Inter-study reproducibility of arterial spin labelling magnetic resonance imaging for measurement of renal perfusion in healthy volunteers at 3 Tesla

Background: Measurement of renal perfusion is a crucial part of measuring kidney function. Arterial spin labelling magnetic resonance imaging (ASL MRI) is a non-invasive method of measuring renal perfusion using magnetised blood as endogenous contrast. We studied the reproducibility of ASL MRI in normal volunteers.<p></p> Methods: ASL MRI was performed in healthy volunteers on 2 occasions using a 3.0 Tesla MRI scanner with flow-sensitive alternating inversion recovery (FAIR) perfusion preparation with a steady state free precession (True-FISP) pulse sequence. Kidney volume was measured from the scanned images. Routine serum and urine biochemistry were measured prior to MRI scanning.<p></p> Results: 12 volunteers were recruited yielding 24 kidneys, with a mean participant age of 44.1 ± 14.6 years, blood pressure of 136/82 mmHg and chronic kidney disease epidemiology formula estimated glomerular filtration rate (CKD EPI eGFR) of 98.3 ± 15.1 ml/min/1.73 m2. Mean kidney volumes measured using the ellipsoid formula and voxel count method were 123.5 ± 25.5 cm3, and 156.7 ± 28.9 cm3 respectively. Mean kidney perfusion was 229 ± 41 ml/min/100 g and mean cortical perfusion was 327 ± 63 ml/min/100 g, with no significant differences between ASL MRIs. Mean absolute kidney perfusion calculated from kidney volume measured during the scan was 373 ± 71 ml/min. Bland Altman plots were constructed of the cortical and whole kidney perfusion measurements made at ASL MRIs 1 and 2. These showed good agreement between measurements, with a random distribution of means plotted against differences observed. The intra class correlation for cortical perfusion was 0.85, whilst the within subject coefficient of variance was 9.2%. The intra class correlation for whole kidney perfusion was 0.86, whilst the within subject coefficient of variance was 7.1%.<p></p> Conclusions: ASL MRI at 3.0 Tesla provides a repeatable method of measuring renal perfusion in healthy subjects without the need for administration of exogenous compounds. We have established normal values for renal perfusion using ASL MRI in a cohort of healthy volunteers.<p></p&gt

Targeted nasal vaccination provides antibody-independent protection against Staphylococcus aureus.

Despite showing promise in preclinical models, anti-Staphylococcus aureus vaccines have failed in clinical trials. To date, approaches have focused on neutralizing/opsonizing antibodies; however, vaccines exclusively inducing cellular immunity have not been studied to formally test whether a cellular-only response can protect against infection. We demonstrate that nasal vaccination with targeted nanoparticles loaded with Staphylococcus aureus antigen protects against acute systemic S. aureus infection in the absence of any antigen-specific antibodies. These findings can help inform future developments in staphylococcal vaccine development and studies into the requirements for protective immunity against S. aureus

Coupled oscillators as models of phantom and scalar field cosmologies

We study a toy model for phantom cosmology recently introduced in the literature and consisting of two oscillators, one of which carries negative kinetic energy. The results are compared with the exact phase space picture obtained for similar dynamical systems describing, respectively, a massive canonical scalar field conformally coupled to the spacetime curvature, and a conformally coupled massive phantom. Finally, the dynamical system describing exactly a minimally coupled phantom is studied and compared with the toy model.Comment: 18 pages, LaTeX, to appear in Physical Review

High stakes and low bars: How international recognition shapes the conduct of civil wars

When rebel groups engage incumbent governments in war for control of the state, questions of international recognition arise. International recognition determines which combatants can draw on state assets, receive overt military aid, and borrow as sovereigns—all of which can have profound consequences for the military balance during civil war. How do third-party states and international organizations determine whom to treat as a state's official government during civil war? Data from the sixty-one center-seeking wars initiated from 1945 to 2014 indicate that military victory is not a prerequisite for recognition. Instead, states generally rely on a simple test: control of the capital city. Seizing the capital does not foreshadow military victory. Civil wars often continue for many years after rebels take control and receive recognition. While geopolitical and economic motives outweigh the capital control test in a small number of important cases, combatants appear to anticipate that holding the capital will be sufficient for recognition. This expectation generates perverse incentives. In effect, the international community rewards combatants for capturing or holding, by any means necessary, an area with high concentrations of critical infrastructure and civilians. In the majority of cases where rebels contest the capital, more than half of its infrastructure is damaged or the majority of civilians are displaced (or both), likely fueling long-term state weakness

