Electrotonic modulation of cardiac impulse conduction by myofibroblasts

Structural remodeling of the myocardium associated with mechanical overload or cardiac infarction is accompanied by the appearance of myofibroblasts. These fibroblast-like cells express alpha-smooth muscle actin (alphaSMA) and have been shown to express connexins in tissues other than heart. The present study examined whether myofibroblasts of cardiac origin establish heterocellular gap junctional coupling with cardiomyocytes and whether ensuing electrotonic interactions affect impulse propagation. For this purpose, impulse conduction characteristics (conduction velocity [theta] and maximal upstroke velocity [dV/dtmax]) were assessed optically in cultured strands of cardiomyocytes, which were coated with fibroblasts of cardiac origin. Immunocytochemistry showed that cultured fibroblasts underwent a phenotype switch to alphaSMA-positive myofibroblasts that expressed connexin 43 and 45 both among themselves and at contact sites with cardiomyocytes. Myofibroblasts affected theta and dV/dtmax in a cell density-dependent manner; a gradual increase of myofibroblast-to-cardiomyocyte ratios up to 7:100 caused an increase of both theta and dV/dtmax, which was followed by a progressive decline at higher ratios. On full coverage of the strands with myofibroblasts (ratio >20:100), theta fell <200 mm/s. This biphasic dependence of theta and dV/dtmax on myofibroblast density is reminiscent of "supernormal conduction" and is explained by a myofibroblast density-dependent gradual depolarization of the cardiomyocyte strands from -78 mV to -50 mV as measured using microelectrode recordings. These findings suggest that myofibroblasts, apart from their role in structural remodeling, might contribute to arrhythmogenesis by direct electrotonic modulation of conduction and that prevention of their appearance might represent an antiarrhythmic therapeutic target.

Gap junction channels and cardiac impulse propagation

The role of gap junction channels on cardiac impulse propagation is complex. This review focuses on the differential expression of connexins in the heart and the biophysical properties of gap junction channels under normal and disease conditions. Structural determinants of impulse propagation have been gained from biochemical and immunocytochemical studies performed on tissue extracts and intact cardiac tissue. These have defined the distinctive connexin coexpression patterns and relative levels in different cardiac tissues. Functional determinants of impulse propagation have emerged from electrophysiological experiments carried out on cell pairs. The static properties (channel number and conductance) limit the current flow between adjacent cardiomyocytes and thus set the basic conduction velocity. The dynamic properties (voltage-sensitive gating and kinetics of channels) are responsible for a modulation of the conduction velocity during propagated action potentials. The effect is moderate and depends on the type of Cx and channel. For homomeric-homotypic channels, the influence is small to medium; for homomeric-heterotypic channels, it is medium to strong. Since no data are currently available on heteromeric channels, their influence on impulse propagation is speculative. The modulation by gap junction channels is most prominent in tissues at the boundaries between cardiac tissues such as sinoatrial node-atrial muscle, atrioventricular node-His bundle, His bundle-bundle branch and Purkinje fibers-ventricular muscle. The data predict facilitation of orthodromic propagation.

[Gerodontology consultation in geriatric facilities: general health status (I)]

Dental undertreatment is often seen in the older population. This is particularly true for the elderly living in nursing homes and geriatric hospitals. The progression of chronic diseases results in loss of their independence. They rely on daily support and care due to physical or mental impairment. The visit of a dentist in private praxis becomes difficult or impossible and is a logistic problem. These elderly patients are often not aware of oral and dental problems or these are not addressed. The geriatric hospital Bern, Ziegler, has integrated dental care in the concept of physical rehabilitation of geriatric patients. A total of 139 patients received dental treatment in the years 2005/2006. Their mean age was 83 years, but the segment with > 85 years of age amounted to 46%. The general health examinations reveald multiple and complex disorders. The ASA classification (American Society of Anesthesiologists, Physical Status Classification System) was applied and resulted in 15% = P2 (mild systemic disease, no functional limitation), 47% = P3 (severe systemic disease, definite functional limitations) and 38% = P4 (severe systemic disease, constant threat to life). Eighty-seven of the patients exhibited 3 or more chronic diseases with a prevalence of cardiovascular diseases, musculoskelettal disorders and dementia. Overall the differences between men and women were small, but broncho-pulmonary dieseases were significantly more frequent in women, while men were more often diagnosed with dementia and depression. Verbal communication was limited or not possible with 60% of the patients due to cognitive impairment or aphasia after a stroke. Although the objective treatment need is high, providing dentistry for frail and geriatric patients is characterized by risks due to poor general health conditions, difficulties in communication, limitations in feasibility and lack of adequate aftercare. In order to prevent the problem of undertreatment, elderly independently living people should undergo dental treatment regularly and in time. Training of nurses and doctors of geriatric hospitals in oral hygiene should improve the awareness. A multidisciplinary assessment of geriatric patients should include the oral and dental aspect if they enter the hospital.

