Implementation of large, multi-site hospital interventions: a realist evaluation of strategies for developing capability.

BACKGROUND: This study presents guidelines for implementation distilled from the findings of a realist evaluation. The setting was local health districts in New South Wales, Australia that implemented three clinical improvement initiatives as part of a state-wide program. We focussed on implementation strategies designed to develop health professionals' capability to deliver value-based care initiatives for multisite programs. Capability, which increases implementers' ability to cope with unexpected scenarios is key to managing change. METHODS: We used a mixed methods realist evaluation which tested and refined program theories elucidating the complex dynamic between context (C), mechanism (M) and outcome (O) to determine what works, for whom, under what circumstances. Data was drawn from program documents, a realist synthesis, informal discussions with implementation designers, and interviews with 10 key informants (out of 37 identified) from seven sites. Data analysis employed a retroductive approach to interrogate the causal factors identified as contributors to outcomes. RESULTS: CMO statements were refined for four initial program theories: Making it Relevant- where participation in activities was increased when targeted to the needs of the staff; Investment in Quality Improvement- where engagement in capability development was enhanced when it was valued by all levels of the organisation; Turnover and Capability Loss- where the effects of staff turnover were mitigated; and Community-Wide Priority- where there was a strategy of spanning sites. From these data five guiding principles for implementers were distilled: (1) Involve all levels of the health system to effectively implement large-scale capability development, (2) Design capability development activities in a way that supports a learning culture, (3) Plan capability development activities with staff turnover in mind, (4) Increased capability should be distributed across teams to avoid bottlenecks in workflows and the risk of losing key staff, (5) Foster cross-site collaboration to focus effort, reduce variation in practice and promote greater cohesion in patient care. CONCLUSIONS: A key implementation strategy for interventions to standardise high quality practice is development of clinical capability. We illustrate how leadership support, attention to staff turnover patterns, and making activities relevant to current issues, can lead to an emergent learning culture.

Consumer and provider perceptions of the specialist unit model of care: A qualitative study.

BACKGROUND: Specialist care units cater to targeted cohorts of patients, applying evidence-based practice to people with a specific condition (e.g., dementia) or meeting other specific criteria (e.g., children). This paper aimed to collate perceptions of local consumers and health providers around specialist care units, as a model of care that may be considered for a new local healthcare facility. METHODS: This was a qualitative study using two-hour workshops and interviews to collect data. Participants were consumers and health providers in the planned facility's catchment: 49 suburbs in metropolitan Australia. Consumers and health providers were recruited through advertisements and emails. An initial survey collected demographic details. Consumers and health providers participated in separate two-hour workshops in which a scenario around the specialist unit model was presented and discussion on benefits, barriers and enablers of the model was led by researchers. Detailed notes were taken for analysis. RESULTS: Five consumer workshops (n = 22 participants) and five health provider workshops (n = 42) were conducted. Participants were representative of this culturally diverse region. Factors identified by participants as relevant to the specialist unit model of care included: accessibility; a perceived narrow scope of practice; coordination with other services; resources and infrastructure; and awareness and expectations of the units. Some factors identified as risks or barriers when absent were identified as strengths and enablers when present by both groups of participants. CONCLUSIONS: Positive views of the model centred on the higher perceived quality of care received in the units. Negative views centred on a perceived narrow scope of care and lack of flexibility. Consumers hinted, and providers stated explicitly, that the model needed to be complemented by an integrated model of care model to enable continuity of care and easy transfer of patients into and out of the specialist unit.

How Important Is Sexual Isolation to Speciation?

A central role for sexual isolation in the formation of new species and establishment of species boundaries has been noticed since Darwin and is frequently emphasized in the modern literature on speciation. However, an objective evaluation of when and how sexual isolation plays a role in speciation has been carried out in few taxa. We discuss three approaches for assessing the importance of sexual isolation relative to other reproductive barriers, including the relative evolutionary rate of sexual trait differentiation, the relative strength of sexual isolation in sympatry, and the role of sexual isolation in the long-term persistence of diverging forms. First, we evaluate evidence as to whether sexual isolation evolves faster than other reproductive barriers during the early stages of divergence. Second, we discuss available evidence as to whether sexual isolation is as strong or stronger than other barriers between closely related sympatric species. Finally, we consider the effect of sexual isolation on long-term species persistence, relative to other reproductive barriers. We highlight challenges to our knowledge of and opportunities to improve upon our understanding of sexual isolation from different phases of the speciation process.

Four System Enablers of Large-System Transformation in Health Care: A Mixed Methods Realist Evaluation.

Policy Points The implementation of large-scale health care interventions relies on a shared vision, commitment to change, coordination across sites, and a spanning of siloed knowledge. Enablers of the system should include building an authorizing environment; providing relevant, meaningful, transparent, and timely data; designating and distributing leadership and decision making; and fostering the emergence of a learning culture. Attention to these four enablers can set up a positive feedback loop to foster positive change that can protect against the loss of key staff, the presence of lone disruptors, and the enervating effects of uncertainty. CONTEXT: Large-scale transformative initiatives have the potential to improve the quality, efficiency, and safety of health care. However, change is expensive, complex, and difficult to implement and sustain. This paper advances system enablers, which will help to guide large-scale transformation in health care systems. METHODS: A realist study of the implementation of a value-based health care program between 2017 and 2021 was undertaken in every public hospital (n = 221) in New South Wales (NSW), Australia. Four data sources were used to elucidate initial program theories beginning with a set of literature reviews, a program document review, and informal discussions with key stakeholders. Semistructured interviews were then conducted with 56 stakeholders to confirm, refute, or refine the theories. A retroductive analysis produced a series of context-mechanism-outcome (CMO) statements. Next, the CMOs were validated with three health care quality expert panels (n = 51). Synthesized data were interrogated to distill the overarching system enablers. FINDINGS: Forty-two CMO statements from the eight initial program theory areas were developed, refined, and validated. Four system enablers were identified: (1) build an authorizing environment; (2) provide relevant, authentic, timely, and meaningful data; (3) designate and distribute leadership and decision making; and (4) support the emergence of a learning culture. The system enablers provide a nuanced understanding of large-system transformation that illustrates when, for whom, and in what circumstances large-system transformation worked well or worked poorly. CONCLUSIONS: System enablers offer nuanced guidance for the implementation of large-scale health care interventions. The four enablers may be portable to similar contexts and provide the empirical basis for an implementation model of large-system value-based health care initiatives. With concerted application, these findings can pave the way not just for a better understanding of greater or lesser success in intervening in health care settings but ultimately to contribute higher quality, higher value, and safer care.

Audit and feedback to reduce unwarranted clinical variation at scale: a realist study of implementation strategy mechanisms.

BACKGROUND: Unwarranted clinical variation in hospital care includes the underuse, overuse, or misuse of services. Audit and feedback is a common strategy to reduce unwarranted variation, but its effectiveness varies widely across contexts. We aimed to identify implementation strategies, mechanisms, and contextual circumstances contributing to the impact of audit and feedback on unwarranted clinical variation. METHODS: Realist study examining a state-wide value-based healthcare program implemented between 2017 and 2021 in New South Wales, Australia. Three initiatives within the program included audit and feedback to reduce unwarranted variation in inpatient care for different conditions. Multiple data sources were used to formulate the initial audit and feedback program theory: a systematic review, realist review, program document review, and informal discussions with key program stakeholders. Semi-structured interviews were then conducted with 56 participants to refute, refine, or confirm the initial program theories. Data were analysed retroductively using a context-mechanism-outcome framework for 11 transcripts which were coded into the audit and feedback program theory. The program theory was validated with three expert panels: senior health leaders (n = 19), Agency for Clinical Innovation (n = 11), and Ministry of Health (n = 21) staff. RESULTS: The program's audit and feedback implementation strategy operated through eight mechanistic processes. The strategy worked well when clinicians (1) felt ownership and buy-in, (2) could make sense of the information provided, (3) were motivated by social influence, and (4) accepted responsibility and accountability for proposed changes. The success of the strategy was constrained when the audit process led to (5) rationalising current practice instead of creating a learning opportunity, (6) perceptions of unfairness and concerns about data integrity, 7) development of improvement plans that were not followed, and (8) perceived intrusions on professional autonomy. CONCLUSIONS: Audit and feedback strategies may help reduce unwarranted clinical variation in care where there is engagement between auditors and local clinicians, meaningful audit indicators, clear improvement plans, and respect for clinical expertise. We contribute theoretical development for audit and feedback by proposing a Model for Audit and Feedback Implementation at Scale. Recommendations include limiting the number of audit indicators, involving clinical staff and local leaders in feedback, and providing opportunities for reflection.

