We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
OBJECTIVES/GOALS: To introduce the new Team Science Community Toolkit, co-created by community and academic partners, and showcase its potential to empower Community Organizations (COs) in achieving equity in community-engaged research (CER). METHODS/STUDY POPULATION: In response to the challenges faced by COs in CER collaborations, qualitative interviews were conducted with CO staff from historically marginalized communities. These interviews informed the development of the Team Science Community Toolkit, a collaborative effort involving a Community Advisory Board (CAB) and Team Science experts from Northwestern University. The toolkit, designed using a community-based participatory research approach, incorporates the Science of Team Science and User-Centered Design principles. Integrated into the NIH-sponsored COALESCE website, it includes templates, checklists, and interactive tools, along with a real-world simulation, to support COs in all stages of the research process. RESULTS/ANTICIPATED RESULTS: Focus groups and usability testing involving external community experts validated the toolkit’s content and usability. Participants expressed enthusiasm and a sense of empowerment, indicating that the toolkit allows them to actively shape research processes and infuse their specific voices and needs into their partnerships. The toolkit is designed to support breaking down barriers like jargon and cultural adaptability to improve accessibility and open conversation. The impact of this Team Science focused toolkit is under evaluation. This presentation will showcase the toolkit, detail its collaborative development, and explore potential applications, ultimately offering a path to more equitable and valuable community-based research. DISCUSSION/SIGNIFICANCE: By providing COs with the resources and knowledge to participate as equal partners in research collaborations, it enhances self-advocacy, transparency, and equity. The toolkit has the potential to utilize Team Science to foster productive communication in community-academic research partnerships.
Infants and children born with CHD are at significant risk for neurodevelopmental delays and abnormalities. Individualised developmental care is widely recognised as best practice to support early neurodevelopment for medically fragile infants born premature or requiring surgical intervention after birth. However, wide variability in clinical practice is consistently demonstrated in units caring for infants with CHD. The Cardiac Newborn Neuroprotective Network, a Special Interest Group of the Cardiac Neurodevelopmental Outcome Collaborative, formed a working group of experts to create an evidence-based developmental care pathway to guide clinical practice in hospital settings caring for infants with CHD. The clinical pathway, “Developmental Care Pathway for Hospitalized Infants with Congenital Heart Disease,” includes recommendations for standardised developmental assessment, parent mental health screening, and the implementation of a daily developmental care bundle, which incorporates individualised assessments and interventions tailored to meet the needs of this unique infant population and their families. Hospitals caring for infants with CHD are encouraged to adopt this developmental care pathway and track metrics and outcomes using a quality improvement framework.
In November 1995, the Laboratory of Archaeology at the University of Georgia submitted inventories and summaries of Indigenous ancestors and funerary objects in its holdings to comply with the passage of the Native American Graves Protection and Repatriation Act (NAGPRA). However, after this submission, the Laboratory attempts at consultation with federally recognized descendant Tribal communities who have cultural ties in the state of Georgia were not successful, and NAGPRA-related activities essentially stalled at the Laboratory. Beginning in 2019, the Laboratory's staff recognized a lack of formal NAGPRA policies or standards, which led to a complete reevaluation of the Laboratory's approach to NAGPRA. In essence, it was the Laboratory's renewed engagement with NAGPRA and descendan tribal communities that became the catalyst for change in the Laboratory's philosophy as a curation repository. This shift in thinking set the Laboratory on a path toward building a descendant community–informed institutional integrity (DCIII) level of engagement with consultation and collaborative efforts in all aspects of collections management and archaeological research. In this article, we outline steps that the Laboratory has taken toward implementing meaningful policies and practices created with descendant Tribal communities that both fulfill and extend bounds of NAGPRA compliance.
Data from neurocognitive assessments may not be accurate in the context of factors impacting validity, such as disengagement, unmotivated responding, or intentional underperformance. Performance validity tests (PVTs) were developed to address these phenomena and assess underperformance on neurocognitive tests. However, PVTs can be burdensome, rely on cutoff scores that reduce information, do not examine potential variations in task engagement across a battery, and are typically not well-suited to acquisition of large cognitive datasets. Here we describe the development of novel performance validity measures that could address some of these limitations by leveraging psychometric concepts using data embedded within the Penn Computerized Neurocognitive Battery (PennCNB).
Methods:
We first developed these validity measures using simulations of invalid response patterns with parameters drawn from real data. Next, we examined their application in two large, independent samples: 1) children and adolescents from the Philadelphia Neurodevelopmental Cohort (n = 9498); and 2) adult servicemembers from the Marine Resiliency Study-II (n = 1444).
