Estimating HIV incidence rates from age prevalence data in epidemic situations

We present a method of estimating HIV incidence rates in epidemic situations from data on age-specific prevalence and changes in the overall prevalence over time. The method is applied to women attending antenatal clinics in Hlabisa, a rural district of KwaZulu/Natal, South Africa, where transmission of HIV is overwhelmingly through heterosexual contact. A model which gives age-specific prevalence rates in the presence of a progressing epidemic is fitted to prevalence data for 1998 using maximum likelihood methods and used to derive the age-specific incidence. Error estimates are obtained using a Monte Carlo procedure. Although the method is quite general some simplifying assumptions are made concerning the form of the risk function and sensitivity analyses are performed to explore the importance of these assumptions. The analysis shows that in 1998 the annual incidence of infection per susceptible woman increased from 5.4 per cent (3.3-8.5 per cent; here and elsewhere ranges give 95 per cent confidence limits) at age 15 years to 24.5 per cent (20.6-29.1 per cent) at age 22 years and declined to 1.3 per cent (0.5-2.9 per cent) at age 50 years; standardized to a uniform age distribution, the overall incidence per susceptible woman aged 15 to 59 was 11.4 per cent (10.0-13.1 per cent); per women in the population it was 8.4 per cent (7.3-9.5 per cent). Standardized to the age distribution of the female population the average incidence per woman was 9.6 per cent (8.4-11.0 per cent); standardized to the age distribution of women attending antenatal clinics, it was 11.3 per cent (9.8-13.3 per cent). The estimated incidence depends on the values used for the epidemic growth rate and the AIDS related mortality. To ensure that, for this population, errors in these two parameters change the age specific estimates of the annual incidence by less than the standard deviation of the estimates of the age specific incidence, the AIDS related mortality should be known to within +/-50 per cent and the epidemic growth rate to within +/-25 per cent, both of which conditions are met. In the absence of cohort studies to measure the incidence of HIV infection directly, useful estimates of the age-specific incidence can be obtained from cross-sectional, age-specific prevalence data and repeat cross-sectional data on the overall prevalence of HIV infection. Several assumptions were made because of the lack of data but sensitivity analyses show that they are unlikely to affect the overall estimates significantly. These estimates are important in assessing the magnitude of the public health problem, for designing vaccine trials and for evaluating the impact of interventions. Copyright (C) 2001 John Wiley & Sons, Ltd.

Modelling life history strategies with capture-recapture data: Evolutionary demography of the water skink Eulamprus tympanum

Matrix population models, elasticity analysis and loop analysis can potentially provide powerful techniques for the analysis of life histories. Data from a capture-recapture study on a population of southern highland water skinks (Eulamprus tympanum) were used to construct a matrix population model. Errors in elasticities were calculated by using the parametric bootstrap technique. Elasticity and loop analyses were then conducted to identify the life history stages most important to fitness. The same techniques were used to investigate the relative importance of fast versus slow growth, and rapid versus delayed reproduction. Mature water skinks were long-lived, but there was high immature mortality. The most sensitive life history stage was the subadult stage. It is suggested that life history evolution in E. tympanum may be strongly affected by predation, particularly by birds. Because our population declined over the study, slow growth and delayed reproduction were the optimal life history strategies over this period. Although the techniques of evolutionary demography provide a powerful approach for the analysis of life histories, there are formidable logistical obstacles in gathering enough high-quality data for robust estimates of the critical parameters.

Disaggregation of polygons of surficial geology and soil maps using spatial modelling and legacy data

Examples from the Murray-Darling basin in Australia are used to illustrate different methods of disaggregation of reconnaissance-scale maps. One approach for disaggregation revolves around the de-convolution of the soil-landscape paradigm elaborated during a soil survey. The descriptions of soil ma units and block diagrams in a soil survey report detail soil-landscape relationships or soil toposequences that can be used to disaggregate map units into component landscape elements. Toposequences can be visualised on a computer by combining soil maps with digital elevation data. Expert knowledge or statistics can be used to implement the disaggregation. Use of a restructuring element and k-means clustering are illustrated. Another approach to disaggregation uses training areas to develop rules to extrapolate detailed mapping into other, larger areas where detailed mapping is unavailable. A two-level decision tree example is presented. At one level, the decision tree method is used to capture mapping rules from the training area; at another level, it is used to define the domain over which those rules can be extrapolated. (C) 2001 Elsevier Science B.V. All rights reserved.