"Somewhere to turn to with my questions": A pre-post pilot of an information linker service for caregivers who have a child with a Developmental and Epileptic Encephalopathy.

BACKGROUND: Caregivers of a child with a Developmental and Epileptic Encephalopathy (DEE) often report challenges accessing relevant and understandable information regarding their child's condition. We developed GenE Compass, an information linker service where caregivers are invited to submit questions and receive high-quality, personalised reports. We conducted a pilot evaluation to determine the feasibility and acceptability of GenE Compass. METHODS: We invited eligible caregivers to complete a baseline questionnaire (Q1) prior to receiving three months access to submit an unlimited number of questions to GenE Compass. We then invited caregivers to complete a follow-up questionnaire (Q2) and optional interview. Caregivers also had the opportunity to share report-specific feedback at the time of receiving each report. RESULTS: Seventy-two caregivers completed Q1, of which 41 submitted at least one question (range = 1-7). We received a total of 76 questions. The median turnaround time was 12 working days for our information linker (range = 1-28). Thirty-seven caregivers completed Q2, of whom 32 submitted at least one question (87 %). Overall, caregivers were highly satisfied with GenE Compass and their reports, and indicated that they would use it in the future if they had another question. Caregivers' qualitative data from Q1 and interviews highlighted the ongoing need for an information linker service like GenE Compass due to a lack of understandable information and limited resources, and the benefit in reducing burden of constant information searching. CONCLUSION: Our study shows that GenE Compass is feasible with the appropriate allocation of resources and highly acceptable to caregivers who have a child with a DEE.

The Digital Hospital: A Scoping Review of How Technology Is Transforming Cardiopulmonary Care.

BACKGROUND: Innovative models of health care that involve advanced technology in the form of a digital hospital are emerging globally. Models include technology such as machine learning and smart wearables, that can be used to integrate patient data and improve continuity of care. This model may have benefits in situations where patient deterioration must be detected quickly so that a rapid response can occur such as cardiopulmonary settings. AIM: The purpose of this scoping review was to examine the evidence for a digital hospital model of care, in the context of cardiac and pulmonary settings. DESIGN: Scoping review. DATA SOURCES: Databases searched were using PsycInfo, Ovid MEDLINE, and CINAHL. Studies written in English and containing key terms related to digital hospital and cardiopulmonary care were included. The Joanna Briggs Institute methodology for systematic reviews was used to assess the risk of bias. RESULTS: Thirteen (13) studies fulfilled the inclusion criteria. For cardiac conditions, a deep-learning-based rapid response system warning system for predicting patient deterioration leading to cardiac arrest had up to 257% higher sensitivity than conventional methods. There was also a reduction in the number of patients who needed to be examined by a physician. Using continuous telemonitoring with a wireless real-time electrocardiogram compared with non-monitoring, there was improved initial resuscitation and 24-hour post-event survival for high-risk patients. However, there were no benefits for survival to discharge. For pulmonary conditions, a natural language processing algorithm reduced the time to asthma diagnosis, demonstrating high predictive values. Virtual inhaler education was found to be as effective as in-person education, and prescription error was reduced following the implementation of computer-based physician order entry electronic medical records and a clinical decision support tool. CONCLUSIONS: While we currently have only a brief glimpse at the impact of technology care delivery for cardiac and respiratory conditions, technology presents an opportunity to improve quality and safety in care, but only with the support of adequate infrastructure and processes. PROTOCOL REGISTRATION: Open Science Framework (OSF: DOI 10.17605/OSF.IO/PS6ZU).

Perioperative interventions to improve early mobilisation and physical function after hip fracture: a systematic review and meta-analysis.

