Diversity of Mosquitoes (Diptera: Culicidae) Attracted to Human Subjects in Rubber Plantations, Secondary Forests, and Villages in Luang Prabang Province, Northern Lao PDR

The impact of the rapid expansion of rubber plantations in South-East Asia on mosquito populations is uncertain. We compared the abundance and diversity of adult mosquitoes using human-baited traps in four typical rural habitats in northern Lao PDR: secondary forests, immature rubber plantations, mature rubber plantations, and villages. Generalized estimating equations were used to explore differences in mosquito abundance between habitats, and Simpson’s diversity index was used to measure species diversity. Over nine months, 24,927 female mosquitoes were collected, including 51 species newly recorded in Lao PDR. A list of the 114 mosquito species identified is included. More mosquitoes, including vector species, were collected in the secondary forest than immature rubber plantations (rainy season, odds ratio [OR] 0.33, 95% confidence interval [CI] 0.31–0.36; dry season, 0.46, 95% CI 0.41–0.51), mature rubber plantations (rainy season, OR 0.25, 95% CI 0.23–0.27; dry season, OR 0.25, 95% CI 0.22–0.28), and villages (rainy season, OR 0.13, 95% CI 0.12–0.14; dry season, 0.20, 95% CI 0.18–0.23). All habitats showed high species diversity (Simpson’s indexes between 0.82–0.86) with vectors of dengue, Japanese encephalitis (JE), lymphatic filariasis, and malaria. In the secondary forests and rubber plantations, Aedes albopictus (Skuse), a dengue vector, was the dominant mosquito species, while in the villages, Culex vishnui (Theobald), a JE vector, was most common. This study has increased the overall knowledge of mosquito fauna in Lao PDR. The high abundance of Ae. albopictus in natural and man-made forests warrants concern, with vector control measures currently only implemented in cities and villages

Safety and efficacy of GABAA α5 antagonist S44819 in patients with ischaemic stroke: a multicentre, double-blind, randomised, placebo-controlled trial

