Tumor resistance to alkylating agents conferred by mechanisms operative only in vivo.

EMT-6 murine mammary tumors were made resistant to cis-diamminedichloroplatinum (II) (CDDP), carboplatin, cyclophosphamide (CTX), or thiotepa in vivo by treatment of tumor-bearing animals with the drug during a 6-month period. In spite of high levels of in vivo resistance, no significant resistance was observed when the cells from these tumors were exposed to the drugs in vitro. The pharmacokinetics of CDDP and CTX were altered in animals bearing the respective resistant tumors. The resistance of all tumor lines except for the EMT-6/thiotepa decreased during 3 to 6 months in vivo passage in the absence of drugs. These results indicate that very high levels of resistance to anticancer drugs can develop through mechanisms that are expressed only in vivo.

Ontario Child Health Study. I. Methodology.

We developed the methodology for a community survey to determine the prevalence of emotional and behavioral disorders among children 4 to 16 years of age in Ontario, Canada. Our discussion includes the objectives of the survey, the measurement of disorder, sampling methods and survey design, and a description of the data collected and instrumentation. Among 2052 households with eligible children, 1869 (91%) participated in the survey. The results can be used to help plan the future allocation of mental health resources in Ontario.

Ontario Child Health Study. II. Six-month prevalence of disorder and rates of service utilization.

We studied the six-month prevalence of four child psychiatric disorders (conduct disorder, hyperactivity, emotional disorder, and somatization) and patterns of service utilization for mental health and social services, ambulatory medical care and special education by different regions of Ontario, urban-rural residence, and age and sex groupings. Among children 4 to 16 years of age, the overall six-month prevalence rate of one or more of these disorders was 18.1%. The prevalences of hyperactivity and one or more disorders were significantly higher in urban areas than rural areas. The utilization data indicated that children with these psychiatric disorders, compared with children without these disorders, were almost four times more likely to have received mental health or social services in the six months preceding this study. However, five of six of these children had not received these specialized services in the previous six-month period. Over 50% of the children in the province had received ambulatory medical care in the last six months. Over 15% of the children in the province had received special education services at some time thus far in their school careers. Implications of these findings, especially for the provision of child mental health services, are discussed.

Research in psychiatry: a co-citation analysis.

Co-citation analysis provides a methodology for investigating the structure of scientific specialties. The authors did such an analysis for psychiatry by using some 2 million references from the Social Sciences Citation Index to identify 155 clusters of publication that represent psychiatry-related areas. They report on the distribution of publications among research areas, the rate of growth in research activity, and interrelationships among disciplines.

Plant roots release phospholipid surfactants that modify the physical and chemical properties of soil.

• Plant root mucilages contain powerful surfactants that will alter the interaction of soil solids with water and ions, and the rates of microbial processes. • The lipid composition of maize, lupin and wheat root mucilages was analysed by thin layer chromatography and gas chromatography-mass spectrometry. A commercially available phosphatidylcholine (lecithin), chemically similar to the phospholipid surfactants identified in the mucilages, was then used to evaluate its effects on selected soil properties. • The lipids found in the mucilages were principally phosphatidylcholines, composed mainly of saturated fatty acids, in contrast to the lipids extracted from root tissues. In soil at low tension, lecithin reduced the water content at any particular tension by as much as 10 and 50% in soil and acid-washed sand, respectively. Lecithin decreased the amount of phosphate adsorption in soil and increased the phosphate concentration in solution by 10%. The surfactant also reduced net rates of ammonium consumption and nitrate production in soil. • These experiments provide the first evidence we are aware of that plant-released surfactants will significantly modify the biophysical environment of the rhizosphere.

Nutritional influence on fungal colony growth and biomass distribution in response to toxic metals.

This work examines nutritional influence on fungal colony growth and biomass distribution in response to toxic metals. In low-substrate solid medium, 0.1 mM Cd, Cu and Zn caused a decrease in radial expansion of both Trichoderma viride and Rhizopus arrhizus. However, as the amount of available carbon source (glucose) increased, the apparent toxicity of the metals decreased. These metals also affected the overall length of the fungal mycelium and branching patterns. In low-nutrient conditions, T. viride showed a decrease in overall mycelial length and number of branches in response to Cu, resulting in an extremely sparsely branched colony. Conversely, although Cd also reduced overall mycelial length to about one-third of the control length, the number of branches decreased only slightly which resulted in a highly branched colony with many aberrant features. Cu and Cd induced similar morphological changes in R. arrhizus. A large-scale mycelial-mapping technique showed that disruption of normal growth by Cu and Cd resulted in altered biomass distribution within the colony. When grown on metal-free low-substrate medium, T. viride showed an even distribution of biomass within the colony with some allocation to the periphery. However, Cu caused most of the biomass to be allocated to the colony periphery, while in the presence of Cd, most biomass was located at the interior of the colony. These results imply that such alterations of growth and resource allocation by Cu and Cd may influence success in locating nutrients as well as survival, and that these metals have individual and specific effects on the growing fungus.

Purification and radioimmunoassay of human alpha-1-fetoprotein: the effect of aggregates on the radioimmunoassay.

A simple method for the extraction of alpha1-fetoprotein from fetal serum in high yield and of sufficient purity for use as radio-iodinated tracer in a radioimmunoassay is described. The purified alpha1-fetoprotein formed aggregates during storage. The presence of 125I-labelled aggregates affected the double antibody radioimmunoassay by increasing the non-specific bound, resulting in decreases assay sensitivity. Freshly prepared 125I-labelled monomer alpha1-fetoprotein is prepared for each assay. The radioimmunoassay described is sensitive to between 100 and 200 pg per tube. Normal adult serum levels were found to be in the range from less than 1 mug/l to 16 mug/l.

Transitions and new dynamical states induced by noise in a multiply regulated biochemical system.

Noise-induced transitions between coexisting states, and the emergence of a new oscillatory state, are examined in a model for a multiply regulated biochemical system. For the undisturbed system, three oscillatory states, I, II, and III, coexist. It is found that noise above a critical amplitude can cause a transition between states III and II and between states III or II and state I, whereas a transition from state I to either states II or III is never observed. This indicates that the relative stability under noise perturbations is greatest for state I, and progressively less for states II and III. In addition to this transition behaviour, a purely noise-induced state is found. Under noise perturbations, the average concentration of metabolites may depend on both the time duration and amplitude of the superimposed noise. The implications of these results for understanding the in vivo behaviour of complex biochemical systems are discussed.

An approach for treating the uncertainties in the impact of climate change.

Past accumulated data supported by the predictions of climate models suggest that our world is getting warmer. Scientists are trying to construct mathematical models of both climate and crop systems to identify what types of climate changes could constitute a significant risk or benefit for agriculture. However, due to the many uncertainties regarding these models, it is impossible to make unequivocal predictions. At present, almost all the research in this area is carried out without considering the uncertain nature of the problem. The approach outlined here attempts to find a way to deal with the above uncertainty problem. Artificial intelligence techniques are being developed with the aim of performing inferences based on uncertain information. In our method, causal graphs are used for explicit representation of the relationships between climatic factors and yield. Probabilities are used to express the uncertainties associated with these links, and Bayes' theorem is applied to deal with uncertainty reasonings. This approach has the additional advantage of allowing the prediction to be readily updated as results from improved climate and crop models become available. These opportunities are being evaluated initially by using the model for potato growth developed at the Scottish Crop Research Institute.

Modelling of healthcare-associated infections: a study on the dynamics of pathogen transmission by using an individual-based approach.

Prevention and control of Healthcare Associated Infections (HAIs) has become a high priority for most healthcare organizations. Mathematical models can provide insights into the dynamics of nosocomial infections and help to evaluate the effect of infection control measures. The model presented in this paper adopts an individual-based and stochastic approach to investigate MRSA outbreaks in a hospital ward. A computer simulation was implemented to analyze the dynamics of the system associated with the spread of the infection and to carry out studies on space and personnel management. This study suggests that a strict spatial cohorting might be ineffective, if it is not combined with personnel cohorting.

Effects of carbon dioxide on the searching behaviour of the root-feeding clover weevil Sitona lepidus (Coleoptera: Curculionidae).