BACKGROUND: Perioperative interventions could enhance early mobilisation and physical function after hip fracture surgery. OBJECTIVE: Determine the effectiveness of perioperative interventions on early mobilisation and physical function after hip fracture. METHODS: Ovid MEDLINE, CINAHL, Embase, Scopus and Web of Science were searched from January 2000 to March 2022. English language experimental and quasi-experimental studies were included if patients were hospitalised for a fractured proximal femur with a mean age 65 years or older and reported measures of early mobilisation and physical function during the acute hospital admission. Data were pooled using a random effect meta-analysis. RESULTS: Twenty-eight studies were included from 1,327 citations. Studies were conducted in 26 countries on 8,192 participants with a mean age of 80 years. Pathways and models of care may provide a small increase in early mobilisation (standardised mean difference [SMD]: 0.20, 95% confidence interval [CI]: 0.01-0.39, I2 = 73%) and physical function (SMD: 0.07, 95% CI 0.00 to 0.15, I2 = 0%) and transcutaneous electrical nerve stimulation analgesia may provide a moderate improvement in function (SMD: 0.65, 95% CI: 0.24-1.05, I2 = 96%). The benefit of pre-operative mobilisation, multidisciplinary rehabilitation, recumbent cycling and clinical supervision on mobilisation and function remains uncertain. Evidence of no effect on mobilisation or function was identified for pre-emptive analgesia, intraoperative periarticular injections, continuous postoperative epidural infusion analgesia, occupational therapy training or nutritional supplements. CONCLUSIONS: Perioperative interventions may improve early mobilisation and physical function after hip fracture surgery. Future studies are needed to model the causal mechanisms of perioperative interventions on mobilisation and function after hip fracture.

Distinct genetic origins of eumelanin intensity and barring patterns in cichlid fishes.

Pigment patterns are incredibly diverse across vertebrates and are shaped by multiple selective pressures from predator avoidance to mate choice. A common pattern across fishes, but for which we know little about the underlying mechanisms, is repeated melanic vertical bars. In order to understand genetic factors that modify the level or pattern of vertical barring, we generated a genetic cross of 322 F2 hybrids between two cichlid species with distinct barring patterns, Aulonocara koningsi and Metriaclima mbenjii. We identify 48 significant quantitative trait loci that underlie a series of seven phenotypes related to the relative pigmentation intensity, and four traits related to patterning of the vertical bars. We find that genomic regions that generate variation in the level of eumelanin produced are largely independent of those that control the spacing of vertical bars. Candidate genes within these intervals include novel genes and those newly-associated with vertical bars, which could affect melanophore survival, fate decisions, pigment biosynthesis, and pigment distribution. Together, this work provides insights into the regulation of pigment diversity, with direct implications for an animal's fitness and the speciation process.

The diversity of providers' and consumers' views of virtual versus inpatient care provision: a qualitative study.

BACKGROUND: A broad-based international shift to virtual care models over recent years has accelerated following COVID-19. Although there are increasing numbers of studies and reviews, less is known about clinicians' and consumers' perspectives concerning virtual modes in contrast to inpatient modes of delivery. METHODS: We conducted a mixed-methods study in late 2021 examining consumers' and providers' expectations of and perspectives on virtual care in the context of a new facility planned for the north-western suburbs of Sydney, Australia. Data were collected via a series of workshops, and a demographic survey. Recorded qualitative text data were analysed thematically, and surveys were analysed using SPSS v22. RESULTS: Across 12 workshops, 33 consumers and 49 providers from varied backgrounds, ethnicities, language groups, age ranges and professions participated. Four advantages, strengths or benefits of virtual care reported were: patient factors and wellbeing, accessibility, better care and health outcomes, and additional health system benefits, while four disadvantages, weaknesses or risks of virtual care were: patient factors and wellbeing, accessibility, resources and infrastructure, and quality and safety of care. CONCLUSIONS: Virtual care was widely supported but the model is not suitable for all patients. Health and digital literacy and appropriate patient selection were key success criteria, as was patient choice. Key concerns included technology failures or limitations and that virtual models may be no more efficient than inpatient care models. Considering consumer and provider views and expectations prior to introducing virtual models of care may facilitate greater acceptance and uptake.

Guiding principles for effective collaborative implementation strategies for multisite hospital improvement initiatives: a mixed-method realist evaluation of collaborative strategies used in four multisite initiatives at public hospitals in New South Wales, Australia.

OBJECTIVE: Large-scale, multisite hospital improvement initiatives can advance high-quality care for patients. Implementation support is key to adoption of change in this context. Strategies that foster collaboration within local teams, across sites and between initiative developers and users are important. However not all implementation strategies are successful in all settings, sometimes realising poor or unintended outcomes. Our objective here is to develop guiding principles for effective collaborative implementation strategies for multi-site hospital initiatives. DESIGN: Mixed-method realist evaluation. Realist studies aim to examine the underlying theories that explain differing outcomes, identifying mechanisms and contextual factors that may trigger them. SETTING: We report on collaborative strategies used in four multi-site initiatives conducted in all public hospitals in New South Wales, Australia (n>100). PARTICIPANTS: Using an iterative process, information was gathered on collaborative implementation strategies used, then initial programme theories hypothesised to underlie the strategies' outcomes were surfaced using a realist dialogic approach. A realist interview schedule was developed to elicit evidence for the posited initial programme theories. Fourteen participants from 20 key informants invited participated. Interviews were conducted via Zoom, transcribed and analysed. From these data, guiding principles of fostering collaboration were developed. RESULTS: Six guiding principles were distilled: (1) structure opportunities for collaboration across sites; (2) facilitate meetings to foster learning and problem-solving across sites; (3) broker useful long-term relationships; (4) enable support agencies to assist implementers by giving legitimacy to their efforts in the eyes of senior management; (5) consider investment in collaboration as effective well beyond the current projects; (6) promote a shared vision and build momentum for change by ensuring inclusive networks where everyone has a voice. CONCLUSION: Structuring and supporting collaboration in large-scale initiatives is a powerful implementation strategy if contexts described in the guiding principles are present.

Does ASMR propensity reflect a mentally flexible mindset? Exploring the relationship between ASMR propensity, transliminality, emotional contagion, schizotypal traits, roleplaying ability, and creativity.

Autonomous Sensory Meridian Response (ASMR) is an alternative state of consciousness characterised by changes in affect, feelings of relaxation, and tingling sensations on the body. Online videos designed to stimulate ASMR in viewers have become increasingly popular. Although there is evidence that ASMR may improve sleep, emotion regulation, and relaxation, the current understanding of ASMR propensity remains limited. This study examined whether a mentally flexible cognitive style may underlie the ability to experience ASMR. Undergraduate students (N = 376) completed an online survey involving a series of self-report questionnaires and two performance-based creative ability tasks. Findings did not provide support for an overall mentally flexible mindset, however, transliminality, emotional contagion susceptibility, positive schizotypal traits, and roleplaying ability all significantly positively predicted ASMR propensity. These findings suggest that ASMR propensity represents several possible underlying cognitive styles relating to enhanced imagination and perceptual ability, and cannot be simply characterised by mental flexibility.

Genetic basis of ecologically relevant body shape variation among four genera of cichlid fishes.

Divergence in body shape is one of the most widespread and repeated patterns of morphological variation in fishes and is associated with habitat specification and swimming mechanics. Such ecological diversification is the first stage of the explosive adaptive radiation of cichlid fishes in the East African Rift Lakes. We use two hybrid crosses of cichlids (Metriaclima sp. × Aulonocara sp. and Labidochromis sp. × Labeotropheus sp., >975 animals total) to determine the genetic basis of body shape diversification that is similar to benthic-pelagic divergence across fishes. Using a series of both linear and geometric shape measurements, we identified 34 quantitative trait loci (QTL) that underlie various aspects of body shape variation. These QTL are spread throughout the genome, each explaining 3.2-8.6% of phenotypic variation, and are largely modular. Further, QTL are distinct both between these two crosses of Lake Malawi cichlids and compared to previously identified QTL for body shape in fishes such as sticklebacks. We find that body shape is controlled by many genes of small effect. In all, we find that convergent body shape phenotypes commonly observed across fish clades are most likely due to distinct genetic and molecular mechanisms.

Innovative models of healthcare delivery: an umbrella review of reviews.

OBJECTIVE: To undertake a synthesis of evidence-based research for seven innovative models of care to inform the development of new hospitals. DESIGN: Umbrella review. SETTING: Interventions delivered inside and outside of acute care settings. PARTICIPANTS: Children and adults with one or more identified acute or chronic health conditions. DATA SOURCES: PsycINFO, Ovid MEDLINE and CINAHL. PRIMARY AND SECONDARY OUTCOME MEASURES: Clinical indicators and mortality, healthcare utilisation, quality of life, self-management and self-care and patient knowledge. RESULTS: A total of 66 reviews were included, synthesising evidence from 1272 primary studies across the 7 models of care. Virtual care was the most common model studied, addressed by 47 (73%) of the reviews. Common outcomes evaluated across reviews were clinical indicators and mortality, healthcare utilisation, self-care and self-management, patient knowledge, quality of life and cost-effectiveness. The findings indicate that the innovative models of healthcare we identified in this review may be effective in managing patients with a range of acute and chronic conditions. Most of the included reviews reported evidence of comparable or improved care. CONCLUSIONS: A consideration of local infrastructure and individual patient characteristics, such as health literacy, may be critical in determining the suitability of models of care for patients and their implementation in local health systems. TRIAL REGISTRATION NUMBER: 10.17605/OSF.IO/PS6ZU.

