Public involvement in the governance of population-level biomedical research: unresolved questions and future directions.

Population-level biomedical research offers new opportunities to improve population health, but also raises new challenges to traditional systems of research governance and ethical oversight. Partly in response to these challenges, various models of public involvement in research are being introduced. Yet, the ways in which public involvement should meet governance challenges are not well understood. We conducted a qualitative study with 36 experts and stakeholders using the World Café method to identify key governance challenges and explore how public involvement can meet these challenges. This brief report discusses four cross-cutting themes from the study: the need to move beyond individual consent; issues in benefit and data sharing; the challenge of delineating and understanding publics; and the goal of clarifying justifications for public involvement. The report aims to provide a starting point for making sense of the relationship between public involvement and the governance of population-level biomedical research, showing connections, potential solutions and issues arising at their intersection. We suggest that, in population-level biomedical research, there is a pressing need for a shift away from conventional governance frameworks focused on the individual and towards a focus on collectives, as well as to foreground ethical issues around social justice and develop ways to address cultural diversity, value pluralism and competing stakeholder interests. There are many unresolved questions around how this shift could be realised, but these unresolved questions should form the basis for developing justificatory accounts and frameworks for suitable collective models of public involvement in population-level biomedical research governance

Transitioning to home and beyond following stroke: a prospective cohort study of outcomes and needs

Introduction: Understanding of the needs of people with stroke at hospital discharge and in the first six-months is limited. This study aim was to profile and document the needs of people with stroke at hospital discharge to home and thereafter. Methods: A prospective cohort study recruiting individuals with stroke, from three hospitals, who transitioned home, either directly, through rehabilitation, or with early supported discharge teams. Their outcomes (global-health, cognition, function, quality of life, needs) were described using validated questionnaires and a needs survey, at 7–10 days, and at 3-, and 6-months, post-discharge. Results: 72 patients were available at hospital discharge; mean age 70 (SD 13); 61% female; median NIHSS score of 4 (IQR 0–20). 62 (86%), 54 (75%), and 45 (63%) individuals were available respectively at each data collection time-point. Perceived disability was considerable at hospital discharge (51% with mRS ≥ 3), and while it improved at 3-months, it increased thereafter (35% with mRS ≥ 3 at 6-months). Mean physical health and social functioning were “fair” at hospital discharge and ongoing; while HR-QOL, although improved over time, remained impaired at 6-months (0.69+/-0.28). At 6-months cognitive impairment was present in 40%. Unmet needs included involvement in transition planning and care decisions, with ongoing rehabilitation, information, and support needs. The median number of unmet needs at discharge to home was four (range:1–9), and three (range:1–7) at 6-months. Conclusion: Stroke community reintegration is challenging for people with stroke and their families, with high levels of unmet need. Profiling outcomes and unmet needs for people with stroke at hospital-to-home transition and onwards are crucial for shaping the development of effective support interventions to be delivered at this juncture

Haemophilus influenzae Infection Drives IL-17-Mediated Neutrophilic Allergic Airways Disease

A subset of patients with stable asthma has prominent neutrophilic and reduced eosinophilic inflammation, which is associated with attenuated airways hyper-responsiveness (AHR). Haemophilus influenzae has been isolated from the airways of neutrophilic asthmatics; however, the nature of the association between infection and the development of neutrophilic asthma is not understood. Our aim was to investigate the effects of H. influenzae respiratory infection on the development of hallmark features of asthma in a mouse model of allergic airways disease (AAD). BALB/c mice were intraperitoneally sensitized to ovalbumin (OVA) and intranasally challenged with OVA 12–15 days later to induce AAD. Mice were infected with non-typeable H. influenzae during or 10 days after sensitization, and the effects of infection on the development of key features of AAD were assessed on day 16. T-helper 17 cells were enumerated by fluorescent-activated cell sorting and depleted with anti-IL-17 neutralizing antibody. We show that infection in AAD significantly reduced eosinophilic inflammation, OVA-induced IL-5, IL-13 and IFN-γ responses and AHR; however, infection increased airway neutrophil influx in response to OVA challenge. Augmented neutrophilic inflammation correlated with increased IL-17 responses and IL-17 expressing macrophages and neutrophils (early, innate) and T lymphocytes (late, adaptive) in the lung. Significantly, depletion of IL-17 completely abrogated infection-induced neutrophilic inflammation during AAD. In conclusion, H. influenzae infection synergizes with AAD to induce Th17 immune responses that drive the development of neutrophilic and suppress eosinophilic inflammation during AAD. This results in a phenotype that is similar to neutrophilic asthma. Infection-induced neutrophilic inflammation in AAD is mediated by IL-17 responses

