Burnout and distress affect a significant proportion of oncology staff. There is a need for additional conceptually based, longitudinal, multivariate studies regarding burnout and its associated risk factors and consequences.

This article aims to identify how accessible general dental practitioners thought that their services were and to identify the barriers they face in providing care for disabled people. A postal questionnaire survey was undertaken of all general dental practices in the Liverpool, Sefton, St Helens and Knowsley Health Authorities. Only one quarter of practices described themselves as having full physical access for disabled patients. However, despite this, over 90% of practices reported treating disabled patients and most were willing to treat more disabled patients. Dentists identified physical barriers, lack of time and the lack of domiciliary equipment as the main barriers to providing care for disabled people. Although dentists were willing to treat disabled patients few dental practices were accessible at the time of the survey. Further work is needed to ensure that dental practices comply with the Disability Discrimination Act.

We developed a dynamic model of HIV transmission to evaluate the costs and benefits of HIV-vaccine programs in a population of homosexual men. We examined how changes in high-risk sexual behavior and the growth pattern of the epidemic influence the cost-effectiveness of preventive vaccines and of therapeutic vaccines. We found that the effect of reductions in condom use is more important for therapeutic vaccines than for preventive vaccines. Therapeutic vaccines may increase HIV seroprevalence in the population, unless the vaccine program is accompanied by increased condom use. Epidemic growth patterns also influence the cost-effectiveness of both vaccines, but the effects are more pronounced for preventive vaccines, which are more cost-effective in an early-stage epidemic than in a late-stage epidemic.

Structural modifications at the pyrimidine ring and at the C9,N10-bridge region of the thymidylate synthase (TS) inhibitors N10-propargyl-5,8-dideazafolate (1; PDDF; CB 3717), 2-desamino-N10-propargyl-5,8-dideazafolate (2, DPDDF), and 2-desamino-2-methyl-N10-propargyl-5,8-dideazafolate (3, DMPDDF) have been carried out. Methods for the synthesis of 2-desamino-N10-propargyl-1,5,8-trideazafolate (4), 2-desamino-2-methyl-N10-propargyl-3,5,8-trideazafolate (5a), and 2-desamino-2-methyl-N10-propargyl-5,8-dideaza-1,2-dihydrofolate (6) have been developed. The bridge-extended analogues isohomo-PDDF (7) and isohomo-DMPDDF (8) contain an additional methylene group interposed between N10 and the phenyl ring of 1 and 3, respectively. All new compounds were evaluated as inhibitors of TS and the growth of tumor cells in culture. Selected analogues were tested as substrates of folylpolyglutamate synthetase (FPGS) and striking differences in substrate activity were observed among these compounds, indicating that structural modifications at the pyrimidine ring of classical antifolates profoundly influence their polyglutamylation. Enzyme inhibition data established that both N1 and N3-H of the pyrimidine ring are essential for efficient binding of quinazoline-type antifolates to human TS.

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