Psychosocial burden in adult patients with atopic dermatitis

P16 Objective: Atopic dermatitis affects patients’ quality of life (QoL) in many ways. It is important to analyze the impact that the disease produces in order to better define the healthcare needs of adult patients with atopic dermatitis. Patients and Methods: 14 adult patients with atopic dermatitis were interviewed. The qualitative interviews were semi-structured and supported by a simple script, which allowed a complete and flexible interview. Results: Six affected areas of the patient’s life with atopic dermatitis were identified: economic, work-related, personal, psychosocial, clinical and relational. It is emphasized that atopic dermatitis has a great psychosocial impact on the adult patient, since it alters interpersonal relationships, generates rejection, stigmatization and social isolation, limits the patient in various areas and activities of their daily life or alters sleep, among others. The visible aspect, the itching-scratching cycle, the lack of awareness and ignorance of the disease, the lack of a definitive solution among the treatments and the side effects of some of them are of great concern. Conclusions: The QoL of the patients with atopic dermatitis is negatively affected and a holistic multidisciplinary intervention is necessary in order to mitigate the negative impact of the disease

Quality of life in hidradenitis suppurativa: psychometric properties of HSQOL-24

P14 Introduction: Hidradenitis Suppurativa (HS) has been associated with impaired quality of life (QoL). There are various measuring systems to assess physical severity; however, there are no specific QoL questionnaires for this disease in the Spanish language. Objective: To develop and validate a disease-specific instrument to measure QoL in patients with HS. Methods: A literature search was carried out to prepare a semi structured interview for patients with HS, as well as a Delphi expert consensus among health professionals. The validation with a sample of 130 patients is presented. The preliminary validation of the HSQoL-24 was passed twice to a group of 30 patients with 30 ± 10 days of interval. The DLQI and the Skindex-29 were used for its validation. Results: Cronbach alpha 0.87 indicates a good internal consistency of the questionnaire. The intraclass correlation coefficient (ICC) with the DLQI was 0.70 (p-value) (< 0.001), and 0.87 (p-value) (< 0.001) with the Skindex-29. Conclusions: The HSQoL-24 is the first specific self-administered questionnaire to assess QoL in patients with HS in Spanish. It is user friendly and easy to. This study demonstrates the excellent properties of the instrument: comprehensibility, reliability (test-retest), internal consistency, validity, comparison with DLQI and SKINDEX-29, and discriminative capacity

Suppression of decoherence in quantum registers by entanglement with a nonequilibrium environment

It is shown that a nonequilibrium environment can be instrumental in suppressing decoherence between distinct decoherence free subspaces in quantum registers. The effect is found in the framework of exact coherent-product solutions for model registers decohering in a bath of degenerate harmonic modes, through couplings linear in bath coordinates. These solutions represent a natural nonequilibrium extension of the standard solution for a decoupled initial register state and a thermal environment. Under appropriate conditions, the corresponding reduced register distribution can propagate in an unperturbed manner, even in the presence of entanglement between states belonging to distinct decoherence free subspaces, and despite persistent bath entanglement. As a byproduct, we also obtain a refined picture of coherence dynamics under bang-bang decoherence control. In particular, it is shown that each radio-frequency pulse in a typical bang-bang cycle induces a revival of coherence, and that these revivals are exploited in a natural way by the time-symmetrized version of the bang-bang protocol.Comment: RevTex3, 26 pgs., 2 figs.. This seriously expanded version accepted by Phys.Rev.A. No fundamentally new content, but rewritten introduction to problem, self-contained introduction of thermal coherent-product states in standard operator formalism, examples of zero-temperature decoherence free Davydov states. Also fixed a typo that propagated into an interpretational blunder in old Sec.3 [fortunately of no consequence

Patient reported outcomes (PROS) in psoriasis patients

P20 Introduction: Psoriasis is a chronic skin disease with negative physical, mental and social manifestations. Method: We carried out a longitudinal and prospective study under routine clinical practice conditions. The objective of the study was to measure quality of life with the Short Form-36 Survey (SF-36) and correlate the results with clinical variables using the PASI and BSA in a group of 17 patients with moderate to severe psoriasis treated with Ustekinumab. Results: In the baseline evaluation we observed the following results: 35.3% reported physical malfunction, 64.7% debilitating pain, 82.3% poor health in general, 76.4% bad vitality, 88.2% social malfunction, 100% emotional malfunction and 82.3% poor mental health. At week 78 we observed the following results: 41.15% reported very good physical functioning, 76.1% no pain, 58.8% good general health, 58.8% very good vitality, 70%, 5% good social functioning, 70.5% good emotional functioning and 52.9% good mental health. Conclusion: We observed that the perception of patients with moderate-severe psoriasis regarding their health at the beginning of treatment with Ustekinumab was poor and that they experienced a significant improvement throughout the successive weeks of treatment

