Interventions for hand eczema

BackgroundHand eczema is an inflammation of the skin of the hands that tends to run a chronic, relapsing course. This common condition is often associated with itch, social stigma, and impairment in employment. Many different interventions of unknown effectiveness are used to treat hand eczema.ObjectivesTo assess the effects of topical and systemic interventions for hand eczema in adults and children.Search methodsWe searched the following up to April 2018: Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, AMED, LILACS, GREAT, and four trials registries. We checked the reference lists of included studies for further references to relevant trials.Selection criteriaWe included randomised controlled trials (RCTs) that compared interventions for hand eczema, regardless of hand eczema type and other affected sites, versus no treatment, placebo, vehicle, or active treatments.Data collection and analysisWe used standard methodological procedures expected by Cochrane. Primary outcomes were participant‐ and investigator‐rated good/excellent control of symptoms, and adverse events.Main resultsWe included 60 RCTs, conducted in secondary care (5469 participants with mild to severe chronic hand eczema). Most participants were over 18 years old. The duration of treatment was short, generally up to four months. Only 24 studies included a follow‐up period. Clinical heterogeneity in treatments and outcome measures was evident. Few studies performed head‐to‐head comparisons of different interventions. Risk of bias varied considerably, with only five studies at low risk in all domains. Twenty‐two studies were industry‐funded.Eighteen trials studied topical corticosteroids or calcineurin inhibitors; 10 studies, phototherapy; three studies, systemic immunosuppressives; and five studies, oral retinoids. Most studies compared an active intervention against no treatment, variants of the same medication, or placebo (or vehicle). Below, we present results from the main comparisons.Corticosteroid creams/ointments: when assessed 15 days after the start of treatment, clobetasol propionate 0.05% foam probably improves participant‐rated control of symptoms compared to vehicle (risk ratio (RR) 2.32, 95% confidence interval (CI) 1.38 to 3.91; number needed to treat for an additional beneficial outcome (NNTB) 3, 95% CI 2 to 8; 1 study, 125 participants); the effect of clobetasol compared to vehicle for investigator‐rated improvement is less clear (RR 1.43, 95% CI 0.86 to 2.40). More participants had at least one adverse event with clobetasol (11/62 versus 5/63; RR 2.24, 95% CI 0.82 to 6.06), including application site burning/pruritus. This evidence was rated as moderate certainty.When assessed 36 weeks after the start of treatment, mometasone furoate cream used thrice weekly may slightly improve investigator‐rated symptom control compared to twice weekly (RR 1.23, 95% CI 0.94 to 1.61; 1 study, 72 participants) after remission is reached. Participant‐rated symptoms were not measured. Some mild atrophy was reported in both groups (RR 1.76, 95% CI 0.45 to 6.83; 5/35 versus 3/37). This evidence was rated as low certainty.Irradiation with ultraviolet (UV) light: local combination ultraviolet light therapy (PUVA) may lead to improvement in investigator‐rated symptom control when compared to local narrow‐band UVB after 12 weeks of treatment (RR 0.50, 95% CI 0.22 to 1.16; 1 study, 60 participants). However, the 95% CI indicates that PUVA might make little or no difference. Participant‐rated symptoms were not measured. Adverse events (mainly erythema) were reported by 9/30 participants in the narrow‐band UVB group versus none in the PUVA group. This evidence was rated as moderate certainty.Topical calcineurin inhibitors: tacrolimus 0.1% over two weeks probably improves investigator‐rated symptom control measured after three weeks compared to vehicle (14/14 tacrolimus versus 0/14 vehicle; 1 study). Participant‐rated symptoms were not measured. Four of 14 people in the tacrolimus group versus zero in the vehicle group had well‐tolerated application site burning/itching.A within‐participant study in 16 participants compared 0.1% tacrolimus to 0.1% mometasone furoate but did not measure investigator‐ or participant‐rated symptoms. Both treatments were well tolerated when assessed at two weeks during four weeks of treatment.Evidence from these studies was rated as moderate certainty.Oral interventions: oral cyclosporin 3 mg/kg/d probably slightly improves investigator‐rated (RR 1.88, 95% CI 0.88 to 3.99; 1 study, 34 participants) or participant‐rated (RR 1.25, 95% CI 0.69 to 2.27) control of symptoms compared to topical betamethasone dipropionate 0.05% after six weeks of treatment. The risk of adverse events such as dizziness was similar between groups (up to 36 weeks; RR 1.22, 95% CI 0.80 to 1.86, n = 55; 15/27 betamethasone versus 19/28 cyclosporin). The evidence was rated as moderate certainty.Alitretinoin 10 mg improves investigator‐rated symptom control compared with placebo (RR 1.58, 95% CI 1.20 to 2.07; NNTB 11, 95% CI 6.3 to 26.5; 2 studies, n = 781) and alitretinoin 30 mg also improves this outcome compared with placebo (RR 2.75, 95% CI 2.20 to 3.43; NNTB 4, 95% CI 3 to 5; 2 studies, n = 1210). Similar results were found for participant‐rated symptom control: alitretinoin 10 mg RR 1.73 (95% CI 1.25 to 2.40) and 30 mg RR 2.75 (95% CI 2.18 to 3.48). Evidence was rated as high certainty. The number of adverse events (including headache) probably did not differ between alitretinoin 10 mg and placebo (RR 1.01, 95% CI 0.66 to 1.55; 1 study, n = 158; moderate‐certainty evidence), but the risk of headache increased with alitretinoin 30 mg (RR 3.43, 95% CI 2.45 to 4.81; 2 studies, n = 1210; high‐certainty evidence). Outcomes were assessed between 48 and 72 weeks.Authors' conclusionsMost findings were from single studies with low precision, so they should be interpreted with caution. Topical corticosteroids and UV phototherapy were two of the major standard treatments, but evidence is insufficient to support one specific treatment over another. The effect of topical calcineurin inhibitors is not certain. Alitretinoin is more effective than placebo in controlling symptoms, but advantages over other treatments need evaluating.Well‐designed and well‐reported, long‐term (more than three months), head‐to‐head studies comparing different treatments are needed. Consensus is required regarding the definition of hand eczema and its subtypes, and a standard severity scale should be established.The main limitation was heterogeneity between studies. Small sample size impacted our ability to detect differences between treatments

Generation of Long-Lived Isomeric States via Bremsstrahlung Irradiation

A method to generate long-lived isomeric states effectively for Mossbauer applications is reported. We demonstrate that this method is better and easier to provide highly sensitive Mossbauer effect of long-lived isomers (>1ms) such as 103Rh. Excitation of (gamma,gamma) process by synchrotron radiation is painful due mainly to their limited linewidth. Instead,(gamma,gamma') process of bremsstrahlung excitation is applied to create these long-lived isomers. Isomers of 45Sc, 107Ag, 109Ag, and 103Rh have been generated from this method. Among them, 103Rh is the only one that we have obtained the gravitational effect at room temperature.Comment: ICAME 05 conference repor

Modeling electrolytically top gated graphene

We investigate doping of a single-layer graphene in the presence of electrolytic top gating. The interfacial phenomena is modeled using a modified Poisson-Boltzmann equation for an aqueous solution of simple salt. We demonstrate both the sensitivity of graphene's doping levels to the salt concentration and the importance of quantum capacitance that arises due to the smallness of the Debye screening length in the electrolyte.Comment: 7 pages, including 4 figures, submitted to Nanoscale Research Letters for a special issue related to the NGC 2009 conference (http://asdn.net/ngc2009/index.shtml

Are galaxy distributions scale invariant? A perspective from dynamical systems theory

