Catheter ablation in patients with atrial fibrillation : mapping refinements, outcome prediction and effect on quality of life

PhD ThesisChapter 1 presents a literature review, focused primarily on the pathophysiology and management of atrial fibrillation (AF). Chapter 2 examines correlations between the dominant frequency of AF - calculated using principal component analysis from a modified surface 12-lead ECG (which included posterior leads), a standard 12-lead ECG and intracardiac recordings from both atria. The inclusion of posterior leads did not improve correlation with left atrial activity because of the dominance of lead V1 in both ECG configurations. Chapter 3 explores whether acute and 12-month outcome following catheter ablation for AF can be predicted beforehand from clinical and surface AF waveform parameters. Multivariate risk scores combining these parameters can predict arrhythmia outcome following ablation, and could therefore be used to identify those most likely to benefit from this therapy. Chapter 4 examines the effect of catheter ablation on AF symptoms and quality of life (QoL). AF symptom and QoL scores improved significantly in patients who maintained sinus rhythm after ablation but did not change in those with recurrent AF. AF-specific QoL scales are more responsive to change and correlate better with ablation outcome. Chapter 5 examines inter-atrial frequency gradients in patients with persistent AF using multipolar contact mapping. A right-to-left atrial frequency gradient was found in a quarter of the patients studied, implying that their arrhythmia was being maintained by high frequency sources in the right rather than the left atrium. Chapter 6 examines whether targeting high frequency and highly repetitive complex fractionated atrial electrogram sites, identified using multipolar contact mapping during persistent AF, resulted in arrhythmia termination and maintenance of sinus rhythm long-term. The utility of administering flecainide to distinguish critical from bystander AF sites was also investigated. Flecainide did not help refine ablation targets and 12-month outcome after targeting these sites was not superior to other ablation strategies

Distinct gelatinous zooplankton communities across a dynamic shelf sea

Abstract: Understanding how gelatinous zooplankton communities are structured by local hydrography and physical forcing has important implications for fisheries and higher trophic predators. Although a large body of research has described how fronts, hydrographic boundaries, and different water masses (e.g., mixed vs. stratified) influence phytoplankton and zooplankton communities, comparatively few studies have investigated their influence on gelatinous zooplankton communities. In July 2015, 49 plankton samples were collected from 50 m depth to the surface, across five transects in the Celtic Sea, of which, four crossed the Celtic Sea Front. Two distinct gelatinous communities were found in this dynamic shelf sea: a cold water community in the cooler mixed water that mainly contained neritic taxa and a warm water community in the warmer stratified water that contained a mixture of neritic and oceanic taxa. The gelatinous biomass was 40% greater in the warm water community (∼ 2 mg C m−3) compared with the cold water community (∼ 1.3 mg C m−3). The warm water community was dominated by Aglantha digitale, Lizzia blondina, and Nanomia bijuga, whereas the cold water community was dominated by Clytia hemisphaerica and ctenophores. Physonect siphonophores contributed > 36% to the gelatinous biomass in the warm water community, and their widespread distribution suggests they are ecologically more important than previously thought. A distinct oceanic influence was also recorded in the wider warm water zooplankton community, accounting for a ∼ 20 mg C m−3 increase in biomass in that region

