Towards a Multi-Subject Analysis of Neural Connectivity

Directed acyclic graphs (DAGs) and associated probability models are widely used to model neural connectivity and communication channels. In many experiments, data are collected from multiple subjects whose connectivities may differ but are likely to share many features. In such circumstances it is natural to leverage similarity between subjects to improve statistical efficiency. The first exact algorithm for estimation of multiple related DAGs was recently proposed by Oates et al. 2014; in this letter we present examples and discuss implications of the methodology as applied to the analysis of fMRI data from a multi-subject experiment. Elicitation of tuning parameters requires care and we illustrate how this may proceed retrospectively based on technical replicate data. In addition to joint learning of subject-specific connectivity, we allow for heterogeneous collections of subjects and simultaneously estimate relationships between the subjects themselves. This letter aims to highlight the potential for exact estimation in the multi-subject setting.Comment: to appear in Neural Computation 27:1-2

Revisiting Tocqueville: Citizenship Norms, Political Repertoires, and Cultural Participation

What are the reasons for Tocqueville’s eternal youth?” This is the question Raymond Boudon asks in his recent book, Tocqueville for Today (Boudon 2006: 2). In other words, why do we keep reading Democracy in America, a book written in the 1830s, in order to understand how liberal democracy works today, both in the US and elsewhere? Boudon’s answer — that Tocqueville gave us a new and innovative sociological analysis that has yet to be surpassed — points to the exceptional character of his contribution to the understanding of modern societies. Alongside the names of Weber and Durkheim, Boudon doubtless includes Tocqueville as one of his most admired classic social thinkers. Curiously enough, Boudon’s assessment of Tocqueville as a sociological classic was itself an exceptional judgment only a generation ago

Can we use postal surveys with anonymous testing to monitor chlamydia prevalence in young women in England? Pilot study incorporating randomised controlled trial of recruitment methods

OBJECTIVES: Chlamydia prevalence in the general population is a potential outcome measure for the evaluation of chlamydia control programmes. We carried out a pilot study to determine the feasibility of using a postal survey for population-based chlamydia prevalence monitoring. METHODS: Postal invitations were sent to a random sample of 2000 17-year-old to 18-year-old women registered with a general practitioner in two pilot areas in England. Recipients were randomised to receive either a self-sampling kit (n=1000), a self-sampling kit and offer of £5 voucher on return of sample (n=500) or a self-sampling kit on request (n=500). Participants returned a questionnaire and self-taken vulvovaginal swab sample for unlinked anonymous Chlamydia trachomatis testing. Non-responders were sent a reminder letter 3 weeks after initial invitation. We calculated the participation rate (number of samples returned/number of invitations sent) and cost per sample returned (including cost of consumables and postage) in each group. RESULTS: A total of 155/2000 (7.8%) samples were returned with consent for testing. Participation rates varied by invitation group: 7.8% in the group who were provided with a self-sampling kit, 14% in the group who were also offered a voucher and 1.0% in the group who were not sent a kit. The cost per sample received was lowest (£36) in the group who were offered both a kit and a voucher. CONCLUSIONS: The piloted survey methodology achieved low participation rates. This approach is not suitable for population-based monitoring of chlamydia prevalence among young women in England

Simultaneous determination of wave speed and arrival time of reflected waves using the pressure-velocity loop

This is the post print version of the article. The official published version can be found at the link below.In a previous paper we demonstrated that the linear portion of the pressure–velocity loop (PU-loop) corresponding to early systole could be used to calculate the local wave speed. In this paper we extend this work to show that determination of the time at which the PU-loop first deviates from linearity provides a convenient way to determine the arrival time of reflected waves (Tr). We also present a new technique using the PU-loop that allows for the determination of wave speed and Tr simultaneously. We measured pressure and flow in elastic tubes of different diameters, where a strong reflection site existed at known distances away form the measurement site. We also measured pressure and flow in the ascending aorta of 11 anaesthetised dogs where a strong reflection site was produced through total arterial occlusion at four different sites. Wave speed was determined from the initial slope of the PU-loop and Tr was determined using a new algorithm that detects the sampling point at which the initial linear part of the PU-loop deviates from linearity. The results of the new technique for detecting Tr were comparable to those determined using the foot-to-foot and wave intensity analysis methods. In elastic tubes Tr detected using the new algorithm was almost identical to that detected using wave intensity analysis and foot-to-foot methods with a maximum difference of 2%. Tr detected using the PU-loop in vivo highly correlated with that detected using wave intensity analysis (r 2 = 0.83, P < 0.001). We conclude that the new technique described in this paper offers a convenient and objective method for detecting Tr, and allows for the dynamic determination of wave speed and Tr, simultaneously

