1,521 research outputs found

    Reach-scale bankfull channel types can exist independently of catchment hydrology

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    © 2020 John Wiley & Sons, Ltd. Reach-scale morphological channel classifications are underpinned by the theory that each channel type is related to an assemblage of reach- and catchment-scale hydrologic, topographic, and sediment supply drivers. However, the relative importance of each driver on reach morphology is unclear, as is the possibility that different driver assemblages yield the same reach morphology. Reach-scale classifications have never needed to be predicated on hydrology, yet hydrology controls discharge and thus sediment transport capacity. The scientific question is: do two or more regions with quantifiable differences in hydrologic setting end up with different reach-scale channel types, or do channel types transcend hydrologic setting because hydrologic setting is not a dominant control at the reach scale? This study answered this question by isolating hydrologic metrics as potential dominant controls of channel type. Three steps were applied in a large test basin with diverse hydrologic settings (Sacramento River, California) to: (1) create a reach-scale channel classification based on local site surveys, (2) categorize sites by flood magnitude, dimensionless flood magnitude, and annual hydrologic regime type, and (3) statistically analyze two hydrogeomorphic linkages. Statistical tests assessed the spatial distribution of channel types and the dependence of channel type morphological attributes by hydrologic setting. Results yielded 10 channel types. Nearly all types existed across all hydrologic settings, which is perhaps a surprising development for hydrogeomorphology. Downstream hydraulic geometry relationships were statistically significant. In addition, cobble-dominated uniform streams showed a consistent inverse relationship between slope and dimensionless flood magnitude, an indication of dynamic equilibrium between transport capacity and sediment supply. However, most morphological attributes showed no sorting by hydrologic setting. This study suggests that median hydraulic geometry relations persist across basins and within channel types, but hydrologic influence on geomorphic variability is likely due to local influences rather than catchment-scale drivers. © 2020 John Wiley & Sons, Ltd

    Jay Forrester

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    Jay Wright Forrester was an American engineer and management thinker. He founded System Dynamics, an approach based on computer modelling which arguably has done more than any other method to provide a practical and realistic analysis of change processes in systems. System Dynamics (SD) has been taken up across the world, initially by Forrester’s students and colleagues, but increasingly by a much wider community. It has had profound and influential applications in a range of fields, most prominently organisational management, urban planning and environmental policy. Forrester summed up his concerns and his understanding of SD in an ‘elevator pitch’ (a statement short enough to be spoken in an elevator ride) on an email list: System dynamics deals with how things change through time, which includes most of what most people find important. It uses computer simulation to take the knowledge we already have about details in the world around us and to show why our social and physical systems behave the way they do. System dynamics demonstrates how most of our own decision-making policies are the cause of the problems that we usually blame on others, and how to identify policies we can follow to improve our situation. (Forrester JW. System dynamics in the elevator. System-dynamics email list. https://www.ventanasystems.co.uk/forum/viewtopic.php?t=1787#p1964. Accessed 25 Sept 2019, 1997

    Physics Opportunities of e+e- Linear Colliders

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    We describe the anticipated experimental program of an e+e- linear collider in the energy range 500 GeV -- 1.5 TeV. We begin with a description of current collider designs and the expected experimental environment. We then discuss precision studies of the W boson and top quark. Finally, we review the range of models proposed to explain the physics of electroweak symmetry breaking and show, for each case, the central role that the linear collider experiments will play in elucidating this physics. (to appear in Annual Reviews of Nuclear and Particle Science)Comment: 93 pages, latex + 23 figures; typos corrections + 1 reference adde

    Accelerated in vivo proliferation of memory phenotype CD4+ T-cells in human HIV-1 infection irrespective of viral chemokine co-receptor tropism.

