A cascaded laser acceleration scheme for the generation of spectrally controlled proton beams

We present a novel, cascaded acceleration scheme for the generation of spectrally controlled ion beams using a laser-based accelerator in a 'double-stage' setup. An MeV proton beam produced during a relativistic laser–plasma interaction on a thin foil target is spectrally shaped by a secondary laser–plasma interaction on a separate foil, reliably creating well-separated quasi-monoenergetic features in the energy spectrum. The observed modulations are fully explained by a one-dimensional (1D) model supported by numerical simulations. These findings demonstrate that laser acceleration can, in principle, be applied in an additive manner.Deutsche Forschungsgemeinschaft (DFG contract no. TR18)Deutsche Forschungsgemeinschaft (contract no. 03ZIK052)European Union (Laserlab Europe

A system theory based digital model for predicting the cumulative fluid balance course in intensive care patients

Background: Surgical interventions can cause severe fluid imbalances in patients undergoing cardiac surgery, affecting length of hospital stay and survival. Therefore, appropriate management of daily fluid goals is a key element of postoperative intensive care in these patients. Because fluid balance is influenced by a complex interplay of patient-, surgery- and intensive care unit (ICU)-specific factors, fluid prediction is difficult and often inaccurate.Methods: A novel system theory based digital model for cumulative fluid balance (CFB) prediction is presented using recorded patient fluid data as the sole parameter source by applying the concept of a transfer function. Using a retrospective dataset of n = 618 cardiac intensive care patients, patient-individual models were created and evaluated. RMSE analyses and error calculations were performed for reasonable combinations of model estimation periods and clinically relevant prediction horizons for CFB.Results: Our models have shown that a clinically relevant time horizon for CFB prediction with the combination of 48 h estimation time and 8–16 h prediction time achieves high accuracy. With an 8-h prediction time, nearly 50% of CFB predictions are within ±0.5 L, and 77% are still within the clinically acceptable range of ±1.0 L.Conclusion: Our study has provided a promising proof of principle and may form the basis for further efforts in the development of computational models for fluid prediction that do not require large datasets for training and validation, as is the case with machine learning or AI-based models. The adaptive transfer function approach allows estimation of CFB course on a dynamically changing patient fluid balance system by simulating the response to the current fluid management regime, providing a useful digital tool for clinicians in daily intensive care

Phylogenetic analysis of a highly specific association between ectosymbiotic, sulfur-oxidizing bacteria and a marine nematode

The phylogenetic relationship of chemoautotrophic, sulfur-oxidizing, ectosymbiotic bacteria growing on a marine nematode, a Laxus sp. (formerly a Catanema sp.), to known endosymbionts and free-living bacteria was determined. Comparative 16S rRNA sequencing was used to investigate the unculturable nematode epibionts, and rRNA-targeted oligonucleotide hybridization probes were used to identify the ectosymbionts in situ. Both analyses revealed a remarkably specific and stable symbiosis. Unique hybridization of a specific probe to the ectosymbionts indicated that only one species of bacteria was present and growing on the cuticle of the nematode. Distance and parsimony methods used to infer phylogenetic trees both placed the nematode ectosymbionts at the base of a branch containing chemoautotrophic, sulfur-oxidizing endosymbionts of three bivalve families and of the tube worm Riftia pachyptila. The most closely related free-living bacteria were chemoautotrophic sulfur oxidizers belonging to the genus Thiomicrospira. Furthermore, our results suggested that a second, only distantly related group of thioautotrophic endosymbionts has as its deepest branch surface-colonizing bacteria belonging to the genus Thiothrix, some of which are capable of sulfur-oxidizing chemoautotrophic growth.Organismic and Evolutionary Biolog

Pathways of carbon and energy metabolism of the epibiotic community associated with the deep-sea hydrothermal vent shrimp Rimicaris exoculata

© The Authors, 2011. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 6 (2011): e16018, doi:10.1371/journal.pone.0016018.The shrimp Rimicaris exoculata dominates the faunal biomass at many deep-sea hydrothermal vent sites at the Mid-Atlantic Ridge. In its enlarged gill chamber it harbors a specialized epibiotic bacterial community for which a nutritional role has been proposed. We analyzed specimens from the Snake Pit hydrothermal vent field on the Mid-Atlantic Ridge by complementing a 16S rRNA gene survey with the analysis of genes involved in carbon, sulfur and hydrogen metabolism. In addition to Epsilon- and Gammaproteobacteria, the epibiotic community unexpectedly also consists of Deltaproteobacteria of a single phylotype, closely related to the genus Desulfocapsa. The association of these phylogenetic groups with the shrimp was confirmed by fluorescence in situ hybridization. Based on functional gene analyses, we hypothesize that the Gamma- and Epsilonproteobacteria are capable of autotrophic growth by oxidizing reduced sulfur compounds, and that the Deltaproteobacteria are also involved in sulfur metabolism. In addition, the detection of proteobacterial hydrogenases indicates the potential for hydrogen oxidation in these communities. Interestingly, the frequency of these phylotypes in 16S rRNA gene clone libraries from the mouthparts differ from that of the inner lining of the gill chamber, indicating potential functional compartmentalization. Our data show the specific association of autotrophic bacteria with Rimicaris exoculata from the Snake Pit hydrothermal vent field, and suggest that autotrophic carbon fixation is contributing to the productivity of the epibiotic community with the reductive tricarboxylic acid cycle as one important carbon fixation pathway. This has not been considered in previous studies of carbon fixation and stable carbon isotope composition of the shrimp and its epibionts. Furthermore, the co-occurrence of sulfur-oxidizing and sulfur-reducing epibionts raises the possibility that both may be involved in the syntrophic exchange of sulfur compounds, which could increase the overall efficiency of this epibiotic community.Funding was provided through NSF grant OCE-0452333 and the Alfried Krupp Wissenschaftskolleg Greifswald, Germany (SMS), the Max Planck Society, the German Research Foundation (DFG) Cluster of Excellence at Marum, and MOMARnet (ND, JMP), and IFM-GEOMAR (MH, JFI)