What do consumer and providers view as important for integrated care? A qualitative study.

BACKGROUND: Integrated care is a model recognised internationally, however, there is limited evidence about its usability in the community. This study aimed to elicit community and provider views about integrated care and how implementation could meet their healthcare needs in a new hospital. METHODS: Using a qualitative approach, consumer and provider views on the strengths, barriers and enablers for integrated care were collected via a series of online workshops and supplementary interviews. RESULTS: A total of 22 consumers and 49 providers participated in 11 focus groups; all perceived integrated care to be an accessible and efficient model that offers a high level of care which enhanced staff and patient well-being. Providers expressed concerns about longer waiting times and safety risks associated with communication gaps and insufficient staff. Enablers include supporting consumers in navigating the integrated care process, co-ordinating and integrating primary care into the model as well as centralising patient electronic medical records. DISCUSSION: Primary, tertiary and community linkages are key for integrated care. Successful interoperability of services and networks requires an investment in resources and infrastructure to build the capability for providers to seamlessly access information at all points along the patient pathway. CONCLUSION: Integrated care is perceived by consumers and providers to be a flexible and patient-focused model of healthcare that offers benefits for a hospital of the future.

The evolutionary history and spectral tuning of vertebrate visual opsins.

Many animals depend on the sense of vision for survival. In eumetazoans, vision requires specialized, light-sensitive cells called photoreceptors. Light reaches the photoreceptors and triggers the excitation of light-detecting proteins called opsins. Here, we describe the story of visual opsin evolution from the ancestral bilaterian to the extant vertebrate lineages. We explain the mechanisms determining color vision of extant vertebrates, focusing on opsin gene losses, duplications, and the expression regulation of vertebrate opsins. We describe the sequence variation both within and between species that has tweaked the sensitivities of opsin proteins towards different wavelengths of light. We provide an extensive resource of wavelength sensitivities and mutations that have diverged light sensitivity in many vertebrate species and predict how these mutations were accumulated in each lineage based on parsimony. We suggest possible natural and sexual selection mechanisms underlying these spectral differences. Understanding how molecular changes allow for functional adaptation of animals to different environments is a major goal in the field, and therefore identifying mutations affecting vision and their relationship to photic selection pressures is imperative. The goal of this review is to provide a comprehensive overview of our current understanding of opsin evolution in vertebrates.

Innovative models of care for the health facility of the future: a protocol for a mixed-methods study to elicit consumer and provider views.

INTRODUCTION: To address the challenges of rapidly changing healthcare, governments and health services are increasingly emphasising healthcare delivery models that are flexible, person centred, cost-effective and integrate hospital services more closely with primary healthcare and social services. In addition, such models increasingly embed consumer codesign, integration of services, and leverage digital technologies such as telehealth and sophisticated medical records systems. OBJECTIVES: This paper provides a study protocol to describe a method to elicit consumer and healthcare provider needs and expectations for the development of innovative care models. METHODS AND ANALYSIS: A literature review identified six key models of care, supported by a common theme of consumer-focused care, along with the international evidence supporting the efficacy of these models. A mixed-methods study of the needs and expectations of consumer members and health providers who reside or work in the area of a new hospital catchment will be undertaken. They will complete a community-specific and provider-specific, short demographic questionnaire (delivered during the recruitment process) and be assigned to facilitator-coordinated online workshops comprising small focus groups. Follow-up interviews will be offered. Culturally and linguistically diverse members and Aboriginal and Torres Strait Islander Elders and their communities will also be consulted. Data will be analysed thematically (qualitative) and statistically (quantitative), and findings synthesised using a triangulated approach. ETHICS AND DISSEMINATION: The results will be actively disseminated through peer-reviewed journals, conference presentations and in a report to stakeholders. This study was reviewed and approved by the relevant Ethics Committee in New South Wales, Australia.

The diversity of invertebrate visual opsins spanning Protostomia, Deuterostomia, and Cnidaria.

