Impact of platelet rich plasma and adipose stem cells on lymphangiogenesis in a murine tail lymphedema model.

BACKGROUND Lymphedema is an underdiagnosed pathology which in industrialized countries mainly affects cancer patients that underwent lymph node dissection and/or radiation. Currently no effective therapy is available so that patients' life quality is compromised by swellings of the concerned body region. This unfortunate condition is associated with body imbalance and subsequent osteochondral deformations and impaired function as well as with an increased risk of potentially life threatening soft tissue infections. METHODS The effects of PRP and ASC on angiogenesis (anti-CD31 staining), microcirculation (Laser Doppler Imaging), lymphangiogenesis (anti-LYVE1 staining), microvascular architecture (corrosion casting) and wound healing (digital planimetry) are studied in a murine tail lymphedema model. RESULTS Wounds treated by PRP and ASC healed faster and showed a significantly increased epithelialization mainly from the proximal wound margin. The application of PRP induced a significantly increased lymphangiogenesis while the application of ASC did not induce any significant change in this regard. CONCLUSIONS PRP and ASC affect lymphangiogenesis and lymphedema development and might represent a promising approach to improve regeneration of lymphatic vessels, restore disrupted lymphatic circulation and treat or prevent lymphedema alone or in combination with currently available lymphedema therapies.

Systematic analysis of the radiologic findings of aortic dissections on unenhanced postmortem computed tomography

The aim of this study was to evaluate the diagnostic criteria and to identify the radiological signs (derived from known radiological signs) for the detection of aortic dissections using postmortem computed tomography (PMCT). Thirty-three aortic dissection cases were retrospectively evaluated; all underwent PMCT and autopsy. The images were initially evaluated independently by two readers and were subsequently evaluated in consensus. Known radiological signs, such as dislocated calcification and an intimomedial flap, were identified. The prevalence of the double sedimentation level in the true and false lumen of the dissected aorta was assessed and defined as a postmortem characteristic sign of aortic dissection. Dislocated calcification was detected in 85% of the cases with aortic calcification; whereas in 54% of the non-calcified aortas, the intimomedial flap could also be recognized. Double sedimentation was identified in 16/33 of the cases. Overall, in 76% (25/33) of the study cases, the described signs, which are indicative for aortic dissection, could be identified. In this study, three diagnostic criteria of aortic dissection were identified using non-enhanced PMCT images of autopsy-confirmed dissection cases.

Emergency management of ischemic stroke in children.

OPINION STATEMENT Children who present with acute neurological symptoms suggestive of a stroke need immediate clinical assessment and urgent neuroimaging to confirm diagnosis. Magnetic resonance imaging (MRI) is the investigation of first choice due to limited sensitivity of computed tomography (CT) for detection of ischaemia. Acute monitoring should include monitoring of blood pressure and body temperature, and neurological observations. Surveillance in a paediatric high dependency or intensive care unit and neurosurgical consultation are mandatory in children with large infarcts at risk of developing malignant oedema or haemorrhagic transformation. Thrombolysis and/or endovascular treatment, whilst not currently approved for use in children, may be considered when stroke diagnosis is confirmed within 4.5 to 6 h, provided there are no contraindications on standard adult criteria. Standard treatment consists of aspirin, but anticoagulation therapy is frequently prescribed in stroke due to cardiac disease and extracranial dissection. Steroids and immunosuppression have a definite place in children with proven vasculitis, but their role in focal arteriopathies is less clear. Decompressive craniotomy should be considered in children with deteriorating consciousness or signs of raised intracranial pressure.

Older patients with low Charlson score and high-risk prostate cancer benefit from radical prostatectomy

INTRODUCTION The aim of the study was to identify the appropriate level of Charlson comorbidity index (CCI) in older patients (>70 years) with high-risk prostate cancer (PCa) to achieve survival benefit following radical prostatectomy (RP). METHODS We retrospectively analyzed 1008 older patients (>70 years) who underwent RP with pelvic lymph node dissection for high-risk prostate cancer (preoperative prostate-specific antigen >20 ng/mL or clinical stage ≥T2c or Gleason ≥8) from 14 tertiary institutions between 1988 and 2014. The study population was further grouped into CCI < 2 and ≥2 for analysis. Survival rate for each group was estimated with Kaplan-Meier method and competitive risk Fine-Gray regression to estimate the best explanatory multivariable model. Area under the curve (AUC) and Akaike information criterion were used to identify ideal 'Cut off' for CCI. RESULTS The clinical and cancer characteristics were similar between the two groups. Comparison of the survival analysis using the Kaplan-Meier curve between two groups for non-cancer death and survival estimations for 5 and 10 years shows significant worst outcomes for patients with CCI ≥ 2. In multivariate model to decide the appropriate CCI cut-off point, we found CCI 2 has better AUC and p value in log rank test. CONCLUSION Older patients with fewer comorbidities harboring high-risk PCa appears to benefit from RP. Sicker patients are more likely to die due to non-prostate cancer-related causes and are less likely to benefit from RP.

Theileria parva: taking control of host cell proliferation and survival mechanisms.

The intracellular parasite Theileria parva infects and transforms bovine T-cells, inducing their uncontrolled proliferation and spread in non-lymphoid as well as lymphoid tissues. This parasite-induced transformation is the predominant factor contributing to the pathogenesis of a lymphoproliferative disease, called East Coast fever. T. parva-transformed cells become independent of antigenic stimulation or exogenous growth factors. A dissection of the signalling pathways that are activated in T. parva-infected cells shows that the parasite bypasses signalling pathways that normally emanate from the T-cell antigen receptor to induce continuous proliferation. This review concentrates on the influence of the parasite on the state of activation of the mitogen-activated protein kinase (MAPK), NF-kappaB and phosphoinositide-3-kinase (PI3-K) pathways in the host cell. Of the MAPKs, JNK, but not ERK or p38, is active, inducing constitutive activation of the transcription factors AP-1 and ATF-2. A crucial step in the transformation process is the persistent activation of the transcription factor NF-kappaB, which protects T. parva-transformed cells from spontaneous apoptosis accompanying the transformation process. Inhibitor studies also suggest an important role for the lipid kinase, PI-3K, in the continuous proliferation of T. parva-transformed lymphocytes.

Gender associated risk factors of aortic aneurysms and dissections

Objectives. Predict who will develop a dissection. To create male and female prediction models using the risk factors: age, ethnicity, hypertension, high cholesterol, smoking, alcohol use, diabetes, heart attack, congestive heart failure, congenital and non-congenital heart disease, Marfan syndrome, and bicuspid aortic valve. ^ Methods. Using 572 patients diagnosed with aortic aneurysms, a model was developed for each of males and females using 80% of the data and then verified using the remaining 20% of the data. ^ Results. The male model predicted the probability of a male in having a dissection (p=0.076) and the female model predicted the probability of a female in having a dissection (p=0.054). The validation models did not support the choice of the developmental models. ^ Conclusions. The best models obtained suggested that those who are at a greater risk of having a dissection are males with non-congenital heart disease and who drink alcohol, and females with non-congenital heart disease and bicuspid aortic valve.^

Anesthetic choices and breast cancer recurrence: A retrospective cohort study of risk factors

Background: The impact of anesthetic techniques for breast cancer surgery traditionally has been centered on the incidence of acute pain syndromes and complications immediately after surgery. Evaluating anesthesia management beyond short-term effects is an emerging science. Several animal studies have concluded that regional anesthesia independently reduces cancer recurrence and metastasis. A small number of retrospective clinical studies indicate that reductions in cancer recurrence are attributable to anesthesia technique; however, individual risk factors need to be taken into consideration. ^ Purpose: The aims were to: 1) investigate differences in patient, disease and treatment factors between women who received surgical treatment for breast cancer with paravertebral regional and general anesthesia compared to women who received general anesthesia alone; 2) explore patient, disease and treatment factors associated with recurrence of breast cancer; and 3) test the association between type of anesthesia and breast cancer recurrence and survival over 22–46 months following surgery. ^ Methods: This retrospective cohort study included 358 patients with stage 0-III disease who received a partial or total mastectomy without axillary node dissection between October 2006 and October 2008 at a large academic cancer center. Follow-up ended in August 2010 with a median follow-up time of 28.8 months. ^ Results: The patient demographics were equally represented across anesthesia groups. Mean BMI (kg/m2) was greater for the patients who received general anesthesia (GA) alone (29±6.8) compared to those that received paravertebral regional block (PVB) with GA (28±5.1), p=0.001. The PVB with GA group had more advanced stages of disease (p=0.01) and longer surgeries (p=0.01) than the GA only group. Breast cancer recurrence was detected in only 1.7% of the study population. The mean age was 51±18 in those who had a recurrence compared to 58±11 in the non-recurrent group (p=0.06). Overall, no association between anesthesia type and recurrence was found (p=0.53), with an unadjusted estimated hazard ratio of 1.84 (95% CI 0.34–10.08). ^ Conclusions: In contrast to previous retrospective studies in cancer patients receiving surgical and anesthesia treatment, this study was unable to detect a difference in relating type of anesthesia with decreased breast cancer recurrence. Nonetheless, a significant association between BMI and type of anesthesia was observed and should be taken into account in future studies. Because the overall rate of recurrence was very small in this population, a larger study would be needed to detect any differences in rates of recurrence attributable to type of anesthesia. ^