Target Region Selection Is a Critical Determinant of Community Fingerprints Generated by 16S Pyrosequencing

Pyrosequencing of 16S rRNA genes allows for in-depth characterization of complex microbial communities. Although it is known that primer selection can influence the profile of a community generated by sequencing, the extent and severity of this bias on deep-sequencing methodologies is not well elucidated. We tested the hypothesis that the hypervariable region targeted for sequencing and primer degeneracy play important roles in influencing the composition of 16S pyrotag communities. Subgingival plaque from deep sites of current smokers with chronic periodontitis was analyzed using Sanger sequencing and pyrosequencing using 4 primer pairs. Greater numbers of species were detected by pyrosequencing than by Sanger sequencing. Rare taxa constituted nearly 6% of each pyrotag community and less than 1% of the Sanger sequencing community. However, the different target regions selected for pyrosequencing did not demonstrate a significant difference in the number of rare and abundant taxa detected. The genera Prevotella, Fusobacterium, Streptococcus, Granulicatella, Bacteroides, Porphyromonas and Treponema were abundant when the V1–V3 region was targeted, while Streptococcus, Treponema, Prevotella, Eubacterium, Porphyromonas, Campylobacer and Enterococcus predominated in the community generated by V4–V6 primers, and the most numerous genera in the V7–V9 community were Veillonella, Streptococcus, Eubacterium, Enterococcus, Treponema, Catonella and Selenomonas. Targeting the V4–V6 region failed to detect the genus Fusobacterium, while the taxa Selenomonas, TM7 and Mycoplasma were not detected by the V7–V9 primer pairs. The communities generated by degenerate and non-degenerate primers did not demonstrate significant differences. Averaging the community fingerprints generated by V1–V3 and V7–V9 primers providesd results similar to Sanger sequencing, while allowing a significantly greater depth of coverage than is possible with Sanger sequencing. It is therefore important to use primers targeted to these two regions of the 16S rRNA gene in all deep-sequencing efforts to obtain representational characterization of complex microbial communities

Improved Detection of Bifidobacteria with Optimised 16S rRNA-Gene Based Pyrosequencing

The 16S rRNA gene is conserved across all bacteria and as such is routinely targeted in PCR surveys of bacterial diversity. PCR primer design aims to amplify as many different 16S rRNA gene sequences from as wide a range of organisms as possible, though there are no suitable 100% conserved regions of the gene, leading to bias. In the gastrointestinal tract, bifidobacteria are a key genus, but are often under-represented in 16S rRNA surveys of diversity. We have designed modified, ‘bifidobacteria-optimised’ universal primers, which we have demonstrated detection of bifidobacterial sequence present in DNA mixtures at 2% abundance, the lowest proportion tested. Optimisation did not compromise the detection of other organisms in infant faecal samples. Separate validation using fluorescence in situ hybridisation (FISH) shows that the proportions of bifidobacteria detected in faecal samples were in agreement with those obtained using 16S rRNA based pyrosequencing. For future studies looking at faecal microbiota, careful selection of primers will be key in order to ensure effective detection of bifidobacteria

Global Distribution of Polaromonas Phylotypes - Evidence for a Highly Successful Dispersal Capacity

Bacteria from the genus Polaromonas are dominant phylotypes in clone libraries and culture collections from polar and high-elevation environments. Although Polaromonas has been found on six continents, we do not know if the same phylotypes exist in all locations or if they exhibit genetic isolation by distance patterns. To examine their biogeographic distribution, we analyzed all available, long-read 16S rRNA gene sequences of Polaromonas phylotypes from glacial and periglacial environments across the globe. Using genetic isolation by geographic distance analyses, including Mantel tests and Mantel correlograms, we found that Polaromonas phylotypes are globally distributed showing weak isolation by distance patterns at global scales. More focused analyses using discrete, equally sampled distances classes, revealed that only two distance classes (out of 12 total) showed significant spatial structuring. Overall, our analyses show that most Polaromonas phylotypes are truly globally distributed, but that some, as yet unknown, environmental variable may be selecting for unique phylotypes at a minority of our global sites. Analyses of aerobiological and genomic data suggest that Polaromonas phylotypes are globally distributed as dormant cells through high-elevation air currents; Polaromonas phylotypes are common in air and snow samples from high altitudes, and a glacial-ice metagenome and the two sequenced Polaromonas genomes contain the gene hipA, suggesting that Polaromonas can form dormant cells

