Research Priorities Research Articles

Conducting Patient-Oriented Research in Pediatric Populations: A Narrative Review.

It has become increasingly common for researchers to partner with patients as members of the research team and collaborate to use their lived experiences to shape research priorities, interventions, dissemination, and more. The patient-oriented research (POR) model has been adopted by both adult and pediatric health researchers. This cultural change to conducting pediatric health research brings with it new methodologies, tools, challenges, and benefits. In this review, we aim to provide guidance on how to conduct POR for pediatric populations using examples from the literature. We describe considerations for engagement before the project begins, for engagement across the research cycle, and for measurement and evaluation. We aim to show that conducting POR is feasible, beneficial, and that many common challenges and barriers can be overcome with preparation and usage of specific tools.

Using stakeholder knowledge to co-produce research priorities for a raptor species vulnerable to impacts of wind energy facilities

The global energy transition necessitates a rapid increase in infrastructure in developing countries, including for wind energy facilities (WEFs). Concerns arise regarding the negative impacts of WEFs on biodiversity, especially on birds of prey or raptors and other volant animals. In Africa, South Africa has the largest installed wind energy capacity and also hosts several raptor species of conservation importance. One such raptor is the regionally endemic Jackal Buzzard Buteo rufofuscus (family Accipitridae), which has its core population in South Africa. Despite frequent fatalities from collisions with wind turbine blades, this species is understudied. To address this gap, we conducted interviews with key stakeholders in the wind energy sector, including avifaunal specialists, wind energy developers, government representatives, and conservation nongovernmental organisations. The goal was to begin a cooperative process to identify crucial research gaps and to establish a future research agenda for Jackal Buzzards in the context of wind energy development. Stakeholders expressed confidence in current environmental impact assessment (EIA) techniques but highlighted a concern for direct collisions as a significant threat to Jackal Buzzards. The consensus was that WEFs are more likely to cause local rather than national population-level impacts. Although stakeholders generally shared similar opinions, minor differences emerged between groups. Movement ecology studies were identified as a high priority for future research on this species. By collaboratively formulating research priorities, this study aims to improve the relevance of future investigations, fostering stakeholder buy-in for potential policy and EIA practice recommendations.

NF-κB signaling pathway in tumor microenvironment

The genesis and progression of tumors are multifaceted processes influenced by genetic mutations within the tumor cells and the dynamic interplay with their surrounding milieu, which incessantly impacts the course of cancer. The tumor microenvironment (TME) is a complex and dynamic entity that encompasses not only the tumor cells but also an array of non-cancerous cells, signaling molecules, and the extracellular matrix. This intricate network is crucial in tumor progression, metastasis, and response to treatments. The TME is populated by diverse cell types, including immune cells, fibroblasts, endothelial cells, alongside cytokines and growth factors, all of which play roles in either suppressing or fostering tumor growth. Grasping the nuances of the interactions within the TME is vital for the advancement of targeted cancer therapies. Consequently, a thorough understanding of the alterations of TME and the identification of upstream regulatory targets have emerged as a research priority. NF-κB transcription factors, central to inflammation and innate immunity, are increasingly recognized for their significant role in cancer onset and progression. This review emphasizes the crucial influence of the NF-κB signaling pathway within the TME, underscoring its roles in the development and advancement of cancer. By examining the interactions between NF-κB and various components of the TME, targeting the NF-κB pathway appears as a promising cancer treatment approach.

Autophagy is required for mammary tumor recurrence by promoting dormant tumor cell survival following therapy

