29 research outputs found

    Wavelength Accuracy of the Keck HIRES Spectrograph and Measuring Changes in the Fine Structure Constant

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    We report on an attempt to accurately wavelength calibrate four nights of data taken with the Keck HIRES spectrograph on QSO PHL957, for the purpose of determining whether the fine structure constant was different in the past. Using new software and techniques, we measured the redshifts of various Ni II, Fe II, Si II, etc. lines in a damped Ly-alpha system at z=2.309. Roughly half the data was taken through the Keck iodine cell which contains thousands of well calibrated iodine lines. Using these iodine exposures to calibrate the normal Th-Ar Keck data pipeline output we found absolute wavelength offsets of 500 m/s to 1000 m/s with drifts of more than 500 m/s over a single night, and drifts of nearly 2000 m/s over several nights. These offsets correspond to an absolute redshift of uncertainty of about Delta z=10^{-5} (Delta lambda= 0.02 Ang), with daily drifts of around Delta z=5x10^{-6} (Delta lambda =0.01 Ang), and multiday drifts of nearly Delta z=2x10^{-5} (0.04 Ang). The causes of the wavelength offsets are not known, but since claimed shifts in the fine structure constant would result in velocity shifts of less than 100 m/s, this level of systematic uncertainty makes may make it difficult to use Keck HIRES data to constrain the change in the fine structure constant. Using our calibrated data, we applied both our own fitting software and standard fitting software to measure (Delta alpha)/alpha, but discovered that we could obtain results ranging from significant detection of either sign, to strong null limits, depending upon which sets of lines and which fitting method was used. We thus speculate that the discrepant results on (Delta alpha)/alpha reported in the literature may be due to random fluctuations coming from under-estimated systematic errors in wavelength calibration and fitting procedure.Comment: 19 pages, 10 figures, to appear in ApJ, Dec 2009 Many corrections and changes made, some new figure

    Analysis of the History and Spread of HIV-1 in Uganda using phylodynamics

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    HIV prevalence has decreased in Uganda since the 1990s, but remains substantial within high-risk groups. Here, we reconstruct the history and spread of HIV subtypes A1 and D in Uganda and explore the transmission dynamics in high-risk populations. We analysed HIV pol sequences from female sex workers in Kampala (n = 42), Lake Victoria fisher-folk (n = 46) and a rural clinical cohort (n = 74), together with publicly available sequences from adjacent regions in Uganda (n = 412) and newly generated sequences from samples taken in Kampala in 1986 (n = 12). Of the sequences from the three Ugandan populations, 60 (37.1 %) were classified as subtype D, 54 (33.3 %) as subtype A1, 31 (19.1 %) as A1/D recombinants, six (3.7 %) as subtype C, one (0.6 %) as subtype G and 10 (6.2 %) as other recombinants. Among the A1/D recombinants we identified a new candidate circulating recombinant form. Phylodynamic and phylogeographic analyses using BEAST indicated that the Ugandan epidemics originated in 1960 (1950-1968) for subtype A1 and 1973 (1970-1977) for D, in rural south-western Uganda with subsequent spread to Kampala. They also showed extensive interconnection with adjacent countries. The sequence analysis shows both epidemics grew exponentially during the 1970s-1980s and decreased from 1992, which agrees with HIV prevalence reports in Uganda. Inclusion of sequences from the 1980s indicated the origin of both epidemics was more recent than expected and substantially narrowed the confidence intervals in comparison to previous estimates. We identified three transmission clusters and ten pairs, none of them including patients from different populations, suggesting active transmission within a structured transmission network

    A predictive model using the mesoscopic architecture of the living brain to detect Alzheimer’s disease

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    Background: Alzheimer’s disease, the most common cause of dementia, causes a progressive and irreversible deterioration of cognition that can sometimes be difficult to diagnose, leading to suboptimal patient care. Methods: We developed a predictive model that computes multi-regional statistical morpho-functional mesoscopic traits from T1-weighted MRI scans, with or without cognitive scores. For each patient, a biomarker called “Alzheimer’s Predictive Vector” (ApV) was derived using a two-stage least absolute shrinkage and selection operator (LASSO). Results: The ApV reliably discriminates between people with (ADrp) and without (nADrp) Alzheimer’s related pathologies (98% and 81% accuracy between ADrp - including the early form, mild cognitive impairment - and nADrp in internal and external hold-out test sets, respectively), without any a priori assumptions or need for neuroradiology reads. The new test is superior to standard hippocampal atrophy (26% accuracy) and cerebrospinal fluid beta amyloid measure (62% accuracy). A multiparametric analysis compared DTI-MRI derived fractional anisotropy, whose readout of neuronal loss agrees with ADrp phenotype, and SNPrs2075650 is significantly altered in patients with ADrp-like phenotype. Conclusions: This new data analytic method demonstrates potential for increasing accuracy of Alzheimer diagnosis

    Argon redistribution during a metamorphic cycle: Consequences for determining cooling rates

