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"Jacobs, Michael"
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The Andalucâia guide
Michael Jacobs looks with fresh eyes at all the traditional delights of Andalucia while doing full justice to the lesser-known aspects of the region. He examines the underrated local food and drink, the extraordinarily varied natural scenery, the composers and writers who created the romantic myths and legends of the nineteenth century, the strange legacy of Lorca and the Spanish Civil War. Andalucia's Moorish remains, its outstanding prehistoric and classical heritage and its exuberant Renaissance and Baroque monuments make it one of the richest regions of Europe for the visitor. Nearly a hundred Andalucian villages and towns are described in the gazetteer, some of which--Seville, Granada, Cordoba and Cadiz--are as lovely and as haunting as anywhere in the world. -- Amazon.com.
Book
Multiparametric radiomics methods for breast cancer tissue characterization using radiological imaging
Background and purpose
Multiparametric radiological imaging is vital for detection, characterization, and diagnosis of many different diseases. Radiomics provide quantitative metrics from radiological imaging that may infer potential biological meaning of the underlying tissue. However, current methods are limited to regions of interest extracted from a single imaging parameter or modality, which limits the amount of information available within the data. This limitation can directly affect the integration and applicable scope of radiomics into different clinical settings, since single image radiomics are not capable of capturing the true underlying tissue characteristics in the multiparametric radiological imaging space. To that end, we developed a multiparametric imaging radiomic (mpRad) framework for extraction of first and second order radiomic features from multiparametric radiological datasets.
Methods
We developed five different radiomic techniques that extract different aspects of the inter-voxel and inter-parametric relationships within the high-dimensional multiparametric magnetic resonance imaging breast datasets. Our patient cohort consisted of 138 breast patients, where, 97 patients had malignant lesions and 41 patients had benign lesions. Sensitivity, specificity, receiver operating characteristic (ROC) and areas under the curve (AUC) analysis were performed to assess diagnostic performance of the mpRad parameters. Statistical significance was set at
p
< 0.05.
Results
The mpRad features successfully classified malignant from benign breast lesions with excellent sensitivity and specificity of 82.5% and 80.5%, respectively, with Area Under the receiver operating characteristic Curve (AUC) of 0.87 (0.81–0.93). mpRad provided a 9–28% increase in AUC metrics over single radiomic parameters.
Conclusions
We have introduced the mpRad framework that extends radiomic analysis from single images to multiparametric datasets for better characterization of the underlying tissue biology.
Journal Article
Rapid 16S rRNA Next-Generation Sequencing of Polymicrobial Clinical Samples for Diagnosis of Complex Bacterial Infections
Classifying individual bacterial species comprising complex, polymicrobial patient specimens remains a challenge for culture-based and molecular microbiology techniques in common clinical use. We therefore adapted practices from metagenomics research to rapidly catalog the bacterial composition of clinical specimens directly from patients, without need for prior culture. We have combined a semiconductor deep sequencing protocol that produces reads spanning 16S ribosomal RNA gene variable regions 1 and 2 (∼360 bp) with a de-noising pipeline that significantly improves the fraction of error-free sequences. The resulting sequences can be used to perform accurate genus- or species-level taxonomic assignment. We explore the microbial composition of challenging, heterogeneous clinical specimens by deep sequencing, culture-based strain typing, and Sanger sequencing of bulk PCR product. We report that deep sequencing can catalog bacterial species in mixed specimens from which usable data cannot be obtained by conventional clinical methods. Deep sequencing a collection of sputum samples from cystic fibrosis (CF) patients reveals well-described CF pathogens in specimens where they were not detected by standard clinical culture methods, especially for low-prevalence or fastidious bacteria. We also found that sputa submitted for CF diagnostic workup can be divided into a limited number of groups based on the phylogenetic composition of the airway microbiota, suggesting that metagenomic profiling may prove useful as a clinical diagnostic strategy in the future. The described method is sufficiently rapid (theoretically compatible with same-day turnaround times) and inexpensive for routine clinical use.
Journal Article
The robber of memories : a river journey through Colombia
A gripping journey up the River Magdalena into the central regions of Colombia, and a moving, deeply personal meditation on memory and its loss in the footsteps of Gabriel Garcia Marquez.
Book
Genomic heterogeneity underlies multidrug resistance in Pseudomonas aeruginosa: A population-level analysis beyond susceptibility testing
Pseudomonas aeruginosa is a persistent and difficult-to-treat pathogen in many patients, especially those with Cystic Fibrosis (CF). Herein, we describe a longitudinal analysis of a series of multidrug resistant (MDR) P. aeruginosa isolates recovered in a 17-month period, from a young female CF patient who underwent double lung transplantation. Our goal was to understand the genetic basis of the observed resistance phenotypes, establish the genomic population diversity, and define the nature of sequence evolution over time.
Twenty-two sequential P. aeruginosa isolates were obtained within a 17-month period, before and after a double-lung transplant. At the end of the study period, antimicrobial susceptibility testing, whole genome sequencing (WGS), phylogenetic analyses and RNAseq were performed in order to understand the genetic basis of the observed resistance phenotypes, establish the genomic population diversity, and define the nature of sequence changes over time.
The majority of isolates were resistant to almost all tested antibiotics. A phylogenetic reconstruction revealed 3 major clades representing a genotypically and phenotypically heterogeneous population. The pattern of mutation accumulation and variation of gene expression suggested that a group of closely related strains was present in the patient prior to transplantation and continued to change throughout the course of treatment. A trend toward accumulation of mutations over time was observed. Different mutations in the DNA mismatch repair gene mutL consistent with a hypermutator phenotype were observed in two clades. RNAseq performed on 12 representative isolates revealed substantial differences in the expression of genes associated with antibiotic resistance and virulence traits.
The overwhelming current practice in the clinical laboratories setting relies on obtaining a pure culture and reporting the antibiogram from a few isolated colonies to inform therapy decisions. Our analyses revealed significant underlying genomic heterogeneity and unpredictable evolutionary patterns that were independent of prior antibiotic treatment, highlighting the need for comprehensive sampling and population-level analysis when gathering microbiological data in the context of CF P. aeruginosa chronic infection. Our findings challenge the applicability of antimicrobial stewardship programs based on single-isolate resistance profiles for the selection of antibiotic regimens in chronic infections such as CF.
Journal Article
Molecular dissection of the evolution of carbapenem-resistant multilocus sequence type 258 Klebsiella pneumoniae
Infections caused by drug-resistant bacteria are a major problem worldwide. Carbapenem-resistant Klebsiella pneumoniae , most notably isolates classified as multilocus sequence type (ST) 258, have emerged as an important cause of hospital deaths. ST258 isolates are predominantly multidrug resistant, and therefore infections caused by them are difficult to treat. It is not known why the ST258 lineage is the most prevalent cause of multidrug-resistant K. pneumoniae infections in the United States and other countries. Here we tested the hypothesis that carbapenem-resistant ST258 K. pneumoniae is a single genetic clone that has disseminated worldwide. We sequenced to closure the genomes of two ST258 clinical isolates and used these genomes as references for comparative genome sequencing of 83 additional clinical isolates recovered from patients at diverse geographic locations worldwide. Phylogenetic analysis of the SNPs in the core genome of these isolates revealed that ST258 K. pneumoniae organisms are two distinct genetic clades. This unexpected finding disproves the single-clone hypothesis. Notably, genetic differentiation between the two clades results from an ∼215-kb region of divergence that includes genes involved in capsule polysaccharide biosynthesis. The region of divergence appears to be a hotspot for DNA recombination events, and we suggest that this region has contributed to the success of ST258 K. pneumoniae . Our findings will accelerate research on novel diagnostic, therapeutic, and vaccine strategies designed to prevent and/or treat infections caused by multidrug resistant K. pneumoniae .
Journal Article
Thermophysical properties and phase diagrams in the system MgO–SiO2–FeO at lower mantle conditions derived from a multiple-Einstein method
In a previous paper we showed that the multiple Einstein method is suitable to determine consistency of data on thermophysical properties and phase diagrams in the system MgO–FeO–SiO
2
for upper mantle and transition zone conditions in the Earth. Here we extend this work to conditions covering the lower mantle, in the temperature range between 0 and 3000 K and pressure range between 20 and 140 GPa, with the goal to determine which data are consistent with each other. The resulting database is used to study the effect of the spin transition in ferropericlase on thermophysical properties and phase diagrams. Although trade-off is present in the model parameters due to the lack of experimental data, we show that models, reduced in complexity, can be used to study the effect of Fe
3+
on these properties and phase equilibria. We show that the effect of the miscibility gap in ferropericlase, its spin transition and the valence state of Fe does not have a significant visibility in seismic density and velocities isentropes. We demonstrate that the overall composition derived by Chust et al. (J Geophys Res Solid Earth 122:9881–9920, 2018) is suitable to represent PREM and AK135 seismic data to within experimental uncertainty.
Journal Article