BackgroundMortality from breast cancer is principally due to tumor recurrence. Recurrent breast cancers arise from the pool of residual tumor cells, termed minimal residual disease, that survive treatment and may exist in a dormant state for 20 years or more following treatment of the primary tumor. As recurrent breast cancer is typically incurable, understanding the mechanisms underlying dormant tumor cell survival is a critical priority in breast cancer research. The importance of this goal is further underscored by emerging evidence suggesting that targeting dormant residual tumor cells in early-stage breast cancer patients may be a means to prevent tumor recurrence and its associated mortality. In this regard, the role of autophagy in dormant tumor cell survival and recurrence remains unresolved, with conflicting reports of both pro-survival/recurrence-promoting and pro-death/recurrence-suppressing effects of autophagy inhibition in dormant tumor cells. Resolving this question has important clinical implications.MethodsWe used genetically engineered mouse models that faithfully recapitulate key features of human breast cancer progression, including minimal residual disease, tumor dormancy, and recurrence. We used genetic and pharmacological approaches to inhibit autophagy, including treatment with chloroquine, genetic knockdown of ATG5 or ATG7, or deletion of BECN and determined their effects on dormant tumor cell survival and recurrence.ResultsWe demonstrate that the survival and recurrence of dormant mammary tumor cells following therapy is dependent upon autophagy. We find that autophagy is induced in vivo following HER2 downregulation and remains activated in dormant residual tumor cells. Using genetic and pharmacological approaches we show that inhibiting autophagy by chloroquine administration, ATG5 or ATG7 knockdown, or deletion of a single allele of the tumor suppressor Beclin 1 is sufficient to inhibit mammary tumor recurrence, and that autophagy inhibition results in the death of dormant mammary tumor cells in vivo.ConclusionsOur findings demonstrate a pro-tumorigenic role for autophagy in tumor dormancy and recurrence following therapy, reveal that dormant tumor cells are uniquely reliant upon autophagy for their survival, and indicate that targeting dormant residual tumor cells by inhibiting autophagy impairs tumor recurrence. These studies identify a pharmacological target for a cellular state that is resistant to commonly used anti-neoplastic agents and suggest autophagy inhibition as an approach to reduce dormant minimal residual disease in order to prevent lethal tumor recurrence.

Phenotypic Evaluation of Rare Cystic Fibrosis Transmembrane Conductance Regulator Mutation Combinations in People with Cystic Fibrosis in Queensland, Australia.

Background: Cystic fibrosis (CF) is a multisystem disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. We describe the distribution of CFTR mutation profiles in sub-tropical Queensland, Australia, and characterise the phenotypes associated with 'rare' CFTR mutation combinations. Methods: We conducted a retrospective observational study to analyse the CFTR mutation profiles of 322 people with CF (pwCF) under the care of a large adult CF centre in Queensland, Australia. Molecular pathology results were available for all identifiable CFTR mutations. The CFTR2 database was utilised to characterise the less common CFTR mutations to define mutation classes and explore associated phenotypic sequelae. Results: In total, eighty-seven different genotypes were identified within our CF cohort, with the most abundant mutation being the F508del mutation, 298/322 (92.5%). Thirty-six pwCF with CFTR mutations are considered to have 'rare' CFTR mutations, and eleven with previously undefined phenotypes. For these eleven pwCF, late diagnosis in adulthood was confirmed in 5/11 pwCF (45.5%) with CFTR modulator therapy only initiated in 5/11 (45.5%). Conclusions: The profile of more common CFTR genotypes within our cohort of adult pwCF living in Queensland, Australia, generally reflects the global predominance of F508del, G542X, G551D, N1303K, and R117H. The phenotypic heterogeneity of disease seen within the eleven pwCF in our cohort with previously undefined CFTR genotypes highlights that rare mutations can also be associated with severe disease and continue to be at risk of delayed diagnosis. Access to CFTR modulator therapies for this group of pwCF remains limited and should remain a research priority.

Bringing it all together: science priorities for improved understanding of Earth system change and to support international climate policy

Abstract. We review how the international modelling community, encompassing integrated assessment models, global and regional Earth system and climate models, and impact models, has worked together over the past few decades to advance understanding of Earth system change and its impacts on society and the environment and thereby support international climate policy. We go on to recommend a number of priority research areas for the coming decade, a timescale that encompasses a number of newly starting international modelling activities, as well as the IPCC Seventh Assessment Report (AR7) and the second UNFCCC Global Stocktake. Progress in these priority areas will significantly advance our understanding of Earth system change and its impacts, increasing the quality and utility of science support to climate policy. We emphasize the need for continued improvement in our understanding of, and ability to simulate, the coupled Earth system and the impacts of Earth system change. There is an urgent need to investigate plausible pathways and emission scenarios that realize the Paris climate targets – for example, pathways that overshoot 1.5 or 2 °C global warming, before returning to these levels at some later date. Earth system models need to be capable of thoroughly assessing such warming overshoots – in particular, the efficacy of mitigation measures, such as negative CO2 emissions, in reducing atmospheric CO2 and driving global cooling. An improved assessment of the long-term consequences of stabilizing climate at 1.5 or 2 °C above pre-industrial temperatures is also required. We recommend Earth system models run overshoot scenarios in CO2-emission mode to more fully represent coupled climate–carbon-cycle feedbacks and, wherever possible, interactively simulate other key Earth system phenomena at risk of rapid change during overshoot. Regional downscaling and impact models should use forcing data from these simulations, so impact and regional climate projections cover a more complete range of potential responses to a warming overshoot. An accurate simulation of the observed, historical record remains a fundamental requirement of models, as does accurate simulation of key metrics, such as the effective climate sensitivity and the transient climate response to cumulative carbon emissions. For adaptation, a key demand is improved guidance on potential changes in climate extremes and the modes of variability these extremes develop within. Such improvements will most likely be realized through a combination of increased model resolution, improvement of key model parameterizations, and enhanced representation of important Earth system processes, combined with targeted use of new artificial intelligence (AI) and machine learning (ML) techniques. We propose a deeper collaboration across such efforts over the coming decade. With respect to sampling future uncertainty, increased collaboration between approaches that emphasize large model ensembles and those focussed on statistical emulation is required. We recommend an increased focus on high-impact–low-likelihood (HILL) outcomes – in particular, the risk and consequences of exceeding critical tipping points during a warming overshoot and the potential impacts arising from this. For a comprehensive assessment of the impacts of Earth system change, including impacts arising directly as a result of climate mitigation actions, it is important that spatially detailed, disaggregated information used to generate future scenarios in integrated assessment models be available for use in impact models. Conversely, there is a need to develop methods that enable potential societal responses to projected Earth system change to be incorporated into scenario development. The new models, simulations, data, and scientific advances proposed in this article will not be possible without long-term development and maintenance of a robust, globally connected infrastructure ecosystem. This system must be easily accessible and useable by modelling communities across the world, allowing the global research community to be fully engaged in developing and delivering new scientific knowledge to support international climate policy.

Research Priorities of the Oncology Nursing Society: 2024-2027.

To define the Oncology Nursing Society Research Agenda for 2024-2027. An iterative, multiple data sources consolidation through the Research Agenda Project Team. Previous research priorities, literature review, stakeholder survey, and research priorities from other cancer care organizations and funding agencies. 10 evergreen statements articulated foundational values for oncology nurse scientists, and 5 topics emerged as research priorities for the upcoming three years: Advance patient-centric, precision symptom science; provide evidence for safe and effective cancer care delivery models and support of the oncology nursing workforce; describe the impact of the environment on cancer care outcomes; integrate patient navigation into cancer care across the trajectory; and advance the use of innovative methodologies in oncology nursing research. The Oncology Nursing Society Research Agenda is an effective resource for directing the organization's research vision. This foundational document directs funding awards and requests, mentorship, and policy initiatives.

Translational research priorities for bacteriophage therapeutics.

The growing threat of antimicrobial resistant (AMR) bacterial pathogens coupled with the relative dearth of promising novel antibiotics requires the discovery and development additional medical interventions. Over the past decade bacteriophages have emerged one of the most promising new tools to combat AMR pathogens. Anecdotal clinical experiences under so-called 'compassionate use' regulatory pathways as well as a limited number of clinical trials have provided ample evidence of safety and early evidence of efficacy. For phages to reach their full potential it is critical that rigorous clinical trials be conducted that define their optimal use and that enable regulatory authorities to support the commercialization required to afford global access. The clinical development of phage therapeutics requires the design and execution of clinical trials that take full advantage of lessons learned from a century of antibiotic development and that use clinical investigation as a platform in which aspects of phage biology that are critical to therapeutics are more clearly elucidated. Translational research that elucidates phage biology in the context of clinical trials will promote highly relevant hypothesis-driven work in basic science laboratories and will greatly accelerate the development of the field of phage therapeutics.

Development of a Refugee Health Research Agenda in North America.

