Prognostic ability of practitioners of traditional arabic medicine: comparison with Western methods through a relative patient progress scale.

The ancient Greek medical theory based on balance or imbalance of humors disappeared in the western world, but does survive elsewhere. Is this survival related to a certain degree of health care efficiency? We explored this hypothesis through a study of classical Greco-Arab medicine in Mauritania. Modern general practitioners evaluated the safety and effectiveness of classical Arabic medicine in a Mauritanian traditional clinic, with a prognosis/follow-up method allowing the following comparisons: (i) actual patient progress (clinical outcome) compared with what the traditional 'tabib' had anticipated (= prognostic ability) and (ii) patient progress compared with what could be hoped for if the patient were treated by a modern physician in the same neighborhood. The practice appeared fairly safe and, on average, clinical outcome was similar to what could be expected with modern medicine. In some cases, patient progress was better than expected. The ability to correctly predict an individual's clinical outcome did not seem to be better along modern or Greco-Arab theories. Weekly joint meetings (modern and traditional practitioners) were spontaneously organized with a modern health centre in the neighborhood. Practitioners of a different medical system can predict patient progress. For the patient, avoiding false expectations with health care and ensuring appropriate referral may be the most important. Prognosis and outcome studies such as the one presented here may help to develop institutions where patients find support in making their choices, not only among several treatment options, but also among several medical systems.

Stochastic time-concentration activity models for cytotoxicity in 3D brain cell cultures.

BACKGROUND: In vitro aggregating brain cell cultures containing all types of brain cells have been shown to be useful for neurotoxicological investigations. The cultures are used for the detection of nervous system-specific effects of compounds by measuring multiple endpoints, including changes in enzyme activities. Concentration-dependent neurotoxicity is determined at several time points. METHODS: A Markov model was set up to describe the dynamics of brain cell populations exposed to potentially neurotoxic compounds. Brain cells were assumed to be either in a healthy or stressed state, with only stressed cells being susceptible to cell death. Cells may have switched between these states or died with concentration-dependent transition rates. Since cell numbers were not directly measurable, intracellular lactate dehydrogenase (LDH) activity was used as a surrogate. Assuming that changes in cell numbers are proportional to changes in intracellular LDH activity, stochastic enzyme activity models were derived. Maximum likelihood and least squares regression techniques were applied for estimation of the transition rates. Likelihood ratio tests were performed to test hypotheses about the transition rates. Simulation studies were used to investigate the performance of the transition rate estimators and to analyze the error rates of the likelihood ratio tests. The stochastic time-concentration activity model was applied to intracellular LDH activity measurements after 7 and 14 days of continuous exposure to propofol. The model describes transitions from healthy to stressed cells and from stressed cells to death. RESULTS: The model predicted that propofol would affect stressed cells more than healthy cells. Increasing propofol concentration from 10 to 100 μM reduced the mean waiting time for transition to the stressed state by 50%, from 14 to 7 days, whereas the mean duration to cellular death reduced more dramatically from 2.7 days to 6.5 hours. CONCLUSION: The proposed stochastic modeling approach can be used to discriminate between different biological hypotheses regarding the effect of a compound on the transition rates. The effects of different compounds on the transition rate estimates can be quantitatively compared. Data can be extrapolated at late measurement time points to investigate whether costs and time-consuming long-term experiments could possibly be eliminated.

