Heart rate is a prognostic risk factor for myocardial infarction: a post hoc analysis in the PERFORM (Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic attack) study population

BACKGROUND Elevated resting heart rate is known to be detrimental to morbidity and mortality in cardiovascular disease, though its effect in patients with ischemic stroke is unclear. We analyzed the effect of baseline resting heart rate on myocardial infarction (MI) in patients with a recent noncardioembolic cerebral ischemic event participating in PERFORM. METHODS We compared fatal or nonfatal MI using adjusted Cox proportional hazards models for PERFORM patients with baseline heart rate <70 bpm (n=8178) or ≥70 bpm (n=10,802). In addition, heart rate was analyzed as a continuous variable. Other cerebrovascular and cardiovascular outcomes were also explored. RESULTS Heart rate ≥70 bpm was associated with increased relative risk for fatal or nonfatal MI (HR 1.32, 95% CI 1.03-1.69, P=0.029). For every 5-bpm increase in heart rate, there was an increase in relative risk for fatal and nonfatal MI (11.3%, P=0.0002). Heart rate ≥70 bpm was also associated with increased relative risk for a composite of fatal or nonfatal ischemic stroke, fatal or nonfatal MI, or other vascular death (excluding hemorrhagic death) (P<0001); vascular death (P<0001); all-cause mortality (P<0001); and fatal or nonfatal stroke (P=0.04). For every 5-bpm increase in heart rate, there were increases in relative risk for fatal or nonfatal ischemic stroke, fatal or nonfatal MI, or other vascular death (4.7%, P<0.0001), vascular death (11.0%, P<0.0001), all-cause mortality (8.0%, P<0.0001), and fatal and nonfatal stroke (2.4%, P=0.057). CONCLUSION Elevated heart rate ≥70 bpm places patients with a noncardioembolic cerebral ischemic event at increased risk for MI.

Syntheses, characterization and crystal structures of a new functionalised TTF derivative and its Ni(II) complex

The new ligand 4,5-bis (2-pyridylmethylsulfanyl)-4',5'-bis(cyanoethylthio)tetrathiafulvalene (BPM-BCET-TTF) and its nickel(II) complex have been prepared and crystallographically characterized. The Ni(II) complex shows octahedral geometry around the metal ion with the coordination site occupied by the pyridyl nitrogen atoms, the thioether sulfur atoms of the ligand and cis coordination of the halide ions.

The first batteryless, solar-powered cardiac pacemaker

BACKGROUND: Contemporary pacemakers (PMs) are powered by primary batteries with a limited energy-storing capacity. PM replacements because of battery depletion are common and unpleasant and bear the risk of complications. Batteryless PMs that harvest energy inside the body may overcome these limitations. OBJECTIVE: The goal of this study was to develop a batteryless PM powered by a solar module that converts transcutaneous light into electrical energy. METHODS: Ex vivo measurements were performed with solar modules placed under pig skin flaps exposed to different irradiation scenarios (direct sunlight, shade outdoors, and indoors). Subsequently, 2 sunlight-powered PMs featuring a 4.6-cm2 solar module were implanted in vivo in a pig. One prototype, equipped with an energy buffer, was run in darkness for several weeks to simulate a worst-case scenario. RESULTS: Ex vivo, median output power of the solar module was 1963 μW/cm2 (interquartile range [IQR] 1940-2107 μW/cm2) under direct sunlight exposure outdoors, 206 μW/cm2 (IQR 194-233 μW/cm2) in shade outdoors, and 4 μW/cm2 (IQR 3.6-4.3 μW/cm2) indoors (current PMs use approximately 10-20 μW). Median skin flap thickness was 4.8 mm. In vivo, prolonged SOO pacing was performed even with short irradiation periods. Our PM was able to pace continuously at a rate of 125 bpm (3.7 V at 0.6 ms) for 1½ months in darkness. CONCLUSION: Tomorrow's PMs might be batteryless and powered by sunlight. Because of the good skin penetrance of infrared light, a significant amount of energy can be harvested by a subcutaneous solar module even indoors. The use of an energy buffer allows periods of darkness to be overcome.

