The application of trend surface models to the analysis of time factors in Swiss cancer mortality.

To study different temporal components on cancer mortality (age, period and cohort) methods of graphic representation were applied to Swiss mortality data from 1950 to 1984. Maps using continuous slopes ("contour maps") and based on eight tones of grey according to the absolute distribution of rates were used to represent the surfaces defined by the matrix of various age-specific rates. Further, progressively more complex regression surface equations were defined, on the basis of two independent variables (age/cohort) and a dependent one (each age-specific mortality rate). General patterns of trends in cancer mortality were thus identified, permitting definition of important cohort (e.g., upwards for lung and other tobacco-related neoplasms, or downwards for stomach) or period (e.g., downwards for intestines or thyroid cancers) effects, besides the major underlying age component. For most cancer sites, even the lower order (1st to 3rd) models utilised provided excellent fitting, allowing immediate identification of the residuals (e.g., high or low mortality points) as well as estimates of first-order interactions between the three factors, although the parameters of the main effects remained still undetermined. Thus, the method should be essentially used as summary guide to illustrate and understand the general patterns of age, period and cohort effects in (cancer) mortality, although they cannot conceptually solve the inherent problem of identifiability of the three components.

Analysis of TNF-antagonist switch over time and associated risk factors in the Swiss Inflammatory Bowel Disease Cohort

Abstract Background and aims. Limited data from large cohorts are available on tumor necrosis factor (TNF) antagonists (infliximab, adalimumab, certolizumab pegol) switch over time. We aimed to evaluate the prevalence of switching from one TNF antagonist to another and to identify associated risk factors. Methods. Data from the Swiss Inflammatory Bowel Diseases Cohort Study (SIBDCS) were analyzed. Results. Of 1731 patients included into the SIBDCS (956 with Crohn's disease [CD] and 775 with ulcerative colitis [UC]), 347 CD patients (36.3%) and 129 UC patients (16.6%) were treated with at least one TNF antagonist. A total of 53/347 (15.3%) CD patients (median disease duration 9 years) and 20/129 (15.5%) of UC patients (median disease duration 7 years) needed to switch to a second and/or a third TNF antagonist, respectively. Median treatment duration was longest for the first TNF antagonist used (CD 25 months; UC 14 months), followed by the second (CD 13 months; UC 4 months) and third TNF antagonist (CD 11 months; UC 15 months). Primary nonresponse, loss of response and side effects were the major reasons to stop and/or switch TNF antagonist therapy. A low body mass index, a short diagnostic delay and extraintestinal manifestations at inclusion were identified as risk factors for a switch of the first used TNF antagonist within 24 months of its use in CD patients. Conclusion. Switching of the TNF antagonist over time is a common issue. The median treatment duration with a specific TNF antagonist is diminishing with an increasing number of TNF antagonists being used.

Suboptimal filtering and nonlinear time scale transformation for the analysis of multiexponential decays

Multiexponential decays may contain time-constants differing in several orders of magnitudes. In such cases, uniform sampling results in very long records featuring a high degree of oversampling at the final part of the transient. Here, we analyze a nonlinear time scale transformation to reduce the total number of samples with minimum signal distortion, achieving an important reduction of the computational cost of subsequent analyses. We propose a time-varying filter whose length is optimized for minimum mean square error

A comparative long-memory Analysis between Spanish, Mexican and U.S. interest rates

Evidence exists that many natural facts are described better as a fractal. Although fractals are very useful for describing nature, it is also appropiate to review the concept of random fractal in finance. Due to the extraordinary importance of Brownian motion in physics, chemistry or biology, we will consider the generalization that supposes fractional Brownian motion introduced by Mandelbrot.The main goal of this work is to analyse the existence of long range dependence in instantaneous forward rates of different financial markets. Concretelly, we perform an empirical analysis on the Spanish, Mexican and U.S. interbanking interest rate. We work with three time series of daily data corresponding to 1 day operations from 28th March 1996 to 21st May 2002. From among all the existing tests on this matter we apply the methodology proposed in Taqqu, Teverovsky and Willinger (1995).

Differential equations driven by fractional Brownian motion

A global existence and uniqueness result of the solution for multidimensional, time dependent, stochastic differential equations driven by a fractional Brownian motion with Hurst parameter H> is proved. It is shown, also, that the solution has finite moments. The result is based on a deterministic existence and uniqueness theorem whose proof uses a contraction principle and a priori estimates.

A comparative long-memory Analysis between Spanish, Mexican and U.S. interest rates

Evidence exists that many natural facts are described better as a fractal. Although fractals are very useful for describing nature, it is also appropiate to review the concept of random fractal in finance. Due to the extraordinary importance of Brownian motion in physics, chemistry or biology, we will consider the generalization that supposes fractional Brownian motion introduced by Mandelbrot.The main goal of this work is to analyse the existence of long range dependence in instantaneous forward rates of different financial markets. Concretelly, we perform an empirical analysis on the Spanish, Mexican and U.S. interbanking interest rate. We work with three time series of daily data corresponding to 1 day operations from 28th March 1996 to 21st May 2002. From among all the existing tests on this matter we apply the methodology proposed in Taqqu, Teverovsky and Willinger (1995).

