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  • Amole, C., et al. (författare)
  • Silicon vertex detector upgrade in the ALPHA experiment
  • 2013
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 732, s. 134-136
  • Tidskriftsartikel (refereegranskat)abstract
    • The Silicon Vertex Detector (SVD) is the main diagnostic tool in the ALPHA-experiment. It provides precise spatial and timing information of antiproton (antihydrogen) annihilation events (vertices), and most importantly, the SVD is capable of directly identifying and analysing single annihilation events, thereby forming the basis of ALPHA's analysis. This paper describes the ALPHA SVD and its upgrade, installed in the ALPHA's new neutral atom trap.
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  • Amole, C., et al. (författare)
  • Resonant quantum transitions in trapped antihydrogen atoms
  • 2012
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 483:7390, s. 439-U86
  • Tidskriftsartikel (refereegranskat)abstract
    • The hydrogen atom is one of the most important and influential model systems in modern physics. Attempts to understand its spectrum are inextricably linked to the early history and development of quantum mechanics. The hydrogen atom's stature lies in its simplicity and in the accuracy with which its spectrum can be measured(1) and compared to theory. Today its spectrum remains a valuable tool for determining the values of fundamental constants and for challenging the limits of modern physics, including the validity of quantum electrodynamics and-by comparison with measurements on its antimatter counterpart, antihydrogen-the validity of CPT (charge conjugation, parity and time reversal) symmetry. Here we report spectroscopy of a pure antimatter atom, demonstrating resonant quantum transitions in antihydrogen. We have manipulated the internal spin state(2,3) of antihydrogen atoms so as to induce magnetic resonance transitions between hyperfine levels of the positronic ground state. We used resonant microwave radiation to flip the spin of the positron in antihydrogen atoms that were magnetically trapped(4-6) in the ALPHA apparatus. The spin flip causes trapped anti-atoms to be ejected from the trap. We look for evidence of resonant interaction by comparing the survival rate of trapped atoms irradiated with microwaves on-resonance to that of atoms subjected to microwaves that are off-resonance. In one variant of the experiment, we detect 23 atoms that survive in 110 trapping attempts with microwaves off-resonance (0.21 per attempt), and only two atoms that survive in 103 attempts with microwaves on-resonance (0.02 per attempt). We also describe the direct detection of the annihilation of antihydrogen atoms ejected by the microwaves.
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  • Amole, C., et al. (författare)
  • An experimental limit on the charge of antihydrogen
  • 2014
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 3955-
  • Tidskriftsartikel (refereegranskat)abstract
    • The properties of antihydrogen are expected to be identical to those of hydrogen, and any differences would constitute a profound challenge to the fundamental theories of physics. The most commonly discussed antiatom- based tests of these theories are searches for antihydrogen- hydrogen spectral differences (tests of CPT (charge- parity- time) invariance) or gravitational differences (tests of the weak equivalence principle). Here we, the ALPHA Collaboration, report a different and somewhat unusual test of CPT and of quantum anomaly cancellation. A retrospective analysis of the influence of electric fields on antihydrogen atoms released from the ALPHA trap finds a mean axial deflection of 4.1 +/- 3.4mm for an average axial electric field of 0.51Vmm1. Combined with extensive numerical modelling, this measurement leads to a bound on the charge Qe of antihydrogen of Q (+/- 1.3 +/- 1.1 +/- 0.4)10 8. Here, e is the unit charge, and the errors are from statistics and systematic effects.
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  • Amole, C., et al. (författare)
  • Autoresonant-spectrometric determination of the residual gas composition in the ALPHA experiment apparatus
  • 2013
  • Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 84:6, s. 065110-
  • Tidskriftsartikel (refereegranskat)abstract
    • Knowledge of the residual gas composition in the ALPHA experiment apparatus is important in our studies of antihydrogen and nonneutral plasmas. A technique based on autoresonant ion extraction from an electrostatic potential well has been developed that enables the study of the vacuum in our trap. Computer simulations allow an interpretation of our measurements and provide the residual gas composition under operating conditions typical of those used in experiments to produce, trap, and study antihydrogen. The methods developed may also be applicable in a range of atomic and molecular trap experiments where Penning-Malmberg traps are used and where access is limited.