Detection of haemorrhagic shock: Are vital signs obsolete? A commentary by Dr M. Luginbühl

The ATLS program by the American college of surgeons is probably the most important globally active training organization dedicated to improve trauma management. Detection of acute haemorrhagic shock belongs to the key issues in clinical practice and thus also in medical teaching. (In this issue of the journal William Schulz and Ian McConachrie critically review the ATLS shock classification Table 1), which has been criticized after several attempts of validation have failed [1]. The main problem is that distinct ranges of heart rate are related to ranges of uncompensated blood loss and that the heart rate decrease observed in severe haemorrhagic shock is ignored [2]. Table 1. Estimated blood loos based on patient's initial presentation (ATLS Students Course Manual, 9th Edition, American College of Surgeons 2012). Class I Class II Class III Class IV Blood loss ml Up to 750 750–1500 1500–2000 >2000 Blood loss (% blood volume) Up to 15% 15–30% 30–40% >40% Pulse rate (BPM) <100 100–120 120–140 >140 Systolic blood pressure Normal Normal Decreased Decreased Pulse pressure Normal or ↑ Decreased Decreased Decreased Respiratory rate 14–20 20–30 30–40 >35 Urine output (ml/h) >30 20–30 5–15 negligible CNS/mental status Slightly anxious Mildly anxious Anxious, confused Confused, lethargic Initial fluid replacement Crystalloid Crystalloid Crystalloid and blood Crystalloid and blood Table options In a retrospective evaluation of the Trauma Audit and Research Network (TARN) database blood loss was estimated according to the injuries in nearly 165,000 adult trauma patients and each patient was allocated to one of the four ATLS shock classes [3]. Although heart rate increased and systolic blood pressure decreased from class I to class IV, respiratory rate and GCS were similar. The median heart rate in class IV patients was substantially lower than the value of 140 min−1 postulated by ATLS. Moreover deterioration of the different parameters does not necessarily go parallel as suggested in the ATLS shock classification [4] and [5]. In all these studies injury severity score (ISS) and mortality increased with in increasing shock class [3] and with increasing heart rate and decreasing blood pressure [4] and [5]. This supports the general concept that the higher heart rate and the lower blood pressure, the sicker is the patient. A prospective study attempted to validate a shock classification derived from the ATLS shock classes [6]. The authors used a combination of heart rate, blood pressure, clinically estimated blood loss and response to fluid resuscitation to classify trauma patients (Table 2) [6]. In their initial assessment of 715 predominantly blunt trauma patients 78% were classified as normal (Class 0), 14% as Class I, 6% as Class II and only 1% as Class III and Class IV respectively. This corresponds to the results from the previous retrospective studies [4] and [5]. The main endpoint used in the prospective study was therefore presence or absence of significant haemorrhage, defined as chest tube drainage >500 ml, evidence of >500 ml of blood loss in peritoneum, retroperitoneum or pelvic cavity on CT scan or requirement of any blood transfusion >2000 ml of crystalloid. Because of the low prevalence of class II or higher grades statistical evaluation was limited to a comparison between Class 0 and Class I–IV combined. As in the retrospective studies, Lawton did not find a statistical difference of heart rate and blood pressure among the five groups either, although there was a tendency to a higher heart rate in Class II patients. Apparently classification during primary survey did not rely on vital signs but considered the rather soft criterion of “clinical estimation of blood loss” and requirement of fluid substitution. This suggests that allocation of an individual patient to a shock classification was probably more an intuitive decision than an objective calculation the shock classification. Nevertheless it was a significant predictor of ISS [6]. Table 2. Shock grade categories in prospective validation study (Lawton, 2014) [6]. Normal No haemorrhage Class I Mild Class II Moderate Class III Severe Class IV Moribund Vitals Normal Normal HR > 100 with SBP >90 mmHg SBP < 90 mmHg SBP < 90 mmHg or imminent arrest Response to fluid bolus (1000 ml) NA Yes, no further fluid required Yes, no further fluid required Requires repeated fluid boluses Declining SBP despite fluid boluses Estimated blood loss (ml) None Up to 750 750–1500 1500–2000 >2000 Table options What does this mean for clinical practice and medical teaching? All these studies illustrate the difficulty to validate a useful and accepted physiologic general concept of the response of the organism to fluid loss: Decrease of cardiac output, increase of heart rate, decrease of pulse pressure occurring first and hypotension and bradycardia occurring only later. Increasing heart rate, increasing diastolic blood pressure or decreasing systolic blood pressure should make any clinician consider hypovolaemia first, because it is treatable and deterioration of the patient is preventable. This is true for the patient on the ward, the sedated patient in the intensive care unit or the anesthetized patients in the OR. We will therefore continue to teach this typical pattern but will continue to mention the exceptions and pitfalls on a second stage. The shock classification of ATLS is primarily used to illustrate the typical pattern of acute haemorrhagic shock (tachycardia and hypotension) as opposed to the Cushing reflex (bradycardia and hypertension) in severe head injury and intracranial hypertension or to the neurogenic shock in acute tetraplegia or high paraplegia (relative bradycardia and hypotension). Schulz and McConachrie nicely summarize the various confounders and exceptions from the general pattern and explain why in clinical reality patients often do not present with the “typical” pictures of our textbooks [1]. ATLS refers to the pitfalls in the signs of acute haemorrhage as well: Advanced age, athletes, pregnancy, medications and pace makers and explicitly state that individual subjects may not follow the general pattern. Obviously the ATLS shock classification which is the basis for a number of questions in the written test of the ATLS students course and which has been used for decades probably needs modification and cannot be literally applied in clinical practice. The European Trauma Course, another important Trauma training program uses the same parameters to estimate blood loss together with clinical exam and laboratory findings (e.g. base deficit and lactate) but does not use a shock classification related to absolute values. In conclusion the typical physiologic response to haemorrhage as illustrated by the ATLS shock classes remains an important issue in clinical practice and in teaching. The estimation of the severity haemorrhage in the initial assessment trauma patients is (and was never) solely based on vital signs only but includes the pattern of injuries, the requirement of fluid substitution and potential confounders. Vital signs are not obsolete especially in the course of treatment but must be interpreted in view of the clinical context. Conflict of interest None declared. Member of Swiss national ATLS core faculty.

