Desenvolupament d'estructures interferomètriques bimodals de cristall fotònic en nitrur de silici per a aplicacions de sensat

[ES] La tecnología fotónica es una de las que mayor interés despierta en el campo del desarrollo de dispositivos de sensado, ya que haciendo uso de la interacción de la luz con las sustancias a detectar es posible alcanzar sensibilidades tremendamente elevadas, lo que nos permite detectar bajas concentraciones de esas sustancias de interés. Además, el uso de la tecnología fotónica también aporta otras ventajas relevantes como por ejemplo el tamaño extremadamente reducido de esas estructuras de sensado, la posibilidad de incluir múltiples estructuras en un único chip para realizar un análisis simultáneo de diferentes sustancias o la posibilidad de realizar una detección sin la necesidad de usar marcadores (label-free), entre otras. Una de las principales estructuras fotónicas utilizadas a la hora de desarrollar elementos de sensado son los interferómetros. En este tipo de estructuras, la luz se divide en dos caminos ópticos independientes, donde uno de ellos estará aislado del medio a analizar (y actuará como referencia) y el otro estará en contacto con ese medio de cara a realizar la detección de la sustancia de interés. A la salida, ambas señales ópticas serán combinadas de nuevo, dando lugar a una respuesta interferométrica determinada por la interacción constructiva/destructiva de esas señales, respuesta que variará cuando se produzca la detección debido al cambio de fase acumulado en el camino de sensado. Este tipo de estructuras de sensado interferométricas tienen la ventaja de que su sensibilidad es proporcional a la longitud de los caminos ópticos, de forma que será posible aumentar la sensibilidad simplemente incrementando esta longitud. Sin embargo, esto hará que el tamaño de estas estructuras de sensado sea elevado, reduciendo así el nivel de integración que se podrá obtener. En este Trabajo Final de Grado, que se realizará en el Centro de Tecnología Nanofotónica (NTC) de la UPV, se plantea trabajar en el desarrollo de una nueva configuración de estructura interferométrica en la que se hace uso únicamente de una guía de cristal fotónico para conseguir la respuesta deseada. En esta configuración, se excitarán de forma simultánea dos modos ópticos en la guía de cristal fotónico, los cuales interferirán a la salida de la estructura. De esta forma, se reducirá el tamaño de la estructura en un factor de al menos 2 debido a que ya no será necesario disponer de dos caminos ópticos independientes. Pero además, la ventaja principal de esta configuración es que se hará uso del fenómeno de onda lenta que se produce en estas estructuras, de forma que será posible amplificar el cambio de fase experimentado por uno de los modos, consiguiendo así una significativa mejora de la sensibilidad y una reducción del tamaño final. Este concepto ya ha sido demostrado anteriormente por nuestro grupo haciendo uso de estructuras basadas en silicio, de forma que en este Trabajo Final de Grado se plantea la adaptación de este concepto a estructuras basadas en nitruro de silicio, donde se espera que el menor contraste de índices del que se dispone nos permita obtener un aumento de la sensibilidad, así como poder realizar una futura adaptación de la estructura al régimen visible del espectro (en lugar de trabajar en el infrarrojo, como se propone en este trabajo).Llorente Cerezuela, P. (2022). Desarrollo de estructuras interferométricas bimodales de cristal fotónico en nitruro de silicio para aplicaciones de sensado. Universitat Politècnica de València. http://hdl.handle.net/10251/18781

Intermittent BRAF inhibition in advanced BRAF mutated melanoma results of a phase II randomized trial

Combination treatment with BRAF (BRAFi) plus MEK inhibitors (MEKi) has demonstrated survival benefit in patients with advanced melanoma harboring activating BRAF mutations. Previous preclinical studies suggested that an intermittent dosing of these drugs could delay the emergence of resistance. Contrary to expectations, the first published phase 2 randomized study comparing continuous versus intermittent schedule of dabrafenib (BRAFi) plus trametinib (MEKi) demonstrated a detrimental effect of the “on−off” schedule. Here we report confirmatory data from the Phase II randomized open-label clinical trial comparing the antitumoral activity of the standard schedule versus an intermittent combination of vemurafenib (BRAFi) plus cobimetinib (MEKi) in advanced BRAF mutant melanoma patients (NCT02583516). The trial did not meet its primary endpoint of progression free survival (PFS) improvement. Our results show that the antitumor activity of the experimental intermittent schedule of vemurafenib plus cobimetinib is not superior to the standard continuous schedule. Detection of BRAF mutation in cell free tumor DNA has prognostic value for survival and its dynamics has an excellent correlation with clinical response, but not with progression. NGS analysis demonstrated de novo mutations in resistant cases

Image matching algorithms in stereo vision using address-event- representation: a theoretical study and evaluation of the different algorithms