Background: S44819, a selective GABAA α5 receptor antagonist, reduces tonic post-ischaemic inhibition of the peri-infarct cortex. S44819 improved stroke recovery in rodents and increased cortical excitability in a transcranial magnetic stimulation study in healthy volunteers. The Randomized Efficacy and Safety Trial of Oral GABAA α5 antagonist S44819 after Recent ischemic Event (RESTORE BRAIN) aimed to evaluate the safety and efficacy of S44819 for enhancing clinical recovery of patients with ischaemic stroke. Methods: RESTORE BRAIN was an international, randomised, double-blind, parallel-group, placebo-controlled, multicentre phase 2 trial that evaluated the safety and efficacy of oral S44189 in patients with recent ischaemic stroke. The study was done in specialised stroke units in 92 actively recruiting centres in 14 countries: ten were European countries (Belgium, Czech Republic, France, Germany, Hungary, Italy, Netherlands, Poland, Spain, and the UK) and four were non-European countries (Australia, Brazil, Canada, and South Korea). Patients aged 18–85 years with acute ischaemic stroke involving cerebral cortex (National Institute of Health Stroke Scale [NIHSS] score 7–20) without previous disability were eligible for inclusion. Participants were randomly assigned to receive 150 mg S44819 twice a day, 300 mg S44819 twice a day, or placebo twice a day by a balanced, non-adaptive randomisation method with a 1:1:1 ratio. Treatment randomisation and allocation were centralised via the interactive web response system using computer-generated random sequences with a block size of 3. Blinding of treatment was achieved by identical appearance and taste of all sachets. Patients, investigators and individuals involved in the analysis of the trial were masked to group assignment. The primary endpoint was the modified Rankin Scale (mRS) score 90 days from onset of treatment, evaluated by shift analysis (predefined main analysis) or by dichotomised analyses using 0–1 versus 2–6 and 0–2 versus 3–6 cutoffs (predefined secondary analysis). Secondary endpoints were the effects of S44819 on the NIHSS and Montreal Cognitive Assessment (MoCA) scores, time needed to complete parts A and B of the Trail Making Test, and the Barthel index. Efficacy analyses were done on all patients who received at least one dose of treatment and had at least one mRS score taken after day 5 (specifically, on or after day 30). Safety was compared across treatment groups for all patients who received at least one dose of treatment. The study was registered at ClinicalTrials.gov, NCT02877615. Findings: Between Dec 19, 2016, and Nov 16, 2018, 585 patients were enrolled in the study. Of these, 197 (34%) were randomly assigned to receive 150 mg S44819 twice a day, 195 (33%) to receive 300 mg S44819 twice a day, and 193 (33%) to receive placebo twice a day. 189 (96%) of 197 patients in the 150 mg S44819 group, 188 (96%) of 195 patients in the 300 mg S44819 group, and 191 (99%) patients in the placebo group received at least one dose of treatment and had at least one mRS score taken after day 5, and were included in efficacy analyses. 195 (99%) of 197 patients in the 150 mg S44819 group, 194 (99%) of 195 patients in the 300 mg S44819 group, and 193 (100%) patients in the placebo group received at least one dose of treatment, and were included in safety analyses. The primary endpoint of mRS at day 90 did not differ between each of the two S44819 groups and the placebo group (OR 0·91 [95% CI 0·64–1·31]; p=0·80 for 150 mg S44819 compared with placebo and OR 1·17 [95% CI 0·81–1·67]; p=0·80 for 300 mg S44819 compared with placebo). Likewise, dichotomised mRS scores at day 90 (mRS 0–2 vs 3–6 or mRS 0–1 vs 2–6) did not differ between groups. Secondary endpoints did not reveal any significant group differences. The median NIHSS score at day 90 did not differ between groups (4 [IQR 2–8] in 150 mg S44819 group, 4 [2–7] in 300 mg S44819 group, and 4 [2–6] in placebo group), nor did the number of patients at day 90 with an NIHSS score of up to 5 (95 [61%] of 156 in 150 mg S44819 group, 106 [66%] of 161 in 300 mg S44819 group, and 104 [66%] of 157 in placebo group) versus more than 5 (61 [39%] in 150 mg S44819 group, 55 [34%] in 300 mg S44819 group, and 53 [34%] in placebo group). Likewise, the median MoCA score (22·0 [IQR 17·0–26·0] in 150 mg S44819 group, 23·0 [19·0–26·5] in 300 mg S44819 group, and 22·0 [17·0–26·0] in placebo group), time needed to complete parts A (50 s [IQR 42–68] in 150 mg S44819 group, 49 s [36–63] in 300 mg S44819 group, and 50 s [38–68] in placebo group) and B (107 s [81–144] in 150 mg S44819 group, 121 s [76–159] in 300 mg S44819 group, and 130 s [86–175] in placebo group) of the Trail Making Test, and the Barthel index (90 [IQR 60–100] in 150 mg S44819 group, 90 [70–100] in 300 mg S44819 group, and 90 [70–100] in placebo group) were similar in all groups. Number and type of adverse events were similar between the three groups. There were no drug-related adverse events and no drug-related deaths. Interpretation: There was no evidence that S44819 improved clinical outcome in patients after ischaemic stroke, and thus S44819 cannot be recommended for stroke therapy. The concept of tonic inhibition after stroke should be re-evaluated in humans. Funding: Servier

A water balance model for characterization of length of growing period and water stress development for rainfed lowland rice

There is large year-to-year variation in rice production across the Mekong region (Laos, Cambodia and Thailand) due to uncertainty in the timing of the onset of the wet season and drought stress that may develop at any time during the growth of rainfed lowland rice. Unique to the nature of lowland water balance is a large component of deep percolation water loss, which depends on soil texture. The objectives of this study were to develop a soil water balance model for calculating the amount of water held in field storage (i.e. in soil and, if there is standing water, above the soil surface) and to apply it to determine the length of growing period (LGP) and water stress development in relation to soil type and rainfall pattern for the rice ecosystem. The water balance is computed separately for above-ground plus topsoil layer and subsoil layer. Components of the water balance are the existing amount of stored water, rainfall, evapotranspiration, deep percolation, and runoff. The deep percolation rate was determined from clay content in each soil layer. The model runs with daily or weekly weather data to estimate the soil water level for the growing period in the wet season. The model was validated with data collected from top, middle and bottom of rainfed lowland fields in Savannakhet province, Laos. The best correlation between the observed and simulated water level was obtained (r=0.41) for middle fields. The simulation results showed that LGP varied greatly from year to year, particularly in locations with sandy soils, due mostly to variation in monthly rainfall occurring at the early part of the growing season (April), but also to some extent by variation at the end of growing season (October). Soil texture on the other hand is shown to have a large influence on the end of the rice growing period and hence LGP, and also water stress development during growth. Sandy soils with clay content less than 7% that are prevalent in the province are shown to cause frequent water stress and early finish in rainfed lowland rice. The model accordingly provides reasonable outputs that can provide a geographical dimension of soil hydrological patterns for various rice growing environments, and also identify the spatial pattern of drought stress that is likely to occur. Model outputs can be used to provide guidelines for practical advice to the rice farmers and researchers for determination of appropriate crop management strategies (e.g. time of planting, varieties), and policy makers for investment decisions on inputs (e.g. fertilizer price) aimed at increasing rice productivity in this Mekong region