A thermochemical and theoretical study of the phenylpyridine isomers

The standard (p° = 0.1 MPa) molar enthalpies of formation for 2-, 3-, and 4-phenylpyridine in the gas phase were derived from the standard molar enthalpies of combustion, in oxygen, at 298.15 K, measured by static bomb combustion calorimetry. The standard molar enthalpies of vaporization for 2-, 3-, and 4-phenylpyridine at T = 298.15 K were measured by correlation-gas chromatography. The enthalpy of sublimation of 4-phenylpyridine was obtained as a weighted mean of the value derived from the vaporization and fusion enthalpy values and the value measured directly by Calvet microcalorimetry. The following enthalpies of formation were then derived:  2-phenylpyridine, g = 228.3 ± 5.8 kJ·mol-1; 3-phenylpyridine, g = 240.9 ± 5.5 kJ·mol-1; 4-phenylpyridine, g = 240.0 ± 3.3 kJ·mol-1. The most stable geometries of all phenylpyridine isomers were obtained using both restricted Hartree−Fock (RHF) and density functional theory (DFT/B3LYP) methods. The resulting geometries were then used to obtain estimates of enthalpies of formation of the three isomers of phenylpyridine, which are in good agreement with the experimental values. A theoretical interpretation of the effect of the phenyl ring has on the relative stabilities of the three molecules is presented

Heterozygosity but not inbreeding coefficient predicts parasite burdens in the banded mongoose

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.Inbreeding, reproduction between relatives, often impinges on the health and survival of resulting offspring. Such inbreeding depression may manifest itself through immunological costs as inbred individuals suffer increased propensity to disease, infection and parasites compared to outbred conspecifics. Here, we assess how the intestinal parasite loads of wild banded mongooses (Mungos mungo) vary with pedigree inbreeding coefficient (ƒ) and standardized multi-locus heterozygosity. We find a significant association between increased heterozygosity and lower parasite loads; however, this correlation does not stand when considering ƒ. Such findings may be explained by local genetic effects, linkage between genetic markers and genes influencing parasite burdens. Indeed, we find heterozygosity at certain loci to correlate with parasite load. Although these tentative local effects are lost following multiple test correction, they warrant future investigation to determine their strength and impact. We also suggest frequent inbreeding within banded mongooses may mean heterozygosity is a better predictor of inbreeding than pedigree ƒ. This is because inbreeding facilitates linkage disequilibrium, increasing the chances of neutral markers representing genome-wide heterozygosity. Finally, neither ƒ nor heterozygosity had a significant influence on the loads of two specific gastrointestinal parasites. Nevertheless, more heterozygous individuals benefited from reduced overall parasitic infection and genetic diversity appears to explain some variation in parasite burdens in the banded mongoose

A discrete geometric approach for simulating the dynamics of thin viscous threads

We present a numerical model for the dynamics of thin viscous threads based on a discrete, Lagrangian formulation of the smooth equations. The model makes use of a condensed set of coordinates, called the centerline/spin representation: the kinematical constraints linking the centerline's tangent to the orientation of the material frame is used to eliminate two out of three degrees of freedom associated with rotations. Based on a description of twist inspired from discrete differential geometry and from variational principles, we build a full-fledged discrete viscous thread model, which includes in particular a discrete representation of the internal viscous stress. Consistency of the discrete model with the classical, smooth equations is established formally in the limit of a vanishing discretization length. The discrete models lends itself naturally to numerical implementation. Our numerical method is validated against reference solutions for steady coiling. The method makes it possible to simulate the unsteady behavior of thin viscous jets in a robust and efficient way, including the combined effects of inertia, stretching, bending, twisting, large rotations and surface tension

REEP6 Deficiency Leads to Retinal Degeneration through Disruption of ER Homeostasis and Protein Trafficking

Retinitis pigmentosa (RP) is the most common form of inherited retinal dystrophy. We recently identified mutations in REEP6, which encodes the receptor expression enhancing protein 6, in several families with autosomal recessive RP. REEP6 is related to the REEP and Yop1p family of ER shaping proteins and potential receptor accessory proteins, but the role of REEP6 in the retina is unknown. Here we characterise the disease mechanisms associated with loss of REEP6 function using a Reep6 knockout mouse generated by CRISPR/Cas9 gene editing. In control mice REEP6 was localised to the inner segment and outer plexiform layer of rod photoreceptors. The Reep6-/- mice exhibited progressive photoreceptor degeneration from P20 onwards. Ultrastructural analyses at P20 by transmission electron microscopy and 3View serial block face scanning EM revealed an expansion of the distal ER in the Reep6-/- rods and an increase in their number of mitochondria. Electroretinograms revealed photoreceptor dysfunction preceded degeneration, suggesting potential defects in phototransduction. There was no effect on the traffic of rhodopsin, Rom1 or peripherin/rds; however, the retinal guanylate cyclases GC1 and GC2 were severely affected in the Reep6 knockout animals, with almost undetectable expression. These changes correlated with an increase in C/EBP homologous protein (CHOP) expression and the activation of caspase 12, suggesting that ER stress contributes to cell death. Collectively, these data suggest that REEP6 plays an essential role in maintaining cGMP homeostasis though facilitating the stability and/or trafficking of guanylate cyclases and maintaining ER and mitochondrial homeostasis