Development and validation of an HPLC method for the determination of spironolactone and its metabolites in paediatric plasma samples

Abstract An HPLC method has been developed and validated for the determination of spironolactone, 7a-thiomethylspirolactone and canrenone in paediatric plasma samples. The method utilises 200 µl of plasma and sample preparation involves protein precipitation followed by Solid Phase Extraction (SPE). Determination of standard curves of peak height ratio (PHR) against concentration was performed by weighted least squares linear regression using a weighting factor of 1/concentration2. The developed method was found to be linear over concentration ranges of 30–1000 ng/ml for spironolactone and 25–1000 ng/ml for 7a-thiomethylspirolactone and canrenone. The lower limit of quantification for spironolactone, 7a-thiomethylspirolactone and canrenone were calculated as 28, 20 and 25 ng/ml, respectively. The method was shown to be applicable to the determination of spironolactone, 7a-thiomethylspirolactone and canrenone in paediatric plasma samples and also plasma from healthy human volunteers.

Genetic programming based formulation for fresh and hardened properties of self-compacting concrete containing pulverised fuel ash

Self-compacting concrete (SCC) flows into place and around obstructions under its own weight to fill the formwork completely and self-compact without any segregation and blocking. Elimination of the need for compaction leads to better quality concrete and substantial improvement of working conditions. This investigation aimed to show possible applicability of genetic programming (GP) to model and formulate the fresh and hardened properties of self-compacting concrete (SCC) containing pulverised fuel ash (PFA) based on experimental data. Twenty-six mixes were made with 0.38 to 0.72 water-to-binder ratio (W/B), 183–317 kg/m³ of cement content, 29–261 kg/m³ of PFA, and 0 to 1% of superplasticizer, by mass of powder. Parameters of SCC mixes modelled by genetic programming were the slump flow, JRing combined to the Orimet, JRing combined to cone, and the compressive strength at 7, 28 and 90 days. GP is constructed of training and testing data using the experimental results obtained in this study. The results of genetic programming models are compared with experimental results and are found to be quite accurate. GP has showed a strong potential as a feasible tool for modelling the fresh properties and the compressive strength of SCC containing PFA and produced analytical prediction of these properties as a function as the mix ingredients. Results showed that the GP model thus developed is not only capable of accurately predicting the slump flow, JRing combined to the Orimet, JRing combined to cone, and the compressive strength used in the training process, but it can also effectively predict the above properties for new mixes designed within the practical range with the variation of mix ingredients.

Opportunity cost based analysis of corporate eco-efficiency: A methodology and its application to the CO2-efficiency of German companies

In this paper, we propose the return-to-cost-ratio (RCR) as an alternative approach to the analysis of operational eco-efficiency of companies based on the notion of opportunity costs. RCR helps to overcome two fundamental deficits of existing approaches to eco-efficiency. (1) It translates eco-efficiency into managerial terms by applying the well-established notion of opportunity costs to eco-efficiency analysis. (2) RCR allows to identify and quantify the drivers behind changes in corporate eco-efficiency. RCR is applied to the analysis of the CO2-efficiency of German companies in order to illustrate its usefulness for a detailed analysis of changes in corporate eco-efficiency as well as for the development of effective environmental strategies. (C) 2010 Elsevier Ltd. All rights reserved.

Novel linkage to chromosome 20p using latent classes of psychotic illness in 270 Irish high-density families

Background: Several lines of evidence suggest that the clinical heterogeneity of schizophrenia is due to genetic heterogeneity. Genetic heterogeneity may decrease the signal-to-noise ratio in linkage and association studies. Therefore, linkage studies of clinically homogeneous classes of psychotic illness may result in greater power to detect at least some loci.

A high C/O ratio and weak thermal inversion in the atmosphere of exoplanet WASP-12b

The carbon-to-oxygen ratio (C/O) in a planet provides critical information about its primordial origins and subsequent evolution. A primordial C/O greater than 0.8 causes a carbide-dominated interior, as opposed to the silicate-dominated composition found on Earth; the atmosphere can also differ from those in the Solar System. The solar C/O is 0.54 (ref. 3). Here we report an analysis of dayside multi-wavelength photometry of the transiting hot-Jupiter WASP-12b (ref. 6) that reveals C/O>=1 in its atmosphere. The atmosphere is abundant in CO. It is depleted in water vapour and enhanced in methane, each by more than two orders of magnitude compared to a solar-abundance chemical-equilibrium model at the expected temperatures. We also find that the extremely irradiated atmosphere (T>2,500K) of WASP-12b lacks a prominent thermal inversion (or stratosphere) and has very efficient day-night energy circulation. The absence of a strong thermal inversion is in stark contrast to theoretical predictions for the most highly irradiated hot-Jupiter atmospheres.

