1H PARASHIFT Probes for Magnetic Resonance

The strong 1H NMR signals from water and fat impose significant limitations to magnetic resonance spectroscopic imaging in vivo. Herein, novel paramagnetic lanthanide probes for 1H magnetic resonance imaging and spectroscopy studies are described, in which a tert-butyl reporter group is incorporated and placed about 6 to 7 Å from a lanthanide(III) ion in a kinetically stable macrocyclic complex. At such a distance, the tert-butyl reporter is shifted to a 1H NMR window that is well removed from the diamagnetic range, allowing its selective observation. Additionally, prudent selection of the lanthanide(III) ion, in accord with magnetic field strength, leads to an enhancement in the longitudinal relaxation rates, R1, permitting faster data acquisition per unit time in spectroscopy and imaging protocols. Further sensitivity gains are achieved by selecting a tert-butyl reporter group, within which the number of magnetically equivalent nuclei is maximised. As a result, the development of 1H PARASHIFT probes with carboxylate chelating arms possess tert-butyl groups that are shifted up to 25 ppm away from the water signal. At such frequencies, the enhanced sensitivity associated with the zero-background signal in vivo, allows the detection of these complexes in live mice, and due to the achievement of the required R1 values, data acquisition occurs within a few minutes following tail vein injection of well-tolerated doses that are of the same size as clinically administered contrast agents (0.1 mmol kg-1). Remarkable tert-butyl chemical shift enhancements up to 85 ppm away from the water signal are observed for 1H PARASHIFT probes possessing phosphinate chelating arms, moving the goal posts further still for 1H MRS studies. Such a shift magnitude means that larger spectral imaging bandwidths (such as 20 kHz) can be used, to further reduce data acquisition times. Minimal structural modifications, in the 4-position of the coordinated pyridyl moiety, have led to the development of ‘smart’ pH responsive 1H PARASHIFT probes, and also a covalently bound high-molecular weight glycol chitosan adduct. In the latter case, a strategy for increasing the retention time of these complexes is presented

Repetition and transformation : the housing project and the city of New York

University of Technology Sydney. Faculty of Design, Architecture and Building.From the early decades of the twentieth century the housing project has, with varying intensities, acquired a critical instrumentality within urban spatial reasoning. The following thesis examines this reasoning across several terrains. The first concerns architecture’s disciplinary outside: an agonistic governmental rationality regarding the constellation of home, work, leisure and transport in the formation of urban and domestic subjects. It is a disputed terrain that can be seen to consistently cut through the urban diagram of the housing project. The second is seen through architecture’s limited and iterative autonomy to engage and experiment with this diagram via a strategic field of material and formal organization, that is, through the disciplinary specific work of architectural typology in its negotiation with this outside. The decades 1960-1980 are generally identified within architectural and urban history and theory as marking a dramatic critique and transformation in the field of architecture. This critique involved a review of architecture’s relationship to the city and is particularly evident with reference to the tower in the park housing type of the Modern Movement and its perceived failure in terms of an ‘existing and traditional city’. This thesis reframes several projects argued to be definitional of such change. Examples here are drawn from the specificity of the city that throughout the twentieth century has repeatedly been held up as the exemplar of all that the delirious metropolis of change might be: the City of New York. Through an examination of specific projects, this thesis aims to clarify where architecture’s iterative and limited autonomy can be seen in action through this period. In the first instance this is examined through the housing project’s definitional role as part of its coming into form, of understandings of the city itself. Evident here is an inherent instability to understandings of the city that has not been central to historical accounts of change as part of architectural history’s writing around transformation. In the second instance, the thesis proposes the typological burden, first identified by Kenneth Frampton, as evidence of sustained trajectories of spatial and formal experimentation that belong entirely to architecture’s disciplinary autonomy. As such the typological burden, in this instance the ground, is the site of space and form emerging prior to, rather then as a consequence of, function, challenging the Modern Movement’s account of its own design process and understanding of architectural agency. Finally, the thesis demonstrates the discipline’s agency relative to legislative change in the United States during this period and the transformation of the Fifth Amendment of the United States Constitution in the context of Eminent Domain and slum clearance in cities on the occasion of the housing project. In clarifying architecture’s disciplinary interior and exploring its iterative and conditional autonomy to a discursive exterior, each of these instances demonstrates a unique kind of directed material politics that is specific to architecture’s disciplinary skill set, and quite different to either the passive reflective role typically attributed to it by historical accounts of change, or the formal political role that many contemporary accounts of architecture claim for it. By bringing together the two lenses of governmental rationality and architecture’s limited and iterative autonomy this thesis has clarified, to a field that insists on defining itself in terms of the new, where architecture’s limited actual agency for transformation is – not the avant-garde edge of a discipline defined in terms of the disciplines of philosophy, sociology, political science or anthropology, or the politics of revolution and subjugation found in contemporary art practice, but rather architecture’s disciplinary agency involves a significantly more nuanced directed material politics transformative of both the city and we its urban and domestic subjects

