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Medical and surgical advancements have enabled a 95% survival rate for children with CHD. However, these survivors are disproportionately affected by neurodevelopmental disabilities. In particular, they have behavioural problems in toddlerhood. Because there is a known relationship between behavioural problems and early language delay, we hypothesise that children with critical CHD have early detectable language deficits. To test our hypothesis, we performed a retrospective study on a cohort of children with critical CHD to visualise their early language developmental trajectories.
Methods:
We identified a cohort of 27 children with two diagnoses: single ventricle physiology (19) and transposition of the great arteries (8). As part of their routine clinical care, all of these children had serial developmental evaluations with the language subsection of the Capute Scales. We visualised their developmental language trajectories as a function of chronologic age, and we used a univariate linear regression model to calculate diagnosis-specific expected developmental age equivalents.
Results:
In each group, language development is age-appropriate in infancy. Deviation from age-appropriate development is apparent by 18 months. This results in borderline-mild language delay by 30 months.
Discussion:
Using the Capute Scales, our team quantified early language development in infants and toddlers with critical CHD. Our identification of deceleration in skill acquisition reinforces the call for ongoing neurodevelopmental surveillance in these children. Understanding early language development will help clinicians provide informed anticipatory guidance to families of children with critical CHD.
Social Media Synopsis:
Children with single ventricle physiology and transposition of the great arteries have measurable early language delays.
To evaluate the motor proficiency, identify risk factors for abnormal motor scores, and examine the relationship between motor proficiency and health-related quality of life in school-aged patients with CHD.
Study design:
Patients ≥ 4 years old referred to the cardiac neurodevelopmental program between June 2017 and April 2020 were included. Motor skills were evaluated by therapist-administered Bruininks-Oseretsky Test of Motor Proficiency Second-Edition Short Form and parent-reported Adaptive Behavior Assessment System and Patient-Reported Outcomes Measurement Inventory System Physical Functioning questionnaires. Neuropsychological status and health-related quality of life were assessed using a battery of validated questionnaires. Demographic, clinical, and educational variables were collected from electronic medical records. General linear modelling was used for multivariable analysis.
Results:
The median motor proficiency score was the 10th percentile, and the cohort (n = 272; mean age: 9.1 years) scored well below normative values on all administered neuropsychological questionnaires. In the final multivariable model, worse motor proficiency score was associated with family income, presence of a genetic syndrome, developmental delay recognised in infancy, abnormal neuroimaging, history of heart transplant, and executive dysfunction, and presence of an individualised education plan (p < 0.03 for all predictors). Worse motor proficiency correlated with reduced health-related quality of life. Parent-reported adaptive behaviour (p < 0.001) and physical functioning (p < 0.001) had a strong association with motor proficiency scores.
Conclusion:
This study highlights the need for continued motor screening for school-aged patients with CHD. Clinical factors, neuropsychological screening results, and health-related quality of life were associated with worse motor proficiency.
Cancer health research relies on large-scale cohorts to derive generalizable results for different populations. While traditional epidemiological cohorts often use costly random sampling or self-motivated, preselected groups, a shift toward health system-based cohorts has emerged. However, such cohorts depend on participants remaining within a single system. Recent consumer engagement models using smartphone-based communication, driving projects, and social media have begun to upend these paradigms.
Methods:
We initiated the Healthy Oregon Project (HOP) to support basic and clinical cancer research. HOP study employs a novel, cost-effective remote recruitment approach to effectively establish a large-scale cohort for population-based studies. The recruitment leverages the unique email account, the HOP website, and social media platforms to direct smartphone users to the study app, which facilitates saliva sample collection and survey administration. Monthly newsletters further facilitate engagement and outreach to broader communities.
Results:
By the end of 2022, the HOP has enrolled approximately 35,000 participants aged 18–100 years (median = 44.2 years), comprising more than 1% of the Oregon adult population. Among those who have app access, ∼87% provided consent to genetic screening. The HOP monthly email newsletters have an average open rate of 38%. Efforts continue to be made to improve survey response rates.
