High performance graph analysis on parallel architectures

PhD ThesisOver the last decade pharmacology has been developing computational methods to enhance drug development and testing. A computational method called network pharmacology uses graph analysis tools to determine protein target sets that can lead on better targeted drugs for diseases as Cancer. One promising area of network-based pharmacology is the detection of protein groups that can produce better e ects if they are targeted together by drugs. However, the e cient prediction of such protein combinations is still a bottleneck in the area of computational biology. The computational burden of the algorithms used by such protein prediction strategies to characterise the importance of such proteins consists an additional challenge for the eld of network pharmacology. Such computationally expensive graph algorithms as the all pairs shortest path (APSP) computation can a ect the overall drug discovery process as needed network analysis results cannot be given on time. An ideal solution for these highly intensive computations could be the use of super-computing. However, graph algorithms have datadriven computation dictated by the structure of the graph and this can lead to low compute capacity utilisation with execution times dominated by memory latency. Therefore, this thesis seeks optimised solutions for the real-world graph problems of critical node detection and e ectiveness characterisation emerged from the collaboration with a pioneer company in the eld of network pharmacology as part of a Knowledge Transfer Partnership (KTP) / Secondment (KTS). In particular, we examine how genetic algorithms could bene t the prediction of protein complexes where their removal could produce a more e ective 'druggable' impact. Furthermore, we investigate how the problem of all pairs shortest path (APSP) computation can be bene ted by the use of emerging parallel hardware architectures as GPU- and FPGA- desktop-based accelerators. In particular, we address the problem of critical node detection with the development of a heuristic search method. It is based on a genetic algorithm that computes optimised node combinations where their removal causes greater impact than common impact analysis strategies. Furthermore, we design a general pattern for parallel network analysis on multi-core architectures that considers graph's embedded properties. It is a divide and conquer approach that decomposes a graph into smaller subgraphs based on its strongly connected components and computes the all pairs shortest paths concurrently on GPU. Furthermore, we use linear algebra to design an APSP approach based on the BFS algorithm. We use algebraic expressions to transform the problem of path computation to multiple independent matrix-vector multiplications that are executed concurrently on FPGA. Finally, we analyse how the optimised solutions of perturbation analysis and parallel graph processing provided in this thesis will impact the drug discovery process.This research was part of a Knowledge Transfer Partnership (KTP) and Knowledge Transfer Secondment (KTS) between e-therapeutics PLC and Newcastle University. It was supported as a collaborative project by e-therapeutics PLC and Technology Strategy boar

The Organisational Justice as a Human Resources Management Practice and its Impact on Employee Engagement: The case of the Prefecture of Attica (Greece)

Organisational justice is a key component in the practice of human resources management in any work environment. The aim of this research survey is to highlight the meaning and importance of organisational justice and its impact on employee engagement. To achieve this aim, except for the literature review, the survey examines the extent to which the distributive, procedural and interactional justice impact on work and organisational engagement, through a research in a certain Greek public organisation. As regards the statistical analysis of the research hypotheses, we used methods of the SPSS 17.00 statistical package. The results showed that the distributive justice significantly impacts on both types of engagement, while no effect was detected between procedural justice and the two types of engagement. The interactional justice was found to determine, partly, only the organisational engagement. The findings overwhelmingly verified the existing bibliographical references, resulting in a noteworthy empirical precedent which could contribute to the field concerning the impact that organisational justice exerts on certain aspects of organisational behaviour.JEL Codes - M1; M1

Relationship between molecular characteristics of glioblastoma multiforme and the subventricular zone

Objective: This study aims to assess the relationship between the molecular characteristics of glioblastoma multiforme (GBM) and the subventricular zone (SVZ) Material and Methods: Eligible patients had their data anonymously collected from an institutional database, including age, sex, preoperative performance status, the extent of tumour resection, anatomical location, IDH mutation and MGMT methylation status. An Institutional picture archiving and communications system was used for volumetric and morphometric analysis. All measurements were made on T1-weighted magnetic resonance images with gadolinium contrast enhancement. IDH wild-type and mutant GBMs were stratified by MGMT methylation status. The relationship between tumour volume, distance from the tumour’s enhancing edge and the tumour’s geometric centre to the SVZ and their molecular characteristics were assessed. Results: Fifty IDH wild-type GBMs were studied. Twenty-three were MGMT methylated, Twenty-seven were unmethylated. IDH wild-type MGMT methylated GBMs were significantly associated with a tumour’s enhancing boundary being contiguous to the SVZ (P < 0.001). Ninety percent of tumours contiguous to the SVZ were wild-type methylated (n = 18) and 10% were unmethylated (n = 2). Mean GBM geometric centre distance to SVZ was significantly less for methylated wild-type GBMs compared to unmethylated (P = 0.025) and median GBM distance from the tumour’s edge of enhancement to the SVZ was significantly shorter in methylated tumours compared to unmethylated (P < 0.001). Mean and median distances to SVZ from the edge of enhancement was 3.8 millimetres (mm) and 0 mm, respectively, for wild-type methylated GBMs, while for unmethylated wild-types, 14.6 mm, and 12.5 mm. There was no anatomical localisation of IDH wild-type GBMs by MGMT methylation status to a cerebral hemisphere or lobe. Conclusion: IDH wild-type GBMs contiguous to the SVZ are highly likely to be MGMT methylated. Replication by further studies is required to affirm our results and conclusion

