An investigation of the clinical utility of preoperative cardiopulmonary exercise testing in patients undergoing major pancreatic surgery

Pancreaticoduodenectomy with or without adjuvant chemotherapy remains the only modality of possible cure in patients with cancer involving the head of the pancreas and the periampullary region. While mortality rates after pancreaticoduodenectomy have improved considerably over the course of the last century, morbidity remains high. Patient selection is of paramount importance in ensuring that major surgery is offered to individuals who will most benefit from a pancreaticoduodenectomy. Moreover, identifying preoperative risk factors provides potential targets for prehabilitation and optimisation of the patient's physiology before undertaking surgery. In addition to this, early identification of patients who are likely to develop postoperative complications allows for better allocation of critical care resources and more aggressive management high risk patients. Cardiopulmonary exercise testing is becoming an increasingly popular tool in the preoperative risk assessment of the surgical patient. However, very little work has been done to investigate the role of cardiopulmonary exercise testing in predicting complications after pancreaticoduodenectomy. The impact of jaundice, systemic inflammation and other preoperative clinicopathological characteristics on cardiopulmonary exercise physiology has not been studied in detail before in this cohort of patients. The overall aim of the thesis was to examine the relationships between preoperative clinico-pathological characteristics including cardiopulmonary exercise physiology, obstructive jaundice, body composition and systemic inflammation and complications and the post-surgical systemic inflammatory response in patients undergoing pancreaticoduodenectomy. Chapter 1 reviews the existing literature on preoperative cardiopulmonary exercise testing, the impact of obstructive jaundice, perioperative systemic inflammation and the importance of body composition in determining outcomes in patients undergoing major surgery with particular reference to pancreatic surgery. Chapter 2 reports on the role of cardiopulmonary exercise testing in predicting postoperative complications after pancreaticoduodenectomy. The results demonstrate that patients with V˙O2AT less than 10 ml/kg/min are more likely to develop a postoperative pancreatic fistula, stay longer in hospital and less likely to receive adjuvant therapy. These results emphasise the importance of aerobic fitness to recover from the operative stress of major surgery without significant morbidity. Cardiopulmonary exercise testing may prove useful in selecting patients for intensive prehabilitation programmes as well as for other optimisation measures to prepare them for major surgery. Chapter 3 evaluates the relationship between cardiopulmonary exercise physiology and other clinicopathological characteristics of the patient. A detailed analysis of cardiopulmonary exercise test parameters in jaundiced versus non-jaundiced patients demonstrates that obstructive jaundice does not impair cardiopulmonary exercise physiology. This further supports emerging evidence in contemporary literature that jaundiced patients can proceed directly to surgery without preoperative biliary drainage. The results of this study also show an interesting inverse relationship between body mass index and anaerobic threshold which is analysed in more detail in Chapter 4. Chapter 4 examines the relationship between preoperative cardiopulmonary exercise physiology and body composition in depth. All parameters measured at cardiopulmonary exercise test are compared against body composition and body mass index. The results of this chapter report that the current method of reporting V˙O2, both at peak exercise and anaerobic threshold, is biased against obese subjects and advises caution in the interpretation of cardiopulmonary exercise test results in patients with a high BMI. This is particularly important as current evidence in literature suggests that postoperative outcomes in obese subjects are comparable to non-obese subjects while cardiopulmonary exercise test results are also abnormally low in this very same cohort of patients. Chapter 5 analyses the relationship between preoperative clinico-pathological characteristics including systemic inflammation and the magnitude of the postoperative systemic inflammatory response. Obstructive jaundice appears to have an immunosuppressive effect while elevated preoperative CRP and hypoalbuminemia appear to have opposite effects with hypoalbuminemia resulting in a lower response while elevated CRP in the absence of hypoalbuminemia resulted in a greater postoperative systemic inflammatory response. Chapter 6 evaluates the role of the early postoperative systemic inflammatory response in predicting complications after pancreaticoduodenectomy and aims to establish clinically relevant thresholds for C-Reactive Protein for the prediction of complications. The results of this chapter demonstrate that CRP levels as early as the second postoperative day are associated with complications. While post-operative CRP was useful in the prediction of infective complications, this was the case only in patients who did not develop a post-operative pancreatic fistula. The predictive ability of inflammatory markers for infectious complications was blunted in patients with a pancreatic fistula. Chapter 7 summarises the findings of this thesis, their place in current literature and future directions. The results of this thesis add to the current knowledge regarding the complex pathophysiological abnormalities in patients undergoing pancreaticoduodenectomy, with specific emphasis on the interaction between cardiopulmonary exercise physiology, obstructive jaundice, systemic inflammation and postoperative outcomes. The work presented in this thesis lays the foundations for further studies aimed at improving outcomes after pancreaticoduodenectomy through the development of individualised, goal-directed therapies that are initiated well before this morbid yet necessary operation is performed.