Embedding Moose Facilities Directly in IDEs

Moose is a powerful reverse engineering platform, but its facilities and means to analyze software are separated from the tools developers typically use to develop and maintain their software systems: development environments such as Eclipse, VisualWorks, or Squeak. In practice, this requires developers to work with two distinct environments, one to actually develop the software, and another one (e.g., Moose) to analyze it. We worked on several different techniques, using both dynamic and static analyzes to provide software analysis capabilities to developers directly in the IDE. The immediate availability of analysis tools in an IDE significantly increases the likelihood that developers integrate software analysis in their daily work, as we discovered by conducting user studies with developers. Finally, we identified several important aspect of integrating software analysis in IDEs that need to be addressed in the future to increase the adoption of these techniques by developers.

Distributed Control Nodes for Material Flow System Controls on the Example of Unit Load Conveyor and Sorter Facilities

The Chair of Transportation and Ware-housing at the University of Dortmund together with its industrial partner has developed and implemented a decentralized control system based on embedded technology and Internet standards. This innovative, highly flexible system uses autonomous software modules to control the flow of unit loads in real-time. The system is integrated into Chair’s test facility consisting of a wide range of conveying and sorting equipment. It is built for proof of concept purposes and will be used for further research in the fields of decentralized automation and embedded controls. This presentation describes the implementation of this decentralized control system.

Weighted Majoritarian Rules for the Location of Multiple Public Facilities

We consider collective decision problems given by a profile of single-peaked preferences defined over the real line and a set of pure public facilities to be located on the line. In this context, Bochet and Gordon (2012) provide a large class of priority rules based on efficiency, object-population monotonicity and sovereignty. Each such rule is described by a fixed priority ordering among interest groups. We show that any priority rule which treats agents symmetrically — anonymity — respects some form of coherence across collective decision problems — reinforcement — and only depends on peak information — peakonly — is a weighted majoritarian rule. Each such rule defines priorities based on the relative size of the interest groups and specific weights attached to locations. We give an explicit account of the richness of this class of rules.

Carbon dioxide and climate impulse response functions for the computation of greenhouse gas metrics: a multi-model analysis

The responses of carbon dioxide (CO2) and other climate variables to an emission pulse of CO2 into the atmosphere are often used to compute the Global Warming Potential (GWP) and Global Temperature change Potential (GTP), to characterize the response timescales of Earth System models, and to build reduced-form models. In this carbon cycle-climate model intercomparison project, which spans the full model hierarchy, we quantify responses to emission pulses of different magnitudes injected under different conditions. The CO2 response shows the known rapid decline in the first few decades followed by a millennium-scale tail. For a 100 Gt-C emission pulse added to a constant CO2 concentration of 389 ppm, 25 ± 9% is still found in the atmosphere after 1000 yr; the ocean has absorbed 59 ± 12% and the land the remainder (16 ± 14%). The response in global mean surface air temperature is an increase by 0.20 ± 0.12 °C within the first twenty years; thereafter and until year 1000, temperature decreases only slightly, whereas ocean heat content and sea level continue to rise. Our best estimate for the Absolute Global Warming Potential, given by the time-integrated response in CO2 at year 100 multiplied by its radiative efficiency, is 92.5 × 10−15 yr W m−2 per kg-CO2. This value very likely (5 to 95% confidence) lies within the range of (68 to 117) × 10−15 yr W m−2 per kg-CO2. Estimates for time-integrated response in CO2 published in the IPCC First, Second, and Fourth Assessment and our multi-model best estimate all agree within 15% during the first 100 yr. The integrated CO2 response, normalized by the pulse size, is lower for pre-industrial conditions, compared to present day, and lower for smaller pulses than larger pulses. In contrast, the response in temperature, sea level and ocean heat content is less sensitive to these choices. Although, choices in pulse size, background concentration, and model lead to uncertainties, the most important and subjective choice to determine AGWP of CO2 and GWP is the time horizon.

The temporal impulse response function in infantile nystagmus.

