Micro-CT Scanning in the Investigation of Squat Defects in Rail Steel

This thesis contains the results from an investigation into Squats, a discrete rail steel defect. Micro-computed tomography (micro-CT) scanning was used to scan the entire structure of four out of five defects removed from railway track. The fifth was not scanned as it shelled in track. The difficulty turning these raw X-ray images into a segmented 3D model were overcome by developing a new technique. Isolating separate regions of the scans created areas where voxel value variation was at a minimum (i.e. the histogram became one narrow peak rather than multiple broad peaks). This allowed the automatic crack segregation module to work fairly well, and then enhanced using the region growing modules within the software. These scan results were then verified to be accurate using metallographic sample preparation, optical and electron microscopy. Micro CT scanning was performed on a custom 450KeV scanner, allowing the capture of the first entire Squat crack network morphology. Full defect imaging allowed the different defects to be compared to each other, highlighting differences and similarities. The defects came from metro, mixed and high-speed railways and one was found within an aluminothermic weld. The verification process and investigations of the scan volumes yielded further information about the defect’s origins. These origins were used to determine that, for the five defects investigated, there were four different causes. The two that shared a cause were from the same track section. Based on the causes, the defects were identified as a Stud, two Grinding Induced Squats (GIS), a Squat (caused by the legacy issue of MnS inclusions) and possibly a Squat or Stud in a slightly contaminated weld. None of the defects were considered to be a classic Squat, which is caused by Rolling Contact Fatigue (RCF), because there were other factors in their initiation. One of the defects contained a transverse defect, which is a crack that grows down through the railhead and can break the rail. This transverse defect was ~9mm deep into the rail when it was removed, meaning it would not have returned to the surface to shell. A high-resolution volume of the transverse defect region was created and its origin gives an important insight into the potential causes of rail-breaking defects. The origin of this transverse defect was a cluster of debris-filled voids that had formed due to the corrosion and cyclic loading (fretting) of a crack branch. These voids aligned with a deep grinding mark on the surface of the rail, which acted as a stress raiser. Because corrosion is a factor in this transverse defect case, the age of a rail and its environment are factors for defect development as well as traffic volume, given the correlation of corrosion with time. Results of this work highlight both the importance of a good surface finish and the diversity of causes found within the term “Squat”. Thus the identification of the Stud variant may be the beginning of a more comprehensive group of Squat type defects being established. This refining of the category could lead to fruitful big data analyses of the Squat type defect occurrences. The CT volumes of the defects created in this work can easily be stored for comparison in future investigations. The virtual nature of the volumes allows the sharing of defect information more readily than physical and sectioned defects, which deteriorate with time and require physical storage and transport

Generation of Genic Diversity among Streptococcus pneumoniae Strains via Horizontal Gene Transfer during a Chronic Polyclonal Pediatric Infection

Although there is tremendous interest in understanding the evolutionary roles of horizontal gene transfer (HGT) processes that occur during chronic polyclonal infections, to date there have been few studies that directly address this topic. We have characterized multiple HGT events that most likely occurred during polyclonal infection among nasopharyngeal strains of Streptococcus pneumoniae recovered from a child suffering from chronic upper respiratory and middle-ear infections. Whole genome sequencing and comparative genomics were performed on six isolates collected during symptomatic episodes over a period of seven months. From these comparisons we determined that five of the isolates were genetically highly similar and likely represented a dominant lineage. We analyzed all genic and allelic differences among all six isolates and found that all differences tended to occur within contiguous genomic blocks, suggestive of strain evolution by homologous recombination. From these analyses we identified three strains (two of which were recovered on two different occasions) that appear to have been derived sequentially, one from the next, each by multiple recombination events. We also identified a fourth strain that contains many of the genomic segments that differentiate the three highly related strains from one another, and have hypothesized that this fourth strain may have served as a donor multiple times in the evolution of the dominant strain line. The variations among the parent, daughter, and grand-daughter recombinant strains collectively cover greater than seven percent of the genome and are grouped into 23 chromosomal clusters. While capturing in vivo HGT, these data support the distributed genome hypothesis and suggest that a single competence event in pneumococci can result in the replacement of DNA at multiple non-adjacent loci

Verification of the use of micro-CT scanning to assess the features of entire squat type defects

