Bradford Scholars: Recent submissions
Now showing items 1-20 of 10628
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Pathways to public life for professional women in Afghanistan: Negotiating shifting patriarchal political regimes and gender regimesThis thesis examines how Afghan women from the professional social class have negotiated the patriarchy in that country and claimed their agency and public life during different political regimes. Resisting the Western representation of Afghan women as passive victims, it uses the life story method, based on interviews with a wide range of women in public life during the period of US-sponsored democracy and intervention, to analyse the complex factors involved in enabling women to access public life. From a historical sociological viewpoint it examines the shifts in the forms of patriarchy and their sustaining gender regimes from 19th century to the present, and draws on Walby’s six structures of patriarchy in order to understand how those shift affected the ability of women to access public life and employment. Those structures – culture, religion, education, employment, family – are explored through the experiences and life histories of my interviewees. The thesis also pays attention to the involvement of external, foreign actors in the affairs of Afghanistan and the impact of those interventions on the possibility for women’s agency and participation in professional and public life through different political regimes. It thus challenges a simplistic view 9/11 was a water-shed moment for women’s empowerment, and notes that the economic is-sues, an aid-dependent economy and political regimes, security and safety, poverty and psychological trauma, corruption and power struggles among different forces (local and foreign) in many ways undermined women’s prospects in public life. The finding of the research shows that the rights and position of women in Afghanistan have fluctuated over the last 100 years depending on the patriarchal cultural, political and religious ideology and practice of the political regimes, and in no small part due to the influence and interference of external actors in the country.
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Microscopic Sampling of Dentine and Bone Collagen: Development of Sampling Methods for Carbon and Nitrogen Isotope AnalysisSampling methods for dentine and bone collagen have been evolving for several decades. Incremental dentine collagen sampling and bone collagen sampling have been limited by the available technology throughout that time. As the technology for isotope ratio mass spectrometry analysis improves, the sampling methods should improve as well. This research focused on developing a new incremental dentine collagen sampling method and bone collagen microsampling method for stable isotope analysis. This research aimed to increase the temporal resolution of incremental dentine collagen sampling and provided sequential collagen sampling from bone collagen for stable carbon and nitrogen isotope analysis while limiting the destructive nature of bioarchaeological analysis. It was determined that the temporal resolution for incremental analysis could be reduced to approximate three months, opposed to the nine months found in other sampling methods. It was also determined that detailed isotopic data could be obtained from bone collagen when sampling the microstructures. The increased amount of isotopic data from the bone collagen was an improvement on the commonly used bulk collagen sampling. This research can be utilised to answer several of the questions that archaeologists have been asking about past populations. Isotopic analysis using the methods developed in the research can provide a more detailed observation of the diet and health of past populations. In addition, the developed methods for bone and dentine collagen reduced the amount of tissue subjected to destructive analysis.
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Role of N-terminal residues of CCL19 and CCL21 in binding and activation of CCR7Chemokines are chemotactic cytokines, which mediate cell trafficking and play a key role in mobilisation of leukocytes. More recently, chemokines and their cognate receptors have been described as key players in different aspects of cancer biology contributing to proliferation, angiogenesis and metastasis. In particular, chemokines CCL19 and CCL21 acting on their associated receptor CCR7 are postulated to be key drivers of lymph node metastasis in a number of malignancies including breast, colon, gastric, & thyroid cancers. It has been reported that the cleavage of the pre-cysteine bridge N-terminal residues of CCL21 (SDGGAQD) and of CCL19 (GTNDAED) renders both peptides incapable of fully activating CCR7. However, little is known about the nature of the interactions that occur between the N-terminal residues of CCL19 or CCL21 and the CCR7 receptor, or the role they have in activation of CCR7. The aim of this study is to investigate the role of the residues in the N-terminus of CCL19 and in particular CCL21 in the context of CCR7 activation and to use this information in the discovery of novel CCR7 antagonists or agonists. To achieve this, we synthesised a number of short (three to seven amino acids) peptides and peptidomimetics inspired by the seven N-terminal amino acid residues of CCL19 and CCL21 and pharmacologically characterised their ability to activate CCR7 or block the activation of CCR7 using a number of in vitro assays such as calcium flux, trans-well (Boyden chamber), and Western blotting. We also carried out computational studies to better understand and predict the activity of these peptides. Our results demonstrate that some of these peptides are indeed capable of acting as agonists or antagonists of CCR7.
