Fitness benefits of the fruit fly <i>Rhagoletis alternata</i> on a non-native rose host

Many species have been introduced worldwide into areas outside their natural range. Often these non-native species are introduced without their natural enemies, which sometimes leads to uncontrolled population growth. It is rarely reported that an introduced species provides a new resource for a native species. The rose hips of the Japanese rose, Rosa rugosa, which has been introduced in large parts of Europe, are infested by the native monophagous tephritid fruit fly Rhagoletis alternata. We studied differences in fitness benefits between R. alternata larvae using R. rugosa as well as native Rosa species in the Netherlands. R. alternata pupae were larger and heavier when the larvae fed on rose hips of R. rugosa. Larvae feeding on R. rugosa were parasitized less frequently by parasitic wasps than were larvae feeding on native roses. The differences in parasitization are probably due to morphological differences between the native and non-native rose hips: the hypanthium of a R. rugosa hip is thicker and provides the larvae with the possibility to feed deeper into the hip, meaning that the parasitoids cannot reach them with their ovipositor and the larvae escape parasitization. Our study shows that native species switching to a novel non-native host can experience fitness benefits compared to the original native host

A review and meta-analysis of the enemy release hypothesis in plant-herbivorous insect systems

A suggested mechanism for the success of introduced non-native species is the enemy release hypothesis (ERH). Many studies have tested the predictions of the ERH using the community approach (native and non-native species studied in the same habitat) or the biogeographical approach (species studied in their native and non-native range), but results are highly variable, possibly due to large variety of study systems incorporated. We therefore focused on one specific system: plants and their herbivorous insects. We performed a systematic review and compiled a large number (68) of datasets from studies comparing herbivorous insects on native and non-native plants using the community or biogeographical approach. We performed a meta-analysis to test the predictions from the ERH for insect diversity (number of species), insect load (number of individuals) and level of herbivory for both the community and biogeographical approach. For both the community and biogeographical approach insect diversity was significantly higher on native than on non-native plants. Insect load tended to be higher on native than non-native plants at the community approach only. Herbivory was not different between native and non-native plants at the community approach, while there was too little data available for testing the biogeographical approach. Our meta-analysis generally supports the predictions from the ERH for both the community and biogeographical approach, but also shows that the outcome is importantly determined by the response measured and approach applied. So far, very few studies apply both approaches simultaneously in a reciprocal manner while this is arguably the best way for testing the ERH

Human Direct Skin Feeding Versus Membrane Feeding to Assess the Mosquitocidal Efficacy of High-Dose Ivermectin (IVERMAL Trial)

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Efficacy and Safety of High-Dose Ivermectin for Reducing Malaria Transmission (IVERMAL): Protocol for a Double-Blind, Randomized, Placebo-Controlled, Dose-Finding Trial in Western Kenya

Background: Innovative approaches are needed to complement existing tools for malaria elimination. Ivermectin is a broad spectrum antiparasitic endectocide clinically used for onchocerciasis and lymphatic filariasis control at single doses of 150‐200 mcg/kg. It also shortens the lifespan of mosquitoes that feed on individuals recently treated with ivermectin. However, the effect after a 150‐200 mcg/kg oral dose is short‐lived (6‐11 days). Modelling suggests higher doses, that prolong the mosquitocidal effects, are needed to make a significant contribution to malaria elimination. Ivermectin has a wide therapeutic index and previous studies have shown doses up to 2,000 mcg/kg, i.e. 10x the US Food and Drug Administration approved dose, are well tolerated and safe; the highest dose used for onchocerciasis is single‐dose 800 mcg/kg. Objective: To determine the safety, tolerability, and efficacy of ivermectin 0, 300, 600 mcg/kg/day for 3 days, when provided with a standard 3‐day course of the antimalarial dihydroartemisinin‐piperaquine, on mosquito survival. Methods: This is a double‐blind, randomised, placebo‐controlled, parallel‐group, 3‐arm, dose‐finding trial in adults with uncomplicated malaria. Monte Carlo simulations based on pharmacokinetic modelling were performed to determine the optimum dosing regimens to be tested. Modelling showed that a 3‐day regimen of 600 mcg/kg/day achieves similar median (5‐95 percentiles) Cmax concentrations of ivermectin to single‐dose of 800 mcg/kg, while increasing the median time above the LC50 (16 ng/mL) from 1.9 days (1.0‐5.7) to 6.8 (3.8‐13.4) days. The 300 mcg/kg/day dose was chosen at 50% of the higher dose to allow evaluation of the dose response. Mosquito survival will be assessed daily up to 28 days in laboratory‐reared Anopheles gambiae s.s. populations fed on patients’ blood taken at days 0, 2 (Cmax), 7 (primary outcome), 10, 14, 21, and 28 after the start of treatment. Safety outcomes include QT‐prolongation and mydriasis. The trial will be conducted in 6 health facilities in western Kenya and requires a sample size of 141 participants (47 per arm). Sub‐studies include: (1) rich pharmacokinetics and (2) direct skin vs membrane feeding assays. Results: Recruitment started July 20th, 2015. Data collection was completed on July 2nd, 2016. Unblinding and analysis will commence once the database has been completed, cleaned and locked. Discussion: High‐dose ivermectin, if found to be safe and well tolerated, might offer a promising new tool for malaria elimination. Trial registration: ClinicalTrials.gov: NCT02511353 (July 15, 2015)