Local-global splitting for spatiotemporal-adaptive multiscale methods

We present a novel spatiotemporal-adaptive Multiscale Finite Volume (MsFV) method, which is based on the natural idea that the global coarse-scale problem has longer characteristic time than the local fine-scale problems. As a consequence, the global problem can be solved with larger time steps than the local problems. In contrast to the pressure-transport splitting usually employed in the standard MsFV approach, we propose to start directly with a local-global splitting that allows to locally retain the original degree of coupling. This is crucial for highly non-linear systems or in the presence of physical instabilities. To obtain an accurate and efficient algorithm, we devise new adaptive criteria for global update that are based on changes of coarse-scale quantities rather than on fine-scale quantities, as it is routinely done before in the adaptive MsFV method. By means of a complexity analysis we show that the adaptive approach gives a noticeable speed-up with respect to the standard MsFV algorithm. In particular, it is efficient in case of large upscaling factors, which is important for multiphysics problems. Based on the observation that local time stepping acts as a smoother, we devise a self-correcting algorithm which incorporates the information from previous times to improve the quality of the multiscale approximation. We present results of multiphase flow simulations both for Darcy-scale and multiphysics (hybrid) problems, in which a local pore-scale description is combined with a global Darcy-like description. The novel spatiotemporal-adaptive multiscale method based on the local-global splitting is not limited to porous media flow problems, but it can be extended to any system described by a set of conservation equations.

The role of ceramide trihexoside (globotriaosylceramide) in the diagnosis and follow-up of the efficacy of treatment of Fabry disease: a review of the literature.

Fabry disease is caused by a deficiency of a-galactosidase A which leads to the progressive intra-lysosomal accumulation of ceramide trihexoside (CTH), also known as globotriaosylceramide (Gb3), in different cell types and body fluids. The clinical manifestations are multisystemic and predominantly affect the heart, kidney and central nervous system. The role of CTH in the pathophysiological process of Fabry disease is not established, and the link between the degree of accumulation and disease manifestations is not systematic. The use of CTH as a diagnostic tool has been proposed for several decades. The recent introduction of a specific treatment for Fabry disease in the form of enzyme replacement therapy (ERT) has led to the need for a biological marker, in place of a clinical sign, for evaluating the efficacy of treatment and also as a tool for following the long term effects of treatment. The ideal biomarker must adhere to strict criteria, and there should be a correlation between the degree of clinical efficacy of treatment and a change in its concentration. This review of the literature assesses the utility of CTH as a diagnostic tool and as a marker of the efficacy of ERT in patients with Fabry disease. Several techniques have been developed for measuring CTH; the principles and the sensitivity thresholds of these methods and the units used to express the results should be taken into consideration when interpreting data. The use of CTH measurement in Fabry disease should be re-evaluated in light of recent published data.

Comparing Multilevel Clustering Methods on Weighted Graphs : The Case of Worldwide Air Passenger Traffic 2000-2004

Specific properties emerge from the structure of large networks, such as that of worldwide air traffic, including a highly hierarchical node structure and multi-level small world sub-groups that strongly influence future dynamics. We have developed clustering methods to understand the form of these structures, to identify structural properties, and to evaluate the effects of these properties. Graph clustering methods are often constructed from different components: a metric, a clustering index, and a modularity measure to assess the quality of a clustering method. To understand the impact of each of these components on the clustering method, we explore and compare different combinations. These different combinations are used to compare multilevel clustering methods to delineate the effects of geographical distance, hubs, network densities, and bridges on worldwide air passenger traffic. The ultimate goal of this methodological research is to demonstrate evidence of combined effects in the development of an air traffic network. In fact, the network can be divided into different levels of âeurooecohesionâeuro, which can be qualified and measured by comparative studies (Newman, 2002; Guimera et al., 2005; Sales-Pardo et al., 2007).

Imaging molasse and quaternary sediments in Lake Geneva, Switzerland, with 3-D high-resolution seismic reflection methods: A case study

A high-resolution three-dimensional (3-D) seismic reflection survey was conducted in Lake Geneva, near the city of Lausanne, Switzerland, as part of a project for developing such seismic techniques. Using a single 48-channel streamer, the 3-D site with an area of 1200 m x 600 m was surveyed in 10 days. A variety of complex geologic structures (e.g. thrusts, folds, channel-fill) up to similar to150 m below the water bottom were obtained with a 15 in.(3) water gun. The 3-D data allowed the construction of an accurate velocity model and the distinction of five major seismic facies within the Lower Freshwater Molasse (Aquitanian) and the Quaternary sedimentary units. Additionally, the Plateau Molasse (PM) and Subalpine Molasse (SM) erosional surface, "La Paudeze" thrust fault (PM-SM boundary) and the thickness of Quaternary sediments were accurately delineated in 3-D.

