Diffusion Tensor Imaging in Pediatric Brain Tumor Patients

In this dissertation, we outline our efforts to introduce an advanced MRI imaging technique called Diffusion Tensor Imaging (DTI) to the pediatric brain tumor population. We discuss the theory and application of DTI as it was performed in a series of translational investigations at St. Jude Children’s Research Hospital. We present evidence of how the introduction of this technique impacted diagnosis, and treatment. And finally, we demonstrate how DTI was used to investigate cognitive morbidities associated with cancer treatment and how this research provided insight into the underlying pathophysiology involved in the development of these treatment sequela. This research has generated important insights into the fundamental causes of neuroanatomical and cognitive deficits associated with cancer and cancer therapy. The use of DTI has permitted us to identify potential targets for improved radiological and surgical techniques as well as targets for pharmacological and behavioral interventions that might improve cognitive function in cancer survivors. The discoveries here afford us an opportunity to reduce the negative effects of cancer therapy on patients treated in the future while maintaining successful survival rates

Statistical Power, the Bispectrum and the Search for Non-Gaussianity in the CMB Anisotropy

We use simulated maps of the cosmic microwave background anisotropy to quantify the ability of different statistical tests to discriminate between Gaussian and non-Gaussian models. Despite the central limit theorem on large angular scales, both the genus and extrema correlation are able to discriminate between Gaussian models and a semi-analytic texture model selected as a physically motivated non-Gaussian model. When run on the COBE 4-year CMB maps, both tests prefer the Gaussian model. Although the bispectrum has comparable statistical power when computed on the full sky, once a Galactic cut is imposed on the data the bispectrum loses the ability to discriminate between models. Off-diagonal elements of the bispectrum are comparable to the diagonal elements for the non-Gaussian texture model and must be included to obtain maximum statistical power.Comment: Accepted for publication in ApJ; 20 pages, 6 figures, uses AASTeX v5.

Acute presentations of HIV are still missed in low prevalence areas

Objectives To evaluate missed opportunities and delays in the diagnosis of HIV in a low prevalence setting over a 24 year period. Methods Patients with acute presentations of HIV were included in a retrospective note based review. Data were compared from acute presentations in 1985e2001 (88/241 new patients) with 2005e2007 (99/136 new patients). The number of recorded clinical and laboratory clues to infection and subsequent time delays to diagnosis of HIV were evaluated. Results The findings reflect the shifting demographics of HIV in the UK over the past two decades, exemplified by an eightfold increase in tuberculosis at presentation. Despite recording clinical stigmata of HIV (clues) in the notes, the number of missed clues increased, and many clinicians failed to request HIV testing. The median delay between presentation and diagnosis reduced from 5 to 1 day (p<0.001), and mortality dropped from 14% to 4% among patients presenting with acute symptoms. However, there was still a delay of more than 30 days before diagnosis for almost one in five patients. Conclusions Despite some improvement and better awareness, there are still significant delays before hospital doctors consider the diagnosis of HIV for patients in low prevalence areas, even among some patient groups with high risk. Hospitals should consider moving to opt-out routine HIV testing of all medical admission

A Search for Environmental Effects on Type Ia Supernovae

We use integrated colors and B and V absolute magnitudes of Type Ia supernova (SN) host galaxies in order to search for environmental effects on the SN optical properties. With the new sample of 44 SNe we confirm the conclusion by Hamuy et al. (1996a) that bright events occur preferentially in young stellar environments. We find also that the brightest SNe occur in the least luminous galaxies, a possible indication that metal-poorer neighbourhoods produce the more luminous events. The interpretation of these results is made difficult, however, due to the fact that galaxies with younger stellar populations are also lower in luminosity. In an attempt to remove this ambiguity we use models for the line strengths in the absorption spectrum of five early-type galaxies, in order to estimate metallicities and ages of the SN host galaxies. With the addition of abundance estimates from nebular analysis of the emission spectra of three spiral galaxies, we find possible further evidence that luminous SNe are produced in metal-poor neighborhoods. Further spectroscopic observations of the SN host galaxies will be necessary to test these results and assist in disentangling the age/metallicity effects on Type Ia SNe.Comment: 14 pages, 5 figures, to appear in the September 2000 issue of The Astronomical Journa

Selective primary alcohol oxidation of lignin streams from butanol-pretreated agricultural waste biomass

