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4 Risk Factor and Biomarker Correlates of FLAIR White Matter Hyperintensities in Former American Football Players
- Monica T Ly, Fatima Tuz-Zahra, Yorghos Tripodis, Charles H Adler, Laura J Balcer, Charles Bernick, Elaine Peskind, Megan L Mariani, Rhoda Au, Sarah J Banks, William B Barr, Jennifer V Wethe, Mark W Bondi, Lisa Delano-Wood, Robert C Cantu, Michael J Coleman, David W Dodick, Michael D McClean, Jesse Mez, Joseph N Palmisano, Brett Martin, Kaitlin Hartlage, Alexander P Lin, Inga K Koerte, Jeffrey L Cummings, Eric M Reiman, Martha E Shenton, Robert A Stern, Sylvain Bouix, Michael L Alosco
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 608-610
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Objective:
White matter hyperintensity (WMH) burden is greater, has a frontal-temporal distribution, and is associated with proxies of exposure to repetitive head impacts (RHI) in former American football players. These findings suggest that in the context of RHI, WMH might have unique etiologies that extend beyond those of vascular risk factors and normal aging processes. The objective of this study was to evaluate the correlates of WMH in former elite American football players. We examined markers of amyloid, tau, neurodegeneration, inflammation, axonal injury, and vascular health and their relationships to WMH. A group of age-matched asymptomatic men without a history of RHI was included to determine the specificity of the relationships observed in the former football players.
Participants and Methods:240 male participants aged 45-74 (60 unexposed asymptomatic men, 60 male former college football players, 120 male former professional football players) underwent semi-structured clinical interviews, magnetic resonance imaging (structural T1, T2 FLAIR, and diffusion tensor imaging), and lumbar puncture to collect cerebrospinal fluid (CSF) biomarkers as part of the DIAGNOSE CTE Research Project. Total WMH lesion volumes (TLV) were estimated using the Lesion Prediction Algorithm from the Lesion Segmentation Toolbox. Structural equation modeling, using Full-Information Maximum Likelihood (FIML) to account for missing values, examined the associations between log-TLV and the following variables: total cortical thickness, whole-brain average fractional anisotropy (FA), CSF amyloid ß42, CSF p-tau181, CSF sTREM2 (a marker of microglial activation), CSF neurofilament light (NfL), and the modified Framingham stroke risk profile (rFSRP). Covariates included age, race, education, APOE z4 carrier status, and evaluation site. Bootstrapped 95% confidence intervals assessed statistical significance. Models were performed separately for football players (college and professional players pooled; n=180) and the unexposed men (n=60). Due to differences in sample size, estimates were compared and were considered different if the percent change in the estimates exceeded 10%.
Results:In the former football players (mean age=57.2, 34% Black, 29% APOE e4 carrier), reduced cortical thickness (B=-0.25, 95% CI [0.45, -0.08]), lower average FA (B=-0.27, 95% CI [-0.41, -.12]), higher p-tau181 (B=0.17, 95% CI [0.02, 0.43]), and higher rFSRP score (B=0.27, 95% CI [0.08, 0.42]) were associated with greater log-TLV. Compared to the unexposed men, substantial differences in estimates were observed for rFSRP (Bcontrol=0.02, Bfootball=0.27, 994% difference), average FA (Bcontrol=-0.03, Bfootball=-0.27, 802% difference), and p-tau181 (Bcontrol=-0.31, Bfootball=0.17, -155% difference). In the former football players, rFSRP showed a stronger positive association and average FA showed a stronger negative association with WMH compared to unexposed men. The effect of WMH on cortical thickness was similar between the two groups (Bcontrol=-0.27, Bfootball=-0.25, 7% difference).
Conclusions:These results suggest that the risk factor and biological correlates of WMH differ between former American football players and asymptomatic individuals unexposed to RHI. In addition to vascular risk factors, white matter integrity on DTI showed a stronger relationship with WMH burden in the former football players. FLAIR WMH serves as a promising measure to further investigate the late multifactorial pathologies of RHI.
Axisymmetric gravity currents in anisotropic porous media
- Graham P. Benham, Jerome A. Neufeld, Andrew W. Woods
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- Journal:
- Journal of Fluid Mechanics / Volume 952 / 10 December 2022
- Published online by Cambridge University Press:
- 24 November 2022, A23
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We explore the motion of an axisymmetric gravity current in an anisotropic porous medium in which the horizontal permeability is larger than the vertical permeability. It is well known that the classical axisymmetric gravity current supplied by a constant point source of fluid has an unphysical singularity near the origin. We address this by considering a pressure-dominated region near the origin which allows for vertical flow from the source, such that the current remains of finite depth, whilst beyond this region the flow is gravity dominated. At early times the inner pressure-driven region controls the spreading of the current, but at late times the inner region occupies a progressively smaller fraction of the current such that the radius increases as ${\sim }t^{3/7}$, while the depth near the origin increases approximately as ${\sim }t^{1/7}$. The presence of anisotropy highlights this phenomenon, since the vertical permeability maintains an effect on the flow at late times through the pressure-driven flow near the origin. Using these results we provide some quantitative insights into the dominant dynamics which controls CO$_2$ migration through permeable aquifers, as occurs in the context of carbon capture and storage.
“Do I Have a Memory Problem? I Can’t Recall”: An Evaluation of Measurement Invariance in Subjective Reporting of Memory Symptoms among Persons with and without Objective HIV-Associated Memory Impairment
- David P. Sheppard, Matthew W. Gallagher, Erin E. Morgan, Angulique Y. Outlaw, Sylvie Naar, Steven Paul Woods
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- Journal:
- Journal of the International Neuropsychological Society / Volume 28 / Issue 2 / February 2022
- Published online by Cambridge University Press:
- 06 May 2021, pp. 166-176
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Objective:
Memory symptoms and objective impairment are common in HIV disease and are associated with disability. A paradoxical issue is that objective episodic memory failures can interfere with accurate recall of memory symptoms. The present study assessed whether responses on a self-report scale of memory symptoms demonstrate measurement invariance in persons with and without objective HIV-associated memory impairment.
