Combining the platinum(ii) drug candidate kiteplatin with 1,10-phenanthroline analogues

Platinum complexes of the type [Pt(PL)(AL)]2+ where PL is a derivative of 1,10-phenanthroline and AL is cis-1,4-diaminocyclohexane (1,4-dach), have been synthesised and characterised by ultraviolet spectroscopy, elemental microanalysis, nuclear magnetic resonance and X-ray crystallography. The calf-thymus DNA binding affinity of these complexes was determined by isothermal titration calorimetry, revealing higher DNA affinity than their 1S,2S-diaminocyclohexane analogues. In vitro cytotoxicity was assessed in eleven human cell lines, revealing unexpectedly low activity for the 1,4-dach complexes

Synthesis and analysis of the anticancer activity of platinum(ii) complexes incorporating dipyridoquinoxaline variants

Eight platinum(ii) complexes with anticancer potential have been synthesised and characterised. These complexes are of the type [Pt(I)(A)], where I is either dipyrido[3,2-f:2′,3′-h]quinoxaline (dpq) or 2,3-dimethyl-dpq (23Medpq) and A is one of the R,R or S,S isomers of either 1,2-diaminocyclohexane (SS-dach or RR-dach) or 1,2-diaminocyclopentane (SS-dacp or RR-dacp). The CT-DNA binding of these complexes and a series of other complexes were assessed using fluorescent intercalator displacement assays, resulting in unexpected trends in DNA binding affinity. The cytotoxicity of the eight synthesised compounds was determined in the L1210 cell line; the most cytotoxic of these were [Pt(dpq)(SS-dach)]Cl and [Pt(dpq)(RR-dach)]Cl, with IC values of 0.19 and 0.80 μM, respectively. The X-ray crystal structure of the complex [Pt(dpq)(SS-dach)](ClO)·1.75HO is also reported. This journal i

Self-assembly of an imidazolate-bridged FeIII/CuII heterometallic cage

A rare, discrete, mixed-valent, heterometallic Fe(III)/Cu(II) cage, [CuFeL](ClO)χ solvent (HL = tris{[2-{(imidazole-4-yl)methylidene}amino]ethyl} amine), was designed and synthesized via metal-ion-directed self-assembly with neutral tripodal metalloligands. The formation of this coordination cage was demonstrated by X-ray crystallography, ESI mass spectrometry, FT-IR, and UV-vis-NIR spectroscopy

Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial

Background: Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome. Methods: In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134. Findings: Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88–1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90–1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41–0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22–3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31–0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64–0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37–3·91], p=0·771) was similar. Interpretation: In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status

What is values work? A review of values work in organisations. Kap. 3

I: H.Askeland, G. Espedal, B. Jelstad Løvaas & S. Sirris (Eds.), Understanding values work : Institutional perspectives in organizations and leadershipThrough a review of the existing empirical studies and emerging literature on values work in organisations, this paper aims to disambiguate the phenomenon of values work. Values work is understood as ongoing value performances situated in everyday practice in organisations. As such, values work is identified as social and institutional processes of constructing agency, actions and practice in organisations. In this chapter, I show how values work is part of both a performative tradition of process studies and an institutional work tradition that strives to change, disrupt and maintain institutions. Further, I outline how future studies can broaden the field of values work.publishedVersio

Wages in high-tech start-ups - do academic spin-offs pay a wage premium?