We would like to thank the CRITICAT Centre for Doctoral Training for financial support [Ph.D. studentship to IP; Grant code: EP/L016419/1] and BBSRC Global Challenges Research Fund Impact Acceleration Account at St Andrews BB/GCRFIAA/20. CSL thanks the Leverhulme Trust for funding an Early Career Fellowship.Chemically modified lignins are important for the generation of biomass-derived materials and as precursors to renewable aromatic monomers. A butanol-based organosolv pretreatment has been used to convert an abundant agricultural waste product, rice husks, into a cellulose pulp and three additional product streams. One of these streams, a butanol-modified lignin, was oxidized at the γ position to give a carboxylic acid functionalized material. Subsequent coupling of the acid with aniline aided lignin characterization and served as an example of the flexibility of this approach for grafting side chains onto a lignin core structure. The pretreatment was scaled up for use on a multi-kilogram scale, a development that enabled the isolation of an anomeric mixture of butoxylated xylose in high purity. The robust and scalable butanosolv pretreatment has been developed further and demonstrates considerable potential for the processing of rice husks.PostprintPeer reviewe

Quantifying Vitamin K-dependent Holoprotein Compaction caused by differential γ-carboxylation using HPSEC

This study uses high-pressure size exclusion chromatography (HPSEC) to quantify divalent metal ion (X2+)-induced compaction found in vitamin K dependent (VKD) proteins. Multiple X2+ binding sites formed by the presence of up to 12 -carboxyglutamic acid residues (Gla) are present in plasma-derived (pd-) and recombinant (r-) Factor IX (FIX). Analytical ultracentrifugation (AUC) was used to calibrate the Stokes radius (R) measured by HPSEC. A compaction of pd-FIX caused by the filling of Ca2+ and Mg2+ binding sites resulting in a 5-6% decrease in radius of hydration as observed by HPSEC. The filling of Ca2+ sites resulted greater compaction than for Mg2+ alone where this effect was additive or greater when both ions were present at physiologic levels. Less X2+ induced compaction was observed in r-FIX with lower Gla content populations which enabled the separation of biologically active from inactive r-FIX species by HPSEC. HPSEC was sensitive to R changes of ~0.01 nm that enabled the detection of FIX compaction that was likely cooperative in nature between lower avidity X2+ sites of the Gla domain and higher X2+ avidity sites of the EGF1-like domain

Middle pleistocene glaciation in Patagonia dated by cosmogenic-nuclide measurements on outwash gravels

The well-preserved glacial record in Argentine Patagonia offers a ~ 1 Ma archive of terrestrial climate extremes in southern South America. These glacial deposits remain largely undated beyond the range of radiocarbon dating at ca. 40 ka. Dating old glacial deposits (> several 105 a) by cosmogenic surface exposure methods is problematic because of the uncertainty in moraine degradation and boulder erosion rates. Here, we show that cobbles on outwash terraces can reliably date ‘old’ glacial deposits in the Lago Pueyrredón valley, 47.5° S, Argentina. Favorable environmental conditions (e.g., aridity and strong winds) have enabled continuous surface exposure of cobbles and preservation of outwash terraces. The data demonstrate that nuclide inheritance is negligible and we therefore use the oldest surface cobbles to date the deposit. 10Be concentrations in outwash cobbles reveal a major glacial advance at ca. 260 ka, concurrent with Marine Isotope Stage 8 (MIS 8) and dust peaks in Antarctic ice cores. A 10Be concentration depth-profile in the outwash terrace supports the age and suggests a low terrace erosion rate of ca. 0.5 mm ka− 1. We compare these data to exposure ages obtained from associated moraines and find that surface boulders underestimate the age of the glaciation by ~ 100 ka; thus the oldest boulders in this area do not date closely moraine deposition. The 10Be concentration in moraine cobbles help to constrain moraine degradation rates. These data together with constraints from measured 26Al/10Be ratios suggest that all moraine boulders were likely exhumed after original deposition. We determine the local Last Glacial Maximum (LGM) occurred at ~ 27–25 ka, consistent with the maximum LGM in other parts of Patagonia

The Carnegie Supernova Project: The Low-Redshift Survey

Supernovae are essential to understanding the chemical evolution of the Universe. Type Ia supernovae also provide the most powerful observational tool currently available for studying the expansion history of the Universe and the nature of dark energy. Our basic knowledge of supernovae comes from the study of their photometric and spectroscopic properties. However, the presently available data sets of optical and near-infrared light curves of supernovae are rather small and/or heterogeneous, and employ photometric systems that are poorly characterized. Similarly, there are relatively few supernovae whose spectral evolution has been well sampled, both in wavelength and phase, with precise spectrophotometric observations. The low-redshift portion of the Carnegie Supernova Project (CSP) seeks to remedy this situation by providing photometry and spectrophotometry of a large sample of supernovae taken on telescope/filter/detector systems that are well understood and well characterized. During a five-year program which began in September 2004, we expect to obtain high-precision u'g'r'i'BVYJHKs light curves and optical spectrophotometry for about 250 supernovae of all types. In this paper we provide a detailed description of the CSP survey observing and data reduction methodology. In addition, we present preliminary photometry and spectra obtained for a few representative supernovae during the first observing campaign.Comment: 45 pages, 13 figures, 3 tables, accepted by PAS