The Biodiversity Value of Urban Hedges

Human populations are urbanising rapidly, and this is causing concern about the impact that a lack of contact with nature has on health and wellbeing. Including green infrastructure, such as hedges, in our towns and cities potentially provides space for wildlife whilst also improving human habitat. Urban hedges vary based on their establishment and management history and differ from rural hedgerows in species composition and quality but still provide habitat for birds, mammals, and invertebrates as well as increased floral biodiversity. Hedges are perceived by people to be more attractive than other boundary types and offer greater benefits to wellbeing. Urban hedges offer opportunities for experiences of nature and many other ecosystem services but managing them to maximise benefit for wildlife in a manner that is acceptable for the human population requires careful consideration

Biodiversity Value of Urban Hedges

Rural hedges are ubiquitous features in the British landscape and are recognised for their biological, cultural and aesthetic importance. Hedges are also present in urban settings; as relicts of previously farmed landscapes and as planted boundaries. Relatively little is known about their composition, spatial distribution nor their biodiversity value to our cities. This thesis responds to this knowledge gap by evaluating the ecological value of urban hedges in the UK with a focus on their use by birds, small mammals and insects. The research involved habitat surveys undertaken in the city of Stoke-on-Trent (2015 – 2017) to collect data including: hedge species and physical structure, surrounding land-use and floral composition of verges. Associated field surveys of birds, insects and small mammals were also completed. In addition to the ecological assessment, a photographic perception study was conducted to investigate the public perceptions of Stoke-on-Trent’s hedges. This sought to identify which type of hedge species, management style and appearance was most valued in the urban context. Results indicated that birds, insects and small mammals all preferred wide hedges with verges, associated with woody habitats. Significant preference was shown by birds and mammals for hawthorn hedges over beech, privet or non-hedged controls. For the first time, arboreal use of urban hedges by small mammals was also demonstrated. The visual and aesthetic characteristics of hedges favoured by the public were in-line with those that enhanced biodiversity. Hedges provide a range of ecosystem services as well as opportunities for contact with nature and their continued existence in cities should be supported. As such, this thesis concludes with a set of management guidelines for local authority staff to use in order to maximise their benefit to the people who live alongside them and the wildlife that lives within them

Tetra-methoxystilbene modulates ductal growth of the developing murine mammary gland

Extensive data suggest that estradiol contributes to the development of breast cancer by acting as a mitogen and exerting direct genotoxic effects after enzymatic conversion to 4-hydroxyestradiol (4-OHE2) via cytochrome P450 1B1 (CYP1B1). The mammary gland, ovary, and uterus all express CYP1B1. Overexpression of this enzyme has been associated with an increased risk of breast cancer and blockade might reduce this carcinogenic effect. For this reason, we conducted systematic in vitro and in vivo studies of a CYP1B1 inhibitor, TMS (2,3',4,5'-tetramethoxystilbene). We found that TMS blocked the enzymatic conversion of radiolabeled estradiol to both 2-hydroxyestradiol (2-OHE2) and 4-OHE2, but did not inhibit Cyp1b1 message formation. In vivo studies using mass spectrometry showed that TMS inhibited formation of 2-OHE2 and 4-OHE2 and the resulting estrogen-DNA adducts. To examine its biologic actions in vivo, we investigated whether TMS could block the hyperplastic changes that occur in the developing breast of aromatase-transfected mice. We found that TMS induced a significant reduction of ductal structures in mice less than 6 months in age. In older mice, no reduction in breast morphology occurred. These latter studies uncovered unexpected estrogen agonistic actions of TMS at high doses, including a paradoxical stimulation of breast ductal structures and the endometrium. These studies suggest that the enzyme inhibitory properties of TMS, as well as the effects on developing breast, could implicate a role for TMS in breast cancer prevention, but only in low doses and on developing breast

Evaluation of the ICD-10 system in coding revascularisation procedures in patients with peripheral arterial disease in England: A retrospective cohort study using national administrative and clinical databases.

