Relative intensity noise transfer in higher-order distributed amplification through ultra-long fiber cavities

Among the different possible amplification solutions offered by Raman scattering in optical fibers, ultra-long Raman lasers are particularly promising as they can provide quasi-losless second order amplification with reduced complexity, displaying excellent potential in the design of low-noise long-distance communication systems. Still, some of their advantages can be partially offset by the transfer of relative intensity noise from the pump sources and cavity-generated Stokes to the transmitted signal. In this paper we study the effect of ultra-long cavity design (length, pumping, grating reflectivity) on the transfer of RIN to the signal, demonstrating how the impact of noise can be greatly reduced by carefully choosing appropriate cavity parameters depending on the intended application of the system. © 2010 Copyright SPIE - The International Society for Optical Engineering.

Effects of alternating current voltage amplitude and oxide capacitance on mid-gap interface state defect density extractions in In0.53Ga 0.47As capacitors

This work looks at the effect on mid-gap interface state defect density estimates for In0.53Ga0.47As semiconductor capacitors when different AC voltage amplitudes are selected for a fixed voltage bias step size (100 mV) during room temperature only electrical characterization. Results are presented for Au/Ni/Al2O3/In0.53Ga0.47As/InP metal–oxide–semiconductor capacitors with (1) n-type and p-type semiconductors, (2) different Al2O3 thicknesses, (3) different In0.53Ga0.47As surface passivation concentrations of ammonium sulphide, and (4) different transfer times to the atomic layer deposition chamber after passivation treatment on the semiconductor surface—thereby demonstrating a cross-section of device characteristics. The authors set out to determine the importance of the AC voltage amplitude selection on the interface state defect density extractions and whether this selection has a combined effect with the oxide capacitance. These capacitors are prototypical of the type of gate oxide material stacks that could form equivalent metal–oxide–semiconductor field-effect transistors beyond the 32 nm technology node. The authors do not attempt to achieve the best scaled equivalent oxide thickness in this work, as our focus is on accurately extracting device properties that will allow the investigation and reduction of interface state defect densities at the high-k/III–V semiconductor interface. The operating voltage for future devices will be reduced, potentially leading to an associated reduction in the AC voltage amplitude, which will force a decrease in the signal-to-noise ratio of electrical responses and could therefore result in less accurate impedance measurements. A concern thus arises regarding the accuracy of the electrical property extractions using such impedance measurements for future devices, particularly in relation to the mid-gap interface state defect density estimated from the conductance method and from the combined high–low frequency capacitance–voltage method. The authors apply a fixed voltage step of 100 mV for all voltage sweep measurements at each AC frequency. Each of these measurements is repeated 15 times for the equidistant AC voltage amplitudes between 10 mV and 150 mV. This provides the desired AC voltage amplitude to step size ratios from 1:10 to 3:2. Our results indicate that, although the selection of the oxide capacitance is important both to the success and accuracy of the extraction method, the mid-gap interface state defect density extractions are not overly sensitive to the AC voltage amplitude employed regardless of what oxide capacitance is used in the extractions, particularly in the range from 50% below the voltage sweep step size to 50% above it. Therefore, the use of larger AC voltage amplitudes in this range to achieve a better signal-to-noise ratio during impedance measurements for future low operating voltage devices will not distort the extracted interface state defect density.

(Table T2) Relative signal intensity of intact polar lipids in sediments from ODP Sites 207-1257 and 207-1258

We report results from the analysis of intact polar lipids (IPLs) in sediments from Ocean Drilling Program Sites 1257 and 1258. IPLs, constituting the cell membranes of living organisms, were detected in organic-lean sediments but not in underlying organic-rich black shales. Microbial activity in organic-lean sediments is likely due to sulfate-dependent oxidation of methane whereas difficulties detecting IPLs in black shales are interpreted to result from unfavorable signal-to-noise ratios due to low cell concentrations in combination with extremely high analytical noise created by uncharacterized organic matrix. IPLs found are consistent with a low-diversity community of archaea and bacteria. The concentrations of IPLs are more than one order of magnitude lower than those in Neogene deep subsurface sediments at the Peruvian margin, suggestive of significantly lower cell concentrations in Demerara Rise. This finding is consistent with inferred low rates of subsurface microbial activity.

