Modal Analysis of Millimetre-wave and Terahertz Imaging Systems

This thesis presents the theory and applications of electromagnetic field calculation using orthogonal Gaussian beam modes within the context of far-infrared imaging systems. Laguerre and Hermite-Gaussian modes have been frequently reported in the analysis of paraxial millimetre-wave propagation in astronomical optical systems. Here the method of Gaussian beam mode analysis (GBMA) is extended to fields of optical research that have until recently been associated with wavelengths in the visible band. Using recently derived expressions for the non-paraxial diffraction of Hermite-Gaussian modes, the author demonstrates the modal calculation of far-field intensity distributions with less angular restriction on the accuracy of the method compared to the conventional paraxial description of orthogonal Gaussian modes. This method shows excellent agreement with predictions from more rigourous fullwave numerical methods such as the finite-difference time-domain algorithm, which is also described as a software tool in the modelling of horn and lens antennas. The properties of diffraction limited Bessel beams is described using the Laguerre-Gaussian expansion of conical lenses, and experimental measurements of a conical lens is presented to explore the validity of the use of these optical elements as horn coupled devices in millimetre wave imaging systems. A study of diffractive Fresnel lenses has been undertaken with a comparison of experimentally measured fields with those predicted by the modal techniques. The effects of such lenses on ultrashort paraxial pulses are also investigated using a novel numerical description of few-cycle fields as a superposition of pulsed Laguerre- Gaussian modes. The application of digital holography in the far-infra red band has the prospect of diffraction limited imaging systems without creating distortions and aberrations which is a common problem in conventional techniques using lenses and mirrors. The author presents results from a simple proof-of-concept system which exhibits the potential of this technique for application in, for example, mm-wave security imaging

Modal Analysis of Millimetre-wave and Terahertz Imaging Systems

This thesis presents the theory and applications of electromagnetic field calculation using orthogonal Gaussian beam modes within the context of far-infrared imaging systems. Laguerre and Hermite-Gaussian modes have been frequently reported in the analysis of paraxial millimetre-wave propagation in astronomical optical systems. Here the method of Gaussian beam mode analysis (GBMA) is extended to fields of optical research that have until recently been associated with wavelengths in the visible band. Using recently derived expressions for the non-paraxial diffraction of Hermite-Gaussian modes, the author demonstrates the modal calculation of far-field intensity distributions with less angular restriction on the accuracy of the method compared to the conventional paraxial description of orthogonal Gaussian modes. This method shows excellent agreement with predictions from more rigourous fullwave numerical methods such as the finite-difference time-domain algorithm, which is also described as a software tool in the modelling of horn and lens antennas. The properties of diffraction limited Bessel beams is described using the Laguerre-Gaussian expansion of conical lenses, and experimental measurements of a conical lens is presented to explore the validity of the use of these optical elements as horn coupled devices in millimetre wave imaging systems. A study of diffractive Fresnel lenses has been undertaken with a comparison of experimentally measured fields with those predicted by the modal techniques. The effects of such lenses on ultrashort paraxial pulses are also investigated using a novel numerical description of few-cycle fields as a superposition of pulsed Laguerre- Gaussian modes. The application of digital holography in the far-infra red band has the prospect of diffraction limited imaging systems without creating distortions and aberrations which is a common problem in conventional techniques using lenses and mirrors. The author presents results from a simple proof-of-concept system which exhibits the potential of this technique for application in, for example, mm-wave security imaging

TEMPORAL UNCERTAINTY IN COST-EFFECTIVENESS DECISION MODELS: METHODS TO ADDRESS THE UNCERTAINTIES THAT ARISE WHEN THE APPROPRIATE ANALYSIS TIME HORIZON EXCEEDS THE EVIDENCE TIME HORIZON IN COST-EFFECTIVENESS DECISION MODELS AS APPLIED TO HEALTHCARE INTERVENTIONS