Background: Many studies evaluating care in hospitals in England use the Hospital Episode Statistics (HES) administrative database. The aim of this study was to explore whether the International Classification of Diseases 10th Revision (ICD-10) system used by HES supported the evaluation of care received by patients with peripheral arterial disease (PAD) who had revascularisation. Methods: This retrospective cohort study used records on patients who had revascularisation for PAD between 1st January 2017 and 31st December 2019 in England, collected prospectively in the National Vascular Registry (NVR) and linked to HES. Patients were excluded if their NVR record did not have a match in HES, due to lack of consent or different admission and procedure dates. Agreement between different presentations of PAD recorded in the NVR and the ICD-10 diagnostic codes recorded in HES was evaluated using the unweighted Kappa statistic and sensitivity and specificity. Agreement between the NVR and HES was also assessed for gender, age, comorbidities, mode of admission, and procedure type and side. Findings: In total, 20,603 patients who had 24,621 admissions were included in the study. Agreement between NVR and HES on patient gender (Kappa = 0.98), age (Kappa = 0.98), mode of admission (Kappa = 0.80), and procedure type and side (Kappa = 0.92 and 0.87, respectively) was excellent. When all diagnostic fields in HES were explored, substantial agreement was observed for chronic ischaemia with tissue loss (Kappa = 0.63), but it was lower for chronic ischaemia without tissue loss (Kappa = 0.32) and acute limb ischaemia (Kappa = 0.15). Agreement on comorbidities was mixed; excellent for diabetes (Kappa = 0.82), moderate for chronic lung disease (Kappa = 0.56), chronic kidney disease (Kappa = 0.56), and ischaemic heart disease (Kappa = 0.45) and fair for chronic heart failure (Kappa = 0.35). Interpretation: The diagnostic ICD-10 codes currently used in HES cannot accurately differentiate between stages of PAD. Therefore, studies using HES to examine patterns of care and outcomes for patients with PAD are likely to suffer from misclassification bias. Adopting an extended ICD-10 system or the ICD-11 version released to the World Health Organisation member states in 2022, may overcome this problem. Funding: Healthcare Quality Improvement Partnership (HQIP)

Sex ratio and the evolution of aggression in fruit flies

Aggressive behaviours are among the most striking displayed by animals, and aggression strongly impacts fitness in many species. Aggression varies plastically in response to the social environment, but we lack direct tests of how aggression evolves in response to intra-sexual competition. We investigated how aggression in both sexes evolves in response to the competitive environment, using populations of Drosophila melanogaster that we experimentally evolved under female-biased, equal, and male-biased sex ratios. We found that after evolution in a female-biased environment—with less male competition for mates—males fought less often on food patches, although the total frequency and duration of aggressive behaviour did not change. In females, evolution in a female-biased environment—where female competition for resources is higher—resulted in more frequent aggressive interactions among mated females, along with a greater increase in post-mating aggression. These changes in female aggression could not be attributed solely to evolution either in females or in male stimulation of female aggression, suggesting that coevolved interactions between the sexes determine female post-mating aggression. We found evidence consistent with a positive genetic correlation for aggression between males and females, suggesting a shared genetic basis. This study demonstrates the experimental evolution of a behaviour strongly linked to fitness, and the potential for the social environment to shape the evolution of contest behaviours

Outcomes after minor lower limb amputation for peripheral arterial disease and diabetes: population-based cohort study

BACKGROUND: Patients with diabetes and peripheral arterial disease are at increased risk of minor amputation. The aim of study was to assess the rate of re-amputations and death after an initial minor amputation, and to identify associated risk factors. METHODS: Data on all patients aged 40 years and over with diabetes and/or peripheral arterial disease, who underwent minor amputation between January 2014 and December 2018, were extracted from Hospital Episode Statistics. Patients who had bilateral index procedures or an amputation in the 3 years before the study were excluded. Primary outcomes were ipsilateral major amputation and death after the index minor amputation. Secondary outcomes were ipsilateral minor re-amputations, and contralateral minor and major amputations. RESULTS: In this study of 22 118 patients, 16 808 (76.0 per cent) were men and 18 473 (83.5 per cent) had diabetes. At 1 year after minor amputation, the estimated ipsilateral major amputation rate was 10.7 (95 per cent c.i. 10.3 to 11.1) per cent. Factors associated with a higher risk of ipsilateral major amputation included male sex, severe frailty, diagnosis of gangrene, emergency admission, foot amputation (compared with toe amputation), and previous or concurrent revascularization. The estimated mortality rate was 17.2 (16.7 to 17.7) per cent at 1 year and 49.4 (48.6 to 50.1) per cent at 5 years after minor amputation. Older age, severe frailty, comorbidity, gangrene, and emergency admission were associated with a significantly higher mortality risk. CONCLUSION: Minor amputations were associated with a high risk of major amputation and death. One in 10 patients had an ipsilateral major amputation within the first year after minor amputation and half had died by 5 years

The Impact of Pre-Operative Anaemia on One Year Amputation Free Survival and Re-Admissions in Patients Undergoing Vascular Surgery for Peripheral Arterial Disease: a National Vascular Registry Study