Unless there is evidence for fractal scaling with a single exponent over distances .1 <= r <= 100 h^-1 Mpc then the widely accepted notion of scale invariance of the correlation integral for .1 <= r <= 10 h^-1 Mpc must be questioned. The attempt to extract a scaling exponent \nu from the correlation integral n(r) by plotting log(n(r)) vs. log(r) is unreliable unless the underlying point set is approximately monofractal. The extraction of a spectrum of generalized dimensions \nu_q from a plot of the correlation integral generating function G_n(q) by a similar procedure is probably an indication that G_n(q) does not scale at all. We explain these assertions after defining the term multifractal, mutually--inconsistent definitions having been confused together in the cosmology literature. Part of this confusion is traced to a misleading speculation made earlier in the dynamical systems theory literature, while other errors follow from confusing together entirely different definitions of ``multifractal'' from two different schools of thought. Most important are serious errors in data analysis that follow from taking for granted a largest term approximation that is inevitably advertised in the literature on both fractals and dynamical systems theory.Comment: 39 pages, Latex with 17 eps-files, using epsf.sty and a4wide.sty (included) <[email protected]

Targeting the Stress-Induced Protein NUPR1 to Treat Pancreatic Adenocarcinoma

Cancer cells activate stress-response mechanisms to adapt themselves to a variety of stressful conditions. Among these protective mechanisms, those controlled by the stress-induced nuclear protein 1 (NUPR1 ) belong to the most conserved ones. NUPR1 is an 82-residue-long, monomeric, basic and intrinsically disordered protein (IDP), which was found to be invariably overexpressed in some, if not all, cancer tissues. Remarkably, we and others have previously showed that genetic inactivation of the Nupr1 gene antagonizes the growth of pancreatic cancer as well as several other tumors. With the use of a multidisciplinary strategy by combining biophysical, biochemical, bioinformatic, and biological approaches, a trifluoperazine-derived compound, named ZZW-115, has been identified as an inhibitor of the NUPR1 functions. The anticancer activity of the ZZW-115 was first validated on a large panel of cancer cells. Furthermore, ZZW-115 produced a dose-dependent tumor regression of the tumor size in xenografted mice. Mechanistically, we have demonstrated that NUPR1 binds to several importins. Because ZZW-115 binds NUPR1 through the region around the amino acid Thr68, which is located into the nuclear location signal (NLS) region of the protein, we demonstrated that treatment with ZZW-115 inhibits completely the translocation of NUPR1 from the cytoplasm to the nucleus by competing with importins

Streamer Wave Events Observed in Solar Cycle 23

In this paper we conduct a data survey searching for well-defined streamer wave events observed by the Large Angle and Spectrometric Coronagraph (LASCO) on-board the Solar and Heliospheric Observatory (SOHO) throughout Solar Cycle 23. As a result, 8 candidate events are found and presented here. We compare different events and find that in most of them the driving CMEs ejecta are characterized by a high speed and a wide angular span, and the CME-streamer interactions occur generally along the flank of the streamer structure at an altitude no higher than the bottom of the field of view of LASCO C2. In addition, all front-side CMEs have accompanying flares. These common observational features shed light on the excitation conditions of streamer wave events. We also conduct a further analysis on one specific streamer wave event on 5 June 2003. The heliocentric distances of 4 wave troughs/crests at various exposure times are determined; they are then used to deduce the wave properties like period, wavelength, and phase speeds. It is found that both the period and wavelength increase gradually with the wave propagation along the streamer plasma sheet, and the phase speed of the preceding wave is generally faster than that of the trailing ones. The associated coronal seismological study yields the radial profiles of the Alfv\'en speed and magnetic field strength in the region surrounding the streamer plasma sheet. Both quantities show a general declining trend with time. This is interpreted as an observational manifestation of the recovering process of the CME-disturbed corona. It is also found that the Alfv\'enic critical point is at about 10 R$_\odot$ where the flow speed, which equals the Alfv\'en speed, is $\sim$ 200 km s$^{-1}$

Effects and Detectability of Quasi-Single Field Inflation in the Large-Scale Structure and Cosmic Microwave Background

