190 results on '"Wickham, H."'
Search Results
152. Using dissolved organic matter fluorescence to identify the provenance of nutrients in a lowland catchment; the River Thames, England.
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Old GH, Naden PS, Harman M, Bowes MJ, Roberts C, Scarlett PM, Nicholls DJE, Armstrong LK, Wickham HD, and Read DS
- Abstract
Catchment based solutions are being sought to mitigate water quality pressures and achieve multiple benefits but their success depends on a sound understanding of catchment functioning. Novel approaches to monitoring and data analysis are urgently needed. In this paper we explore the potential of river water fluorescence at the catchment scale in understanding nutrient concentrations, sources and pathways. Data were collected from across the River Thames basin from January 2012 to March 2015. Analysing emission excitation matrices (EEMs) using both PARAFAC and optimal area averaging produced consistent results for humic-like component 1 and tryptophan-like component 4 in the absence of a subset of samples that exhibited an unusual peak; illustrating the importance of inspecting the entire EEM before using peak averaging methods. Strong relationships between fluorescence components and dissolved organic carbon (DOC), soluble reactive phosphorus (SRP), and ammonium clearly demonstrated its potential, in this study basin, as a field based surrogate for nutrients. Analysing relationships between fluorescence, catchment characteristics and boron from across the basin enabled new insights into the provenance of nutrients. These include evidence for diffuse sources of DOC from near surface hydrological pathways (i.e. soil horizons); point source inputs of nutrients from sewage effluent discharges; and diffuse contributions of nutrients from agriculture and/or sewage (e.g. septic tanks). The information gained by broad scale catchment wide monitoring of fluorescence could support catchment managers in (a) prioritising subcatchments for nutrient mitigation; (b) providing information on relative nutrient source contributions; and (c) providing evidence of the effectiveness of investment in pollution mitigation measures. The collection of high resolution fluorescence data at the catchment scale and, in particular, over shorter event timescales would complement broad scale assessments by enhancing our hydro-biogeochemical process understanding., (Copyright © 2018. Published by Elsevier B.V.)
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- 2019
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153. FGF23 Induction of O-Linked N-Acetylglucosamine Regulates IL-6 Secretion in Human Bronchial Epithelial Cells.
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Krick S, Helton ES, Hutcheson SB, Blumhof S, Garth JM, Denson RS, Zaharias RS, Wickham H, and Barnes JW
- Abstract
The hexosamine biosynthetic pathway (HBP) generates the substrate for the O-linked β-N-acetylglucosamine (O-GlcNAc) modification of proteins. The HBP also serves as a stress sensor and has been reported to be involved with nuclear factor of activated T-cells (NFAT) activation, which can contribute to multiple cellular processes including cell metabolism, proliferation, and inflammation. In our previously published report, Fibroblast Growth Factor (FGF) 23, an important endocrine pro-inflammatory mediator, was shown to activate the FGFR4/phospholipase Cγ (PLCγ)/nuclear factor of activated T-cells (NFAT) signaling in chronic inflammatory airway diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). Here, we demonstrate that FGF23 increased the O-GlcNAc modification of proteins in HBECs. Furthermore, the increase in O-GlcNAc levels by FGF23 stimulation resulted in the downstream activation of NFAT and secretion of interleukin-6 (IL-6). Conversely, inhibition of FGF23 signaling and/or O-GlcNAc transferase (OGT)/O-GlcNAc reversed these effects. Collectively, these data suggest that FGF23 induced IL-6 upregulation and secretion is, at least, partially mediated via the activation of the HBP and O-GlcNAc levels in HBECs. These findings identify a novel link whereby FGF23 and the augmentation of O-GlcNAc levels regulate airway inflammation through NFAT activation and IL-6 upregulation in HBECs. The crosstalk between these signaling pathways may contribute to the pathogenesis of chronic inflammatory airway diseases such as COPD and CF as well as metabolic syndromes, including diabetes.
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- 2018
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154. Characterisation of a major phytoplankton bloom in the River Thames (UK) using flow cytometry and high performance liquid chromatography.
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Moorhouse HL, Read DS, McGowan S, Wagner M, Roberts C, Armstrong LK, Nicholls DJE, Wickham HD, Hutchins MG, and Bowes MJ
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- Chlorophyll analysis, Chlorophyll A, Chromatography, High Pressure Liquid, Flow Cytometry, United Kingdom, Environmental Monitoring, Eutrophication, Phytoplankton growth & development, Rivers
- Abstract
Recent river studies have observed rapid phytoplankton dynamics, driven by diurnal cycling and short-term responses to storm events, highlighting the need to adopt new high-frequency characterisation methods to understand these complex ecological systems. This study utilised two such analytical methods; pigment analysis by high performance liquid chromatography (HPLC) and cell counting by flow cytometry (FCM), alongside traditional chlorophyll spectrophotometry and light microscopy screening, to characterise the major phytoplankton bloom of 2015 in the River Thames, UK. All analytical techniques observed a rapid increase in chlorophyll a concentration and cell abundances from March to early June, caused primarily by a diatom bloom. Light microscopy identified a shift from pennate to centric diatoms during this period. The initial diatom bloom coincided with increased HPLC peridinin concentrations, indicating the presence of dinoflagellates which were likely to be consuming the diatom population. The diatom bloom declined rapidly in early June, coinciding with a storm event. There were low chlorophyll a concentrations (by both HPLC and spectrophotometric methods) throughout July and August, implying low biomass and phytoplankton activity. However, FCM revealed high abundances of pico-chlorophytes and cyanobacteria through July and August, showing that phytoplankton communities remain active and abundant throughout the summer period. In combination, these techniques are able to simultaneously characterise a wider range of phytoplankton groups, with greater certainty, and provide improved understanding of phytoplankton functioning (e.g. production of UV inhibiting pigments by cyanobacteria in response to high light levels) and ecological status (through examination of pigment degradation products). Combined HPLC and FCM analyses offer rapid and cost-effective characterisation of phytoplankton communities at appropriate timescales. This will allow a more-targeted use of light microscopy to capture phytoplankton peaks or to investigate periods of rapid community succession. This will lead to greater system understanding of phytoplankton succession in response to biogeochemical drivers., (Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.)
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- 2018
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155. Identifying multiple stressor controls on phytoplankton dynamics in the River Thames (UK) using high-frequency water quality data.
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Bowes MJ, Loewenthal M, Read DS, Hutchins MG, Prudhomme C, Armstrong LK, Harman SA, Wickham HD, Gozzard E, and Carvalho L
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- Chlorophyll analysis, England, Environmental Monitoring, Seasons, Stress, Physiological, Temperature, Water Movements, Eutrophication, Phytoplankton growth & development, Rivers chemistry, Water Quality
- Abstract
River phytoplankton blooms can pose a serious risk to water quality and the structure and function of aquatic ecosystems. Developing a greater understanding of the physical and chemical controls on the timing, magnitude and duration of blooms is essential for the effective management of phytoplankton development. Five years of weekly water quality monitoring data along the River Thames, southern England were combined with hourly chlorophyll concentration (a proxy for phytoplankton biomass), flow, temperature and daily sunlight data from the mid-Thames. Weekly chlorophyll data was of insufficient temporal resolution to identify the causes of short term variations in phytoplankton biomass. However, hourly chlorophyll data enabled identification of thresholds in water temperature (between 9 and 19°C) and flow (<30m(3)s(-1)) that explained the development of phytoplankton populations. Analysis showed that periods of high phytoplankton biomass and growth rate only occurred when these flow and temperature conditions were within these thresholds, and coincided with periods of long sunshine duration, indicating multiple stressor controls. Nutrient concentrations appeared to have no impact on the timing or magnitude of phytoplankton bloom development, but severe depletion of dissolved phosphorus and silicon during periods of high phytoplankton biomass may have contributed to some bloom collapses through nutrient limitation. This study indicates that for nutrient enriched rivers such as the Thames, manipulating residence time (through removing impoundments) and light/temperature (by increasing riparian tree shading) may offer more realistic solutions than reducing phosphorus concentrations for controlling excessive phytoplankton biomass., (Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.)
- Published
- 2016
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156. Practical management of chronic breathlessness.
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Wickham H, Spathis A, Chin C, Ryan R, and Booth S
- Abstract
Competing Interests: Competing interests: RR is funded by a National Institute for Health Research doctoral research fellowship award. The views expressed are those of the authors and not necessarily those of the NHS, National Institute for Health Research, or the Department of Health.
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- 2016
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157. Design, evaluation, and dissemination of a plastic syringe clip to improve dosing accuracy of liquid medications.
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Spiegel GJ, Dinh C, Gutierrez A, Lukomnik J, Lu B, Shah K, Slough T, Yeh PT, Mirabal Y, Gray LV, Marton S, Adler M, Schutze GE, Wickham H, Oden M, and Richards-Kortum R
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- Administration, Oral, Adult, Equipment Design methods, Female, Humans, Male, Syringes trends, Antidiarrheals administration & dosage, Bismuth administration & dosage, Organometallic Compounds administration & dosage, Salicylates administration & dosage, Syringes standards
- Abstract
Pediatricians in Africa requested a tool to improve caregiver dosing of liquid antiretroviral medication. We developed, evaluated and disseminated a clip to control the amount of medication drawn into an oral syringe. In a laboratory, a user tested clips of different lengths, corresponding to different volumes, by drawing water into a syringe with a clip. In Texas and Malawi, 149 adults attempted to measure Pepto-Bismol™ using a syringe with a clip, a syringe without a clip, and a dosing cup, in a randomly assigned order. In the laboratory, the volume of liquid, ranging from 1 to 4.5 mL, drawn into the syringe was always within at least 5 μL of the intended dose. In Texas, 84% of doses were accurate within ±10%, vs. 63% using the syringe alone, and 21% with the dosing cup. In Malawi, 98% of doses were accurate to within ±10%, vs. 90% using the syringe alone, and 27% with the dosing cup. For target accuracy values within ±45% (±21%), a significantly higher fraction of Houston (Kamangira) participants delivered an accurate dose using the syringe with the clip than with the syringe alone (p < 0.05). The clip enables a greater proportion of users to accurately measure liquid medication.
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- 2013
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158. Gradient-based habitat affinities predict species vulnerability to drought.
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Debinski DM, Caruthers JC, Cook D, Crowley J, and Wickham H
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- Animals, Demography, Species Specificity, Time, Time Factors, Butterflies classification, Droughts, Ecosystem
- Abstract
Ecological fingerprints of climate change are becoming increasingly evident at broad geographical scales as measured by species range shifts and changes in phenology. However, finer-scale species-level responses to environmental fluctuations may also provide an important bellwether of impending future community responses. Here we examined changes in abundance of butterfly species along a hydrological gradient of six montane meadow habitat types in response to drought. Our data collection began prior to the drought, and we were able to track changes for 11 years, of which eight were considered mild to extreme drought conditions. We separated the species into those that had an affinity for hydric vs. xeric habitats. We suspected that drought would favor species with xeric habitat affinities, but that there could be variations in species-level responses along the hydrological gradient. We also suspected that mesic meadows would be most sensitive to drought conditions. Temporal trajectories were modeled for both species groups (hydric vs. xeric affinity) and individual species. Abundances of species with affinity for xeric habitats increased in virtually all meadow types. Conversely, abundances of species with affinity for hydric habitats decreased, particularly in mesic and xeric meadows. Mesic meadows showed the most striking temporal abundance trajectory: Increasing abundances of species with xeric habitat affinity were offset by decreasing or stable abundances of species with hydric habitat affinity. The one counterintuitive finding was that, in some hydric meadows, species with affinity for hydric habitats increased. In these cases, we suspect that decreasing moisture conditions in hydric meadows actually increased habitat suitability because sites near the limit of moisture extremes for some species became more acceptable. Thus, species responses were relatively predictable based upon habitat affinity and habitat location along the hydrological gradient, and mesic meadows showed the highest potential for changes in community composition. The implications of these results are that longer-term changes due to drought could simplify community composition, resulting in prevalence of species tolerant to drying conditions and a loss of species associated with wetter conditions. We contend that this application of gradient analysis could be valuable in assessing species vulnerability of other taxa and ecosystems.
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- 2013
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159. High-frequency water quality time series in precipitation and streamflow: from fragmentary signals to scientific challenge.
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Neal C, Reynolds B, Rowland P, Norris D, Kirchner JW, Neal M, Sleep D, Lawlor A, Woods C, Thacker S, Guyatt H, Vincent C, Hockenhull K, Wickham H, Harman S, and Armstrong L
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- Environmental Monitoring, Quality Control, Rain, Water Movements, Water Quality
- Abstract
Eighteen months of 7-hourly analyses of rainfall and stream water chemistry are presented, spanning a wide range of chemical determinands and building on over 20 years of weekly records for the moorland headwaters of the river Severn. The high-frequency time series data show that hydrochemical responses to major hydrological and biological drivers of short-term variability in rainfall and rivers are not captured by conventional low-frequency monitoring programmes. A wealth of flow related, flow independent, diurnal, seasonal and annual fluctuations indicate a cacophony of interactions within the catchment and stream. The complexity of the chemical dynamics is visually obvious, although there appears to be no clear way of translating this complexity into a simple algorithm. The work provides a proof of concept for the complex structure of catchment functioning revealed by extensive high-frequency measurements coupled with high analytical sensitivity and reproducibility. It provides new insights into hydrogeochemical functioning and a novel resource for catchment modelling., (Copyright © 2011 Elsevier B.V. All rights reserved.)
- Published
- 2012
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160. Nutrient and light limitation of periphyton in the River Thames: implications for catchment management.
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Bowes MJ, Ings NL, McCall SJ, Warwick A, Barrett C, Wickham HD, Harman SA, Armstrong LK, Scarlett PM, Roberts C, Lehmann K, and Singer AC
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- Biomass, England, Phosphorus analysis, Sewage, Water chemistry, Light
- Abstract
Soluble reactive phosphorus (SRP) concentrations in the River Thames, south east England, have significantly decreased from an annual maximum of 2100 μg l(-1) in 1997 to 344 in 2010, primarily due to the introduction of phosphorus (P) removal at sewage treatment works within the catchment. However, despite this improvement in water quality, phytoplankton biomass in the River Thames has greatly increased in recent years, with peak chlorophyll concentrations increasing from 87 μg l(-1) in the period 1997 to 2002, to 328 μg l(-1) in 2009. A series of within-river flume mesocosm experiments were performed to determine the effect of changing nutrient concentrations and light levels on periphyton biomass accrual. Nutrient enrichment experiments showed that phosphorus, nitrogen and silicon were not limiting or co-limiting periphyton growth in the Thames at the time of the experiment (August-September 2010). Decreasing ambient SRP concentration from 225 μg l(-1) to 173 μg l(-1) had no effect on periphyton biomass accrual rate or diatom assemblage. Phosphorus limitation became apparent at 83 μg SRP l(-1), at which point a 25% reduction in periphyton biomass was observed. Diatom assemblage significantly changed when the SRP concentration was reduced to 30 μg l(-1). Such stringent phosphorus targets are costly and difficult to achieve for the River Thames, due to the high population density and intensive agriculture within the Thames basin. Reducing light levels by shading reduced the periphyton accrual rate by 50%. Providing shading along the River Thames by planting riparian tree cover could be an effective measure to reduce the risk of excessive algal growth. If the ecology of the Thames is to reach the WFD's "good ecological status", then both SRP concentration reductions (probably to below 100 μg l(-1)) and increased shading will be required., (Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.)
- Published
- 2012
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161. Spatial and temporal changes in chlorophyll-a concentrations in the River Thames basin, UK: are phosphorus concentrations beginning to limit phytoplankton biomass?
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Bowes MJ, Gozzard E, Johnson AC, Scarlett PM, Roberts C, Read DS, Armstrong LK, Harman SA, and Wickham HD
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- Biomass, England, Environmental Monitoring, Eutrophication, Microalgae growth & development, Nitrogen analysis, Phytoplankton growth & development, Water Pollution, Chemical statistics & numerical data, Chlorophyll analysis, Phosphorus analysis, Rivers chemistry, Water Pollutants, Chemical analysis
- Abstract
Chlorophyll-a and nutrient concentrations were monitored at weekly intervals across 21 river sites throughout the River Thames basin, southern England, between 2009 and 2011. Despite a 90% decrease in soluble reactive phosphorus (SRP) concentration of the lower River Thames since the 1990s, very large phytoplankton blooms still occur. Chlorophyll concentrations were highest in the mid and lower River Thames and the larger tributaries. Lowest chlorophyll concentrations were observed in the smaller tributaries, despite some having very high phosphorus concentrations of over 300 μg l(-1). There was a strong positive correlation between river length and mean chlorophyll concentration (R(2)=0.82), and rivers connected to canals had ca. six times greater chlorophyll concentration than 'natural' rivers with similar phosphorus concentrations, indicating the importance that residence time has on determining phytoplankton biomass. Phosphorus concentration did have some influence, with phosphorus-enriched rivers having much larger phytoplankton blooms than nutrient-poor rivers of a similar length. Water quality improvements may now be capping chlorophyll peaks in the Rivers Thames and Kennet, due to SRP depletion during the spring/early summer phytoplankton bloom period. Dissolved reactive silicon was also depleted to potentially-limiting concentrations for diatom growth in the River Thames during these phytoplankton blooms, but nitrate remained in excess for all rivers throughout the study period. Other potential mitigation measures, such as increasing riparian shading and reducing residence times by removing impoundments may be needed, alongside phosphorus mitigation, to reduce the magnitude of phytoplankton blooms in the future., (Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.)
- Published
- 2012
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162. Changes in water quality of the River Frome (UK) from 1965 to 2009: is phosphorus mitigation finally working?
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Bowes MJ, Smith JT, Neal C, Leach DV, Scarlett PM, Wickham HD, Harman SA, Armstrong LK, Davy-Bowker J, Haft M, and Davies CE
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- Calcium analysis, Carbon Dioxide analysis, Environmental Monitoring, Environmental Policy, Hydrogen-Ion Concentration, Magnesium analysis, Nitrogen analysis, Potassium analysis, Seasons, Silicon analysis, Sodium analysis, United Kingdom, Water Pollution, Chemical prevention & control, Phosphorus analysis, Rivers chemistry, Water Pollutants, Chemical analysis, Water Pollution, Chemical statistics & numerical data
- Abstract
The water quality of the River Frome, Dorset, southern England, was monitored at weekly intervals from 1965 until 2009. Determinands included phosphorus, nitrogen, silicon, potassium, calcium, sodium, magnesium, pH, alkalinity and temperature. Nitrate-N concentrations increased from an annual average of 2.4 mg l⁻¹ in the mid to late 1960s to 6.0 mg l⁻¹ in 2008-2009, but the rate of increase was beginning to slow. Annual soluble reactive phosphorus (SRP) concentrations increased from 101 μg l⁻¹ in the mid 1960s to a maximum of 190 μg l⁻¹ in 1989. In 2002, there was a step reduction in SRP concentration (average=88 μg l⁻¹ in 2002-2005), with further improvement in 2007-2009 (average=49 μg l⁻¹), due to the introduction of phosphorus stripping at sewage treatment works. Phosphorus and nitrate concentrations showed clear annual cycles, related to the timing of inputs from the catchment, and within-stream bioaccumulation and release. Annual depressions in silicon concentration each spring (due to diatom proliferation) reached a maximum between 1980 and 1991, (the period of maximum SRP concentration) indicating that algal biomass had increased within the river. The timing of these silicon depressions was closely related to temperature. Excess carbon dioxide partial pressures (EpCO₂) of 60 times atmospheric CO₂ were also observed through the winter periods from 1980 to 1992, when phosphorus concentration was greatest, indicating very high respiration rates due to microbial decomposition of this enhanced biomass. Declining phosphorus concentrations since 2002 reduced productivity and algal biomass in the summer, and EpCO₂ through the winter, indicating that sewage treatment improvements had improved riverine ecology. Algal blooms were limited by phosphorus, rather than silicon concentration. The value of long-term water quality data sets is discussed. The data from this monitoring programme are made freely available to the wider science community through the CEH data portal (http://gateway.ceh.ac.uk/)., (Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.)
- Published
- 2011
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163. Graphical inference for Infovis.
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Wickham H, Cook D, Hofmann H, and Buja A
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- Data Interpretation, Statistical, Databases, Factual, Humans, Models, Statistical, Neoplasms mortality, Computer Graphics
- Abstract
How do we know if what we see is really there? When visualizing data, how do we avoid falling into the trap of apophenia where we see patterns in random noise? Traditionally, infovis has been concerned with discovering new relationships, and statistics with preventing spurious relationships from being reported. We pull these opposing poles closer with two new techniques for rigorous statistical inference of visual discoveries. The "Rorschach" helps the analyst calibrate their understanding of uncertainty and "line-up" provides a protocol for assessing the significance of visual discoveries, protecting against the discovery of spurious structure.
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- 2010
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164. Montane meadow change during drought varies with background hydrologic regime and plant functional group.
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Debinski DM, Wickham H, Kindscher K, Caruthers JC, and Germino M
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- Montana, Time Factors, Water metabolism, Wyoming, Droughts, Ecosystem, Plants classification, Plants metabolism
- Abstract
Climate change models for many ecosystems predict more extreme climatic events in the future, including exacerbated drought conditions. Here we assess the effects of drought by quantifying temporal variation in community composition of a complex montane meadow landscape characterized by a hydrological gradient. The meadows occur in two regions of the Greater Yellowstone Ecosystem (Gallatin and Teton) and were classified into six categories (M1-M6, designating hydric to xeric) based upon Satellite pour l'Observation de la Terre (SPOT) satellite imagery. Both regions have similar plant communities, but patch sizes of meadows are much smaller in the Gallatin region. We measured changes in the percent cover of bare ground and plants by species and functional groups during five years between 1997 and 2007. We hypothesized that drought effects would not be manifested evenly across the hydrological gradient, but rather would be observed as hotspots of change in some areas and minimally evident in others. We also expected varying responses by plant functional groups (forbs vs. woody plants). Forbs, which typically use water from relatively shallow s,oils compared to woody plants, were expected to decrease in cover in mesic meadows, but increase in hydric meadows. Woody plants, such as Artemisia, were expected to increase, especially in mesic meadows. We identified several important trends in our meadow plant communities during this period of drought: (1) bare ground increased significantly in xeric meadows of both regions (Gallatin M6 and Teton M5) and in mesic (M3) meadows of the Teton, (2) forbs decreased significantly in the mesic and xeric meadows in both regions, (3) forbs increased in hydric (M1) meadows of the Gallatin region, and (4) woody species showed increases in M2 and M5 meadows of the Teton region and in M3 meadows of the Gallatin region. The woody response was dominated by changes in Artemisia spp. and Chrysothamnus viscidiflorus. Thus, our results supported our expectations that community change was not uniform across the landscape, but instead could be predicted based upon functional group responses to the spatial and temporal patterns of water availability, which are largely a function of plant water use and the hydrological gradient.
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- 2010
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165. Decreasing boron concentrations in UK rivers: insights into reductions in detergent formulations since the 1990s and within-catchment storage issues.
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Neal C, Williams RJ, Bowes MJ, Harrass MC, Neal M, Rowland P, Wickham H, Thacker S, Harman S, Vincent C, and Jarvie HP
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- Environmental Monitoring, Seasons, Sewage chemistry, Sodium analysis, United Kingdom, Water Pollution, Chemical statistics & numerical data, Water Supply analysis, Boron analysis, Detergents chemistry, Rivers chemistry, Water Pollutants, Chemical analysis
- Abstract
The changing patterns of riverine boron concentration are examined for the Thames catchment in southern/southeastern England using data from 1997 to 2007. Boron concentrations are related to an independent marker for sewage effluent, sodium. The results show that boron concentrations in the main river channels have declined with time especially under baseflow conditions when sewage effluent dilution potential is at its lowest. While boron concentrations have reduced, especially under low-flow conditions, this does not fully translate to a corresponding reduction in boron flux and it seems that the "within-catchment" supplies of boron to the river are contaminated by urban sources. The estimated boron reduction in the effluent input to the river based on the changes in river chemistry is typically around 60% and this figure matches with an initial survey of more limited data for the industrial north of England. Data for effluent concentrations at eight sewage treatment works within the Kennet also indicate substantial reductions in boron concentrations: 80% reduction occurred between 2001 and 2008. For the more contaminated rivers there are issues of localised rather than catchment-wide sources and uncertainties over the extent and nature of water/boron stores. Atmospheric sources average around 32 to 61% for the cleaner and 4 to 14% for the more polluted parts. The substantial decreases in the boron concentrations correspond extremely well with the timing and extent of European wide trends for reductions in the industrial and domestic usage of boron-bearing compounds. It clearly indicates that such reductions have translated into lower average and peak concentrations of boron in the river although the full extent of these reductions has probably not yet occurred due to localised stores that are still to deplete.
- Published
- 2010
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166. Declines in phosphorus concentration in the upper River Thames (UK): links to sewage effluent cleanup and extended end-member mixing analysis.
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Neal C, Jarvie HP, Williams R, Love A, Neal M, Wickham H, Harman S, and Armstrong L
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- Environmental Monitoring, Time, United Kingdom, Phosphorus analysis, Rivers chemistry, Sewage chemistry, Waste Disposal, Fluid methods, Water Pollutants, Chemical analysis
- Abstract
Phosphorus concentrations in the upper River Thames Basin (southeastern England) are described and linked to sewage effluent sources. Weekly surveys between 1997 and 2007 of the Thames and two of its major tributaries, the Thame and the Kennet indicated that phosphorus was mainly in soluble reactive (SRP) form. Baseflow concentrations in the Thames reduced from 1584microg/l in 1998 to 376microg/l in 2006 and from 2655 to 715microg/l for the Thame. Flow response, flux and endmember mixing analysis indicated that these declines resulted from SRP reductions in sewage treatment works (STW) effluent following phosphorus stripping for the major STWs in the region. This was confirmed by comparing our analysis with direct measurements of SRP in the effluents based on Environment Agency data. A within-river loss under baseflow of approximately 64% (range 56-78%) of the SRP-effluent input was estimated for the Thames, with a near balance for the Thame. SRP concentrations in the Kennet were an order of magnitude lower than the Thames/Thame: non-point sources dominated and were important for all the rivers at high flows. It was concluded that removal of SRP from effluents would be insufficient SRP in the Thames and Thame to meet annual average environmental targets of 50 to 120microg/l. The paper flags the value of combining hydrological/chemical tracing and concentration/flux approaches to data interrogation and the bonus of having actual measurements of the effluent. It highlights the need for fuller assessment of water storage/sediment/biota interactions for phosphorus and for caution in using boron as a long-term tracer for effluent inputs, its concentrations having declined markedly in response to reduced usage in washing powders: the value of using sodium as a tracer for examining SRP changes is shown.
