Inference and reconstruction of the heimdallarchaeial ancestry of eukaryotes

In the ongoing debates about eukaryogenesis—the series of evolutionary events leading to the emergence of the eukaryotic cell from prokaryotic ancestors— members of the Asgard archaea play a key part as the closest archaeal relatives of eukaryotes1. However, the nature and phylogenetic identity of the last common ancestor of Asgard archaea and eukaryotes remain unresolved2–4. Here we analyse distinct phylogenetic marker datasets of an expanded genomic sampling of Asgard archaea and evaluate competing evolutionary scenarios using state-of-the-art phylogenomic approaches. We find that eukaryotes are placed, with high confidence, as a well-nested clade within Asgard archaea and as a sister lineage to Hodarchaeales, a newly proposed order within Heimdallarchaeia. Using sophisticated gene tree and species tree reconciliation approaches, we show that analogous to the evolution of eukaryotic genomes, genome evolution in Asgard archaea involved significantly more gene duplication and fewer gene loss events compared with other archaea. Finally, we infer that the last common ancestor of Asgard archaea was probably a thermophilic chemolithotroph and that the lineage from which eukaryotes evolved adapted to mesophilic conditions and acquired the genetic potential to support a heterotrophic lifestyle. Our work provides key insights into the prokaryote-to-eukaryote transition and a platform for better understanding the emergence of cellular complexity in eukaryotic cells

Protocol for a feasibility trial for improving breastfeeding initiation and continuation: Assets-based infant feeding help Before and After birth (ABA)

Introduction: Breastfeeding improves the health of mothers and infants; the UK has low rates, with marked socio-economic inequalities. Whilst trials of peer support services have been effective in some settings, UK trials have not improved breastfeeding rates. Qualitative research suggests many women are alienated by the focus on breastfeeding. We propose a change from breastfeeding focussed interactions to respecting a woman’s feeding choices, inclusion of behaviour change theory and an increased intensity of contacts in the two weeks after birth when many women cease to breastfeed. This will take place alongside an assets-based approach which focuses on the positive capability of individuals, their social networks and communities. We propose a feasibility study for a multicentre randomised controlled trial of the ABA infant feeding service versus usual care. Methods and analysis: A two-arm, non-blinded randomised feasibility study will be conducted in two UK localities. Women expecting their first baby will be eligible, regardless of feeding intention. The ABA infant feeding intervention will apply a proactive, assets-based, woman-centred, non-judgemental approach, delivered antenatally and postnatally tailored through face-to face contacts, telephone and SMS texts. Outcomes will test the feasibility of delivering the intervention with recommended intensity and duration to disadvantaged women; acceptability to women, feeding helpers and professionals; and feasibility of a future randomised controlled trial, detailing recruitment rates, willingness to be randomised, follow-up rates at 3 days, 8 weeks and 6 months and level of outcome completion. Outcomes of the proposed full trial will also be collected. Mixed methods will include qualitative interviews with women/partners, feeding helpers and health service staff; feeding helper logs and review of audio-recorded helper-women interactions to assess intervention fidelity. Ethics and dissemination: Study results will inform the design of a larger multicentre RCT. The National Research Ethics Service Committee approved the study protocol. Trial registration number: ISRCTN14760978. STRENGTHS AND LIMITATIONS OF THE STUDY • This study uses a two-centre randomised controlled trial design to determine the feasibility of a definitive trial. • The intervention design draws on evidence from best practice to support women who want to breastfeed behavioural change theory and makes use of women’s personal social and community assets. • A process evaluation will explore reach, fidelity of intervention delivery and the experience of women, feeding helpers and other key stakeholders

An assets-based intervention before and after birth to improve breastfeeding initiation and continuation: the ABA feasibility RCT

