The Banality of Virtue: A Multifaceted View of George Orwell as Champion of the Common Man

This dissertation focuses on several aspects of the life and works of one Eric Arthur Blair, better known as George Orwell. It views Orwell as a servant of empire, as a revolutionary, as an intellectual, as an optimistic skeptic, as a writer, as a sort of prophet, and as a critic. It makes the case that Orwell wrote with the interests of the common people at the forefront of his mind, and that the threats to humanity and the liberal Western tradition existing in the 1930s and 1940s still exist today, albeit in a form that would have surprised Orwell himself. The passing of the year 1984 prompted a sigh of relief in Western societies who celebrated Big Brother's failure to arise in that celebrated year. As we end the first decade of the twenty-first century, we should consider whether or not we truly have avoided the perils of totalitarianism and the possible nightmare world that Orwell envisioned. This work engages Orwell's past, his present, and his unseen future: our own present. It applies Orwell to the postmodern world in an effort to emphasize that his work still matters

Looking Below the Surface: The Role of Superficial White Matter in Alzheimer’s Disease

Superficial white matter (SWM) contains short fibres and has largely been overlooked in Alzheimer’s disease (AD). Standard MRI approaches face confounding effects of complex fibre organisation and proximity to the cortex when measuring SWM in vivo. This thesis investigates SWM in AD by applying advanced MRI techniques to overcome these limitations. First, SWM in a cohort of young-onset AD and healthy controls was investigated using an advanced diffusion MRI model. Findings showed that young-onset AD participants have lower density, but increased dispersion, of SWM neurites compared to healthy controls. The second project found that these advanced diffusion MRI metrics are associated with independent quantitative MRI metrics sensitive to microstructure, and indicate previous findings are linked to losses in SWM myelin and iron. Project three explored the confounding effect of nearby CSF on cortical diffusion MRI measures and showed that a tissue-weighting approach can ameliorate CSF’s influence on regional averages. Project four investigated whether SWM is affected in autosomal dominant AD. Results supported earlier findings of lower density and higher dispersion of SWM neurites in symptomatic mutation carriers compared to non-carriers. Presymptomatic mutation carriers also had a lower density of neurites in entorhinal SWM. The final project used high-resolution 7T MRI to limit the influence of partial volume effects from nearby tissues on SWM measures in typical and atypical AD participants and healthy controls. An interim analysis qualitatively supports a loss of myelin and iron, with a potential increase in dispersion, occurring in the SWM during AD. In summary, SWM undergoes both degenerative and organisational changes during AD that coincide with a loss of iron. This extends the literature by overcoming limitations of standard MRI techniques previously used to investigate SWM in AD. SWM represents an overlooked region of brain changes in AD that may help detect and characterise the disease

The MASSIVE Survey - VIII. Stellar Velocity Dispersion Profiles and Environmental Dependence of Early-Type Galaxies

We measure the radial profiles of the stellar velocity dispersions, $\sigma(R)$, for 90 early-type galaxies (ETGs) in the MASSIVE survey, a volume-limited integral-field spectroscopic (IFS) galaxy survey targeting all northern-sky ETGs with absolute $K$-band magnitude $M_K < -25.3$ mag, or stellar mass $M_* > 4 \times 10^{11} M_\odot$, within 108 Mpc. Our wide-field 107" $\times$ 107" IFS data cover radii as large as 40 kpc, for which we quantify separately the inner (2 kpc) and outer (20 kpc) logarithmic slopes $\gamma_{\rm inner}$ and $\gamma_{\rm outer}$ of $\sigma(R)$. While $\gamma_{\rm inner}$ is mostly negative, of the 56 galaxies with sufficient radial coverage to determine $\gamma_{\rm outer}$ we find 36% to have rising outer dispersion profiles, 30% to be flat within the uncertainties, and 34% to be falling. The fraction of galaxies with rising outer profiles increases with $M_*$ and in denser galaxy environment, with 10 of the 11 most massive galaxies in our sample having flat or rising dispersion profiles. The strongest environmental correlations are with local density and halo mass, but a weaker correlation with large-scale density also exists. The average $\gamma_{\rm outer}$ is similar for brightest group galaxies, satellites, and isolated galaxies in our sample. We find a clear positive correlation between the gradients of the outer dispersion profile and the gradients of the velocity kurtosis $h_4$. Altogether, our kinematic results suggest that the increasing fraction of rising dispersion profiles in the most massive ETGs are caused (at least in part) by variations in the total mass profiles rather than in the velocity anisotropy alone.Comment: Accepted/in press, MNRA