Anthropogenic noise affects vocal interactions

Animal communication plays a crucial role in many species, and it involves a sender producing a signal and a receiver responding to that signal. The shape of a signal is determined by selection pressures acting upon it. One factor that exerts selection on acoustic signals is the acoustic environment through which the signal is transmitted. Recent experimental studies clearly show that senders adjust their signals in response to increased levels of anthropogenic noise. However, to understand how noise affects the whole process of communication, it is vital to know how noise affects the receiver’s response during vocal interactions. Therefore, we experimentally manipulated ambient noise levels to expose male European robins (Erithacus rubecula) to two playback treatments consisting of the same song: one with noise and another one without noise. We found that males responding to a conspecific in a noise polluted environment increased minimum frequency and decreased song complexity and song duration. Thus, we show that the whole process of communication is affected by noise, not just the behaviour of the sender.

Parallel Cyclostationarity-Exploiting Algorithm for Energy-Efficient Spectrum Sensing

The evolution of wireless communication systems leads to Dynamic Spectrum Allocation for Cognitive Radio, which requires reliable spectrum sensing techniques. Among the spectrum sensing methods proposed in the literature, those that exploit cyclostationary characteristics of radio signals are particularly suitable for communication environments with low signal-to-noise ratios, or with non-stationary noise. However, such methods have high computational complexity that directly raises the power consumption of devices which often have very stringent low-power requirements. We propose a strategy for cyclostationary spectrum sensing with reduced energy consumption. This strategy is based on the principle that p processors working at slower frequencies consume less power than a single processor for the same execution time. We devise a strict relation between the energy savings and common parallel system metrics. The results of simulations show that our strategy promises very significant savings in actual devices.

Estimation de la direction d'arrivée d'échos sonores à large bande noyés dans le signal direct

Ce mémoire présente deux algorithmes qui ont pour but d’améliorer la précision de l’estimation de la direction d’arrivée de sources sonores et de leurs échos. Le premier algorithme, qui s’appelle la méthode par élimination des sources, permet d’améliorer l’estimation de la direction d’arrivée d’échos qui sont noyés dans le bruit. Le second, qui s’appelle Multiple Signal Classification à focalisation de phase, utilise l’information dans la phase à chaque fréquence pour déterminer la direction d’arrivée de sources à large bande. La combinaison de ces deux algorithmes permet de localiser des échos dont la puissance est de -17 dB par rapport à la source principale, jusqu’à un rapport échoà- bruit de -15 dB. Ce mémoire présente aussi des mesures expérimentales qui viennent confirmer les résultats obtenus lors de simulations.

Child Safety Signal Learning in the Context of Parental Worry, Overprotection, PTSD, and Depression

