Drug design for ever, from hype to hope.

In its first 25 years JCAMD has been disseminating a large number of techniques aimed at finding better medicines faster. These include genetic algorithms, COMFA, QSAR, structure based techniques, homology modelling, high throughput screening, combichem, and dozens more that were a hype in their time and that now are just a useful addition to the drug-designers toolbox. Despite massive efforts throughout academic and industrial drug design research departments, the number of FDA-approved new molecular entities per year stagnates, and the pharmaceutical industry is reorganising accordingly. The recent spate of industrial consolidations and the concomitant move towards outsourcing of research activities requires better integration of all activities along the chain from bench to bedside. The next 25 years will undoubtedly show a series of translational science activities that are aimed at a better communication between all parties involved, from quantum chemistry to bedside and from academia to industry. This will above all include understanding the underlying biological problem and optimal use of all available data.

The cost of transport in an extended trot.

We hypothesised that trotters during an extended trot have lower energetic costs of locomotion (CT) than horses not bred for this behaviour. VO2 was measured as a function of speed in 7 Arabian horses (3 trained to extend their trotting speeds) and in 2 horses, of similar mass, bred to trot (Hackney). Both oxygen consumption and CT increased with speed and there was, contrary to our hypothesis, no difference between breeds. In Arabians at 6.5 m/s, CT had increased 25% above the CT at 5.0 m/s (normal transition speed). For Hackneys at 6.8 m/s, the CT was almost 35% higher. Stride frequencies increased linearly in all horses up to 5.0 m/s. At the canter at 5.0 m/s, the frequency increased 9% to 111 strides/min, but then increased minimally with speed. In the Hackneys and the Arabians that extended the trot, stride frequencies were approximately 102 and did not increase with speed. Stride length (SL) increased linearly with speed in both trotting and cantering horses, and cantering SL were lower than trotting (at 5.0 m/s, SL for trotting = 3.04 m and for cantering SL = 2.68 m). There were no differences between breeds in stride frequency or stride length. Extending the trot can have profound energetic requirements that could limit athletic performance and may lead to increased concussive impact on the limbs.

Total system performance assessment for waste disposal using a logic tree approach.

The Electric Power Research Institute (EPRI) has sponsored the development of a model to assess the long-term, overall "performance" of the candidate spent fuel and high-level radioactive waste (HLW) disposal facility at Yucca Mountain, Nevada. The model simulates the processes that lead to HLW container corrosion, HLW mobilization from the spent fuel, and transport by groundwater, and contaminated groundwater usage by future hypothetical individuals leading to radiation doses to those individuals. The model must incorporate a multitude of complex, coupled processes across a variety of technical disciplines. Furthermore, because of the very long time frames involved in the modeling effort (>> 10(4) years), the relative lack of directly applicable data, and many uncertainties and variabilities in those data, a probabilistic approach to model development was necessary. The developers of the model chose a logic tree approach to represent uncertainties in both conceptual models and model parameter values. The developers felt the logic tree approach was the most appropriate. This paper discusses the value and use of logic trees applied to assessing the uncertainties in HLW disposal, the components of the model, and a few of the results of that model. The paper concludes with a comparison of logic trees and Monte Carlo approaches.

Financial management of academic clinical departments.

Based on their ten years of experience, the authors describe how they have organized and managed the financial resources in the department of medicine at the University of Maryland School of Medicine. They outline how to develop realistic budgets to best account for different sources of income and expenses and how to utilize subsidies and incentives to challenge division heads and faculty to administer their units efficiently and maximize income. The values of regular financial reports, of an annual retreat of the division heads, and of effective departmental administration to maintain financial stability and progress of are emphasized. Finally ,the authors explain why they favor a more open policy of sharing much of the department's financial information rather than restricting such data to leadership.

Rehabilitation status: a measure of medicosocial dysfunction.

The Edinburgh Rehabilitation Status Scale (ERSS) measures four dimensions in which changes may occur in the course of a disabling illness or during rehabilitation: independence; activity; social integration; and effects of symptoms on lifestyle. It provides a profile of measures, the scores of which can be summated to indicate the overall level of performance of individuals or groups. Studies of its inter-observer reliability and of its application in various disability groups indicate that the ERSS reliably defines the characteristics of individual patients and of groups. The scale can be used conveniently by professional staff working independently or by a multiprofessional rehabilitation team to assess status and changes in patients. It can also be used for measurement of the effectiveness of services and for purposes of research, teaching, and administration.