Conclusion:
This study underscores the efficacy of remote recruitment approaches in establishing large-scale cohorts for population-based cancer studies. The implementation of the study facilitates the collection of extensive survey and biological data into a repository that can be broadly shared and supports collaborative clinical and translational research.
Non-clinical aspects of life, such as social, environmental, behavioral, psychological, and economic factors, what we call the sociome, play significant roles in shaping patient health and health outcomes. This paper introduces the Sociome Data Commons (SDC), a new research platform that enables large-scale data analysis for investigating such factors.
Methods:
This platform focuses on “hyper-local” data, i.e., at the neighborhood or point level, a geospatial scale of data not adequately considered in existing tools and projects. We enumerate key insights gained regarding data quality standards, data governance, and organizational structure for long-term project sustainability. A pilot use case investigating sociome factors associated with asthma exacerbations in children residing on the South Side of Chicago used machine learning and six SDC datasets.
Results:
The pilot use case reveals one dominant spatial cluster for asthma exacerbations and important roles of housing conditions and cost, proximity to Superfund pollution sites, urban flooding, violent crime, lack of insurance, and a poverty index.
Conclusion:
The SDC has been purposefully designed to support and encourage extension of the platform into new data sets as well as the continued development, refinement, and adoption of standards for dataset quality, dataset inclusion, metadata annotation, and data access/governance. The asthma pilot has served as the first driver use case and demonstrates promise for future investigation into the sociome and clinical outcomes. Additional projects will be selected, in part for their ability to exercise and grow the capacity of the SDC to meet its ambitious goals.
Paleoproterozoic massive Cu-Zn±Pb±Au±Ag sulphide deposits metamorphosed to the middle-upper amphibolite facies in central-south Colorado formed in a volcanic arc setting on the edge of the Yavapai crustal province. Previously published U-Pb ages on spatially related granitoids range from ∼1.9 to ∼1.1 Ga, while Pb isotope studies on galena from massive sulphides suggest mineralization formed at around 1.8–1.7 Ga. Some deposits in the Dawson-Green Mountain trend (DGMT) and the Gunnison belt are composed of Cu-Zn-Au-(Pb-Ag) mineralization that were overprinted by later Au-(Ag-Cu-Bi-Se-Te) mineralization. Sulphide mineralization is spatially related to amphibolite and bimodal, mafic-felsic volcanic rocks (gabbro, amphibolite, rhyolite and dacite) and granitoids, but it occurs mostly in biotite-garnet-quartz±sillimanite±cordierite schists and gneisses, spatially related to nodular sillimanite rocks, and in some locations, exhalative rocks (iron formations, gahnite-rich rocks and quartz-garnetite). The major metallic minerals of the massive sulphides include chalcopyrite, sphalerite, pyrite, pyrrhotite, and magnetite, with minor galena and gahnite. Altered rocks intimately associated with mineralization primarily consist of various amphiboles (gedrite, tremolite and hornblende), gahnite, biotite, garnet, cordierite, carbonate and rare högbomite. The Zn/Cd ratios of sphalerite (44 to 307) in deposits in the DGMT fall within the range of global volcanogenic massive sulphide (VMS) deposits but overlap with sphalerite from sedimentary exhalative (Sedex) deposits. Sulphur isotope values of sulphides (δ34S = −3.3 to +6.5) suggest sulphur was largely derived from magmatic sources, and that variations in isotopic values resulting from thermochemical sulphate reduction are due to small differences in physicochemical conditions. The preferred genetic model is for the deposits to be bimodal-mafic (Gunnison) to mafic-siliciclastic VMS deposits (Cotopaxi, Cinderella-Bon Ton, DGMT).
