Cruise Report 73-KB-31: Abalone investigations

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Our Space: Being a Responsible Citizen of the Digital World

Our Space is a set of curricular materials designed to encourage high school students to reflect on the ethical dimensions of their participation in new media environments. Through role-playing activities and reflective exercises, students are asked to consider the ethical responsibilities of other people, and whether and how they behave ethically themselves online. These issues are raised in relation to five core themes that are highly relevant online: identity, privacy, authorship and ownership, credibility, and participation.Our Space was co-developed by The Good Play Project and Project New Media Literacies (established at MIT and now housed at University of Southern California's Annenberg School for Communications and Journalism). The Our Space collaboration grew out of a shared interest in fostering ethical thinking and conduct among young people when exercising new media skills

Challenges and Opportunities for Improving Eco-Efficiency of Tropical Forage-Based Systems to Mitigate Greenhouse Gas Emissions

Forage-based livestock production plays a key role in national and regional economies, for food security and poverty alleviation. Livestock production is also considered as a major contributor to agricultural GHG emissions, however. While demand for livestock products is predicted to continue to increase, there is political and societal pressure both to reduce environmental impacts and to convert some of the pasture area to alternative uses such as crop production and environmental conservation. Thus it is essential to develop approaches for sustainable intensification of livestock systems to mitigate GHG emissions, addressing biophysical, socioeconomic and policy challenges. This paper highlights the potential of improved tropical forages in crop-livestock systems, and linked with policy incentives, to enhance livestock production while reducing its environmental footprint. We give examples for sustainable intensification to mitigate GHG emissions based on improved forages in Brazil and Colombia and suggest future perspectives

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

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Impact of Cluster Thinning on Wine Grape Yield and Fruit Composition: A Review and Meta-Analysis

For wine grape producers, achieving an optimal balance between vegetative and reproductive growth is a key factor in producing high quality fruit and meeting production quotas. This balance is often measured as the leaf-area-to-yield ratio. To increase this ratio, producers often use “cluster thinning” (CT), a management practice involving a selective removal of grape clusters from vines. Despite this, no consensus has been established regarding the optimal CT timing and severity for consistently improving fruit composition. The objective of this work was to identify whether CT “timing” (bloom, pea-size, lag phase, and veraison) or “severity” (15–35%, 36–55%, and 56–75%) influences yield and fruit composition. To achieve this objective, a meta-analysis of 160 publications on CT in grape was reduced to 78 studies via 10 data curation steps. We reported the influence of CT timing and severity on yield and fruit composition, as well as their impact on the yield-fruit composition tradeoff. First, CT timing showed little influence on fruit composition, which provides producers with greater flexibility when using this practice. Second, CT severity was impactful on improving fruit composition (TSS and pH); only the moderate range (36–55%) was effective. In conclusion, wine grape composition is more influenced by CT severity than timing. This work has important implications for grape producers and their approach to improving grape composition

Detection of Critical Spinal Epidural Lesions on CT Using Machine Learning.

BACKGROUND: Critical spinal epidural pathologies can cause paralysis or death if untreated. Although magnetic resonance imaging is the preferred modality for visualizing these pathologies, computed tomography (CT) occurs far more commonly than magnetic resonance imaging in the clinical setting. OBJECTIVE: A machine learning model was developed to screen for critical epidural lesions on CT images at a large-scale teleradiology practice. This model has utility for both worklist prioritization of emergent studies and identifying missed findings. MATERIALS AND METHODS: There were 153 studies with epidural lesions available for training. These lesions were segmented and used to train a machine learning model. A test data set was also created using previously missed epidural lesions. The trained model was then integrated into a teleradiology workflow for 90 days. Studies were sent to secondary manual review if the model detected an epidural lesion but none was mentioned in the clinical report. RESULTS: The model correctly identified 50.0% of epidural lesions in the test data set with 99.0% specificity. For prospective data, the model correctly prioritized 66.7% of the 18 epidural lesions diagnosed on the initial read with 98.9% specificity. There were 2.0 studies flagged for potential missed findings per day, and 17 missed epidural lesions were found during a 90-day time period. These results suggest almost half of critical spinal epidural lesions visible on CT imaging are being missed on initial diagnosis. CONCLUSION: A machine learning model for identifying spinal epidural hematomas and abscesses on CT can be implemented in a clinical workflow

Challenges and opportunities for improving eco-efficiency of tropical forage-based systems to mitigate greenhouse gas emissions

Forage-based livestock production plays a key role in national and regional economies, for food security and poverty alleviation, but is considered a major contributor to agricultural GHG emissions. While demand for livestock products is predicted to increase, there is political and societal pressure both to reduce environmental impacts and to convert some of the pasture area to alternative uses, such as crop production and environmental conservation. Thus, it is essential to develop approaches for sustainable intensification of livestock systems to mitigate GHG emissions, addressing biophysical, socio-economic and policy challenges. This paper highlights the potential of improved tropical forages, linked with policy incentives, to enhance livestock production, while reducing its environmental footprint. Emphasis is on crop-livestock systems. We give examples for sustainable intensification to mitigate GHG emissions, based on improved forages in Brazil and Colombia, and suggest future perspectives