Critical analysis of the limitations of Bleaney's theory of magnetic anisotropy in paramagnetic lanthanide coordination complexes

The origins of the breakdown of Bleaney's theory of magnetic anisotropy are described, based on an analysis of eleven different complexes of the second half of the 4f elements that form isostructural series. An examination of the chemical shift and relaxation rate behaviour of resonances located at least four bonds away from the paramagnetic centre was undertaken, and correlated to theoretical predictions. The key limitations relate to comparability of ligand field splitting with spin–orbit coupling, variation in the position of the principal magnetic axis between Ln complexes and the importance of multipolar terms in describing lanthanide ligand field interactions

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Local deprivation and the labour market integration of new migrants to England

Using data on new migrants to England from the Quarterly Labour Force Survey, we show how a key component of migrant integration - labour market progress in terms of wages and unemployment rates - is broadly positive in the early years after arrival across a range of migrant groups and across gender. However the precise level of labour market success achieved varies considerably across groups reflecting both the initial entry level and labour market trajectories after migration. Migrants from Western Europe and the Old Commonwealth countries have unemployment rates (wages) which are generally lower (higher) than other groups, particularly non-white groups, while migrants from the Accession countries experience relatively low unemployment but also low wages. Groups which have better outcomes on entry also tend to experience higher rates of progress over time in England. However, the extent of multiple deprivation in the local authority where migrants reside interacts with years since migration to dampen wage trajectories for some groups and accounting for deprivation highlights the importance of internal migration for access to employment. The results emphasise structural explanations for patterns of labour market integration of new migrants to England

Neo-assimilationist citizenship and belonging policies in Britain: Meanings for transnational migrants in northern England

The overall aim of this paper is to contribute to debates on the relationships between citizenship and migration in the UK context in the light of recent changes in UK immigration policy. In particular, it focuses on the question of what an increasingly neo-assimilationist state articulation of national belonging means for transnational migrants living in Britain. The paper begins by charting the evolving nature of citizenship conceptualisations in Western neoliberal contexts and illustrates how Britain has responded to this shifting landscape. The context is one of enhanced ‘migration securitization’ wherein the state implies that the integrity of the nation state and its security can only be assured if migration flows and migrants themselves are closely controlled and monitored. This has led to Britain attempting to bolster the formal institution of citizenship (with its attendant rights and responsibilities) and tie it more explicitly to notions of belonging to the nation. Through research with national/regional policy officials and migrant organisations this paper firstly examines the political landscape of citizenship and belonging in Britain as it relates to migrants. Secondly, it draws on research with African transnational migrants in northern England to explore their senses of belonging and ask whether these cohere with the described state discourse or whether their feelings of belonging exist in tension with neo-assimilationist policies designed to promote a core national identity

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention