An Analysis of Resting-State Functional Transcranial Doppler Recordings from Middle Cerebral Arteries

Functional transcrannial Doppler (fTCD) is used for monitoring the hemodynamics characteristics of major cerebral arteries. Its resting-state characteristics are known only when considering the maximal velocity corresponding to the highest Doppler shift (so called the envelope signals). Significantly more information about the resting-state fTCD can be gained when considering the raw cerebral blood flow velocity (CBFV) recordings. In this paper, we considered simultaneously acquired envelope and raw CBFV signals. Specifically, we collected bilateral CBFV recordings from left and right middle cerebral arteries using 20 healthy subjects (10 females). The data collection lasted for 15 minutes. The subjects were asked to remain awake, stay silent, and try to remain thought-free during the data collection. Time, frequency and time-frequency features were extracted from both the raw and the envelope CBFV signals. The effects of age, sex and body-mass index were examined on the extracted features. The results showed that the raw CBFV signals had a higher frequency content, and its temporal structures were almost uncorrelated. The information-theoretic features showed that the raw recordings from left and right middle cerebral arteries had higher content of mutual information than the envelope signals. Age and body-mass index did not have statistically significant effects on the extracted features. Sex-based differences were observed in all three domains and for both, the envelope signals and the raw CBFV signals. These findings indicate that the raw CBFV signals provide valuable information about the cerebral blood flow which can be utilized in further validation of fTCD as a clinical tool. © 2013 Sejdić et al

Making Sense of a New Transport System: An Ethnographic Study of the Cambridgeshire Guided Busway

An increase in public transport use has the potential to contribute to improving population health, and there is growing interest in innovative public transport systems. Yet how new public transport infrastructure is experienced and integrated (or not) into daily practice is little understood. We investigated how the Cambridgeshire Guided Busway, UK, was used and experienced in the weeks following its opening, using the method of participant observation (travelling on the busway and observing and talking to passengers) and drawing on Normalization Process Theory to interpret our data. Using excerpts of field notes to support our interpretations, we describe how the ease with which the new transport system could be integrated into existing daily routines was important in determining whether individuals would continue to use it. It emerged that there were two groups of passengers with different experiences and attitudes. Passengers who had previously travelled frequently on regular bus services did not perceive the new system to be an improvement; consequently, they were frustrated that it was differentiated from and not coherent with the regular system. In contrast, passengers who had previously travelled almost exclusively by car appraised the busway positively and perceived it to be a novel and superior form of travel. Our rich qualitative account highlights the varied and creative ways in which people learn to use new public transport and integrate it into their everyday lives. This has consequences for the introduction and promotion of future transport innovations. It is important to emphasise the novelty of new public transport, but also the ways in which its use can become ordinary and routine. Addressing these issues could help to promote uptake of other public transport interventions, which may contribute to increasing physical activity and improving population health. © 2013 Jones et al

Understanding local ethnic inequalities in childhood BMI through cross-sectional analysis of routinely collected local data

Background: Local-level analysis of ethnic inequalities in health is lacking, prohibiting a comprehensive understanding of the health needs of local populations and the design of effective health services. Knowledge of ethnic disparities in child weight status is particularly limited by overlooking both the heterogeneity within ethnic groupings; and the complex ecological contexts in which obesity arises. This study aimed to establish whether there was variation in childhood BMI across ethnic groups in Coventry, and the influence of individual, school and neighbourhood contexts, using routinely collected local data. Methods: National Child Measurement Programme data were compiled for the period 2007/8-2014/15 and combined with routinely collected local data reflecting school performance and demographics, and school and neighbourhood physical environments. Multi-level modelling using Monte Carlo Markov Chain methods was used to account for the clustering of children within schools and neighbourhoods. Ethnic group differences in BMI z-score (zBMI) were explored at 4-5 years and 10-11 years for girls and boys alongside individual, school and neighbourhood covariates. Results: At age 4-5 years (n = 28,407), ethnic group differences were similar for boys and girls, with children from South Asian, White other, Chinese and 'any other' ethnic groups having a significantly lower zBMI, and Black African children having a higher zBMI, versus White British (WB) children. Patterns differed considerably at age 10-11 years (n = 25,763) with marked sex differences. Boys from White other, Bangladeshi and Black African groups had a significantly higher zBMI than WB boys. For girls, only children from Black ethnic groups showed a significantly higher zBMI. Area-level deprivation was the only important school or neighbourhood covariate, but its inclusion did not explain ethnic group differences in child zBMI. Conclusion: This analysis contributes to the existing literature by identifying nuanced patterns of ethnic disparities in childhood adiposity in Coventry, supporting the targeting of early obesity prevention for children from Black African groups, as well as girls from Black Caribbean and Black other ethnic backgrounds; and boys from Bangladeshi and White other ethnic backgrounds. It also demonstrates the utility of exploring routinely collected local data sets in building a comprehensive understanding of local population needs.</p