The MASSIVE Survey - VII. The Relationship of Angular Momentum, Stellar Mass and Environment of Early-Type Galaxies

We analyse the environmental properties of 370 local early-type galaxies (ETGs) in the MASSIVE and ATLAS3D surveys, two complementary volume-limited integral-field spectroscopic (IFS) galaxy surveys spanning absolute $K$-band magnitude $-21.5 > M_K > -26.6$, or stellar mass $8 \times 10^{9} < M_* < 2 \times 10^{12} M_\odot$. We find these galaxies to reside in a diverse range of environments measured by four methods: group membership (whether a galaxy is a brightest group/cluster galaxy, satellite, or isolated), halo mass, large-scale mass density (measured over a few Mpc), and local mass density (measured within the $N$th neighbour). The spatially resolved IFS stellar kinematics provide robust measurements of the spin parameter $\lambda_e$ and enable us to examine the relationship among $\lambda_e$, $M_*$, and galaxy environment. We find a strong correlation between $\lambda_e$ and $M_*$, where the average $\lambda_e$ decreases from $\sim 0.4$ to below 0.1 with increasing mass, and the fraction of slow rotators $f_{\rm slow}$ increases from $\sim 10$% to 90%. We show for the first time that at fixed $M_*$, there are almost no trends between galaxy spin and environment; the apparent kinematic morphology-density relation for ETGs is therefore primarily driven by $M_*$ and is accounted for by the joint correlations between $M_*$ and spin, and between $M_*$ and environment. A possible exception is that the increased $f_{\rm slow}$ at high local density is slightly more than expected based only on these joint correlations. Our results suggest that the physical processes responsible for building up the present-day stellar masses of massive galaxies are also very efficient at reducing their spin, in any environment.Comment: Accepted to MNRA

The MASSIVE Survey - X. Misalignment between Kinematic and Photometric Axes and Intrinsic Shapes of Massive Early-Type Galaxies

We use spatially resolved two-dimensional stellar velocity maps over a $107"\times 107"$ field of view to investigate the kinematic features of 90 early-type galaxies above stellar mass $10^{11.5}M_\odot$ in the MASSIVE survey. We measure the misalignment angle $\Psi$ between the kinematic and photometric axes and identify local features such as velocity twists and kinematically distinct components. We find 46% of the sample to be well aligned ($\Psi < 15^{\circ}$), 33% misaligned, and 21% without detectable rotation (non-rotators). Only 24% of the sample are fast rotators, the majority of which (91%) are aligned, whereas 57% of the slow rotators are misaligned with a nearly flat distribution of $\Psi$ from $15^{\circ}$ to $90^{\circ}$. 11 galaxies have $\Psi \gtrsim 60^{\circ}$ and thus exhibit minor-axis ("prolate") rotation in which the rotation is preferentially around the photometric major axis. Kinematic misalignments occur more frequently for lower galaxy spin or denser galaxy environments. Using the observed misalignment and ellipticity distributions, we infer the intrinsic shape distribution of our sample and find that MASSIVE slow rotators are consistent with being mildly triaxial, with mean axis ratios of $b/a=0.88$ and $c/a=0.65$. In terms of local kinematic features, 51% of the sample exhibit kinematic twists of larger than $20^{\circ}$, and 2 galaxies have kinematically distinct components. The frequency of misalignment and the broad distribution of $\Psi$ reported here suggest that the most massive early-type galaxies are mildly triaxial, and that formation processes resulting in kinematically misaligned slow rotators such as gas-poor mergers occur frequently in this mass range.Comment: Accepted to MNRA

Like an open book? Accessibility of e-book content for academic study in a diverse student population

This paper reviews previous research on e-books and the information seeking behaviour of scholars. It presents the initial findings from an in-depth study of the behaviour and experiences of seven students (including students with dyslexia and visual impairment) using e-books for their academic coursework assignments and highlights the information accessibility issues they encountered. It discusses the need to develop a new model of e-book content delivery and proposes a framework for the evaluation of academic e-books from a commercial or "business" perspectiv