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Crystal Engineering of Pharmaceuticals: Modulating Physicochemical Properties of Active Ingredients by the Formation of CocrystalsPharmaceuticals with suitable therapeutic properties often found to encounter challenges with dosage form development due to their poor physicochemical properties. Aim of thesis is to evaluate potential of crystal engineering directed cocrystallisation of active ingredients in modulating their physical attributes. The model compounds considered are isoniazid, caffeine, nifedipine, glyburide, chlorpropamide and riboflavin. Co-formers selected are based on the suitability of functional groups for hydrogen bond formation. Co-crystal screening and preparation methods used include neat grinding (NG), liquid assisted grinding (LAG) and solution crystallisation. Antituberculosis drug, isoniazid, upon cocrystallisation with melamine, solubility has reduced as per high performance liquid chromatography assay, however, antimicrobial properties determined using REMA assay confirms that cocrystal anti-mycobacterial activity is not compromised. Next, caffeine-glutaric acid cocrystal polymorphic forms (Forms I and II) subjected to mechanical property evaluations in multiple faces using nanoindentation and correlated relationship between crystal structure and mechanical property. The results suggest that metastable form, Form I, could display suitable tablet properties to that of thermodynamically stable form, Form II. Subsequently, photosensitive drug, nifedipine, cocrystallised with theophylline and caffeine. Notably, photochemical stability along with solubility and drug release of cocrystals is found to be superior to that of nifedipine. Lastly, crystal engineering principles utilised in preparation of multicomponent crystals of antidiabetic model drugs, glyburide and chlorpropamide with various coformers. Interestingly, during the preparation of chlorpropamide-2-nitrobenzyl alcohol, high Z prime crystal (Z’=3) of 2- nitrobenzyl alcohol is serendipitously identified. In conclusion, crystal engineering based cocrystallisation is a viable technology for modulating physicochemical properties of pharma and nutraceuticals.
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En face OCT imaging for the assessment of glaucomaGlaucoma is a leading cause of irreversible vision loss globally, and demands early and accurate diagnosis. OCT has become a key investigative technique in glaucoma, and, although it provides invaluable clinical support, detection of early glaucoma remains imperfect. Recent OCT developments enabled direct assessment of retinal nerve fibre bundle (RNFB) reflectance in en face OCT images. The technique has considerable potential in the assessment of glaucoma, yet it has limited clinical usability due to an incomplete understanding of RNFB features in healthy and glaucoma eyes and the lack of accepted methods to identify reflectance defects. This thesis aimed to better understand characteristics of RNFB reflectance in en face OCT imaging and to develop objective methods to extract defects in this domain. Structural and functional measures of glaucoma changes were collected in eyes with established glaucoma and age-similar controls. Results showed that the healthy configuration of RNFB varies across the retina and between different eyes. We developed a method for automated and objective examination of reflectivity changes in en face images. This method considers individual anatomy and varying RNFB configuration, and found more abnormalities than previous approaches. Measures of en face reflectance and conventional retinal nerve fibre layer thickness were strongly related. The agreement between changes of reflectance and visual function was moderate-to-good, and both testing domains presented concordant abnormalities in all tested eyes. Following further minimisation of artefacts in en face images, direct use of reflectance analysis or its combination with perimetry appear viable and with significant potential for clinical examination of glaucoma.