The respiratory emission of CO2 from roots is frequently proposed as an attractant that allows soil-dwelling insects to locate host plant roots, but this role has recently become less certain. CO2 is emitted from many sources other than roots, so does not necessarily indicate the presence of host plants, and because of the high density of roots in the upper soil layers, spatial gradients may not always be perceptible by soil-dwelling insects. The role of CO2 in host location was investigated using the clover root weevil Sitona lepidus Gyllenhall and its host plant white clover (Trifolium repens L.) as a model system. Rhizochamber experiments showed that CO2 concentrations were approximately 1000 ppm around the roots of white clover, but significantly decreased with increasing distance from roots. In behavioural experiments, no evidence was found for any attraction by S. lepidus larvae to point emissions of CO2, regardless of emission rates. Fewer than 15% of larvae were attracted to point emissions of CO2, compared with a control response of 17%. However, fractal analysis of movement paths in constant CO2 concentrations demonstrated that searching by S. lepidus larvae significantly intensified when they experienced CO2 concentrations similar to those found around the roots of white clover (i.e. 1000 ppm). It is suggested that respiratory emissions of CO2 may act as a 'search trigger' for S. lepidus, whereby it induces larvae to search a smaller area more intensively, in order to detect location cues that are more specific to their host plant.

Limitations of current fetal monitoring technology.

Continuous recordings with a cardiotocograph are confused with the concept of monitoring. One of the continuing problems is ensuring that recordings are properly monitored by the clinical staff. Previous simplistic attempts at producing true monitors which failed to work inhibited the development of more sophisticated approaches which modern technology now make possible. The use of computers in this field would not only reduce the monitoring load on the staff but also have advantages in data storage, data transfer and in audit. The profession has failed to demand, and the manufacturers to offer, the advantages of modern technology which could improve our level of intra-partum care.

Follow-up of hydatidiform mole by radioimmunoassay of human chorionic gonadotrophin.

An improved method for the follow-up of patients delivered of a hydatidiform mole using radioimmunoassay of human chorionic gonadotrophin is employed to ensure adequate sensitivity. Four illustrative case histories are described. Their HCG findings are presented to show that this is the principal basis on which decisions should be made.There are three aspects to the work of the laboratory. The technical work of the assay, the clerical effort of patient follow-up, and the clinical interpretation of results. The laboratory keeps a close check on follow-up (one of its most important functions) and receives specimens direct from patients. Overall control of all three aspects is by a clinician. It has been found useful to organize a special clinic for these patients to be seen. In this region it has been possible for this to be run by the same clinician.

Computer monitoring of fetal heart rate and uterine pressure.

With the introduction of continuous recording cardiotocographs in the labor room the large quantity of numerical data produced suggested the computer would be of use. In this preliminary study two computers were used: one initially to collect data and later to give comment and advice as the data was collected and the other for in-depth anaylsis of the previously collected data. On the basis of this new information a new way of analyzing and categorizing labor is suggested and some of the clinical impact so far achieved is described.

Letter: Complications of laparoscopy.

PIP: Of 83 patients who were admitted for outpatient laparoscopic sterilization, 8 chose to remain overnight. 2 of these 8 women underwent laparotomy and sterilization. The 83 patients (not counting the 2 laparotomies) required 89 bed days, which is a shorter period of time than that previously reported for laparoscopy. No complications of any consequence occurred. Most patients were given follow-up appointments. The day approach to laparoscopic sterilization appeared to be popular with the patients.^ieng

Mother-infant interaction in premature and full-term infants.

The interactions of 16 premature and 17 full-term infants and their mothers were studied at 6, 8, 10, and 14 months of age. The infants were matched on sex, maternal age, parity, and social class. Premature infants vocalized less, played less, and were more fretful than full-term infants of the same chronological age but looked at objects and looked around their environment more. These differences, with the exception of vocalization, disappeared by 14 months. Mothers of premature infants demonstrated more caretaking and affectionate behavior toward their infants. With increasing age the differences between groups decreased. Premature dyads experienced as much interaction as full-term dyads, but premature mothers were not constant over the period under study in the amount of time they spend in the same room as their infants. Mothers responded to the developmental level of their infants. Premature infants behaved increasingly like full-term infants as they grew older.

Omphalocoele and raised alpha-fetoprotein in maternal serum. Case report.

We describe a pregnant patient with raised serum AFP levels. The infant had multiple congenital abnormalities which included an omphalocoele.