Method:In total, 505 persons with HIV completed the Prospective and Retrospective Memory Questionnaire (PRMQ). Objective memory impairment (n = 141) was determined using a 1-SD cutoff on clinical tests of episodic memory. PRMQ measurement invariance was assessed by confirmatory factor analyses examining a one-factor model with increasing cross-group equality constraints imposed on factor loadings and item thresholds (i.e., configural, weak, and strong invariance).
Results:Configural model fit indicated that identical items measured a one-factor model for both groups. Comparison to the weak model indicated that factor loadings were equivalent across groups. However, there was evidence of partial strong invariance, with two PRMQ item thresholds differing across memory impairment groups. Post hoc analyses using a 1.5-SD memory impairment cutoff (n = 77) revealed both partial weak and partial strong invariance, such that PRMQ item loadings differed across memory groups for three items.
Conclusions:The PRMQ demonstrated a robust factor structure among persons with and without objective HIV-associated memory impairment. However, on select PRMQ items, individuals with memory impairment reported observed scores that were relatively higher than their latent score, while items were more strongly associated with the memory factor in a group with greater memory impairment.
An MRI study of subjects in the prodromal phase of psychosis
- P. McGuire, D. Velakoulis, P.D. McGorry, S.J. Wood, J. Suckling, L.J. Philips, A.R. Yung, E.T. Bullmore, W. Brewer, B. Soulsby, P. Desmond, C. Pantelis
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- Journal:
- European Psychiatry / Volume 17 / Issue S1 / May 2002
- Published online by Cambridge University Press:
- 16 April 2020, pp. 16s-17s
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New Intrusion Analyses on the CVLT-3: Utility in Distinguishing the Memory Disorders of Alzheimer’s versus Huntington’s Disease
- Lisa V. Graves, Heather M. Holden, Emily J. Van Etten, Lisa Delano-Wood, Mark W. Bondi, David P. Salmon, Jody Corey-Bloom, Paul E. Gilbert, Dean C. Delis
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- Journal:
- Journal of the International Neuropsychological Society / Volume 25 / Issue 8 / September 2019
- Published online by Cambridge University Press:
- 07 May 2019, pp. 878-883
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Objectives: Research has shown that analyzing intrusion errors generated on verbal learning and memory measures is helpful for distinguishing between the memory disorders associated with Alzheimer’s disease (AD) and other neurological disorders, including Huntington’s disease (HD). Moreover, preliminary evidence suggests that certain clinical populations may be prone to exhibit different types of intrusion errors. Methods: We examined the prevalence of two new California Verbal Learning Test-3 (CVLT-3) intrusion subtypes – across-trial novel intrusions and across/within trial repeated intrusions – in individuals with AD or HD. We hypothesized that the encoding/storage impairment associated with medial-temporal involvement in AD would result in a greater number of novel intrusions on the delayed recall trials of the CVLT-3, whereas the executive dysfunction associated with subcortical-frontal involvement in HD would result in a greater number of repeated intrusions across trials. Results: The AD group generated significantly more across-trial novel intrusions than across/within trial repeated intrusions on the delayed cued-recall trials, whereas the HD group showed the opposite pattern on the delayed free-recall trials. Conclusions: These new intrusion subtypes, combined with traditional memory analyses (e.g., recall versus recognition performance), promise to enhance our ability to distinguish between the memory disorders associated with primarily medial-temporal versus subcortical-frontal involvement.
A prospective study of transmission of Multidrug-Resistant Organisms (MDROs) between environmental sites and hospitalized patients—the TransFER study
- Luke F. Chen, Lauren P. Knelson, Maria F. Gergen, Olga M. Better, Bradly P. Nicholson, Christopher W. Woods, William A. Rutala, David J. Weber, Daniel J. Sexton, Deverick J. Anderson, for the CDC Prevention Epicenters Program
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- Journal:
- Infection Control & Hospital Epidemiology / Volume 40 / Issue 1 / January 2019
- Published online by Cambridge University Press:
- 14 November 2018, pp. 47-52
- Print publication:
- January 2019
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Objective
Hospital environmental surfaces are frequently contaminated by microorganisms. However, the causal mechanism of bacterial contamination of the environment as a source of transmission is still debated. This prospective study was performed to characterize the nature of multidrug-resistant organism (MDRO) transmission between the environment and patients using standard microbiological and molecular techniques.
SettingProspective cohort study at 2 academic medical centers.
DesignA prospective multicenter study to characterize the nature of bacterial transfer events between patients and environmental surfaces in rooms that previously housed patients with 1 of 4 ‘marker’ MDROs: methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, Clostridium difficile, and MDR Acinetobacter baumannii. Environmental and patient microbiological samples were obtained on admission into a freshly disinfected inpatient room. Repeat samples from room surfaces and patients were taken on days 3 and 7 and each week the patient stayed in the same room. The bacterial identity, antibiotic susceptibility, and molecular sequences were compared between organisms found in the environment samples and patient sources.
ResultsWe enrolled 80 patient–room admissions; 9 of these patients (11.3%) were asymptomatically colonized with MDROs at study entry. Hospital room surfaces were contaminated with MDROs despite terminal disinfection in 44 cases (55%). Microbiological Bacterial Transfer events either to the patient, the environment, or both occurred in 12 patient encounters (18.5%) from the microbiologically evaluable cohort.
ConclusionsMicrobiological Bacterial Transfer events between patients and the environment were observed in 18.5% of patient encounters and occurred early in the admission. This study suggests that research on prevention methods beyond the standard practice of room disinfection at the end of a patient’s stay is needed to better prevent acquisition of MDROs through the environment.
