Objetos fractales y arquitectura

Este trabajo final de grado versa acerca de la fractalidad y su posible aplicación arquitectónica. Se parte del concepto de fractal quedándose con la idea de que “un fractal es un diseño que se repite indefinidamente hacia el infinito cada vez a escala menor” y se presentan los diferentes conjuntos haciendo especial hincapié en los fractales clásicos. La fractalidad se puede apreciar en la naturaleza (p.e: un árbol tiene un tronco, este se divide en ramas, cada una de ellas en ramas más pequeñas y así hasta llegar a las hojas). Así pues, de manera similar, se aplica a la arquitectura. Pese a que el término fractal no fue acuñado hasta 1975 (Benoît Mandelbrot), el hombre, a lo largo de la historia, ha ido aplicando este concepto a sus diseños de manera intuitiva. Es así como Carlos Ferrater comienza a usar este recurso en el Jardín Botánico de Barcelona (1988-1999) como herramienta para dar solución a un programa funcional así como para integrar el proyecto en el entorno. Esta obra, marca un antes y un después en la geometría de sus proyectos. A partir de aquí, el arquitecto, sigue trabajando en esta línea, pero sin cesar de evolucionar. Así, nacen con posterioridad el Paseo Marítimo de la Playa Poniente de Benidorm y la Bodega FrontauraThis study focuses on fractality and its possible use in architecture. This dissertation is based on the concept of fractal as a “design that is repeated indefinitely each time in a smaller scale” and the classical fractal sets are introduced. Fractality can also be appreciated in nature (e.g: a tree has a trunk, this is divided into branches, every of them into smaller branches and so on until reaching the leaves). In a similar way, this is used in architecture. Despite the fact that the “fractal” term was not registered until 1975 (Benoît Mandelbrot), throughout history, the human being has been using this idea in an intuitive way. That is how Carlos Ferrater starts using the resource in Barcelona Botanical Garden (1988-1999) as a tool for solving a functional program as well as in order to integrate the project into the surroundings. This architectural work, marks a turning point in his project’s geometry. From that moment, the architect keeps working in this direction, but without stopping in his evolution. As a result, Benidorm West Beach Promenade and Frontaura Winery are later designed.Aquest treball final de grau versa sobre la fractalitat i la seua possible aplicació arquitectònica. Es partix del concepte de fractal quedant-se amb la idea de que “un fractal és un diseny que es repetix indefinidament cap a l’infinit cada vegada a escala menor” i es presenten els diferents conjunts fent especial èmfasi en els fractals clàssics. La fractalitat es pot apreciar en la naturalesa (p.e: un arbre té un tronc, aquest es dividix en branques, cada una d’elles en branques més xicotetes i així fins a arribar a les fulles). Així doncs, de manera similar, s’aplica a l’arquitectura. Malgrat que el terme fractal no va ser encunyat fins 1975 (Benoît Mandelbrot), l’home, al llarg de la història ha anat aplicant aquest concepte als seus disenys de manera intuïtiva. És així com Carlos Ferrater comença a utilitzar aquest recurs al Jardí Botànic de Barcelona (1988-1999) com a ferramenta per a donar solució a un programa funcional, així com per a integrar el projecte en l’entorn. Aquesta obra, suposa un abans i un després en la geometría dels seus projectes. A partir d’ací, l’arquitecte, continua treballant en aquesta línia, però sense parar d’evolucionar. Així, naixen amb posterioritat el Passeig Marítim de la Platja Ponent de Benidorm i la Bodega FrontauraMartínez Requena, CA. (2015). Objetos fractales y arquitectura. http://hdl.handle.net/10251/58637.TFG

Variants at the 9p21 locus and melanoma risk

Background: The influence of variants at the 9p21 locus on melanoma risk has been reported through investigation of CDKN2A variants through candidate gene approach as well as by genome wide association studies (GWAS). Methods: In the present study we genotyped, 25 SNPs that tag 273 variants on chromosome 9p21 in 837 melanoma cases and 1154 controls from Spain. Ten SNPs were selected based on previous associations, reported in GWAS, with either melanocytic nevi or melanoma risk or both. The other 15 SNPs were selected to fine map the CDKN2A gene region. Results: All the 10 variants selected from the GWAS showed statistically significant association with melanoma risk. Statistically significant association with melanoma risk was also observed for the carriers of the variant T-allele of rs3088440 (540 C>T) at the 3' UTR of CDKN2A gene with an OR 1.52 (95% CI 1.14-2.04). Interaction analysis between risk associated polymorphisms and previously genotyped MC1R variants, in the present study, did not show any statistically significant association. Statistical significant association was observed for the interaction between phototypes and the rs10811629 (located in intron 5 of MTAP). The strongest association was observed between the homozygous carrier of the A-allele and phototype II with an OR of 15.93 (95% CI 5.34-47.54). Conclusions: Our data confirmed the association of different variants at chromosome 9p21 with melanoma risk and we also found an association of a variant with skin phototypes

Suitability of melanoma FFPE samples for NGS libraries: time and quality thresholds for downstream molecular tests