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    CD4(+) T-cell loss is the hallmark of HIV-1 infection. CD4 counts fall more rapidly in advanced disease when CCR5-tropic viral strains tend to be replaced by X4-tropic viruses. We hypothesized: (i) that the early dominance of CCR5-tropic viruses results from faster turnover rates of CCR5(+) cells, and (ii) that X4-tropic strains exert greater pathogenicity by preferentially increasing turnover rates within the CXCR4(+) compartment. To test these hypotheses we measured in vivo turnover rates of CD4(+) T-cell subpopulations sorted by chemokine receptor expression, using in vivo deuterium-glucose labeling. Deuterium enrichment was modeled to derive in vivo proliferation (p) and disappearance (d*) rates which were related to viral tropism data. 13 healthy controls and 13 treatment-naive HIV-1-infected subjects (CD4 143-569 cells/ul) participated. CCR5-expression defined a CD4(+) subpopulation of predominantly CD45R0(+) memory cells with accelerated in vivo proliferation (p = 2.50 vs 1.60%/d, CCR5(+) vs CCR5(-); healthy controls; P<0.01). Conversely, CXCR4 expression defined CD4(+) T-cells (predominantly CD45RA(+) naive cells) with low turnover rates. The dominant effect of HIV infection was accelerated turnover of CCR5(+)CD45R0(+)CD4(+) memory T-cells (p = 5.16 vs 2.50%/d, HIV vs controls; P<0.05), naïve cells being relatively unaffected. Similar patterns were observed whether the dominant circulating HIV-1 strain was R5-tropic (n = 9) or X4-tropic (n = 4). Although numbers were small, X4-tropic viruses did not appear to specifically drive turnover of CXCR4-expressing cells (p = 0.54 vs 0.72 vs 0.44%/d in control, R5-tropic, and X4-tropic groups respectively). Our data are most consistent with models in which CD4(+) T-cell loss is primarily driven by non-specific immune activation

    Hippocampal subfield volumes and pre-clinical Alzheimer's disease in 408 cognitively normal adults born in 1946

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    BACKGROUND: The human hippocampus comprises a number of interconnected histologically and functionally distinct subfields, which may be differentially influenced by cerebral pathology. Automated techniques are now available that estimate hippocampal subfield volumes using in vivo structural MRI data. To date, research investigating the influence of cerebral β-amyloid deposition-one of the earliest hypothesised changes in the pathophysiological continuum of Alzheimer's disease-on hippocampal subfield volumes in cognitively normal older individuals, has been limited. METHODS: Using cross-sectional data from 408 cognitively normal individuals born in mainland Britain (age range at time of assessment = 69.2-71.9 years) who underwent cognitive assessment, 18F-Florbetapir PET and structural MRI on the same 3 Tesla PET/MR unit (spatial resolution 1.1 x 1.1 x 1.1. mm), we investigated the influences of β-amyloid status, age at scan, and global white matter hyperintensity volume on: CA1, CA2/3, CA4, dentate gyrus, presubiculum and subiculum volumes, adjusting for sex and total intracranial volume. RESULTS: Compared to β-amyloid negative participants (n = 334), β-amyloid positive participants (n = 74) had lower volume of the presubiculum (3.4% smaller, p = 0.012). Despite an age range at scanning of just 2.7 years, older age at time of scanning was associated with lower CA1 (p = 0.007), CA4 (p = 0.004), dentate gyrus (p = 0.002), and subiculum (p = 0.035) volumes. There was no evidence that white matter hyperintensity volume was associated with any subfield volumes. CONCLUSION: These data provide evidence of differential associations in cognitively normal older adults between hippocampal subfield volumes and β-amyloid deposition and, increasing age at time of scan. The relatively selective effect of lower presubiculum volume in the β-amyloid positive group potentially suggest that the presubiculum may be an area of early and relatively specific volume loss in the pathophysiological continuum of Alzheimer's disease. Future work using higher resolution imaging will be key to exploring these findings further

    Improving Student Engagement in Veterinary Business Studies

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    In a densely packed veterinary curriculum, students may find it particularly challenging to engage in the less overtly clinical subjects, yet pressure from industry and an increasingly competitive employment market necessitate improved veterinary student education in business and management skills. We describe a curriculum intervention (formative reflective assignment) that optimizes workplace learning opportunities and aims to provide better student scaffolding for their in-context business learning. Students were asked to analyze a business practice they experienced during a period of extra-mural studies (external work placement). Following return to the college, they were then instructed to discuss their findings in their study group, and produce a group reflection on their learning. To better understand student engagement in this area, we analyzed individual and group components of the assignment. Thematic analysis revealed evidence of various depths of student engagement, and provided indications of the behaviors they used when engaging at different levels. Interactive and social practices (discussing business strategies with veterinary employees and student peers) appeared to facilitate student engagement, assist the perception of relevance of these skills, and encourage integration with other curriculum elements such as communication skills and clinical problem solving

    Losartan to slow the progression of mild-to-moderate Alzheimer's disease through angiotensin targeting: the RADAR RCT

