Tunneling and Metastability of continuous time Markov chains

We propose a new definition of metastability of Markov processes on countable state spaces. We obtain sufficient conditions for a sequence of processes to be metastable. In the reversible case these conditions are expressed in terms of the capacity and of the stationary measure of the metastable states

The efficacy of flecainide versus digoxin in the management of fetal supraventricular tachycardia

Fetal supraventricular tachycardia (SVT) can be successfully treated transplacentally, but in cases where fetal hydrops develops there is considerable morbidity and mortality. The present study was carried out to establish whether the introduction of flecainide altered obstetric management and fetal outcome. A retrospective analysis took place of 51 singleton pregnancies which were referred to the division of prenatal diagnosis because of fetal tachycardia between 1982 and 1993. SVT was documented in 50 out of 51 fetuses, one of which displayed a combination of extensive rhabdomyomas and severe hydrops and died shortly after referral. In the other fetus ventricular tachycardia was diagnosed. Of the remaining 49 fetuses, 14 did not receive any prenatal treatment, but nine needed postnatal treatment. Transplacental treatment of SVT took place in 35 fetuses, of which 22 presented without hydrops and 13 with hydrops. These subsets differed significantly with respect to restoration of normal sinus rhythm (73% vs. 30%; p<0.001) and mortality (0% vs. 46%; p<0.001). Digoxin was effective in restoring sinus rhythm in 55 per cent of the non‐hydropic fetuses but in only eight per cent of the hydropic fetuses. Flecainide was effective in restoring sinus rhythm in all non‐hydropic fetuses where digoxin treatment failed, and in 43 per cent of hydropic fetuses. Administration of flecainide resulted in a significantly reduced mortality (p<0.001) compared with digoxin treatment. No adverse effects were seen. Postnatal anti‐arrhythmic treatment was necessary in 23 infants. Treatment could be withdrawn within one year in all cases but one. Copyrigh

Maternal engineered nanomaterial inhalation during gestation alters the fetal transcriptome

Background: The integration of engineered nanomaterials (ENM) is well-established and widespread in clinical, commercial, and domestic applications. Cardiovascular dysfunctions have been reported in adult populations after exposure to a variety of ENM. As the diversity of these exposures continues to increase, the fetal ramifications of maternal exposures have yet to be determined. We, and others, have explored the consequences of ENM inhalation during gestation and identified many cardiovascular and metabolic outcomes in the F1 generation. The purpose of these studies was to identify genetic alterations in the F1 generation of Sprague-Dawley rats that result from maternal ENM inhalation during gestation. Pregnant dams were exposed to nano-titanium dioxide (nano-TiO2) aerosols (10 ± 0. 5 mg/m3) for 7-8 days (calculated, cumulative lung deposition = 217 ± 1 μg) and on GD (gestational day) 20 fetal hearts were isolated. DNA was extracted and immunoprecipitated with modified chromatin marks histone 3 lysine 4 tri-methylation (H3K4me3) and histone 3 lysine 27 tri-methylation (H3K27me3). Following chromatin immunoprecipitation (ChIP), DNA fragments were sequenced. RNA from fetal hearts was purified and prepared for RNA sequencing and transcriptomic analysis. Ingenuity Pathway Analysis (IPA) was then used to identify pathways most modified by gestational ENM exposure. Results: The results of the sequencing experiments provide initial evidence that significant epigenetic and transcriptomic changes occur in the cardiac tissue of maternal nano-TiO2 exposed progeny. The most notable alterations in major biologic systems included immune adaptation and organismal growth. Changes in normal physiology were linked with other tissues, including liver and kidneys. Conclusions: These results are the first evidence that maternal ENM inhalation impacts the fetal epigenome

Maternal engineered nanomaterial inhalation during gestation alters the fetal transcriptome

