Objective assessment of microcirculatory response in venous disease to therapy

Venous stasis is associated with leucocyte & endothelial activation as well as local growth factor response in chronic venous distasease (CVD). There is no good data on the response of this increased activation to treatment. The theme of this thesis was to show changes in leucocyte/endothelial activation as well as microcirculatory stasis in response to medical, surgical and compression therapy. Thus these may act as objective measures of response to treatment. Vascular endothelial growth factor (VEGF) is being investigated extensively in various arterial scenarios I demonstrated high plasma levels of among patients with CVD for the first time. Levels in patients were about 60% higher (82pg Vs 52 pg in controls). This may represent an (reparative!) angiogenic response existing along with the leucocyte inflammatory response. I used a model of medical treatment (60 days oral flavonoid therapy) and demonstrated significant change in plasma VEGF (50% reduction i.e. 98 pg to 57 pg/dl), ICAM (32%), VCAM (29%) & lactoferrin (36%) levels in patients. Thus I showed that endothelial cell activation (ECA) as well as VEGF might be used as an objective surrogate marker in CVD. I propose that amelioration of endothelial activation may be a mechanism of action for these compounds. I studied the response of these parameters to surgical treatment of varicose veins in 20 patients. I showed that there is an increased plasma lactoferrin at 4 weeks that goes below starting base line levels at 6 months (865 Vs 870 Vs 519). VEGF levels continued to increase (65 Vs 83 Vs 134 pg/dl) in these patients and this may represent vascular remodelling. Although not all of them are easily explainable, the microcirculatory parameters were shown to have a definable response to therapy. I used a new apparatus (Laser capillary anemometer) to assess the response of the velocity of blood in the microvasculature of patients with venous, arterial or mixed disease. I demonstrated that compression increases velocity of blood in the sub-papillary plexus & lower levels of compression (20 mm Hg) are more effective in increasing velocity in patients with mixed disease. This may explain the basis for using compression therapy in these patients. Thus I have shown that various parameters of microcirculation may be used to assess the response to therapy in CVD. Future uses of these findings may include design of new and novel therapeutic approaches and to prognosticate for the development of skin changes and ulceration of the leg in CVD

Investigation of Fatigue Response with Analytical and Machine Learning Models and Hygroscopic Analysis of Asymmetric Bistable CFRP Composites

Asymmetric bistable carbon fibre reinforced plastic (CFRP) composites enable a broad range of applications as they can sustain multiple stable configurations and have small snap-through load requirements. These unique features, coupled with their light strength-to-weight and stiffness-to-weight ratios, have made them preferred options for multifunctional systems. This study investigates the fatigue and hygroscopic response of 2-ply, [0/90] bistable CFRP laminates and proposes predictive modeling approaches for improved performance. While previous studies widely researched and documented the fatigue of general composites in axial loading, fatigue analysis of asymmetric bistable composites in the out-of-plane snap-through direction is inadequate. This study performs fatigue tests in this direction to snap the laminate between the two stable states during the cyclic loading and capture the stiffness and damage evolution for different combinations of test parameters incorporating frequencies from 1 to 10 Hz, two boundary conditions, and temperatures from 22°C to 150°C. The fatigue tests reveal that stiffness degradation and damage progression occur in two stages, while the specimens never experience global failure for any test combination. This analysis proposes a damage definition in terms of load, adopts the damage index with two analytical models: (1) Shiri Model and (2) Wu Model, and presents a range of model parameter values to predict damage during the first two stages for the specified conditions. The curvature and snap-through load evaluation demonstrates that fatigue loading does not affect these parameters. This finding enables application protocols to maintain bistable performance for a broad range of loading and environmental conditions. This study extends the predictive analysis by proposing machine learning (ML) modeling approaches to predict the non-linear load response of bistable composites in fatigue loading and utilizing the load response to predict stiffness and damage with six selected ML models: decision tree (DT), random forest (RF), adaptive boosting (ADA), gradient boosting machine (gb), artificial neural network (ANN) and k-nearest neighbors (KNN). The ML models are trained on the fatigue data acquired during the first part of the analysis. This approach evaluates the model performances with five validation tests incorporating tests with frequency and temperatures inside and outside the domain of the training data. The model assessment reveals that the ML models can capture the non-linear load-displacement response and provides a reasonable prediction of load, stiffness, and damage while offering expandability of prediction outside the training feature domain. Another aspect of this study is investigating the hygroscopic response of bistable composites in a variable relative humidity environment. The moisture absorption of asymmetric 2-ply, 4-ply, and 6-ply laminates is inspected in the laboratory environment to determine their curvature and snap-through load at different moisture content levels. The analysis reports a combined thermal and moisture expansion coefficient to predict these parameters with an improved analytical model and a finite element model. The models predict a linear drop in both parameters with increasing moisture content due to the plasticization of the epoxy polymer network and the subsequent relaxation of residual thermal strain, and these predictions demonstrate good agreement with test results

Robust Sampling Clock Recovery Algorithm for Wideband Networking Waveform of SDR

A novel technique for sampling clock recovery in a wideband networking waveform of a software defined radio is proposed. Sampling clock recovery is very important in wideband networking radio operation as it directly affects the Medium Access adaptive time slot switching rate. The proposed Sampling clock recovery algorithm consists of three stages. In the first stage, Sampling Clock Offset (SCO) is estimated at chip level. In the second stage, the SCO estimates are post-filtered to improve the tracking performance. We present a new post-filtering method namely Steady-State State-Space Recursive Least Squares with Adaptive Memory (S4RLSWAM). For the third stage of SCO compensation, a feedforward Lagrange interpolation based algorithm is proposed. Real-time hardware results have been presented to demonstrate the effectiveness of the proposed algorithms and architecture for systems requiring high data throughput. It is shown that both the proposed algorithms achieve better performance as compared to existing algorithms

A Robust Carrier Frequency Offset Estimation Algorithm in Burst Mode Multicarrier CDMA based Ad Hoc Networks

The future wireless communication systems demand very high data rates, anti-jamming ability and multiuser support. People want large amount of data to be continuously accessible in their personal devices. Direct Sequence (DS) spread spectrum based techniques such as Code Division Multiple Access (CDMA) fulfil these requirements but, at the same time, suffer from the Intersymbol Interference (ISI). Multicarrier CDMA (MC-CDMA) is an emerging technology to be used in mobile devices operating in an ad hoc setting due to its immunity towards ISI and having all the advantages of spread spectrum communication. One of the major problems with MC-CDMA is the high sensitivity towards carrier frequency offsets caused due to the inherent inaccuracy of crystal oscillators. This carrier frequency offset destroys the orthogonality of the subcarriers resulting in Intercarrier Interference (ICI). In this paper, we propose a computationally efficient algorithm based on Fast Fourier Transform (FFT) and biquadratic Lagrange interpolation. The FFT is based on the use of overlapping windows for each frame of the data instead of non-overlapping windows. This gives a coarse estimate of the frequency offset which is refined by the successive application of Lagrange quadratic interpolation to the samples in the vicinity of FFT peak. The proposed algorithm has been applied to the multiuser ad hoc network and simulated in Stanford University Interim (SUI) channels. It has been shown by simulations that the proposed algorithm provides better performance of almost 1~2 dB as compared to the well-known algorithms

Valproate Used in Women of Childbearing Age with Epilepsy

Valproate is one of the oldest known anti-epileptic drugs (AED) in practice which was discovered in 1881 and later in 1962 was approved for treating epilepsy. It is indicated in most of the seizure types including generalized onset (motor, non-motor and myoclonic), focal onset, unknown onset and unclassified. Valproate has other indications in migraine prophylaxis, and bipolar disorder

Novel Therapies in Acute Kidney Injury

PhDRenal ischaemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) which is in turn the leading cause of morbidity and mortality in hospitalized patients. The principle aim of this thesis was to evaluate potential new therapies that might afford protection against IRI in both in vitro and in vivo settings. Recent evidence suggests that nitrite (NO2-) may play an important role in protecting the myocardium from IRI. Our initial work into the role of NO2- in an in vitro model of renal IRI in proximal tubular epithelial cells provided evidence that NO2- can prevent apoptosis and preserve cell viability. This lead to an in vivo study where high NO2- concentrations (50 mg/L) were given orally to rats for 7 days prior to inducing renal IRI but no beneficial effects of this treatment were observed. Another potential treatment identified was thiamine (vitamin B1) and this, like NO2-was investigated to see if it had the potential to protect rats from AKI injury. It has been previously recognized that in renal IRI the high energy phosphate ATP is found to be severely depleted whilst is is known that thiamine can play a pivotal role in generating ATP. Furthermore, thiamine has previously been demonstrated to protect against myocardial ischaemic injury and has the ability to reduce myocardial infarct size. In vitro, thiamine was found to reduce the degree of apoptosis in cultured HK-2 cells caused by ischaemia whilst in vivo it afforded protection against AKI caused by renal IRI by anti-apoptotic, anti-inflammatory and anti-oxidant mechanisms. Finally, a study into the possible therapeutic role of gene therapy with bone morphogenic protein 7 (BMP-7) in renal IRI was undertaken. Previous work has established that i.v. BMP-7 is able to protect against renal IRI but it has also been associated with ectopic bone formation at the site of injection. Therefore another method to increase circulating BMP-7 was sought. We initially found that BMP-7 gene therapy could attenuate apoptosis and preserves cell viability in an in vitro model of renal IRI. However, whilst in vivo gene therapy with electroporation of BMP-7 plasmid DNA increased BMP-7 expression in mice serum 2 days post electroporation, it was unable to protect the animals against IRI induced AKI. In rats the direct injection of naked DNA BMP-7 plasmid systematic 2 days prior to renal IRI was able to upregulate BMP-7 expression 4 days later in kidney tissue. Despite this it was unable to afford protection against renal IRI. Apoptosis and necrosis play a crucial role in the pathogenesis of renal IRI induced AKI. In this thesis we investigated the role of three putative therapeutic agents and their role in apoptosis and necrosis in vitro in PTECs and in vivo against renal IRI induced AKI. All three therapeutic drugs were able to attenuate apoptosis in PTECs but were unable to protect against necrosis, whilst against renal IRI induced AKI only thiamine was found to be protective. Thiamine appears to hold the most promise and more work needs to be undertaken so that its potential benefit in AKI can be realised

Deployment of social nets in multilayer model to identify key individuals using majority voting

Social web and social media are evidenced to be a rich source of user-generated social content. Social media includes multiple numbers of social dimensions represented by different social networks. The identification of important player in these real-world social networks has been in high emphasis due to its effectiveness in multiple disciplines, especially in law enforcement areas working on dark networks. Many algorithms have been proposed to identify key players according to the objective of interest using suitable network centrality measures. This paper proposes a new perspective of dealing with key player identification by redefining it as a problem of “Key Individual Identification,” across multiple social dimensions. Research deals with each social dimension as a layer in the multiple-layer social network model. The proposed technique extracts a number of features from each network based on social network analysis. The features are assembled to formulate a global feature set representing the behaviors of individuals in all networks individually. The technique then attempts to find key individuals using hybrid classifiers. The results from all classifiers are formulated, and the final decision of an individual to be part of the individual key set is based on majority voting. This novel technique gives good results on a number of known networks