The Role of Unimodal and Transmodal Cortex in Perceptually-Coupled and Decoupled Semantic Cognition: Evidence from fMRI

Semantic retrieval extends beyond the here-and-now, to draw on abstract knowledge that has been extracted across multiple experiences; for instance, we can easily bring to mind what a dog looks and sounds like, even when a dog is not present in our environment. However, a clear understanding of the neural substrates that support patterns of semantic retrieval that are not immediately driven by stimuli in the environment is lacking. This thesis sought to investigate the neural basis of semantic retrieval within unimodal and heteromodal networks, whilst manipulating the availability of information in the environment. Much of the empirical work takes inspiration from modern accounts of transmodal regions (Lambon Ralph et al. 2017; Margulies et al. 2016), which suggest the anterior temporal lobe (ATL) and default mode network (DMN) support both abstraction and perceptual decoupling. The first empirical chapter examines whether words and experiences activate common neural substrates in sensory regions and where, within the ATLs, representations are transmodal. The second empirical chapter investigates how perceptually-decoupled forms of semantic retrieval in imagination are represented across unimodal and transmodal regions. The third empirical chapter interrogates whether transmodal regions respond in a similar manner to conceptually-guided and perceptually-decoupled cognition, and whether these two factors interact. The data suggests ventrolateral ATL processes both abstract modality-invariant semantic representations (Chapter 3) and decoupled semantic processing during imagination (Chapter 4). In addition, this thesis found comparable networks recruited for both conceptual processing and perceptually-decoupled retrieval corresponding to the broader DMN (Chapter 5). Further interrogation of these sites confirmed lateral MTG and bilateral angular gyrus were pivotal in the combination of conceptual retrieval from memory. Collectively, this data suggests that brain regions situated farthest from sensory input systems in both functional and connectivity space are required for the most abstract forms of cognition

Think Small, Build Big:Lessons from SME Housebuilding in Germany

There has been a catastrophic decline in the size of England’s SME housebuilding sector. This is not the case in Germany, where the SME sector dominates the housebuilding market. We diagnose a ‘toxic triangle’ of problems facing English SME builders, with mutually reinforcing problems stemming from the planning system, the land market, and insufficient access to finance. Drawing on experience from Germany, we recommend to government a seven-point plan to give England the greatest prospect of revitalising its SME building sector, thus making a substantially greater contribution to housing output

The Irish House of Lords, 1780-1800: politics and ideology

This thesis covers the Irish House of Lords in the last two decades of its life. A number of important themes run through the work - the regency crisis, patronage, the management of the Lords, the relationship between the Lords and Commons. These themes, explored from different angles, are vital to an understanding of the political role of the upper house in the 1780s and 1790s. This study is confined to the Lords as a political institution and thus its judicial role as final court of appeal, which was restored to it in 1782, will not be explored here. The thesis consists of two parts. Part one examines the structure and powers of the House of Lords while part two looks at the parties and policies of the house. Chapter one discusses the British constitution as imposed upon Ireland. Chapter two suggests the reasons why constitutional changes were introduced in 1782, and looks at the contribution made by the Irish House of Lords in securing these changes. Chapter three explores the various channels of influence which the peers enjoyed. Chapter four explores the sometimes tense relationship between Lords and Commons. Chapter five examines management of the House of Lords by Dublin Castle. Part two, begins at chapter six. This chapter explores the leadership of both parties within the Lords. Chapter seven looks at how patronage was used to reward those who were loyal to the government. Chapter eight explores the influence of the Whig opposition. Chapter nine looks at the controversial attempts made by Pitt and his ministry during the 1790s to win the support of catholics and turn them from the lure of French ideas, and of the response of the peers to these attempts. Chapter ten is concerned with the relationship between the peers of the House of Lords and the lords lieutenant during the 1790s. Chapter eleven looks at the Union and the House of Lords and attempts to answer the question historians have long asked: why did the Irish parliament and the House of Lords in particular, look favourably on the proposed union of the two kingdoms and the end of their own institution? The House of Lords in the closing decades of the eighteenth century was an institution within which the wealth and power of the kingdom could be found. Its members were politically active, both inside and outside the house. It contained a majority who saw the Crown as the source of stability, but it was a living and evolving political organism and therefore it contained men who believed that the Crown should have its influence limited. This evolution is also demonstrated in its desire for political change in 1782 and 1788. Its last, and perhaps most radical decision, was to vote for its own demise in 1900

Investigating obesity as a risk factor for influenza-like illness during the 2009 H1N1 influenza pandemic using the Health Survey for England.

