Modelling the distribution of Rhipicephalus microplus and R. decoloratus in Zimbabwe.

Species distribution modelling is a very useful tool in vector management. Ticks are vectors of various pathogens which cause serious problems in livestock production in tropical countries. They have a high dispersal potential which is mainly facilitated by the movement of animals from one area to another. In light of the observed geographic expansion of Rhipicephalus microplus in Zimbabwe, we used species distribution modelling techniques to identify areas which may provide suitable habitats for the occurrence of this invasive tick species as well as the autochthonous Rhipicephalus decoloratus. Our results suggest that, despite the geographic expansion of R. microplus, climate will continue to be a limiting factor for the further expansion of this tick species. We expect its distribution to be restricted to the most favourable areas in the eastern and northern parts. The greater part of Zimbabwe is suitable for R. decoloratus, although in areas where R. microplus occurs, displacement of the former by the latter will be expected to occur. A heterogeneous climate, unregulated movement of cattle and episodic droughts are suggested to be possible factors for the continued existence of R. microplus and R. decoloratus in Zimbabwe and the partial displacement.

THE INFLUENCE OF VARIABLE TEMPERATURE AND HUMIDITY ON THE PREDATION EFFICIENCY OF P. PERSIMILIS, N. CALIFORNICUS AND N. FALLACIS.

Predatory mites like Phytoseiulus persimilis Athias-Henriot, Neoseiulus californicus McGregor and N. fallacis (Garman) (Acari: Phytoseiidae) are essential in sustainable control strategies of the two-spotted spider mite Tetranychus urticae Koch (Acari: Tetranychidae) in warm greenhouse cultures to complement imited available pesticides and to tackle emerging resistance. However, in response to high energy prices, greenhouse plant breeders have recently changed their greenhouse steering strategies, allowing more variation in temperature and humidity. The impact of these variations on biological control agents is poorly understood. Therefore, we constructed functional response models to demonstrate the impact of realistic climate variations on predation efficiency. First, two temperature regimes were compared at constant humidity (70%) and photoperiod (16L:8D): DIF0 (constant temperature) and DIF15 (variable temperature with day-night difference of 15°C). At mean temperatures of 25°C, DIF15 had a negative influence on the predation efficiency of P. persimilis and N. californicus, as compared to DIF0. At low mean temperatures of 15°C, however, DIF15 showed a higher predation efficiency for P. persimilis and N. californicus. For N. fallacis no difference was observed at both 15°C and 25°C. Secondly, two humidity regimes were compared, at a mean temperature of 25°C (DIFO) and constant photoperiod (16L:8D): RHCTE (constant 70% humidity) and RHALT (alternating 40% L:70%D humidity). For P. persimilis and N. fallacis RHCTE resulted in a higher predation efficiency than RHALT, for N. californicus this effect was opposite. This shows that N. californicus is more adapted to dry climates as compared to the other predatory mites. We conclude that variable greenhouse climates clearly affect predation efficiency of P. persimilis, N. californicus and N. fallacis. To obtain optimal control efficiency, the choice of predatory mites (including dose and application frequency) should be adapted to the actual greenhouse climate.

A proteomic approach on the effects of TX527, a 1α,25-dihydroxyvitamin D3 analog, in human T lymphocytes.

1α,25-Dihydroxyvitamin D3 (1α,25(OH)2D3), and its analogs (i.e. 14,20-bis-epi-19-nor-23-yne-1α,25(OH)2D3 - TX527) have been shown to prevent autoimmunity and prolong islet graft survival in the non-obese diabetic (NOD) mouse. Their effects are mediated by their action on various immune cell types, such as dendritic cells (DC) and T cells. We have previously reported important direct effects of TX527 on human T cells, on their cytokine/chemokine profiles, T regulatory cell markers, homing characteristics and chemotaxis. In order to fully understand the molecular mechanisms underlying the beneficial properties of TX527 on human T cells, we applied here 2-dimensional difference gel electrophoresis (2-D DIGE) to analyze the global protein alterations induced by TX527 on human synchronized T cells. We detected differential expression of 64 protein spots upon TX527 treatment, of which 65.6% could be successfully identified using tandem mass spectrometry (MALDI-TOF/TOF). The identified proteins function in various processes, such as metabolism and energy pathways, cytoskeleton and protein metabolism. When comparing the proteomics data to our previously performed microarray data on the same set of cells, we found an overlap of 17 different mRNAs/proteins. For some of these (e.g. PSME2, HSPA8), the direction of regulation was not similar, hereby reinforcing the important role of post-transcriptional/translational processes in the functionality of proteins. In addition, although 2-D DIGE offers the possibility of picking up post-translational processes, it lacks the ability to detect molecules with extreme molecular weight (MW) and isoelectrical point (pI) values, or very low abundant/hydrophobic proteins. This study highlights therefore the importance of combining different experimental approaches to obtain a complete picture of the underlying mechanisms and general processes being affected in T cells upon TX527 treatment. These processes lead altogether to the generation of T cells with interesting immunomodulatory features for clinical applications in the treatment of autoimmune diseases or in the prevention of graft rejection. This article is part of a Special Issue entitled '16th Vitamin D Workshop'.