- Published
- 2010
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167. Software for generating liability distributions for pedigrees conditional on their observed disease states and covariates.
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Campbell DD, Sham PC, Knight J, Wickham H, and Landau S
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- Depression genetics, Genetic Markers, Humans, Models, Statistical, Predictive Value of Tests, Probability, Risk Assessment, Software Validation, Genetic Predisposition to Disease genetics, Models, Genetic, Pedigree, Software
- Abstract
For many multifactorial diseases, aetiology is poorly understood. A major research aim is the identification of disease predictors (environmental, biological, and genetic markers). In order to achieve this, a two-stage approach is proposed. The initial or synthesis stage combines observed pedigree data with previous genetic epidemiological research findings, to produce estimates of pedigree members' disease risk and predictions of their disease liability. A further analysis stage uses the latter as inputs to look for associations with potential disease markers. The incorporation of previous research findings into an analysis should lead to power gains. It also allows separate predictions for environmental and genetic liabilities to be generated. This should increase power for detecting disease predictors that are environmental or genetic in nature. Finally, the approach brings pragmatic benefits in terms of data reduction and synthesis, improving comprehensibility, and facilitating the use of existing statistical genetics tools. In this article we present a statistical model and Gibbs sampling approach to generate liability predictions for multifactorial disease for the synthesis stage. We have implemented the approach in a software program. We apply this program to a specimen disease pedigree, and discuss the results produced, comparing its results with those generated under a more naïve model. We also detail simulation studies that validate the software's operation., (2009 Wiley-Liss, Inc.)
- Published
- 2010
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168. Statistical inference for exploratory data analysis and model diagnostics.
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Buja A, Cook D, Hofmann H, Lawrence M, Lee EK, Swayne DF, and Wickham H
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- Housing statistics & numerical data, Humans, Data Interpretation, Statistical, Models, Theoretical
- Abstract
We propose to furnish visual statistical methods with an inferential framework and protocol, modelled on confirmatory statistical testing. In this framework, plots take on the role of test statistics, and human cognition the role of statistical tests. Statistical significance of 'discoveries' is measured by having the human viewer compare the plot of the real dataset with collections of plots of simulated datasets. A simple but rigorous protocol that provides inferential validity is modelled after the 'lineup' popular from criminal legal procedures. Another protocol modelled after the 'Rorschach' inkblot test, well known from (pop-)psychology, will help analysts acclimatize to random variability before being exposed to the plot of the real data. The proposed protocols will be useful for exploratory data analysis, with reference datasets simulated by using a null assumption that structure is absent. The framework is also useful for model diagnostics in which case reference datasets are simulated from the model in question. This latter point follows up on previous proposals. Adopting the protocols will mean an adjustment in working procedures for data analysts, adding more rigour, and teachers might find that incorporating these protocols into the curriculum improves their students' statistical thinking.
- Published
- 2009
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169. Gonadotropin hormone releasing hormone agonists alter prefrontal function during verbal encoding in young women.
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Craig MC, Fletcher PC, Daly EM, Rymer J, Cutter WJ, Brammer M, Giampietro V, Wickham H, Maki PM, and Murphy DG
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- Adult, Brain anatomy & histology, Brain drug effects, Female, Hormones blood, Humans, Magnetic Resonance Imaging, Memory drug effects, Middle Aged, Prefrontal Cortex physiology, Recognition, Psychology drug effects, Gonadotropin-Releasing Hormone agonists, Goserelin pharmacology, Prefrontal Cortex drug effects, Verbal Behavior drug effects
- Abstract
Gonadotropin hormone releasing hormone agonists (GnRHa) are commonly used in clinical practice to suppress gonadal hormone production in the management of various gynaecological conditions and as a treatment for advanced breast and prostate cancer. Animal and human behavioural studies suggest that GnRHa may also have significant effects on memory. However, despite the widespread use of GnRHa, the underlying brain networks and/or stages of memory processing that might be modulated by GnRHa remain poorly understood. We used event-related functional magnetic resonance imaging to examine the effect of GnRHa on verbal encoding and retrieval. Neuroimaging outcomes from 15 premenopausal healthy women were assessed at baseline and 8 weeks after Gonadotrophin Releasing Hormone analogue (GnRHa) treatment. Fifteen matched wait-listed volunteers served as the control group and were assessed at similar intervals during the late follicular phase of the menstrual cycle. GnRHa was associated with changes in brain response during memory encoding but not retrieval. Specifically, GnRHa administration led to a change in the typical pattern of prefrontal activation during successful encoding, with decreased activation in left prefrontal cortex, anterior cingulate, and medial frontal gyrus. Our study suggests that the memory difficulties reported by some women following GnRHa, and possibly at other times of acute ovarian hormone withdrawal (e.g. following surgical menopause and postpartum), may have a clear neurobiological basis; one that manifest during encoding of words and that is evident in decreased activation in prefrontal regions known to sub-serve deep processing of to-be-learned words.
- Published
- 2007
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170. Distribution of symptom dimensions across Kraepelinian divisions.
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Dikeos DG, Wickham H, McDonald C, Walshe M, Sigmundsson T, Bramon E, Grech A, Toulopoulou T, Murray R, and Sham PC
- Subjects
- Adult, Diagnosis, Differential, Factor Analysis, Statistical, Female, Humans, Male, Affective Disorders, Psychotic diagnosis, Schizophrenia diagnosis
- Abstract
Background: Dimensional structures are established for many psychiatric diagnoses, but dimensions have not been compared between diagnostic groups., Aims: To examine the structure of dimensions in psychosis, to analyse their correlations with disease characteristics and to assess the relative contribution of dimensions v. diagnosis in explaining these characteristics., Method: Factor analysis of the OPCRIT items of 191 Maudsley Family Study patients with schizophrenia, mood disorders with psychosis, schizoaffective disorder, and other psychotic illnesses, followed by regression of disease characteristics from factor scores and diagnosis., Results: Five factors were identified (mania, reality distortion, depression, disorganisation, negative); all were more variable in schizophrenia than in affective psychosis. Mania was the best discriminator between schizophrenia and affective psychosis; the negative factor was strongly correlated with poor premorbid functioning, insidious onset and worse course. Dimensions explained more of the disease characteristics than did diagnosis, but the explanatory power of the latter was also high., Conclusions: Kraepelinian diagnostic categories suffice for understanding illness characteristics, but the use of dimensions adds substantial information.
- Published
- 2006
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171. Chlorophyll-a in the rivers of eastern England.
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Neal C, Hilton J, Wade AJ, Neal M, and Wickham H
- Subjects
- Agriculture, Carbon analysis, Carbon chemistry, Chlorophyll A, England, Environmental Monitoring, Geologic Sediments analysis, Nitrates analysis, Nitrates metabolism, Nitrogen analysis, Nitrogen metabolism, Organic Chemicals analysis, Organic Chemicals chemistry, Phosphorus analysis, Phosphorus metabolism, Seasons, Chlorophyll analysis, Eutrophication, Geologic Sediments chemistry, Rivers chemistry, Water Pollutants, Chemical analysis
- Abstract
Chlorophyll-a concentration variations are described for two major river basins in England, the Humber and the Thames and related to catchment characteristics and nutrient concentrations across a range of rural, agricultural and urban/industrial settings. For all the rivers there are strong seasonal variations, with concentrations peaking in the spring and summer time when biological activity is at its highest. However, there are large variations in the magnitude of the seasonal effects across the rivers. For the spring-summer low-flow periods, average concentrations of chlorophyll-a correlate with soluble reactive phosphorus (SRP). Chlorophyll-a is also correlated with particulate nitrogen (PN), organic carbon (POC) and suspended sediments. However, the strongest relationships are with catchment area and flow, where two straight line relationships are observed. The results indicate the importance of residence times for determining planktonic growth within the rivers. This is also indicated by the lack of chlorophyll-a response to lowering of SRP concentrations in several of the rivers in the area due to phosphorus stripping of effluents at major sewage treatment works. A key control on chlorophyll-a concentration may be the input of canal and reservoir waters during the growing period: this too relates to issues of residence times. However, there may well be a complex series of factors influencing residence time across the catchments due to features such as inhomogeneous flow within the catchments, a fractal distribution of stream channels that leads to a distribution of residence times and differences in planktonic inoculation sources. Industrial pollution on the Aire and Calder seems to have affected the relationship of chlorophyll-a with PN and POC. The results are discussed in relation to the Water Framework Directive.
- Published
- 2006
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172. Nitrate concentrations in river waters of the upper Thames and its tributaries.