OBJECTIVES/GOALS: By establishing a youth-centric web-app as a central hub of information and inspiration in an attempt to engage a young demographic, this project aims to increase community awareness and reduce misconceptions surrounding clinical trials, in hopes of fairly representing marginalized communities among future clinical trial participants. METHODS/STUDY POPULATION: We designed a children’s web-app to host a collection of child-friendly educational materials (such as picture books, games, and age-appropriate articles about advances in clinical research) explaining clinical research and its process. An emphasis was put on ensuring the web-app and its contents were understandable and appealing to children. The effectiveness of this tool will be tested through a focus group study. Children ages 7-10 will be given a preliminary survey measuring their knowledge and opinions about clinical research, and then given time to explore the web-app. Afterwards, they will be given a secondary survey to gauge their acquired knowledge from the website and asked about their opinion on the design and usability of the web-app and its materials, as well as how likely they were to revisit the site. RESULTS/ANTICIPATED RESULTS: We anticipate a very positive response from the children regarding the design and usability of the web-app and its materials. By using an adolescent-focused design methodology at every step of the design process, we will ensure that all materials are attractive and engaging to our younger target audience. Exposing children to accessible information about clinical trials at a young age allows us to build their trust in the research process prior to the possible internalization and acceptance of cultural misconceptions. Over time, we hope to see a change in attitudes toward clinical research as well as increased participation, whether from under-represented groups or a younger demographic, and positively contribute to T3 and onwards in the translational continuum. DISCUSSION/SIGNIFICANCE: In a rapidly changing world, the best approach to making change is through targeting the younger demographic, the leaders of tomorrow. Our project will allow adolescents to foster a more well-rounded opinion of clinical research, increasing their participation and better paving a more positively received future for translational science as a whole.
OBJECTIVES/GOALS: Biomedical research fields are facing the challenges of demand for skilled workers as well as challenges related to diversity in that workforce. It is important that the healthcare workforce reflect the population it serves. The Exposures Internship seeks to address this by building pathways for youth to pursue careers in research and medicine. METHODS/STUDY POPULATION: In 2021, the Yale Cultural Ambassadors expressed concern about the lack of free high quality, educational offerings for youth that summer. They asked YCCI to consider developing a summer program for students aged 15 and older that focused on spurring interest in careers in healthcare, medicine, and clinical and translational research. The result was a 4-week virtual learning experience for 34 interns who met daily via Zoom and participated in course work, lectures, journal clubs, group projects, and virtual lunches with internationally renowned clinical research and healthcare leaders. Sessions were designed to help interns gain knowledge of and exposure to current topics in clinical and translational science and to observe the various steps of proposing, designing, undertaking, and analyzing clinical trials. RESULTS/ANTICIPATED RESULTS: YCCI received over 900 inquiries from around the world with more than 200 completed applications for participation in the internship for the pilot year. Since then, YCCI leadership has worked with community partners to engage young scholars from 17 different states, Canada, Mexico and Puerto Rico. Of those, we estimate 75% are minority, ~50% female and 20% from rural areas with limited similar opportunities. During the four weeks of the program these highly motivated students worked on projects aimed at increasing participation in pediatric research through a revised Informed consent and adolescent assent process and a youth centered awareness campaign. Interns were so inspired that they requested the program be continued beyond the initial four weeks. As such, YCCI continued to offer sessions throughout the year. DISCUSSION/SIGNIFICANCE: In evaluation of the pilot program 95% of respondents strongly agreed that the program exposed them to new information about clinical and translational research. One intern shared, This program has unquestionably made me consider becoming a researcher in the future with the goal of becoming a principal investigator within my interest in medicine.
Plenoptic particle image velocimetry and surface pressure measurements were used to analyse the early development of leading-edge vortices (LEVs) created by a flat-plate wing of aspect ratio 2 rolling in a uniform flow parallel to the roll axis. Four cases were constructed by considering two advance coefficients, $J=0.54$ and 1.36, and two wing radii of gyration, $R_g/c=2.5$ and 3.25. In each case, the wing pitch angle was articulated such as to achieve an angle of attack of $33^{\circ }$ at the radius of gyration of the wing. The sources and sinks of vorticity were quantified for a chordwise rectangular control region, using a vorticity transport framework in a non-inertial coordinate system attached to the wing. Within this framework, terms associated with Coriolis acceleration provide a correction to tilting and spanwise convective fluxes measured in the rotating frame and, for the present case, have insignificant values. For the baseline case ($J=0.54, R_g/c=3.25$), three distinct spanwise regions were observed within the LEV, with distinct patterns of vortex evolution and vorticity transport mechanisms in each region. Reducing the radius of gyration to $R_g/c=2.5$ resulted in a more stable vortex with the inboard region extending over a broader spanwise range. Increasing advance ratio eliminated the conical vortex, resulting in transport processes resembling the mid-span region of the baseline case. Although the circulation of the LEV system was generally stronger at the larger advance coefficient, the shear-layer contribution was diminished.
