Elektrochemische Potentiale während Hochfrequenz-Katheterablation von Herzrhythmusstörungen : In vitro und in vivo Experimente und erste klinische Erfahrungen

Einleitung: Die temperaturkontrollierte Katheterablation besitzt eine Reihe von Limitationen wie u.a. moderate Korrelation mit der Gewebetemperatur und Läsionsentwicklung. Ziel der vorliegenden Arbeit war es, ein Steuerungsparameter zu entwickeln, der die Qualität des Elektrodenkontaktes mit dem Gewebe und das Wachstum der Koagulationsnekrose direkt anhand zellulärer bzw. biologischer Prozesse des Zielgewebes wiedergibt. Material und Methodik: Endomyokard-Präparate frisch geschlachteter Rinder wurden in einem Tankbad mit physiologischer Kochsalzlösung für die in vitro Experimente verwandt, wo bei das elektrochemische Potential (eP) wie bei allen Untersuchungen zwischen der distalen und der proximalen Elektrode abgeleitet wurde. Tierexperimente wurden bei 8 intubiert, beatmeten Schweinen durchgeführt, wobei der experimentelle Aufbau adäquat zu den Bedingungen in vitro- elektrochemisches Potential zwischen distaler und proximaler Elektrode - war. Die ersten klinischen Untersuchungen wurden an 50 konsekutiven Patienten (m/w 29:21; 49,7 ± 9,8 Jahre), die zur elektiven Katheter-Ablation von supraventrikulären Tachykardien AVNRT bzw. WPW-Syndrom eingewiesen wurden, durchgeführt. Der meßtechnische Aufbau war unverändert zu den in vitro bzw. Tierexperimenten. Ergebnisse: Der Nachweis von eP gelang sowohl invitro, tierexperimentell als auch im klinischen Teil der Arbeit. Ferner konnte eine hohe Korrelation des elektrochemischen Potentials mit dem bisher üblichen Parameter \u27Temperatur\u27 errechnet werden (r=0,87). Eine ebenfalls hohe Korrelation wurde zwischen der Läsionsentwicklung und den eP festgestellt: r=0,85; p<0,001. Auch bei den \u27Routine-Kateterablationen\u27 konnte die Messung der eP bei Patienten durchgeführt werden. Ferner konnte mittels eP-gesteuerter Energieabgabe die Durchführbarkeit einer Katheterablation mit dem Parameters \u27eP\u27 gezeigt werden. Diskussion: Der Ursprung des eP liegt in der Läsionsentwicklung durch Erhitzung des myokardialen Gewebes. Die elektromotorische Kraftquelle des eP ist die Diffusion von freien Radikalen und intrazellulären Elektrolyten aus der Koagulationsläsion. Die eP stellt einen zusätzlichen Parameter neben der Temperatur und Impedanz - mit besserer Korrelation zur Läsion- dar. Die Steuerung der HF-Strom-Energieabgabe durch die eP ist möglich und erlaubt den Einsatz thermosensorfreier Elektroden. Potentiell klinische Anwendungen stellen die gekühlte Ablation sowie der Einsatz von multipolaren Ablationskathetern dar.Introduction: Temperature controlled radiofrequency catheter ablation (TRF) is widely introduced in current clinical practice with several limitations as the moderate correlation between catheter tip temperature (CTT) and lesion size (LS), and the increase in stiffness of multielectrode thermosensor catheters for the creation of linear lesions. Thermal injury of subendocardial tissue leads to a release of electrolytes and free radicals from the intracellular site creating a change in potential (dP) between distal and proximal catheter tip electrode. The aim of the doctorate was to verify the detection of ablation-induced release of electrolytes and free radicals and the possibility to control energy delivery in ablation by measuring dP. Energieabgabe die Durchführbarkeit einer Katheterablation mit dem Parameters \u27eP\u27 gezeigt werden. Methods and Results: In vitro tests at constant flow condition were performed in a 10 l bath of physiological saline solution and cattle blood. Endomyocardial preparations of fresh cattle hearts were used. Closed-loop temperature-controlled and closed-loop dP-controlled ablations were performed. In vivo animal investigations were performed in anesthetized and ventilated pigs. The existence of the dP was established in the tank model and was confirmed in the animal investigations. Good correlations were found between dP and CTT (r=0.87) and between maximum dP and induced LS (r=0.85). A high correlation (r=0.85, p<0.001) was found between dP and lesion volume. During routinely catheter ablation in 50 patients with supraventicular tachycardia dP-measurement was performed. Energieabgabe die Durchführbarkeit einer Katheterablation mit dem Parameters \u27eP\u27 gezeigt werden. Conclusions: Control of energy delivery during RF-ablation by the measurement of dP is feasible. In comparison to TRF, ablation steered by dP-measurement revealed superior correlation to induced LS. During irrigated catheter ablation, dP measurement is the only tool for energy control. To our knowledge, this is the first report on this novel method of ablation control

