A practical approach to the sensitivity analysis for kinetic Monte Carlo simulation of heterogeneous catalysis

Lattice kinetic Monte Carlo simulations have become a vital tool for predictive quality atomistic understanding of complex surface chemical reaction kinetics over a wide range of reaction conditions. In order to expand their practical value in terms of giving guidelines for the atomic level design of catalytic systems, it is very desirable to readily evaluate a sensitivity analysis for a given model. The result of such a sensitivity analysis quantitatively expresses the dependency of the turnover frequency, being the main output variable, on the rate constants entering the model. In the past, the application of sensitivity analysis, such as degree of rate control, has been hampered by its exuberant computational effort required to accurately sample numerical derivatives of a property that is obtained from a stochastic simulation method. In this study, we present an efficient and robust three-stage approach that is capable of reliably evaluating the sensitivity measures for stiff microkinetic models as we demonstrate using the CO oxidation on RuO2(110) as a prototypical reaction. In the first step, we utilize the Fisher information matrix for filtering out elementary processes which only yield negligible sensitivity. Then we employ an estimator based on the linear response theory for calculating the sensitivity measure for non- critical conditions which covers the majority of cases. Finally, we adapt a method for sampling coupled finite differences for evaluating the sensitivity measure for lattice based models. This allows for an efficient evaluation even in critical regions near a second order phase transition that are hitherto difficult to control. The combined approach leads to significant computational savings over straightforward numerical derivatives and should aid in accelerating the nano-scale design of heterogeneous catalysts

Rest-Frame Optical Spectra of Three Strongly Lensed Galaxies at z~2

We present Keck II NIRSPEC rest-frame optical spectra for three recently discovered lensed galaxies: the Cosmic Horseshoe (z = 2.38), the Clone (z = 2.00), and SDSS J090122.37+181432.3 (z = 2.26). The boost in signal-to-noise ratio (S/N) from gravitational lensing provides an unusually detailed view of the physical conditions in these objects. A full complement of high S/N rest-frame optical emission lines is measured, spanning from rest-frame 3600 to 6800AA, including robust detections of fainter lines such as H-gamma, [SII]6717,6732, and in one instance [NeII]3869. SDSS J090122.37+181432.3 shows evidence for AGN activity, and therefore we focus our analysis on star-forming regions in the Cosmic Horseshoe and the Clone. For these two objects, we estimate a wide range of physical properties, including star-formation rate (SFR), metallicity, dynamical mass, and dust extinction. In all respects, the lensed objects appear fairly typical of UV-selected star-forming galaxies at z~2. The Clone occupies a position on the emission-line diagnostic diagram of [OIII]/H-beta vs. [NII]/H-alpha that is offset from the locations of z~0 galaxies. Our new NIRSPEC measurements may provide quantitative insights into why high-redshift objects display such properties. From the [SII] line ratio, high electron densities (~1000 cm^(-3)) are inferred compared to local galaxies, and [OIII]/[OII] line ratios indicate higher ionization parameters compared to the local population. Building on previous similar results at z~2, these measurements provide further evidence (at high S/N) that star-forming regions are significantly different in high-redshift galaxies, compared to their local counterparts (abridged).Comment: 16 pages, 8 figures. Accepted for publication in the Astrophysical Journa

“There’s a Catch-22”. The complexities of pain management for people with advanced dementia nearing the end of life: a qualitative exploration of physicians’ perspectives

Background: Pain management is a cornerstone of palliative care. The clinical issues encountered by physicians when managing pain in patients dying with advanced dementia, and how these may impact on prescribing and treatment, are unknown. Aim: To explore physicians’ experiences of pain management for patients nearing the end of life, the impact of these on prescribing and treatment approaches, and the methods employed to overcome these challenges. Design: Qualitative, semi-structured interview study exploring: barriers to and facilitators of pain management, prescribing and treatment decisions, and training needs. Thematic analysis was used to elicit key themes. Settings/Participants: Twenty-three physicians, responsible for treating patients with advanced dementia approaching the end of life, were recruited from primary care (n=9), psychiatry (n=7) and hospice care (n=7). Results: Six themes emerged: diagnosing pain, complex prescribing and treatment approaches, side-effects and adverse events, route of administration, importance of sharing knowledge and training needs. Knowledge exchange was often practised through liaison with physicians from other specialties. Cross-specialty mentoring, and the creation of knowledge networks were believed to improve pain management in this patient population. Conclusions: Pain management in end-stage dementia is complex, requiring cross-population of knowledge between palliative care specialists and non-specialists, in addition to collateral information provided by other health professionals and patients’ families. Regular, cost- and time-effective mentoring and ongoing professional development are perceived to be essential in empowering physicians to meet clinical challenges in this area

The furan microsolvation blind challenge for quantum chemical methods: First steps

© 2018 Author(s). Herein we present the results of a blind challenge to quantum chemical methods in the calculation of dimerization preferences in the low temperature gas phase. The target of study was the first step of the microsolvation of furan, 2-methylfuran and 2,5-dimethylfuran with methanol. The dimers were investigated through IR spectroscopy of a supersonic jet expansion. From the measured bands, it was possible to identify a persistent hydrogen bonding OH-O motif in the predominant species. From the presence of another band, which can be attributed to an OH-π interaction, we were able to assert that the energy gap between the two types of dimers should be less than or close to 1 kJ/mol across the series. These values served as a first evaluation ruler for the 12 entries featured in the challenge. A tentative stricter evaluation of the challenge results is also carried out, combining theoretical and experimental results in order to define a smaller error bar. The process was carried out in a double-blind fashion, with both theory and experimental groups unaware of the results on the other side, with the exception of the 2,5-dimethylfuran system which was featured in an earlier publication

Hubble Space Telescope WFC3 Early Release Science: Emission-Line Galaxies from Infrared Grism Observations

We present grism spectra of emission-line galaxies (ELGs) from 0.6-1.6 microns from the Wide Field Camera 3 on the Hubble Space Telescope. These new infrared grism data augment previous optical Advanced Camera for Surveys G800L 0.6-0.95 micron grism data in GOODS-South from the PEARS program, extending the wavelength covereage well past the G800L red cutoff. The ERS grism field was observed at a depth of 2 orbits per grism, yielding spectra of hundreds of faint objects, a subset of which are presented here. ELGs are studied via the Ha, [OIII], and [OII] emission lines detected in the redshift ranges 0.2<z<1.4, 1.2<z<2.2 and 2.0<z<3.3 respectively in the G102 (0.8-1.1 microns; R~210) and G141 (1.1-1.6 microns; R~130) grisms. The higher spectral resolution afforded by the WFC3 grisms also reveals emission lines not detectable with the G800L grism (e.g., [SII] and [SIII] lines). From these relatively shallow observations, line luminosities, star-formation rates, and grism spectroscopic redshifts are determined for a total of 48 ELGs to m(AB)~25 mag. Seventeen GOODS-South galaxies that previously only had photometric redshifts now have new grism-spectroscopic redshifts, in some cases with large corrections to the photometric redshifts (Delta(z)~0.3-0.5). Additionally, one galaxy had no previously-measured redshift but now has a secure grism-spectroscopic redshift, for a total of 18 new GOODS-South spectroscopic redshifts. The faintest source in our sample has a magnitude m(AB)=26.9 mag. The ERS grism data also reflect the expected trend of lower specific star formation rates for the highest mass galaxies in the sample as a function of redshift, consistent with downsizing and discovered previously from large surveys. These results demonstrate the remarkable efficiency and capability of the WFC3 NIR grisms for measuring galaxy properties to faint magnitudes and redshifts to z>2.Comment: Accepted for publication in AJ. Updated to include referee comments. Updated sample using improved reduction contains 23 new galaxies (Table 1; Figures 2 & 3

Effects of Pharmacogenetic Screening for CYP2D6 Among Elderly Starting Therapy With Nortriptyline or Venlafaxine:A Pragmatic Randomized Controlled Trial (CYSCE Trial)

PURPOSE/BACKGROUND: The duration of untreated depression is a predictor for poor future prognosis, making rapid dose finding essential. Genetic variation of the CYP2D6 isoenzyme can influence the optimal dosage needed for individual patients. The aim of this study was to determine the effectiveness of CYP2D6 pharmacogenetic screening to accelerate drug dosing in older patients with depression initiating nortriptyline or venlafaxine. METHODS/PROCEDURES: In this randomized controlled trial, patients were randomly allocated to one of the study arms. In the intervention arm (DG-I), the specific genotype accompanied by a standardized dosing recommendation based on the patients' genotype and the prescribed drug was directly communicated to the physician of the participant. In both the deviating genotype control arm (DG-C) and the nonrandomized control arm, the physician of the participants was not informed about the genotype and the associated dosing advise. The primary outcome was the time needed to reach adequate drug levels: (1) blood levels within the therapeutic range and (2) no dose adjustments within the previous 3 weeks. FINDINGS/RESULTS: No significant difference was observed in mean time to reach adequate dose or time to adequate dose between DG-I and DG-C. Compared with the nonrandomized control arm group, adequate drug levels were reached significantly faster in the DG-I group (log-rank test; P = 0.004), and there was a similar nonsignificant trend for the DG-C group (log-rank test; P = 0.087). IMPLICATIONS/CONCLUSIONS: The results of this study do not support pharmacogenetic CYP2D6 screening to accelerate dose adjustment for nortriptyline and venlafaxine in older patients with depression

Evolution of costs of inflammatory bowel disease over two years of follow-up

Background: With the increasing use of anti-TNF therapy in inflammatory bowel disease (IBD), a shift of costs has been observed with medication costs replacing hospitalization and surgery as major cost driver. We aimed to explore the evolution of IBD-related costs over two years of follow-up. Methods and Findings: In total 1,307 Crohn's disease (CD) patients and 915 ulcerative colitis (UC) patients were prospectively followed for two years by three-monthly web-based questionnaires. Changes of healthcare costs, productivity costs and out-of-pocket costs over time were assessed using mixed model analysis. Multivariable logistic regression analysis was used to identify costs drivers. In total 737 CD patients and 566 UC were included. Total costs were stable over two years of follow-up, with annual total costs of € 7,835 in CD and € 3,600 in UC. However, within healthcare costs, the proportion of anti-TNF therapy-related costs increased from 64% to 72% in CD (p<0.01) and from 31% to 39% in UC (p < 0.01). In contrast, the proportion of hospitalization costs decreased from 19% to 13% in CD (p<0.01), and 22% to 15% in UC (p < 0.01). Penetrating disease course predicted an increase of healthcare costs (adjusted odds ratio (adj. OR) 1.95 (95% CI 1.02-3.37) in CD and age <40 years in UC (adj. OR 4.72 (95% CI 1.61-13.86)). Conclusions: BD-related costs remained stable over two years. However, the proportion of anti-TNFrelated healthcare costs increased, while hospitalization costs decreased. Factors associated with increased costs were penetrating disease course in CD and age <40 in UC

The first microsolvation step for furans : new experiments and benchmarking strategies

The site-specific first microsolvation step of furan and some of its derivatives with methanol is explored to benchmark the ability of quantum-chemical methods to describe the structure, energetics, and vibrational spectrum at low temperature. Infrared and microwave spectra in supersonic jet expansions are used to quantify the docking preference and some relevant quantum states of the model complexes. Microwave spectroscopy strictly rules out in-plane docking of methanol as opposed to the top coordination of the aromatic ring. Contrasting comparison strategies, which emphasize either the experimental or the theoretical input, are explored. Within the harmonic approximation, only a few composite computational approaches are able to achieve a satisfactory performance. Deuteration experiments suggest that the harmonic treatment itself is largely justified for the zero-point energy, likely and by design due to the systematic cancellation of important anharmonic contributions between the docking variants. Therefore, discrepancies between experiment and theory for the isomer abundance are tentatively assigned to electronic structure deficiencies, but uncertainties remain on the nuclear dynamics side. Attempts to include anharmonic contributions indicate that for systems of this size, a uniform treatment of anharmonicity with systematically improved performance is not yet in sight