The Effects of Salinity and pH on Fertilization, Early Development and Hatching in the Crown-of-Thorns Seastar

Understanding the influence of environmental factors on the development and dispersal of crown-of-thorns seastars is critical to predicting when and where outbreaks of these coral-eating seastars will occur. Outbreaks of the crown-of-thorns seastars are hypothesized to be driven by terrestrial runoff events that increase nutrients and the phytoplankton food for the larvae. In addition to increasing larval food supply, terrestrial runoff may also reduce salinity in the waters where seastars develop. We investigated the effects of reduced salinity on the fertilisation and early development of seastars, up to and including their hatching from the fertilisation envelope. We also tested the interactive effects of reduced salinity and reduced pH on the hatching of crown-of-thorns seastars. Overall, we found that reduced salinity has strong negative effects on fertilisation and early development, as has been shown in other echinoderm species. We also found that reduced salinity delays hatching but that reduced pH, in isolation or in combination with lower salinity, had no detectable effects on this developmental milestone. Models that assess the positive effects of terrestrial runoff on the development of crown-of-thorns seastars should also consider the strong negative effects of lower salinity on early development including lower levels of fertilisation, increased frequency of abnormal development and delayed time to hatching

Priority species to support the functional integrity of coral reefs

Ecosystem-based management on coral reefs has historically focussed on biodiversity conservation through the establishment of marine reserves, but it is increasingly recognised that a subset of species can be key to the maintenance of ecosystem processes and functioning. Specific provisions for these key taxa are essential to biodiversity conservation and resilience-based adaptive management. While a wealth of literature addresses ecosystem functioning on coral reefs, available information covers only a subset of specific taxa, ecological processes and environmental stressors. What is lacking is a comparative assessment across the diverse range of coral reef species to synthesise available knowledge to inform science and management. Here we employed expert elicitation coupled with a literature review to generate the first comprehensive assessment of 70 taxonomically diverse and functionally distinct coral reef species from microbes to top predators to summarise reef functioning. Although our synthesis is largely through the lens of the Great Barrier Reef, Australia, a particularly data-rich system, it is relevant to coral reefs in general. We use this assessment to evaluate which taxa drive processes that maintain a healthy reef and whether management of these taxa is considered a priority (i.e. are they vulnerable?) or is feasible (i.e. can they be managed?). Scientific certainty was scored to weight our recommendations, particularly when certainty was low. We use five case studies to highlight critical gaps in knowledge that limit our understanding of ecosystem functioning. To inform the development of novel management strategies and research objectives, we identify taxa that support positive interactions and enhance ecosystem performance, including those where these roles are currently underappreciated. We conclude that current initiatives effectively capture many priority taxa but that there is significant room to increase opportunities for underappreciated taxa in both science and management to maximally safeguard coral reef functioning

Chapter 5 Priority Species to Support the Functional Integrity of Coral Reefs

Ecosystem-based management on coral reefs has historically focused on biodiversity conservation through the establishment of marine reserves, but it is increasingly recognised that a subset of species can be key to the maintenance of ecosystem processes and functioning. Specific provisions for these key taxa are essential to biodiversity conservation and resilience-based adaptive management. While a wealth of literature addresses ecosystem functioning on coral reefs, available information covers only a subset of specific taxa, ecological processes and environmental stressors. What is lacking is a comparative assessment across the diverse range of coral reef species to synthesise available knowledge to inform science and management. Here we employed expert elicitation coupled with a literature review to generate the first comprehensive assessment of 70 taxonomically diverse and functionally distinct coral reef species from microbes to top predators to summarise reef functioning. Although our synthesis is largely through the lens of the Great Barrier Reef, Australia, a particularly data-rich system, it is relevant to coral reefs in general. We use this assessment to evaluate which taxa drive processes that maintain a healthy reef, and whether or not management of these taxa is considered a priority (i.e. are they vulnerable?) or is feasible (i.e. can they be managed?). Scientific certainty was scored to weight our recommendations, particularly when certainty was low. We use five case studies to highlight critical gaps in knowledge that limit our understanding of ecosystem functioning. To inform the development of novel management strategies and research objectives, we identify taxa that support positive interactions and enhance ecosystem performance, including those where these roles are currently underappreciated. We conclude that current initiatives effectively capture many priority taxa, but that there is significant room to increase opportunities for underappreciated taxa in both science and management to maximally safeguard coral reef functioning

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Suitability of external controls for drug evaluation in Duchenne muscular dystrophy

