90 research outputs found

    Investigating dark matter substructure with pulsar timing: I. Constraints on ultracompact minihalos

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    Small-scale dark matter structure within the Milky Way is expected to affect pulsar timing. The change in gravitational potential induced by a dark matter halo passing near the line of sight to a pulsar would produce a varying delay in the light travel time of photons from the pulsar. Individual transits produce an effect that would either be too rare or too weak to be detected in 30-year pulsar observations. However, a population of dark matter subhalos would be expected to produce a detectable effect on the measured properties of pulsars if the subhalos constitute a significant fraction of the total halo mass. The effect is to increase the dispersion of measured period derivatives across the pulsar population. By statistical analysis of the ATNF pulsar catalogue, we place an upper limit on this dispersion of logσP˙17.05\log \sigma_{\dot{P}} \leq -17.05. We use this to place strong upper limits on the number density of ultracompact minihalos within the Milky Way. These limits are completely independent of the particle nature of dark matter.Comment: 9 pages, 5 figues, includes erratum published in MNRA

    Heating of galactic gas by dark matter annihilation in ultracompact minihalos

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    The existence of substructure in halos of annihilating dark matter would be expected to substantially boost the rate at which annihilation occurs. Ultracompact minihalos of dark matter (UCMHs) are one of the more extreme examples of this. The boosted annihilation can inject significant amounts of energy into the gas of a galaxy over its lifetime. Here we determine the impact of the boost factor from UCMH substructure on the heating of galactic gas in a Milky Way-type galaxy, by means of N-body simulation. If 1%1\% of the dark matter exists as UCMHs, the corresponding boost factor can be of order 10510^5. For reasonable values of the relevant parameters (annihilation cross section 3×1026 cm3 s13\times10^{-26} ~\textrm{cm}^3~ \textrm{s}^{-1}, dark matter mass 100 GeV, 10% heating efficiency), we show that the presence of UCMHs at the 0.1% level would inject enough energy to eject significant amounts of gas from the halo, potentially preventing star formation within \sim1 kpc of the halo centre.Comment: 14 pages, 3 figure

    Interface characteristics in an {\alpha}+{\beta} titanium alloy

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    The alpha/beta interface in Ti-6Al-2Sn-4Zr-6Mo (Ti-6246) is investigated via centre of symmetry analysis, both as-grown and after 10% cold work. Semi-coherent interface steps are observed at a spacing of 4.5 +/-1.13 atoms in the as-grown condition, in good agreement with theory prediction (4.37 atoms). Lattice accommodation is observed, with elongation along [-1 2 -1 0]alpha and contraction along [1 0 -1 0]alpha . Deformed alpha exhibited larger, less coherent steps with slip bands lying in {110}beta. This indicates dislocation pile-up at the grain boundary, a precursor to globularisation, offering insight into the effect of deformation processing on the interface, which is important for titanium alloy processing route design.Comment: Revised after revie

    Interface characteristics in an α+β titanium alloy

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    The α/β interface in Ti-6Al-2Sn-4Zr-6Mo (Ti-6246) was investigated via center of symmetry analysis, both as-grown and after 10% cold work. Semicoherent interface steps are observed at a spacing of 4.5±1.13 atoms in the as-grown condition, in good agreement with theory. Lattice accommodation is observed, with elongation along [1210]α and contraction along [1010]α. Deformed α exhibited larger, less coherent steps with slip bands lying in {110}β. This indicates dislocation pile-up at the grain boundary, a precursor to globularization during heat treatment. Atom probe tomography measurements of secondary α plates in the fully heat-treated condition showed a Zr excess at the interface, which was localized into regular structures indicative of Zr association with interface defects, such as dislocations. Such chemo-mechanical stabilization of the interface defects would both inhibit plate growth during elevated temperature service and the interaction of interface defects with gliding dislocations during deformation

    The impact of cancer on subsequent chance of pregnancy: a population-based analysis