When LEP and Tevatron combined with WMAP and XENON100 shed light on the nature of Dark Matter

Recently, several astrophysical data or would-be signals has been observed in different dark-matter oriented experiments. In each case, one could fit the data at the price of specific nature of the coupling between the Standard Model (SM) particles and a light Dark Matter candidate: hadrophobic (INTEGRAL, PAMELA) or leptophobic (WMAP Haze, dijet anomalies of CDF, FERMI Galactic Center observation). In this work, we show that when one takes into account the more recent LEP and Tevatron analysis, a light thermal fermionic Dark Matte (\lesssim 10 GeV) that couples to electrons is mainly ruled out if one combines the analysis with WMAP constraints. We also study the special case of scalar dark matter, using a mono-photon events simulation to constrain the coupling of dark matter to electron.Comment: 8 pages, 6 figure

Altered Brain Structure in Infants with Turner Syndrome

Turner syndrome (TS) is a genetic disorder affecting approximately 1:2000 live-born females. It results from partial or complete X monosomy and is associated with a range of clinical issues including a unique cognitive profile and increased risk for certain behavioral problems. Structural neuroimaging studies in adolescents, adults, and older children with TS have revealed altered neuroanatomy but are unable to identify when in development differences arise. In addition, older children and adults have often been exposed to years of growth hormone and/or exogenous estrogen therapy with potential implications for neurodevelopment. The study presented here is the first to test whether brain structure is altered in infants with TS. Twenty-six infants with TS received high-resolution structural MRI scans of the brain at 1 year of age and were compared to 47 typically developing female and 39 typically developing male infants. Results indicate that the typical neuroanatomical profile seen in older individuals with TS, characterized by decreased gray matter volumes in premotor, somatosensory, and parietal-occipital cortex, is already present at 1 year of age, suggesting a stable phenotype with origins in the prenatal or early postnatal period

The Self Model and the Conception of Biological Identity in Immunology

The self/non-self model, first proposed by F.M. Burnet, has dominated immunology for sixty years now. According to this model, any foreign element will trigger an immune reaction in an organism, whereas endogenous elements will not, in normal circumstances, induce an immune reaction. In this paper we show that the self/non-self model is no longer an appropriate explanation of experimental data in immunology, and that this inadequacy may be rooted in an excessively strong metaphysical conception of biological identity. We suggest that another hypothesis, one based on the notion of continuity, gives a better account of immune phenomena. Finally, we underscore the mapping between this metaphysical deflation from self to continuity in immunology and the philosophical debate between substantialism and empiricism about identity

A holistic measurement model of movement competency in children

Different countries have different methods for assessing movement competence in children; however, it is unclear whether the test batteries that are used measure the same aspects of movement competence. The aim of this paper was to (1) investigate whether the Test of Gross Motor Development (TGMD-2) and Körperkoordinations Test für Kinder (KTK) measure the same aspects of children’s movement competence and (2) examine the factorial structure of the TGMD-2 and KTK in a sample of Australian children. A total of 158 children participated (M age = 9.5; SD = 2.2). First, confirmatory factor analysis examined the independent factorial structure of the KTK and TGMD-2. Second, it was investigated whether locomotor, object control and body coordination loaded on the latent variable Movement Competency. Confirmatory factor analysis indicated an adequate fit for both the KTK and TGMD-2. An adequate fit was also achieved for the final model. In this model, locomotor (r = .86), object control (r = .71) and body coordination (r = .52) loaded on movement competence. Findings support our hypothesis that the TGMD-2 and KTK measure discrete aspects of movement competence. Future researchers and practitioners should consider using a wider range of test batteries to assess movement competence

Size Doesn't Matter: Towards a More Inclusive Philosophy of Biology

notes: As the primary author, O’Malley drafted the paper, and gathered and analysed data (scientific papers and talks). Conceptual analysis was conducted by both authors.publication-status: Publishedtypes: ArticlePhilosophers of biology, along with everyone else, generally perceive life to fall into two broad categories, the microbes and macrobes, and then pay most of their attention to the latter. ‘Macrobe’ is the word we propose for larger life forms, and we use it as part of an argument for microbial equality. We suggest that taking more notice of microbes – the dominant life form on the planet, both now and throughout evolutionary history – will transform some of the philosophy of biology’s standard ideas on ontology, evolution, taxonomy and biodiversity. We set out a number of recent developments in microbiology – including biofilm formation, chemotaxis, quorum sensing and gene transfer – that highlight microbial capacities for cooperation and communication and break down conventional thinking that microbes are solely or primarily single-celled organisms. These insights also bring new perspectives to the levels of selection debate, as well as to discussions of the evolution and nature of multicellularity, and to neo-Darwinian understandings of evolutionary mechanisms. We show how these revisions lead to further complications for microbial classification and the philosophies of systematics and biodiversity. Incorporating microbial insights into the philosophy of biology will challenge many of its assumptions, but also give greater scope and depth to its investigations

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele