Carboplatin/taxane-induced gastrointestinal toxicity: a pharmacogenomics study on the SCOTROC1 trial

Carboplatin/taxane combination is first-line therapy for ovarian cancer. However, patients can encounter treatment delays, impaired quality of life, even death because of chemotherapy-induced gastrointestinal (GI) toxicity. A candidate gene study was conducted to assess potential association of genetic variants with GI toxicity in 808 patients who received carboplatin/taxane in the Scottish Randomized Trial in Ovarian Cancer 1 (SCOTROC1). Patients were randomized into discovery and validation cohorts consisting of 404 patients each. Clinical covariates and genetic variants associated with grade III/IV GI toxicity in discovery cohort were evaluated in replication cohort. Chemotherapy-induced GI toxicity was significantly associated with seven single-nucleotide polymorphisms in the ATP7B, GSR, VEGFA and SCN10A genes. Patients with risk genotypes were at 1.53 to 18.01 higher odds to develop carboplatin/taxane-induced GI toxicity (P<0.01). Variants in the VEGF gene were marginally associated with survival time. Our data provide potential targets for modulation/inhibition of GI toxicity in ovarian cancer patients

Professionalism and the Millbank Tendency: The Political Sociology of New Labour's employees

This article analyses party employees, one of the most under-researched subjects in the study of British political parties. We draw on a blend of quantitative and qualitative data in order to shed light on the social and political profiles of Labour Party staff, and on the question of their professionalisation. The latter theme is developed through a model derived from the sociology of professions. While a relatively limited proportion of party employees conform to the pure ideal-type of professionalism, a considerably greater number manifest enough of the core characteristics of specialisation, commitment, mobility, autonomy and self-regulation to be reasonably described as 'professionals in pursuit of political outcomes'

Photophysical and Optical Properties of Semiconducting Polymer Nanoparticles Prepared from Hyaluronic Acid and Polysorbate 80

Copyright © 2019 American Chemical Society. A nanoprecipitation procedure was utilized to prepare novel diketopyrrolopyrrole-based semiconducting polymer nanoparticles (SPNs) with hyaluronic acid (HA) and polysorbate 80. The nanoprecipitation led to the formation of spherical nanoparticles with average diameters ranging from 100 to 200 nm, and a careful control over the structure of the parent conjugated polymers was performed to probe the influence of π-conjugation on the final photophysical and thermal stability of the resulting SPNs. Upon generation of a series of novel SPNs, the optical and photophysical properties of the new nanomaterials were probed in solution using various techniques including transmission electron microscopy, dynamic light scattering, small-angle neutron scattering, transient absorption, and UV-vis spectroscopy. A careful comparison was performed between the different SPNs to evaluate their excited-state dynamics and photophysical properties, both before and after nanoprecipitation. Interestingly, although soluble in organic solution, the nanoparticles were found to exhibit aggregative behavior, resulting in SPNs that exhibit excited-state behaviors that are very similar to aggregated polymer solutions. Based on these findings, the formation of HA- and polysorbate 80-based nanoparticles does not influence the photophysical properties of the conjugated polymers, thus opening new opportunities for the design of bioimaging agents and nanomaterials for health-related applications

Deterministic delivery of externally cold and precisely positioned single molecular ions

We present the preparation and deterministic delivery of a selectable number of externally cold molecular ions. A laser cooled ensemble of Mg^+ ions subsequently confined in several linear Paul traps inter-connected via a quadrupole guide serves as a cold bath for a single or up to a few hundred molecular ions. Sympathetic cooling embeds the molecular ions in the crystalline structure. MgH^+ ions, that serve as a model system for a large variety of other possible molecular ions, are cooled down close to the Doppler limit and are positioned with an accuracy of one micrometer. After the production process, severely compromising the vacuum conditions, the molecular ion is efficiently transfered into nearly background-free environment. The transfer of a molecular ion between different traps as well as the control of the molecular ions in the traps is demonstrated. Schemes, optimized for the transfer of a specific number of ions, are realized and their efficiencies are evaluated. This versatile source applicable for broad charge-to-mass ratios of externally cold and precisely positioned molecular ions can serve as a container-free target preparation device well suited for diffraction or spectroscopic measurements on individual molecular ions at high repetition rates (kHz).Comment: 11 pages, 8 figure

The dust budget crisis in high-redshift submillimetre galaxies

We apply a chemical evolution model to investigate the sources and evolution of dust in a sample of 26 high-redshift (z > 1) submillimetre galaxies (SMGs) from the literature, with complete photometry from ultraviolet to the submillimetre. We show that dust produced only by low–intermediate-mass stars falls a factor 240 short of the observed dust masses of SMGs, the well-known ‘dust-budget crisis’. Adding an extra source of dust from supernovae can account for the dust mass in 19 per cent of the SMG sample. Even after accounting for dust produced by supernovae the remaining deficit in the dust mass budget provides support for higher supernova yields, substantial grain growth in the interstellar medium or a top-heavy IMF. Including efficient destruction of dust by supernova shocks increases the tension between our model and observed SMG dust masses. The models which best reproduce the physical properties of SMGs have a rapid build-up of dust from both stellar and interstellar sources and minimal dust destruction. Alternatively, invoking a top-heavy IMF or significant changes in the dust grain properties can solve the dust budget crisis only if dust is produced by both low-mass stars and supernovae and is not efficiently destroyed by supernova shocks

Anti-inflammatory and anticholinesterase activity of six flavonoids isolated from Polygonum and Dorstenia species

This study was aimed at investigating the anti-inflammatory and anticholinesterase activity of six naturally occurring flavonoids: (-) pinostrobin (1), 2’,4’-dihydroxy-3’,6’-dimethoxychalcone (2), 6-8-diprenyleriodictyol (3), isobavachalcone (4), 4-hydroxylonchocarpin (5) and 6- prenylapigenin (6). These compounds were isolated from Dorstenia and Polygonum species used traditionally to treat pain. The anti-inflammatory activity was determined by using the Griess assay and the 15-lipoxygenase inhibitory activity was determined with the ferrous oxidationxylenol orange assay. Acetylcholinesterase (AChE) inhibition was determined by the Ellman’s method. At the lowest concentration tested (3.12 μg/mL), compounds 2, 3 and 4 had significant NO inhibitory activity with 90.71%, 84.65 and 79.57% inhibition respectively compared to the positive control quercetin (67.93%). At this concentration there was no significant cytotoxicity against macrophages with 91.67%, 72.86 and 70.86% cell viability respectively, compared to 73.1% for quercetin. Compound 4 had the most potent lipoxygenase inhibitory activity (IC50 of 25.92 μg/mL). With the exception of (-) pinostrobin (1), all the flavonoids had selective anticholinesterase activity with IC50 values ranging between 5.93 and 8.76 μg/mL compared to the IC50 4.94 μg/mL of eserine the positive control. These results indicate that the studied flavonoids especially isobavachalcone are potential anti-inflammatory natural products that may have the potential to be developed as therapeutic agents against inflammatory conditions and even Alzheimer’s disease.National Research Foundation (NRF) and Medical Research Council (MRC).http://link.springer.com/journal/122722016-05-08hb201