Due to their origin from universities, academic spin‐offs operate at the forefront of the technological development. Therefore, spin‐offs exhibit a skill‐biased labour demand, i.e. spin‐offs have a high demand for employees with cutting edge knowledge and technical skills. In order to accommodate this demand, spin‐offs may have to pay a relative wage premium compared to other high‐tech start‐ups. However, neither a comprehensive theoretical assessment nor the empirical literature on wages in start‐ups unambiguously predicts the existence and the direction of wage differentials between spin‐offs and non‐spin‐offs. This paper addresses this research gap and examines empirically whether or not spin‐offs pay their employees a wage premium. Using a unique linked employer‐employee data set of German high‐tech start‐ups, we estimate Mincer‐type wage regressions applying the Hausman‐Taylor panel estimator. Our results show that spin‐offs do not pay a wage premium in general. However, a notable exception from this general result is that spin‐offs that commercialise new scientific results or methods provide higher wages to employees with linkages to the university sector – either as university graduates or as student workers

Social capital of venture capitalists and start-up funding

How does the social capital of venture capitalists (VCs) affect the funding of start-ups? By building on the rich social capital literature, we hypothesize a positive effect of VCs' social capital, derived from past syndication, on the amount of money that start-ups receive. Specifically, we argue that both structural and relational aspects of VCs' social networks provide VCs with superior access to information about current investment objects and opportunities to leverage them in the future, increasing their willingness to invest in these firms. Our empirical results, derived from a novel dataset containing more than 1,500 first funding rounds in the Internet and IT sector, strongly confirm our hypotheses. We discuss the implications of our findings for theories of venture capital and entrepreneurship, showing that the role and effect of VCs' social capital on start-up firms may be more complex than previously argued in the literature

Social Participation and Disaster Risk Reduction Behaviors in Tsunami Prone Areas

This paper examines the relationships between social participation and disaster risk reduction actions. A survey of 557 households in tsunami prone areas in Phang Nga, Thailand was conducted following the 2012 Indian Ocean earthquakes. We use a multivariate probit model to jointly estimate the likelihood of undertaking three responses to earthquake and tsunami hazards (namely, (1) following disaster-related news closely, (2) preparing emergency kits and/or having a family emergency plan, and (3) having an intention to migrate) and community participation.We find that those who experienced losses from the 2004 tsunami are more likely to participate in community activities and respond to earthquake hazards. Compared to men, women are more likely to prepare emergency kits and/or have an emergency plan and have a greater intention to migrate. Living in a community with a higher proportion of women with tertiary education increases the probability of engaging in community activities and carrying out disaster risk reduction measures. Individuals who participate in village-based activities are 5.2% more likely to undertake all three risk reduction actions compared to those not engaging in community activities. This implies that encouraging participation in community activities can have positive externalities in disaster mitigation

Locating sex-specific evidence on clinical questions in MEDLINE: a search filter for use on OvidSP™

<p>Abstract</p> <p>Background</p> <p>Many recently published clinical studies report sex-specific data. This information may help to improve clinical decision-making for both sexes, but it is not easily accessible in MEDLINE. The aim of this project was to develop and validate a search filter that would facilitate the retrieval of studies reporting high quality sex-specific data on clinical questions.</p> <p>Methods</p> <p>A filter was developed by screening titles, abstracts and Medical Subject Headings (MeSH) in a set of 80 high quality and relevant papers, 75 of which were identified through a review of clinical guidelines and five through other means. The filter, for use on OvidSP™, consists of nine command lines for searching free text words in the title, abstract and MeSH of a paper. It was able to identify 74/80 (92.5%) of the articles from which it was derived. The filter was evaluated in a set of 622 recently published original studies on Alzheimer's disease and on asthma. It was validated against a reference of 98 studies from this set, which provided high quality, clinically relevant, sex-specific evidence. Recall and precision were used as performance measures.</p> <p>Results</p> <p>The filter demonstrated 81/98 (83%) recall and 81/125 (65%) precision in retrieving relevant articles on Alzheimer's disease and on asthma. In comparison, only 30/98 (31%) recall would have been achieved if sex-specific MeSH terms only had been used.</p> <p>Conclusion</p> <p>This sex-specific search filter performs well in retrieving relevant papers, while its precision rate is good. It performs better than a search with sex-specific MeSH. The filter can be useful to anyone seeking sex-specific clinical evidence (e.g., guideline organizations, researchers, medical educators, clinicians).</p