Thesis (Ph.D.)--University of Washington, 2016-08

Phase noise and spur reduction in an array of direct digital synthesizers

Many applications, including communications, test and measurement, and radar, require the generation of signals with a high degree of spectral purity. One method for producing tunable, low-noise source signals is to combine the outputs of multiple direct digital synthesizers (DDSs) arranged in a parallel configuration. In such an approach, if all noise is uncorrelated across channels, the noise will decrease relative to the combined signal power, resulting in a reduction of sideband noise and an increase in SNR. However, in any real array, the broadband noise and spurious components will be correlated to some degree, limiting the gains achieved by parallelization. This thesis examines the potential performance benefits that may arise from using an array of DDSs, with a focus on several types of common DDS errors, including phase noise, phase truncation spurs, quantization noise spurs, and quantizer nonlinearity spurs. Measurements to determine the level of correlation among DDS channels were made on a custom 14-channel DDS testbed. The investigation of the phase noise of a DDS array indicates that the contribution to the phase noise from the DACs can be decreased to a desired level by using a large enough number of channels. In such a system, the phase noise qualities of the source clock and the system cost and complexity will be the main limitations on the phase noise of the DDS array. The study of phase truncation spurs suggests that, at least in our system, the phase truncation spurs are uncorrelated, contrary to the theoretical prediction. We believe this decorrelation is due to the existence of an unidentified mechanism in our DDS array that is unaccounted for in our current operational DDS model. This mechanism, likely due to some timing element in the FPGA, causes some randomness in the relative phases of the truncation spurs from channel to channel each time the DDS array is powered up. This randomness decorrelates the phase truncation spurs, opening the potential for SFDR gain from using a DDS array. The analysis of the correlation of quantization noise spurs in an array of DDSs shows that the total quantization noise power of each DDS channel is uncorrelated for nearly all values of DAC output bits. This suggests that a near N gain in SQNR is possible for an N-channel array of DDSs. This gain will be most apparent for low-bit DACs in which quantization noise is notably higher than the thermal noise contribution. Lastly, the measurements of the correlation of quantizer nonlinearity spurs demonstrate that the second and third harmonics are highly correlated across channels for all frequencies tested. This means that there is no benefit to using an array of DDSs for the problems of in-band quantizer nonlinearities. As a result, alternate methods of harmonic spur management must be employed.

High Quality Acoustic Time History Measurements of Rotor Harmonic Noise in Confined Spaces

A methodology has been developed and presented to enable the use of small to medium scale acoustic hover facilities for the quantitative measurement of rotor impulsive noise. The methodology was applied to the University of Maryland Acoustic Chamber resulting in accurate measurements of High Speed Impulsive (HSI) noise for rotors running at tip Mach numbers between 0.65 and 0.85 – with accuracy increasing as the tip Mach number was increased. Several factors contributed to the success of this methodology including: • High Speed Impulsive (HSI) noise is characterized by very distinct pulses radiated from the rotor. The pulses radiate high frequency energy – but the energy is contained in short duration time pulses. • The first reflections from these pulses can be tracked (using ray theory) and, through adjustment of the microphone position and suitably applied acoustic treatment at the reflected surface, reduced to small levels. A computer code was developed that automates this process. The code also tracks first bounce reflection timing, making it possible to position the first bounce reflections outside of a measurement window. • Using a rotor with a small number of blades (preferably one) reduces the number of interfering first bounce reflections and generally improves the measured signal fidelity. The methodology will help the gathering of quantitative hovering rotor noise data in less than optimal acoustic facilities and thus enable basic rotorcraft research and rotor blade acoustic design.

Parallel Cyclostationarity-Exploiting Algorithm for Energy-Efficient Spectrum Sensing

The evolution of wireless communication systems leads to Dynamic Spectrum Allocation for Cognitive Radio, which requires reliable spectrum sensing techniques. Among the spectrum sensing methods proposed in the literature, those that exploit cyclostationary characteristics of radio signals are particularly suitable for communication environments with low signal-to-noise ratios, or with non-stationary noise. However, such methods have high computational complexity that directly raises the power consumption of devices which often have very stringent low-power requirements. We propose a strategy for cyclostationary spectrum sensing with reduced energy consumption. This strategy is based on the principle that p processors working at slower frequencies consume less power than a single processor for the same execution time. We devise a strict relation between the energy savings and common parallel system metrics. The results of simulations show that our strategy promises very significant savings in actual devices.

Test-Retest Reliability of Resting-State Magnetoencephalography Power in Sensor and Source Space

Several studies have reported changes in spontaneous brain rhythms that could be used asclinical biomarkers or in the evaluation of neuropsychological and drug treatments in longitudinal studies using magnetoencephalography (MEG). There is an increasing necessity to use these measures in early diagnosis and pathology progression; however, there is a lack of studies addressing how reliable they are. Here, we provide the first test-retest reliability estimate of MEG power in resting-state at sensor and source space. In this study, we recorded 3 sessions of resting-state MEG activity from 24 healthy subjects with an interval of a week between each session. Power values were estimated at sensor and source space with beamforming for classical frequency bands: delta (2–4 Hz), theta (4–8 Hz), alpha (8–13 Hz), low beta (13–20 Hz), high beta (20–30 Hz), and gamma (30–45 Hz). Then, test-retest reliability was evaluated using the intraclass correlation coefficient (ICC). We also evaluated the relation between source power and the within-subject variability. In general, ICC of theta, alpha, and low beta power was fairly high (ICC > 0.6) while in delta and gamma power was lower. In source space, fronto-posterior alpha, frontal beta, and medial temporal theta showed the most reliable profiles. Signal-to-noise ratio could be partially responsible for reliability as low signal intensity resulted inhigh within-subject variability, but also the inherent nature of some brain rhythms in resting-state might be driving these reliability patterns. In conclusion, our results described the reliability of MEG power estimates in each frequency band, which could be considered in disease characterization or clinical trials.