Hemodynamic changes associated with manual and automated lateral rotation in mechanically ventilated intensive care patients

Objective: To investigate hemodynamic responses to lateral rotation. ^ Design: Time-series within a randomized controlled trial pilot study. ^ Setting: A medical intensive care unit (ICU) and a medical-surgical ICU in two tertiary care hospitals. ^ Patients: Adult patients receiving mechanical ventilation. ^ Interventions: Two-hourly manual or continuous automated lateral rotation. ^ Measurements and Main Results: Heart rate (HR) and arterial pressure were sampled every 6 seconds for > 24 hours, and pulse pressure (PP) was computed. Turn data were obtained from a turning flow sheet (manual turn) or with an angle sensor (automated turn). Within-subject ensemble averages were computed for HR, mean arterial pressure (MAP), and PP across turns. Sixteen patients were randomized to either the manual (n = 8) or automated (n = 8) turn. Three patients did not complete the study due to hemodynamic instability, bed malfunction or extubation, leaving 13 patients (n = 6 manual turn and n = 7 automated turn) for analysis. Seven patients (54%) had an arterial line. Changes in hemodynamic variables were statistically significant increases ( p < .05), but few changes were clinically important, defined as ≥ 10 bpm (HR) or ≥ 10 mmHg (MAP and PP), and were observed only in the manual-turn group. All manual-turn patients had prolonged recovery to baseline in HR, MAP and PP of up to 45 minutes (p ≤ .05). No significant turning-related periodicities were found for HR, MAP, or PP. Cross-correlations between variables showed variable lead-lag relations in both groups. A statistically, but not clinically, significant increase in HR of 3 bpm was found for the manual-turn group in the back compared with the right lateral position ( F = 14.37, df = 1, 11, p = .003). ^ Conclusions: Mechanically ventilated critically ill patients experience modest hemodynamic changes with manual lateral rotation. A clinically inconsequential increase in HR, MAP, and PP may persist for up to 45 minutes. Automated lateral rotation has negligible hemodynamic effects. ^

Grain size investigations of sediments off the coast of Istria

Composition, grain-size distribution, and areal extent of Recent sediments from the Northern Adriatic Sea along the Istrian coast have been studied. Thirty one stations in four sections vertical to the coast were investigated; for comparison 58 samples from five small bays were also analyzed. Biogenic carbonate sediments are deposited on the shallow North Adriatic shelf off the Istrian coast. Only at a greater distance from the coast are these carbonate sediments being mixed with siliceous material brought in by the Alpine rivers Po, Adige, and Brenta. Graphical analysis of grain-size distribution curves shows a sediment composition of normally three, and only in the most seaward area, of four major constituents. Constituent 1 represents the washed-in terrestrial material of clay size (Terra Rossa) from the Istrian coastal area. Constituent 2 consists of fine to medium sand. Constituent 3 contains the heterogeneous biogenic material. Crushing by organisms and by sediment eaters reduces the coarse biogenic material into small pieces generating constituent 2. Between these two constituents there is a dynamic equilibrium. Depending upon where the equilibrium is, between the extremes of production and crushing, the resulting constituent 2 is finer or coarser. Constituent 4 is composed of the fine sandy material from the Alpine rivers. In the most seaward area constituents 2 and 4 are mixed. The total carbonate content of the samples depends on the distance from the coast. In the near coastal area in high energy environments, the carbonate content is about 80 %. At a distance of 2 to 3 km from the coast there is a carbonate minimum because of the higher rate of sedimentation of clay-sized terrestrial, noncarbonate material at extremely low energy environments. In an area between 5 and 20 km off the coast, the carbonate content is about 75 %. More than 20 km from the shore, the carbonate content diminishes rapidly to values of about 30 % through mixing with siliceous material from the Alpine rivers. The carbonate content of the individual fractions increases with increasing grain-size to a maximum of about 90 % within the coarse sand fractions. Beyond 20 km from the coast the samples show a carbonate minimum of about 13 % within the sand-size classes from 1.5 to 0.7 zeta¬? through mixing with siliceous material from the alpine rivers. By means of grain-size distribution and carbonate content, four sediment zones parallel to the coast were separated. Genetically they are closely connected with the zonation of the benthic fauna. Two cores show a characteristic vertical distribution of the sediment. The surface zone is inversely graded, that means the coarse fractions are at the top and the fine fractions are at the bottom. This is the effect of crushing of the biogenic material produced at the surface by predatory organisms and by sediment eaters. lt is proposed that at a depth of about 30 cm a chemical solution process begins which leads to diminution of the original sediment from a fine to medium sand to a silt. The carbonate content decreases from about 75 % at the surface to 65 % at a depth of 100 cm. The increase of the noncarbonate components by 10 % corresponds to a decrease in the initial amount of sediment (CaC03=75 %) by roughly 30 % through solution. With increasing depth the carbonate content of the individual fractions becomes more and more uniform. At the surface the variation is from 30 % to 90 %, at the bottom it varies only between 50 % and 75 %. Comparable investigations of small-bay sediments showed a c1ear dependence of sediment/faunal zonation from the energy of the environment. The investigations show that the composition and three-dimensional distribution of the Istrian coastal sediments can not be predicted only from one or a few measurable factors. Sedimentation and syngenetic changes must be considered as a complex interaction between external factors and the actions of producing and destroying organisms that are in dynamic equilibrium. The results obtained from investigations of these recent sediments may be of value for interpreting fossil sediments only with strong limitations.

Optimization of a label-free biosensor vertically characterized based on a periodic lattice of high aspect ratio SU-8 nano-pillars with a simplified 2D theoretical model

We have recently demonstrated a biosensor based on a lattice of SU8 pillars on a 1 μm SiO2/Si wafer by measuring vertically reflectivity as a function of wavelength. The biodetection has been proven with the combination of Bovine Serum Albumin (BSA) protein and its antibody (antiBSA). A BSA layer is attached to the pillars; the biorecognition of antiBSA involves a shift in the reflectivity curve, related with the concentration of antiBSA. A detection limit in the order of 2 ng/ml is achieved for a rhombic lattice of pillars with a lattice parameter (a) of 800 nm, a height (h) of 420 nm and a diameter(d) of 200 nm. These results correlate with calculations using 3D-finite difference time domain method. A 2D simplified model is proposed, consisting of a multilayer model where the pillars are turned into a 420 nm layer with an effective refractive index obtained by using Beam Propagation Method (BPM) algorithm. Results provided by this model are in good correlation with experimental data, reaching a reduction in time from one day to 15 minutes, giving a fast but accurate tool to optimize the design and maximizing sensitivity, and allows analyzing the influence of different variables (diameter, height and lattice parameter). Sensitivity is obtained for a variety of configurations, reaching a limit of detection under 1 ng/ml. Optimum design is not only chosen because of its sensitivity but also its feasibility, both from fabrication (limited by aspect ratio and proximity of the pillars) and fluidic point of view. (© 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Propagation losses by tunnelling in barrier optical waveguides

An analytical model is proposed in order to estimate the optical propagation losses due to tunnelling in barrier waveguides. The results are validated by means of a beam propagation method (BPM) simulations for different waveguides conditions.

