Usefulness of electrocardiographic parameters for risk prediction in arrhythmogenic right ventricular dysplasia

The value of electrocardiographic findings predicting adverse outcome in patients with arrhythmogenic right ventricular dysplasia (ARVD) is not well known. We hypothesized that ventricular depolarization and repolarization abnormalities on the 12-lead surface electrocardiogram (ECG) predict adverse outcome in patients with ARVD. ECGs of 111 patients screened for the 2010 ARVD Task Force Criteria from 3 Swiss tertiary care centers were digitized and analyzed with a digital caliper by 2 independent observers blinded to the outcome. ECGs were compared in 2 patient groups: (1) patients with major adverse cardiovascular events (MACE: a composite of cardiac death, heart transplantation, survived sudden cardiac death, ventricular fibrillation, sustained ventricular tachycardia, or arrhythmic syncope) and (2) all remaining patients. A total of 51 patients (46%) experienced MACE during a follow-up period with median of 4.6 years (interquartile range 1.8 to 10.0). Kaplan-Meier analysis revealed reduced times to MACE for patients with repolarization abnormalities according to Task Force Criteria (p = 0.009), a precordial QRS amplitude ratio (∑QRS mV V1 to V3/∑QRS mV V1 to V6) of ≤ 0.48 (p = 0.019), and QRS fragmentation (p = 0.045). In multivariable Cox regression, a precordial QRS amplitude ratio of ≤ 0.48 (hazard ratio [HR] 2.92, 95% confidence interval [CI] 1.39 to 6.15, p = 0.005), inferior leads T-wave inversions (HR 2.44, 95% CI 1.15 to 5.18, p = 0.020), and QRS fragmentation (HR 2.65, 95% CI 1.1 to 6.34, p = 0.029) remained as independent predictors of MACE. In conclusion, in this multicenter, observational, long-term study, electrocardiographic findings were useful for risk stratification in patients with ARVD, with repolarization criteria, inferior leads TWI, a precordial QRS amplitude ratio of ≤ 0.48, and QRS fragmentation constituting valuable variables to predict adverse outcome.

Similarity Mapplet: Interactive Visualization of the Directory of Useful Decoys and ChEMBL in High Dimensional Chemical Spaces

An Internet portal accessible at www.gdb.unibe.ch has been set up to automatically generate color-coded similarity maps of the ChEMBL database in relation to up to two sets of active compounds taken from the enhanced Directory of Useful Decoys (eDUD), a random set of molecules, or up to two sets of user-defined reference molecules. These maps visualize the relationships between the selected compounds and ChEMBL in six different high dimensional chemical spaces, namely MQN (42-D molecular quantum numbers), SMIfp (34-D SMILES fingerprint), APfp (20-D shape fingerprint), Xfp (55-D pharmacophore fingerprint), Sfp (1024-bit substructure fingerprint), and ECfp4 (1024-bit extended connectivity fingerprint). The maps are supplied in form of Java based desktop applications called “similarity mapplets” allowing interactive content browsing and linked to a “Multifingerprint Browser for ChEMBL” (also accessible directly at www.gdb.unibe.ch) to perform nearest neighbor searches. One can obtain six similarity mapplets of ChEMBL relative to random reference compounds, 606 similarity mapplets relative to single eDUD active sets, 30 300 similarity mapplets relative to pairs of eDUD active sets, and any number of similarity mapplets relative to user-defined reference sets to help visualize the structural diversity of compound series in drug optimization projects and their relationship to other known bioactive compounds.

A study of the relationship of support systems and adolescent pregnancy outcomes in an adolescent family life project

This study analyzed the relationship of family support systems and adolescent pregnancy outcomes. The population for the study was 390 adolescents who had attended the Marion County Health Department Adolescent Family Life Project in Indianapolis, Indiana during a two-year period.^ The study is unique in that it afforded the opportunity to compare adolescent pregnancy-related characteristics, of white and non-white adolescents in the same study.^ The pregnancy outcomes studied were: Infant birthweight, school attendance, and pregnancy recidivism.^ Significant results were found in the analysis that supported other research in regard to factors that are associated with school attendance when family support, adolescent's age, and ethnicity were controlled. Infant birthweight and repeat pregnancy outcome relationships were not found to have any consistently significant relationship with independent variables anticipated to be associated. However, the comparisons of infant birthweight among the adolescents with, and without, family support, by ethnicity resulted in some interesting findings. Repeat pregnancy proved an enigma, in that there seemed to be almost no variables in this study that were associated with the adolescent having a repeat pregnancy.^ Familial support in this study seemed to be of less importance as a factor in adolescent pregnancy outcomes than was ethnicity. The non-white adolescents in this study had a better record for remaining in school, both those non-white adolescents who lived with parents, and those who did not live with parents. More low birthweight occurred in the non-white adolescent, both those adolescents who lived with parents, and those who did not live with parents. Repeat pregnancy occurred more in the non-white adolescent whether she lived with parents, or did not live with parents. ^

Global practice experience: A useful lens for understanding patient and staff perceptions of successful integration of health information technology in primary care

Making healthcare comprehensive and more efficient remains a complex challenge. Health Information Technology (HIT) is recognized as an important component of this transformation but few studies describe HIT adoption and it's effect on the bedside experience by physicians, staff and patients. This study applied descriptive statistics and correlation analysis to data from the Patient-Centered Medical Home National Demonstration Project (NDP) of the American Academy of Family Physicians. Thirty-six clinics were followed for 26 months by clinician/staff questionnaires and patient surveys. This study characterizes those clinics as well as staff and patient perspectives on HIT usefulness, the doctor-patient relationship, electronic medical record (EMR) implementation, and computer connections in the practice throughout the study. The Global Practice Experience factor, a composite score related to key components of primary care, was then correlated to clinician and patient perspectives. This study found wide adoption of HIT among NDP practices. Patient perspectives on HIT helpfulness on the doctor-patient showed a suggestive trend that approached statistical significance (p = 0.172). Clinicians and staff noted successful integration of EMR into clinic workflow and their perception of helpfulness to the doctor-patient relationship show a suggestive increase also approaching statistical significance (p=0.06). GPE was correlated with clinician/staff assessment of a helpful doctor-patient relationship midway through the study (R 0.460, p = 0.021) with the remaining time points nearing statistical significance. GPE was also correlated to both patient perspectives of EMR helpfulness in the doctor-patient relationship (R 0.601, p = 0.001) and computer connections (R 0.618, p = 0.0001) at the start of the study. ^

Estimates of life expectancy gains from reducing/eliminating major causes of death in the USA: An update analysis for population in 2001--2008

Evaluation of the impact of a disease on life expectancy is an important part of public health. Potential gains in life expectancy (PGLE) that can properly take into account the competing risks are an effective indicator for measuring the impact of the multiple causes of death. This study aimed to measure the PGLEs from reducing/eliminating the major causes of death in the USA from 2001 to 2008. To calculate the PGLEs due to the elimination of specific causes of death, the age-specific mortality rates for heart disease, malignant neoplasms, Alzheimer disease, kidney diseases and HIV/AIDS and life table constructing data were obtained from the National Center for Health Statistics, and the multiple decremental life tables were constructed. The PGLEs by elimination of heart disease, malignant neoplasms or HIV/AIDS continued decreasing from 2001 to 2008, but the PGLE by elimination of Alzheimer's disease or kidney diseases revealed increased trends. The PGLEs (by years) for all race, male, female, white, white male, white female, black, black male and black female at birth by complete elimination of heart disease 2001–2008 were 0.336–0.299, 0.327–0.301, 0.344–0.295, 0.360–0.315, 0.349–0.317, 0.371–0.316,0.278–0.251, 0.272–0.255, and 0.282–0.246 respectively. Similarly, the PGLEs (by years) for all race, male, female, white, white male, white female, black, black male and black female at birth by complete elimination of malignant neoplasms, Alzheimer's disease, kidney disease or HIV/AIDS 2001–2008 were also uncovered, respectively. Most diseases affect specific population, such as, HIV/AIDS tends to have a greater impact on people of working age, heart disease and malignant neoplasms have a greater impact on people over 65 years of age, but Alzheimer's disease and kidney diseases have a greater impact on people over 75 years of age. To measure the impact of these diseases on life expectancy in people of working age, partial multiple decremental life tables were constructed and the PGLEs were computed by partial or complete elimination of various causes of death during the working years. Thus, the results of the study outlined a picture of how each single disease could affect the life expectancy in age-, race-, or sex-specific population in USA. Therefore, the findings would not only assist to evaluate current public health improvements, but also provide useful information for future research and disease control programs.^