Modelling of post-irradiation events in polymer gel dosimeters

The nuclear magnetic resonance (NMR) spin-spin relaxation time (T-2) is related to the radiation-dependent concentration of polymer formed in polymer gel dosimeters manufactured from monomers in an aqueous gelatin matrix. Changes in T-2 with time post-irradiation have been reported in the literature but their nature is not fully understood. We investigated those changes with time after irradiation using FT-Raman spectroscopy and the precise determination of T-2 at high magnetic field in a polymer gel dosimeter, A model of fast exchange of magnetization taking into account ongoing gelation and strengthening of the gelatin matrix as well as the polymerization of the monomers with time is presented. Published data on the changes of T-2 in gelatin gels as a function of post-manufacture time are used and fitted closely by the model presented. The same set of parameters characterizing the variations of T-2 in gelatin gels and the increasing concentration of polymer determined from Fr-Raman spectroscopy are used successfully in the modelling of irradiated polymer gel dosimeters. Minimal variations in T-2 in an irradiated PAG dosimeter are observed after 13 h.

Nuclear calcium signaling evoked by cholinergic stimulation in hippocampal CA1 pyramidal neurons

The cholinergic system is thought to play an important role in hippocampal-dependent learning and memory. However, the mechanism of action of the cholinergic system in these actions in not well understood. Here we examined the effect of muscarinic receptor stimulation in hippocampal CA1 pyramidal neurons using whole-cell recordings in acute brain slices coupled with high-speed imaging of intracellular calcium. Activation of muscarinic acetylcholine receptors by synaptic stimulation of cholinergic afferents or application of muscarinic agonist in CA1 pyramidal neurons evoked a focal rise in free calcium in the apical dendrite that propagated as a wave into the soma and invaded the nucleus. The calcium rise to a single action potential was reduced during muscarinic stimulation. Conversely, the calcium rise during trains of action potentials was enhanced during muscarinic stimulation. The enhancement of free intracellular calcium was most pronounced in the soma and nuclear regions. In many cases, the calcium rise was distinguished by a clear inflection in the rising phase of the calcium transient, indicative of a regenerative response. Both calcium waves and the amplification of action potential-induced calcium transients were blocked the emptying of intracellular calcium stores or by antagonism of inositol 1,4,5-trisphosphate receptors with heparin or caffeine. Ryanodine receptors were not essential for the calcium waves or enhancement of calcium responses. Because rises in nuclear calcium are known to initiate the transcription of novel genes, we suggest that these actions of cholinergic stimulation may underlie its effects on learning and memory.

Baseline laboratory bioassay data for spinosad against populations of Australian sheep blowfly, Lucilia cuprina (Wiedemann) (Diptera : Calliphoridae)

Spinosad was an effective larvicide against the Australian sheep blowfly, Lucilia cuprina. A survey of 41 field populations indicated no cross-resistance to spinosad from existing organophosphate resistance. The data presented serve as baseline data for future resistance surveys.

Ultrasound evaluation of polymer gel dosimeters

A new method for the evaluation of radiotherapy 3D polymer gel dosimeters has been developed using ultrasound to assess the significant structural changes that occur following irradiation of the dosimeters. The ultrasonic parameters of acoustic speed of propagation, attenuation and transmitted signal intensity were measured as a function of absorbed radiation dose. The dose sensitivities for each parameter were determined as 1.8 x 10(-4) s m(-1) Gy(-1), 3.9 dB m(-1) Gy(-1) and 3.2 V-1 Gy(-1) respectively. All parameters displayed a strong variation with absorbed dose that continued beyond absorbed doses of 15 Gy. The ultrasonic measurements demonstrated a significantly larger dynamic range in dose response curves than that achieved with previously published magnetic resonance imaging (MRI) dose response data. It is concluded that ultrasound shows great potential as a technique for the evaluation of polymer gel dosimeters.

