“A Fit of Absence of Mind?” Learning about British Imperialism in the 21st Century

The British Empire was instrumental in shaping the modern world as we know it. Despite its significance for today, controversies rage over how we should teach it to younger generations. Writing for Frontier, Dr Adam D. Burns discusses his recent investigations into the different educational factors influencing students’ perceptions of the British Empire

Applications of next-generation technologies in the diagnosis of haematological diseases and cancer

The advent of massively-parallel next-generation sequencing (NGS) methods has provided researchers with a powerful tool with which to interrogate and characterise the molecular landscape of cancer genomes. Compared to existing methods of DNA sequencing, NGS platforms generate massive amounts of sequence data and, as a consequence, can reveal information not just on single nucleotide variations (SNVs), but also on copy-number aberrations, translocations and large insertions and deletions in a single experiment. Furthermore, targeted NGS provides the capability to focus on a small number of targets simultaneously, with high accuracy and sensitivity. The presence of specific molecular markers acts as predictors of disease outcome, survival rates and treatment response in individual patients. Screening for such markers has become routine practice in diagnostic laboratories using traditional methods of DNA analysis, are widely used in diagnostic laboratories around the world. Whilst these methods are proven and reliable, their limitations lie in the fact that they focus on only the most prevalent mutations in a particular cancer. The ability to investigate multiple gene targets within individual patients, to a high level of accuracy, and to monitor these changes over time will be a valuable tool in cancer diagnostics. As such, there is a potential use case for NGS techniques in routine diagnostics. Therefore, this thesis investigated the extent to which NGS platforms could be used in a clinical setting for the diagnosis and risk-stratification of both lymphoid and myeloid malignancies. A targeted next-generation sequencing panel was designed and validated against existing diagnostic methods. All mutations in the validation cohort were correctly identified. Both the specificity and sensitivity of the assay were determined and were considerably better than those of the current ‘gold-standard’ techniques. This panel has been fully validated and implemented into the diagnostic service at the John Radcliffe Hospital. The research applications of this panel were also demonstrated through the sequencing of a cohort of del(5q) MDS patients. It was not only found that mutations in TP53 and ASXL1 may be key drivers in the progression of del(5q) MDS into AML but also that 40% of del(5q) patients harboured at least one mutation. A number of mutations were below the limit of detection for Sanger sequencing, and so this study expands our knowledge of the del(5q) mutational landscape. Whole genome sequencing of 42 CLL cases revealed a high level of molecular heterogeneity, with mutations in key CLL driver genes including TP53, SF3B1, NOTCH1 and ATM. Both clinically relevant CNAs and translocations were detected in the cohort. Four mutation signatures were detected across the CLL genomes and are both associated with, and vary in their prevalence according to, specific clinical characteristics, including age and chemo-refractoriness. Mutations introduced as part of the SHM process in B-cells are present throughout the genome, including in patients with unmutated IgHV genes. Regions of localised hypermutation are present in CLL, with a number affecting genes associated with coding mutations in CLL, including ATM, KLHL6 and MEGF9. A number of mutation clusters are also identified in potentially regulatory regions of genes. In summary, this thesis demonstrates that both whole genome sequencing and targeted sequencing panels can be introduced into diagnostics to aid the clinical decision-making process and also reveal important new findings that increase our understanding of the pathogenesis of leukaemia