Inferring the origin of populations introduced from a genetically structured native range by approximate Bayesian computation: case study of the invasive ladybird Harmonia axyridis.

Correct identification of the source population of an invasive species is a prerequisite for testing hypotheses concerning the factors responsible for biological invasions. The native area of invasive species may be large, poorly known and/or genetically structured. Because the actual source population may not have been sampled, studies based on molecular markers may generate incorrect conclusions about the origin of introduced populations. In this study, we characterized the genetic structure of the invasive ladybird Harmonia axyridis in its native area using various population genetic statistics and methods. We found that native area of H. axyridis most probably consisted of two geographically distinct genetic clusters located in eastern and western Asia. We then performed approximate Bayesian computation (ABC) analyses on controlled simulated microsatellite data sets to evaluate (i) the risk of selecting incorrect introduction scenarios, including admixture between sources, when the populations of the native area are genetically structured and sampling is incomplete and (ii) the ability of ABC analysis to minimize such risks by explicitly including unsampled populations in the scenarios compared. Finally, we performed additional ABC analyses on real microsatellite data sets to retrace the origin of biocontrol and invasive populations of H. axyridis, taking into account the possibility that the structured native area may have been incompletely sampled. We found that the invasive population in eastern North America, which has served as the bridgehead for worldwide invasion by H. axyridis, was probably formed by an admixture between the eastern and western native clusters. This admixture may have facilitated adaptation of the bridgehead population.

Development of a web-based decision support system for insulin self-titration.

Insulin is the most potent agent for the treatment of diabetes mellitus. However insulin treatment requires frequent evaluation of blood glucose levels and adjustment of the insulin dose. This process is called titration. To guide patients with type 2 diabetes using once-daily long-acting insulin, we have developed a web-based decision support system for insulin self-titration. The purpose of this paper is to provide an overview of the phases of development and the final design of the system. We reviewed the literature, consulted an expert panel, and conducted interviews with patients to elicit system requirements. This revealed four important aspects: the insulin titration algorithm, the handling of hypoglycemic events, telemedicine functionalities, and visiting frequency monitoring. We used these requirements to develop a fully functional system.

Experimental evidence for the phenotypic impact of admixture between wild and biocontrol Asian ladybird (Harmonia axyridis) involved in the European invasion.

Hybridization can fuel evolutionary processes during biological invasions. The harlequin ladybird Harmonia axyridis has long been used as a biocontrol agent before the species became invasive worldwide. Previous analysis based on microsatellite data has shown that European invasive populations bear traces of admixture between an eastern North American source, which is at the origin of the worldwide invasion, and biocontrol strains used in Europe. In this study, we tested the hypothesis that this early admixture event may have fostered the European invasion by impacting on the phenotypes of wild European populations. Mean life history traits of experimental F(1) hybrids are compared with pure parental sources and wild European crosses. Our results reveal a biased impact whereby North American beetles benefitted from being admixed with European biocontrol strains. Resemblance between experimental hybrids and wild European invasive crosses further suggests a long-lasting effect of admixture that may still be at work and fostering invasiveness.

Development of a computerised alert system, ADEAS, to identify patients at risk for an adverse drug event.

