's disease: the MADE Phase II, three-arm RCT

Background: Minocycline is an anti-inflammatory drug and protects against the toxic effects of β-amyloid in vitro and in animal models of Alzheimer’s disease. To the best of our knowledge, no randomised placebo-controlled clinical trials in patients with Alzheimer’s disease looking at the efficacy and tolerability of minocycline have been carried out. Objectives: The trial investigated whether or not minocycline was superior to placebo in slowing down the rate of decline in cognitive and functional ability over 2 years. The safety and tolerability of minocycline were also assessed. Design: A Phase II, three-arm, randomised, double-blind, multicentre trial with a semifactorial design. Participants continued on trial treatment for up to 24 months. Setting: Patients were identified from memory services, both within the 32 participating NHS trusts and within the network of memory services supported by the Dementias and Neurodegenerative Diseases Research Network (also known as DeNDRoN). Participants: Patients with standardised Mini Mental State Examination scores of > 23 points and with Alzheimer’s disease assessed by the National Institute on Aging–Alzheimer’s Association’s criteria were identified from memory services. Intervention: Patients with mild Alzheimer’s disease were randomly allocated 1 : 1 : 1 to receive one of three treatments: arm 1 – 400 mg per day of minocycline; arm 2 – 200 mg per day of minocycline; or arm 3 – placebo. Patients continued treatment for 24 months. Participants, investigators and outcome assessors were blind to treatment allocation. Main outcome measures: Primary outcome measures were decline in standardised Mini Mental State Examination and Bristol Activities of Daily Living Scale scores of combined minocycline treatment arms versus placebo, as analysed by intention-to-treat repeated measures regression. Results: Between 23 May 2014 and 14 April 2016, 554 participants were randomised. Of the 544 eligible participants, the mean age was 74.3 years and the average standardised Mini Mental State Examination score was 26.4 points. A total of 252 serious adverse events were reported, with the most common categories being neuropsychiatric and cardiocirculatory. Significantly fewer participants completed treatment with 400 mg of minocycline [29% (53/184)] than 200 mg [62% (112/181)] or placebo [64% (114/179)] (p < 0.0001), mainly because of gastrointestinal symptoms (p = 0.0008), dermatological side effects (p = 0.02) and dizziness (p = 0.01). Assessment rates were also lower in the 400-mg treatment arm: 68% (119 of 174 expected) for standardised Mini Mental State Examination scores at 24 months, compared with 82% (144/176) for the 200-mg treatment arm and 84% (140/167) for the placebo arm. Decline in standardised Mini Mental State Examination scores over the 24-month study period in the combined minocycline arms was similar to that in the placebo arm (4.1- vs. 4.3-point reduction; p = 0.9), as was the decline in the 400- and 200-mg treatment arms (3.3 vs. 4.7 points; p = 0.08). Likewise, worsening of Bristol Activities of Daily Living Scale scores over 24 months was similar in all trial arms (5.7, 6.6 and 6.2 points in the 400-mg treatment arm, 200-mg treatment arm and placebo arm, respectively; a p-value of 0.57 for minocycline vs. placebo and a p-value of 0.77 for 400 vs. 200 mg of minocycline). Results were similar in different patient subgroups and in sensitivity analyses adjusting for missing data. Limitations: Potential limitations of the study include that biomarkers were not used to confirm the diagnosis of Alzheimer’s disease, as these and apolipoprotein E (APOE) genotyping are not routinely available within the NHS. Compliance was also worse than expected and differential follow-up rates were observed, with fewer assessments obtained for the 400-mg treatment arm than for the 200-mg treatment and placebo arms. Conclusions: Minocycline does not delay the progress of cognitive or functional impairment in people with mild Alzheimer’s disease over a 2-year period. Minocycline at a dose of 400 mg is poorly tolerated in this population. Future work: The Minocycline in mild Alzheimer’s DiseasE (MADE) study provides a framework for a streamlined trial design that can be usefully applied to test other disease-modifying therapies

Whole home exercise intervention for depression in older care home residents (the OPERA study) : a process evaluation