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  • Amole, C., et al. (författare)
  • Experimental and computational study of the injection of antiprotons into a positron plasma for antihydrogen production
  • 2013
  • Ingår i: Physics of Plasmas. - : AIP Publishing. - 1070-664X .- 1089-7674. ; 20:4, s. 043510-
  • Tidskriftsartikel (refereegranskat)abstract
    • One of the goals of synthesizing and trapping antihydrogen is to study the validity of charge-parity-time symmetry through precision spectroscopy on the anti-atoms, but the trapping yield achieved in recent experiments must be significantly improved before this can be realized. Antihydrogen atoms are commonly produced by mixing antiprotons and positrons stored in a nested Penning-Malmberg trap, which was achieved in ALPHA by an autoresonant excitation of the antiprotons, injecting them into the positron plasma. In this work, a hybrid numerical model is developed to simulate antiproton and positron dynamics during the mixing process. The simulation is benchmarked against other numerical and analytic models, as well as experimental measurements. The autoresonant injection scheme and an alternative scheme are compared numerically over a range of plasma parameters which can be reached in current and upcoming antihydrogen experiments, and the latter scheme is seen to offer significant improvement in trapping yield as the number of available antiprotons increases.
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8.
  • Amole, C., et al. (författare)
  • In situ electromagnetic field diagnostics with an electron plasma in a Penning-Malmberg trap
  • 2014
  • Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 16, s. 013037-
  • Tidskriftsartikel (refereegranskat)abstract
    • We demonstrate a novel detection method for the cyclotron resonance frequency of an electron plasma in a Penning-Malmberg trap. With this technique, the electron plasma is used as an in situ diagnostic tool for the measurement of the static magnetic field and the microwave electric field in the trap. The cyclotron motion of the electron plasma is excited by microwave radiation and the temperature change of the plasma is measured non-destructively by monitoring the plasma's quadrupole mode frequency. The spatially resolved microwave electric field strength can be inferred from the plasma temperature change and the magnetic field is found through the cyclotron resonance frequency. These measurements were used extensively in the recently reported demonstration of resonant quantum interactions with antihydrogen.
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  • Butler, C.C., et al. (författare)
  • Antibiotic prescribing for discoloured sputum in acute cough/lower respiratory tract infection
  • 2011
  • Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 38:1, s. 119-125
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated whether discoloured sputum and feeling unwell were associated with antibiotic prescription and benefit from antibiotic treatment for acute cough/lower respiratory tract infection (LTRI) in a prospective study of 3,402 adults in 13 countries. A two-level model investigated the association between producing discoloured sputum or feeling generally unwell and an antibiotic prescription. A three-level model investigated the association between an antibiotic prescription and symptom resolution. Patients producing discoloured sputum were prescribed antibiotics more frequently than those not producing sputum (OR 3.2, 95% CI 2.1-5.0), unlike those producing clear/white sputum (OR 0.95, 95% CI 0.61-1.48). Antibiotic prescription was not associated with a greater rate or magnitude of symptom score resolution (as measured by a 13-item questionnaire completed by patients each day) among those who: produced yellow (coefficient 0.00; p=0.68) or green (coefficient -0.01; p=0.11) sputum; reported any of three categories of feeling unwell; or produced discoloured sputum and felt generally unwell (coefficient -0.01; p=0.19). Adults with acute cough/LRTI presenting in primary care settings with discoloured sputum were prescribed antibiotics more often compared to those not producing sputum. Sputum colour, alone or together with feeling generally unwell, was not associated with recovery or benefit from antibiotic treatment.
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  • Abi-Rached, Laurent, et al. (författare)
  • The Shaping of Modern Human Immune Systems by Multiregional Admixture with Archaic Humans
  • 2011
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 334:6052, s. 89-94
  • Tidskriftsartikel (refereegranskat)abstract
    • Whole genome comparisons identified introgression from archaic to modern humans. Our analysis of highly polymorphic human leukocyte antigen (HLA) class I, vital immune system components subject to strong balancing selection, shows how modern humans acquired the HLA-B*73 allele in west Asia through admixture with archaic humans called Denisovans, a likely sister group to the Neandertals. Virtual genotyping of Denisovan and Neandertal genomes identified archaic HLA haplotypes carrying functionally distinctive alleles that have introgressed into modern Eurasian and Oceanian populations. These alleles, of which several encode unique or strong ligands for natural killer cell receptors, now represent more than half the HLA alleles of modern Eurasians and also appear to have been later introduced into Africans. Thus, adaptive introgression of archaic alleles has significantly shaped modern human immune systems.
