First Clear Signature of an Extended Dark Matter Halo in the Draco Dwarf Spheroidal

We present the first clear evidence for an extended dark matter halo in the Draco dwarf spheroidal galaxy based on a sample of new radial velocities for 159 giant stars out to large projected radii. Using a two parameter family of halo models spanning a range of density profiles and velocity anisotropies, we are able to rule out (at about the 2.5 sigma confidence level) haloes in which mass follows light. The data strongly favor models in which the dark matter is significantly more extended than the visible dwarf. However, haloes with harmonic cores larger than the light distribution are also excluded. When combined with existing measurements of the proper motion of Draco, our data strongly suggest that Draco has not been tidally truncated within ~1 kpc. We also show that the rising velocity dispersion at large radii represents a serious problem for modified gravity (MOND).Comment: to be published in ApJL; 5 pages, 4 figure

Reclaiming the political : emancipation and critique in security studies

The critical security studies literature has been marked by a shared commitment towards the politicization of security – that is, the analysis of its assumptions, implications and the practices through which it is (re)produced. In recent years, however, politicization has been accompanied by a tendency to conceive security as connected with a logic of exclusion, totalization and even violence. This has resulted in an imbalanced politicization that weakens critique. Seeking to tackle this situation, the present article engages with contributions that have advanced emancipatory versions of security. Starting with, but going beyond, the so-called Aberystwyth School of security studies, the argument reconsiders the meaning of security as emancipation by making the case for a systematic engagement with the notions of reality and power. This revised version of security as emancipation strengthens critique by addressing political dimensions that have been underplayed in the critical security literature

Desensitization of Gonadotropin-releasing Hormone Action in αT3-1 Cells Due to Uncoupling of Inositol 1,4,5-Trisphosphate Generation and Ca 2+ Mobilization

Gonadotropin-releasing hormone (GnRH) acts via a G-protein coupled receptor on gonadotropes to increase cytosolic Ca2+ and stimulate gonadotropin secretion. Sustained exposure causes desensitization of these effects, but the GnRH receptor has no C-terminal tail and does not undergo rapid (<5 min) desensitization. Nevertheless, pretreatment of alphaT3-1 cells with GnRH reduced the spike Ca2+ response to GnRH and decreased the GnRH effect on inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) by 30-50%. Ca2+-free medium with or without thapsigargin also decreased GnRH-stimulated Ins(1,4,5)P3 generation, implying that attenuation of the Ca2+ response underlies the Ins(1,4,5)P3 reduction rather than vice versa. Intracellular Ca2+ pool depletion cannot explain desensitization of the Ca2+ response because pool depletion and repletion were faster (half-times, <1 min) than the onset of and recovery from desensitization (half-times 10-20 min and 4-6 h). Moreover, 1-h GnRH pre-treatment attenuated the spike Ca2+ response to GnRH but not that to ionomycin, and brief GnRH exposure in Ca2+-free medium reduced the response to ionomycin more effectively in controls than in desensitized cells. GnRH pretreatment also attenuated the Ca2+ response to PACAP38. This novel form of desensitization does not reflect uncoupling of GnRH receptors from their immediate effector system but rather a reduced efficiency of mobilization by Ins(1,4,5)P3 of Ca2+ from an intact intracellular pool

Exacerbated inflammatory arthritis in response to hyperactive gp130 signalling is independent of IL-17A

Objective Interleukin (IL)-17A producing CD4 T-cells (TH-17 cells) are implicated in rheumatoid arthritis (RA). IL-6/STAT3 signalling drives TH-17 cell differentiation, and hyperactive gp130/STAT3 signalling in the gp130F/F mouse promotes exacerbated pathology. Conversely, STAT1-activating cytokines (eg, IL-27, IFN-γ) inhibit TH-17 commitment. Here, we evaluate the impact of STAT1 ablation on TH-17 cells during experimental arthritis and relate this to IL-17A-associated pathology. Methods Antigen-induced arthritis (AIA) was established in wild type (WT), gp130F/F mice displaying hyperactive gp130-mediated STAT signalling and the compound mutants gp130F/F:Stat1−/− and gp130F/F: Il17a−/− mice. Joint pathology and associated peripheral TH-17 responses were compared. Results Augmented gp130/STAT3 signalling enhanced TH-17 commitment in vitro and exacerbated joint pathology. Ablation of STAT1 in gp130F/F mice (gp130F/F: Stat1−/− ) promoted the hyperexpansion of TH-17 cells in vitro and in vivo during AIA. Despite this heightened peripheral TH-17 cell response, disease severity and the number of joint-infiltrating T-cells were comparable with that of WT mice. Thus, gp130-mediated STAT1 activity within the inflamed synovium controls T-cell trafficking and retention. To determine the contribution of IL-17A, we generated gp130F/F:IL-17a−/− mice. Here, loss of IL-17A had no impact on arthritis severity. Conclusions Exacerbated gp130/STAT-driven disease in AIA is associated with an increase in joint infiltrating T-cells but synovial pathology is IL-17A independent