The Transportation Dividend: Transit Investments and the Massachusetts Economy

As home to America's first subway, Boston has been a transit-oriented city for more than a century. In fact, much of our regional economic success is due to the connectivity that a transit system provides. It is no coincidence that the area served by the MBTA houses almost 70 percent of the state's population, offers 74 percent of the jobs, and generates 84 percent of Massachusetts's gross domestic product. The MBTA is the backbone of our economy and any successful strategy for continued growth and prosperity for the region must begin with smart investment in this system.Luckily, the calculus is straightforward as the benefits from our transit system far outweigh the costs we dedicate to support it. A new report from A Better City, made possible through support from both the Barr Foundation and The Boston Foundation, measured the MBTA's performance and economic impact. It found that through travel time and cost savings, vehicular crashes avoided and reduced auto emissions, the MBTA provides an estimated $11.4 billion in value to Greater Boston each year for both transit users and non-users alike. Boston residents experience all of these benefits from the T's annual operating budget of approximately$2 billion.The report also considered the alternative, examining what would it cost if our transit system did not exist. Our economy would require the capital cost of nearly 2,300 additional lane miles of roads and 400,000 more parking spaces. If we needed to build that today, the cost for this vehicular infrastructure would be over $15 billion. The MBTA is a bargain today and for the future

Understanding low colorectal cancer screening uptake in South Asian faith communities in England - a qualitative study.

BACKGROUND: Colorectal cancer screening uptake within the South Asian population in England is approximately half that of the general population (33 % vs 61 %), and varies by Muslim (31.9 %), Sikh (34.6 %) and Hindu (43.7 %) faith background. This study sought to explore reasons for low uptake of CRC screening in South Asian communities and for the variability of low uptake between three faith communities; and to identify strategies by which uptake might be improved. METHODS: We interviewed 16 'key informants' representing communities from the three largest South Asian faith backgrounds (Islam, Hinduism and Sikhism) in London, England. RESULTS: Reasons for low colorectal cancer screening uptake were overwhelmingly shared across South Asian faith groups. These were: limitations posed by written English; limitations posed by any written language; reliance on younger family members; low awareness of colorectal cancer and screening; and difficulties associated with faeces. Non-written information delivered verbally and interactively within faith or community settings was preferred across faith communities. CONCLUSIONS: Efforts to increase accessibility to colorectal cancer screening in South Asian communities should use local language broadcasts on ethnic media and face-to-face approaches within community and faith settings to increase awareness of colorectal cancer and screening, and address challenges posed by written materials

Breaking and Fixing Garbled Circuits when a Gate has Duplicate Input Wires

Garbled circuits are a fundamental cryptographic primitive that allows two or more parties to securely evaluate an arbitrary Boolean circuit without revealing any information beyond the output using a constant number of communication rounds. Garbled circuits have been introduced by Yao (FOCS’86) and generalized to the multi-party setting by Beaver, Micali and Rogaway (STOC’90). Since then, several works have improved their efficiency by providing different garbling schemes and several implementations exist. Starting with the seminal Fairplay compiler (USENIX Security’04), several implementation frameworks decoupled the task of compiling the function to be evaluated into a Boolean circuit from the engine that securely evaluates that circuit, e.g., using a secure two-party computation protocol based on garbled circuits. In this paper, we show that this decoupling of circuit generation and evaluation allows a subtle attack on several prominent garbling schemes. It occurs when violating the implicit assumption on the circuit that gates have different input wires which is most often not explicitly specified in the respective papers. The affected garbling schemes use separate calls to a deterministic encryption function for the left and right input wire of a gate to derive pseudo-random encryption pads that are XORed together. When a circuit contains a gate where the left and right input wire are the same, these two per-wire encryption pads cancel out and we demonstrate that this can result in a complete break of privacy. We show how the vulnerable garbling schemes can be fixed easily

Workplace-based interventions to promote healthy lifestyles in the NHS workforce : a rapid scoping and evidence map

