Pan-genome analysis of the emerging foodborne pathogen Cronobacter spp. suggests a species-level bidirectional divergence driven by niche adaptation

Background: Members of the genus Cronobacter are causes of rare but severe illness in neonates and preterm infants following the ingestion of contaminated infant formula. Seven species have been described and two of the species genomes were subsequently published. In this study, we performed comparative genomics on eight strains of Cronobacter, including six that we sequenced (representing six of the seven species) and two previously published, closed genomes.

Results: We identified and characterized the features associated with the core and pan genome of the genus Cronobacter in an attempt to understand the evolution of these bacteria and the genetic content of each species. We identified 84 genomic regions that are present in two or more Cronobacter genomes, along with 45 unique genomic regions. Many potentially horizontally transferred genes, such as lysogenic prophages, were also identified. Most notable among these were several type six secretion system gene clusters, transposons that carried tellurium, copper and/or silver resistance genes, and a novel integrative conjugative element.

Conclusions: Cronobacter have diverged into two clusters, one consisting of C. dublinensis and C. muytjensii (Cdub-Cmuy) and the other comprised of C. sakazakii, C. malonaticus, C. universalis, and C. turicensis, (Csak-Cmal-Cuni-Ctur) from the most recent common ancestral species. While several genetic determinants for plant-association and human virulence could be found in the core genome of Cronobacter, the four Cdub-Cmuy clade genomes contained several accessory genomic regions important for survival in a plant-associated environmental niche, while the Csak-Cmal-Cuni-Ctur clade genomes harbored numerous virulence-related genetic traits.

External validation of the OHTS-EGPS model for predicting the 5-year risk of open-angle glaucoma in ocular hypertensives

To independently evaluate and compare the performance of the Ocular Hypertension Treatment Study-European Glaucoma Prevention Study (OHTS-EGPS) prediction equation for estimating the 5-year risk of open-angle glaucoma (OAG) in four cohorts of adults with ocular hypertension.

Whole-mitochondrial genome sequencing in primary open-angle glaucoma using massively parallel sequencing identifies novel and known pathogenic variants

Purpose:The aim of this study was to determine whether mutations in mitochondrial DNA play a role in high-pressure primary open-angle glaucoma (OMIM 137760) by analyzing new data from massively parallel sequencing of mitochondrial DNA.
Methods:Glaucoma patients with high-tension primary open-angle glaucoma and ethnically matched and age-matched control subjects without glaucoma were recruited. The entire human mitochondrial genome was amplified in two overlapping fragments by long-range polymerase chain reaction and used as a template for massively parallel sequencing on an Ion Torrent Personal Genome Machine. All variants were confirmed by conventional Sanger sequencing.
Results:Whole-mitochondrial genome sequencing was performed in 32 patients with primary open-angle glaucoma from India (n = 16) and Ireland (n = 16). In 16 of the 32 patients with primary open-angle glaucoma (50% of cases), there were 22 mitochondrial DNA mutations consisting of 7 novel mutations and 8 previously reported disease-associated sequence variants. Eight of 22 (36.4%) of the mitochondrial DNA mutations were in complex I mitochondrial genes.
Conclusion:Massively parallel sequencing using the Ion Torrent Personal Genome Machine with confirmation by Sanger sequencing detected a pathogenic mitochondrial DNA mutation in 50% of the primary open-angle glaucoma cohort. Our findings support the emerging concept that mitochondrial dysfunction results in the development of glaucoma and, more specifically, that complex I defects play a significant role in primary open-angle glaucoma pathogenesis.

Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial

Background
Treatments for open-angle glaucoma aim to prevent vision loss through lowering of intraocular pressure, but to our knowledge no placebo-controlled trials have assessed visual function preservation, and the observation periods of previous (unmasked) trials have typically been at least 5 years. We assessed vision preservation in patients given latanoprost compared with those given placebo.

Methods
In this randomised, triple-masked, placebo-controlled trial, we enrolled patients with newly diagnosed open-angle glaucoma at ten UK centres (tertiary referral centres, teaching hospitals, and district general hospitals). Eligible patients were randomly allocated (1:1) with a website-generated randomisation schedule, stratified by centre and with a permuted block design, to receive either latanoprost 0·005% (intervention group) or placebo (control group) eye drops. Drops were administered from identical bottles, once a day, to both eyes. The primary outcome was time to visual field deterioration within 24 months. Analyses were done in all individuals with follow-up data. The Data and Safety Monitoring Committee (DSMC) recommended stopping the trial on Jan 6, 2011 (last patient visit July, 2011), after an interim analysis, and suggested a change in primary outcome from the difference in proportions of patients with incident progression between groups to time to visual field deterioration within 24 months. This trial is registered, number ISRCTN96423140.