Increasing Inaccuracy of Self-Reported Subjective Cognitive Complaints Over 24 Months in Empirically Derived Subtypes of Mild Cognitive Impairment
- Emily C. Edmonds, Alexandra J. Weigand, Kelsey R. Thomas, Joel Eppig, Lisa Delano-Wood, Douglas R. Galasko, David P. Salmon, Mark W. Bondi
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- Journal:
- Journal of the International Neuropsychological Society / Volume 24 / Issue 8 / September 2018
- Published online by Cambridge University Press:
- 02 October 2018, pp. 842-853
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Objectives: Although subjective cognitive complaints (SCC) are an integral component of the diagnostic criteria for mild cognitive impairment (MCI), previous findings indicate they may not accurately reflect cognitive ability. Within the Alzheimer’s Disease Neuroimaging Initiative, we investigated longitudinal change in the discrepancy between self- and informant-reported SCC across empirically derived subtypes of MCI and normal control (NC) participants. Methods: Data were obtained for 353 MCI participants and 122 “robust” NC participants. Participants were classified into three subtypes at baseline via cluster analysis: amnestic MCI, mixed MCI, and cluster-derived normal (CDN), a presumptive false-positive group who performed within normal limits on neuropsychological testing. SCC at baseline and two annual follow-up visits were assessed via the Everyday Cognition Questionnaire (ECog), and discrepancy scores between self- and informant-report were calculated. Analysis of change was conducted using analysis of covariance. Results: The amnestic and mixed MCI subtypes demonstrated increasing ECog discrepancy scores over time. This was driven by an increase in informant-reported SCC, which corresponded to participants’ objective cognitive decline, despite stable self-reported SCC. Increasing unawareness was associated with cerebrospinal fluid Alzheimer’s disease biomarker positivity and progression to Alzheimer’s disease. In contrast, CDN and NC groups over-reported cognitive difficulty and demonstrated normal cognition at all time points. Conclusions: MCI participants’ discrepancy scores indicate progressive underappreciation of their evolving cognitive deficits. Consistent over-reporting in the CDN and NC groups despite normal objective cognition suggests that self-reported SCC do not predict impending cognitive decline. Results demonstrate that self-reported SCC become increasingly misleading as objective cognitive impairment becomes more pronounced. (JINS, 2018, 24, 842–853)
New Yes/No Recognition Memory Analysis on the California Verbal Learning Test-3: Clinical Utility in Alzheimer’s and Huntington’s Disease
- Lisa V. Graves, Heather M. Holden, Emily J. Van Etten, Lisa Delano-Wood, Mark W. Bondi, David P. Salmon, Jody Corey-Bloom, Dean C. Delis, Paul E. Gilbert
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- Journal of the International Neuropsychological Society / Volume 24 / Issue 8 / September 2018
- Published online by Cambridge University Press:
- 16 August 2018, pp. 833-841
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Objectives: The third edition of the California Verbal Learning Test (CVLT-3) includes a new index termed List A versus Novel/Unrelated recognition discriminability (RD) on the Yes/No Recognition trial. Whereas the Total RD index incorporates false positive (FP) errors associated with all distractors (including List B and semantically related items), the new List A versus Novel/Unrelated RD index incorporates only FP errors associated with novel, semantically unrelated distractors. Thus, in minimizing levels of source and semantic interference, the List A versus Novel/Unrelated RD index may yield purer assessments of yes/no recognition memory independent of vulnerability to source memory difficulties or semantic confusion, both of which are often seen in individuals with primarily frontal-system dysfunction (e.g., early Huntington’s disease [HD]). Methods: We compared the performance of individuals with Alzheimer’s disease (AD) and HD in mild and moderate stages of dementia on CVLT-3 indices of Total RD and List A versus Novel/Unrelated RD. Results: Although AD and HD subgroups exhibited deficits on both RD indices relative to healthy comparison groups, those with HD generally outperformed those with AD, and group differences were more robust on List A versus Novel/Unrelated RD than on Total RD. Conclusions: Our findings highlight the clinical utility of the new CVLT-3 List A versus Novel/Unrelated RD index, which (a) maximally assesses yes/no recognition memory independent of source and semantic interference; and (b) provides a greater differentiation between individuals whose memory disorder is primarily at the encoding/storage level (e.g., as in AD) versus at the retrieval level (e.g., as in early HD). (JINS, 2018, 24, 833–841)
Aguilarite from the Camoola Reef, Maratoto Valley, New Zealand
- J. V. Main, K. A. Rodgers, H. W. Kobe, C. P. Woods
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- Mineralogical Magazine / Volume 38 / Issue 300 / December 1972
- Published online by Cambridge University Press:
- 05 July 2018, pp. 961-964
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Aguilarite, Ag4SeS, occurs in a hydrothermal vein deposit associated with sphalerite, chalcopyrite, galena, and native silver. Physical and chemical data agree with descriptions from Guanajuato (type locality). Differential thermal analysis of synthetic material indicates an inversion temperature of 122±1 °C. The mineral crystallized late in the paragenetic sequence, probably slightly above 200 °C.
Pressure corrections for a selection of piston-cylinder cell assemblies
- P. McDade, B. J. Wood, W. Van Westrenen, R. Brooker, G. Gudmundsson, H. Soulard, J. Najorka, J. Blundy
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- Mineralogical Magazine / Volume 66 / Issue 6 / December 2002
- Published online by Cambridge University Press:
- 05 July 2018, pp. 1021-1028
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Piston-cylinder cell assemblies experience inhomogeneous pressure distribution upon pressurization due to the variable compressibilities of the cell components. This results in the sample experiencing a pressure lower than expected, given the applied force of the piston. Although the effect is generally compensated for by applying a ‘friction’ correction, there have been wide variations in the corrections applied for some of the harder cell materials. We have determined friction correction factors for a range of cell assemblies commonly used in our laboratory relative to select well-characterized phase equilibria. Single-sleeve NaCl cells require, using the piston-in technique, very small corrections of the order −0.05 GPa for 12.7 mm diameter, and less for larger diameter assemblies. Four separate calibrations of the single sleeve 12.7 mm BaCO3 cell show that it requires a correction of −9%. This factor is entirely independent of temperature and pressure within the range 1000 to 1600°C and 1.5 to 3.2 GPa. This result is in contrast to the results of Fram and Longhi (1992) who claim that the correction for BaCO3 cells is highly dependent on pressure. For the assemblies included in this study there is an increase in the pressure correction required in the order of 12.7 mm diameter NaCl-pyrex −3%; 19 mm talc-pyrex −3.6%; 12.7 mm BaCO3 −9% and 12.7 mm BaCO3-silica glass −13%.
Development of nuclear criticality safety controls on intermediate-level waste packages
- T. W. Hicks, P. Wood, D. Putley, T. D. Baldwin
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- Journal:
- Mineralogical Magazine / Volume 76 / Issue 8 / December 2012
- Published online by Cambridge University Press:
- 05 July 2018, pp. 2949-2956
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Intermediate-level wastes (ILW) include substantial quantities of fissile material and controls are required to ensure that its storage, transport and disposal does not present a nuclear criticality hazard. This paper describes the Radioactive Waste Management Directorate's research to develop package fissile material limits (in the form of screening levels) for four different categories of ILW, defined according to uranium or plutonium composition: (1) irradiated natural and slightly enriched uranium (uranium containing up to 1.9 wt.% 235U); (2) low-enriched uranium (uranium containing up to 4 wt.% 235U); (3) high-enriched uranium (uranium containing up to 100 wt.% 235U); and (4) separated plutonium (plutonium containing up to 100 wt.% 239Pu).
The derivation of package screening levels was supported by neutron transport calculations that addressed conditions during waste package transport to a geological disposal facility (GDF), during the GDF operational phase and after GDF closure. The analysis included consideration of combinations of events and processes that could result in fissile material accumulation and concentration after GDF closure, when waste packages have deteriorated sufficiently for fissile material to be mobilized. The results of the calculations have provided input to Radioactive Waste Management Directorate's decision making on setting waste package screening levels.
Deterioration of visuospatial associative memory following a first psychotic episode: a long-term follow-up study
- C. M. J. Wannan, C. F. Bartholomeusz, V. L. Cropley, T. E. Van Rheenen, A. Panayiotou, W. J. Brewer, T. M. Proffitt, L. Henry, M. G. Harris, D. Velakoulis, P. McGorry, C. Pantelis, S. J. Wood
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- Journal:
- Psychological Medicine / Volume 48 / Issue 1 / January 2018
- Published online by Cambridge University Press:
- 19 June 2017, pp. 132-141
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Background
Cognitive deficits are a core feature of schizophrenia, and impairments in most domains are thought to be stable over the course of the illness. However, cross-sectional evidence indicates that some areas of cognition, such as visuospatial associative memory, may be preserved in the early stages of psychosis, but become impaired in later established illness stages. This longitudinal study investigated change in visuospatial and verbal associative memory following psychosis onset.
MethodsIn total 95 first-episode psychosis (FEP) patients and 63 healthy controls (HC) were assessed on neuropsychological tests at baseline, with 38 FEP and 22 HCs returning for follow-up assessment at 5–11 years. Visuospatial associative memory was assessed using the Cambridge Neuropsychological Test Automated Battery Visuospatial Paired-Associate Learning task, and verbal associative memory was assessed using Verbal Paired Associates subtest of the Wechsler Memory Scale - Revised.
ResultsVisuospatial and verbal associative memory at baseline did not differ significantly between FEP patients and HCs. However, over follow-up, visuospatial associative memory deteriorated significantly for the FEP group, relative to healthy individuals. Conversely, verbal associative memory improved to a similar degree observed in HCs. In the FEP cohort, visuospatial (but not verbal) associative memory ability at baseline was associated with functional outcome at follow-up.
ConclusionsAreas of cognition that develop prior to psychosis onset, such as visuospatial and verbal associative memory, may be preserved early in the illness. Later deterioration in visuospatial memory ability may relate to progressive structural and functional brain abnormalities that occurs following psychosis onset.
Patterns of Cortical and Subcortical Amyloid Burden across Stages of Preclinical Alzheimer’s Disease
- Emily C. Edmonds, Katherine J. Bangen, Lisa Delano-Wood, Daniel A. Nation, Ansgar J. Furst, David P. Salmon, Mark W. Bondi, for the Alzheimer’s Disease Neuroimaging Initiative
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- Journal:
- Journal of the International Neuropsychological Society / Volume 22 / Issue 10 / November 2016
- Published online by Cambridge University Press:
- 01 December 2016, pp. 978-990
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Objectives: We examined florbetapir positron emission tomography (PET) amyloid scans across stages of preclinical Alzheimer’s disease (AD) in cortical, allocortical, and subcortical regions. Stages were characterized using empirically defined methods. Methods: A total of 312 cognitively normal Alzheimer’s Disease Neuroimaging Initiative participants completed a neuropsychological assessment and florbetapir PET scan. Participants were classified into stages of preclinical AD using (1) a novel approach based on the number of abnormal biomarkers/cognitive markers each individual possessed, and (2) National Institute on Aging and the Alzheimer’s Association (NIA-AA) criteria. Preclinical AD groups were compared to one another and to a mild cognitive impairment (MCI) sample on florbetapir standardized uptake value ratios (SUVRs) in cortical and allocortical/subcortical regions of interest (ROIs). Results: Amyloid deposition increased across stages of preclinical AD in all cortical ROIs, with SUVRs in the later stages reaching levels seen in MCI. Several subcortical areas showed a pattern of results similar to the cortical regions; however, SUVRs in the hippocampus, pallidum, and thalamus largely did not differ across stages of preclinical AD. Conclusions: Substantial amyloid accumulation in cortical areas has already occurred before one meets criteria for a clinical diagnosis. Potential explanations for the unexpected pattern of results in some allocortical/subcortical ROIs include lack of correspondence between (1) cerebrospinal fluid and florbetapir PET measures of amyloid, or between (2) subcortical florbetapir PET SUVRs and underlying neuropathology. Findings support the utility of our novel method for staging preclinical AD. By combining imaging biomarkers with detailed cognitive assessment to better characterize preclinical AD, we can advance our understanding of who is at risk for future progression. (JINS, 2016, 22, 978–990)
Photometry and Spectroscopy of Long Period Variables in the Magellanic Clouds
- P. R. Wood, M. S. Bessell, M. W. Fox
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- Journal:
- Publications of the Astronomical Society of Australia / Volume 4 / Issue 2 / 1981
- Published online by Cambridge University Press:
- 25 April 2016, pp. 203-205
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Many of the important events in the life of a star occur, or are thought to occur, during the red giant or supergiant phase of evolution. For example, in heavy and intermediate mass stars supernova explosions terminate normal evolutionary processes while in lower mass stars the stellar envelope is entirely removed giving rise to planetary nebulae and, subsequently, white dwarfs. Theoretical calculations suggest that before the onset of these rather drastic events, a significant amount of nucleosynthesis occurs, giving rise to enhanced surface abundances of He, C, N and s-process elements (e.g., Iben and Truran 1978; Renzini and Voli 1981); loss of the envelope material by stellar winds, planetary nebula ejection and supernova explosions produce overall galactic enrichment in these elements.