A distance learning university and its economic impact in a country’s peripheries: the case of Hellenic Open University

Higher education institutions can contribute into regional growth via the services of teaching they provide, the research activity they develop and the administration spillover effects on the local markets they operate. This paper attempts to quantify the impact of university expenditures on the regionally produced product (GDP). More specifically, we focus on the expenditure effects of the Hellenic Open University on the GDP of the 13 Greek regions. In our analysis we distinguish between direct and indirect effects by identifying as direct effects all initial expenditures incurred by the HOU while we identify and subsequently calculate as indirect effects the increases in local output caused by the interactions of different sectors of the regional economy. For the calculation of indirect effects we use the input–output methodology. An input–output system shows the intermediate transactions between sectors and the primary inputs, as well as, the final demand of each sector. This is a general equilibrium system that records all the inter-sector transactions presenting a complete picture of the economy under examination and being the appropriate system to be used for calculating the total effect of university expenditure on regional GDP. Our results suggest that the economic impact of HOU is (a) significant to the Greek peripheries and its size varies across regions; (b) indirect regional effects boost the direct regional effects by 60 % creating an overall size of the HOU expenses GDP multiplier by 1.6 on average. Moreover, our findings may have two straightforward policy implications that could be useful to those exercising policy making: first, the quantification of HOU economic impact on all Greek peripheries is not only useful for assessing the economic role of HOU at regional level but it could also been seen as a benchmark in assessing the impact of other similar regional educational activities. Secondly, the economic impact of HOU in each periphery can be a useful tool in assessing alternative non-educational, regional projects, aiming to fight the high unemployment arisen due to economic crisis that bedevils Greece and its peripheries in the last 5 years

Development of the preterm gut microbiome in twins at risk of necrotising enterocolitis and sepsis

The preterm gut microbiome is a complex dynamic community influenced by genetic and environmental factors and is implicated in the pathogenesis of necrotising enterocolitis (NEC) and sepsis. We aimed to explore the longitudinal development of the gut microbiome in preterm twins to determine how shared environmental and genetic factors may influence temporal changes and compared this to the expressed breast milk (EBM) microbiome. Stool samples (n = 173) from 27 infants (12 twin pairs and 1 triplet set) and EBM (n = 18) from 4 mothers were collected longitudinally. All samples underwent PCR-DGGE (denaturing gradient gel electrophoresis) analysis and a selected subset underwent 454 pyrosequencing. Stool and EBM shared a core microbiome dominated by Enterobacteriaceae, Enterococcaceae, and Staphylococcaceae. The gut microbiome showed greater similarity between siblings compared to unrelated individuals. Pyrosequencing revealed a reduction in diversity and increasing dominance of Escherichia sp. preceding NEC that was not observed in the healthy twin. Antibiotic treatment had a substantial effect on the gut microbiome, reducing Escherichia sp. and increasing other Enterobacteriaceae. This study demonstrates related preterm twins share similar gut microbiome development, even within the complex environment of neonatal intensive care. This is likely a result of shared genetic and immunomodulatory factors as well as exposure to the same maternal microbiome during birth, skin contact and exposure to EBM. Environmental factors including antibiotic exposure and feeding are additional significant determinants of community structure, regardless of host genetics

Prenatal Treatment for Serious Neurological Sequelae of Congenital Toxoplasmosis: An Observational Prospective Cohort Study

