Identifying neonatal transport research priorities: a modified Delphi consensus.

OBJECTIVES: With increasing advances in neonatal transport, a focused research strategy is required to increase the evidence base towards providing optimal care. We aimed to identify the most important neonatal transport research questions as prioritised by parents and healthcare professionals (HCPs). DESIGN: Key stakeholders participated in a modified three-stage Delphi consensus process. Research questions were identified and submitted through two survey stages before the final priority setting workshop. PARTICIPANTS: Parents of babies who received neonatal care, neonatal HCPs and stakeholders. OUTCOME: Identify the top 10 research priorities for neonatal transport. RESULTS: Overall, 269 survey responses from HCPs/stakeholders (n=161) and parents (n=108) were analysed from two survey rounds. Consensus was reached on 22 of 43 research priorities for the final priority setting workshop. The agreed top research priorities covered the domains of: (1) Pain assessment and management, (2) Long-term neurological outcomes, (3) Impact of transfer on birth-related brain injury, (4) Investigating risk of transport, (5) Safety restraints for infants, (6) Optimal temperature management, (7) Respiratory management and outcomes, (8) Benchmarking of important of transport measures, (9) Understanding transport environmental exposures, (10) Mental health and burden of transfer on families. CONCLUSION: We have identified the top research questions for neonatal transport through an extensive process actively engaging parents, HCPs and key stakeholders. Targeted funding and research resources, directed towards addressing these prioritised research areas, will inform evidence-based practices and international frameworks specific to neonatal transport, helping minimise research waste and ultimately improve outcomes for these high-risk infants and their families.

On the road to retirement: Predicting nighttime driving difficulty and cessation using self-reported health factors.

Introduction: Older drivers now expect to drive longer than previous cohorts and will make up about 25% of licensed U.S. drivers by 2050. Identifying early predictors of nighttime driving difficulty, a precursor to driving retirement, can inform screening procedures and timely linkage to interventions supporting driving or transitioning to driving cessation. Methods: We examined self-reported physical and mental health baseline predictors of greater nighttime driving difficulty in five and ten years using weighted multivariate logistic analyses of 2261 drivers, aged 57 to 85, from the National Social Life, Health, and Aging Project (NSHAP). Transition matrix models describe probabilities of having greater, lesser, or the same nighttime driving difficulty after five years based on baseline driving conditions and the significant logistic model factors. We built a transition matrix tool that offers users the ability to calculate expected probabilities of change in nighttime driving difficulty based on the identified salient factors. Results: Five-year predictors of greater nighttime driving difficulty included perceived poor physical health (OR = 3.75), limitations to activities of daily living (ADLs; OR = 1.97), and clinical levels of depressive and anxiety symptoms (OR = 1.63; OR = 1.71). Excellent physical health (OR = 0.52), mental health (OR = 0.60), and any frequency of physical activity compared to 'never' were protective (OR = 0.37-0.51). Physical health, walking pain, and limitations to ADLs were predictive at ten-years. Transition models showed physical health and anxiety were most indicative of greater nighttime driving difficulty at 5-years for those reporting no difficulty at baseline, but limitations to ADLs were more predictive otherwise. Conclusions: Lay practitioners could capitalize on the use of self-report screening measures to identify older adults who may experience near-term nighttime driving difficulty. Earlier identification may better guide long-term driving retirement planning or engagement in appropriate health interventions. The transition matrix modeling tool is freely available to facilitate development and validation of related measures.

Tracking national neonatal transport activity and metrics using the UK Neonatal Transport Group dataset 2012-2021: a narrative review.

