Regional geothermal aquifer architecture of the fluvial Lower Cretaceous Nieuwerkerk Formation – a palynological analysis

The primary challenge for efficient geothermal doublet design and deployment is the adequate prediction of the size, shape, lateral extent and thickness (or aquifer architecture) of aquifers. In the West Netherlands Basin, fluvial Lower Cretaceous sandstone-rich successions form the main aquifers for geothermal heat exploitation. Large variations in the thickness of these successions are recognised in currently active doublet systems that cannot be explained. This creates an uncertainty in aquifer thickness prediction, which increases the uncertainty in doublet lifetime prediction as it has an impact on net aquifer volume. The goal of this study was to improve our understanding of the thickness variations and regional aquifer architecture of the Nieuwerkerk Formation geothermal aquifers. For this purpose, new palynological data were evaluated to correlate aquifers in currently active doublet systems based on their chronostratigraphic position and regional Maximum Flooding Surfaces. Based on the palynological cuttings analysis, the fluvial interval of the Nieuwerkerk Formation was subdivided into two successions: a Late Ryazanian to Early Valanginian succession and a Valanginian succession. Within these successions trends were identified in sandstone content. In combination with seismic interpretation, maps were constructed that predict aquifer thickness and their lateral extent in the basin. The study emphasises the value of palynological analyses to reduce the uncertainty of fluvial hot sedimentary aquifer exploitation

Effect of posttranslational modification on the Na+, K+ ATPase kinetics

The Na+, K+ ATPase is an essential membrane protein in eukaryotic cells, which transports Na+ out of the cell in exchange for K+ into the cell. For this transport it hydrolyses one molecule of ATP for each cycle. The partial reactions of the ATPase cycle and the effects of posttranslational modifications on ATPase activity have been studied extensively. However, amalgamation of the reported rate constants for the partial reactions along with the effect of posttranslational modifications have never been attempted. We have designed a simplified four-state mathematical model of the Na+, K+ ATPase using published results for the partial reactions. We have incorporated the effect of the Na+ allosteric site and poise dependent glutathionylation and attempted to replicate K+ activated transient currents reported in voltage clamped cardiomyocytes. Our voltage clamped cardiomyocyte results indicate the K+ activated transient is an effect of poise dependent glutathionylation rather than the Na+ subsarcolemmal space. These results can be replicated to some extent by the proposed kinetic model. This is the first kinetic model of the Na+, K+ ATPase that incorporates both partial rate constants and a reported posttranslational modification which is able to reproduce voltage clamped cardiomyocyte data

Public perception of geothermal energy at the local level in the UK

Successful development of a new renewable energy technology does not only rely on the success of pilot projects but also to a significant extent on the development of an adequate public engagement strategy. To be able to develop such a strategy a good understanding is required of the public perception of the new technology. Geothermal energy is still an emerging technology in the UK; in the absence of public debate on this topic, media reporting provides a suitable proxy for its public perception. Therefore, this study has gauged the public perception of geothermal energy in the UK by evaluating local news articles from 1980 to 2018. A coding scheme was developed to derive the main themes and to identify both the perceived advantages and hurdles for geothermal development. We focussed on local newspapers to be able to compare public perception in different regions in the UK. Results show a mainly positive perception of geothermal energy in all geographical regions across the UK. Only few articles mention risks, induced seismicity and environmental pollution. In contrast, advantages and positive aspects of geothermal energy, such as its carbon neutral footprint, the enormous amount of available geothermal heat and the potential contribution of geothermal development to the revival of local economies, are much more frequently mentioned. Perceived hurdles that are mostly described in the articles are: (1) the absence of geothermal legislation and subsidies in the UK; (2) the lack of available funding; and finally (3) technological and geological challenges or uncertainties. Finally, we show that geothermal energy is most often related to electricity generation and granite resources, while the only successful deep geothermal site in the UK is a direct-use heating scheme exploiting a sedimentary aquifer

Global Spread of Vancomycin-resistant Enterococcus faecium from Distinct Nosocomial Genetic Complex

