There is an urgent need to identify biomarkers to guide personalized therapy in castration-resistant prostate cancer (CRPC). We aimed to clinically qualify androgen receptor (AR) gene status ...measurement in plasma DNA using multiplex droplet digital PCR (ddPCR) in pre- and post-chemotherapy CRPC.
We optimized ddPCR assays for AR copy number and mutations and retrospectively analyzed plasma DNA from patients recruited to one of the three biomarker protocols with prospectively collected clinical data. We evaluated associations between plasma AR and overall survival (OS) and progression-free survival (PFS) in 73 chemotherapy-naïve and 98 post-docetaxel CRPC patients treated with enzalutamide or abiraterone (Primary cohort) and 94 chemotherapy-naïve patients treated with enzalutamide (Secondary cohort; PREMIERE trial).
In the primary cohort, AR gain was observed in 10 (14%) chemotherapy-naïve and 33 (34%) post-docetaxel patients and associated with worse OS hazard ratio (HR), 3.98; 95% CI 1.74–9.10; P < 0.001 and HR 3.81; 95% CI 2.28–6.37; P < 0.001, respectively, PFS (HR 2.18; 95% CI 1.08–4.39; P = 0.03, and HR 1.95; 95% CI 1.23–3.11; P = 0.01, respectively) and rate of PSA decline≥50% odds ratio (OR), 4.7; 95% CI 1.17–19.17; P = 0.035 and OR, 5.0; 95% CI 1.70–14.91; P = 0.003, respectively. AR mutations 2105T>A (p.L702H) and 2632A>G (p.T878A) were observed in eight (11%) post-docetaxel but no chemotherapy-naïve abiraterone-treated patients and were also associated with worse OS (HR 3.26; 95% CI 1.47–not reached; P = 0.004). There was no interaction between AR and docetaxel status (P = 0.83 for OS, P = 0.99 for PFS). In the PREMIERE trial, 11 patients (12%) with AR gain had worse PSA-PFS (sPFS) (HR 4.33; 95% CI 1.94–9.68; P < 0.001), radiographic-PFS (rPFS) (HR 8.06; 95% CI 3.26–19.93; P < 0.001) and OS (HR 11.08; 95% CI 2.16–56.95; P = 0.004). Plasma AR was an independent predictor of outcome on multivariable analyses in both cohorts.
Plasma AR status assessment using ddPCR identifies CRPC with worse outcome to enzalutamide or abiraterone. Prospective evaluation of treatment decisions based on plasma AR is now required.
NCT02288936 (PREMIERE trial).
Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) allows a fast and reliable bacterial identification from culture plates. Direct analysis of clinical ...samples may increase its usefulness in samples in which a fast identification of microorganisms can guide empirical treatment, such as blood cultures (BC). Three hundred and thirty BC, reported as positive by the automated BC incubation device, were processed by conventional methods for BC processing, and by a fast method based on direct MALDI-TOF MS. Three hundred and eighteen of them yield growth on culture plates, and 12 were false positive. The MALDI-TOF MS-based method reported that no peaks were found, or the absence of a reliable identification profile, in all these false positive BC. No mixed cultures were found. Among these 318 BC, we isolated 61 Gram-negatives (GN), 239 Gram-positives (GP) and 18 fungi. Microorganism identifications in GN were coincident with conventional identification, at the species level, in 83.3% of BC and, at the genus level, in 96.6%. In GP, identifications were coincident with conventional identification in 31.8% of BC at the species level, and in 64.8% at the genus level. Fungaemia was not reliably detected by MALDI-TOF. In 18 BC positive for Candida species (eight C. albicans, nine C. parapsilosis and one C. tropicalis), no microorganisms were identified at the species level, and only one (5.6%) was detected at the genus level. The results of the present study show that this fast, MALDI-TOF MS-based method allows bacterial identification directly from presumptively positive BC in a short time (<30 min), with a high accuracy, especially when GN bacteria are involved.
ABSTRACT
An electrochemical approach to directly measure the dynamic process of H2O2 release from cultures of Arabidopsis thaliana cells is reported. This approach is based on H2O2 oxidation on a Pt ...electrode in conjunction with continuous measurement of sample pH. For H2O2 <1 mm, calibration plots were linear and the amperometric response of the electrode was maximum at pH 6. At higher concentrations (H2O2 >1 mm), the amperometric response can be described by Michaelian‐type kinetics and a mathematical expression relating current intensity and pH was obtained to quantitatively determine H2O2 concentration. At pH 5.5, the detection limit of the sensor was 3.1 µm (S/N = 3), with a response sensitivity of 0.16 Am−1 cm−2 and reproducibility was within 6.1% in the range 1–5 × 10−3 m (n = 5). Cell suspensions under normal physiological conditions had a pH between 5.5–5.7 and H2O2 concentrations in the range 7.0–20.5 µm (n = 5). The addition of exogenous H2O2, as well as other potential stress stimuli, was made to the cells and the change in H2O2 concentration was monitored. This real‐time quantitative H2O2 analysis is a potential marker for the evaluation of oxidative stress in plant cell cultures.
Evaluation of H2O2 content in extracellular media can be an important oxidative burst marker in plant cell cultures. This paper shows an electrochemical method based on a Pt‐electrode which can be used for real‐time course analysis of H2O2 concentrations in plant cell suspensions. The protocol has been satisfactory applied in Arabidopsis thaliana cell suspensions and could be a first step in the development of future electrodes for in vivo monitoring of H2O2.
Summary
Background
We have observed an increase in hepatotoxicity (DILI) reporting related to the use of anabolic androgenic steroids (AAS) for bodybuilding.