REGULATION OF ALTERNATIVE CARBON METABOLISM IN CANDIDA ALBICANS

Candida albicans is the most important fungal pathogen of humans. Transcript profiling studies show that upon phagocytosis by macrophages, C. albicans undergoes a massive metabolic reorganization activating genes involved in alternative carbon metabolism, including the glyoxylate cycle, β-oxidation and gluconeogenesis. Mutations in key enzymes such as ICL1 (glyoxylate cycle) and FOX2 (fatty acid β-oxidation) revealed that alternative carbon metabolic pathways are required for full virulence in C. albicans. These studies indicate C. albicans uses non-preferred carbon sources allowing its adaptation to microenvironments were nutrients are scarce. It has become apparent that the regulatory networks required for regulation of alternative carbon metabolism in C. albicans are considerably different from the Saccharomyces cerevisiae paradigm and appear more analogous to the Aspergillus nidulans systems. Well-characterized transcription factors in S. cerevisiae have no apparent phenotype or are missing in C. albicans. CTF1 was found to be a single functional homolog of the A. nidulans FarA/FarB proteins, which are transcription factors required for fatty acid utilization. Both FOX2 and ICL1 were found to be part of a large CTF1 regulon. To increase our understanding of how CTF1 regulates its target genes, including whether regulation is direct or indirect, the FOX2 and ICL1 promoter regions were analyzed using a combination of bioinformatics and promoter deletion analysis. To begin characterizing the FOX2 and ICL1 promoters, 5’ rapid amplification of cDNA ends (5’RACE) was used to identify two transcriptional initiation sites in FOX2 and one in ICL1. GFP reporter assays show FOX2 and ICL1 are rapidly expressed in the presence of alternative carbon sources. Both FOX2 and ICL1 harbor the CCTCGG sequence known to be bound by the Far proteins, hence rendering the motif as a putative CTF1 DNA binding element. In this study, the CCTCGG sequence was found to be essential for FOX2 regulation. However, this motif does not appear to be equally important for the regulation of ICL1. This study supports the notion that although C. albicans has diverged from the paradigms of model fungi, C. albicans has made specific adaptations to its transcription-based regulatory network that may contribute to its metabolic flexibility.

Delayed Thrombus Resolution and Fibroproliferative Vascular Wound Healing From Deficiency of Type III Collagen: a Paradoxical Mechanism for Tissue Fragility

Vascular Ehlers-Danlos syndrome is a heritable disease of connective tissue caused by mutations in COL3A1, conferring a tissue deficiency of type III collagen. Cutaneous wounds heal poorly in these patients, and they are susceptible to spontaneous and catastrophic rupture of expansible hollow organs like the gut, uterus, and medium-sized to large arteries, which leads to premature death. Although the predisposition for organ rupture is often attributed to inherent tissue fragility, investigation of arteries from a haploinsufficient Col3a1 mouse model (Col3a1+/-) demonstrates that mutant arteries withstand even supraphysiologic pressures comparably to wild-type vessels. We hypothesize that injury that elicits occlusive thrombi instead unmasks defective thrombus resolution resulting from impaired production of type III collagen, which causes deranged remodeling of matrix, persistent inflammation, and dysregulated behavior by resident myofibroblasts, culminating in the development of penetrating neovascular channels that disrupt the mechanical integrity of the arterial wall. Vascular injury and thrombus formation following ligation of the carotid artery reveals an abnormal persistence and elevated burden of occlusive thrombi at 21 post-operative days in vessels from Col3a1+/- mice, as opposed to near complete resolution and formation of a patent and mature neointima in wild-type mice. At only 14 days, both groups harbor comparable burdens of resolving thrombi, but wild-type mice increase production of type III collagen in actively resolving tissues, while mutant mice do not. Rather, thrombi in mutant mice contain higher burdens of macrophages and proliferative myofibroblasts, which persist through 21 days while wild-type thrombi, inflammatory cells, and proliferation all regress. At the same time that increased macrophage burdens were observed at 14 and 21 days post ligation, the medial layer of mutant arterial walls concurrently harbored a significantly higher incidence of penetrating neovessels compared with those in wild-type mice. To assess whether limited type III collagen production alters myofibroblast behavior, fibroblasts from vEDS patients with COL3A1 missense mutations were seeded into three-dimensional fibrin gel constructs and stimulated with transforming growth factor-β1 to initiate myofibroblast differentiation. Although early signaling events occur similarly in all cell lines, late extracellular matrix- and mechanically-regulated events like transcriptional upregulation of type I and type III collagen secretion are delayed in mutant cultures, while transcription of genes encoding intracellular contractile machinery is increased. Sophisticated imaging of collagen synthesized de novo by resident myofibroblasts visualizes complex matrix reorganization by control cells but only meager remodeling by COL3A1 mutant cells, concordant with their compensatory contraction to maintain tension in the matrix. Finally, administration of immunosuppressive rapamycin to mice following carotid ligation sufficiently halts the initial inflammatory phase of thrombus resolution and fully prevents both myofibroblast migration into the thrombus and the differential development of neovessels between mutant and wild-type mice, suggesting that pathological defects in mutant arteries develop secondarily to myofibroblast dysfunction and chronic inflammatory stimulation, rather than as a manifestation of tissue fragility. Together these data establish evidence that pathological defects in the vessel wall architecture develop in mutant arteries as sequelae to abnormal healing and remodeling responses activated by arterial injury. Thus, these data support the hypothesis that events threatening the integrity of type III collagen-deficient vessels develop not as a result of inherent tissue weakness and fragility at baseline but instead as an episodic byproduct of abnormally persistent granulation tissue and fibroproliferative intravascular remodeling.

