291 research outputs found
Geochemical and mineralogical record of the impact of mining on the Teign Estuary, Devon, UK
Previous mineralogical and geochemical studies on the sediments in the Teign Estuary, Devon, UK, have shown that there are elevated levels of barium present within the surface sediments and the river catchment due to historical mining. For this investigation, 8 shallow cores (<1 m) were recovered from various locations in the estuary. These cores were subsequently logged, photographed and divided into approximately 5 cm depth intervals. The geochemistry and mineralogy of 68 samples from the cores were analysed. Bulk sediment geochemistry was determined by XRF and data for Ba, Cu, Pb and Zn are presented here. The mineralogy of the samples was determined by XRD. In addition, the samples from two cores were selected for mineralogical analysis using automated SEM-EDS (QEMSCAN®). The data show a sediment depth related geochemical trend with typically the lowest concentrations of Ba, Cu, Zn and Pb at the bases of the cores. Several of the sampling sites reveal a marked peak in the concentration of Pb and Zn mid-core; however, Cu values are low and invariant throughout. Postdating the Pb-Zn peak, there is a subsequent elevation in Ba in many of the cores studied, at a sediment depth of between 10 and 20 cm. Maximum concentrations of Ba reach 3360 ppm; Pb, 2220 ppm; Zn, 887 ppm and Cu, 258 ppm. Detrital minerals present include: barite, rutile, ilmenite, zircon, monazite, pyrite, cassiterite, sphalerite, galena and chalcopyrite. Framboidal pyrite is the only diagenetic mineral observed. The geochemical results are consistent with the historical mining records in the catchment, with barite mining postdating Pb-Zn mining. Both episodes of mining have released particulate mine waste, which has accumulated within the estuarine sediments
Clustering in 18O - absolute determination of branching ratios via high-resolution particle spectroscopy
The determination of absolute branching ratios for high-energy states in light nuclei is an important and useful tool for probing the underlying nuclear structure of individual resonances: for example, in establishing the tendency of an excited state towards
α
-cluster structure. Difficulty arises in measuring these branching ratios due to similarities in available decay channels, such as (
18
O,
n
) and (
18
O,
2
n
), as well as differences in geometric efficiencies due to population of bound excited levels in daughter nuclei. Methods are presented using Monte Carlo techniques to overcome these issues
The Godrevy dog; Early canine or lost pet ?
During sampling of the late Devensian St. Loy Member of the Penwith Formation at Godrevy, Cornwall, several ribs and vertebrae were discovered within the cliff face. The visible bones appeared in context with the surrounding geology with no evidence for later site disturbance or burial. During the excavation the skeleton was entirely enclosed within the coarse grained head deposits. The skeleton was articulated and nearly complete and is identified as Canis familiaris, the"domestic" dog. The recovery of this skeleton from the St. Loy Member of the Penwith Formation, generally regarded to be of mid to late Devensian age, is scientifically problematic. The accepted age for the late Devensian is 12-15,000 years BP. The oldest known domestic dogs are dated at about 10,000 years BP, although the burial of a dog or wolf puppy with a human skeleton from Israel 12,000 yrs BP is taken as early evidence of domestication. There are three possible interpretations: (1) the St. Loy Member of the Penwith Formation is younger than previously thought; (2) that Godrevy dog is a very early domestic dog; (3) that it is possible to incorporate a rcent articulated dog skeleton into Quaternary head deposits without any signs of physical disturbance at the site. Dating of the right radius bone by accelerator mass spectrometry has given a likely age for the skeleton of between 1620 AD and 1680 AD. Thus a 17th century domestic dog has been enclosed within Devensian coarse grained head deposits with no signs of disturbance to the site
Cool early Albian climates; new data from Argentina
Previous studies on the stable isotope geochemistry of dimitobelid belemnites from Antarctica and Australia indicated cool climatic conditions during the early Albian in the shelf seas around the Gondwanan margin. In this paper new analyses from diagenetically unaltered specimens of Dimitobelus cf. stimulus from early Albian deposits of the Rio Mayer Formation of Lago San Martin, southern Argentina are presented. Oxygen isotope values for diagenetically least altered samples give values ranging between d18O C0.07 and C0.96 vPDB, which equate to a mean palaeotemperature of 9.5 (C (assuming dw of 1.2& SMOW). These data are consistent with a model of cool early Albian shelf seas in the Southern Hemisphere.Facultad de Ciencias Naturales y Muse
Cool early Albian climates; new data from Argentina
Previous studies on the stable isotope geochemistry of dimitobelid belemnites from Antarctica and Australia indicated cool climatic conditions during the early Albian in the shelf seas around the Gondwanan margin. In this paper new analyses from diagenetically unaltered specimens of Dimitobelus cf. stimulus from early Albian deposits of the Rio Mayer Formation of Lago San Martin, southern Argentina are presented. Oxygen isotope values for diagenetically least altered samples give values ranging between d18O C0.07 and C0.96 vPDB, which equate to a mean palaeotemperature of 9.5 (C (assuming dw of 1.2& SMOW). These data are consistent with a model of cool early Albian shelf seas in the Southern Hemisphere.Facultad de Ciencias Naturales y Muse
Cool early Albian climates; new data from Argentina
Previous studies on the stable isotope geochemistry of dimitobelid belemnites from Antarctica and Australia indicated cool climatic conditions during the early Albian in the shelf seas around the Gondwanan margin. In this paper new analyses from diagenetically unaltered specimens of Dimitobelus cf. stimulus from early Albian deposits of the Rio Mayer Formation of Lago San Martin, southern Argentina are presented. Oxygen isotope values for diagenetically least altered samples give values ranging between d18O C0.07 and C0.96 vPDB, which equate to a mean palaeotemperature of 9.5 (C (assuming dw of 1.2& SMOW). These data are consistent with a model of cool early Albian shelf seas in the Southern Hemisphere.Facultad de Ciencias Naturales y Muse
Clinical Outcomes and Survival Following Treatment of Metastatic Castrate-Refractory Prostate Cancer With Docetaxel Alone or With Strontium-89, Zoledronic Acid, or Both
Importance Bony metastatic castrate-refractory prostate cancer (CRPC) has a poor prognosis and high morbidity. Zoledronic acid (ZA) is commonly combined with docetaxel in practice but lacks evidence that combining is effective, and strontium-89 (Sr89) is generally used palliatively in patients unfit for chemotherapy. Phase 2 analysis of the TRAPEZE trial confirmed combining the agents was safe and feasible, and the objectives of phase 3 include assessment of the treatments on survival.
Objective To determine clinical effectiveness and cost-effectiveness of combining docetaxel, ZA, and Sr89, all having palliative benefits and used in bony metastatic CRPC to control bone symptoms and, for docetaxel, to prolong survival.
Design, Setting, and Participants The TRAPEZE trial is a 2 × 2 factorial trial comparing docetaxel alone or with ZA, Sr89, or both. A cohort of 757 participants were recruited between February 2005 and February 2012 from hospitals in the United Kingdom. Overall, 169 participants (45%) had received palliative radiotherapy, and the median (IQR) prostate-specific antigen level was 146 (51-354). Follow-ups were performed for at least 12 months.
Interventions Up to 10 cycles of docetaxel alone; docetaxel with ZA; docetaxel with a single Sr89 dose after 6 cycles; or docetaxel with both ZA and Sr89.
Main Outcomes and Measures Primary outcomes included clinical progression-free survival (CPFS) (pain progression, skeletal-related events [SREs], or death) and cost-effectiveness. Secondary outcomes included SRE-free interval, pain progression–free interval, total SREs, and overall survival (OS).
Results Overall, of 757 participants, 349 (46%) completed docetaxel treatment. Median (IQR) age was 68 (63-73) years. Clinical progression-free survival did not reach statistical significance for either Sr89 or ZA. Cox regression analysis adjusted for all stratification variables showed benefit of Sr89 on CPFS (hazard ratio [HR], 0.85; 95% CI, 0.73-0.99; P = .03) and confirmed no effect of ZA (HR, 0.98; 95% CI, 0.85-1.14; P = .81); ZA had a significant effect on SRE-free interval (HR, 0.78; 95% CI, 0.65-0.95; P = .01). For OS, there was no effect of either Sr89 (HR, 0.92; 95% CI, 0.79-1.08; P = 0.34) or ZA (HR, 0.99; 95% CI, 0.84-1.16; P = 0.91).
