Discordant transmission of bacteria and viruses from mothers to babies at birth

BACKGROUND: The earliest microbial colonizers of the human gut can have life-long consequences for their hosts. Precisely how the neonatal gut bacterial microbiome and virome are initially populated is not well understood. To better understand how the maternal gut microbiome influences acquisition of the infant gut microbiome, we studied the early life bacterial microbiomes and viromes of 28 infant twin pairs and their mothers. RESULTS: Infant bacterial and viral communities more closely resemble those of their related co-twin than unrelated infants. We found that 63% of an infant\u27s bacterial microbiome can be traced to their mother\u27s gut microbiota. In contrast, only 15% of their viral communities are acquired from their mother. Delivery route did not determine how much of the bacterial microbiome or virome was shared from mother to infant. However, bacteria-bacteriophage interactions were altered by delivery route. CONCLUSIONS: The maternal gut microbiome significantly influences infant gut microbiome acquisition. Vertical transmission of the bacterial microbiome is substantially higher compared to vertical transmission of the virome. However, the degree of similarity between the maternal and infant gut bacterial microbiome and virome did not vary by delivery route. The greater similarity of the bacterial microbiome and virome between twin pairs than unrelated twins may reflect a shared environmental exposure. Thus, differences of the inter-generation transmissibility at birth between the major kingdoms of microbes indicate that the foundation of these microbial communities are shaped by different rules. Video Abstract

Partnerships for Enhanced Engagement in Research (PEER) health: a new programme to facilitate LMIC research capacity

AbstractBackgroundThe Partnership for Enhanced Engagement in Research (PEER) Health programme, funded by the United States Agency for International Development (USAID), is a new research partnership programme that directly supports researchers from developing countries as Principal Investigators in partnership with collaborators at the US National Institutes of Health (NIH). The goals of this programme are threefold: (1) to advance critical evidence to address crucial health challenges facing LMICs; (2) to support collaboration and build on existing relationships between local public health and research institutions, global health practitioners, host country government, NIH researchers, and USAID Missions and Embassy staff; and (3) to build capacity by supporting researchers in LMICs thereby enabling local solutions to context specific challenges.MethodsMore than 180 preproposals from 25 LMICs were submitted to the first PEER Health research solicitation focused on Child Survival. After consultation with USAID Missions to ensure relevance to host country health priorities, about 80 applicants were invited to submit a full proposal. The National Institute of Child Health and Human Development organised a special emphasis panel for the scientific review of PEER Health full proposals to address both scientific merit and research capacity building aspects of the grant proposals, whilst maintaining key elements of the standard NIH peer review model. 40 experienced NIH reviewers, representing a wide variety of scientific disciplines and global public health experience, did the peer review of grants using a novel IT system developed for the PEER Health initiative. The National Academies of Sciences hosted an interagency protocol review to ensure scientific validity and compliance with international human subject guidelines.FindingsSixteen diverse grant partnerships were awarded in ten USAID Child Survival priority countries in Africa and Asia. Research funded under this programme is varied and includes studies from diverse topical areas, including malaria, neonatal sepsis, breast-feeding, tuberculosis, prevention of mother-to-child transmission, among others. Studies include investigation of both facility and community level interventions. NIH partners are largely US based and half are support by the National Institute of Allergy and Infectious Disease (NIAID).InterpretationBroad interest in this novel programme and applications from 25 countries show a crucial need for more directed funding for research strengthening and partnerships with LMIC Principal Investigators.FundingUSAID, in-kind support from NIH

The canopy cover Webmap of the United Kingdom’s towns and cities

Urban trees and other green infrastructure are advocated as a cost-effective sustainable solution to ameliorate the socio-economic and environmental challenges of urbanisation. UK research has only recently started to quantify urban trees. Tree canopy cover percentage (TCC) is a useful indicator of tree presence. Its estimation can be reproducible, simple, fast, and cost-effective; it can also be evaluated through citizen science, improving people’s appreciation for urban trees and widening the data collection resource pool. This research summarises a citizen science assessment of the TCC of the UK’s 5,749 urban wards. Descriptive statistics are presented spanning local authority to country. The area-weighted mean (and standard error) of TCC across urban wards was 17.3 ± 0.1%. Nationally, the TCC were 11.8 ± 0.5%, 15.7 ± 0.5%, 17.5 ± 0.2%, and 18.1 ± 0.5%, for Northern Ireland, Scotland, England, and Wales, respectively. Results show that only 27.6% of urban wards had a TCC higher than 20%, previously suggested as a minimum target for UK towns. The findings highlight substantial geographical variance in TCC equity, as well as a negative correlation between TCC and deprivation. This information will be of value in urban forest strategy and management