Conformations of platypus venom C-type natriuretic peptide in aqueous solution and sodium dodecyl sulfate micelles

Nuclear magnetic resonance spectroscopy was used to investigate the conformations of the platypus venom C-type natriuretic peptide A (OvCNPa) in aqueous solutions and in solutions containing sodium dodecyl sulfate (SDS) micelles. The chemically synthesized OvCNPa showed a substantial decrease in flexibility in aqueous solution at 10 degreesC, allowing the observation of medium- and long-range nuclear Overhauser enhancement (NOE) connectivities. Three-dimensional structures calculated using these data showed flexible and reasonably well-defined regions, the locations of which were similar in the two solvents. In aqueous solution, the linear part that spans residues 3-14 was basically an extended conformation while the cyclic portion, defined by residues 23-39, contained a series of beta-turns. The overall shape of the cyclic portion was similar to that observed for an atrial natriuretic peptide (ANP) variant in aqueous solution. OvCNPa adopted a different conformation in SDS micelles wherein the N-terminal region, defined by residues 2-10, was more compact, characterised by turns and a helix, while the cyclic region had turns and an overall shape that was fundamentally different from those structures observed in aqueous solution. The hydrophobic cluster, situated at the centre of the ring of the structure in aqueous solution, was absent in the structure in the presence of SDS micelles. Thus, OvCNPa interacts with SDS micelles and can possibly form ion-channels in cell membranes. (C) 2002 Elsevier Science Ltd. All rights reserved.

CD40 ligation conditions dendritic cell antigen-presenting function through sustained activation of NF-kappa B

An understanding of the biochemical control of dendritic cell (DC) differentiation/activation is essential for improving T cell immunity by various immunotherapeutic approaches, including DC immunization. Ligation of CD40 enhances DC function, including conditioning for CTL priming. NF-kappaB, and particularly RelB, is an essential control pathway for myeloid DC differentiation. Furthermore, RelB regulates B cell Ag-presenting function. We hypothesized that CD40 ligand (CD40L) and TNF-alpha, which differ in their capacity to condition DC, would also differ in their capacity to activate NF-kappaB. DC differentiated for 2 days from monocytes in the presence of GM-CSF and IL-4 were used as a model, as NF-kappaB activity was constitutively low. The capacity of DC to activate T cells following CD40L treatment was enhanced compared with TNF-alpha treatment, and this was NF-kappaB dependent. Whereas RelB/p50 translocation induced by TNF-alpha was attenuated after 6 h, RelB/p50 nuclear translocation induced by CD40L was sustained for at least 24 h. The mechanism of this difference related to enhanced degradation of IkappaBalpha following CD40L stimulation. However, NF-kappaB activation induced by TNF-alpha could be sustained by blocking autocrine IL-10. These data indicate that NF-kappaB activation is essential for T cell activation by DC, and that this function is enhanced if DC NF-kappaB activation is prolonged. Because IL-10 moderates DC NF-kappaB activation by TNF-alpha, sustained NF-kappaB activation can be achieved by blocking IL-10 in the presence of stimuli that induce TNF-alpha.

Are we too busy to volunteer? The relationship between time and volunteering using the 1997 ABS Time Use Data

Time availability is a key concept in relation to volunteering, leading to organisations and governments targeting those outside paid work as a potential source of volunteers. It may be that factors such as a growth in female participation in the labour market and an increase in work hours will lead to more people saying they are simply too busy to volunteer This paper discusses how social and economic change, such as changing work patterns, are impacting on time availability. Using the 1997 ABS Time Use data, it identifies a predictive model of spare time by looking at demographic, life stage and employment related variables. Results confirm that those outside paid work, particularly the young, males and those without partners or children, are the groups most likely to have time to spare. These groups do not currently report high rates of volunteering. The paper concludes by questioning the premise that people will volunteer simply because they have time to spare. This is just one component of a range of motivations and factors that influence the decision to volunteer.

An economic evaluation of plasma production via erythroplasmapheresis and whole blood collection

This paper presents cost-effectiveness analyses (CEAs) of plasma collection via two alternative methods: whole blood collection (WBC) and erythroplasmapheresis collection (EPC). The objective of the study is to provide an answer to the question 'What is the least-cost method of plasma production'. This question is answered, both from the viewpoint of the blood collection agency (using financial CEA) and from that of 'society' as a whole (using economic CEA). We employ detailed financial data and economic survey data for collections made by a blood collection agency and to WBC and EPC donors in Brisbane, Australia. The results indicate that, despite the superior yield provided by EPC, WBC is actually more cost-effective. This result is robust to thorough sensitivity analysis and arises regardless of whether an economic or financial perspective is taken. We conclude that, ceteris paribus, the cost of recruiting new plasma donors would need to be quite substantial for marginal investments in EPC to be considered cost-effective. Crown Copyright (C) 2002 Published by Elsevier Science Ltd. All rights reserved.