Expression of the gene encoding the high-Km glucose transporter 2 by the early postimplantation mouse embryo is essential for neural tube defects associated with diabetic embryopathy.

AIMS/HYPOTHESIS: Excess glucose transport to embryos during diabetic pregnancy causes congenital malformations. The early postimplantation embryo expresses the gene encoding the high-Km GLUT2 (also known as SLC2A2) glucose transporter. The hypothesis tested here is that high-Km glucose transport by GLUT2 causes malformations resulting from maternal hyperglycaemia during diabetic pregnancy. MATERIALS AND METHODS: Glut2 mRNA was assayed by RT-PCR. The Km of embryo glucose transport was determined by measuring 0.5-20 mmol/l 2-deoxy[3H]glucose transport. To test whether the GLUT2 transporter is required for neural tube defects resulting from maternal hyperglycaemia, Glut2+/- mice were crossed and transient hyperglycaemia was induced by glucose injection on day 7.5 of pregnancy. Embryos were recovered on day 10.5, and the incidence of neural tube defects in wild-type, Glut2+/- and Glut2-/- embryos was scored. RESULTS: Early postimplantation embryos expressed Glut2, and expression was unaffected by maternal diabetes. Moreover, glucose transport by these embryos showed Michaelis-Menten kinetics of 16.19 mmol/l, consistent with transport mediated by GLUT2. In pregnancies made hyperglycaemic on day 7.5, neural tube defects were significantly increased in wild-type embryos, but Glut2+/- embryos were partially protected from neural tube defects, and Glut2-/- embryos were completely protected from these defects. The frequency of occurrence of wild-type, Glut2+/- and Glut2-/- embryos suggests that the presence of Glut2 alleles confers a survival advantage in embryos before day 10.5. CONCLUSIONS/INTERPRETATIONS: High-Km glucose transport by the GLUT2 glucose transporter during organogenesis is responsible for the embryopathic effects of maternal diabetes.

Determination of 13C/12C ratios of endogenous urinary 5-amino-imidazole-4-carboxamide 1-D-ribofuranoside (AICAR)

RATIONALE: AICAR (5-aminoimidazole-4-carboxamide 1β-D-ribofuranoside) is prohibited in sport according to rules established by the World Anti-Doping Agency. Doping control laboratories identify samples where AICAR abuse is suspected by measuring its urinary concentration and comparing the observed level with naturally occurring concentrations. As the inter-individual variance of urinary AICAR concentrations is large, this approach requires a complementary method to unambiguously prove the exogenous origin of AICAR. Therefore, a method for the determination of carbon isotope ratios (CIRs) of urinary AICAR has been developed and validated. METHODS: Concentrated urine samples were fractionated by means of liquid chromatography for analyte cleanup. Derivatization of AICAR yielding the trimethylsilylated analog was necessary to enable CIR determinations by gas chromatography/combustion/isotope ratio mass spectrometry. The method was tested for its repeatability and stability over time and a linear mixing model was applied to test for possible isotopic discrimination. A reference population of n = 63 males and females was investigated to calculate appropriate reference limits to differentiate endogenous from exogenous urinary AICAR. These limits were tested by an AICAR elimination study. RESULTS: The developed method fulfills all the requirements for adequate sports drug testing and was found to be fit for purpose. The investigated reference population showed a larger variability in the CIR of AICAR than of the endogenous steroids. Nevertheless, the calculated thresholds for differences between AICAR and endogenous steroids can be applied straightforwardly to evaluate suspicious doping control samples with the same statistical confidence as established e.g. for testosterone misuse. These thresholds enabled the detection of a single oral AICAR administration for more than 40 h. CONCLUSIONS: Determination of thee CIRs is the method of choice to distinguish between an endogenous and an exogenous source of urinary AICAR. The developed method will enable investigations into doping control samples with elevated urinary concentrations of AICAR and clearly differentiate between naturally produced/elevated and illicitly administered AICAR.