Average luminosity distance in inhomogeneous universes

The paper studies the correction to the distance modulus induced by inhomogeneities and averaged over all directions from a given observer. The inhomogeneities are modeled as mass-compensated voids in random or regular lattices within Swiss-cheese universes. Void radii below 300 Mpc are considered, which are supported by current redshift surveys and limited by the recently observed imprint such voids leave on CMB. The averaging over all directions, performed by numerical ray tracing, is non-perturbative and includes the supernovas inside the voids. Voids aligning along a certain direction produce a cumulative gravitational lensing correction that increases with their number. Such corrections are destroyed by the averaging over all directions, even in non-randomized simple cubic void lattices. At low redshifts, the average correction is not zero but decays with the peculiar velocities and redshift. Its upper bound is provided by the maximal average correction which assumes no random cancelations between different voids. It is described well by a linear perturbation formula and, for the voids considered, is 20% of the correction corresponding to the maximal peculiar velocity. The average correction calculated in random and simple cubic void lattices is severely damped below the predicted maximal one after a single void diameter. That is traced to cancellations between the corrections from the fronts and backs of different voids. All that implies that voids cannot imitate the effect of dark energy unless they have radii and peculiar velocities much larger than the currently observed. The results obtained allow one to readily predict the redshift above which the direction-averaged fluctuation in the Hubble diagram falls below a required precision and suggest a method to extract the background Hubble constant from low redshift data without the need to correct for peculiar velocities.Comment: 34 pages, 21 figures, matches the version accepted in JCA

SRAO CO Observation of 11 Supernova Remnants in l = 70 to 190 deg

We present the results of 12CO J = 1-0 line observations of eleven Galactic supernova remnants (SNRs) obtained using the Seoul Radio Astronomy Observatory (SRAO) 6-m radio telescope. The observation was made as a part of the SRAO CO survey of SNRs between l = 70 and 190 deg, which is intended to identify SNRs interacting with molecular clouds. The mapping areas for the individual SNRs are determined to cover their full extent in the radio continuum. We used halfbeam grid spacing (60") for 9 SNRs and full-beam grid spacing (120") for the rest. We detected CO emission towards most of the remnants. In six SNRs, molecular clouds showed a good spatial relation with their radio morphology, although no direct evidence for the interaction was detected. Two SNRs are particularly interesting: G85.4+0.7, where there is a filamentary molecular cloud along the radio shell, and 3C434.1, where a large molecular cloud appears to block the western half of the remnant. We briefly summarize the results obtained for individual SNRs.Comment: Accepted for publication in Astrophysics & Space Science. 12 pages, 12 figures, and 3 table

Cosmological evolution of interacting dark energy in Lorentz violation

The cosmological evolution of an interacting scalar field model in which the scalar field interacts with dark matter, radiation, and baryon via Lorentz violation is investigated. We propose a model of interaction through the effective coupling $\bar{\beta}$. Using dynamical system analysis, we study the linear dynamics of an interacting model and show that the dynamics of critical points are completely controlled by two parameters. Some results can be mentioned as follows. Firstly, the sequence of radiation, the dark matter, and the scalar field dark energy exist and baryons are sub dominant. Secondly, the model also allows the possibility of having a universe in the phantom phase with constant potential. Thirdly, the effective gravitational constant varies with respect to time through $\bar{\beta}$. In particular, we consider a simple case where $\bar{\beta}$ has a quadratic form and has a good agreement with the modified $\Lambda$CDM and quintessence models. Finally, we also calculate the first post--Newtonian parameters for our model.Comment: 14 pages, published versio

Migration and horizontal gene transfer divide microbial genomes into multiple niches.

Horizontal gene transfer is central to microbial evolution, because it enables genetic regions to spread horizontally through diverse communities. However, how gene transfer exerts such a strong effect is not understood. Here we develop an eco-evolutionary model and show how genetic transfer, even when rare, can transform the evolution and ecology of microbes. We recapitulate existing models, which suggest that asexual reproduction will overpower horizontal transfer and greatly limit its effects. We then show that allowing immigration completely changes these predictions. With migration, the rates and impacts of horizontal transfer are greatly increased, and transfer is most frequent for loci under positive natural selection. Our analysis explains how ecologically important loci can sweep through competing strains and species. In this way, microbial genomes can evolve to become ecologically diverse where different genomic regions encode for partially overlapping, but distinct, ecologies. Under these conditions ecological species do not exist, because genes, not species, inhabit niches

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

The evolution of strategy in bacterial warfare via the regulation of bacteriocins and antibiotics

Bacteria inhibit and kill one another with a diverse array of compounds, including bacteriocins and antibiotics. These attacks are highly regulated, but we lack a clear understanding of the evolutionary logic underlying this regulation. Here, we combine a detailed dynamic model of bacterial competition with evolutionary game theory to study the rules of bacterial warfare. We model a large range of possible combat strategies based upon the molecular biology of bacterial regulatory networks. Our model predicts that regulated strategies, which use quorum sensing or stress responses to regulate toxin production, will readily evolve as they outcompete constitutive toxin production. Amongst regulated strategies, we show that a particularly successful strategy is to upregulate toxin production in response to an incoming competitor’s toxin, which can be achieved via stress responses that detect cell damage (competition sensing). Mirroring classical game theory, our work suggests a fundamental advantage to reciprocation. However, in contrast to classical results, we argue that reciprocation in bacteria serves not to promote peaceful outcomes but to enable efficient and effective attacks