Application of the Cre/lox System to Construct Auxotrophic Markers for Quantitative Genetic Analyses in Fusarium graminearum.

The bacteriophage P1 Cre/lox system has been utilized in diverse fungi for marker recycling and exchange, generation of targeted chromosome translocations, and targeted deletion of interstitial chromosome segments. Here we show the application of this tool in the wheat and maize pathogen, Fusarium graminearum. We explored three different ways to introduce Cre into strains with floxed genes, namely transformation with an episomal or integrative plasmid (pLC28), fusion of protoplasts of strains carrying floxed genes with strains expressing Cre by forcing heterokaryons, and crosses between strains with floxed genes and strains expressing Cre to isolate progeny in which the target genes had been deleted during the cross. We used this system for the construction of strains bearing auxotrophic markers that were generated by gene replacement with positively selectable markers followed by Cre-mediated marker excision. In addition, updated protocols for transformation and crosses for F. graminearum are provided. In combination, strains and tools developed here add to the arsenal of methods that can be used to carry out molecular genetics with F. graminearum.

Explosion probability of unexploded ordnance: expert beliefs.

This article reports on a study to quantify expert beliefs about the explosion probability of unexploded ordnance (UXO). Some 1,976 sites at closed military bases in the United States are contaminated with UXO and are slated for cleanup, at an estimated cost of $15-140 billion. Because no available technology can guarantee 100% removal of UXO, information about explosion probability is needed to assess the residual risks of civilian reuse of closed military bases and to make decisions about how much to invest in cleanup. This study elicited probability distributions for the chance of UXO explosion from 25 experts in explosive ordnance disposal, all of whom have had field experience in UXO identification and deactivation. The study considered six different scenarios: three different types of UXO handled in two different ways (one involving children and the other involving construction workers). We also asked the experts to rank by sensitivity to explosion 20 different kinds of UXO found at a case study site at Fort Ord, California. We found that the experts do not agree about the probability of UXO explosion, with significant differences among experts in their mean estimates of explosion probabilities and in the amount of uncertainty that they express in their estimates. In three of the six scenarios, the divergence was so great that the average of all the expert probability distributions was statistically indistinguishable from a uniform (0, 1) distribution-suggesting that the sum of expert opinion provides no information at all about the explosion risk. The experts' opinions on the relative sensitivity to explosion of the 20 UXO items also diverged. The average correlation between rankings of any pair of experts was 0.41, which, statistically, is barely significant (p= 0.049) at the 95% confidence level. Thus, one expert's rankings provide little predictive information about another's rankings. The lack of consensus among experts suggests that empirical studies are needed to better understand the explosion risks of UXO.

The origin and course of schizophrenia: implications for clinical practice.

The authors first review current evidence concerning abnormalities of brain structure and function in schizophrenia and interpret them within a "network" pathophysiological model of the disorder. This information is then placed within a contemporary neurodevelopmental framework that "roots" the illness in adverse events during early pregnancy, which result in a developmentally compromised nervous system. They then consider the controversy as to whether the subsequent expression of psychosis reflects an active morbid process and, in a more general sense, whether the disorder is characterized by subsequent progression and clinical deterioration. The authors argue that the developmental and progressive models should not be considered in an either-or manner, since this perspective is not logical and favors nihilistic approaches to intervention and treatment, but rather should be integrated within a lifetime trajectory model. Finally, implications for current psychiatric practice are considered.

A deliberative method for ranking risks (I): Overview and test bed development.

Risk ranking offers a potentially powerful means for gathering public input to help set risk-management priorities. In most rankings conducted to date, the categories and attributes used to describe the risks have varied widely, the materials and procedures have not been designed to facilitate comparisons among risks on all important attributes, and the validity and reproducibility of the resulting rankings have not been assessed. To address these needs, a risk-ranking method was developed in which risk experts define and categorize the risks to be ranked, identify the relevant risk attributes, and characterize the risks in a set of standardized risk summary sheets, which are then used by lay or other groups in structured ranking exercises. To evaluate this method, a test bed involving 22 health and safety risks in a fictitious middle school was created. This article provides an overview of the risk-ranking method and describes the challenges faced in designing the middle school test bed. A companion article in this issue reports on the validity of the ranking procedures and the level of agreement among risk managers regarding ranking of risks and attributes.

A deliberative method for ranking risks (II): Evaluation of validity and agreement among risk managers.

A deliberative method for ranking risks was evaluated in a study involving 218 risk managers. Both holistic and multiattribute procedures were used to assess individual and group rankings of health and safety risks facing students at a fictitious middle school. Consistency between the rankings that emerged from these two procedures was reasonably high for individuals and for groups, suggesting that these procedures capture an underlying construct of riskiness. Participants reported high levels of satisfaction with their groups' decision-making processes and the resulting rankings, and these reports were corroborated by regression analyses. Risk rankings were similar across individuals and groups, even though individuals and groups did not always agree on the relative importance of risk attributes. Lower consistency between the risk rankings from the holistic and multiattribute procedures and lower agreement among individuals and groups regarding these rankings were observed for a set of high-variance risks. Nonetheless, the generally high levels of consistency, satisfaction, and agreement suggest that this deliberative method is capable of producing risk rankings that can serve as informative inputs to public risk-management decision making.

Fungal surveillance of an open haematology ward.