Results:
Our performance validity metrics detected patterns of invalid responding in simulated data, even at subtle levels. Furthermore, a combination of these metrics significantly predicted previously established validity rules for these tests in both developmental and adult datasets. Moreover, most clinical diagnostic groups did not show reduced validity estimates.
Conclusions:
These results provide proof-of-concept evidence for multivariate, data-driven performance validity metrics. These metrics offer a novel method for determining the performance validity for individual neurocognitive tests that is scalable, applicable across different tests, less burdensome, and dimensional. However, more research is needed into their application.
Two mean-field models for polyelectrolytes in simultaneous electric field and pressure-driven flow field were developed and compared. The models predict migration perpendicular to the anti-parallel or parallel fields, where the migration is caused by electrohydrodynamic interactions calculated using either a short- or long-range approximation. Inputs for the mean-field models were determined from Brownian dynamics simulations in a simple shear flow. Both models qualitatively reproduce experimental observations of DNA focusing as reported in previous publications. Specifically, it is observed that combination of the shear and electric fields leads to polyelectrolyte motion in the direction transverse to the flow and electric field direction, which in turn leads to concentration of the polyelectrolyte in the centre of a microfluidic channel. Furthermore, both models predict that there is an optimal strength of electric field that leads to the narrowest distribution profile of the polyelectrolyte in the centre of the channel. The analysis suggests that this is due to dispersion induced by the electrohydrodynamic interactions. However, quantitative disagreement between the model predictions and the experimental data indicates that further progress in the model development is needed.
The separation dynamics of a sphere released from the surface of a ramp into a hypersonic flow is investigated, focusing on the influence of the ramp boundary layer on the sphere behaviour. First, numerical simulations are conducted of a sphere interacting with an isolated high-speed boundary layer to determine the influence on the sphere force coefficients as the sphere diameter and wall-normal location are varied. It is found that the lift coefficient is strongly affected by the near-wall interactions, becoming increasingly negative as the ratio of the sphere radius to boundary-layer thickness, $r/\delta$, is decreased. These results are combined with force coefficients derived from simulations of the sphere interacting with the ramp-generated oblique shock to enable numerical predictions of the sphere trajectories for a $10^{\circ }$ ramp at Mach 6 (using a similar decoupled approach to Part 1 of this work). It is found that the three trajectory types of the inviscid situation – shock surfing, ejection followed by re-entrainment within the shock layer and direct entrainment – also characterize the sphere behaviour here. Their relative prevalence, however, is influenced by the sphere size: for smaller values of $r/\delta$, direct entrainment dominates because of the wall suction, while shock surfing and then ejection/re-entrainment become increasingly likely at larger values of $r/\delta$. Increasing the ramp angle and/or the free-stream Mach number reduces the relative influence of the boundary-layer interactions. Finally, experiments are conducted using free-flying spheres released from a ramp surface in a hypersonic shock tunnel, confirming the major trends predicted numerically.
The Kilmaluag Formation on the Isle of Skye, Scotland, provides one of the richest Mesozoic vertebrate fossil assemblages in the UK, and is among the richest globally for Middle Jurassic tetrapods. Since its discovery in 1971, this assemblage has predominantly yielded small-bodied tetrapods, including salamanders, choristoderes, lepidosaurs, turtles, crocodylomorphs, pterosaurs, dinosaurs, non-mammalian cynodonts and mammals, alongside abundant fish and invertebrates. It is protected as a Site of Special Scientific Interest and by Nature Conservancy Order. Unlike contemporaneous localities from England, this assemblage yields associated partial skeletons, providing unprecedented new data. We present a comprehensive updated overview of the Kilmaluag Formation, including its geology and the fossil collections made to date, with evidence of several species occurrences presented here for the first time. We place the vertebrate faunal assemblage in an international context through comparisons with relevant contemporaneous localities from the UK, Europe, Africa, Asia and the US. This wealth of material reveals the Kilmaluag Formation as a vertebrate fossil assemblage of global significance, both in terms of understanding Middle Jurassic faunal composition and the completeness of specimens, with implications for the early evolutionary histories of mammals, squamates and amphibians.
Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.
Methods:
The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.
Results:
The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.
Conclusion:
Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.
Acute respiratory tract infections (ARIs) are commonly diagnosed and major drivers of antibiotic prescribing. Clinician-focused interventions can reduce unnecessary antibiotic prescribing for ARIs. We elicited clinician feedback to design sustainable interventions to improve ARI management by understanding the mental framework of clinicians surrounding antibiotic prescribing within Veterans’ Health Administration clinics.
