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Sökning: WFRF:(Pritchard Jonathan R.)

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1.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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2.
  • Drake, Thomas M., et al. (författare)
  • Outcomes following small bowel obstruction due to malignancy in the national audit of small bowel obstruction
  • 2019
  • Ingår i: European Journal of Surgical Oncology. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 45:12, s. 2319-2324
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology Introduction: Patients with cancer who develop small bowel obstruction are at high risk of malnutrition and morbidity following compromise of gastrointestinal tract continuity. This study aimed to characterise current management and outcomes following malignant small bowel obstruction. Methods: A prospective, multicentre cohort study of patients with small bowel obstruction who presented to UK hospitals between 16th January and 13th March 2017. Patients who presented with small bowel obstruction due to primary tumours of the intestine (excluding left-sided colonic tumours) or disseminated intra-abdominal malignancy were included. Outcomes included 30-day mortality and in-hospital complications. Cox-proportional hazards models were used to generate adjusted effects estimates, which are presented as hazard ratios (HR) alongside the corresponding 95% confidence interval (95% CI). The threshold for statistical significance was set at the level of P ≤ 0.05 a-priori. Results: 205 patients with malignant small bowel obstruction presented to emergency surgery services during the study period. Of these patients, 50 had obstruction due to right sided colon cancer, 143 due to disseminated intraabdominal malignancy, 10 had primary tumours of the small bowel and 2 patients had gastrointestinal stromal tumours. In total 100 out of 205 patients underwent a surgical intervention for obstruction. 30-day in-hospital mortality rate was 11.3% for those with primary tumours and 19.6% for those with disseminated malignancy. Severe risk of malnutrition was an independent predictor for poor mortality in this cohort (adjusted HR 16.18, 95% CI 1.86 to 140.84, p = 0.012). Patients with right-sided colon cancer had high rates of morbidity. Conclusions: Mortality rates were high in patients with disseminated malignancy and in those with right sided colon cancer. Further research should identify optimal management strategy to reduce morbidity for these patient groups.
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3.
  • Haas, Brian J., et al. (författare)
  • Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans
  • 2009
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 461:7262, s. 393-398
  • Tidskriftsartikel (refereegranskat)abstract
    • Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement(1). To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population(1). Current annual worldwide potato crop losses due to late blight are conservatively estimated at $6.7 billion(2). Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars(3,4). Here we report the sequence of the P. infestans genome, which at similar to 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for similar to 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.
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4.
  • Mellema, Garrelt, et al. (författare)
  • Reionization and the Cosmic Dawn with the Square Kilometre Array
  • 2013
  • Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 36:1-2, s. 235-318
  • Tidskriftsartikel (refereegranskat)abstract
    • The Square Kilometre Array (SKA) will have a low frequency component (SKA-low) which has as one of its main science goals the study of the redshifted 21 cm line from the earliest phases of star and galaxy formation in the Universe. This 21 cm signal provides a new and unique window both on the time of the formation of the first stars and accreting black holes and the subsequent period of substantial ionization of the intergalactic medium. The signal will teach us fundamental new things about the earliest phases of structure formation, cosmology and even has the potential to lead to the discovery of new physical phenomena. Here we present a white paper with an overview of the science questions that SKA-low can address, how we plan to tackle these questions and what this implies for the basic design of the telescope.
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5.