An alternative benchmarking approach for electricity utility regulation using maximum entropy

The main purpose of this study is to present an alternative benchmarking approach that can be used by national regulators of utilities. It is widely known that the lack of sizeable data sets limits the choice of the benchmarking method and the specification of the model to set price controls within incentive-based regulation. Ill-posed frontier models are the problem that some national regulators have been facing. Maximum entropy estimators are useful in the estimation of such ill-posed models, in particular in models exhibiting small sample sizes, collinearity and non-normal errors, as well as in models where the number of parameters to be estimated exceeds the number of observations available. The empirical study involves a sample data used by the Portuguese regulator of the electricity sector to set the parameters for the electricity distribution companies in the regulatory period of 2012-2014. DEA and maximum entropy methods are applied and the efficiency results are compared.

Sorghum Crop Modeling and Its Utility in Agronomy and Breeding

Crop models are simplified mathematical representations of the interacting biological and environmental components of the dynamic soil–plant–environment system. Sorghum crop modeling has evolved in parallel with crop modeling capability in general, since its origins in the 1960s and 1970s. Here we briefly review the trajectory in sorghum crop modeling leading to the development of advanced models. We then (i) overview the structure and function of the sorghum model in the Agricultural Production System sIMulator (APSIM) to exemplify advanced modeling concepts that suit both agronomic and breeding applications, (ii) review an example of use of sorghum modeling in supporting agronomic management decisions, (iii) review an example of the use of sorghum modeling in plant breeding, and (iv) consider implications for future roles of sorghum crop modeling. Modeling and simulation provide an avenue to explore consequences of crop management decision options in situations confronted with risks associated with seasonal climate uncertainties. Here we consider the possibility of manipulating planting configuration and density in sorghum as a means to manipulate the productivity–risk trade-off. A simulation analysis of decision options is presented and avenues for its use with decision-makers discussed. Modeling and simulation also provide opportunities to improve breeding efficiency by either dissecting complex traits to more amenable targets for genetics and breeding, or by trait evaluation via phenotypic prediction in target production regions to help prioritize effort and assess breeding strategies. Here we consider studies on the stay-green trait in sorghum, which confers yield advantage in water-limited situations, to exemplify both aspects. The possible future roles of sorghum modeling in agronomy and breeding are discussed as are opportunities related to their synergistic interaction. The potential to add significant value to the revolution in plant breeding associated with genomic technologies is identified as the new modeling frontier.

Study of led lamps technologies impact on the utility

With the growing interest in the issue of reducing powerconsumption in electricity applications, energy-saving devises and the problem of their operation gains more attention. The increase in the utilization of energy-saving lamps, especially LED lamps, leads to the wide interest in their influence on the power system. The impact of discussed devices on the voltage and current in the grid must be thoroughly studied before launching devices into the market. The studies undertaken on the LED lamps present in a wide range the issue of harmonic emission from lamps and their influence on power quality. Due to many anufacturing technologies, different LED devices can have various effects on the utility. It is significant to carry out researches concerning the adverse effects of energy-saving lamps in order to utilize devices that meet certain requirements which are set by the international commissions.

The reliability and utility of spirometry performed on people with asthma in community pharmacies

Evaluation of influenza vaccination services and users’ perception about its utility: a study in a community pharmacy in Lisbon, Portugal

Poster presented at the 25th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID). Copenhagen, Denmark, 25–28 April 2015

Beta depicta, or, Remarks on mangel wurzel, with an exposition on its utility reduced from practical experiments, and with full directions for its culture, and the management in feeding and fattening of cattle,

Mode of access: Internet.

