PCASTt/SPCG-17-a randomised trial of active surveillance in prostate cancer : rationale and design

Introduction Overtreatment of localised prostate cancer is substantial despite increased use of active surveillance. No randomised trials help define how to monitor patients or when to initiate treatment with curative intent. Methods and analysis A randomised, multicentre, intervention trial designed to evaluate the safety of an MRI-based active surveillance protocol, with standardised triggers for repeated biopsies and radical treatment. The aim is to reduce overtreatment of prostate cancer. 2000 men will be randomly allocated to either surveillance according to current practice or to standardised triggers at centres in Sweden, Norway, Finland and the UK. Men diagnosed in the past 12 months with prostate cancer, 0.2ng/mL/cc, any International Society of Urological Pathology (ISUP) grade 1 are eligible. Men with ISUP grade 2 in Ethics and dissemination Ethical approval was obtained in each participating country. Results for the primary and secondary outcome measures will be submitted for publication in peer-reviewed journals. Trial registration number NCT02914873.Peer reviewe

The under-ice microbiome of seasonally frozen lakes

Compared to the well-studied open water of the “growing” season, under-ice conditions in lakes are characterized by low and rather constant temperature, slow water movements, limited light availability, and reduced exchange with the surrounding landscape. These conditions interact with ice-cover duration to shape microbial processes in temperate lakes and ultimately influence the phenology of community and ecosystem processes. We review the current knowledge on microorganisms in seasonally frozen lakes. Specifically, we highlight how under-ice conditions alter lake physics and the ways that this can affect the distribution and metabolism of auto- and heterotrophic microorganisms. We identify functional traits that we hypothesize are important for understanding under-ice dynamics and discuss how these traits influence species interactions. As ice coverage duration has already been seen to reduce as air temperatures have warmed, the dynamics of the under-ice microbiome are important for understanding and predicting the dynamics and functioning of seasonally frozen lakes in the near future

Safety of the Deferral of Coronary Revascularization on the Basis of Instantaneous Wave-Free Ratio and Fractional Flow Reserve Measurements in Stable Coronary Artery Disease and Acute Coronary Syndromes

OBJECTIVES The aim of this study was to investigate the clinical outcomes of patients deferred from coronary revascularization on the basis of instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) measurements in stable angina pectoris (SAP) and acute coronary syndromes (ACS). BACKGROUND Assessment of coronary stenosis severity with pressure guidewires is recommended to determine the need for myocardial revascularization. METHODS The safety of deferral of coronary revascularization in the pooled per-protocol population (n = 4,486) of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) and iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trials was investigated. Patients were stratified according to revascularization decision making on the basis of iFR or FFR and to clinical presentation (SAP or ACS). The primary endpoint was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year. RESULTS Coronary revascularization was deferred in 2,130 patients. Deferral was performed in 1,117 patients (50%) in the iFR group and 1,013 patients (45%) in the FFR group (p <0.01). At 1 year, the MACE rate in the deferred population was similar between the iFR and FFR groups (4.12% vs. 4.05%; fully adjusted hazard ratio: 1.13; 95% confidence interval: 0.72 to 1.79; p = 0.60). A clinical presentation with ACS was associated with a higher MACE rate compared with SAP in deferred patients (5.91% vs. 3.64% in ACS and SAP, respectively; fully adjusted hazard ratio: 0.61 in favor of SAP; 95% confidence interval: 0.38 to 0.99; p = 0.04). CONCLUSIONS Overall, deferral of revascularization is equally safe with both iFR and FFR, with a low MACE rate of about 4%. Lesions were more frequently deferred when iFR was used to assess physiological significance. In deferred patients presenting with ACS, the event rate was significantly increased compared with SAP at 1 year. (C) 2018 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.Peer reviewe

Microbial and Chemical Characterization of Underwater Fresh Water Springs in the Dead Sea

Due to its extreme salinity and high Mg concentration the Dead Sea is characterized by a very low density of cells most of which are Archaea. We discovered several underwater fresh to brackish water springs in the Dead Sea harboring dense microbial communities. We provide the first characterization of these communities, discuss their possible origin, hydrochemical environment, energetic resources and the putative biogeochemical pathways they are mediating. Pyrosequencing of the 16S rRNA gene and community fingerprinting methods showed that the spring community originates from the Dead Sea sediments and not from the aquifer. Furthermore, it suggested that there is a dense Archaeal community in the shoreline pore water of the lake. Sequences of bacterial sulfate reducers, nitrifiers iron oxidizers and iron reducers were identified as well. Analysis of white and green biofilms suggested that sulfide oxidation through chemolitotrophy and phototrophy is highly significant. Hyperspectral analysis showed a tight association between abundant green sulfur bacteria and cyanobacteria in the green biofilms. Together, our findings show that the Dead Sea floor harbors diverse microbial communities, part of which is not known from other hypersaline environments. Analysis of the water’s chemistry shows evidence of microbial activity along the path and suggests that the springs supply nitrogen, phosphorus and organic matter to the microbial communities in the Dead Sea. The underwater springs are a newly recognized water source for the Dead Sea. Their input of microorganisms and nutrients needs to be considered in the assessment of possible impact of dilution events of the lake surface waters, such as those that will occur in the future due to the intended establishment of the Red Sea−Dead Sea water conduit

CO2 utilization options .1. An emission assessment framework

The utilization of CO2 in various products and services must be carefully assessed in order to achieve reduced CO2 emissions and simultaneously to add to the net economic benefit of society. In this paper, a framework for the assessment of CO2 utilization options in the chemical industry is outlined in which the total CO2 emission is estimated in four steps. First, the processes under study are surveyed to establish the consumption of different raw materials (reactants). Second, the CO2 emission due to the content of fossil carbon in the reactants is determined, i.e. the material-related emission. Third, the CO2 emission related to energy consumption in the studied processes is estimated, i.e. the direct energy-related emission. Fourth, the CO2 emission related to energy consumption in the reactant production processes is estimated, i.e. the indirect energy-related emission. Copyright (C) 1996 Elsevier Science Lt

CO2 utilization options .2. Assessment of dimethyl carbonate production

In this paper, the potential to reduce CO2 emissions from dimethyl carbonate production by switching from the traditional phosgene-based production to a urea-based CO2 utilization process is assessed. The total CO2 emission for each process is estimated, including emissions related to the carbon content of the products, energy consumption in the production process, and energy consumption in the production processes of the required reactants. Implementation of the CO2 utilization process probably will reduce total CO2 emissions. However, in order to achieve substantially reduced CO2 emissions, serious consideration must be given to the optimization and design of the CO2 utilization process. Furthermore, the fuel-mix employed is one of the factors that influences the total CO2 emission the most. Copyright (C) 1996 Elsevier Science Lt

Send reprint requests to: METABOLISM OF CARBAMAZEPINE AND ITS EPOXIDE METABOLITE IN HUMAN AND RAT LIVER IN VITRO GUNNEL TYBRING, CHRISTER

ABSTRACT: The epoxidation of carbamazepine (CBZ) and the hydration of the primary epoxide metabolite was studied in microsomes isolated from ten human livers. To study the epoxide hydrolase activity a high-performance liquid-chromatographic method was developed for the analysis of dlhydro-CBZ-trans-diol. There was a pronounced variation between the specimens in the activity of both enzymes