Rescue of embryonic lethality in mdmx null mice by loss of p53 suggests a non-overlapping pathway with MDM2 to regulate p53

The tumor suppressor p53 is mutated in over 50% of human sporadic tumors originating from diverse tissues. p53 responds to DNA damage and cell stress by activating the transcription of a variety of target genes, the protein products of which then initiate either growth arrest or apoptosis. ^ A p53 target with a particularly intriguing function is the oncogene MDM2. MDM2 functions, in part, by binding to and inhibiting p53's activity. Overexpression of MDM2, by gene amplification, has been found in 30% of human sarcomas harboring a wild type p53, indicating that an increase in MDM2 levels is sufficient for p53 inactivation. Mice carrying a homozygous null allele for mdm2 exhibit an early embryonic lethality that is completely rescued in a p53-null background. These data indicate that MDM2's only critical function in early mouse embryogenesis is the negative regulation of p53. ^ The mdmx gene is the first additional member of the mdm2 gene family to be isolated. MDMX, like MDM2, contains a RING-finger domain, ATP binding domain and a p53 binding domain, which retains the ability to bind and inhibit p53 transactivation in vitro. However, mdmx does not appear to be transcriptionally regulated by p53. We have cloned and characterized the murine mdmx genomic locus from a mouse 129 genomic library. The mdmx gene contains 11 exons, spans approximately 37 Kb of DNA, and is located on mouse chromosome 1. The genomic organization of the mdmx gene is identical to that of mdm2 except at the 5′ end of the gene near the p53 responsive element. Northern expression analysis of mdmx transcripts during mouse embryogenesis and in adult tissues revealed constitutive and ubiquitous expression throughout adult tissues and embryonic development. To determine the in vivo function of MDMX, mice carrying a null allele of mdmx have been generated. Mdmx homozygous null mice are early embryonic lethal. Mdmx null mice do not develop beyond 9.5 dpc and can be discerned by gross dissection as early as 7.5 dpc. Utilizing TUNEL and BrdU assays on 7.5 dpc histological sections we have determined that the mutant embryos are dying due to increased levels of growth arrest, but not apoptosis. Surprisingly, Mdmx homozygous null mice are viable in a p53 null background, indicating that MDMX is also very important in the negative regulation of p53. ^

Heavy and light minerals in turbidites from DSDP Hole 19-183, the Aleutian abyssal plain