Specific measures for data-intensive health research without consent: a systematic review of soft law instruments and academic literature

It is a common misunderstanding of current European data protection law that when consent is not being used as lawful basis, the processing of personal data is prohibited. Article 9(2)(j) of the European General Data Protection Regulation (GDPR) permits Member States to establish a legal basis in national law that allows for the processing of personal data for scientific research purposes without consent. However, the European legislator has formulated this "research exemption" as an opening clause, rendering the GDPR not specific as to what measures exactly are required to comply with the research exemption. This may have significant implications for both the protection of personal data and the advancement of data-intensive health research. We performed a systematic review of relevant soft law instruments and academic literature to identify what measures are mentioned in those documents. Our analysis resulted in the identification of four overarching themes of suggested measures: organizational measures; technical measures; oversight and review mechanisms; and public engagement and participation. Some of the suggested measures do not substantially contribute to the clarification of the GDPR's "suitable and specific measures" requirement because they remain vague or broad in nature and encompass all types of data processing. However, the themes oversight and review mechanisms and public engagement and participation provide valuable insights which can be put to practice. Nevertheless, further clarification of the measures and safeguards that should be installed when invoking the research exemption remains necessary

Overcoming ethical and legal obstacles to data linkage in health research: stakeholder perspectives

Introduction Data linkage for health research purposes enables the answering of countless new research questions, is said to be cost effective and less intrusive than other means of data collection. Nevertheless, health researchers are currently dealing with a complicated, fragmented, and inconsistent regulatory landscape with regard to the processing of data, and progress in health research is hindered. Aim We designed a qualitative study to assess what different stakeholders perceive as ethical and legal obstacles to data linkage for health research purposes, and how these obstacles could be overcome. Methods Two focus groups and eighteen semi-structured in-depth interviews were held to collect opinions and insights of various stakeholders. An inductive thematic analysis approach was used to identify overarching themes. Results This study showed that the ambiguity regarding the `correct' interpretation of the law, the fragmentation of policies governing the processing of personal health data, and the demandingness of legal requirements are experienced as causes for the impediment of data linkage for research purposes by the participating stakeholders. To remove or reduce these obstacles authoritative interpretations of the laws and regulations governing data linkage should be issued. The participants furthermore encouraged the harmonisation of data linkage policies, as well as promoting trust and transparency and the enhancement of technical and organisational measures. Lastly, there is a demand for legislative and regulatory modifications amongst the participants. Conclusions To overcome the obstacles in data linkage for scientific research purposes, perhaps we should shift the focus from adapting the current laws and regulations governing data linkage, or even designing completely new laws, towards creating a more thorough understanding of the law and making better use of the flexibilities within the existing legislation. Important steps in achieving this shift could be clarification of the legal provisions governing data linkage by issuing authoritative interpretations, as well as the strengthening of ethical-legal oversight bodies

Overcoming ethical and legal obstacles to data linkage in health research: stakeholder perspectives

INTRODUCTION: Data linkage for health research purposes enables the answering of countless new research questions, is said to be cost effective and less intrusive than other means of data collection. Nevertheless, health researchers are currently dealing with a complicated, fragmented, and inconsistent regulatory landscape with regard to the processing of data, and progress in health research is hindered. AIM: We designed a qualitative study to assess what different stakeholders perceive as ethical and legal obstacles to data linkage for health research purposes, and how these obstacles could be overcome. METHODS: Two focus groups and eighteen semi-structured in-depth interviews were held to collect opinions and insights of various stakeholders. An inductive thematic analysis approach was used to identify overarching themes. RESULTS: This study showed that the ambiguity regarding the 'correct' interpretation of the law, the fragmentation of policies governing the processing of personal health data, and the demandingness of legal requirements are experienced as causes for the impediment of data linkage for research purposes by the participating stakeholders. To remove or reduce these obstacles authoritative interpretations of the laws and regulations governing data linkage should be issued. The participants furthermore encouraged the harmonisation of data linkage policies, as well as promoting trust and transparency and the enhancement of technical and organisational measures. Lastly, there is a demand for legislative and regulatory modifications amongst the participants. CONCLUSIONS: To overcome the obstacles in data linkage for scientific research purposes, perhaps we should shift the focus from adapting the current laws and regulations governing data linkage, or even designing completely new laws, towards creating a more thorough understanding of the law and making better use of the flexibilities within the existing legislation. Important steps in achieving this shift could be clarification of the legal provisions governing data linkage by issuing authoritative interpretations, as well as the strengthening of ethical-legal oversight bodies