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What were the effects of the post-colonial experience of counterinsurgency on UK forces in southern Iraq? Were the lessons absorbed and implemented?This thesis examines the British army and its legacy of counterinsurgency from the 20th century. It analyses the effects of post-colonial counterinsurgency and the army’s ability to learn from previous counterinsurgency conflicts to create new doctrine from earlier examples that could have had lessons for the UK forces in southern Iraq. Doctrine (both official and unofficial) ranges from endorsed army field manuals to theory written by experts while on defence fellowships. The army’s ability to create new doctrine from previous campaigns lessons and how it is diffused across the armed forces is also assessed. The conflicts used as post-colonial counterinsurgencies scrutinise Oman and Northern Ireland. These two case studies provide mixed lessons, that should advance and expand British counterinsurgency theory and models. The previous historical occurrences of counterinsurgency have created a British approach which has established a four-pillar framework which encompasses minimum force, civil-military co-operation, use of intelligence and tactical flexibility. This approach could identify lessons for a modern British army deployed to Iraq. If lessons and previous outcomes are analysed to create new doctrine, strategy and tactics that encompass the four pillars framework, what went wrong in southern Iraq? Could lessons from earlier campaigns have assisted British efforts?
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Impact of Foreign Directors on Firms’ Corporate Governance, Risk and PerformanceThis thesis explores board nationality diversity, focusing on foreign non-executive directors and their relationship with CEO compensation, firm performance, and crash risk for a sample of UK firms from 2002 to 2015. First, we examine the changes in board composition over the years and find an increase in foreign non-executive directors and in the number of foreign CEOs managing UK firms. We discover boards have become smaller, more independent and CEOs occupying dual roles have considerably reduced. Next, we analyse the relationship between foreign non executive directors and CEO compensation and note that firms with more foreign non executive directors pay less to their CEO. Moreover, European and other international non-executive directors are particularly effective at limiting CEO compensation. Then we examine the impact of foreign non-executive directors on firm performance and show that foreign non-executive directors positively impact firm value. CEO and executive directors’ equity-like compensation and share ownership also positively influences firm performance. Our findings suggest that European and American non executive directors are more effective in improving corporate performance. Finally, we analyse the relationship between foreign non-executive directors, CEO compensation and crash risk. Foreign non-executive directors monitor the board and mitigate the impact of CEO equity-linked pay on stock price crash risk. Our analysis reveals that leverage increases crash risk, but that foreign non-executive directors, of high leverage firms lower crash risk. Overall, foreign non-executive directors serve as effective monitors and advisors to moderate executive pay, improve firm performance and reduce stock price crash risk.
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Development of ambient-cured geopolymer mortars with construction and demolition waste-based materialsDegrading infrastructure and applications of structural demolition create tremendous amounts of construction and demolition waste (CDW) all around the world. To address this issue in an effective way, recycling CDW in a most appropriate way has become a global concern in recent years. To this end, this study focused on the valorization of CDW-based materials such as tile, bricks, glass, and concrete in the development of geopolymer mortars. CDWs were first collected from demolition zone and then subjected to crushing-milling operations. To investigate the influence of slag (S) addition to the mixtures, 20% S substituted mixture designs were also made. Fine recycled concrete aggregates (FRCA) obtained from crushing and sieving of the waste concrete were used as the aggregate. A series of mixtures were designed using different proportions of three distinct alkali activators such as sodium hydroxide (NaOH), sodium silicate (Na2SiO3), and calcium hydroxide (CH; Ca(OH)2). To improve their applicability, the mixtures were left to cure at room temperature rather than the heat curing which is frequently applied in the literature. After 28 days ambient curing, the 100% CDW-based geopolymer mortar activated with three different activators reached a compressive strength of 31.6 MPa, whereas the 20% S substituted geopolymer mortar showed a 51.9 MPa compressive strength. While the geopolymer mortars activated with only NaOH exhibited poor performance, it was found that the use of Na2SiO3 and CH improved the mechanical performance. Main geopolymerization products were related to NASH (Sodium alumino-silicate hydrate), CASH (Calcium alumino-silicate hydrate), and C(N)ASH gel formations. Results demonstrated that mixed CDWs can be employed in the manufacturing geopolymers, making them potential alternatives to Portland cement (PC)-based systems by being eco-friendly, energy-efficient, and comparable in compressive strength.
