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Feasibility and utility of a sickle cell disease registry for research and patient management
This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.This thesis aimed to evaluate the feasibility and utility of a sickle cell disease registry for
clinical patient management and research. Five hospitals out of nine in the North West
London health region participated in the registry, with 78 percent coverage of the sickle
cell disease population. There was 80% case ascertainment in participating hospitals.
Aggregated anonymised demographic and diagnostic data was collected for all
haemoglobinopathy patients. This provided the core dataset for quantifying prevalence of
sickle cell and thalassaemia and mapping local hospital workloads and service
requirements. Thirteen percent of HbSS adult patients were taking hydroxycarbamide.
The cohort of patients treated with hydroxycarbamide was evaluated. Sixty two of the 80
patients started on treatment were included. Follow-up was censored after 9 years, totalling
249 person-years of data with a median follow-up of three years (IQR, 1-6). Results
showed that haematological benefits were maintained in the long-term with treatment, but
evidence of long-term clinical effectiveness was less strong. This appeared to be due to the
patterns of clinical management in everyday practice. Patients tend to be treated with
modest doses of hydroxycarbamide due to intolerance or inability to attain or maintain
maximum tolerated dose. For example maximum tolerated dose was the aim of treatment
for 91% of patients but it was achieved for 65% of participants. Non- compliance with
treatment and monitoring schedule was the main reason for non- attainment.
Results suggest that it is sensible to strive for maximum tolerated dose to ensure therapy
remains effective, but with more realistic expectations of the dose patients can attain and
maintain. Doses in adult patients average 20mg/kg/day and 25mg/kg/day in children. Adult
patients may be able to achieve a higher dose, if there was more stringent monitoring and
improved management of non-compliance.
The North West London HU Sub-Registry proved useful for measuring long-term
effectiveness and tolerability of hydroxycarbamide. Routinely collected data was utilized
for both clinical management and research purposes. The novelty lay in examination of the
nuances of routine clinical practice. An electronic patient record was developed as a
clinical management tool. It is the first study reporting long-term outcomes for UK sickle
cell disease patients on hydroxycarbamide.
Findings should help clinicians devise effective treatment protocols and strategies for
managing patients commenced on this therapy. Interventions need to be targeted at
increasing utilisation, patient adherence and persistence with treatment. The electronic
patient record could be used to maximise treatment benefit and improve adherence. More
effective involvement of the multidisciplinary team and primary care colleagues in patient
education and management should improve usage. Patients and carers need up to date and
easy to assimilate information to make informed decisions about treatment options.
Maintaining a SCD registry is challenging. Models which operate as clinical information
systems provide an incentive for participation. These enable active involvement of local
care providers in registry management and the ability to keep and utilize their own data.
Clinicians require accurate and current data for patient management and to enable them to
benchmark their local outcomes against national outcomes and care standards
Albatross: Rolling on a Sea of Data
Big deals and journal package incentives are an increasing reality for academic libraries, yet the solutions for evaluating these package scenarios in a timely, cost-effective manner are few. The proliferation of these offers requires the examination of numerous and complex questions. There is a need to know the utilization and strength of a package, the inflation costs for various titles and packages, and the ability to identify cost trends. A team of librarians at Virginia Tech created a solution for addressing these concerns and for managing their journal data by designing and developing an in-house database. Albatross, named in reference to The Rime of the Ancient Mariner, is a database created to gather journal usage data and cost data in a central environment where the data can then be queried to use in return-on-investment analysis and journal package assessments
On the Nature of Andromeda IV
Lying at a projected distance of 40' or 9 kpc from the centre of M31,
Andromeda IV is an enigmatic object first discovered during van den Bergh's
search for dwarf spheroidal companions to M31. Being bluer, more compact and
higher surface brightness than other known dwarf spheroidals, it has been
suggested that And IV is either a relatively old `star cloud' in the outer disk
of M31 or a background dwarf galaxy. We present deep HST WFPC2 observations of
And IV and the surrounding field which, along with ground-based long-slit
spectroscopy and Halpha imagery, are used to decipher the true nature of this
puzzling object. We find compelling evidence that And IV is a background galaxy
seen through the disk of M31. The moderate surface brightness (SB(V)~24), very
blue colour (V-I<~0.6), low current star formation rate (~0.001 solar mass/yr)
and low metallicity (~10% solar) reported here are consistent with And IV being
a small dwarf irregular galaxy, perhaps similar to Local Group dwarfs such as
IC 1613 and Sextans A. Although the distance to And IV is not tightly
constrained with the current dataset, various arguments suggest it lies in the
range 5<~D<~8 Mpc, placing it well outside the confines of the Local Group. It
may be associated with a loose group of galaxies, containing major members UGC
64, IC 1727 and NGC 784. We report an updated position and radial velocity for
And IV.Comment: 26 pages, LaTex with 9 figures (including 6 jpg plates). Accepted for
publication in A
Compatibility of quantitative X-ray spectroscopy with continuous distribution models of water at ambient conditions