  • Bacon, David J., et al. (författare)
  • Cosmology with Phase 1 of the Square Kilometre Array Red Book 2018 : Technical specifications and performance forecasts
  • 2020
  • Ingår i: Publications Astronomical Society of Australia. - : Cambridge University Press (CUP). - 1323-3580 .- 1448-6083. ; 37
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a detailed overview of the cosmological surveys that we aim to carry out with Phase 1 of the Square Kilometre Array (SKA1) and the science that they will enable. We highlight three main surveys: a medium-deep continuum weak lensing and low-redshift spectroscopic HI galaxy survey over 5 000 deg2; a wide and deep continuum galaxy and HI intensity mapping (IM) survey over 20 000 deg2 from z = 0.35 to 3; and a deep, high-redshift HI IM survey over 100 deg2 from z = 3 to 6. Taken together, these surveys will achieve an array of important scientific goals: measuring the equation of state of dark energy out to z = 3 with percent-level precision measurements of the cosmic expansion rate; constraining possible deviations from General Relativity on cosmological scales by measuring the growth rate of structure through multiple independent methods; mapping the structure of the Universe on the largest accessible scales, thus constraining fundamental properties such as isotropy, homogeneity, and non-Gaussianity; and measuring the HI density and bias out to z = 6. These surveys will also provide highly complementary clustering and weak lensing measurements that have independent systematic uncertainties to those of optical and near-infrared (NIR) surveys like Euclid, LSST, and WFIRST leading to a multitude of synergies that can improve constraints significantly beyond what optical or radio surveys can achieve on their own. This document, the 2018 Red Book, provides reference technical specifications, cosmological parameter forecasts, and an overview of relevant systematic effects for the three key surveys and will be regularly updated by the Cosmology Science Working Group in the run up to start of operations and the Key Science Programme of SKA1.
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6.
  • Kamran, Mohd, et al. (författare)
  • Redshifted 21-cm bispectrum - II. Impact of the spin temperature fluctuations and redshift space distortions on the signal from the Cosmic Dawn
  • 2021
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 502:3, s. 3800-3813
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a study of the 21-cm signal bispectrum (which quantifies the non-Gaussianity in the signal) from the Cosmic Dawn (CD). For our analysis, we have simulated the 21-cm signal using radiative transfer code GRIZZLY, while considering two types of sources (mini-QS05 and HMXBs) for Ly alpha coupling and the X-ray heating of the IGM. Using this simulated signal, we have, for the first time, estimated the CD 21-cm bispectra for all unique kappa-triangles and for a range of kappa modes. We observe that the redshift evolution of the bispectrum magnitude and sign follow a generic trend for both source models. However, the redshifts at which the bispectrum magnitude reaches their maximum and minimum values and show their sign reversal depends on the source model. When the Ly alpha coupling and the X-ray heating of the IGM occur simultaneously, we observe two consecutive sign reversals in the bispectra for small kappa-triangles (irrespective of the source models). One arising at the beginning of the IGM heating and the other at the end of Ly alpha-coupling saturation. This feature can be used in principle to constrain the CD history and/or to identify the specific CD scenarios. We also quantify the impact of the spin temperature (T-S) fluctuations on the bispectra. We find that T-S fluctuations have maximum impact on the bispectrum magnitude for small k-triangles and at the stage when Ly alpha coupling reaches saturation. Furthermore, we are also the first to quantify the impact of redshift space distortions (RSD), on the CD bispectra. We find that the impact of RSD on the CD 21-cm bispectra is significant (> 20 per cent) and the level depends on the stages of the CD and the k-triangles for which the bispectra are being estimated.
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7.
  • Majumdar, Suman, et al. (författare)
  • Quantifying the non-Gaussianity in the EoR 21-cm signal through bispectrum
  • 2018
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 476:3, s. 4007-4024
  • Tidskriftsartikel (refereegranskat)abstract
    • The epoch of reionization (EoR) 21-cm signal is expected to be highly non-Gaussian in nature and this non-Gaussianity is also expected to evolve with the progressing state of reionization. Therefore the signal will be correlated between different Fourier modes (k). The power spectrum will not be able capture this correlation in the signal. We use a higher order estimator - the bispectrum - to quantify this evolving non-Gaussianity. We study the bispectrum using an ensemble of simulated 21-cm signal and with a large variety of k triangles. We observe two competing sources driving the non-Gaussianity in the signal: fluctuations in the neutral fraction (X-HT) field and fluctuations in the matter density field. We find that the non-Gaussian contribution from these two sources varies, depending on the stage of reionization and on which k modes are being studied. We show that the sign of the bispectrum works as a unique marker to identify which among these two components is driving the non-Gaussianity. We propose that the sign change in the bispectrum, when plotted as a function of triangle configuration cos 0 and at a certain stage of the EoR can be used as a confirmative test for the detection of the 21-cm signal. We also propose a new consolidated way to visualize the signal evolution (with evolving (x) over bar (HT) or redshift), through the trajectories of the signal in a power spectrum and equilateral bispectrum i.e. P(k) - B(k, k, k) space.