Individual Tree Data Standard

It is estimated that 40 million trees in the UK have been surveyed and the data stored in local authority databases. Data for just 1.1 million of these trees are included in the UK’s and world’s largest open-access tree database, Treezilla (https://treezilla.org/). Tree surveys are carried out for different purposes and often to different specifications. Many tree data collection protocols and methods overlap in their recommendations but differences between them make it difficult or impossible to compare, combine, or reuse data. To address these problems in 2019 the COMMUNITREE project partners drafted a new data standard for surveys of individual trees. The steps taken to develop the data standard are described in detail here: https://www.forestresearch.gov.uk/research/quantification-and-valuation-of-benefits-provided-by-urban-trees/individual-tree-data-standard/ . Standardised tree data collection and recording will enable people to easily share their data so that a single dataset can be recycled for many purposes. The Individual Tree Data Standard is a partnership between Forest Research, The Open University, Treework Environmental Practice, Natural Apptitude and was funded by Innovate UK and the Geospatial Commission

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

Out of the Pacific and Back Again: Insights into the Matrilineal History of Pacific Killer Whale Ecotypes

Killer whales (Orcinus orca) are the most widely distributed marine mammals and have radiated to occupy a range of ecological niches. Disparate sympatric types are found in the North Atlantic, Antarctic and North Pacific oceans, however, little is known about the underlying mechanisms driving divergence. Previous phylogeographic analysis using complete mitogenomes yielded a bifurcating tree of clades corresponding to described ecotypes. However, there was low support at two nodes at which two Pacific and two Atlantic clades diverged. Here we apply further phylogenetic and coalescent analyses to partitioned mitochondrial genome sequences to better resolve the pattern of past radiations in this species. Our phylogenetic reconstructions indicate that in the North Pacific, sympatry between the maternal lineages that make up each ecotype arises from secondary contact. Both the phylogenetic reconstructions and a clinal decrease in diversity suggest a North Pacific to North Atlantic founding event, and the later return of killer whales to the North Pacific. Therefore, ecological divergence could have occurred during the allopatric phase through drift or selection and/or may have either commenced or have been consolidated upon secondary contact due to resource competition. The estimated timing of bidirectional migration between the North Pacific and North Atlantic coincided with the previous inter-glacial when the leakage of fauna from the Indo-Pacific into the Atlantic via the Agulhas current was particularly vigorous

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

BACKGROUND: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. METHODS: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). FINDINGS: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29-146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0- 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25-1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39-1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65-1·60]; p=0·92). INTERPRETATION: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. FUNDING: British Heart Foundation

Two Novel Superantigens Found in Both Group A and Group C Streptococcus

Two novel streptococcal superantigen genes (speL(Se) and speM(Se)) were identified from the Streptococcus equi genome database at the Sanger Center. Genotyping of 8 S. equi isolates and 40 Streptococcus pyogenes isolates resulted in the detection of the orthologous genes speL and speM in a restricted number of S. pyogenes isolates (15 and 5%, respectively). Surprisingly, the novel superantigen genes could not be found in any of the analyzed S. equi isolates. The results suggest that both genes are located on a mobile element that enables gene transfer between individual isolates and between streptococci from different Lancefield groups. S. equi pyrogenic exotoxin L (SPE-L(Se))/streptococcal pyrogenic exotoxin L (SPE-L) and SPE-M(Se)/SPE-M are most closely related to SMEZ, SPE-C, SPE-G, and SPE-J, but build a separate branch within this group. Recombinant SPE-L (rSPE-L) and rSPE-M were highly mitogenic for human peripheral blood lymphocytes, with half-maximum responses at 1 and 10 pg/ml, respectively. The results from competitive binding experiments suggest that both proteins bind major histocompatibility complex class II at the β-chain, but not at the α-chain. The most common targets for both toxins were human Vβ1.1 expressing T cells. Seroconversion against SPE-L and SPE-M was observed in healthy blood donors, suggesting that the toxins are expressed in vivo. Interestingly, the speL gene is highly associated with S. pyogenes M89, a serotype that is linked to acute rheumatic fever in New Zealand