There are no internationally agreed descriptors for categories of neonatal transports which facilitate comparisons between settings. To continually review and enhance neonatal transport care we need robust categories to develop benchmarks. This review aimed to report on the development and application of key measures across a national neonatal transport service. The UK Neonatal Transport Group (UK-NTG) developed a core dataset and benchmarks for transported infants and collected annual national data. Data were reported back to teams to allow benchmarking and improvements. From 2012 to 2021, the rate of UK neonatal transfers increased from 18 to 22/1000 live births despite a falling birth rate. Neonatal transfers on nitric oxide increased until 2016 before plateauing. The proportion of transport services able to provide high frequency oscillation and servo-controlled therapeutic hypothermia increased over the study period. High-flow nasal cannula oxygen use increased, becoming the most frequently used non-invasive respiratory support mode. For infants <27 weeks of gestational age, transfers for uplift of care in the first 3 days of life have fallen from 420 (2016) to 288 (2020/2021) and for lack of neonatal capacity from 24 (2016) to 2 (2020/2021). The rate of ventilated infants completing transfer with CO2 out of the benchmark range varied from 9% to 13% with marked variation between transport services' rates of hypocapnia (0-10%) and hypercapnia with acidosis (0-9%). The development of the UK-NTG dataset supports national tracking of activity and clinical trends allowing comparison of patient-focused benchmarks across teams.

Hidden functional complexity in the flora of an early land ecosystem.

The first land ecosystems were composed of organisms considered simple in nature, yet the morphological diversity of their flora was extraordinary. The biological significance of this diversity remains a mystery largely due to the absence of feasible study approaches. To study the functional biology of Early Devonian flora, we have reconstructed extinct plants from fossilised remains in silico. We explored the morphological diversity of sporangia in relation to their mechanical properties using finite element method. Our approach highlights the impact of sporangia morphology on spore dispersal and adaptation. We discovered previously unidentified innovations among early land plants, discussing how different species might have opted for different spore dispersal strategies. We present examples of convergent evolution for turgor pressure resistance, achieved by homogenisation of stress in spherical sporangia and by torquing force in Tortilicaulis-like specimens. In addition, we show a potential mechanism for stress-assisted sporangium rupture. Our study reveals the deceptive complexity of this seemingly simple group of organisms. We leveraged the quantitative nature of our approach and constructed a fitness landscape to understand the different ecological niches present in the Early Devonian Welsh Borderland flora. By connecting morphology to functional biology, these findings facilitate a deeper understanding of the diversity of early land plants and their place within their ecosystem.

The ontogeny of disparity in Cupressaceae seed cones.

Ontogenetic shape change has long been recognized to be important in generating patterns of morphological diversity and may be especially important in plant reproductive structures. We explore how seed cone disparity in Cupressaceae changes over ontogeny by comparing pollination-stage and mature cones. We sampled cones at pollen and seed release and measured cone scales using basic morphometric shape variables. We used multivariate statistical methods, particularly hypervolume overlap calculations, to measure morphospace occupation and disparity. Cone scales at both pollination and maturity exhibit substantial variability, although the disparity is greater at maturity. Mature cone scales are also more clustered in trait space, showing less overlap with other taxa than at pollination. These patterns reflect two growth strategies that generate closed cones over maturation, either through thin laminar scales or relatively thick, peltate scales, resulting in two distinct regions of morphospace occupation. Disparity patterns in Cupressaceae seed cones change over ontogeny, reflecting shifting functional demands that require specific patterns of cone scale growth. The evolution of Cupressaceae reproductive disparity therefore represents selection for trajectories of ontogenetic shape change, a phenomenon that should be widespread across seed plants.

Quantifying the complexity of plant reproductive structures reveals a history of morphological and functional integration.

Vascular plant reproductive structures have undoubtedly become more complex through time, evolving highly differentiated parts that interact in specialized ways. But quantifying these patterns at broad scales is challenging because lineages produce disparate reproductive structures that are often difficult to compare and homologize. We develop a novel approach for analysing interactions within reproductive structures using networks, treating component parts as nodes and a suite of physical and functional interactions among parts as edges. We apply this approach to the plant fossil record, showing that interactions have generally increased through time and that the concentration of these interactions has shifted towards differentiated surrounding organs, resulting in more compact, functionally integrated structures. These processes are widespread across plant lineages, but their extent and timing vary with reproductive biology; in particular, seed-producing structures show them more strongly than spore or pollen-producing structures. Our results demonstrate that major reproductive innovations like the origin of seeds and angiospermy were associated with increased integration through greater interactions among parts. But they also reveal that for certain groups, particularly Mesozoic gymnosperms, millions of years elapsed between the origin of reproductive innovations and increased interactions among parts within their reproductive structures.

A large-scale, targeted metabolomics method for the analysis and quantification of metabolites in human plasma via liquid chromatography-mass spectrometry.

Metabolomics is the study of small molecules, primarily metabolites, that are produced during metabolic processes. Analysis of the composition of an organism's metabolome can yield useful information about an individual's health status at any given time. In recent years, the development of large-scale, targeted metabolomic methods has allowed for the analysis of biological samples using analytical techniques such as LC-MS/MS. This paper presents a large-scale metabolomics method for analysis of biological samples, with a focus on quantification of metabolites found in blood plasma. The method comprises a 10-min chromatographic separation using HILIC and RP stationary phases combined with positive and negative electrospray ionization in order to maximize metabolome coverage. Complete analysis of a single sample can be achieved in as little as 40 min using the two columns and dual modes of ionization. With 540 metabolites and the inclusion of over 200 analytical standards, this method is comprehensive and quantitatively robust when compared to current targeted metabolomics methods. This study uses a large-scale evaluation of metabolite recovery from plasma that enables absolute quantification of metabolites by correcting for analyte loss throughout processes such as extraction, handling, or storage. In addition, the method was applied to plasma collected from adjuvant breast cancer patients to confirm the suitability of the method to clinical samples.

A targeted isotope dilution mass spectrometry assay for osteopontin quantification in plasma of metastatic breast cancer patients.

Osteopontin (OPN) is a secreted glycophosphoprotein that derives its name from its high abundance in bone and secretion by osteoblasts. It is also secreted by a number of immune cells and, therefore, is present in human plasma at nanogram per millilitre levels where it affects cell adhesion and motility. OPN is involved in several normal physiological processes; however, OPN dyregulation leads to overexpression by tumor cells leading to immune evasion and increased metastasis. Plasma OPN is primarily measured by enzyme-linked immunosorbent assay (ELISA). However, due to the complexity of the various OPN isoforms, conflicting results have been obtained on the use of OPN as a biomarker even in the same disease condition. These discrepant results may result from the difficulty in comparing ELISA results obtained with different antibodies that target unique OPN epitopes. Mass spectrometry can be used to quantify proteins in plasma and, by targeting OPN regions that do not bear post-translational modifications, may provide more consistent quantification. However, the low (ng/mL) levels in plasma present a significant analytical challenge. In order to develop a sensitive assay for plasma OPN, we explored a single-step precipitation method using a recently developed spin-tube format. Quantification was performed using isotope-dilution mass spectrometry. The concentration detection limit of this assay was 39 ± 15 ng/mL. The assay was applied to the analysis of plasma OPN in metastatic breast cancer patients, where levels from 17 to 53 ng/mL were detected. The sensitivity of the method is higher than previously published methods and sufficient for OPN detection in large, high grade tumors but still requires improvement in sensitivity to be widely applicable.

The CCP4 suite: integrative software for macromolecular crystallography.

The Collaborative Computational Project No. 4 (CCP4) is a UK-led international collective with a mission to develop, test, distribute and promote software for macromolecular crystallography. The CCP4 suite is a multiplatform collection of programs brought together by familiar execution routines, a set of common libraries and graphical interfaces. The CCP4 suite has experienced several considerable changes since its last reference article, involving new infrastructure, original programs and graphical interfaces. This article, which is intended as a general literature citation for the use of the CCP4 software suite in structure determination, will guide the reader through such transformations, offering a general overview of the new features and outlining future developments. As such, it aims to highlight the individual programs that comprise the suite and to provide the latest references to them for perusal by crystallographers around the world.

Critical success factors for school-based integrated health care models: Learnings from an Australian example.