Identifying and enhancing risk thresholds in the detection of elder financial abuse: A signal detection analysis of professionals' decision making

Background: Financial abuse of elders is an under acknowledged problem and professionals' judgements contribute to both the prevalence of abuse and the ability to prevent and intervene. In the absence of a definitive "gold standard" for the judgement, it is desirable to try and bring novice professionals' judgemental risk thresholds to the level of competent professionals as quickly and effectively as possible. This study aimed to test if a training intervention was able to bring novices' risk thresholds for financial abuse in line with expert opinion. Methods: A signal detection analysis, within a randomised controlled trial of an educational intervention, was undertaken to examine the effect on the ability of novices to efficiently detect financial abuse. Novices (n = 154) and experts (n = 33) judged "certainty of risk" across 43 scenarios; whether a scenario constituted a case of financial abuse or not was a function of expert opinion. Novices (n = 154) were randomised to receive either an on-line educational intervention to improve financial abuse detection (n = 78) or a control group (no on-line educational intervention, n = 76). Both groups examined 28 scenarios of abuse (11 "signal" scenarios of risk and 17 "noise" scenarios of no risk). After the intervention group had received the on-line training, both groups then examined 15 further scenarios (5 "signal" and 10 "noise" scenarios). Results: Experts were more certain than the novices, pre (Mean 70.61 vs. 58.04) and post intervention (Mean 70.84 vs. 63.04); and more consistent. The intervention group (mean 64.64) were more certain of abuse post-intervention than the control group (mean 61.41, p = 0.02). Signal detection analysis of sensitivity (Á) and bias (C) revealed that this was due to the intervention shifting the novices' tendency towards saying "at risk" (C post intervention -.34) and away from their pre intervention levels of bias (C-.12). Receiver operating curves revealed more efficient judgments in the intervention group. Conclusion: An educational intervention can improve judgements of financial abuse amongst novice professionals.

MODELING OF TRANSFER PATH FOR DETERMINATION OF COMBUSTION AND NOISE METRICS ON DIESEL ENGINES

Determination of combustion metrics for a diesel engine has the potential of providing feedback for closed-loop combustion phasing control to meet current and upcoming emission and fuel consumption regulations. This thesis focused on the estimation of combustion metrics including start of combustion (SOC), crank angle location of 50% cumulative heat release (CA50), peak pressure crank angle location (PPCL), and peak pressure amplitude (PPA), peak apparent heat release rate crank angle location (PACL), mean absolute pressure error (MAPE), and peak apparent heat release rate amplitude (PAA). In-cylinder pressure has been used in the laboratory as the primary mechanism for characterization of combustion rates and more recently in-cylinder pressure has been used in series production vehicles for feedback control. However, the intrusive measurement with the in-cylinder pressure sensor is expensive and requires special mounting process and engine structure modification. As an alternative method, this work investigated block mounted accelerometers to estimate combustion metrics in a 9L I6 diesel engine. So the transfer path between the accelerometer signal and the in-cylinder pressure signal needs to be modeled. Depending on the transfer path, the in-cylinder pressure signal and the combustion metrics can be accurately estimated - recovered from accelerometer signals. The method and applicability for determining the transfer path is critical in utilizing an accelerometer(s) for feedback. Single-input single-output (SISO) frequency response function (FRF) is the most common transfer path model; however, it is shown here to have low robustness for varying engine operating conditions. This thesis examines mechanisms to improve the robustness of FRF for combustion metrics estimation. First, an adaptation process based on the particle swarm optimization algorithm was developed and added to the single-input single-output model. Second, a multiple-input single-output (MISO) FRF model coupled with principal component analysis and an offset compensation process was investigated and applied. Improvement of the FRF robustness was achieved based on these two approaches. Furthermore a neural network as a nonlinear model of the transfer path between the accelerometer signal and the apparent heat release rate was also investigated. Transfer path between the acoustical emissions and the in-cylinder pressure signal was also investigated in this dissertation on a high pressure common rail (HPCR) 1.9L TDI diesel engine. The acoustical emissions are an important factor in the powertrain development process. In this part of the research a transfer path was developed between the two and then used to predict the engine noise level with the measured in-cylinder pressure as the input. Three methods for transfer path modeling were applied and the method based on the cepstral smoothing technique led to the most accurate results with averaged estimation errors of 2 dBA and a root mean square error of 1.5dBA. Finally, a linear model for engine noise level estimation was proposed with the in-cylinder pressure signal and the engine speed as components.