Rapid whole genome sequencing (rapid WGS) is a powerful diagnostic tool that is becoming increasingly practical for widespread clinical use. However, protocols for its use are challenging to implement. A significant obstacle to clinical adoption is that laboratory certification requires an initial research development phase, which is constrained by regulations from returning results. Regulations preventing return of results have ethical implications in cases which might impact patient outcomes. Here, we describe our experience with the development of a rapid WGS research protocol, that balanced the requirements for laboratory-validated test development with the ethical needs of clinically relevant return of results.
Most clinical microbiology laboratories have replaced toxin immunoassay (EIA) alone with multistep testing (MST) protocols or nucleic acid amplification testing (NAAT) alone for the detection of C. difficile.
Objective:
Study the effect of changing testing strategies on C. difficile detection and strain diversity.
Design:
Retrospective study.
Setting:
A Veterans’ Affairs hospital.
Methods:
Initially, toxin EIA testing was replaced by an MST approach utilizing a glutamate dehydrogenase (GDH) and toxin EIA followed by tcdB NAAT for discordant results. After 18 months, MST was replaced by a NAAT-only strategy. Available patient stool specimens were cultured for C. difficile. Restriction endonuclease analysis (REA) strain typing and quantitative in vitro toxin testing were performed on recovered isolates.
Results:
Before MST (toxin EIA), 79 of 708 specimens (11%) were positive, and after MST (MST-A), 121 of 517 specimens (23%) were positive (P < .0001). Prior to NAAT-only testing (MST-B), 80 of the 490 specimens (16%) were positive by MST, and after NAAT-only testing was implemented, 67 of the 368 specimens (18%) were positive (P = nonsignificant). After replacing toxin EIA testing, REA strain group diversity increased (8, 13, 13, and 10 REA groups in the toxin EIA, MST-A, MST-B, and NAAT-only periods, respectively) and in vitro toxin concentration decreased. The average log10 toxin concentration of the isolates were 2.08, 1.88, 1.20 and 1.55 ng/mL for the same periods, respectively.
Conclusions:
MST and NAAT had similar detection rates for C. difficile. Compared to toxin testing alone, they detected increased diversity of C. difficile strains, many of which were low toxin producing.
WHEN THE CANADIAN Confederation Group poet William Wilfred Campbell turned to the Matter of Britain in his medievalist verse-drama Mordred, composed 1893–94, he was embarking upon politically fraught aesthetic terrain that was just beginning to be explored by writers of the new Dominion. Prior to 1892 – the year Campbell published his Arthurian poem, “Sir Lancelot” – the principal texts in this nascent tradition of Canadian Arthuriana were Irish emigrant and Anglican clergyman John Reade's “The Prophecy of Merlin” (1870) and Charles G.D. Roberts's “Launcelot and the Four Queens” (1880). In both of these early works, much of what D.M.R. Bentley aptly refers to as “the politically complex … habitus” of post-Confederation Canadian literature is made apparent by their authors’ self-conscious engagements with a tradition of British medievalism whose availability as a site of national self-recognition was no longer self-evident. Reade, for instance, in his reprising of Alfred Tennyson's “The Passing of Arthur,” feels compelled to justify his ex-centric (post?)colonial site of enunciation by inscribing Canada directly into Arthurian history in the form of a consoling prophecy, spoken by Merlin to Bedivere, about the founding of a new kingdom “In a far land beneath the setting sun / Now and long hence undreamed of… / … a land of stately woods, / Of swift broad rivers, and of ocean lakes,” that Queen Victoria and Prince Albert's son, a new Arthur, will visit and eventually oversee as Governor-General. In this way, Reade “celebrate[s] the British Empire's high destiny,” includes Canada in that destiny, and secures his own poetic authority in a single stroke.
Roberts's participation in the Victorian Medieval Revival in Canada was more straightforward than Reade's but no less significant: his poem's dramatization of Morgan le Fay's machinations and Launcelot's guilty conscience simply present no contradiction to him as subjects for Canadian poetry. As a self-described “cosmopolitan nationalist” Roberts was to argue in “The Beginnings of Canadian Literature” (1883) that a Canadian literary tradition should not require works exclusively based on “Canadian themes” to be considered authentic; Canadians were inheritors of “the whole heritage of English song,” and “the domain of English letters knows no boundaries of Canadian Dominion, of American Commonwealth, nor yet of British Empire.”
The growing prevalence of non-communicable diseases, combined with greater recognition of the effectiveness of lipid lowering agents (LLAs), has fuelled their increasing use in recent years. Similarly, increasing recognition of mental health and, arguably, societal expectations and pressures, has driven appreciable growth in antidepressant prescribing in recent years. Concurrent with this, growing resource pressures enhanced by the continual launch of new premium priced medicines necessitates reforms and initiatives within finite budgets. Scotland has introduced multiple measures in recent years to improve both the quality and efficiency of prescribing. There is a need to document these initiatives and outcomes to provide future direction.
Methods
Assessment of the utilization (items dispensed) and expenditure of key LLAs (mainly statins) and SSRIs between 2001 and 2017 in Scotland alongside initiatives.
Results
Multiple interventions have increased international non-proprietary name (INN) prescribing (99% for statins and up to 99.9% for SSRIs). They have also increased preferential prescribing of generic versus patented statins with low costs for generics, reduced inappropriate prescribing of ezetimibe due to effectiveness concerns, and increased the prescribing of higher dose statins (71% in 2015). These measures have resulted in a 50% reduction in LLA expenditure between 2001 and 2015 despite a 412% increase in utilization. Initiatives to reduce the prescribing of escitalopram as lack of evidence demonstrating cost-benefits over generic citalopram, along with high INN prescribing, achieved a 73.7% reduction in SSRI expenditure between 2001 and 2017 despite a 2.34-fold increase in utilisation. Concerns with paroxetine, and more recently citalopram and escitalopram following safety warnings, resulted in a considerable reduction in their use alongside a significant increase in sertraline.
Conclusions
Generic availability coupled with multiple measures has resulted in appreciable shifts in statin and SSRI prescribing behavior and reduced ezetimibe prescribing, resulting in improvements in both the quality and efficiency of prescribing to provide future direction.
Neuropathologist Bennett Omalu arguably sparked a revolution. Although previous scholars detected what appeared to be deleterious human brain change years or decades after exposure to repetitive concussive brain injuries (CBIs), in 2005 Dr. Omalu published more eloquent evidence suggesting that such exposure might provoke a somewhat homogeneous microscopic pathological profile. His timing was fortuitous: in the preceding decade, shaky scholarship had been invoked by a small cadre of researchers with the transparent agenda of demonstrating that American football rarely harms brains. The published possibility that, in fact, repetitive CBI often triggers persistent or delayed-onset neurodegeneration may eventually save many tens of thousands of years of productive human life. The problem: the observed brain changes are difficult to detect ante-mortem. Neuroimagers have stepped up to the challenge. This chapter introduces some of the evidence from in vivo brain imaging supporting the concerns raised by Dr. Omalu and his forebears.
To examine the relationship between protein intake and the risk of incident premenstrual syndrome (PMS).
Design
Nested case–control study. FFQ were completed every 4 years during follow-up. Our main analysis assessed protein intake 2–4 years before PMS diagnosis (for cases) or reference year (for controls). Baseline (1991) protein intake was also assessed.
Setting
Nurses’ Health Study II (NHS2), a large prospective cohort study of registered female nurses in the USA.
Participants
Participants were premenopausal women between the ages of 27 and 44 years (mean: 34 years), without diagnosis of PMS at baseline, without a history of cancer, endometriosis, infertility, irregular menstrual cycles or hysterectomy. Incident cases of PMS (n 1234) were identified by self-reported diagnosis during 14 years of follow-up and validated by questionnaire. Controls (n 2426) were women who did not report a diagnosis of PMS during follow-up and confirmed experiencing minimal premenstrual symptoms.