A detailed urinary excretion time course study of captan and folpet biomarkers in workers for the estimation of dose, main route-of-entry and most appropriate sampling and analysis strategies

Captan and folpet are two fungicides largely used in agriculture, but biomonitoring data are mostly limited to measurements of captan metabolite concentrations in spot urine samples of workers, which complicate interpretation of results in terms of internal dose estimation, daily variations according to tasks performed, and most plausible routes of exposure. This study aimed at performing repeated biological measurements of exposure to captan and folpet in field workers (i) to better assess internal dose along with main routes-of-entry according to tasks and (ii) to establish most appropriate sampling and analysis strategies. The detailed urinary excretion time courses of specific and non-specific biomarkers of exposure to captan and folpet were established in tree farmers (n = 2) and grape growers (n = 3) over a typical workweek (seven consecutive days), including spraying and harvest activities. The impact of the expression of urinary measurements [excretion rate values adjusted or not for creatinine or cumulative amounts over given time periods (8, 12, and 24 h)] was evaluated. Absorbed doses and main routes-of-entry were then estimated from the 24-h cumulative urinary amounts through the use of a kinetic model. The time courses showed that exposure levels were higher during spraying than harvest activities. Model simulations also suggest a limited absorption in the studied workers and an exposure mostly through the dermal route. It further pointed out the advantage of expressing biomarker values in terms of body weight-adjusted amounts in repeated 24-h urine collections as compared to concentrations or excretion rates in spot samples, without the necessity for creatinine corrections.

Estimating the apparent transverse relaxation time (R2(*)) from images with different contrasts (ESTATICS) reduces motion artifacts.

Relaxation rates provide important information about tissue microstructure. Multi-parameter mapping (MPM) estimates multiple relaxation parameters from multi-echo FLASH acquisitions with different basic contrasts, i.e., proton density (PD), T1 or magnetization transfer (MT) weighting. Motion can particularly affect maps of the apparent transverse relaxation rate R2(*), which are derived from the signal of PD-weighted images acquired at different echo times. To address the motion artifacts, we introduce ESTATICS, which robustly estimates R2(*) from images even when acquired with different basic contrasts. ESTATICS extends the fitted signal model to account for inherent contrast differences in the PDw, T1w and MTw images. The fit was implemented as a conventional ordinary least squares optimization and as a robust fit with a small or large confidence interval. These three different implementations of ESTATICS were tested on data affected by severe motion artifacts and data with no prominent motion artifacts as determined by visual assessment or fast optical motion tracking. ESTATICS improved the quality of the R2(*) maps and reduced the coefficient of variation for both types of data-with average reductions of 30% when severe motion artifacts were present. ESTATICS can be applied to any protocol comprised of multiple 2D/3D multi-echo FLASH acquisitions as used in the general research and clinical setting.

SDF 1-alpha (CXCL12) triggers glutamate exocytosis from astrocytes on a millisecond time scale: Imaging analysis at the single-vesicle level with TIRF microscopy

Chemokines are small chemotactic molecules widely expressed throughout the central nervous system. A number of papers, during the past few years, have suggested that they have physiological functions in addition to their roles in neuroinflammatory diseases. In this context, the best evidence concerns the CXC-chemokine stromal cell-derived factor (SDF-1alpha or CXCL12) and its receptor CXCR4, whose signalling cascade is also implicated in the glutamate release process from astrocytes. Recently, astrocytic synaptic like microvesicles (SLMVs) that express vesicular glutamate transporters (VGLUTs) and are able to release glutamate by Ca(2+)-dependent regulated exocytosis, have been described both in tissue and in cultured astrocytes. Here, in order to elucidate whether SDF-1alpha/CXCR4 system can participate to the brain fast communication systems, we investigated whether the activation of CXCR4 receptor triggers glutamate exocytosis in astrocytes. By using total internal reflection (TIRF) microscopy and the membrane-fluorescent styryl dye FM4-64, we adapted an imaging methodology recently developed to measure exocytosis and recycling in synaptic terminals, and monitored the CXCR4-mediated exocytosis of SLMVs in astrocytes. We analyzed the co-localization of VGLUT with the FM dye at single-vesicle level, and observed the kinetics of the FM dye release during single fusion events. We found that the activation of CXCR4 receptors triggered a burst of exocytosis on a millisecond time scale that involved the release of Ca(2+) from internal stores. These results support the idea that astrocytes can respond to external stimuli and communicate with the neighboring cells via fast release of glutamate.

Prospective and retrospective motion correction in diffusion magnetic resonance imaging of the human brain.

