Metabolic biomarker responses in acute cerebral events

Aims The aims of this study were to identify a potential blood biomarker for acute stroke and additionally to identify biomarkers capable of differentiating hyper-acute ischaemic from haemorrhagic stroke using metabonomic techniques. Methodology Following ethical approval participants were recruited from the hyper-acute stroke unit at Charing Cross Hospital and acute blood samples taken from patients who were suspected of having an acute stroke. Serum was extracted and frozen prior to MS and NMR analysis. Sub-acute TIA patients were used as a comparative group and patients with known atherosclerotic disease as a non-acute control group. A total of 90 participants were recruited for analysis. Positive and negative mode reverse phase UPLC-MS and additionally 1H-NMR spectroscopy were used to analyse prepared serum samples. Modelling was performed using OPLS-DA and CA-PLS techniques where appropriate following permutation analysis to detect discriminatory metabolites between participant groups. Results Positive mode mass spectrometry detected metabolites that could differentiate between participants who had suffered an acute cerebral ischaemic event (inclusive of stroke and acute TIA) and those participants that were known to have established atherosclerotic disease. The metabolites detected include phosphatidylcholines, sphingomyelins and a ganglioside. Unfortunately, due to a relatively small sample size the CA-PLS false discovery rate analysis found the initial results to lack statistical significance (Q value = 0.95). It was not possible to metabolically differentiate between acute ischaemic and haemorrhagic strokes. Conclusion Despite the relatively small sample size leading to a confirmed false discovery rate analysis the initial findings of elevated phosphatidylcholines, sphingomyelins and the peripheral detection of a ganglioside in relation to acute cerebral ischaemia is promising and follows a trend in the published literature. Further studies with a larger sample size, rigorous follow up and temporal trend analysis using dedicated lipidomic techniques may find a sensitive diagnostic serological biomarker for hyper-acute stroke and transient ischaemic attack.Open Acces

Inference of Temporally Varying Bayesian Networks

When analysing gene expression time series data an often overlooked but crucial aspect of the model is that the regulatory network structure may change over time. Whilst some approaches have addressed this problem previously in the literature, many are not well suited to the sequential nature of the data. Here we present a method that allows us to infer regulatory network structures that may vary between time points, utilising a set of hidden states that describe the network structure at a given time point. To model the distribution of the hidden states we have applied the Hierarchical Dirichlet Process Hideen Markov Model, a nonparametric extension of the traditional Hidden Markov Model, that does not require us to fix the number of hidden states in advance. We apply our method to exisiting microarray expression data as well as demonstrating is efficacy on simulated test data

The Influence of in-medium NN cross-sections, symmetry potential and impact parameter on the isospin observables

We explore the influence of in-medium nucleon-nucleon cross section, symmetry potential and impact parameter on isospin sensitive observables in intermediate-energy heavy-ion collisions with the ImQMD05 code, a modified version of Quantum Molecular Dynamics model. At incident velocities above the Fermi velocity, we find that the density dependence of symmetry potential plays a more important role on the double neutron to proton ratio $DR(n/p)$ and the isospin transport ratio $R_i$ than the in-medium nucleon-nucleon cross sections, provided that the latter are constrained to a fixed total NN collision rate. We also explore both $DR(n/p)$ and $R_i$ as a function of the impact parameter. Since the copious production of intermediate mass fragments is a distinguishing feature of intermediate-energy heavy-ion collisions, we examine the isospin transport ratios constructed from different groups of fragments. We find that the values of the isospin transport ratios for projectile rapidity fragments with $Z\ge20$ are greater than those constructed from the entire projectile rapidity source. We believe experimental investigations of this phenomenon can be performed. These may provide significant tests of fragmentation time scales predicted by ImQMD calculations.Comment: 24 pages, 9 figures, to be published in Phys. Rev.

