Survival data analysis using neural networks

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT

Handling high level of censoring for endovascular aortic repair risk prediction

Feature selection is important in medical field for many reasons. However, selecting important variables is a difficult task with the presence of censoring that is a unique feature in survival data analysis. This paper proposed an approach to deal with the censoring problem in endovascular aortic repair survival data through Bayesian networks. It was merged and embedded with a hybrid feature selection process that combines cox's univariate analysis with machine learning approaches such as ensemble artificial neural networks to select the most relevant predictive variables. The proposed algorithm was compared with common survival variable selection approaches such as; least absolute shrinkage and selection operator LASSO, and Akaike information criterion AIC methods. The results showed that it was capable of dealing with high censoring in the datasets. Moreover, ensemble classifiers increased the area under the roc curves of the two datasets collected from two centers located in United Kingdom separately. Furthermore, ensembles constructed with center 1 enhanced the concordance index of center 2 prediction compared to the model built with a single network. Although the size of the final reduced model using the neural networks and its ensembles is greater than other methods, the model outperformed the others in both concordance index and sensitivity for center 2 prediction. This indicates the reduced model is more powerful for cross center prediction.

Studies on survival of Pseudomonas aeruginosa 6750

The growth of Pseudomonas aeruginosa 6750 as a biofilm was investigated using a novel system based on that of Gilbert et al (1989). The aim was to test the effect of controlled growth of the organism on antibiotic susceptibility and examine the survival of the organism as a biofilm. During the investigations it became clear that, because of the increasing growth of P.aeruginosa and production of exopolysaccharide, a growth rate controlled monolayer could not be achieved and so the method was not used further. The data, however, showed that there was an increase in the smooth colony type of the organism during growth. Investigations were focused on the survival of P.aeruginosa in batch and chemostat studies. Survival or percentage culturability, as measured by total and colony count ratio, was found to decrease both in extended batch culture and for chemostat cells with decreasing growth rate. Extended batch culture, however, did not exhibit further increases in resistance to ciprofloxacin and polymyxin B. Survival was also measured using other parameters namely the direct viable count, vital staining, effect of temperature downshift and measurement of lag. In batch culture, the most notable change was a decrease in cell size along the growth curve. This was accompanied by an increase in the cellular protein content. Protein per volume was calculated from the data which showed a marked increase in batch culture, which was not demonstrated for chemostat cells with decreasing growth rate. Outer membrane protein profiles were obtained for batch and chemostat cells. An LPS profile of batch culture cells was also demonstrated. In general, there was little difference in the outer membrane protein profiles of cells from early and late stationary phases.The result of the LPS profile showed that there appeared to be an increase in the B-band of the region of the LPS in the older stationary phase cultures.

Which factors drive firm survival within an industry boundary over time?:the UK onshore oil and gas production industry 1984-1999

This thesis looks at the UK onshore oil and gas production industry and follows the history of a population of firms over a fifteen-year period following the industry's renaissance. It examines the linkage between firm survival, selection pressures and adaptation responses at the firm level, especially the role of discretionary adaptation, specifically exploration and exploitation strategies.Taking a Realist approach and using quantitative and qualitative methods for triangulation on a new data base derived from archival data, as well as informant interviews, it tests seven hypotheses' about post-entry survival of firms. The quantitative findings suggest that firm survival within this industry is linked to discretionary adaptation, when measured at the firm level, and to a mixture of selection and adaptation forces when measured for each firm for each individual year. The qualitative research suggests that selection factors dominate. This difference in views is unresolved. However the small, sparse population and the nature of the oil and gas industry compared with other common research contexts such as manufacturing or service firms suggests the results be treated with caution as befits a preliminary investigation. The major findings include limited support for the theory that the external environment is the major determinant of firm survival, though environment components affect firms differentially; resolution of apparent literature differences relating to the sequencing of exploration and exploitation and potential tangible evidence of coevolution. The research also finds that, though selection may be considered important by industry players, discretionary adaptation appears to play the key role, and that the key survival drivers for thispopulation are intra-industry ties, exploitation experience and a learning/experience component. Selection has a place, however, in determining the life-cycle of the firm returning to be a key survival driver at certain ages of the firm inside the industry boundary.

Survival or success? A critical exploration of the use of 'double-voiced discourse' by women business leaders in the UK

This article considers whether using leadership language may be one under-explored reason why there continues to be a significant lack of women at executive level. Do women make less of a linguistic impact in the boardroom than men? By analysing linguistic data from senior management meetings and follow-up interviews in seven multinational UK companies, we suggest that senior women and men use a very similar range of linguistic strategies to lead their teams except in one key respect. Women appear to monitor and regulate their use of language more than men, adjusting what they say in the light of their colleagues’ concerns and agendas. This use of ‘double-voiced discourse’ (Bakhtin, 1994/1963) enables women to survive in a male-dominated business world, but this can sometimes make their voice ‘harder to hear’. However, double-voiced discourse is also a form of linguistic expertise and potentially might offer women leaders a strategy for success.

