Exacerbation of signs and symptoms of allergic conjunctivitis by a controlled adverse environment challenge in subjects with a history of dry eye and ocular allergy

Background: The goal of this study was to assess the effect of a controlled adverse environment (CAE) challenge on subjects with both allergic conjunctivitis and dry eye. Methods: Thirty-three subjects were screened and 17 completed this institutional review board-approved study. Subjects underwent baseline ocular assessments and conjunctival allergen challenge (CAC) on days 0 and 3. Those who met the ocular redness and itching criteria were randomized to receive either the controlled adverse environment (CAE) challenge (group A, n = 9) or no challenge (group B, n = 8) at day 6. Thirty minutes after CAE/no-CAE, subjects were challenged with allergen and their signs and symptoms graded. Exploratory confocal microscopy was carried out in a subset of subjects at hourly intervals for 5 hours post-CAC on days 3 and 6. Results: Seven minutes post-CAC, subjects exposed to the CAE had significantly greater itching (difference between groups, 0.55 ± 0.25, P = 0.028), conjunctival redness (0.59 ± 0.19, P = 0.002), episcleral redness (0.56 ± 0.19, P = 0.003) and mean overall redness (mean of conjunctival, episcleral, and ciliary redness, 0.59 ± 0.14, P < 0.001). The mean score at 7, 15, and 20 minutes post-CAC for conjunctival redness (0.43 ± 0.17, P = 0.012), episcleral redness (0.49 ± 0.15, P = 0.001), mean overall redness in all regions (0.43 ± 0.15, P = 0.005), and mean chemosis (0.20 ± 0.08, P = 0.017) were also all significantly greater in CAE-treated subjects. Confocal microscopic images of conjunctival vessels after CAC showed more inflammation in CAE-treated subjects. Conclusion: In subjects with both dry eye and allergic conjunctivitis, exposure to adverse environmental conditions causes an ocular surface perturbation that can intensify allergic reactions

Welfare, work, and the conditions of social solidarity: British campaigns to defend healthcare and social security

When the welfare state is under attack from neoliberal reformers, how can trade unionists and other campaigners build solidarity to defend it? Based on 45 qualitative interviews, this article compares campaigns to defend British health services and social security benefits between 2007 and 2016. Building on the macro-insights of comparative welfare-state literature and the more micro-level insights of studies on mobilisation, community unionism, and union strategy, we examine the effects of welfare-state architectures on the building of solidarity. We find that building solidarity is more difficult when defending targeted benefits than universal ones, not only because of differences in public opinion and political support for services, but also because the labour process associated with targeting benefits, namely the assessing and sanctioning of clients, can generate conflicts among campaigners

Removing krypton from xenon by cryogenic distillation to the ppq level

The XENON1T experiment aims for the direct detection of dark matter in a cryostat filled with 3.3 tons of liquid xenon. In order to achieve the desired sensitivity, the background induced by radioactive decays inside the detector has to be sufficiently low. One major contributor is the $\beta$-emitter $^{85}$Kr which is an intrinsic contamination of the xenon. For the XENON1T experiment a concentration of natural krypton in xenon $\rm{^{nat}}$Kr/Xe < 200 ppq (parts per quadrillion, 1 ppq = 10$^{-15}$ mol/mol) is required. In this work, the design of a novel cryogenic distillation column using the common McCabe-Thiele approach is described. The system demonstrated a krypton reduction factor of 6.4$\cdot$10$^5$ with thermodynamic stability at process speeds above 3 kg/h. The resulting concentration of $\rm{^{nat}}$Kr/Xe < 26 ppq is the lowest ever achieved, almost one order of magnitude below the requirements for XENON1T and even sufficient for future dark matter experiments using liquid xenon, such as XENONnT and DARWIN

Specific involvement of atypical PKCζ/PKMζ in spinal persistent nociceptive processing following peripheral inflammation in rat.

BACKGROUND: Central sensitization requires the activation of various intracellular signalling pathways within spinal dorsal horn neurons, leading to a lowering of activation threshold and enhanced responsiveness of these cells. Such plasticity contributes to the manifestation of chronic pain states and displays a number of features of long-term potentiation (LTP), a ubiquitous neuronal mechanism of increased synaptic strength. Here we describe the role of a novel pathway involving atypical PKCζ/PKMζ in persistent spinal nociceptive processing, previously implicated in the maintenance of late-phase LTP. RESULTS: Using both behavioral tests and in vivo electrophysiology in rats, we show that inhibition of this pathway, via spinal delivery of a myristoylated protein kinase C-ζ pseudo-substrate inhibitor, reduces both pain-related behaviors and the activity of deep dorsal horn wide dynamic range neurons (WDRs) following formalin administration. In addition, Complete Freund's Adjuvant (CFA)-induced mechanical and thermal hypersensitivity was also reduced by inhibition of PKCζ/PKMζ activity. Importantly, this inhibition did not affect acute pain or locomotor behavior in normal rats and interestingly, did not inhibited mechanical allodynia and hyperalgesia in neuropathic rats. Pain-related behaviors in both inflammatory models coincided with increased phosphorylation of PKCζ/PKMζ in dorsal horn neurons, specifically PKMζ phosphorylation in formalin rats. Finally, inhibition of PKCζ/PKMζ activity decreased the expression of Fos in response to formalin and CFA in both superficial and deep laminae of the dorsal horn. CONCLUSIONS: These results suggest that PKCζ, especially PKMζ isoform, is a significant factor involved in spinal persistent nociceptive processing, specifically, the manifestation of chronic pain states following peripheral inflammation

