Gravitational lensing analysis of galaxy clusters in the Southern Cosmology Survey

In this thesis I present the first gravitational lensing results from the Southern Cosmology Survey (SCS). I provide a preliminary study of an automated pipeline analysis of a large survey, in preparation for larger surveys. Future large-area sky surveys, such as Pan-STARRS-1 (PS1), have similar characteristics to the SCS data and will require full automation of the processing. Therefore, this data set provides an ideal test case to highlight the problems which will be faced by such surveys. To analyse the large SCS dataset, I develop an automated weak lensing pipeline based on the KSB. This pipeline has been rigorously verified using simulations and data which I detail here. Results are shown from a weak lensing analysis of 152 optically-selected clusters in 56 square degrees. I fit universal Navarro, Frenk and White (NFW) profiles to measure cluster masses, and use the relatively large area of the survey to test the universal shape of cluster profiles using stacking of the tangential shears. I present the first lensing mass measurements of Sunyaev-Zel’dovich (SZ) selected clusters. It has been long thought that SZ surveys would be a powerful way to detect galaxy clusters for cosmological studies. Simulations show that the SZ detection is independent of redshift and that the threshold corresponds very closely to a threshold in mass. It was, however, not guaranteed that the first blind SZ experiments would detect mass. Using optical imaging from the SCS, I present lensing masses for three clusters selected by their SZ emission in the South Pole Telescope survey (SPT). I confirm that the SZ selection procedure is successful in detecting mass concentrations and find that the SZ clusters have amongst the largest masses, as high as 15x1014M . Consequently I can confirm that the first installment of SZ detections has detected large mass concentrations. Using the best fit masses for all the clusters, I analytically calculate the expected SZ integrated Y parameter. Finally, the scaling relation of Reyes et al. (2008) of lensing Mlens 200 against optical L200 is tested over the redshift range z = 0:1 - 0:3 and extended to z = 0:3 - 0:8. While there is some discrepancy in the lower redshift-range, we agree with Reyes et al (2008) in the higherredshift sample if we assume no evolution of the scaling relation. To test the tangential shear profile of these clusters, 98 clusters are stacked. We find that by allowing the model to vary from an NFW, a very good fit can be found with a higher normalisation of the shears and a lower concentration. This study supports that of Mandelbaum et al. (2008) who show that that massive halos have a lower concentration than expected. Like the SCS, new large area surveys such as PS1 are not very deep, and it is crucial to understand not only how to analyse this size of dataset, but also the sort of results one could expect to achieve. I show in this thesis that 2D mass reconstructions can be done on data of this quality, and large galaxy clusters successfully reconstructed. With a number density of n ~ 9 it is possible to detect the most massive clusters with lensing, but it is difficult. With the lower number density of n ~ 6 or lower expected from PS1 it will prove very difficult to detect individual clusters. However, PS1 will survey a massive area, and so the stacking analysis should work extremely well, and it should be possible to further test the shape of the cluster profiles with stacking as I demonstrated here with the smaller SCS dataset

Adoption of digital technology in the New Zealand motion picture industry

This research applies Frambach's integrated model of the adoption and diffusion of innovations to the adoption of digital technology in the New Zealand motion picture industry. Previous models concerning innovation adoption have typically focused on adopter side variables. The model employed here integrates supply-side variables with the adopter-side variables focused on in traditional research. This research extends Frambach's model to consider the time and extent of adoption. The model is tested through a mail-out survey. Tests of associations between dependent and independent variables are carried out through four measures of association in a bivariate fashion. The results show that supply-side and adopter-side variables are both important influencers of the extent of adoption of digital technology in the motion picture industry. However supply-side factors do not appear to be important determinants of the time of adoption of digital technology in this industry

What individual and neighbourhood-level factors increase the risk of heat-related mortality? A case-crossover study of over 185,000 deaths in London using high-resolution climate datasets.

OBJECTIVE: Management of the natural and built environments can help reduce the health impacts of climate change. This is particularly relevant in large cities where urban heat island makes cities warmer than the surrounding areas. We investigate how urban vegetation, housing characteristics and socio-economic factors modify the association between heat exposure and mortality in a large urban area. METHODS: We linked 185,397 death records from the Greater London area during May-Sept 2007-2016 to a high resolution daily temperature dataset. We then applied conditional logistic regression within a case-crossover design to estimate the odds of death from heat exposure by individual (age, sex) and local area factors: land-use type, natural environment (vegetation index, tree cover, domestic garden), built environment (indoor temperature, housing type, lone occupancy) and socio-economic factors (deprivation, English language, level of employment and prevalence of ill-health). RESULTS: Temperatures were higher in neighbourhoods with lower levels of urban vegetation and with higher levels of income deprivation, social-rented housing, and non-native English speakers. Heat-related mortality increased with temperature increase (Odds Ratio (OR), 95% CI?=?1.039, 1.036-1.043 per 1?°C temperature increase). Vegetation cover showed the greatest modification effect, for example the odds of heat-related mortality in quartiles with the highest and lowest tree cover were OR, 95%CI 1.033, 1.026-1.039 and 1.043, 1.037-1.050 respectively. None of the socio-economic variables were a significant modifier of heat-related mortality. CONCLUSIONS: We demonstrate that urban vegetation can modify the mortality risk associated with heat exposure. These findings make an important contribution towards informing city-level climate change adaptation and mitigation policies