ISSUES ADDRESSED: Integrated school-based health services have the potential to address the unmet health needs of children experiencing disadvantage, yet these models remain poorly evaluated. The current article examines an integrated social and health care hub located on the grounds of a regional Australian public primary school, the Our Mia Mia Wellbeing Hub, to identify critical success factors for this service and others like it. METHODS: Semi-structured qualitative interviews were conducted with N = 55 multi-sector stakeholders comprising parents, students, school staff, social and health care providers, and local Aboriginal community members. Interview transcripts were analysed according to a grounded theory approach. RESULTS: Six themes emerged from the analysis, reflecting important success factors for the model: service accessibility; service coordination; integration of education and health systems; trust; community partnerships; and perceptions of health. CONCLUSIONS: Findings highlighted Our Mia Mia as a promising model of care, yet also revealed important challenges for the service as it responds to the varied priorities of the stakeholders it serves. SO WHAT?: Through capturing the perspectives of a large number of stakeholders, the current study provides valuable insight into key challenges and success factors for Our Mia Mia; these learnings can guide the development of other emerging school-based health services and integrated care hubs.

CCP4 Cloud for structure determination and project management in macromolecular crystallography.

Nowadays, progress in the determination of three-dimensional macromolecular structures from diffraction images is achieved partly at the cost of increasing data volumes. This is due to the deployment of modern high-speed, high-resolution detectors, the increased complexity and variety of crystallographic software, the use of extensive databases and high-performance computing. This limits what can be accomplished with personal, offline, computing equipment in terms of both productivity and maintainability. There is also an issue of long-term data maintenance and availability of structure-solution projects as the links between experimental observations and the final results deposited in the PDB. In this article, CCP4 Cloud, a new front-end of the CCP4 software suite, is presented which mitigates these effects by providing an online, cloud-based environment for crystallographic computation. CCP4 Cloud was developed for the efficient delivery of computing power, database services and seamless integration with web resources. It provides a rich graphical user interface that allows project sharing and long-term storage for structure-solution projects, and can be linked to data-producing facilities. The system is distributed with the CCP4 software suite version 7.1 and higher, and an online publicly available instance of CCP4 Cloud is provided by CCP4.

Dissemination and Implementation of a Google Apple Exposure Notification System for COVID-19 Risk Mitigation at a National Public University: Protocol for a Pilot Evaluation Study in a Real-World Setting.

BACKGROUND: As SARS-CoV-2, the virus that causes COVID-19, spread rapidly across the United States in the spring of 2020, institutions of higher education faced numerous challenges associated with minimizing risk of exposure to COVID-19 among their students, faculty, staff, and surrounding communities. This paper describes the protocol, South Carolina (SC) Safer Together, developed by Clemson University (Clemson) to design, deploy, and evaluate multi-level communication and dissemination and implementation (D&I) strategies in line with recommendations from governmental and educational agencies to mitigate the risk of exposure to COVID-19. Safer Together was enhanced by the addition of the Google/Apple Exposure Notification app, an alternative strategy to support a recommendation of COVID-19 testing outcomes: contact tracing, isolation, and quarantine. OBJECTIVE: This study aimed to (1) describe the content and intended audiences of D&I strategies used to deploy recommended COVID-19 mitigation strategies on a major college campus; (2) determine the reach, acceptability, adoption, and use of D&I strategies among target audiences among university students, faculty, and staff; and (3) characterize barriers and facilitators to the implementation and use of recommended mitigation strategies. METHODS: The study team incorporated elements of the Health Belief Model, the Technology Acceptance Model, communication and social marketing models, and the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework to identify and develop appropriate constructs and specific outcomes for inclusion in our approach to evaluate the communication, dissemination and implementation processes related to deployment of Safer Together at Clemson. A parallel convergent mixed methods design was used to (1) inform implementation strategies used to launch the program and (2) evaluate program reach, acceptability, adoption, and use guided by the RE-AIM framework. Data collection tools include surveys, data analytics-tracking, and focus groups or interviews with key stakeholders (students, employees, and university leadership). RESULTS: Rigorously studying both the dissemination and implementation of Safer Together in a national public university setting is expected to yield lessons that will be valuable at many organizational and governmental settings. On a local level, broad adoption and use of the Safer Together may help reduce COVID-19 transmission and keep the university "open." On a larger scale, lessons learned on how to influence student and employee behavior with respect to the use of a public health outbreak prevention tool including Safer Together may be applicable in future pandemic and outbreak situations. CONCLUSIONS: This study proposes a structured, theory-driven approach to evaluate dissemination and implementation strategies associated with the deployment of Safer Together in a university setting from the viewpoint of students, employees, and university leadership. Our results will inform future implementation of apps such as Safer Together at major state universities in SC. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/32567.