INTRODUCTION: Adverse drug events (ADEs) are frequent and pose an important risk for patients treated with drugs. Fortunately, a substantial part of ADEs is preventable, and computerised physician order entry with a sophisticated clinical decision support system may be used to reach this goal. OBJECTIVE: To develop a new automated system that could improve the quality of medication surveillance. The system should focus on detecting patients at risk for an ADE by combining data from the hospital information system and computerised physician order entry (drug prescription data, drug-drug interaction alerts, clinical chemical laboratory parameters, demographic features), using clinical rules. METHODS: The clinical rules were formulated in a multidisciplinary team, based on seven risk categories. The new system was composed in a guideline-based decision support framework consisting of both a guideline development module and a decision support module. A total of 121 clinical rules were built into the system. Validation of the system and a proof of principle test were performed. RESULTS: The adverse drug event alerting system (ADEAS) was developed and validated successfully. The proof of principle test showed that ADEAS has potential clinical usefulness. ADEAS generated alerts and detected additional potential risk situations, which were not generated by the conventional medication surveillance. CONCLUSION: We developed a pharmacy decision support system ADEAS that focuses on the detection of situations prone to lead to an ADE and might help clinicians to take timely corrective interventions and thereby can prevent patient harm.

Wolbachia induces strong cytoplasmic incompatibility in the predatory bug Macrolophus pygmaeus.

Macrolophus pygmaeus is a heteropteran predator that is widely used in European glasshouses for the biological control of whiteflies, aphids, thrips and spider mites. We have demonstrated that the insect is infected with the endosymbiotic bacterium Wolbachia pipientis. Several gene fragments of the endosymbiont were sequenced and subsequently used for phylogenetic analysis, revealing that it belongs to the Wolbachia supergroup B. The endosymbiont was visualized within the ovarioles using immunolocalization. Tetracycline treatments were used to cure M. pygmaeus from its infection. Although a completely cured line could not be obtained by this approach, the application of a constant antibiotic pressure over 13 generations resulted in a line with a significantly reduced Wolbachia concentration. Crosses performed with this tetracycline-treated line revealed that the endosymbiont causes severe cytoplasmic incompatibility. This is the first report of a reproductive effect induced by Wolbachia in an economically important heteropteran predator that may have vital implications for its commercial production and use in biological control.

Intention-based expressions in GASTINE.

OBJECTIVES: 1) To evaluate the design of the framework for computerized intention-based clinical practice guidelines; 2) to implement runtime features such as plan recognition and backtracking. METHOD: To evaluate the design, we implemented the heart failure guideline into GASTINE, a tool for representing and executing intention-based clinical guidelines. RESULT: Description of the current implementation of intention-based expressions in GASTINE and analysis of some generic shortcomings. Explanation of how these shortcomings are addressed. Presentation of how plan recognition and backtracking work and how they improve the system. CONCLUSION: The improved guideline system is rather flexible, i.e., it allows deviations from the guideline as long as they are in the spirit of the guideline. The recognition of actions as intended by the users facilitates a flexible decision support system. The intentions are used to explain why certain actions were suggested. Therefore it is assumed that showing the intention behind suggested actions provides a better insight into why these actions are advised.

Developmental and reproductive fitness of Orius laevigatus (Hemiptera: Anthocoridae) reared on factitious and artificial diets.

The developmental and reproductive fitness of the polyphagous predator Orius laevigatus (Fieber) (Hemiptera: Anthocoridae) was compared on two factitious foods and four artificial diets. Adults fed factitious foods (Ephestia kuehniella Zeller eggs and Artemia franciscana Kellogg cysts) performed better than those fed artificial diets. Among the artificial diets, a diet composed of liver and ground beef scored better than meridic diets based on egg yolk. Within the egg yolk-based artificial diets, the developmental fitness varied proportionally with the amount of egg yolk present in the diet. A food switching experiment, in which nymphs and adults of the predator were fed either E. kuehniella eggs or an egg yolk-based artificial diet, showed that the impact of adult food on reproductive capacity was greater than that of nymphal food. An optimal adult food was able to wholly compensate for deficiencies incurred by an inferior artificial diet in the nymphal stage. A strong correlation was found between oocyte counts, lifetime oviposition, and the number of eggs laid after 8 d. A rapid dissection assay may thus be effective to reliably and economically assess the fitness of O. laevigatus as a function of the diet. This method also may prove useful as part of quality assurance procedure for commercially produced predators.

Mechanism and potential of the growth-inhibitory actions of vitamin D and ana-logs.