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    40Ar/39Ar thermochronology is commonly used to constrain the rates and times of cooling in exhumed metamorphic terranes, with ages usually linked to temperature via Dodson's closure temperature (TC) formulation. Whilst many metamorphic 40Ar/39Ar data are consistent with the timing of crystallisation or cooling within a chronological framework defined by other, higher temperature, chronometers, other 40Ar/39Ar data are more difficult to interpret. We report white mica and biotite single grain fusion and laser ablation 40Ar/39Ar ages from felsic gneisses from the Western Gneiss Region, Norway. The rocks record isothermal decompression from peak eclogite-facies conditions (white mica stable) to amphibolite-facies conditions (biotite stable) at c. 700 °C. White mica and biotite yield dispersed single grain fusion dates from 416 to 373 Ma and 437 to 360 Ma respectively. In-situ laser ablation analyses provide a similar range, with white mica spot ages ranging from 424 to 370 Ma and biotite spot ages ranging from 437 to 370 Ma. The dates span the duration of the metamorphic cycle suggested by previous studies, and cannot be reconciled with the results of simple models of Ar loss by diffusion during cooling. Samples that show evidence for different physical processes, such as the chemical breakdown of white mica, partial melting, and fluid ingress, generated different age populations to samples that did not experience or record obvious petrological evidence for these processes. Samples that record significant recrystallization and deformation yielded younger white mica (but older biotite) single grain fusion ages than more pristine samples. Amphibolite-facies gneisses that preserve evidence for significant partial melting generated younger biotite ages than samples that recorded evidence for significant hydration. Our data support other reported observations that high-temperature metamorphic mica 40Ar/39Ar dates cannot be assumed to record the timing of cooling through a specific temperature window. Careful assessment of the petrographic context of the dated minerals and consideration of their post-crystallisation history may provide a more robust insight into whether ‘age’ links to ‘stage’ in a temporally meaningful way

    The IMPROVE guidelines (Ischaemia Models: Procedural Refinements Of in Vivo Experiments)

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    Most in vivo models of ischaemic stroke target the middle cerebral artery and a spectrum of stroke severities, from mild to substantial, can be achieved. This review describes opportunities to improve the in vivo modelling of ischaemic stroke and animal welfare. It provides a number of recommendations to minimise the level of severity in the most common rodent models of middle cerebral artery occlusion, while sustaining or improving the scientific outcomes. The recommendations cover basic requirements pre-surgery, selecting the most appropriate anaesthetic and analgesic regimen, as well as intraoperative and post-operative care. The aim is to provide support for researchers and animal care staff to refine their procedures and practices, and implement small incremental changes to improve the welfare of the animals used and to answer the scientific question under investigation. All recommendations are recapitulated in a summary poster (see supplementary information)

    Source and sink carbon dynamics and carbon allocation in the Amazon basin

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    Changes to the carbon cycle in tropical forests could affect global climate, but predicting such changes has been previously limited by lack of field-based data. Here we show seasonal cycles of the complete carbon cycle for 14, 1ha intensive carbon cycling plots which we separate into three regions: humid lowland, highlands, and dry lowlands. Our data highlight three trends: (1) there is differing seasonality of total net primary productivity (NPP) with the highlands and dry lowlands peaking in the dry season and the humid lowland sites peaking in the wet season, (2) seasonal reductions in wood NPP are not driven by reductions in total NPP but by carbon during the dry season being preferentially allocated toward either roots or canopy NPP, and (3) there is a temporal decoupling between total photosynthesis and total carbon usage (plant carbon expenditure). This decoupling indicates the presence of nonstructural carbohydrates which may allow growth and carbon to be allocated when it is most ecologically beneficial rather than when it is most environmentally available

    Composition operators with maximal norm on weighted Bergman spaces

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    We prove that any composition operator with maximal norm on one of the weighted Bergman spaces is induced by a disk automorphism or a map that fixes the origin. This result demonstrates a major difference between the weighted Bergman spaces and the Hardy space H2, where every inner function induces a composition operator with maximal norm

    Clinical utility of amyloid PET imaging with (18)F-florbetapir: a retrospective study of 100 patients

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    Background and objective Amyloid-positron emission tomography (PET) imaging (API) detects amyloid-beta pathology early in the course of Alzheimer’s disease (AD) with high sensitivity and specificity. (18)F-florbetapir (Amyvid) is an amyloid-binding PET ligand with a half-life suitable for clinical use outside of the research setting. How API affects patient investigation and management in the ‘real-world’ arena is unknown. To address this, we retrospectively documented the effect of API in patients in the memory clinic. Methods We reviewed the presenting clinical features, the pre-API and post-API investigations, diagnosis and outcomes for the first 100 patients who had API as part of their routine work-up at the Imperial Memory Centre, a tertiary referral clinic in the UK National Health Service. Results API was primarily used to investigate patients with atypical clinical features (56 cases) or those that were young at onset (42 cases). MRI features of AD did not always predict positive API (67%), and 6 of 23 patients with MRIs reported as normal were amyloid-PET positive. There were significantly more cases categorised as non-AD dementia post-API (from 11 to 23). Patients investigated when API was initially available had fewer overall investigations and all patients had significantly fewer investigations in total post-API. Conclusions API has a clear impact on the investigation of young-onset or complex dementia while reducing the overall burden of investigations. It was most useful in younger patients, atypical presentations or individuals with multiple possible causes of cognitive impairment
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