A new transfer function analyser

This thesis investigates the concept and design of a portable on-line transfer function analyser (TFA). It is eminently suitable for the identification of plants and other controlled feedback systems in which normal operating records are available. A point by point representation in the frequency domain, requiring a maximum of three records, allows Nyquist plots to be carried out, either visually or by plotter facilities. The basic theory relies heavily upon statistical concepts whereby, least squares estimates of the transfer function are obtained from a combination of heterodyning, exact filtering and adaptive loops. The resultant output, on both channels (real and imaginary), is the culmination of the solution to two linear differential equations with stochastic coefficients, so mechanised when the adaptive loops reach a stable equilibrium. Throughout, emphasis is placed upon the electronics combining the best of analog and digital techniques, in order that six parallel paths may be analysed in similar mode. This is especially true of the heterodyning and filtering operations. Practical shortcomings of the instrument noted by comparing estimates with those from the best currently available commercial apparatus, operating on deterministic signals. Examples of a feedback loop, subjected to both deterministic and random stimuli, with and without the presence of extraneous noise sources, are used to illustrate the ease and simplicity by which the instrument can be used in place of complex computing schemes, which tend, in consequence, to be solely of local academic interest. The practical features of the thesis have led to the submission of four papers to the technical press. Two of them deal, exclusively, with a capacitor ratio commutated filter – not apparently described in publications to date - which is also the subject of a proposed patent application in conjunction with NRDC. It is intended, in the near future, to submit the complete instrument as the basis for a second patent proposal

Association between benzodiazepine coprescription and mortality in people on opioid replacement therapy:a population-based cohort study

Objective To investigate the association between opioid replacement therapy (ORT) and benzodiazepine (BZD) coprescription and all-cause mortality compared with the prescription of ORT alone.Design Population-based cohort study.Setting Scotland, UK.Participants Participants were people prescribed ORT between January 2010 and end of December 2020 aged 18 years or above.Main outcome measures All-cause mortality, drug-related deaths and non-drug related deaths.Secondary outcome ORT continuous treatment duration.Analysis Cox regression with time-varying covariates.Results During follow-up, 5776 of 46 899 participants died: 1398 while on coprescription and 4378 while on ORT only. The mortality per 100 person years was 3.11 during coprescription and 2.34 on ORT only. The adjusted HR for all-cause mortality was 1.17 (1.10 to 1.24). The adjusted HR for drug-related death was 1.14 (95% CI, 1.04 to 1.24) and the hazard for death not classified as drug-related was 1.19 (95% CI, 1.09 to 1.30).Conclusion Coprescription of BZDs in ORT was associated with an increased risk of all-cause mortality, although with a small effect size than the international literature. Coprescribing was also associated with longer retention in treatment. Risk from BZD coprescription needs to be balanced against the risk from illicit BZDs and unplanned treatment discontinuation. A randomised controlled trial is urgently needed to provide a clear clinical direction.Trial registration number NCT04622995.</p

Counter and Complicit Masculine Discourse Among Men’s Shed Members

Men’s Sheds is a growing international movement aimed at providing men with places and activities that facilitate social connectedness. Despite Men’s Sheds’ focus on males, little attention has been paid to masculinities within the specific context of these settings. The current study used a gender relations framework to explore the ways in which attendees discussed Men’s Sheds, with particular attention to discussions that were complicit and counter to traditional, hegemonic views of masculinity, and diverse positions in between these binaries. The data consisted of transcripts and field notes from four focus groups comprised of mostly older, White, retired male members of a Canadian shed (N = 22). The analysis revealed three overall themes: (1) focus on work, (2) independence, and (3) need for male-focused spaces. These themes and associated subthemes suggest that shed members ascribe to dominant masculine values and ideals, but also support more fluid and flexible views of masculinity. Implications are discussed for how working with an array of masculinities within the Men’s Sheds movement will be helpful with respect to their future growth in Canada and internationally

Association between benzodiazepine coprescription and mortality in people on opioid replacement therapy: a population-based cohort study