Background: The effectiveness of prenatal treatment to prevent serious neurological sequelae (SNSD) of congenital toxoplasmosis is not known.Methods and Findings: Congenital toxoplasmosis was prospectively identified by universal prenatal or neonatal screening in 14 European centres and children were followed for a median of 4 years. We evaluated determinants of postnatal death or SNSD defined by one or more of functional neurological abnormalities, severe bilateral visual impairment, or pregnancy termination for confirmed congenital toxoplasmosis. Two-thirds of the cohort received prenatal treatment (189/293; 65%). 23/293 (8%) fetuses developed SNSD of which nine were pregnancy terminations. Prenatal treatment reduced the risk of SNSD. The odds ratio for prenatal treatment, adjusted for gestational age at maternal seroconversion, was 0.24 (95% Bayesian credible intervals 0.07-0.71). This effect was robust to most sensitivity analyses. The number of infected fetuses needed to be treated to prevent one case of SNSD was three (95% Bayesian credible intervals 2-15) after maternal seroconversion at 10 weeks, and 18 (9-75) at 30 weeks of gestation. Pyrimethamine-sulphonamide treatment did not reduce SNSD compared with spiramycin alone (adjusted odds ratio 0.78, 0.21-2.95). The proportion of live-born infants with intracranial lesions detected postnatally who developed SNSD was 31.0% (17.0%-38.1%).Conclusion: The finding that prenatal treatment reduced the risk of SNSD in infected fetuses should be interpreted with caution because of the low number of SNSD cases and uncertainty about the timing of maternal seroconversion. As these are observational data, policy decisions about screening require further evidence from a randomized trial of prenatal screening and from cost-effectiveness analyses that take into account the incidence and prevalence of maternal infection

The Milky Way Tomography With SDSS. III. Stellar Kinematics

We study Milky Way kinematics using a sample of 18.8 million main-sequence stars with r 20 degrees). We find that in the region defined by 1 kpc < Z < 5 kpc and 3 kpc < R < 13 kpc, the rotational velocity for disk stars smoothly decreases, and all three components of the velocity dispersion increase, with distance from the Galactic plane. In contrast, the velocity ellipsoid for halo stars is aligned with a spherical coordinate system and appears to be spatially invariant within the probed volume. The velocity distribution of nearby (Z < 1 kpc) K/M stars is complex, and cannot be described by a standard Schwarzschild ellipsoid. For stars in a distance-limited subsample of stars (< 100 pc), we detect a multi-modal velocity distribution consistent with that seen by HIPPARCOS. This strong non-Gaussianity significantly affects the measurements of the velocity-ellipsoid tilt and vertex deviation when using the Schwarzschild approximation. We develop and test a simple descriptive model for the overall kinematic behavior that captures these features over most of the probed volume, and can be used to search for substructure in kinematic and metallicity space. We use this model to predict further improvements in kinematic mapping of the Galaxy expected from Gaia and the Large Synoptic Survey Telescope.NSF AST-615991, AST-0707901, AST-0551161, AST-02-38683, AST-06-07634, AST-0807444, PHY05-51164NASA NAG5-13057, NAG5-13147, NNXO-8AH83GPhysics Frontier Center/Joint Institute for Nuclear Astrophysics (JINA) PHY 08-22648U.S. National Science FoundationMarie Curie Research Training Network ELSA (European Leadership in Space Astrometry) MRTN-CT-2006-033481Fermi Research Alliance, LLC, United States Department of Energy DE-AC02-07CH11359Alfred P. Sloan FoundationParticipating InstitutionsJapanese MonbukagakushoMax Planck SocietyHigher Education Funding Council for EnglandMcDonald Observator

The Milky Way Tomography with SDSS: III. Stellar Kinematics

We study Milky Way kinematics using a sample of 18.8 million main-sequence stars with r<20 and proper-motion measurements derived from SDSS and POSS astrometry, including ~170,000 stars with radial-velocity measurements from the SDSS spectroscopic survey. Distances to stars are determined using a photometric parallax relation, covering a distance range from ~100 pc to 10 kpc over a quarter of the sky at high Galactic latitudes (|b|>20 degrees). We find that in the region defined by 1 kpc <Z< 5 kpc and 3 kpc <R< 13 kpc, the rotational velocity for disk stars smoothly decreases, and all three components of the velocity dispersion increase, with distance from the Galactic plane. In contrast, the velocity ellipsoid for halo stars is aligned with a spherical coordinate system and appears to be spatially invariant within the probed volume. The velocity distribution of nearby ($Z<1$ kpc) K/M stars is complex, and cannot be described by a standard Schwarzschild ellipsoid. For stars in a distance-limited subsample of stars (<100 pc), we detect a multimodal velocity distribution consistent with that seen by HIPPARCOS. This strong non-Gaussianity significantly affects the measurements of the velocity ellipsoid tilt and vertex deviation when using the Schwarzschild approximation. We develop and test a simple descriptive model for the overall kinematic behavior that captures these features over most of the probed volume, and can be used to search for substructure in kinematic and metallicity space. We use this model to predict further improvements in kinematic mapping of the Galaxy expected from Gaia and LSST.Comment: 90 pages, 26 figures, submitted to Ap

