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Paul A Ellis

Publications and source records attributed to Paul A Ellis.

11 recordsLinked to original sources
PubMed2006

Quantifying urban river-aquifer fluid exchange processes: a multi-scale problem.

Groundwater-river exchanges in an urban setting have been investigated through long term field monitoring and detailed modelling of a 7 km reach of the Tame river as it traverses the unconfined Triassic Sandstone aquifer that lies beneath the City of Birmingham, UK. Field investigations and numerical modelling have been completed at a range of spatial and temporal scales from the metre to the kilometre scale and from event (hourly) to multi-annual time scales. The objective has been to quantify the spatial and temporal flow distributions governing mixing processes at the aquifer-river interface that can affect the chemical activity in the hyporheic zone of this urbanised river. The hyporheic zone is defined to be the zone of physical mixing of river and aquifer water. The results highlight the multi-scale controls that govern the fluid exchange distributions that influence the thickness of the mixing zone between urban rivers and groundwater and the patterns of groundwater flow through the bed of the river. The morphologies of the urban river bed and the adjacent river bank sediments are found to be particularly influential in developing the mixing zone at the interface between river and groundwater. Pressure transients in the river are also found to exert an influence on velocity distribution in the bed material. Areas of significant mixing do not appear to be related to the areas of greatest groundwater discharge and therefore this relationship requires further investigation to quantify the actual remedial capacity of the physical hyporheic zone.

Cities↗
PubMed2006

Assessing the impact of VOC-contaminated groundwater on surface water at the city scale.

This study is believed to be one of the first to assess the impact of urban VOC-(volatile organic compound) contaminated groundwater on river-water quality at the city scale. A network of riverbed piezometers was used to study the 7.4-km urbanised reach of the River Tame that flows across the groundwater-effluent unconfined Triassic sandstone aquifer underlying the city of Birmingham (UK). Aquifer groundwater contained significant chlorinated VOC contamination due to the city's industrial heritage. Chlorinated VOC-contaminated baseflow was widespread along the reach with trichloroethene (TCE) dominant. VOC concentrations in riverbed piezometers were in the range 0.1-100 microg/l with typical regulatory limits occasionally exceeded by an order of magnitude. Although anaerobic biodegradation products such as cis-dichloroethene were widespread, they were unlikely to have formed in the generally aerobic riverbed. The lack of anaerobic conditions was ascribed to insufficient accumulation of low-permeability, organic-carbon rich riverbed sediments in this medium-high energy river. Assumptions a priori that natural attenuation of chlorinated VOCs will occur via reductive dechlorination in urban riverbeds are likely in error, particularly where deposits of medium-high permeability exist transmitting much of the baseflow. Surface-water quality impacts were nevertheless still low with in-river TCE increasing by just 2 microg/l over the 7.4-km reach. Agreement of baseflow contaminant flux estimates based on five flow-concentration product methods was achieved to within an order of magnitude with 22-200 kg/yr of TCE estimated to discharge to the 7.4-km reach (equivalent to 0.8-7.5 mg/d/m2 of riverbed). Such uncertainty was not regarded as unreasonable when the large measurement scale and geological and chemical heterogeneities are considered. Improved flux estimation methods and greater monitoring densities are nevertheless warranted. Considering Birmingham's long industrial history and known incidence of VOC-contaminated groundwater, the city-scale impact of VOC-contaminated groundwater upon surface-water quality was judged to be relatively modest.

Aerobiosis↗
PubMed2006

Tyrosine kinase inhibitors. 19. 6-Alkynamides of 4-anilinoquinazolines and 4-anilinopyrido[3,4-d]pyrimidines as irreversible inhibitors of the erbB family of tyrosine kinase receptors.