Genetic stability of pneumococcal isolates during 35 days of human experimental carriage

Background Pneumococcal carriage is a reservoir for transmission and a precursor to pneumococcal disease. The experimental human pneumococcal carriage model provides a useful tool to aid vaccine licensure through the measurement of vaccine efficacy against carriage (VEcol). Documentation of the genetic stability of the experimental human pneumococcal carriage model is important to further strengthen confidence in its safety and conclusions, enabling it to further facilitate vaccine licensure through providing evidence of VEcol. Methods 229 isolates were sequenced from 10 volunteers in whom experimental human pneumococcal carriage was established, sampled over a period of 35 days. Multiple isolates from within a single volunteer at a single time provided a deep resolution for detecting variation. HiSeq data from the isolates were mapped against a PacBio reference of the inoculum to call variable sites. Results The observed variation between experimental carriage isolates was minimal with the maximum SNP distance between any isolate and the reference being 3 SNPs. Conclusion The low-level variation described provides evidence for the stability of the experimental human pneumococcal carriage model over 35 days, which can be reliably and confidently used to measure VEcol and aid future progression of pneumococcal vaccination

Influence of Transport Variables on Isospin Transport Ratios

The symmetry energy in the nuclear equation of state affects many aspects of nuclear astrophysics, nuclear structure, and nuclear reactions. Recent constraints from heavy ion collisions, including isospin diffusion observables, have started to put constraints on the symmetry energy below nuclear saturation density, but these constraints depend on the employed transport model and input physics other than the symmetry energy. To understand these dependencies, we study the influence of the symmetry energy, isoscaler mean field compressibility and momentum dependence, in-medium nucleon-nucleon cross sections, and light cluster production on isospin diffusion within the pBUU transport code. In addition to the symmetry energy, several uncertain issues strongly affect isospin diffusion, most notably the cross sections and cluster production. In addition, there is a difference in the calculated isospin transport ratios, depending upon whether they are computed using the isospin asymmetry of either the residue or of all forward moving fragments. Measurements that compare the isospin transport ratios of these two quantities would help place constraints on the input physics, such as the density dependence of the symmetry energy.Comment: 31 pages, 15 figures, submitted to PR

Trends in the epidemiology of larynx and lung cancer in south-east England, 1985–2004

We analysed data on 8987 larynx and 174060 lung cancer patients diagnosed between 1985 and 2004, of which 17.3% of larynx and 35.5% of lung cancers were in females. The age-standardised rates for each cancer declined in both sexes, but since the 1990s, the rates in females over 70 years of age have been diverging

Evaluation of PacBio sequencing for full-length bacterial 16S rRNA gene classification.

BACKGROUND: Currently, bacterial 16S rRNA gene analyses are based on sequencing of individual variable regions of the 16S rRNA gene (Kozich, et al Appl Environ Microbiol 79:5112-5120, 2013).This short read approach can introduce biases. Thus, full-length bacterial 16S rRNA gene sequencing is needed to reduced biases. A new alternative for full-length bacterial 16S rRNA gene sequencing is offered by PacBio single molecule, real-time (SMRT) technology. The aim of our study was to validate PacBio P6 sequencing chemistry using three approaches: 1) sequencing the full-length bacterial 16S rRNA gene from a single bacterial species Staphylococcus aureus to analyze error modes and to optimize the bioinformatics pipeline; 2) sequencing the full-length bacterial 16S rRNA gene from a pool of 50 different bacterial colonies from human stool samples to compare with full-length bacterial 16S rRNA capillary sequence; and 3) sequencing the full-length bacterial 16S rRNA genes from 11 vaginal microbiome samples and compare with in silico selected bacterial 16S rRNA V1V2 gene region and with bacterial 16S rRNA V1V2 gene regions sequenced using the Illumina MiSeq. RESULTS: Our optimized bioinformatics pipeline for PacBio sequence analysis was able to achieve an error rate of 0.007% on the Staphylococcus aureus full-length 16S rRNA gene. Capillary sequencing of the full-length bacterial 16S rRNA gene from the pool of 50 colonies from stool identified 40 bacterial species of which up to 80% could be identified by PacBio full-length bacterial 16S rRNA gene sequencing. Analysis of the human vaginal microbiome using the bacterial 16S rRNA V1V2 gene region on MiSeq generated 129 operational taxonomic units (OTUs) from which 70 species could be identified. For the PacBio, 36,000 sequences from over 58,000 raw reads could be assigned to a barcode, and the in silico selected bacterial 16S rRNA V1V2 gene region generated 154 OTUs grouped into 63 species, of which 62% were shared with the MiSeq dataset. The PacBio full-length bacterial 16S rRNA gene datasets generated 261 OTUs, which were grouped into 52 species, of which 54% were shared with the MiSeq dataset. Alpha diversity index reported a higher diversity in the MiSeq dataset. CONCLUSION: The PacBio sequencing error rate is now in the same range of the previously widely used Roche 454 sequencing platform and current MiSeq platform. Species-level microbiome analysis revealed some inconsistencies between the full-length bacterial 16S rRNA gene capillary sequencing and PacBio sequencing