Conclusions and Relevance Strontium-89 combined with docetaxel improved CPFS but did not improve OS, SRE-free interval, or total SREs; ZA did not improve CPFS or OS but did significantly improve median SRE-free interval and reduced total SREs by around one-third, suggesting a role as postchemotherapy maintenance therapy
Urinary EpCAM in urothelial bladder cancer patients: characterisation and evaluation of biomarker potential
Background:
Epithelial cell adhesion molecule is overexpressed in bladder tumours and released from bladder cancer cells in vitro. We test the hypotheses that urinary EpCAM could act as a biomarker for primary bladder cancer detection and risk stratification.
Methods:
Epithelial cell adhesion molecule was measured by ELISA in urine from 607 patients with primary bladder tumours and in urine from 53 non-cancer controls. Mann–Whitney tests and ROC analyses were used to determine statistical significance and discrimination between non-cancer controls and different stages and grades of disease. Multivariable modelling and Kaplan–Meier analyses were used to determine prognostic significance. The structure of urinary EpCAM was investigated by western blotting and mass spectrometry.
Results:
Urinary EpCAM levels increase with stage and grade of bladder cancer. Alongside grade and stage, elevated urinary EpCAM is an independent indicator of poor prognosis with a hazard ratio of 1.76 for bladder cancer-specific mortality. The soluble form of EpCAM in urine is the extracellular domain generated by cleavage between ala243 and gly244. Further studies are required to define the influence of other urinary tract malignancies and benign urological conditions on urinary EpCAM.
Conclusion:
The extracellular domain of EpCAM is shed into urine by bladder tumours. Urinary EpCAM is a strong indicator of bladder cancer-specific survival, and may be useful within a multi-marker panel for disease detection or as a stand-alone marker to prioritise the investigation and treatment of patients. The mechanisms and effects of EpCAM cleavage in bladder cancer are worthy of further investigation, and may identify novel therapeutic targets
Hepatic transcriptional responses to copper in the three-spined stickleback are affected by their pollution exposure history
This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Some fish populations inhabiting contaminated environments show evidence of increased chemical tolerance, however the mechanisms contributing to this tolerance, and whether this is heritable, are poorly understood. We investigated the responses of two populations of wild three-spined stickleback (Gasterosteus aculeatus) with different histories of contaminant exposure to an oestrogen and copper, two widespread aquatic pollutants. Male stickleback originating from two sites, the River Aire, with a history of complex pollution discharges, and Siblyback Lake, with a history of metal contamination, were depurated and then exposed to copper (46μg/L) and the synthetic oestrogen ethinyloestradiol (22ng/L). The hepatic transcriptomic response was compared between the two populations and to a reference population with no known history of exposure (Houghton Springs, Dorset). Gene responses included those typical for both copper and oestrogen, with no discernable difference in response to oestrogen between populations. There was, however, some difference in the magnitude of response to copper between populations. Siblyback fish showed an elevated baseline transcription of genes encoding metallothioneins and a lower level of metallothionein induction following copper exposure, compared to those from the River Aire. Similarly, a further experiment with an F1 generation of Siblyback fish bred in the laboratory found evidence for elevated transcription of genes encoding metallothioneins in unexposed fish, together with an altered transcriptional response to 125μg/L copper, compared with F1 fish originating from the clean reference population exposed to the same copper concentration. These data suggest that the stickleback from Siblyback Lake have a differential response to copper, which is inherited by the F1 generation in laboratory conditions, and for which the underlying mechanism may include an elevation of baseline transcription of genes encoding metallothioneins. The genetic and/or epigenetic mechanisms contributing to this inherited alteration of metallothionein transcription have yet to be established.This work was funded by the UK NERC postgenomic and proteomic programme grant NE/C507661/1 and by a Fisheries Society of the British Isles research grant to EMS. Birmingham functional genomics facilities were funded by BBSRC grant 6/JIF13209. We thank R.E. Godfrey, S. Jondhale, A. Jones, and L. Klovrza for technical assistance, J.K. Chipman for help and support, and the Environment Agency for provision of water chemistry data
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