Background: The ‘Older People’s Exercise intervention in Residential and nursing Accommodation’ (OPERA) cluster randomised trial evaluated the impact of training for care home staff together with twice-weekly, physiotherapist-led exercise classes on depressive symptoms in care home residents, but found no effect. We report a process evaluation exploring potential explanations for the lack of effect. Methods: The OPERA trial included over 1,000 residents in 78 care homes in the UK. We used a mixed methods approach including quantitative data collected from all homes. In eight case study homes, we carried out repeated periods of observation and interviews with residents, care staff and managers. At the end of the intervention, we held focus groups with OPERA research staff. We reported our first findings before the trial outcome was known. Results: Homes showed large variations in activity at baseline and throughout the trial. Overall attendance rate at the group exercise sessions was low (50%). We considered two issues that might explain the negative outcome: whether the intervention changed the culture of the homes, and whether the residents engaged with the intervention. We found low levels of staff training, few home champions for the intervention and a culture that prioritised protecting residents from harm over encouraging activity. The trial team delivered 3,191 exercise groups but only 36% of participants attended at least 1 group per week and depressed residents attended significantly fewer groups than those who were not depressed. Residents were very frail and therefore most groups only included seated exercises. Conclusions: The intervention did not change the culture of the homes and, in the case study homes, activity levels did not change outside the exercise groups. Residents did not engage in the exercise groups at a sufficient level, and this was particularly true for those with depressive symptoms at baseline. The physical and mental frailty of care home residents may make it impossible to deliver a sufficiently intense exercise intervention to impact on depressive symptoms

Inter-rater reliability of data elements from a prototype of the Paul Coverdell National Acute Stroke Registry

<p>Abstract</p> <p>Background</p> <p>The Paul Coverdell National Acute Stroke Registry (PCNASR) is a U.S. based national registry designed to monitor and improve the quality of acute stroke care delivered by hospitals. The registry monitors care through specific performance measures, the accuracy of which depends in part on the reliability of the individual data elements used to construct them. This study describes the inter-rater reliability of data elements collected in Michigan's state-based prototype of the PCNASR.</p> <p>Methods</p> <p>Over a 6-month period, 15 hospitals participating in the Michigan PCNASR prototype submitted data on 2566 acute stroke admissions. Trained hospital staff prospectively identified acute stroke admissions, abstracted chart information, and submitted data to the registry. At each hospital 8 randomly selected cases were re-abstracted by an experienced research nurse. Inter-rater reliability was estimated by the kappa statistic for nominal variables, and intraclass correlation coefficient (ICC) for ordinal and continuous variables. Factors that can negatively impact the kappa statistic (i.e., trait prevalence and rater bias) were also evaluated.</p> <p>Results</p> <p>A total of 104 charts were available for re-abstraction. Excellent reliability (kappa or ICC > 0.75) was observed for many registry variables including age, gender, black race, hemorrhagic stroke, discharge medications, and modified Rankin Score. Agreement was at least moderate (i.e., 0.75 > kappa ≥; 0.40) for ischemic stroke, TIA, white race, non-ambulance arrival, hospital transfer and direct admit. However, several variables had poor reliability (kappa < 0.40) including stroke onset time, stroke team consultation, time of initial brain imaging, and discharge destination. There were marked systematic differences between hospital abstractors and the audit abstractor (i.e., rater bias) for many of the data elements recorded in the emergency department.</p> <p>Conclusion</p> <p>The excellent reliability of many of the data elements supports the use of the PCNASR to monitor and improve care. However, the poor reliability for several variables, particularly time-related events in the emergency department, indicates the need for concerted efforts to improve the quality of data collection. Specific recommendations include improvements to data definitions, abstractor training, and the development of ED-based real-time data collection systems.</p

COMAP Early Science: II. Pathfinder Instrument

Line intensity mapping (LIM) is a new technique for tracing the global properties of galaxies over cosmic time. Detection of the very faint signals from redshifted carbon monoxide (CO), a tracer of star formation, pushes the limits of what is feasible with a total-power instrument. The CO Mapping Project (COMAP) Pathfinder is a first-generation instrument aiming to prove the concept and develop the technology for future experiments, as well as delivering early science products. With 19 receiver channels in a hexagonal focal plane arrangement on a 10.4 m antenna, and an instantaneous 26-34 GHz frequency range with 2 MHz resolution, it is ideally suited to measuring CO($J$=1-0) from $z\sim3$. In this paper we discuss strategies for designing and building the Pathfinder and the challenges that were encountered. The design of the instrument prioritized LIM requirements over those of ancillary science. After a couple of years of operation, the instrument is well understood, and the first year of data is already yielding useful science results. Experience with this Pathfinder will drive the design of the next generations of experiments.Comment: Paper 2 of 7 in series. 27 pages, 28 figures, submitted to Ap

