Kinetic and Mechanistic Studies on Compounds With Strained Rings

A theory explaining the stabilisation of carbonium ion intermediates, termed "vertical stabilisation", has been put forward by T. G. Traylor and co-workers. Vertical stabilisation has been defined as that stabilisation in Y-CH2+ or Y-CH2- which is afforded while the internal geometry of Y and the Y-C bond length remain essentially as they were in the reactant. Traylor suggests that vertical stabilisation is a form of sigma-pi conjugation (hyperconjugation) and that it may be determined whether a group acts to stabilise a positive charge by internal nucleophilic displacement or by sigma-pi conjugation by studying the effect of that group in a vertical process. The reaction studied by Traylor was the charge transfer between substituted benzenes and a standard acceptor, tetracyanoethylene (T. C. N. E.). A relationship has been shown by various workers to exist between ionisation potentials and reactivity, i. e. sigma+, in another vertical process, gas-phase removal of an electron. Traylor believes that as the absorption frequencies of the charge transfer complexes are directly related to ionisation potentials then a relationship should be apparent between charge transfer frequency and sigma+. Evidence is given by Traylor for a linear correlation between absorption frequency and reactivity and it is postulated that a method of directly estimating the sigma+ constant for a particular substituent is possible by determining the charge transfer absorption frequency for the respective substituted benzene - T. C. N. E. complex. In particular, Traylor has suggested that strained cyclic substituents should exhibit vertical stabilisation in reactions involving carbonium ion formation. Traylor has attempted to demonstrate this theory of stabilisation by comparing the rates of solvolysis of various cyclic substituted carbinyl derivatives relative to the neopentyl derivative with the charge transfer frequencies of their respective substituted benzene - T. C. N. E. complexes. A plot of log relative rate of solvolysis against charge transfer frequency obtained by Traylor is shown. Using this plot Traylor has predicted the rate of solvolysis of the 1-norcaryl-and homocubyl-carbinyl systems. The scope of the present work has been to test this theory by determining the kinetics of electrophilic aromatic substitution of these cyclic substituted benzenes to see if, in fact, the rates predicted by Traylor are correct. Also, the homocubyl carbinyl compound was synthesised and the kinetics of solvolysis of the 3,5-dinitrobenzoate derivative in aqueous acetone were determined. Finally, the charge transfer absorption spectra of the cyclic substituted benzenes were recorded to see how accurately the absorption frequency could be determined for a particular substituent and to corroborate Traylor's results. The results obtained in this work suggest that Traylor's hypothesis of a method of estimating reaction rates by measuring the absorption maxima of the charge transfer complexes with T. C. N. E. needs to be taken with a great deal of reservation for several reasons. Firstly the inability to estimate accurately enough the exact position of the charge transfer absorption maxima. Secondly, the fact that the results of the electrophilic aromatic substitution reaction studied in this work, i. e. nitration, do not corroborate Traylor's theory. Finally, the rate of solvolysis of the homocubyl carbinyl system is much slower than that predicted by Traylor

Practical Implementation of Multiple Model Adaptive Estimation Using Neyman-Pearson Based Hypothesis Testing and Spectral Estimation Tools

This study investigates and develops various modifications to the Multiple Model Adaptive Estimation (MMAE) algorithm. The standard MMAE uses a bank of Kalman filters, each based on a different model of the system. Each of the filters predict the system response, based on its system model, to a given input and form the residual difference between the prediction and sensor measurements of the system response. Model differences in the input matrix, output matrix, and state transition matrix, which respectively correspond to an actuator failure, sensor failure, and an incorrectly modeled flight condition for a flight control failure application, were investigated in this research. An alternative filter bank structure is developed that uses a linear transform on the residual from a single Kalman filter to produce the equivalent residuals of the other Kalman filters in the standard MMAE. A Neyman Pearson based hypothesis testing algorithm is developed that results in significant improvement in failure detection performance when compared to the standard hypothesis testing algorithm. Hypothesis testing using spectral estimation techniques is also developed which provides superior failure identification performance at extremely small input levels

Long-term condition management in adults with intellectual disability in primary care: a systematic review