1alpha,25-Dihydroxyvitamin D(3) [1,25-(OH) (2)D(3)] can exert its biological actions through binding with the nuclear vitamin D receptor (VDR), a ligand-activated transcription factor. Next to control of bone and mineral homeostasis, these actions include an immunomodulatory effect and a potent growth-inhibitory, antiproliferative or prodifferentiating action on a wide variety of cell types. The molecular mechanisms underlying this antiproliferative action form an intriguing research topic and they remain, although thoroughly studied, not completely understood. Important cell cycle regulators are involved such as cyclins, cyclin dependent kinases and their corresponding inhibitors as well as E2F transcription factors and accompanying pocket proteins. Whether 1,25-(OH)(2)D(3) influences the expression of all these proteins directly through the nuclear VDR or rather in an indirect manner is not always clear. The antiproliferative action makes 1,25-(OH) (2)D(3) a possible therapeutic tool to treat hyperproliferative disorders, among which different types of cancer. Clinical application, however, is severely hampered by calcemic effects such as hypercalcemia, hypercalciuria and increased bone resorption. Rational design of chemically modified 1,25-(OH) (2)D(3)-analogs tries to overcome this problem. As such, several thousands of analogs have been synthesized and evaluated, some of which display the desired dissociation between beneficial antiproliferative and unwanted calcemic effects. A number of those analogs are 'superagonistic' and have a several-fold stronger antiproliferative action than the parent compound. This review focuses on recent findings about the complex mechanisms behind the antiproliferative and prodifferentiating effect of 1,25-(OH) (2)D(3). Furthermore, the mode of action and possible clinical application of chemically modified 1,25-(OH) (2)D(3)-analogs will be discussed.

The effect of computer reminders on GPs' prescribing behaviour: a cluster-randomised trial.

OBJECTIVE: It is difficult to control drug-prescribing behaviour in general practice, despite the development and distribution of guidelines. The purpose of this study was to assess the effect on drug-prescribing behaviour of implementing prescribing guidelines by means of a reactive computer reminder system (CRS). DESIGN: Cluster-randomised controlled trial with an incomplete block design in the south of the Netherlands: 25 GPs (7 GP practices) received reminders about antibiotics and asthma/COPD prescriptions, 28 GPs (7 GP practices) received reminders about cholesterol prescriptions. Prescription guidelines were integrated into the computerised GP information system. MEASUREMENTS: Both performance indicators and prescription volumes were calculated as the main outcome measures. Next to individual volume measure, sum scores were constructed on the volume measures per drug group (antibiotics, asthma/COPD and cholesterol). RESULTS: Variation between GPs turned out to be larger and more skewed than expected. No differences between groups were found for indicators and volumes related to recommendations advocating certain drugs. Although there was a tendency towards clinically relevant results for prescription volumes that were supposed to drop, the difference in sum score between the groups was not significant. For antibiotic prescriptions that were supposed to drop, the sum score for the intervention group was 28.2 (95% CI: 20.8-44.5) prescriptions per 1000 patients per GP, while this was 39.7 (95% CI: 29.7-64.1) for the control group (p 0.2). For prescriptions asthma/COPD that were supposed to drop, the sum score for the intervention group was 1.1 (95% CI: 0.6-2.6) prescriptions per 1000 patients per GP, while this was 2.2 (95% CI: 1.4-4.3) for the control group (p 0.1). On three specific recommendations (on quinolones for cystitis, corticosteroids for CPOD, and antibiotics for acute sore throat) significant differences were found. CONCLUSIONS: This study turned out to be underpowered due to high inter doctor variation in prescribing behaviour. Nevertheless, computerised reminders sometimes have a favourable effect on restricting certain drugs that are not or no longer indicated in general practice.

Effects of temperature on predation by the stinkbugs Picromerus bidens and Podisus maculiventris (Heteroptera: Pentatomidae) on noctuid caterpillars.