Utility of a panviral microarray for detection of swine respiratory viruses in clinical samples

Several factors have recently converged, elevating the need for highly parallel diagnostic platforms that have the ability to detect many known, novel, and emerging pathogenic agents simultaneously. Panviral DNA microarrays represent the most robust approach for massively parallel viral surveillance and detection. The Virochip is a panviral DNA microarray that is capable of detecting all known viruses, as well as novel viruses related to known viral families, in a single assay and has been used to successfully identify known and novel viral agents in clinical human specimens. However, the usefulness and the sensitivity of the Virochip platform have not been tested on a set of clinical veterinary specimens with the high degree of genetic variance that is frequently observed with swine virus field isolates. In this report, we investigate the utility and sensitivity of the Virochip to positively detect swine viruses in both cell culture-derived samples and clinical swine samples. The Virochip successfully detected porcine reproductive and respiratory syndrome virus (PRRSV) in serum containing 6.10 × 10(2) viral copies per microliter and influenza A virus in lung lavage fluid containing 2.08 × 10(6) viral copies per microliter. The Virochip also successfully detected porcine circovirus type 2 (PCV2) in serum containing 2.50 × 10(8) viral copies per microliter and porcine respiratory coronavirus (PRCV) in turbinate tissue homogenate. Collectively, the data in this report demonstrate that the Virochip can successfully detect pathogenic viruses frequently found in swine in a variety of solid and liquid specimens, such as turbinate tissue homogenate and lung lavage fluid, as well as antemortem samples, such as serum.

Utility and safety of invasive (fractional flow reserve) and non-invasive (cardiac magnetic resonance imaging) diagnostic tests in patients with NSTEMI

A prospective randomised controlled clinical trial of treatment decisions informed by invasive functional testing of coronary artery disease severity compared with standard angiography-guided management was implemented in 350 patients with a recent non-ST elevation myocardial infarction (NSTEMI) admitted to 6 hospitals in the National Health Service. The main aims of this study were to examine the utility of both invasive fractional flow reserve (FFR) and non-invasive cardiac magnetic resonance imaging (MRI) amongst patients with a recent diagnosis of NSTEMI. In summary, the findings of this thesis are: (1) the use of FFR combined with intravenous adenosine was feasible and safe amongst patients with NSTEMI and has clinical utility; (2) there was discordance between the visual, angiographic estimation of lesion significance and FFR; (3). The use of FFR led to changes in treatment strategy and an increase in prescription of medical therapy in the short term compared with an angiographically guided strategy; (4) in the incidence of major adverse cardiac events (MACE) at 12 months follow up was similar in the two groups. Cardiac MRI was used in a subset of patients enrolled in two hospitals in the West of Scotland. T1 and T2 mapping methods were used to delineate territories of acute myocardial injury. T1 and T2 mapping were superior when compared with conventional T2-weighted dark blood imaging for estimation of the ischaemic area-at-risk (AAR) with less artifact in NSTEMI. There was poor correlation between the angiographic AAR and MRI methods of AAR estimation in patients with NSTEMI. FFR had a high accuracy at predicting inducible perfusion defects demonstrated on stress perfusion MRI. This thesis describes the largest randomized trial published to date specifically looking at the clinical utility of FFR in the NSTEMI population. We have provided evidence of the diagnostic and clinical utility of FFR in this group of patients and provide evidence to inform larger studies. This thesis also describes the largest ever MRI cohort, including with myocardial stress perfusion assessments, specifically looking at the NSTEMI population. We have demonstrated the diagnostic accuracy of FFR to predict reversible ischaemia as referenced to a non-invasive gold standard with MRI. This thesis has also shown the futility of using dark blood oedema imaging amongst all comer NSTEMI patients when compared to novel T1 and T2 mapping methods.

An investigation into the utility of the Mini Addenbrooke's Cognitive Examination (M-ACE) for the early detection of dementia and mild cognitive impairment in people aged 75 and over

Background/Aims: The Mini Addenbrooke’s Cognitive Examination (M-ACE) is the abbreviated version of the widely-used Addenbrooke’s Cognitive Examination (ACE-III), a cognitive screening tool that is used internationally in the assessment of mild cognitive impairment (MCI) and dementia. The objectives of this study were to investigate the diagnostic accuracy of the M-ACE with individuals aged 75 and over to distinguish between those who do and do not have a dementia or MCI, and also to establish whether the cut-off scores recommended by Hsieh et al. (2014) [9] in the original validation study for the M-ACE are optimal for this age group. Methods: The M-ACE was administered to 58 participants (24 with a diagnosis of dementia, 17 with a diagnosis of MCI and 17 healthy controls). The extent to which scores distinguished between groups (dementia, MCI or no diagnosis) was explored using receiver operating characteristic curve analysis. Results: The optimal cut-off for detecting dementia was ≤ 21/30 (score ≤ 21/30 indicating dementia with a sensitivity of 0.95, a specificity of 1 and a positive predictive value of 1) compared to the original higher published cut-off of ≤ 25/30 (sensitivity of 0.95, specificity of 0.70 and a positive predictive value of 0.82 in this sample). Conclusions: The M-ACE has excellent diagnostic accuracy for the detection of dementia in a UK clinical sample. It may be necessary to consider lower cut-offs than those given in the original validation study.