Spatial data mining for enhanced soil map modelling

The principle of using induction rules based on spatial environmental data to model a soil map has previously been demonstrated Whilst the general pattern of classes of large spatial extent and those with close association with geology were delineated small classes and the detailed spatial pattern of the map were less well rendered Here we examine several strategies to improve the quality of the soil map models generated by rule induction Terrain attributes that are better suited to landscape description at a resolution of 250 m are introduced as predictors of soil type A map sampling strategy is developed Classification error is reduced by using boosting rather than cross validation to improve the model Further the benefit of incorporating the local spatial context for each environmental variable into the rule induction is examined The best model was achieved by sampling in proportion to the spatial extent of the mapped classes boosting the decision trees and using spatial contextual information extracted from the environmental variables.

Cytokine-related genes identified from the RIKEN full-length mouse cDNA data set

To identify novel cytokine-related genes, we searched the set of 60,770 annotated RIKEN mouse cDNA clones (FANTOM2 clones), using keywords such as cytokine itself or cytokine names (such as interferon, interleukin, epidermal growth factor, fibroblast growth factor, and transforming growth factor). This search produced 108 known cytokines and cytokine-related products such as cytokine receptors, cytokine-associated genes, or their products (enhancers, accessory proteins, cytokine-induced genes). We found 15 clusters of FANTOM2 clones that are candidates for novel cytokine-related genes. These encoded products with strong sequence similarity to guanylate-binding protein (GBP-5), interleukin-1 receptor-associated kinase 2 (IRAK-2), interleukin 20 receptor alpha isoform 3, a member of the interferon-inducible proteins of the Ifi 200 cluster, four members of the membrane-associated family 1-8 of interferon-inducible proteins, one p27-like protein, and a hypothetical protein containing a Toll/Interleukin receptor domain. All four clones representing novel candidates of gene products from the family contain a novel highly conserved cross-species domain. Clones similar to growth factor-related products included transforming growth factor beta-inducible early growth response protein 2 (TIEG-2), TGFbeta-induced factor 2, integrin beta-like 1, latent TGF-binding protein 4S, and FGF receptor 4B. We performed a detailed sequence analysis of the candidate novel genes to elucidate their likely functional properties.

Identification of novel "pathologs" (human disease-related gene candidates) from the RIKEN full-length mouse cDNA data set

The majority of common diseases such as cancer, allergy, diabetes, or heart disease are characterized by complex genetic traits, in which genetic and environmental components contribute to disease susceptibility. Our knowledge of the genetic factors underlying most of such diseases is limited. A major goal in the post-genomic era is to identify and characterize disease susceptibility genes and to use this knowledge for disease treatment and prevention. More than 500 genes are conserved across the invertebrate and vertebrate genomes. Because of gene conservation, various organisms including yeast, fruitfly, zebrafish, rat, and mouse have been used as genetic models.

pH dependence of the progression in NMR T-2 relaxation times in post-mortem muscle

Continuous NMR T-2 relaxation measurements were carried out on seven rabbit longissimus muscle samples in the period from 25 min to 28 h post-mortem at 200 MHz for H-1. To display differences in post-mortern pH progress and extent of changes in water characteristics during conversion of muscle to meat, three of the seven animals were pre-slaughter injected with adrenaline (0.5 mg/kg live weight 4 h before sacrifice) to differentiate muscle glycogen stores at the time of slaughter. Distributed analysis of T-2 data displayed clear differences in the characteristics of the various transverse relaxation components dependent on progress in pH, as did the water-holding capacity of samples 24 h postmortem. This reveals a pronounced effect of the progressive change in pH on the subsequent development in physical/chemical states of water during the conversion of muscle to meat. Finally, the relaxation characteristics are discussed in relation to supposed post-mortem processes of protein denaturation.