Castillos japoneses: reconstrucción y restauración

[ES] Este trabajo estudia la síntesis histórica del castillo japonés moderno, así como los procesos de destrucción, reconstrucción y conservación que ha experimentado, mediante la recopilación de datos y análisis posterior de 200 castillos. el castillo moderno se gestó en Japón en un período de apenas 35 años de constante evolución para quedar después esclerotizado durante más de 2 siglos como máximo exponente del orden feudal. La entrada del castillo japonés en la era contemporánea fue turbulenta: desde su destrucción sistemática como símbolo del antiguo régimen a su redescubrimiento, resignificación y uso como instrumento de construcción nacional. Las mecánicas de postguerra de reconstrucción de castillos responden a idiosincrasias de la cultura japonesa y ponen en relieve la función del castillo como símbolo de cohesión local y nacional y epítome de la recuperación tras un desastre, bien sea guerra o terremoto. Sólo en los últimos años ha empezado a aparecer la preocupación por la autenticidad y el valor del castillo como documento histórico, como atestigua el abandono del hormigón a favor de la madera y de las técnicas tradicionales a la hora de abordar una reconstrucción. Por lo demás, la filosofía que sustenta la conservación de los castillos originales está alineada a grandes rasgos con las principales cartas internacionales.[EN] This work studies the origin and development of the modern Japanese castle, as well as its processes of destruction, reconstruction, and preservation. For this, data of about 200 castles were compiled and analyzed. The modern castle was born in Japan in a short period of 35 years of constant evolution and remained stagnated for more than 2 centuries as the embodiment of the feudal order. The history of the Japanese castle from 1868 is troubled: from its methodical destruction as symbol of the ancient regime to its re-discovery, re-purposing and usage as a nation-building tool. The post-war castle reconstruction movement was related to Japanese society¿s idiosyncrasy and makes clear the function of the castle as a symbol of both local and national cohesion, and of economical and spiritual recovery after a war or earthquake. the concern about authenticity and the castle¿s role as a historical document is a recent phenomenon, evidenced by the rejection of reinforced concrete in favor of timber and traditional techniques when considering reconstruction. Apart from this, the philosophy behind the preservation of original castles is aligned with the major international preservation charters.Almenar Ruiz, S. (2020). Castillos japoneses: reconstrucción y restauración. http://hdl.handle.net/10251/150254TFG

A polymorphism at the 3'-UTR region of the aromatase gene defines a subgroup of postmenopausal breast cancer patients with poor response to neoadjuvant letrozole

<p>Abstract</p> <p>Background</p> <p>Aromatase (<it>CYP19A1</it>) regulates estrogen biosynthesis. Polymorphisms in <it>CYP19A1 </it>have been related to the pathogenesis of breast cancer (BC). Inhibition of aromatase with letrozole constitutes the best option for treating estrogen-dependent BC in postmenopausal women. We evaluate a series of polymorphisms of <it>CYP19A1 </it>and their effect on response to neoadjuvant letrozole in early BC.</p> <p>Methods</p> <p>We analyzed 95 consecutive postmenopausal women with stage II-III ER/PgR [+] BC treated with neoadjuvant letrozole. Response to treatment was measured by radiology at 4^thmonth by World Health Organization (WHO) criteria. Three polymorphisms of <it>CYP19A1</it>, one in exon 7 (rs700519) and two in the 3'-UTR region (rs10046 and rs4646) were evaluated on DNA obtained from peripheral blood.</p> <p>Results</p> <p>Thirty-five women (36.8%) achieved a radiological response to letrozole. The histopathological and immunohistochemical parameters, including hormonal receptor status, were not associated with the response to letrozole. Only the genetic variants (AC/AA) of the rs4646 polymorphism were associated with poor response to letrozole (p = 0.03). Eighteen patients (18.9%) reported a progression of the disease. Those patients carrying the genetic variants (AC/AA) of rs4646 presented a lower progression-free survival than the patients homozygous for the reference variant (p = 0.0686). This effect was especially significant in the group of elderly patients not operated after letrozole induction (p = 0.009).</p> <p>Conclusions</p> <p>Our study reveals that the rs4646 polymorphism identifies a subgroup of stage II-III ER/PgR [+] BC patients with poor response to neoadjuvant letrozole and poor prognosis. Testing for the rs4646 polymorphism could be a useful tool in order to orientate the treatment in elderly BC patients.</p