Test methods: anabolics.

In the International Olympic Committee (IOC) accredited laboratories, specific methods have been developed to detect anabolic steroids in athletes' urine. The technique of choice to achieve this is gas-chromatography coupled with mass spectrometry (GC-MS). In order to improve the efficiency of anti-doping programmes, the laboratories have defined new analytical strategies. The final sensitivity of the analytical procedure can be improved by choosing new technologies for use in detection, such as tandem mass spectrometry (MS-MS) or high resolution mass spectrometry (HRMS). A better sample preparation using immuno-affinity chromatography (IAC) is also a good tool for improving sensitivity. These techniques are suitable for the detection of synthetic anabolic steroids whose structure is not found naturally in the human body. The more and more evident use, on a large scale, of substances chemically similar to the endogenous steroids obliges both the laboratory and the sports authorities to use the steroid profile of the athlete in comparison with reference ranges from a population or with intraindividual reference values.

Orthogonal organic and aqueous-based washes of tissue sections to enhance protein sensitivity by MALDI imaging mass spectrometry.

Imaging mass spectrometry (IMS) is an emergent and innovative approach for measuring the composition, abundance and regioselectivity of molecules within an investigated area of fixed dimension. Although providing unprecedented molecular information compared with conventional MS techniques, enhancement of protein signature by IMS is still necessary and challenging. This paper demonstrates the combination of conventional organic washes with an optimized aqueous-based buffer for tissue section preparation before matrix-assisted laser desorption/ionization (MALDI) IMS of proteins. Based on a 500 mM ammonium formate in water-acetonitrile (9:1; v/v, 0.1% trifluororacetic acid, 0.1% Triton) solution, this buffer wash has shown to significantly enhance protein signature by profiling and IMS (~fourfold) when used after organic washes (70% EtOH followed by 90% EtOH), improving the quality and number of ion images obtained from mouse kidney and a 14-day mouse fetus whole-body tissue sections, while maintaining a similar reproducibility with conventional tissue rinsing. Even if some protein losses were observed, the data mining has demonstrated that it was primarily low abundant signals and that the number of new peaks found is greater with the described procedure. The proposed buffer has thus demonstrated to be of high efficiency for tissue section preparation providing novel and complementary information for direct on-tissue MALDI analysis compared with solely conventional organic rinsing.

Iterative reconstruction methods in two different MDCT scanners: Physical metrics and 4-alternative forced-choice detectability experiments - A phantom approach.

This paper characterizes and evaluates the potential of three commercial CT iterative reconstruction methods (ASIR?, VEO? and iDose(4 ()?())) for dose reduction and image quality improvement. We measured CT number accuracy, standard deviation (SD), noise power spectrum (NPS) and modulation transfer function (MTF) metrics on Catphan phantom images while five human observers performed four-alternative forced-choice (4AFC) experiments to assess the detectability of low- and high-contrast objects embedded in two pediatric phantoms. Results show that 40% and 100% ASIR as well as iDose(4) levels 3 and 6 do not affect CT number and strongly decrease image noise with relative SD constant in a large range of dose. However, while ASIR produces a shift of the NPS curve apex, less change is observed with iDose(4) with respect to FBP methods. With second-generation iterative reconstruction VEO, physical metrics are even further improved: SD decreased to 70.4% at 0.5 mGy and spatial resolution improved to 37% (MTF(50%)). 4AFC experiments show that few improvements in detection task performance are obtained with ASIR and iDose(4), whereas VEO makes excellent detections possible even at an ultra-low-dose (0.3 mGy), leading to a potential dose reduction of a factor 3 to 7 (67%-86%). In spite of its longer reconstruction time and the fact that clinical studies are still required to complete these results, VEO clearly confirms the tremendous potential of iterative reconstructions for dose reduction in CT and appears to be an important tool for patient follow-up, especially for pediatric patients where cumulative lifetime dose still remains high.