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    BACKGROUND: Medications that modify the renin–angiotensin system may reduce Alzheimer’s disease pathology and reduce the rate of disease progression. OBJECTIVE: This study investigated whether taking the antihypertensive drug losartan, in addition to normal care, would slow the progression of Alzheimer’s disease when compared with a placebo. DESIGN: A double-blind multicentre randomised controlled trial, after a 4-week open-label phase, with follow-up at 14 days and at 3, 6, 9 and 12 months. The primary outcome was based on measured imaging differences in brain volume between baseline and 12 months. SETTING: Twenty-three NHS hospital trusts across England, Scotland and Northern Ireland. PARTICIPANTS: Patients diagnosed with mild-to-moderate Alzheimer’s disease were eligible to participate if they met the following criteria: (1) aged ≥ 55 years; (2) a Mini Mental State Examination score of 15–28; (3) a modified Hachinski Ischaemic Score of ≤ 5; (4) a previous computerised tomography, single-photon emission computed tomography or magnetic resonance imaging scan consistent with a diagnosis of Alzheimer’s disease; (5) a study companion who was willing to participate in the study; and (6) capacity to consent for themselves. Patients were ineligible if they were (1) taking or intolerant to renin–angiotensin system-related medications, (2) unlikely to undergo magnetic resonance imaging or (3) unlikely to complete the trial protocol. People who had blood pressure outside the normal ranges, defined cardiovascular issues, impaired liver or renal function, or a primary neurodegenerative disease that was not Alzheimer’s disease were also excluded, as were women who had not reached menopause and were unwilling to take relevant protocol-specific safety precautions. INTERVENTION: The intervention was either 100 mg of overencapsulated losartan (Teva Pharmaceuticals Industries Ltd, Petah Tikva, Israel) daily or a matched placebo for 12 months. MAIN OUTCOMES AND MEASURES: Difference in brain atrophy, represented by measurement of whole-brain volume before and following 12 months of treatment post randomisation, was measured using volumetric MRI and determined by boundary shift interval analysis. Secondary outcomes included changes in rates of Alzheimer’s disease progression (as assessed using the ADAS-Cog, Mini Mental State Examination and Neuropsychiatric Inventory), the volume of white matter hyperintensities, cerebral blood flow (assessed by magnetic resonance imaging), blood pressure, magnetic resonance imaging measures of atrophy and association with measures of cognitive decline, and drug compliance and tolerability. RESULTS: A total of 261 participants entered the open-label phase, of whom 211 were randomised to the intervention (n = 105) or placebo (n = 106) arms. Of the 197 people (93%) who completed the study, 81% (n = 171) had a valid primary outcome. The difference in brain volume between arms was consistent with chance (–2.79 ml, 95% confidence interval –6.46 to 0.89 ml; p = 0.19), and there was no evidence of benefit for any of the secondary outcome measures. LIMITATIONS: Our study had 82% power to detect treatment-based changes and, as a result, may have been underpowered or, more likely, the intervention, which may not have crossed the blood–brain barrier as much as expected, may have been given too late or for an insufficient amount of time in the disease process to influence the outcomes. CONCLUSIONS: Losartan administered over 12 months did not alter brain atrophy in Alzheimer’s disease. FUTURE WORK: Other related ‘sartans’ could be tested in patient groups with mild cognitive impairment and for longer to fully test this hypothesis. TRIAL REGISTRATION: Current Controlled Trials ISRCTN93682878 and EudraCT 2012-003641-15. FUNDING: This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 19. See the NIHR Journals Library website for further project information

    Ovine pedomics : the first study of the ovine foot 16S rRNA-based microbiome

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    We report the first study of the bacterial microbiome of ovine interdigital skin based on 16S rRNA by pyrosequencing and conventional cloning with Sanger-sequencing. Three flocks were selected, one a flock with no signs of footrot or interdigital dermatitis, a second flock with interdigital dermatitis alone and a third flock with both interdigital dermatitis and footrot. The sheep were classified as having either healthy interdigital skin (H), interdigital dermatitis (ID) or virulent footrot (VFR). The ovine interdigital skin bacterial community varied significantly by flock and clinical condition. The diversity and richness of operational taxonomic units was greater in tissue from sheep with ID than H or VFR affected sheep. Actinobacteria, Bacteriodetes, Firmicutes and Proteobacteria were the most abundant phyla comprising 25 genera. Peptostreptococcus, Corynebacterium and Staphylococcus were associated with H, ID and VFR respectively. Sequences of Dichelobacter nodosus, the causal agent of ovine footrot, were not amplified due to mismatches in the 16S rRNA universal forward primer (27F). A specific real time PCR assay was used to demonstrate the presence of D. nodosus which was detected in all samples including the flock with no signs of ID or VFR. Sheep with ID had significantly higher numbers of D. nodosus (104-109 cells/g tissue) than those with H or VFR feet
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