Human Interindividual Variability in Cancer Risks—Technical and Management Challenges

Existing risk assessment procedures for carcinogens are intended to be “conservative” in the uncertainty dimension—giving estimates that are expected to be higher than true risks for typical people. However, these procedures do not consider the likely variability in susceptibility among individual people. This paper updates previous estimates of the likely extent of this variability for metabolically activated, genetically-acting carcinogens based on recent information on human interindividual variability in metabolic activation, detoxification, and DNA repair. The resulting expected skewness of cancer risk distributions is estimated using Monte Carlo simulations of both variability and uncertainty.

Some risk management implications are:

1. When evaluating the fairness of a particular risk distribution, managers need to gain familiarity with a three-dimensional characterization—X level of risk, for the Yth percentile individual (addressing variability) with Z degree of confidence (addressing uncertainty).

2. To the extent that variability distributions are skewed (e.g., with a long tail extending to high values) population mean risks will tend to exceed risks for median individuals. Together with the skewness in uncertainty distributions, this implies that “expected value” estimates of aggregate population risks—the estimates of interest for cost benefit analyses—are likely to be closer to traditional upper confidence limit risk estimates than has often been assumed in the past.

The role of the National Trust in the conservation of British butterflies

The National Trust is of paramount importance in the conservation of butterflies in the UK on account of the scale of its land holding and its ability to manage habitats beneficially. Fifty two of the fifty four species currently regarded as resident in Britain occur on Trust land. The Trust has major responsibilities for the conservation of all bar one of the British rarities, and is of special significance in the conservation of the high brown fritillary and heath fritillary, two protected species. The Trust owns some 35 areas (many of which are large) of national importance for butterflies, plus much other property where the butterfly fauna is of regional importance. The Trust is implementing many dynamic projects aimed at conserving rare species, maintains a butterfly site data base and is developing a butterfly population monitoring programme. It is well placed to address the key issue of butterfly conservation on a metapopulation scale. To do this, it must work in partnership with other conservation organizations.     

Towards an understanding of the relations between tree nutrition,nutrient cycling and environment

The paper contains a discussion of the interrelations between the sciences used by managers of forest land to improve their management, in particular with respect to the plant nutrient economy of the forest ecosystems. Both site studies and studies of nutrient cycling have been carried out for long periods without proper consideration of tree nutrition. Therefore these studies contributed less to the understanding of the role of nutrients as regulators of processes in ecosystems than might have been expected. This situation has improved, especially within the last decade. In addition the necessity to manage forest land for environmental values as well as for forest yield requires new interdisciplinary approaches in the study of the roles of plant nutrients in the forest. Even more branches of biological and environmental sciences than those just mentioned must be involved.     

Simulation and dynamic optimisation of animal cell culture

In animal cell culture, there are some 25 substrates that both have a significant effect on the culture performance and which can be measured with relative ease. A detailed dynamic simulation for such a culture has been produced and an optimisation policy that use this model to identify ideal media conditions has been developed. This paper describes an extension of that work to include the dynamic optimisation of cultures under fed-batch operation. Two different types of feeding policy were considered – in the first, discrete shots of feed were supplied, while in the second, feed was added continuously. Both policies offered significant improvements in the predicted productivity of the culture - up to 30% that of an experimentally optimisedbatch culture.     

Rehabilitating degraded forests in Central Europe into self–sustaining forest ecosystems

There is a need for a consistent forest restoration strategy for the `Black Triangle', Central Europe. In the past 50 years, forests in this area have been heavily affected by industrial pollution. Recently, the amount of pollutants has decreased. This means that effective forest restoration programmes can be started. Forest decline must be seen as an ecological disturbance which cannot be solved by applying technical measures only. An ecosystem approach to forest restoration must be introduced into restoration policy and management. Basic principles and working methods of such an approach are briefly described and proposals are made for forest restoration policy, management and research in the area.     

Isozymes and DNA markers in gene conservation of forest trees

For long-lived plants that have to cope with high temporal and spatial environmental heterogeneity, genetic diversity is of prime importance for species persistence. Detrimental anthropogenic impact on the gene pool of forest trees calls for conservation of genetic resources. Potentials and limitations of isozymes and DNA markers in forest genetic conservation are reviewed. These markers can contribute to conservation with respect to the delimitations of species and hybrid zones, as well as the assessment of genetic diversity within and among populations. Markers are valuable to identify resource populations, since today‘s genetic diversity in forest trees is predominantly the result of plant history (e.g. glacial refuges, migration). Several suggestions have been put forward to optimize sampling of in situ or ex situ populations on the grounds of marker data. Restraint in this area is recommended. Different types of genetic markers (terpenes, isozymes, nuclear and extrachromosomal DNA polymorphisms) and quantitative traits yield different information about genetic diversity and population differentiation. Hence identification of resource populations should not solely be based upon a certain marker type or on quantitative traits alone. The capability of available markers to predict or assess adaptive potentials in forest tree populations is still very limited. This revised version was published online in August 2006 with corrections to the Cover Date.     

The Human Obesity Gene Map: The 1996 Update

An update of the human obesity gene map up to October 1996 is presented. Evidence from Mendelian disorders exhibiting obesity as a clinical feature, single-gene mutation rodent models, quantitative trait loci uncovered in crossbreeding experiments with mouse, rat, and pig models, association and case-control studies with candidate genes, and linkage studies with genes and other markers is reviewed. All chromosomal locations of the animal loci are converted into human genome locations based on syntenic relationships between the genomes. A complete listing of all these loci reveals that only 4 of the 24 human chromosomes are not yet represented, i.e., 9, 18, 21, and Y. Several chromosome arms are characterized by the presence of several putative loci. The following arms include at least three such loci: 1p, 1q, 3p, 4q, 6p, 7q, 8p, 8q, 11p, 11q, 15q, 20q, and Xq. Studies with negative association and linkage results are also reviewed.     

Brief overview of control of genetic expression by antisense oligonucleotides and in vivo applications

Over the past several years, the use of synthetic oligonucleotides and functional analogs thereof as a possibly general means of controlling genetic expression has received widespread attention. Following a brief overview of some of the basic principles and strategies for this approach, attention is focused here on summarizing some recent reports of in vitro and, in particular, in vivo investigations in various animal models using phosphorothioate analogs of 2′-deoxyoligo-nucleotides. In view of these findings, which include studies related to neurobiology, this field should find significant utility in applications of the antisense method for controlling genetic expression.     

Keep all the pieces: Systematics 2000 and world conservation

Conserving biological diversity requires a major effort in conducting survey and inventories, establishing priorities, selecting protected areas, managing resources and monitoring the effects of management. Systematics has an important contribution to make to each of these five major activities. Further, the new Convention on Biological Diversity requires systematics information to support action under virtually all of its substantive conservation and sustainable use articles. It seems apparent that large reference collections contribute directly to development, and development assistance agencies should recognize that investing in maintaining these collections is a legitimate form of development assistance.