Nrf2 activation supports cell survival during hypoxia and hypoxia/reoxygenation in cardiomyoblasts; the roles of reactive oxygen and nitrogen species

Adaptive mechanisms involving upregulation of cytoprotective genes under the control of transcription factors such as Nrf2 exist to protect cells from permanent damage and dysfunction under stress conditions. Here we explore of the hypothesis that Nrf2 activation by reactive oxygen and nitrogen species modulates cytotoxicity during hypoxia (H) with and without reoxygenation (H/R) in H9C2 cardiomyoblasts. Using MnTBap as a cell permeable superoxide dismutase (SOD) mimetic and peroxynitrite scavenger and L-NAME as an inhibitor of nitric oxide synthase (NOS), we have shown that MnTBap inhibited the cytotoxic effects of hypoxic stress with and without reoxygenation. However, L-NAME only afforded protection during H. Under reoxygenation, conditions, cytotoxicity was increased by the presence of L-NAME. Nrf2 activation was inhibited independently by MnTBap and L-NAME under H and H/R. The increased cytotoxicity and inhibition of Nrf2 activation by the presence of L-NAME during reoxygenation suggests that NOS activity plays an important role in cell survival at least in part via Nrf2-independent pathways. In contrast, O2 -• scavenging by MnTBap prevented both toxicity and Nrf2 activation during H and H/R implying that toxicity is largely dependent on O2 -.To confirm the importance of Nrf2 for myoblast metabolism, Nrf2 knockdown with siRNA reduced cell survival by 50% during 4h hypoxia with and without 2h of reoxygenation and although cellular glutathione (GSH) was depleted during H and H/R, GSH loss was not exacerbated by Nrf2 knockdown. These data support distinctive roles for ROS and RNS during H and H/R for Nrf2 induction which are important for survival independently of GSH salvage. © 2013 The Authors.

Innovation and the survival of new firms in the UK

This paper analyzes the survival over the subsequent 5-year period of the complete cohort of nearly 162,000 limited companies that incorporated in Britain in 2001. The paper focuses on the relationship between innovation and survival at the firm-level. The data available allow us to look at the intellectual property (IP) activity of all British firms, including that of the cohort of new firms in 2001. The results indicate that IP activity, measured as patenting and trade-marking, is associated with a considerably lower probability of exit. We also find substantial differences in survival probabilities across sectors. In some sectors patenting is associated with a lower probability of exit; however, trade-marking is associated with lower probability in almost all sectors.

Infection with Anaplasma phagocytophilum activates the phosphatidylinositol 3-Kinase/Akt and NF-κB survival pathways in neutrophil granulocytes

Anaplasma phagocytophilum, a Gram-negative, obligate intracellular bacterium infects primarily neutrophil granulocytes. Infection with A. phagocytophilum leads to inhibition of neutrophil apoptosis and consequently contributes to the longevity of the host cells. Previous studies demonstrated that the infection inhibits the executionary apoptotic machinery in neutrophils. However, little attempt has been made to explore which survival signals are modulated by the pathogen. The aim of the present study was to clarify whether the phosphatidylinositol 3-kinase (PI3K)/Akt and NF-?B signaling pathways, which are considered as important survival pathways in neutrophils, are involved in A. phagocytophilum-induced apoptosis delay. Our data show that infection of neutrophils with A. phagocytophilum activates the PI3K/Akt pathway and suggest that this pathway, which in turn maintains the expression of the antiapoptotic protein Mcl-1, contributes to the infection-induced apoptosis delay. In addition, the PI3K/Akt pathway is involved in the activation of NF-?B in A. phagocytophilum-infected neutrophils. Activation of NF-?B leads to the release of interleukin-8 (IL-8) from infected neutrophils, which, in an autocrine manner, delays neutrophil apoptosis. In addition, enhanced expression of the antiapoptotic protein cIAP2 was observed in A. phagocytophilum-infected neutrophils. Taken together, the data indicate that upstream of the apoptotic cascade, signaling via the PI3K/Akt pathway plays a major role for apoptosis delay in A. phagocytophilum-infected neutrophils.

Innovation and the survival of new firms across British regions

This paper analyses the survival of the complete cohort of more than 162,000 limited companies incorporated in Britain in 2001 over the subsequent five-year period. For this purpose, we estimate firms' hazards of failure and survival functions using nonparametric and semi-parametric techniques. The paper focuses on two important policy-related issues.The first is to what extent survival rates vary across regions in Britain. A second, and related, policy issue concerns innovation. The data available allows us to look at the intellectual property (IP) activity of all British firms, including that of the 162,000 new firms in 2001. The results indicate substantial differences in survival rates across regions, and also that IP activity is associated with a higher probability of survival. These differences across regions, and the importance of IP activity, remain when we condition on a large range of regional, industry and firm-level characteristics shifting firms' hazards of failure.

