Fluid-Structure-Jet Interaction Effects on High-Speed Vehicles

This dissertation is focused on two design considerations for supersonic intercept missiles: (i) increased structural slenderness and (ii) attitude control jets. The resulting new designs have the potential to increase vehicle performance, but will lead to a coupled fluid-structure-jet interaction that has yet to be studied. Numerical results of the vehicle response across the design space and flight envelope can be used as guidelines for assessment of improved control effectiveness, maneuverability and agility. First, vehicle models are developed that include slender structures and attitude control jets to conduct flight simulations. The numerical analysis of fluid-structure-jet interaction using these vehicle models deleted{helps to fill the gap in the literature and} provides insight into how this interaction can be leveraged during the design to improve performance. Next, approximate methods for including jet interaction effects are developed for slender high-speed vehicles. These methods allow for more complex geometry, a range of flight conditions, and varying control inputs. The jet interaction models are developed for flight simulation to maintain accuracy without significant computational cost. A detailed computational model of the maneuverable vehicle with fluid-structure-jet interaction is created to study the sensitivity to changes in flight conditions. These steady and dynamic results of the nonlinear system identify the conditions that may be difficult to model as well as those that can be exploited for improved performance. Next, modeling methods for the fluid-structure-jet interaction dynamics in flight are developed and evaluated using aggressive maneuvers throughout the flight envelope. Previous methods are evaluated to identify their effectiveness and a new method is developed specifically to model the nonlinear vehicle response to aggressive maneuvers. Finally, fluid-structure-jet interaction effects introduced by a slender missile body and attitude control jets are modeled during flight simulations. Multiple vehicle configurations are considered and the simulation results demonstrate the corresponding design modifications can impact vehicle maneuverability and agility. Overall, this dissertation explores a new topic in fluid-structure-jet interaction that arises due to new design trends that seek to improve intercept missile performance. New modeling methods were developed to analyze the problem and numerical simulation results identify regions where the fluid-structure-jet interaction significantly affects the vehicle response.PHDAerospace EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/147571/1/kitson_1.pd

High Speed Vehicle Fluid-Structure-Jet Interaction Analysis and Modeling

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143047/1/6.2017-0405.pd

Unsteady Fluid-Structure-Jet Interaction Modeling Methods for Agile High-Speed Vehicles

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143063/1/6.2017-4356.pd

Unsteady Fluid-Structure-Jet Interactions of Agile High-Speed Vehicles

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143059/1/6.2017-3549.pd

Polygenic risk score opportunities for early detection and prevention strategies in endometrial cancer

From Springer Nature via Jisc Publications RouterHistory: received 2020-04-08, rev-recd 2020-06-03, accepted 2020-06-10, registration 2020-06-12, pub-electronic 2020-07-06, online 2020-07-06, pub-print 2020-09-29Publication status: PublishedSummary: Recent large-scale genetic studies, particularly genome-wide association studies (GWAS), have emphasised the importance of common genetic variation in endometrial cancer susceptibility. Although each of these variants only confer modest effects on endometrial cancer risk, together they are likely to explain a substantial amount of the familial relative risk of the disease. Therefore, methods to combine genetic risk variants, such as polygenic risk scores (PRS) have gained traction as an attractive method for individualised risk prediction and management. Here, we discuss the benefits of a PRS for endometrial cancer and considerations required for clinical implementation

Detecting Endometrial Cancer by Blood Spectroscopy: A Diagnostic Cross-Sectional Study

Endometrial cancer is the sixth most common cancer in women, with a rising incidence worldwide. Current approaches for the diagnosis and screening of endometrial cancer are invasive, expensive or of moderate diagnostic accuracy, limiting their clinical utility. There is a need for cost-effective and minimally invasive approaches to facilitate the early detection and timely management of endometrial cancer. We analysed blood plasma samples in a cross-sectional diagnostic accuracy study of women with endometrial cancer (n = 342), its precursor lesion atypical hyperplasia (n = 68) and healthy controls (n = 242, total n = 652) using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy and machine learning algorithms. We show that blood-based infrared spectroscopy has the potential to detect endometrial cancer with 87% sensitivity and 78% specificity. Its accuracy is highest for Type I endometrial cancer, the most common subtype, and for atypical hyperplasia, with sensitivities of 91% and 100%, and specificities of 81% and 88%, respectively. Our large-cohort study shows that a simple blood test could enable the early detection of endometrial cancer of all stages in symptomatic women and provide the basis of a screening tool in high-risk groups. Such a test has the potential not only to differentially diagnose endometrial cancer but also to detect its precursor lesion atypical hyperplasia—the early recognition of which may allow fertility sparing management and cancer prevention

Public awareness and healthcare professional advice for obesity as a risk factor for cancer in the UK:a cross-sectional survey

BACKGROUND: Overweight and obesity is the second biggest preventable cause of cancer after smoking, causing ~3.4 million deaths worldwide. This study provides current UK data on awareness of the link between obesity and cancer by socio-demographic factors, including BMI, and explores to what degree healthcare professionals provide weight management advice to patients. METHODS: Cross-sectional survey of 3293 adults completed an online survey in February/March 2016, weighted to be representative of the UK population aged 18+. RESULTS: Public awareness of the link between obesity and cancer is low (25.4% unprompted and 57.5% prompted). Higher levels of awareness existed for least deprived groups (P < 0.001), compared to more deprived groups. Most respondents had seen a healthcare practitioner in the past 12 months (91.6%) and 17.4% had received advice about their weight, although 48.4% of the sample were overweight/obese. CONCLUSION: Cancer is not at the forefront of people’s minds when considering health conditions associated with overweight or obesity. Socio-economic disparities exist in health knowledge across the UK population, with adults from more affluent groups being most aware. Healthcare professionals are uniquely positioned to provide advice about weight, but opportunities for intervention are currently under-utilized in healthcare settings

The Proportion of Endometrial Tumours Associated with Lynch Syndrome (PETALS): a prospective cross-sectional study

This is the final version. Available on open access from the Public Library of Science via the DOI in this recordBackground: Lynch syndrome (LS) predisposes to endometrial (EC), colorectal and other cancers through inherited pathogenic variants affecting mismatch-repair (MMR) genes. Diagnosing LS in women with EC can reduce subsequent cancer mortality through colonoscopic surveillance and aspirin chemoprevention; it also enables cascade testing of relatives. A growing consensus supports LS screening in EC, however, the expected proportion of test-positives and optimal testing strategy is uncertain. Previous studies from insurance-based healthcare systems were limited by narrow selection criteria, failure to apply reference standard tests consistently and poor conversion to definitive testing. The aim of this study was to establish the prevalence of LS and the diagnostic accuracy of LS testing strategies in an unselected EC population. Methods and Findings: This was a prospective cross-sectional study carried out at a large UK gynaecological cancer centre between October/2015 and January/2017. Women diagnosed with EC or atypical hyperplasia (AH) were offered LS testing. Tumours underwent MMR immunohistochemistry (IHC), microsatellite instability (MSI) and targeted MLH1-methylation testing. Women <50 years, with strong family histories and/or indicative tumour molecular features underwent MMR germline sequencing. Somatic MMR sequencing was performed when indicative molecular features were unexplained by LS or MLH1-hypermethylation. The main outcome measures were the prevalence of LS in an unselected EC population and the diagnostic accuracy of clinical and tumour testing strategies for risk stratifying women with EC for MMR germline sequencing. In total, 500 women participated in the study; only 2 (<1%) declined. Germline sequencing was indicated and conducted for 136 and 135 women, respectively. 16/500 women (3.2%, 95% CI 1.8% to 5.1%) had LS and 11 more (2.2%) had MMR variants of uncertain significance. Restricting testing to age <50 years, indicative family history (revised Bethesda guidelines or Amsterdam-II criteria) or endometrioid histology alone would have missed 9 (56%), 11 (69%) or 12 (75%), and 5 (31%) of the 16 cases of LS, respectively. In total 132/500 tumours were MMR-deficient by IHC, of which 83/132 (63%) had MLH1-hypermethylation and 16/49 (33%) of the remaining patients had LS (16/132 with MMR-deficiency, 12%). MMR-IHC with targeted MLH1-methylation testing was more discriminatory for LS than MSI/methylation testing, with 100% versus 56.3% (16/16 versus 9/16) sensitivity (p=0.016) and equal 97.5% (468/484) specificity. 64% MSI-H and 73% MMR-deficient tumours unexplained by LS or MLH1-hypermethylation had somatic MMR-mutations. The main limitation of the study was failure to conduct MMR germline sequencing for the whole study population, which means that the sensitivity and specificity of tumour triage strategies for LS detection may be over-estimated, although the risk of LS in women with no clinical or tumour predictors is expected to be extremely low. Conclusions: In this study, we observed that age, family history and histology are imprecise clinical correlates of LS-EC. IHC outperformed MSI for tumour triage, and reliably identified both germline and somatic MMR mutations. The 3.2% proportion of LS-EC is similar to colorectal cancer, supporting unselected screening of EC for LS.

Divorce, conflict and mental health: how the quality of intimate relationships is linked to post-divorce well-being

Partner relationships, including new relationships after divorce, are found to be beneficial for mental health. However, the impact of their quality remains unclear; this uncertainty applies to past and ongoing relationships between ex-spouses as well. We study the relationship between conflict—in the prior marriage, with the ex-partner, with a new partner—and both positive and negative mental health. Multilevel linear models are carried out on a subsample of 892 divorcees from the dataset “Divorce in Flanders.” Living together with a new partner, either in marriage or cohabitation, seems beneficial for mental health, even in cases of (high) conflict. Nevertheless, conflict places a burden on well-being, especially for women in non-marital relationships. Ongoing conflict with the ex-spouse is also damaging for mental health. In contrast, prior marital conflict does not relate to lower, but to slightly higher, levels of life satisfaction after divorce

The Manchester International Consensus Group recommendations for the management of gynecological cancers in Lynch syndrome.

PURPOSE: There are no internationally agreed upon clinical guidelines as to which women with gynecological cancer would benefit from Lynch syndrome screening or how best to manage the risk of gynecological cancer in women with Lynch syndrome. The Manchester International Consensus Group was convened in April 2017 to address this unmet need. The aim of the Group was to develop clear and comprehensive clinical guidance regarding the management of the gynecological sequelae of Lynch syndrome based on existing evidence and expert opinion from medical professionals and patients. METHODS: Stakeholders from Europe and North America worked together over a two-day workshop to achieve consensus on best practice. RESULTS: Guidance was developed in four key areas: (1) whether women with gynecological cancer should be screened for Lynch syndrome and (2) how this should be done, (3) whether there was a role for gynecological surveillance in women at risk of Lynch syndrome, and (4) what preventive measures should be recommended for women with Lynch syndrome to reduce their risk of gynecological cancer. CONCLUSION: This document provides comprehensive clinical guidance that can be referenced by both patients and clinicians so that women with Lynch syndrome can expect and receive appropriate standards of care