The MASSIVE Survey - V. Spatially-Resolved Stellar Angular Momentum, Velocity Dispersion, and Higher Moments of the 41 Most Massive Local Early-Type Galaxies

We present spatially-resolved two-dimensional stellar kinematics for the 41 most massive early-type galaxies (MK ~ 10^11.8 Msun) of the volume-limited (D < 108 Mpc) MASSIVE survey. For each galaxy, we obtain high-quality spectra in the wavelength range of 3650 to 5850 A from the 246-fiber Mitchell integral-field spectrograph (IFS) at McDonald Observatory, covering a 107" x 107" field of view (often reaching 2 to 3 effective radii). We measure the 2-D spatial distribution of each galaxy's angular momentum (lambda and fast or slow rotator status), velocity dispersion (sigma), and higher-order non-Gaussian velocity features (Gauss-Hermite moments h3 to h6). Our sample contains a high fraction (~80% ) of slow and non-rotators with lambda <~ 0.2. When combined with the lower-mass ETGs in the ATLAS3D survey, we find the fraction of slow-rotators to increase dramatically with galaxy mass, reaching ~50% at MK ~ -25.5 mag and ~90% at MK <~ -26 mag. All of our fast rotators show a clear anti-correlation between h3 and V/sigma, and the slope of the anti-correlation is steeper in more round galaxies. The radial profiles of sigma show a clear luminosity and environmental dependence: the 12 most luminous galaxies in our sample (MK <~ -26 mag) are all brightest cluster/group galaxies (except NGC 4874) and all have rising or nearly flat sigma profiles, whereas five of the seven "isolated" galaxies are all fainter than MK = -25.8 mag and have falling sigma. All of our galaxies have positive average h4; the most luminous galaxies have average h4 ~ 0.05 while less luminous galaxies have a range of values between 0 and 0.05. Most of our galaxies show positive radial gradients in h4, and those galaxies also tend to have rising sigma profiles. We discuss the implications for the relationship among dynamical mass, sigma, h4, and velocity anisotropy for these massive galaxies.Comment: 32 pages, 14 figures, 16 appendix figures. Accepted to MNRA

The MASSIVE Survey - XII Connecting Stellar Populations of Early-Type Galaxies to Kinematics and Environment

We measure the stellar populations as a function of radius for 90 early-type galaxies (ETGs) in the MASSIVE survey, a volume-limited integral-field spectroscopic (IFS) galaxy survey targeting all northern-sky ETGs with absolute K-band magnitude M_K < -25.3 mag, or stellar mass M* 4x10^11 M_sun, within 108 Mpc. We are able to measure reliable stellar population parameters for individual galaxies out to 10-20 kpc (1-3 R_e) depending on the galaxy. Focusing on ~R_e (~10 kpc), we find significant correlations between the abundance ratios, sigma, and M* at large radius, but we also find that the abundance ratios saturate in the highest-mass bin. We see a strong correlation between the kurtosis of the line of sight velocity distribution (h4) and the stellar population parameters beyond R_e. Galaxies with higher radial anisotropy appear to be older, with metal-poorer stars and enhanced [alpha/Fe]. We suggest that the higher radial anisotropy may derive from more accretion of small satellites. Finally, we see some evidence for correlations between environmental metrics (measured locally and on >5 Mpc scales) and the stellar populations, as expected if satellites are quenched earlier in denser environments.Comment: 17 pages, 7 figures, Appendix not included here due to size constraints. Posted after responding to referee's comment

Loss and dispersion of superficial white matter in Alzheimer's disease: a diffusion MRI study

