Efficacy of combined peroxisome proliferator-activated receptor-α ligand and glucocorticoid therapy in a murine model of atopic dermatitis.

Although topical glucocorticoids (GCs) show potent anti-inflammatory activity in inflamed skin, they can also exert numerous harmful effects on epidermal structure and function. In contrast, topical applications of ligands of peroxisome proliferator-activated receptor-α (PPARα) not only reduce inflammation but also improve cutaneous barrier homeostasis. Therefore, we examined whether sequential topical GCs followed by topical Wy14643 (a ligand of PPARα) might be more effective than either alone for atopic dermatitis (AD) in a hapten (oxazolone (Ox))-induced murine model with multiple features of AD (Ox-AD). Despite expected anti-inflammatory benefits, topical GC alone induced (i) epidermal thinning; (ii) reduced expression of involucrin, loricrin, and filaggrin; and (iii) allowed outside-to-inside penetration of an epicutaneous tracer. Although Wy14643 alone yielded significant therapeutic benefits in mice with mild or moderate Ox-AD, it was less effective in severe Ox-AD. Yet, topical application of Wy14643 after GC was not only significantly effective comparable with GC alone, but it also prevented GC-induced structural and functional abnormalities in permeability barrier homeostasis. Moreover, rebound flares were largely absent after sequential treatment with GC and Wy14643. Together, these results show that GC and PPARα ligand therapy together is not only effective but also prevents development of GC-induced side effects, including rebound flares, in murine AD

Spatio-temporal chaos of one-dimensional thin elastic layer with the rate-and-state friction law

The rate-and-state friction (RSF) law is an empirical law often used to model the behavior of rock friction and reproduce the behavior of earthquakes. Recently, the model has been expanded to include so-called slow earthquakes, which are observed at the margins between steadily sliding aseismic and seismogenic zones. In this study, we incorporate the RSF law into a one-dimensional elastic layer spanned perpendicular to the loading direction as a model for the marginal area between aseismic and seismogenic zones. We obtained the complex Ginzburg-Landau equation near a Hopf bifurcation, and showed that the system has Benjamin-Fair instability, leading to spatio-temporal chaos. We conducted numerical calculations near the Hopf bifurcation point, and showed that an irregular oscillation appears when parameters with Benjamin-Feir instability are employed. The size of slip event showed an exponential distribution that resembles a type of slow earthquake.Comment: 33 pages, 7 figure

Gauge Theory Description of Spin Ladders

A s=1/2 antiferromagnetic spin chain is equivalent to the two-flavor massless Schwinger model in an uniform background charge density in the strong coupling. The gapless mode of the spin chain is represented by a massless boson of the Schwinger model. In a two-leg spin ladder system the massless boson aquires a finite mass due to inter-chain interactions. The gap energy is found to be about .25 k |J'| when the inter-chain Heisenberg coupling J' is small compared with the intra-chain Heisenberg coupling. k is a constant of O(1). It is also shown that a cyclically symmetric N-leg ladder system is gapless or gapful for an odd or even N, respectively.Comment: 8 pages. CORRIGENDUM has been incorporated. (A factor 2 error has been corrected.

Pharmacovigilance in hospice/palliative care: the net immediate and short-term effects of dexamethasone for anorexia

Objectives Loss of appetite is prevalent in palliative care and distressing for patients and families. Therapies include corticosteroids or progestogens. This study explores the net effect of dexamethasone on anorexia. Methods Prospective data were collected when dexamethasone was started for anorexia as part of routine care. The National Cancer Institute’s Common Toxicity Criteria for Adverse Events (NCICTCAE) Likert scales assessed severity of anorexia and immediate and short-term harms at 2 time points: baseline and 7 days. Results This study (41 sites, 8 countries) collected data (July 2013 to July 2014) from 114 patients (mean age 71 (SD 11), 96% with cancer). Median Australian-modified Karnofsky Performance Scale was 50% (range 20–70). Mean baseline NCICTCAE anorexia score was 2.7 (SD 0.6; median 3). 6 patients died by day 7. Of 108 evaluable patients, 74 (68.5%; 95% CI 59.0% to 76.7%) reported ≥1 reduction anorexia scores by day 7, of whom 30 were 0. Mean dexamethasone dose on day 7 was 4.1 mg/day (SD 3.4; median 4; range 0–46 mg). 24 patients reported ≥1 harms (32.4% CI 22.6% to 44.1%; insomnia n=10, depression n=7, euphoria n=7 and hyperglycaemia n=7). Of 24 patients with no benefit, 10 reported ≥1 harms. Conclusions This study shows positive and negative effects of 7 days of dexamethasone as an appetite stimulant in patients with advanced life-limiting illnesses. Identifying clinicodemographic characteristics of people most at risk of harms with no benefit is a crucial next step. Longer term follow-up will help to understand longer term and cumulative harms