Caracterización Dinámica de Partículas Magnéticas y su Uso en Aplicaciones Biomédicas

El uso de las partículas magnéticas ha venido a más durante los últimos 10 años. Lo anterior ha estado condicionado por factores como la amplia investigación en materiales a nivel atómico, los retos propuestos por las diferentes áreas de investigación donde los niveles nanométricos cobran importancia, la inherente innovación tecnológica que pueden aportar a la industria dichas escalas y finalmente, el impacto socioeconómico que pueden tener estos avances tecnológicos. Sin embargo, la traslación a la industria de los avances tecnológicos se ha visto limitada por la falta de estrategias, ya que el 88% del conocimiento se queda en Universidades y Centros de Investigación y el resto, 12%, pasa a la industria o es obtenido en ella. En este trabajo de investigación se ha tratado de completar el círculo de idea, conceptualización, generación de conocimiento, prototipo, prueba in vitro y prueba in vivo; todo ello para dejar el menor espacio posible entre Investigación e Industria. Se ha fabricado un recinto que permite la observación del comportamiento de las partículas magnéticas cuando están inmersas en un medio con viscosidad controlada y con una fuente magnética estática. De la observación experimental se han encontrado fenómenos magnéticos como la aglomeración y la autoorganización, que han sido aprovechados, no solo para ofrecer una solución alternativa a la corrección del desprendimiento de retina, sino también para promover las mejoras de métodos de separación y/o filtrado celular, ayuda en correcciones ortopédicas o en el diagnóstico y tratamiento de enfermedades degenerativas. Particularizando en la corrección del desprendimiento de retina, se ha desarrollado y patentado un Dispositivo Ocular cuya función es la de tapón del agujero retiniano, ayudando en la cicatrización de la retina. Dicho dispositivo ha sido evaluado en conejos albinos neozelandeses obteniéndose un éxito en la reaplicación de la retina del 80% y resultando su toxicidad en condición difusa tras evaluación anatomopatológica. Así mismo, el ferrofluido diseñado y fabricado se ha localizado en la zona de interacción magnética siempre y su disposición ha sido en el mayor de los casos en forma de placa pero también se han formado anillos; lo anterior no ha afectado en ningún sentido el éxito en la reaplicación de la retina. Por otro lado, no se han encontrado indicios de siderosis en la zona de interacción magnética, sus alrededores o el resto del globo ocular; ni las células han presentado apoptosis inducida por los materiales introducidos en el ojo. Sin embargo, se ha encontrado una fuerte necrosis inducida por la presión ejercida sobre la retina por el dispositivo ocular, evidenciando la necesidad de un mejor control de dicha presión. Tras la caracterización de los copos y la presión que éstos ejercen, se ha podido identificar que el dispositivo ocular se puede sintonizar para inducir una presión entre 0.5 y 2.5 mmHg; por tanto se puede vislumbrar que es posible minimizar la muerte celular causada en las células retinianas. Finalmente, tras la experimentación con conejos se ha observado que el dispositivo ocular resuelve los problemas inducidos por las siliconas o los gases e inclusive aporta ventajas competitivas de alto valor añadido como: no requerir de posiciones incómodas en el post-operatorio, no modifica las propiedades ópticas del ojo ya que no es necesario dejar silicona o gases en el interior del ojo, se pueden sellar múltiples agujeros retinianos, corrección de desprendimiento de retina inferior sin complicaciones asociadas, etc.; en definitiva mejora la calidad de vida domiciliaria del paciente además de solventar los problemas inducidos por las soluciones actuales. The using of magnetic particles has become more important during last 10 years. This event has been conditioned by several factors like a wide researching on materials at atomic level, the challenges proposed by different research areas where nanometric levels became important, the inherent technological innovation to the industry and finally, the socioeconomic impact of these kinds of technologies. However, the nanotechnological advances have not been well addressed to the industry since 88% of the acknowledge keeps on Universities and Research Centers, and the remaining 12% goes through the industry or is obtained in it. In this research work, we have tried to complete the entire process about idea, concept, acknowledge generation, prototyping and in vitro and in vivo testing; all to leave as little space as possible between Research and Industry. We have built an experimental hall which allows us the observation of magnetic particles' behavior when are immersing in a controlled viscous medium and under a static magnetic field. The experimental observation has been useful to identify and use two magnetic phenomena: agglomeration and self-organization; no only for retinal detachment, but also to improve cellular separation and/or filtered methods, orthopedic solutions or the diagnostic and treatment of degenerative diseases. Particularizing on retinal detachment, we have developed and patented an Ocular Device which its function is acting like a tampon of the retinal hole for helping with the scarring retina. The device has been evaluated in animals and the results show that we can achieve a success of 80% before rabbit’s death and non cell apoptosis, only necrosis, over the retina attached by the ocular device after anatomopathological evaluation. Also we have identified a diffuse toxicity after anatomopathological evaluation, so more experimenting must be proposed. Otherwise, the ferrofluid has been localized where the magnetic interaction area is located and its deposition has been in most cases plaque shape like but rings have also been observed; this has not affected in any way the successful reattachment of the retina. On the other hand, we have not found any evidence of siderosis in the magnetic interaction zone, near of or some other place of the ocular globe; and we did not find any apoptosis induced by the materials inserted within the eye. However full necrosis, exactly on the magnetic interaction zone, has been found and induced by the pressure exerted over the retina by the ocular device, evidencing the needing of its better control. After flakes’ characterization and its pressure exerted, we identified that the ocular device can be tuned in order to induce a pressure between 0.5 and 2.5 mmHg; therefore we can perceive that death caused to the retinal cells can be minimized. Finally, the experimentation has shown that the ocular device solves all problems induced by silicone or gases an even contributes with some other competitive advantages of high added value like: no uncomfortable postoperative positions, it does not modify any optical property of the eye because there is no needing of leaving silicone or gases inside the eye, many holes can be sealed, the inferior retinal detachment can be solve without any complications, etc.; definitively the ocular device improves patients’ quality of life.

