Human brain networks: consensus, reproducibility, inter-modal comparison and epilepsy pathology

Classical and contemporary research in neuroscience postulates that connectivity is a fundamental component of human brain function. Recently, advances in computational neuroimaging have enabled reconstruction of macroscopic human brain structural connectivity in vivo using diffusion MRI. Studies show that the structural network topology may discriminate between neurological phenotypes or relate to individual brain function. To investigate disease effectively, it is necessary to determine the network methodological and biological variability. Reproducibility was calculated for two state-of-the-art reconstruction pipelines in healthy subjects. High reproducibility of connection weights was observed, which increased with connection strength. A high agreement between pipelines was found across network density thresholds. In addition, a robust core network was identified coinciding with a peak in similarity across thresholds, and replicated with alternative atlases. This study demonstrates the utility of applying multiple structural network pipelines to diffusion data in order to identify the most important connections. Focal epilepsy is characterised by seizures that can spread to contiguous and non-contiguous sites. Diffusion MRI and cortico-cortical evoked potentials were acquired in focal epilepsy patients to reconstruct and correlate their structural and effective brain networks and examine connectivity of the ictal-onset zone and propagative regions. Automated methods are described to reconstruct comparable largescale structural and effective networks. A high overlap and low correlation was observed between network modalities. Low correlation may be due to imperfections in methodology, such as difficulty tracing U-fibers using tractography. Effective connectivity amplitude, baseline fluctuation, and outward connectivity tended to be higher at ictal-onset regions, while higher structural connectivity between ictal-onset regions was observed. Furthermore, a high prevalence of structural and effective connections to sites of non-contiguous seizure spread was found. These results support the concept of highly excitable cortex underlying ictal-onset regions which promotes non-contiguous seizure spread via high outward connectivity

Generalised Hierarchical Bayesian Microstructure Modelling for Diffusion MRI

Microstructure imaging combines tailored diffusion MRI acquisition protocols with a mathematical model to give insights into subvoxel tissue features. The model is typically fit voxel-by-voxel to the MRI image with least squares minimisation to give voxelwise maps of parameters relating to microstructural features, such as diffusivities and tissue compartment fractions. However, this fitting approach is susceptible to voxelwise noise, which can lead to erroneous values in parameter maps. Data-driven Bayesian hierarchical modelling defines prior distributions on parameters and learns them from the data, and can hence reduce such noise effects. Bayesian hierarchical modelling has been demonstrated for microstructure imaging with diffusion MRI, but only for a few, relatively simple, models. In this paper, we generalise hierarchical Bayesian modelling to a wide range of multi-compartment microstructural models, and fit the models with a Markov chain Monte Carlo (MCMC) algorithm. We implement our method by utilising Dmipy, a microstructure modelling software package for diffusion MRI data. Our code is available at github.com/PaddySlator/dmipy-bayesian

MATERNAL PREVALENCE OF TOXOPLASMA ANTIBODY BASED ON ANONYMOUS NEONATAL SEROSURVEY - A GEOGRAPHICAL ANALYSIS

A total of 12902 neonatal samples collected on absorbent paper for routine metabolic screening were tested anonymously for antibodies to toxoplasma. Seroprevalence varied from 19.5% in inner London, to 11.6% in suburban London, and 7.6% in non-metropolitan districts. Much of this variation appeared to be associated with the proportions of livebirths in each district to women born outside the UK. However, additional geographical variation remained and seroprevalence in UK-born women was estimated to be 12.7% in inner London. 7.5% in suburban London, and 5.5% in non-metropolitan areas. These estimates are considerably lower than any previously reported in antenatal sera in the UK. The wide geographical variation highlights a need for further research to determine the relative importance of different routes of transmission

High-throughput amplicon sequencing reveals distinct communities within a corroding concrete sewer system

This study investigated the variation in microbially induced concrete corrosion communities at different circumferential locations of a real sewer pipe and the effects of a wastewater flooding event on the community. Three distinct microbial community groups were found in different corrosion samples. The physico-chemical properties of the corrosion layers and the microbial communities were distinct for the cross-sectional positions within the pipe, ie ceiling, wall and tidal zones. The microbial communities detected from the same positions in the pipe were consistent over the length of the pipe, as well as being consistent between the replicate pipes. The dominating ceiling communities were members of the bacterial orders Rhodospirillales, Acidithiobacillales, Actinomycetales, Xanthomonadales and Acidobacteriales. The wall communities were composed of members of the Xanthomonadales, Hydrogenophilales, Chromatiales and Sphingobacteriales. The tidal zones were dominated by eight bacterial and one archaeal order, with the common physiological trait of anaerobic metabolism. Sewage flooding within the sewer system did not change the tidal and wall communities, although the corrosion communities in ceiling samples were notably different, becoming more similar to the wall and tidal samples. This suggests that sewage flooding has a significant impact on the corrosion community in sewers

X-ray lags in PDS 456 revealed by Suzaku observations

X-ray reverberation lags from the vicinity of supermassive black holes have been detected in almost 30 active galactic nuclei (AGNs). The soft lag, which is the time delay between the hard and soft X-ray light curves, is usually interpreted as the time difference between the direct and reflected emission, but is alternatively suggested to arise from the direct and scattering emission from distant clouds. By analysing the archival Suzaku observations totalling an exposure time of ∼770 ks, we discover a soft lag of 10 ± 3.4 ks at 9.58 × 10−6 Hz in the luminous quasar PDS 456, which is the longest soft lag and lowest Fourier frequency reported to date. In this study, we use the maximum likelihood method to deal with non-continuous nature of the Suzaku light curves. The result follows the mass–scaling relation for soft lags, which further supports that soft lags originate from the innermost areas of AGNs and hence are best interpreted by the reflection scenario. Spectral analysis has been performed in this work and we find no evidence of clumpy partial-covering absorbers. The spectrum can be explained by a self-consistent relativistic reflection model with warm absorbers, and spectral variations over epochs can be accounted for by the change of the continuum, and of column density and ionization states of the warm absorbers.EMC gratefully acknowledges support from the NSF through CAREER award number AST-1351222. CSR thanks NASA for support under grant NNX15AU54G. ACF acknowledges ERC Advanced Grant 340442

Broadband Observations of High Redshift Blazars

We present a multi-wavelength study of four high redshift blazars, S5 0014+81 (z = 3.37), CGRaBS J0225+1846 (z = 2.69), BZQ J1430+4205 (z = 4.72), and 3FGL J1656.2−3303 (z = 2.40) using quasi-simultaneous data from the Swift, Nuclear Spectroscopic Telescope Array (NuSTAR) and the Fermi-Large Area Telescope (LAT) and also archival XMM-Newton observations. Other than 3FGL J1656.2−3303, none of the sources were known as γ-ray emitters, and our analysis of ~7.5 yr of LAT data reveals the first time detection of statistically significant γ-ray emission from CGRaBS J0225+1846. We generate the broadband spectral energy distributions (SED) of all the objects, centering at the epoch of NuSTAR observations and reproduce them using a one-zone leptonic emission model. The optical−UV emission in all the objects can be explained by radiation from the accretion disk, whereas the X-ray to γ-ray windows of the SEDs are found to be dominated by inverse Compton scattering off the broad line region photons. All of them host black holes that are billions of solar masses. Comparing the accretion disk luminosity and the jet power of these sources with a large sample of blazars, we find them to occupy a high disk luminosity–jet power regime. We also investigate the X-ray spectral properties of the sources in detail with a major focus on studying the causes of soft X-ray deficit, a feature generally seen in high redshift radio-loud quasars. We summarize that this feature could be explained based on the intrinsic curvature in the jet emission rather than being due to the external effects predicted in earlier studies, such as host galaxy and/or warm absorption.A.C.F. thanks Greg Madejski for discussions on the curvature of blazar X-ray spectra and acknowledges support from ERC Advanced Grant 340442. This research has made use of data, software, and/or web tools obtained from NASAs High Energy Astrophysics Science Archive Research Center (HEASARC), a service of Goddard Space Flight Center and the Smithsonian Astrophysical Observatory. Part of this work is based on archival data, software, or online services provided by the ASI Science Data Center (ASDC). This research has made use of the XRT Data Analysis Software (XRTDAS) developed under the responsibility of the ASDC, Italy. This research has also made use of the NuSTAR Data Analysis Software (NuSTARDAS) jointly developed by the ASI Science Data Center (ASDC, Italy) and the California Institute of Technology (Caltech, USA). This research has made use of the NASA/IPAC Extragalactic Database (NED) which is operated by the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration. Funding for SDSS-III has been provided by the Alfred P. Sloan Foundation, the Participating Institutions, the National Science Foundation, and the U.S. Department of Energy Office of Science. The SDSS-III web site is http://www.sdss3.org/