The Aleutian abyssal plain is a fossil abyssal plain of Paleogene age in the western Gulf of Alaska. The plain is a large, southward-thinning turbidite apron now cut off from sediment sources by the Aleutian Trench. Turbidite sedimentation ceased about 30 m.y. ago, and the apron is now buried under a thick blanket of pelagic deposits. Turbidites of the plain were recovered at site 183 of the Deep Sea Drilling Project on the northern edge of the apron. The heavy-mineral fraction of sand-sized samples is mostly amphibole and epidote with minor pyroxene, garnet, and sphene. The light-mineral fraction is mostly quartzose debris and feldspars. Subordinate lithic fragments consist of roughly equal amounts of metamorphic, plutonic, sedimentary, and volcanic grains. The sand compositions are arkoses in many sandstone classifications, although if fine silt is included with clay as matrix, the sand deposits are feldspathic or lithofeldspathic graywacke. The sands are apparently first-cycle products of deep dissection into a plutonic terrane, and they contrast sharply with arc-derived volcanic sandstones of similar age common on the adjacent North American continental margin. The turbidite sands are stratigraphically remarkably constant in composition, which indicates derivation from virtually the same terrane through a time span approaching 20 m.y. Comparison of Aleutian plain data with the compositions of coeval sedimentary rocks from the northeast Pacific margin shows that the Kodiak shelf area includes possible proximal equivalents of the more distal turbidites. Derivation from the volcaniclastic Mesozoic flysch of the Shumagin-Kodiak shelf is unlikely; more probably the sediments were derived from primary plutonic sources. The turbidites also resemble deposits in the Chugach Mountains and the younger turbidites of the Alaskan abyssal plain and could conceivably have been derived from the coast ranges of southeastern Alaska or western British Columbia. The Aleutian plain sediment most likely was not derived from as far south as the Oregon-Washington continental margin, where coeval sedimentary deposits are dominantly volcaniclastic.

Feeding of Sagitta setosa in the Black Sea

Gut dissection of fixed individuals from samples collected during Cruise 6 of R/V Vityaz-2 in April-May 1984 was used to study feeding of Sagitta setosa in the layers of daytime plankton accumulation at the lower boundary of the oxycline. The principal food was copepodite stage V of Calanus and females of Calanus and Pseudocalanus. Analysis of daytime and night data with reference to length of migratory alterations of Sagitta populations and gut passage time indicates that they feed actively in the layers of day¬time plankton accumulations. Total food consumption during time spent in the subsurface layers ranged from 0.025-0.097 cal/indiv. in 12 h, equivalent to 37-143% of their metabolic energy expenditure. Over the course of 12 h Sagitta population consumes 0.3-5% and 0.5-6% of population of stage V copepodites and females of Calanus and Pseudocalanus females, respectively.