Diffusion-weighting in magnetic resonance imaging (MRI) increases the sensitivity to molecular Brownian motion, providing insight in the micro-environment of the underlying tissue types and structures. At the same time, the diffusion weighting renders the scans sensitive to other motion, including bulk patient motion. Typically, several image volumes are needed to extract diffusion information, inducing also inter-volume motion susceptibility. Bulk motion is more likely during long acquisitions, as they appear in diffusion tensor, diffusion spectrum and q-ball imaging. Image registration methods are successfully used to correct for bulk motion in other MRI time series, but their performance in diffusion-weighted MRI is limited since diffusion weighting introduces strong signal and contrast changes between serial image volumes. In this work, we combine the capability of free induction decay (FID) navigators, providing information on object motion, with image registration methodology to prospectively--or optionally retrospectively--correct for motion in diffusion imaging of the human brain. Eight healthy subjects were instructed to perform small-scale voluntary head motion during clinical diffusion tensor imaging acquisitions. The implemented motion detection based on FID navigator signals is processed in real-time and provided an excellent detection performance of voluntary motion patterns even at a sub-millimetre scale (sensitivity≥92%, specificity>98%). Motion detection triggered an additional image volume acquisition with b=0 s/mm2 which was subsequently co-registered to a reference volume. In the prospective correction scenario, the calculated motion-parameters were applied to perform a real-time update of the gradient coordinate system to correct for the head movement. Quantitative analysis revealed that the motion correction implementation is capable to correct head motion in diffusion-weighted MRI to a level comparable to scans without voluntary head motion. The results indicate the potential of this method to improve image quality in diffusion-weighted MRI, a concept that can also be applied when highest diffusion weightings are performed.

Fast analysis of doping agents in urine by ultra-high-pressure liquid chromatography-quadrupole time-of-flight mass spectrometry I. Screening analysis.

The general strategy to perform anti-doping analyses of urine samples starts with the screening for a wide range of compounds. This step should be fast, generic and able to detect any sample that may contain a prohibited substance while avoiding false negatives and reducing false positive results. The experiments presented in this work were based on ultra-high-pressure liquid chromatography coupled to hybrid quadrupole time-of-flight mass spectrometry. Thanks to the high sensitivity of the method, urine samples could be diluted 2-fold prior to injection. One hundred and three forbidden substances from various classes (such as stimulants, diuretics, narcotics, anti-estrogens) were analysed on a C(18) reversed-phase column in two gradients of 9min (including two 3min equilibration periods) for positive and negative electrospray ionisation and detected in the MS full scan mode. The automatic identification of analytes was based on retention time and mass accuracy, with an automated tool for peak picking. The method was validated according to the International Standard for Laboratories described in the World Anti-Doping Code and was selective enough to comply with the World Anti-Doping Agency recommendations. In addition, the matrix effect on MS response was measured on all investigated analytes spiked in urine samples. The limits of detection ranged from 1 to 500ng/mL, allowing the identification of all tested compounds in urine. When a sample was reported positive during the screening, a fast additional pre-confirmatory step was performed to reduce the number of confirmatory analyses.

Impact of bulk cardiac motion on right coronary MR angiography and vessel wall imaging.

The purpose of this study was to investigate the impact of in-plane coronary artery motion on coronary magnetic resonance angiography (MRA) and coronary MR vessel wall imaging. Free-breathing, navigator-gated, 3D-segmented k-space turbo field echo ((TFE)/echo-planar imaging (EPI)) coronary MRA and 2D fast spin-echo coronary vessel wall imaging of the right coronary artery (RCA) were performed in 15 healthy adult subjects. Images were acquired at two different diastolic time periods in each subject: 1) during a subject-specific diastasis period (in-plane velocity <4 cm/second) identified from analysis of in-plane coronary artery motion, and 2) using a diastolic trigger delay based on a previously implemented heart-rate-dependent empirical formula. RCA vessel wall imaging was only feasible with subject-specific middiastolic acquisition, while the coronary wall could not be identified with the heart-rate-dependent formula. For coronary MRA, RCA border definition was improved by 13% (P < 0.001) with the use of subject-specific trigger delay (vs. heart-rate-dependent delay). Subject-specific middiastolic image acquisition improves 3D TFE/EPI coronary MRA, and is critical for RCA vessel wall imaging.

Gas analysis of exhumed cadavers buried for 30 years: a case report about long time alteration.

Due to important alteration caused by long time decomposition, the gases in human bodies buried for more than a year have not been investigated. For the first time, the results of gas analysis sampled from bodies recently exhumed after 30 years are presented. Adipocere formation has prevented the bodies from too important alteration, and gaseous areas were identified. The sampling was performed with airtight syringes assisted by multi-detector computed tomography (MDCT) in those specific areas. The important amount of methane (CH4), coupled to weak amounts of hydrogen (H2) and carbon dioxide (CO2), usual gaseous alteration indicators, have permitted to confirm methanogenesis mechanism for long period of alteration. H2 and CO2 produced during the first stages of the alteration process were consumed through anaerobic oxidation by methanogenic bacteria, generating CH4.