Squats and studs are defects in railheads that share features, but have different causes. This paper examined four squat and stud samples from three different traffic environments to compare features using μ-CT X-ray scans, surface and subsurface inspection. μ-CT scanning has been used before as a non-destructive method to investigate rail defects, but not the entire defect. The scans were verified and allowed the identification of areas of interest when sectioning the samples further. The scan volumes were also used to create 3D models of the crack networks for the 3 samples that were scanned. All defects contain similar superficial features but the depth and severity of the subsurface damage varies. This work provides a visualisation of the 3D nature of studs in a way not seen before, as a 3D model the crack network from an in-service defect. The models of two of the defects showed the influence of hollow wheels initiating defects, as the crack seemed to initiate on the field side, grow down and towards the gauge side, before resurfacing as the longitudinal crack noted in all four defect samples. One sample is believed to have initiated due to contamination of the weld and the only squat sample, which failed in track, was believed to be ingot cast steel containing many inclusions. Three samples were studs and one was a squat. Each defect developed for different reasons, although the two metro samples were similar. One of the studs shows branching of cracks that, based on its changing angle of growth, could continue to grow into transverse defects, breaking the rail. The three defects that were scanned would all be classed as studs, but their crack morphology varies, possibly because they are all from different traffic environments. They also show slight differences to other studs in literature

Assemblathon 2: evaluating de novo methods of genome assembly in three vertebrate species

Background: The process of generating raw genome sequence data continues to become cheaper, faster, and more accurate. However, assembly of such data into high-quality, finished genome sequences remains challenging. Many genome assembly tools are available, but they differ greatly in terms of their performance (speed, scalability, hardware requirements, acceptance of newer read technologies) and in their final output (composition of assembled sequence). More importantly, it remains largely unclear how to best assess the quality of assembled genome sequences. The Assemblathon competitions are intended to assess current state-of-the-art methods in genome assembly. Results: In Assemblathon 2, we provided a variety of sequence data to be assembled for three vertebrate species (a bird, a fish, and snake). This resulted in a total of 43 submitted assemblies from 21 participating teams. We evaluated these assemblies using a combination of optical map data, Fosmid sequences, and several statistical methods. From over 100 different metrics, we chose ten key measures by which to assess the overall quality of the assemblies. Conclusions: Many current genome assemblers produced useful assemblies, containing a significant representation of their genes and overall genome structure. However, the high degree of variability between the entries suggests that there is still much room for improvement in the field of genome assembly and that approaches which work well in assembling the genome of one species may not necessarily work well for another

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease

BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .)

Identifying Barriers to Preventive/Primary Care Utilization of Men in a Rural Setting

The purpose of the project was to identify barriers preventing men living in a rural setting, ages 19-60 from participating in routine preventative/primary care. Nationally and globally, men experience greater rates of morbidity and mortality due to chronic illness (Xu, Murphy, Kochanek, Bastian, & Arius, 2018). The literature suggests men do not routinely engage in primary care services (Centers for Disease Control and Prevention [CDC], 2015). The lack of participation leads to men experiencing poorer health outcomes (Banks & Baker, 2013; Baker & Shand, 2017; Pinkashov et al., 2013). Consistent and early access to primary care will help reduce the disparity and improve male health outcomes. The objectives of the practice improvement project (PIP) were: (1) identify actual and potential primary care uptake barriers of men aged 19-60 in a rural ND community; (2) discuss those barriers with rural ND healthcare clinic providers and clinical director and provide recommendations to improve men’s uptake in primary care services; and (3) measure effectiveness of providers implementing recommendations to reduce those barriers. Participants were recruited to voluntarily complete a 20-item questionnaire, free blood pressure screening, body fat analysis, and grip test. The survey results identified barriers in the areas of health literacy, confidentiality, empowerment, and self-efficacy. Through the utilization of a barrier screening survey, the coinvestigator was able to implement an educational presentation to the rural providers. The educational session provided interventional strategies for improving male utilization of primary care services. As result of the PIP, the rural healthcare organization was able to adopt two of the recommendations into practice. Additionally, the coinvestigator recommended incorporating body fat analysis and grip testing into the yearly examination. The screenings are relatively low-cost and non-invasive. Both screenings can offer the provider additional information regarding the overall health of their patients (Legrand et al., 2014; Park et al., 2019; Prasitsiriphon & Pothisiri, 2018). The additional health information can lead to more informed decision making and potentially aid in improved health outcomes for the patients