Seeing Measurements at Freeling Heights and Siding Spring Observatory
- P. R. Wood, A. W. Rodgers, K. S. Russell
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- Journal:
- Publications of the Astronomical Society of Australia / Volume 12 / Issue 1 / April 1995
- Published online by Cambridge University Press:
- 25 April 2016, pp. 97-105
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A low-cost differential image motion monitor (DIMM), consisting of an 11-inch Celestron, an SBIG ST-4 autoguiding CCD camera and a PC, is described. Two such systems were used during June–July and November–December 1993 to make near-simultaneous seeing measurements at Freeling Heights in the Northern Flinders Ranges and at Siding Spring Observatory. The results of these campaigns show that the seeing-distribution is generally similar at both sites, with the most common seeing value being ~l·2″. Siding Spring does, however, have slightly more bad seeing (>2″) than Freeling Heights. Weather records from Arkaroola Resort (15 km south of Freeling Heights) indicate that there is ~15% less cloud cover at Freeling Heights than at Siding Spring. Episodes of rapid seeing deterioration at Siding Spring in winter are shown to coincide with warm air masses crossing the mountain.
Estimating the critical immunity threshold for preventing hepatitis A outbreaks in men who have sex with men
- D. G. REGAN, J. G. WOOD, C. BENEVENT, H. ALI, L. WATCHIRS SMITH, P. W. ROBERTSON, M. J. FERSON, C. K. FAIRLEY, B. DONOVAN, M. G. LAW
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- Journal:
- Epidemiology & Infection / Volume 144 / Issue 7 / May 2016
- Published online by Cambridge University Press:
- 13 November 2015, pp. 1528-1537
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Several outbreaks of hepatitis A in men who have sex with men (MSM) were reported in the 1980s and 1990s in Australia and other countries. An effective hepatitis A virus (HAV) vaccine has been available in Australia since 1994 and is recommended for high-risk groups including MSM. No outbreaks of hepatitis A in Australian MSM have been reported since 1996. In this study, we aimed to estimate HAV transmissibility in MSM populations in order to inform targets for vaccine coverage in such populations. We used mathematical models of HAV transmission in a MSM population to estimate the basic reproduction number (R0) and the probability of an HAV epidemic occurring as a function of the immune proportion. We estimated a plausible range for R0 of 1·71–3·67 for HAV in MSM and that sustained epidemics cannot occur once the proportion immune to HAV is greater than ~70%. To our knowledge this is the first estimate of R0 and the critical population immunity threshold for HAV transmission in MSM. As HAV is no longer endemic in Australia or in most other developed countries, vaccination is the only means of maintaining population immunity >70%. Our findings provide impetus to promote HAV vaccination in high-risk groups such as MSM.
Polygenic interactions with environmental adversity in the aetiology of major depressive disorder
- N. Mullins, R. A. Power, H. L. Fisher, K. B. Hanscombe, J. Euesden, R. Iniesta, D. F. Levinson, M. M. Weissman, J. B. Potash, J. Shi, R. Uher, S. Cohen-Woods, M. Rivera, L. Jones, I. Jones, N. Craddock, M. J. Owen, A. Korszun, I. W. Craig, A. E. Farmer, P. McGuffin, G. Breen, C. M. Lewis
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- Journal:
- Psychological Medicine / Volume 46 / Issue 4 / March 2016
- Published online by Cambridge University Press:
- 03 November 2015, pp. 759-770
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Background
Major depressive disorder (MDD) is a common and disabling condition with well-established heritability and environmental risk factors. Gene–environment interaction studies in MDD have typically investigated candidate genes, though the disorder is known to be highly polygenic. This study aims to test for interaction between polygenic risk and stressful life events (SLEs) or childhood trauma (CT) in the aetiology of MDD.
MethodThe RADIANT UK sample consists of 1605 MDD cases and 1064 controls with SLE data, and a subset of 240 cases and 272 controls with CT data. Polygenic risk scores (PRS) were constructed using results from a mega-analysis on MDD by the Psychiatric Genomics Consortium. PRS and environmental factors were tested for association with case/control status and for interaction between them.
ResultsPRS significantly predicted depression, explaining 1.1% of variance in phenotype (p = 1.9 × 10−6). SLEs and CT were also associated with MDD status (p = 2.19 × 10−4 and p = 5.12 × 10−20, respectively). No interactions were found between PRS and SLEs. Significant PRSxCT interactions were found (p = 0.002), but showed an inverse association with MDD status, as cases who experienced more severe CT tended to have a lower PRS than other cases or controls. This relationship between PRS and CT was not observed in independent replication samples.
ConclusionsCT is a strong risk factor for MDD but may have greater effect in individuals with lower genetic liability for the disorder. Including environmental risk along with genetics is important in studying the aetiology of MDD and PRS provide a useful approach to investigating gene–environment interactions in complex traits.
Buoyancy-induced turbulent mixing in a narrow tilted tank
- Tiras Y. Lin, C. P. Caulfield, Andrew W. Woods
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- Journal:
- Journal of Fluid Mechanics / Volume 773 / 25 June 2015
- Published online by Cambridge University Press:
- 20 May 2015, pp. 267-297
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We describe a series of experiments in which a constant buoyancy flux $B_{s}$ of salty dyed water of density ${\it\rho}_{s}$ is introduced at the top of a long narrow tank of square cross-section tilted at an angle ${\it\theta}$ to the vertical. The tank is initially filled with fresh clear water of density ${\it\rho}_{0}<{\it\rho}_{s}$, and we investigate the resulting buoyancy-driven turbulent mixing at various tilt angles ${\it\theta}$. Using a light-attenuation image analysis method, we determine the evolution of the reduced gravity $g^{\prime }=g({\it\rho}-{\it\rho}_{0})/{\it\rho}_{0}$ of the mixed fluid in time and space as it propagates towards the bottom of the tank. For all tilt angles tested (${\it\theta}=0^{\circ }$ to ${\it\theta}=45^{\circ }$), we focus exclusively on high-Reynolds-number experiments, where the flow remains turbulent both along the length and across the width of the tank. We find that when ${\it\theta}>0^{\circ }$, the cross-tank component of gravity acts to segregate the dense fluid from the relatively lighter fluid, and a statically stable gradient of $g^{\prime }$ across the width of the tank occurs more frequently than a statically unstable gradient, i.e. $(\partial g^{\prime }/\partial x)<0$ occurs more frequently than $(\partial g^{\prime }/\partial x)>0$. This is in contrast to the case when ${\it\theta}=0^{\circ }$, where instantaneous cross-tank gradients of reduced gravity may be positive or negative, but are equal to zero in an ensemble average. We observe that when ${\it\theta}>0^{\circ }$, the cross-tank gradient of reduced gravity induces a turbulent counterflow where dense fluid flows down the upward-facing surface of the tank and lighter fluid flows in the opposing direction above. We model the evolution of the cross-tank averaged, ensemble averaged reduced gravity $\langle \overline{g^{\prime }}\rangle _{e}$ as a diffusive process using Prandtl’s mixing length theory, building on the model of van Sommeren et al. (J. Fluid Mech., vol. 701, 2012, pp. 278–303) who considered purely vertical tanks. We model the fluctuations (from the cross-tank averaged quantity) of reduced gravity $\langle {\hat{g}}^{\prime }\rangle _{e}$ and counterflow velocity $\langle {\hat{w}}\rangle _{e}$ by characterising the mixing across the width of the tank with a cross-tank turbulent diffusivity ${\it\kappa}_{T,x}$, which we assume is constant in the cross-tank coordinate $x$. We show that the counterflow that exists when ${\it\theta}>0^{\circ }$ acts directly to enhance the effective along-tank turbulent diffusivity ${\it\kappa}_{T,z}$, and from experiments, we find that the mixing length increases approximately linearly with ${\it\theta}$, and that both ${\it\kappa}_{T,x}$ and ${\it\kappa}_{T,z}$ are proportional to $(\partial \langle \overline{g^{\prime }}\rangle _{e}/\partial z)^{1/2}$.
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- By Mitchell Aboulafia, Frederick Adams, Marilyn McCord Adams, Robert M. Adams, Laird Addis, James W. Allard, David Allison, William P. Alston, Karl Ameriks, C. Anthony Anderson, David Leech Anderson, Lanier Anderson, Roger Ariew, David Armstrong, Denis G. Arnold, E. J. Ashworth, Margaret Atherton, Robin Attfield, Bruce Aune, Edward Wilson Averill, Jody Azzouni, Kent Bach, Andrew Bailey, Lynne Rudder Baker, Thomas R. Baldwin, Jon Barwise, George Bealer, William Bechtel, Lawrence C. Becker, Mark A. Bedau, Ernst Behler, José A. Benardete, Ermanno Bencivenga, Jan Berg, Michael Bergmann, Robert L. Bernasconi, Sven Bernecker, Bernard Berofsky, Rod Bertolet, Charles J. Beyer, Christian Beyer, Joseph Bien, Joseph Bien, Peg Birmingham, Ivan Boh, James Bohman, Daniel Bonevac, Laurence BonJour, William J. Bouwsma, Raymond D. Bradley, Myles Brand, Richard B. Brandt, Michael E. Bratman, Stephen E. Braude, Daniel Breazeale, Angela Breitenbach, Jason Bridges, David O. Brink, Gordon G. Brittan, Justin Broackes, Dan W. Brock, Aaron Bronfman, Jeffrey E. Brower, Bartosz Brozek, Anthony Brueckner, Jeffrey Bub, Lara Buchak, Otavio Bueno, Ann E. Bumpus, Robert W. Burch, John Burgess, Arthur W. Burks, Panayot Butchvarov, Robert E. Butts, Marina Bykova, Patrick Byrne, David Carr, Noël Carroll, Edward S. Casey, Victor Caston, Victor Caston, Albert Casullo, Robert L. Causey, Alan K. L. Chan, Ruth Chang, Deen K. Chatterjee, Andrew Chignell, Roderick M. Chisholm, Kelly J. Clark, E. J. Coffman, Robin Collins, Brian P. Copenhaver, John Corcoran, John Cottingham, Roger Crisp, Frederick J. Crosson, Antonio S. Cua, Phillip D. Cummins, Martin Curd, Adam Cureton, Andrew Cutrofello, Stephen Darwall, Paul Sheldon Davies, Wayne A. Davis, Timothy Joseph Day, Claudio de Almeida, Mario De Caro, Mario De Caro, John Deigh, C. F. Delaney, Daniel C. Dennett, Michael R. DePaul, Michael Detlefsen, Daniel Trent