COMAP Early Science: I. Overview

The CO Mapping Array Project (COMAP) aims to use line intensity mapping of carbon monoxide (CO) to trace the distribution and global properties of galaxies over cosmic time, back to the Epoch of Reionization (EoR). To validate the technologies and techniques needed for this goal, a Pathfinder instrument has been constructed and fielded. Sensitive to CO(1-0) emission from $z=2.4$-$3.4$ and a fainter contribution from CO(2-1) at $z=6$-8, the Pathfinder is surveying $12$ deg$^2$ in a 5-year observing campaign to detect the CO signal from $z\sim3$. Using data from the first 13 months of observing, we estimate $P_\mathrm{CO}(k) = -2.7 \pm 1.7 \times 10^4\mu\mathrm{K}^2 \mathrm{Mpc}^3$ on scales $k=0.051-0.62 \mathrm{Mpc}^{-1}$ - the first direct 3D constraint on the clustering component of the CO(1-0) power spectrum. Based on these observations alone, we obtain a constraint on the amplitude of the clustering component (the squared mean CO line temperature-bias product) of $\langle Tb\rangle^2<49$ $\mu$K$^2$ - nearly an order-of-magnitude improvement on the previous best measurement. These constraints allow us to rule out two models from the literature. We forecast a detection of the power spectrum after 5 years with signal-to-noise ratio (S/N) 9-17. Cross-correlation with an overlapping galaxy survey will yield a detection of the CO-galaxy power spectrum with S/N of 19. We are also conducting a 30 GHz survey of the Galactic plane and present a preliminary map. Looking to the future of COMAP, we examine the prospects for future phases of the experiment to detect and characterize the CO signal from the EoR.Comment: Paper 1 of 7 in series. 18 pages, 16 figures, submitted to Ap

The Cosmic Background Imager 2

We describe an upgrade to the Cosmic Background Imager instrument to increase its surface brightness sensitivity at small angular scales. The upgrade consisted of replacing the 13 0.9-m antennas with 1.4-m antennas incorporating a novel combination of design features, which provided excellent sidelobe and spillover performance for low manufacturing cost. Off-the-shelf spun primaries were used, and the secondary mirrors were oversized and shaped relative to a standard Cassegrain in order to provide an optimum compromise between aperture efficiency and low spillover lobes. Low-order distortions in the primary mirrors were compensated for by custom machining of the secondary mirrors. The secondaries were supported on a transparent dielectric foam cone to minimize scattering. The antennas were tested in the complete instrument, and the beam shape and spillover noise contributions were as expected. We demonstrate the performance of the telescope and the intercalibration with the previous system using observations of the Sunyaev–Zel’dovich effect in the cluster Abell 1689. The enhanced instrument has been used to study the cosmic microwave background, the Sunyaev–Zel’dovich effect and diffuse Galactic emission

The nature and function of talent identification in junior-elite football in English category one academies

The focus of this study was to examine the nature and function of talent identification in category one football academies in the UK. Data were collected from three participant groups: heads of recruitment (n = 12), recruitment staff (n = 18) and scouts (n = 7). Data were collected by means of semi-structured interviews, conducted either face-to-face or via Skype®. Four themes emerged from the data: (1) league structures in junior grassroots football; (2) reflective practice; (3) looking at the whole player; and (4) luck. The paper concludes by suggesting that there are issues that need to be considered by the football association, county football associations and clubs. Those issues include the organization of leagues in junior football, the education of scouts and recruitment staff around reflective practice and understanding how to identify psycho-social attributes whilst identifying talent

Clinical outcomes and response to treatment of patients receiving topical treatments for pyoderma gangrenosum: a prospective cohort study

Background: pyoderma gangrenosum (PG) is an uncommon dermatosis with a limited evidence base for treatment. Objective: to estimate the effectiveness of topical therapies in the treatment of PG. Methods: prospective cohort study of UK secondary care patients with a clinical diagnosis of PG suitable for topical treatment (recruited July 2009 to June 2012). Participants received topical therapy following normal clinical practice (mainly Class I-III topical corticosteroids, tacrolimus 0.03% or 0.1%). Primary outcome: speed of healing at 6 weeks. Secondary outcomes: proportion healed by 6 months; time to healing; global assessment; inflammation; pain; quality-of-life; treatment failure and recurrence. Results: Sixty-six patients (22 to 85 years) were enrolled. Clobetasol propionate 0.05% was the most commonly prescribed therapy. Overall, 28/66 (43.8%) of ulcers healed by 6 months. Median time-to-healing was 145 days (95% CI: 96 days, ∞). Initial ulcer size was a significant predictor of time-to-healing (hazard ratio 0.94 (0.88;80 1.00); p = 0.043). Four patients (15%) had a recurrence. Limitations: No randomised comparator Conclusion: Topical therapy is potentially an effective first-line treatment for PG that avoids possible side effects associated with systemic therapy. It remains unclear whether more severe disease will respond adequately to topical therapy alone