Vancomycin-resistant enterococci (VRE) have caused hospital outbreaks worldwide, and the vancomycin-resistance gene (vanA) has crossed genus boundaries to methicillin-resistant Staphylococcus aureus. Spread of VRE, therefore, represents an immediate threat for patient care and creates a reservoir of mobile resistance genes for other, more virulent pathogens. Evolutionary genetics, population structure, and geographic distribution of 411 VRE and vancomycin-susceptible Enterococcus faecium isolates, recovered from human and nonhuman sources and community and hospital reservoirs in 5 continents, identified a genetic lineage of E. faecium (complex-17) that has spread globally. This lineage is characterized by 1) ampicillin resistance, 2) a pathogenicity island, and 3) an association with hospital outbreaks. Complex-17 is an example of cumulative evolutionary processes that improved the relative fitness of bacteria in hospital environments. Preventing further spread of this epidemic E. faecium subpopulation is critical, and efforts should focus on the early disclosure of ampicillin-resistant complex-17 strains

Epidemic and Nonepidemic Multidrug-Resistant Enterococcus faecium

The epidemiology of vancomycin-resistant Enterococcus faecium (VREF) in Europe is characterized by a large community reservoir. In contrast, nosocomial outbreaks and infections (without a community reservoir) characterize VREF in the United States. Previous studies demonstrated host-specific genogroups and a distinct genetic lineage of VREF associated with hospital outbreaks, characterized by the variant esp-gene and a specific allele-type of the purK housekeeping gene (purK1). We investigated the genetic relatedness of vanA VREF (n=108) and vancomycin-susceptible E. faecium (VSEF) (n=92) from different epidemiologic sources by genotyping, susceptibility testing for ampicillin, sequencing of purK1, and testing for presence of esp. Clusters of VSEF fit well into previously described VREF genogroups, and strong associations were found between VSEF and VREF isolates with resistance to ampicillin, presence of esp, and purK1. Genotypes characterized by presence of esp, purK1, and ampicillin resistance were most frequent among outbreak-associated isolates and almost absent among community surveillance isolates. Vancomycin-resistance was not specifically linked to genogroups. VREF and VSEF from different epidemiologic sources are genetically related; evidence exists for nosocomial selection of a subtype of E. faecium, which has acquired vancomycin-resistance through horizontal transfer

Anacetrapib reduces progression of atherosclerosis, mainly by reducing non-HDL-cholesterol, improves lesion stability and adds to the beneficial effects of atorvastatin

The present study is the first intervention study in a well-established, translational mouse model for hyperlipidaemia and atherosclerosis showing that anacetrapib dose-dependently reduces atherosclerosis development and adds to the anti-atherogenic effects of atorvastatin. This effect is mainly ascribed to the reduction in non-HDL-C despite a remarkable increase in HDL-C and without affecting HDL functionality. In addition, anacetrapib improves lesion stabilit

Micro-costing diagnostics in oncology: From single-gene testing to whole genome sequencing

Purpose: Predictive diagnostics play an increasingly important role in personalized medicine for cancer treatment. Whole genome sequencing (WGS) based treatment selection is expected to rapidly increase worldwide. Detailed and comparative cost analyses of diagnostic techniques are an essential element in decision-making. This study aimed to calculate and compare the total cost of currently used diagnostic techniques and of WGS in treatment of non-small cell lung carcinoma (NSCLC), melanoma, colorectal cancer (CRC) and gastrointestinal stromal tumor (GIST) in the Netherlands. Methods: The activity-based costing (ABC) method was conducted to calculate the total cost of included diagnostic techniques based on data provided by Dutch pathology laboratories and the Dutch centralized cancer WGS facility. Costs were allocated to four categories: capital costs, maintenance costs, software costs and operational costs. Outcome measures were total cost per cancer patient per included technique, and the total cost per cancer patient per most commonly applied technique (combination) for each cancer type. Results: The total cost per cancer patient per technique varied from € 58 (Sanger sequencing, 3 amplicons) to € 4738 (paired tumor-normal WGS). The operational costs accounted for the vast majority over 90 % of the total per cancer patient technique costs. The most important operational cost drivers were consumables followed by personnel (for sample preparation and primary data analysis). Conclusion: This study outlined in detail all costing aspects and cost prices of current and new diagnostic modalities used in treatment of NSCLC, melanoma, CRC and GIST in the Netherlands. Detailed cost differences and value comparisons between these diagnostic techniques enable future economic evaluations to support decision-making on implementation of WGS and other diagnostic modalities in routine clinical practice