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Ritus de pas. Un temple ecumènic a Natzaret

[ES] Se propone un espacio de meditación y congregación multiconfesional en el extremo norte del barrio de Nazaret, Valencia. Nuestro ámbito es una zona en suave pendiente hacia el antiguo lecho del río Turia, ahora convertido en parque urbano. Esta área puede caracterizarse como un espacio liminal entre la ciudad de Valencia y Nazaret, entre el mundo urbano y el mundo natural (encarnado en el parque del Turia). Pese a la progresiva secularización de occidente, las necesidades espirtuales son inherentes al ser humano. El catolicismo pierde relevancia en España aunque se mantiene como la religión predominante, mientras que cada vez más personas optan por una relación íntima y no reglada con lo sagrado. Por otra parte, la inmigración ha creado un panorama complejo de minorías religiosas que, pese a su creciente número, continúan siendo poco visibles y sus espacios de culto, precarios. Al intervenir en esta zona de Nazaret se pretende crear un espacio de introspección y espiritualidad más acorde a la religiosidad contemporánea; fomentar el diálogo interreligioso y la visibilidad de las confesiones minoritarias; crear un marco sobrio y solemne para la celebración comunitaria de la fe; y articular la transición entre el espacio urbano y el espacio natural del parque del Turia, ayudando a configurar el desdibujado entorno urbano del extremo norte de Nazaret. La retórica de los ritos de paso supone la caracterización del propio templo como un rito de paso en sí mismo, un recorrido ascendente desde lo terrenal (profano) hasta la luz (lo sagrado). El programa del edificio se divide en dos zonas: una profana y otra sagrada. La zona profana adquiere la forma de un zócalo semi-enterrado que resuelve el desnivel de la parcela y alberga todos los espacios comunitarios y sociales. Este zócalo está atravesado por una grieta que comunica el parque fluvial con el ámbito urbano de Nazaret. Sobre el zócalo se sitúa la parte ¿sagrada¿ del templo, conformada por dos cilindros concéntricos: uno exterior ascendente que se desmaterializa a medida que gana altura y otro interior descendente que actúa como entrada de luz y configura el espacio central. Entre estos dos cilindros se sitúan dos rampas helicoidales que circulan en paralelo, simulando esta ascensión hacia la luz.[EN] A multi-confessional space of meditation is proposed at the northernmost edge of the neighborhood of Nazaret, Valencia. The proposed landplot is a slope that descends smoothly towards the old Turia riverbed, now turned into an urban park. This area can be regarded as a liminal space between the city of Valencia and the neighborhood of Nazaret, between the urban world and the natural world (represented by the Turia park). In spite of the progressive secularization of the West, spiritual needs are inherent to human beings. Catholicism loses ground in Spain but remains the prevalent religious confession, while more and more people tilt towards a more intimate, unorthodox relationship with the divine. Furthermore, immigration has created a complex panorama of religious minorities that, despite their growing numbers, remain rather invisible, and their cult spaces, rather precarious. With our intervention in this specific area of Nazaret we aim: to create a space of introspection and spirituality that is more aligned with today¿s religious needs; to spur interreligious communication and to make religious minorities more visible; to create an understated, solemn space for communitarian celebrations; and to articulate the transition between the urban and the natural worlds, helping to configurate the now undefined urban landscape of northern Nazaret. The temple becomes by itself a rite of passage, an ascending journey from the mundane (profane) towards the light (sacred). The building¿s programme is divided into two major areas: a profane zone and a sacred one. La profane zone takes the shape of a low podium that spans from one edge to the slope to the other and shelters all the community and social spaces. This podium is cut in two by a fissure that links the river park with the urban landscape of Nazaret. On top of the podium rests the temple itself, the sacred zone, made up of two concentric cylinders. The ¿ascending¿ outer cylinder loses mass as it gains height; the inner ¿descending¿ cylinder acts as light inlet and shapes the central space. A pair of helical ramps run between these two cylinders, acting as a real an metaphorical ascension to the divineAlmenar Ruiz, S. (2023). Ritos de paso. Un templo ecuménico en Nazaret. Universitat Politècnica de València. http://hdl.handle.net/10251/19300