An automatic classifier of emotions built from entropy of noise

The electrocardiogram (ECG) signal has been widely used to study the physiological substrates of emotion. However, searching for better filtering techniques in order to obtain a signal with better quality and with the maximum relevant information remains an important issue for researchers in this field. Signal processing is largely performed for ECG analysis and interpretation, but this process can be susceptible to error in the delineation phase. In addition, it can lead to the loss of important information that is usually considered as noise and, consequently, discarded from the analysis. The goal of this study was to evaluate if the ECG noise allows for the classification of emotions, while using its entropy as an input in a decision tree classifier. We collected the ECG signal from 25 healthy participants while they were presented with videos eliciting negative (fear and disgust) and neutral emotions. The results indicated that the neutral condition showed a perfect identification (100%), whereas the classification of negative emotions indicated good identification performances (60% of sensitivity and 80% of specificity). These results suggest that the entropy of noise contains relevant information that can be useful to improve the analysis of the physiological correlates of emotion.

An investigation of the relationship between the components of tumour microenvironment, signal transduction pathways and outcome in breast cancer

Breast cancer, the most commonly diagnosed type of cancer in women, is a major cause of morbidity and mortality in the western world. Well-established risk factors of breast cancer are mostly related to women’s reproductive history, such as early menarche, late first pregnancy and late menopause. Survival rates have improved due to a combination of factors, including better health education, early detection with large-scale use of screening mammogram, improved surgical techniques, as well as widespread use of adjuvant therapy. At initial presentation, clinicopathological features of breast cancer such as age, nodal status, tumour size, tumour grade, and hormonal receptor status are considered to be the standard prognostic and predictive markers of patient survival, and are used to guide appropriate treatment strategies. Lymphovascular invasion (LBVI), including lymphatic (LVI) and blood (BVI) vessel invasion, has been reported to be prognostic and merit accurate evaluation, particularly in patients with node negative tumours who might benefit from adjuvant chemotherapy. There is a lack of standard assessment and agreement on distinguishing LVI from BVI despite the major challenges in the field. A systematic review of the literatures, examining methods of detection and the prognostic significance of LBVI, LVI and BVI, was carried out. The majority of studies used haematoxylin and eosin (H&E) and classical histochemistry to identify LVI and BVI. Only few recent studies used immunohistochemistry (IHC) staining of the endothelium lining lymphatic and blood vessels, and were able to show clear differences between LVI and BVI. The prognostic significance of LBVI and LVI was well-documented and strongly associated with aggressive features of breast tumours, while the prognostic value and the optimal detection method of BVI were unclear. Assessment and prognostic value of LBVI on H&E sections (LBVIH&E) was examined and compared to that of LVI and BVI detected using IHC with D2-40 for LVI (LVID2–40) and Factor VIII for BVI (BVIFVIII) in patients with breast cancer including node negative and triple negative patients (n=360). LBVIH&E, LVID2–40 and BVIFVIII were present in 102 (28%), 127 (35%) and 59 (16%) patients respectively. In node negative patients (206), LBVIH&E, LVID2–40 and BVIFVIII were present in 41 (20%), 53 (26%) and 21 (10%) respectively. In triple negative patients (102), LBVIH&E, LVID2–40 and BVIFVIII were present in 35 (29%), 36 (35%) and 14 (14%) respectively. LBVIH&E, LVID2–40 and BVIFVIII were all significantly associated with tumour recurrence in all cohorts. On multivariate survival analysis, only LVID2–40 and BVIFVIII were independent predictors of cancer specific survival (CSS) in the whole cohort (P=0.022 and P<0.001 respectively), node negative (P=0.008 