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.

Interactions and self-organization in the soil-microbe complex.

Soil is the most complicated biomaterial on the planet. As with any material, the physical habitat is of prime importance in determining and regulating biological activity. However, until recently the opaque nature of soil has meant that any interrogation of its interior architecture has been relatively rudimentary, restricted to simple qualitative expressions of the physical heterogeneity that fail to relate to any specific function. However, new techniques and insights into the biophysical and biochemical processes of this inner space are leading to the developments of theoretical frameworks and experimental approaches that will allow us to sustainably manage Earth's most important resource. We introduce the concept that the soil-microbe system is self-organized and suggest new priorities for research based on an integrative approach that combines biochemistry and biophysics.

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.

In situ spatial patterns of soil bacterial populations, mapped at multiple scales, in an arable soil.

Very little is known about the spatial organization of soil microbes across scales that are relevant both to microbial function and to field-based processes. The spatial distributions of microbes and microbially mediated activity have a high intrinsic variability. This can present problems when trying to quantify the effects of disturbance, management practices, or climate change on soil microbial systems and attendant function. A spatial sampling regime was implemented in an arable field. Cores of undisturbed soil were sampled from a 3 x 3 x 0.9 m volume of soil (topsoil and subsoil) and a biological thin section, in which the in situ distribution of bacteria could be quantified, prepared from each core. Geostatistical analysis was used to quantify the nature of spatial structure from micrometers to meters and spatial point pattern analysis to test for deviations from complete spatial randomness of mapped bacteria. Spatial structure in the topsoil was only found at the microscale (micrometers), whereas evidence for nested scales of spatial structure was found in the subsoil (at the microscale, and at the centimeter to meter scale). Geostatistical ranges of spatial structure at the micro scale were greater in the topsoil and tended to decrease with depth in the subsoil. Evidence for spatial aggregation in bacteria was stronger in the topsoil and also decreased with depth in the subsoil, though extremely high degrees of aggregation were found at very short distances in the deep subsoil. The data suggest that factors that regulate the distribution of bacteria in the subsoil operate at two scales, in contrast to one scale in the topsoil, and that bacterial patches are larger and more prevalent in the topsoil.

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.

Towards a general theory of biodiversity.

The study of patterns in living diversity is driven by the desire to find the universal rules that underlie the organization of ecosystems. The relative abundance distribution, which characterizes the total number and abundance of species in a community, is arguably the most fundamental measure in ecology. Considerable effort has been expended in striving for a general theory that can explain the form of the distribution. Despite this, a mechanistic understanding of the form in terms of physiological and environmental parameters remains elusive. Recently, it has been proposed that space plays a central role in generating the patterns of diversity. Here we show that an understanding of the observed form of the relative abundance distribution requires a consideration of how individuals pack in time. We present a framework for studying the dynamics of communities which generalizes the prevailing species-based approach to one based on individuals that are characterized by their physiological traits. The observed form of the abundance distribution and its dependence on richness and disturbance are reproduced, and can be understood in terms of the trade-off between time to reproduction and fecundity.

Prospects for advancing the understanding of complex biochemical systems.

The application of mathematical theories to understanding the behaviour of complex biochemical systems is reviewed. Key aspects of behaviour are identified as the flux through particular pathways in a steady state, the nature and stability of dynamical states, and the thermodynamic properties of systems. The first of these is dealt primarily in theories of metabolic control, and metabolic control analysis (MCA) is an important example. The valid application of this theory is limited to steady-state systems, and the cases where the essential features of control can be derived from calibration experiments which perturb the state of the system by a sufficiently small amount from its operating point. In practice, time-dependent systems exist, it is not always possible to know a priori whether applied perturbations are sufficiently small, and important features of control may lie farther from the operating point than the application of the theory permits. The nature and stability of dynamical and thermodynamical states is beyond the scope of MCA. To understand the significance of these limitations fully, and to address the dynamical and thermodynamical properties, more complete theories are required. Non-linear systems theory offers the possibility of studying important questions regarding control of steady and dynamical states. It can also link to thermodynamic properties of the system including the energetic efficiency of particular pathways. However, its application requires a more detailed characterisation of the system under study. This extra detail may be an essential feature of the study of non-equilibrium states in general, and non-ideal pathways in particular. Progress requires considerably more widespread integration of theoretical and experimental approaches than currently exists.

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.

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.

Prenatal exclusion testing for Huntington's disease: a problem of too much information.

At eight weeks of pregnancy a couple were informed that the prospective father's mother had died of Huntington's disease (HD). There were no living affected members in the immediate family to confirm the diagnosis. By inspection of the local genetic register, it was established that it was indeed HD segregating in the extended family. Genotyping of the prospective mother and father, the father's unaffected father, and his unaffected maternal grandmother was carried out using a battery of polymorphic DNA markers, including a new probe which has a very low recombination rate with the HD locus. Analysis of DNA from a chorionic villus sample taken at 10 weeks of pregnancy showed that the fetus must have inherited a chromosome from its father's affected mother. Its risk of developing HD was 47%. If the genotype of the unaffected maternal grandmother was taken into account, the risk was reduced to 42%. Neither risk was considered acceptable by the prospective parents and the pregnancy was terminated at 12 weeks' gestation. Prospects for future pregnancies are good, with a 50% chance of having a child whose risk of inheriting the HD gene is less than 1.5%. In retrospect it was noted that although genotyping of the maternal grandmother had refined the fetal risk, it had also nearly contributed to an inadvertent and unwanted predictive test for HD on the father. This case makes the point that in prenatal exclusion testing, linkage information must be generated with considerable care.

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.

The effect of fetal heart rate on umbilical artery flow velocity waveforms.

Umbilical artery flow velocity waveforms were obtained using continuous wave Doppler ultrasound in 85 normal pregnancies (25 antepartum, 60 intrapartum) to examine the relation between fetal heart rate, end systolic/end diastolic ratio (A/B ratio) and resistance index (RI). Our results demonstrated a significant negative correlation between fetal heart rate, A/B ratio and RI (in the antepartum group r = -0.49, and in the labouring group r = -0.65). It is therefore important when performing mathematical analysis of umbilical artery flow velocity profiles to make a statistical allowance for fetal heart rate.

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.