Devereux, Philip E. Devine, John M. Dillon, Martin C. Dillon, Robert DiSalle, Mary Domski, Alan Donagan, Paul Draper, Fred Dretske, Mircea Dumitru, Wilhelm Dupré, Gerald Dworkin, John Earman, Ellery Eells, Catherine Z. Elgin, Berent Enç, Ronald P. Endicott, Edward Erwin, John Etchemendy, C. Stephen Evans, Susan L. Feagin, Solomon Feferman, Richard Feldman, Arthur Fine, Maurice A. Finocchiaro, William FitzPatrick, Richard E. Flathman, Gvozden Flego, Richard Foley, Graeme Forbes, Rainer Forst, Malcolm R. Forster, Daniel Fouke, Patrick Francken, Samuel Freeman, Elizabeth Fricker, Miranda Fricker, Michael Friedman, Michael Fuerstein, Richard A. Fumerton, Alan Gabbey, Pieranna Garavaso, Daniel Garber, Jorge L. A. Garcia, Robert K. Garcia, Don Garrett, Philip Gasper, Gerald Gaus, Berys Gaut, Bernard Gert, Roger F. Gibson, Cody Gilmore, Carl Ginet, Alan H. Goldman, Alvin I. Goldman, Alfonso Gömez-Lobo, Lenn E. Goodman, Robert M. Gordon, Stefan Gosepath, Jorge J. E. Gracia, Daniel W. Graham, George A. Graham, Peter J. Graham, Richard E. Grandy, I. Grattan-Guinness, John Greco, Philip T. Grier, Nicholas Griffin, Nicholas Griffin, David A. Griffiths, Paul J. Griffiths, Stephen R. Grimm, Charles L. Griswold, Charles B. Guignon, Pete A. Y. Gunter, Dimitri Gutas, Gary Gutting, Paul Guyer, Kwame Gyekye, Oscar A. Haac, Raul Hakli, Raul Hakli, Michael Hallett, Edward C. Halper, Jean Hampton, R. James Hankinson, K. R. Hanley, Russell Hardin, Robert M. Harnish, William Harper, David Harrah, Kevin Hart, Ali Hasan, William Hasker, John Haugeland, Roger Hausheer, William Heald, Peter Heath, Richard Heck, John F. Heil, Vincent F. Hendricks, Stephen Hetherington, Francis Heylighen, Kathleen Marie Higgins, Risto Hilpinen, Harold T. Hodes, Joshua Hoffman, Alan Holland, Robert L. Holmes, Richard Holton, Brad W. Hooker, Terence E. Horgan, Tamara Horowitz, Paul Horwich, Vittorio Hösle, Paul Hoβfeld, Daniel Howard-Snyder, Frances Howard-Snyder, Anne Hudson, Deal W. Hudson, Carl A. Huffman, David L. Hull, Patricia Huntington, Thomas Hurka, Paul Hurley, Rosalind Hursthouse, Guillermo Hurtado, Ronald E. Hustwit, Sarah Hutton, Jonathan Jenkins Ichikawa, Harry A. Ide, David Ingram, Philip J. Ivanhoe, Alfred L. Ivry, Frank Jackson, Dale Jacquette, Joseph Jedwab, Richard Jeffrey, David Alan Johnson, Edward Johnson, Mark D. Jordan, Richard Joyce, Hwa Yol Jung, Robert Hillary Kane, Tomis Kapitan, Jacquelyn Ann K. Kegley, James A. Keller, Ralph Kennedy, Sergei Khoruzhii, Jaegwon Kim, Yersu Kim, Nathan L. King, Patricia Kitcher, Peter D. Klein, E. D. Klemke, Virginia Klenk, George L. Kline, Christian Klotz, Simo Knuuttila, Joseph J. Kockelmans, Konstantin Kolenda, Sebastian Tomasz Kołodziejczyk, Isaac Kramnick, Richard Kraut, Fred Kroon, Manfred Kuehn, Steven T. Kuhn, Henry E. Kyburg, John Lachs, Jennifer Lackey, Stephen E. Lahey, Andrea Lavazza, Thomas H. Leahey, Joo Heung Lee, Keith Lehrer, Dorothy Leland, Noah M. Lemos, Ernest LePore, Sarah-Jane Leslie, Isaac Levi, Andrew Levine, Alan E. Lewis, Daniel E. Little, Shu-hsien Liu, Shu-hsien Liu, Alan K. L. Chan, Brian Loar, Lawrence B. Lombard, John Longeway, Dominic McIver Lopes, Michael J. Loux, E. J. Lowe, Steven Luper, Eugene C. Luschei, William G. Lycan, David Lyons, David Macarthur, Danielle Macbeth, Scott MacDonald, Jacob L. Mackey, Louis H. Mackey, Penelope Mackie, Edward H. Madden, Penelope Maddy, G. B. Madison, Bernd Magnus, Pekka Mäkelä, Rudolf A. Makkreel, David Manley, William E. Mann (W.E.M.), Vladimir Marchenkov, Peter Markie, Jean-Pierre Marquis, Ausonio Marras, Mike W. Martin, A. P. Martinich, William L. McBride, David McCabe, Storrs McCall, Hugh J. McCann, Robert N. McCauley, John J. McDermott, Sarah McGrath, Ralph McInerny, Daniel J. McKaughan, Thomas McKay, Michael McKinsey, Brian P. McLaughlin, Ernan McMullin, Anthonie Meijers, Jack W. Meiland, William Jason Melanson, Alfred R. Mele, Joseph R. Mendola, Christopher Menzel, Michael J. Meyer, Christian B. Miller, David W. Miller, Peter Millican, Robert N. Minor, Phillip Mitsis, James A. Montmarquet, Michael S. Moore, Tim Moore, Benjamin Morison, Donald R. Morrison, Stephen J. Morse, Paul K. Moser, Alexander P. D. Mourelatos, Ian Mueller, James Bernard Murphy, Mark C. Murphy, Steven Nadler, Jan Narveson, Alan Nelson, Jerome Neu, Samuel Newlands, Kai Nielsen, Ilkka Niiniluoto, Carlos G. Noreña, Calvin G. Normore, David Fate Norton, Nikolaj Nottelmann, Donald Nute, David S. Oderberg, Steve Odin, Michael O’Rourke, Willard G. Oxtoby, Heinz Paetzold, George S. Pappas, Anthony J. Parel, Lydia Patton, R. P. Peerenboom, Francis Jeffry Pelletier, Adriaan T. Peperzak, Derk Pereboom, Jaroslav Peregrin, Glen Pettigrove, Philip Pettit, Edmund L. Pincoffs, Andrew Pinsent, Robert B. Pippin, Alvin Plantinga, Louis P. Pojman, Richard H. Popkin, John F. Post, Carl J. Posy, William J. Prior, Richard Purtill, Michael Quante, Philip L. Quinn, Philip L. Quinn, Elizabeth S. Radcliffe, Diana Raffman, Gerard Raulet, Stephen L. Read, Andrews Reath, Andrew Reisner, Nicholas Rescher, Henry S. Richardson, Robert C. Richardson, Thomas Ricketts, Wayne D. Riggs, Mark Roberts, Robert C. Roberts, Luke Robinson, Alexander Rosenberg, Gary