Air sampling and surveillance cultures for fungi were performed in a Scottish general haematology ward over a five-month period in 1997. The mean total fungal count from the air sampling appeared to be correlated with the number of patients colonized by Aspergillus. The most commonly isolated species were Aspergillus versicolor, A. fumigatus and A. niger. Rooms with portable air filtration units had significantly lower total fungal counts than the others. Swabs were taken from 70 patients (mean age 62 years); 114 of the 563 cultures (20.2%) were positive. The most commonly isolated species were A. fumigatus, Candida albicans, C. glabrata and C. parapsilosis. Samples taken from the tongue and perineum showed colonization more often than those taken from the nostrils. Almost half the patients (48.6%) were colonized on, or within seven days of, admission; 11.4% became colonized whilst on the unit. One patient developed fatal aspergillosis. We conclude that colonization or high air-borne spore concentrations are not necessarily predictive of fungal infection but may prompt early treatment or more aggressive prophylaxis of potentially fatal invasive infections.

Categorizing risks for risk ranking.

Any practical process of risk ranking must group hazards into a manageable number of categories. Defining such categories requires value choices that can have important implications for the rankings that result. Most risk-management organizations will find it useful to begin defining categories in terms of environmental loadings or initiating events. However, the resulting categories typically need to be modified in light of other considerations. Risk-ranking projects can benefit from considering several alternative categorization strategies and drawing upon elements of each in developing their final categorization of risks. In principle, conducting multiple ranking exercises by using different categorizations could be interesting and useful. In practice, agencies are unlikely to have either the resources or patience to do this, but other groups in society might. Done well, such additional independent rankings could add valuable inputs to democratic risk-management decision making.

Peer reviewed: risk management should be about efficiency and equity.

A hybrid strategy that addresses both issues can be developed, and its feasability should be explored.

The efficacy of different methods for informing the public about the range dependency of magnetic fields from high voltage power lines.

The AC electric and magnetic fields associated with high voltage power lines have become a concern as a possible health risk. In most cases the strength of these fields decreases as the inverse square of the distance from the line. In earlier work, we found that laypeople do not understand how rapidly field strength decreases with distance. Most believe that any high voltage power line they can see is exposing them to strong fields. This paper confirms the earlier finding and explores a number of strategies which might be used in risk communications to correct this misperception. We found it relatively easy to provide subjects with a better understanding of the range-dependency of magnetic field strength. Moreover, the quality of this acquisition was apparently independent of the manner in which they were instructed. Such successful instruction is markedly different from the well-established difficulty of teaching people about many qualitative domains, such as physics or ideas in probability. Clearly, while some erroneous beliefs are highly resistant to change, others can be altered quite readily. We suspect that an important distinction between knowledge about the range-dependency of power-frequency magnetic fields and less tractable topics involves the presence or absence of prior folk-theories or "mental models" of the domain.

Influence of biological and analytical variation on urine measurements for monitoring exposure to cadmium.

OBJECTIVE: To define the mean intraindividual biological variation in urinary concentrations of cadmium and retinol binding protein (RBP) in untimed, random urine samples and the influence of creatinine or specific gravity correction on reducing this variation. The relation between biological variation and analytical variation in defining uncertainty in a single measurement and significant differences between successive measurements was explored. METHODS: Repeat measurement study in subjects with either high historical exposure to cadmium but without current exposure, or unexposed volunteers. Standard statistical tools used in clinical laboratory medicine were applied to define intraindividual biological and analytical variation. RESULTS AND CONCLUSION: Both creatinine and specific gravity correction of urinary cadmium measurements in random urine samples seem to reduce the intraindividual variability compared with uncorrected values. With a standard definition, acceptable long term analytical precision for measurements of cadmium and RBP combined with creatinine analyses should be < 9% and < 15% respectively. The mean intraindividual biological variation of cadmium and RBP, expressed as creatinine corrected, was 18% and 40% respectively in the subjects exposed to cadmium. With the analytical precision used, significant differences (p < 0.05) between consecutive measurements for creatinine corrected urinary cadmium and RBP would need to show changes of > 54% and > 110% respectively. The relation between significant differences in consecutive results and differences in the analytical precision of the method used to measure the samples is described.

Effects function simulation of residential appliance field exposures.

This paper demonstrates the application of effects function analysis to residential magnetic field exposure, focusing on appliance sources and mitigation choices. Residential field exposure time series were synthesized by using a sample of background household field measurements, a model of average daily appliance use, and a small sample of EMDEX data of field exposure from 12 household strength window, sudden field changes) were simulated by using the synthesized time series data for different exposure situations, such as high and low levels of appliance use, simple avoidance, and use of a set of hypothetical "low field" appliances (50% lower fields). In particular, field exposure from the use of bedside clocks and electric blankets was examined. Results demonstrate that the choice of effects function is critical for the ranks of field sources and exposure reduction choices. For the effects function of average field strength with or without a threshold, exposure from background fields dominated exposure from all appliances except for bedside clocks and electric blankets. In the case of the field strength window effects function, the dominant field sources changed with the width of the window. For the effects function based on rapid field changes, appliance use was the major source of exposure. Because of the small sample of our data set and other simplifications, specific results should be viewed as illustrative.

A method for evaluating transmission line magnetic field mitigation strategies that incorporates biological uncertainty.

A method to determine how much reduction in public exposure to power frequency magnetic fields can be obtained for different levels of investment is presented. Which if any "effects function" best describes the relationship between field exposure and biological effect is uncertain at this time. Also, in a particular context such as construction of new transmission lines there are a variety of different technologies which might be used to reduce exposure. We describe and demonstrate a method by which exposure reduction supply curves (i.e., the cost of purchasing different amounts of exposure reduction given various mitigation options) can be estimated parametrically for different exposure conditions and effects functions, and we display illustrative results.