Objective To investigate the association between opioid replacement therapy (ORT) and benzodiazepine (BZD) coprescription and all-cause mortality compared with the prescription of ORT alone. Design Population-based cohort study. Setting Scotland, UK. Participants Participants were people prescribed ORT between January 2010 and end of December 2020 aged 18 years or above. Main outcome measures All-cause mortality, drug-related deaths and non-drug related deaths. Secondary outcome ORT continuous treatment duration. Analysis Cox regression with time-varying covariates. Results During follow-up, 5776 of 46 899 participants died: 1398 while on coprescription and 4378 while on ORT only. The mortality per 100 person years was 3.11 during coprescription and 2.34 on ORT only. The adjusted HR for all-cause mortality was 1.17 (1.10 to 1.24). The adjusted HR for drug-related death was 1.14 (95% CI, 1.04 to 1.24) and the hazard for death not classified as drug-related was 1.19 (95% CI, 1.09 to 1.30). Conclusion Coprescription of BZDs in ORT was associated with an increased risk of all-cause mortality, although with a small effect size than the international literature. Coprescribing was also associated with longer retention in treatment. Risk from BZD coprescription needs to be balanced against the risk from illicit BZDs and unplanned treatment discontinuation. A randomised controlled trial is urgently needed to provide a clear clinical direction. Trial registration number NCT0462299

Ethnic and social inequalities in COVID-19 outcomes in Scotland:protocol for early pandemic evaluation and enhanced surveillance of COVID-19 (EAVE II)

Introduction: Evidence from previous pandemics, and the current COVID-19 pandemic, has found that risk of infection/severity of disease is disproportionately higher for ethnic minority groups, and those in lower socioeconomic positions. It is imperative that interventions to prevent the spread of COVID-19 are targeted towards high-risk populations. We will investigate the associations between social characteristics (such as ethnicity, occupation and socioeconomic position) and COVID-19 outcomes and the extent to which characteristics/risk factors might explain observed relationships in Scotland. The primary objective of this study is to describe the epidemiology of COVID-19 by social factors. Secondary objectives are to (1) examine receipt of treatment and prevention of COVID-19 by social factors; (2) quantify ethnic/social differences in adverse COVID-19 outcomes; (3) explore potential mediators of relationships between social factors and SARS-CoV-2 infection/COVID-19 prognosis; (4) examine whether occupational COVID-19 differences differ by other social factors and (5) assess quality of ethnicity coding within National Health Service datasets. Methods and analysis: We will use a national cohort comprising the adult population of Scotland who completed the 2011 Census and were living in Scotland on 31 March 2020 (~4.3 million people). Census data will be linked to the Early Assessment of Vaccine and Anti-Viral Effectiveness II cohort consisting of primary/secondary care, laboratory data and death records. Sensitivity/specificity and positive/negative predictive values will be used to assess coding quality of ethnicity. Descriptive statistics will be used to examine differences in treatment and prevention of COVID-19. Poisson/Cox regression analyses and mediation techniques will examine ethnic and social differences, and drivers of inequalities in COVID-19. Effect modification (on additive and multiplicative scales) between key variables (such as ethnicity and occupation) will be assessed. Ethics and dissemination: Ethical approval was obtained from the National Research Ethics Committee, South East Scotland 02. We will present findings of this study at international conferences, in peer-reviewed journals and to policy-makers

Impact of COVID-19 lockdown on the incidence and mortality of acute exacerbations of chronic obstructive pulmonary disease: national interrupted time series analyses for Scotland and Wales

The COVID-19 pandemic and ensuing national lockdowns have dramatically changed the healthcare landscape. The pandemic’s impact on people with chronic obstructive pulmonary disease (COPD) remains poorly understood. We hypothesised that the UK-wide lockdown restrictions were associated with reductions in severe COPD exacerbations. We provide the first national level analyses of the impact of the COVID-19 pandemic and first lockdown on severe COPD exacerbations resulting in emergency hospital admissions and/or leading to death as well as those recorded in primary care or emergency departments

Interim findings from first-dose mass COVID-19 vaccination roll-out and COVID-19 hospital admissions in Scotland: a national prospective cohort study

