The vascular targeting agent combretastatin-A4 and a novel cis-Restricted {beta}-Lactam Analogue, CA-432, induce apoptosis in human chronic myeloid leukemia cells and ex vivo patient samples including those displaying multidrug resistance

Combretastatin-A4 (CA-4) is a natural derivative of the African willow tree Combretum caffrum. CA-4 is one of the most potent antimitotic components of natural origin, but it is, however, intrinsically unstable. A novel series of CA-4 analogs incorporating a 3,4-diaryl-2-azetidinone (β-lactam) ring were designed and synthesized with the objective to prevent cis -trans isomerization and improve the intrinsic stability without altering the biological activity of CA-4. Evaluation of selected β-lactam CA-4 analogs demonstrated potent antitubulin, antiproliferative, and antimitotic effects in human leukemia cells. A lead β-lactam analog, CA-432, displayed comparable antiproliferative activities with CA-4. CA-432 induced rapid apoptosis in HL-60 acute myeloid leukemia cells, which was accompanied by depolymerization of the microtubular network, poly(ADP-ribose) polymerase cleavage, caspase-3 activation, and Bcl-2 cleavage. A prolonged G(2)M cell cycle arrest accompanied by a sustained phosphorylation of mitotic spindle checkpoint protein, BubR1, and the antiapoptotic proteins Bcl-2 and Bcl-x(L) preceded apoptotic events in K562 chronic myeloid leukemia (CML) cells. Molecular docking studies in conjunction with comprehensive cell line data rule out CA-4 and β-lactam derivatives as P-glycoprotein substrates. Furthermore, both CA-4 and CA-432 induced significantly more apoptosis compared with imatinib mesylate in ex vivo samples from patients with CML, including those positive for the T315I mutation displaying resistance to imatinib mesylate and dasatinib. In summary, synthetic intrinsically stable analogs of CA-4 that display significant clinical potential as antileukemic agents have been designed and synthesized.

HRM and the employment of older workers: Germany and Britain compared

This study examines Human Resource Management (HRM) policies and practices towards older workers in Britain and Germany. While it is widely suggested that older workers have to be better integrated into the labour market, youth-centric HRM is still prevalent. However, HRM is shaped by multiple and contradictory pressures from the international and national institutional environments. We test this dynamic by analysing two national surveys, the German firm panel (IAB)1 and the British Workplace and Employment Relations Survey (WERS).2 Our findings suggest that the institutional environment shapes HR policies and practices distinctively in both countries. We find that age discrimination at the workplace is more prevalent in Germany than in Britain, which can be explained by divergent institutional patterns. As a result, we argue that although both countries will have to continue fostering an age-neutral HR approach, this has to take country-specific institutional peculiarities into account.

Empathy in UK pharmacy students: assessing differences by gender, level in the degree programme, part-time employment and medical status

Background: Empathy is an important aspect of patient–healthcare professional interactions.Aims: To investigate whether gender, level in the degree programme, employment and health status affected empathy scores of undergraduate pharmacy students.Method: All undergraduate pharmacy students (n=529) at Queen’s University Belfast were invited via email to completean online validated empathy questionnaire. Empathy scores were calculated and non-parametric tests used to determine associations between factors.Results: Response rate was 60.1% (318/529) and the mean empathy score was 106.19. Scores can range from 20 to 140,with higher scores representing a greater degree of empathy. There was no significant difference between genders (p=0.211). There was a significant difference in scores across the four levels of the programme (p<0.001); scores were lowest at Level 1 and greatest at Level 4 (final year). There were no significant differences in scores for respondents who had a part-time job, a chronic condition, or took regular medication in comparison to those who did not (p=0.028,p=0.880, p=0.456, respectively).Conclusion: A reasonable level of empathy was found relative to other studies; this could be further enhanced at lower levels of the degree pathway.

Work-related training and the probability of transitioning from non-permanent to permanent employment

It is widely believed that work-related training increases a worker’s probability of moving up the job-quality ladder. This is usually couched in terms of effects on wages, but it has also been argued that training increases the probability of moving from non-permanent forms of employment to more permanent employment. This hypothesis is tested using nationally representative panel data for Australia, a country where the incidence of non-permanent employment, and especially casual employment, is high by international standards. While a positive association between participation in work-related training and the subsequent probability of moving from either casual or fixed-term contract employment to permanent employment is observed among men, this is shown to be driven not by a causal impact of training on transitions but by differences between those who do and do not receive training; i.e., selection bias.

Employment regulation, game theory, and the lacuna in employee participation in liberal economies

Employee participation is a vital ingredient of what the International Labour Organization (ILO) calls ‘representation security’. This article provides theoretical and empirical insights relating to social policy impact of worker participation, specifically the European Information and Consultation Directive (ICD) for employee voice rights. While existing research on the ICD offers important empirical insights, there is a need for further theoretical analysis to examine the potential effectiveness of the regulations in liberal market economies (LMEs). Drawing on data from 16 case studies, the article uses game theory and the prisoner's dilemma framework to explain why national implementing legislation is largely ineffective in diffusing mutual gains cooperation in two LMEs: UK and the Republic of Ireland. Three theoretical (metaphorical) propositions advance understanding of the policy impact of national information & consultation regulations in LMEs.