Theory of Decoherence-Free Fault-Tolerant Universal Quantum Computation

Universal quantum computation on decoherence-free subspaces and subsystems (DFSs) is examined with particular emphasis on using only physically relevant interactions. A necessary and sufficient condition for the existence of decoherence-free (noiseless) subsystems in the Markovian regime is derived here for the first time. A stabilizer formalism for DFSs is then developed which allows for the explicit understanding of these in their dual role as quantum error correcting codes. Conditions for the existence of Hamiltonians whose induced evolution always preserves a DFS are derived within this stabilizer formalism. Two possible collective decoherence mechanisms arising from permutation symmetries of the system-bath coupling are examined within this framework. It is shown that in both cases universal quantum computation which always preserves the DFS (*natural fault-tolerant computation*) can be performed using only two-body interactions. This is in marked contrast to standard error correcting codes, where all known constructions using one or two-body interactions must leave the codespace during the on-time of the fault-tolerant gates. A further consequence of our universality construction is that a single exchange Hamiltonian can be used to perform universal quantum computation on an encoded space whose asymptotic coding efficiency is unity. The exchange Hamiltonian, which is naturally present in many quantum systems, is thus *asymptotically universal*.Comment: 40 pages (body: 30, appendices: 3, figures: 5, references: 2). Fixed problem with non-printing figures. New references added, minor typos correcte

Constraints on Dark Matter Annihilation in Clusters of Galaxies with the Fermi Large Area Telescope

Nearby clusters and groups of galaxies are potentially bright sources of high-energy gamma-ray emission resulting from the pair-annihilation of dark matter particles. However, no significant gamma-ray emission has been detected so far from clusters in the first 11 months of observations with the Fermi Large Area Telescope. We interpret this non-detection in terms of constraints on dark matter particle properties. In particular for leptonic annihilation final states and particle masses greater than ~200 GeV, gamma-ray emission from inverse Compton scattering of CMB photons is expected to dominate the dark matter annihilation signal from clusters, and our gamma-ray limits exclude large regions of the parameter space that would give a good fit to the recent anomalous Pamela and Fermi-LAT electron-positron measurements. We also present constraints on the annihilation of more standard dark matter candidates, such as the lightest neutralino of supersymmetric models. The constraints are particularly strong when including the fact that clusters are known to contain substructure at least on galaxy scales, increasing the expected gamma-ray flux by a factor of ~5 over a smooth-halo assumption. We also explore the effect of uncertainties in cluster dark matter density profiles, finding a systematic uncertainty in the constraints of roughly a factor of two, but similar overall conclusions. In this work, we focus on deriving limits on dark matter models; a more general consideration of the Fermi-LAT data on clusters and clusters as gamma-ray sources is forthcoming.Comment: accepted to JCAP, Corresponding authors: T.E. Jeltema and S. Profumo, minor revisions to be consistent with accepted versio

Dysfunctional autophagy induced by the pro-apoptotic natural compound climacostol in tumour cells

Autophagy occurs at a basal level in all eukaryotic cells and may support cell survival or activate death pathways. Due to its pathophysiologic significance, the autophagic machinery is a promising target for the development of multiple approaches for anti-neoplastic agents. We have recently described the cytotoxic and pro-apoptotic mechanisms, targeting the tumour suppressor p53, of climacostol, a natural product of the ciliated protozoan Climacostomum virens. We report here on how climacostol regulates autophagy and the involvement of p53-dependent mechanisms. Using both in vitro and in vivo techniques, we show that climacostol potently and selectively impairs autophagy in multiple tumour cells that are committed to die by apoptosis. In particular, in B16-F10 mouse melanomas climacostol exerts a marked and sustained accumulation of autophagosomes as the result of dysfunctional autophagic degradation. We also provide mechanistic insights showing that climacostol affects autophagosome turnover via p53-AMPK axis, although the mTOR pathway unrelated to p53 levels plays a role. In particular, climacostol activated p53 inducing the upregulation of p53 protein levels in the nuclei through effects on p53 stability at translational level, as for instance the phosphorylation at Ser15 site. Noteworthy, AMPK\u3b1 activation was the major responsible of climacostol-induced autophagy disruption in the absence of a key role regulating cell death, thus indicating that climacostol effects on autophagy and apoptosis are two separate events, which may act independently on life/death decisions of the cell. Since the activation of p53 system is at the molecular crossroad regulating both the anti-autophagic action of climacostol and its role in the apoptosis induction, it might be important to explore the dual targeting of autophagy and apoptosis with agents acting on p53 for the selective killing of tumours. These findings also suggest the efficacy of ciliate bioactive molecules to identify novel lead compounds in drug discovery and development

