Genomic variations define divergence of water/wildlife-associated Campylobacter jejuni niche specialists from common clonal complexes

Although the major food-borne pathogen Campylobacter jejuni has been isolated from diverse animal, human and environmental sources, our knowledge of genomic diversity in C. jejuni is based exclusively on human or human food-chain-associated isolates. Studies employing multilocus sequence typing have indicated that some clonal complexes are more commonly associated with particular sources. Using comparative genomic hybridization on a collection of 80 isolates representing diverse sources and clonal complexes, we identified a separate clade comprising a group of water/wildlife isolates of C. jejuni with multilocus sequence types uncharacteristic of human food-chain-associated isolates. By genome sequencing one representative of this diverse group (C. jejuni 1336), and a representative of the bank-vole niche specialist ST-3704 (C. jejuni 414), we identified deletions of genomic regions normally carried by human food-chain-associated C. jejuni. Several of the deleted regions included genes implicated in chicken colonization or in virulence. Novel genomic insertions contributing to the accessory genomes of strains 1336 and 414 were identified. Comparative analysis using PCR assays indicated that novel regions were common but not ubiquitous among the water/wildlife group of isolates, indicating further genomic diversity among this group, whereas all ST-3704 isolates carried the same novel accessory regions. While strain 1336 was able to colonize chicks, strain 414 was not, suggesting that regions specifically absent from the genome of strain 414 may play an important role in this common route of Campylobacter infection of humans. We suggest that the genomic divergence observed constitutes evidence of adaptation leading to niche specialization

Community exposure and vulnerability to water quality and availability: a case study in the mining-affected Pazña Municipality, Lake Poopó Basin, Bolivian Altiplano

This is the final version of the article. Available from Springer Verlag via the DOI in this record.Assessing water sources for drinking and irrigation along with community vulnerability, especially in developing and rural regions, is important for reducing risk posed by poor water quality and limited water availability and accessibility. We present a case study of rural mining-agricultural communities in the Lake Poopó Basin, one of the poorest regions on the Bolivian Altiplano. Here, relatively low rainfall, high evaporation, salinization and unregulated mining activity have contributed to environmental degradation and water issues, which is a situation facing many Altiplano communities. Social data from 72 households and chemical water quality data from 27 surface water and groundwater sites obtained between August 2013 and July 2014 were used to develop locally relevant vulnerability assessment methodologies and ratings with respect to water availability and quality, and Chemical Water Quality Hazard Ratings to assess water quality status. Levels of natural and mining-related contamination in many waters (CWQHR ≥ 6; 78% of assessed sites) mean that effective remediation would be challenging and require substantial investment. Although waters of fair to good chemical quality (CWQHR ≤ 5; 22% of assessed sites) do exist, treatment may still be required depending on use, and access issues remain problematic. There is a need to comply with water quality legislation, improve and maintain basic water supply and storage infrastructure, build and operate water and wastewater treatment plants, and adequately and safely contain and treat mine waste. This study serves as a framework that could be used elsewhere for assessing and mitigating water contamination and availability affecting vulnerable populations.This project was funded by the University College London (UCL) Institute for Risk and Disaster Reduction and the Catholic Agency for Overseas Development (CAFOD) under the initiative of water risk and its management in Bolivia’s Altiplano development strategy, which was led by Stephen Edwards. The Natural Environment Research Council Probability, Uncertainty and Risk in the Environment grant PA13-010 (risk visualisation and quantification for enhanced disaster risk reduction) to Stephen Edwards informed the approach to and outputs from the project

Group work and the change of obstacles over time: The influence of learning style and group composition

It is through working in groups that students develop cooperative learning skills and experience. However, group work activity often leads students into a difficult experience, especially for first-year students who are not familiar with group work activities at university. This study explores obstacles faced by first-year students during their group work activities. It investigates whether a group of students with a similar learning style (homogeneous group) experience different obstacles compared to a group of students with a diverse learning style (heterogeneous group). In addition, to identify the difference, if any, between a group formed by a tutor and one where the students form the group themselves, tutor and self-allocated group allocations are explored. This study focuses on obstacles experienced by these students during group work activities. Using a sample of more than 200 students over a period of 3 years, the types and the changes of obstacles in different stages of group life are explored. The findings show that students experience obstacles which can be classified into personal and social, leadership and management, and task-related obstacles. Those obstacles were not static but increased over time. The study also investigates the impact of different methods of forming groups and whether this impacted on obstacles experienced. Overall, different interventions prompted different patterns of obstacle development

IMI Risk Factors for Myopia

Risk factor analysis provides an important basis for developing interventions for any condition. In the case of myopia, evidence for a large number of risk factors has been presented, but they have not been systematically tested for confounding. To be useful for designing preventive interventions, risk factor analysis ideally needs to be carried through to demonstration of a causal connection, with a defined mechanism. Statistical analysis is often complicated by covariation of variables, and demonstration of a causal relationship between a factor and myopia using Mendelian randomization or in a randomized clinical trial should be aimed for. When strict analysis of this kind is applied, associations between various measures of educational pressure and myopia are consistently observed. However, associations between more nearwork and more myopia are generally weak and inconsistent, but have been supported by meta-analysis. Associations between time outdoors and less myopia are stronger and more consistently observed, including by meta-analysis. Measurement of nearwork and time outdoors has traditionally been performed with questionnaires, but is increasingly being pursued with wearable objective devices. A causal link between increased years of education and more myopia has been confirmed by Mendelian randomization, whereas the protective effect of increased time outdoors from the development of myopia has been confirmed in randomized clinical trials. Other proposed risk factors need to be tested to see if they modulate these variables. The evidence linking increased screen time to myopia is weak and inconsistent, although limitations on screen time are increasingly under consideration as interventions to control the epidemic of myopia

Mechanistic model of natural killer cell proliferative response to IL-15 receptor stimulation

Natural killer (NK) cells are innate lymphocytes that provide early host defense against intracellular pathogens, such as viruses. Although NK cell development, homeostasis, and proliferation are regulated by IL-15, the influence of IL-15 receptor (IL-15R)-mediated signaling at the cellular level has not been quantitatively characterized. We developed a mathematical model to analyze the kinetic interactions that control the formation and localization of IL-15/IL-15R complexes. Our computational results demonstrated that IL-15/IL-15R complexes on the cell surface were a key determinant of the magnitude of the IL-15 proliferative signal and that IL-15R occupancy functioned as an effective surrogate measure of receptor signaling. Ligand binding and receptor internalization modulated IL-15R occupancy. Our work supports the hypothesis that the total number and duration of IL-15/IL-15R complexes on the cell surface crosses a quantitative threshold prior to the initiation of NK cell division. Furthermore, our model predicted that the upregulation of IL-15Rα on NK cells substantially increased IL-15R complex formation and accelerated the expansion of dividing NK cells with the greatest impact at low IL-15 concentrations. Model predictions of the threshold requirement for NK cell recruitment to the cell cycle and the subsequent exponential proliferation correlated well with experimental data. In summary, our modeling analysis provides quantitative insight into the regulation of NK cell proliferation at the receptor level and provides a framework for the development of IL-15 based immunotherapies to modulate NK cell proliferation

Root phenotyping pipeline for cereal plants

The proposed system for the phenotypic analysis of root traits that is presented here enables the precise description of the root growth kinetics of cereal plants. The designed pipeline is composed of a drip irrigation system to supplement plants with a medium, a high-resolution root system scanning facility and a method for comprehensive image analysis. The system enables low-effort, accurate and highly repeatable analysis of features of the root system of cereal seedlings and young plants until the early tillering stage. This system employs an automatic drip irrigation line, which is controlled remotely by a programmable logic controller (PLC). The PLC adapter used facilitates the automated control of all system modules, thus allowing the rate of the medium flow to be adjusted for the supplementation of plants. The system employs measuring sensors for the continuous monitoring of the parameters of the culture medium. This continuous sensing of medium parameters can be applicable for mineral nutrition studies and abiotic stress response testing. The installed drip lines are injected into transparent acrylic tubes (500 mm high, 32/30 mm in outer and inner diameter, with a circular opening in the bottom of 3 mm in diameter) that are filled with glass beads. The acrylic tubes are placed in opaque cover tubes that permit the non-destructive observation of the growth of the root system. Enhanced imaging quality contributes to an increase in the precision of the results that are obtained in the course of the analysis of root parameters using specialised root scanners coupled with the WinRHIZO system. This novel phenotyping pipeline permits noninvasive observation of root system growth adjusted for the subsequent root image acquisition with a reduced background noise. The method combines automated control of plant growth conditions with good imaging quality and high replicability of growth parameters

Upper- and mid-mantle interaction between the Samoan plume and the Tonga-Kermadec slabs

Mantle plumes are thought to play a key role in transferring heat from the core\u2013mantle boundary to the lithosphere, where it can significantly influence plate tectonics. On impinging on the lithosphere at spreading ridges or in intra-plate settings, mantle plumes may generate hotspots, large igneous provinces and hence considerable dynamic topography. However, the active role of mantle plumes on subducting slabs remains poorly understood. Here we show that the stagnation at 660 km and fastest trench retreat of the Tonga slab in Southwestern Pacific are consistent with an interaction with the Samoan plume and the Hikurangi plateau. Our findings are based on comparisons between 3D anisotropic tomography images and 3D petrological-thermo-mechanical models, which self-consistently explain several unique features of the Fiji\u2013Tonga region. We identify four possible slip systems of bridgmanite in the lower mantle that reconcile the observed seismic anisotropy beneath the Tonga slab (VSH4VSV) with thermo-mechanical calculations

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. CONCLUSIONS: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality

HIV research in Australia: linking basic research findings with clinical and public health outcomes

Despite a population of only 20 million and sustained low prevalence of HIV infection in Australia, Australian researchers have provided many substantial original findings to the fields of HIV pathogenesis, treatment and prevention. More recently, Australian clinicians and scientists have turned their attention to assisting other countries in developing effective responses, particularly within the Asia-Pacific region. It is therefore fitting that the 4th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention will be held in Sydney in July 2007. The meeting is expected to attract over 5000 participants and will have a dynamic and innovative programme within the three major themes of HIV basic science, clinical research and biomedical prevention