The lack of a cohesive, stakeholder-informed refugee health research agenda has been a barrier to promoting, funding, and conducting health research with refugee populations in North America. A cross-sectional study was conducted among individuals working in refugee health in North America (N = 93) to describe major domains within the field of refugee health research and to develop refugee health research priorities. Open-ended survey questions included: (1) What research topics specific to refugee research would you like to see in an international research agenda? (2) Please describe current and important gaps that you believe exist in refugee research and why? Overarching themes focused on the need for the development of research partnerships with refugee communities that are intentional, effective, and driven by the needs of refugee communities. The survey also identified a need for best practices in creating sustainable, community-based research partnerships (effective models and evidence-based strategies) that translate across 12 domains. The refugee health research priorities for North America described in this manuscript should continue to be modified over time as political, economic, social, and medical contexts change.

Current State and Challenges of Tissue and Organ Cryopreservation in Biobanking

Recent years have witnessed significant advancements in the cryopreservation of various tissues and cells, yet several challenges persist. This review evaluates the current state of cryopreservation, focusing on contemporary methods, notable achievements, and ongoing difficulties. Techniques such as slow freezing and vitrification have enabled the successful preservation of diverse biological materials, including embryos and ovarian tissue, marking substantial progress in reproductive medicine and regenerative therapies. These achievements highlight improved post-thaw survival and functionality of cryopreserved samples. However, there are remaining challenges such as ice crystal formation, which can lead to cell damage, and the cryopreservation of larger, more complex tissues and organs. This review also explores the role of cryoprotectants and the importance of optimizing both cooling and warming rates to enhance preservation outcomes. Future research priorities include developing new cryoprotective agents, elucidating the mechanisms of cryoinjury, and refining protocols for preserving complex tissues and organs. This comprehensive overview underscores the transformative potential of cryopreservation in biomedicine, while emphasizing the necessity for ongoing innovation to address existing challenges.

The associations of post-stroke delirium with outcomes: a systematic review and meta-analysis

BackgroundPublished data on whether post-stroke delirium (PSD) is an independent predictor of outcomes in patients with acute stroke are inconsistent and have not yet been synthesized and quantified via meta-analyses.MethodsThis systematic review and meta-analysis followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The study protocol involved a search of the PubMed, Embase, PsycINFO, and Medline databases from 1946 to November 1, 2023, of which prospective observational and case–control studies were included. The quality of the included studies was rated using the Newcastle Ottawa Scale. Pooled effect estimates calculated using a random-effects model were expressed as the odds ratios (ORs), hazard ratios (HRs), and standardized mean differences (SMDs) with 95% confidence intervals (CIs). The protocol was registered in PROSPERO (CRD42023472551).ResultsThe search yielded 39 eligible articles comprising 3295 and 9643 patients with and without PSD, respectively. Thirty studies were high quality, while 9 had moderate quality. The primary analyses, adequately adjusting for predefined confounders, showed that PSD was significantly associated with mortality risk (average follow-up of 19.50 months; OR, 3.47; 95% CI, 2.35–5.12; I2, 26.0%) and poor neurological function (average follow-up of 21.75 months; OR, 3.62; 95% CI, 2.15–6.09; I2, 0). Secondary analyses, with or without inadequate adjustment, showed that PSD was significantly associated with prolonged hospital length of stay, increased risk of institutionalization, poor cognitive outcomes, and quality of life after discharge.ConclusionsThis systematic review and meta-analysis provides evidence that PSD was independently associated with mortality and poor neurological function after controlling for pre-specified confounders. The prevention of PSD remains a high clinical and research priority.