Planktonic Microbes in the Gulf of Maine Area

In the Gulf of Maine area (GoMA), as elsewhere in the ocean, the organisms of greatest numerical abundance are microbes. Viruses in GoMA are largely cyanophages and bacteriophages, including podoviruses which lack tails. There is also evidence of Mimivirus and Chlorovirus in the metagenome. Bacteria in GoMA comprise the dominant SAR11 phylotype cluster, and other abundant phylotypes such as SAR86-like cluster, SAR116-like cluster, Roseobacter, Rhodospirillaceae, Acidomicrobidae, Flavobacteriales, Cytophaga, and unclassified Alphaproteobacteria and Gammaproteobacteria clusters. Bacterial epibionts of the dinoflagellate Alexandrium fundyense include Rhodobacteraceae, Flavobacteriaceae, Cytophaga spp., Sulfitobacter spp., Sphingomonas spp., and unclassified Bacteroidetes. Phototrophic prokaryotes in GoMA include cyanobacteria that contain chlorophyll (mainly Synechococcus), aerobic anoxygenic phototrophs that contain bacteriochlorophyll, and bacteria that contain proteorhodopsin. Eukaryotic microalgae in GoMA include Bacillariophyceae, Dinophyceae, Prymnesiophyceae, Prasinophyceae, Trebouxiophyceae, Cryptophyceae, Dictyochophyceae, Chrysophyceae, Eustigmatophyceae, Pelagophyceae, Synurophyceae, and Xanthophyceae. There are no records of Bolidophyceae, Aurearenophyceae, Raphidophyceae, and Synchromophyceae in GoMA. In total, there are records for 665 names and 229 genera of microalgae. Heterotrophic eukaryotic protists in GoMA include Dinophyceae, Alveolata, Apicomplexa, amoeboid organisms, Labrynthulida, and heterotrophic marine stramenopiles (MAST). Ciliates include Strombidium, Lohmaniella, Tontonia, Strobilidium, Strombidinopsis and the mixotrophs Laboea strobila and Myrionecta rubrum (ex Mesodinium rubra). An inventory of selected microbial groups in each of 14 physiographic regions in GoMA is made by combining information on the depth-dependent variation of cell density and the depth-dependent variation of water volume. Across the entire GoMA, an estimate for the minimum abundance of cell-based microbes is 1.7×1025 organisms. By one account, this number of microbes implies a richness of 105 to 106 taxa in the entire water volume of GoMA. Morphological diversity in microplankton is well-described but the true extent of taxonomic diversity, especially in the femtoplankton, picoplankton and nanoplankton – whether autotrophic, heterotrophic, or mixotrophic, is unknown

Peanut‐induced anaphylaxis in children and adolescents: Data from the European Anaphylaxis Registry

Background Peanut allergy has a rising prevalence in high-income countries, affecting 0.5%-1.4% of children. This study aimed to better understand peanut anaphylaxis in comparison to anaphylaxis to other food triggers in European children and adolescents. Methods Data was sourced from the European Anaphylaxis Registry via an online questionnaire, after in-depth review of food-induced anaphylaxis cases in a tertiary paediatric allergy centre. Results 3514 cases of food anaphylaxis were reported between July 2007 - March 2018, 56% in patients younger than 18 years. Peanut anaphylaxis was recorded in 459 children and adolescents (85% of all peanut anaphylaxis cases). Previous reactions (42% vs. 38%; p = .001), asthma comorbidity (47% vs. 35%; p < .001), relevant cofactors (29% vs. 22%; p = .004) and biphasic reactions (10% vs. 4%; p = .001) were more commonly reported in peanut anaphylaxis. Most cases were labelled as severe anaphylaxis (Ring&Messmer grade III 65% vs. 56% and grade IV 1.1% vs. 0.9%; p = .001). Self-administration of intramuscular adrenaline was low (17% vs. 15%), professional adrenaline administration was higher in non-peanut food anaphylaxis (34% vs. 26%; p = .003). Hospitalization was higher for peanut anaphylaxis (67% vs. 54%; p = .004). Conclusions The European Anaphylaxis Registry data confirmed peanut as one of the major causes of severe, potentially life-threatening allergic reactions in European children, with some characteristic features e.g., presence of asthma comorbidity and increased rate of biphasic reactions. Usage of intramuscular adrenaline as first-line treatment is low and needs to be improved. The Registry, designed as the largest database on anaphylaxis, allows continuous assessment of this condition

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe