Semiclassical interferences and catastrophes in the ionization of Rydberg atoms by half-cycle pulses

A multi-dimensional semiclassical description of excitation of a Rydberg electron by half-cycle pulses is developed and applied to the study of energy- and angle-resolved ionization spectra. Characteristic novel phenomena observable in these spectra such as interference oscillations and semiclassical glory and rainbow scattering are discussed and related to the underlying classical dynamics of the Rydberg electron. Modifications to the predictions of the impulse approximation are examined that arise due to finite pulse durations

Excitation of weakly bound Rydberg electrons by half-cycle pulses

The interaction of a weakly bound Rydberg electron with an electromagnetic half-cycle pulse (HCP) is described with the help of a multidimensional semiclassical treatment. This approach relates the quantum evolution of the electron to its underlying classical dynamics. The method is nonperturbative and is valid for arbitrary spatial and temporal shapes of the applied HCP. On the basis of this approach angle- and energy-resolved spectra resulting from the ionization of Rydberg atoms by HCPs are analyzed. The different types of spectra obtainable in the sudden-impact approximation are characterized in terms of the appearing semiclassical scattering phenomena. Typical modifications of the spectra originating from finite pulse effects are discussed.Comment: Submitted to Phys. Rev.

Quantum Tunneling in the Wigner Representation

Time dependence for barrier penetration is considered in the phase space. An asymptotic phase-space propagator for nonrelativistic scattering on a one - dimensional barrier is constructed. The propagator has a form universal for various initial state preparations and local potential barriers. It is manifestly causal and includes time-lag effects and quantum spreading. Specific features of quantum dynamics which disappear in the standard semi-classical approximation are revealed. The propagator may be applied to calculation of the final momentum and coordinate distributions, for particles transmitted through or reflected from the potential barrier, as well as for elucidating the tunneling time problem.Comment: 18 pages, LATEX, no figure

Ice‐marginal proglacial lakes across Greenland: Present status and a possible future

Ice-marginal lakes can affect glacier dynamics but are ignored in studies of the evolution of the Greenland ice sheet (GrIS) and of peripheral mountain glaciers and ice caps (PGICs). Here we show that lakes occupy 10 % of the GrIS ice margin and occur on 5 % of PGICs. Ice velocity at the GrIS margin is enhanced by ∼ 25 % at lakes versus on land. Mean ice discharge into lakes is ∼ 4.9 Gt.yr, which is ∼1 % of ice discharged through marine termini. We locate thousands of subglacial overdeepenings within which 7,404 km2 of future lakes could form, all of which will be ice-marginal at some time. Future lakes in the west and east will be restricted to the margin of the GrIS and within alpine valleys, respectively. This status and possible future leads us to contend that lakes should be incorporated into projections of Greenland ice loss

Ice‐Marginal Proglacial Lakes Across Greenland: Present Status and a Possible Future

Abstract: Ice‐marginal lakes can affect glacier dynamics but are ignored in studies of the evolution of the Greenland ice sheet (GrIS) and of peripheral mountain glaciers and ice caps (PGICs). Here we show that lakes occupy 10% of the GrIS ice margin and occur on 5% of PGICs. Ice velocity at the GrIS margin is enhanced by ∼ 25% at lakes versus on land. Mean ice discharge into lakes is ∼4.9 Gt.yr, which is ∼1% of ice discharged through marine termini. We locate thousands of subglacial overdeepenings within which 7,404 km2 of future lakes could form, all of which will be ice‐marginal at some time. Future lakes in the west and east will be restricted to the margin of the GrIS and within alpine valleys, respectively. This status and possible future leads us to contend that lakes should be incorporated into projections of Greenland ice loss

Intravenous dosing of tocilizumab in patients younger than two years of age with systemic juvenile idiopathic arthritis