Background: Adults with intellectual disabilities have higher morbidity and earlier mortality than the general population. Access to primary health care is lower, despite a higher prevalence of many long-term conditions. Aim: To synthesise the evidence for the management of long-term conditions in adults with intellectual disabilities and identify barriers and facilitators to management in primary care. Design & setting: Mixed-methods systematic review. Method: Seven electronic databases were searched to identify both quantitative and qualitative studies concerning identification and management of long-term conditions in adults with intellectual disability in primary care. Both the screening of titles, abstracts, and full texts, and the quality assessment were carried out in duplicate. Findings were combined in a narrative synthesis. Results: Fifty-two studies were identified. Adults with intellectual disabilities are less likely than the general population to receive screening and health promotion interventions. Annual health checks may improve screening, identification of health needs, and management of long-term conditions. Health checks have been implemented in various primary care contexts, but the long-term impact on outcomes has not been investigated. Qualitative findings highlighted barriers and facilitators to primary care access, communication, and disease management. Accounts of experiences of adults with intellectual disabilities reveal a dilemma between promoting self-care and ensuring access to services, while avoiding paternalistic care. Conclusion: Adults with intellectual disabilities face numerous barriers to managing long-term conditions. Reasonable adjustments, based on the experience of adults with intellectual disability, in addition to intervention such as health checks, may improve access and management, but longer-term evaluation of their effectiveness is required

Systematic review and meta-analysis of the sero-epidemiological association between Epstein-Barr virus and rheumatoid arthritis

Acknowledgements The authors would like to thank Cynthia Fraser for helping run the literature search, Dr Neil Basu for providing advice on search terms for rheumatoid arthritis and to Xueli Jia, Katie Bannister and Kubra Boza for their help with foreign language papers. The authors would also like to thank the University of Aberdeen librarians at the Foresterhill medical library for their help in locating articles used for this systematic review and meta-analysis.Peer reviewedPublisher PD

Waring's Problem in Finite Rings

In this paper we obtain sharp results for Waring's problem over general finite rings, by using a combination of Artin-Wedderburn theory and Hensel's lemma and building on new proofs of analogous results over finite fields that are achieved using spectral graph theory. We also prove an analogue of S\'ark\"ozy's theorem for finite fields.Comment: 34 page

Influence of Sediment Nutrients on Growth of Emergent Hygrophila

Hygrophila ( Hygrophila polysperma (Roxb.) T. Anderson) is a plants which forms serious aquatic weed problems. Both submerged and emergent growth forms occur. Nutritional studies with a controlled release fertilizer and sediments collected from hygrophila-infested areas were conducted with the emergent growth habit to provide insights into growth of this introduced plant. Plant dry weights for experimental 16- week culture periods with low average temperatures were associated with low amounts of hygrophila biomass as compared to culture periods with high average temperatures. Hygrophila cultured in sand rooting media with the controlled release fertilizer produced as much as 20 times more dry weight than plants cultured in sediments only. First-degree linear regression statistics showed hygrophila dry weights were highly related to ammonia nitrogen, magnesium, sodium, and pH values in the sediments. These findings show the close relationship of the emergent growth habit of hygrophila to sediment nutrients. Analyses for certain sediment characteristics may provide an indication of the potential growth that may be expected for weed infestations of this plant. Hygrophila grows year round in south Florida; however, visual observations of canals and other bodies of water indicate that lower amounts of hygrophila plants occur during the cooler months of year than during the summer season. These findings show the seasonal growth of emergent hygrophila occurs with biomass dependent on both sediment nutrients and temperature

Interventions by healthcare professionals to improve management of physical long-term conditions in adults who are homeless: a systematic review protocol

Introduction People experiencing homelessness are at increased risk of, and have poorer outcomes from, a range of physical long-term conditions (LTCs). It is increasingly recognised that interventions targeting people who are homeless should be tailored to the specific needs of this population. This systematic review aims to identify, describe and appraise trials of interventions that aim to manage physical LTCs in homeless adults and are delivered by healthcare professionals. Methods and analysis Seven electronic databases (Medline, EMBASE, Cochrane Central Register of Controlled Trials, Assia, Scopus, PsycINFO and CINAHL) will be searched from 1960 (or inception) to October 2016 and supplemented by forward citation searching, handsearching of reference lists and searching grey literature. Two reviewers will independently review titles, abstract and full-texts using DistillerSR software. Inclusion criteria include (1) homeless adults with any physical LTC, (2) interventions delivered by a healthcare professional (any professional trained to provide any form of healthcare, but excluding social workers and professionals without health-related training), (3) comparison with usual care or an alternative intervention, (4) report outcomes such as healthcare usage, physical and psychological health or well-being or cost-effectiveness, (5) randomised controlled trials, non-randomised controlled trials, controlled before-after studies. Quality will be assessed using the Cochrane EPOC Risk of Bias Tool. A meta-analysis will be performed if sufficient data are identified; however, we anticipate a narrative synthesis will be performed. Ethics and dissemination This review will synthesise existing evidence for interventions delivered by healthcare professionals to manage physical LTCs in adults who are homeless. The findings will inform the development of future interventions and research aiming to improve the management of LTCs for people experiencing homelessness. Ethical approval will not be required for this systematic review as it does not contain individual patient data. We will disseminate the results of this systematic review via conference presentations, healthcare professional networks, social media and peer-reviewed publication