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Neal C, Jarvie HP, Neal M, Hill L, and Wickham H
- Subjects
- Agriculture, Fertilizers, Geography, Geologic Sediments analysis, Geologic Sediments chemistry, Nitrogen analysis, Nitrogen metabolism, Permeability, Phosphorus analysis, Phosphorus metabolism, Water Movements, Water Supply analysis, Environmental Monitoring, Eutrophication, Nitrates analysis, Rivers chemistry, Water Pollutants, Chemical analysis
- Abstract
The spatial and temporal patterns of in-stream nitrate concentrations for the upper Thames and selected tributaries are described in relation to point and diffuse sources for these rural catchments. The rivers associated with catchments dominated by permeable (Cretaceous Chalk) bedrock show a smaller range in nitrate concentrations than those associated with clay and mixed sedimentary bedrock of lower permeability. The differences reflect the contrasting nature of water storage within the catchments and the influence of point and diffuse sources of nitrate. Nitrate concentrations often increase in a gradual way as a function of flow for the rivers draining the permeable catchments, although there is usually a minor dip in nitrate concentrations at low to intermediate flow due to (1) within-river uptake of nitrate during the spring and the summer when biological activity is particularly high and (2) a seasonal fall in the water table and a change in preferential flow-pathway in the Chalk. There is also a decrease in the average nitrate concentration downstream for the Kennet where average concentrations decrease from around 35 to 25 mg NO(3) l(-1). For the lower permeability catchments, when point source inputs are not of major significance, nitrate concentrations in the rivers increase strongly with increasing flow and level off and in some cases then decline at higher flows. When point source inputs are important, the initial increase in nitrate concentrations do not always occur and there can even be an initial dilution, since the dilution of point sources of nitrate will be lowest under low-flow conditions. For the only two tributaries of the Thames which we have monitored for over 5 years (the Pang and the Kennet), nitrate concentrations have increased over time. For the main stem of the Thames, which was also monitored for over 5 years, there is no clear increase over time. As the Pang and the Kennet river water is mainly supplied from the Chalk, the increasing nitrate concentrations over time clearly reflect increasing nitrate concentrations within the groundwater. It primarily reflects long-term trends for agricultural fertilizer inputs and significant aquifer storage and long water residence times. The results are discussed in terms of hydrogeochemical processes and the Water Framework Directive and are compared with data from other eastern UK rivers. The importance of diffuse sources of nitrate contamination is highlighted. On a flow weighted basis, the average diffuse component of nitrate is around 95% for the Thames Basin rivers draining Chalk and for the corresponding rivers draining less permeable strata, there is a more significant but not major point source component (at least in terms of flux); the average diffuse component is 79% in this case. These data fit well with earlier assessments of agricultural sources to UK surface waters. Under baseflow conditions the diffuse sources remain dominant for the Chalk fed Thames Basin rivers, but point sources can be dominant for the low permeability cases. On a proportionate basis, the Thames Basin rivers are similar to the rural rivers of the Tweed and Humber Basins in terms of percentage diffuse components although the lower intensity agriculture occurring for the rivers monitored means that the average nitrate concentrations are lower for the rural rivers of central and northern England and the borders with Scotland: the Humber and Tweed.
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- 2006
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173. River water quality of the River Cherwell: an agricultural clay-dominated catchment in the upper Thames Basin, southeastern England.
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Neal C, Neal M, Hill L, and Wickham H
- Subjects
- Agriculture, Aluminum Silicates, Anions analysis, Boron analysis, Carbon Dioxide analysis, Clay, England, Environmental Monitoring, Metals analysis, Phosphorus analysis, Rivers chemistry, Water Pollutants, Chemical analysis
- Abstract
The water quality of the River Cherwell and a tributary of it, the Ray, are described in terms of point and diffuse sources of pollution, for this rural area of the upper Thames Basin. Point sources of pollution dominate at the critical ecological low flow periods of high biological activity. Although the surface geology is predominantly clay, base flow is partly supplied from springs in underlying carbonate-bearing strata, which influences the water quality particularly with regards to calcium and alkalinity. The hydrogeochemistry of the river is outlined and the overall importance of urban point sources even in what would normally be considered to be rural catchments is stressed in relation to the European Unions Water Framework Directive. Issues of phosphorus stripping at sewage treatment works are also considered: such stripping on the Cherwell has reduced phosphorus concentrations by about a factor of two, but this is insufficient for the needs of the Water Framework Directive.
- Published
- 2006
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174. The water quality of the River Thame in the Thames Basin of south/south-eastern England.
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Neal C, Neal M, Hill L, and Wickham H
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- Anions analysis, Boron analysis, Carbon Dioxide analysis, Chlorophyll analysis, Chlorophyll A, England, Environmental Monitoring, Metals analysis, Sewage, Water Movements, Phosphorus analysis, Rivers chemistry, Water Pollutants, Chemical analysis
- Abstract
The water quality of the River Thame, a tributary of the River Thames in the Thames basin, is described in relation to point and diffuse contaminant inputs and runoff from permeable and impermeable bedrock geology with their own characteristic water quality. The data is examined to see if the market town of Aylesbury in the upper part of the catchment influences water quality. Previous studies highlighted the influence of Aylesbury sewage treatment works (STW) on soluble reactive phosphorus (SRP) concentrations in the river before and after phosphorus (P) stripping at the STW. Variations in water quality along the river are described and the study indicates that, apart from SRP, water quality determinants seem to be relatively unaffected by Aylesbury. The Thame water quality is compared with other catchment typologies and it is very similar to that of the main stem of the Thames even though the Thames is mainly Chalk groundwater fed. Differences in water quality largely link to the amount of STW effluent within the rivers and to the endmember compositions of the groundwater and near surface water sources.
- Published
- 2006
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175. Diagnostic value of written referral and/or images for skin lesions.
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Oakley AM, Reeves F, Bennett J, Holmes SH, and Wickham H
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- Adolescent, Adult, Aged, Aged, 80 and over, Diagnosis, Differential, Female, Humans, Internet, Male, Middle Aged, Photography, Remote Consultation instrumentation, Reproducibility of Results, Dermatology standards, Remote Consultation standards, Skin Diseases diagnosis
- Abstract
We examined whether it is possible for a dermatologist to diagnose benign and malignant skin lesions by telemedicine, given a comprehensive history and/or clinical images. A medical student recorded a standardized history and description of 109 skin lesions and took digital photographs of the presenting lesion(s) immediately prior to a normal outpatient dermatology consultation. About 52 dermatologists were invited to participate in online diagnosis. In all, 38 took part and they were provided with the text and/or the image(s) online on a secure Website. When the images and text were provided, 53% of teledermatology diagnoses were the same as the face-to-face diagnosis. When images alone were provided, 57% of diagnoses were the same. When text alone was provided, 41% of diagnoses were the same. The relatively low diagnostic concordance may have been due to the inexperience of many teledermatologists and poor quality image display systems. The teledermatologists were less confident in their diagnoses than face-to-face specialists, especially in the absence of images. The teledermatology management plan was more likely to include biopsy, excision or review than was the case at the face-to-face consultation. Teledermatology may result in an increase in follow-up appointments and surgical procedures.
- Published
- 2006
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176. Dermatoglyphics and Schizophrenia: a meta-analysis and investigation of the impact of obstetric complications upon a-b ridge count.
- Author
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Bramon E, Walshe M, McDonald C, Martín B, Toulopoulou T, Wickham H, van Os J, Fearon P, Sham PC, Fañanás L, and Murray RM
- Subjects
- Female, Humans, Pregnancy, Dermatoglyphics, Pregnancy Complications physiopathology, Schizophrenia etiology, Schizophrenia physiopathology
- Abstract
Background: Patients with schizophrenia show deviances in their dermatoglyphics, in particular reductions in palmar a-b ridge counts (ABRCs), which are evidence of an early developmental deviance. However, the severity or the origin of these ABRC changes has not been established., Method: (i) We examined the published literature on the ABRC in patients with schizophrenia against controls with a random effects meta-analysis. (ii) We used linear regression to study the ABRC in our sample of families including 125 patients with schizophrenia, 107 of their unaffected relatives and 98 controls. (iii) The effect of obstetric complications on the patient's ABRC was examined using the Lewis Murray scale., Results: The pooled standardised effect size of ABRC differences between patients and controls obtained by our meta-analysis was 0.39 (95% CI: 0.05-0.73; p=0.03). In our sample, there were no significant differences in ABRCs between those with schizophrenia, their relatives and controls. Only those patients with obstetric complications had significantly reduced ABRC compared to controls (p=0.01)., Conclusions: We confirmed the presence of significant yet mild ABRC reductions in schizophrenia. These represent a subtle deviance from the norm and could be present in certain subsets of patients, possibly those who suffered early developmental insults.
- Published
- 2005
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177. Phosphorus concentrations in the River Dun, the Kennet and Avon Canal and the River Kennet, southern England.