Legibility, privacy and creativity:linked data in a surveillance society

This paper looks at the issue of privacy and anonymity through the prism of Scott's concept of legibility i.e. the desire of the state to obtain an ever more accurate mapping of its domain and the actors in its domain. We argue that privacy was absent in village life in the past, and it has arisen as a temporary phenomenon arising from the lack of appropriate technology to make all life in the city legible. Cities have been the loci of creativity for the major part of human civilisation. There is something specific about the illegibility of cities which facilitates creativity and innovation. By providing the technology to catalogue and classify all objects and ideas around us, this leads to a consideration of semantic web technologies, Linked Data and the Internet of Things as unwittingly furthering this ever greater legibility. There is a danger that the over description of a domain will lead to a loss in creativity and innovation. We conclude by arguing that our prime concern must be to preserve illegibility because the survival of some form, any form, of civilisation depends upon it.

The Long-Term impact of Business Support? - Exploring the Role of Evaluation Timing using Micro Data

The original contribution of this work is threefold. Firstly, this thesis develops a critical perspective on current evaluation practice of business support, with focus on the timing of evaluation. The general time frame applied for business support policy evaluation is limited to one to two, seldom three years post intervention. This is despite calls for long-term impact studies by various authors, concerned about time lags before effects are fully realised. This desire for long-term evaluation opposes the requirements by policy-makers and funders, seeking quick results. Also, current ‘best practice’ frameworks do not refer to timing or its implications, and data availability affects the ability to undertake long-term evaluation. Secondly, this thesis provides methodological value for follow-up and similar studies by using data linking of scheme-beneficiary data with official performance datasets. Thus data availability problems are avoided through the use of secondary data. Thirdly, this thesis builds the evidence, through the application of a longitudinal impact study of small business support in England, covering seven years of post intervention data. This illustrates the variability of results for different evaluation periods, and the value in using multiple years of data for a robust understanding of support impact. For survival, impact of assistance is found to be immediate, but limited. Concerning growth, significant impact centres on a two to three year period post intervention for the linear selection and quantile regression models – positive for employment and turnover, negative for productivity. Attribution of impact may present a problem for subsequent periods. The results clearly support the argument for the use of longitudinal data and analysis, and a greater appreciation by evaluators of the factor time. This analysis recommends a time frame of four to five years post intervention for soft business support evaluation.

Survival in the pre-senile dementia frontotemporal lobar degeneration with TDP-43 proteinopathy:effects of genetic, demographic and neuropathological variables

Factors associated with survival were studied in 84 neuropathologically documented cases of the pre-senile dementia frontotemporal dementia lobar degeneration (FTLD) with transactive response (TAR) DNA-binding protein of 43 kDa (TDP-43) proteinopathy (FTLD-TDP). Kaplan-Meier survival analysis estimated mean survival as 7.9 years (range: 1-19 years, SD = 4.64). Familial and sporadic cases exhibited similar survival, including progranulin (GRN) gene mutation cases. No significant differences in survival were associated with sex, disease onset, Braak disease stage, or disease subtype, but higher survival was associated with lower post-mortem brain weight. Survival was significantly reduced in cases with associated motor neuron disease (FTLD-MND) but increased with Alzheimer's disease (AD) or hippocampal sclerosis (HS) co-morbidity. Cox regression analysis suggested that reduced survival was associated with increased densities of neuronal cytoplasmic inclusions (NCI) while increased survival was associated with greater densities of enlarged neurons (EN) in the frontal and temporal lobes. The data suggest that: (1) survival in FTLD-TDP is more prolonged than typical in pre-senile dementia but shorter than some clinical subtypes such as the semantic variant of primary progressive aphasia (svPPA), (2) MND co-morbidity predicts poor survival, and (3) NCI may develop early and EN later in the disease. The data have implications for both neuropathological characterization and subtyping of FTLD-TDP.

The long-term impact of business support? - Exploring the role of evaluation timing using micro data

The original contribution of this work is threefold. Firstly, this thesis develops a critical perspective on current evaluation practice of business support, with focus on the timing of evaluation. The general time frame applied for business support policy evaluation is limited to one to two, seldom three years post intervention. This is despite calls for long-term impact studies by various authors, concerned about time lags before effects are fully realised. This desire for long-term evaluation opposes the requirements by policy-makers and funders, seeking quick results. Also, current ‘best practice’ frameworks do not refer to timing or its implications, and data availability affects the ability to undertake long-term evaluation. Secondly, this thesis provides methodological value for follow-up and similar studies by using data linking of scheme-beneficiary data with official performance datasets. Thus data availability problems are avoided through the use of secondary data. Thirdly, this thesis builds the evidence, through the application of a longitudinal impact study of small business support in England, covering seven years of post intervention data. This illustrates the variability of results for different evaluation periods, and the value in using multiple years of data for a robust understanding of support impact. For survival, impact of assistance is found to be immediate, but limited. Concerning growth, significant impact centres on a two to three year period post intervention for the linear selection and quantile regression models – positive for employment and turnover, negative for productivity. Attribution of impact may present a problem for subsequent periods. The results clearly support the argument for the use of longitudinal data and analysis, and a greater appreciation by evaluators of the factor time. This analysis recommends a time frame of four to five years post intervention for soft business support evaluation.