Across eumetazoans, the ability to perceive and respond to visual stimuli is largely mediated by opsins, a family of proteins belonging to the G protein-coupled receptor (GPCR) superclass. Lineage-specific gains and losses led to a striking diversity in the numbers, types, and spectral sensitivities conferred by visual opsin gene expression. Here, we review the diversity of visual opsins and differences in opsin gene expression from well-studied protostome, invertebrate deuterostome, and cnidarian groups. We discuss the functional significance of opsin expression differences and spectral tuning among lineages. In some cases, opsin evolution has been linked to the detection of relevant visual signals, including sexually selected color traits and host plant features. In other instances, variation in opsins has not been directly linked to functional or ecological differences. Overall, the array of opsin expression patterns and sensitivities across invertebrate lineages highlight the diversity of opsins in the eumetazoan ancestor and the labile nature of opsins over evolutionary time.

Morphometric and Genetic Description of Trophic Adaptations in Cichlid Fishes.

Since Darwin, biologists have sought to understand the evolution and origins of phenotypic adaptations. The skull is particularly diverse due to intense natural selection on feeding biomechanics. We investigated the genetic and molecular origins of trophic adaptation using Lake Malawi cichlids, which have undergone an exemplary evolutionary radiation. We analyzed morphological differences in the lateral and ventral head shape among an insectivore that eats by suction feeding, an obligate biting herbivore, and their F2 hybrids. We identified variation in a series of morphological traits-including mandible width, mandible length, and buccal length-that directly affect feeding kinematics and function. Using quantitative trait loci (QTL) mapping, we found that many genes of small effects influence these craniofacial adaptations. Intervals for some traits were enriched in genes related to potassium transport and sensory systems, the latter suggesting co-evolution of feeding structures and sensory adaptations for foraging. Despite these indications of co-evolution of structures, morphological traits did not show covariation. Furthermore, phenotypes largely mapped to distinct genetic intervals, suggesting that a common genetic basis does not generate coordinated changes in shape. Together, these suggest that craniofacial traits are mostly inherited as separate modules, which confers a high potential for the evolution of morphological diversity. Though these traits are not restricted by genetic pleiotropy, functional demands of feeding and sensory structures likely introduce constraints on variation. In all, we provide insights into the quantitative genetic basis of trophic adaptation, identify mechanisms that influence the direction of morphological evolution, and provide molecular inroads to craniofacial variation.

Protocol for a phase 3 trial to evaluate the effectiveness and safety of a heterologous, two-dose vaccine for Ebola virus disease in the Democratic Republic of the Congo.

INTRODUCTION: Ebola virus disease (EVD) continues to be a significant public health problem in sub-Saharan Africa, especially in the Democratic Republic of the Congo (DRC). Large-scale vaccination during outbreaks may reduce virus transmission. We established a large population-based clinical trial of a heterologous, two-dose prophylactic vaccine during an outbreak in eastern DRC to determine vaccine effectiveness. METHODS AND ANALYSIS: This open-label, non-randomised, population-based trial enrolled eligible adults and children aged 1 year and above. Participants were offered the two-dose candidate EVD vaccine regimen VAC52150 (Ad26.ZEBOV, Modified Vaccinia Ankara (MVA)-BN-Filo), with the doses being given 56 days apart. After vaccination, serious adverse events (SAEs) were passively recorded until 1 month post dose 2. 1000 safety subset participants were telephoned at 1 month post dose 2 to collect SAEs. 500 pregnancy subset participants were contacted to collect SAEs at D7 and D21 post dose 1 and at D7, 1 month, 3 months and 6 months post dose 2, unless delivery was before these time points. The first 100 infants born to these women were given a clinical examination 3 months post delivery. Due to COVID-19 and temporary suspension of dose 2 vaccinations, at least 50 paediatric and 50 adult participants were enrolled into an immunogenicity subset to examine immune responses following a delayed second dose. Samples collected predose 2 and at 21 days post dose 2 will be tested using the Ebola viruses glycoprotein Filovirus Animal Non-Clinical Group ELISA. For qualitative research, in-depth interviews and focus group discussions were being conducted with participants or parents/care providers of paediatric participants. ETHICS AND DISSEMINATION: Approved by Comité National d'Ethique et de la Santé du Ministère de la santé de RDC, Comité d'Ethique de l'Ecole de Santé Publique de l'Université de Kinshasa, the LSHTM Ethics Committee and the MSF Ethics Review Board. Findings will be presented to stakeholders and conferences. Study data will be made available for open access. TRIAL REGISTRATION NUMBER: NCT04152486.