Whole genome sequence analysis of antimicrobial resistance genes, multilocus sequence types and plasmid sequences in ESBL/AmpC Escherichia coli isolated from broiler caecum and meat

Plasmid-encoded extended-spectrum β-lactamase and AmpC gene-carrying Escherichia coli (ESBL/AmpC E. coli) is an increasing cause of human infections worldwide. Increasing carbapenem and colistin resistance further complicate treatment of these infections. The aim of this study was to assess the occurrence of ESBL/AmpC E. coli in different broiler flocks and farms, as well as in broiler meat, in a country with no antimicrobial usage in broiler production. An additional goal was to assess the genetic characteristics of ESBL/AmpC E. coli isolates by using whole genome sequencing (WGS). Altogether 520 caecal swabs and 85 vacuum-packed broiler meat samples were investigated at the slaughterhouse level. WGS of the bacterial isolates revealed acquired antimicrobial resistance (AMR) genes, multilocus sequence types (MLST) and plasmid sequences. ESBL/AmpC E. coli was identified in 92 (18%) of the caecum and 27 (32%) of the meat samples. ESBL/AmpC E. coli-carrying birds derived from six (33%) out of 18 farms. Of the two blaESBL/AmpC genes detected by PCR, blaCMY-2 (96%) was predominant over blaCTX-M-1 (4%). Furthermore, WGS revealed an additional AMR gene sul2. Carbapenemase, colistin, and other AMR genes were not detected from the isolates of either the caecal or meat samples. Altogether seven MLSTs (ST101, ST117, ST212, ST351, ST373, ST1594 and an unknown ST) and a variety of different plasmid sequences (IncB/O/K/Z, IncI1, IncFII, IncII, IncFIB, IncFIC, IncX1 and an additional set of Col-plasmids) were detected. This is the first study on genomic epidemiology of ESBL/AmpC E. coli on broiler farms and flocks with no antimicrobial usage, by using WGS analysis. Results show that ESBL/AmpC E. coli occurrence is common both in the caecum and in the packaged meat. However, compared to other European countries, the occurrence is low and the presence of AMR genes other than blaCMY-2 and blaCTX-M-1 is rare. More studies are needed to understand the ESBL/AmpC E. coli occurrence in broiler production to prevent the meat from contamination during slaughter and processing, thereby also preventing zoonotic transmission of ESBL/AmpC E. coli. Additionally, more studies are needed to understand the ecology and fitness cost of Enterobacteriaceae plasmids in animal production in order to prevent their acquisition of plasmid-encoded antimicrobial resistance genes such as carbapenem and colistin resistance genes, as this would pose a great hazard to food safety.Peer reviewe

Inverse problems with partial data for a magnetic Schr\"odinger operator in an infinite slab and on a bounded domain

In this paper we study inverse boundary value problems with partial data for the magnetic Schr\"odinger operator. In the case of an infinite slab in $R^n$, $n\ge 3$, we establish that the magnetic field and the electric potential can be determined uniquely, when the Dirichlet and Neumann data are given either on the different boundary hyperplanes of the slab or on the same hyperplane. This is a generalization of the results of [41], obtained for the Schr\"odinger operator without magnetic potentials. In the case of a bounded domain in $R^n$, $n\ge 3$, extending the results of [2], we show the unique determination of the magnetic field and electric potential from the Dirichlet and Neumann data, given on two arbitrary open subsets of the boundary, provided that the magnetic and electric potentials are known in a neighborhood of the boundary. Generalizing the results of [31], we also obtain uniqueness results for the magnetic Schr\"odinger operator, when the Dirichlet and Neumann data are known on the same part of the boundary, assuming that the inaccessible part of the boundary is a part of a hyperplane

Key components of learning ecologies: a Delphi assessment

This is the accepted version of the following article: González‐Sanmamed, M. , Muñoz‐Carril, P. and Santos‐Caamaño, F. (2019), Key components of learning ecologies: A Delphi assessment. Br J Educ Technol, 50: 1639-1655, which has been published in final form at https://doi.org/10.1111/bjet.12805. This article may be used for non-commercial purposes in accordance with the Wiley Self-Archiving Policy (http://www.wileyauthors.com/self-archiving)The educational landscape has changed in recent years, requiring reflection about new pedagogical methods and theories. There are three important perspectives as drivers of pedagogical reflection: lifelong and life‐wide learning, the idea of learning as a social construct in which internal elements and changing external factors converge, and the recognition of technology as a resource that can promote ubiquitous and expanded learning. Learning ecology has been proposed as a conceptual and empirical framework, but its still emergent nature along with its multidimensionality and complexity require further exploration. The Delphi study we present as part of a broader research project aims to identify the components of learning ecologies. Three panel rounds with international experts were carried out, after which two important dimensions emerged in the structure of learning ecologies. The first is related to intrinsic “learning dispositions,” which is made up of three categories: the subject's ideas about learning, their motivations and expectations. The second dimension, called “learning processes,” comprises four components: relationships, resources, actions and context. The identification of the components of learning ecologies and their influence on formal, non‐formal and informal training processes will provide guidance for educational policies and help to better organize training programmesWe thank the Spanish Ministry of Economy and Competitiveness for their support of our study under a research project entitled “How the best University Teachers Learn: Impact on Learning Ecologies on Quality of Teaching” (ECO4LEARN‐HE) (Reference: EDU2015‐67907‐R)S

Cargo Cults in Information Systems Development: a Definition and an Analytical Framework

Organizations today adopt agile information systems development methods (ISDM), but many do not succeed with the adoption process and in achieving desired results. Systems developers sometimes fail in efficient use of ISDM, often due to a lack of understanding the fundamental intentions of the chosen method. In many cases organizations simply imitate the behavior of others without really understanding why. This conceptual paper defines this phenomenon as an ISDM cargo cult behavior and proposes an analytical framework to identify such situations. The concept of cargo cults originally comes from the field of social anthropology and has been used to explain irrational, ritualistic imitation of certain behavior. By defining and introducing the concept in the field of information systems development we provide a diagnostic tool to better understand one of the reasons why ISDM adoption sometimes fail

Cognitive decline in Huntington's disease expansion gene carriers

BACKGROUND: In Huntington's Disease (HD) cognitive decline can occur before unequivocal motor signs become apparent. As cognitive decline often starts early in the course of the disease and has a progressive nature over time, cognition can be regarded as a key target for symptomatic treatment. The specific progressive profile of cognitive decline over time is unknown. OBJECTIVE: The aim of this study is to quantify the progression of cognitive decline across all HD stages, from pre-motormanifest to advanced HD, and to investigate if CAG length mediates cognitive decline. METHODS: In the European REGISTRY study 2669 HD expansion gene carriers underwent annual cognitive assessment. General linear mixed models were used to model the cognitive decline for each cognitive task across all disease stages. Additionally, a model was developed to evaluate the cognitive decline based on CAG length and age rather than disease stage. RESULTS: There was significant cognitive decline on all administered tasks throughout pre-motormanifest (close to estimated disease onset) participants and the subsequent motormanifest participants from stage 1 to stage 4. Performance on the Stroop Word and Stroop Color tests additionally declined significantly across the two pre-motormanifest groups: far and close to estimated disease onset. The evaluation of cognition performance in relation to CAG length and age revealed a more rapid cognitive decline in participants with longer CAG length than participants with shorter CAG length over time. CONCLUSION: Cognitive performance already shows decline in pre-motormanifest HD gene expansion carriers and gradually worsens to late stage HD. HD gene expansion carriers with certain CAG length have their own cognitive profile, i.e., longer CAG length is associated with more rapid decline

The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients

The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the “REGISTRY” cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a modifying effect of ATG7 in these REGISTRY patients and in patients of our previous HD cohort according to their ethnic origin, we identified a significant effect of the ATG7 V471A polymorphism on the HD age at onset only in the Italian population (327 patients). In these Italian patients, the polymorphism is associated with a 6-years earlier disease onset and thus seems to have an aggravating effect. We could specify the role of ATG7 as a genetic modifier for HD particularly in the Italian population. This result affirms the modifying influence of the autophagic pathway on the course of HD, but also suggests population-specific modifying mechanisms in HD pathogenesis

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation