The detection of intracranial aneurysms by non-invasive imaging methods and the epidemiology of aneurysmal subarachnoid haemorrhage within the Scottish population

The aims of the research project, which led to the writing of this thesis were to: Examine whether non -invasive imaging methods could replace intra- arterial angiography (IADSA) in the detection of intracranial aneurysms by: a) systematically reviewing the literature; b) prospectively determining the accuracy of the non -invasive imaging methods currently available in Scotland, including the effect of observer experience on diagnostic performance and the patient acceptability of the alternative imaging modalities. To establish the incidence of aneurysmal subarachnoid haemorrhage (SAH) in families by a national retrospective study of occurrences of SAH in a one year period in Scotland, in parallel with a follow -up study of the families of patients who were admitted to the Institute of Neurosciences with aneurysmal SAH a decade earlier. The thesis is divided into three parts:PART ONE: a) summarises the current understanding of the epidemiology and pathophysiology of intracranial aneurysms; b) an overview of cerebrovascular anatomy with reference to aneurysm formation; c) the modalities available for imaging intracranial aneurysms and the current knowledge about their diagnostic performance are considered; d) an overview of the methods available for the treatment of intracranial aneurysms; e) the concept of screening for unruptured intracranial aneurysms is discussed and placed in context by comparison to other screening programmes.PART TWO: a) describes a systematic review of the non -invasive imaging of intracranial aneurysms. CT and MR angiography had similar accuracy compared to IADSA of ~90 %. Data on Transcranial Doppler Sonography (TCDS) were scanty but indicated poorer performance. Detection of very small aneurysms (<3mm diameter) was significantly poorer for the non -invasive tests; b) describes a prospective study of 200 patients examining CTA, MRA and TCDS vs IADSA in the detection of intracranial aneurysms. CTA and MRA had an accuracy (per subject) of 0.85. TCDS had similar accuracy per subject but poorer accuracy per aneurysm than CTA or MRA. Detection of aneurysms ≤5mm was significantly poorer than for those >5mm. Interobserver agreement was good for all modalities; c) combining TCDS with CTA or MRA improved the detection of aneurysms on a per subject basis. Non-invasive imaging tests, especially when used in combination, are reliable at detecting aneurysms >5mm; d) examines the effect of observer experience. Neuroradiologists were more consistent and had better agreement with IADSA than non - neuroradiologists. Small aneurysms and cavernous /terminal internal carotid aneurysms were poorly detected by all observers; e) assessment of patient preferences indicated that TCDS was preferred to the other non -invasive tests and CTA to MRA, with the differences being statistically significant.PART THREE describes: a) the rationale behind the epidemiological studies; b) the methodology used; c) describes the results: Comparative risk for 1st vs 2nd degree relatives suffering a SAH was 2.29 for the Scotland wide study (SWS) and 2.43 for the West of Scotland study (WOS). Absolute lifetime SAH risk was 4.7% for 1st degree and 1.9% for 2nd degree relatives in the SWS compared to 4.2% and 2.3% respectively in the WOS. Prospective 10 -year SAH risk was 1.2% for a 1st degree and 0.5% for a 2nd degree relative compared to background population risk of ~0.1%. The hierarchy of risk was greatest for a member of a family with ≥ 2 other 1st degree relatives affected by SAH, with a more than 20-fold increased risk over the background population risk; d) discusses the implications of the findings and examines the strengths and weaknesses of the study. Routine screening of families of patients who have had a SAH is not supported by these data; e) reviews the implications for i) clinical practice and ii) future research arising from the imaging and epidemiological studies

A Contracting, Turbulent, Starless Core in the Serpens Cluster

We present combined single-dish and interferometric CS(2--1) and N2H+(1--0) observations of a compact core in the NW region of the Serpens molecular cloud. The core is starless according to observations from optical to millimeter wavelengths and its lines have turbulent widths and ``infall asymmetry''. Line profile modeling indicates supersonic inward motions v_in>0.34 km/s over an extended region L>12000AU. The high infall speed and large extent exceeds the predictions of most thermal ambipolar diffusion models and points to a more dynamical process for core formation. A short (dynamic) timescale, ~1e5 yr=L/v_in, is also suggested by the low N2H+ abundance ~1e-10.Comment: 11 pages including 2 figures. Accepted for publication in the Astrophysical Journal Letter