Sobre la Arquitectura en la definición del Paisaje

Comúnmente la Arquitectura se manifiesta en los edificios como un hecho de la realidad que tiene siempre carácter contemporáneo y ése debe ser el valor supremo de un arte que no distingue entre antiguo y moderno, por afectar al presente y ser contemporáneo como experiencia. Los objetos se insertan irremediablemente en su medio e incluso llegan a definirlo en ocasiones: así, arquitectura y paisaje, aparecerán a veces confundidos con diferencias difíciles de determinar. El término “paisaje” es relativamente moderno y se deriva de ciertas representaciones gráficas o pictóricas producidas en Occidente en época algo posterior al Renacimiento. No obstante, el hecho de que una palabra se pueda escribir o se cite no quiere decir que la realidad a la que responde no pueda existir, pues lo escrito es solamente un medio de expresión, y es obvio que existen otros quizá más antiguos y de idéntica importancia, pues la propia escritura no es más que el reflejo de un fenómeno que ya se ha producido con anterioridad. Parece así que el testimonio de la realidad viene dado por distintos contextos en lo que suele llamarse “cultura” de modo que las culturas pueden tener aspectos de gran interés mediante diferentes sistemas de expresión variados sin que eso tenga que pasar forzosamente por el filtro de un alfabeto y una escritura. A tenor de los primeros descubrimientos, parece que la cuestión de escribir tuvo originalmente un carácter de constatación de apunte contable y tampoco se puede establecer con certeza si algunos utilizaron la escritura como el so-porte adecuado para referir mitos o historias, pues la Arqueología no ha proporcionado sino testimonios fragmentarios; de lo que si está repleta sin duda la historia es de apuntes contables. Otra cuestión que suscita dudas es la propia definición de escritura, pues parece que los más antiguos modos de expresión escrita se reducen a pictogramas que resultan aún indescifrables. Lenguas y toponimia son también herramientas muy útiles para bucear en el pasado, pero aún así persisten dudas en las escrituras que pro-vienen de las representaciones primordiales: la propia escritura en sus orígenes parece alimentarse de las propias intuiciones inmediatas de la representación, algo que evolucionaría representando esa realidad urgente e inmediata del control o el abastecimiento que luego se convertirían en los fragmentos de texto que han podido conservarse. Es notorio, sin embargo, que ese conjunto enorme de convenios gráficos estaba sujeto a la palabra y la desaparición de las culturas determinó también la desaparición consecuente de sus lenguas, y esos signos - fueran o no escritura - han pasado definitivamente a las zonas oscuras del conocimiento. Escribir supone también disponer de capacidad de abstracción gráfica que diferencie la palabra y la cosa, y es posible que la razón que llevara a ese descubrimiento fuera simplemente el de una economía de signos, pues escritura y lenguaje son limitados por definición, mientras que las cosas del mundo son innumerables: ningún idioma contiene todas las palabras para describir todo lo que puede aparecer. Aparentemente, ese el motivo por el cual existe un localismo – un término específico que refiere algo que existe en un lugar y no en otros - en lo que se refiere a dar el nombre a la cosa y también fuente de paradigma entre los pueblos que se consideran primitivos y los que se consideran civilizados. Debe tenerse en cuenta también que esa transposición se da en ambos sentidos, de modo que las culturas más aisladas también incorporan conceptos que carecen de una explicación racional consistente. Las mitologías son así eternas, pues sirven para explicar realidades que carecen de un entendimiento alcanzable y está también bastante claro que los lenguajes resultan ser un enigma, como realidad autónoma que queda en-cerrada y se explica en sí misma. Parece también que los primeros en escribir las consonantes aisladas fueron los pueblos semíticos occidentales de las orillas del Mediterráneo, pueblos que crearon un alfabeto silábico que llegó a ser utilizado incluso por los tartesios en el sur de la península ibérica como el primer alfabeto de toda Europa occidental. Resulta patente que el término “paisaje” se ha nutrido siempre de representaciones, bien escritas o artísticas, pero queda también claro que esas representaciones se suponen derivadas de la creencia en una idea de paisaje como algo que se ve representado en sí mismo, es decir, como la imagen de una realidad externa situada fuera del individuo. Eso es un hecho trascendente, pues el paisaje requiere lejanía de la cosa, de modo que el actor – aún sabiéndose inserto en su paisaje – es incapaz de percibirlo desde dentro. En el paisaje ocurre igual que en un teatro o en una representación: los actores son conscientes de su papel y su posible cometido, pero no son los que realmente pueden disfrutar de la eficacia o de la propia presencia de la obra, pues forman parte de ella. La idea de paisaje proviene de una lectura externa a la de los propios protagonistas del drama, de modo que si quieren ser un crítico del paisaje se debe abandonar la representación para mirar el espectáculo desde una distancia adecuada, al fin y a cabo externa. De ese modo, aparece la primera constatación del hecho del paisaje como una realidad construida por objetos y personajes, pero, sobre todo, es una realidad construida por miradas. Llama también la atención otorgada en las lecturas de los especialistas hacia esa referencia externa - artística si se quiere - sobre el término “paisaje”, de modo que la bibliografía no especializada sobre el particular siempre acaba en tratados de pintura o poesía. Parece sin embargo que el hombre y sus paisajes son realidades indisolubles desde la propia aparición de la especie, de modo que llevar la cuestión hacia términos exclusivamente esteticistas parece una posición parcial. Hombre y medio han formado siempre una sola unidad, aunque esa unidad se haya convertido en determinados casos en sinónimo de depredación y destrozo. Sin embargo, esa destrucción crea igualmente un paisaje como desolación que es resultado del propio quehacer del hombre: elementos que también poseen un contenido sustancial de memoria en los paisajes industriales como un momento de la Historia previo a la automatización y a la globalización de la vida actuales. Quizá el concepto más interesante desde el punto de vista teórico sea precisamente el de esa cualidad del paisaje como mirada, algo externo producido por el contemplador en un momento ajeno a la pertenencia, una mirada que no es tan sólo estética sino comprensiva, gozosa, activa o analítica - pues existen tantas maneras de mirar como sujetos - sin que pueda definirse con precisión esa contemplación más que en términos que alcanzan la propia individualidad. En términos poéticos, también podría establecerse como ese conjunto de miradas individuales crean también una estructura que hace que ese paisaje se valore y se comprenda, de modo que desde ese punto de vista ese paisaje supone una creación colectiva. Con respeto o como depredador, el hombre se ha instalado en su medio, y al hacerlo, ha dejado huellas dentro del propio paisaje que hacen que tome una determinada significación. Naturalmente, existe una teoría que distingue entre “país” y “paisaje”, asumiendo para el primero la noción exclusiva de territorio en la cual el hombre no tiene papel estético alguno. He intentado muchas veces comprender esa posición, sin acabar de entender el planteamiento que la sustenta: parece que la visión de la cosa estará siempre humanizada, aún en las zonas “vírgenes” o intactas, pues la propia visión hace que el objeto se modifique en su propia unidad perceptiva, creando una curiosa indeterminación que lleva a los conocidos equívocos entre imagen real y representación. Efectivamente, la visión de la cosa requiere de una cultura y unos medios que la informan, de modo que un texto, una pintura, una descripción o una fotografía quedarán ya humanizadas por el propio hecho de ser informadas, pues ello otorga una forma a priori. De ese modo, el paisaje figura inscrito en una función que establece tanto aspectos de un paisaje posible como aspectos del paisaje descrito y solamente podrá hablarse sobre la potencialidad del estado final de ese paisaje y nada del propio paisaje en sí, mientras ese paisaje no quede humanizado por el propio observador. Esta cuestión obliga a elegir una definición de paisaje alejada de presupuestos esteticistas para acercarla a los puramente culturales, de modo que no existe otra vía para la investigación que contemplar esa realidad física en función de las coordenadas del hombre que la habita, dotada del contenido correspondiente a esa revelación. Lejos de las posiciones de la geomorfología, el término “paisaje” implicará así unas condiciones determinadas de contemplación por parte de un sujeto por el cual el espectáculo queda humanizado en dicho acto.Cabe pensar también si no es cierto que todos los paisajes requieren de esa condición humanizada, pues aunque no estén habitados están siempre ocupados por esa mirada que los habita, al igual que un escenario sin público que carece de vigencia. A partir de ahí se sitúan las coordenadas en donde este trabajo configura la presencia de la arquitectura en la definición del paisaje, una premisa que parece ya venir otorgada desde el principio, pues esa misma mirada del espectador ya está dotando de un sentido de orden y jerarquía a la contemplación, unas cualidades que están en la base de toda actividad arquitectónica, De hecho la propia definición de “monumento natural” - en si misma una contradicción – expresa ese conflicto, dotado de un fenómeno de admiración y solape entre cultura y naturaleza, como conceptos enfrentados desde su origen. La conclusión sobre el dilema propuesta en la tesis no ha sido otra que suponer que esas dos realidades que son la cultura y el paisaje se han solapado desde el principio de los tiempos del hombre formando un binomio indeslindable. Se ha dicho antes que el proceso de invasión del territorio por el hombre es significativo, y esa significación es la que origina una creación autónoma que se aísla como un concepto abstracto de los entes naturales, tomándolos como material de trabajo, y estableciendo una oposición conceptual en la realidad perforada e interpretada por el hombre que viene a oponerse a lo que supone la caja cerrada e ignota del enigma del mundo. La cuestión de la significación del hombre sobre el territorio se subsume en la creación de unos productos que permanecen y que son testimonio de la propia cultura, de forma que la cantidad de rastro que el hombre deja sobre el territorio contribuye en mayor medida a la cualificación del paisaje como concepto. Eso lleva a establecer que cualquier paisaje - por el mero hecho de serlo y ser definido así – es ya cultural, puesto que está configurado por los productos de la cultura. Las palabras que puedan quedar encerradas en las piedras de los monumentos o de las ciudades son las de los hombres que trabajaron allí, y también las de los que las habitaron: más aún, el propio sentido del paisaje y su conservación vienen determinados por la presencia del hombre como único interprete de conceptos como ecología o conservación, algo que se pone de