Revealing the ultrafast outflow in IRAS 13224-3809 through spectral variability

We present an analysis of the long-term X-ray variability of the extreme narrow-line Seyfert 1 (NLS1) galaxy IRAS 13224-3809 using principal component analysis (PCA) and fractional excess variability (Fvar) spectra to identify model-independent spectral components. We identify a series of variability peaks in both the first PCA component and Fvar spectrum which correspond to the strongest predicted absorption lines from the ultra-fast outflow (UFO) discovered by Parker et al. (2017). We also find higher order PCA components, which correspond to variability of the soft excess and reflection features. The subtle differences between RMS and PCA results argue that the observed flux-dependence of the absorption is due to increased ionization of the gas, rather than changes in column density or covering fraction. This result demonstrates that we can detect outflows from variability alone, and that variability studies of UFOs are an extremely promising avenue for future research

Ultrafast outflows disappear in high-radiation fields

Ultrafast outflows (UFOs) are the most extreme winds launched by active galactic nuclei (AGN) due to their mildly-relativistic speeds (~0.1-0.3c) and are thought to significantly contribute to galactic evolution via AGN feedback. Their nature and launching mechanism are however not well understood. Recently, we have discovered the presence of a variable UFO in the narrow-line Seyfert 1 IRAS 13224-3809. The UFO varies in response to the brightness of the source. In this work we perform flux-resolved X-ray spectroscopy to study the variability of the UFO and found that the ionisation parameter is correlated with the luminosity. In the brightest states the gas is almost completely ionised by the powerful radiation field and the UFO is hardly detected. This agrees with our recent results obtained with principal component analysis. We might have found the tip of the iceberg: the high ionisation of the outflowing gas may explain why it is commonly difficult to detect UFOs in AGN and possibly suggest that we may underestimate their actual feedback. We have also found a tentative correlation between the outflow velocity and the luminosity, which is expected from theoretical predictions of radiation-pressure driven winds. This trend is rather marginal due to the Fe XXV-XXVI degeneracy. Further work is needed to break such degeneracy through time-resolved spectroscopy

Positron kinetics in an idealized PET environment

The kinetic theory of non-relativistic positrons in an idealized positron emission tomography PET environment is developed by solving the Boltzmann equation, allowing for coherent and incoherent elastic, inelastic, ionizing and annihilating collisions through positronium formation. An analytic expression is obtained for the positronium formation rate, as a function of distance from a spherical source, in terms of the solutions of the general kinetic eigenvalue problem. Numerical estimates of the positron range - a fundamental limitation on the accuracy of PET, are given for positrons in a model of liquid water, a surrogate for human tissue. Comparisons are made with the 'gas-phase' assumption used in current models in which coherent scattering is suppressed. Our results show that this assumption leads to an error of the order of a factor of approximately 2, emphasizing the need to accurately account for the structure of the medium in PET simulations

Joining the conspiracy? Negotiating ethics and emotions in researching (around) AIDS in southern Africa

AIDS is an emotive subject, particularly in southern Africa. Among those who have been directly affected by the disease, or who perceive themselves to be personally at risk, talking about AIDS inevitably arouses strong emotions - amongst them fear, distress, loss and anger. Conventionally, human geography research has avoided engagement with such emotions. Although the ideal of the detached observer has been roundly critiqued, the emphasis in methodological literature on 'doing no harm' has led even qualitative researchers to avoid difficult emotional encounters. Nonetheless, research is inevitably shaped by emotions, not least those of the researchers themselves. In this paper, we examine the role of emotions in the research process through our experiences of researching the lives of 'Young AIDS migrants' in Malawi and Lesotho. We explore how the context of the research gave rise to the production of particular emotions, and how, in response, we shaped the research, presenting a research agenda focused more on migration than AIDS. This example reveals a tension between universalised ethics expressed through ethical research guidelines that demand informed consent, and ethics of care, sensitive to emotional context. It also demonstrates how dualistic distinctions between reason and emotion, justice and care, global and local are unhelpful in interpreting the ethics of research practice