Catalytic hydrogenation of α,β-unsaturated carboxylic acid derivatives using copper(i)/N-heterocyclic carbene complexes

A simple and air-stable copper(I)/N-heterocyclic carbene complex enables the catalytic hydrogenation of enoates and enamides, hitherto unreactive substrates employing homogeneous copper catalysis and H2 as a terminal reducing agent. This atom economic transformation replaces commonly employed hydrosilanes and can also be carried out in an asymmetric fashion.TU Berlin, Open-Access-Mittel - 201

Pygmy dipole strength close to particle-separation energies - the case of the Mo isotopes

The distribution of electromagnetic dipole strength in 92, 98, 100 Mo has been investigated by photon scattering using bremsstrahlung from the new ELBE facility. The experimental data for well separated nuclear resonances indicate a transition from a regular to a chaotic behaviour above 4 MeV of excitation energy. As the strength distributions follow a Porter-Thomas distribution much of the dipole strength is found in weak and in unresolved resonances appearing as fluctuating cross section. An analysis of this quasi-continuum - here applied to nuclear resonance fluorescence in a novel way - delivers dipole strength functions, which are combining smoothly to those obtained from (g,n)-data. Enhancements at 6.5 MeV and at ~9 MeV are linked to the pygmy dipole resonances postulated to occur in heavy nuclei.Comment: 6 pages, 5 figures, proceedings Nuclear Physics in Astrophysics II, May 16-20, Debrecen, Hungary. The original publication is available at www.eurphysj.or

Trajectories of long-term exposure to anticholinergic and sedative drugs: A latent class growth analysis

Introduction: A variety of drugs, which are frequently prescribed to older people, have anticholinergic and sedative effects whereby they may impair cognitive and physical function. Although substantial inter-individual variation in anticholinergic and sedative exposure has been documented, little is known about subpopulations with distinct trajectories of exposure. Methods: Data from the Longitudinal Aging Study Amsterdam (LASA), an ongoing Dutch population-based cohort study, collected over 20 years (1992-2012) at seven occasions, were analyzed. On each occasion, cumulative anticholinergic and sedative exposure was quantified with the Drug Burden Index, a linear additive pharmacological dose-response model. The most likely number of trajectories were empirically derived with Latent Class Growth Analysis using "Goodness of fit" statistics. Trajectories were then compared on physical and cognitive function. Results: A total of 763 participants completed all follow-ups (61% women; mean age 83, ±6). "Goodness of fit" statistics (Bayesian In-formation Criterion = 22916, Bootstrapped Likelihood Ratio Test of 3 vs. 2 classes = 514.12

A phase I study of bendamustine hydrochloride administered day 1+2 every 3 weeks in patients with solid tumours

The aim of the study was to determine the maximum tolerated dose (MTD), the dose limiting toxicity (DLT), and the pharmacokinetic profile (Pk) of bendamustine (BM) on a day 1 and 2 every 3 weeks schedule and to recommend a safe phase II dose for further testing. Patients with solid tumours beyond standard therapy were eligible. A 30-min intravenous infusion of BM was administered d1+d2 q 3 weeks. The starting dose was 120 mg m−2 per day and dose increments of 20 mg m−2 were used. Plasma and urine samples were analysed using validated high-performance liquid chromatography/fluorescence assays. Fifteen patients were enrolled. They received a median of two cycles (range 1–8). The MTD was reached at the fourth dose level. Thrombocytopaenia (grade 4) was dose limiting in two of three patients at 180 mg m−2. One patient also experienced febrile neutropaenia. Lymphocytopaenia (grade 4) was present in every patient. Nonhaematologic toxicity including cardiac toxicity was not dose limiting with this schedule. Mean plasma Pk values of BM were tmax 35 min, t1/2 49.1 min, Vd 18.3 l m−2, and clearance 265 ml min−1 m−2. The mean total amount of BM and its metabolites recovered in the first micturition was 8.3% (range 2.7–26%). The MTD of BM in the present dose schedule was 180 mg m−2 on day 1+2. Thrombocytopaenia was dose limiting. The recommended dose for future phase II trials with this schedule is 160 mg m−2 per day

Structural and magnetic properties of Mn-implanted Si

Structural and ferromagnetic properties in Mn implanted, p-type Si were investigated. High resolution structural analysis techniques like synchrotron X-ray diffraction revealed the formation of MnSi1.7 nanoparticles already in the as implanted samples. Depending on the Mn-fluence, the size increases from 5 nm to 20 nm upon rapid thermal annealing. No significant evidence is found for Mn substituting Si sites either in the as-implanted or annealed samples. The observed ferromagnetism yields a saturation moment of 0.21 mu_B per implanted Mn at 10 K, which could be assigned to MnSi1.7 nanoparticles as revealed by a temperature dependent magnetization measurement.Comment: 21 pages, 6 figures, accepted for publicaiton at Phys. Rev.

Filled prescriptions of age-related contraindicated drugs in children: a one-year nationwide cohort study in the Netherlands

Background Children are still prescribed age contraindicated drugs, but information about the number and type of these drugs dispensed for children in the Netherlands is limited. Objective To determine the incidence and prevalence of contraindicated drugs that were dispensed for the use by children. Setting The study was conducted in the Netherlands with routinely collected data from 95% of all community pharmacies. Method We performed a one-year nationwide observational study where all patients aged 17 years or younger who have received at least one prescription in 2016 were included. Contraindicated drugs were selected, according to the 5th level of ATC code, using different information sources. Main outcome measure The proportion of (newly) contraindicated drugs that were dispensed to children. Results In total, 3.9% of all children received at least one drug that was contraindicated for their age. The highest percentage of contraindicated drugs that was dispensed, was observed in patients aged 1–2 years and 13–17 years (7.0 and 5.7%, respectively) and the percentage of contraindicated drugs that were dispensed was higher in female than in male patients (4.3 and 3.6%, respectively; p value < 0.001). Conclusion The results of this study show that a substantial percentage of children received a drug that was conta-indicated for their age, and it happes more in female than in male patients. Furthermore, the information about this type of contraindications is limited and inconsistent