Aim
To characterise phenotype ...presentation, outcome and severity of AAS DILI.
Methods
Data on 25 cases of AAS DILI reported to the Spanish (20) and Latin‐American (5) DILI Registries were collated and compared with previously published cases.
Results
AAS DILI increased from representing less than 1% of the total cases in the Spanish DILI Registry in the period 2001–2009 to 8% in 2010–2013. Young men (mean age 32 years), requiring hospitalisation, hepatocellular injury and jaundice were predominating features among the AAS cases. AAS DILI caused significantly higher bilirubin values independent of type of damage when compared to other drug classes (P = 0.001). Furthermore, the cholestatic AAS cases presented significantly higher mean peak bilirubin (P = 0.029) and serum creatinine values (P = 0.0002), compared to the hepatocellular cases. In a logistic regression model, the interaction between peak bilirubin values and cholestatic damage was associated with the development of AAS‐induced acute kidney impairment (AKI) OR 1.26 (95% CI: 1.035–1.526); P = 0.021, with 21.5 ×ULN being the best bilirubin cut‐off point for predicting AKI risk (AUCROC 0.92). No fatalities occurred.
Conclusions
Illicit recreational AAS use is a growing cause of reported DILI that can lead to severe hepatic and renal injury. AAS DILI is associated with a distinct phenotype, characterised by considerable bilirubin elevations independent of type of damage. Although hepatocellular injury predominates, acute kidney injury develops in cholestatic cases with pronounced jaundice.
The journal
Impact Factor
(IF) is not comparable among fields of science and social science because of systematic differences in publication and citation behaviour across disciplines. In this work, a ...decomposing of the field aggregate impact factor into five normally distributed variables is presented. Considering these factors, a principal component analysis is employed to find the sources of the variance in the
Journal Citation Reports
(
JCR
)
subject categories
of science and social science. Although publication and citation behaviour differs largely across disciplines, principal components explain more than 78 % of the total variance and the average number of references per paper is not the primary factor explaining the variance in impact factors across categories. The categories normalized impact factor based on the JCR subject category list is proposed and compared with the IF. This normalization is achieved by considering all the indexing categories of each journal. An empirical application, with one hundred journals in two or more subject categories of economics and business, shows that the
gap
between rankings is reduced around 32 % in the journals analyzed. This
gap
is obtained as the maximum distance among the ranking percentiles from all categories where each journal is included.
•Proposed methodology selects the optimal solution for energy valorisation of MSW.•Economic, environmental and territorial factors for WtE have been analysed.•Energy valorization is economically ...viable in medium-low production areas.•WtE generate territorial and environmental benefits in MSW management.
The application of Directive 2008/98/CE on Municipal Solid Waste (MSW) implies the need to introduce technologies to generate energy from waste. Incineration, the most widely used method, is difficult to implement in low populated areas because it requires a large amount of waste to be viable (100,000 tons per year). This paper analyses the economic and environmental costs of different MSW-to-Energy technologies (WtE) in an area comprising of 13 municipalities in southern Spain. We analyse anaerobic digestion (Biomethanization), the production of solid recovered fuel (SRF) and gasification, and compare these approaches to the present Biological Mechanical Treatment (BMT) with elimination of the reject in landfill, and incineration with energy recovery. From an economic standpoint the implementation of WtE systems reduces the cost of running present BMT systems and incineration; gasification presents the lowest value. From the environmental standpoint, Life Cycle Assessment shows that any WtE alternatives, including incineration, present important advantages for the environment when compared to BMT. Finally, in order to select the best alternative, a multi-criteria method is applied, showing that anaerobic digestion is the optimal solution for the area studied.
Abstract Metals are being utilized of ways in industries and agriculture; particularly heavy metals such as mercury, cadmium, lead and arsenic constitute a significant potential threat to human ...health because they are associated to many adverse effects on health. The consumption of fish is recommended because it is a good source of omega-3 fatty acids, which have been associated with health benefits due to its cardio-protective effects. However, the content of heavy metals discovered in some fish makes it difficult to establish clearly the role of fish consumption on a healthy diet. Therefore the present mini-review accounts for the recent evidence of the effect of these toxic metals on the human health and their possible implications in fish consumption.
•Applications of rice husk and its derivatives.•Study the available technologies for production of SiC, pure Si, Si3N4, Mg2Si, SiO2 from rice husk.•Explanation of different furnaces for production of ...rice husk ash.•Study the available technologies for production of activated carbon from rice husk.
Recently, much attention has been focused on the utilization of plant biomass to produce engineering materials, encompassing the technological/scientific aspects as well as the economic, environmental and social issues. Amongst the variety of agricultural wastes or biomasses available, rice-husk (RH) occupies a preeminent position, not only in terms of its amount produced worldwide, but also because of its unique chemistry-related features. In this sense, some attempts have been made to produce advanced materials – including SiO2, SiC, Si3N4, elemental Si, Mg2Si and more recently, active carbon –, using RH. The production of those mentioned advanced materials depends largely on the treatments used (physical and/or chemical) and the reactions involved in the process, such as pyrolysis, carbothermal and reduction processes. In this contribution, a critical review on the processing and application of rice husks (RHs) for the production of various silicon-based materials and of active carbon is presented. The review addresses the different processing methods, the effects of various process parameters on the pyrolysis stage, the influence of physical, chemical and thermal treatments, activating conditions and activated carbon consolidation mechanisms. A flow chart with all the possible routes to produce SiO2 was purposely constructed.
This report includes the reanalysis of data from a clinical trial showing a lower rate of cardiovascular events among persons assigned to a Mediterranean diet supplemented with extra-virgin olive oil ...or nuts than among those assigned to a low-fat diet.
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