One Health-ness Evaluation of Cysticercosis Surveillance Design in Portugal

The increasing occurrence of human cysticercosis, a zoonotic neglected disease, is challenging the traditional prevention and control paradigm and calling for One Health (OH) solutions in industrialized countries. OH solutions for health interventions are increasingly being used to capture expected and unexpected outcomes across people, animals, and the environment. The Network for Evaluation of One Health (NEOH) proposes an evidence-based framework, relying on systems and mixed methods approaches to evaluate the One Health-ness. In this case study, this tool is used to evaluate the design of the Observatory of Taeniasis and Cysticercosis, as an example of intersectorial collaboration for surveillance in Portugal. The OH Initiative (drivers and expected outcomes) and its system (boundaries, aim, dimensions, actors, and stakeholders) were described. The different aspects of this Initiative were scored with values from 0 (=no OH approach) to 1 (=perfect OH approach). The OH index was 0.31. Its OH ratio is 1.98. Overall scores were as follows: OH thinking 0.75; OH planning 0.60; OH working 0.60; OH sharing 0.35; OH learning 0.50; and systemic organization 0.50. Operational levels of the Initiative are the main strengths, indicating a comprehensive multidimensional innovative approach and transdisciplinarity. Critical issues in the supporting infrastructure were observed, related to communication, learning and organizational gaps in the project, with the evaluation being conducted as the project is being designed and implemented. The strengths and weaknesses detected may be used to refine the Initiative. This case study therefore exemplifies and supports OH assessment also for ongoing projects, at design and early implementation stages for guiding and guaranteeing an OH-oriented perspective.publishersversionpublishe

An Approximate Dynamic Programming Approach to Urban Freight Distribution with Batch Arrivals

We study an extension of the delivery dispatching problem (DDP) with time windows, applied on LTL orders arriving at an urban consolidation center. Order properties (e.g., destination, size, dispatch window) may be highly varying, and directly distributing an incoming order batch may yield high costs. Instead, the hub operator may wait to consolidate with future arrivals. A consolidation policy is required to decide which orders to ship and which orders to hold. We model the dispatching problem as a Markov decision problem. Dynamic Programming (DP) is applied to solve toy-sized instances to optimality. For larger instances, we propose an Approximate Dynamic Programming (ADP) approach. Through numerical experiments, we show that ADP closely approximates the optimal values for small instances, and outperforms two myopic benchmark policies for larger instances. We contribute to literature by (i) formulating a DDP with dispatch windows and (ii) proposing an approach to solve this DDP

Pathotypic diversity of Hyaloperonospora brassicae collected from Brassica oleracea

Downy mildew caused by Hyaloperonospora brassicae is an economically destructive disease of brassica crops in many growing regions throughout the world. Specialised pathogenicity of downy mildews from different Brassica species and closely related ornamental or wild relatives has been described from host range studies. Pathotypic variation amongst Hyaloperonospora brassicae isolates from Brassica oleracea has also been described; however, a standard set of B. oleracea lines that could enable reproducible classification of H. brassicae pathotypes was poorly developed. For this purpose, we examined the use of eight genetically refined host lines derived from our previous collaborative work on downy mildew resistance as a differential set to characterise pathotypes in the European population of H. brassicae. Interaction phenotypes for each combination of isolate and host line were assessed following drop inoculation of cotyledons and a spectrum of seven phenotypes was observed based on the level of sporulation on cotyledons and visible host responses. Two host lines were resistant or moderately resistant to the entire collection of isolates, and another was universally susceptible. Five lines showed differential responses to the H. brassicae isolates. A minimum of six pathotypes and five major effect resistance genes are proposed to explain all of the observed interaction phenotypes. The B. oleracea lines from this study can be useful for monitoring pathotype frequencies in H. brassicae populations in the same or other vegetable growing regions, and to assess the potential durability of disease control from different combinations of the predicted downy mildew resistance genes

Using technology to deliver cancer follow-up : a systematic review

Peer reviewedPublisher PD

CYP2C19 and ABCB1 gene polymorphisms are differently distributed according to ethnicity in the Brazilian general population