Proteomic Analysis of Urine Exosomes Reveals Renal Tubule Response to Leptospiral Colonization in Experimentally Infected Rats

BACKGROUND: Infectious Leptospira colonize the kidneys of reservoir (e.g. rats) and accidental hosts such as humans. The renal response to persistent leptospiral colonization, as measured by urinary protein biosignatures, has not been systematically studied. Urinary exosomes--bioactive membrane-bound nanovesicles--contain cell-state specific cargo that additively reflect formation all along the nephron. We hypothesized that Leptospira-infection will alter the content of urine exosomes, and further, that these Leptospira-induced alterations will hold clues to unravel novel pathways related to bacterial-host interactions. METHODOLOGY/PRINCIPAL FINDINGS: Exosome protein content from 24 hour urine samples of Leptospira-infected rats was compared with that of uninfected rats using SDS-PAGE and liquid chromatography/tandem mass spectrometry (LC-MS/MS). Statistical models were used to identify significantly dysregulated proteins in Leptospira-infected and uninfected rat urine exosomes. In all, 842 proteins were identified by LC-MS/MS proteomics of total rat urine and 204 proteins associated specifically with exosomes. Multivariate analysis showed that 25 proteins significantly discriminated between uninfected control and infected rats. Alanyl (membrane) aminopeptidase, also known as CD13 topped this list with the highest score, a finding we validated by Western immunoblotting. Whole urine analysis showed Tamm-Horsfall protein level reduction in the infected rat urine. Total urine and exosome proteins were significantly different in male vs. female infected rats. CONCLUSIONS: We identified exosome-associated renal tubule-specific responses to Leptospira infection in a rat chronic colonization model. Quantitative differences in infected male and female rat urine exosome proteins vs. uninfected controls suggest that urine exosome analysis identifies important differences in kidney function that may be of clinical and pathological significance

Intercalibration of the barrel electromagnetic calorimeter of the CMS experiment at start-up

Calibration of the relative response of the individual channels of the barrel electromagnetic calorimeter of the CMS detector was accomplished, before installation, with cosmic ray muons and test beams. One fourth of the calorimeter was exposed to a beam of high energy electrons and the relative calibration of the channels, the intercalibration, was found to be reproducible to a precision of about 0.3%. Additionally, data were collected with cosmic rays for the entire ECAL barrel during the commissioning phase. By comparing the intercalibration constants obtained with the electron beam data with those from the cosmic ray data, it is demonstrated that the latter provide an intercalibration precision of 1.5% over most of the barrel ECAL. The best intercalibration precision is expected to come from the analysis of events collected in situ during the LHC operation. Using data collected with both electrons and pion beams, several aspects of the intercalibration procedures based on electrons or neutral pions were investigated

Search for supersymmetry with a dominant R-parity violating LQDbar couplings in e+e- collisions at centre-of-mass energies of 130GeV to 172 GeV

A search for pair-production of supersymmetric particles under the assumption that R-parity is violated via a dominant LQDbar coupling has been performed using the data collected by ALEPH at centre-of-mass energies of 130-172 GeV. The observed candidate events in the data are in agreement with the Standard Model expectation. This result is translated into lower limits on the masses of charginos, neutralinos, sleptons, sneutrinos and squarks. For instance, for m_0=500 GeV/c^2 and tan(beta)=sqrt(2) charginos with masses smaller than 81 GeV/c^2 and neutralinos with masses smaller than 29 GeV/c^2 are excluded at the 95% confidence level for any generation structure of the LQDbar coupling.Comment: 32 pages, 30 figure