Background:The health and well-being of staff working in the NHS is a significant issue for UK health care. We sought to identify research relevant to the promotion of healthy lifestyles among NHS staff on behalf of NHS England. Objectives:To map existing reviews on workplace-based interventions to promote health and well-being, and to assess the scope for further evidence synthesis work. Design:Rapid and responsive scoping search and evidence map. Participants:Adult employees in any occupational setting and in any role. Interventions:Any intervention aimed at promoting or maintaining physical or mental health and well-being. Early intervention initiatives and those addressing violence against staff, workplace bullying or harassment were also included. Main outcome measures:Any outcome related to the effectiveness, cost-effectiveness or implementation of interventions.Data sources:A scoping search of nine databases was conducted to identify systematic reviews on health and well-being at work. Searches were limited by publication date (2000 to January/February 2019). Review methods:The titles and abstracts of over 8241 records were screened and a total of 408 potentially relevant publications were identified. Information on key characteristics were extracted from the titles and abstracts of all potentially relevant publications. Descriptive statistics (counts and percentages) for key characteristics were generated and data from reviews and ‘reviews of reviews’ were used to produce the evidence map. Results:Evidence related to a broad range of physical and mental health issues was identified across 12 ‘reviews of reviews’ and 312 other reviews, including 16 Cochrane reviews. There also exists National Institute for Health and Care Excellence guidance addressing multiple issues of potential relevance. A large number of reviews focused on mental health, changing lifestyle behaviour, such as physical activity, or on general workplace health/health promotion. Most of the reviews that focused only on health-care staff addressed mental health issues, and stress/burnout in particular. Limitations:The scoping search process was extensive and clearly effective at identifying relevant publications, but the strategy used may not have identified every potentially relevant review. Owing to the large number of potentially relevant reviews identified from the scoping search, it was necessary to produce the evidence map using information from the titles and abstracts of reviews only. Conclusions: It is doubtful that further evidence synthesis work at this stage would generate substantial new knowledge, particularly within the context of the NHS Health and Wellbeing Framework published in 2018. Additional synthesis work may be useful if it addressed an identifiable need and it was possible to identify one of the following: (1) a specific and focused research question arising from the current evidence map; it may then be appropriate to focus on a smaller number of reviews only, and provide a more thorough and critical assessment of the available evidence; and (2) a specific gap in the literature (i.e. an issue not already addressed by existing reviews or guidance); it may then be possible to undertake further literature searching and conduct a new evidence review

Impact and experiences of delayed discharge: A mixed-studies systematic review

BACKGROUND: The impact of delayed discharge on patients, health-care staff and hospital costs has been incompletely characterized. AIM: To systematically review experiences of delay from the perspectives of patients, health professionals and hospitals, and its impact on patients' outcomes and costs. METHODS: Four of the main biomedical databases were searched for the period 2000-2016 (February). Quantitative, qualitative and health economic studies conducted in OECD countries were included. RESULTS: Thirty-seven papers reporting data on 35 studies were identified: 10 quantitative, 8 qualitative and 19 exploring costs. Seven of ten quantitative studies were at moderate/low methodological quality; 6 qualitative studies were deemed reliable; and the 19 studies on costs were of moderate quality. Delayed discharge was associated with mortality, infections, depression, reductions in patients' mobility and their daily activities. The qualitative studies highlighted the pressure to reduce discharge delays on staff stress and interprofessional relationships, with implications for patient care and well-being. Extra bed-days could account for up to 30.7% of total costs and cause cancellations of elective operations, treatment delay and repercussions for subsequent services, especially for elderly patients. CONCLUSIONS: The poor quality of the majority of the research means that implications for practice should be cautiously made. However, the results suggest that the adverse effects of delayed discharge are both direct (through increased opportunities for patients to acquire avoidable ill health) and indirect, secondary to the pressures placed on staff. These findings provide impetus to take a more holistic perspective to addressing delayed discharge

