Doctor of Philosophy

dissertationInfertility is traditionally defined as failure to achieve pregnancy after 12 or more months of regular unprotected intercourse; an estimated 10-15% of women experience infertility at some point in their reproductive life. The majority of infertility research has been focused on couples actively seeking treatment in specialty clinics, overlooking individuals who are infertile but not seeking medical specialty treatment. This dissertation uses data from the Fertility Experiences to examine the complexities of infertility research, treatment and interventions, and outcomes. Aim 1 compares approaches to collecting information about pregnancy attempt duration and identifies predictors of misestimating time at risk for pregnancy when assessing duration using a single question compared to discrete date event histories. Aim 2 provides information on the use of interventions to enhance fertility over the course of the reproductive life. Aim 3 examines the association between infertility treatment (ovulation stimulation, intrauterine insemination (IUI), and in-vitro fertilization (IVF)) used during the cycle of conception and preterm birth (<37 weeks completed gestation) using subfertile women who conceived spontaneously, without medical treatment, as controls. Aim one found that two-thirds of women substantially misestimated their biological time at risk for pregnancy when asked a single question. Detailed attempt histories, capturing specific dates, can provide a more nuanced assessment of biological time at risk of pregnancy, duration of intentional pregnancy attempt, and specifically the number of cycles where fertility focused intercourse is being used to ensure appropriately timed intercourse. Aim two found that women commonly use both medical and nonmedical interventions while trying to conceive. Primary care clinicians and fertility specialists should assume that nearly all their patients are using some type of nonmedical intervention and should take a full history that includes assessment of behavioral changes and complementary and alternative medicine. Aim three found that all fertility treatments (ovulation drugs, IUI, and IVF) were associated with a higher incidence of preterm birth, predominantly related to multiple gestation births. The findings support the use of treatment protocols that maximize singleton gestation. In addition, the findings highlight the increased risk of preterm birth in pregnancies conceived using any medical fertility treatment, not just IVF

The Correlation between Confidence and Knowledge of Evidence-Based Practice among Occupational Therapy Students

Evidence-based practice (EBP) is used throughout multiple health-care professions and includes the use of best research available, client preferences, and the practitioner’s experience. Occupational therapy educational programs are required to incorporate EBP into their curriculum. A convenience sample of occupational therapy students from a private university completed a survey designed to measure students’ knowledge and confidence in EBP. The survey consisted of the Knowledge of Research Evidence Competencies (K-REC) and the Evidence-Based Practice Confidence (EPIC) scale, as well as demographic questions. Of the respondents (n = 47), third-year students indicated higher confidence in the ability to utilize EBP and higher levels of knowledge related to EBP than second- or first-year students. The more didactic and clinical experience that the students had, the more knowledge related to EBP they had, which increased their confidence in the implementation of EBP. The knowledge and confidence that students gain of EBP within their educational training and clinical experiences can influence their future use and implementation of EBP as clinicians. Without this information, therapists will lack the confidence and ability to apply EBP principles in a changing and demanding health-care environment

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M&gt;70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0&lt;e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

The Correlation between Confidence and Knowledge of Evidence-Based Practice among Occupational Therapy Students

Evidence-based practice (EBP) is used throughout multiple health-care professions and includes the use of best research available, client preferences, and the practitioner’s experience. Occupational therapy educational programs are required to incorporate EBP into their curriculum. A convenience sample of occupational therapy students from a private university completed a survey designed to measure students’ knowledge and confidence in EBP. The survey consisted of the Knowledge of Research Evidence Competencies (K-REC) and the Evidence-Based Practice Confidence (EPIC) scale, as well as demographic questions. Of the respondents (n = 47), third-year students indicated higher confidence in the ability to utilize EBP and higher levels of knowledge related to EBP than second- or first-year students. The more didactic and clinical experience that the students had, the more knowledge related to EBP they had, which increased their confidence in the implementation of EBP. The knowledge and confidence that students gain of EBP within their educational training and clinical experiences can influence their future use and implementation of EBP as clinicians. Without this information, therapists will lack the confidence and ability to apply EBP principles in a changing and demanding health-care environment