Image processing in digital computer systems usually considers the visual information as a sequence of frames. These frames are from cameras that capture reality for a short period of time. They are renewed and transmitted at a rate of 25-30 fps (typical real-time scenario). Digital video processing has to process each frame in order to obtain a filter result or detect a feature on the input. In stereo vision, existing algorithms use frames from two digital cameras and process them pixel by pixel until it is found a pattern match in a section of both stereo frames. Spike-based processing is a relatively new approach that implements the processing by manipulating spikes one by one at the time they are transmitted, like a human brain. The mammal nervous system is able to solve much more complex problems, such as visual recognition by manipulating neuron’s spikes. The spike-based philosophy for visual information processing based on the neuro-inspired Address-Event- Representation (AER) is achieving nowadays very high performances. In this work we study the existing digital stereo matching algorithms and how do they work. After that, we propose an AER stereo matching algorithm using some of the principles shown in digital stereo methodsMinisterio de Ciencia e Innovación TEC2009-10639-C04-02 (VULCANO)European Union (UE) FP7-248582 (CARDIAC

Prognostic value of procalcitonin and lipopolysaccharide binding protein in cancer patients with chemotherapy-associated febrile neutropenia presenting to an emergency department

Introduction: Cancer patients with chemotherapy-induced febrile neutropenia are a heterogeneous group with a significant risk of serious medical complications. In these patients, the Multinational Association for Supportive Care in Cancer (MASCC) score is the most widely used tool for risk-stratification. The aim of this prospective study was to analyse the value of procalcitonin (PCT) and lipopolysaccharide binding protein (LBP) to predict serious complications and bacteraemia in cancer patients with febrile neutropenia, compared with MASCC score. Materials and methods: Data were collected from 111 episodes of febrile neutropenia admitted consecutively to the emergency department. In all of them, MASCC score was calculated and serum samples were collected for measurement of PCT and LBP by well-established methods. The main and secondary outcomes were the development of serious complications and bacteraemia, respectively. Results: A serious complication occurred in 20 (18%) episodes and in 16 (14%) bacteraemia was detected. Areas under the receiver operating characteristic curve (ROC AUC) of MASCC score, PCT and LBP to select low-risk patients were 0.83 (95% confidence interval (CI): 0.74 - 0.89), 0.85 (95% CI: 0.77 - 0.91) and 0.70 (95% CI: 0.61 - 0.78), respectively. For bacteraemia, MASCC score, PCT and LBP showed ROC AUCs of 0.74 (95% CI: 0.64 - 0.82), 0.86 (95% CI: 0.78 - 0.92) and 0.76 (95% CI: 0.67 - 0.83), respectively. Conclusion: A single measurement of PCT performs similarly as MASCC score to predict serious medical complications in cancer patients with febrile neutropenia and can be a useful tool for risk stratification. Besides, low PCT concentrations can be used to rule-out the presence of bacteraemia

Frequency and Clinicopathological Profile Associated with Braf Mutations in Patients with Advanced Melanoma in Spain

Real-world data on BRAF mutation frequency in advanced melanoma are lacking in Spain. Moreover, data available on clinicopathological profile of patients with advanced BRAF-mutant melanoma are currently limited. This study aimed to assess the frequency of BRAF V600 mutations in Spanish patients with advanced or metastatic melanoma and to identify clinical and histopathological features associated with BRAF-mutated tumors. A multicenter, cross-sectional epidemiological study was conducted in 33 Spanish hospitals in adult patients with stage IIIc/IV melanoma. A total of 264 patients were included. The median age was 68 years and 57% were male. Melanoma mainly involved skin with intermittent (40.4%) and low or no sun exposure (43.5%). Most patients (85.6%) had stage IV disease (M1a: 19.3%; M1b: 13.3%; M1c: 22.7%). Serum lactate dehydrogenase levels were elevated in 20% of patients. Superficial spreading melanoma was the most frequent histological type (29.9%). Samples were predominantly obtained from metastases (62.7%), mostly from skin and soft tissues (80%). BRAF mutation analysis was primarily performed using the Cobas 4800 BRAF V600 Mutation Test (92.8%) on formalin-fixed, paraffin-embedded tissue (95.8%). BRAF mutations were detected in 41.3% of samples. Multivariate analysis identified age (odd ratio [OR] 0.975) and stage IV M1a (OR 2.716) as independent factors associated with BRAF mutation. The frequency of BRAF mutations in tumor samples from patients with advanced or metastatic melanoma in Spain was 41.3%. BRAF mutations seem to be more frequent in younger patients and stage M1a patients. This study provides the basis for further investigation regarding BRAF-mutated advanced melanoma in larger cohorts.This study was sponsored by Roche Farma S.A

Adjuvant dabrafenib and trametinib for patients with resected BRAF-mutated melanoma: DESCRIBE-AD real-world retrospective observational study

BRAF and MEK inhibitor, dabrafenib plus trametinib, adjuvant therapy is effective for high-risk resected melanoma patients with BRAF-V600 mutations. However, real-world evidence is limited. We aimed to determine the feasibility of this therapy in routine clinical practice. DESCRIBE-AD, a retrospective observational study, collected real-world data from 25 hospitals in Spain. Histologically confirmed and resected BRAF-mutated melanoma patients aged & GE;18 years who were previously treated with dabrafenib plus trametinib adjuvant therapy, were included. The primary objectives were treatment discontinuation rate and time to discontinuation. The secondary objectives included safety and efficacy. From October 2020 to March 2021, 65 patients were included. Dabrafenib and trametinib discontinuation rate due to treatment-related adverse events (TRAEs) of any grade was 9%. Other reasons for discontinuation included patients' decisions (6%), physician decisions (6%), unrelated adverse events (3%), disease progression (5%), and others (5%). The median time to treatment discontinuation was 9 months [95% confidence interval (CI), 5-11]. G3-4 TRAEs occurred in 21.5% of patients, the most common being pyrexia (3%), asthenia (3%), and diarrhoea (3%). Unscheduled hospitalisations and clinical tests occurred in 6 and 22% of patients, respectively. After 20-month median follow-up (95% CI, 18-22), 9% of patients had exitus due to disease progression, with a 12-month relapse-free survival and overall survival rates of 95.3% and 100%, respectively. Dabrafenib and trametinib adjuvant therapy proved effective for melanoma patients in a real-world setting, with a manageable toxicity profile. Toxicity frequencies were low leading to low incidence of unscheduled medical visits, tests, and treatment discontinuations

Cancer immunotherapy in special challenging populations: recommendations of the Advisory Committee of Spanish Melanoma Group (GEM)

Cancer immunotherapy based on the use of antibodies targeting the so-called checkpoint inhibitors, such as programmed cell death-1 receptor, its ligand, or CTLA-4, has shown durable clinical benefit and survival improvement in melanoma and other tumors. However, there are some special situations that could be a challenge for clinical management. Persons with chronic infections, such as HIV-1 or viral hepatitis, latent tuberculosis, or a history of solid organ transplantation, could be candidates for cancer immunotherapy, but their management requires a multidisciplinary approach. The Spanish Melanoma Group (GEM) panel in collaboration with experts in virology and immunology from different centers in Spain reviewed the literature and developed evidence-based guidelines for cancer immunotherapy management in patients with chronic infections and immunosuppression. These are the first clinical guidelines for cancer immunotherapy treatment in special challenging populations. Cancer immunotherapy in chronically infected or immunosuppressed patients is feasible but needs a multidisciplinary approach in order to decrease the risk of complications related to the coexistent comorbidities

Frequency and Characteristics of familial melanoma in Spain: the FAM-GEM-1 Study.

Familial history of melanoma is a well-known risk factor for the disease, and 7% melanoma patients were reported to have a family history of melanoma. Data relating to the frequency and clinical and pathological characteristics of both familial and non-familial melanoma in Spain have been published, but these only include patients from specific areas of Spain and do not represent the data for the whole of Spain. PATIENTS AND METHODS: An observational study conducted by the Spanish Group of Melanoma (GEM) analyzed the family history of patients diagnosed with melanoma between 2011 and 2013 in the dermatology and oncology departments. RESULTS: In all, 1047 patients were analyzed, and 69 (6.6%) fulfilled criteria for classical familial melanoma (two or more first-degree relatives diagnosed with melanoma). Taking into account other risk factors for familial melanoma, such as multiple melanoma, pancreatic cancer in the family or second-degree relatives with melanoma, the number of patients fulfilling the criteria increased to 165 (15.8%). Using a univariate analysis, we determined that a Breslow index of less than 1 mm, negative mitosis, multiple melanoma, and a history of sunburns in childhood were more frequent in familial melanoma patients, but a multivariate analysis revealed no differences in any pathological or clinical factor between the two groups. CONCLUSIONS: Similar to that observed in other countries, familial melanoma accounts for 6.6% of melanoma diagnoses in Spain. Although no differences in the multivariate analysis were found, some better prognosis factors, such as Breslow index, seem more frequent in familial melanoma, which reflect a better early detection marker and/or a different biological behavior

Frequency and characteristics of familial melanoma in Spain: The FAM-GEM-1 Study

Similar to that observed in other countries, familial melanoma accounts for 6.6% of melanoma diagnoses in Spain. Although no differences in the multivariate analysis were found, some better prognosis factors, such as Breslow index, seem more frequent in familial melanoma, which reflect a better early detection marker and/or a different biological behavior

AUTOMATIZACIÓN DEL ANÁLISIS DE ESPECTROSCOPÍA POR RESONANCIA MAGNÉTICA CEREBRAL

La espectroscopía por resonancia magnética constituye una técnica de exploración biológica que permite cuantificar compuestos químicos presentes en el cuerpo humano. El objetivo fundamental de este proyecto es el de ofrecer a la comunidad científica una aplicación que facilite el uso de esta técnica como herramienta de análisis gracias a su elevado nivel de automatización. Por ello se realiza el desarrollo de una aplicación sencilla que integra todas las fases que se siguen en este análisis con el fin de obtener resultados clínicos concluyentes.Villa Cerezuela, P. (2014). AUTOMATIZACIÓN DEL ANÁLISIS DE ESPECTROSCOPÍA POR RESONANCIA MAGNÉTICA CEREBRAL. http://hdl.handle.net/10251/46602.Archivo delegad