Methods:
We conducted one-on-one interviews with clinicians (n = 20) from clinics targeted for intervention at 5 facilities. The theory of planned behavior guided interview questions. Interviews were audio recorded and transcribed for qualitative analysis. An iterative coding approach identified 6 themes.
Results:
Emergent themes: (1) barriers to appropriate prescribing are multifactorial and include challenges of behavior change; (2) antibiotic prescribing decisions are perceived as autonomous yet, diagnostic uncertainty and perceptions of patient demand can make prescribing decisions difficult; (3) clinicians perceive variation in peer prescribing practices and influences; (4) clinician-focused interventions are valuable if delivered with sensitivity; (5) communication strategies for educating patients are preferred to a shared decisions process; and (6) team standardization of practice and communication are key to facilitate appropriate prescribing. Clinicians perceived audit-and-feedback with peer comparison, academic detailing, and enhanced patient communication strategies as viable approaches to improving appropriate prescribing.
Conclusion:
Implementation strategies that enable clinicians to overcome diagnostic uncertainty, perceived patient demand, and improve patient education are desired. Implementation strategies were welcomed, and some were more readily accepted (eg, audit feedback) than others (eg, shared decision making). Implementation strategies should address clinicians’ perceptions of antibiotic prescribing practices and should enhance their patient communication skills.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
The DESGW program is a collaboration between members of the Dark Energy Survey, the wider astronomical community, and the LIGO-Virgo Collaboration to search for optical counterparts of gravitational wave events, such as those expected from binary neutron star mergers or neutron star-black hole mergers. While binary black hole (BBH) events are not expected to produce an electromagnetic (EM) signature, emission is certainly not impossible. The DESGW program has performed follow-up observations of four BBH events detected by LIGO in order to search for any possible EM counterpart. Failure to find such counterparts is still relevant in that it produces limits on optical emission from such events. This is a review of follow-up results from O1 BBH events and a discussion of the status of ongoing uniform re-analysis of all BBH events that DESGW has followed up to date.
Pesticide drift studies were conducted in which two formulations were sprayed simultaneously to eliminate meteorological differences. One formulation was traced with Brilliant Sulfo Flavine (BSF) dye and the other with Rhodamine B (RhB) dye. Combined drift from both formulations was caught downwind on Mylar sheets. A filter fluorometer was used to analyze the deposits. By proper selection of a light source, primary filters, and secondary filters, the BSF was excluded while the RhB was analyzed, and vice versa. Concentrations below 1.0 μg/L were accurately measured.
Since the mid-19th century, western Oregon's Willamette Valley has been a source of remains from a wide variety of extinct megafauna. Few of these have been previously described or dated, but new chronologic and isotopic analyses in conjunction with updated evaluations of stratigraphic context provide substantial new information on the species present, timing of losses, and paleoenvironmental conditions. Using subfossil material from the northern valley, we use AMS radiocarbon dating, stable isotope (δ13C and δ15N) analyses, and taxonomic dietary specialization and habitat preferences to reconstruct environments and to develop a local chronology of events that we then compare with continental and regional archaeological and paleoenvironmental data. Analysis of twelve bone specimens demonstrates the presence of bison, mammoth, horse, sloth, and mastodon from ~ 15,000–13,000 cal yr BP. The latest ages coincide with changing regional climate corresponding to the onset of the Younger Dryas. It is suggested that cooling conditions led to increased forest cover, and along with river aggradation, reduced the area of preferred habitat for the larger bodied herbivores, which contributed to the demise of local megafauna. Archaeological evidence for megafauna–human interactions in the Pacific Northwest is scarce, limiting our ability to address the human role in causing extinction.
A plausible mechanism underlying flavonoid-associated cognitive effects is increased cerebral blood flow (CBF). However, behavioural and CBF effects following flavanone-rich juice consumption have not been explored. The aim of this study was to investigate whether consumption of flavanone-rich juice is associated with acute cognitive benefits and increased regional CBF in healthy, young adults. An acute, single-blind, randomised, cross-over design was applied with two 500-ml drink conditions – high-flavanone (HF; 70·5 mg) drink and an energy-, and vitamin C- matched, zero-flavanone control. A total of twenty-four healthy young adults aged 18–30 years underwent cognitive testing at baseline and 2-h after drink consumption. A further sixteen, healthy, young adults were recruited for functional MRI assessment, whereby CBF was measured with arterial spin labelling during conscious resting state at baseline as well as 2 and 5 h after drink consumption. The HF drink was associated with significantly increased regional perfusion in the inferior and middle right frontal gyrus at 2 h relative to baseline and the control drink. In addition, the HF drink was associated with significantly improved performance on the Digit Symbol Substitution Test at 2 h relative to baseline and the control drink, but no effects were observed on any other behavioural cognitive tests. These results demonstrate that consumption of flavanone-rich citrus juice in quantities commonly consumed can acutely enhance blood flow to the brain in healthy, young adults. However, further studies are required to establish a direct causal link between increased CBF and enhanced behavioural outcomes following citrus juice ingestion.