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  • Weiner, M. W., et al. (författare)
  • Military risk factors for Alzheimer's disease
  • 2013
  • Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 9:4, s. 445-451
  • Tidskriftsartikel (refereegranskat)abstract
    • Traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are signature injuries of the wars in Iraq and Afghanistan and have been linked to an increased risk of Alzheimer's disease (AD) and other dementias. A meeting hosted by the Alzheimer's Association and the Veterans' Health Research Institute (NCIRE) in May 2012 brought together experts from the U.S. military and academic medical centers around the world to discuss current evidence and hypotheses regarding the pathophysiological mechanisms linking TBI, PTSD, and AD. Studies underway in civilian and military populations were highlighted, along with new research initiatives such as a study to extend the Alzheimer's Disease Neuroimaging Initiative (ADNI) to a population of veterans exposed to TBI and PTSD. Greater collaboration and data sharing among diverse research groups is needed to advance an understanding and appropriate interventions in this continuum of military injuries and neurodegenerative disease in the aging veteran. (C) 2013 The Alzheimer's Association. All rights reserved.
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17.
  • Alatalo, Juha M., et al. (författare)
  • Dominance hierarchies, diversity and species richness of vascular plants in an alpine meadow: Contrasting short and medium termresponses to simulated global change
  • 2014
  • Ingår i: PeerJ. - : PeerJ Inc.. - 2167-8359. ; 2014:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We studied the impact of simulated global change on a high alpine meadow plant community. Specifically, we examined whether short-term (5 years) responses are good predictors for medium-term (7 years) changes in the system by applying a factorial warming and nutrient manipulation to 20 plots in Latnjajaure, subarctic Sweden. Seven years of experimental warming and nutrient enhancement caused dramatic shifts in dominance hierarchies in response to the nutrient and the combined warming and nutrient enhancement treatments. Dominance hierarchies in the meadow moved from a community being dominated by cushion plants, deciduous, and evergreen shrubs to a community being dominated by grasses, sedges, and forbs. Short-termresponses were shown to be inconsistent in their ability to predict medium-term responses for most functional groups, however, grasses showed a consistent and very substantial increase in response to nutrient addition over the seven years. The non-linear responses over time point out the importance of longer-term studies with repeated measurements to be able to better predict future changes. Forecasted changes to temperature and nutrient availability have implications for trophic interactions, and may ultimately influence the access to and palatability of the forage for grazers. Depending on what anthropogenic change will be most pronounced in the future (increase in nutrient deposits, warming, or a combination of them both), different shifts in community dominance hierarchies may occur. Generally, this study supports the productivity-diversity relationship found across arctic habitats, with community diversity peaking in mid-productivity systems and degrading as nutrient availability increases further. This is likely due the increasing competition in plant-plant interactions and the shifting dominance structure with grasses taking over the experimental plots, suggesting that global change could have high costs to biodiversity in the Arctic. © 2014 Alatalo et al.
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18.
  • Alatalo, Juha M., et al. (författare)
  • Simulated global change : contrasting short and medium term growth and reproductive responses of a common alpine/Arctic cushion plant to experimental warming and nutrient enhancement
  • 2014
  • Ingår i: SpringerPlus. - : Springer Science and Business Media LLC. - 2193-1801. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • Cushion plants are important components of alpine and Arctic plant communities around the world. They fulfill important roles as facilitators, nurse plants and foundation species across trophic levels for vascular plants, arthropods and soil microorganisms, the importance of these functions increasing with the relative severity of the environment. Here we report results from one of the few experimental studies simulating global change impacts on cushion plants; a factorial experiment with warming and nutrient enhancement that was applied to an alpine population of the common nurse plant, Silene acaulis, in sub-arctic Sweden. Experimental perturbations had significant short-term impacts on both stem elongation and leaf length. S. acaulis responded quickly by increasing stem elongation and (to a lesser extent) leaf length in the warming, nutrient, and the combined warming and nutrient enhancements. Cover and biomass also initially increased in response to the perturbations. However, after the initial positive short-term responses, S. acaulis cover declined in the manipulations, with the nutrient and combined warming and nutrient treatments having largest negative impact. No clear patterns were found for fruit production. Our results show that S. acaulis living in harsh environments has potential to react quickly when experiencing years with favorable conditions, and is more responsive to nutrient enhancement than to warming in terms of vegetative growth. While these conditions have an initial positive impact, populations experiencing longer-term increased nutrient levels will likely be negatively affected.