The UK has low levels of breastfeeding initiation and continuation, with evident socioeconomic disparities. To be inclusive, peer-support interventions should be woman-centred rather than breastfeeding-centred. Assets-based approaches to public health focus on the positive capabilities of individuals and communities, rather than their deficits and problems. The Assets-based feeding help Before and After birth (ABA) intervention offers an assets-based approach based on behaviour change theory. Objective To investigate the feasibility of delivering the ABA infant feeding intervention in a randomised controlled trial. Design This was an individually randomised controlled feasibility trial; women were randomised in a 1 : 1 ratio to either the intervention group or the comparator (usual care) group. Setting Two separate English sites were selected because they had an existing breastfeeding peer support service, relatively high levels of socioeconomic disadvantage and low rates of breastfeeding. Participants Women aged ≥ 16 years who were pregnant with their first child, irrespective of feeding intention (n = 103), were recruited by researchers in antenatal clinics. Interventions Proactive, woman-centred support, using an assets-based approach and including behaviour change techniques, was provided by an infant-feeding helper (a breastfeeding peer supporter trained in the ABA intervention) and delivered through face-to-face contact, telephone conversations and text messages. The intervention commenced at around 30 weeks’ gestation and could continue until 5 months postnatally. Main outcome measures The main outcome measures were feasibility of intervention delivery with the requisite intensity and duration; acceptability to women, infant-feeding helpers and maternity services; and feasibility of a future randomised controlled trial. Outcomes included recruitment rates and follow-up rates at 3 days, 8 weeks and 6 months postnatally, and outcomes for a future full trial were collected via participant questionnaires. A mixed-methods process evaluation included qualitative interviews with women, infant-feeding helpers and maternity services; infant-feeding helper logs; and audio-recordings of antenatal contacts to check intervention fidelity. Results Of the 135 eligible women approached, 103 (76.3%) agreed to participate. The study was successful in recruiting teenagers (8.7%) and women living in areas of socioeconomic disadvantage (37.3% resided in the most deprived 40% of small areas in England). Postnatal follow-up rates were 68.0%, 85.4% and 80.6% at 3 days, 8 weeks and 6 months, respectively. Feeding status at 8 weeks was obtained for 95.1% of participants. Recruitment took place from February 2017 until August 2017. It was possible to recruit and train existing peer supporters to the infant-feeding helper role. The intervention was delivered to most women with relatively high fidelity. Among the 50 women in the intervention group, 39 received antenatal visits and 40 received postnatal support. Qualitative data showed that the intervention was acceptable. There was no evidence of intervention-related harms. Limitations Birth notification delays resulted in delays in the collection of postnatal feeding status data and in the offer of postnatal support. In addition, the intervention needs to better consider all infant-feeding types and did not adequately accommodate women who delivered prematurely. Conclusion It is feasible to deliver the intervention and trial. Future work The intervention should be tested in a fully powered randomised controlled trial. Trial registration Current Controlled Trials ISRCTN14760978. Funding This project was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 8, No. 7. See the NIHR Journals Library website for further project information

The ABA intervention for improving breastfeeding initiation and continuation: Feasibility study results

The UK has low breastfeeding rates, with socioeconomic disparities. The Assets‐based feeding help Before and After birth (ABA) intervention was designed to be inclusive and improve infant feeding behaviours. ABA is underpinned by the behaviour change wheel and offers an assets‐based approach focusing on positive capabilities of individuals and communities, including use of a Genogram. This study aimed to investigate feasibility of intervention delivery within a randomised controlled trial (RCT). Nulliparous women ≥16 years, (n = 103) from two English sites were recruited and randomised to either intervention or usual care. The intervention – delivered through face‐to‐face, telephone and text message by trained Infant Feeding Helpers (IFHs) – ran from 30‐weeks' gestation until 5‐months postnatal. Outcomes included recruitment rates and follow‐up at 3‐days, 8‐weeks and 6‐months postnatal, with collection of future full trial outcomes via questionnaires. A mixed‐methods process evaluation included qualitative interviews with 30 women, 13 IFHs and 17 maternity providers; IFH contact logs; and fidelity checking of antenatal contact recordings. This study successfully recruited women, including teenagers, from socioeconomically disadvantaged areas; postnatal follow‐up rates were 68.0%, 85.4% and 80.6% at 3‐days, 8‐weeks and 6‐months respectively. Breastfeeding at 8‐weeks was obtained for 95.1% using routine data for non‐responders. It was possible to recruit and train peer supporters to deliver the intervention with adequate fidelity. The ABA intervention was acceptable to women, IFHs and maternity services. There was minimal contamination and no evidence of intervention‐related harm. In conclusion, the intervention is feasible to deliver within an RCT, and a definitive trial required