Despite rapid to-and-fro motion of the retinal image that results from their incessant involuntary eye movements, persons with infantile nystagmus (IN) rarely report the perception of motion smear. We performed two experiments to determine if the reduction of perceived motion smear in persons with IN is associated with an increase in the speed of the temporal impulse response. In Experiment 1, increment thresholds were determined for pairs of successively presented flashes of a long horizontal line, presented on a 65-cd/m2 background field. The stimulus-onset asynchrony (SOA) between the first and second flash varied from 5.9 to 234 ms. In experiment 2, temporal contrast sensitivity functions were determined for a 3-cpd horizontal square-wave grating that underwent counterphase flicker at temporal frequencies between 1 and 40 Hz. Data were obtained for 2 subjects with predominantly pendular IN and 8 normal observers in Experiment 1 and for 3 subjects with IN and 4 normal observers in Experiment 2. Temporal impulse response functions (TIRFs) were estimated as the impulse response of a linear second-order system that provided the best fit to the increment threshold data in Experiment 1 and to the temporal contrast sensitivity functions in Experiment 2. Estimated TIRFs of the subjects with pendular IN have natural temporal frequencies that are significantly faster than those of normal observers (ca. 13 vs. 9 Hz), indicating an accelerated temporal response to visual stimuli. This increase in response speed is too small to account by itself for the virtual absence of perceived motion smear in subjects with IN, and additional neural mechanisms are considered.

Commentary on "The Impact of Family Stressors on the Social Development of Adolescents in Residential Facilities"

This is a commentary on “The impact of family stressors on the social development of adolescents admitted to a residential treatment facility,” by Cynthia Harr. This article examines the important but relatively understudied relationship of family dynamics in the social development of high risk teens in residential treatment facility (RTF) care. The commentary supports the author’s calls for a continuum of care involving greater cooperation with parents, and critiques and expands on some of the recommendations.

The influence of staff and organizational characteristics on social environment in substance abuse treatment facilities

The staff of 20 substance abuse treatment facilities were administered the Ward Atmosphere Scale, an instrument which measures treatment environment. Ten facilities were freestanding and ten were hospital based, and were drawn from a large, not-for-profit national chain using a random selection process. Controlling for several staff and facility attributes, it was found that no substantial effects on treatment environment existed due to facility type, freestanding or hospital-based. Implications of the study exist in selection of facility type for purchasers of substance abuse treatment and for the hiring and training of clinical staff for treatment facilities. Study findings also suggest that inadequate or insufficient measures exist to examine the construct 'treatment environment'. ^

The location of majority and minority populations with respect to commercial treatment, storage, and disposal facilities in Texas

There is a growing interest in the location of Treatment, Storage, and Disposal (TSDF) sites in relation to minority communities. A number of studies have been completed, and the results of these studies have been varied. Some of the studies have shown a strong positive correlation between the location of TSDF sites and minority populations, while a few have shown no significance in that relationship. The major difference between these studies has been in the areal unit used.^ This study compared the minority populations of Texas census tracts and ZIP codes containing a TSDF using the associated county as the comparison population. The hypothesis of this study was that there was no difference between using census tracts and ZIP codes to analyze the relationship of minority populations and TSDF's. The census data used was from 1990, and the initial list of TSDF sites was supplied by the Texas Natural Resource Conservation Commission. The TSDF site locations were checked using graphical information systems (GIS) programs, in order to increase the accuracy of the identity of exposed ZIP codes and census tracts. The minority populations of the exposed areal units were compared using proportional differences, crosstables, maps, and logistic regression. The dependent variable used was the exposure status of the areal units under study, including counties, census tracts, and ZIP codes. The independent variables used included minority group proportion and grouping of the proportions, educational status, household income, and home value.^ In all cases, education was significant or near significant at the.05 level. Education rather than minority proportion was therefore the most significant predictor of the exposure status of a census tract or ZIP code. ^

Unterrichtliche Konzepte individueller Lernförderung. Theoretische Impulse für die individualisierte und bildungsstandardbezogene Lernförderung auf Mikro-Ebene: ein Lehr-Lern-Modell zur Ko-Konstruktion im Unterricht

Im vorliegenden Beitrag wird versucht, den [Lehr-Lern-Prozess] in Hinblick auf individualisierten Unterricht genauer zu klären und auf die aktuelle Diskussion zur wirksamen Implementierung von Bildungsstandards zu beziehen. Dabei wird ein lehr-lerntheoretisches Modell dargestellt, das Orientierungshilfen für die lern-wirksame Gestaltung von unterrichtlichen Prozessen bieten soll. Es wird im Weiteren auf die folgenden Qualitätsmerkmale guten Unterrichts bezogen: das Fördern einer positiven Lernatmosphäre, das Herstellen einer (bildungsstandardbezogenen) Zielorientierung und die Berücksichtigung von Lernvoraussetzungen durch pädagogische Diagnostik, die mit aufgabenbasierten und protokollierten Lernförderungskreisläufen gekoppelt ist. Abschließend werden Anwendungsmöglichkeiten dieses Modells insbesondere in der Unterrichtsgestaltung und -evaluation kurz aufgezeigt und kritisch diskutiert.