Decision-analytic cost-effectiveness model to compare prostate cryotherapy to androgen deprivation therapy for treatment of radiation recurrent prostate cancer

Objective: To determine the cost-effectiveness of salvage cryotherapy (SC) in men with radiation recurrent prostate cancer (RRPC). Design: Cost-utility analysis using decision analytic modelling by a Markov model. Setting and methods: Compared SC and androgen deprivation therapy (ADT) in a cohort of patients with RRPC (biopsy proven local recurrence, no evidence of metastatic disease). A literature review captured published data to inform the decision model, and resource use data were from the Scottish Prostate Cryotherapy Service. The model was run in monthly cycles for RRPC men, mean age of 70 years. The model was run over the patient lifetime, to assess changes in patient health states and the associated quality of life, survival and cost impacts. Results are reported in terms of the discounted incremental costs and discounted incremental quality-adjusted life years (QALYs) gained between the 2 alternative interventions. Probabilistic sensitivity analysis used a 10 000 iteration Monte Carlo simulation. Results: SC has a high upfront treatment cost, but delays the ongoing monthly cost of ADT. SC is the dominant strategy over the patient lifetime; it is more effective with an incremental 0.56 QALY gain (95% CI 0.28 to 0.87), and less costly with a reduced lifetime cost of £29 719 (€37 619) (95% CI −51 985 to −9243). For a ceiling ratio of £30 000, SC has a 100% probability to be cost-effective. The cost neutral point was at 3.5 years, when the upfront cost of SC (plus any subsequent cumulative cost of side effects and ADT) equates the cumulative cost in the ADT arm. Limitations of our model may arise from its insensitivity to parameter or structural uncertainty. Conclusions: The platform for SC versus ADT cost-effective analysis can be employed to evaluate other treatment modalities or strategies in RRPC. SC is the dominant strategy, costing less over a patient's lifetime with improvements in QALYs

Using comparative genomic hybridization to survey genomic sequence divergence across species: a proof-of-concept from Drosophila

<p>Abstract</p> <p>Background</p> <p>Genome-wide analysis of sequence divergence among species offers profound insights into the evolutionary processes that shape lineages. When full-genome sequencing is not feasible for a broad comparative study, we propose the use of array-based comparative genomic hybridization (aCGH) in order to identify orthologous genes with high sequence divergence. Here we discuss experimental design, statistical power, success rate, sources of variation and potential confounding factors. We used a spotted PCR product microarray platform from <it>Drosophila melanogaster </it>to assess sequence divergence on a gene-by-gene basis in three fully sequenced heterologous species (<it>D. sechellia</it>, <it>D. simulans</it>, and <it>D. yakuba</it>). Because complete genome assemblies are available for these species this study presents a powerful test for the use of aCGH as a tool to measure sequence divergence.</p> <p>Results</p> <p>We found a consistent and linear relationship between hybridization ratio and sequence divergence of the sample to the platform species. At higher levels of sequence divergence (< 92% sequence identity to <it>D. melanogaster</it>) ~84% of features had significantly less hybridization to the array in the heterologous species than the platform species, and thus could be identified as "diverged". At lower levels of divergence (≥ 97% identity), only 13% of genes were identified as diverged. While ~40% of the variation in hybridization ratio can be accounted for by variation in sequence identity of the heterologous sample relative to <it>D. melanogaster</it>, other individual characteristics of the DNA sequences, such as GC content, also contribute to variation in hybridization ratio, as does technical variation.</p> <p>Conclusions</p> <p>Here we demonstrate that aCGH can accurately be used as a proxy to estimate genome-wide divergence, thus providing an efficient way to evaluate how evolutionary processes and genomic architecture can shape species diversity in non-model systems. Given the increased number of species for which microarray platforms are available, comparative studies can be conducted for many interesting lineages in order to identify highly diverged genes that may be the target of natural selection.</p

Enhancing thermoelectric properties of NaCo2O4 ceramics through Na pre-treatment induced nano-decoration

High quality NaCo2O4 thermoelectrics are challenging to process due to the volatile nature of Na, the slow densification kinetics, and degradation of NaCo2O4 above 900–950 °C leading to the formation of Na-poor second phases. Fine grained sol-gel derived powders have been used to enhance the densification kinetics while pre-treatment of the NaCo2O4 powder with NaOH, to provide a Na rich environment, has been shown to mitigate Na loss at elevated temperatures. While insufficient to compensate for Na loss at processing temperatures of 1000 °C and above, at lower temperatures it is able to enhance densification and facilitate the formation of complex crystal structures yielding low thermal conductivity (0.66 Wm−1K−1) coupled with high electrical conductivity (3.8 × 103 Sm−1) and a Seebeck coefficient of 34.9. The resultant room temperature power factor and ZT were 6.19 × 10−6 Wm−1K−2 and 0.0026, respectively

Lithospheric structure of an Archean craton and adjacent mobile belt revealed from 2-D and 3-D inversion of magnetotelluric data : example from southern Congo craton in northern Namibia

Author Posting. © American Geophysical Union, 2013. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Solid Earth 118 (2013): 4378–4397, doi:10.1002/jgrb.50258.Archean cratons, and the stitching Proterozoic orogenic belts on their flanks, form an integral part of the Southern Africa tectonic landscape. Of these, virtually nothing is known of the position and thickness of the southern boundary of the composite Congo craton and the Neoproterozoic Pan-African orogenic belt due to thick sedimentary cover. We present the first lithospheric-scale geophysical study of that cryptic boundary and define its geometry at depth. Our results are derived from two-dimensional (2-D) and three-dimensional (3-D) inversion of magnetotelluric data acquired along four semiparallel profiles crossing the Kalahari craton across the Damara-Ghanzi-Chobe belts (DGC) and extending into the Congo craton. Two-dimensional and three-dimensional electrical resistivity models show significant lateral variation in the crust and upper mantle across strike from the younger DGC orogen to the older adjacent cratons. We find Damara belt lithosphere to be more conductive and significantly thinner than that of the adjacent Congo craton. The Congo craton is characterized by very thick (to depths of  250 km) and resistive (i.e., cold) lithosphere. Resistive upper crustal features are interpreted as caused by igneous intrusions emplaced during Pan-African magmatism. Graphite-bearing calcite marbles and sulfides are widespread in the Damara belt and account for the high crustal conductivity in the Central Zone. The resistivity models provide new constraints on the southern extent of the greater Congo craton and suggest that the current boundary drawn on geological maps needs revision and that the craton should be extended further south.The SAMTEX consortiummembers (Dublin Institute for Advanced Studies, Woods Hole Oceanographic Institution, Council for Geoscience (South Africa), De Beers Group Services, The University of the Witwatersrand, Geological Survey of Namibia, Geological Survey of Botswana, Rio Tinto Mining and Exploration, BHP Billiton, Council for Scientific and Industrial Research (South Africa), and ABB Sweden) are thanked for their funding and logistical support during the four phases of data acquisition. This work is also supported by research grants from the National Science Foundation (EAR-0309584 and EAR-0455242 through the Continental Dynamics Program to R. L. Evans), the Department of Science and Technology, South Africa, and Science Foundation of Ireland (grant 05/RFP/ GEO001to A. G. Jones).2014-02-0

Efficacy of temsirolimus in metastatic chromophobe renal cell carcinoma

&lt;p&gt;Background: Renal cell carcinoma (RCC) is a histopathologically and molecularly heterogeneous disease with the chromophobe subtype (chRCC) accounting for approximately 5% of all cases. The median overall survival of advanced RCC has improved significantly since the advent of tyrosine kinase inhibitors and mammalian target of rapamycin (mTOR) inhibitors. However, high-quality evidence for the use of new generation tyrosine kinase inhibitors in patients with advanced chRCC is lacking. Few published case reports have highlighted the use of temsirolimus in chRCC.&lt;/p&gt; &lt;p&gt;Case presentation: Here, we report the case of a 36-year-old Caucasian woman with metastatic chRCC with predominantly skeletal metastases who was refractory to sunitinib who demonstrated a durable clinical response to temsirolimus lasting 20 months. We review the available evidence pertaining to the use of new generation molecularly targeted agents, in particular mTOR inhibitors in chRCC and discuss their emerging role in the management of this disease which would aid the oncologists faced with the challenge of treating this rare type of RCC.&lt;/p&gt; &lt;p&gt;Conclusion: Conducting randomised clinical trials in this rarer sub-group of patients would be challenging and our case report and the evidence reviewed would guide the physicians to make informed decision regarding the management of these patients.&lt;/p&gt

Site selection strategy for environmental monitoring in connection with shale-gas exploration: Vale of Pickering, Yorkshire and Fylde, Lancashire

This report outlines the strategies for site selection adopted as part of a baseline environmental monitoring investigation in connection with shale-gas exploration and development in the Vale of Pickering, North Yorkshire. The project forms an extension to an ongoing baseline investigation being carried out in the Fylde, Lancashire, and the current project incorporates an air-quality monitoring component that was not within the original remit of the Fylde study. The DECC-funded investigation is led by the British Geological Survey, and is being carried out as a collaboration with the Universities of Birmingham, Bristol, Liverpool, Manchester and York (National Centre for Atmospheric Science, NCAS) and Public Health England (PHE). The project incorporates work packages in monitoring of water quality, air quality and greenhouse gases, soil gas, ground motion and seismicity, and air radon and is being carried out over the period September 2015 to March 2016. Site selection is a critical consideration in setting up a monitoring programme as chosen sites need to be representative of conditions to be tested. While sites will necessarily be subject to practical constraints (land access agreements, existing infrastructure, geological conditions, cost implications etc), site selection has a large part to play in ensuring collection of quantifiable, unbiased data. This report sets out the rationale for site selection in each of the work packages and the steps taken to ensure defensible site-selection decisions and to minimise the impact of practical constraints

Anomalous mid-twentieth century atmospheric circulation change over the South Atlantic compared to the last 6000 years

Determining the timing and impact of anthropogenic climate change in data-sparse regions is a considerable challenge. Arguably, nowhere is this more difficult than the Antarctic Peninsula and the subantarctic South Atlantic where observational records are relatively short but where high rates of warming have been experienced since records began. Here we interrogate recently developed monthly-resolved observational datasets from the Falkland Islands and South Georgia, and extend the records back using climate-sensitive peat growth over the past 6000 years. Investigating the subantarctic climate data with ERA-Interim and Twentieth Century Reanalysis, we find that a stepped increase in precipitation across the 1940s is related to a change in synoptic atmospheric circulation: a westward migration of quasi-permanent positive pressure anomalies in the South Atlantic has brought the subantarctic islands under the increased influence of meridional airflow associated with the Amundsen Sea Low. Analysis of three comprehensively multi-dated (using 14C and 137Cs) peat sequences across the two islands demonstrates unprecedented growth rates since the mid-twentieth century relative to the last 6000 years. Comparison to observational and reconstructed sea surface temperatures suggests this change is linked to a warming tropical Pacific Ocean. Our results imply 'modern' South Atlantic atmospheric circulation has not been under this configuration for millennia