Field trial of an automated ground-based infrared cloud classification system

Automated classification of cloud types using a ground-based infrared imager can provide invaluable high resolution and localised information for Air Traffic Controllers. Observations can be made consistently, continuously in real time and accurately during both day and night operation. Details of a field trial of an automated, ground-based infrared cloud classification system are presented. The system was designed at Campbell Scientific ltd in collaboration with Loughborough University, UK. The main objective of the trial was to assess the performance of an automated infrared camera system with a lightning detector in classifying several types of clouds, specifically Cumulonimbus and Towering Cumulus, during continuous day and night operation. Results from the classification system were compared with those obtained from Meteorological Aerodrome Reports (METAR) and with data generated by the UK Meteorological Office from their radar and sferics automated cloud reports system. In comparisons with METAR data, a Probability of Detection of up to 82% was achieved, together with a minimum Probability of False Detection of 18%

Diversification of bacterial genome content through distinct mechanisms over different timescales

Bacterial populations often consist of multiple co-circulating lineages. Determining how such population structures arise requires understanding what drives bacterial diversification. Using 616 systematically sampled genomes, we show that Streptococcus pneumoniae lineages are typically characterized by combinations of infrequently transferred stable genomic islands: those moving primarily through transformation, along with integrative and conjugative elements and phage-related chromosomal islands. The only lineage containing extensive unique sequence corresponds to a set of atypical unencapsulated isolates that may represent a distinct species. However, prophage content is highly variable even within lineages, suggesting frequent horizontal transmission that would necessitate rapidly diversifying anti-phage mechanisms to prevent these viruses sweeping through populations. Correspondingly, two loci encoding Type I restriction-modification systems able to change their specificity over short timescales through intragenomic recombination are ubiquitous across the collection. Hence short-term pneumococcal variation is characterized by movement of phage and intragenomic rearrangements, with the slower transfer of stable loci distinguishing lineages

It is all in the looks: A rapid field-based visual assessment tool for evaluating the spawning likelihood of the Asian green mussel, Perna viridis (Linnaeus, 1758)

Numerous interceptions of Perna viridis on vessels entering Western Australian waters prompted the development of a rapid field-based assessment technique for determining reproductive status and hence spawning likelihood of P. viridis. The visual assessment tool and spawning likelihood matrix were developed using correlations between laboratory-based assessments of P. viridis size, colour and egg size in combination with field-based validations from mussels collected on vessels in Western Australian waters. The spawning likelihood matrix provides an immediate indicator of whether the mussel is low, medium or high likelihood of spawning. Mussels were recorded initiating gonad tissue development from approximately 6.5 mm in length, with the mean size of mature animals 59.6 mm. There was a positive correlation between mussel size and stage of reproductive development. Gonad colour, however, appeared to be a more accurate indicator of gonad maturity than mussel size. Female mussels showed a decrease in gonad colour intensity following spawning. Mussels that scored 1 for colour (potential score 1–3) generally had a low proportion of mature eggs (< 70 % mature eggs). Over 60% of the mussels with a colour score of 2 contained 70–100% mature eggs, indicating the capacity for further spawning. Mussels were assigned an overall spawning likelihood score (through the spawning likelihood matrix) based on the proportion of the visceral mass occupied by gonad tissues (% gonad cover, value from 1–3) and overall colour of gonads (value from 1–3). The spawning likelihood score was significantly related to the percentage of mature eggs present, and hence the spawning potential of the mussel. The matrix provides an immediate indicator of the risk of spawning posed by the sample. As such, it is expected that application of the matrix in situ would enable the potential likelihood posed by P. viridis translocated on vessels to be determined quickly and efficiently