The interdependence between screening methods and screening libraries

The most common methods for discovery of chemical compounds capable of manipulating biological function involves some form of screening. The success of such screens is highly dependent on the chemical materials - commonly referred to as libraries - that are assayed. Classic methods for the design of screening libraries have depended on knowledge of target structure and relevant pharmacophores for target focus, and on simple count-based measures to assess other properties. The recent proliferation of two novel screening paradigms, structure-based screening and high-content screening, prompts a profound rethink about the ideal composition of small-molecule screening libraries. We suggest that currently utilized libraries are not optimal for addressing new targets by high-throughput screening, or complex phenotypes by high-content screening.     

Cervical cancer screening, screening errors and reporting

Screening for cervical carcinoma by cervicovaginal cytology has led to a marked reduction in the incidence of and mortality from this tumor over the last 50 years in essentially all countries with a functioning screening program. It is the most successful cancer prevention program of all times. Consequently, approximately 80% of the current incidence of and mortality from this disease occurs in geographic areas of underserved and underscreened women. Essential components of a successful program are a high coverage rate of the female population, screening at regular intervals, well-trained clinical and laboratory staff, and an efficient follow-up and treatment system. Deficiencies in any of these areas may lead to a failing screening system. Thus, the most important reason for the remaining mortality from cervical carcinoma in developed countries is lack of complete coverage. It is questionable if new and more expensive technologies will be able to renmedy the remaining failures of the system if no improvement in the coverage rate is achieved. Screening errors do occur but represent only a small fraction of screening failures. Currently, there are a number of terminology systems around the world; thus, a unified terminology is currently not a realistic goal.     

Dual screening

We discuss the problem of screening a general population for characteristics such as HIV or drug use. Our main approach is Bayesian, which allows for the incorporation of prior information about parameters. In the particular problem we consider, there is currently no information in the data for estimating the sensitivity of the screening test, and consequently, the prevalence of the characteristic among screened negatives cannot be estimated from the collected data alone. Our inferences are straightforward to obtain using Gibbs sampling techniques, and they are valid for large or small samples and for arbitrary prevalence or accuracy of screening tests. We also develop the maximum-likelihood approach using the EM algorithm.     

Practical approaches to efficient screening: information-rich screening protocol

The past approach of high-throughput screening of everything in the corporate collection has been shown to be very expensive in terms of reagents cost, disposal cost, and compound collection depletion. It is well known that screening campaigns produce several hits, of which only 50% confirm on average. More efficient ways of screening can provide an informative structure-activity relationship (SAR), which in turn can be used to build mathematical models for further probing the activity space and directing chemical synthesis. The authors report new methods and insights to extract the maximum possible information from a screening experiment and find most of the possible hits in the corporate collection while screening as few compounds as possible.     

Immunological screening of welders

74 healthy welders were subjected to immunological screening. Serum immunoglobulins (IgG, IgA, IgM) were measured as well as total and active E-RFC and cellular immunity was evaluated using the intradermal testing of PPD, candidin D-7, trichophytin D-5 and tetanus anatoxin. The obtained results suggest suppression of the T and B lymphocyte immune systems as expressed by decreased levels of serum IgG and total E-RFC. Cell-mediated immune deficiency was found in 21.6% welders. Suppression of the immune system may be accounted for by a complex effect of occupational factors, such as manganese compounds, vibration and noise.     

Probability screening model

A comparative analysis is given of various types of systems of selecting biologically active substances. A theoretical probability model of tests on chemical compounds for biological activity (screening) has been constructed which permits an evaluation of the efficacy of screening on the basis of fairly reasonable assumptions. It has been shown that this efficacy decreases in time with a fixed number of types of activity taken into consideration and rises sharply with an increase in the number of types of activity of chemical compounds taken into account in the tests.     

Cervical screening revisited

Some of the achievements of cervical screening in the reduction of morbidity and mortality in different countries are briefly reviewed, along with a consideration of some of the aspects of cervical cancer screening programs. The latter include the organization of the program (e.g., whether it is organized by the national health authorities), the protection afforded by routine screening, the assurance of quality in cervical sampling and in the screening program, the screening interval, the age groups to be screened, the compliance of women to present themselves for screening and of health care personnel to provide appropriate follow-up and/or treatment for the lesions diagnosed, the problem of false positives and its relation to overdiagnosis and overtreatment and, finally, the cost effectiveness. It is concluded that a centrally organized and well supervised cervical screening program, cautiously executed and with all involved parties closely cooperating, can be a cost-effective means of combatting cervical cancer.