Breeding for improved nitrogen use efficiency in oilseed rape

Oilseed rape has a high requirement for nitrogen (N) fertiliser relative to its seed yield. This paper uses published and unpublished work to explore the extent to which the N use efficiency (seed yield ÷ N supply) of oilseed rape could be improved without reducing seed yield. It was estimated that if the concentration of N in the stem and pod wall at crop maturity could be reduced from 1.0 to 0.6%, the root length density increased to 1 cm/cm3 to 100 cm soil depth and the post flowering N uptake increased by 20 kg N/ha then the fertiliser requirement could be reduced from 191 to 142 kg N/ha and the N use efficiency could be increased from 15.2 to 22.4 kg of seed dry matter per kg N. Genetic variation was found for all of the traits that were estimated to be important for N use efficiency. This indicates that there is significant scope for plant breeders to reduce N use efficiency in oilseed rape

A long Quaternary terrace sequence in the Orontes River Valley, Syria: a record of uplift and of human occupation

Mapping in the Homs region of Syria has revealed a hitherto unrecognized staircase of at least 12 gravel terraces of the upper Orontes River. The terrace gravels overlie Pliocene lacustrine marl and have been calcareously cemented into conglomerates, sometimes interbedded with cemented fine-grained alluvium. A tentative dating scheme, based on modelling the regional-scale surface uplift that has driven fluvial incision of ~ 400 m since the latest Miocene, and incorporating correlation with the dated terraces in the valley of the middle Orontes using height above the river, envisages terrace formation spanning at least the last 1.2 Ma

Scarf\u27s Procedure for Integer Programming and a Dual Simplex Algorithm

Herbert Scarf has recently introduced an algorithm for integer programs based on the concept of primitive sets. We show that as the choice variables become continuous, this algorithm converges to a dual simplex algorithm. This result is robust in the sense that even before the limit is reached, the simplex path is contained in the primitive sets which define Scarf’s path to the solution of the integer program

Genetic associations with childhood brain growth, defined in two longitudinal cohorts

Genome-wide association studies (GWASs) are unraveling the genetics of adult brain neuroanatomy as measured by cross-sectional anatomic magnetic resonance imaging (aMRI). However, the genetic mechanisms that shape childhood brain development are, as yet, largely unexplored. In this study we identify common genetic variants associated with childhood brain development as defined by longitudinal aMRI. Genome-wide single nucleotide polymorphism (SNP) data were determined in two cohorts: one enriched for attention-deficit/hyperactivity disorder (ADHD) (LONG cohort: 458 participants; 119 with ADHD) and the other from a population-based cohort (Generation R: 257 participants). The growth of the brain's major regions (cerebral cortex, white matter, basal ganglia, and cerebellum) and one region of interest (the right lateral prefrontal cortex) were defined on all individuals from two aMRIs, and a GWAS and a pathway analysis were performed. In addition, association between polygenic risk for ADHD and brain growth was determined for the LONG cohort. For white matter growth, GWAS meta-analysis identified a genome-wide significant intergenic SNP (rs12386571, P = 9.09 × 10-9 ), near AKR1B10. This gene is part of the aldo-keto reductase superfamily and shows neural expression. No enrichment of neural pathways was detected and polygenic risk for ADHD was not associated with the brain growth phenotypes in the LONG cohort that was enriched for the diagnosis of ADHD. The study illustrates the use of a novel brain growth phenotype defined in vivo for further study