Soil clay content, rainfall, and toposequence positions determining spatial variation in field water availability as estimated by a water balance model for rainfed lowland rice

Drought is a major limiting factor for the production of rainfed rice in the Mekong Region. Thus, estimation of the length of growing period (LGP) based on estimation of the development of water deficit is essential for sound planning of agricultural development. A recently developed soil-water balance model was used to quantify the availability of water for rice crops and yield reduction due to water deficit. Field water availability is known to be largely affected by soil type and rainfall pattern, and their separate effects were investigated in this study of a spatial analysis of LGP, using inputs for rainfed lowland rice in Savannakhet province in central Laos. The analysis showed that the start of growing period (SGP) and end of growing period (EGP) were affected largely by geographical variations in rainfall and soil clay content, respectively. Also, the areas having relatively short LGP were generally associated with large yield reduction because of low water availability associated with coarse-textured soils. At local scale, field water availability varied from upper to lower positions of a sloping land (toposequence) in the rainfed lowland ecosystem of the Mekong region, causing variation in yield within the toposequence. Using the level of field water determined around flowering time at different toposequence positions in 45 farms, estimated yield reduction was compared in seven main rice-growing districts of the province. Variability of yield loss, associated with variation in water availability, was larger across the toposequence positions than across districts, showing the importance of local variability in determining yield in rainfed lowland rice. The present approach of a combination of simulation model and GIS is adopted for characterisation of the water environment for rainfed lowland rice in other parts of Laos, as well as in neighbouring Thailand and Cambodia

Estimation of separate effects of water and nutrient limitation for rainfed lowland rice within a province in the Mekong region

Drought and low soil fertility are major constraints for high yield in rainfed lowland rice in Laos. To examine the separate effects of low water and nutrient availability and then to provide regional-scale fertilizer recommendations for rainfed lowland rice, a simulation study, together with field measurements, was carried out for Savannakhet province in the 2007 and 2008 seasons. To achieve this, a soil nutrient model QUEFTS (Quantitative Evaluation of the Fertility of Tropical Soils) was combined with a recently developed soil water balance (SWB) model. The nutrient model was used to estimate yield from N, P and K uptake under various supply of nutrient in the soil, and then yield reduction due to water stress was calculated from the water balance model. The combined model was validated with the yield results of field experiments conducted in the dry season with no water limitation and also with yields obtained from 101 farms across the province in two wet seasons where both water and nutrient may have been limiting yield. The yield under inherent nutrient supply without fertilizer input was calculated from soil organic carbon, available P and K, and pH, and without water limitation, and was estimated to range widely between 1 and 2tha for the central Lao province of Savannakhet. Yield was estimated to increase on average from 1.6tha to 2.9tha with the recommended fertilizer application rate of 60-13-16 N-P-K kgha, and up to around 6tha under non-limited nutrient conditions. Yield reduction due to water stress alone, estimated from the soil water balance model, was 4-12%. These results indicate that the influence of water stress on the yield estimated for the two wet seasons was rather small, compared with that of nutrient stress. Fertilizer rates to achieve a particular yield target, which were calculated by subtracting inherent nutrient supply from nutrient uptake required for the yield target and then dividing by fertilizer nutrient taken up per kg applied, were also estimated to determine the variability of nutrient requirements at different locations. In most of the rice-growing areas, nitrogen, phosphorus and potassium required to achieve the yield target of 3tha varied widely between 20 and 70kgha, 5 and 35kgha and 10 and 30kgha, respectively, suggesting the importance of utilizing the site-specific fertilizer recommendation for rainfed lowland rice