Research Priorities in Neuroeducation: Exploring the Views of Early Career Neuroscientists and Educators

The field of neuroeducation, which integrates neuroscience findings into educational practice, has gained significant attention in recent years. Establishing research priorities in neuroeducation is crucial for guiding future studies and ensuring that the field benefits both neuroscience and education. This study aimed to address the need for collaboration between neuroscientists and educators by conducting a priority-setting exercise with early career professionals from both fields. Using the nominal group technique (NGT) with interquartile range (IQR) analysis, we identified seven key priorities in neuroeducation and assessed the level of consensus on these priorities. The top-ranked priorities were “Emotional and Mental Well-being”, “Neurodiversity and Special Education Needs”, and “Active and Inclusive Teaching Methods”, though IQR analysis revealed varying levels of consensus. Lower-ranked priorities, such as “Role of Technology on Learning and the Brain”, showed a higher consensus. This discrepancy between ranking and consensus highlights the complex nature of neuroeducation, reflecting differing perspectives between neuroscientists and educators. These findings suggest the need for interdisciplinary collaboration to bridge these gaps and foster evidence-based practices. We recommend that future research focuses on the specific neural mechanisms underlying emotional well-being, strategies for supporting neurodivergent learners, and practical approaches to integrating inclusive teaching methods in diverse educational contexts.

The Experiences of Women Transitioning from Unhoused to Housed in High-Income Countries: A Systematic Review and Meta-Aggregation

There are pathways in and out of homelessness that are gender-specific. However, little is known about the range of existing studies on the experiences of women who recently transitioned from homeless to housed in high-income countries. To date, no systematic reviews have brought together qualitative analyses from studies exploring women’s experiences who are re-housed in high-income countries. To fill this gap in existing literature, we performed a systematic review, utilizing the methods described by the Joanna Briggs Institute (JBI) (Lockwood et al., 2020) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Moher et al., 2010) to understand the meaning and experience of women exiting homelessness in high-income countries. We combined the search terms related to women, homelessness, and housing transitions and deployed them in six databases. Our research yielded 3025 titles and abstracts following the removal of duplicates. After conducting a title and abstract screening, 91 full-text articles remained. 14 articles were deemed to meet pre-established inclusion criteria. Our meta-aggregation revealed four themes generated through our analysis: a) ongoing presence of trauma in women’s lives; b) healing through providing support to others; c) lack of control over circumstances that enable survival; and d) support in housing decreases marginalization. This review deepens knowledge of the current research priorities as well as practical policy and practice strategies that can be utilized to support recently rehoused women to prevent recurrent periods of homelessness and its devastating impacts.

Human-ocean relationships: Exploring alignment and collaboration between ocean literacy research and marine conservation

In recent years, global attention on marine conservation and sustainability has surged. Understanding the relationship between society and the ocean is crucial for achieving conservation targets, ocean sustainability, and community well-being. Toward these ends, the UN Ocean Decade recognizes ocean literacy as a transformative mechanism to reshape society-ocean relationships. Ocean literacy seeks to empower global communities to better understand, value, and care for the ocean in ways that support, restore, and ensure ocean-human health and well-being. By extension, ocean literacy research is an emergent transdisciplinary field of inquiry that explores diverse dimensions, drivers, and impacts of human-ocean relationships. It considers these relations across different socio-cultural, economic, political, and geographic contexts and perspectives. In this article, we position ocean literacy research and the wider concept of ocean literacy as a framework for exploring the relational aspects of marine conservation to inform effective policy and conservation. We begin by situating ocean literacy and ocean literacy dimensions, research priorities, and community alongside broader ocean conservation efforts. We next share insights gleaned from the third edition of the Ocean Literacy Dialogues series, led by the Canadian Ocean Literacy Coalition and the Marine Social Sciences Network, with support from IOC-UNESCO, held during the fifth International Marine Protected Area Congress (IMPAC5) in Vancouver, in early 2023. Through a series of participatory sessions, we explored the application of ocean literacy research in supporting future marine conservation and management. Drawing on insights co-developed through this process, we outline potential agenda alignment between IMPAC5 marine conservation themes and co-identified ocean literacy research priority areas. We lastly speak to the importance of ongoing collaborative initiatives like the Ocean Literacy Dialogues series to foster global collaborations, dialogue, and capacity sharing to advance ocean literacy, marine conservation, and policy efforts.

What are the research priorities in dance for dementia? A co-created agenda to support equitable research

ABSTRACT Background There is a gap in the field of dance for dementia regarding how to engage in and improve equitable, moral, and rights-based ways of working with those with lived experience to co-design research priorities. We set out to create a collaborative research agenda for this field. Methods A series of collaborative activities were conducted, including an in-person workshop (n = 59 people), online workshop (n = 23 people), digital communications, podcasts, and co-writing, including with people living with dementia (PLWD), health and social care professionals, artists, arts organisational representatives, and academic researchers. Results Three key themes were constructed: 1) Improving access to dance participation; 2) Prioritising co-produced approaches; and 3) Enabling innovation in measurement and methods. Conclusion This is the first co-produced agenda for the field of dance for dementia. Underpinned by diverse perspectives and lived experience, it outlines themes and associated research questions that can be used in future research.

Current policy and practice for the identification, management, and treatment of postpartum anxiety in the United Kingdom: a focus group study

BackgroundPostpartum Anxiety [PPA] is a prevalent problem in society, posing a significant burden to women, infant health, and the National Health Service [NHS]. Despite this, it is poorly detected by current maternal mental health practices. Due to the current lack of appropriate psychometric measures, insufficiency in training of healthcare professionals, fragmentation of maternal mental healthcare policy and practice, and the magnitude of the effects of PPA on women and their infants, PPA is a critical research priority. This research aims to develop a clear understanding from key stakeholders, of the current landscape of maternal mental health and gain consensus of the needs associated with clinically identifying, measuring, and targeting intervention for women with PPA, in the NHS.MethodsFour focus groups were conducted with a total of 21 participants, via Zoom. Data were analysed using Template Analysis.ResultsAnalysis rendered four main themes: (1) Defining Postpartum Anxiety; (2) Postpartum Anxiety in Relation to other Mental Health Disorders; (3) Challenges to Measurement and Identification of Maternal Mental Health; and (4) An Ideal Measure of Postpartum Anxiety.ConclusionsFindings can begin to inform maternal mental healthcare policy as to how to better identify and measure PPA, through the implementation of a postpartum-specific measure within practice, better training and resources for staff, and improved interprofessional communication.

Enhancing Clinical Data Quality to Improve Patient Care in Rural Health Facilities

WHO recognizes that high-quality research is not just a scientific pursuit but a crucial factor in achieving global health, health equity, and economic development. It is not just about the numbers but about the lives we can save and improve. In this context, four research priority areas have been identified: prioritizing health needs, building research capacity, ensuring good research practice, and ensuring good evidence is translated into practice. Local health research tailored to local needs remains an important global health goal, with the potential to revolutionize patient care in rural health facilities. Researchers and policymakers in low- and middle-income countries have expressed serious concerns about the limited access to high-quality data, a fundamental requirement for reliable and valid research. The assessment of data quality is typically categorized into five key areas: availability, usability, dependability, relevance, and presentation quality. This concept is further clarified by demonstrating how a robust healthcare data environment can enhance patient management through research efforts. The term ‘health data environment' encompasses the entire process of gathering, storing, managing, analysing, and utilizing health-related data to improve patient care and healthcare policies through informed decision-making. In this context, we present the challenges that undermine the quality of research data and propose solutions. Specifically, we identify the lack of adequate human resources, reliance on paper-based records systems, and the high costs of internet connectivity as the primary barriers to collecting and sharing high-quality data for research in low-resource settings. To tackle these challenges, we advocate for governments and funding institutions to invest in data management and communication systems, recruit and train data management staff to support clinicians, and reduce connectivity costs. Furthermore, we propose the deployment of a decentralized system as a cost-effective and less labor-intensive solution that only requires data entry staff at health facilities in resource-limited settings. This article explores current data collection, storage, and interpretation challenges and proposes innovative improvement solutions. It emphasizes the transformative potential of digitization, standardization, and staff training to enhance data quality. It further addresses the impact of quality data on evidence-based practice, ultimately leading to improved health outcomes. Focusing on rural healthcare facilities sheds light on the unique barriers these settings face, proposing tailored strategies that can bridge the gap between urban and rural health service delivery. These insights offer valuable guidance for policymakers, healthcare administrators, and practitioners striving to improve patient care in rural areas through data-driven strategies.

Insights, recommendations, and research priorities for central sleep apnea: report from an expert panel.