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Mandatory CSR disclosure, institutional ownership and firm value: Evidence from ChinaThis study aims to contribute to the relevant accounting, corporate gover-nance, and corporate social responsibility (CSR) literature by examining thevalue relevance of mandatory CSR disclosures in China. Using a difference-in-differences (DID) research design and a sample based on propensity scorematching (PSM) over the period from 2003 to 2020, our findings suggest thatmandatory CSR disclosures are negatively associated with firm' values. We alsofind that firms with a high level of institutional ownership and leverage experi-ence a relatively lower drop in firms' values as a result of the mandatory CSRdisclosures. These findings remain robust to alternative sampling design, use of market to book value as an alternative measure of firms' market-based performance, and a parallel test to validate our DID analysis. Our findings have useful implications for managers, regulators, policy makers and other stakeholders.
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Financing constraints, intellectual property rights protection and incremental innovation: Evidence from transition economy firmsDespite a growing literature, the relationship between financing constraints (FC), intellectual property rights (IPR) protection and firm innovation remains unclear within the transitional country context. Drawing on endogenous growth theory and extending the Gorodnichenko and Schnitzer (2013) framework, we hypothesize that in addition to firm-specific factors, country-level variables manifested within FC hamper incremental innovation, albeit in varying degrees due to industry heterogeneity. Secondly, as opposed to previous studies that solely focus on FC affecting firm innovation, we propose that due to resource constraints, firms in transition economies tend to follow an imitational innovation strategy, and therefore, from this perspective, IPR protection can be crucial for firm-level innovation within those economies. Using data from the World Bank Enterprise Survey (WBES) consisting of information for about 21,960 firms from 27 Eastern European and Central Asian transition countries and employing a two-step probit model with endogenous regressors, we find that adverse effects of FC and IPR on firms' innovation activities are driven from within as well as between industries. Focusing on the differential impacts of FC and IPR protection across industries, we direct potential causal pathways from easing FC and optimal IPR protection to encourage firms' innovation. Based on the findings, while very strict IPR protection is detrimental to firms' product and process innovation in industries with limited resource and skill capabilities, it is nevertheless helpful for research and development (R&D) activities in industries characterised by strong R&D and IP capacities. Our results offer useful insights for policymakers to support incremental innovation as well as boost invention. IPR protection policies require to be customised to the industries and firms, since invariably tight or lax IPR enforcement can be discouraging to both incremental and radical innovation, causing all industries suffering from the same treatment.
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PotteryAn interim report on pottery recovered during underwater surveys undertaken around a series of artificial islets on the islands of North and South Uist in 2022.
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PotteryAn interim report on pottery excavated at the Neolithic islet of Loch Bhorgastail, Isle of Lewis, Scotland, in 2021.
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Interfacial characteristics of nano-engineered concrete compositesThis study investigates the interfacial characteristics between aggregates and cement paste matrix in nanofillers modified concrete. A three-point bend test on the specimens composed of two pieces of aggregates bonded with a thin layer of cement pastes with/without nanofillers was carried out to characterize the interfacial bond strength of the composites. The scanning electron microscope observations and energy dispersive x-ray spectrometry analysis were also performed to characterize the interfacial microstructures and compositions of the composites. The experimental results indicated that the nanocomposites have higher interfacial bond strength and narrower interfacial transition zone thickness as well as more optimized intrinsic compositions and microstructures than that of composites without nanofillers. Specifically, the interfacial bond strength of nanocomposites can reach 7.67 MPa, which is 3.03 MPa/65.3% higher than that of composites without nanofillers. The interfacial transition zone thickness of nanocomposites ranges from 9 μm to 12 μm, while that of composites without nanofillers is about 18 μm. The ratio of CaO to SiO2 in the interface of composites without nanofillers is 0.69, and that of nanocomposites increases to 0.75–1.12. Meanwhile, the nanofiller content in nanocomposite interface is 1.65–1.98 times more than that in the bulk matrix. The interfacial microstructures of nanocomposites are more compact and the content and crystal size of calcium hydroxide were significantly reduced compared with that of composites without nanofillers.