<p>Abstract</p> <p>Background</p> <p>Recent studies have reported the clinical importance of <it>CYP2C19 </it>and <it>ABCB1 </it>polymorphisms in an individualized approach to clopidogrel treatment. The aims of this study were to evaluate the frequencies of <it>CYP2C19 </it>and <it>ABCB1 </it>polymorphisms and to identify the clopidogrel-predicted metabolic phenotypes according to ethnic groups in a sample of individuals representative of a highly admixtured population.</p> <p>Methods</p> <p>One hundred and eighty-three Amerindians and 1,029 subjects of the general population of 4 regions of the country were included. Genotypes for the <it>ABCB1</it>c.C3435T (rs1045642), <it>CYP2C19*2 </it>(rs4244285), <it>CYP2C19*3 </it>(rs4986893), <it>CYP2C19*4 </it>(rs28399504), <it>CYP2C19*5 </it>(rs56337013), and <it>CYP2C19*17 </it>(rs12248560) polymorphisms were detected by polymerase chain reaction followed by high resolution melting analysis. The <it>CYP2C19*3</it>, <it>CYP2C19*4 </it>and <it>CYP2C19*5 </it>variants were genotyped in a subsample of subjects (300 samples randomly selected).</p> <p>Results</p> <p>The <it>CYP2C19*3 </it>and <it>CYP2C19*5 </it>variant alleles were not detected and the <it>CYP2C19*4 </it>variant allele presented a frequency of 0.3%. The allelic frequencies for the <it>ABCB1</it>c.C3435T, <it>CYP2C19*2 </it>and <it>CYP2C19*17 </it>polymorphisms were differently distributed according to ethnicity: Amerindian (51.4%, 10.4%, 15.8%); Caucasian descent (43.2%, 16.9%, 18.0%); Mulatto (35.9%, 16.5%, 21.3%); and African descent (32.8%, 20.2%, 26.3%) individuals, respectively. As a result, self-referred ethnicity was able to predict significantly different clopidogrel-predicted metabolic phenotypes prevalence even for a highly admixtured population.</p> <p>Conclusion</p> <p>Our findings indicate the existence of inter-ethnic differences in the <it>ABCB1 </it>and <it>CYP2C19 </it>variant allele frequencies in the Brazilian general population plus Amerindians. This information could help in stratifying individuals from this population regarding clopidogrel-predicted metabolic phenotypes and design more cost-effective programs towards individualization of clopidogrel therapy.</p

NIS expression in thyroid tumors, relation with prognosis clinicopathological and molecular features

Thyroid cancer therapy is based on surgery followed by radioiodine treatment. The incorporation of radioiodine by cancer cells is mediated by sodium iodide symporter (NIS) (codified by the SLC5A5 gene), that is functional only when targeted to the cell membrane. We aimed to evaluate if NIS expression in thyroid primary tumors would be helpful in predicting tumor behavior, response to therapy and prognosis. NIS expression was addressed by qPCR and immunohistochemistry. In order to validate our data, we also studied SLC5A5 expression on 378 primary papillary thyroid carcinomas from The Cancer Genome Atlas (TCGA) database. In our series, SLC5A5 expression was lower in carcinomas with vascular invasion and with extrathyroidal extension and in those harboring BRAFV600E mutation. Analysis of SLC5A5 expression from TCGA database confirmed our results. Furthermore, it showed that larger tumors, with locoregional recurrences and/or distant metastases or harboring RAS, BRAF and/or TERT promoter (TERTp) mutations presented significantly less SLC5A5 expression. Regarding immunohistochemistry, 12/211 of the cases demonstrated NIS in the membrane of tumor cells, those cases showed variable outcomes concerning therapy success, prognosis and all but one were wild type for BRAF, NRAS and TERTp mutations. SLC5A5 mRNA lower expression is associated with features of aggressiveness and with key genetic alterations involving BRAF, RAS and TERTp. Mutations in these genes seem to decrease protein expression and its targeting to the cell membrane. SLC5A5 mRNA expression is more informative than NIS immunohistochemical expression regarding tumor aggressiveness and prognostic features.This study was supported by FCT (‘Portuguese Foundation for Science and Technology’) through PhD grants to Catarina Tavares (SFRH/BD/87887/2012), Ana Pestana (SFRH/BD/110617/2015), Rui Batista (SFRH/BD/111321/2015) and by a CNPq PhD grant (‘National Counsel of Technological and Scientific Development’, Brazil), Science without Borders, Process n# 237322/2012-9 for Luciana Ferreira. Miguel Melo received a grant from Genzyme for the research project ‘Molecular biomarkers of prognosis and response to therapy in differentiated thyroid carcinomas’. Further funding was obtained from FEDER – Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 – Operational Program for Competitiveness and Internationalization (POCI), Portugal 2020, and by Portuguese funds through FCT – Fundação para a Ciência e a Tecnologia/ Ministério da Ciência, Tecnologia e Inovação in the framework of the project ‘Institute for Research and Innovation in Health Sciences’ (POCI-01-0145-FEDER-007274) and by the project ‘Advancing cancer research: from basic knowledgement to application’; NORTE-01-0145-FEDER-000029; ‘Projetos Estruturados de I&D&I’, funded by Norte 2020-Programa Operacional Regional do Norte. This work was also financed by Sociedade Portuguesa de Endocrinologia Diabetes e Metabolismo through a grant ‘Prof. E Limbert Sociedade Portuguesa de Endocrinologia Diabetes e Metabolismo/Sanofi-Genzyme in thyroid pathology’

Rietveld-based quantitative phase analysis of sugars in confectionery

Sugars are a near-ubiquitous ingredient in food products, yet rising rates of obesity and related illnesses have prompted a drive to reduce their content. The use of amorphous sugars in confectionery may be one way of achieving this by providing a similarly sweet sensation due to increased dissolution rate. However, accurate amorphous and crystalline form characterisation and quantification of complex foodstuffs can be difficult. In this study, a method for the quantification of crystalline and amorphous sugars in chocolate precursors, using powder X ray powder diffraction, is presented. The method was first validated by the use of known compositions of mixtures of amorphous and crystalline sugars, then employed in assessing two chocolate crumb samples. The results show that the method can reliably determine the absolute quantity of amorphous and crystalline components in a confectionery sample, whilst maintaining sample integrity, apart from the addition of an inert internal standard. As such, it is a valuable addition to other techniques currently used

Direct comparison of methionine restriction with leucine restriction on the metabolic health of C57BL/6J mice

EKL was the recipient of a BBSRC postgraduate studentship. This work was funded by Tenovus Scotland project grant to MD and NM (G13/07) and BBSRC DTG. MD is also supported by the British Heart Foundation (PG/09/048/27675, PG/11/8/28703 and PG/14/43/30889) and Diabetes UK (14/0004853). NM is funded by British Heart Foundation (PG/16/90/32518).Peer reviewedPublisher PD

Streaming histogram sketching for rapid microbiome analytics

Background: The growth in publically available microbiome data in recent years has yielded an invaluable resource for genomic research, allowing for the design of new studies, augmentation of novel datasets and reanalysis of published works. This vast amount of microbiome data, as well as the widespread proliferation of microbiome research and the looming era of clinical metagenomics, means there is an urgent need to develop analytics that can process huge amounts of data in a short amount of time. To address this need, we propose a new method for the compact representation of microbiome sequencing data using similarity-preserving sketches of streaming k-mer spectra. These sketches allow for dissimilarity estimation, rapid microbiome catalogue searching and classification of microbiome samples in near real time. Results: We apply streaming histogram sketching to microbiome samples as a form of dimensionality reduction, creating a compressed ‘histosketch’ that can efficiently represent microbiome k-mer spectra. Using public microbiome datasets, we show that histosketches can be clustered by sample type using the pairwise Jaccard similarity estimation, consequently allowing for rapid microbiome similarity searches via a locality sensitive hashing indexing scheme. Furthermore, we use a ‘real life’ example to show that histosketches can train machine learning classifiers to accurately label microbiome samples. Specifically, using a collection of 108 novel microbiome samples from a cohort of premature neonates, we trained and tested a random forest classifier that could accurately predict whether the neonate had received antibiotic treatment (97% accuracy, 96% precision) and could subsequently be used to classify microbiome data streams in less than 3 s. Conclusions: Our method offers a new approach to rapidly process microbiome data streams, allowing samples to be rapidly clustered, indexed and classified. We also provide our implementation, Histosketching Using Little K-mers (HULK), which can histosketch a typical 2 GB microbiome in 50 s on a standard laptop using four cores, with the sketch occupying 3000 bytes of disk space