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  • Butler, Christopher C, et al. (författare)
  • Treatment of acute cough/lower respiratory tract infection by antibiotic class and associated outcomes: a 13 European country observational study in primary care
  • 2010
  • Ingår i: JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY. - : Oxford University Press. - 0305-7453 .- 1460-2091. ; 65:11, s. 2472-2478
  • Tidskriftsartikel (refereegranskat)abstract
    • Acute cough/lower respiratory tract infection (LRTI) is one of the commonest reasons for consulting and antibiotic prescribing. There are theoretical reasons why treatment with particular antibiotic classes may aid recovery more than others, but empirical, pragmatic evidence is lacking. We investigated whether treatment with a particular antibiotic class (amoxicillin) was more strongly associated with symptom score resolution and time to patients reporting recovery than each of eight other antibiotic classes or no antibiotic treatment for acute cough/LRTI. Clinicians recorded history, examination findings, symptom severity and antibiotic treatment for 3402 patients in a 13 country prospective observational study of adults presenting in 14 primary care research networks with acute cough/LRTI. 2714 patients completed a symptom score daily for up to 28 days and recorded the day on which they felt recovered. A three-level autoregressive moving average model (1,1) model investigated logged daily symptom scores to analyse symptom resolution. A two-level survival model analysed time to reported recovery. Clinical presentation was controlled for using clinician-recorded symptoms, sputum colour, temperature, age, co-morbidities, smoking status and duration of illness prior to consultation. Compared with amoxicillin, no antibiotic class (and no antibiotic treatment) was associated with clinically relevant improved symptom resolution (all coefficients in the range -0.02 to 0.01 and all P values greater than 0.12). No antibiotic class (and no antibiotic treatment) was associated with faster time to recovery than amoxicillin. Treatment by antibiotic class was not associated with symptom resolution or time to recovery in adults presenting to primary care with acute cough/LRTI.
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22.
  • Decaestecker, Ellen, et al. (författare)
  • Candidate innate immune system gene expression in the ecological model Daphnia
  • 2011
  • Ingår i: Developmental and Comparative Immunology. - : Elsevier BV. - 0145-305X .- 1879-0089. ; 35:10, s. 1066-1075
  • Tidskriftsartikel (refereegranskat)abstract
    • The last ten years have witnessed increasing interest in host-pathogen interactions involving invertebrate hosts. The invertebrate innate immune system is now relatively well characterised, but in a limited range of genetic model organisms and under a limited number of conditions. Immune systems have been little studied under real-world scenarios of environmental variation and parasitism. Thus, we have investigated expression of candidate innate immune system genes in the water flea Daphnia, a model organism for ecological genetics, and whose capacity for clonal reproduction facilitates an exceptionally rigorous control of exposure dose or the study of responses at many time points. A unique characteristic of the particular Daphnia clones and pathogen strain combinations used presently is that they have been shown to be involved in specific host-pathogen coevolutionary interactions in the wild. We choose five genes, which are strong candidates to be involved in Daphnia-pathogen interactions, given that they have been shown to code for immune effectors in related organisms. Differential expression of these genes was quantified by qRT-PCR following exposure to the bacterial pathogen Pasteuria ramosa. Constitutive expression levels differed between host genotypes, and some genes appeared to show correlated expression. However, none of the genes appeared to show a major modification of expression level in response to Pasteuria exposure. By applying knowledge from related genetic model organisms (e.g. Drosophila) to models for the study of evolutionary ecology and coevolution (i.e. Daphnia), the candidate gene approach is temptingly efficient. However, our results show that detection of only weak patterns is likely if one chooses target genes for study based on previously identified genome sequences by comparison to homologues from other related organisms. Future work on the Daphnia-Pasteuria system will need to balance a candidate gene approach with more comprehensive approaches to de novo identify immune system genes specific to the Daphnia-Pasteuria interaction.
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  • Fortier, Isabel, et al. (författare)
  • Is rigorous retrospective harmonization possible? : Application of the DataSHaPER approach across 53 large studies
  • 2011
  • Ingår i: International Journal of Epidemiology. - : OXFORD UNIV PRESS. - 0300-5771 .- 1464-3685. ; 40:5, s. 1314-1328
  • Tidskriftsartikel (refereegranskat)abstract
    • Methods This article examines the value of using the DataSHaPER for retrospective harmonization of established studies. Using the DataSHaPER approach, the potential to generate 148 harmonized variables from the questionnaires and physical measures collected in 53 large population-based studies (6.9 million participants) was assessed. Variable and study characteristics that might influence the potential for data synthesis were also explored. Results Out of all assessment items evaluated (148 variables for each of the 53 studies), 38% could be harmonized. Certain characteristics of variables (i.e. relative importance, individual targeted, reference period) and of studies (i.e. observational units, data collection start date and mode of questionnaire administration) were associated with the potential for harmonization. For example, for variables deemed to be essential, 62% of assessment items paired could be harmonized. Conclusion The current article shows that the DataSHaPER provides an effective and flexible approach for the retrospective harmonization of information across studies. To implement data synthesis, some additional scientific, ethico-legal and technical considerations must be addressed. The success of the DataSHaPER as a harmonization approach will depend on its continuing development and on the rigour and extent of its use. The DataSHaPER has the potential to take us closer to a truly collaborative epidemiology and offers the promise of enhanced research potential generated through synthesized databases.