BACKGROUND: Following the 2009 H1N1 influenza pandemic, obesity was shown to be associated with severe influenza outcomes. It remains unclear whether obesity was a risk factor for milder influenza-like illness (ILI). OBJECTIVES: To determine whether obesity was associated with an increased risk of self-reported ILI during the 2009 H1N1 influenza pandemic using Health Survey for England (HSE) 2010 cross-sectional data. METHODS: This study used HSE data collected from English households between January and December 2010. Weight and height measurements were taken by trained fieldworkers to determine obesity. ILI was defined as a positive response to the question "Have you had a flu-like illness where you felt feverish and had a cough or sore throat?" with illness occurring between May and December 2009. Multivariable logistic regression was used to evaluate the association between obesity and ILI. RESULTS: The study comprised 8407 participants (6984 adults, 1436 children), among whom 24.7% (95% CI: 23.6-25.9) were classified as obese. Of obese participants, 12.8% (95% CI: 11.1-14.8) reported ILI compared to 11.8% (95% CI: 10.8-12.8) of non-obese participants. The adjusted OR for ILI associated with obesity was 1.16 (95% CI: 0.98-1.38, P=.093). For adults and children, the adjusted ORs were 1.16 (95% CI: 0.97-1.38, P=.101) and 1.26 (95% CI: 0.72-2.21, P=.422), respectively. CONCLUSION: Household survey data showed no evidence that obesity was associated with an increase in self-reported ILI during the 2009 H1N1 influenza pandemic in England. Further studies using active prospective ILI surveillance combined with laboratory reporting would reduce bias and improve accuracy of outcome measurements

Likelihood of ‘falling through the net’ relates to contemporary prevalence of gestational diabetes. Reply to Ikomi A, Mannan S, Anthony R, Kiss S

This project was not supported by any specific funding. Claire Meek receives salary funding from the European Union Seventh Framework Programme (FP7/2007-2013; grant agreement n° 266408) and from the Wellcome Trust Translational Medicine and Therapeutics Programme which is funded by the Wellcome Trust in association with Glaxo SmithKline.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s00125-015-3737-

Bald eagle

The South Carolina Department of Natural Resources published guides to many threatened animals living in the state. This guide gives information about the Bald eagle, including description, status, habitat, conservation challenges & recommendations, and measures of success

Likelihood of 'falling through the net' relates to contemporary prevalence of gestational diabetes. Reply to Ikomi A, Mannan S, Anthony R, Kiss S [letter].

This project was not supported by any specific funding. Claire Meek receives salary funding from the European Union Seventh Framework Programme (FP7/2007-2013; grant agreement n° 266408) and from the Wellcome Trust Translational Medicine and Therapeutics Programme which is funded by the Wellcome Trust in association with Glaxo SmithKline.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s00125-015-3737-

Nonsegmented negative strand RNA viruses : viral RNA cap methylation and potential applications as an anticancer therapy

The viruses of the order Mononegavirales include important human, animal, and plant pathogens and additionally, have great potential as vaccine, oncolytic and gene therapy vectors. This dissertation focuses on two prototypic Mononegavirales, vesicular stomatitis virus (VSV) and Sendai virus (SeV), their virus-encoded cap methylation function, and potential applications as an anticancer therapy. The L protein of Mononegavirales has six conserved domains postulated to constitute the specific enzymatic activities of this multifunctional protein. We conducted a comprehensive mutational analysis by targeting the entire SeV L protein domain VI, creating twenty-four infectious L mutants. Our analysis identified several residues required for successful cap methylation and virus replication. This study confirms structural and functional similarity of this domain across different families of the order Mononegavirales. Additionally, the oncolytic potential of VSV was analyzed for the first time in a panel of human pancreatic ductal adenocarcinoma (PDA) cell lines and compared to other oncolytic viruses. VSV showed superior oncolytic abilities; however, cells were heterogeneous in their susceptibility to virus-induced oncolysis and several cell lines were resistant to all tested viruses. Four cell lines that varied in their permissiveness to VSV were tested in mice, and in vivo results closely mimicked those in vitro. While our results demonstrate VSV is a promising oncolytic agent against PDA, further studies are needed to better understand the molecular mechanisms of resistance to oncolytic virotherapy

The COVID-19 pandemic and its impact on tic symptoms in children and young people: a prospective cohort study

To understand how children and young people with tic disorders were affected by COVID-19, we compared pre and during pandemic scores on the Yale Global Tic Severity Scale (YGTSS). Participants were young people (N = 112; male:78%; 9–17 years) randomised to the control arm of the “ORBIT-Trial” (ISRCTN70758207, ClinicalTrials.gov-NCT03483493). For this analysis, the control arm was split into two groups: one group was followed up to 12-months’ post-randomisation before the pandemic started (pre-COVID group, n = 44); the other group was impacted by the pandemic at the 12-month follow-up (during-COVID group, n = 47). Mixed effects linear regression modelling was conducted to explore differences in YGTSS at 6- and 12-months post-randomisation. There were no significant differences in tic symptom or severity between participants who were assessed before and during COVID-19. This finding was not influenced by age, gender, symptoms of anxiety or autism spectrum disorder. Thus, the COVID-19 pandemic did not significantly impact existing tic symptoms