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)

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

Post-Discharge Risk of Mortality in Children Under Five Years of Age in Western Kenya: A Retrospective Cohort Study

Limited evidence suggests that children in sub-Saharan Africa hospitalized with all-cause severe anemia or severe acute malnutrition (SAM) are at high risk of dying in the first few months post-discharge. We aimed to compare the risks of post-discharge mortality by health condition among hospitalized children in an area with high malaria transmission in western Kenya. We conducted a retrospective cohort study among recently discharged children aged <5 years using mortality data from a Health and Demographic Surveillance System that included household and pediatric in-hospital surveillance. Cox regression was used to compare post-discharge mortality. Between 2008 and 2013, overall, in-hospital mortality was 2∙8% (101/3,639). The mortality by six months post-discharge (primary outcome) was 6.2% (159/2,556) and highest in children with severe acute malnutrition (SAM) (21·6%), followed by severe anemia (15·5%), severe pneumonia (5·6%), ‘other conditions’ (5·6%), and severe malaria (0·7%). Overall, the six-month post-discharge mortality in children hospitalized with SAM (HR=3·95, 2·60-6·00, p<0∙001) or severe anemia (HR=2·55, 1·74-3·71, p<0.001) was significantly higher than in children without these conditions. Severe malaria was associated with lower 6-month post-discharge mortality (HR=0·33, 0·21-0·53, p<0.001). The odds of dying by six months post-discharge tended to be higher than during the in-hospital period for all children, except for those admitted with severe malaria. The first six months post-discharge is a high-risk period for mortality among children admitted with severe anemia and SAM in western Kenya. Strategies to address this risk period are urgently needed

Guideline thyroid cancer including diagnostics of the nodule

Thyroid cancer is comparatively rare. Thyroid nodules, on the other hand, are frequently diagnosed as a result of increasing use of diagnostic imaging. Cytological investigation of small nodules that have been found by chance often reveals micropapillary carcinoma that is probably not clinically relevant. The new guideline 'Thyroid cancer' advises that cytological investigation of these non-palpable, incidentally discovered thyroid nodules should only be performed on indication. The standard treatment for patients with papillary or follicular thyroid cancer consists of thyroidectomy followed by, if indicated, lymph-node dissection, ablation therapy with radioactive iodine and TSH-suppression. The extent of this treatment is determined on the basis of known prognostic factors and the results of initial treatment. Targeted systemic therapy is available for patients with metastatic progressive disease. There is more focus on the effects of short- and long-term treatment, in order to optimise quality of life.</p

Ivermectin as a novel complementary malaria control tool to reduce incidence and prevalence: a modelling study.

BACKGROUND: Ivermectin is a potential new vector control tool to reduce malaria transmission. Mosquitoes feeding on a bloodmeal containing ivermectin have a reduced lifespan, meaning they are less likely to live long enough to complete sporogony and become infectious. We aimed to estimate the effect of ivermectin on malaria transmission in various scenarios of use. METHODS: We validated an existing population-level mathematical model of the effect of ivermectin mass drug administration (MDA) on the mosquito population and malaria transmission against two datasets: clinical data from a cluster- randomised trial done in Burkina Faso in 2015 wherein ivermectin was given to individuals taller than 90 cm and entomological data from a study of mosquito outcomes after ivermectin MDA for onchocerciasis or lymphatic filariasis in Burkina Faso, Senegal, and Liberia between 2008 and 2013. We extended the existing model to include a range of complementary malaria interventions (seasonal malaria chemoprevention and MDA with dihydroartemisinin-piperaquine) and to incorporate new data on higher doses of ivermectin with a longer mosquitocidal effect. We consider two ivermectin regimens: a single dose of 400 μg/kg (1 × 400 μg/kg) and three consecutive daily doses of 300 μg/kg per day (3 × 300 μg/kg). We simulated the effect of these two doses in a range of usage scenarios in different transmission settings (highly seasonal, seasonal, and perennial). We report percentage reductions in clinical incidence and slide prevalence. FINDINGS: We estimate that MDA with ivermectin will reduce prevalence and incidence and is most effective in areas with highly seasonal transmission. In a highly seasonal moderate transmission setting, three rounds of ivermectin only MDA at 3 × 300 μg/kg (rounds spaced 1 month apart) and 70% coverage is predicted to reduce clinical incidence by 71% and prevalence by 34%. We predict that adding ivermectin MDA to seasonal malaria chemoprevention in this setting would reduce clinical incidence by an additional 77% in children younger than 5 years compared with seasonal malaria chemoprevention alone; adding ivermectin MDA to MDA with dihydroartemisinin-piperaquine in this setting would reduce incidence by an additional 75% and prevalence by an additional 64% (all ages) compared with MDA with dihydroartemisinin-piperaquine alone. INTERPRETATION: Our modelling predictions suggest that ivermectin could be a valuable addition to the malaria control toolbox, both in areas with persistently high transmission where existing interventions are insufficient and in areas approaching elimination to prevent resurgence. FUNDING: Imperial College Junior Research Fellowship