The problem of predicting outcomes over time and expressing uncertainty about the future is one common to many scientific disciplines. For cost-effectiveness analysis used to aid resource allocation decisions in healthcare, this problem presents itself in the form of a disparity between the evidence time horizon (which is typically short-term) and the appropriate analysis time horizon (which is often long-term). To date, this problem has been primarily characterised as one of a need to extrapolate, i.e. an imperative to interpret the available short-term evidence and project this into the long-term in order to plug the evidence gap. Furthermore, the issue has been strongly associated with estimations of survival, but less so with other measures of disease progression, with estimates of cost, or with estimates of health-related quality of life. This thesis strives to take a broad and thoughtful approach to examining the general problem of a dearth of evidence pertaining to the long-term. It is argued that this problem is most accurately and most usefully thought of as one of uncertainty. As such, in this thesis, the term ‘temporal uncertainty’ is employed. Consideration is given to the nature of temporal uncertainty and when it is of significance in the context of decision making with evidence development. Where a full expression of temporal uncertainty is necessary in order to make an informed decision, a number of approaches are described and appraised. Caution is advised in relation to extrapolating evidence over time due to the implicit assumption that outcomes in the short-term are good predictors of outcomes in the long-term. It is recommended that temporal uncertainty be characterised by a single uncertain ‘temporal’ parameter and incorporated into a probabilistic analysis in order to provide a true estimate of expected cost-effectiveness and to estimate the value of obtaining information that would lessen temporal uncertainty. In the context of these principles, a review of the health technology assessment (HTA) literature reveals that approaches to addressing temporal uncertainty to date have been inconsistent and largely inadequate. The review also makes apparent the full range of model parameters that are regularly exposed to temporal uncertainty and the specific analytical challenges that must be overcome. A motivating example (the RITA-3 decision model) is employed in order to develop and apply methods that appropriately quantify temporal uncertainty for a range of model parameters given the available evidence. The motivating example also facilitates an examination of the effects of expressing temporal uncertainty throughout a decision model. It is found that the replacement of ‘conservative’ temporal assumptions with expressions of temporal uncertainty alters the adoption recommendation for several of the risk groups under examination, that overall uncertainty around costs and health benefits is greatly inflated, that there is likely to be value in obtaining further information specifically in relation to the long-term temporal nature of certain model parameters and that there may also be value in ‘waiting’ for further evidence to be revealed if there is the potential for significant irrecoverable costs to be incurred. In summary, this thesis represents a contribution to the development of methods to aid decision making in healthcare. In particular, the significant issue of temporal uncertainty is expounded and methods to appropriately address temporal uncertainty are developed and demonstrated

How to Appropriately Extrapolate Costs and Utilities in Cost-Effectiveness Analysis

Costs and utilities are key inputs into any cost-effectiveness analysis. Their estimates are typically derived from individual patient-level data collected as part of clinical studies the follow-up duration of which is often too short to allow a robust quantification of the likely costs and benefits a technology will yield over the patient’s entire lifetime. In the absence of long-term data, some form of temporal extrapolation—to project short-term evidence over a longer time horizon—is required. Temporal extrapolation inevitably involves assumptions regarding the behaviour of the quantities of interest beyond the time horizon supported by the clinical evidence. Unfortunately, the implications for decisions made on the basis of evidence derived following this practice and the degree of uncertainty surrounding the validity of any assumptions made are often not fully appreciated. The issue is compounded by the absence of methodological guidance concerning the extrapolation of non-time-to-event outcomes such as costs and utilities. This paper considers current approaches to predict long-term costs and utilities, highlights some of the challenges with the existing methods, and provides recommendations for future applications. It finds that, typically, economic evaluation models employ a simplistic approach to temporal extrapolation of costs and utilities. For instance, their parameters (e.g. mean) are typically assumed to be homogeneous with respect to both time and patients’ characteristics. Furthermore, costs and utilities have often been modelled to follow the dynamics of the associated time-to-event outcomes. However, cost and utility estimates may be more nuanced, and it is important to ensure extrapolation is carried out appropriately for these parameters

Modal Analysis of Millimetre-wave and Terahertz Imaging Systems

This thesis presents the theory and applications of electromagnetic field calculation using orthogonal Gaussian beam modes within the context of far-infrared imaging systems. Laguerre and Hermite-Gaussian modes have been frequently reported in the analysis of paraxial millimetre-wave propagation in astronomical optical systems. Here the method of Gaussian beam mode analysis (GBMA) is extended to fields of optical research that have until recently been associated with wavelengths in the visible band. Using recently derived expressions for the non-paraxial diffraction of Hermite-Gaussian modes, the author demonstrates the modal calculation of far-field intensity distributions with less angular restriction on the accuracy of the method compared to the conventional paraxial description of orthogonal Gaussian modes. This method shows excellent agreement with predictions from more rigourous fullwave numerical methods such as the finite-difference time-domain algorithm, which is also described as a software tool in the modelling of horn and lens antennas. The properties of diffraction limited Bessel beams is described using the Laguerre-Gaussian expansion of conical lenses, and experimental measurements of a conical lens is presented to explore the validity of the use of these optical elements as horn coupled devices in millimetre wave imaging systems. A study of diffractive Fresnel lenses has been undertaken with a comparison of experimentally measured fields with those predicted by the modal techniques. The effects of such lenses on ultrashort paraxial pulses are also investigated using a novel numerical description of few-cycle fields as a superposition of pulsed Laguerre- Gaussian modes. The application of digital holography in the far-infra red band has the prospect of diffraction limited imaging systems without creating distortions and aberrations which is a common problem in conventional techniques using lenses and mirrors. The author presents results from a simple proof-of-concept system which exhibits the potential of this technique for application in, for example, mm-wave security imaging

Simulated propagation of ultrashort pulses modulated by low-Fresnel-number lenses using truncated series expansions

Numerical simulation of the paraxial propagation of pulses modulated by lenses is demonstrated using the Laguerre–Gaussian (LG) series expansion method. This technique allows for relatively swift evaluation of the structures of several individual monochromatic fields transformed by arbitrary amplitude and phase modulating pupil functions, which can be superimposed via the inverse Fourier transform to determine the structure of a modulated pulse. The transformation of ultrashort pulses by spherical, diffractive, and conical lenses is simulated using this method, which is particularly effective with the use of vector and matrix techniques available in many popular numerical software packages. A description of the convergence of the LG series to the results of the conventional integral techniques is presented for a conical lens under illumination by a continuous wave from which a simple but robust criterion for axial accuracy in problems of circular symmetry is suggested

Diffraction of an optical pulse as an expansion in ultrashort orthogonal Gaussian beam modes

The Laguerre–Gaussian (LG) beam expansion is described as a numerical and physical model of paraxial ultrashort pulse diffraction in the time domain. An overview of the dynamics of higher-order ultrashort planar LG modes is given through numerical simulations, and the finite width of these beams is shown to induce a dispersive-like axial broadening of the fields, which creates related variations in the on-axis amplitude of such pulses. The propagation of a pulsed plane wave scattered at an aperture is then illustrated as a finite weighted sum of individual planar LG pulses, which allows for intuitive illustration of the convergence of this expansion technique. By applying such an expansion to diffraction at a hard aperture, the planar pulsed LG beams are described as the paraxial analogs of the Bessel boundary waves typically observed in such situations, with both exhibiting superluminal group velocities along the optical axis. Numerical results of pulse diffraction at an aperture highlight the suitability of the LG expansion method for efficient and practical simulation of ultrashort fields in the paraxial regime

Mesenchymal Stromal Cells Protect Against Caspase 3-Mediated Apoptosis of CD19+ Peripheral B Cells Through Contact-Dependent Upregulation of VEGF

The immune suppressive and anti-inflammatory capabilities of bone marrow-derived mesenchymal stromal cells (MSCs) represent an innovative new tool in regenerative medicine and immune regulation. The potent immune suppressive ability of MSC over T cells, dendritic cells, and natural killer cells has been extensively characterized, however, the effect of MSC on B cell function has not yet been clarified. In this study, the direct effect of MSC on peripheral blood B cell function is defined and the mechanism utilized by MSC in enhancing B cell survival in vitro identified. Human MSC supported the activation, proliferation, and survival of purified CD19+ B cells through a cell contact-dependent mechanism. These effects were not mediated through B cell activating factor or notch signaling. However, cell contact between MSC and B cells resulted in increased production of vascular endothelial growth factor (VEGF) by MSC facilitating AKT phosphorylation within the B cell and inhibiting caspase 3-mediated apoptosis. Blocking studies demonstrated that this cell contactdependent effect was not dependent on signaling through CXCR4-CXCL12 or through the epidermal growth factor receptor (EGFR). These results suggest that direct cell contact between MSC and B cells supports B cell viability and function, suggesting that MSC may not represent a suitable therapy for B cell-mediated disease

Cost-utility of ranibizumab versus aflibercept for treating Greek patients with visual impairment due to diabetic macular edema

Background: To conduct a cost-utility analysis of ranibizumab versus aflibercept for the treatment of patients with visual impairment due to diabetic macular edema (DME) in the Greek setting. Methods: A Markov model was adapted to compare the use of ranibizumab 0.5 mg (pro re nata-PRN and treat and extend-T&E) to aflibercept 2 mg (every 8 weeks after five initial doses) in DME. Patients transitioned at a 3-month cycle among nine specified health states (including death) over a lifetime horizon. Transition probabilities, utilities, as well as DME-related mortality were extracted from relevant clinical trials, a network meta-analysis and other published studies. The analysis was conducted from payer perspective and as such only costs reimbursed by the payer were considered (year 2014). The incremental cost per quality-adjusted life year (QALY) gained and the net monetary benefit was the main outcome measures. Results: The use of PRN and T& E ranibizumab regimens were shown to be cost saving comparing to aflibercept (by (sic)2824 and (sic)22, respectively), and more beneficial in terms of QALYs gained (+0.05) and time without visual impairment (0.031 and 0.034 years), thereby dominating aflibercept. Moreover, ranibizumab used as PRN or T& E resulted in a net monetary benefit of (sic)3984 and (sic)1278, respectively. Conclusions: Both PRN and T& E ranibizumab regimens were more beneficial and less costly compared to aflibercept for the management of DME. Hence, ranibizumab seems to be a dominant option for the treatment of visual impairment due to DME in the Greek setting