319 research outputs found
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,
, 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 -band magnitude mag, or
stellar mass , within 108 Mpc. Our wide-field
107" 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
and of . While
is mostly negative, of the 56 galaxies with sufficient
radial coverage to determine 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
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 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 . 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 -band
magnitude , or stellar mass . 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 th neighbour). The spatially resolved IFS stellar kinematics provide
robust measurements of the spin parameter and enable us to examine
the relationship among , , and galaxy environment. We find a
strong correlation between and , where the average
decreases from to below 0.1 with increasing mass, and the fraction
of slow rotators increases from % to 90%. We show for
the first time that at fixed , there are almost no trends between galaxy
spin and environment; the apparent kinematic morphology-density relation for
ETGs is therefore primarily driven by and is accounted for by the joint
correlations between and spin, and between and environment. A
possible exception is that the increased 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
field of view to investigate the kinematic features of 90
early-type galaxies above stellar mass in the MASSIVE
survey. We measure the misalignment angle 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
(), 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 from to . 11
galaxies have 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 and . In terms of local kinematic features,
51% of the sample exhibit kinematic twists of larger than , and 2
galaxies have kinematically distinct components. The frequency of misalignment
and the broad distribution of 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
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