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Ice shelves restrain flow from the Greenland and Antarctic ice sheets. Climate-ocean warming could force thinning or collapse of floating ice shelves and subsequently accelerate flow, increase ice discharge and raise global mean sea levels. Petermann Glacier (PG), northwest Greenland, recently lost large sections of its ice shelf, but its response to total ice shelf loss in the future remains uncertain. Here, we use the ice flow model Úa to assess the sensitivity of PG to changes in ice shelf extent, and to estimate the resultant loss of grounded ice and contribution to sea level rise. Our results have shown that under several scenarios of ice shelf thinning and retreat, removal of the shelf will not contribute substantially to global mean sea level (<1 mm). We hypothesize that grounded ice loss was limited by the stabilization of the grounding line at a topographic high ~12 km inland of its current grounding line position. Further inland, the likelihood of a narrow fjord that slopes seawards suggests that PG is likely to remain insensitive to terminus changes in the near future.
This study examined the perceived competence of Clinical Research Coordinators (CRCs) using several conceptual frameworks. Accurate self-assessment of one’s professional competence is a critical component in the career navigation process and contributes to (a) identifying and securing professional development (training), (b) leveraging professional strengths, and (c) integrating self-knowledge into a comprehensive career plan.
A survey design gathered responses from a sample of 119 CRCs in a southeastern region of the USA Two conceptual frameworks were used to represent aspects of CRC professional competence: the eight Joint Task Force (JTF) competence domains, and perceptions of strengths and training needs from a list of 12 task categories.
The JTF domain with the lowest competence level was Development and Regulations, while the highest was Communication. Perceived competence increased incrementally with years of experience. Top strengths involved direct patient interaction and data management. Tasks in need of training included project management and reporting issues. Variations in responses were based on years of experience as a CRC.
Our results demonstrate an association between the self-reported strengths and training needs of CRCs and experience. This information can contribute to the self-directed career navigation of CRCs.
The Eating Assessment in Toddlers FFQ (EAT FFQ) has been shown to have good reliability and comparative validity for ranking nutrient intakes in young children. With the addition of food items (n 4), we aimed to re-assess the validity of the EAT FFQ and estimate calibration factors in a sub-sample of children (n 97) participating in the Growing Up Milk – Lite (GUMLi) randomised control trial (2015–2017). Participants completed the ninety-nine-item GUMLi EAT FFQ and record-assisted 24-h recalls (24HR) on two occasions. Energy and nutrient intakes were assessed at months 9 and 12 post-randomisation and calibration factors calculated to determine predicted estimates from the GUMLi EAT FFQ. Validity was assessed using Pearson correlation coefficients, weighted kappa (κ) and exact quartile categorisation. Calibration was calculated using linear regression models on 24HR, adjusted for sex and treatment group. Nutrient intakes were significantly correlated between the GUMLi EAT FFQ and 24HR at both time points. Energy-adjusted, de-attenuated Pearson correlations ranged from 0·3 (fibre) to 0·8 (Fe) at 9 months and from 0·3 (Ca) to 0·7 (Fe) at 12 months. Weighted κ for the quartiles ranged from 0·2 (Zn) to 0·6 (Fe) at 9 months and from 0·1 (total fat) to 0·5 (Fe) at 12 months. Exact agreement ranged from 30 to 74 %. Calibration factors predicted up to 56 % of the variation in the 24HR at 9 months and 44 % at 12 months. The GUMLi EAT FFQ remained a useful tool for ranking nutrient intakes with similar estimated validity compared with other FFQ used in children under 2 years.
Emergency Medical Services (EMS) systems have developed protocols for prehospital activation of the cardiac catheterization laboratory for patients with suspected ST-elevation myocardial infarction (STEMI) to decrease first-medical-contact-to-balloon time (FMC2B). The rate of “false positive” prehospital activations is high. In order to decrease this rate and expedite care for patients with true STEMI, the American Heart Association (AHA; Dallas, Texas USA) developed the Mission Lifeline PreAct STEMI algorithm, which was implemented in Los Angeles County (LAC; California USA) in 2015. The hypothesis of this study was that implementation of the PreAct algorithm would increase the positive predictive value (PPV) of prehospital activation.
This is an observational pre-/post-study of the effect of the implementation of the PreAct algorithm for patients with suspected STEMI transported to one of five STEMI Receiving Centers (SRCs) within the LAC Regional System. The primary outcome was the PPV of cardiac catheterization laboratory activation for percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). The secondary outcome was FMC2B.