Background: The integration of engineered nanomaterials (ENM) is well-established and widespread in clinical, commercial, and domestic applications. Cardiovascular dysfunctions have been reported in adult populations after exposure to a variety of ENM. As the diversity of these exposures continues to increase, the fetal ramifications of maternal exposures have yet to be determined. We, and others, have explored the consequences of ENM inhalation during gestation and identified many cardiovascular and metabolic outcomes in the F1 generation. The purpose of these studies was to identify genetic alterations in the F1 generation of Sprague-Dawley rats that result from maternal ENM inhalation during gestation. Pregnant dams were exposed to nano-titanium dioxide (nano-TiO2) aerosols (10 ± 0. 5 mg/m3) for 7-8 days (calculated, cumulative lung deposition = 217 ± 1 μg) and on GD (gestational day) 20 fetal hearts were isolated. DNA was extracted and immunoprecipitated with modified chromatin marks histone 3 lysine 4 tri-methylation (H3K4me3) and histone 3 lysine 27 tri-methylation (H3K27me3). Following chromatin immunoprecipitation (ChIP), DNA fragments were sequenced. RNA from fetal hearts was purified and prepared for RNA sequencing and transcriptomic analysis. Ingenuity Pathway Analysis (IPA) was then used to identify pathways most modified by gestational ENM exposure. Results: The results of the sequencing experiments provide initial evidence that significant epigenetic and transcriptomic changes occur in the cardiac tissue of maternal nano-TiO2 exposed progeny. The most notable alterations in major biologic systems included immune adaptation and organismal growth. Changes in normal physiology were linked with other tissues, including liver and kidneys. Conclusions: These results are the first evidence that maternal ENM inhalation impacts the fetal epigenome

Cancer centre information and support services and patient needs:participatory action research study

Objectives:Clear information and supportive care are necessary for oncology patients and their relatives to manage the disease (trajectory). Centres for information and support aim to address their needs by offering informal and non-medical formal services. This study evaluated whether the centres’ services offered meet the needs of its visitors, and whether there is interest for these among oncology patients treated at affiliated hospitals.Methods:In this participatory action research, interviews were conducted among visitors of two centres (Patient Information Center Oncology (PATIO) and IntermeZZo) and among patients treated at the affiliated hospitals. Visitors were interviewed to share their experiences regarding the centres’ services offered. Patients from the hospitals were interviewed about their interest in such support. Data were collected during three different periods and adjustments were made to the centres’ services between measurements. Results:111 (PATIO) and 123 visitors (IntermeZZo) were interviewed, and 189 and 149 patients at the respective hospitals. Reasons to visit PATIO/IntermeZZo were to relax (93.1%), seek professional advice (54.6%) and meet peers (36.3%). Visitors indicated that the visits met their needs (99.1%), citing the accessible support and the expertise in oncology. 20% of patients interviewed at the hospitals expressed interest in visiting PATIO/ IntermeZZo. The majority of patients (89.6%) considered these centres an integral part of their treatment process. These findings were stable over time. Conclusions:Patients and their relatives highly value the services of hospital-affiliated centres for information and support. Future research should address how such centres best be integrated in the Dutch healthcare system.</p

Dynamical aspects of mean field plane rotators and the Kuramoto model

The Kuramoto model has been introduced in order to describe synchronization phenomena observed in groups of cells, individuals, circuits, etc... We look at the Kuramoto model with white noise forces: in mathematical terms it is a set of N oscillators, each driven by an independent Brownian motion with a constant drift, that is each oscillator has its own frequency, which, in general, changes from one oscillator to another (these frequencies are usually taken to be random and they may be viewed as a quenched disorder). The interactions between oscillators are of long range type (mean field). We review some results on the Kuramoto model from a statistical mechanics standpoint: we give in particular necessary and sufficient conditions for reversibility and we point out a formal analogy, in the N to infinity limit, with local mean field models with conservative dynamics (an analogy that is exploited to identify in particular a Lyapunov functional in the reversible set-up). We then focus on the reversible Kuramoto model with sinusoidal interactions in the N to infinity limit and analyze the stability of the non-trivial stationary profiles arising when the interaction parameter K is larger than its critical value K_c. We provide an analysis of the linear operator describing the time evolution in a neighborhood of the synchronized profile: we exhibit a Hilbert space in which this operator has a self-adjoint extension and we establish, as our main result, a spectral gap inequality for every K>K_c.Comment: 18 pages, 1 figur