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8.
  • Majumdar, Suman, et al. (författare)
  • Redshifted 21-cm bispectrum – I. Impact of the redshift space distortions on the signal from the Epoch of Reionization
  • 2020
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 499:4, s. 5090-5106
  • Tidskriftsartikel (refereegranskat)abstract
    • The bispectrum can quantify the non-Gussianity present in the redshifted 21-cm signal produced by the neutral hydrogen (⁠HI⁠) during the Epoch of Reionization (EoR). Motivated by this, we perform a comprehensive study of the EoR 21-cm bispectrum using simulated signals. Given a model of reionization, we demonstrate the behaviour of the bispectrum for all unique triangles in k space. For ease of identification of the unique triangles we parametrize the k-triangle space with two parameters, namely the ratio of the two arms of the triangle (n = k2/k1) and the cosine of the angle between them (cos θ). Furthermore, for the first time we quantify the impact of the redshift space distortions (RSD) on the spherically averaged EoR 21-cm bispectrum in the entire unique triangle space. We find that the real space signal bispectra for small and intermediate k1-triangles (⁠k1≤0.6Mpc−1⁠) is negative in most of the unique triangle space. It takes a positive sign for squeezed, stretched, and linear k1-triangles, specifically for large k1 values (⁠k1≥0.6Mpc−1⁠). The RSD affects both the sign and magnitude of the bispectra significantly. It changes (increases/decreases) the magnitude of the bispectra by 50−100 per cent without changing its sign (mostly) during the entire period of the EoR for small and intermediate k1-triangles. For larger k1-triangles, RSD affects the magnitude by 100−200 per cent and also flips the sign from negative to positive. We conclude that it is important to take into account the impact of RSD for a correct interpretation of the EoR 21-cm bispectra.
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9.
  • Ollila, Hanna M., et al. (författare)
  • Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy
  • 2023
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix (R). Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix (R).
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10.
  • Watkinson, Catherine A., et al. (författare)
  • The 21-cm bispectrum as a probe of non-Gaussianities due to X-ray heating
  • 2019
  • Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 482:2, s. 2653-2669
  • Tidskriftsartikel (refereegranskat)abstract
    • We present analysis of the normalized 21-cm bispectrum from fully-numerical simulations of intergalactic-medium heating by stellar sources and high-mass X-ray binaries (HMXBs) during the cosmic dawn. Ly-alpha coupling is assumed to be saturated, we therefore probe the nature of non-Gaussianities produced by X-ray heating processes. We find the evolution of the normalized bispectrum to be very different from that of the power spectrum. It exhibits a turnover whose peak moves from large to small scales with decreasing redshift, and corresponds to the typical separation of emission regions. This characteristic scale reduces as more and more regions move into emission with time. Ultimately, small-scale fluctuations within heated regions come to dominate the normalized bispectrum, which at the end of the simulation is almost entirely driven by fluctuations in the density field. To establish how generic the qualitative evolution of the normalized bispectrum we see in the stellar + HMXB simulation is, we examine several other simulations - two fully numerical simulations that include quasi-stellar object (QSO) sources, and two with contrasting source properties produced with the semi-numerical simulation 21CMFAST. We find the qualitative evolution of the normalized bispectrum during X-ray heating to be generic, unless the sources of X-rays are, as with QSOs, less numerous and so exhibit more distinct isolated heated profiles. Assuming mitigation of foreground and instrumental effects are ultimately effective, we find that we should be sensitive to the normalized bispectrum during the epoch of heating, so long as the spin temperature has not saturated by z approximate to 19.
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