Findings
We enrolled 516 individuals between Dec 1, 2006, and March 16, 2010. Baseline mean intraocular pressure was 19·6 mm Hg (SD 4·6) in 258 patients in the latanoprost group and 20·1 mm Hg (4·8) in 258 controls. At 24 months, mean reduction in intraocular pressure was 3·8 mm Hg (4·0) in 231 patients assessed in the latanoprost group and 0·9 mm Hg (3·8) in 230 patients assessed in the placebo group. Visual field preservation was significantly longer in the latanoprost group than in the placebo group: adjusted hazard ratio (HR) 0·44 (95% CI 0·28–0·69; p=0·0003). We noted 18 serious adverse events, none attributable to the study drug.

Interpretation
This is the first randomised placebo-controlled trial to show preservation of the visual field with an intraocular-pressure-lowering drug in patients with open-angle glaucoma. The study design enabled significant differences in vision to be assessed in a relatively short observation period

Effects of resistive magnetic field on fast electron divergence measured in experiments

Transport of fast electrons driven by an ultraintense laser through a tracer layer buried in solid targets is studied by particle-in-cell simulations. It is found that intense resistive magnetic fields, having a magnitude of several thousand Tesla, are generated at the interfaces of the materials due to the steep resistivity gradient between the target and tracer layer. Such magnetic fields can significantly inhibit the fast electron propagation. The electrons that can penetrate the first interface are mostly confined in the buried layer by the magnetic fields and cause heating of the tracer layer. The lateral extent of the heated region can be significantly larger than that of the relativistic electron beam. This finding suggests that the relativistic electron divergence inferred from Ká x-ray emission in experiments might be overestimated.

A compact broadband ion beam focusing device based on laser-driven megagauss thermoelectric magnetic fields

Ultra-intense lasers can nowadays routinely accelerate kiloampere ion beams. These unique sources of particle beams could impact many societal (e.g., proton-therapy or fuel recycling) and fundamental (e.g., neutron probing) domains. However, this requires overcoming the beam angular divergence at the source. This has been attempted, either with large-scale conventional setups or with compact plasma techniques that however have the restriction of short (<1 mm) focusing distances or a chromatic behavior. Here, we show that exploiting laser-triggered, long-lasting (>50 ps), thermoelectric multi-megagauss surface magnetic (B)-fields, compact capturing, and focusing of a diverging laser-driven multi-MeV ion beam can be achieved over a wide range of ion energies in the limit of a 5° acceptance angle.

Where the Lake Meets the Sea: Strong Reproductive Isolation Is Associated with Adaptive Divergence between Lake Resident and Anadromous Three-Spined Sticklebacks

Contact zones between divergent forms of the same species are often characterised by high levels of phenotypic diversity over small geographic distances. What processes are involved in generating such high phenotypic diversity? One possibility is that introgression and recombination between divergent forms in contact zones results in greater phenotypic and genetic polymorphism. Alternatively, strong reproductive isolation between forms may maintain distinct phenotypes, preventing homogenisation by gene flow. Contact zones between divergent freshwater-resident and anadromous stickleback (Gasterosteus aculeatus L.) forms are numerous and common throughout the species distribution, offering an opportunity to examine these contrasting hypotheses in greater detail. This study reports on an interesting new contact zone located in a tidally influenced lake catchment in western Ireland, characterised by high polymorphism for lateral plate phenotypes. Using neutral and QTL-linked microsatellite markers, we tested whether the high diversity observed in this contact zone arose as a result of introgression or reproductive isolation between divergent forms: we found strong support for the latter hypothesis. Three phenotypic and genetic clusters were identified, consistent with two divergent resident forms and a distinct anadromous completely plated population that migrates in and out of the system. Given the strong neutral differentiation detected between all three morphotypes (mean FST = 0.12), we hypothesised that divergent selection between forms maintains reproductive isolation. We found a correlation between neutral genetic and adaptive genetic differentiation that support this. While strong associations between QTL linked markers and phenotypes were also observed in this wild population, our results support the suggestion that such associations may be more complex in some Atlantic populations compared to those in the Pacific. These findings provide an important foundation for future work investigating the dynamics of gene flow and adaptive divergence in this newly discovered stickleback contact zone.