Mapping allergenic pollen vegetation in UK to study environmental exposure and human health

Allergenic pollen is produced by the flowers of a number of trees, grasses and weeds found throughout the UK. Exposure to such pollen grains can exacerbate pollen-related asthma and allergenic conditions such as allergic rhinitis (hay fever). Maps showing the location of these allergenic taxa have many applications: they can be used to provide advice on risk assessments; combined with health data to inform research on health impacts such as respiratory hospital admissions; combined with weather data to improve pollen forecasting systems; or as inputs to pollen emission models. In this study we present 1 km resolution maps of 12 taxa of trees, grass and weeds found in the UK. We have selected the main species recorded by the UK pollen network. The taxa mapped in this study were: Alnus (alder), Fraxinus (ash), Betula (birch), Corylus (hazel), Quercus (oak), Pinus (pine) and Salix (willow), Poaceae (grass), Artemisia (mugwort), Plantago (plantain), Rumex (dock, sorrels) and Urtica (nettle). We also focus on one high population centre and present maps showing local level detail around the city of London. Our results show the different geographical distributions of the 12 taxa of trees, weeds and grass, which can be used to study plants in the UK associated with allergy and allergic asthma. These maps have been produced in order to study environmental exposure and human health, although there are many possible applications. This novel method not only provides maps of many different plant types, but also at high resolution across regions of the UK, and uniquely present 12 key plant taxa using a consistent methodology. To consider the impact on human health due to exposure of the pollen grains, it is important to consider the timing of pollen release, and its dispersal, as well as the effect on air quality, which is also discussed here

Neto1 Is a Novel CUB-Domain NMDA Receptor–Interacting Protein Required for Synaptic Plasticity and Learning

The N-methyl-D-aspartate receptor (NMDAR), a major excitatory ligand-gated ion channel in the central nervous system (CNS), is a principal mediator of synaptic plasticity. Here we report that neuropilin tolloid-like 1 (Neto1), a complement C1r/C1s, Uegf, Bmp1 (CUB) domain-containing transmembrane protein, is a novel component of the NMDAR complex critical for maintaining the abundance of NR2A-containing NMDARs in the postsynaptic density. Neto1-null mice have depressed long-term potentiation (LTP) at Schaffer collateral-CA1 synapses, with the subunit dependency of LTP induction switching from the normal predominance of NR2A- to NR2B-NMDARs. NMDAR-dependent spatial learning and memory is depressed in Neto1-null mice, indicating that Neto1 regulates NMDA receptor-dependent synaptic plasticity and cognition. Remarkably, we also found that the deficits in LTP, learning, and memory in Neto1-null mice were rescued by the ampakine CX546 at doses without effect in wild-type. Together, our results establish the principle that auxiliary proteins are required for the normal abundance of NMDAR subunits at synapses, and demonstrate that an inherited learning defect can be rescued pharmacologically, a finding with therapeutic implications for humans

Pollen exposure and hospitalization due to asthma exacerbations: daily time series in a European city.

Exposure to pollen can contribute to increased hospital admissions for asthma exacerbation. This study applied an ecological time series analysis to examine associations between atmospheric concentrations of different pollen types and the risk of hospitalization for asthma in London from 2005 to 2011. The analysis examined short-term associations between daily pollen counts and hospital admissions in the presence of seasonal and long-term patterns, and allowed for time lags between exposure and admission. Models were adjusted for temperature, precipitation, humidity, day of week, and air pollutants. Analyses revealed an association between daily counts (continuous) of grass pollen and adult hospital admissions for asthma in London, with a 4-5-day lag. When grass pollen concentrations were categorized into Met Office pollen 'alert' levels, 'very high' days (vs. 'low') were associated with increased admissions 2-5 days later, peaking at an incidence rate ratio of 1.46 (95%, CI 1.20-1.78) at 3 days. Increased admissions were also associated with 'high' versus 'low' pollen days at a 3-day lag. Results from tree pollen models were inconclusive and likely to have been affected by the shorter pollen seasons and consequent limited number of observation days with higher tree pollen concentrations. Future reductions in asthma hospitalizations may be achieved by better understanding of environmental risks, informing improved alert systems and supporting patients to take preventive measures

