Interpretable and fast dimension reduction of multivariate data

The main objective of this thesis is to propose new techniques to simplify the interpretation of newly formed 'variables' or components, while reducing the dimensionality of multivariate data. Most attention is given to the interpretation of principal components, although one chapter is devoted to that of factors in factor analysis. Sparse principal components are proposed, in which some of the component loadings are made exactly zero. One approach is to make use of the idea of correlation biplots, where orthogonal matrix of sparse loadings is obtained from computing the biplot factors of the product of principal component loading matrix and functions of their variances. Other approaches in volve clustering of variables as a pre-processings tep, so that sparse components are computed from the data or correlation matrix of each cluster. New clustering techniques are proposed for this purpose. In addition, a penalized varimax approach is proposed for simplifying the interpretation of factors in factor analysis, especially for factor solutions with considerably different sum of squares. This is done by adding a penalty term to the ordinary varimax criterion. Data sets of varying sizes, both synthetic and real, are used to illustrate the proposed methods, and the results are compared with those of existing ones. In the case of principal component analysis, the resulting sparse components are found to be more interpretable (sparser) and explain higher cumulative percentage of adjusted variance compared to their counterparts from other techniques. The penalized varimax approach contributes in finding a factor solution with simple structures which are not revealed by the standard varimax solution. The proposed methods are very simple to understand and involve fast algorithms compared to some of the existing methods. They contribute much to the interpretation of components in a reduced dimension while dealing with dimensionality reduction of multivariate data

A time-varying shared frailty model with application to infectious diseases

We propose a new parametric time-varying shared frailty model to represent changes over time in population heterogeneity, for use with bivariate current status data. The model uses a power transformation of a time-invariant frailty U, and is particularly convenient when U is a member of the generalized gamma family. This model avoids some shortcomings of a previously suggested time-varying frailty model, notably time-dependent support. We describe some key properties of the model, including its relative frailty variance function in different settings and how the model can be fitted to data. We describe several applications to shared frailty modeling of bivariate current status data on infectious diseases, in which the frailty represents age-dependent heterogeneity in contact rates or susceptibility to infection

Male seminal parameters are not associated with Leydig cell functional capacity in men

Background: Insulin-like peptide 3 (INSL3) is a constitutive, secreted peptide produced in the male uniquely by the Leydig cells of the testes. It is a biomarker for Leydig cell functional capacity, which is a measure of the numbers and differentiation status of these steroidogenic cells and lacks the biological and technical variance of the steroid testosterone. This retrospective study was carried out to examine the relationship between seminal parameters and the Leydig cell compartment, and secondarily to assess other factors responsible for determining Leydig cell functional capacity. Methods: INSL3 was assessed together with seminal, anthropometric, and hormonal parameters in a Swedish cohort of 18-year-old men, representing the average population, and in a smaller, more heterogeneous cohort of men visiting an Australian infertility clinic. Results and discussion: Average INSL3 concentration at 18years is greater than that reported at younger or older ages and indicated a large 10-fold variation. In neither cohort was there a relationship between INSL3 concentration and any semen parameter. For the larger, more uniform Swedish cohort of young men, there was a significant negative relationship between INSL3 and BMI, supporting the idea that adult Leydig cell functional capacity may be established during puberty. In both cohorts, there was a significant relationship between INSL3 and FSH, but not LH concentration. No relationship was found between INSL3 and androgen receptor trinucleotide repeat polymorphisms, reinforcing the notion that Leydig cell functional capacity is unlikely to be determined by androgen influence alone. Nor did INSL3 correlate with the T/LH ratio, an alternative measure of Leydig cell functional capacity, supporting the view that these are independent measures of Leydig cell function

Paediatric traumatic cardiac arrest: A Delphi study to establish consensus on definition and management

Aims Paediatric traumatic cardiac arrest (TCA) is associated with low survival and poor outcomes. The mechanisms that underlie TCA are different from medical cardiac arrest; the approach to treatment of TCA may therefore also need to differ to optimise outcomes. The aim of this study was to explore the opinion of subject matter experts regarding the diagnosis and treatment of paediatric TCA, and to reach consensus on how best to manage this group of patients.Methods An online Delphi study was conducted over three rounds, with the aim of achieving consensus (defined as 70% agreement) on statements related to the diagnosis and management of paediatric TCA. Participants were invited from paediatric and adult emergency medicine, paediatric anaesthetics, paediatric ICU and paediatric surgery, as well as Paediatric Major Trauma Centre leads and representatives from the Resuscitation Council UK. Statements were informed by literature reviews and were based on elements of APLS resuscitation algorithms as well as some concepts used in the management of adult TCA; they ranged from confirmation of cardiac arrest to the indications for thoracotomy.Results 73 experts completed all three rounds between June and November 2016. Consensus was reached on 14 statements regarding the diagnosis and management of paediatric TCA; oxygenation and ventilatory support, along with rapid volume replacement with warmed blood, improve survival. The duration of cardiac arrestand the lack of a response to intervention, along with cardiac standstill on ultrasound, help to guide the decision to terminate resuscitation.Conclusion This study has given a consensus-based framework to guide protocol development in the management of paediatric TCA, though further work is required in other key areas including its acceptability to clinicians

Detection of Infectious Disease Outbreaks From Laboratory Data With Reporting Delays

