The Water Absorption and Thermal Properties of Green Pterocarpus Angolensis (Mukwa)-Polylactide Composites

The water absorption, chemical resistance, and biological properties are contributing factors to the overall performance of bio-composites, especially for outdoor applications. The functional properties of bio-composites are dependent on the interfacial bonding mechanism, which is controlled by the surface modification and processing parameters of natural fibers. Therefore, this study aims to investigate the potential of enhancing the mukwa/polylactide (mukwa/PLA) interface through an economic and ecological surface modification of recycled mukwa wood fibers via alkali-laccase modification. The fabricated bio-composites intended for making durable farm poles for semi-arid conditions of Southern Africa were characterized via water absorption, chemical resistance, thickness swelling, hardness, and thermal properties. Less thickness swelling and water absorption were found on the alkali-laccase/PLA composites. The less-dense (1.09 g/cm3) alkali-laccase treated composites showed better chemical resistance. Much swelling of the composites was observed on the 40% nitric acid (HNO3), while 60%NaOH shrunk the composites and PLA by <3.5%. The laccase/PLA bio-composite showed a maximum thermal stability of 733 °C. The activation energy (Ea) optimized on the laccase/PLA composite with the highest of 104 kJ mol−1. Maximum crystallinity of 45.8% was achieved on the untreated/PLA composites. The alkali-laccase modification maximized the hardness of composites with 35.45 HV on alkali-laccase/PLA

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir

Field and laboratory experiments to investigate infiltration processes and clogging effects from a ponding recharge system at Ban Nong Na, Bangrakum District, Phitsanulok Province, Lower Yom River Basin, Thailand

Paper presented at ISMAR7, Theme - Water Reuse and MAR, Abu Dhabi, UAE, 9-13 October 2010A small-scale field experiment consisting of surface infiltration tests was conducted at Ban Nong Na, located in Bangrakum District, Phitsanulok Province, situated in the Lower Yom River Basin. The shallow groundwater in this area has been heavily pumped for growing rice all year round, and within the past decade static water levels within the gravel, sand and silt aquifers have decreased to a depth of up to ten meters below the ground surface. Research is currently being conducted to investigate the feasibility of managed aquifer recharge by surface ponding methods in the Lower Yom River Basin. This study, which forms one component of the broader project, aims to assess infiltration processes and clogging effects at the laboratory (column) scale and at the small scale (25 m2) in the field. The laboratory experiment consisted of two main components: 1) physical, chemical and biological analyses of raw water and the ambient groundwater and 2) soil column testing under constant head conditions over a period of 100 hours. The field experiment consisted of three main components: 1) characterization of the physical and hydraulic properties of the unsaturated and saturated media 2) pretreatment design considering levels of turbidity removal using synthetic poly and sand filter, and 3) infiltration testing under constant head conditions over a period of 30 hours. These works are intended to provide the design criteria for establishing a larger scale (1,600 m2) pilot recharge system at the study site. Average infiltration rates for the laboratory experiment for source waters with mean turbidities of 0.5 and 100 NTU were found to be 3.27 and 0.15 m/d respectively. The infiltration rate from the field experiment with an average turbidity 50 NTU was 2.53 m/d; a magnitude commensurate with the lab study. Since infiltration rates in excess of 1 m/day are desirable for the pilot trial, the turbidity of the raw canal water used for recharge will be controlled to be less than 50 NTU. Whilst both the laboratory and field experiments were brief and longer test periods needed, more extensive investigations will be performed over the 2010 monsoon season during the full-scale pilot trial