The use of NGS in clinical practice for precision diagnosis requires a quality starting material. Despite the broadly established use of formalin-fixed paraffin-embedded (FFPE) samples in molecular testing, these usually have low-quality DNA. We established a method to determine the suitability of melanoma FFPE samples for an amplicon-based NGS custom panel analysis. DNA was extracted from unstained melanoma samples and wide local excision samples. Amplicon-based libraries were constructed and tested using time and quality parameters as variables. Time elapsed from sample retrieval >7 years, a quality control value > 5.63 and a DNA integrity value < 2.05 indicated samples were not suitable. A decision tree is provided with rate of samples suitable for analysis according to the combination of these parametersThis study has been funded by the Instituto de Salud Carlos III grant number PI15/01860, the Junta Provincial de Valencia de la Asociación Española contra el Cancer through a PhD grant, and by the Universidad Católica de Valencia San Vicente Mártir. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscrip

Mutational Characterization of Cutaneous Melanoma Supports Divergent Pathways Model for Melanoma Development

This article belongs to the Special Issue Melanoma: Prevention and Molecular Epidemiology.[Simple Summary] The divergent pathway model established at least two approaches for melanoma development. One was related to a propensity to melanocytic proliferation (nevogenic), and the other was associated with an accumulation of solar damage (CSD). We conducted a retrospective study to examine whether this model had a molecular support using sequencing and bioinformatic tools on a set of cutaneous melanomas corresponding to these two groups. We found that the nevogenic melanomas were associated with mutations in BRAF, while the CSD melanomas were associated with mutations in NF1, ROS1, GNA11, and RAC1. We concluded that nevogenic and CSD melanomas constitute two different biological entities.[Abstract] According to the divergent pathway model, cutaneous melanoma comprises a nevogenic group with a propensity to melanocyte proliferation and another one associated with cumulative solar damage (CSD). While characterized clinically and epidemiologically, the differences in the molecular profiles between the groups have remained primarily uninvestigated. This study has used a custom gene panel and bioinformatics tools to investigate the potential molecular differences in a thoroughly characterized cohort of 119 melanoma patients belonging to nevogenic and CSD groups. We found that the nevogenic melanomas had a restricted set of mutations, with the prominently mutated gene being BRAF. The CSD melanomas, in contrast, showed mutations in a diverse group of genes that included NF1, ROS1, GNA11, and RAC1. We thus provide evidence that nevogenic and CSD melanomas constitute different biological entities and highlight the need to explore new targeted therapies.This study was supported by the Ministerio de Ciencia e Innovación-Instituto de Salud Carlos III (PI15/01860; PI19/00667), the Asociación Española Contra el Cáncer-Valencia through “Ayudas predoctorales en Oncología” grant, and the European Academy of Dermatology and Venereology (PPRC-2018-36)

Public healthcare costs associated with long-term exposure to mixtures of persistent organic pollutants in two areas of Southern Spain: A longitudinal analysis

Background: Polychlorinated biphenyls and organochlorine pesticides are persistent organic pollutants (POPs) that had been banned or restricted in many countries, including Spain. However, their ubiquity still poses environmental and human health threats. Objective: To longitudinally explore public healthcare costs associated with long-term exposure to a mixture of 8 POPs in a cohort of residents of two areas of Granada Province, Southern Spain. Methods: Longitudinal study in a subsample (n = 385) of GraMo adult cohort. Exposure assessment was performed by analyzing adipose tissue POP concentrations at recruitment. Average primary care (APC) and average hospital care (AHC) expenditures of each participant over 14 years were estimated using the data from their medical records. Data analyses were performed by robust MM regression, weighted quantile sum regression (WQS) and G-computation analysis. Results: In the adjusted robust MM models for APC, most POPs showed positive beta coefficients, being Hexachlorobenzene (HCB) significantly associated (beta 1.87; 95% Confidence interval (95%CI): 0.17, 3.57). The magnitude of this association increased (beta: 3.72; 95%CI: 0.80, 6.64) when the analyses were restricted to semirural residents, where p-HCH was also marginally-significantly associated to APC (beta: 3.40; 95%CI: -0.10, 6.90). WQS revealed a positive but non-significant mixture association with APC (beta: 0.14; 95%CI: -0.06, 0.34), mainly accounted for by p-HCH (54%) and HCB (43%), that was borderline-significant in the semi-rural residents (beta: 0.23; 95%CI: -0.01, 0.48). No significant results were observed in G-Computation analyses. Conclusion: Long-term exposure to POP mixtures might represent a modifiable factor increasing healthcare costs, thus affecting the efficiency of the healthcare systems. However, and owing the complexity of the potential causal pathways and the limitations of the present study, further research is warranted to fully elucidate ascertain whether interventions to reduce human exposure should be considered in healthcare policies.CIBER de Epidemiologia y Salud Publica (CIBERESP), Instituto de Salud Carlos III, Spain PI16/01858 PI18/01573 PI20/01568European CommissionRamon y Cajal Program (Ministerio de Economia, Industria y Competitividad, Spain) RYC-2016-20,155PFIS (Instituto de Salud Carlos III, Spain) FI17/00310Universidad de Granada/CBU