The Precision Interventions for Severe and/or Exacerbation-Prone (PrecISE) Asthma Network: an overview of Network organization, procedures and interventions

Asthma is a heterogeneous disease, with multiple underlying inflammatory pathways and structural airway abnormalities that impact disease persistence and severity. Recent progress has been made in developing targeted asthma therapeutics, especially for subjects with eosinophilic asthma. However, there is an unmet need for new approaches to treat patients with severe and exacerbation prone asthma, who contribute disproportionately to disease burden. Extensive deep phenotyping has revealed the heterogeneous nature of severe asthma and identified distinct disease subtypes. A current challenge in the field is to translate new and emerging knowledge about different pathobiologic mechanisms in asthma into patient-specific therapies, with the ultimate goal of modifying the natural history of disease. Here we describe the Precision Interventions for Severe and/or Exacerbation Prone Asthma (PrecISE) Network, a groundbreaking collaborative effort of asthma researchers and biostatisticians from around the U.S. The PrecISE Network was designed to conduct phase II/proof of concept clinical trials of precision interventions in the severe asthma population, and is supported by the National Heart Lung and Blood Institute of the National Institutes of Health. Using an innovative adaptive platform trial design, the Network will evaluate up to six interventions simultaneously in biomarker-defined subgroups of subjects. We review the development and organizational structure of the Network, and choice of interventions being studied. We hope that the PrecISE Network will enhance our understanding of asthma subtypes and accelerate the development of therapeutics for of severe asthma

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Dragonflies (Insecta: Odonata), indicators of the diversity and ecological integrity of alluvial river ecosystems?

After decades of regulation, sectors of the French Upper Rhône River were restored. In this study, we aim to assess the ecological status of a set of seven floodplain channels of the area of Belley using a relatively inexpensive bioindicator: adult Odonata. Surveys were carried out during summer 2019 by following the RhoMeO Odonate protocol. The number of observed species (19) was low compared with a theoretical list of expected species (31). Several existing indices based on adult Odonata assemblages led to different characterisations of the floodplain, with an ecological status varying from bad to good, which highlights the divergence between indices depending on their thresholds and focus. A comparison with other bioindicators sampled between 2003 and 2019 as part of the monitoring of the restoration revealed correlations between adult Odonata and macrophytes in terms of alpha diversity. An analysis of beta diversity showed that variations in adult odonate community composition between sites reflect different levels of lateral hydrological connectivity within the floodplain. This perspective is the same as for other aquatic macroinvertebrates. Moreover, an analysis of links between macroinvertebrates and water temperature showed negative correlations between macroinvertebrate taxonomic richness and maximum water temperature or annual temperature range as well as a positive correlation between macroinvertebrate abundance and minimum summer temperature

Long-term monitoring of water temperature and macroinvertebrates highlights climate change threat to alpine ponds in protected areas

