Compliance analysis for cyber security marine standards : Evaluation of compliance using application lifecycle management tools

The aim of this thesis is to analyse cyber security requirements and notations from marine classification societies and other entities to understand how to meet compliance in current cyber security requirements from maritime class societies and other maritime organizations. The methods used in this research involved a desk review of cyber security requirements from IACS members, IACS UR E 27 and IEC 62443, a survey questionnaire of relevant cyber security standards pertinent to maritime product development, and Polarion, an application lifecycle management solution used to synthesize the cyber security requirements from the maritime class societies and determine their correlations to IEC 62443 as a baseline. Results indicate that IEC 62443 correlates to the standards from DNV and IACS (UR E 27) and majority of the requirements were deemed compliant in compliance gap assessments of a maritime product. The conclusion is that IEC 62443 can be utilised as a baseline cyber requirement with a requirements management tool like Polarion to analyse and satisfy compliance requirements from maritime class societies and maritime organizations that base their cyber security requirements according to IACS UR E27 and IEC 62443-3-3 and should be adopted in addressing future compliance analysis of cyber requirements focusing on autonomous shipping

Analysis of Expression Patterns: The Scope of the Problem, the Problem of Scope

Studies of the expression patterns of many genes simultaneously lead to the observation that even in closely related pathologies, there are numerous genes that are differentially expressed in consistent patterns correlated to each sample type. The early uses of the enabling technology, microarrays, was focused on gathering mechanistic biological insights. The early findings now pose another clear challenge, finding ways to effectively use this kind of information to develop diagnostics

Reperfusion after Fibrinolytic Therapy (RAFT) : an open-label, multi-centre, randomised controlled trial of bivalirudin versus heparin in rescue percutaneous coronary intervention

Background The safety and efficacy profile of bivalirudin has not been examined in a randomised controlled trial of patients undergoing rescue PCI. Objectives We conducted an open-label, multi-centre, randomised controlled trial to compare bivalirudin with heparin ± glycoprotein IIb/IIIa inhibitors (GPIs) in patients undergoing rescue PCI. Methods Between 2010–2015, we randomly assigned 83 patients undergoing rescue PCI to bivalirudin (n = 42) or heparin ± GPIs (n = 41). The primary safety endpoint was any ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) bleeding at 90 days. The primary efficacy endpoint was infarct size measured by peak troponin levels as a multiple of the local upper reference limit (Tn/URL). Secondary endpoints included periprocedural change in haemoglobin adjusted for red cells transfused, TIMI (Thrombolysis in Myocardial Infarction) bleeding, ST-segment recovery and infarct size determined by the Selvester QRS score. Results The trial was terminated due to slow recruitment and futility after an interim analysis of 83 patients. The primary safety endpoint occurred in 6 (14%) patients in the bivalirudin group (4.8% GPIs) and 3 (7.3%) in the heparin ± GPIs group (54% GPIs) (risk ratio, 1.95, 95% confidence interval [CI], 0.52–7.3, P = 0.48). Infarct size was similar between the two groups (mean Tn/URL, 730 [±675] for bivalirudin, versus 984 [±1585] for heparin ± GPIs, difference, 254, 95% CI, -283-794, P = 0.86). There was a smaller decrease in the periprocedural haemoglobin level with bivalirudin than heparin ± GPIs (-7.5% [±15] versus -14% [±17], difference, -6.5%, 95% CI, -0.83–14, P = 0.0067). The rate of complete (≥70%) ST-segment recovery post-PCI was higher in patients randomised to heparin ± GPIs compared with bivalirudin. Conclusions Whether bivalirudin compared with heparin ± GPI reduces bleeding in rescue PCI could not be determined. Slow recruitment and futility in the context of lower-than-expected bleeding event rates led to the termination of this trial (ANZCTR.org.au, ACTRN12610000152022)

Dysregulation of Biomarkers of Hemostatic Activation and Inflammatory Processes are Associated with Adverse Outcomes in Pulmonary Embolism

Introduction: The pathophysiology of pulmonary embolism (PE) represents complex, multifactorial processes involving blood cells, vascular endothelium, and the activation of inflammatory pathways. Platelet (P), endothelial (E), and leukocyte (L)-selectin molecules may play an important role in PE pathophysiology. We aimed to profile the biomarkers of inflammation, including selectins in PE patients, and compare them to healthy individuals. Materials and methods: 100 acute PE patients and 50 controls were included in this case control study. ELISA methods were used to quantify levels of selectins, inflammatory, and hemostatic biomarkers. Results: In PE patients, levels of selectin molecules as compared to controls convey increased P-selectin levels (95 ng/mL vs 40 ng/mL, p \u3c .0001) and decreased L-selectin levels (1468 ng/mL vs 1934 ng/mL, p \u3c .0001). Significant correlations were found between selectins and Plasminogen Activating Inhibitor-1 (PAI-1), Tumor Necrosis Factor-a (TNFa), and D-dimer. Fold change between selectins and controls is compared to other biomarkers, illustrating degrees of change comparable to TNFa, alpha-2-antiplasmin, and microparticles. L-selectin levels are inversely associated with all-cause-mortality in PE patients, (p = .040). Conclusion: These studies suggest that various thrombo-inflammatory biomarkers are elevated in PE patients. Furthermore, L-selectin levels are inversely associated with mortality outcomes

Upregulation of Inflammatory Cytokines in Pulmonary Embolism Using Biochip-Array Profiling.

The complex pathophysiology of pulmonary embolism (PE) involves hemostatic activation, inflammatory processes, cellular dysfunction, and hemodynamic derangements. Due to the heterogeneity of this disease, risk stratification and diagnosis remains challenging. Biochip-array technology provides an integrated high throughput method for analyzing blood plasma samples for the simultaneous measurement of multiple biomarkers for potential risk stratification. Using biochip-array method, this study aimed to quantify the inflammatory biomarkers such as interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, vascular endothelial growth factor (VEGF), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and epidermal growth factor (EGF) in 109 clinically confirmed PE patients in comparison to the control group comprised of plasma samples collected from 48 healthy subjects. Cytokines IL-4, IL-6, IL-8, IL-10, IL-1β, and MCP-1 demonstrated varying level of significant increase (P \u3c 0.05) in massive-risk PE patients compared to submassive- and low-risk PE patients. The upregulation of inflammatory cytokines in PE patients observed in this study suggest that inflammation plays an important role in the overall pathophysiology of this disease. The application of biochip-array technology may provide a useful approach to evaluate these biomarkers to understand the pathogenesis and risk stratification of PE patients

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file

Genome-Wide Analyses Reveal a Role for Peptide Hormones in Planarian Germline Development

Genomic/peptidomic analyses of the planarian Schmidtea mediterranea identifies >200 neuropeptides and uncovers a conserved neuropeptide required for proper maturation and maintenance of the reproductive system