Results
In logistic regression models adjusting for smoking, BMI, B-vitamins and other factors, total protein intake was not associated with PMS development. For example, the OR for women with the highest intake of total protein 2–4 years before their reference year (median: 103·6 g/d) v. those with the lowest (median: 66·6 g/d) was 0·94 (95 % CI 0·70, 1·27). Additionally, intakes of specific protein sources and amino acids were not associated with PMS. Furthermore, results substituting carbohydrates and fats for protein were also null.
Conclusions
Overall, protein consumption was not associated with risk of developing PMS.
In response to concerns about acetolactate synthase (ALS) inhibitor–resistant weeds in wheat production systems, we explored the efficacy of managing Bromus spp., downy and Japanese bromes, in a winter wheat system using alternative herbicide treatments applied in either fall or spring. Trials were established at Lethbridge and Kipp, Alberta, and Scott, Saskatchewan, Canada over three growing seasons (2012–2014) to compare the efficacy of pyroxasulfone (a soil-applied very-long-chain fatty acid elongase inhibitor; WSSA Group 15) and flumioxazin (a protoporphyrinogen oxidase inhibitor; WSSA Group 14) against industry-standard ALS-inhibiting herbicides for downy and Japanese brome control. Winter wheat injury from herbicide application was minor, with the exception of flucarbazone application at Scott. Bromus spp. control was greatest with pyroxsulam and all herbicide treatments containing pyroxasulfone. Downy and Japanese bromes were controlled least by thiencarbazone and flumioxazin, respectively, whereas Bromus spp. had intermediate responses to the other herbicides tested. Herbicides applied in fall resulted in reduced winter wheat yield relative to the spring applications. Overall, pyroxasulfone or pyroxsulam provided the most efficacious Bromus spp. control compared with the other herbicides and consistently maintained optimal winter wheat yields. Therefore, pyroxasulfone could facilitate management of Bromus spp. resistant to ALS inhibitors in winter wheat in the southern growing regions of western Canada. Improved weed control and delayed herbicide resistance may be achieved when pyroxasulfone is applied in combination with flumioxazin.
Mercury is the only terrestrial planet other than Earth that possesses a global magnetic field, and the unique solar wind environment of the inner heliosphere has profound consequences for both the structure and dynamics of its magnetosphere. The first in situ observations of Mercury and its space environment made four decades ago by the Mariner 10 spacecraft revealed a magnetic field that is sufficiently strong to stand off the solar wind and form a magnetosphere. Many new insights into Mercury’s magnetosphere were enabled by data returned by the MESSENGER spacecraft. The extensive magnetic field and particle observations allowed detailed characterization of the magnetospheric structure and configuration. MESSENGER magnetic field observations definitively determined the orientation, moment, and location of the internal planetary magnetic dipole field. Furthermore, these observations established the configuration of the magnetopause, bow shock, and magnetospheric current systems. Plasma observations revealed the distribution and composition of plasma in the magnetosphere. We review the geometry and dominant physical processes of Mercury’s unique magnetosphere inferred from MESSENGER data, including the solar wind environment, the shape and location of magnetospheric boundaries, and the fundamental regions and configuration of the magnetosphere and transport and heating of plasma therein.
The MESSENGER mission provided a wealth of discoveries regarding Mercury’s present and past magnetic field and completed the first-order characterization of the magnetic fields of the solar system’s inner planets. MESSENGER demonstrated that Mercury is the only inner planet other than Earth to possess a global magnetic field generated by fluid motions in its liquid iron core. The field possesses some similarities to that of Earth, particularly its dipolar nature, but it is more than a factor of 100 weaker at the surface and unlike Earth’s field is highly asymmetric about the geographic equator. This structure constrains the dynamo process that generates the field and in turn the compositional and thermal structure of Mercury’s interior. Measurements made by MESSENGER less than 100 km above the planetary surface revealed signatures of crustal magnetization, at least some of which were acquired in a very ancient global magnetic field. Electric currents flow in the planet’s interior as a result of the dynamic interactions of the global magnetic field with the solar wind. These currents provide information on the radius of Mercury’s electrically conductive core, as well as the conductivity structure of the crust and mantle, which in turn reflects interior composition and temperature.