manifiesto también en la espantosa devastación que producen los fenómenos propios de la naturaleza. La historia natural, al igual que la vida, están conformadas por éxito y devastación, sin que uno y otra tengan especial preferencia, pues la preferencia se alimenta de otra clase de conceptos. La cuestión de atribuir valores morales al mundo natural es algo muy antiguo, y quizá sea la fuente o el manantial de las primeras religiones, una cuestión que se une a la indefectible noción de mortalidad que define la existencia del hombre frente a la inmanencia de la naturaleza. Esa propia naturaleza está dotada intuitivamente de un carácter “inocente” suponiendo que la inocencia es lo opuesto a la sabiduría. La cuestión es bien otra, ya que la naturaleza no posee ni siquiera algo que pueda definirse como “carácter”, en el sentido personal del término. La cuestión no cae, evidentemente, del lado de las definiciones o de las cualidades, sino del propio análisis de la realidad que el hombre va construyendo, destruyendo, embelleciendo o perjudicando para definir el territorio que habita, interponiendo a su manera recursos, instalaciones y en definitiva todos los testimonios posibles como principal manifestación de su esencia. Entre los artefactos que el hombre produce, uno de los más persistentes y más conspicuamente descritos es el de la arquitectura - entendida aquí en un sentido amplio - es decir, como el conjunto de modificaciones del espacio y del territorio. El espacio se puede modificar de muchos modos, pero en cualquiera de los casos constituye una de las huellas más características que el hombre establece como manifestación física de su propio ser discursivo. También la arquitectura ha demostrado ser una de los fenómenos más persistentes, incluso más que la propia lengua que la origina en su discurso primero antes que pueda ac-cederse a una idea sobre la conformación del material. Es paradigmático que el episodio descrito sobre la Torre de Babel en la Biblia la cuestión de la ambición de los hombres frente a Dios, representada precisamente en una arquitectura, se asimile a la discusión sobre el lenguaje primordial. La cuestión no es baladí, pues el fenómeno de la creación es algo que se concede exclusivamente a los dioses, que por esa razón habitan los territorios a los que los hombres no pueden llegar; territorios de albergue en los que las mitologías sitúan a dioses y demonios, con amplios espacios intermedios donde situar a las divinidades menores, héroes o seres híbridos en los que la coyunda de los dioses con los humanos produce sujetos que alivian el sentido de la mortalidad. El comentario del Génesis también concede un valor a la técnica, al mito de Prometeo y al fuego como creador de excelencia. Frente al progreso prometeico, se postula el valor divino, y la única forma posible de paliar ese progreso es la confusión del lenguaje, pues eso será lo que produzca la dispersión y la falta de acuerdo. La cuestión también puede explicar esa afición tan común por lo canónico en arquitectura que se mantiene a lo largo de grandes períodos, al igual que una gran máquina de inercia. Parece que los conceptos primordiales de la arquitectura basados en elementos simples como el hito, el dintel, lo recto y lo curvo, la rampa o la escalera, y el uso distinto o cualificado que se otorga a la piedra, el ladrillo, la madera o el metal como componentes primordiales del material arquitectónico se haya mantenido a lo largo de muchos milenios sin apenas cambios, al igual que ocurre con las costumbres alimenticias que siguen una progresión ascendente a través de lo crudo, lo asado y lo cocido, hasta obtener distintos grados de refina-miento, pero que siempre se sustentan en la sensación primigenia. El descubrimiento de la arquitectura proviene de un cierto manejo de las dimensiones, y consiguientemente de la geometría. Pero la geometría es cosa abstracta al igual que el lenguaje, de modo que para poder realizar arquitectura se hace necesaria esa capacidad de abstracción primera que luego permite la realización de un dispositivo. La realidad y su número exhiben un divorcio, al igual que las cosas y sus nombres exhiben el suyo, y el análisis numérico es solamente una forma de ver la realidad, una forma rigurosa y exacta – aunque parcial - que solamente representa el modelo ideal al cual la realidad se aproxima en mayor o menor medida: esa aproximación matemática hace que el universo pueda condensarse parcialmente en números, al igual que la realidad puede condensarse en nombres, pero ni el nombre ni el número reflejarán el mundo en toda su complejidad. El número es quizá solamente un medio de describir las cosas, como lo serían las formas puras que responden a una configuración matemática que pueda producirse en teoría en cualquier parte del Universo. Sin embargo, para el ejercicio de la arquitectura es preciso acudir a esa simplificación que exige la visión abstracta del plano como una sección cierta realidad como un corte abstracto del elemento considerado. Con su traza o sin ella, con la propia expresión matemática que lo describa o sin precisarla, esa intuición del plano como elemento generador del espacio es anterior a aquella expresión, al igual que el habla fue anterior a la escritura, pues solamente se produjo a través de ella y como refuerzo y sustituto de la memoria. Existen así abstracciones de la memoria que aparecen derivadas de los signos de la naturaleza aparecidos solamente de forma eventual y fragmentaría: así ocurre con la línea, el cuadrado y el círculo, formas iniciales y abstractas sonsacadas en cierta medida de la observación que dan origen a los primeros signos de la arquitectura primordial, de modo que cuadrados y círculos, elevados a prismas y superficies esféricas o esferoides aparecen en tumbas y edificios elementales de los primeros tiempos mediante una geometría primordial que se superpone al paisaje en el que se inserta. Es cierto también que esas formas se encuentran ya aproximadas en objetos que se encuentran en el medio físico, líneas en extremidades, ramas y miembros; ángulos rectos en algunos cristales que se observan mediante corte o formas circulares en astros y cráteres, pero esa realidad solamente presenta su forma aproximada y no su abstracción pura, de igual modo que el jeroglífico propondrá al ave rapaz para representar la idea de vigilancia y la buena vista, o incluso que la imagen del propio ojo sustituya la idea del Dios que todo lo ve en las culturas anti-guas. La elección fue resuelta, después de muchos intentos y aproximaciones, con la adopción del ángulo recto como un artificio fácil para el replanteo a través del triángulo sagrado 3:4:5 que ya se utilizó para construir las pirámides de Egipto, y que dio origen también a la mayor parte del urbanismo antiguo, coexistiendo con la forma circular primordial en el tipo denominado “tholo”. Aquella trama cuadrangular era uno de los patrones de relleno del espacio más comunes y compactos, y esa fue probablemente la razón por la que en tiempos muy posteriores fuera adoptada como una forma eficaz permanente de organización frente al desorden topológico que procura el conjunto de asociación de plantas circulares. Otra cuestión paradigmática es que esos conceptos primordiales e ignotos - que convergen en el mismo origen de las civilizaciones - se conviertan luego en algo canónico, a través del uso. El canon en sí mismo es algo ideal, como una norma aplicable a objetos de una realidad que ha sido creada solamente como indicio del ca-non, algo abstracto que tiene proporciones estrictas que son siempre las mismas y no obedece a criterios racionales: será absurdo sin embargo buscar el canon griego entre los templos de época como algunos lo hicieron, pues los edificios solamente se aproximan a los ejemplos canónicos y por esa razón se habla del “dórico del Partenón” que es diferente del de Egina o del de Paestum, siendo todos ellos evidentemente dóricos. Sin embargo, esa idea resulta útil al tratadista, al teórico de la arquitectura y al historiador, aun-que solamente refleje una vaga idea de lo que sucede más allá del tratado. Otra cuestión es la sutileza de los ejemplos de arquitectura, y del mismo modo que los cuerpos de los seres vivos jamás son simétricos, aunque respondan a un diseño simétrico general derivado de las condiciones de la división celular, los edificios supuestamente canónicos en los que los especialistas se inspiraron para definir los órdenes clásicos no disponen de esa simetría modular exacta, sino que adaptan un modelo general al lugar siempre cambiante del emplazamiento, es decir, se adaptan con habilidad a la vez que configuran el paisaje en el que se insertan. La luz de los distintos intercolumnios del Partenón es ligeramente distinta, aunque guarde un evidente sentido de simetría axial, de manera que aquellos “órdenes” que formaron la Teoría de la Arquitectura no son más que una bella interpretación sectorial de la arquitectura antigua elaborada por los tratadistas del Renacimiento y, posteriormente, por los neoclásicos. Parece, sin embargo, que ese ansia por el canon como claridad de lenguaje es algo consustancial al desarrollo de la arquitectura, una lingua franca que tiende a evitar la dispersión producida entre los mortales por los dioses antiguos, de modo que si no era posible llegar al cielo de los dioses se procuró que el lenguaje de la Tierra fuera al menos inteligible para poder entenderse entre los hombres. Parece que la estructura del poder siempre requirió de un determinado nivel de organización, y también que las instrucciones se entendieran con claridad: parece que en nuestros tiempos esos antiguos cánones se han sustituido por la obediencia a normas abstractas, dictadas por instituciones también algo abstractas y que tienen nombres divertidos compuestos por siglas, aunque no se conozca bien su virtud. El canon actual está constituido por “normas” que dejan tranquilos a algunos, aunque parece quizá que todo ese entramado formal que sirve como anestesia para el cuerpo social procura también la destrucción de los bosques en formas de montañas ingentes de papel burocrático. Durante muchos siglos las normas fueron otras, en la forma de un canon del cual nadie podía escapar: aún así, mediante la utilización de cánones o sin ellos, la arquitectura prosperó en la civilización desde los primeros refugios cavernarios o los abrigos primigenios y de ese modo fue configurando la realidad, es decir, el paisaje. Como antes se dijo, ese es un viaje de ida y vuelta en el cual ambos se confundían y subsumían: el manejo de las formas y lenguajes de la arquitectura posibilitaría con el tiempo la distinción entre el campo en donde reina el caos y la ciudad, en donde reina teóricamente el orden, creando un divorcio que duraría milenios y que aún persiste. Esa oposición generaría también una forma de paisaje y una serie de usos simbólicos y sagrados de los elementos de la arquitectura - como son puertas y murallas - que se han mantenido conceptualmente aunque hoy las ciudades ya no posean murallas físicas, ni puertas que se cierran con la llegada de la noche. En ese sentido, la arquitectura ha podido definir el paisaje, entendiendo la arquitectura no solamente como los edificios en sí, sino como el hecho de la manifestación del hombre sobre el territorio, de modo que no podrá hablarse de paisaje