Esophagectomy in Combination with a Resection of Involved Lung for Esophageal Cancer

The combined resection with involved lung for esophageal carcinoma was evaluated in terms of surgical indication and outcome in the 6 patients who underwent subtotal esophagectomy with pulmonary resection. It was confirmed that the operation was technically feasible but the surgical results were unsatisfactory. It was reasoned that grave surgical insult and adjuvant therapy to prevent recurrence result in immunodepressive status of the host and tends to accompany postoperative complications related to operative death. In conclusion, prevention of immunosuppression for the host is required by meticulous cares of nutrition and elimination of surgical stress by staged operation in order to obtain satisfactory result after surgery

First-year Sloan Digital Sky Survey-II (SDSS-II) Supernova Results: Hubble Diagram and Cosmological Parameters

We present measurements of the Hubble diagram for 103 Type Ia supernovae (SNe) with redshifts 0.04 < z < 0.42, discovered during the first season (Fall 2005) of the Sloan Digital Sky Survey-II (SDSS-II) Supernova Survey. These data fill in the redshift "desert" between low- and high-redshift SN Ia surveys. We combine the SDSS-II measurements with new distance estimates for published SN data from the ESSENCE survey, the Supernova Legacy Survey, the Hubble Space Telescope, and a compilation of nearby SN Ia measurements. Combining the SN Hubble diagram with measurements of Baryon Acoustic Oscillations from the SDSS Luminous Red Galaxy sample and with CMB temperature anisotropy measurements from WMAP, we estimate the cosmological parameters w and Omega_M, assuming a spatially flat cosmological model (FwCDM) with constant dark energy equation of state parameter, w. For the FwCDM model and the combined sample of 288 SNe Ia, we find w = -0.76 +- 0.07(stat) +- 0.11(syst), Omega_M = 0.306 +- 0.019(stat) +- 0.023(syst) using MLCS2k2 and w = -0.96 +- 0.06(stat) +- 0.12(syst), Omega_M = 0.265 +- 0.016(stat) +- 0.025(syst) using the SALT-II fitter. We trace the discrepancy between these results to a difference in the rest-frame UV model combined with a different luminosity correction from color variations; these differences mostly affect the distance estimates for the SNLS and HST supernovae. We present detailed discussions of systematic errors for both light-curve methods and find that they both show data-model discrepancies in rest-frame $U$-band. For the SALT-II approach, we also see strong evidence for redshift-dependence of the color-luminosity parameter (beta). Restricting the analysis to the 136 SNe Ia in the Nearby+SDSS-II samples, we find much better agreement between the two analysis methods but with larger uncertainties.Comment: Accepted for publication by ApJ

EMPRESS. IX. Extremely Metal-Poor Galaxies are Very Gas-Rich Dispersion-Dominated Systems: Will JWST Witness Gaseous Turbulent High-z Primordial Galaxies?

We present kinematics of 6 local extremely metal-poor galaxies (EMPGs) with low metallicities ($0.016-0.098\ Z_{\odot}$) and low stellar masses ($10^{4.7}-10^{7.6} M_{\odot}$). Taking deep medium-high resolution ($R\sim7500$) integral-field spectra with 8.2-m Subaru, we resolve the small inner velocity gradients and dispersions of the EMPGs with H$\alpha$ emission. Carefully masking out sub-structures originated by inflow and/or outflow, we fit 3-dimensional disk models to the observed H$\alpha$ flux, velocity, and velocity-dispersion maps. All the EMPGs show rotational velocities ($v_{\rm rot}$) of 5--23 km s$^{-1}$ smaller than the velocity dispersions ($\sigma_{0}$) of 17--31 km s$^{-1}$, indicating dispersion-dominated ($v_{\rm rot}/\sigma_{0}=0.29-0.80<1$) systems affected by inflow and/or outflow. Except for two EMPGs with large uncertainties, we find that the EMPGs have very large gas-mass fractions of $f_{\rm gas}\simeq 0.9-1.0$. Comparing our results with other H$\alpha$ kinematics studies, we find that $v_{\rm rot}/\sigma_{0}$ decreases and $f_{\rm gas}$ increases with decreasing metallicity, decreasing stellar mass, and increasing specific star-formation rate. We also find that simulated high-$z$ ($z\sim 7$) forming galaxies have gas fractions and dynamics similar to the observed EMPGs. Our EMPG observations and the simulations suggest that primordial galaxies are gas-rich dispersion-dominated systems, which would be identified by the forthcoming James Webb Space Telescope (JWST) observations at $z\sim 7$.Comment: Submitted to ApJ; After revisio