Central sleep apnea (CSA) is commonly encountered among patients with sleep-disordered breathing, however its clinical consequences are less well-characterized. We therefore convened an expert panel to discuss the common presentations of CSA, as well as challenges and knowledge gaps in the diagnosis and management of CSA. The panel identified several key research priorities essential for advancing our understanding of the disorder. Within the diagnostic realm, panel members discussed the utility of multi-night assessments, and importance of the development and validation of novel metrics and automated assessments for differentiating central versus obstructive hypopneas, such that their impact on clinical outcomes and management may be better evaluated. The panel also discussed the current therapeutic landscape for the management of CSA and agreed that therapies should primarily aim to alleviate sleep-related symptoms, after optimizing treatment to address the underlying cause. Most importantly, the panel concluded that there is a need to further investigate the clinical consequences of CSA, as well as the implications of therapy on clinical outcomes, particularly among those who are asymptomatic. Future research should focus on endo-phenotyping central events for a better mechanistic understanding of the disease, validating novel diagnostic methods for implementation in routine clinical practice, as well as the use of combination therapy and comparative effectiveness trials in elucidating the most efficacious interventions for managing CSA.

AOP Report: Development of an adverse outcome pathway for deposition of energy leading to bone loss.

Bone loss, commonly seen in osteoporosis, is a condition that entails a progressive decline of bone mineral density and microarchitecture, often seen in post-menopausal women. Bone loss has also been widely reported in astronauts exposed to a plethora of stressors and in patients with osteoporosis following radiotherapy for cancer. Studies on mechanisms are well documented but the causal connectivity of events to bone loss development remains incompletely understood. Herein, the adverse outcome pathway (AOP) framework was used to organize data and develop a qualitative AOP beginning from deposition of energy (the molecular initiating event) to bone loss (the adverse outcome). This qualitative AOP was developed in collaboration with bone loss research experts to aggregate relevant findings, supporting ongoing efforts to understand and mitigate human system risks associated with radiation exposures. A literature review was conducted to compile and evaluate the state of knowledge based on the modified Bradford Hill criteria. Following review of 2029 studies, an empirically supported AOP was developed, showing the progression to bone loss through many factors affecting the activities of bone-forming osteoblasts and bone-resorbing osteoclasts. The structural, functional, and quantitative basis of each proposed relationship was defined, for inference of causal changes between key events. Current knowledge and its gaps relating to dose-, time- and incidence-concordance across the key events were identified, as well as modulating factors that influence linkages. The new priorities for research informed by the AOP highlight areas for improvement to enable development of a quantitative AOP used to support risk assessment strategies for space travel or cancer radiotherapy.

Establishing Consensus on Biopsychosocial Factors Associated with Pediatric Chronic Pain: a Modified Delphi Study

A variety of factors are associated with the development and maintenance of chronic pain in children. Identifying modifiable factors associated with pediatric chronic pain is important to use them as target outcomes in the development and evaluation of interventions for the prevention and management of chronic pain. This study aimed to reach expert consensus on factors associated with pediatric chronic pain and their modifiability and population-level effect. Pediatric pain experts were questioned using a web-based two-round modified Delphi method. Two rounds of questions with Likert scaling were used to identify influencing factors (Round 1) and to reach consensus on each factor (Round 2) in terms of: 1) strength of association with chronic pain in children; 2) modifiability; and 3) population-level effect. An inductive approach was used to derive categories (ranging from 'very low' to 'very high') and subcategories (ranging from 'low' to 'high'). In total, 48 experts from 14 different countries completed Round 1, and 31 completed Round 2. A list of 47 factors was considered to be associated with pediatric chronic pain. Four factors (physical activity (PA), sedentary behavior (SB), pain-related school absence, and pain concept/knowledge of the child) were considered highly modifiable and three factors having a high population-level effect (PA, SB, and the child's depressive or negative emotional feelings). Expert consensus was established about modifiable and population-level factors associated with pediatric chronic pain through this web-based modified Delphi study, guiding target outcomes for its prevention and management. PERSPECTIVE: This article presents the results of a modified Delphi study with pediatric pain experts to gain consensus on factors associated with pediatric chronic pain. Relationship strength, modifiability, and population-level effect of associated factors were rated to identify areas of research priority and interventions aiming to reduce the development and maintenance of chronic pain in children.