Low energy secondary electron induced damage of condensed nucleotides.

Radiation damage and stimulated desorption of nucleotides 2'-deoxyadenosine 5'-monophosphate (dAMP), adenosine 5'-monophosphate (rAMP), 2'-deoxycytidine 5'-monophosphate (dCMP), and cytidine 5'-monophosphate (rCMP) deposited on Au have been measured using x-rays as both the probe and source of low energy secondary electrons. The fluence dependent behavior of the O-1s, C-1s, and N-1s photoelectron transitions was analyzed to obtain phosphate, sugar, and nucleobase damage cross sections. Although x-ray induced reactions in nucleotides involve both direct ionization and excitation, the observed bonding changes were likely dominated by the inelastic energy-loss channels associated with secondary electron capture and transient negative ion decay. Growth of the integrated peak area for the O-1s component at 531.3 eV, corresponding to cleavage of the C-O-P phosphodiester bond, yielded effective damage cross sections of about 23 Mb and 32 Mb (1 Mb = 10-18 cm2) for AMP and CMP molecules, respectively. The cross sections for sugar damage, as determined from the decay of the C-1s component at 286.4 eV and the glycosidic carbon at 289.0 eV, were slightly lower (about 20 Mb) and statistically similar for the r- and d- forms of the nucleotides. The C-1s component at 287.6 eV, corresponding to carbons in the nucleobase ring, showed a small initial increase and then decayed slowly, yielding a low damage cross section (∼5 Mb). Although there is no statistical difference between the sugar forms, changing the nucleobase from adenine to cytidine has a slight effect on the damage cross section, possibly due to differing electron capture and transfer probabilities.

Size, myths and the clinical pharmacokinetics of analgesia in paediatric patients.

In the paediatric population, developmental changes can be predicted by age and are independent of size, which is predicted by bodyweight. Size is commonly standardised using either the per kilogram or the body surface area models. A great many physiological-, structural- and time-related variables scale predictably within and between species with weight exponents of 0.75, 1 and 0.25, respectively. Use of the per kilogram size model has led to the misconception that children have an enhanced capacity to metabolise drugs because of their relatively large liver size or increased hepatic blood flow. This is not necessarily the case. For example, the clearance of opioids often approaches adult rates within the first few months of life when an allometric 3/4 power model is used to scale for size. Age-related changes in physiological processes, such as respiration and cardiac output, disappear with appropriate size models. Size is an important, but little recognised, component in the speed of onset of drugs effects and uptake of inhalational anaesthetic agents. Size models cannot be reliably used to predict dose regimens for children from schedules established for adult patients. Dosage regimens are dependent on clearance and volume of distribution as well as pharmacodynamic factors, which change with age. The age-dependent pharmacodynamic changes described for some opioids in the very young have not yet been completely disentangled from age-related pharmacokinetic changes. When bodyweight is standardised and disentangled from age, developmental changes can be understood more clearly. The future investigation of drugs used in paediatric practice must also include an appropriate size model in order to differentiate age-related factors from size-related factors.

The British Airways Employee Assistance Programme: a community response to a company's problems.

Employee Assistance Programmes have developed since the early 1940s, particularly in North America, and are now part of many UK companies benefits packages for their staff (particularly in North America). This article details the development, philosophy, structure and practice of the British Airways Employee Assistance Programme.