Active strain and activation models in cardiac electromechanics

We present a model for mechanical activation of the cardiac tissue depending on the evolution of the transmembrane electrical potential and certain gating/ionic variables that are available in most of electrophysiological descriptions of the cardiac membrane. The basic idea consists in adding to the chosen ionic model one ordinary differential equation for the kinetics of the mechanical activation function. A relevant example illustrates the desired properties of the proposed model, such as delayed muscle contraction and correct magnitude of the muscle fibers' shortening.

A hierarchical approach to model parameter optimization for developmental systems.

In the context of Systems Biology, computer simulations of gene regulatory networks provide a powerful tool to validate hypotheses and to explore possible system behaviors. Nevertheless, modeling a system poses some challenges of its own: especially the step of model calibration is often difficult due to insufficient data. For example when considering developmental systems, mostly qualitative data describing the developmental trajectory is available while common calibration techniques rely on high-resolution quantitative data. Focusing on the calibration of differential equation models for developmental systems, this study investigates different approaches to utilize the available data to overcome these difficulties. More specifically, the fact that developmental processes are hierarchically organized is exploited to increase convergence rates of the calibration process as well as to save computation time. Using a gene regulatory network model for stem cell homeostasis in Arabidopsis thaliana the performance of the different investigated approaches is evaluated, documenting considerable gains provided by the proposed hierarchical approach.

The application of Fick's law to evaluate the period of stay of mega-olivines in alkaline lavas

The integration of the differential equation of the second law of Fick applied to the diffusion of chemical elements in a semi-infinite solid made it easier to estimate the time of stay of olivine mega-cristals in contact with the host lava The results of this research show the existence of two groups of olivine. The first remained in contact with the magmatic liquid during 19 to 22 days, while the second remained so during only 5 to 9 days. This distinction is correlative to that based on the qualitative observation.

Ruin Theory with Excess of Loss Reinsurance and Reinstatements

The present paper studies the probability of ruin of an insurer, if excess of loss reinsurance with reinstatements is applied. In the setting of the classical Cramer-Lundberg risk model, piecewise deterministic Markov processes are used to describe the free surplus process in this more general situation. It is shown that the finite-time ruin probability is both the solution of a partial integro-differential equation and the fixed point of a contractive integral operator. We exploit the latter representation to develop and implement a recursive algorithm for numerical approximation of the ruin probability that involves high-dimensional integration. Furthermore we study the behavior of the finite-time ruin probability under various levels of initial surplus and security loadings and compare the efficiency of the numerical algorithm with the computational alternative of stochastic simulation of the risk process. (C) 2011 Elsevier Inc. All rights reserved.

Differential association of drinking motives with alcohol use on weekdays and weekends.

Drinking motives (DM) reflect the reasons why individuals drink alcohol. Weekdays are mainly dedicated to work, whereas weekends are generally associated with spending time with friends during special events or leisure activities; using alcohol on weekdays and weekends may also be related to different DM. This study examined whether DM were differentially associated with drinking volume (DV) on weekdays and weekends. A representative sample of 5,391 young Swiss men completed a questionnaire assessing weekday and weekend DV, as well as their DM, namely, enhancement, social, coping, and conformity motives. Associations of DM with weekday and weekend DV were examined using structural equation models. Each DM was tested individually in a separate model; all associations were positive and generally stronger (except conformity) for weekend rather than for weekday DV. Further specific patterns of association were found when DM were entered into a single model simultaneously. Associations with weekday and with weekend DV were positive for enhancement and coping motives. However, associations were stronger with weekend rather than with weekday DV for enhancement, and stronger with weekday than with weekend DV for coping motives. Associations of social motives were not significant with weekend DV and negative with weekday DV. Conformity motives were negatively associated with weekend DV and positively related to weekday DV. These results suggest that interventions targeting enhancement motives should be particularly effective at decreasing weekend drinking, whereas interventions targeted at coping motives would be particularly effective at reducing alcohol use on weekdays. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Delayed otogenic hydrocephalus after acute otitis media in pediatric patients: the changing presentation of a serious otologic complication.

CONCLUSIONS: The clinical presentation of otogenic dural sinus thrombosis (DST) as a complication of acute otitis media (AOM) can be masked by antibiotic treatment. Morning episodes of vomiting and/or headache, visual impairment and a history of AOM seem to be indicative of otogenic hydrocephalus. We therefore advocate that the MRI scans of patients with similar symptoms should be carefully studied to facilitate the early diagnosis of a potentially life-threatening complication. OBJECTIVE: To describe the frequency, pathognomonic signs, clinical course and outcome of otogenic hydrocephalus and DST as complications of AOM in pediatric patients. MATERIAL AND METHODS: We undertook a retrospective chart review of all pediatric patients (age 1-14 years) treated for otitis media and its complications at an academic medical center between 1999 and 2003. The main outcome measures were otologic and ophthalmologic findings and CT and MRI scans at the beginning of treatment and 3 months later. RESULTS: We report on five cases with otogenic DST following AOM. All but one of them presented initially with diplopia caused by otogenic hydrocephalus. In four cases the otologic complaints had already disappeared by the time of MRI confirmation of the diagnosis. Only one child was referred with severe otologic symptoms. Management included systemic antibiotics, short-term heparin anticoagulation and surgical decompression. In our cases, even after intensive i.v. antibiotic treatment, only surgery led to a significant improvement in the clinical condition.