Various medications and devices are available for facilitation of emergent endotracheal intubations (EETIs). The objective of this study was to survey which medications and devices are being utilized for intubation by Canadian physicians.
Methods
A clinical scenario-based survey was developed to determine which medications physicians would administer to facilitate EETI, their first choice of intubation device, and backup strategy should their first choice fail. The survey was distributed to Canadian emergency medicine (EM) and intensive care unit (ICU) physicians using web-based and postal methods. Physicians were asked questions based on three scenarios (trauma; pneumonia; heart failure) and responded using a 5-point scale ranging from “always” to “never” to capture usual practice.
Results
The survey response rate was 50.2% (882/1,758). Most physicians indicated a Macintosh blade with direct laryngoscopy would “always/often” be their first choice of intubation device in the three scenarios (mean 85% [79%-89%]) followed by video laryngoscopy (mean 37% [30%-49%]). The most common backup device chosen was an extraglottic device (mean 59% [56%-60%]). The medications most physicians would “always/often” administer were fentanyl (mean 45% [42%-51%]) and etomidate (mean 38% [25%-50%]). EM physicians were more likely than ICU physicians to paralyze patients for EETI (adjusted odds ratio 3.40; 95% CI 2.90-4.00).
Conclusions
Most EM and ICU physicians utilize direct laryngoscopy with a Macintosh blade as a primary device for EETI and an extraglottic device as a backup strategy. This survey highlights variation in Canadian practice patterns for some aspects of intubation in critically ill patients.
Physical health and, in particular, frailty may be associated with psychological factors among older adults. We aimed to investigate the relationships between aspects of psychological distress and progression of frailty over time among older adults.
Methods
We used a longitudinal observational study design with 624 participants aged over 60 years (mean age=72.75, s.d.=7.21, 68% female) completing a baseline comprehensive biopsychosocial geriatric assessment, and 447 returning for a follow-up assessment 2 years later. Aspects of psychological distress, physical health, and frailty were analysed for the purposes of this study. We employed a series of logistic regression analyses to determine psychological predictors of changing states of aspects of frailty over time.
Results
With individual components of frailty, neuroticism and age predicted negative transitions of exhaustion and grip strength, respectively, whereas age alone was a predictor of transitions in overall frailty scores based on four components.
Conclusion
We conclude that neuroticism and age may impact upon physical frailty and its progression over time in an ageing population. These findings may reflect the tendency for those with high levels of neuroticism to endorse negative symptoms, or alternatively, neuroticism may result in exhaustion via worry in an older population. Further research is required to further elucidate this relationship.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
Schizophrenia is characterized by profound and disabling deficits in the ability to recognize emotion in facial expression and tone of voice. Although these deficits are well documented in established schizophrenia using recently validated tasks, their predictive utility in at-risk populations has not been formally evaluated.
Method.
The Penn Emotion Recognition and Discrimination tasks, and recently developed measures of auditory emotion recognition, were administered to 49 clinical high-risk subjects prospectively followed for 2 years for schizophrenia outcome, and 31 healthy controls, and a developmental cohort of 43 individuals aged 7–26 years. Deficit in emotion recognition in at-risk subjects was compared with deficit in established schizophrenia, and with normal neurocognitive growth curves from childhood to early adulthood.
Results.
Deficits in emotion recognition significantly distinguished at-risk patients who transitioned to schizophrenia. By contrast, more general neurocognitive measures, such as attention vigilance or processing speed, were non-predictive. The best classification model for schizophrenia onset included both face emotion processing and negative symptoms, with accuracy of 96%, and area under the receiver-operating characteristic curve of 0.99. In a parallel developmental study, emotion recognition abilities were found to reach maturity prior to traditional age of risk for schizophrenia, suggesting they may serve as objective markers of early developmental insult.
Conclusions.
Profound deficits in emotion recognition exist in at-risk patients prior to schizophrenia onset. They may serve as an index of early developmental insult, and represent an effective target for early identification and remediation. Future studies investigating emotion recognition deficits at both mechanistic and predictive levels are strongly encouraged.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.