Distance limits to intermediate- and high-velocity clouds

We present optical spectra of 403 stars and quasi-stellar objects in order to obtain distance limits towards intermediate- and high-velocity clouds (IHVCs), including new Fibre-fed Extended Range Optical Spectrograph (FEROS) observations plus archival ELODIE, FEROS, High Resolution Echelle Spectrometer (HIRES) and Ultraviolet and Visual Echelle Spectrograph (UVES) data. The non-detection of Ca II K interstellar (IS) absorption at a velocity of −130 to −60 km s−1 towards HDE 248894 (d ∼ 3 kpc) and HDE 256725 (d ∼ 8 kpc) in data at signal-to-noise ratio (S/N) > 450 provides a new firm lower distance limit of 8 kpc for the anti-centre shell HVC. Similarly, the non-detection of Ca II K IS absorption towards HD 86248 at S/N ∼ 500 places a lower distance limit of 7.6 kpc for Complex EP, unsurprising since this feature is probably related to the Magellanic System. The lack of detection of Na I D at S/N = 35 towards Mrk 595 puts an improved upper limit for the Na I column density of log (NNaD <) 10.95 cm−2 towards this part of the Cohen Stream where Ca II was detected by Wakker et al. Absorption at ∼ −40 km s−1 is detected in Na I D towards the Galactic star PG 0039+049 at S/N = 75, placing a firm upper distance limit of 1 kpc for the intermediate-velocity cloud south (IVS), where a tentative detection had previously been obtained by Centurion et al. Ca ´ II K and Na I D absorption is detected at −53 km s−1 towards HD 93521, which confirms the upper distance limit of 2.4 kpc for part of the IV arch complex obtained using the International Ultraviolet Explorer (IUE) data by Danly. Towards HD 216411 in Complex H a non-detection in Na D towards gas with log(NH I) = 20.69 cm−2 puts a lower distance limit of 6.6 kpc towards this HVC complex. Additionally, Na I D absorption is detected at −43.7 km s−1 in the star HD 218915 at a distance of 5.0 kpc in gas in the same region of the sky as Complex H. Finally, the Na I/Ca II and Ca II/H I ratios of the current sample are found to lie in the range observed for previous studies of IHVCs.

Resonant Rayleigh light scattering response of individual Au nanoparticles to antigen--antibody interaction

A proof-of-concept study was reported on analysis of antigen–antibody recognition based on resonant Rayleigh scattering response of single Au nanoparticles in an imaging chamber. As benefited by a traditional dark-field microscope and a spectrograph, individual Au nanoparticles (30 nm) were observed with high signal-to-noise ratio and they were effectively utilized to monitor changes in refractive index induced by specific binding of the adsorbates. Using PSA antigen as a model, a LSPR ?max shift of about 2.85 nm was recorded for a molecular binding corresponding to 0.1 pg ml-1 of the protein biomarker. This result successfully demonstrates a non-labeling detection system for proteins as well as thousands of different chemical or biological species, and it possesses a great potential as a sensitive, on-chip and multiplexing detection.

Design methodology for low power and arametric robustness through output-quality modulation:Application to color-interpolation filtering

Power dissipation and robustness to process variation have conflicting design requirements. Scaling of voltage is associated with larger variations, while Vdd upscaling or transistor upsizing for parametric-delay variation tolerance can be detrimental for power dissipation. However, for a class of signal-processing systems, effective tradeoff can be achieved between Vdd scaling, variation tolerance, and output quality. In this paper, we develop a novel low-power variation-tolerant algorithm/architecture for color interpolation that allows a graceful degradation in the peak-signal-to-noise ratio (PSNR) under aggressive voltage scaling as well as extreme process variations. This feature is achieved by exploiting the fact that all computations used in interpolating the pixel values do not equally contribute to PSNR improvement. In the presence of Vdd scaling and process variations, the architecture ensures that only the less important computations are affected by delay failures. We also propose a different sliding-window size than the conventional one to improve interpolation performance by a factor of two with negligible overhead. Simulation results show that, even at a scaled voltage of 77% of nominal value, our design provides reasonable image PSNR with 40% power savings. © 2006 IEEE.