Assessment of speed of human locomotion using a differential satellite global positioning system.

PURPOSE: The objective was to explore whether a satellite-based navigation system, global positioning system used in differential mode (DGPS), could accurately assess the speed of running in humans. METHODS: A subject was equipped with a portable GPS receptor coupled to a receiver for differential corrections, while running outdoors on a straight asphalt road at 27 different speeds. Actual speed (reference method) was assessed by chronometry. RESULTS: The accuracy of speed prediction had a standard deviation (SD) of 0.08 km x h(-1) for walking, 0.11 km x h(-1) for running, yielding a coefficient of variation (SD/mean) of 1.38% and 0.82%, respectively. There was a highly significant linear relationship between actual and DGPS speed assessment (r2 = 0.999) with little bias in the prediction equation, because the slope of the regression line was close to unity (0.997). CONCLUSION: the DGPS technique appears to be a valid and inconspicuous tool for "on line" monitoring of the speed of displacement of individuals located on any field on earth, for prolonged periods of time and unlimited distance, but only in specific environmental conditions ("open sky"). Furthermore, the accuracy of speed assessment using the differential GPS mode was improved by a factor of 10 as compared to non-differential GPS.

Termination of major ductile strike-slip shear and differential cooling along the Insubric line (Central Alps): U-Pb, Rb-Sr and 40Ar/39Ar ages of cross-cutting pegmatites

To constrain the age of strike-slip shear, related granitic magmatism, and cooling along the Insubric line, 29 size fractions of monazite and xenotime were dated by the U-Pb method, and a series of 25 Rb-Sr and Ar-40/Ar-39 ages were measured on different size fractions of muscovite and biotite. The three pegmatitic intrusions analyzed truncate high-grade metamorphic mylonite gneisses of the Simplon shear zone, a major Alpine structure produced in association with dextral strike-slip movements along the southern edge of the European plate, after collision with its Adriatic indenter. Pegmatites and aplites were produced between 29 and 25 Ma in direct relation to right-lateral shear along the Insubric line, by melting of continental crust having Sr-87/Sr-86 between 0.7199 and 0.7244 at the time of melting. High-temperature dextral strike-slip shear was active at 29.2 +/- 0.2 (2 sigma) Ma, and it terminated before 26.4 +/- 0.1 Ma. During dike injection, temperatures in the country rocks of the Isorno-Orselina and Monte Rosa structural units did not exceed approximate to 500 degrees C, leading to fast initial cooling, followed by slower cooling to approximate to 350 degrees C within several million years. In one case, initial cooling to approximate to 500 degrees C was significantly delayed by about 4 m.y., with final cooling to approximate to 300 degrees C at 20-19 Ma in all units. For the period between 29 and 19 Ma, cooling of the three sample localities was non-uniform in space and time, with significant variations on the kilometre scale. These differences are most likely due to strongly varying heat flow, and/or heterogeneous distribution of unroofing rates within the continuously deforming Insubric line. If entirely ascribed to differences in unroofing, corresponding rates would vary between 0.5 and 2.5 mm/y, for a thermal gradient of 30 degrees/km.

Differential effects of GABAB receptor subtypes, {gamma}-hydroxybutyric Acid, and Baclofen on EEG activity and sleep regulation.

The role of GABA(B) receptors in sleep is still poorly understood. GHB (γ-hydroxybutyric acid) targets these receptors and is the only drug approved to treat the sleep disorder narcolepsy. GABA(B) receptors are obligate dimers comprised of the GABA(B2) subunit and either one of the two GABA(B1) subunit isoforms, GABA(B1a) and GABA(B1b). To better understand the role of GABA(B) receptors in sleep regulation, we performed electroencephalogram (EEG) recordings in mice devoid of functional GABA(B) receptors (1(-/-) and 2(-/-)) or lacking one of the subunit 1 isoforms (1a(-/-) and 1b(-/-)). The distribution of sleep over the day was profoundly altered in 1(-/-) and 2(-/-) mice, suggesting a role for GABA(B) receptors in the circadian organization of sleep. Several other sleep and EEG phenotypes pointed to a more prominent role for GABA(B1a) compared with the GABA(B1b) isoform. Moreover, we found that GABA(B1a) protects against the spontaneous seizure activity observed in 1(-/-) and 2(-/-) mice. We also evaluated the effects of the GHB-prodrug GBL (γ-butyrolactone) and of baclofen (BAC), a high-affinity GABA(B) receptor agonist. Both drugs induced a state distinct from physiological sleep that was not observed in 1(-/-) and 2(-/-) mice. Subsequent sleep was not affected by GBL whereas BAC was followed by a delayed hypersomnia even in 1(-/-) and 2(-/-) mice. The differential effects of GBL and BAC might be attributed to differences in GABA(B)-receptor affinity. These results also indicate that all GBL effects are mediated through GABA(B) receptors, although these receptors do not seem to be involved in mediating the BAC-induced hypersomnia.