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Neal C, House WA, Jarvie HP, Neal M, Hill L, and Wickham H
- Subjects
- England, Models, Theoretical, Seasons, Solubility, Agriculture, Environmental Monitoring, Phosphorus analysis, Rivers chemistry, Water Pollutants, Chemical analysis
- Abstract
Variations in phosphorus (P) concentrations in an agriculturally impacted river draining a Chalk aquifer and an associated canal in the west of the Thames Basin, southern England are examined and linked to agricultural and sewage sources and within river/canal process controls. The study area comprises the River Dun, the adjacent River Kennet and the Kennet and Avon (K&A) Canal. Large seasonal variations are observed for soluble reactive phosphorus (SRP) and dissolved silicon (Si) with low concentrations in the spring and summer times when biological activity is high. The K&A Canal shows the largest SRP and Si concentration declines. This reflects high biological activity coupled with higher temperatures and higher water residence times. The extent of SRP removal is examined in relation to organic (uptake/release with phytoplankton growth/decay) and, to a lesser extent, inorganic (SRP coprecipitation with calcite) mechanisms. Boron (B) is used as a tracer of sewage sources. Agricultural inputs of both dissolved and particulate P (PP) can be important particularly under conditions where the catchment is wet and near surface/overland flow is important: sewage treatment works effluent and septic tank discharges to groundwater also probably provide a major component of the SRP occurring within the water column. The canal, and to a lesser extent the river, acts as sink for P in sewage effluent sources due to the high biological activity especially during the spring and summer. The aquifer probably acts as a major sink for agricultural and septic tank inputs of P.
- Published
- 2005
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178. Association between BDNF val66 met genotype and episodic memory.
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Dempster E, Toulopoulou T, McDonald C, Bramon E, Walshe M, Filbey F, Wickham H, Sham PC, Murray RM, and Collier DA
- Subjects
- Algorithms, Female, Genotype, Humans, Linkage Disequilibrium, Male, Mutation, Missense, Regression Analysis, Wechsler Scales, Brain-Derived Neurotrophic Factor genetics, Memory, Polymorphism, Single Nucleotide
- Abstract
The val66 met polymorphism of brain derived neurotrophic factor (BDNF) has been associated with variability in episodic memory [Egan et al., 2003]. In an attempt to replicate this finding, we genotyped 206 individuals (92 affected with schizophrenia or a related disorder and 114 unaffected relatives) from the Maudsley Family Study for the BDNF val66 met polymorphism. We analyzed the effect of this polymorphism on episodic memory using the Wechsler Memory Scale, revised version (WMS-R) by regression analysis between the WMS delayed score of logical memory and genotype (corrected for age, sex, and IQ). We found the met66 allele conferred a lower score on the WMS delayed measure (R2 = 0.014 P = 0.09), which was not significant. When cases and unaffected relatives were analyzed separately, met66 was associated with a lower score on the WMS delayed measure in the relatives only (R2 = 0.077 P = 0.01), which is consistent with previous findings., (Copyright 2005 Wiley-Liss, Inc.)
- Published
- 2005
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179. Association of genetic risks for schizophrenia and bipolar disorder with specific and generic brain structural endophenotypes.
- Author
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McDonald C, Bullmore ET, Sham PC, Chitnis X, Wickham H, Bramon E, and Murray RM
- Subjects
- Adolescent, Adult, Aged, Bipolar Disorder diagnosis, Family Health, Female, Frontal Lobe anatomy & histology, Genetic Predisposition to Disease genetics, Humans, Magnetic Resonance Imaging statistics & numerical data, Male, Middle Aged, Models, Genetic, Regression Analysis, Schizophrenia diagnosis, Temporal Lobe anatomy & histology, Bipolar Disorder genetics, Brain anatomy & histology, Phenotype, Schizophrenia genetics
- Abstract
Context: For more than a century, it has been uncertain whether or not the major diagnostic categories of psychosis--schizophrenia and bipolar disorder--are distinct disease entities with specific genetic causes and neuroanatomical substrates., Objective: To investigate the relationship between genetic risk and structural variation throughout the entire brain in patients and their unaffected relatives sampled from multiply affected families with schizophrenia or bipolar disorder., Design: Analysis of the association between genetic risk and variation in tissue volume on magnetic resonance images., Setting: Psychiatric research center., Participants: Subjects comprised 25 patients with schizophrenia, 36 of their unaffected first-degree relatives, 37 patients with bipolar 1 disorder who experienced psychotic symptoms during illness exacerbation, and 50 of their unaffected first-degree relatives., Main Outcome Measures: We used computational morphometric techniques to map significant associations between a continuous measure of genetic liability for each subject and variation in gray or white matter volume., Results: Genetic risk for schizophrenia was specifically associated with distributed gray matter volume deficits in the bilateral fronto-striato-thalamic and left lateral temporal regions, whereas genetic risk for bipolar disorder was specifically associated with gray matter deficits only in the right anterior cingulate gyrus and ventral striatum. A generic association between genetic risk for both disorders and white matter volume reduction in the left frontal and temporoparietal regions was consistent with left frontotemporal disconnectivity as a genetically controlled brain structural abnormality common to both psychotic disorders., Conclusions: Genetic risks for schizophrenia and bipolar disorder are associated with specific gray matter but generic white matter endophenotypes. Thus, Emil Kraepelin's pivotal distinction was neither wholly right nor wholly wrong: the 2 major psychoses show both distinctive and similar patterns of brain structural abnormality related to variable genetic risk.
- Published
- 2004
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180. Joint analysis of the DRD5 marker concludes association with attention-deficit/hyperactivity disorder confined to the predominantly inattentive and combined subtypes.
- Author
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Lowe N, Kirley A, Hawi Z, Sham P, Wickham H, Kratochvil CJ, Smith SD, Lee SY, Levy F, Kent L, Middle F, Rohde LA, Roman T, Tahir E, Yazgan Y, Asherson P, Mill J, Thapar A, Payton A, Todd RD, Stephens T, Ebstein RP, Manor I, Barr CL, Wigg KG, Sinke RJ, Buitelaar JK, Smalley SL, Nelson SF, Biederman J, Faraone SV, and Gill M
- Subjects
- Attention Deficit Disorder with Hyperactivity classification, Female, Humans, Male, Odds Ratio, Attention Deficit Disorder with Hyperactivity genetics, Genetic Markers
- Abstract
Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable, heterogeneous disorder of early onset, consisting of a triad of symptoms: inattention, hyperactivity, and impulsivity. The disorder has a significant genetic component, and theories of etiology include abnormalities in the dopaminergic system, with DRD4, DAT1, SNAP25, and DRD5 being implicated as major susceptibility genes. An initial report of association between ADHD and the common 148-bp allele of a microsatellite marker located 18.5 kb from the DRD5 gene has been followed by several studies showing nonsignificant trends toward association with the same allele. To establish the postulated association of the (CA)(n) repeat with ADHD, we collected genotypic information from 14 independent samples of probands and their parents, analyzed them individually and, in the absence of heterogeneity, analyzed them as a joint sample. The joint analysis showed association with the DRD5 locus (P=.00005; odds ratio 1.24; 95% confidence interval 1.12-1.38). This association appears to be confined to the predominantly inattentive and combined clinical subtypes.
- Published
- 2004
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181. Familiality of clinical characteristics in schizophrenia.
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Wickham H, Walsh C, Asherson P, Gill M, Owen MJ, McGuffin P, Murray R, and Sham P
- Subjects
- Adult, Age of Onset, Female, Humans, Male, Psychiatric Status Rating Scales, Random Allocation, Schizophrenia epidemiology, Severity of Illness Index, Schizophrenia diagnosis, Schizophrenia genetics
- Abstract
Few studies have assessed the familiality of clinical characteristics in schizophrenia. Therefore, we set out to investigate the familiality of the following characteristics; age of onset, course of disorder, employment status at onset, impairment during disorder, marital status at onset, mode of onset and premorbid functioning. Clinical characteristics were recorded using the Operational Criteria Checklist for Psychotic Illness for 155 subjects with an RDC diagnosis of schizophrenia, schizoaffective disorder, or psychosis of unknown origin, from 61 families multiply affected by schizophrenia. Age of onset, course of disorder, impairment during disorder, mode of onset, and premorbid functioning were shown to be familial. The familiality of these clinical characteristics supports their use in the delineation of homogeneous subsets for future genetic studies.
- Published
- 2002
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182. Phosphorus-calcium carbonate saturation relationships in a lowland chalk river impacted by sewage inputs and phosphorus remediation: an assessment of phosphorus self-cleansing mechanisms in natural waters.
