Experimental benchmark data for Monte Carlo simulated radiation effects of gold nanoparticles. Part II: Comparison of measured and simulated electron spectra from gold nanofoils

Electron emission spectra of a thin gold foil after photon interaction were measured over the energy range between 50 eV and 9500 eV to provide reference data for Monte Carlo radiation-transport simulations. Experiments were performed with the HAXPES spectrometer at the PETRA III high-brilliance beamline P22 at DESY (Hamburg, Germany) for photon energies just below and above each of the gold L-edges, i.e., at 11.9 keV, 12.0 keV, 13.7 keV, 13.8 keV, 14.3 keV, and 14.4 keV. The data were analyzed to obtain the absolute values of the particle radiance of the emitted electrons per incident photon flux. Simulations of the experiment were performed using the Monte Carlo radiation-transport codes Penelope and Geant4. Comparison of the measured and simulated results shows good qualitative agreement. When simulation results are convolved with curves that take into account the effect of lifetime broadening, line shapes of photoelectron and Auger peaks similar to those observed experimentally are obtained. On an absolute scale, the experiments tend to give higher electron radiance values at the lower photon energies studied as well as at the higher photon energies for electron energies below the energy of the Au L3 photoelectron. This is attributed to the linear polarization of the photon beam in the experiments which is not considered in the simulation codes.Comment: Revised manuscript after peer review, 13 pages, 9 figure

Experimental benchmark data for Monte Carlo simulated radiation effects of gold nanoparticles. Part II: comparison of measured and simulated electron spectra from gold nanofoils

Electron emission spectra of a thin gold foil after photon interaction were measured over the energy range between 50 eV and 9500 eV to provide reference data for Monte Carlo radiation-transport simulations. Experiments were performed with the HAXPES spectrometer at the PETRA III high-brilliance beamline P22 at DESY (Hamburg, Germany) for photon energies just below and above each of the gold L-edges, that is, at 11.9 keV, 12.0 keV, 13.7 keV, 13.8 keV, 14.3 keV, and 14.4 keV. The data were analyzed to obtain the absolute values of the particle radiance of the emitted electrons per incident photon flux. Simulations of the experiment were performed using the Penelope and Geant4 Monte Carlo radiation-transport codes. Comparison of the measured and simulated results shows good qualitative agreement. On an absolute scale, the experiments tend to produce higher electron radiance values at the lower photon energies studied as well as at the higher photon energies for electron energies below the energy of the Au L3 photoelectron. This is attributed to the linear polarization of the photon beam in the experiments, something which is not considered in the simulation codes

Increased interleukin-17 production via a phosphoinositide 3-kinase/Akt and nuclear factor κB-dependent pathway in patients with rheumatoid arthritis

Inflammatory mediators have been recognized as being important in the pathogenesis of rheumatoid arthritis (RA). Interleukin (IL)-17 is an important regulator of immune and inflammatory responses, including the induction of proinflammatory cytokines and osteoclastic bone resorption. Evidence for the expression and proinflammatory activity of IL-17 has been demonstrated in RA synovium and in animal models of RA. Although some cytokines (IL-15 and IL-23) have been reported to regulate IL-17 production, the intracellular signaling pathways that regulate IL-17 production remain unknown. In the present study, we investigated the role of the phosphoinositide 3-kinase (PI3K)/Akt pathway in the regulation of IL-17 production in RA. Peripheral blood mononuclear cells (PBMC) from patients with RA (n = 24) were separated, then stimulated with various agents including anti-CD3, anti-CD28, phytohemagglutinin (PHA) and several inflammatory cytokines and chemokines. IL-17 levels were determined by sandwich enzyme-linked immunosorbent assay and reverse transcription–polymerase chain reaction. The production of IL-17 was significantly increased in cells treated with anti-CD3 antibody with or without anti-CD28 and PHA (P < 0.05). Among tested cytokines and chemokines, IL-15, monocyte chemoattractant protein-1 and IL-6 upregulated IL-17 production (P < 0.05), whereas tumor necrosis factor-α, IL-1β, IL-18 or transforming growth factor-β did not. IL-17 was also detected in the PBMC of patients with osteoarthritis, but their expression levels were much lower than those of RA PBMC. Anti-CD3 antibody activated the PI3K/Akt pathway; activation of this pathway resulted in a pronounced augmentation of nuclear factor κB (NF-κB) DNA-binding activity. IL-17 production by activated RA PBMC is completely or partly blocked in the presence of the NF-κB inhibitor pyrrolidine dithiocarbamate and the PI3K/Akt inhibitor wortmannin and LY294002, respectively. However, inhibition of activator protein-1 and extracellular signal-regulated kinase 1/2 did not affect IL-17 production. These results suggest that signal transduction pathways dependent on PI3K/Akt and NF-κB are involved in the overproduction of the key inflammatory cytokine IL-17 in RA

Comparative effectiveness and safety of concomitant treatment with Chuna Manual Therapy and usual care for whiplash injuries: a multicenter randomized controlled trial

Objectives: We aimed to compare the effectiveness and safety of Chuna manual therapy combined with usual care to those of usual care alone for treating whiplash injuries. Design: A two-arm, parallel, assessor-blinded, multicenter pragmatic randomized clinical trial. Setting: Three hospitals in Korea. Participants: Overall, 132 participants between 19 and 70 years of age, involved in traffic accidents and treated at three hospitals in Korea, >2 but <13 weeks prior to enrollment, with neck pain consistent with whiplash-associated disorder grades I and II and a numeric rating scale score ≥5 were included. Interventions: Participants were equally and randomly allocated to the Chuna manual therapy and usual care (n = 66) or usual care (n = 66) groups and underwent corresponding treatment for three weeks. Primary and secondary outcome measures: The primary outcome was the number of days to achieve a 50% pain reduction. Secondary outcomes included areas under the 50% numeric rating scale reduction curve: pain, disability, quality of life, and safety. Results: The Chuna manual therapy + usual care group (23.31 ± 21.36 days; p = 0.01) required significantly fewer days to achieve 50% pain reduction compared to the usual care group (50.41 ± 48.32 days; p = 0.01). Regarding pain severity, functional index, and quality of life index, Chuna manual therapy and usual care were more effective than usual care alone. Safety was acceptable in both groups. Conclusions: In patients with subacute whiplash injury, Chuna manual therapy showed a rapid rate of recovery, high effectiveness, and safety

Metformin Attenuates Experimental Autoimmune Arthritis through Reciprocal Regulation of Th17/Treg Balance and Osteoclastogenesis

Metformin is widely used to suppress certain functions of the cells found in diseases including diabetes and obesity. In this study, the effects of metformin on downregulating IL-17-producing T (Th17) cells, activating and upregulating regulatory T (Treg) cells, suppressing osteoclastogenesis, and clinically scoring collagen-induced arthritis (CIA) were investigated. To evaluate the effect of metformin on CIA, mice were orally fed with either metformin or saline as control three times a week for nine weeks. Histological analysis of the joints was performed using immunohistochemistry and Th17 cells and Treg cells of the spleen tissue were examined by confocal microscopy staining. Metformin mitigated the severity of CIA, reduced serum immunoglobulin concentrations, and reciprocally regulated Th17/Treg axis. Also, metformin treatment of normal cells cultured in Th17 conditions decreased the number of Th17 cells and increased the number of Treg cells. Metformin decreased gene expression and osteoclastogenic activity in CIA and normal mice. These results indicate that metformin had immunomodulatory actions influencing anti-inflammatory action on CIA through the inhibition of Th17 cell differentiation and the upregulation of Treg cell differentiation along with the suppression of osteoclast differentiation. Our results suggest that metformin may be a potential therapeutic for rheumatoid arthritis

Does Al4H14— cluster anion exist? High-level ab initio study

A comprehensive ab initio investigation using coupled cluster theory with the aug-cc-pVnZ, n = D,T basis sets is carried out to identify distinct structures of the Al4H14— cluster anion and to evaluate its fragmentation stability. Both thermodynamic and mechanistic aspects of the fragmentation reactions are studied. The observation of this so far the most hydrogenated aluminum tetramer was reported in the recent mass spectrometry study of Li et al. (2010) J Chem Phys 132:241103–241104. The four Al4H14— anion structures found are chain-like with the multiple-coordinate Al center and can be viewed approximately as comprising Al2H7— and Al2H7 moieties. Locating computationally some of the Al4H14— minima on the correlated ab initio potential energy surfaces required the triple-zeta quality basis set to describe adequately the Al multi-coordinate bonding. For the two most stable Al4H14— isomers, the mechanism of their low-barrier interconversion is described. The dissociation of Al4H14— into the Al2H7— and Al2H7 units is predicted to require 20-22 (10-13) kcal mol-1 in terms of ΔH (ΔG) estimated at T = 298.15 K and p = 1 atm. However, Al4H14— is found to be a metastable species in the gas phase: the H2 loss from the radical moiety of its most favorable isomer is exothermic by 18 kcal mol-1 in terms of ΔH (298.15 K) and by 25 kcal mol-1 in terms of ΔG(298.15 K), with the enthalpic/free energy barrier involved being less than 1 kcal mol-1. By contrast with alane Al4H14—, only a weakly bound complex between Ga4H12— and H2 has been identified for the gallium analogue using the relativistic effective core potential