The phase diagram of water harbors controversial views on underlying structural properties of its constituting molecular moieties, its fluctuating hydrogen-bonding network, as well as pair-correlation functions. In this work, long energy-range detection of the X-ray absorption allows us to unambiguously calibrate the spectra for water gas, liquid, and ice by the experimental atomic ionization cross-section. In liquid water, we extract the mean value of 1.74 +/- 2.1% donated and accepted hydrogen bonds per molecule, pointing to a continuous-distribution model. In addition, resonant inelastic X-ray scattering with unprecedented energy resolution also supports continuous distribution of molecular neighborhoods within liquid water, as do X-ray emission spectra once the femtosecond scattering duration and proton dynamics in resonant X-ray-matter interaction are taken into account. Thus, X-ray spectra of liquid water in ambient conditions can be understood without a two-structure model, whereas the occurrence of nanoscale-length correlations within the continuous distribution remains open
FjordPhyto: la experiencia de un proyecto de ciencia ciudadana en la Antártida que involucra turistas y microalgas
Desde hace más de 5 años las y los viajeros que visitan el continente antártico durante los meses de verano (noviembre - marzo) ayudan a las y los investigadores a monitorear cambios en la comunidad fitoplanctónica en relación al derretimiento glaciar. La Península Antártica es una región que está experimentando cambios rápidos debidos al calentamiento global. El fitoplancton (microalgas) es la base de la red alimenticia marina y es ignorado por la sociedad debido a su tamaño microscópico. A su vez, el turismo antártico es una industria actualmente en aumento y diversificación. Los proyectos de ciencia ciudadana son una excelente herramienta para educar al turismo en cuanto a conservación e impactos del cambio climático. El proyecto FjordPhyto nace como una colaboración entre investigadores (principalmente de Estados Unidos y Argentina) con la Asociación Internacional de Operadores de Tours Antárticos (IAATO por sus siglas en inglés). Este proyecto de ciencia ciudadana aprovecha las embarcaciones turísticas como plataformas para tomar muestras e involucrar a la comunidad viajera en el legado de la investigación polar. El proyecto FjordPhyto busca crear concientización en las y los turistas sobre estas comunidades microscópicas, que incluso tienen la oportunidad de observar con un microscopio a bordo.Facultad de Informátic
Tractography of developing white matter of the internal capsule and corpus callosum in very preterm infants
To investigate in preterm infants associations between Diffusion Tensor Imaging (DTI) parameters of the posterior limb of the internal capsule (PLIC) and corpus callosum (CC) and age, white matter (WM) injury and clinical factors. In 84 preterm infants DTI was performed between 40-62 weeks postmenstrual age on 3 T MR. Fractional anisotropy (FA), apparent diffusion coefficient (ADC) values and fibre lengths through the PLIC and the genu and splenium were determined. WM injury was categorised as normal/mildly, moderately and severely abnormal. Associations between DTI parameters and age, WM injury and clinical factors were analysed. A positive association existed between FA and age at imaging for fibres through the PLIC (r = 0.48 p < 0.001) and splenium (r = 0.24 p < 0.01). A negative association existed between ADC and age at imaging for fibres through the PLIC (r = -0.65 p < 0.001), splenium (r = -0.35 p < 0.001) and genu (r = -0.53 p < 0.001). No association was found between DTI parameters and gestational age, degree of WM injury or categorical clinical factors. These results indicate that in our cohort of very preterm infants, at this young age, the development of the PLIC and CC is ongoing and independent of the degree of prematurity or WM injury.Neuro Imaging Researc
Triangulum II: A Very Metal-poor and Dynamically Hot Stellar System
We present a study of the recently discovered compact stellar system
Triangulum II. From observations conducted with the DEIMOS spectrograph on Keck
II, we obtained spectra for 13 member stars that follow the CMD features of
this very faint stellar system and include two bright red giant branch stars.
Tri II has a very negative radial velocity (=-383.7^{+3.0}_{-3.3} km/s)
that translates to ~ -264 km/s and confirms it is a Milky Way
satellite. We show that, despite the small data set, there is evidence that Tri
II has complex internal kinematics. Its radial velocity dispersion increases
from 4.4^{+2.8}_{-2.0} km/s in the central 2' to 14.1^{+5.8}_{-4.2} km/s
outwards. The velocity dispersion of the full sample is inferred to be
\sigma_{vr}=9.9^{+3.2}_{-2.2} km/s. From the two bright RGB member stars we
measure an average metallicity =-2.6+/-0.2, placing Tri II among the
most metal-poor Milky Way dwarf galaxies. In addition, the spectra of the
fainter member stars exhibit differences in their line widths that could be the
indication of a metallicity dispersion in the system. All these properties
paint a complex picture for Tri II, whose nature and current state are largely
speculative. The inferred metallicity properties of the system however lead us
to favor a scenario in which Tri II is a dwarf galaxy that is either disrupting
or embedded in a stellar stream.Comment: 8 pages, 6 figures, 2 tables. ApJ, in press. v2: only minor changes
to the tex
Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease
BACKGROUND:
Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes.
METHODS:
We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization.
RESULTS:
During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events.
CONCLUSIONS:
Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)
Compatibility of quantitative X-ray spectroscopy with continuous distribution models of water at ambient conditions
The phase diagram of water harbors controversial views on underlying structural properties of its constituting molecular moieties, its fluctuating hydrogen-bonding network, as well as pair-correlation functions. In this work, long energy-range detection of the X-ray absorption allows us to unambiguously calibrate the spectra for water gas, liquid, and ice by the experimental atomic ionization cross-section. In liquid water, we extract the mean value of 1.74 ± 2.1% donated and accepted hydrogen bonds per molecule, pointing to a continuous-distribution model. In addition, resonant inelastic X-ray scattering with unprecedented energy resolution also supports continuous distribution of molecular neighborhoods within liquid water, as do X-ray emission spectra once the femtosecond scattering duration and proton dynamics in resonant X-ray–matter interaction are taken into account. Thus, X-ray spectra of liquid water in ambient conditions can be understood without a two-structure model, whereas the occurrence of nanoscale-length correlations within the continuous distribution remains open