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    This study was funded by NHS Lothian Cancer and Leukaemia Endowments Fund. Part of this work was undertaken in the MRC Centre for Reproductive Health which is funded by the MRC Centre grant MR/N022556/1 .STUDY QUESTION What is the impact of cancer in females aged ≤39 years on subsequent chance of pregnancy? SUMMARY ANSWER Cancer survivors achieved fewer pregnancies across all cancer types, and the chance of achieving a first pregnancy was also lower. WHAT IS KNOWN ALREADY The diagnosis and treatment of cancer in young females may be associated with reduced fertility but the true pregnancy deficit in a population is unknown. STUDY DESIGN, SIZE, DURATION We performed a retrospective cohort study relating first incident cancer diagnosed between 1981 and 2012 to subsequent pregnancy in all female patients in Scotland aged 39 years or less at cancer diagnosis (n = 23 201). Pregnancies were included up to end of 2014. Females from the exposed group not pregnant before cancer diagnosis (n = 10 271) were compared with general population controls matched for age, deprivation quintile and year of diagnosis. PARTICIPANTS/MATERIALS, SETTING, METHODS Scottish Cancer Registry records were linked to hospital discharge records to calculate standardized incidence ratios (SIR) for pregnancy, standardized for age and year of diagnosis. Linkage to death records was also performed. We also selected women from the exposed group who had not been pregnant prior to their cancer diagnosis who were compared with a matched control group from the general population. Additional analyses were performed for breast cancer, Hodgkin lymphoma, leukaemia, cervical cancer and brain/CNS cancers. MAIN RESULTS AND THE ROLE OF CHANCE Cancer survivors achieved fewer pregnancies: SIR 0.62 (95% CI: 0.60, 0.63). Reduced SIR was observed for all cancer types. The chance of achieving a first pregnancy was also lower, adjusted hazard ratio = 0.57 (95% CI: 0.53, 0.61) for women >5 years after diagnosis, with marked reductions in women with breast, cervical and brain/CNS tumours, and leukaemia. The effect was reduced with more recent treatment period overall and in cervical cancer, breast cancer and Hodgkin lymphoma, but was unchanged for leukaemia or brain/CNS cancers. The proportion of pregnancies that ended in termination was lower after a cancer diagnosis, and the proportion ending in live birth was higher (78.7 vs 75.6%, CI of difference: 1.1, 5.0). LIMITATIONS, REASONS FOR CAUTION Details of treatments received were not available, so the impact of specific treatment regimens on fertility could not be assessed. Limited duration of follow-up was available for women diagnosed in the most recent time period. WIDER IMPLICATIONS OF THE FINDINGS This analysis provides population-based quantification by cancer type of the effect of cancer and its treatment on subsequent pregnancy across the reproductive age range, and how this has changed in recent decades. The demonstration of a reduced chance of pregnancy across all cancer types and the changing impact in some but not other common cancers highlights the need for appropriate fertility counselling of all females of reproductive age at diagnosis. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by NHS Lothian Cancer and Leukaemia Endowments Fund. Part of this work was undertaken in the MRC Centre for Reproductive Health which is funded by the MRC Centre grant MR/N022556/1. RAA has participated in Advisory Boards and/or received speaker’s fees from Beckman Coulter, IBSA, Merck and Roche Diagnostics. He has received research support from Roche Diagnostics, Ansh labs and Ferring. The other authors have no conflicts to declare.Publisher PDFPeer reviewe

    A vertical profile of PM10 dust concentrations measured during a regional dust event identified by MODIS Terra, western Queensland, Australia

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    Accurate determination of the spatiotemporal properties of dust plumes and their dust concentrations is essential for calibration of satellite products and the initialization and validation of numerical models that simulate the physical properties and affects of dust events. In this paper, we present a 500 m vertical profile of PM10 dust concentrations measured during a regional dust event in western Queensland, Australia. PM10 dust concentrations within the haze were found to be >20 times background ambient values and decreased with height following an exponential function. We apply an over-land algorithm to MODIS Terra satellite images of the dust haze to enhance its visual appearance against the bright land surface and define its size. In conjunction with the measured attenuation of dust concentrations with height we calculate the PM10 dust load of the plume to be ∼60% of that which would have been calculated assuming a constant dust concentration up to the dust ceiling height. Results extend previous findings from tower-based studies made close to the surface and confirm that atmospheric dust concentrations decrease rapidly with increasing height, thereby enabling more accurate calculation of atmospheric dust loads during synoptic-scale dust outbreaks

    Global, regional, and national estimates of the population at increased risk of severe COVID-19 due to underlying health conditions in 2020: a modelling study

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    Background: The risk of severe COVID-19 if an individual becomes infected is known to be higher in older individuals and those with underlying health conditions. Understanding the number of individuals at increased risk of severe COVID-19 and how this varies between countries should inform the design of possible strategies to shield or vaccinate those at highest risk. Methods: We estimated the number of individuals at increased risk of severe disease (defined as those with at least one condition listed as “at increased risk of severe COVID-19” in current guidelines) by age (5-year age groups), sex, and country for 188 countries using prevalence data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 and UN population estimates for 2020. The list of underlying conditions relevant to COVID-19 was determined by mapping the conditions listed in GBD 2017 to those listed in guidelines published by WHO and public health agencies in the UK and the USA. We analysed data from two large multimorbidity studies to determine appropriate adjustment factors for clustering and multimorbidity. To help interpretation of the degree of risk among those at increased risk, we also estimated the number of individuals at high risk (defined as those that would require hospital admission if infected) using age-specific infection–hospitalisation ratios for COVID-19 estimated for mainland China and making adjustments to reflect country-specific differences in the prevalence of underlying conditions and frailty. We assumed males were twice at likely as females to be at high risk. We also calculated the number of individuals without an underlying condition that could be considered at increased risk because of their age, using minimum ages from 50 to 70 years. We generated uncertainty intervals (UIs) for our estimates by running low and high scenarios using the lower and upper 95% confidence limits for country population size, disease prevalences, multimorbidity fractions, and infection–hospitalisation ratios, and plausible low and high estimates for the degree of clustering, informed by multimorbidity studies. Findings: We estimated that 1·7 billion (UI 1·0–2·4) people, comprising 22% (UI 15–28) of the global population, have at least one underlying condition that puts them at increased risk of severe COVID-19 if infected (ranging from <5% of those younger than 20 years to >66% of those aged 70 years or older). We estimated that 349 million (186–787) people (4% [3–9] of the global population) are at high risk of severe COVID-19 and would require hospital admission if infected (ranging from <1% of those younger than 20 years to approximately 20% of those aged 70 years or older). We estimated 6% (3–12) of males to be at high risk compared with 3% (2–7) of females. The share of the population at increased risk was highest in countries with older populations, African countries with high HIV/AIDS prevalence, and small island nations with high diabetes prevalence. Estimates of the number of individuals at increased risk were most sensitive to the prevalence of chronic kidney disease, diabetes, cardiovascular disease, and chronic respiratory disease. Interpretation: About one in five individuals worldwide could be at increased risk of severe COVID-19, should they become infected, due to underlying health conditions, but this risk varies considerably by age. Our estimates are uncertain, and focus on underlying conditions rather than other risk factors such as ethnicity, socioeconomic deprivation, and obesity, but provide a starting point for considering the number of individuals that might need to be shielded or vaccinated as the global pandemic unfolds. Funding: UK Department for International Development, Wellcome Trust, Health Data Research UK, Medical Research Council, and National Institute for Health Research

    Gene Network Disruptions and Neurogenesis Defects in the Adult Ts1Cje Mouse Model of Down Syndrome

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    Background: Down syndrome (DS) individuals suffer mental retardation with further cognitive decline and early onset Alzheimer's disease. Methodology/Principal Findings: To understand how trisomy 21 causes these neurological abnormalities we investigated changes in gene expression networks combined with a systematic cell lineage analysis of adult neurogenesis using the Ts1Cje mouse model of DS. We demonstrated down regulation of a number of key genes involved in proliferation and cell cycle progression including Mcm7, Brca2, Prim1, Cenpo and Aurka in trisomic neurospheres. We found that trisomy did not affect the number of adult neural stem cells but resulted in reduced numbers of neural progenitors and neuroblasts. Analysis of differentiating adult Ts1Cje neural progenitors showed a severe reduction in numbers of neurons produced with a tendency for less elaborate neurites, whilst the numbers of astrocytes was increased. Conclusions/Significance: We have shown that trisomy affects a number of elements of adult neurogenesis likely to result in a progressive pathogenesis and consequently providing the potential for the development of therapies to slow progression of, or even ameliorate the neuronal deficits suffered by DS individuals.Chelsee A. Hewitt, King-Hwa Ling, Tobias D. Merson, Ken M. Simpson, Matthew E. Ritchie, Sarah L. King, Melanie A. Pritchard, Gordon K. Smyth, Tim Thomas, Hamish S. Scott and Anne K. Vos
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