Design methodology to trade off power, output quality and error resiliency: Application to color interpolation filtering

Power dissipation and tolerance to process variations pose conflicting design requirements. Scaling of voltage is associated with larger variations, while Vdd upscaling or transistor up-sizing for process tolerance can be detrimental for power dissipation. However, for certain signal processing systems such as those used in color image processing, we noted that effective trade-offs can be achieved between Vdd scaling, process tolerance and "output quality". In this paper we demonstrate how these tradeoffs can be effectively utilized in the development of novel low-power variation tolerant architectures for color interpolation. The proposed architecture supports a graceful degradation in the PSNR (Peak Signal to Noise Ratio) under aggressive voltage scaling as well as extreme process variations in. sub-70nm technologies. This is achieved by exploiting the fact that some computations are more important and contribute more to the PSNR improvement compared to the others. The computations are mapped to the hardware in such a way that only the less important computations are affected by Vdd-scaling and process variations. Simulation results show that even at a scaled voltage of 60% of nominal Vdd value, our design provides reasonable image PSNR with 69% power savings.

Strength model for end cover separation failure in RC beams strengthened with near-surface mounted (NSM) FRP strips

As an alternative to externally bonded FRP reinforcement, near-surface mounted (NSM) FRP reinforcement can be used to effectively improve the flexural performance of RC beams. In such FRP strengthened RC beams, end cover separation failure is one of the common failure modes. This failuremode involves the detachment of the NSM FRP reinforcement together with the concrete cover along the level of the tension steel reinforcement. This paper presents a new strength model for end cover separation failure in RC beams strengthened in flexure with NSM FRP strips (i.e. rectangular FRP bars with asectional height-to-thickness ratio not less than 5), which was formulated on the basis of extensive numerical results from a parametric study undertaken using an efficient finite element approach. The proposed strength model consists of an approximate equation for the debonding strain of the FRP reinforcement at the critical cracked section and a conventional section analysis to relate this debondingstrain to the moment acting on the same section (i.e. the debonding strain). Once the debonding strain is known, the load level at end cover separation of an FRP-strengthened RC beam can be easily determined for a given load distribution. Predictions from the proposed strength model are compared with those of two existing strength models of the same type and available test results, which shows that the proposed strength model is in close agreement with test results and is far more accurate than the existing strength models.

Large scale test of a novel back-pass non-perforated unglazed solar air collector

This paper describes large scale tests conducted on a novel unglazed solar air collector system. The proposed system, referred to as a back-pass solar collector (BPSC), has on-site installation and aesthetic advantages over conventional unglazed transpired solar collectors (UTSC) as it is fully integrated within a standard insulated wall panel. This paper presents the results obtained from monitoring a BPSC wall panel over one year. Measurements of temperature, wind velocity and solar irradiance were taken at multiple air mass flow rates. It is shown that the length of the collector cavities has a direct impact on the efficiency of the system. It is also shown that beyond a height-to-flow ratio of 0.023m/m³/hr/m², no additional heat output is obtained by increasing the collector height for the experimental setup in this study, but these numbers would obviously be different if the experimental setup or test environment (e.g. location and climate) change. An equation for predicting the temperature rise of the BPSC is proposed.

Protocol-driven adjustment of ocular hypotensive medication in patients at low risk of conversion to glaucoma

AIM: To investigate the safety and potential savings of decreasing medication use in low-risk patients with ocular hypertension (OH).
METHODS: Patients with OH receiving pressure-lowering medication identified by medical record review at a university hospital underwent examination by a glaucoma specialist with assessment of visual field (VF), vertical cup-to-disc ratio (vCDR), central corneal thickness and intraocular pressure (IOP). Subjects with estimated 5-year risk of glaucoma conversion <15% were asked to discontinue ≥1 medication, IOP was remeasured 1 month later and risk was re-evaluated at 1 year.
RESULTS: Among 212 eyes of 126 patients, 44 (20.8%) had 5-year risk >15% and 14 (6.6%) had unreliable baseline VF. At 1 month, 15 patients (29 eyes, 13.7%) defaulted follow-up or refused to discontinue medication and 11 eyes (5.2%) had risk >15%. The remaining 69 patients (107 eyes, 50.7%) successfully discontinued 141 medications and completed 1-year follow-up. Mean IOP (20.5±2.65 mm Hg vs 20.3±3.40, p=0.397) did not change, though mean VF pattern SD (1.58±0.41 dB vs 1.75±0.56 dB, p=0.001) and glaucoma conversion risk (7.31±3.74% vs 8.76±6.28%, p=0.001) increased at 1 year. Mean defect decreased (-1.42±1.60 vs -1.07±1.52, p=0.022). One eye (0.47%) developed a repeatable VF defect and 13 eyes (6.1%) had 5-year risk >15% at 1 year. The total 1-year cost of medications saved was US$4596.
CONCLUSIONS: Nearly half (43.9%) of low-risk OH eyes in this setting could safely reduce medications over 1 year, realising substantial savings.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Resistance of alkali activated slag concretes to chloride environments based on chloride penetration measurements

ABSTRACT

One of the binder systems with low environmental footprint is alkali activated slag concretes (AASC), made by adding alkalis such as sodium hydroxide and sodium silicate to industrial by-products such as ground granulated blast furnace slag (GGBS). Whilst they have the similar behaviour as that of traditional cement systems in terms of strength and structural behaviour, AASC do exhibit superior performance in terms of abrasion and acid resistance and fire protection.
In this article, the authors focus their attention on chloride ingress into different grades of AASC. The mix variables in AASC included water-to-binder, binder to aggregate ratio, percentage of alkali and the SiO2/Na2O ratio (silica modulus, Ms). The first challenge is to get mixes for different range of workability (with slump values from 40mm to 240mm) and reasonable early age and long term compressive strength according to each one. Then the chloride diffusion and migration in those mixes were measured and compared with same normal concretes in the existed literature based on chloride penetration depth. Comparing the chloride ingress between tradition concretes and AASCs is worthwhile to prove the possibility of increasing concrete lifetime in proximity to sea and deciding while such concretes are practical for use. Findings show that compared to the PC concretes, the AAS concretes have lower rate of chloride ingress.

Resistance of alkali activated slag concretes to chloride environments

ABSTRACT: Researchers are focusing their attention on alternative binder systems using 100% supplementary cementitious materials as it allows better control over the microstructure formation and low to moderate environmental footprint. One such system being considered is alkali activated slag concretes (AASC), made by adding alkalis such as sodium hydroxide and sodium silicate to ground granulated blast furnace slag (GGBS). Whilst they have a similar behaviour as that of traditional cement systems in terms of strength and structural behaviour, AASC are reported to exhibit superior performance in terms of abrasion,acid resistance and fire protection.
In this article, the authors investigate chloride ingress into different grades of AASC. The mix variables in AASC included water to binder, and binder to aggregate ratio, percentage of alkali and the SiO2/Na2O ratio (silica modulus, Ms). The first challenge was to develop mixes for different range of workability (with slump values from 40mm to 240mm) and reasonable early age and long term compressive strength. Further chloride ingress into those mixes were assessed and compared with the data from normal concretes based on literature. Findings show that compared to the PC concretes, the AAS concretes have lower rate of chloride ingress.

A genome-wide linkage scan for genes controlling variation in urinary albumin excretion in type ll diabetes

The main hallmark of diabetic nephropathy is elevation in urinary albumin excretion. We performed a genome-wide linkage scan in 63 extended families with multiple members with type II diabetes. Urinary albumin excretion, measured as the albumin-to-creatinine ratio (ACR), was determined in 426 diabetic and 431 nondiabetic relatives who were genotyped for 383 markers. The data were analyzed using variance components linkage analysis. Heritability (h2) of ACR was significant in diabetic (h2=0.23, P=0.0007), and nondiabetic (h2=0.39, P=0.0001) relatives. There was no significant difference in genetic variance of ACR between diabetic and nondiabetic relatives (P=0.16), and the genetic correlation (rG=0.64) for ACR between these two groups was not different from 1 (P=0.12). These results suggested that similar genes contribute to variation in ACR in diabetic and nondiabetic relatives. This hypothesis was supported further by the linkage results.