A systematic review of interventions by healthcare professionals to improve management of non-communicable diseases and communicable diseases requiring long-term care in adults who are homeless

Objective: Identify, describe and appraise trials of interventions delivered by healthcare professionals to manage non-communicable diseases (NCDs) and communicable diseases that require long-term care or treatment (LT-CDs), excluding mental health and substance use disorders, in homeless adults. Design: Systematic review of randomised controlled trials (RCTs), non-RCTs and controlled before–after studies. Interventions characterised using Effective Practice and Organisation of Care (EPOC) taxonomy. Quality assessed using EPOC risk of bias criteria. Data sources: Database searches (MEDLINE, Embase, PsycINFO, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Applied Social Sciences Index and Abstracts (ASSIA) and Cochrane Central Register of Controlled Trials), hand searching reference lists, citation searches, grey literature and contact with study authors. Setting: Community. Participants: Adults (≥18 years) fulfilling European Typology of Homelessness criteria. Intervention: Delivered by healthcare professionals managing NCD and LT-CDs. Outcomes: Primary outcome: unscheduled healthcare utilisation. Secondary outcomes: mortality, biological markers of disease control, adherence to treatment, engagement in care, patient satisfaction, knowledge, self-efficacy, quality of life and cost-effectiveness. Results: 11 studies were included (8 RCTs, 2 quasi-experimental and 1 feasibility) involving 9–520 participants (67%–94% male, median age 37–49 years). Ten from USA and one from UK. Studies included various NCDs (n=3); or focused on latent tuberculosis (n=4); HIV (n=2); hepatitis C (n=1) or type 2 diabetes (n=1). All interventions were complex with multiple components. Four described theories underpinning intervention. Three assessed unscheduled healthcare utilisation: none showed consistent reduction in hospitalisation or emergency department attendance. Six assessed adherence to specific treatments, of which four showed improved adherence to latent tuberculosis therapy. Three concerned education case management, all of which improved disease-specific knowledge. No improvements in biological markers of disease (two studies) and none assessed mortality. Conclusions: Evidence for management of NCD and LT-CDs in homeless adults is sparse. Educational case-management interventions may improve knowledge and medication adherence. Large trials of theory-based interventions are needed, assessing healthcare utilisation and outcomes as well as assessment of biological outcomes and cost-effectiveness