Mutational Characterization of Cutaneous Melanoma Supports Divergent Pathways Model for Melanoma Development

From MDPI via Jisc Publications RouterHistory: accepted 2021-10-14, pub-electronic 2021-10-18Publication status: PublishedFunder: Instituto de Salud Carlos III; Grant(s): PI15/01860; PI19/00667Funder: EADV; Grant(s): PPRC-2018-36, Ayuda predoctoral en OncologíaAccording to the divergent pathway model, cutaneous melanoma comprises a nevogenic group with a propensity to melanocyte proliferation and another one associated with cumulative solar damage (CSD). While characterized clinically and epidemiologically, the differences in the molecular profiles between the groups have remained primarily uninvestigated. This study has used a custom gene panel and bioinformatics tools to investigate the potential molecular differences in a thoroughly characterized cohort of 119 melanoma patients belonging to nevogenic and CSD groups. We found that the nevogenic melanomas had a restricted set of mutations, with the prominently mutated gene being BRAF. The CSD melanomas, in contrast, showed mutations in a diverse group of genes that included NF1, ROS1, GNA11, and RAC1. We thus provide evidence that nevogenic and CSD melanomas constitute different biological entities and highlight the need to explore new targeted therapies

Effect of time to sentinel-node biopsy on the prognosis of cutaneous melanoma

Introduction: In patients with primary cutaneous melanoma, there is generally a delay between excisional biopsy of the primary tumour and sentinel-node biopsy. The objective of this study is to analyse the prognostic implications of this delay. Patients and method: This was an observational, retrospective, cohort study in four tertiary referral hospitals. A total of 1963 patients were included. The factor of interest was the interval between the date of the excisional biopsy of the primary melanoma and the date of the sentinel-node biopsy (delay time) in the prognosis. The primary outcome was melanoma-specific survival and disease-free survival. Results: A delay time of 40 days or less (hazard ratio (HR), 1.7; confidence interval (CI), 1.2-2.5) increased Breslow thickness (Breslow ⩾2 mm, HR, >3.7; CI, 1.4-10.7), ulceration (HR, 1.6; CI, 1.1-2.3), sentinel-node metastasis (HR, 2.9; CI, 1.9-4.2), and primary melanoma localised in the head or neck were independently associated with worse melanoma-specific survival (all P < 0.03). The stratified analysis showed that the effect of delay time was at the expense of the patients with a negative sentinel-node biopsy and without regression. Conclusion: Early sentinel-node biopsy is associated with worse survival in patients with cutaneous melanoma

Characterization of individuals at high risk of developing melanoma in Latin America: bases for genetic counseling in melanoma

PURPOSE: CDKN2A is the main high-risk melanoma-susceptibility gene, but it has been poorly assessed in Latin America. We sought to analyze CDKN2A and MC1R in patients from Latin America with familial and sporadic multiple primary melanoma (SMP) and compare the data with those for patients from Spain to establish bases for melanoma genetic counseling in Latin America. METHODS: CDKN2A and MC1R were sequenced in 186 Latin American patients from Argentina, Brazil, Chile, Mexico, and Uruguay, and in 904 Spanish patients. Clinical and phenotypic data were obtained. RESULTS: Overall, 24 and 14% of melanoma-prone families in Latin America and Spain, respectively, had mutations in CDKN2A. Latin American families had CDKN2A mutations more frequently (P = 0.014) than Spanish ones. Of patients with SMP, 10% of those from Latin America and 8.5% of those from Spain had mutations in CDKN2A (P = 0.623). The most recurrent CDKN2A mutations were c.-34G>T and p.G101W. Latin American patients had fairer hair (P = 0.016) and skin (P < 0.001) and a higher prevalence of MC1R variants (P = 0.003) compared with Spanish patients. CONCLUSION: The inclusion criteria for genetic counseling of melanoma in Latin America may be the same criteria used in Spain, as suggested in areas with low to medium incidence, SMP with at least two melanomas, or families with at least two cases among first- or second-degree relatives.Genet Med 18 7, 727-736

Catálogo y distribución geográfica de los Odonatos en la Región de Murcia (SE España).

Se actualiza el catálogo y la distribución del orden Odonata en la Región de Murcia, comparándolo a uno anterior realizado en los años 50 del siglo XX. Los resultados indican que a mitad del siglo pasado se localizaron 40 especies en 17 localidades, mientras que las 2.087 citas recopiladas entre 1991-2017 confirman la presencia de 47 especies en 191 localidades. Se han identificado 11 nuevas especies para la Región de Murcia, que se pueden haber visto favorecidas por la construcción de charcas, embalses y otras infraestructuras para abastecer a las 225.000 ha de regadíos. De ellas, 9 especies se están expandiendo su área de distribución hacia el norte de Europa y/o Asia, efecto que podría estar relacionado con el proceso de cambio climático actual. Por el contrario, en la revisión actual no han sido detectadas 4 especies citadas en el estudio realizado a mediados del siglo XX