Pathological cerebral white matter changes in Alzheimer’s disease have been shown using diffusion tensor imaging. Superficial white matter changes are relatively understudied despite their importance in cortico-cortical connections. Measuring superficial white matter degeneration using diffusion tensor imaging is challenging due to its complex organizational structure and proximity to the cortex. To overcome this, we investigated diffusion MRI changes in young-onset Alzheimer’s disease using standard diffusion tensor imaging and Neurite Orientation Dispersion and Density Imaging to distinguish between disease-related changes that are degenerative (e.g. loss of myelinated fibres) and organizational (e.g. increased fibre dispersion). Twenty-nine young-onset Alzheimer’s disease patients and 22 healthy controls had both single-shell and multi-shell diffusion MRI. We calculated fractional anisotropy, mean diffusivity, neurite density index, orientation dispersion index and tissue fraction (1-free water fraction). Diffusion metrics were sampled in 15 a priori regions of interest at four points along the cortical profile: cortical grey matter, grey/white boundary, superficial white matter (1 mm below grey/white boundary) and superficial/deeper white matter (2 mm below grey/white boundary). To estimate cross-sectional group differences, we used average marginal effects from linear mixed effect models of participants’ diffusion metrics along the cortical profile. The superficial white matter of young-onset Alzheimer’s disease individuals had lower neurite density index compared to controls in five regions (superior and inferior parietal, precuneus, entorhinal and parahippocampus) (all P < 0.05), and higher orientation dispersion index in three regions (fusiform, entorhinal and parahippocampus) (all P < 0.05). Young-onset Alzheimer’s disease individuals had lower fractional anisotropy in the entorhinal and parahippocampus regions (both P < 0.05) and higher fractional anisotropy within the postcentral region (P < 0.05). Mean diffusivity was higher in the young-onset Alzheimer’s disease group in the parahippocampal region (P < 0.05) and lower in the postcentral, precentral and superior temporal regions (all P < 0.05). In the overlying grey matter, disease-related changes were largely consistent with superficial white matter findings when using neurite density index and fractional anisotropy, but appeared at odds with orientation dispersion and mean diffusivity. Tissue fraction was significantly lower across all grey matter regions in young-onset Alzheimer’s disease individuals (all P < 0.001) but group differences reduced in magnitude and coverage when moving towards the superficial white matter. These results show that microstructural changes occur within superficial white matter and along the cortical profile in individuals with young-onset Alzheimer’s disease. Lower neurite density and higher orientation dispersion suggests underlying fibres undergo neurodegeneration and organizational changes, two effects previously indiscernible using standard diffusion tensor metrics in superficial white matter

Changes in lipid levels and incidence of cardiovascular events following tofacitinib treatment in patients with psoriatic arthritis: a pooled analysis acrossphase III and long‐term extension studies

Objective: The risk of cardiovascular disease (CVD) is higher in patients with psoriatic arthritis (PsA) compared to the general population. Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. Because tofacitinib increases circulating lipid levels in some patients, we evaluated CVD risk factors and major adverse cardiovascular events (MACE) in patients with active PsA receiving tofacitinib 5 or 10 mg twice daily plus conventional synthetic disease‐modifying antirheumatic drugs. Methods: Data were pooled from 2 phase III studies (Efficacy and Safety of Tofacitinib in Psoriatic Arthritis [OPAL Broaden] and Tofacitinib in Patients with Psoriatic Arthritis With Inadequate Response to TNF Inhibitors [OPAL Beyond]) and 1 ongoing long‐term extension (Open‐Label Extension Study of Tofacitinib in Psoriatic Arthritis [OPAL Balance], data cutoff January 2017; database not locked). Outcomes included fasting lipid levels, blood pressure, hypertension‐related adverse events (AEs; including hypertension, high blood pressure, and increased blood pressure), and MACE. Results: Overall, 783 tofacitinib‐treated patients were included. Percentage increases from baseline in low‐density lipoprotein cholesterol (LDL‐c) and high‐density lipoprotein cholesterol (HDL‐c) levels ranged from 9% to 14% for tofacitinib 5 mg and 10 mg at 3 and 6 months; no meaningful changes in LDL‐c:HDL‐c or total cholesterol:HDL‐c ratios were observed. Blood pressure remained stable for 24 months. Fifty‐eight patients (7.4%) had hypertension‐related AEs; none were fatal (incidence rate [IR] per 100 patient‐years 4.81 [95% confidence interval (95% CI) 3.65–6.22]). Five patients (0.6%) had MACE (IR 0.24 [95% CI 0.05–0.70]); 2 were fatal. Conclusion: Serum lipid level increases at month 3 following tofacitinib treatment in PsA were consistent with observations in rheumatoid arthritis and psoriasis. The IR of hypertension‐related AEs and MACE was low; long‐term follow‐up is ongoing