Assessing construction and demolition waste on masonry works to avoid future generation

The difficulty of dealing with construction and demolition waste (CDW) on construction sites is not new and continues to be a significant environmental problem. Currently the CDW collection system in Spain is done in a decentralized manner by each sub-contracted company, being necessary to implement effective waste management measures ensuring a correct management and minimization. During the last years several measures have been launched in order to improve and encourage the reuse and recycling of CDW. A widespread solution for CDW recovery is using them as a landscaping aggregate or for road bases and sub-bases. However, measures encouraging onsite prevention still need to be enhanced. This paper studies the major work stage generating CDW and analyses the categories of CDW produced during its execution. For this, several real building sites have been analysed in order to quantify the estimation of CDW generated. Results of this study show that a significant contributor to the CDW generation on building construction sites in Spain are the masonry works. Finally, a Best Practices Manual (BPM) is proposed containing several strategies on masonry works aimed not only at CDW prevention, but also at improving their management and minimization. The use of this BPM together with the Study and Plan of CDW management --required by law--, promotes the environmental management of the company, favouring the cohesion of the construction process organization at all stages giving rise to establishing responsibilities in the field of waste and providing a greater control over the process. Keywords: construction and demolition waste, management, masonry works, good practice measures, prevention.

Enhancing Guideline-based decision support with distributed computation through local mobile application

We introduce the need for a distributed guideline-based decision sup-port (DSS) process, describe its characteristics, and explain how we implement-ed this process within the European Union?s MobiGuide project. In particular, we have developed a mechanism of sequential, piecemeal projection, i.e., 'downloading' small portions of the guideline from the central DSS server, to the local DSS in the patient's mobile device, which then applies that portion, us-ing the mobile device's local resources. The mobile device sends a callback to the central DSS when it encounters a triggering pattern predefined in the pro-jected module, which leads to an appropriate predefined action by the central DSS, including sending a new projected module, or directly controlling the rest of the workflow. We suggest that such a distributed architecture that explicitly defines a dialog between a central DSS server and a local DSS module, better balances the computational load and exploits the relative advantages of the cen-tral server and of the local mobile device.

Sustainable Living. Environmental integration in 15 vernacular Spanish houses

This research was published online by the Spanish Ministry of Public Works in 2012. It collects 20 years of work that contributes to recognizing and enhancing the vernacular architecture in Spain, which has no known author, but has significant values and shows a wide variety of adaptation examples to climatic and environmental conditions. The research analyzes in detail and from different scales 15 houses in different climatic conditions and geographic regions in order to go deeper into the specific characteristics of each one of them from the perspective of sustainability. These houses are located in Tenerife, Salamanca, Huelva, Granada, Toledo, Madrid, Menorca, Alicante, Mallorca, Almería, La Coruña, Cantabria, Huesca and Lugo. The article analyzes the traditional dwelling, the natural environment and conditions that surround it and intends to discover the formal dialogue among them, as well as the origin of the design strategies

Calidad ambiental electromagnética : atenuación de las radiaciones electromagnéticas en los espacios habitados

La perspectiva del arquitecto en calidad ambiental, y salud en un contexto sostenible, se amplía al considerar las radiaciones electromagnéticas no ionizantes en el diseño arquitectónico. En ese sentido, además del confort higrotérmico, acústico, lumínico y de la calidad del aire, se podría considerar el confort electromagnético de un lugar. Dado que existe gran controversia en cuales han de ser los límites de exposición a radiaciones electromagnéticas no ionizantes, establezco como punto de referencia los valores límite más restrictivos, que son los recomendados por la norma SBM-2008, desarrollada por el Institut für Baubiologie & Oekologie Neubeuern (IBN)1. Se plantean como hipótesis que podemos modificar el entorno electromagnético con materiales de construcción y geometría; y que determinados trazados geométricos tienen la capacidad de reducir el impacto de los campos electromagnéticos sobre los organismos vivos. El objetivo consiste en demostrar experimentalmente que podemos trabajar sobre la calidad ambiental electromagnética de un espacio, a través de la elección de materiales de construcción y trazados geométricos, intentando demostrar que existe una relación causa - efecto entre ambos. La metodología plantea tres aproximaciones experimentales, cada una con un tipo de radiación electromagnética, pues se pretende abarcar las situaciones que comúnmente se pueden presentar en un entorno habitado, ya sea urbano o rural. La primera aproximación trata sobre las alteraciones del campo geomagnético natural (nT / m) provocadas por los materiales de construcción. Utilizo el geomagnetómetro BPM 2010, para realizar un ensayo con cuatro tipos de materiales de distinta procedencia: origen vegetal muy poco procesado (corcho aglomerado negro) y más procesado (OSB), origen derivado del petróleo (tablero rígido de poliuretano) y de origen mineral metálico (chapa minionda). De la lectura de los datos se observa relación causa-efecto entre los materiales de construcción estudiados y las modificaciones que pueden ejercer sobre el campo magnético de un lugar. A continuación se estudia el entorno de radiación electromagnética artificial a baja frecuencia (3 Hz a 3 kHz) y a alta frecuencia, (800 MHz a 10 GHz) en vivienda y en oficina utilizando unas geometrías concretas: las tarjetas de corrección de radiaciones. Estas tarjetas se ubican en paramentos verticales y horizontales de un espacio sometido a radiación propia de un entorno urbano. Se concluye que en una habitación inciden múltiples variables simultáneas muy difíciles de trabajar por separado y que aparentemente no se pueden identificar cambios significativos en las mediciones con y sin las tarjetas de corrección de radiaciones. A continuación estudio el entorno de radiación electromagnética artificial a baja frecuencia asociada a la red de distribución eléctrica. Para poder ver cómo este entorno electromagnético lo podemos modificar, utilizo las tarjetas de corrección de radiaciones ubicadas en relación directa con organismos vivos, por un lado germinados de semillas de haba mungo sometidas a campos electromagnéticos complejos a alta y baja frecuencia, propios de una oficina; y por otro lado germinados de semillas de haba mungo, sometidas a campos electromagnéticos puros a 50 Hz, sin influencias de radiación a alta frecuencia. Se concluye que se observa relación causa - efecto entre los trazados geométricos estudiados y su capacidad para reducir el impacto de los campos electromagnéticos a altas y bajas frecuencias sobre las semillas de haba mungo. También utilizo las tarjetas de corrección de radiaciones en un ensayo normalizado en el laboratorio de bioelectromagnetismo del Hospital Universitario Ramón y Cajal, con células de neuroblastoma humano. Se concluye que se observa relación causa - efecto entre los trazados geométricos estudiados y su capacidad para reducir el impacto de los campos electromagnéticos de 50 Hz Y 100 μT sobre células de neuroblastoma humano y además disminuyen la velocidad de proliferación celular respecto del grupo de células de control. Finalmente se estudia el entorno de radiación electromagnética artificial a alta frecuencia, asociado a comunicaciones inalámbricas. Para ello realizo simulaciones con el software CST Studio, sobre las tarjetas de corrección de radiaciones a alta frecuencia. A la luz de los datos se observa relación causa - efecto entre el trazado geométrico estudiado y su capacidad para reducir radiaciones electromagnéticas de alta frecuencia. Se comprueba además que, las tarjetas de corrección de radiaciones disminuyen la intensidad de la radiación acercándose a los límites de exposición establecidos por el instituto de la biología de la construcción alemán, que podrían estar señalando los estándares de biocompatibilidad. ABSTRACT The perspective of the architect in environmental quality, and health in a sustainable context is extended to consider non-ionizing electromagnetic radiation in architectural design. In that sense, besides the hygrothermal, acoustic, lighting and air quality comfort, the electromagnetic comfort of an indoor space could be considered. There is still great controversy about which should be the limits of exposure to nonionizing electromagnetic radiation, as a benchmark, the more restrictive limits are considered, by the SBM- 2008 standard, developed by the Institut für Baubiologie & Oekologie Neubeuern (IBN). The hypotheses that arise are the following: the electromagnetic environment can be modified by using certain construction materials and geometry; and certain geometric design have the ability to reduce the impact of electromagnetic fields on living organisms. The aim is to demonstrate experimentally that we can work on electromagnetic environmental quality of a indoor space, by using certain construction materials and geometric design, trying to demonstrate a cause - effect relationship between them. The methodology raises three experimental approaches, each with a type of radiation, it is intend to cover situations commonly may occur in an inhabited environment, whether urban or rural. The first approach discusses the alteration of the natural magnetic field (nT / m) caused by the building materials. Geomagnetometre BPM 2010 is used for conducting a test with four types of materials from different sources: vegetable origin less processing (black agglomerate cork) and vegetable origin more processed (OSB), petroleum origin (rigid polyurethane board) and metallic origin (miniwave plate). It is observed across the data information that exist cause-effect relationship between the construction materials studied and the modifications that they can exercise on the magnetic field of a place. Then I study the environment of artificial electromagnetic radiation at low frequency (3 Hz to 3 kHz) and high frequency (800 MHz to 10 GHz) in housing and office, using some specific geometries: correcting radiation cards. These cards are placed in vertical and horizontal surfaces of an indoor space concerned by radiation. I conclude that an indoor space is affected by multiple simultaneous variables difficult to work separately and apparently it is not possible identify significant changes in measurements with and without correcting radiation cards. Then the artificial electromagnetic environment of low-frequency radiation associated with the electricity distribution network is studied. To see how the electromagnetic environment can be changed, correcting radiation cards are placed directly related to living organisms. On one hand, mung bean seeds subject to complex electromagnetic fields at low and high frequency, typical of an office; and on the other hand mung bean seeds, subjected to pure electromagnetic fields at 50 Hz, no influenced by high frequency radiation. It is observed that exist cause-effect relationship between the geometric design and their ability to reduce the impact of electromagnetic fields at high and low frequencies that arrives on on mung bean seeds. The correcting radiation cards were also used in a standard test in the bioelectromagnetics laboratory of Ramón y Cajal University Hospital, on human neuroblastoma cells. It is observed that exist cause-effect relationship between the geometric design and their ability to reduce the impact of electromagnetic fields at 50 Hz and 100 μT on human neuroblastoma cells and also decrease the rate of cell proliferation compared to the group of cells control. Finally the artificial electromagnetic radiation environment at high frequency associated with wireless communications was studied. Simulations with CST Study software were made to determine the behavior of correcting radiation cards in high-frequency. It is observed across the data information that exist causeeffect relationship between the geometric design and the ability to reduce the levels of high-frequency electromagnetic radiation. It also checks that radiation correcting cards decrease the intensity of radiation approaching exposure limits established by Institut für Baubiologie & Oekologie Neubeuern (IBN), which could be signaling biocompatibility standards.

Myocardial signaling defects and impaired cardiac function of a human beta 2-adrenergic receptor polymorphism expressed in transgenic mice.

A threonine to isoleucine polymorphism at amino acid 164 in the fourth transmembrane spanning domain of the beta 2-adrenergic receptor (beta 2AR) is known to occur in the human population. The functional consequences of this polymorphism to catecholamine signaling in relevant cells or to end-organ responsiveness, however, are not known. To explore potential differences between the two receptors, site-directed mutagenesis was carried out to mimic the polymorphism. Transgenic FVB/N mice were then created overexpressing wild-type (wt) beta 2AR or the mutant Ile-164 receptor in a targeted manner in the heart using a murine alpha myosin heavy chain promoter. The functional properties of the two receptors were then assessed at the level of in vitro cardiac myocyte signaling and in vivo cardiac responses in intact animals. The expression levels of these receptors in the two lines chosen for study were approximately 1200 fmol/mg protein in cardiac membranes, which represents a approximately 45-fold increase in expression over endogenous beta AR. Myocyte membrane adenylyl cyclase activity in the basal state was significantly lower in the Ile-164 mice (19.5 +/- 2.7 pmol/min/mg) compared with wt beta 2AR mice (35.0 +/- 4.1 pmol/min/mg), as was the maximal isoproterenol-stimulated activity (49.8 +/- 7.8 versus 77.1 +/ 7.3 pmol/min/mg). In intact animals, resting heart rate (441 +/- 21 versus 534 +/- 17 bpm) and dP/dtmax (10,923 +/- 730 versus 15,308 +/- 471 mmHg/sec) were less in the Ile-164 mice as compared with wt beta 2AR mice. Similarly, the physiologic responses to infused isoproterenol were notably less in the mutant expressing mice. Indeed, these values, as well as other contractile parameters, were indistinguishable between Ile-164 mice and nontransgenic littermates. Taken together, these results demonstrate that the Ile-164 polymorphism is substantially dysfunctional in a relevant target tissue, as indicated by depressed receptor coupling to adenylyl cyclase in myocardial membranes and impaired receptor mediated cardiac function in vivo. Under normal homeostatic conditions or in circumstances where sympathetic responses are compromised due to diseased states, such as heart failure, this impairment may have important pathophysiologic consequences.