sin su arquitectura, del mismo modo que no puede hablarse de paisaje sin hombres. Por esta razón, la Tesis habla sobre Arquitectura y Paisaje, pero más particularmente sobre el hecho de la arquitectura en la definición del paisaje, es decir, de como los hechos arquitectónicos van a determinar o no la cualidad y la calificación de un paisaje. Deberá partirse en primer lugar de una definición de lo que se entiende y se ha entendido comúnmente por paisaje: igualmente, y habida cuenta del contexto en el que sitúa el propio trabajo de tesis, la cuestión solamente se circunscribirá a lo que se entiende como cultura occidental, pues el desarrollo de la civilización presenta siempre un color local que hace que el análisis de un fenómeno de esta envergadura tenga distintas connotaciones en las distintas áreas de civilización. De igual modo, y habida cuenta también que el paisaje se construye a través de todas las manifestaciones culturales, se hará a veces necesario indagar en otras disciplinas no arquitectónicas para comprender el alcance de algunos casos en los cuales los restos arquitectónicos han desaparecido, o en los que subsisten escasas trazas. Una definición tan amplia de la Arquitectura llevaría a escribir un relato sobre toda la cultura occidental y por ese motivo solamente se han esbozado ideas sobre la aparición de esos signos sobre el paisaje basados en elementos antiguos y primigenios que se repiten con insistencia y van dando lugar al variado repertorio de la arquitectura occidental cómo conformación de ideas sobre el me-dio y sobre el mundo que se percibe y se habita. ABSTRACT About Architecture in defining Landscape. Abstract Architecture is commonly manifested in buildings as a fact of reality that has always a contemporary character and that should be the highest value of an art that does not distinguish between ancient and modern, to affect the present and be contemporary as experience. Objects are inserted irremediably in their midst and even sometimes come to define it: thus, architecture and landscape, appear sometimes confused with differences difficult to determine. However, the term "landscape" is relatively modern and is derived from certain graphical or pictorial representations produced in the West in some subsequent period to the Renaissance. The fact that a word can be written or quoting does not mean that the reality that can not be answered, because the writing is only a mean of expression, and it is obvious that there are other and perhaps older equally important, because the writing itself is nothing more than the reflection of a phenomenon that has occurred before. It thus appears that the testimony of reality is given by different contexts in what is called "culture", so that cultures can have aspects of great interest by many different expression systems without this necessarily have to pass through the filter of alphabet and writing. Under the initial findings, it appears that the question of writing originally had a character and finding accounting entries, and it can not be established with certainty whether some used writing as the support appropriate to refer myths or stories, because archaeology has provided only fragmentary evidence. Another issue that raises questions is what can properly be defined as writing, it seems that the oldest modes are reduced to writing pictograms are still indecipherable. Languages and place names are also very useful tools for diving in the past, but still questions remain in the scriptures that come from the primordial representations: either it is very well defined what the own writing in its origins: the beginnings seem to feed on immediate intuitions of representation, which would evolve representing reality that urgent and immediate control or supply which is then inherited into fragments. It is noteworthy, however, that this huge set of graphics agreements was subject to the word and the disappearance of cultures determined also the consequent disappearance of their languages, and those signs - whether or not they write - have passed definitively to dark areas of knowledge. Writings supposed also the capacity of abstraction graph differentiates the word and the thing, and it is possible that the reason to carry this discovery was simply that of an economy of signs, for writing and language are limited by definition, while the things of the world are innumerable: no language contains all words to describe all that may appear. Apparently, that's why there is a localism - a specific term that refers to something that exists in one place and not in others - in regards to name the thing and also the source of paradigm among peoples are considered primitive and civilized. It should be noted also that transposition occurs in both directions, so that the most isolated cultures also incorporate concepts that lack a consistent rational explanation. Mythologies are eternal and therefore serve to explain realities that lack an understanding achievable and also pretty clear that languages happen to be an enigma, as an autonomous reality that is enclosed and explains itself. It also seems that the first to write consonants were isolated western Semitic peoples from the shores of the Mediterranean, peoples who created a syllabic alphabet came to be used even by tartesios in southern Iberia as the first alphabet in Western Europe. It is clear that the term "landscape" has always nurtured representations, either written or artis-tic, but it is also clear that these representations are assumed arising from belief in an idea of landscape as something that is represented in itself, as the image of a reality external located outside the individual. That is an important fact because the landscape requires remoteness of the thing, so that the actor - even knowing insert in landscape - is unable to perceive from within. The landscape is just as in a theatre or a performance: the actors are aware of their role and their possible role, but they are not the ones who can really enjoy the efficiency or the presence of the work itself, as part of it. The idea comes from an external landscape reading the principles of players in the drama, so if you want to be a critic of the landscape should leave the actual representation to watch the spectacle from a safe distance, finally external. Thus, the first finding of fact of the landscape appears as a reality constructed by objects and characters, but above all, a reality constructed by looks. Also noteworthy given the readings of specialists to the external reference - art if it could be - on the term "landscape", so no specialized literature on the subject always ends in treatises on painting or poetry. It seems however that the man and his landscapes are inseparable realities from the very onset of the species, so bring the issue into terms exclusively aesthetics seems a partial position. Man and environment have always been a single unit, but that unit has become synonymous with certain cases predation and destruction. Nevertheless, this destruction also creates a landscape as desolation that results from proper task of man elements that also have substantial contents of memory in industrial landscapes as a time of pre-automation history and globalization of current life. Perhaps the most interesting from a theoretical point of view is precisely that quality of landscape as something external produced by the viewer in a strange time of membership, a look that is not only aesthetic but sympathetic, joyful, active concept or analytical - because there are so many ways to look as subjects - it may not be precisely defined that contemplation rather than in terms that reach one's individuality. In poetic terms, it could also be set as the set of individual gazes also create a structure that makes this landscape is valued and understood, so from that point of view that landscape is a collective creation. With respect or as a predator, man has settled in his environment and in doing so has left traces in the landscape itself that make take a certain significance. Naturally, there is a theory that distinguishes what is "home" and what is "nature" providing for the first notion of the exclusive territory in which man has no aesthetic role. I tried many times to understand this position, without understanding the approach that supports: it seems that the vision of the thing is always humane, even in the "virgin" or untouched areas, as the vision itself makes the object modified in its own perceptual unit, creating a curious indeterminacy leading to the known misunderstandings between real image and representation. Indeed, the vision of the thing requires a culture and means that the report, so that a text, a picture, a description or photograph will be humanized by the very fact of being informed, as this provides a way a priori. Thus, the landscape provides a function that sets both aspects of a potential landscape as described aspects of the landscape and can only talk about the potential of the final state of the landscape, while the landscape remains humanized by the observer himself. This question forces to choose a definition of remote landscape budgets purely cultural, so there is another way for research to contemplate that physical reality in terms of the coordinates of the man who inhabits gifted content corresponding to that revelation. Far from the positions of the geomorphology, the term "landscape" and involve a certain condition by contemplation of a subject for which the show is humanized in the act. It should also consider, in the light of the above, if it is not true that all landscapes require that humanized condition, because although they are not inhabited they are always occupied by the look that dwells, like a stage without audience produces no consistent effect. From there the coordinates where this work sets the presence of architecture in defining landscape, a premise which seems to come from the beginning given lie, because that same look is already giving the viewer a sense of order and hierarchy to contemplation, qualities that are at the basis of all architectural activity, in fact the very definition of "natural monument" - in itself a contradiction - expresses this conflict, which has a phenomenon of admiration and overlap between culture and nature as concepts faced since its inception. The conclusion on the dilemma proposed in the thesis has not been another to assume that these two realities are the culture and landscape have overlapped since the beginning of man time forming a pair. It has been said before that the process of invasion of the territory by man is significant, and that meaning is the originating autonomous creation that is isolated as an abstract concept of nature, taking them as working material, and establishing a conceptual opposition in reality and punched by the man who comes to oppose representing the closed and unknown to the enigma of the world interpreted. The question of the significance of the man on the land is subsumed in the creation of products that remain and are testimony of their own culture, so that the trace amount that the man leaves the territory contributes most to the qualification landscape as a concept. That brought into any landscape - by the mere fact of being and being well defined - is already cultural, as it is