Climate change increasingly threatens alpine natural areas and notably aquatic systems. Alpine waterbodies, such as ponds, are particularly vulnerable to changes in temperature. Their biodiversity faces rising threats, especially for cold stenothermal species. Located at high elevation (>2600 m a.s.l.), the aquatic network of the Macun catchment (35 ponds and several streams) was put under a strict protection framework in 2000 (“Swiss National Park”) to mitigate threats to alpine biodiversity. The pond network has been regularly monitored as a sentinel of change, through aquatic macroinvertebrate sampling and physico-chemical measurements. Monitoring shows an alarmingly sharp increase in summer water temperature, rising by 4 °C between 2005 and 2020 (2.7 °C per decade). In contrast, nutrient concentrations have remained low and stable over these 15 years. The aquatic macroinvertebrate species richness has also been mostly stable between 2002 and 2021, with no negative impacts on the monitored cold stenotherms. Indeed, as the ponds are located at high elevation, these cold stenotherms are still living within their thermal range. Some cold stenothermal species have colonised the ponds from lower elevations, so the Macun pondscape acts as a refuge for these migrating taxa. In synthesis, our investigation highlights the alarming abiotic condition of the high-elevation freshwater biodiversity habitats, including a sharp temperature increase. It also provides evidence that their high elevation allows theses waterbodies to remain refuges for cold stenotherms, for now. In the longer term, however, a tipping point is likely to be reached, with a potential collapse of cold stenothermal biodiversity. This demonstrates the critical need to continue longer-term monitoring of high-elevation ecosystems to assess the magnitude of the impairment and to implement suitable conservation strategies, such as enhanced protection or the creation of new suitable habitats

Ornamental ponds as nature-based solutions to implement in cities

Small waterbodies such as ponds are widely represented in cities, contributing to the blue-green infrastructure, improving human well-being. Ornamental ponds are particularly abundant in the densest urbanized areas, especially in parks, in private grounds such as gardens and also imbedded in the green infrastructure. However, their multifunctionality remains infrequent, as generally aesthetic enjoyment is the main ecosystem service targeted. The promotion of native biodiversity is rarely a priority, as are other ecosystem services (e.g. flood mitigation or water purification). It is nevertheless questionable if such mono-functional ponds could also be able to provide other services. Indeed, an innovative approach would be to increase the multifunctionality of ornamental ponds, especially for biodiversity. This was investigated in 41 ornamental ponds designed for providing aesthetic enjoyment in the city of Geneva (Switzerland). The biodiversity was assessed, as well as selected ecosystem services (water retention, phytopurification, cooling effect, carbon sequestration). A survey among the population was also conducted. This survey underlined a recognized contribution of ornamental ponds to well-being. However, the assessment of the ecosystem services evidenced a lack of multifunctionality for most of these ponds. They presented a low biodiversity, compared to more natural ponds and to unimpaired ponds. Furthermore, they performed poorly for most other ecosystem services investigated. There were nevertheless exceptions, with selected ponds displaying a multifunctionality, even for ecosystem services for which they were not designed. It was also shown that ornamental ponds could easily be optimized for biodiversity by simple low-cost management measures. Additional ecosystem services could also be promoted. The performance of small ornamental ponds is best when ponds are considered collectively, as pondscapes, with their cumulative benefits. New ornamental pond implementation is therefore encouraged, as their multifunctionality turns them into Nature-based Solutions able to contribute to solving several societal challenges and to improve human well-being

Submerged Sea Caves of Southern California’s Continental Borderland

In 2016, funding from NOAA OER supported systematic mapping of portions of Channel Islands National Marine Sanctuary (CINMS) by E/V Nautilus. One focus of that effort was to locate and explore submerged paleoshorelines formed over the last 22,000 years when sea level stopped rising for 2,000 to 3,000 years at a time. These lulls in sea level rise permitted pounding waves, typical of the high-energy coast of today’s Southern California shoreline,to excavate caves, as they continue to now. The goal of our 2017 expedition in the Channel Islands area of the Southern California Continental Borderland was to search for submerged sea caves. Areas initially selected for investigation were the islands of Santa Cruz, Catalina, and Santa Barbara, where numerous sea caves are known to exist above present sea level, as well as where divers have already located them at the base of rock scarps resting at the 8 m to 10 m and 33 m paleo-shorelines