EAVE II is funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE—The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. Additional support has been provided through Public Health Scotland and the Scottish Government's director-general of Health and Social Care. FDRH acknowledges part support from the National Institutes of Health Research (NIHR) School for Primary Care Research, the NIHR Collaboration for Leadership in Applied Health Research and Care Oxford, and the NIHR Oxford Biomedical Research Centre. SVK acknowledges funding from an NRS Senior Clinical Fellowship (SCAF/15/02), the Medical Research Council (MC_UU_00022/2), and Scottish Government Chief Scientist Office (SPHSU13).Background The BNT162b2 mRNA (Pfizer–BioNTech) and ChAdOx1 nCoV-19 (Oxford–AstraZeneca) COVID-19 vaccines have shown high efficacy against disease in phase 3 clinical trials and are now being used in national vaccination programmes in the UK and several other countries. Studying the real-world effects of these vaccines is an urgent requirement. The aim of our study was to investigate the association between the mass roll-out of the first doses of these COVID-19 vaccines and hospital admissions for COVID-19.  Methods We did a prospective cohort study using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19—EAVE II—database comprising linked vaccination, primary care, real-time reverse transcription-PCR testing, and hospital admission patient records for 5·4 million people in Scotland (about 99% of the population) registered at 940 general practices. Individuals who had previously tested positive were excluded from the analysis. A time-dependent Cox model and Poisson regression models with inverse propensity weights were fitted to estimate effectiveness against COVID-19 hospital admission (defined as 1–adjusted rate ratio) following the first dose of vaccine.  Findings Between Dec 8, 2020, and Feb 22, 2021, a total of 1 331 993 people were vaccinated over the study period. The mean age of those vaccinated was 65·0 years (SD 16·2). The first dose of the BNT162b2 mRNA vaccine was associated with a vaccine effect of 91% (95% CI 85–94) for reduced COVID-19 hospital admission at 28–34 days post-vaccination. Vaccine effect at the same time interval for the ChAdOx1 vaccine was 88% (95% CI 75–94). Results of combined vaccine effects against hospital admission due to COVID-19 were similar when restricting the analysis to those aged 80 years and older (83%, 95% CI 72–89 at 28–34 days post-vaccination).  Interpretation Mass roll-out of the first doses of the BNT162b2 mRNA and ChAdOx1 vaccines was associated with substantial reductions in the risk of hospital admission due to COVID-19 in Scotland. There remains the possibility that some of the observed effects might have been due to residual confounding.  Funding UK Research and Innovation (Medical Research Council), Research and Innovation Industrial Strategy Challenge Fund, Health Data Research UK.proofPeer reviewe

First dose ChAdOx1 and BNT162b2 COVID-19 vaccinations and cerebral venous sinus thrombosis : a pooled self-controlled case series study of 11.6 million individuals in England, Scotland, and Wales