and P=0.001 respectively) and triple negative patients (P=0.014 and P<0.001 respectively). Assessment of LVI and BVI by IHC, using D2-40 and Factor VIII, improves prediction of outcome in patients with node negative and triple negative breast cancer and was superior to the conventional detection method. Breast cancer is recognised as a complex molecular disease and histologically identical tumours may have highly variable outcomes, including different responses to therapy. Therefore, there is a compelling need for new prognostic and predictive markers helpful of selecting patients at risk and patients with aggressive diseases who might benefit from adjuvant and targeted therapy. It is increasingly recognised that the development and progression of human breast cancer is not only determined by genetically abnormal cells, but also dependent on complex interactions between malignant cells and the surrounding microenvironment. This has led to reconsider the features of tumour microenvironment as potential predictive and prognostic markers. Among these markers, tumour stroma percentage (TSP) and tumour budding, as well as local tumour inflammatory infiltrate have received recent attention. In particular, the local environment of cytokines, proteases, angiogenic and growth factors secreted by inflammatory cells and stromal fibroblasts has identified crucial roles in facilitating tumour growth, and metastasis of cancer cells through lymphatic and/or blood vessel invasion. This might help understand the underlying process promoting tumour invasion into these vessels. An increase in the proportion of tumour stroma and an increase in the dissociation of tumour cells have been associated with poorer survival in a number of solid tumours, including breast cancer. However, the interrelationship between these variables and other features of the tumour microenvironment in different subgroups of breast cancer are not clear. Also, whether their prognostic values are independent of other components of the tumour microenvironment have yet to be identified. Therefore, the relationship between TSP, clinicopathological characteristics and outcome in patients with invasive ductal breast cancer, in particular node negative and triple negative disease was examined in patients with invasive ductal breast cancer (n=361). The TSP was assessed on the haematoxylin and eosin-stained tissue sections. With a cut-off value of 50% TSP, patients with ≤50% stroma were classified as the low-TSP group and those with >50% stroma were classified as the high-TSP group. A total of 109 (30%) patients had high TSP. Patients with high TSP were old age (P=0.035), had involved lymph node (P=0.049), Her-2 positive tumours (P=0.029), low-grade peri-tumoural inflammatory infiltrate (P=0.034), low CD68+ macrophage infiltrate (P<0.001), low CD4+ (P=0.023) and low CD8+ T-lymphocytes infiltrate (P=0.017), tumour recurrence (P=0.015) and shorter CSS (P<0.001). In node negative patients (n=207), high TSP was associated with low CD68+ macrophage infiltrate (P=0.001), low CD4+ (P=0.040) and low CD8+ T-lymphocytes infiltrate (P=0.016) and shorter CSS (P=0.005). In triple negative patients (n=103), high TSP was associated with increased tumour size (P=0.017) high tumour grade (P=0.014), low CD8+ T-lymphocytes infiltrate (P=0.048) and shorter CSS (P=0.041). The 15-year cancer specific survival rate was 79% vs 21% in the low-TSP group vs high-TSP group. On multivariate survival analysis, a high TSP was associated with reduced CSS in the whole cohort (P=0.007), node negative patients (P=0.005) and those who received systemic adjuvant therapy (P=0.016), independent of other pathological characteristics including local host inflammatory responses. Therefore, a high TSP in invasive ductal breast cancer was associated with recurrence and poorer long-term survival. The inverse relation with the tumour inflammatory infiltrate highlights the importance of the amount of tumour stroma on immunological response in patients with invasive ductal breast cancer. Implementing this simple and reproducible parameter in routine pathological examination may help optimise risk stratification in patients with breast cancer. Similarly, the relationship between tumour budding, clinicopathological characteristics and outcome was examined in