Morphometric characterization of the human portal and hepatic venous trees: A quantitative support to the liver micro-anatomic models free of subunits

Conventional models of liver microanatomy assume the presence of subunits. Nevertheless, some researchers propose that the liver is a continuous structure, free of these subunits, but with a characteristic vascular pattern. The present study describes a morphometric analysis of portal and hepatic veins in 50 human autopsy non-pathological liver samples. The main objective was to measure three proportions: 1. portal tracts / hepatic veins, 2. distributing portal veins / distributing hepatic veins and 3. terminal portal veins / terminal hepatic veins. These ratios were compared with the traditional microcirculatory liver models. Our material comprised 3,665 portal veins and 3,761 hepatic veins. The minimum diameter of half of the venous vessels of both types belongs to the interval (25 μm , 60 μm), given that 1881 portal veins (49.434%) and 1924 hepatic veins (50.565%) fall within this interval. We have statistically shown with the χ2 test (α=0.990) that the portal and hepatic veins belonging to the interval (25 μm, 400 μm) (distributing veins) had an identical proportion. If the portal and hepatic veins are arranged according to the principle of interdigitation of Takashasi (1970), there should be an almost identical number of both types of veins. Our results contradict the presumably numeric preponderance of distributing portal veins with regard to the distributing hepatic veins that is inherent in the models of Kiernan, Matsumoto and Rappaport

Randomized phase 3 trial of fluorouracil, epirubicin, and cyclophosphamide alone or followed by Paclitaxel for early breast cancer.

Clinical Trial, Phase III; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't;BACKGROUND Taxanes are among the most active drugs for the treatment of metastatic breast cancer, and, as a consequence, they have also been studied in the adjuvant setting. METHODS After breast cancer surgery, women with lymph node-positive disease were randomly assigned to treatment with fluorouracil, epirubicin, and cyclophosphamide (FEC) or with FEC followed by weekly paclitaxel (FEC-P). The primary endpoint of study-5-year disease-free survival (DFS)-was assessed by Kaplan-Meier analysis. Secondary endpoints included overall survival and analysis of the prognostic and predictive value of clinical and molecular (hormone receptors by immunohistochemistry and HER2 by fluorescence in situ hybridization) markers. Associations and interactions were assessed with a multivariable Cox proportional hazards model for DFS for the following covariates: age, menopausal status, tumor size, lymph node status, type of chemotherapy, tumor size, positive lymph nodes, HER2 status, and hormone receptor status. All statistical tests were two-sided. RESULTS Among the 1246 eligible patients, estimated rates of DFS at 5 years were 78.5% in the FEC-P arm and 72.1% in the FEC arm (difference = 6.4%, 95% confidence interval [CI] = 1.6% to 11.2%; P = .006). FEC-P treatment was associated with a 23% reduction in the risk of relapse compared with FEC treatment (146 relapses in the 614 patients in the FEC-P arm vs 193 relapses in the 632 patients in the FEC arm, hazard ratio [HR] = 0.77, 95% CI = 0.62 to 0.95; P = .022) and a 22% reduction in the risk of death (73 and 95 deaths, respectively, HR = 0.78, 95% CI = 0.57 to 1.06; P = .110). Among the 928 patients for whom tumor samples were centrally analyzed, type of chemotherapy (FEC vs FEC-P) (P = .017), number of involved axillary lymph nodes (P < .001), tumor size (P = .020), hormone receptor status (P = .004), and HER2 status (P = .006) were all associated with DFS. We found no statistically significant interaction between HER2 status and paclitaxel treatment or between hormone receptor status and paclitaxel treatment. CONCLUSIONS Among patients with operable breast cancer, FEC-P treatment statistically significantly reduced the risk of relapse compared with FEC as adjuvant therapy.Department of Medical Oncology, Hospital Ciudad de Jaén, Jaén, SpainYe

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)