Software and Hardware-based Tools for Improving Ultrasound Guided Prostate Brachytherapy

Minimally invasive procedures for prostate cancer diagnosis and treatment, including biopsy and brachytherapy, rely on medical imaging such as two-dimensional (2D) and three-dimensional (3D) transrectal ultrasound (TRUS) and magnetic resonance imaging (MRI) for critical tasks such as target definition and diagnosis, treatment guidance, and treatment planning. Use of these imaging modalities introduces challenges including time-consuming manual prostate segmentation, poor needle tip visualization, and variable MR-US cognitive fusion. The objective of this thesis was to develop, validate, and implement software- and hardware-based tools specifically designed for minimally invasive prostate cancer procedures to overcome these challenges. First, a deep learning-based automatic 3D TRUS prostate segmentation algorithm was developed and evaluated using a diverse dataset of clinical images acquired during prostate biopsy and brachytherapy procedures. The algorithm significantly outperformed state-of-the-art fully 3D CNNs trained using the same dataset while a segmentation time of 0.62 s demonstrated a significant reduction compared to manual segmentation. Next, the impact of dataset size, image quality, and image type on segmentation performance using this algorithm was examined. Using smaller training datasets, segmentation accuracy was shown to plateau with as little as 1000 training images, supporting the use of deep learning approaches even when data is scarce. The development of an image quality grading scale specific to 3D TRUS images will allow for easier comparison between algorithms trained using different datasets. Third, a power Doppler (PD) US-based needle tip localization method was developed and validated in both phantom and clinical cases, demonstrating reduced tip error and variation for obstructed needles compared to conventional US. Finally, a surface-based MRI-3D TRUS deformable image registration algorithm was developed and implemented clinically, demonstrating improved registration accuracy compared to manual rigid registration and reduced variation compared to the current clinical standard of physician cognitive fusion. These generalizable and easy-to-implement tools have the potential to improve workflow efficiency and accuracy for minimally invasive prostate procedures

A low cost advance encryption standard (AES) co-processor implementation

The need for privacy has become a major priority for both governments and civilians desiring protection from signal interception. Widespread use of personal communications devices has only increased demand for a level of security on previously insecure communications. This paper presents a novel low-cost architecture for the Advanced Encryption Standard (AES) algorithm utilizing a field programmable gate array (FPGA). In as much as possible, this architecture uses a bit-serial approach, and it is also suitable for VLSI implementations. In this implementation, the primary objective was not to increase throughput or decrease latency, but to balance these factors in order to lower the cost. A focus on low cost resulted in a design well-suited for SoC implementations. This allows for scaling of the architecture towards vulnerable portable and cost-sensitive communications devices in consumer and military applications.Facultad de Informátic

New insights on single-stranded versus double-stranded DNA library preparation for ancient DNA

An innovative single-stranded DNA (ssDNA) library preparation method has sparked great interest among ancient DNA (aDNA) researchers, especially after reports of endogenous DNA content increases &gt;20-fold in some samples. To investigate the behavior of this method, we generated ssDNA and conventional double-stranded DNA (dsDNA) libraries from 23 ancient and historic plant and animal specimens. We found ssDNA library preparation substantially increased endogenous content when dsDNA libraries contained &lt;3% endogenous DNA, but this enrichment is less pronounced when dsDNA preparations successfully recover short endogenous DNA fragments (mean size &lt; 70 bp). Our findings can help researchers determine when to utilize the time- and resource-intensive ssDNA library preparation method. </jats:p

Genomic characterization of a South American <i>Phytophthora </i>hybrid mandates reassessment of the geographic origins of <i>Phytophthora infestans</i>

As the oomycete pathogen causing potato late blight disease, Phytophthora infestans triggered the famous 19th-century Irish potato famine and remains the leading cause of global commercial potato crop destruction. But the geographic origin of the genotype that caused this devastating initial outbreak remains disputed, as does the New World center of origin of the species itself. Both Mexico and South America have been proposed, generating considerable controversy. Here, we readdress the pathogen’s origins using a genomic data set encompassing 71 globally sourced modern and historical samples of P. infestans and the hybrid species P. andina, a close relative known only from the Andean highlands. Previous studies have suggested that the nuclear DNA lineage behind the initial outbreaks in Europe in 1845 is now extinct. Analysis of P. andina’s phased haplotypes recovered eight haploid genome sequences, four of which represent a previously unknown basal lineage of P. infestans closely related to the famine-era lineage. Our analyses further reveal that clonal lineages of both P. andina and historical P. infestans diverged earlier than modern Mexican lineages, casting doubt on recent claims of a Mexican center of origin. Finally, we use haplotype phasing to demonstrate that basal branches of the clade comprising Mexican samples are occupied by clonal isolates collected from wild Solanum hosts, suggesting that modern Mexican P. infestans diversified on Solanum tuberosum after a host jump from a wild species and that the origins of P. infestans are more complex than was previously thought

Reconstructing genome evolution in historic samples of the Irish potato famine pathogen

Responsible for the Irish potato famine of 1845–49, the oomycete pathogen Phytophthora infestans caused persistent, devastating outbreaks of potato late blight across Europe in the 19th century. Despite continued interest in the history and spread of the pathogen, the genome of the famine-era strain remains entirely unknown. Here we characterize temporal genomic changes in introduced P. infestans. We shotgun sequence five 19th-century European strains from archival herbarium samples—including the oldest known European specimen, collected in 1845 from the first reported source of introduction. We then compare their genomes to those of extant isolates. We report multiple distinct genotypes in historical Europe and a suite of infection-related genes different from modern strains. At virulence-related loci, several now-ubiquitous genotypes were absent from the historical gene pool. At least one of these genotypes encodes a virulent phenotype in modern strains, which helps explain the 20th century’s episodic replacements of European P. infestans lineages

Viewpoints on Acid-Induced Inflammatory Mediators in Esophageal Mucosa

We have focused on understanding the onset of gastroesophageal reflux disease by examining the mucosal response to the presence of acid in the esophageal lumen. Upon exposure to HCl, inflammation of the esophagus begins with activation of the transient receptor potential channel vanilloid subfamily member-1 (TRPV1) in the mucosa, and production of IL-8, substance P (SP), calcitonin gene related peptide (CGRP) and platelet activating factor (PAF). Production of SP and CGRP, but not PAF, is abolished by the neural blocker tetrodotoxin suggesting that SP and CGRP are neurally released and that PAF arises from non neural pathways. Epithelial cells contain TRPV1 receptor mRNA and protein and respond to HCl and to the TRPV1 agonist capsaicin with production of PAF. PAF, SP and IL-8 act as chemokines, inducing migration of peripheral blood leukocytes. PAF and SP activate peripheral blood leukocytes inducing the production of H2O2. In circular muscle, PAF causes production of IL-6, and IL-6 causes production of additional H2O2, through activation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidases. Among these, NADPH oxidase 5 cDNA is significantly up-regulated by exposure to PAF; H2O2 content of esophageal and lower esophageal sphincter circular muscle is elevated in human esophagitis, causing dysfunction of esophageal circular muscle contraction and reduction in esophageal sphincter tone. Thus esophageal keratinocytes, that constitute the first barrier to the refluxate, may also serve as the initiating cell type in esophageal inflammation, secreting inflammatory mediators and pro-inflammatory cytokines and affecting leukocyte recruitment and activity

Ancient genomics

The past decade has witnessed a revolution in ancient DNA (aDNA) research. Although the field's focus was previously limited to mitochondrial DNA and a few nuclear markers, whole genome sequences from the deep past can now be retrieved. This breakthrough is tightly connected to the massive sequence throughput of next generation sequencing platforms and the ability to target short and degraded DNA molecules. Many ancient specimens previously unsuitable for DNA analyses because of extensive degradation can now successfully be used as source materials. Additionally, the analytical power obtained by increasing the number of sequence reads to billions effectively means that contamination issues that have haunted aDNA research for decades, particularly in human studies, can now be efficiently and confidently quantified. At present, whole genomes have been sequenced from ancient anatomically modern humans, archaic hominins, ancient pathogens and megafaunal species. Those have revealed important functional and phenotypic information, as well as unexpected adaptation, migration and admixture patterns. As such, the field of aDNA has entered the new era of genomics and has provided valuable information when testing specific hypotheses related to the past.No Full Tex

Effectiveness of core needle biopsy in the diagnosis of thyroid lymphoma and anaplastic thyroid carcinoma: A systematic review and meta-analysis

Both anaplastic thyroid carcinoma (ATC) and thyroid lymphoma (TL) clinically present as rapidly enlarging neck masses. Unfortunately, in this situation, like in any other thyroid swelling, a routine fine-needle aspiration (FNA) cytology is the first and only diagnostic test performed at the initial contact in the average thyroid practice. FNA, however, has a low sensitivity in diagnosing ATC and TL, and by the time the often "inconclusive" result is known, precious time has evolved, before going for core-needle biopsy (CNB) or incisional biopsy (IB) as the natural next diagnostic steps