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Performance of single and hybrid nanoparticles added concrete at ambient and elevated temperaturesThe main aim of this study is to investigate the effects of nano-SiO2 (NS), nano-Al2O3 (NA), nano-TiO2 (NT) and nano-Fe2O3 (NF) particles in single, binary, ternary, and quaternary combinations on compressive, splitting tensile, and flexural strengths of concrete. The residual compressive strength of control and nano-added concretes are also determined at 300, 500, and 800 °C elevated temperatures. Furthermore, X-ray diffraction (XRD) and scanning electron microscope (SEM) analyses have been conducted to examine the chemical composition and microstructure of concrete samples. The main parameters investigated were the amount and various combinations of NS, NA, NT and NF, producing thirty-one concrete batches, one control and thirty NS, NA, NT and NF added concrete mixes. The total nanoparticle amounts in the concrete mixes of 0.5%, 1%, and 1.5% by weight of cement were studied. A total of 558 concrete specimens with nanoparticles were tested at 28 days to determine compressive, splitting tensile, flexural, and residual compressive strength of concretes at ambient and elevated temperatures. It can be clearly concluded that NS and NA particles are more effective than NT and NF particles in improving the mechanical properties of concrete. The largest increase in compressive, splitting tensile, and flexural strength was obtained for 1.5% of NS and NA hybrid combination as 13.95%, 18.55%, and 21.88%, respectively. Furthermore, the residual compressive strength of single and hybrid nano-added concrete specimens significantly reduced, especially at 800 °C. Although the largest decrease in residual compressive strength of 57.65% was recorded for control concrete, the lowest reduction of 41.59% was observed for concrete with 1.5% of NS and NA hybrid combination at 800 °C.
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Compressive properties and underlying mechanisms of nickel coated carbon nanotubes modified concreteNickel coated multi-walled carbon nanotubes (Ni-MWCNTs) having exceptional mechanical properties, thermal conductivity and dispersibility can effectively overlap in cementitious matrix, thus forming an enhanced and thermal conductive network. They are therefore a promising nanofiller for modifying cement and concrete materials. This paper studies the compressive properties of reactive powder concrete (RPC) filled with different aspect ratios of Ni-MWCNTs, including strength, toughness, Young's modulus and Poisson's ratio. It is concluded that the incorporation of 0.06 vol.% Ni-MWCNTs with an aspect ratio of 1500 maximally increases the compressive strength and toughness of RPC by 20.24%/20.39 MPa and 43.89%/56.35 (N·m), respectively. However, Young's modulus and Poisson's ratio of Ni-MWCNTs modified composites do not significantly be improved. Besides, a constitutive model of Ni-MWCNTs reinforced RPC under uniaxial compression is established based on the continuum damage mechanics theory, reasonably predicting the relationship between compressive strength and deformation of composites. The modification mechanism of Ni-MWCNTs is also investigated through the temperature distribution monitoring inside composites, Scanning Electron Microscope (SEM) observation and energy dispersive x-ray spectrometry (EDS) analysis of Ni-MWCNTs reinforced RPC. The thermal conductive network formed by Ni-MWCNTs in matrix reduces the temperature difference and improves the temperature uniformity inside composites, thereby decreasing thermal stresses, primary cracks and defects of composites. Furthermore, the incorporation of Ni-MWCNTs makes the RPC microstructures dense, decreases the average CaO to SiO2 ratio, and inhibits the development of cracks inside RPC, thus achieving effective enhancement to RPC.