U.S. vehicle occupancy trends relevant to future automated vehicles and mobility services.

OBJECTIVE: Identifying current occupant travel patterns can inform decision making regarding the design, regulation, and occupant protection systems helpful for automated vehicle systems and mobility services. METHODS: Two travel data sets were analyzed to quantify travel patterns: the 2017 National Household Travel Survey (NHTS), which provides data on household trips logged for a 24-h period, and the 2011-2015 National Automotive Sampling System-General Estimates System (NASS-GES), which contains data sampled from police-reported crashes. Analysis identified trends with driver age and gender, occupant age and gender, time of day, day of week, trip purpose, trip duration, vehicle type, as well as occupant role as solo driver, driver of others, single passenger, or multiple passengers. RESULTS: In NHTS, the median trip duration is 15 min; only 10% of trips last longer than 40 min. Trip duration does not vary with occupant role or vehicle type. Variations with trip time of day and day of week show a unimodal pattern for weekends, as well as weekday trips for those aged 55 years and older and non-solo occupants aged 18 to 29 years. Other occupant groups have a bimodal weekday travel pattern with peak trips corresponding to morning and evening rush hours.In GES, approximately half of occupants are solo drivers. Female drivers aged 55 and older travel alone 60% of the time, and drivers under age 18 and female drivers aged 30 to 54 drive alone on less than 45% of trips. Approximately 13% of occupants are single passengers, and 16% travel with a driver and at least 1 other passenger. About 16% of occupants are front seat passengers. CONCLUSIONS: This analysis of vehicle occupancy provides insights on what ridership of future automated vehicles and expanded ride-hailing services may look like. Because half of occupants are solo drivers, only 16% are multiple passengers, and median trip length is just 15 min, proposed alternative seating arrangements intended to promote comfort and passenger interaction may not represent the typical future vehicle use case in the United States. Knowledge of current occupancy patterns can help automated vehicle designers and regulators develop safe seating scenarios that meet customer needs.

New fossil discoveries illustrate the diversity of past terrestrial ecosystems in New Caledonia.

New Caledonia was, until recently, considered an old continental island harbouring a rich biota with outstanding Gondwanan relicts. However, deep marine sedimentation and tectonic evidence suggest complete submergence of the island during the latest Cretaceous to the Paleocene. Molecular phylogenies provide evidence for some deeply-diverging clades that may predate the Eocene and abundant post-Oligocene colonisation events. Extinction and colonization biases, as well as survival of some groups in refuges on neighbouring paleo-islands, may have obscured biogeographic trends over long time scales. Fossil data are therefore crucial for understanding the history of the New Caledonian biota, but occurrences are sparse and have received only limited attention. Here we describe five exceptional fossil assemblages that provide important new insights into New Caledonia's terrestrial paleobiota from three key time intervals: prior to the submersion of the island, following re-emergence, and prior to Pleistocene climatic shifts. These will be of major importance for elucidating changes in New Caledonia's floristic composition over time.

Reproductive innovations and pulsed rise in plant complexity.

Morphological complexity is a notable feature of multicellular life, although whether it evolves gradually or in early bursts is unclear. Vascular plant reproductive structures, such as flowers, are familiar examples of complex morphology. In this study, we use a simple approach based on the number of part types to analyze changes in complexity over time. We find that reproductive complexity increased in two pulses separated by ~250 million years of stasis, including an initial rise in the Devonian with the radiation of vascular plants and a pronounced increase in the Late Cretaceous that reflects flowering plant diversification. These pulses are associated with innovations that increased functional diversity, suggesting that shifts in complexity are linked to changes in function regardless of whether they occur early or late in the history of vascular plants.

Early Cretaceous abietoid Pinaceae from Mongolia and the history of seed scale shedding.