Effect of Daily Antenatal Iron Supplementation on Plasmodium Infection in Kenyan Women: A Randomized Clinical Trial.

IMPORTANCE: Anemia affects most pregnant African women and is predominantly due to iron deficiency, but antenatal iron supplementation has uncertain health benefits and can increase the malaria burden. OBJECTIVE: To measure the effect of antenatal iron supplementation on maternal Plasmodium infection risk, maternal iron status, and neonatal outcomes. DESIGN, SETTING, AND PARTICIPANTS: Randomized placebo-controlled trial conducted October 2011 through April 2013 in a malaria endemic area among 470 rural Kenyan women aged 15 to 45 years with singleton pregnancies, gestational age of 13 to 23 weeks, and hemoglobin concentration of 9 g/dL or greater. All women received 5.7 mg iron/day through flour fortification during intervention, and usual intermittent preventive treatment against malaria was given. INTERVENTIONS: Supervised daily supplementation with 60 mg of elemental iron (as ferrous fumarate, n = 237 women) or placebo (n = 233) from randomization until 1 month postpartum. MAIN OUTCOMES AND MEASURES: Primary outcome was maternal Plasmodium infection at birth. Predefined secondary outcomes were birth weight and gestational age at delivery, intrauterine growth, and maternal and infant iron status at 1 month after birth. RESULTS: Among the 470 participating women, 40 women (22 iron, 18 placebo) were lost to follow-up or excluded at birth; 12 mothers were lost to follow-up postpartum (5 iron, 7 placebo). At baseline, 190 of 318 women (59.7%) were iron-deficient. In intention-to-treat analysis, comparison of women who received iron vs placebo, respectively, yielded the following results at birth: Plasmodium infection risk: 50.9% vs 52.1% (crude difference, -1.2%, 95% CI, -11.8% to 9.5%; P = .83); birth weight: 3202 g vs 3053 g (crude difference, 150 g, 95% CI, 56 to 244; P = .002); birth-weight-for-gestational-age z score: 0.52 vs 0.31 (crude difference, 0.21, 95% CI, -0.11 to 0.52; P = .20); and at 1 month after birth: maternal hemoglobin concentration: 12.89 g/dL vs 11.99 g/dL (crude difference, 0.90 g/dL, 95% CI, 0.61 to 1.19; P < .001); geometric mean maternal plasma ferritin concentration: 32.1 µg/L vs 14.4 µg/L (crude difference, 123.4%, 95% CI, 85.5% to 169.1%; P < .001); geometric mean neonatal plasma ferritin concentration: 163.0 µg/L vs 138.7 µg/L (crude difference, 17.5%, 95% CI, 2.4% to 34.8%; P = .02). Serious adverse events were reported for 9 and 12 women who received iron and placebo, respectively. There was no evidence that intervention effects on Plasmodium infection risk were modified by intermittent preventive treatment use. CONCLUSIONS AND RELEVANCE: Among rural Kenyan women with singleton pregnancies, administration of daily iron supplementation, compared with administration of placebo, resulted in no significant differences in overall maternal Plasmodium infection risk. Iron supplementation led to increased birth weight. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01308112

Navigation and Exploration in 3D-Game Automated Play Testing

To enable automated software testing, the ability to automatically navigate to a state of interest and to explore all, or at least sufficient number of, instances of such a state is fundamental. When testing a computer game the problem has an extra dimension, namely the virtual world where the game is played on. This world often plays a dominant role in constraining which logical states are reachable, and how to reach them. So, any automated testing algorithm for computer games will inevitably need a layer that deals with navigation on a virtual world. Unlike e.g. navigating through the GUI of a typical web-based application, navigating over a virtual world is much more challenging. This paper discusses how concepts from geometry and graph-based path finding can be applied in the context of game testing to solve the problem of automated navigation and exploration. As a proof of concept, the paper also briefly discusses the implementation of the proposed approach