Cross section ratio and angular distributions of the reaction p + d -> 3He + eta at 48.8 MeV and 59.8 MeV excess energy

We present new data for angular distributions and on the cross section ratio of the p + d -> 3He + eta reaction at excess energies of Q = 48.8 MeV and Q = 59.8 MeV. The data have been obtained at the WASA-at-COSY experiment (Forschungszentrum J\"ulich) using a proton beam and a deuterium pellet target. While the shape of obtained angular distributions show only a slow variation with the energy, the new results indicate a distinct and unexpected total cross section fluctuation between Q = 20 MeV and Q = 60 MeV, which might indicate the variation of the production mechanism within this energy interval.Comment: 9 pages, 9 figure

Intracellular mGluR5 plays a critical role in neuropathic pain

Spinal mGluR5 is a key mediator of neuroplasticity underlying persistent pain. Although brain mGluR5 is localized on cell surface and intracellular membranes, neither the presence nor physiological role of spinal intracellular mGluR5 is established. Here we show that in spinal dorsal horn neurons >80% of mGluR5 is intracellular, of which ∼60% is located on nuclear membranes, where activation leads to sustained Ca(2+) responses. Nerve injury inducing nociceptive hypersensitivity also increases the expression of nuclear mGluR5 and receptor-mediated phosphorylated-ERK1/2, Arc/Arg3.1 and c-fos. Spinal blockade of intracellular mGluR5 reduces neuropathic pain behaviours and signalling molecules, whereas blockade of cell-surface mGluR5 has little effect. Decreasing intracellular glutamate via blocking EAAT-3, mimics the effects of intracellular mGluR5 antagonism. These findings show a direct link between an intracellular GPCR and behavioural expression in vivo. Blockade of intracellular mGluR5 represents a new strategy for the development of effective therapies for persistent pain

Evidence for a New Resonance from Polarized Neutron-Proton Scattering

Exclusive and kinematically complete high-statistics measurements of quasifree polarized $\vec{n}p$ scattering have been performed in the energy region of the narrow resonance structure $d^*$ with $I(J^P) = 0(3^+)$, $M \approx$ 2380 MeV/$c^2$ and $\Gamma \approx$ 70 MeV observed recently in the double-pionic fusion channels $pn \to d\pi^0\pi^0$ and $pn \to d\pi^+\pi^-$. The experiment was carried out with the WASA detector setup at COSY having a polarized deuteron beam impinged on the hydrogen pellet target and utilizing the quasifree process $\vec{d}p \to np + p_{spectator}$. That way the $np$ analyzing power $A_y$ was measured over a large angular range. The obtained $A_y$ angular distributions deviate systematically from the current SAID SP07 NN partial-wave solution. Incorporating the new $A_y$ data into the SAID analysis produces a pole in the $^3D_3 - ^3G_3$ waves as expected from the $d^*$ resonance hypothesis

Measurement of the pn→ppπ0π−pn \to pp\pi^0\pi^- Reaction in Search for the Recently Observed Resonance Structure in dπ0π0d\pi^0\pi^0 and dπ+π−d\pi^+\pi^- systems

Exclusive measurements of the quasi-free $pn \to pp\pi^0\pi^-$ reaction have been performed by means of $pd$ collisions at $T_p$ = 1.2 GeV using the WASA detector setup at COSY. Total and differential cross sections have been obtained covering the energy region $\sqrt s$ = (2.35 - 2.46) GeV, which includes the region of the ABC effect and its associated resonance structure. No ABC effect, {\it i.e.} low-mass enhancement is found in the $\pi^0\pi^-$-invariant mass spectrum -- in agreement with the constraint from Bose statistics that the isovector pion pair can not be in relative s-wave. At the upper end of the covered energy region $t$-channel processes for Roper, $\Delta(1600)$ and $\Delta\Delta$ excitations provide a reasonable description of the data, but at low energies the measured cross sections are much larger than predicted by such processes. Adding a resonance amplitude for the resonance at $m$=~2.37 GeV with $\Gamma$ =~70 MeV and $I(J^P)=~0(3^+)$ observed recently in $pn \to d\pi^0\pi^0$ and $pn \to d\pi^+\pi^-$ reactions leads to an agreement with the data also at low energies