Differential effects of two anti-apo-cytochrome c-specific monoclonal antibodies on the function of apo-cytochrome c-specific murine T cell clones.

A murine monoclonal antibody (SJL 2-4) specific for the antigen apo-cytochrome c was shown to inhibit both antigen-induced proliferation and lymphokine secretion by an apo-cytochrome c-specific BALB/c helper T cell clone. The inhibition was specific because additional apo-cytochrome c-specific T cell clones were not inhibited by the same monoclonal antibody. Time course studies of the inhibition indicated that the initial 8 hr of contact between T cell clones and antigen-presenting cells were critical for activation of the T cell clones. Inhibition of T cell functions by antigen-specific antibodies appeared to correlate with the antibody-antigen binding constant because a second monoclonal antibody (Cyt-1-59), with identical specificity but with a lower affinity constant for apo-cytochrome c, had very little inhibitory effect on the proliferation or lymphokine secretion of apo-cytochrome c-specific T cell clones.

Sclérodermie et risques oncologiques [Systemic sclerosis and cancer]

The combination of skin induration with clinical features such as dyspnea, facial telangiectasia, digital infarctions and/or dysphagia supports the diagnosis of systemic sclerosis. The oesophageal dysmotility is associated with symptoms which may delay the diagnosis of gastro-oesophageal cancer. Herein we report a case of long standing systemic sclerosis with heartburn and dysphagia symptoms which were monitored closely. Unfortunately, these symptoms delayed the diagnosis of gastric adenocarcinoma. This case prompted us to review the evidence of the association of cancer and systemic sclerosis and if any oncologic evaluation is required during the follow-up of patients affected with systemic sclerosis.

Differential effect of long versus short wavelength light exposure on pupillary re-dilation in patients with outer retinal disease.

BACKGROUND: In patients with outer retinal degeneration, a differential pupil response to long wavelength (red) versus short wavelength (blue) light stimulation has been previously observed. The goal of this study was to quantify differences in the pupillary re-dilation following exposure to red versus blue light in patients with outer retinal disease and compare them with patients with optic neuropathy and with healthy subjects. DESIGN: Prospective comparative cohort study. PARTICIPANTS: Twenty-three patients with outer retinal disease, 13 patients with optic neuropathy and 14 normal subjects. METHODS: Subjects were tested using continuous red and blue light stimulation at three intensities (1, 10 and 100 cd/m2) for 13 s per intensity. Pupillary re-dilation dynamics following the brightest intensity was analysed and compared between the three groups. MAIN OUTCOME MEASURES: The parameters of pupil re-dilation used in this study were: time to recover 90% of baseline size; mean pupil size at early and late phases of re-dilation; and differential re-dilation time for blue versus red light. RESULTS: Patients with outer retinal disease showed a pupil that tended to stay smaller after light termination and thus had a longer time to recovery. The differential re-dilation time was significantly greater in patients with outer retinal disease (median = 28.0 s, P < 0.0001) compared with controls and patients with optic neuropathy. CONCLUSIONS: A differential response of pupil re-dilation following red versus blue light stimulation is present in patients with outer retinal disease but is not found in normal eyes or among patients with visual loss from optic neuropathy.

Differential regulations of AQP4 and Kir4.1 by triamcinolone acetonide and dexamethasone in the healthy and inflamed retina.

PURPOSE: Glucocorticoids are used to treat macular edema, although the mechanisms underlying this effect remain largely unknown. The authors have evaluated in the normal and endotoxin-induced uveitis (EIU) rats, the effects of dexamethasone (dex) and triamcinolone acetonide (TA) on potassium channel Kir4.1 and aquaporin-4 (AQP4), the two main retinal Müller glial (RMG) channels controlling retinal fluid movement. METHODS: Clinical as well as relatively low doses of dex and TA were injected in the vitreous of normal rats to evaluate their influence on Kir4.1 and AQP4 expression 24 hours later. The dose-dependent effects of the two glucocorticoids were investigated using rat neuroretinal organotypic cultures. EIU was induced by footpad lipopolysaccharide injection, without or with 100 nM intraocular dex or TA. Glucocorticoid receptor and channel expression levels were measured by quantitative PCR, Western blot, and immunohistochemistry. RESULTS: The authors found that dex and TA exert distinct and specific channel regulations at 24 hours after intravitreous injection. Dex selectively upregulated Kir4.1 (not AQP4) in healthy and inflamed retinas, whereas TA induced AQP4 (not Kir4.1) downregulation in normal retina and upregulation in EIU. The lower concentration (100 nM) efficiently regulated the channels. Moreover, in EIU, an inflammatory condition, the glucocorticoid receptor was downregulated in the retina, which was prevented by intravitreous injections of the low concentration of dex or TA. CONCLUSIONS: The results show that dex and TA are far from being equivalent to modulate RMG channels. Furthermore, the authors suggest that low doses of glucocorticoids may have antiedematous effects on the retina with reduced toxicity.