Structure-activity relationships for inhibition of erbB1, erbB2, and erbB4 were determined for a series of alkynamide analogues of quinazoline- and pyrido[3,4-d]pyrimidine-based compounds. The compounds were prepared by coupling the appropriate 6-aminoquinazolines or 6-aminopyrido[3,4-d]pyrimidines with alkynoic acids, using EDCI.HCl in pyridine. The compounds showed pan-erbB enzyme inhibition but were on average about 10-fold more potent against erbB1 than against erbB2 and erbB4. For cellular inhibition, the nature of the alkylating side chains was an important determinant, with 5-dialkylamino-2-pentynamide type Michael acceptors providing the highest potency. This is suggested to be due to an improved ability of the amine to participate in an autocatalysis of the Michael reaction with enzyme cysteine residues. Pyrido[3,4-d]pyrimidine analogue 39 was selected for in vivo evaluation and achieved tumor regressions at 10 mg/kg in the A431 human epidermoid carcinoma and at 40 mg/kg for the SF767 human glioblastoma and the SKOV3 human ovarian carcinoma. Complete stasis was observed at 40 mg/kg in the BXPC3 human pancreatic carcinoma as well as in the H125 human non-small-cell lung carcinoma.

Alkynes↗
PubMed2006

Adjuvant aromatase inhibitors and bone health.

Adjuvant hormonal therapy results in substantial improvements in disease-free and overall survival for women with operable breast cancer. Use of an aromatase inhibitor (AI) is expected to replace tamoxifen as standard care for many patients. Aromatase is the enzyme responsible for the final step in estrogen biosynthesis. This is the conversion of the androgens testosterone and androstenedione to the estrogens estrone and estradiol. AIs are potent inhibitors of estrogen production and thus one of the major concerns over their use is their effect on bone health and their potential to increase the incidence of osteoporosis and risk of fracture. The American Society of Clinical Oncology has recognized that these patients are at high risk of developing osteoporosis and has published guidelines to aid in their management. These recommend that all patients have an initial dual-energy X-ray absorptiometry (DEXA) bone scan to assess bone mineral density and are offered calcium and vitamin D supplements as well as lifestyle advice. Patients with osteoporosis should be treated with a bisphosphonate to reduce the incidence of fracture. Osteonecrosis of the jaws is a recently described adverse side-effect of bisphosphonate therapy and has been described in women with metastatic breast cancer. Oversuppression of bone turnover is probably the primary mechanism for the development of this condition. The degree of risk for osteonecrosis with bisphosphonates is uncertain and warrants careful monitoring.

Aromatase Inhibitors↗
PubMed2005

Integrated understanding of urban land, groundwater, baseflow and surface-water quality--the City of Birmingham, UK.

Integrated understanding of urban land, groundwater (shallow and deep), baseflow and surface-water quality relationships is required for effective urban water-quality management. Chemical quality data from across these media have been collected for the Birmingham (UK) aquifer--River Tame conurbation to assess chemical transport from contaminated land to groundwater to baseflow to surface water. Although metals concentrations were high in soils, low leachability and attenuation caused concentrations in groundwaters and baseflow discharging to surface water to be generally low with only sporadic elevated concentrations attributed to localised point sources. Hydrocarbon VOCs (volatile organic compounds) were similarly absent or at low concentration attributable to their ready natural attenuation. Chlorinated VOCs, however, were widely encountered in groundwater, discharging as baseflow to surface water and impacting surface-water quality. This is attributed to their DNAPL (dense nonaqueous-phase liquid) properties and relative recalcitrance although there was some evidence of biodegradation, albeit insufficient to protect surface water and groundwater abstraction receptors. Some inorganic trends were evident across the various media; nitrate was the most significant quality concern. Generic conclusions are drawn on urban water-quality management and the need for risk-based management strategies to optimise use of urban, sporadically contaminated groundwater in conjunction with surface water highlighted.

Anions↗
PubMed2005

Taxanes in the treatment of early breast cancer.

The taxanes docetaxel and paclitaxel have established roles as two of the most active agents in the treatment of metastatic breast cancer. These two drugs are now being incorporated into the management of early breast cancer. A first generation of trials has explored whether the addition of taxanes either sequentially or in combination with adjuvant anthracycline-based chemotherapy improves outcome for patients with early breast cancer. A second generation of trials are now underway which are based on the assumption that taxanes are beneficial in the adjuvant setting, and are comparing the different taxanes, dosing regimens and the addition of further agents. Trials in the neoadjuvant setting have recently demonstrated improved response rates with the addition of taxanes into existing anthracycline-based regimes. This review critically appraises these trials and provides an overview of ongoing research in the area.

Antineoplastic Agents, Phytogenic↗
PubMed2005

Chemotherapy for breast cancer during pregnancy: an 18-year experience from five London teaching hospitals.

PURPOSE: The rare association between breast cancer and pregnancy means that few oncologists gain an expertise in this area. In particular, there are few published data concerning the use of chemotherapy for breast cancer during pregnancy. In this retrospective case series, we describe the experiences of five hospitals in London, United Kingdom, and how they manage this condition. PATIENTS AND METHODS: Retrospective searches were performed at five London hospitals in order to identify women who received chemotherapy for breast cancer while pregnant. RESULTS: Twenty-eight women were identified who had received chemotherapy for breast cancer during pregnancy. Twenty-four women received adjuvant or neoadjuvant chemotherapy for early breast cancer, and four women received palliative chemotherapy for metastatic disease. A total of 116 cycles of chemotherapy were administered during pregnancy. Sixteen women were treated with anthracycline-based chemotherapy and 12 received cyclophosphamide, methotrexate, and fluorouracil. All but one of the women were treated after the first trimester. One spontaneous abortion occurred in the woman treated during her first trimester; otherwise, there were no serious adverse consequences for the mothers or neonates. CONCLUSION: These data provide evidence that in terms of peripartum complications and immediate fetal outcome, chemotherapy can be safely administered to women during the second and third trimesters of pregnancy.

Adult↗
PubMed2005

Recent advances in the use of aromatase inhibitors for women with postmenopausal breast cancer.

The aromatase enzyme catalyses the last step in estrogen biosynthesis. There are two classes of third-generation aromatase inhibitors: irreversible steroidal inhibitors (e.g. exemestane) and reversible non-steroidal inhibitors (e.g. anastrozole, letrozole). All three agents have been found to be equivalent or superior to megestrol acetate as second-line therapy for metastatic breast cancer. In the first-line setting, large phase III trials have shown that all three are equivalent or superior to tamoxifen in women with metastatic disease. Several large trials with varying study designs have been launched to analyse their role in the adjuvant setting. The four that have reported found longer average disease-free survival for women who received an aromatase inhibitor than for those who did not. In addition, one trial, MA.17, has shown a survival advantage associated with the use of an aromatase inhibitor in node-positive patients. Guidelines produced by the American Society of Clinical Oncology suggest that adjuvant therapy for postmenopausal women with hormone-receptor-positive breast cancer should include an aromatase inhibitor. However, the long-term consequences of estrogen deprivation in postmenopausal women remain uncertain, particularly with regard to bone and cardiovascular health. The advantages and disadvantages of different hormonal strategies should therefore be carefully considered in each individual case.

Anastrozole↗
PubMed2002

Predictors of response to systemic therapy in breast cancer.

The most appropriate systemic therapy for a population of patients with breast cancer is determined from clinical trial data. However, the heterogeneity of breast cancer is such that within a population individual patients derive variable benefit. There is therefore a need for predictive molecular factors in order that treatment can be individualised. This review describes the roles of HER-2, epidermal growth factor receptor (EGFR), oestrogen receptor (ER)/progesterone receptor (PgR), Ki67, Bcl-2, p53 and gene expression profiling in predicting responses to endocrine, cytotoxic and biological therapies. ER and PgR remain the only well-established predictive markers of responses to endocrine therapy, although HER-2/neu has an emerging role in this area and in choice of adjuvant chemotherapy. There are considerable methodological difficulties in identifying useful predictive factors but on the basis of current evidence other biomarkers add little additional information. The development of targeted therapies means that the molecular targets themselves may become useful predictive factors for directing use of these therapies. HER-2 already has an established role in this area, but the role of EGFR requires further elaboration. The use of DNA microarrays to assess gene expression profiles may revolutionise our ability to predict responses to therapy.

Antibodies, Monoclonal↗