configured by culture products. The words that can be locked in the stones of the monuments or cities are those of the men who worked there, and also of those who inhabited: even more, the sense of the landscape itself and its conservation are determined by the presence of man as the sole interpreter of concepts such as ecology or conservation, something which becomes manifest also in the awful devastation that produce the phenomena of nature. The natural history, like life, are shaped by success and devastation without special preference, the preference is used for feeding on other kinds of concepts. The question of moral values attributed to the natural world is very ancient, and may be the source or the source of the first religions, an issue that joins the unfailing notion of mortality that defines the existence of man against immanence of nature. That nature is endowed intuitively an "innocent" character assuming that innocence is the opposite of wisdom. The other issue is well, since nature does not even have what is defined as "character" because that is something that serves to qualify beings, but not objects. The question does not fall clearly on the side of the definitions or qualities, but from the analysis of the reality that man is building, destroying or damaging to define the territory, interposing his way resources facilities and possible witness as the main manifestation of its essence. Among the artifacts that man produces one of the most persistent and most conspicuously disclosed is architecture as a way of modification of space and territory. The space can be modified in many ways, but in either case is one of the most characteristic traces that man establishes as a physical manifestation of his own discourse being. Architecture has also proven to be one of the most persistent phenomena, even more than their own language that originates in his speech first. The paradigm wrote in the episode described on the Tower of Babel in the Bible shows the question of ambition of men before God - represented precisely in architecture - is assimilated to the discussion about the primary language. The issue is not trivial, since the phenomenon of creation is something that is granted exclusively to the gods, for that reason inhabit the territories to which men can not reach; territories where the hostel located mythologies gods and demons, with large gaps where to place the minor deities, heroes or hybrid beings where the yoke of the gods with human subjects produces relieving sense of mortality. The commentary on Genesis also gives a value to the art, the myth of Prometheus and fire as creator of excellence. In front of promethean progress, divine value is postulated, and the only possible way to alleviate this progress is the confusion of language, because that is what will produce the dispersion and lack of agreement. The issue may also explain such a common passion for the canonical architecture maintained throughout long periods, like a great machine inertia. It seems that the main concepts of architecture based on simple elements like milestone, lintels, straight and curved stairs or ramps, or other qualified and used are granted to the stone, brick, wood or metal as the primary components of the architectural material maintained throughout many millennia are almost unchanged, as is the case with the eating habits that follow a progression through the raw, the cooked and roasted or fried until obtain different degrees of refinement, but always are based on the primal feeling. The discovery of the architecture comes from a management dimensions, and consequently the geometry. But the geometry is abstract thing like the language so that to make architecture that first absorption capacity which then allows the realization of a device is necessary. Reality and its number exhibit a divorce, like things and their names displayed his; numerical analysis is just one way of seeing reality, rigorous and accurate - though partial - only represents the ideal model to which reality is coming to a greater or lesser extent: the mathematical approach makes the universe can condense on numbers, like reality may condense on names, but neither the name nor the number will reflect in all its complexity. The number is only a means of describing things, such as the pure forms that match setup a mathematical theory that occurs anywhere in the universe. However, for the practice of architecture is necessary to go to the simplification that requires abstract view of a section plane of reality, as an abstract element considered cutting. With its trace or not, with the mathematical expression that describes what or without clarify, this intuition of the plane as a generator of space predates his own expression, like speech preceded the writing, which only occurred through it and as reinforcement and replacement of memory. There are abstractions of memory displayed on the signs of nature only on casual and fragmentary, such as line, square and circle: those initials and abstract forms located in abstraction give rise to the first signs of primordial architecture, so that squares and circles, lifting two prisms and spheroids or spherical surfaces appear in tombs and elementary buildings the first few times, and that primordial geometry overlaps the landscape in which it is inserted. It is also true that these forms are approximate objects found in the physical environment, limb lines, branches and limbs; straight in some crystals angles observed by cutting or circular in stars and craters forms, but only the approximate shape and not its abstraction, just as the hieroglyphic of a falcon to represent the idea of surveillance presents the good view, or even the image of the eye itself replace the idea of the all-seeing God. The election was resolved, after many attempts and approaches, with the adoption of the right angle as an easy trick for stake through the sacred triangle 3:4:5 already used to build the pyramids of Egypt, and also gave rise to most of the old urbanism tend coexist with the primary circular form type called "Tholo". That frame homer was one of the fill patterns of common and compact space, and that was probably the reason why in much later times was adopted as a permanent effective form of organization against the topological disorder that seeks the set of association circular plants. Another issue is that these paradigmatic and unknown primary concepts - that converge at the origin of civilizations - then become something canon, through use. The canon itself is something ideal, as a rule for objects of a reality that has been created only as an indication of the ca-non, something abstract that has strict proportions are always the same and not due to rational criteria: be absurd however seek the Greek canon among the temples of time as some did, because the buildings only approximate the canonical examples and for that reason we speak of "doric from Parthenon" which is different from Aegina or Paestum, being all clearly doric. However, this idea is useful to scholar, the architectural theorist and historian, although it reflects only a vague idea of what happens beyond the book. Another issue is the subtlety of the examples of architecture, just as the bodies of living beings are never symmetrical, even if they involve a general symmetrical design derived from the conditions of cell division, the supposedly canonical buildings where specialists were inspired to define the classical orders do not have that exact modular symmetry, but a general model adapted to the ever changing location of the site shaping the landscape in which they are inserted. The light of the various bays of the Parthenon is slightly different, but keep a clear sense of axial symmetry, so that those "orders" that formed the theory of architecture are just a beautiful sectoral interpretation of ancient architecture developed by writers of the Renaissance and later by neoclassical. It seems, however, that craving for clarity of language canon as is inherent to the development of architecture, a lingua franca that tends to avoid scattering among mortals by the ancient gods, so if it was not possible the heaven of the gods sought the language of the Earth was at least intelligible to be understood. Power structure has always required a certain level of organization, and the instructions are clearly understood: it seems that in our times these ancient canons were replaced by obedience to abstract rules, issued by institutions also somewhat abstract and have funny names made up acronym, although not well known virtue. The current canon consists of "rules" that leave some quiet, although it seems that maybe all that interweaves-do formally serving as anaesthesia for the social body also seeks the destruction of forests in forms of huge mountains of bureaucratic paper. For many centuries were other rules, in the form of a canon which no one could escape: still using royalties or without them, civilization flourished in architecture from the earliest cave shelters or shelters and the primordial reality was setting mode in landscape. As noted above, this is a return trip in which both confused and subsumed: the management of forms and languages of architecture over time would allow the distinction between the field where chaos reigns and city, where order reigns theoretically creating a divorce that lasted millennia and still persists. This opposition also generate a form of landscape and a series of symbolic and sacred uses of architectural elements - such as doors and walls - which have remained conceptually although today the cities no longer having physical walls or doors close during the night. In this sense, the architecture could define the landscape, architecture is not only understood as the buildings themselves, but the fact of the manifestation of the man on the premises, so you can not speak without his landscape architecture, the same so we can not speak of landscape without men. For this reason, the thesis discusses architecture and landscape, but more particularly to the fact of architecture in defining landscape, as the facts of architectural or not will determine the quality and qualification of a landscape. One should begin first a definition of what is understood and has been commonly understood by landscape: equally, and given the context in which it places the own thesis work, the issue only be limited to what is understood as western culture, for the development of civilization always has a local colour that makes the analysis of a phenomenon of this magnitude have different connotations in different areas of civilization. Similarly, and given also that the landscape is constructed through all cultural manifestations, will sometimes necessary to investigate other non-architectural disciplines to understand the scope of some cases in which the architectural remains have disappeared, or the remaining few traces. Such a broad definition of architecture take to write a story about all of Western culture and for this reason only been sketched ideas about the appearance of these signs on the landscape based on ancient and primitive elements are repeated insistently and leading the varied repertoire of Western architecture shaping ideas about how the media and the world is perceived and inhabited.

Movement analysis in infancy may be useful for early diagnosis of autism

All of the 17 autistic children studied in the present paper showed disturbances of movement that with our methods could be detected clearly at the age of 4–6 months, and sometimes even at birth. We used the Eshkol–Wachman Movement Analysis System in combination with still-frame videodisc analysis to study videos obtained from parents of children who had been diagnosed as autistic by conventional methods, usually around 3 years old. The videos showed their behaviors when they were infants, long before they had been diagnosed as autistic. The movement disorders varied from child to child. Disturbances were revealed in the shape of the mouth and in some or all of the milestones of development, including, lying, righting, sitting, crawling, and walking. Our findings support the view that movement disturbances play an intrinsic part in the phenomenon of autism, that they are present at birth, and that they can be used to diagnose the presence of autism in the first few months of life. They indicate the need for the development of methods of therapy to be applied from the first few months of life in autism.

Atmospheric energy for subsurface life on Mars?

The location and density of biologically useful energy sources on Mars will limit the biomass, spatial distribution, and organism size of any biota. Subsurface Martian organisms could be supplied with a large energy flux from the oxidation of photochemically produced atmospheric H2 and CO diffusing into the regolith. However, surface abundance measurements of these gases demonstrate that no more than a few percent of this available flux is actually being consumed, suggesting that biological activity driven by atmospheric H2 and CO is limited in the top few hundred meters of the subsurface. This is significant because the available but unused energy is extremely large: for organisms at 30-m depth, it is 2,000 times previous estimates of hydrothermal and chemical weathering energy and far exceeds the energy derivable from other atmospheric gases. This also implies that the apparent scarcity of life on Mars is not attributable to lack of energy. Instead, the availability of liquid water may be a more important factor limiting biological activity because the photochemical energy flux can only penetrate to 100- to 1,000-m depth, where most H2O is probably frozen. Because both atmospheric and Viking lander soil data provide little evidence for biological activity, the detection of short-lived trace gases will probably be a better indicator of any extant Martian life.

A minimal gene set for cellular life derived by comparison of complete bacterial genomes.

The recently sequenced genome of the parasitic bacterium Mycoplasma genitalium contains only 468 identified protein-coding genes that have been dubbed a minimal gene complement [Fraser, C.M., Gocayne, J.D., White, O., Adams, M.D., Clayton, R.A., et al. (1995) Science 270, 397-403]. Although the M. genitalium gene complement is indeed the smallest among known cellular life forms, there is no evidence that it is the minimal self-sufficient gene set. To derive such a set, we compared the 468 predicted M. genitalium protein sequences with the 1703 protein sequences encoded by the other completely sequenced small bacterial genome, that of Haemophilus influenzae. M. genitalium and H. influenzae belong to two ancient bacterial lineages, i.e., Gram-positive and Gram-negative bacteria, respectively. Therefore, the genes that are conserved in these two bacteria are almost certainly essential for cellular function. It is this category of genes that is most likely to approximate the minimal gene set. We found that 240 M. genitalium genes have orthologs among the genes of H. influenzae. This collection of genes falls short of comprising the minimal set as some enzymes responsible for intermediate steps in essential pathways are missing. The apparent reason for this is the phenomenon that we call nonorthologous gene displacement when the same function is fulfilled by nonorthologous proteins in two organisms. We identified 22 nonorthologous displacements and supplemented the set of orthologs with the respective M. genitalium genes. After examining the resulting list of 262 genes for possible functional redundancy and for the presence of apparently parasite-specific genes, 6 genes were removed. We suggest that the remaining 256 genes are close to the minimal gene set that is necessary and sufficient to sustain the existence of a modern-type cell. Most of the proteins encoded by the genes from the minimal set have eukaryotic or archaeal homologs but seven key proteins of DNA replication do not. We speculate that the last common ancestor of the three primary kingdoms had an RNA genome. Possibilities are explored to further reduce the minimal set to model a primitive cell that might have existed at a very early stage of life evolution.

Archaeal-eubacterial mergers in the origin of Eukarya: phylogenetic classification of life.

A symbiosis-based phylogeny leads to a consistent, useful classification system for all life. "Kingdoms" and "Domains" are replaced by biological names for the most inclusive taxa: Prokarya (bacteria) and Eukarya (symbiosis-derived nucleated organisms). The earliest Eukarya, anaerobic mastigotes, hypothetically originated from permanent whole-cell fusion between members of Archaea (e.g., Thermoplasma-like organisms) and of Eubacteria (e.g., Spirochaeta-like organisms). Molecular biology, life-history, and fossil record evidence support the reunification of bacteria as Prokarya while subdividing Eukarya into uniquely defined subtaxa: Protoctista, Animalia, Fungi, and Plantae.

Prenatal monocular enucleation induces a selective loss of low-spatial-frequency cortical responses to the remaining eye.

During early development, interactions between the two eyes are critical in the formation of eye-specific domains within the lateral geniculate nucleus and the visual cortex. When monocular enucleation is done early in prenatal life, it induces remarkable anatomical and functional reorganizations of the visual pathways. Behavioral data have shown a loss in sensitivity to low-spatial-frequency gratings in cats. To correlate the behavioral observations with a possible change in the analysis of contrast at the level of primary visual areas we recorded visual evoked potentials at the 17/18 border in two cats enucleated prenatally (gestational age at enucleation, 39-42 days), three neonatal, two control animals, and one animal with a surgical removal of Y-ganglion fibers. Our results show a strong attenuation in the amplitude of response at all contrast values for gratings of low spatial frequency in prenatally enucleated cats, whereas neonatally enucleated and control animals present responses of comparable amplitude. We conclude that the behavioral results reflect the reduced sensitivity for low frequencies of visual cortical neurons. In addition, we define a critical period for the development of the contrast-sensitivity function that seems to be limited to the prenatal gestation period. We suggest that the prenatal interruption of binocular interactions leads to a functional elimination of the Y-ganglion system.

Intermediate hosts of Toxoplasma gondii and food safety:epidemiology, genetics and parasite survival in meat-producing animals in Italy

Toxoplasma gondii is a coccidian parasite with a global distribution. The definitive host is the cat (and other felids). All warm-blooded animals can act as intermediate hosts, including humans. Sexual reproduction (gametogony) takes place in the final host and oocysts are released in the environment, where they then sporulate to become infective. In intermediate hosts the cycle is extra-intestinal and results in the formation of tachyzoites and bradyzoites. Tachyzoites represent the invasive and proliferative stage and on entering a cell it multiplies asexually by endodyogeny. Bradyzoites within tissue cysts are the latent form. T. gondii is a food-borne parasite causing toxoplasmosis, which can occur in both animals and humans. Infection in humans is asymptomatic in more than 80% of cases in Europe and North-America. In the remaining cases patients present fever, cervical lymphadenopathy and other non-specific clinical signs. Nevertheless, toxoplasmosis is life threatening if it occurs in immunocompromised subjects. The main organs involved are brain (toxoplasmic encephalitis), heart (myocarditis), lungs (pulmonary toxoplasmosis), eyes, pancreas and parasite can be isolated from these tissues. Another aspect is congenital toxoplasmosis that may occur in pregnant women and the severity of the consequences depends on the stage of pregnancy when maternal infection occurs. Acute toxoplasmosis in developing foetuses may result in blindness, deformation, mental retardation or even death. The European Food Safety Authority (EFSA), in recent reports on zoonoses, highlighted that an increasing numbers of animals resulted infected with T. gondii in EU (reported by the European Member States for pigs, sheep, goats, hunted wild boar and hunted deer, in 2011 and 2012). In addition, high prevalence values have been detected in cats, cattle and dogs, as well as several other animal species, indicating the wide distribution of the parasite among different animal and wildlife species. The main route of transmission is consumption of food and water contaminated with sporulated oocysts. However, infection through the ingestion of meat contaminated with tissue cysts is frequent. Finally, although less frequent, other food products contaminated with tachyzoites such as milk, may also pose a risk. The importance of this parasite as a risk for human health was recently highlighted by EFSA’s opinion on modernization of meat inspection, where Toxoplasma gondii was identified as a relevant hazard to be addressed in revised meat inspection systems for pigs, sheep, goats, farmed wild boar and farmed deer (Call for proposals -GP/EFSA/BIOHAZ/2013/01). The risk of infection is more highly associated to animals reared outside, also in free-range or organic farms, where biohazard measure are less strict than in large scale, industrial farms. Here, animals are kept under strict biosecurity measures, including barriers, which inhibit access by cats, thus making soil contamination by oocysts nearly impossible. A growing demand by the consumer for organic products, coming from free-range livestock, in respect of animal-welfare, and the desire for the best quality of derived products, have all led to an increase in the farming of free-range animals. The risk of Toxoplasma gondii infection increases when animals have access to environment and the absence of data in Italy, together with need for in depth study of both the prevalence and genotypes of Toxoplasma gondii present in our country were the main reasons for the development of this thesis project. A total of 152 animals have been analyzed, including 21 free-range pigs (Suino Nero race), 24 transhumant Cornigliese sheep, 77 free-range chickens and 21 wild animals. Serology (on meat juice) and identification of T. gondii DNA through PCR was performed on all samples, except for wild animals (no serology). An in-vitro test was also applied with the aim to find an alternative and valid method to bioassay, actually the gold standard. Meat samples were digested and seeded onto Vero cells, checked every day and a RT-PCR protocol was used to determine an eventual increase in the amount of DNA, demonstrating the viability of the parasite. Several samples were alos genetically characterized using a PCR-RFLP protocol to define the major genotypes diffused in the geographical area studied. Within the context of a project promoted by Istituto Zooprofilattico of Pavia and Brescia (Italy), experimentally infected pigs were also analyzed. One of the aims was to verify if the production process of cured “Prosciutto di Parma” is able to kill the parasite. Our contribution included the digestion and seeding of homogenates on Vero cells and applying the Elisa test on meat juice. This thesis project has highlighted widespread diffusion of T. gondii in the geographical area taken into account. Pigs, sheep, chickens and wild animals showed high prevalence of infection. The data obtained with serology were 95.2%, 70.8%, 36.4%, respectively, indicating the spread of the parasite among numerous animal species. For wild animals, the average value of parasite infection determined through PCR was 44.8%. Meat juice serology appears to be a very useful, rapid and sensitive method for screening carcasses at slaughterhouse and for marketing “Toxo-free” meat. The results obtained on fresh pork meat (derived from experimentally infected pigs) before (on serum) and after (on meat juice) slaughter showed a good concordance. The free-range farming put in evidence a marked risk for meat-producing animals and as a consequence also for the consumer. Genotyping revealed the diffusion of Type-II and in a lower percentage of Type-III. In pigs is predominant the Type-II profile, while in wildlife is more diffused a Type-III and mixed profiles (mainly Type-II/III). The mixed genotypes (Type-II/III) could be explained by the presence of mixed infections. Free-range farming and the contact with wildlife could facilitate the spread of the parasite and the generation of new and atypical strains, with unknown consequences on human health. The curing process employed in this study appears to produce hams that do not pose a serious concern to human health and therefore could be marketed and consumed without significant health risk. Little is known about the diffusion and genotypes of T. gondii in wild animals; further studies on the way in which new and mixed genotypes may be introduced into the domestic cycle should be very interesting, also with the use of NGS techniques, more rapid and sensitive than PCR-RFLP. Furthermore wildlife can become a valuable indicator of environmental contamination with T. gondii oocysts. Other future perspectives regarding pigs include the expansion of the number of free-range animals and farms and for Cornigliese sheep the evaluation of other food products as raw milk and cheeses. It should be interesting to proceed with the validation of an ELISA test for infection in chickens, using both serum and meat juice on a larger number of animals and the same should be done also for wildlife (at the moment no ELISA tests are available and MAT is the reference method for them). Results related to Parma ham do not suggest a concerning risk for consumers. However, further studies are needed to complete the risk assessment and the analysis of other products cured using technological processes other than those investigated in the present study. For example, it could be interesting to analyze products such as salami, produced with pig meat all over the Italian country, with very different recipes, also in domestic and rural contexts, characterized by a very short period of curing (1 to 6 months). Toxoplasma gondii is one of the most diffuse food-borne parasites globally. Public health safety, improved animal production and protection of endangered livestock species are all important goals of research into reliable diagnostic tools for this infection. Future studies into the epidemiology, parasite survival and genotypes of T. gondii in meat producing animals should continue to be a research priority.

[Student essay on life's uncertainty] (fragment), undated

Folio-sized leaf containing a handwritten essay on life's uncertainty with an epitaph from English philosopher and scientist Francis Bacon (1561-1626): "He that to vain mortality does trust, / But limns the water, or but writes in dust." The remaining pages of the essay are missing.

The people's own book of recipes and information for the million : containing directions for the preservation of health, for the treatment of the sick and the conduct of the sick-room : with a full discussion of the more porminent diseases that afflict the human family, with full directions for their rational treatment : also, 1000 practical and useful recipes, embracing every department of domestic economy and human industry : with copious notes and emendations, explanatory and suggestive /

Recipes for domestic wines, cider, etc., on p. 306-315.