Many statistical surveillance systems for the timely detection of outbreaks of infectious disease operate on laboratory data. Such data typically incur reporting delays between the time at which a specimen is collected for diagnostic purposes, and the time at which the results of the laboratory analysis become available. Statistical surveillance systems currently in use usually make some ad hoc adjustment for such delays, or use counts by time of report. We propose a new statistical approach that takes account of the delays explicitly, by monitoring the number of specimens identified in the current and past m time units, where m is a tuning parameter. Values expected in the absence of an outbreak are estimated from counts observed in recent years (typically 5 years). We study the method in the context of an outbreak detection system used in the United Kingdom and several other European countries. We propose a suitable test statistic for the null hypothesis that no outbreak is currently occurring. We derive its null variance, incorporating uncertainty about the estimated delay distribution. Simulations and applications to some test datasets suggest the method works well, and can improve performance over ad hoc methods in current use. Supplementary materials for this article are available online

Does knowledge of liver fibrosis affect high-risk drinking behaviour (KLIFAD)? protocol for a feasibility randomised controlled trial

Introduction: Heavy drinkers in contact with alcohol services do not routinely have access to testing to establish the severity of potential liver disease. Transient elastography by FibroScan can provide this information. A recent systematic review suggested providing feedback to patients based on markers of liver injury can be an effective way to reduce harmful alcohol intake. This randomised control trial (RCT) aims to establish the feasibility of conducting a larger national trial to test the effectiveness of FibroScan advice and Alcohol Recovery Video Stories (ARVS) in changing high-risk drinking behaviour in community alcohol services common to UK practice.Methods and analysis: This feasibility trial consists of three work packages (WP). WP1: To draft a standardised script for FibroScan operators to deliver liver disease-specific advice to eligible participants having FibroScan. WP2: To create a video library of ARVS for use in the feasibility RCT (WP3). WP3: To test the feasibility of the trial design, including the FibroScan script and video stories developed in WP1 and WP2 in a one-to-one individual randomised trial in community alcohol services. Semi-structured interviews will be conducted at 6 months follow-up for qualitative evaluation. Outcomes will be measures of the feasibility of conducting a larger RCT. These outcomes will relate to: participant recruitment and follow-up, intervention delivery, including the use of the Knowledge of LIver Fibrosis Affects Drinking trial FibroScan scripts and videos, clinical outcomes, and the acceptability and experience of the intervention and trial-related procedures. Data analysis will primarily be descriptive to address the feasibility aims of the trial. All proposed analyses will be documented in a Statistical Analysis Plan.Ethics and dissemination: This trial received favourable ethical approval from the West of Scotland Research Ethics Service (WoSRES) on 20 January 2021, REC reference: 20/WS/0179. Results will be submitted for publication to a peer-reviewed journal.Trial registration number ISRCTN16922410

Incidence and prevalence of venous thromboembolism in chronic liver disease: a systematic review and meta-analysis

Background and Aims: Historically, bleeding was thought to be a frequent and fatal complication of liver disease. However, thrombosis due to coagulation disorders in cirrhosis remains a real risk. We aim to systematically analyse published articles to evaluate epidemiology of venous thromboembolism (VTE) in chronic liver disease (CLD). Method: Electronic search was conducted on Ovid Medline, EMBASE and Scopus from inception to November 2021 to identify studies presenting epidemiology VTE (deep vein thrombosis and pulmonary embolism) in CLD in inpatients and/or community settings. Random-effects meta-analysis was performed to determine pooled per-year cumulative incidence, incidence rate and prevalence. Heterogeneity was measured by I² test, and, potential sources of heterogeneity by meta-regression and sensitivity analysis. PROSPERO registration-CRD42021239117. Results: Twenty-nine studies comprising 19,157,018 participants were included, of which 15,2049 (0.79%) had VTE. None of included the studies were done in the community. In hospitalised patients with CLD: pooled cumulative incidence of VTE was 1.07% (95%CI 0.80,1.38) per-year, incidence rate was 157.15 (95%CI 14.74,445.29) per 10,000 person-years, and period prevalence was 1.10% (95%CI 0.85,1.38) per year. There was significant heterogeneity and publication bias. Pooled relative risk (RR) of studies reporting incidence rate was 2.11 (95%CI 1.35,3.31). CLD patients (n=1644), who did not receive pharmacological prophylaxis were at 2.78 times (95% CI 1.11, 6.98) increased risk of VTE compared to those receiving prophylaxis. Conclusion: Hospitalised patients with CLD may be at an increased risk of VTE . For every 1000 hospitalised patients with CLD ten have new, and eleven have pre-existing diagnoses of VTE per-year

Comparison of Statistical Algorithms for the Detection of Infectious Disease Outbreaks in Large Multiple Surveillance Systems

A large-scale multiple surveillance system for infectious disease outbreaks has been in operation in England and Wales since the early 1990s. Changes to the statistical algorithm at the heart of the system were proposed and the purpose of this paper is to compare two new algorithms with the original algorithm. Test data to evaluate performance are created from weekly counts of the number of cases of each of more than 2000 diseases over a twenty-year period. The time series of each disease is separated into one series giving the baseline (background) disease incidence and a second series giving disease outbreaks. One series is shifted forward by twelve months and the two are then recombined, giving a realistic series in which it is known where outbreaks have been added. The metrics used to evaluate performance include a scoring rule that appropriately balances sensitivity against specificity and is sensitive to variation in probabilities near 1. In the context of disease surveillance, a scoring rule can be adapted to reflect the size of outbreaks and this was done. Results indicate that the two new algorithms are comparable to each other and better than the algorithm they were designed to replace

Individual Health Trainers to support health and wellbeing for people under community supervision in the criminal justice system: the STRENGTHEN pilot RCT

No embargo require