Quasi-single field inflation predicts a peculiar momentum dependence in the squeezed limit of the primordial bispectrum which smoothly interpolates between the local and equilateral models. This dependence is directly related to the mass of the isocurvatons in the theory which is determined by the supersymmetry. Therefore, in the event of detection of a non-zero primordial bispectrum, additional constraints on the parameter controlling the momentum-dependence in the squeezed limit becomes an important question. We explore the effects of these non-Gaussian initial conditions on large-scale structure and the cosmic microwave background, with particular attention to the galaxy power spectrum at large scales and scale-dependence corrections to galaxy bias. We determine the simultaneous constraints on the two parameters describing the QSF bispectrum that we can expect from upcoming large-scale structure and cosmic microwave background observations. We find that for relatively large values of the non-Gaussian amplitude parameters, but still well within current uncertainties, galaxy power spectrum measurements will be able to distinguish the QSF scenario from the predictions of the local model. A CMB likelihood analysis, as well as Fisher matrix analysis, shows that there is also a range of parameter values for which Planck data may be able distinguish between QSF models and the related local and equilateral shapes. Given the different observational weightings of the CMB and LSS results, degeneracies can be significantly reduced in a joint analysis.Comment: 27 pages, 14 figure

On the Global Existence of Bohmian Mechanics

We show that the particle motion in Bohmian mechanics, given by the solution of an ordinary differential equation, exists globally: For a large class of potentials the singularities of the velocity field and infinity will not be reached in finite time for typical initial values. A substantial part of the analysis is based on the probabilistic significance of the quantum flux. We elucidate the connection between the conditions necessary for global existence and the self-adjointness of the Schr\"odinger Hamiltonian.Comment: 35 pages, LaTe

Local stochastic non-Gaussianity and N-body simulations

Large-scale clustering of highly biased tracers of large-scale structure has emerged as one of the best observational probes of primordial non-Gaussianity of the local type (i.e. f_{NL}^{local}). This type of non-Gaussianity can be generated in multifield models of inflation such as the curvaton model. Recently, Tseliakhovich, Hirata, and Slosar showed that the clustering statistics depend qualitatively on the ratio of inflaton to curvaton power \xi after reheating, a free parameter of the model. If \xi is significantly different from zero, so that the inflaton makes a non-negligible contribution to the primordial adiabatic curvature, then the peak-background split ansatz predicts that the halo bias will be stochastic on large scales. In this paper, we test this prediction in N-body simulations. We find that large-scale stochasticity is generated, in qualitative agreement with the prediction, but that the level of stochasticity is overpredicted by ~30%. Other predictions, such as \xi independence of the halo bias, are confirmed by the simulations. Surprisingly, even in the Gaussian case we do not find that halo model predictions for stochasticity agree consistently with simulations, suggesting that semi-analytic modeling of stochasticity is generally more difficult than modeling halo bias.Comment: v3: minor changes matching published versio

A Statistical Study on the Morphology of Rays and Dynamics of Blobs in the Wake of Coronal Mass Ejections

In this paper, with a survey through the Large Angle and Spectrometric Coronagraph (LASCO) data from 1996 to 2009, we present 11 events with plasma blobs flowing outwards sequentially along a bright coronal ray in the wake of a coronal mass ejection. The ray is believed to be associated with the current sheet structure that formed as a result of solar eruption, and the blobs are products of magnetic reconnection occurring along the current sheet. The ray morphology and blob dynamics are investigated statistically. It is found that the apparent angular widths of the rays at a fixed time vary in a range of 2.1-6.6 (2.0-4.4) degrees with an average of 3.5 (2.9) degrees at 3 (4) Rs, respectively, and the observed durations of the events vary from 12 h to a few days with an average of 27 h. It is also found, based on the analysis of blob motions, that 58% (26) of the blobs were accelerated, 20% (9) were decelerated, and 22% (10) moved with a nearly-constant speed. Comparing the dynamics of our blobs and those that are observed above the tip of a helmet streamer, we find that the speeds and accelerations of the blobs in these two cases differ significantly. It is suggested that these differences of the blob dynamics stem from the associated magnetic reconnection involving different magnetic field configurations and triggering processes.Comment: 12 pages, 6 figures, accepted by Solar Physic