Assets-based infant feeding help Before and After birth: a randomised controlled feasibility trial for improving breastfeeding initiation and continuation

Background The UK has low levels of breastfeeding initiation and continuation, with evident socioeconomic disparities. To be inclusive, peer support interventions should be woman-centred rather than breastfeeding-centred. Assets-based approaches to public health focus on positive capabilities of individuals and communities, rather than their deficits and problems. The Assets-based feeding help Before and After birth (ABA) intervention offers an assets-based approach based on behaviour change theory. Objective To investigate the feasibility of delivering the ABA infant feeding intervention within a randomised controlled trial. Design Individually randomised controlled feasibility trial; women randomised on a 1:1 ratio to either the intervention or the comparator (usual care). Setting Two separate English sites, selected for having an existing breastfeeding peer support service, relatively high levels of socioeconomic disadvantage, and low rates of breastfeeding. Participants Women aged 16 years or older, pregnant with their first child, irrespective of feeding intention (n=103), recruited by researchers in antenatal clinics. Intervention Proactive, woman-centred support, using an assets-based approach and including Behaviour Change Techniques, provided by an Infant Feeding Helper (a breastfeeding peer supporter trained in ABA intervention), delivered through face-to-face contact, telephone conversations and text messages. The intervention commenced at around 30 weeks gestation and could continue until 5 months postnatally. Main outcome measures Feasibility of intervention delivery with the requisite intensity and duration; acceptability to women, Infant Feeding Helpers and maternity services; feasibility of a future randomised controlled trial. Outcomes included recruitment rates and follow up rates at 3 days, 8 weeks and 6 months postnatal, with collection of outcomes for a future full trial via participant questionnaires. A mixed methods process evaluation included qualitative interviews with women, Infant Feeding Helpers and maternity services; Infant Feeding Helper logs; and audio recordings of antenatal contacts to check intervention fidelity. Results Of 135 eligible women approached, 103 (76.3%) agreed to participate. The study was successful in recruiting teenagers (8.7%) and women living in areas of socioeconomic disadvantage (37.3% resided in the most deprived 40% of small areas in England). Postnatal follow up rates were 68.0%, 85.4% and 80.6% at 3 days, 8 weeks and 6 months respectively. Feeding status at 8-weeks was obtained for 95.1% of participants. Recruitment took place February-August 2017. It was possible to recruit and train existing peer supporters to the Infant Feeding Helper role. The intervention was delivered with relatively high fidelity to most women. Of 50 women, 39 received antenatal visits and 40 postnatal support. Qualitative data showed the intervention to be acceptable. There was no evidence of intervention-related harms. Limitations Birth notification delays resulted in delays in collection of postnatal feeding status data, and the offer of postnatal support. In addition, the intervention needs to better consider all infant feeding types and did not adequately accommodate women who delivered prematurely. Conclusions It is feasible to deliver the intervention and trial. Future work The intervention should be tested in a fully powered randomised controlled trial. Study registration ISRCTN1476097

Establishing a Research Agenda on Mobile Health Technologies and Later-Life Pain Using an Evidence-Based Consensus Workshop Approach

The rapid growth of mHealth devices holds substantial potential for improving care and care outcomes in all patient populations, including older adults with pain. However, existing research reflects a substantial gap in knowledge about how to design, evaluate, and disseminate devices to optimally address the many challenges associated with managing pain in older persons. Given these knowledge gaps, we sought to develop a set of practice-based research priorities to facilitate innovation in this field. We employed the Cornell Research-to-Practice Consensus Workshop Model, an evidence-based approach to generating research priorities. Sixty participants attended the conference, where stakeholder groups included older adults with pain and their caregivers, behavioral and social scientists, healthcare providers, pain experts, and specialists in mHealth and health policy. Participants generated 13 recommendations classified into two categories: 1) Implications for designing research on mHealth among older adults, e.g., conduct research on ways to enhance accessibility of mHealth tools among diverse groups of older adults with pain, expand research on mHealth sensing applications; and 2) Implementation of mHealth technology into practice and associated regulatory issues, e.g., promote research on ways to initiate/sustain patient behavior change, expand research on mHealth cyber-security and privacy issues

Next-level riboswitch development-implementation of Capture-SELEX facilitates identification of a new synthetic riboswitch.