OBJECTIVE: Anaemia is common among patients undergoing surgery, but its association with post-operative outcomes in patients with peripheral arterial disease (PAD) is unclear. The aim of this observational population based study was to examine the association between pre-operative anaemia and one year outcomes after surgical revascularisation for PAD. METHODS: This study used data from the National Vascular Registry, linked with an administrative database (Hospital Episode Statistics), to identify patients who underwent open surgical lower limb revascularisation for PAD in English NHS hospitals between January 2016 and December 2019. The primary outcome was one year amputation free survival. Secondary outcomes were one year re-admission rate, 30 day re-intervention rate, 30 day ipsilateral major amputation rate and 30 day death. Flexible parametric survival analysis and generalised linear regression were performed to assess the effect of anaemia on one year outcomes. RESULTS: The analysis included 13 641 patients, 57.9% of whom had no anaemia, 23.8% mild, and 18.3% moderate or severe anaemia. At one year follow up, 80.6% of patients were alive and amputation free. The risk of one year amputation or death was elevated in patients with mild anaemia (adjusted HR 1.3; 95% CI 1.15 - 1.41) and moderate or severe anaemia (aHR 1.5; 1.33 - 1.67). Patients with moderate or severe anaemia experienced more re-admissions over one year (adjusted IRR 1.31; 1.26 - 1.37) and had higher odds of 30 day re-interventions (aOR 1.22; 1.04 - 1.45), 30 day ipsilateral major amputation (aOR 1.53; 1.17 - 2.01), and 30 day death (aOR 1.39; 1.03 - 1.88) compared with patients with no anaemia. CONCLUSION: Pre-operative anaemia is associated with lower one year amputation free survival and higher one year re-admission rates following surgical revascularisation in patients with PAD. Research is required to evaluate whether interventions to correct anaemia improve outcomes after lower limb revascularisation

Circulating free insulin-like growth factor-I and prostate cancer: a case-control study nested in the European prospective investigation into cancer and nutrition

Background: Circulating total insulin-like growth factor-I (IGF-I) is an established risk factor for prostate cancer. However, only a small proportion of circulating IGF-I is free or readily dissociable from IGF-binding proteins (its bioavailable form), and few studies have investigated the association of circulating free IGF-I with prostate cancer risk. Methods: We analyzed data from 767 prostate cancer cases and 767 matched controls nested within the European Prospective Investigation into Cancer and Nutrition cohort, with an average of 14-years (interquartile range = 2.9) follow-up. Matching variables were study center, length of follow-up, age, and time of day and fasting duration at blood collection. Circulating free IGF-I concentration was measured in serum samples collected at recruitment visit (mean age 55 years old; standard deviation = 7.1) using an enzyme-linked immunosorbent assay (ELISA). Conditional logistic regressions were performed to examine the associations of free IGF-I with risk of prostate cancer overall and subdivided by time to diagnosis (≤ 14 and > 14 years), and tumor characteristics. Results: Circulating free IGF-I concentrations (in fourths and as a continuous variable) were not associated with prostate cancer risk overall (odds ratio [OR] = 1.00 per 0.1 nmol/L increment, 95% CI: 0.99, 1.02) or by time to diagnosis, or with prostate cancer subtypes, including tumor stage and histological grade. Conclusions: Estimated circulating free IGF-I was not associated with prostate cancer risk. Further research may consider other assay methods that estimate bioavailable IGF-I to provide more insight into the well-substantiated association between circulating total IGF-I and subsequent prostate cancer risk

A framework for ensemble modelling of climate change impacts on lakes worldwide : the ISIMIP Lake Sector

Empirical evidence demonstrates that lakes and reservoirs are warming across the globe. Consequently, there is an increased need to project future changes in lake thermal structure and resulting changes in lake biogeochemistry in order to plan for the likely impacts. Previous studies of the impacts of climate change on lakes have often relied on a single model forced with limited scenario-driven projections of future climate for a relatively small number of lakes. As a result, our understanding of the effects of climate change on lakes is fragmentary, based on scattered studies using different data sources and modelling protocols, and mainly focused on individual lakes or lake regions. This has precluded identification of the main impacts of climate change on lakes at global and regional scales and has likely contributed to the lack of lake water quality considerations in policy-relevant documents, such as the Assessment Reports of the Intergovernmental Panel on Climate Change (IPCC). Here, we describe a simulation protocol developed by the Lake Sector of the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP) for simulating climate change impacts on lakes using an ensemble of lake models and climate change scenarios for ISIMIP phases 2 and 3. The protocol prescribes lake simulations driven by climate forcing from gridded observations and different Earth system models under various representative greenhouse gas concentration pathways (RCPs), all consistently bias-corrected on a 0.5 degrees x 0.5 degrees global grid. In ISIMIP phase 2, 11 lake models were forced with these data to project the thermal structure of 62 well-studied lakes where data were available for calibration under historical conditions, and using uncalibrated models for 17 500 lakes defined for all global grid cells containing lakes. In ISIMIP phase 3, this approach was expanded to consider more lakes, more models, and more processes. The ISIMIP Lake Sector is the largest international effort to project future water temperature, thermal structure, and ice phenology of lakes at local and global scales and paves the way for future simulations of the impacts of climate change on water quality and biogeochemistry in lakes.Peer reviewe