- Author
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Neal C, Jarvie HP, Williams RJ, Neal M, Wickham H, and Hill L
- Subjects
- Calcium Carbonate chemistry, Carbon Dioxide analysis, Environmental Monitoring, Hydrogen-Ion Concentration, Phosphorus chemistry, Calcium Carbonate analysis, Eutrophication, Phosphorus analysis, Sewage, Water Pollution analysis, Water Purification
- Abstract
The relationship between calcium carbonate saturation and phosphorus concentrations for seven sites on the upper reaches of the River Kennet are examined. The findings are related to issues of groundwater supplies and the introduction of phosphorus treatment of effluent from the Marlborough sewage treatment works (STW) at part of the way along the study reach. Being supplied from a Cretaceous Chalk aquifer, the Kennet is mainly of a calcium-bicarbonate type and has a relatively constant composition of many major water quality determinands. Typically, the waters average a pH of approximately eight (range approx. 7.5-8.5) during the day with the lowest values occurring at the upstream site. Dissolved carbon dioxide varies from approximately 5 to 35 times atmospheric pressure during the late morning with the highest values occurring at the upstream site. However, in-stream biological activity gives rise to marked diurnal fluctuations in pH and dissolved carbon dioxide concentrations and during the summer months, by mid to late afternoon, pH is at its maximum and dissolved carbon dioxide is at its lowest: this is shown by continuous measurements at one of the river sites. Alkalinity and calcium concentrations remain relatively constant at approximately 4,700 microEq/l (range 3,500-6,000 microEq/l) and 120 mg/l (range 85-150 mg/l), respectively, and the waters are oversaturated with respect to calcium carbonate (calcite) typically by a factor of six (range 2-25). Along the reach, soluble reactive phosphate (SRP) increases from the first to the second site with the introduction of sewage supplies from the Marlborough STW, and then declines further downstream as sewage dilution and uptake by the river bed/aquatic plants increases. The differences in concentration decrease after phosphorus removal from Marlborough STW. Despite this change, there is no clear indication of any calcite solubility control except perhaps at times of extreme baseflow during the growing season when within-stream photosynthesis is maximal and within-stream residence times are longer. A comparison of river and groundwater data shows that the groundwaters have similar alkalinities and calcium concentrations. However, the groundwaters have (a) higher carbon dioxide saturations (a factor of 2-5 times the value for the river), (b) lower pHs (0.5-1.5 units), (c) lower SRP concentrations (a quarter or less of the river values) and (d) waters near calcite saturation (unlike the surface waters which are oversaturated). The findings indicate a river system dominated by the input carbon dioxide laden groundwaters in approximate equilibrium with calcite attenuated by within-channel biological and physical processes. Within the river: (a) the waters degas carbon dioxide increasing the pH, producing oversaturated conditions; and (b) oscillating pH-dissolved carbon dioxide levels occur between day and night due to changing balances between photosynthesis and respiration. It seems that lowering the phosphorus levels have not resulted in calcite precipitation within the water column and that no significant within-stream self-cleansing mechanisms are occurring that might be predicted from theory: other components in the water such as dissolved organic carbon may inhibit calcite nucleation. However, the low SRP levels in the groundwater coupled with calcite saturation, may well indicate that phosphorous concentrations within the groundwater are regulated by such processes: the number of calcite nucleating sites are orders of magnitude higher and the calcite inhibitors may be less prevalent.
- Published
- 2002
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183. Phosphorus uptake into algal biofilms in a lowland chalk river.
- Author
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Jarvi HP, Neal C, Warwick A, White J, Neal M, Wickham HD, Hill LK, and Andrews MC
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- Biomass, Calcium Carbonate, Chlorophyll analysis, Chlorophyll A, Population Dynamics, Seasons, Water chemistry, Water Movements, Biofilms, Eukaryota, Eutrophication, Phosphorus pharmacokinetics
- Abstract
This paper examines the growth and uptake of phosphorus into algal biofilms in the River Kennet, a lowland chalk (Cretaceous-age) stream in southern England. Algal biofilms were grown on artificial plastic substrates (templates) placed (i) on the riverbed and (ii) within the mid-water column. Experiments were set up to examine differences in growth rates of newly colonising biofilms compared with biofilms left to accumulate for periods of up to 6 months. Rates of algal biofilm production were measured by the chlorophyll a concentration that had accumulated per cm2 over the number of days that the biofilm template had been immersed in the river water. An algal biofilm bloom occurred in early spring, prior to peak suspended chlorophyll a concentrations within the water column. Biofilm samples collected in February and March had the highest chlorophyll a and total phosphorus concentrations. The biofilm bloom corresponded with increased solar radiation and declining river flow conditions. Periodic increases in soluble reactive phosphorus concentrations in the overlying river water did not correspond with any significant increase in biofilm production. These results suggest that light, rather than phosphorus is a key factor for biofilm growth in the River Kennet. Higher rates of chlorophyll a development in mid-water column biofilms may be linked to greater light exposure; however, maximum total-P concentrations were similar for both bed and water column biofilms. Newly colonising biofilms exhibited higher chlorophyll a and total-P concentrations than biofilms left to accumulate over longer terms, suggesting that fresh substrate availability promotes high rates of biofilm growth. Both 'condensed and organic' P (stored in biomass) and 'inorganic' (mineral) P fractions within the biofilms were present in varying proportions, although the early spring biofilm bloom resulted in maximum proportions and absolute concentrations of 'condensed and organic' P. Calcite was the only crystalline mineral detected within the biofilms. Ratios of Ca:inorganic P are largely consistent with the presence of CaCO3-P co-precipitates, although one very low value suggested that there may also be additional sources of inorganic P, possibly P adsorbed to clays or organics within the biofilm. However, poor linkages between CaCO3 and inorganic P concentrations suggest that, although the inorganic P fraction within the biofilm may be derived largely from CaCO3-P co-precipitation, the subsequent processes controlling overall CaCO3 and inorganic P concentrations in the biofilm are complex.
- Published
- 2002
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184. Intrauterine contraception: a look at devices and systems.
- Author
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Wickham H
- Subjects
- Female, Humans, Pregnancy, Contraception nursing, Intrauterine Devices
- Published
- 2000
185. The impact of coronary stenting on immediate procedural complication and long-term clinical restenosis at Waikato Hospital.
- Author
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Wickham H, Nunn C, McAlister H, Devlin G, Charleson H, Fisher R, Heald S, and Wade C
- Subjects
- Female, Humans, Male, Middle Aged, Recurrence, Treatment Outcome, Angioplasty, Balloon, Coronary, Coronary Disease therapy, Stents
- Abstract
Aim: Clinical data on coronary stenting from within New Zealand is scarce and, in particular, the impact of current stent technologies is unknown. We reviewed all angioplasties undertaken at Waikato Hospital over a two year period to determine the clinical effect of coronary stenting on the local population., Methods: Data from all patients who underwent coronary angioplasty at Waikato Hospital between July 1, 1995 and July 1, 1997 were included. Stents were deployed either to remedy sub-optimal results, or were electively used for saphenous vein grafts or restenotic lesions. Patient follow-up was obtained through a combination of database review, chart search and GP or patient contact., Results: 662 lesions were dilated in 441 patients. 91 lesions were stented, 52.7% for sub-optimal results following balloon angioplasty. 98% of patients were followed up at six months. Whilst procedural success rate was higher in stented patients compared to unstented patients (96.7% vs 87.5% respectively, p=0.009) the in-hospital sub-acute occlusion rate was also increased (6.8% vs 1.9% respectively, p=0.007). At six months, coronary restenosis requiring repeat angioplasty was infrequent (10.9% overall) with no significant difference between the two groups (8.1% vs. 11.2% for stented vs unstented patients respectively, p=NS)., Conclusions: The use of stents appears effective in improving immediate procedural success rates. Despite stented patients being at higher risk initially, their complication and six month clinical restenosis rates were similar.
- Published
- 2000
186. The water quality of the River Kennet: initial observations on a lowland chalk stream impacted by sewage inputs and phosphorus remediation.