Forward and backward least angle regression for nonlinear system identification

A forward and backward least angle regression (LAR) algorithm is proposed to construct the nonlinear autoregressive model with exogenous inputs (NARX) that is widely used to describe a large class of nonlinear dynamic systems. The main objective of this paper is to improve model sparsity and generalization performance of the original forward LAR algorithm. This is achieved by introducing a replacement scheme using an additional backward LAR stage. The backward stage replaces insignificant model terms selected by forward LAR with more significant ones, leading to an improved model in terms of the model compactness and performance. A numerical example to construct four types of NARX models, namely polynomials, radial basis function (RBF) networks, neuro fuzzy and wavelet networks, is presented to illustrate the effectiveness of the proposed technique in comparison with some popular methods.

Exploring divergence between respondent and researcher definitions of the good in contingent valuation studies

In Contingent Valuation studies, researchers often base their definition of the environmental good on scientific/expert consensus. However, respondents may not hold this same commodity definition prior to the transaction. This raises questions as to the potential for staging a satisfactory transaction, based on Fischoff and Furby's (1988) criteria. Some unresolved issues regarding the provision of information to respondents to facilitate such a transaction are highlighted. In this paper, we apply content analysis to focus group discussions and develop a set of rules which take account of the non-independence of group data to explore whether researcher and respondents' prior definitions are in any way similar. We use the results to guide information provision in a subsequent questionnaire.

Scene From a Different Angle: Attempts to Internationalize Northern Ireland’s Conflict Experience

Reviews the books, Lessons From the Northern Ireland Peace Process edited by Timothy J. White (2013) and Human Rights as War by Other Means by Jennifer Curtis (2014). Edited by a U.S.-based academic with an enduring interest in Ireland, the first book draws together an interdisciplinary group of academics from across North America and the U.K. (though notably not Northern Ireland itself) to cover such topics as third party intervention, nationalism, grassroots change, and community development. The second text to be reviewed may be seen as a thorough analysis of this particular point: what is the role played by human rights in Northern Ireland’s peace process?

A genomic island linked to ecotype divergence in Atlantic cod

The genomic architecture underlying ecological divergence and ecological speciation with gene flow is still largely unknown for most organisms. One central question is whether divergence is genome-wide or localized in 'genomic mosaics' during early stages when gene flow is still pronounced. Empirical work has so far been limited, and the relative impacts of gene flow and natural selection on genomic patterns have not been fully explored. Here, we use ecotypes of Atlantic cod to investigate genomic patterns of diversity and population differentiation in a natural system characterized by high gene flow and large effective population sizes, properties which theoretically could restrict divergence in local genomic regions. We identify a genomic region of strong population differentiation, extending over approximately 20 cM, between pairs of migratory and stationary ecotypes examined at two different localities. Furthermore, the region is characterized by markedly reduced levels of genetic diversity in migratory ecotype samples. The results highlight the genomic region, or 'genomic island', as potentially associated with ecological divergence and suggest the involvement of a selective sweep. Finally, we also confirm earlier findings of localized genomic differentiation in three other linkage groups associated with divergence among eastern Atlantic populations. Thus, although the underlying mechanisms are still unknown, the results suggest that 'genomic mosaics' of differentiation may even be found under high levels of gene flow and that marine fishes may provide insightful model systems for studying and identifying initial targets of selection during ecological divergence.

Wide-Area Phase-Angle Measurements for Islanding Detection—An Adaptive Nonlinear Approach

The integration of an ever growing proportion of large scale distributed renewable generation has increased the probability of maloperation of the traditional RoCoF and vector shift relays. With reduced inertia due to non-synchronous penetration in a power grid, system wide disturbances have forced the utility industry to design advanced protection schemes to prevent system degradation and avoid cascading outages leading to widespread blackouts. This paper explores a novel adaptive nonlinear approach applied to islanding detection, based on wide area phase angle measurements. This is challenging, since the voltage phase angles from different locations exhibit not only strong nonlinear but also time-varying characteristics. The adaptive nonlinear technique, called moving window kernel principal component analysis is proposed to model the time-varying and nonlinear trends in the voltage phase angle data. The effectiveness of the technique is exemplified using both DigSilent simulated cases and real test cases recorded from the Great Britain and Ireland power systems by the OpenPMU project.

Peripheral Iridotomy for Angle-Closure Glaucoma

This chapter covers the indications, contraindications, techniques, outcomes, and complications of LPI. Its role is well defined in most of the areas, but no conclusion can be drawn at present regarding prophylactic use for glaucoma suspects. More studies are needed to define its safety and efficacy. Overall, LPI is a relatively safe procedure and the majority of complications can be avoided if it is performed properly.