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Overview of tailoring cementitious composites with various nanomaterialsIncorporating nanomaterials brings great changes in tailoring the nano-/micro-/macroscale structures of bulk cement paste phase and interfacial transition zone in the cementitious composites through the nano-core effect, thus achieving stronger, more durable, and smart/multi-functional cementitious composites. Owing to the nano-modification of cement paste in combination with the supplement of nanoscale continuity for multiscale raw materials of cementitious composites, nanomaterials gradually show the potential to become the indispensable seventh component of cementitious composites besides cement, water, fine aggregates, coarse aggregates, chemical additives, and mineral additives. Therefore tailoring cementitious composites with nanomaterials provides a promising approach to develop the new generation of cementitious composites (e.g., ultra-high performance, smart/multi-functional, and resilient) and sustainable infrastructures. This chapter aims to provide a systematic overview of tailoring cementitious composites with various types of nanomaterials. It initially covers the principle of tailoring cementitious composites with nanomaterials and dispersion of nanomaterials in cementitious composites. It then presents the properties of cementitious composites with 0D, 1D, and 2D nanomaterials, namely, hydration, rheology, workability, durability, functional, and mechanical properties. It also highlights various applications of cementitious composites with nanomaterials, including structural health monitoring, traffic detection, and pollutant purification. This chapter concludes by presenting the future prospects of cementitious composites with nanomaterials.
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Flexural behavior of UHPCbeam reinforced with steel-FRP composite barsThis paper numerically investigates flexural performance of Ultra-High Performance Concrete (UHPC) beam reinforced with Steel-Fibre-Reinforced Polymer (FRP) Composite Bars (SFCBs) in terms of flexural stiffness, moment capacity, deflection, ductility and energy dissipation. The effect of various parameters, include the inner steel core area ratio of SFCB, yield strength of inner steel core, elastic modulus and ultimate strength of outer-wrapped FRP, reinforcement ratio, type and strength of concrete were studied. The results demonstrate that the inner steel core area ratio of SFCB, reinforcement ratio and the elastic modulus of SFCB's outer FRP have significant effect on the overall flexural performance of SFCB reinforced UHPC beam. The overall flexural performance of SFCB reinforced UHPC beam is slightly improved by increasing the yield strength of inner steel core of SFCB, but not affected by the ultimate strength of SFCB's outer FRP when specimen occurred compression failure. The results also exhibit that the flexural performance of UHPC beam reinforced with SFCBs is significantly improved when compared to those of reinforced high strength concrete (HSC) beam and normal strength concrete (NSC) beam. The flexural stiffness and the moment capacity of SFCB reinforced UHPC beam at the ultimate point were 2.0 and 2.4 times, respectively, of those of reinforced NSC counterpart.
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Eccentric compression behavior of Steel-FRP composite bars RC columns under coupling action of chloride corrosion and loadIn order to investigate the eccentric compression behaviors of steel-FRP composite bar (SFCB) reinforced concrete (RC) columns subjected to chloride corrosion, the mechanical experiments of chloride corroded SFCBs and SFCBs RC eccentric compression columns were conducted. The effect of reinforcement type and ratio, eccentricity, slenderness, stress level and corrosion duration on bearing capacity, deformation, crack and failure pattern were investigated. The results showed that the strength retention ratio of reinforcement decreases with the increase of corrosion duration, the ultimate strengths of steel rebar, SFCB and FRP rebar decreased by 12.2%, 9.9% and 3.6%, respectively, when compared with those of uncorroded counterparts. With the increase of steel content of reinforcement, the load bearing capacity of eccentric compression RC column increases while the deformation decreases gradually. The load bearing capacity of corroded steel, SFCB and FRP RC columns maximally decreased by 16.6%, 12.4% and 7.2%, respectively, when compared with those of uncorroded counterparts. Based on the simplified materials constitutive relations and reasonable basic assumptions, formulae for discriminate failure mode, moment magnification factor and bearing capacity were developed. The predicted failure pattern, moment magnification factor and bearing capacity are in good agreement with the test results, confirming the validity of the proposed formulae, the results can be used as a reference for engineering application.
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Numerical and theoretical research on flexural behaviour of steel-precast UHPC composite beamsIn order to promote the utilization of high strength materials and application of prefabricated structures, flexural behaviour of section steel-precast UHPC (Ultra-High performance concrete) slab composite beams prefabricated with bolt shear connectors are numerically simulated by the finite element (FE) software ABAQUS. The model is verified by three prefabricated steel-concrete composite beams tested. Numerical analysis results are in good accordance with experimental results. Furthermore, parametric studies are conducted to investigate the effects of strength of section steel and concrete of precast slab, thickness of section steel, width and height of precast concrete slab, diameters of steel bars and bolt shear connectors. The flexural behaviour of composite beams, in terms of bearing capacity, deflection, ductility and energy dissipation, are compared. The numerical results indicate that the improvement of strength of section steel results in a decrease of ductility, but a significant increase of the ultimate load and energy dissipation. Compared with composite beam made of section steel with thickness of 10 mm, the ultimate load of beams made of section steel with thickness of 14 and 18 mm improve by 29.0% and 58.8%, respectively, the ductility enhance by 2.8% and 8.3%, respectively, and the energy dissipation improve by 8.0% and 12.3%, respectively. With the increase of concrete strength, the ultimate load, deflection and energy dissipation gradually increase. The ductility of steel-UHPC composite beam is the highest, that of steel-HSC composite beam is the lowest. The effect of reinforcement ratio of concrete slab and diameter of shear bolts on the ultimate load of composite beam is limited. Simplified formulae for two different sectional types of proper-reinforced section steel-precast UHPC slab composite beams occurred bending failure are proposed, and the predicted results fit well with the simulated results. The results can be taken as a reference for the design and construction of section steel-precast UHPC slab composite beams.
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The effect of aspirin and eicosapentaenoic acid on urinary biomarkers of prostaglandin E2 synthesis and platelet activation in participants of the seAFOod polyp prevention trialUrinary prostaglandin (PG) E metabolite (PGE-M) and 11-dehydro (d)-thromboxane (TX) B2 are biomarkers of cyclooxygenase-dependent prostanoid synthesis. We investigated (1) the effect of aspirin 300 mg daily and eicosapentaenoic acid (EPA) 2000 mg daily, alone and in combination, on urinary biomarker levels and, (2) whether urinary biomarker levels predicted colorectal polyp risk, during participation in the seAFOod polyp prevention trial. Urinary PGE-M and 11-d-TXB2 were measured by liquid chromatography-tandem mass spectrometry. The relationship between urinary biomarker levels and colorectal polyp outcomes was investigated using negative binomial (polyp number) and logistic (% with one or more polyps) regression models. Despite wide temporal variability in PGE-M and 11-d-TXB2 levels within individuals, both aspirin and, to a lesser extent, EPA decreased levels of both biomarkers (74% [P ≤ .001] and 8% [P ≤ .05] reduction in median 11-d-TXB2 values, respectively). In the placebo group, a high (quartile [Q] 2-4) baseline 11-d-TXB2 level predicted increased polyp number (incidence rate ratio [IRR] [95% CI] 2.26 [1.11,4.58]) and risk (odds ratio [95% CI] 3.56 [1.09,11.63]). A low (Q1) on-treatment 11-d-TXB2 level predicted reduced colorectal polyp number compared to placebo (IRR 0.34 [0.12,0.93] for combination aspirin and EPA treatment) compared to high on-treatment 11-d-TXB2 values (0.61 [0.34,1.11]). Aspirin and EPA both inhibit PGE-M and 11-d-TXB2 synthesis in keeping with shared in vivo cyclooxygenase inhibition. Colorectal polyp risk and treatment response prediction by 11-d-TXB2 is consistent with a role for platelet activation during early colorectal carcinogenesis. The use of urinary 11-d-TXB2 measurement for a precision approach to colorectal cancer risk prediction and chemoprevention requires prospective evaluation.