Health and climate related ecosystem services provided by street trees in the urban environment

Published onlineJournal ArticleUrban tree planting initiatives are being actively promoted as a planning tool to enable urban areas to adapt to and mitigate against climate change, enhance urban sustainability and improve human health and well-being. However, opportunities for creating new areas of green space within cities are often limited and tree planting initiatives may be constrained to kerbside locations. At this scale, the net impact of trees on human health and the local environment is less clear, and generalised approaches for evaluating their impact are not well developed.In this review, we use an urban ecosystems services framework to evaluate the direct, and locally-generated, ecosystems services and disservices provided by street trees. We focus our review on the services of major importance to human health and well-being which include 'climate regulation', 'air quality regulation' and 'aesthetics and cultural services'. These are themes that are commonly used to justify new street tree or street tree retention initiatives. We argue that current scientific understanding of the impact of street trees on human health and the urban environment has been limited by predominantly regional-scale reductionist approaches which consider vegetation generally and/or single out individual services or impacts without considering the wider synergistic impacts of street trees on urban ecosystems. This can lead planners and policymakers towards decision making based on single parameter optimisation strategies which may be problematic when a single intervention offers different outcomes and has multiple effects and potential trade-offs in different places.We suggest that a holistic approach is required to evaluate the services and disservices provided by street trees at different scales. We provide information to guide decision makers and planners in their attempts to evaluate the value of vegetation in their local setting. We show that by ensuring that the specific aim of the intervention, the scale of the desired biophysical effect and an awareness of a range of impacts guide the choice of i) tree species, ii) location and iii) density of tree placement, street trees can be an important tool for urban planners and designers in developing resilient and resourceful cities in an era of climatic change

Inhibition of SIK2 and SIK3 during differentiation enhances the anti-inflammatory phenotype of macrophages

The salt-inducible kinases (SIKs) control a novel molecular switch regulating macrophage polarization. Pharmacological inhibition of the SIKs induces a macrophage phenotype characterized by the secretion of high levels of anti-inflammatory cytokines, including interleukin (IL)-10, and the secretion of very low levels of pro-inflammatory cytokines, such as tumour necrosis factor α. The SIKs, therefore, represent attractive new drug targets for the treatment of macrophage-driven diseases, but which of the three isoforms, SIK1, SIK2 or SIK3, would be appropriate to target remains unknown. To address this question, we developed knock-in (KI) mice for SIK1, SIK2 and SIK3, in which we introduced a mutation that renders the enzymes catalytically inactive. Characterization of primary macrophages from the single and double KI mice established that all three SIK isoforms, and in particular SIK2 and SIK3, contribute to macrophage polarization. Moreover, we discovered that inhibition of SIK2 and SIK3 during macrophage differentiation greatly enhanced the production of IL-10 compared with their inhibition in mature macrophages. Interestingly, macrophages differentiated in the presence of SIK inhibitors, MRT199665 and HG-9-91-01, still produced very large amounts of IL-10, but very low levels of pro-inflammatory cytokines, even after the SIKs had been reactivated by removal of the drugs. Our data highlight an integral role for SIK2 and SIK3 in innate immunity by preventing the differentiation of macrophages into a potent and stable anti-inflammatory phenotype

New insights into the impact of neuro-inflammation in rheumatoid arthritis.

Rheumatoid arthritis (RA) is considered to be, in many respects, an archetypal autoimmune disease that causes activation of pro-inflammatory pathways resulting in joint and systemic inflammation. RA remains a major clinical problem with the development of several new therapies targeted at cytokine inhibition in recent years. In RA, biologic therapies targeted at inhibition of tumor necrosis factor alpha (TNFα) have been shown to reduce joint inflammation, limit erosive change, reduce disability and improve quality of life. The cytokine TNFα has a central role in systemic RA inflammation and has also been shown to have pro-inflammatory effects in the brain. Emerging data suggests there is an important bidirectional communication between the brain and immune system in inflammatory conditions like RA. Recent work has shown how TNF inhibitor therapy in people with RA is protective for Alzheimer's disease. Functional MRI studies to measure brain activation in people with RA to stimulus by finger joint compression, have also shown that those who responded to TNF inhibition showed a significantly greater activation volume in thalamic, limbic, and associative areas of the brain than non-responders. Infections are the main risk of therapies with biologic drugs and infections have been shown to be related to disease flares in RA. Recent basic science data has also emerged suggesting that bacterial components including lipopolysaccharide induce pain by directly activating sensory neurons that modulate inflammation, a previously unsuspected role for the nervous system in host-pathogen interactions. In this review, we discuss the current evidence for neuro-inflammation as an important factor that impacts on disease persistence and pain in RA