The nature of memory CD8+ T-cell responses in bovine tuberculosis.

M. bovis is a zoonosis and is the aetiological agent of bovine TB. The incidence of bovine TB in the UK is increasing, demonstrating that the current test and slaughter policy is failing. M. bovis-BCG, the vaccine used against human TB, is not used in cattle as it interferes with the tuberculin skin test and only confers partial protection. The control of bovine TB will require the design of a more efficacious vaccine and discriminatory diagnostic test. To achieve this, a greater understanding of both the immune response induced by the mycobacteria and the protective immune response required to clear or control M. bovis infection in cattle is needed. In human and mouse studies, CD8+ T cells have been proposed to play an important role in immunity to mycobacteria. The aim of this study was to identify and define the CD8+ T cells induced by BCG vaccination and/or M. bovis infection in cattle. Initial experiments identified different subsets of CD8+ T cells present in cattle using expression of surface and effector molecules. The CD8+ population is heterogeneous and contains ap (TCR1"CD3+), y8 (TCR1+CD3+) and NK (TCRTCD3") cells. CD8+ cells could be divided into CD8hiCD3+ and CD8loCD3+/ The (CD8hiTCRT) ap+ T cells were analysed in this study as these form part of the adaptive immune response. Age-related increases in the percentage of activated/memory CD8hlTCRl" T cells were observed in blood as shown by increases in expression of the activation marker CD25 and memory marker CD45RO. Concomitant decreases were observed in the percentage of CD8hiTCRlT cells that express CD45RA, CD62L and CD27, surface molecules associated with naive T cells. The percentage of CD8hiTCRl" T cells in blood expressing perforin and IFN-gamma also increased with age. The CD8hlTCRlT cells present in the BAL were mainly activated/memory T cells as shown by a combination of expression of surface and effector molecules. In contrast, the CD8hlTCRlT cells present in the lymph nodes more resembled naive T cells with only a small percentage expressing perforin and IFN-gamma. A minor population of CD8hiTCRl"CD45RO+CD62L+ T cells were present in the LN which may be the bovine equivalent of murine central memory cells. BCG vaccination of cattle induces mycobacteria-reactive CD8hlTCRl"CD45RO+ T cells. These cells mediated recall responses to BCG, detected by proliferation, production of IFN-gamma, up-regulation of perforin expression and lysis of BCG-infected hi + macrophages (M). M. bovis reactive-CD8mTCRl"CD45RO T cells were detected in non-vaccinated and BCG-vaccinated animals after infection with M. bovis. These cells proliferated and produced IFN-gamma in response to M. bovis-infected but not BCG-infected M( ), indicating that they were responding to an M. bovis-specific antigen. Post- challenge responses in the CD8hiTCRl'CD45RO+ T cells from BCG-vaccinees were considerably greater than those of non-vaccinated animals. M 6ov/s-reactive CD8hiTCRl"CD45RO+ T cells reduced mycobacterial viability when cultured with BCG- or M. bovis-infected M( >. CD8hiTCRl"CD45RO+ T cells present in the lungs of M. bovis-infected animals expressed IFN-gamma after culture with mycobacteria. These results demonstrate that mycobacteria-reactive CD8hiTCRl"CD45RO+ T cells that express effector functions are present at the site of infection, and may contribute to the control of M. bovis infection in cattle. This study provides a basis to investigate the role of CD8hiTCRl"CD45RO+ T cells in immunity to M. bovis infection in cattle and to evaluate the effectiveness of new TB vaccines at inducing CD8+ T cell responses

Mapping Antarctic crevasses and their evolution with deep learning applied to satellite radar imagery

The fracturing of glaciers and ice shelves in Antarctica influences their dynamics and stability. Hence, data on the evolving distribution of crevasses are required to better understand the evolution of the ice sheet, though such data have traditionally been difficult and time-consuming to generate. Here, we present an automated method of mapping crevasses on grounded and floating ice with the application of convolutional neural networks to Sentinel-1 synthetic aperture radar backscatter data. We apply this method across Antarctica to images acquired between 2015 and 2022, producing a 7.5-year record of composite fracture maps at monthly intervals and 50 m spatial resolution and showing the distribution of crevasses around the majority of the ice sheet margin. We develop a method of quantifying changes to the density of ice shelf fractures using a time series of crevasse maps and show increases in crevassing on Thwaites and Pine Island ice shelves over the observational period, with observed changes elsewhere in the Amundsen Sea dominated by the advection of existing crevasses. Using stress fields computed using the BISICLES ice sheet model, we show that much of this structural change has occurred in buttressing regions of these ice shelves, indicating a recent and ongoing link between fracturing and the developing dynamics of the Amundsen Sea sector

Non-detection of a statistically anisotropic power spectrum in large-scale structure

We search a sample of photometric luminous red galaxies (LRGs) measured by the Sloan Digital Sky Survey (SDSS) for a quadrupolar anisotropy in the primordial power spectrum, in which P(\vec{k}) is an isotropic power spectrum P(k) multiplied by a quadrupolar modulation pattern. We first place limits on the 5 coefficients of a general quadrupole anisotropy. We also consider axisymmetric quadrupoles of the form P(\vec{k}) = P(k){1 + g_*[(\hat{k}\cdot\hat{n})^2-1/3]} where \hat{n} is the axis of the anisotropy. When we force the symmetry axis \hat{n} to be in the direction (l,b)=(94 degrees,26 degrees) identified in the recent Groeneboom et al. analysis of the cosmic microwave background, we find g_*=0.006+/-0.036 (1 sigma). With uniform priors on \hat{n} and g_* we find that -0.41<g_*<+0.38 with 95% probability, with the wide range due mainly to the large uncertainty of asymmetries aligned with the Galactic Plane. In none of these three analyses do we detect evidence for quadrupolar power anisotropy in large scale structure.Comment: 23 pages; 10 figures; 3 tables; replaced with version published in JCAP (added discussion of scale-varying quadrupolar anisotropy

Coincident Lake Drainage and Grounding Line Retreat at Engelhardt Subglacial Lake, West Antarctica

Antarctica has an active subglacial hydrological system, with interconnected subglacial lakes fed by subglacial meltwater. Subglacial hydrology can influence basal sliding, inject freshwater into the sub-ice-shelf cavity, and impact sediment transport and deposition which can affect the stability of grounding lines (GLs). We used satellite altimetry data from the ICESat, ICESat-2, and CryoSat-2 missions to document the second recorded drainage of Engelhardt Subglacial Lake (SLE), which began in July 2021 and discharged more than 2.3 km3 of subglacial water into the Ross Ice Shelf cavity. We used differential synthetic aperture radar interferometry from RADARSAT-2 and TerraSAR-X alongside ICESat-2 repeat-track laser altimetry (RTLA) and REMA digital elevation model strips to detect 2–13 km of GL retreat since the previous drainage event in 2003–06. Combining these satellite observations, we evaluated the mechanism triggering SLE drainage, the cause of the observed GL retreat, and the interplay between subglacial hydrology and GL dynamics. We find that: (a) SLE drainage was initiated by influx from a newly identified upstream lake; (b) the observed GL retreat is mainly driven by the continued retreat of Engelhardt Ice Ridge and long-term dynamic thinning that caused a grounded ice plain to reach flotation; and (c) SLE drainage and GL retreat were largely independent. We also discuss the possible origins and influence of a 27 km grounded promontory found to protrude seaward from the GL. Our observations demonstrate the importance of high-resolution satellite data for improving the process-based understanding of dynamic and complex regions around the Antarctic Ice Sheet margins

Annual mass budget of Antarctic ice shelves from 1997 to 2021

Antarctic ice shelves moderate the contribution of the Antarctic Ice Sheet to global sea level rise; however, ice shelf health remains poorly constrained. Here, we present the annual mass budget of all Antarctic ice shelves from 1997 to 2021. Out of 162 ice shelves, 71 lost mass, 29 gained mass, and 62 did not change mass significantly. Of the shelves that lost mass, 68 had statistically significant negative mass trends, 48 lost more than 30% of their initial mass, and basal melting was the dominant contributor to that mass loss at a majority (68%). At many ice shelves, mass losses due to basal melting or iceberg calving were significantly positively correlated with grounding line discharge anomalies; however, the strength and form of this relationship varied substantially between ice shelves. Our results illustrate the utility of partitioning high-resolution ice shelf mass balance observations into its components to quantify the contributors to ice shelf mass change and the response of grounded ice

A longitudinal investigation of repressive coping and ageing

This is an Accepted Manuscript of an article published by Taylor & Francis in Aging & Mental Health on October 2016, available online: http://www.tandfonline.com/doi/full/10.1080/13607863.2015.1060941.Two studies investigated the possibility that repressive coping is more prevalent in older adults and that this represents a developmental progression rather than a cohort effect. Study 1 examined repressive coping and mental health cross-sectionally in young and old adults. Study 2 examined whether there was a developmental progression of repressive coping prevalence rates in a longitudinal sample of older adults.Peer reviewedFinal Accepted Versio

Cosmological parameters from SDSS and WMAP

We measure cosmological parameters using the three-dimensional power spectrum P(k) from over 200,000 galaxies in the Sloan Digital Sky Survey (SDSS) in combination with WMAP and other data. Our results are consistent with a ``vanilla'' flat adiabatic Lambda-CDM model without tilt (n=1), running tilt, tensor modes or massive neutrinos. Adding SDSS information more than halves the WMAP-only error bars on some parameters, tightening 1 sigma constraints on the Hubble parameter from h~0.74+0.18-0.07 to h~0.70+0.04-0.03, on the matter density from Omega_m~0.25+/-0.10 to Omega_m~0.30+/-0.04 (1 sigma) and on neutrino masses from <11 eV to <0.6 eV (95%). SDSS helps even more when dropping prior assumptions about curvature, neutrinos, tensor modes and the equation of state. Our results are in substantial agreement with the joint analysis of WMAP and the 2dF Galaxy Redshift Survey, which is an impressive consistency check with independent redshift survey data and analysis techniques. In this paper, we place particular emphasis on clarifying the physical origin of the constraints, i.e., what we do and do not know when using different data sets and prior assumptions. For instance, dropping the assumption that space is perfectly flat, the WMAP-only constraint on the measured age of the Universe tightens from t0~16.3+2.3-1.8 Gyr to t0~14.1+1.0-0.9 Gyr by adding SDSS and SN Ia data. Including tensors, running tilt, neutrino mass and equation of state in the list of free parameters, many constraints are still quite weak, but future cosmological measurements from SDSS and other sources should allow these to be substantially tightened.Comment: Minor revisions to match accepted PRD version. SDSS data and ppt figures available at http://www.hep.upenn.edu/~max/sdsspars.htm

Electromagnetic wave propagation in rain and polarization effects

This paper summarizes our study on microwave and millimeter-wave propagation in rain with special emphasis on the effects of polarization. Starting from a recount of our past findings, we will discuss developments with these and how they are connected with subsequent research

Prevalence of Age-Related Macular Degeneration in Europe: The Past and the Future

Purpose Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. Design Meta-analysis of prevalence data. Participants A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe. Methods AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV). Main Outcome Measures Prevalence of early and late AMD, BCVA, and number of AMD cases. Results Prevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1%–5.0%) in those aged 55–59 years to 17.6% (95%