- Author
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Neal C, Jarvie HP, Howarth SM, Whitehead PG, Williams RJ, Neal M, Harrow M, and Wickham H
- Subjects
- England, Environmental Monitoring, Hydrogen-Ion Concentration, Phosphorus pharmacokinetics, Seasons, Water Microbiology, Phosphorus analysis, Sewage, Water Pollutants, Chemical analysis, Water Pollution prevention & control
- Abstract
The water quality of seven sites on the upper reaches of the River Kennet round the market town of Marlborough is described and related to the introduction of phosphorus treatment of effluent from Marlborough sewage treatment works (STW). The River Kennet is mainly groundwater-fed from a Cretaceous chalk aquifer and hence the river water is calcium- and bicarbonate-bearing and has a relatively constant composition of many major water quality determinants. In-stream biological activity gives rise to marked diurnal fluctuations in pH (of approx. 0.8 units). Dissolved carbon dioxide and dissolved oxygen also show marked diurnal fluctuations. Dissolved carbon dioxide varies from approximately 10 to 70 times atmospheric pressure, indicating net release of carbon dioxide and the dominance of heterotrophic (respiratory) processes over autotrophic processes (photosynthesis). Much of the excess carbon dioxide is probably associated with carbon dioxide laden groundwater inputs and the relatively short within-stream residence times ensures only limited degassing to the atmosphere. Diurnal fluctuations in dissolved oxygen vary from approximately 20% to 200% saturation. For both dissolved carbon dioxide and dissolved oxygen, the amplitude of fluctuations is much lower during the winter period, when biological activity is at its lowest. The concentrations of soluble reactive phosphorus (SRP), total phosphorus (TP) and boron increase markedly just downstream of the sewage works as a result of this point source input. These concentrations slowly decline further downstream as additional groundwater inputs dilute the effluent further. The introduction of chemical treatment of sewage effluent for phosphorus reduction at Marlborough STW resulted in a marked decrease in within-river SRP and TP concentrations to levels approximately the same as those upstream of the STW. A comparison of SRP and boron concentrations reveals a reduction in in-stream SRP concentrations by approximately 75% following effluent treatment. In terms of within-river processes controlling in-stream phosphorus concentrations, previous studies have indicated that one potentially important mechanism within calcium bicarbonate bearing rivers may be related to co-precipitation of phosphorus with calcium carbonate (calcite). The present study shows that the waters are oversaturated with respect to calcium carbonate, that no equilibrium conditions exist and that phosphorus removal has led to undetectable changes in calcium carbonate oversaturation. Hence, it is concluded that the primary changes in phosphorus levels within the river is directly associated with changing point source contributions from the STW and physical dilution within the river. However (1) the results relate to only the first year of study and subsequent differences may become apparent and (2) reactions between the water column and plant and bottom sediment interfaces may be important in regulating phosphorus fluxes within the river. The results presented in this paper mark a pilot phase of a longer-term initiative and this paper provides a background setting. The paper discusses the longer-term objectives and important gaps in knowledge of the system that requires further address.
- Published
- 2000
- Full Text
- View/download PDF
187. Riverine inputs of major ions and trace elements to the tidal reaches of the River Tweed, UK.
- Author
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Jarvie HP, Neal C, Tappin AD, Burton JD, Hill L, Neal M, Harrow M, Hopkins R, Watts C, and Wickham H
- Subjects
- Hydrogen-Ion Concentration, Ions, Models, Theoretical, Trace Elements, United Kingdom, Weather, Eutrophication, Water Movements
- Abstract
This paper examines spatial and temporal variability in freshwater inputs of trace elements and major ions to the tidal reaches of the River Tweed. The relationships between concentrations of major ions and trace elements (in dissolved and acid-available particulate forms) and flow are examined, and a simple two-component endmember mixing analysis performed to link river water chemistry to catchment sources, and to identify whether within-river processes modify concentrations to produce non-conservative behaviour. The results indicate that most dissolved major ions and trace elements behave conservatively in the lower reaches of the River Tweed, the variability in concentrations being dominated by hydrology and the existence of different high-flow and low-flow endmember runoff chemistries. This suggests that the variability in concentration of most dissolved trace elements and major ions in the lower Tweed can be modelled using simple mixing relationships. However, the relationships between pH, Ca, Mg and Gran alkalinity show pronounced non-conservative behaviour, indicating the importance of understanding within-river process for modelling these determinants. The non-conservative behaviour identified is related to biological controls and the resultant diurnal variations in pH which promote daytime removal of Ca from solution by precipitation of calcium carbonate (and corresponding removal of Mg by co-precipitation) during extreme low-flow conditions and algal blooms during the summer.
- Published
- 2000
- Full Text
- View/download PDF
188. The water quality of a tributary of the Thames, the Pang, southern England.
- Author
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Neal C, Neal M, Wickham H, and Harrow M
- Subjects
- Atmospheric Pressure, Calcium analysis, Chlorophyll A, England, Environmental Monitoring, Hydrogen-Ion Concentration, Nitrogen analysis, Nitrogen metabolism, Phosphorus analysis, Phosphorus metabolism, Seasons, Water Microbiology, Agriculture, Carbon Dioxide analysis, Chlorophyll analysis, Sewage, Water Pollution analysis
- Abstract
The water quality of a tributary of the Thames, the Pang, draining a rural part of the Thames basin is described and related to the influences of inputs from farming activity and groundwater from the underlying chalk aquifer as modified by biological within-stream processes. The groundwater inputs ensures that the waters are calcium and bicarbonate bearing and have relatively uniform concentrations. Agricultural inputs result in enhanced levels of nutrients, nitrate and soluble reactive phosphorus (SRP) in particular. For nitrate, the concentrations are higher during the winter months due to increased surface runoff. In contrast, SRP shows a more erratic behaviour with higher concentrations occurring during the early storm hydrograph rise following summer baseflow recession. Within the stream, biological activity results in: (a) marked diurnal fluctuations in the dissolved levels of carbon dioxide and oxygen; (b) a strong seasonal pattern in chlorophyll a levels; and (c) dissolved silica concentration reductions during the early spring period. Carbon dioxide levels are particularly high in the groundwater (typically approximately 60 times the atmospheric value) as observed at a spring discharge. However, within the stream, considerable degassing occurs although values remain an order of magnitude above atmospheric pressure. The findings are discussed in the context of the water quality functioning of agriculturally and sewage impacted southern eastern UK rivers. For example, the work shows that unlike for riverine systems with point sewage discharges or limited groundwater storage, there is a very poor link between chemical concentrations and flow even for components such as SRP and boron which are often connected to sewage discharges.
- Published
- 2000
- Full Text
- View/download PDF
189. The water quality of the River Thames at a rural site downstream of Oxford
- Author
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Neal C, Williams RJ, Neal M, Bhardwaj LC, Wickham H, Harrow M, and Hill LK
- Abstract
Water quality information is presented for the River Thames 34 km downstream of the market town of Oxford in Oxfordshire to provide an overview of the hydrochemical functioning of a major agriculturally impacted river entering the North Sea. The data, which cover the period from the spring of 1997 to the spring of 1999, relate to three types of data. These types are: (1) weekly spot sampling for determination of major, minor and trace elements, pH, alkalinity and herbicides; (2) tri-weekly spot sampling for pH, alkalinity and dissolved silicon; and (3) continuous measurements of pH and dissolved oxygen. Calcium and bicarbonate provide, respectively, the dominant cation and anion in solution and their compositions remain relatively constant through time, irrespective of flow levels. In contrast, many determinands show seasonally related fluctuations. Concentrations for most of the major anions, sodium, potassium as well as soluble reactive phosphorus and several soluble trace elements such as boron, antimony, arsenic and molybdenum decrease as flow increases. A reverse pattern is observed for nitrate, some herbicides and trace elements associated with particulate phases: concentrations increase with increasing flow. These patterns reflect the influence of: (1) a calcium carbonate rich groundwater system which provides the main stream flow component; (2) dilution of point source pollutant inputs associated with sewage and possibly light industry at high flows for several major, nutrient and trace elements; (3) enhanced nitrate and herbicide runoff from agricultural land at high flows; (4) enhanced microparticulate trace metal levels associated with increased suspended sediment loads at high flows; and (5) biological processes which affect pH, dissolved silicon, dissolved carbon dioxide and dissolved oxygen levels. An examination of soluble reactive phosphorus (SRP) and boron relationships reveals a reduction in concentrations for SRP associated possibly with phosphorus removal from a major sewage treatment works on an upstream tributary of the Thames, the Thame.
- Published
- 2000
- Full Text
- View/download PDF
190. Phosphate measurement in natural waters: two examples of analytical problems associated with silica interference using phosphomolybdic acid methodologies
- Author
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Neal C, Neal M, and Wickham H
- Abstract
Assessment of phosphate species for bicarbonate-bearing lowland rivers of the Thames valley, England and acidic Welsh upland streams (the Plynlimon area, mid-Wales) reveal problems of silica interference when employing standard automated 'phosphomolybdic acid' colorimetric methodologies. The interference occurs under a combination of two conditions: (1) when the reagents and samples are heated to speed up the rate of formation of phosphomolybdic acid; and (2) when the strength of a sulfuric acid reagent is too low. While this paper alerts researchers to potential analytical problems with silica interference within phosphomolybdic acid methodologies to determine soluble reactive phosphorus (SRP) concentrations, it cannot detail whether or not there is a general problem. This lack of specificity occurs because there are a variety of phosphomolybdic acid methodologies available which vary in their reagent recipes and it is not clear which methods will or will not suffer from silica interference. Changing the sulfuric acid reagent strength by a factor of two overcame the problem, in this case, with regards to the determination of soluble reactive phosphorus. However, even here, the method may not be applicable to very high alkalinity waters owing to their potential for reducing the acidity of the analyte. With regard to total dissolved phosphorus (TDP) and total phosphorus (TP) measurements, the importance of undertaking the analysis under ambient conditions is clearly shown. There are many small variants on standard phosphomolybdate methods for determining SRP, TDP and TP in use and it is not always clear which methods will or will not show silica interference for particular water types. It is therefore recommended that individual laboratories check their methodologies for silica interference using phosphate-free solutions with similar silica and alkalinity ranges for the waters being assayed.
- Published
- 2000
- Full Text
- View/download PDF
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