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.

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

Probing elastic and inelastic breakup contributions to intermediate-energy two-proton removal reactions

The two-proton removal reaction from 28Mg projectiles has been studied at 93 MeV/u at the NSCL. First coincidence measurements of the heavy 26Ne projectile residues, the removed protons and other light charged particles enabled the relative cross sections from each of the three possible elastic and inelastic proton removal mechanisms to be determined. These more final-state-exclusive measurements are key for further interrogation of these reaction mechanisms and use of the reaction channel for quantitative spectroscopy of very neutron-rich nuclei. The relative and absolute yields of the three contributing mechanisms are compared to reaction model expectations - based on the use of eikonal dynamics and sd-shell-model structure amplitudes.Comment: Accepted for publication in Physical Review C (Rapid Communication

Elastic breakup cross sections of well-bound nucleons

The 9Be(28Mg,27Na) one-proton removal reaction with a large proton separation energy of Sp(28Mg)=16.79 MeV is studied at intermediate beam energy. Coincidences of the bound 27Na residues with protons and other light charged particles are measured. These data are analyzed to determine the percentage contributions to the proton removal cross section from the elastic and inelastic nucleon removal mechanisms. These deduced contributions are compared with the eikonal reaction model predictions and with the previously measured data for reactions involving the re- moval of more weakly-bound protons from lighter nuclei. The role of transitions of the proton between different bound single-particle configurations upon the elastic breakup cross section is also quantified in this well-bound case. The measured and calculated elastic breakup fractions are found to be in good agreement.Comment: Phys. Rev. C 2014 (accepted

Angular Dependence in Proton-Proton Correlation Functions in Central 40Ca+40Ca^{40}Ca+^{40}Ca and 48Ca+48Ca^{48}Ca+^{48}Ca Reactions

The angular dependence of proton-proton correlation functions is studied in central $^{40}Ca+^{40}Ca$ and $^{48}Ca+^{48}Ca$ nuclear reactions at E=80 MeV/A. Measurements were performed with the HiRA detector complemented by the 4$\pi$ Array at NSCL. A striking angular dependence in the laboratory frame is found within p-p correlation functions for both systems that greatly exceeds the measured and expected isospin dependent difference between the neutron-rich and neutron-deficient systems. Sources measured at backward angles reflect the participant zone of the reaction, while much larger sources observed at forward angles reflect the expanding, fragmenting and evaporating projectile remnants. The decrease of the size of the source with increasing momentum is observed at backward angles while a weaker trend in the opposite direction is observed at forward angles. The results are compared to the theoretical calculations using the BUU transport model.Comment: 8 pages, 3 figures, submitted to PR

Correlations in intermediate-energy two-proton removal reactions

We report final-state-exclusive measurements of the light charged fragments in coincidence with 26Ne residual nuclei following the direct two-proton removal from a neutron-rich 28Mg secondary beam. A Dalitz-plot analysis and comparisons with simulations show that a majority of the triple- coincidence events with two protons display phase-space correlations consistent with the (two-body) kinematics of a spatially-correlated pair-removal mechanism. The fraction of such correlated events, 56(12) %, is consistent with the fraction of the calculated cross section, 64 %, arising from spin S = 0 two-proton configurations in the entrance-channel (shell-model) 28Mg ground state wave function. This result promises access to an additional and more specific probe of the spin and spatial correlations of valence nucleon pairs in exotic nuclei produced as fast secondary beams.Comment: accepted for publication in Physical Review Letter

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

Antidepressant use and risk of epilepsy and seizures in people aged 20 to 64 years: cohort study using a primary care database

Background: Epilepsy is a serious condition which can profoundly affect an individual’s life. While there is some evidence to suggest an association between antidepressant use and epilepsy and seizures it is conflicting and not conclusive. Antidepressant prescribing is rising in the UK so it is important to quantify absolute risks with individual antidepressants to enable shared decision making with patients. In this study we assess and quantify the association between antidepressant treatment and the risk of epilepsy and seizures in a large cohort of patients diagnosed with depression aged between 20 and 64 years. Methods: Data on 238,963 patients with a diagnosis of depression aged 20 to 64 from 687 UK practices were extracted from the QResearch primary care database. We used Cox’s proportional hazards to analyse the time to the first recorded diagnosis of epilepsy/seizures, excluding patients with a prior history and estimated hazard ratios for antidepressant exposure adjusting for potential confounding variables. Results: In the first 5 years of follow-up, 878 (0.37 %) patients had a first diagnosis of epilepsy/seizures with the hazard ratio (HR) significantly increased (P < 0.01) for all antidepressant drug classes and for 8 of the 11 most commonly prescribed drugs. The highest risks (in the first 5 years) compared with no treatment were for trazodone (HR 5.41, 95 % confidence interval (CI) 3.05 to 9.61, number needed to harm (NNH) 65), lofepramine (HR 3.09, 95 % CI 1.73 to 5.50, NNH 138), venlafaxine (HR 2.84, 95 % CI 1.97 to 4.08, NNH 156) and combined antidepressant treatment (HR 2.73, 95 % CI 1.52 to 4.91, NNH 166). Conclusions: Risk of epilepsy/seizures is significantly increased for all classes of antidepressant. There is a need for individual risk-benefit assessments in patients being considered for antidepressant treatment, especially those with ongoing mild depression or with additional risk factors. Residual confounding and indication bias may influence our results, so confirmation may be required from additional studies