La Casa Domínguez. Alejandro de la Sota: Construir - Habitar

La Tesis Doctoral nace con una intensa vocación pedagógica. La hipótesis de trabajo se establece en torno a una cuestión de interés personal, un tema sobre el que se vertebran, desde el comienzo del doctorado, los diferentes cursos y trabajos de investigación: LA CASA DOMÍNGUEZ como paradigma de la dialéctica en la obra de Alejandro de la Sota. La clasificación de la realidad en categorías antagónicas determina un orden conceptual polarizado, una red de filiaciones excluyentes sobre las que Sota construye su personal protocolo operativo: la arquitectura intelectual o popular, experimental o tradicional, universal o local, ligera o pesada, elevada o enterrada, etc. Se propone el abordaje de una cuestión latente en el conjunto de la obra ‘sotiana’, desde la disección y el análisis de una de sus obras más pequeñas: la casa Domínguez. Se trata de una organización sin precedentes, que eleva la estrategia dialéctica al paroxismo: la vivienda se separa en dos estratos independientes, la zona de día, elevada, y la zona de noche, enterrada; cada uno de los estratos establece su propio orden geométrico y constructivo, su propio lenguaje y carácter, su propia identidad e incluso su propio presupuesto. Las relaciones entre interior y exterior se especializan en función de la actividad o el reposo, estableciéndose una compleja red de relaciones, algunas evidentes y otras celosamente veladas, entre los diferentes niveles. La estancia destinada a las tareas activas se proyecta como un objeto de armazón ligero y piel fría; la precisa geometría del cubo delimita la estancia vigilante sobre el paisaje conquistado. La ladera habitada se destina al reposo y se configura como una topografía verde bajo la que se desarrollan los dormitorios en torno a patios, grietas y lucernarios, generando un paisaje propio: la construcción del objeto frente a la construcción del lugar La casa Domínguez constituye uno de los proyectos menos estudiados, y por lo tanto menos celebrados, de la obra de Don Alejandro. Las publicaciones sucesivas reproducen la documentación gráfica junto a la memoria (epopeya) que el propio Sota compone para la publicación del proyecto. Apenas un par de breves textos críticos de Miguel Ángel Baldellou y, recientemente de Moisés Puente, abordan la vivienda como tema monográfico. Sin embargo, la producción de proyecto y obra ocupó a De la Sota un periodo no inferior a diez años, con casi cien planos dibujados para dos versiones de proyecto, la primera de ellas, inédita. El empeño por determinar hasta el último detalle de la ‘pequeña’ obra, conduce a Sota a controlar incluso el mobiliario interior, como hiciera en otras obras ‘importantes’ como el Gobierno Civil de Tarragona, el colegio mayor César Carlos o el edificio de Correos y Telecomunicaciones de León. La complicidad del cliente, mantenida durante casi cuarenta años, habilita el despliegue de una importante colección de recursos y herramientas de proyecto. La elección de la casa Domínguez como tema central de la tesis persigue por lo tanto un triple objetivo: en primer lugar, el abordaje del proyecto como paradigma de la dialéctica ‘sotiana’, analizando la coherencia entre el discurso de carácter heroico y la obra finalmente construida; en segundo lugar, la investigación rigurosa, de corte científico, desde la disección y progresivo desmontaje del objeto arquitectónico; y por último, la reflexión sobre los temas y dispositivos de proyecto que codifican la identificación entre la acción de construir y el hecho de habitar, registrando los aciertos y valorando con actitud crítica aquellos elementos poco coherentes con el orden interno de la propuesta. This doctoral thesis is the fruit of a profound pedagogical vocation. The central hypothesis was inspired by a question of great personal interest, and this interest has, since the very beginning of the doctorate, been the driving force behind all subsequent lines of research and investigation. The “Casa Domínguez” represents a paradigm of the dialectics found in the work of Alejandro de la Sota. The perception of reality as antagonistic categories determines a polarized conceptual order, a network of mutually excluding associations upon which Sota builds his own personal operative protocol: intellectual or popular architecture, experimental or traditional, universal or local, heavy or light, above or below ground, etc. Through the analysis and dissection of the “Casa Domínguez”, one of Sota’s smallest projects, an attempt is made to approach the underlying question posed in “Sotian” work as a whole. This is about organization without precedent, raising the strategic dialectics to levels of paroxysm. The house is divided into two separate levels, the day-time level above ground, and the lower night-time level beneath the surface of the ground. Each level has its own geometrical and stuctural order, its own language and character, its own identity and even has its own construction budget. The interaction between the two areas is centered on the two functions of rest and activity, and this in turn establishes a complex relationship network between both, which is sometimes self-evident, but at other times jealously guarded. The living area designed for daily activity is presented as an object of light structure and delicate skin; the precise geometry of the cube delimiting the ever watchful living area’s domain over the land it has conquered. A green topography is created on the slope below which lies an area adapted for rest and relaxation. Two bedrooms, built around patios, skylights and light crevices, generate an entirely independent environment: the construction of an object as opposed to the creation of a landscape. The “Casa Domínguez” project has been subject to much less scrutiny and examination than Don Alejandro’s other works, and is consequently less well-known. A succession of journals have printed the blueprint document together with a poetic description (epopee), composed by Sota himself, to mark the project’s publication. There has, however, scarcely been more than two brief critical appraisals, those by Miguel Ángel Baldellou and more recently by Moisés Puente, that have regarded the project as a monographic work. The project and works nevertheless occupied no less than ten years of De La Sota’s life, with over a hundred draft drawings for two separate versions of the project, the first of which remains unpublished. The sheer determination to design this “small” work in the most meticulous detail, drove Sota to manage and select its interior furniture, as indeed he had previously done with more “important” works like the Tarragona Civil Government, César Carlos College, or the Post Office telecommunications building in León. Client collaboration, maintained over a period of almost forty years, has facilitated an impressive array of the project’s tools and resources. The choice of “Casa Domínguez” as the central subject matter of this thesis, was made in pursuance of a triple objective: firstly, to approach the project as a paradigm of the “Sotian” dialectic, the analysis of the discourse between the heroic character and the finished building; secondly, a rigorous scientific investigation, and progressive disassembling and dissecting of the architectonic object; and finally, a reflection on aspects of the project and its technology which codify the identification between the action of construction and the reality of living, thus marking its achievements, whilst at the same time subjecting incoherent elements of the proposal’s established order to a critical evaluation.

Pulsatile blood flow interaction with arterial walls of aorta : autoregulation and impedance pressure boundary condition and its biomedical applications

Para las decisiones urgentes sobre intervenciones quirúrgicas en el sistema cardiovascular se necesitan simulaciones computacionales con resultados fiables y que consuman un tiempo de cálculo razonable. Durante años los investigadores han trabajado en diversos métodos numéricos de cálculo que resulten atractivos para los cirujanos. Estos métodos, precisos pero costosos desde el punto de vista del coste computacional, crean un desajuste entre la oferta de los ingenieros que realizan las simulaciones y los médicos que operan en el quirófano. Por otra parte, los métodos de cálculo más simplificados reducen el tiempo de cálculo pero pueden proporcionar resultados no realistas. El objetivo de esta tesis es combinar los conceptos de autorregulación e impedancia del sistema circulatorio, la interacción flujo sanguíneo-pared arterial y modelos geométricos idealizados tridimensionales de las arterias pero sin pérdida de realismo, con objeto de proponer una metodología de simulación que proporcione resultados correctos y completos, con tiempos de cálculo moderados. En las simulaciones numéricas, las condiciones de contorno basadas en historias de presión presentan inconvenientes por ser difícil conocerlas con detalle, y porque los resultados son muy sensibles ante pequeñas variaciones de dichas historias. La metodología propuesta se basa en los conceptos de autorregulación, para imponer la demanda de flujo aguas abajo del modelo en el ciclo cardiaco, y la impedancia, para representar el efecto que ejerce el flujo en el resto del sistema circulatorio sobre las arterias modeladas. De este modo las historias de presión en el contorno son resultados del cálculo, que se obtienen de manera iterativa. El método propuesto se aplica en una geometría idealizada del arco aórtico sin patologías y en otra geometría correspondiente a una disección Stanford de tipo A, considerando la interacción del flujo pulsátil con las paredes arteriales. El efecto de los tejidos circundantes también se incorpora en los modelos. También se hacen aplicaciones considerando la interacción en una geometría especifica de un paciente anciano que proviene de una tomografía computarizada. Finalmente se analiza una disección Stanford tipo B con tres modelos que incluyen la fenestración del saco. Clinicians demand fast and reliable numerical results of cardiovascular biomechanic simulations for their urgent pre-surgery decissions. Researchers during many years have work on different numerical methods in order to attract the clinicians' confidence to their colorful contours. Though precise but expensive and time-consuming methodologies create a gap between numerical biomechanics and hospital personnel. On the other hand, simulation simplifications with the aim of reduction in computational time may cause in production of unrealistic outcomes. The main objective of the current investigation is to combine ideas such as autoregulation, impedance, fluid-solid interaction and idealized geometries in order to propose a computationally cheap methodology without excessive or unrealistic simplifications. The pressure boundary conditions are critical and polemic in numerical simulations of cardiovascular system, in which a specific arterial site is of interest and the rest of the netwrok is neglected but represented by a boundary condition. The proposed methodology is a pressure boundary condition which takes advantage of numerical simplicity of application of an imposed pressure boundary condition on outlets, while it includes more sophisticated concepts such as autoregulation and impedance to gain more realistic results. Incorporation of autoregulation and impedance converts the pressure boundary conditions to an active and dynamic boundary conditions, receiving feedback from the results during the numerical calculations and comparing them with the physiological requirements. On the other hand, the impedance boundary condition defines the shapes of the pressure history curves applied at outlets. The applications of the proposed method are seen on idealized geometry of the healthy arotic arch as well as idealized Stanford type A dissection, considering the interaction of the arterial walls with the pulsatile blood flow. The effect of surrounding tissues is incorporated and studied in the models. The simulations continue with FSI analysis of a patient-specific CT scanned geometry of an old individual. Finally, inspiring of the statistic results of mortality rates in Stanford type B dissection, three models of fenestrated dissection sac is studied and discussed. Applying the developed boundary condition, an alternative hypothesis is proposed by the author with respect to the decrease in mortality rates in patients with fenestrations.

De la ciudad a la estancia: casas con patio en la vivienda social madrileña (1956-1961). Saénz de Oíza y Vázquez de Castro

La tesis aborda el estudio de la casa patio y su relación con todas las escalas del proyecto, dentro del ámbito de la vivienda colectiva desarrollada en Madrid desde el comienzo de la década de los cincuenta hasta principio de los sesenta. Se investiga su vínculo con la ciudad a partir de la configuración de la trama y los espacios públicos, la organización de la casa en torno a un vacío y las relaciones espaciales entre el patio exterior y las estancias interiores. Mediante el análisis de los diferentes ejemplos existentes de casas con patio en el contexto señalado, se realiza la selección de los casos de estudio de esta investigación. Los proyectos analizados se organizan a partir del trabajo desarrollado por los arquitectos Francisco Javier Sáenz de Oíza y Antonio Vázquez de Castro, liderando equipos más amplios y como representantes de la construcción definitiva de un verdadero lenguaje moderno en la arquitectura española. Cada uno de los proyectos, estructurados en dos apartados para cada uno de los autores, muestran de forma particular, la evolución de las herramientas arquitectónicas empleadas, a partir de la casa patio, en las distintas escalas de trabajo. En los proyectos de Oíza, se analiza en primer lugar la definición de un modelo mínimo y racional de vivienda con patio en el poblado de absorción de Fuencarral “A” (1956) y con el prototipo del concurso de vivienda experimental (1956). A continuación se estudia, en el Poblado Dirigido de Entrevías (1956), la construcción de la ciudad horizontal a partir del patio como elemento estructurante de las tramas urbanas. Las obras de Vázquez de Castro muestran inicialmente la incorporación del patio como una estancia privada más de la casa con la definición de un modelo tipológico en “L” en el Poblado Dirigido de Caño Roto (1956). Finalmente, se analiza el desarrollo de nuevas y complejas estructuras urbanas en forma de tapiz en el proyecto de la Unidad Vecinal de Costa Rica (1961). Los ejemplos, antes descritos, protagonizan un proceso delimitado desde la importación y adaptación de los modelos de vivienda europeos producidos en el periodo de entreguerras, con un significativo retraso; hasta la apuesta por sistemas complejos como el “mat-building”, en diálogo directo, con los proyectos de las nuevas corrientes arquitectónicas internacionales de principios de los sesenta. El estudio y análisis de los ejemplos se realiza mediante la disección pormenorizada de cada uno de ellos, en los sistemas arquitectónicos que establecen la relación del patio con las tres escalas objeto de estudio: la ciudad, la casa y la estancia. Para ello se realiza una reconstrucción de los proyectos mediante la elaboración de una nueva documentación gráfica a partir de los planos y fotografías originales. Finalmente, a partir de los temas arquitectónicos más significativos extraídos del análisis de los casos de estudio y organizados en función de las distintas escalas de proyecto, se realiza una comparación transversal, a modo de conclusiones, respecto a otros ejemplos de similares características del panorama internacional de casas con patio. De esta forma se produce una síntesis sobre los distintos mecanismos que sirvieron para construir, a partir de la tradición del patio en la casa, la vivienda moderna. ABSTRACT The thesis deals the study of the house with courtyard and its relation with all the scales of the project inside the ambience of the collective housing developed in Madrid from the beginning of the fifties up to beginning of the sixties. This document investigates its link with the city from the configuration of the weave and the public spaces, the organization of the house around a void and the spatial relations between the exterior courtyard and the interior spaces. The selection of the case studies of this research is made Through the analysis of the different existing examples of courtyard houses in this defined context. The analyzed projects are organized from the work developed by the architects Francisco Javier Sáenz de Oíza and Antonio Vázquez de Castro, leading wider teams and as representatives of the definitive construction of a real modern language in the Spanish architecture. Each of the projects, structured in two sections to each one of the authors, show in a particular way, the evolution of the architectural tools employed, from the house with courtyard, at different scales of work. In the projects of Oiza, it´s analyced the definition of a minimum and rational model of a house with courtyard in the absorption village of Fuencarral “A” (1956) and with the experimental housing contest prototype (1956). Next, in “el Poblado Dirigido de Entrevías” (1956), the construction of the horinzontal city with the courtyard as a structuring element of the urban weave will be studied. The works of Vázquez de Castro initially show the incorporation of the courtyard as another private area of the house with the typological model definition as an “L” in El Poblado Dirigido de Caño Roto (1956). Finally, the thesis analyzes the development of new and complex urban structures with a mat-building shape in the project of Unidad Vecinal de Costa Rica (1961). The examples described above, starring a process delimited from the import and the adaptation of european housing models produced in the interwar period, with a significant delay; until the opt for complex systems such as the “mat-building”, in direct dialog, with the projects of the new architectural international flows of the beginning of the sixties. The study and analysis of the examples is made by the dissection of them, in the architectural systems that establish the relation of the courtyard with the three scales of the study: the city, the house and the stay. To reach this objetive this document reconstructs the projects making a new graphic documentation from the original maps and photos. Finally, from the most important architectural issues drawn from the analysis of the case studies and organised by the different scales of project, as conclussions, a cross comparison of similar examples of houses with courtyard around the world is made. This produces a synthesis about the different mechanisms that served to build, from the tradition of the courtyard in the house, the modern housing.