Population-Based Placental Weight Ratio Distributions and Determinants of Placental Weight Ratios

The placental weight ratio (PWR) is a common proxy for the balance between fetal and placental growth, and is defined as the placental weight over the birth weight. The objectives were (1a) to establish PWR distributions by gestational age for the overall population and (1b) for small, average and large for gestational age infants (SGA, AGA, LGA) and (2) to determine what pregnancy related conditions were associated with the PWR. The data were obtained using a hospital based retrospective cohort. Nonparametric quantile regression was used for the first and multinomial logistic regression for the second objective. The results show how the PWR changes across gestation. SGA infants had higher PWR’s than AGA and LGA infants. The multivariable analyses showed that the majority of risk factors were associated with a PWR\u3e90th percentile. The overall curves offer population standards, and the multivariable analysis suggests that the placental may have a particular compensatory response, each with a distinct pathophysiologic mechanism, but similar PWR outcome

Omics measures of ageing and disease susceptibility

While genomics has been a major field of study for decades due to relatively inexpensive genotyping arrays, the recent advancement of technology has also allowed the measure and study of various “omics”. There are now numerous methods and platforms available that allow high throughput and high dimensional quantification of many types of biological molecules. Traditional genomics and transcriptomics are now joined by proteomics, metabolomics, glycomics, lipidomics and epigenomics. I was lucky to have access to a unique resource in the Orkney Complex Disease Study (ORCADES), a cohort of individuals from the Orkney Islands that are extremely deeply annotated. Approximately 1000 individuals in ORCADES have genomics, proteomics, lipidomics, glycomics, metabolomics, epigenomics, clinical risk factors and disease phenotypes, as well as body composition measurements from whole body scans. In addition to these cross-sectional omics and health related measures, these individuals also have linked electronic health records (EHR) available, allowing the assessment of the effect of these omics measures on incident disease over a ~10-year follow up period. In this thesis I use this phenotype rich resource to investigate the relationship between multiple types of omics measures and both ageing and health outcomes. First, I used the ORCADES data to construct measures of biological age (BA). The idea that there is an underlying rate at which the body deteriorates with age that varies between individuals of the same chronological age, this biological age, would be more indicative of health status, functional capacity and risk of age-related diseases than chronological age. Previous models estimating BA (ageing clocks) have predominantly been built using a single type of omics assay and comparison between different omics ageing clocks has been limited. I performed the most exhaustive comparison of different omics ageing clocks yet, with eleven clocks spanning nine different omics assays. I show that different omics clocks overlap in the information they provide about age, that some omics clocks track more generalised ageing while others track specific disease risk factors and that omics ageing clocks are prognostic of incident disease over and above chronological age. Second, I assessed whether individually or in multivariable models, omics measures are associated with health-related risk factors or prognostic of incident disease over 10 years post-assessment. I show that 2,686 single omics biomarkers are associated with 10 risk factors and 44 subsequent incident diseases. I also show that models built using multiple biomarkers from whole body scans, metabolomics, proteomics and clinical risk factors are prognostic of subsequent diabetes mellitus and that clinical risk factors are prognostic of incident hypertensive disorders, obesity, ischaemic heart disease and Framingham risk score. Third, I investigated the genetic architecture of a subset of the proteomics measures available in ORCADES, specifically 184 cardiovascular-related proteins. Combining genome-wide association (GWAS) summary statistics from ORCADES and 17 other cohorts from the SCALLOP Consortium, giving a maximum sample size of 26,494 individuals, I performed 184 genome-wide association meta-analyses (GWAMAs) on the levels of these proteins circulating in plasma. I discovered 592 independent significant loci associated with the levels of at least one protein. I found that between 8-37% of these significant loci colocalise with known expression quantitative trait loci (eQTL). I also find evidence of causal associations between 11 plasma protein levels and disease susceptibility using Mendelian randomisation, highlighting potential candidate drug targets

From upper limits to detection: continuous gravitational waves in the advanced detector era

This thesis concerns continuous gravitational wave signals from non-axisymmetric neutron stars and ground-based interferometric detectors. These detectors are currently being upgraded and this thesis explores relevant issues and methods to prepare for the advanced detector era. A study into sensitivity dependence on the addition of a southern hemisphere detector for a targeted continuous wave search is first presented. Next, we study the effect of close and/or high velocity neutron stars on the ability of a blind, all-sky search to make a detection. Initial results from a narrowband search for signals from the Crab Pulsar and a blind hardware injected signal are then presented. Finally, we describe the development and initial implementation of a large-scale mock data challenge designed to test current continuous wave algorithms to explore various issues before we enter the advanced detector era