Rosenkranz, Bernice Glatzer Rosenthal, Adina L. Roskies, William L. Rowe, T. M. Rudavsky, Michael Ruse, Bruce Russell, Lilly-Marlene Russow, Dan Ryder, R. M. Sainsbury, Joseph Salerno, Nathan Salmon, Wesley C. Salmon, Constantine Sandis, David H. Sanford, Marco Santambrogio, David Sapire, Ruth A. Saunders, Geoffrey Sayre-McCord, Charles Sayward, James P. Scanlan, Richard Schacht, Tamar Schapiro, Frederick F. Schmitt, Jerome B. Schneewind, Calvin O. Schrag, Alan D. Schrift, George F. Schumm, Jean-Loup Seban, David N. Sedley, Kenneth Seeskin, Krister Segerberg, Charlene Haddock Seigfried, Dennis M. Senchuk, James F. Sennett, William Lad Sessions, Stewart Shapiro, Tommie Shelby, Donald W. Sherburne, Christopher Shields, Roger A. Shiner, Sydney Shoemaker, Robert K. Shope, Kwong-loi Shun, Wilfried Sieg, A. John Simmons, Robert L. Simon, Marcus G. Singer, Georgette Sinkler, Walter Sinnott-Armstrong, Matti T. Sintonen, Lawrence Sklar, Brian Skyrms, Robert C. Sleigh, Michael Anthony Slote, Hans Sluga, Barry Smith, Michael Smith, Robin Smith, Robert Sokolowski, Robert C. Solomon, Marta Soniewicka, Philip Soper, Ernest Sosa, Nicholas Southwood, Paul Vincent Spade, T. L. S. Sprigge, Eric O. Springsted, George J. Stack, Rebecca Stangl, Jason Stanley, Florian Steinberger, Sören Stenlund, Christopher Stephens, James P. Sterba, Josef Stern, Matthias Steup, M. A. Stewart, Leopold Stubenberg, Edith Dudley Sulla, Frederick Suppe, Jere Paul Surber, David George Sussman, Sigrún Svavarsdóttir, Zeno G. Swijtink, Richard Swinburne, Charles C. Taliaferro, Robert B. Talisse, John Tasioulas, Paul Teller, Larry S. Temkin, Mark Textor, H. S. Thayer, Peter Thielke, Alan Thomas, Amie L. Thomasson, Katherine Thomson-Jones, Joshua C. Thurow, Vzalerie Tiberius, Terrence N. Tice, Paul Tidman, Mark C. Timmons, William Tolhurst, James E. Tomberlin, Rosemarie Tong, Lawrence Torcello, Kelly Trogdon, J. D. Trout, Robert E. Tully, Raimo Tuomela, John Turri, Martin M. Tweedale, Thomas Uebel, Jennifer Uleman, James Van Cleve, Harry van der Linden, Peter van Inwagen, Bryan W. Van Norden, René van Woudenberg, Donald Phillip Verene, Samantha Vice, Thomas Vinci, Donald Wayne Viney, Barbara Von Eckardt, Peter B. M. Vranas, Steven J. Wagner, William J. Wainwright, Paul E. Walker, Robert E. Wall, Craig Walton, Douglas Walton, Eric Watkins, Richard A. Watson, Michael V. Wedin, Rudolph H. Weingartner, Paul Weirich, Paul J. Weithman, Carl Wellman, Howard Wettstein, Samuel C. Wheeler, Stephen A. White, Jennifer Whiting, Edward R. Wierenga, Michael Williams, Fred Wilson, W. Kent Wilson, Kenneth P. Winkler, John F. Wippel, Jan Woleński, Allan B. Wolter, Nicholas P. Wolterstorff, Rega Wood, W. Jay Wood, Paul Woodruff, Alison Wylie, Gideon Yaffe, Takashi Yagisawa, Yutaka Yamamoto, Keith E. Yandell, Xiaomei Yang, Dean Zimmerman, Günter Zoller, Catherine Zuckert, Michael Zuckert, Jack A. Zupko (J.A.Z.)
- Edited by Robert Audi, University of Notre Dame, Indiana
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- The Cambridge Dictionary of Philosophy
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- 05 August 2015
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- 27 April 2015, pp ix-xxx
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Linear estimation of flux sensitivity to uncertainty in porous media
- A. J. Evans, C. P. Caulfield, Andrew W. Woods
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- Journal of Fluid Mechanics / Volume 768 / 10 April 2015
- Published online by Cambridge University Press:
- 11 March 2015, pp. 600-622
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We derive an integral expression for the flux of a single-phase fluid through a porous medium with prescribed boundary conditions. Taking variations with respect to the parameters of a given permeability model yields an integral expression for the sensitivity of the flux. We then extend the method to consider linear changes in permeability. This yields a linearised flux expression which is independent of changes in the pressure field that result from the changes in the permeability. For demonstration purposes, we first consider an idealised layered porous medium with a point source and point sink. We show how the effects of changes in permeability are affected by the position of the source and sink relative to the layered structure as well as the layer height and orientation of the layered structure. The results demonstrate that, even in a simple porous system, flux estimates are sensitive to the way in which the permeability is represented. We derive relationships between the statistical moments of the flux and of the permeability parameters which are modelled as random variables. This allows us to estimate the number of permeability parameters that should be varied in a fully nonlinear calculation to determine the variance of the flux. We demonstrate application of the methods to permeability fields generated through fast Fourier transform and kriging methods. We show that the linear estimates for the variability in flux show good agreement with fully nonlinear calculations for sufficiently small standard deviations in the underlying permeability.