Racism, crisis, Brexit

This article offers a conjunctural analysis of the financial and political crisis within which Brexit occurred with a specific attentiveness to race and racism. Brexit and its aftermath have been overdetermined by racism, including racist violence. We suggest that the Leave campaign secured its victory by bringing together two contradictory but interlocking visions. The first comprises an imperial longing to restore Britain’s place in the world as primus inter pares that occludes any coming to terms with the corrosive legacies of colonial conquest and racist subjugation. The second takes the form of an insular, Powellite narrative of island retreat from a ‘globalising’ world, one that is no longer recognisably ‘British’. Further, the article argues that an invisible driver of the Brexit vote and its racist aftermath has been a politicization of Englishness. We conclude by outlining some resources of hope that could potentially help to negotiate the current emergency

Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial

BACKGROUND: Antibiotic-associated diarrhoea (AAD) occurs most frequently in older (≥65 years) inpatients exposed to broad-spectrum antibiotics. When caused by Clostridium difficile, AAD can result in life-threatening illness. Although underlying disease mechanisms are not well understood, microbial preparations have been assessed in the prevention of AAD. However, studies have been mostly small single-centre trials with varying quality, providing insufficient data to reliably assess effectiveness. We aimed to do a pragmatic efficacy trial in older inpatients who would be representative of those admitted to National Health Service (NHS) and similar secondary care institutions and to recruit a sufficient number of patients to generate a definitive result. METHODS: We did a multicentre, randomised, double-blind, placebo-controlled, pragmatic, efficacy trial of inpatients aged 65 years and older and exposed to one or more oral or parenteral antibiotics. A computer-generated randomisation scheme was used to allocate participants (in a 1:1 ratio) to receive either a multistrain preparation of lactobacilli and bifidobacteria, with a total of 6 × 10(10) organisms, one per day for 21 days, or an identical placebo. Patients, study staff, and specimen and data analysts were masked to assignment. The primary outcomes were occurrence of AAD within 8 weeks and C difficile diarrhoea (CDD) within 12 weeks of recruitment. Analysis was by modified intention-to-treat. This trial is registered, number ISRCTN70017204. FINDINGS: Of 17,420 patients screened, 1493 were randomly assigned to the microbial preparation group and 1488 to the placebo group. 1470 and 1471, respectively, were included in the analyses of the primary endpoints. AAD (including CDD) occurred in 159 (10·8%) participants in the microbial preparation group and 153 (10·4%) participants in the placebo group (relative risk [RR] 1·04; 95% CI 0·84-1·28; p=0·71). CDD was an uncommon cause of AAD and occurred in 12 (0·8%) participants in the microbial preparation group and 17 (1·2%) participants in the placebo group (RR 0·71; 95% CI 0·34-1·47; p=0·35). 578 (19·7%) participants had one or more serious adverse event; the frequency of serious adverse events was much the same in the two study groups and none was attributed to participation in the trial. INTERPRETATION: We identified no evidence that a multistrain preparation of lactobacilli and bifidobacteria was effective in prevention of AAD or CDD. An improved understanding of the pathophysiology of AAD is needed to guide future studies. FUNDING: Health Technology Assessment programme; National Institute for Health Research, UK

The Local Group dwarf Leo T: HI on the brink of star formation

We present Giant Meterwave Radio Telescope (GMRT) and Westerbork ynthesis Radio Telescope (WSRT) observations of the recently discovered Local Group dwarf galaxy, Leo T. The peak HI column density is measured to be 7x10^20 cm^-2, and the total HI mass is 2.8Xx10^5 Msun, based on a distance of 420 kpc. Leo T has both cold (~ 500 K) and warm (~ 6000 K) HI at its core, with a global velocity dispersion of 6.9 km/s, from which we derive a dynamical mass within the HI radius of 3.3x10^6 Msun, and a mass-to-light ratio of greater than 50. We calculate the Jeans mass from the radial profiles of the HI column density and velocity dispersion, and predict that the gas should be globally stable against star formation. This finding is inconsistent with the half light radius of Leo T, which extends to 170 pc, and indicates that local conditions must determine where star formation takes place. Leo T is not only the lowest luminosity galaxy with on-going star formation discovered to date, it is also the most dark matter dominated, gas-rich dwarf in the Local Group.Comment: 6 pages, 7 figures, accepted for publication in MNRAS on November 15th 2007, full resolution version at: http://www.ast.cam.ac.uk/~eryan/leot.pdf . Typographical error in sound speed equation has led to a new Figure 6 and minor changes to the tex

Star Counts and the Warped and Flaring Milky Way Disk

This paper reports the star count predictions of warped and flaring models of the outer Milky Way disk. These have been suggested as possible locations of the lenses responsible for the microlensing events towards the Large Magellanic Cloud (LMC). Three such models are investigated in detail and the theoretical predictions are confronted with {\it Hubble Space Telescope} (HST) star count data in 7 low latitude fields ($30^\circ < | b| < 40^\circ$). If the warped and flaring disk population has the same characteristics as disk stars in the solar neighbourhood, then the models can be unambiguously ruled out. Metallicity gradients are well-known in disk galaxies and may cause the outer disk population to differ in colors and luminosity from that locally. This effect is studied using a simple ansatz for the variation in the color-magnitude relation with position and while it is shown to lead to better agreement with the star counts, upper limits on the contribution of the warped and flaring disk to the optical depth are still below the value measured towards the LMC. Only if the warp is very asymmetric or if the luminosity function changes strongly with Galactocentric radius can the models be made consistent with the starcounts.Comment: 15 pages, submitted to Ap