The development of synthetic riboswitches has always been a challenge. Although a number of interesting proof-of-concept studies have been published, almost all of these were performed with the theophylline aptamer. There is no shortage of small molecule-binding aptamers; however, only a small fraction of them are suitable for RNA engineering since a classical SELEX protocol selects only for high-affinity binding but not for conformational switching. We now implemented RNA Capture-SELEX in our riboswitch developmental pipeline to integrate the required selection for high-affinity binding with the equally necessary RNA conformational switching. Thus, we successfully developed a new paromomycin-binding synthetic riboswitch. It binds paromomycin with a KD of 20 nM and can discriminate between closely related molecules both in vitro and in vivo. A detailed structure-function analysis confirmed the predicted secondary structure and identified nucleotides involved in ligand binding. The riboswitch was further engineered in combination with the neomycin riboswitch for the assembly of an orthogonal Boolean NOR logic gate. In sum, our work not only broadens the spectrum of existing RNA regulators, but also signifies a breakthrough in riboswitch development, as the effort required for the design of sensor domains for RNA-based devices will in many cases be much reduced

Inference and reconstruction of the heimdallarchaeial ancestry of eukaryotes

In the ongoing debates about eukaryogenesis-the series of evolutionary events leading to the emergence of the eukaryotic cell from prokaryotic ancestors-members of the Asgard archaea play a key part as the closest archaeal relatives of eukaryotes(1). However, the nature and phylogenetic identity of the last common ancestor of Asgard archaea and eukaryotes remain unresolved(2-4). Here we analyse distinct phylogenetic marker datasets of an expanded genomic sampling of Asgard archaea and evaluate competing evolutionary scenarios using state-of-the-art phylogenomic approaches. We find that eukaryotes are placed, with high confidence, as a well-nested clade within Asgard archaea and as a sister lineage to Hodarchaeales, a newly proposed order within Heimdallarchaeia. Using sophisticated gene tree and species tree reconciliation approaches, we show that analogous to the evolution of eukaryotic genomes, genome evolution in Asgard archaea involved significantly more gene duplication and fewer gene loss events compared with other archaea. Finally, we infer that the last common ancestor of Asgard archaea was probably a thermophilic chemolithotroph and that the lineage from which eukaryotes evolved adapted to mesophilic conditions and acquired the genetic potential to support a heterotrophic lifestyle. Our work provides key insights into the prokaryote-to-eukaryote transition and a platform for better understanding the emergence of cellular complexity in eukaryotic cells

Establishing a Research Agenda on Mobile Health Technologies and Later-Life Pain Using an Evidence-Based Consensus Workshop Approach

The rapid growth of mHealth devices holds substantial potential for improving care and care outcomes in all patient populations, including older adults with pain. However, existing research reflects a substantial gap in knowledge about how to design, evaluate, and disseminate devices to optimally address the many challenges associated with managing pain in older persons. Given these knowledge gaps, we sought to develop a set of practice-based research priorities to facilitate innovation in this field. We employed the Cornell Research-to-Practice Consensus Workshop Model, an evidence-based approach to generating research priorities. Sixty participants attended the conference, where stakeholder groups included older adults with pain and their caregivers, behavioral and social scientists, healthcare providers, pain experts, and specialists in mHealth and health policy. Participants generated 13 recommendations classified into two categories: 1) Implications for designing research on mHealth among older adults, e.g., conduct research on ways to enhance accessibility of mHealth tools among diverse groups of older adults with pain, expand research on mHealth sensing applications; and 2) Implementation of mHealth technology into practice and associated regulatory issues, e.g., promote research on ways to initiate/sustain patient behavior change, expand research on mHealth cyber-security and privacy issues. Perspective: This report highlights a set of research priorities in the area of mHealth and later-life pain derived from the joint perspectives of researchers and key stakeholder groups. Addressing these priorities could help to improve the quality of care delivered to older adults with pain