Frailty in chronic diseases: prevalence and implications for clinical management

Summary Background: A growing number of people worldwide live with frailty. Frailty describes an age-related state of reduced physiological reserve, characterised by increased vulnerability to decompensation in response to physiological stress. People living with frailty are at increased risk of adverse health outcomes including mortality and hospital admission. There is often uncertainty over clinical management of long-term conditions in the presence of frailty. This includes uncertainty over how frailty should be identified, how frailty influences the balance of risks and benefits arising from specific diagnostic and therapeutic choices, and over the applicability of trial evidence when trials rarely measure or report frailty. Three conditions in which frailty is common, and in which these uncertainties manifest, are type 2 diabetes, rheumatoid arthritis, and chronic obstructive pulmonary disease (COPD). Aims: This thesis addresses the following aims in each of these exemplar conditions: • assess the prevalence of frailty • quantify the relationship between frailty and adverse clinical outcomes • identify and measure frailty within randomised controlled trials for each condition. Methods: Three approaches were used for each condition: systematic review of observational studies, analysis of observational data, and analysis of individual participant data from industry-sponsored randomised controlled trials. Systematic reviews included observational studies of adults with the condition of interest (each reviewed separately), using any frailty measure, in any setting, and assessing either frailty prevalence or the relationship between frailty and clinical outcomes relevant to the exemplar condition. Observational analyses used UK Biobank (all conditions) and the Scottish Early Rheumatoid Arthritis (SERA) cohort (rheumatoid arthritis only) and assessed frailty using the frailty phenotype and the frailty index. Analyses quantified the relationships between frailty and mortality and hospital admission (all conditions); major adverse cardiovascular events (MACE), falls and hypoglycaemia (type 2 diabetes); rheumatoid arthritis disease activity; and COPD exacerbations. Finally, a frailty index was constructed using individual participant data from industry-sponsored drug trials for type 2 diabetes, rheumatoid arthritis and COPD, the prevalence of frailty examined, and the relationship between frailty and Serious Adverse Events assessed. Results: Research question 1: Frailty prevalence In each exemplar condition, a wide range of frailty measures were used in observational studies within the published literature (20 measures used in 118 studies of frailty in diabetes, 11 measures in 17 studies of frailty in rheumatoid arthritis, and 11 measures in 56 studies of frailty in COPD). For all conditions, the frailty phenotype was the most commonly used (69/118 diabetes studies, 5/17 rheumatoid arthritis studies, and 32/53 COPD studies). In all conditions, prevalence varied considerably by frailty measure (generally lower using the frailty phenotype compared to other measures), age (higher prevalence in studies with greater mean age) and setting (higher in residential care and inpatient settings, lower in community-based studies). However, even among community-based studies using similar frailty measures, prevalence estimates were highly heterogenous. For all three conditions, frailty was present in people under 65-years in all studies in which this was assessed. Research question 2: Frailty and clinical outcomes Among participants aged between 40 and 70, frailty was associated with a range of subsequent adverse health outcomes. In type 2 diabetes frailty was associated with an increased risk of mortality, MACE, and hospital admission with fall or fracture or with hypoglycaemia after adjustment for sociodemographic factors. These findings were similar for the frailty phenotype and frailty index. At any given level of frailty, the absolute risk of each of these outcomes was greater for older participants. The association between higher HbA1c and mortality was stronger in people with frailty compared with pre-frail or robust participants according to the frailty phenotype. In rheumatoid arthritis frailty was associated with mortality and hospital admission using both the frailty phenotype and frailty index after adjustment for sociodemographic factors and disease activity. In SERA, a higher frailty index was also associated with higher disease activity. However, in the two years following initial diagnosis and with initiation of disease-modifying antirheumatic therapy, the mean frailty index of SERA participants reduced indicating an improvement in frailty at the group level. Both the frailty phenotype and frailty index were associated with increased risk of mortality, hospital admission, MACE, and COPD exacerbations in people with COPD. In each case, the magnitude of the association was similar before and after adjusting for the severity of airflow limitation (measured using forced expiratory volume in 1 second [FEV1]). Research question 3: Frailty in clinical trials Out of 39 trials for which individual participant data were obtained, 19 trials (7 type 2 diabetes, 8 rheumatoid arthritis, 4 COPD) provided sufficient data to construct a 40-item frailty index. Based on a cut-off of 0.24, frailty was common in trials for each condition (range 7-21% in type 2 diabetes trials, range 33-73% in rheumatoid arthritis trials and range 15-22% in COPD trials). The mean frailty index was highest in rheumatoid arthritis trials, followed by COPD then type 2 diabetes. The 99th centile of the frailty index in all trials was lower than is seen in most general populations-based estimates. For all three conditions, frailty was associated with increased risk of Serious Adverse Events during trial follow-up (incidence rate ratios per 0.1-point increase in frailty index were 1.46 (95% confidence interval 1.21–1.75), 1.45 (1.13–1.87), and 1.99 (1.43–2.76) for type 2 diabetes, rheumatoid arthritis, and COPD, respectively). Conclusion: Frailty is common in each of the exemplar conditions, including in people aged under 65-years in whom it is far less frequently studied. Frailty in younger people is also associated with a range of clinically significant adverse health outcomes in each condition. However, the absolute risks associated with frailty are considerably lower among younger people. This, along with the observation that frailty can improve within individuals, highlights the need to individualise clinical decisions around the implications of frailty, taking into account factors such as age and clinical context, as the implications of frailty may differ depending on age as well as the nature and severity of underlying long-term conditions. Frailty is also identifiable within clinical trials, a field where frailty is rarely reported. This shows that it is feasible to report frailty for most trials. Doing so could help inform shared clinical decision making for people living with frailty