Portable, field-based neuroimaging using high-density diffuse optical tomography

Behavioral and cognitive tests in individuals who were malnourished as children have revealed malnutrition-related deficits that persist throughout the lifespan. These findings have motivated recent neuroimaging investigations that use highly portable functional near-infrared spectroscopy (fNIRS) instruments to meet the demands of brain imaging experiments in low-resource environments and enable longitudinal investigations of brain function in the context of long-term malnutrition. However, recent studies in healthy subjects have demonstrated that high-density diffuse optical tomography (HD-DOT) can significantly improve image quality over that obtained with sparse fNIRS imaging arrays. In studies of both task activations and resting state functional connectivity, HD-DOT is beginning to approach the data quality of fMRI for superficial cortical regions. In this work, we developed a customized HD-DOT system for use in malnutrition studies in Cali, Colombia. Our results evaluate the performance of the HD-DOT instrument for assessing brain function in a cohort of malnourished children. In addition to demonstrating portability and wearability, we show the HD-DOT instrument\u27s sensitivity to distributed brain responses using a sensory processing task and measurements of homotopic functional connectivity. Task-evoked responses to the passive word listening task produce activations localized to bilateral superior temporal gyrus, replicating previously published work using this paradigm. Evaluating this localization performance across sparse and dense reconstruction schemes indicates that greater localization consistency is associated with a dense array of overlapping optical measurements. These results provide a foundation for additional avenues of investigation, including identifying and characterizing a child\u27s individual malnutrition burden and eventually contributing to intervention development

The photometric variability of massive stars due to gravity waves excited by core convection

Massive stars die in catastrophic explosions, which seed the interstellar medium with heavy elements and produce neutron stars and black holes. Predictions of the explosion's character and the remnant mass depend on models of the star's evolutionary history. Models of massive star interiors can be empirically constrained by asteroseismic observations of gravity wave oscillations. Recent photometric observations reveal a ubiquitous red noise signal on massive main sequence stars; a hypothesized source of this noise is gravity waves driven by core convection. We present the first 3D simulations of massive star convection extending from the star's center to near its surface, with realistic stellar luminosities. Using these simulations, we make the first prediction of photometric variability due to convectively-driven gravity waves at the surfaces of massive stars, and find that gravity waves produce photometric variability of a lower amplitude and lower characteristic frequency than the observed red noise. We infer that the photometric signal of gravity waves excited by core convection is below the noise limit of current observations, so the red noise must be generated by an alternative process.Comment: As accepted for publication in Nature Astronomy except for final editorial revisions. Supplemental materials available online at https://doi.org/10.5281/zenodo.7764997 . We have also sonified our results to make them more accessible, see https://github.com/evanhanders/gmode_variability_paper/blob/main/sound/gmode_sonification.pd

The 3rd Fermi GBM Gamma-Ray Burst Catalog: The First Six Years

Since its launch in 2008, the Fermi Gamma-ray Burst Monitor (GBM) has triggered and located on average approximately two gamma-ray bursts (GRB) every three days. Here we present the third of a series of catalogs of GRBs detected by GBM, extending the second catalog by two more years, through the middle of July 2014. The resulting list includes 1405 triggers identified as GRBs. The intention of the GBM GRB catalog is to provide information to the community on the most important observables of the GBM detected GRBs. For each GRB the location and main characteristics of the prompt emission, the duration, peak flux and fluence are derived. The latter two quantities are calculated for the 50-300~keV energy band, where the maximum energy release of GRBs in the instrument reference system is observed, and also for a broader energy band from 10-1000 keV, exploiting the full energy range of GBM's low-energy NaI(Tl) detectors. Using statistical methods to assess clustering, we find that the hardness and duration of GRBs are better fitted by a two-component model with short-hard and long-soft bursts, than by a model with three components. Furthermore, information is provided on the settings and modifications of the triggering criteria and exceptional operational conditions during years five and six in the mission. This third catalog is an official product of the Fermi GBM science team, and the data files containing the complete results are available from the High-Energy Astrophysics Science Archive Research Center (HEASARC).Comment: 225 pages, 13 figures and 8 tables. Accepted for publication in Astrophysical Journal Supplement 201

Correction to: The Edinburgh Consensus: preparing for the advent of disease-modifying therapies for Alzheimer's disease.