Two cases of SMA syndrome after neurosurgical injury to the frontal aslant tract

Supplementary motor area (SMA) syndrome is characterised by transient disturbance in volitional movement and speech production which classically occurs after injury to the medial premotor area. We present two cases of SMA syndrome following isolated surgical injury to the frontal aslant tract (FAT) with the SMA intact. The first case occurred after resection of a left frontal operculum tumour. The second case occurred after a transcortical approach to a ventricular neurocytoma. The clinical picture and fMRI activation patterns during recovery were typical for SMA syndrome and support the theory that the FAT is a critical bundle in the SMA complex function

Outdoor particulate matter and childhood asthma admissions in Athens, Greece: a time-series study

<p>Abstract</p> <p>Background</p> <p>Particulate matter with diameter less than 10 micrometers (PM₁₀) that originates from anthropogenic activities and natural sources may settle in the bronchi and cause adverse effects possibly via oxidative stress in susceptible individuals, such as asthmatic children. This study aimed to investigate the effect of outdoor PM₁₀concentrations on childhood asthma admissions (CAA) in Athens, Greece.</p> <p>Methods</p> <p>Daily counts of CAA from the three Children's Hospitals within the greater Athens' area were obtained from the hospital records during a four-year period (2001-2004, n = 3602 children). Mean daily PM₁₀concentrations recorded by the air pollution-monitoring network of the greater Athens area were also collected. The relationship between CAA and PM₁₀concentrations was investigated using the Generalized Linear Models with Poisson distribution and logistic analysis.</p> <p>Results</p> <p>There was a statistically significant (95% CL) relationship between CAA and mean daily PM₁₀concentrations on the day of exposure (+3.8% for 10 μg/m³increase in PM₁₀concentrations), while a 1-day lag (+3.4% for 10 μg/m³increase in PM₁₀concentrations) and a 4-day lag (+4.3% for 10 μg/m³increase in PM₁₀concentrations) were observed for older asthmatic children (5-14 year-old). High mean daily PM₁₀concentration (the highest 10%; >65.69 μg/m³) doubled the risk of asthma exacerbations even in younger asthmatic children (0-4 year-old).</p> <p>Conclusions</p> <p>Our results provide evidence of the adverse effect of PM₁₀on the rates of paediatric asthma exacerbations and hospital admissions. A four-day lag effect between PM₁₀peak exposure and asthma admissions was also observed in the older age group.</p

The Organisational Justice as a Human Resources Management Practice and its Impact on Employee Engagement: The case of the Prefecture of Attica (Greece)

Organisational justice is a key component in the practice of human resources management in any work environment. The aim of this research survey is to highlight the meaning and importance of organisational justice and its impact on employee engagement. To achieve this aim, except for the literature review, the survey examines the extent to which the distributive, procedural and interactional justice impact on work and organisational engagement, through a research in a certain Greek public organisation. As regards the statistical analysis of the research hypotheses, we used methods of the SPSS 17.00 statistical package. The results showed that the distributive justice significantly impacts on both types of engagement, while no effect was detected between procedural justice and the two types of engagement. The interactional justice was found to determine, partly, only the organisational engagement. The findings overwhelmingly verified the existing bibliographical references, resulting in a noteworthy empirical precedent which could contribute to the field concerning the impact that organisational justice exerts on certain aspects of organisational behaviour

Immune checkpoint inhibitors in urothelial cancer: recent updates and future outlook

Bladder cancer is the sixth most common cancer in the US and most tumors have urothelial (transitional cell) histology. Platinum-based chemotherapy has long been the standard of care in advanced disease, but long-term outcomes have largely remained poor. Since the peak incidence of bladder cancer is in the eighth decade of life and beyond, medical comorbidities may often limit the use of chemotherapy. Immune checkpoint inhibitors with their favorable toxicity profiles and notable antitumor activity have ushered in a new era in the treatment of advanced urothelial cancer (UC) with five agents targeting the PD-1/PD-L1 pathway being recently approved by the US Food and Drug administration. A plethora of clinical trials are ongoing in diverse disease settings, employing agents targeting PD-1/PD-L1 and related immune checkpoint pathways. While reactivating anti-tumor immunity, these agents may lead to a unique constellation of immune-related adverse events, which may warrant discontinuation of therapy and potential use of immunosuppression. Novel combinations with various treatment modalities and optimal sequencing of active therapies are being investigated in prospective clinical trials and retrospective registries. At the era of precision molecular medicine, and since patients do not respond uniformly to these agents, there is a growing need for identification and validation of biomarkers that can accurately predict treatment response and assist in patient selection. This review discusses current updates and future directions of immunotherapy in advanced UC