Funding: This research is part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant ref MC_PC_20029, AS). EAVE II is funded by the Medical Research Council (https://mrc.ukri.org/) (UKRI MC_PC 19075, AS) with the support of BREATHE, The Health Data Research Hub for Respiratory Health (MC_PC_19004, AS), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. This work was supported by the Con-COV team funded by the Medical Research Council (grant number: MR/V028367/1, RL). This work was supported by Health Data Research UK, which receives its funding from HDR UK Ltd (HDR-9006, RL) funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation (BHF) and the Wellcome Trust. This work was supported by the ADR Wales programme of work (https://www.adruk.org/). ADR Wales is part of the Economic and Social Research Council (part of UK Research and Innovation) funded ADR UK (grant ES/S007393/1, RL). SVK acknowledges funding from NHS Research Scotland Senior Clinical Fellowship (SCAF/15/02, SVK), the MRC (MC_UU_00022/2, SVK), and the Scottish Government Chief Scientist Office (SPHSU17, SVK).Background : Several countries restricted the administration of ChAdOx1 to older age groups in 2021 over safety concerns following case reports and observed versus expected analyses suggesting a possible association with cerebral venous sinus thrombosis (CVST). Large datasets are required to precisely estimate the association between Coronavirus Disease 2019 (COVID-19) vaccination and CVST due to the extreme rarity of this event. We aimed to accomplish this by combining national data from England, Scotland, and Wales. Methods and findings : We created data platforms consisting of linked primary care, secondary care, mortality, and virological testing data in each of England, Scotland, and Wales, with a combined cohort of 11,637,157 people and 6,808,293 person years of follow-up. The cohort start date was December 8, 2020, and the end date was June 30, 2021. The outcome measure we examined was incident CVST events recorded in either primary or secondary care records. We carried out a self-controlled case series (SCCS) analysis of this outcome following first dose vaccination with ChAdOx1 and BNT162b2. The observation period consisted of an initial 90-day reference period, followed by a 2-week prerisk period directly prior to vaccination, and a 4-week risk period following vaccination. Counts of CVST cases from each country were tallied, then expanded into a full dataset with 1 row for each individual and observation time period. There was a combined total of 201 incident CVST events in the cohorts (29.5 per million person years). There were 81 CVST events in the observation period among those who a received first dose of ChAdOx1 (approximately 16.34 per million doses) and 40 for those who received a first dose of BNT162b2 (approximately 12.60 per million doses). We fitted conditional Poisson models to estimate incidence rate ratios (IRRs). Vaccination with ChAdOx1 was associated with an elevated risk of incident CVST events in the 28 days following vaccination, IRR = 1.93 (95% confidence interval (CI) 1.20 to 3.11). We did not find an association between BNT162b2 and CVST in the 28 days following vaccination, IRR = 0.78 (95% CI 0.34 to 1.77). Our study had some limitations. The SCCS study design implicitly controls for variables that are constant over the observation period, but also assumes that outcome events are independent of exposure. This assumption may not be satisfied in the case of CVST, firstly because it is a serious adverse event, and secondly because the vaccination programme in the United Kingdom prioritised the clinically extremely vulnerable and those with underlying health conditions, which may have caused a selection effect for individuals more prone to CVST. Although we pooled data from several large datasets, there was still a low number of events, which may have caused imprecision in our estimates. Conclusions : In this study, we observed a small elevated risk of CVST events following vaccination with ChAdOx1, but not BNT162b2. Our analysis pooled information from large datasets from England, Scotland, and Wales. This evidence may be useful in risk–benefit analyses of vaccine policies and in providing quantification of risks associated with vaccination to the general public.Publisher PDFPeer reviewe

Predictors of incomplete COVID-19 vaccine schedule among adults in Scotland: two retrospective cohort analyses of the primary schedule and third dose

Background: Vaccination continues to be the key public health measure for preventing severe COVID-19 outcomes. Certain groups may be at higher risk of incomplete vaccine schedule, which may leave them vulnerable to COVID-19 hospitalisation and death. Aim: To identify the sociodemographic and clinical predictors for not receiving a scheduled COVID-19 vaccine after previously receiving one. Methods: We conducted two retrospective cohort studies with ≥3.7 million adults aged ≥18 years in Scotland. Multivariable logistic regression was used to estimate adjusted odds ratios (aOR) of not receiving a second, and separately a third dose between December 2020 and May 2022. Independent variables included sociodemographic and clinical factors. Results: Of 3,826,797 people in the study population who received one dose, 3,732,596 (97.5%) received two doses, and 3,263,153 (86.5%) received all doses available during the study period. The most strongly associated predictors for not receiving the second dose were: being aged 18–29 (reference: 50–59 years; aOR:4.26; 95% confidence interval (CI):4.14–4.37); hospitalisation due to a potential vaccine related adverse event of special interest (AESI) (reference: not having a potential AESI, aOR:3.78; 95%CI: 3.29–4.35); and living in the most deprived quintile (reference: least deprived quintile, aOR:3.24; 95%CI: 3.16–3.32). The most strongly associated predictors for not receiving the third dose were: being 18–29 (reference: 50–59 years aOR:4.44; 95%CI: 4.38–4.49), living in the most deprived quintile (reference: least deprived quintile aOR:2.56; 95%CI: 2.53–2.59), and Black, Caribbean, or African ethnicity (reference: White ethnicity aOR:2.38; 95%CI: 2.30–2.46). Pregnancy, previous vaccination with mRNA-1273, smoking history, individual and household severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity, and having an unvaccinated adult in the household were also associated with incomplete vaccine schedule. Conclusion: We observed several risk factors that predict incomplete COVID-19 vaccination schedule. Vaccination programmes must take immediate action to ensure maximum uptake, particularly for populations vulnerable to severe COVID-19 outcomes