PREMISE: Seed cones of extant Pinaceae exhibit two mechanisms of seed release. In "flexers" the cone scales remain attached to the central axis, while flexing and separating from each other to release the seeds. In "shedders" scales are shed from the axis, with the seeds either remaining attached to the scale or becoming detached. The early fossil history of Pinaceae from the Jurassic to Early Cretaceous is dominated by flexing seed cones, while the systematic information provided by shedding fossil cones has been overlooked and rarely integrated with data based on compression and permineralized specimens. We describe the earliest and best-documented evidence of a "shedder" seed cone from the Aptian-Albian of Mongolia. METHODS: Lignite samples from Tevshiin Govi locality were disaggregated in water, washed, and dried in air. Fossils were compared to material of extant Pinaceae using LM and CT scans. RESULTS: Lepidocasus mellonae gen. et sp. nov. is characterized by a seed cone that disarticulated at maturity and shed obovate bract-scale complexes that have a distinctive ribbed surface and an abaxial surface covered with abundant trichomes. The ovuliferous scale has ca. 30-40 resin canals, but only scarce xylem near the attachment to the cone axis. Resin vesicles are present in the seed integument. Phylogenetic analysis places Lepidocasus as sister to extant Cedrus within the abietoid grade. CONCLUSIONS: The exquisite preservation of the trichomes in L. mellonae raises questions about their potential ecological function in the cones of fossil and living Pinaceae. Lepidocasus mellonae also shows that a shedding dispersal syndrome, a feature that has often been overlooked, evolved early in the history of Pinaceae during the Early Cretaceous.

Field effectiveness of general motors advanced driver assistance and headlighting systems.

This study examined the field effectiveness of General Motors advanced driver assistance and headlighting systems. A total of 8,311,707 Model Year 2013-2019 vehicles were matched to police-reported crashes from 12 states. The quasi-induced exposure method was used to compare system-relevant and system-irrelevant (control) crash counts for equipped and unequipped vehicles. Logistic regression was used to adjust for ten covariates. Results indicated fusion/radar Automatic Emergency Braking, camera Automatic Emergency Braking, and Forward Collision Alert systems reduced rear-end striking crashes by 45%, 38%, and 20%, respectively. When restricting data to crashes in which someone in the General Motors striking vehicle was injured, these reductions were elevated to 59%, 54%, and 31%, respectively, providing evidence of additional crash mitigation benefits. Similarly, the Lane Keep Assist with Lane Departure Warning and Lane Departure Warning (alone) systems provided 12% and 10% reductions in lane departure crashes, respectively, with corresponding benefits in the injury analysis increasing to 19% and 18%, respectively. The Lane Change Alert with Side Blind Zone Alert system reduced lane change crashes by 16%. Reverse Automatic Braking, Rear Cross Traffic Alert, Rear Park Assist, and Rear Vision Camera (where each of these systems generally included all of the preceding systems) produced, respectively, an 82%, 55%, 36%, and 24% reduction in backing crashes. For Front Pedestrian Braking, a non-significant 14% reduction was observed for the limited set of available pedestrian crash cases. Intellibeam (auto high beam headlighting), High-Intensity Discharge headlights, and the combination of these two systems provided 26%, 11%, and 32% reductions (relative to halogen headlights) in a combined set of (unlighted) nighttime animal, pedestrian, and bicyclist crashes, respectively. These results provide widespread evidence of the substantial crash avoidance and injury reduction opportunities afforded by the production systems evaluated, as well as identify untapped system opportunities for moving toward a zero crashes vision.

School-based integrated healthcare model: how Our Mia Mia is improving health and education outcomes for children and young people.

Integrating healthcare into education settings represents a promising model to address complex health problems in disadvantaged communities through improving access to health and social services. One such example of an effective school-based health hub is the Our Mia Mia (OMM) Wellbeing Hub, located in a primary school in Nowra and servicing a community experiencing significant socioeconomic disadvantage. The efficacy of OMM rests on its success in facilitating access to services by removing the barriers of cost and transport and establishing connection to community. The OMM fosters collaborations between health professionals and educators to coordinate holistic treatment and implement appropriate student supports in a timely manner. The support of key individuals and groups, in addition to the flexibility of the model, has allowed the hub to pivot and adapt to meet the changing needs of its community, particularly as challenges pertaining to bureaucracy, financial sustainability and community mistrust have presented themselves. Future directions for the OMM hub, and the possibility of adapting and translating school-based healthcare delivery models in other disadvantaged communities, is discussed.