Electron affinities of the first- and second- row atoms: benchmark ab initio and density functional calculations

A benchmark ab initio and density functional (DFT) study has been carried out on the electron affinities of the first- and second-row atoms. The ab initio study involves basis sets of $spdfgh$ and $spdfghi$ quality, extrapolations to the 1-particle basis set limit, and a combination of the CCSD(T), CCSDT, and full CI electron correlation methods. Scalar relativistic and spin-orbit coupling effects were taken into account. On average, the best ab initio results agree to better than 0.001 eV with the most recent experimental results. Correcting for imperfections in the CCSD(T) method improves the mean absolute error by an order of magnitude, while for accurate results on the second-row atoms inclusion of relativistic corrections is essential. The latter are significantly overestimated at the SCF level; for accurate spin-orbit splitting constants of second-row atoms inclusion of (2s,2p) correlation is essential. In the DFT calculations it is found that results for the 1st-row atoms are very sensitive to the exchange functional, while those for second-row atoms are rather more sensitive to the correlation functional. While the LYP correlation functional works best for first-row atoms, its PW91 counterpart appears to be preferable for second-row atoms. Among ``pure DFT'' (nonhybrid) functionals, G96PW91 (Gill 1996 exchange combined with Perdew-Wang 1991 correlation) puts in the best overall performance. The best results overall are obtained with the 1-parameter hybrid modified Perdew-Wang (mPW1) exchange functionals of Adamo and Barone [J. Chem. Phys. {\bf 108}, 664 (1998)], with mPW1LYP yielding the best results for first-row, and mPW1PW91 for second-row atoms. Indications exist that a hybrid of the type $a$ mPW1LYP + $(1-a)$ mPW1PW91 yields better results than either of the constituent functionals.Comment: Phys. Rev. A, in press (revised version, review of issues concerning DFT and electron affinities added

Development and evaluation of a cultural competency training curriculum

BACKGROUND: Increasing the cultural competence of physicians and other health care providers has been suggested as one mechanism for reducing health disparities by improving the quality of care across racial/ethnic groups. While cultural competency training for physicians is increasingly promoted, relatively few studies evaluating the impact of training have been published. METHODS: We recruited 53 primary care physicians at 4 diverse practice sites and enrolled 429 of their patients with diabetes and/or hypertension. Patients completed a baseline survey which included a measure of physician culturally competent behaviors. Cultural competency training was then provided to physicians at 2 of the sites. At all 4 sites, physicians received feedback in the form of their aggregated cultural competency scores compared to the aggregated scores from other physicians in the practice. The primary outcome at 6 months was change in the Patient-Reported Physician Cultural Competence (PRPCC) score; secondary outcomes were changes in patient trust, satisfaction, weight, systolic blood pressure, and glycosylated hemoglobin. Multiple analysis of variance was used to control for differences patient characteristics and baseline levels of the outcome measure between groups. RESULTS: Patients had a mean of 2.8 + 2.2 visits to the study physician during the study period. Changes in all outcomes were similar in the "Training + Feedback" group compared to the "Feedback Only" group (PRPCC: 3.7 vs.1.8; trust: -0.7 vs. -0.2 ; satisfaction: 1.9 vs. 2.5; weight: -2.5 lbs vs. -0.7 lbs; systolic blood pressure: 1.7 mm Hg vs. 0.1 mm Hg; glycosylated hemoglobin 0.02% vs. 0.07%; p = NS for all). CONCLUSION: The lack of measurable impact of physician training on patient-reported and disease-specific outcomes in the current has several possible explanations, including the relatively limited nature of the intervention. We hope that the current study will help provide a basis for future studies, using more intensive interventions with different provider groups