Environmental risks associated with the use of non-indigenous organisms for augmentative biological control have received growing attention. In Europe, the native pentatomid predator Picromerus bidens (Linnaeus) has been considered a potential alternative to the North American pentatomid Podisus maculiventris (Say) for the control of lepidopteran, coleopteran and hymenopteran defoliator pests. In the current study, prey consumption and developmental duration of the predatory stages of P. bidens and P. maculiventris were investigated at three temperatures (18, 23 and 27 degrees C) in the laboratory using caterpillars of Spodoptera littoralis as prey. Development time from second to fifth instar was longer for P. bidens than for P. maculiventris, taking on average 17-44 and 14-32 days, respectively, at the different temperatures. Total nymphal consumption of fourth instar S. littoralis caterpillars indicated a greater voracity of P. bidens as compared with P. maculiventris at both the low and high temperatures tested (18 and 27 degrees C). At 23 degrees C, however, the predation rate of P. maculiventris nymphs exceeded that of P. bidens nymphs. Effect of temperature on the functional response of P. bidens to densities of fourth instar Spodoptera exigua was assessed on potted green bean plants. Female adults of P. bidens exhibited a type II functional response at 18 and 23 degrees C but a type III response at 27 degrees C. Searching efficiency was not affected by temperature but handling time decreased from 4.2 to 1.4 h as temperature increased from 18 to 23 degrees C. However, the predator spent twice as much time handling prey at 27 degrees C (2.9 h) than at 23 degrees C. This study indicates high predation rates of P. bidens at a wide range of temperatures and suggests that the species may be a valuable asset for the biological control of defoliating caterpillars, provided that obstacles to its mass production can be overcome.

Three-Layer Model for the design of a Protocol Support System.

OBJECTIVE: The aim of the PropeR project is to investigate the impact of Active Computerized Protocol Support (ACPS) on daily care processes in different settings (home care and hospital care). ACPS consists of an active Protocol Support System (PSS) that is linked to an Electronic Patient Record system. The aim of this paper is to describe how we have taken the organizational and social aspects into account in the hospital setting and the consequences of this approach for the design of the PSS. METHODS: Socio-technical approaches have been applied. Observations and interviews with various health care providers were performed at the hematology and oncology department of the University Hospital Maastricht. Ten extensive sessions with a specialist physician and research nurse took place to further elaborate a study protocol and to discuss how it is integrated in daily practice. The knowledge editor component of Gaston was used to build a computer interpretable version of the selected protocol. RESULTS AND CONCLUSIONS: To support the representation of a study protocol integrated in routine clinical care, a Three-Layer Model was developed. This model distinguishes the protocol description, local adaptations to the protocol and communication as three separate layers. These layers have been incorporated into the knowledge acquisition tool Gaston. The Three-Layer Model makes easy updating possible, and also supports transferability of computerized (study) protocols to other organizations.

Nymphal development and feeding preference of Podisus maculiventris (Heteroptera: Pentatomidae) on eggs of Ephestia kuehniella (Lepidoptera: Pyralidae) parasitised or not by Trichogramma brassicae (Hymenoptera: Trichogrammatidae).

Predation by Podisus maculiventris nymphs, a predatory pentatomid, was evaluated with eggs of the flour moth Ephestia kuehniella (Pyralidae), parasitised or not by Trichogramma brassicae (pupae stage). Eggs of this pyralid were glued on rectangular cardboard and presented to nymphs of P. maculiventris as food. The pentatomid successfully reached adult stage when feeding on unparasitised eggs, indicating that flour moth eggs can be used as a factitious food for rearing this predator. Pentatomid nymphs that received only parasitised eggs died before reaching fourth instar. In choice tests, P. maculiventris showed a preference for preying on unparasitised eggs of E. kuehniella rather than those containing pupae of T. brassicae. These results show that it is possible to combine the use of P. maculiventris with releases of T. brassicae in control programs of lepidopteran pests.

Nymphal development and feeding preference of Podisus maculiventris (Heteroptera: Pentatomidae) on eggs of Ephestia kuehniella (Lepidoptera: Pyralidae) parasitised or not by Trichogramma brassicae (Hymenoptera: Trichogrammatidae)

Avaliou-se a predação de ninfas de Podisus maculiventris sobre ovos de Ephestia kuehniella parasitados (em fase de pupa) ou não por Trichogramma brassicae. Esses ovos foram colados em cartelas retangulares e oferecidos às ninfas de P. maculiventris como alimento. Esse Pentatomidae só atingiu a fase adulta quando se alimentou de ovos não parasitados desse Pyralidae, indicando que os mesmos podem ser usados como hospedeiro alternativo para criação desse predador. Ninfas de P. maculiventris que receberam ovos parasitados morreram antes do quarto estádio. Em teste de escolha, ninfas desse predador mostraram preferência por ovos não parasitados em vez de por aqueles parasitados que continham em seu interior uma pupa de T. brassicae. Esses resultados mostram que é possível associar o uso de P. maculiventris com liberações de T. brassicae em programas de controle de lepidópteros pragas.