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Aedes aegypti is the main epidemic vector of arboviruses in Africa. In Senegal, control activities are mainly limited to mitigation of epidemics, with limited information available for Ae. aegypti populations. A better understanding of the current Ae. aegypti susceptibility status to various insecticides and relevant resistance mechanisms involved is needed for the implementation of effective vector control strategies. The present study focuses on the detection of insecticide resistance and reveals the related mechanisms in Ae. aegypti populations from Senegal. Bioassays were performed on Ae. aegypti adults from nine Senegalese localities (Matam, Louga, Barkedji, Ziguinchor, Mbour, Fatick, Dakar, Kédougou and Touba). Mosquitoes were exposed to four classes of insecticides using the standard WHO protocols. Resistance mechanisms were investigated by genotyping for pyrethroid target site resistance mutations (V1016G, V1016I, F1534C and S989P) and measuring gene expression levels of key detoxification genes (CYP6BB2, CYP9J26, CYP9J28, CYP9J32, CYP9M6, CCEae3a and GSTD4). All collected populations were resistant to DDT and carbamates except for the ones in Matam (Northern region). Resistance to permethrin was uniformly detected in mosquitoes from all areas. Except for Barkédji and Touba, all populations were characterized by a susceptibility to 0.75% Permethrin. Susceptibility to type II pyrethroids was detected only in the Southern regions (Kédougou and Ziguinchor). All mosquito populations were susceptible to 5% Malathion, but only Kédougou and Matam mosquitoes were susceptible to 0.8% Malathion. All populations were resistant to 0.05% Pirimiphos-methyl, whereas those from Louga, Mbour and Barkédji, also exhibited resistance to 1% Fenitrothion. None of the known target site pyrethroid resistance mutations was present in the mosquito samples included in the genotyping analysis (performed in > 1500 samples). In contrast, a remarkably high (20-70-fold) overexpression of major detoxification genes was observed, suggesting that insecticide resistance is mostly mediated through metabolic mechanisms. These data provide important evidence to support dengue vector control in Senegal.

This study examined the effects of using an online flexible educational game on students' attitude towards mathematics as compared to the traditional method of solving mathematical problems. Moreover, the study assessed the learning effectiveness of the game and investigated potential gender differences in the game's effectiveness on changing students' attitude. The participants of the study were 79 students who were randomly assigned to a control and treatment group, as well as four coordinator teachers. The game was configurable and it was used as a supplementary teaching method. The intervention lasted 14 weeks and the data collection was based on quantitative measures and interviews. The results of the analysis indicated that the game approach was effective on improving students' attitude towards mathematics and that it also resulted in better learning outcomes in the treatment group as compared to that of the control group. Furthermore, it was shown that the gender of the students did not influence the positive effect of the game on students' attitude. These results suggest that the incorporation of flexible games into the traditional teaching of mathematics could possibly bring beneficial effects.

When considering data from many trials, it is likely that some of them present a markedly different intervention effect or exert an undue influence on the summary results. We develop a forward search algorithm for identifying outlying and influential studies in meta-analysis models. The forward search algorithm starts by fitting the hypothesized model to a small subset of likely outlier-free studies and proceeds by adding studies into the set one-by-one that are determined to be closest to the fitted model of the existing set. As each study is added to the set, plots of estimated parameters and measures of fit are monitored to identify outliers by sharp changes in the forward plots. We apply the proposed outlier detection method to two real data sets; a meta-analysis of 26 studies that examines the effect of writing-to-learn interventions on academic achievement adjusting for three possible effect modifiers, and a meta-analysis of 70 studies that compares a fluoride toothpaste treatment to placebo for preventing dental caries in children. A simple simulated example is used to illustrate the steps of the proposed methodology, and a small-scale simulation study is conducted to evaluate the performance of the proposed method.

The aim of this study is to assess the impact of a 3D educational computer game on students' test anxiety and exam performance when used in evaluative situations as compared to the traditional method of examination. The participants of the study were students in tertiary education who were examined using game-based assessment and traditional assessment in a 2 × 2 cross-over design. The game was flexible, providing the instructor with the opportunity to import and edit exam questions and modify several aspects via an administration panel. Following the collection and analysis of both quantitative and interview data, it was revealed that the students' test anxiety was reduced during the game-based assessment. Furthermore, the exam performance of the students was significantly better when the game method was used. The results showed that there is a linear negative relationship between the students' test anxiety and exam performance as well as that these variables are correlated in a causal way. Overall, this study provides evidence that game-based assessment could be potentially beneficial for students.

Human perception differs profoundly between individuals from different cultures. In the present study, we investigated the development of context-sensitive attention (the relative focus on context elements of a visual scene) in a large sample (N = 297) of 5- to 15-year-olds and young adults from rural and urban Brazil, namely from agricultural villages in the Amazon region and the city of São Paulo. We applied several visual tasks which assess context-sensitive attention, including an optical illusion, a picture description, a picture recognition and a facial emotion judgment task. The results revealed that children and adults from the urban sample had a higher level of context-sensitive attention, when compared to children and adults from the rural sample. In particular, participants from São Paulo were more easily deceived by the context elements in an optical illusion task and remembered more context elements in a recognition task than participants from rural Amazon villages. In these two tasks, context-sensitivity increased with age. However, we did not find a cultural difference in the picture description and the facial emotion judgment task. These findings support the idea that visual information processing is highly dependent on the culture-specific learning environments from very early in development. Specifically, they are more consistent with accounts that emphasize the role of the visual environment, than with the social orientation account. However, they also highlight that further research is needed to disentangle the diverse factors that may influence the early development of visual attention, which underlie culture-specific developmental pathways.

Migraine is a chronic and disabling disorder affecting >1 billion individuals worldwide. Current treatments for the prevention of migraine include antihypertensives, antiepileptics, and antidepressants, and all share limited tolerability and adherence, highlighting the need for the development of new disease-specific and mechanism-based agents. In this context, four novel anti-calcitonin gene-related peptide monoclonal antibodies have been investigated in a large Phase II–III clinical programme and showed similar efficacy to the currently used drugs for migraine prevention but with a significantly improved safety profile, as highlighted in this review. It is expected that patient compliance with treatment will increase with the use of these therapies, improving the long-term overall outcome of migraine. However, real-world evidence is needed to confirm the tolerability and safety of anti-calcitonin gene-related peptide monoclonal antibodies before the drugs can be established as first-line agents in the prophylactic treatment of migraine.

Stroke is a frequent occurrence among patients suffering from systemic lupus erythematosus (SLE), but it rarely occurs as the initial manifestation of the disease. We here present the case of a 37 year-old patient who developed an acute cerebellar ischemic stroke as initial event of SLE: elevated partial thromboplastin time and ESR, thrombocytopenia, anti-ds-DNA, anti-SSA, anti-JO-1, and the lupus anticoagulant were detected, and the diagnosis of SLE was established. In addition, we reviewed the literature in order to clarify the demographic, clinical, imaging and outcome characteristics of such a presentation, and found 10 similar cases. Most patients were young (age 31.7 ± 8.5 years) and women (8/11, 72.7%). Stroke most often affected the vertebrobasilar territory (7/11, 63.6%). The stroke mechanism was not clearly defined in these cases. Treatment with immunosuppression and anticoagulation was considered to be a reasonable choice for early secondary stroke prevention. The occurrence of ischemic stroke, primarily in the vertebrobasilar system among young patients, especially women, should always raise suspicion for underlying SLE, and prompt diagnostic investigations to confirm or exclude its presence. Keywords: Ischemic stroke, Systemic lupus erythematosus, Initial manifestation, Stroke in young patient

Abstract Background Overuse injuries are reported to be more common than acute trauma in children and adolescents, causing pain and reduced function. The most common is apophysitis - a traction injury to the apophysis in growing individuals. The duration of symptoms reported in the literature is between 6 weeks to 6 months or more. The objective of this systematic review and network meta-analysis is to compare the effectiveness and safety of all available treatments for any type of apophysitis in children and adolescents. Methods/Design We will conduct a systematic review to retrieve all relevant studies applying a comparative design. Searches will be made in the Cochrane CENTRAL, MEDLINE, EMBASE, CINAHL and SportDiscus databases and via reference searching. The efficacy of treatments will be compared with respect to the outcomes 1) time to pain-free activity and 2) risk of subsequent injury. Risk of bias assessment will be made using revised tool for assessing risk of bias in randomized trials for Randomized trials and Robins-I tool for non-randomized trials. We will explore if different treatment comparisons are sufficiently similar in terms of effect modifiers (transitivity assumption) with the aim to conduct network meta-analyses for randomized and non-randomized studies separately. A treatment hierarchy will be obtained using the surface under the cumulative ranking curve (SUCRA) and mean ranks, visualized using rankograms. We will use the CINeMA software to apply the modified version of Grades of Recommendation, Assessment, Development and Evaluation (GRADE), developed specifically to evaluate the quality of evidence in network meta-analysis. Discussion To date the comparative effects of interventions for apophysitis seem to rely mainly on expert opinion. We aim to identify all comparative treatment designs described in the literature and synthesize data when possible. We will use the estimated treatment effects between injury locations to provide guidance in managing apophysitis. Trial registration PROSPERO ID number: CRD42018083746.