Clinical utility of the personal questionnaire

The demand to implement routine outcome assessment in mental health care services calls for measures with clinical utility, i. e, feasible to therapists, acceptable to clients and generalizable to settings. This research aims to explore the clinical utility of a patient-generated measure, the Personal Questionnaire (PQ). An on-line survey was designed (study I) and administered to an international sample of 25 therapists with experience using the PQ (study II). Results suggest that the PQ is perceived as a clinically significant and fairly practical measure, useful not only in assessing outcome but also in various clinical tasks. Furthermore, it is relatively well accepted by clients and it is extremely generalizable to different clients, clinical approaches and settings. Specific suggestions to increase the PQ’s clinical utility are provided. Exploring therapists’ perspectives and practices will improve the appropriateness of measures to real-world clinical settings; A utilidade clínica do Personal Questionnaire RESUMO: O movimento para implementar a avaliação rotineira de resultados nos serviços de saúde mental pede medidas com utilidade clínica, i. e, práticas para terapeutas, aceitáveis para clientes e generalizáveis para contextos clínicos. Este estudo tem como objetivo explorar a utilidade clínica de uma medida gerada pelo cliente, o Personal Questionnaire (PQ). Um questionário on-line foi desenvolvido (estudo I) e administrado a uma amostra internacional de 25 terapeutas com experiência de uso do PQ (estudo II). Os resultados sugerem que o PQ é considerado um instrumento valioso para a prática clínica, relativamente prático, útil como indicador de resultado e também como ferramenta clínica. Adicionalmente, é bem aceite pelos clientes e bastante generalizável para diferentes clientes, abordagens terapêuticas e contextos clínicos. Sugestões específicas para melhorar a utilidade clínica do PQ são fornecidas. Explorar as perspetivas e práticas dos terapeutas face a medidas de resultado possibilita uma melhor adequação à prática clínica.

Testing a framework for the quality of process models: A case study

Process modeling can be regarded as the currently most popular form of conceptual modeling. Research evidence illustrates how process modeling is applied across the different information system life cycle phases for a range of different applications, such as configuration of Enterprise Systems, workflow management, or software development. However, a detailed discussion of critical factors of the quality of process models is still missing. This paper proposes a framework consisting of six quality factors, which is derived from a comprehensive literature review. It then presents in a case study, a utility provider, who had designed various business process models for the selection of an Enterprise System. The paper summarizes potential means of conducting a successful process modeling initiative and evaluates the described modeling approach within the Guidelines of Modeling (GoM) framework. An outlook shows the potential lessons learnt, and concludes with insights to the next phases of this study.

Applying integrated resource and environmental management to transmission right-of-way maintenance

The concept of a substantive integrator is introduced as a method for integrated resource and environmental management as a means to assimilate different resource values at the operational or field level. A substantive integrator is a strategic management tool for integrating multiple uses into coprorate management regimes that traditionally manage for single values. Wildlife habitat management is presented as a substantive integrator for managing vegetation on electric utility power line corridors. A case study from northern British Columbia provides an example of wildlife habitat management as a means to integrate other resource values such as aesthetics, access and subsistence along British Columbia Hydro and Power Authority's transmission rights-of-way.

The lens of ludic engagement : evaluating participation in interactive art installations

Designers and artists have integrated recent advances in interactive, tangible and ubiquitous computing technologies to create new forms of interactive environments in the domains of work, recreation, culture and leisure. Many designs of technology systems begin with the workplace in mind, and with function, ease of use, and efficiency high on the list of priorities. [1] These priorities do not fit well with works designed for an interactive art environment, where the aims are many, and where the focus on utility and functionality is to support a playful, ambiguous or even experimental experience for the participants. To evaluate such works requires an integration of art-criticism techniques with more recent Human Computer Interaction (HCI) methods, and an understanding of the different nature of engagement in these environments. This paper begins a process of mapping a set of priorities for amplifying engagement in interactive art installations. I first define the concept of ludic engagement and its usefulness as a lens for both design and evaluation in these settings. I then detail two fieldwork evaluations I conducted within two exhibitions of interactive artworks, and discuss their outcomes and the future directions of this research.