Informing NHS policy in 'digital-first primary care': a rapid evidence synthesis

Background In ‘digital-first primary care’ models of health-care delivery, a patient’s first point of contact with a general practitioner or other health professional is through a digital channel, rather than a face-to-face consultation. Patients are able to access advice and treatment remotely from their home or workplace via a number of different technologies. Objectives This rapid responsive evidence synthesis was undertaken to inform NHS England policy in ‘digital-first primary care’. It was conducted in two stages: (1) scoping the published evidence and (2) addressing a refined set of questions produced by NHS England from the evidence retrieved during the scoping stage. Data sources Searches were conducted of five electronic databases (MEDLINE, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, the Health Technology Assessment database and PROSPERO were searched in July 2018) and relevant research/policy and government websites, as well as the National Institute for Health Research Health Service and Delivery Research programme database of ongoing and completed projects. No date or geographical limitations were applied. Review methods After examining the initial scoping material, NHS England provided a list of questions relating to the potential effects of digital modes and models of engagement, and the contracting and integration of these models into primary care. Systematic reviews and evidence syntheses, including evidence on the use of digital (online) modes and models of engagement between patients and primary care, were examined more closely, as was ongoing research and any incidentally identified primary studies focused on the use of digital (online) modes and models of engagement. All records were screened by two reviewers, with disagreements resolved by consensus or consulting a third reviewer. Results Evidence suggests that uptake of existing digital modes of engagement is currently low. Patients who use digital alternatives to face-to-face consultations are likely to be younger, female and have higher income and education levels. There is some evidence that online triage tools can divert demand away from primary care, but results vary between interventions and outcome measures. A number of potential barriers exist to using digital alternatives to face-to-face consultations, including inadequate NHS technology and staff concerns about workload and confidentiality. There are currently insufficient empirical data to either substantiate or allay such concerns. Very little evidence exists on outcomes related to quality of care, service delivery, benefits or harms for patients, or on financial costs/cost-effectiveness. No studies examining how to contract and commission alternatives to face-to-face consultations were identified. Limitations The quality of the included reviews was variable. Poor reporting of methodology and a lack of adequate study details were common issues. Much of the evidence focused on exploring stakeholder views rather than on objective measurement of potential impacts. The current evidence synthesis is based on a rapid scoping exercise and cannot provide the breadth or depth of insight that might have been achieved with a full systematic review. Conclusions Rapid scoping of the literature suggests that there is little high-quality evidence relating to ‘digital-first primary care’ as defined by NHS England. The broader evidence on alternatives to face-to-face consultation addresses certain policy-maker concerns, such as the possible impact of new technologies on workload and workforce, inequalities, local implementation and integration with existing services. However, although this evidence gives an insight into the views and experiences of health professionals in relation to such concerns, quantitative empirical data are lacking

Epithelial expression of mRNA and protein for IL-6, IL-10 and TNF-α in endobronchial biopsies in horses with recurrent airway obstruction

BACKGROUND: The aim of this study was to evaluate the contribution of bronchial epithelium to airway inflammation, with focus on mRNA and protein expression of cytokines of innate immunity IL-6, IL-10 and TNF-alpha, in horses with Recurrent Airway Obstruction (RAO) during exacerbation and in remission. RESULTS: Despite marked clinical and physiologic alterations between exacerbation and after remission in the RAO horses no differences were detected in either cytokine mRNA or protein levels. Moreover, the expression of investigated cytokines in RAO horses on pasture did not differ from controls.In comparing real-time PCR analysis to results of immunohistochemistry only IL-10 mRNA and protein levels in RAO horses on pasture were significantly correlated (rs = 0.893, p = 0.007). Curiously, in controls examined on pasture the TNF-alpha protein level was positively correlated to IL-10 mRNA expression (rs = 0.967, p = 0.007) and negatively correlated to IL-6 mRNA expression (rs = -0.971, p = 0.001). CONCLUSION: Given the complementary relationship of assessing cytokines directly by immunohistochemistry, or indirectly by PCR to mRNA, the lack of significant changes in either mRNA or protein levels of IL-6, IL-10 or TNF-alpha mRNA in RAO horses in exacerbation suggests that these particular cytokines in bronchial tissue may not play a substantive role in the active inflammation of this disease. To support this contention further studies examining time dependency of expression of IL-6, IL-10 or TNF-alpha are needed, as is expansion of the range of cytokines to include other key regulators of airway inflammation.Peer reviewe