OBJECTIVE: To evaluate the suitability of real-world data (RWD) and natural history data (NHD) for use as external controls in drug evaluations for ambulatory Duchenne muscular dystrophy (DMD). METHODS: The consistency of changes in the 6-minute walk distance (Δ6MWD) was assessed across multiple clinical trial placebo arms and sources of NHD/RWD. Six placebo arms reporting 48-week Δ6MWD were identified via literature review and represented 4 sets of inclusion/exclusion criteria (n = 383 patients in total). Five sources of RWD/NHD were contributed by Universitaire Ziekenhuizen Leuven, DMD Italian Group, The Cooperative International Neuromuscular Research Group, ImagingDMD, and the PRO-DMD-01 study (n = 430 patients, in total). Mean Δ6MWD was compared between each placebo arm and RWD/NHD source after subjecting the latter to the inclusion/exclusion criteria of the trial for baseline age, ambulatory function, and steroid use. Baseline covariate adjustment was investigated in a subset of patients with available data. RESULTS: Analyses included ∼1,200 patient-years of follow-up. Differences in mean Δ6MWD between trial placebo arms and RWD/NHD cohorts ranged from -19.4 m (i.e., better outcomes in RWD/NHD) to 19.5 m (i.e., worse outcomes in RWD/NHD) and were not statistically significant before or after covariate adjustment. CONCLUSIONS: We found that Δ6MWD was consistent between placebo arms and RWD/NHD subjected to equivalent inclusion/exclusion criteria. No evidence for systematic bias was detected. These findings are encouraging for the use of RWD/NHD to augment, or possibly replace, placebo controls in DMD trials. Multi-institution collaboration through the Collaborative Trajectory Analysis Project rendered this study feasible

72 weeks post-partum follow-up of dolutegravir versus efavirenz initiated in late pregnancy (DolPHIN-2): an open-label, randomised controlled study.

Late initiation of antiretrovirals in pregnancy is associated with increased risk of perinatal transmission and higher infant mortality. We report the final 72-week postpartum results for efficacy and safety of dolutegravir-based compared with efavirenz-based regimens in mothers and infants. DolPHIN-2 was a randomised, open-label trial. Pregnant women in South Africa and Uganda aged at least 18 years, with untreated but confirmed HIV infection and an estimated gestation of at least 28 weeks, initiating antiretroviral therapy in third trimester were eligible for inclusion. Eligible women were randomly assigned (1:1) to receive either dolutegravir-based (50 mg dolutegravir, 300 mg tenofovir disoproxil fumarate, and either 200 mg emtricitabine in South Africa or 300 mg lamivudine in Uganda) or efavirenz-based (fixed dose combination 600 mg tenofovir disoproxil fumarate plus either emtricitabine in South Africa or lamivudine in Uganda) therapy. The primary efficacy outcome was the time to a viral load of less than 50 copies per mL measured at 6, 12, 24, 48, and 72 weeks postpartum with a Cox model adjusting for viral load and CD4 cell count. Safety endpoints were summarised by the number of women and infants with events. This trial is registered with ClinicalTrials.gov, NCT03249181. Between Jan 23 and Aug 15, 2018, 280 women were screened for inclusion, of whom 268 (96%) women were randomly assigned: 133 (50%) to the efavirenz group and 135 (50%) to the dolutegravir group. 250 (93%; 125 [50%] in the efavirenz group and 125 [50%] in the dolutegravir group) women were included in the intention-to-treat analysis of efficacy. Median time to viral load of less than 50 copies per mL was 4·1 weeks (IQR 4·0-5·1) in the dolutegravir group compared with 12·1 weeks (10·7-13·3) in the efavirenz group (adjusted hazard ratio [HR] 1·93 [95% CI 1·5-2·5]). At 72 weeks postpartum, 116 (93%) mothers in the dolutegravir group and 114 (91%) in the efavirenz group had a viral load of less than 50 copies per mL. Of 57 (21%) mothers with a severe adverse event, three (2%) in the dolutegravir group and five (4%) in the efavirenz group were related to the drug (dolutegravir drug-related events were one woman each with suicidal ideation, suicide attempt, herpes zoster meningitis; efavirenz drug-related events were one woman each with suicide attempt and liver cirrhosis, and three people with drug-induced liver injury). Of 136 (56%) infants in whom severe adverse events were recorded, none were related to the study drugs. In addition to the three infant HIV infections detected at birth in the dolutegravir group that have been previously reported, an additional transmission in the efavirenz group occurred during breastfeeding despite optimal maternal viral suppression and serial negative infant tests in the first year of life. Dolutegravir was safe and well tolerated, supporting updated WHO treatment recommendations in pregnant and breastfeeding women. Infant HIV transmissions can occur during breastfeeding despite persistently undetectable maternal viral load highlighting the need for continued infant testing