Factor analysis for construct validity of a trunk impairment scale in Parkinson’s disease: a cross-sectional study

ObjectivesTo investigate the construct validity of the Trunk Impairment Scale (TIS), which was developed to assess trunk impairment in patients with stroke, in patients with Parkinson’s disease (PD).DesignThis retrospective, cross-sectional study enrolled consecutive PD inpatients. Correlation analysis was performed to clarify whether the TIS assessment was related to other balance functions, lower extremity muscle strength, or walking ability. Factor analysis was performed to see how the background factors of TIS differ from balance function, lower limb muscle strength, and walking ability.ResultsExamining the data of 471 patients with PD, there were relationships between TIS and the Mini-Balance Evaluation Systems Test (r = 0.67), Barthel Index (r = 0.57), general lower limb extension torque (r = 0.51), two-minute walk test (r = 0.54), Hoehn and Yahr stage (r = −0.61), and Movement Disorder Society Unified Parkinson’s Disease Rating Scale part III total points (r = −0.59). Factor analysis showed that TIS items were divided into three factors (an abdominal muscles and righting reflex component; a perception and verticality component; and a rotational component), differing from other scales that included clinical assessment items.ConclusionThe TIS can be useful for assessing the underlying trunk impairment as a basis for activities of daily living, gait function, and balance ability in patients with PD

Sorafenib plus low-dose cisplatin and fluorouracil hepatic arterial infusion chemotherapy versus sorafenib alone in patients with advanced hepatocellular carcinoma (SILIUS): a randomised, open label, phase 3 trial

Background Hepatic arterial infusion chemotherapy plus sorafenib in phase 2 trials has shown favourable tumour control and a manageable safety profile in patients with advanced, unresectable hepatocellular carcinoma. However, no randomised phase 3 trial has tested the combination of sorafenib with continuous arterial infusion chemotherapy. We aimed to compare continuous hepatic arterial infusion chemotherapy plus sorafenib with sorafenib alone in patients with advanced, unresectable hepatocellular carcinoma. Methods We did an open-label, randomised, phase 3 trial (SILIUS) at 31 sites in Japan. Eligible patients were aged 20 years or older, with advanced hepatocellular carcinoma not suitable for resection, local ablation, or transarterial chemoembolisation; Eastern Cooperative Oncology Group (ECOG) performance status 0–1; Child-Pugh score 7 or lower; and adequate bone marrow, liver, and renal function. Patients were randomly assigned (1:1) via an interactive web response system with a computer-generated sequence to receive 400 mg sorafenib orally twice daily or 400 mg sorafenib orally twice daily plus hepatic arterial infusion chemotherapy (cisplatin 20 mg/m 2 on days 1 and 8 and fluorouracil 330 mg/m 2 continuously on days 1–5 and 8–12 of every 28-day cycle via an implanted catheter system). The primary endpoint was overall survival. The primary efficacy analysis comprised all randomised patients (the intention-to-treat population), and the safety analysis comprised all randomised patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01214343. Findings Between Nov 4, 2010, and June 10, 2014, 206 patients were randomly assigned (103 to the sorafenib group, 103 to the sorafenib plus hepatic arterial infusion chemotherapy group). One patient in the sorafenib plus hepatic arterial infusion chemotherapy group withdrew after randomisation. Median overall survival was similar in the sorafenib plus hepatic arterial infusion chemotherapy (n=102) and sorafenib monotherapy (n=103) groups (11·8 months [95% CI 9·1–14·5] vs 11·5 months [8·2–14·8]; hazard ratio 1·009 [95% CI 0·743–1·371]; p=0·955). Grade 3–4 adverse events that were more frequent in the sorafenib plus hepatic arterial infusion chemotherapy group than in the sorafenib monotherapy group included anaemia (15 [17%] of 88 vs six [6%] of 102), neutropenia (15 [17%] vs one [1%]), thrombocytopenia (30 [34%] vs 12 [12%]), and anorexia (12 [14%] vs six [6%]). Interpretation Addition of hepatic arterial infusion chemotherapy to sorafenib did not significantly improve overall survival in patients with advanced hepatocellular carcinoma. Funding Japanese Ministry of Health, Labour and Welfare