Abstract: Lung cancer is one of the most diagnosed cancers among men and women. Actually,
lung cancer accounts for 13% of the total cases with a 5-year global survival
rate in patients. Although Early detection increases survival rate from 38% to 67%, accurate diagnosis remains a challenge. Pathological confirmation requires extracting a sample of the lesion tissue for its biopsy. The preferred procedure for tissue biopsy is called bronchoscopy. A bronchoscopy is an endoscopic technique for the internal exploration of airways which facilitates the performance of minimal invasive interventions with low risk for the patient. Recent advances in bronchoscopic devices have increased their use for minimal invasive diagnostic and intervention procedures, like lung cancer biopsy sampling. Despite the improvement in bronchoscopic device quality, there is a lack of intelligent computational systems for supporting in-vivo clinical decision during examinations. Existing technologies fail to accurately reach the lesion due to several aspects at intervention off-line planning and poor intra-operative guidance at exploration time. Existing guiding systems radiate patients and clinical staff,might be expensive and achieve a suboptimlal 70% of yield boost. Diagnostic yield could be improved reducing radiation and costs by developing intra-operative support systems able to guide the bronchoscopist to the lesion during the intervention. The goal of this PhD thesis is to develop an image-based navigation systemfor intra-operative guidance of bronchoscopists to a target lesion across a path previously planned on a CT-scan. We propose a 3D navigation system which uses the anatomy of video bronchoscopy frames to locate the bronchoscope within the airways. Once the bronchoscope is located, our navigation system is able to indicate the bifurcation which needs to be followed to reach the lesion. In order to facilitate an off-line validation
as realistic as possible, we also present a method for augmenting simulated virtual bronchoscopies with the appearance of intra-operative videos. Experiments performed on augmented and intra-operative videos, prove that our algorithm can be speeded up for an on-line implementation in the operating room.

Abstract: Outlier, or anomaly, detection is essential for optimal performance of machine learning methods and statistical predictive models. It is not just a technical step in a data cleaning process but a key topic in many fields such as fraudulent document detection, in medical applications and assisted diagnosis systems or detecting security threats. In contrast to population-based methods, neighborhood based local approaches are simple flexible methods that have the potential to perform well in small sample size unbalanced problems. However, a main concern of local approaches is the impact that the computation of each sample neighborhood has on the method performance. Most approaches use a distance in the feature space to define a single neighborhood that requires careful selection of several parameters. This work presents a local approach based on a local measure of the heterogeneity of sample labels in the feature space considered as a topological manifold. Topology is computed using the communities of a weighted graph codifying mutual nearest neighbors in the feature space. This way, we provide with a set of multiple neighborhoods able to describe the structure of complex spaces without parameter fine tuning. The extensive experiments on real-world data sets show that our approach overall outperforms, both, local and global strategies in multi and single view settings.

Abstract: In most eukaryotes, pairing of homologous chromosomes is an essential feature of meiosis that ensures homologous recombination and segregation. However, when the pairing process begins, it is still under investigation. Contrasting data exists in Mus musculus, since both leptotene DSB-dependent and preleptotene DSB-independent mechanisms have been described. To unravel this contention, we examined homologous pairing in pre-meiotic and meiotic Mus musculus cells using a threedimensional fuorescence in situ hybridization-based protocol, which enables the analysis of the entire karyotype using DNA painting probes. Our data establishes in an unambiguously manner that 73.83% of homologous chromosomes are already paired at premeiotic stages (spermatogonia-early preleptotene spermatocytes). The percentage of paired homologous chromosomes increases to 84.60% at mid-preleptotene-zygotene stage, reaching 100% at pachytene stage. Importantly, our results demonstrate a high percentage of homologous pairing observed before the onset of meiosis; this pairing does not occur randomly, as the percentage was higher than that observed in somatic cells (19.47%) and between nonhomologous chromosomes (41.1%). Finally, we have also observed that premeiotic homologous pairing is asynchronous and independent of the chromosome size, GC content, or presence of NOR regions.