Towards Precision Cosmology on the Largest Observable Scales

One of the primary goals of cosmology is to extract information about fundamental physics from observations of the universe on large scales. With the advent of increasingly large cosmological datasets (and correspondingly small statistical uncertainties), future progress in the field will fundamentally be determined by our ability to account for systematic errors, understand model predictions, and protect analyses from sources of bias. This thesis presents three projects in this theme. We first examine the interpretation of large-angle features of the Cosmic Microwave Background (CMB) which are statistically unlikely in Lambda-CDM. Particularly, we study some of these features might be due to the imprint of large scale structure (LSS) through the integrated Sachs-Wolfe (ISW) effect, testing the reliability of a method for ISW signal reconstruction based on LSS data. Using simulated ISW and LSS maps, we show that direction-dependent calibration errors are by far the most limiting survey systematic and that for current levels of calibration control, reconstructed ISW maps from existing data are almost entirely noise. Thus, current data cannot be reliably used to separate primordial and late-time contributions to CMB features. We additionally use ensembles of simulated CMB maps to perform a comprehensive study of the covariance between eight features associated with commonly studied large-angle anomalies. The latter part of this thesis shifts its focus to LSS data, introducing a new method for blinding the Dark Energy Survey's (DES) combined analysis of correlations between galaxy positions and weak lensing shear. This technique, which works by modifying LSS tracers' two-point correlation functions, will be used to prevent experimenter bias from influencing DES' precision measurements of dark energy. We demonstrate using simulated DES Year 3 data that this method successfully shifts the analysis pipeline's output cosmological parameters while preserving the ability to check for systematic errors. Given this, the technique will be used to blind the DES Year 3 multi-probe cosmology analyses, and as implemented, will be the most sophisticated blinding strategy for a cosmology analysis to date. Together, these three projects represent varied ways characterizing and developing tools for ensuring future tests of Lambda-CDM are both precise and accurate.PHDPhysicsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/146041/1/jlmuir_1.pd

A new mini-navigation tool allows accurate component placement during anterior total hip arthroplasty.

Introduction: Computer-assisted navigation systems have been explored in total hip arthroplasty (THA) to improve component positioning. While these systems traditionally rely on anterior pelvic plane registration, variances in soft tissue thickness overlying anatomical landmarks can lead to registration error, and the supine coronal plane has instead been proposed. The purpose of this study was to evaluate the accuracy of a novel navigation tool, using registration of the anterior pelvic plane or supine coronal plane during simulated anterior THA. Methods: Measurements regarding the acetabular component position, and changes in leg length and offset were recorded. Benchtop phantoms and target measurement values commonly seen in surgery were used for analysis. Measurements for anteversion and inclination, and changes in leg length and offset were recorded by the navigation tool and compared with the known target value of the simulation. Pearson\u27s Results: The device accurately measured cup position and leg length measurements to within 1° and 1 mm of the known target values, respectively. Across all simulations, there was a strong, positive relationship between values obtained by the device and the known target values ( Conclusion: The preliminary findings of this study suggest that the novel navigation tool tested is a potentially viable tool to improve the accuracy of component placement during THA using the anterior approach

Modulation of RECK levels in Xenopus A6 cells: effects on MT1-MMP, MMP-2 and pERK levels

Background: MT1-MMP is a cell-surface enzyme whose regulation of pro-MMP-2 and ERK activation position it as a key facilitator of ECM remodelling and cell migration. These processes are modulated by endogenous MMP inhibitors, such as RECK, a GPI-anchored protein which has been shown to inhibit both MT1-MMP and MMP-2 activity. Our previous studies have revealed a link between MT1-MMP levels, and pro-MMP-2 and ERK activation in mammalian cells, as well as MT1-MMP and RECK co-localization in Xenopus embryos. We here investigated how modulation of RECK would impact MT1-MMP and MMP-2 levels, as well as ERK signalling in Xenopus A6 cells. Results: We used a Morpholino approach to knockdown RECK, plasmid transfection to overexpress RECK, and PI-PLC treatment to shed RECK from the cell surface of Xenopus A6 cells. RECK reduction did not alter pERK or MT1-MMP levels, nor MMP-2 activity as measured by zymography; thus RECK-knockdown cells maintained the ability to remodel the ECM. RECK overexpression and PI-PLC treatment both increased ECM remodelling potential through increased MT1-MMP protein and relative MMP-2 activation levels. Conclusions: RECK changes that reduce the ability of the cell to remodel the ECM (overexpression and cell surface shedding) are compensated for by increases in MT1-MMP, and MMP-2 levels as seen by zymography

Insight gained from responses to surveys on reference dosimetry practices

PURPOSE: To present the results and discuss potential insights gained through surveys on reference dosimetry practices. METHODS: Two surveys were sent to medical physicists to learn about the current state of reference dosimetry practices at radiation oncology clinics worldwide. A short survey designed to maximize response rate was made publicly available and distributed via the AAPM website and a medical physics list server. Another, much more involved survey, was sent to a smaller group of physicists to gain insight on detailed dosimetry practices. The questions were diverse, covering reference dosimetry practices on topics like measurements required for beam quality specification, the actual measurement of absorbed dose and ancillary equipment required like electrometers and environment monitoring measurements. RESULTS: There were 190 respondents to the short survey and seven respondents to the detailed survey. The diversity of responses indicates nonuniformity in reference dosimetry practices and differences in interpretation of reference dosimetry protocols. CONCLUSIONS: The results of these surveys offer insight on clinical reference dosimetry practices and will be useful in identifying current and future needs for reference dosimetry

Isolation of a New Infectious Pancreatic Necrosis Virus (IPNV) Variant from a Fish Farm in Scotland

The aquatic virus, infectious pancreatic necrosis virus (IPNV), is known to infect various farmed fish, in particular salmonids, and is responsible for large economic losses in the aquaculture industry. Common practices to detect the virus include qPCR tests based on specific primers and serum neutralization tests for virus serotyping. Following the potential presence of IPNV viruses in a fish farm in Scotland containing vaccinated and IPNV-resistant fish, the common serotyping of the IPNV isolates was not made possible. This led us to determine the complete genome of the new IPNV isolates in order to investigate the cause of the serotyping discrepancy. Next-generation sequencing using the Illumina technology along with the sequence-independent single primer amplification (SISPA) approach was conducted to fully characterize the new Scottish isolates. With this approach, the full genome of two isolates, V1810–4 and V1810–6, was determined and analyzed. The potential origin of the virus isolates was investigated by phylogenetic analyses along with tridimensional and secondary protein structure analyses. These revealed the emergence of a new variant from one of the main virus serotypes, probably caused by the presence of selective pressure exerted by the vaccinated IPNV-resistant farmed fish