The anti-interleukin-6 receptor-alpha antibody tocilizumab was approved for intravenous (IV) injection in the treatment of patients with systemic juvenile idiopathic arthritis (sJIA) aged 2 to 17 years based on results of a randomized controlled phase 3 trial. Tocilizumab treatment in systemic juvenile idiopathic arthritis (sJIA) patients younger than 2 was investigated in this open-label phase 1 trial and compared with data from the previous trial in patients aged 2 to 17 years.Patients younger than 2 received open-label tocilizumab 12 mg/kg IV every 2 weeks (Q2W) during a 12-week main evaluation period and an optional extension period. The primary end point was comparability of pharmacokinetics during the main evaluation period to that of the previous trial (in patients aged 2-17 years), and the secondary end point was safety; pharmacodynamics and efficacy end points were exploratory. Descriptive comparisons for pharmacokinetics, pharmacodynamics, safety, and efficacy were made with sJIA patients aged 2 to 17 years weighing < 30 kg (n = 38) who received tocilizumab 12 mg/kg IV Q2W in the previous trial (control group).Eleven patients (mean age, 1.3 years) received tocilizumab during the main evaluation period. The primary end point was met: tocilizumab exposures for patients younger than 2 were within the range of the control group (mean [±SD] μg/mL concentration at the end-of-dosing interval [Cmin]: 39.8 [±14.3] vs 57.5 [±23.3]; maximum concentration [Cmax] postdose: 288 [±40.4] vs 245 [±57.2]). At week 12, pharmacodynamic measures were similar between patients younger than 2 and the control group; mean change from baseline in Juvenile Arthritis Disease Activity Score-71 was - 17.4 in patients younger than 2 and - 28.8 in the control group; rash was reported by 14.3 and 13.5% of patients, respectively. Safety was comparable except for the incidence of serious hypersensitivity reactions (27.3% in patients younger than 2 vs 2.6% in the control group).Tocilizumab 12 mg/kg IV Q2W provided pharmacokinetics, pharmacodynamics, and efficacy in sJIA patients younger than 2 comparable to those in patients aged 2 to 17 years. Safety was comparable except for a higher incidence of serious hypersensitivity events in patients younger than 2 years.Juvenile idiopathic arthritis.ClinicalTrials.gov, NCT01455701 . Registered, October 20, 2011, Date of enrollment of first participant: October 26, 2012

RAMESES: a method for evaluating change in small organisations

The task of planning and implementing systems change is complex. This complexity increases when the system is to be fitted into an existing infrastructure. The interconnections between many of the existing system and business processes can act as a constraint on the range of solutions available to an organisation. The RAMESES method assists small organisations (SMEs) in evaluating the effectiveness of their proposed changes before they are committed to undertaking them. The RAMESES method is discussed in terms of its structural framework. The focus then moves to consider why such a method must be embedded in a software tool to enable accessibility for managers and employees within SMEs. Finally the software prototype is evaluated to assess how well it complies with the requirements of the method and the environment of us

A Real-World Approach to Real-World Research: Appropriateness in Situation, Appropriateness in Method

Working with `real-world&apos; problems is at the centre of the RAMESES research project which focuses on Small - Medium Enterprises (SMEs). In designing the study care had to be taken to ensure the relevance of the research techniques to be used.. This paper outlines the benefits of using a combination of qualitative and quantitative research methods within the bounds of a multi-disciplinary research team to enable effective exploration and investigation. The concept of the research life-cycle has developed the notion of appropriateness in method and approach: this is discussed against the values of the critical and realist paradigms

Safety and Pharmacokinetic Characterization of Nacubactam, a Novel β-Lactamase Inhibitor, Alone and in Combination with Meropenem, in Healthy Volunteers

Nacubactam is a novel, β-lactamase inhibitor with dual mechanism of action as an inhibitor of serine β-lactamases (classes A, C, and some class D) and an inhibitor of penicillin binding protein 2 in Enterobacteriaceae The safety, tolerability, and pharmacokinetics of intravenous nacubactam were evaluated in single and multiple ascending dose, placebo-controlled studies. Healthy participants received single ascending doses of nacubactam 50 to 8,000 mg, multiple ascending doses of nacubactam 1,000 to 4,000 mg every 8 hours (q8h) for up to 7 days, or nacubactam 2,000 mg plus meropenem 2,000 mg q8h for 6 days after a 3-day lead-in period. Nacubactam was generally well tolerated, with the most frequently reported adverse events (AEs) being mild-to-moderate complications associated with intravenous access and headache. There was no apparent relationship between drug dose and the pattern, incidence, or severity of AEs. No clinically relevant dose-related trends were observed in laboratory safety test results. No serious AEs, dose-limiting AEs, or deaths were reported. After single or multiple doses, nacubactam pharmacokinetics appeared linear, and exposure increased in an approximately dose-proportional manner across the dose range investigated. Nacubactam was excreted largely unchanged into urine. Co-administration of nacubactam with meropenem did not significantly alter the pharmacokinetics of either drug. These findings support the continued clinical development of nacubactam and demonstrate the suitability of meropenem as a potential β-lactam partner for nacubactam.ClinicalTrials.gov NCT02134834 (single ascending dose study); ClinicalTrials.gov NCT02972255 (multiple ascending dose study)