The Mass Profile and Accretion History of Cold Dark Matter Halos

We use the Millennium Simulation series to study the relation between the accretion history (MAH) and mass profile of cold dark matter halos. We find that the mean density within the scale radius, r_{-2} (where the halo density profile has isothermal slope), is directly proportional to the critical density of the Universe at the time when the main progenitor's virial mass equals the mass enclosed within r_{-2}. Scaled to these characteristic values of mass and density, the mean MAH, expressed in terms of the critical density of the Universe, M(\rho_{crit}(z)), resembles that of the enclosed density profile, M(), at z=0. Both follow closely the NFW profile, suggesting that the similarity of halo mass profiles originates from the mass-independence of halo MAHs. Support for this interpretation is provided by outlier halos whose accretion histories deviate from the NFW shape; their mass profiles show correlated deviations from NFW and are better approximated by Einasto profiles. Fitting both M() and M(\rho_{crit}) with either NFW or Einasto profiles yield concentration and shape parameters that are correlated, confirming and extending earlier work linking the concentration of a halo with its accretion history. These correlations also confirm that halo structure is insensitive to initial conditions: only halos whose accretion histories differ greatly from the NFW shape show noticeable deviations from NFW in their mass profiles. As a result, the NFW profile provides acceptable fits to hot dark matter halos, which do not form hierarchically, and for fluctuation power spectra other than CDM. Our findings, however, predict a subtle but systematic dependence of mass profile shape on accretion history which, if confirmed, would provide strong support for the link between accretion history and halo structure we propose here.Comment: 12 pages, 8 figures, MNRAS 432 1103L (2013

Development of Occupant-Preferred Landing Profiles for Personal Aerial Vehicles

With recent increased interest in autonomous vehicles and the associated technology, the prospect of realizing a personal aerial vehicle (PAV) seems closer than ever. However, there is likely to be a continued requirement for any occupant of an air vehicle to be comfortable with both the automated portions of the flight and their ability to take manual control as and when required. This paper, using the approach to landing as an example maneuver, examines what a comfortable trajectory for PAV occupants might look like. Based upon simulated flight data, a ‘natural’ flight trajectory was designed and then compared to constant deceleration and constant optic flow descent profiles. It was found that PAV occupants with limited flight training and no artificial guidance followed the same longitudinal trajectory as had been found for professionally trained helicopter pilots. Further, the final stages of the approach to hover could be well described using Tau Theory. For automatic flight, PAV occupants preferred a constant deceleration profile. For approaches flown manually, the newly designed natural profile was preferred

Modeling HER2 Effects on Cell Behavior from Mass Spectrometry Phosphotyrosine Data

Cellular behavior in response to stimulatory cues is governed by information encoded within a complex intracellular signaling network. An understanding of how phenotype is determined requires the distributed characterization of signaling processes (e.g., phosphorylation states and kinase activities) in parallel with measures of resulting cell function. We previously applied quantitative mass spectrometry methods to characterize the dynamics of tyrosine phosphorylation in human mammary epithelial cells with varying human epidermal growth factor receptor 2 (HER2) expression levels after treatment with epidermal growth factor (EGF) or heregulin (HRG). We sought to identify potential mechanisms by which changes in tyrosine phosphorylation govern changes in cell migration or proliferation, two behaviors that we measured in the same cell system. Here, we describe the use of a computational linear mapping technique, partial least squares regression (PLSR), to detail and characterize signaling mechanisms responsible for HER2-mediated effects on migration and proliferation. PLSR model analysis via principal component inner products identified phosphotyrosine signals most strongly associated with control of migration and proliferation, as HER2 expression or ligand treatment were individually varied. Inspection of these signals revealed both previously identified and novel pathways that correlate with cell behavior. Furthermore, we isolated elements of the signaling network that differentially give rise to migration and proliferation. Finally, model analysis identified nine especially informative phosphorylation sites on six proteins that recapitulated the predictive capability of the full model. A model based on these nine sites and trained solely on data from a low HER2-expressing cell line a priori predicted migration and proliferation in a HER2-overexpressing cell line. We identify the nine signals as a “network gauge,” meaning that when interrogated together and integrated according to the quantitative rules of the model, these signals capture information content in the network sufficiently to predict cell migration and proliferation under diverse ligand treatments and receptor expression levels. Examination of the network gauge in the context of previous literature indicates that endocytosis and activation of phosphoinositide 3-kinase (PI3K)-mediated pathways together represent particularly strong loci for the integration of the multiple pathways mediating HER2′s control of mammary epithelial cell proliferation and migration. Thus, a PLSR modeling approach reveals critical signaling processes regulating HER2-mediated cell behavior