Horizontal DNA transfer mechanisms of bacteria as weapons of intragenomic conflict

Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framework for understanding the evolutionary origins of HDT. To test this hypothesis, we developed a mathematical model of a clonally descended bacterial population undergoing HDT through transmission of mobile genetic elements (MGEs) and genetic transformation. Including the known bias of transformation toward the acquisition of shorter alleles into the model suggested it could be an effective means of counteracting the spread of MGEs. Both constitutive and transient competence for transformation were found to provide an effective defence against parasitic MGEs; transient competence could also be effective at permitting the selective spread of MGEs conferring a benefit on their host bacterium. The coordination of transient competence with cell-cell killing, observed in multiple species, was found to result in synergistic blocking of MGE transmission through releasing genomic DNA for homologous recombination while simultaneously reducing horizontal MGE spread by lowering the local cell density. To evaluate the feasibility of the functions suggested by the modelling analysis, we analysed genomic data from longitudinal sampling of individuals carrying Streptococcus pneumoniae. This revealed the frequent within-host coexistence of clonally descended cells that differed in their MGE infection status, a necessary condition for the proposed mechanism to operate. Additionally, we found multiple examples of MGEs inhibiting transformation through integrative disruption of genes encoding the competence machinery across many species, providing evidence of an ongoing "arms race." Reduced rates of transformation have also been observed in cells infected by MGEs that reduce the concentration of extracellular DNA through secretion of DNases. Simulations predicted that either mechanism of limiting transformation would benefit individual MGEs, but also that this tactic's effectiveness was limited by competition with other MGEs coinfecting the same cell. A further observed behaviour we hypothesised to reduce elimination by transformation was MGE activation when cells become competent. Our model predicted that this response was effective at counteracting transformation independently of competing MGEs. Therefore, this framework is able to explain both common properties of MGEs, and the seemingly paradoxical bacterial behaviours of transformation and cell-cell killing within clonally related populations, as the consequences of intragenomic conflict between self-replicating chromosomes and parasitic MGEs. The antagonistic nature of the different mechanisms of HDT over short timescales means their contribution to bacterial evolution is likely to be substantially greater than previously appreciated

Human neutrophil clearance of bacterial pathogens triggers anti-microbial gamma delta T cell responses in early infection

Human blood Vc9/Vd2 T cells, monocytes and neutrophils share a responsiveness toward inflammatory chemokines and are rapidly recruited to sites of infection. Studying their interaction in vitro and relating these findings to in vivo observations in patients may therefore provide crucial insight into inflammatory events. Our present data demonstrate that Vc9/Vd2 T cells provide potent survival signals resulting in neutrophil activation and the release of the neutrophil chemoattractant CXCL8 (IL-8). In turn, Vc9/Vd2 T cells readily respond to neutrophils harboring phagocytosed bacteria, as evidenced by expression of CD69, interferon (IFN)-c and tumor necrosis factor (TNF)-a. This response is dependent on the ability of these bacteria to produce the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), requires cell-cell contact of Vc9/Vd2 T cells with accessory monocytes through lymphocyte function-associated antigen-1 (LFA-1), and results in a TNF-a dependent proliferation of Vc9/Vd2 T cells. The antibiotic fosmidomycin, which targets the HMB-PP biosynthesis pathway, not only has a direct antibacterial effect on most HMB-PP producing bacteria but also possesses rapid anti-inflammatory properties by inhibiting cd T cell responses in vitro. Patients with acute peritoneal-dialysis (PD)-associated bacterial peritonitis – characterized by an excessive influx of neutrophils and monocytes into the peritoneal cavity – show a selective activation of local Vc9/Vd2 T cells by HMB-PP producing but not by HMB-PP deficient bacterial pathogens. The cd T celldriven perpetuation of inflammatory responses during acute peritonitis is associated with elevated peritoneal levels of cd T cells and TNF-a and detrimental clinical outcomes in infections caused by HMB-PP positive microorganisms. Taken together, our findings indicate a direct link between invading pathogens, neutrophils, monocytes and microbe-responsive cd T cells in early infection and suggest novel diagnostic and therapeutic approaches.Martin S. Davey, Chan-Yu Lin, Gareth W. Roberts, Sinéad Heuston, Amanda C. Brown, James A. Chess, Mark A. Toleman, Cormac G.M. Gahan, Colin Hill, Tanya Parish, John D. Williams, Simon J. Davies, David W. Johnson, Nicholas Topley, Bernhard Moser and Matthias Eber