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25.
  • Lyons, Paul A, et al. (författare)
  • Genetically Distinct Subsets within ANCA-Associated Vasculitis
  • 2012
  • Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 367:3, s. 214-223
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND less thanbrgreater than less thanbrgreater thanAntineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a severe condition encompassing two major syndromes: granulomatosis with polyangiitis (formerly known as Wegeners granulomatosis) and microscopic polyangiitis. Its cause is unknown, and there is debate about whether it is a single disease entity and what role ANCA plays in its pathogenesis. We investigated its genetic basis. less thanbrgreater than less thanbrgreater thanMETHODS less thanbrgreater than less thanbrgreater thanA genomewide association study was performed in a discovery cohort of 1233 U. K. patients with ANCA-associated vasculitis and 5884 controls and was replicated in 1454 Northern European case patients and 1666 controls. Quality control, population stratification, and statistical analyses were performed according to standard criteria. less thanbrgreater than less thanbrgreater thanRESULTS less thanbrgreater than less thanbrgreater thanWe found both major-histocompatibility-complex (MHC) and non-MHC associations with ANCA-associated vasculitis and also that granulomatosis with polyangiitis and microscopic polyangiitis were genetically distinct. The strongest genetic associations were with the antigenic specificity of ANCA, not with the clinical syndrome. Anti-proteinase 3 ANCA was associated with HLA-DP and the genes encoding alpha(1)-antitrypsin (SERPINA1) and proteinase 3 (PRTN3) (P = 6.2x10(-89), P = 5.6x10(-12), and P = 2.6x10(-7), respectively). Anti-myeloperoxidase ANCA was associated with HLA-DQ (P = 2.1x10(-8)). less thanbrgreater than less thanbrgreater thanCONCLUSIONS less thanbrgreater than less thanbrgreater thanThis study confirms that the pathogenesis of ANCA-associated vasculitis has a genetic component, shows genetic distinctions between granulomatosis with polyangiitis and microscopic polyangiitis that are associated with ANCA specificity, and suggests that the response against the autoantigen proteinase 3 is a central pathogenic feature of proteinase 3 ANCA-associated vasculitis. These data provide preliminary support for the concept that proteinase 3 ANCA-associated vasculitis and myeloperoxidase ANCA-associated vasculitis are distinct autoimmune syndromes. (Funded by the British Heart Foundation and others.)
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26.
  • Pfeifer-Meister, Laurel, et al. (författare)
  • Pushing the limit : experimental evidence of climate effects on plant range distributions
  • 2013
  • Ingår i: Ecology. - : Wiley. - 0012-9658 .- 1939-9170. ; 94:10, s. 2131-2137
  • Tidskriftsartikel (refereegranskat)abstract
    • Whether species will be extirpated in their current geographic ranges due to rapidly changing climate, and if so, whether they can avoid extinction by shifting their distributions are pressing questions for biodiversity conservation. However, forecasts of climate change impacts on species' geographic distributions rarely incorporate a demographic understanding of species' responses to climate. Because many biotic and abiotic factors at multiple scales control species' range limits, experimentation is essential to establish underlying mechanisms. We used a manipulative climate change experiment embedded within a natural climate gradient to examine demographic responses of 12 prairie species with northern range limits within the Pacific Northwest, USA. During the first year, warming decreased recruitment of species even at the coolest edge of their current ranges, but this effect disappeared when they were moved poleward beyond their current ranges. This response was largely driven by differences in germination rates. Other vital rates responded in unique and sometimes opposing ways (survivorship vs. fitness) to species' current ranges and climate change, and were mediated by indirect effects of climate on competition and nutrient availability. Our results demonstrate the importance of using regional-scale climate manipulations and the need for longer-term experiments on the demographic responses that control species' distributions.
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