Since the publication of this article [1], it has come to the attention of the authors that information for one of the authors was not included in the competing interests section. Craig Richie has declared potential competing interests with the following companies; Janssen, Eisai, Pfizer, Eli Lilly, Roche Diagnostics, Boeringher Ingleheim, Novartis, AC Immune, Ixico, Aridhia, Amgen, Berry Consultants, Lundbeck, Sanofi, Quintiles (IQVIA) and Takeda. The full competing interests section for this article can be found below

The Carnegie Supernova Project: First Near-Infrared Hubble Diagram to z~0.7

The Carnegie Supernova Project (CSP) is designed to measure the luminosity distance for Type Ia supernovae (SNe Ia) as a function of redshift, and to set observational constraints on the dark energy contribution to the total energy content of the Universe. The CSP differs from other projects to date in its goal of providing an I-band {rest-frame} Hubble diagram. Here we present the first results from near-infrared (NIR) observations obtained using the Magellan Baade telescope for SNe Ia with 0.1 < z < 0.7. We combine these results with those from the low-redshift CSP at z <0.1 (Folatelli et al. 2009). We present light curves and an I-band Hubble diagram for this first sample of 35 SNe Ia and we compare these data to 21 new SNe Ia at low redshift. These data support the conclusion that the expansion of the Universe is accelerating. When combined with independent results from baryon acoustic oscillations (Eisenstein et al. 2005), these data yield Omega_m = 0.27 +/- 0.0 (statistical), and Omega_DE = 0.76 +/- 0.13 (statistical) +/- 0.09 (systematic), for the matter and dark energy densities, respectively. If we parameterize the data in terms of an equation of state, w, assume a flat geometry, and combine with baryon acoustic oscillations, we find that w = -1.05 +/- 0.13 (statistical) +/- 0.09 (systematic). The largest source of systematic uncertainty on w arises from uncertainties in the photometric calibration, signaling the importance of securing more accurate photometric calibrations for future supernova cosmology programs. Finally, we conclude that either the dust affecting the luminosities of SNe Ia has a different extinction law (R_V = 1.8) than that in the Milky Way (where R_V = 3.1), or that there is an additional intrinsic color term with luminosity for SNe Ia independent of the decline rate.Comment: 44 pages, 23 figures, 9 tables; Accepted for publication in the Astrophysical Journa

The Multi-Object, Fiber-Fed Spectrographs for SDSS and the Baryon Oscillation Spectroscopic Survey

We present the design and performance of the multi-object fiber spectrographs for the Sloan Digital Sky Survey (SDSS) and their upgrade for the Baryon Oscillation Spectroscopic Survey (BOSS). Originally commissioned in Fall 1999 on the 2.5-m aperture Sloan Telescope at Apache Point Observatory, the spectrographs produced more than 1.5 million spectra for the SDSS and SDSS-II surveys, enabling a wide variety of Galactic and extra-galactic science including the first observation of baryon acoustic oscillations in 2005. The spectrographs were upgraded in 2009 and are currently in use for BOSS, the flagship survey of the third-generation SDSS-III project. BOSS will measure redshifts of 1.35 million massive galaxies to redshift 0.7 and Lyman-alpha absorption of 160,000 high redshift quasars over 10,000 square degrees of sky, making percent level measurements of the absolute cosmic distance scale of the Universe and placing tight constraints on the equation of state of dark energy. The twin multi-object fiber spectrographs utilize a simple optical layout with reflective collimators, gratings, all-refractive cameras, and state-of-the-art CCD detectors to produce hundreds of spectra simultaneously in two channels over a bandpass covering the near ultraviolet to the near infrared, with a resolving power R = \lambda/FWHM ~ 2000. Building on proven heritage, the spectrographs were upgraded for BOSS with volume-phase holographic gratings and modern CCD detectors, improving the peak throughput by nearly a factor of two, extending the bandpass to cover 360 < \lambda < 1000 nm, and increasing the number of fibers from 640 to 1000 per exposure. In this paper we describe the original SDSS spectrograph design and the upgrades implemented for BOSS, and document the predicted and measured performances.Comment: 43 pages, 42 figures, revised according to referee report and accepted by AJ. Provides background for the instrument responsible for SDSS and BOSS spectra. 4th in a series of survey technical papers released in Summer 2012, including arXiv:1207.7137 (DR9), arXiv:1207.7326 (Spectral Classification), and arXiv:1208.0022 (BOSS Overview