Variations in signal-to-noise characteristics of tissue-equivalent attenuators for mammographic automatic exposure control system performance evaluation

PURPOSE: This work investigates the impact of tissue-equivalent attenuator choice on measured signal-to-noise ratio (SNR) for automatic exposure control (AEC) performance evaluation in digital mammography. It also investigates how the SNR changes for each material when used to evaluate AEC performance across different mammography systems. METHODS: AEC performance was evaluated for four mammography systems using seven attenuator sets at two thicknesses (4 and 8 cm). All systems were evaluated in 2D imaging mode, and one system was evaluated in digital breast tomosynthesis (DBT) mode. The methodology followed the 2018 ACR digital mammography quality control (DMQC) manual. Each system-attenuator-thickness combination was evaluated using For Processing images in ImageJ with standard ROI size and location. The closest annual physicist testing results were used to explore the impact of varying measured AEC performance on image quality. RESULTS: The measured SNR varied by 44%-54% within each system across all attenuators at 4 cm thickness in 2D mode. The variation appeared to be largely due to changes in measured noise, with variations of 46%-67% within each system across all attenuators at 4 cm thickness in 2D mode. Two systems had failing SNR levels for two of the materials using the minimum SNR criterion specified in the ACR DMQC manual. Similar trends were seen in DBT mode and at 8 cm thickness. Within each material, there was 115%-131% variation at 4 cm and 82%-114% variation at 8 cm in the measured SNR across the four imaging systems. Variation in SNR did not correlate with system operating level based on visual image quality and average glandular dose (AGD). CONCLUSION: Choice of tissue-equivalent attenuator for AEC performance evaluation affects measured SNR values. Depending on the material, the difference may be enough to result in failure following the longitudinal and absolute thresholds specified in the ACR DMQC manual

Optimal Operator Training Reference Models for Human-in-the-loop Systems

The human operator is an integral part of a stable and safe power system. While there is increasing attention paid to automation improvements, the importance of understanding and training human operators may be understated. This paper discusses a project to enhance operator training programs by evaluating human performance relative to a reference operator model identified using optimal control theory. Along with establishing a simple computer-based operator workstation for future training purpose, this paper describes the optimal control response design methodology for a human-in-the-loop power system experiment. The overall system model is presented. An optimal controller synthesis methodology is applied to the model system and the optimal controller is designed. The performance of the optimal controller is then compared to human subject performance

The Construction of Preference in Engineering Design and Implications for Green Products

This dissertation incorporates the construction of preference into engineering design methodology. Currently, engineers view customer preferences as existing a priori, evoking metaphors such as “need-finding.” For some product design activities this perspective is sufficient, but for others it is limiting. Behavioral psychology research asserts that individuals construct preferences on a case-by-case basis when called to make a decision. Decisions about products that are both psychologically and functionally complex are likely subject to inconsistent preference construction and dependent on context. This is problematic; for example, customer preferences exhibited during design-research interactions may be different from preferences exhibited in the market. This dissertation investigates green products, which resonate with people’s environmental values, yet are difficult to evaluate in terms of environmental impact. A literature review suggests eight cognitive reasons why preference for green products may be highly inconsistent. Three contributions are provided: (1) A framework for identifying and representing decision context in preference models and a related case-study of modeling preference inconsistency versus heterogeneity. It is found that modeling both is useful to designers; and that only some people have inconsistent preference for green products. (2) A design optimization that includes construction of preference as an uncertain parameter and as a variable. It is found that a green product’s success in the market increases when preference is actively controlled, for example, through design, education, and advertising efforts. (3) A design method that uses manipulations of preference construction to identify customer-perceived relationships between product attributes. The crux-sentinel attribute relationship is formally defined, and specific relationships between product attributes are identified in a case-study demonstration. People have an ever-increasing amount of choice in their product decisions, and interpreting and reacting to the nuances of their preferences is crucial to product design success. Manifold psychological issues have become important during product purchase and use, such as concern for the environment, safety, morality, and individualism. This dissertation demonstrates that issues of psychological import can have unanticipated effects on product decisions, via the construction of preference. Designers can use the design methods presented here to address these effects and shape the product decisions of the future.Ph.D.Mechanical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/60660/1/erinmacd_1.pd

NIRDs Unite: Building a Community of Institutional Repository Practitioners in the Northeast

The idea for “Northeast Institutional Repository Day” (NIRD) was conceived by a group of five repository librarians in the northeast. The organizers sent out a pre-conference online survey to the IR community in November 2018 to see if fellow repository practitioners had an interest in attending and/or participating in such a day and the response was a resounding, “Yes!” The survey results suggested that building a stronger regional network of repository managers would foster meaningful discussions on the merits and effectiveness of IRs