patients with invasive ductal breast cancer (n=474), using routine pathological sections. Tumour budding was associated with several adverse pathological characteristics, including positive lymph node (P=0.009), presence of LVI (P<0.001), and high TSP (P=0.001) and low-grade general peri-tumural inflammatory infiltrative (P=0.002). In node negative patients, a high tumour budding was associated with presence of LVI (P<0.001) and low-grade general peri-tumural inflammatory infiltrative (P=0.038). On multivariate survival analysis, tumour budding was associated with reduced CSS (P=0.001), independent of nodal status, tumour necrosis, CD8+ and CD138+ inflammatory cells infiltrate, LVI, BVI and TSP. Furthermore, tumour budding was independently associated with reduced CSS in node negative patients (P=0.004) and in those who have low TSP (P=0.003) and high-grade peri-tumoural inflammatory infiltrative (P=0.012). A high tumour budding was significantly associated with shorter CSS in luminal B and triple negative breast cancer subtypes (all P<0.001). Therefore, tumour budding was a significant predictor of poor survival in patients with invasive ductal breast cancer, independent of adverse pathological characteristics and components of tumour microenvironment. These results suggest that tumour budding may promote disease progression through a direct effect on local and distant invasion into lymph nodes and lymphatic vessels. Therefore, detection of tumour buds at the stroma invasive front might therefore represent a morphologic link between tumour progression, lymphatic invasion, spread of tumour cells to regional lymph nodes, and the establishment of metastatic dissemination. Given the potential importance of the tumour microenvironment, the characterisation of intracellular signalling pathways is important in the tumour microenvironment and is of considerable interest. One plausible signalling molecule that links tumour stroma, inflammatory cell infiltrate and tumour budding is the signal transducer and activator of transcription (STAT). The relationship between total and phosphorylated STAT1 (ph-STAT1), and total and ph-STAT3 tumour cell expression, components of tumour microenvironment and survival in patients with invasive ductal breast cancer was examined. IHC of total and ph-STAT1/STAT3 was performed on tissue microarray of 384 breast cancer specimens. Cellular STAT1 and cellular STAT3 expression at both cytoplasmic and nuclear locations were combined and identified as STAT1/STAT3 tumour cell expression. These results were then related to CSS and phenotypic features of the tumour and host. A high ph-STAT1 and a high ph-STAT3 tumour cell expression was associated with increased ER (P=0.001 and P<0.001 respectively) and PR (all P<0.05), reduced tumour grade (P=0.015 and P<0.001 respectively) and necrosis (all P=0.001). Ph-STAT1 was associated with increased general peri-tumoural inflammatory infiltrate (P=0.007) and ph-STAT3 was associated with lower CD4+ T-lymphocyte infiltrate (P=0.024). On multivariate survival analysis, including both ph-STAT1 and ph-STAT3 tumour cell expression, only high ph-STAT3 tumour cell expression was significantly associated with improved CSS (P=0.010) independent of other tumour and host-based factors. In patients with high necrosis grade, high ph-STAT3 tumour cell expression was independent predictor of improved CSS (P=0.021). Ph-STAT1 and ph-STAT3 were also significantly associated with improved cancer specific survival in luminal A and B subtypes. STAT1 and STAT3 tumour cell expression appeared to be an important determinant of favourable outcome in patients with invasive ductal breast cancer. The present results suggest that STATs may affect disease outcome through direct impact on tumour cells, and the surrounding microenvironment. The above observations of the present thesis point to the importance of the tumour microenvironment in promoting tumour budding, LVI and BVI. The observations from STATs work may suggest that an important driving mechanism for the above associations is the presence of tumour necrosis, probably secondary to hypoxia. Further work is needed to examine the interaction of other molecular pathways involved in the tumour microenvironment, such as HIF and NFkB in patients with invasive ductal breast cancer.