A total of 1,877 patients were analyzed for the primary outcome in the pre-intervention period and 405 patients in the post-intervention period. There was an overall decrease in cardiac catheterization laboratory activations, from 67% in the pre-intervention period to 49% in the post-intervention period (95% CI for the difference, -14% to -22%). The overall rate of cardiac catheterization declined in post-intervention period as compared the pre-intervention period, from 34% to 30% (95% CI, for the difference -7.6% to 0.4%), but actually increased for subjects who had activation (48% versus 58%; 95% CI, 4.6%-15.0%). Implementation of the PreAct algorithm was associated with an increase in the PPV of activation for PCI or CABG from 37.9% to 48.6%. The overall odds ratio (OR) associated with the intervention was 1.4 (95% CI, 1.1-1.8). The effect of the intervention was to decrease variability between medical centers. There was no associated change in average FMC2B.
The implementation of the PreAct algorithm in the LAC EMS system was associated with an overall increase in the PPV of cardiac catheterization laboratory activation.
Registry-based trials have emerged as a potentially cost-saving study methodology. Early estimates of cost savings, however, conflated the benefits associated with registry utilisation and those associated with other aspects of pragmatic trial designs, which might not all be as broadly applicable. In this study, we sought to build a practical tool that investigators could use across disciplines to estimate the ranges of potential cost differences associated with implementing registry-based trials versus standard clinical trials.
We built simulation Markov models to compare unique costs associated with data acquisition, cleaning, and linkage under a registry-based trial design versus a standard clinical trial. We conducted one-way, two-way, and probabilistic sensitivity analyses, varying study characteristics over broad ranges, to determine thresholds at which investigators might optimally select each trial design.
Registry-based trials were more cost effective than standard clinical trials 98.6% of the time. Data-related cost savings ranged from $4300 to $600,000 with variation in study characteristics. Cost differences were most reactive to the number of patients in a study, the number of data elements per patient available in a registry, and the speed with which research coordinators could manually abstract data. Registry incorporation resulted in cost savings when as few as 3768 independent data elements were available and when manual data abstraction took as little as 3.4 seconds per data field.
Registries offer important resources for investigators. When available, their broad incorporation may help the scientific community reduce the costs of clinical investigation. We offer here a practical tool for investigators to assess potential costs savings.
Early growth pattern is increasingly recognized as a determinant of later obesity. This study aimed to identify the association between weight gain in early life and anthropometry, adiposity, leptin, and fasting insulin levels in adolescence. A cross-sectional study was conducted in 366 school children aged 11–13 years. Weight, height, and waist circumference (WC) were measured. Fat mass (FM) was assessed using bioelectrical impedance analysis. Blood was drawn after a 12-h fast for insulin and leptin assay. Birth weight and weight at 6 months and at 18 months were extracted from Child Health Development Records. An increase in weight SD score (SDS) by ≥0.67 was defined as accelerated weight gain. Linear mixed-effects modeling was used to predict anthropometry, adiposity, and metabolic outcomes using sex, pubertal status, accelerated weight gain as fixed factors; age, birth weight, and family income as fixed covariates, and school as a random factor. Children with accelerated weight gain between birth and 18 months had significantly higher body mass index (BMI) SDS, WC SDS, height SDS, %FM, fat mass index (FMI), fat free mass index (FFMI), and serum leptin levels in adolescence. Accelerated weight gain between 6 and 18 months was associated with higher BMI SDS, WC SDS, %FM, and FMI, but not with height SDS or FFMI. Accelerated weight gain at 0–6 months, in children with low birth weight, was associated with higher height SDS, BMI SDS, WC SDS, %FM, and FMI; in children with normal birth weight, it was associated with BMI SDS, WC SDS, height SDS, and FFMI, but not with %FM or FMI. Effects of accelerated weight gain in early life on anthropometry and adiposity in adolescence varied in different growth windows. Accelerated weight gain during 6–18 months was associated with higher FM rather than linear growth. Effects of accelerated weight gain between 0 and 6 months varied with birth weight.
The Wisconsin Twin Project encompasses nearly 30 years of longitudinal research that spans infancy to early adulthood. The twin sample was recruited from statewide birth records for birth cohorts 1989–2004. We summarize early recruitment, assessment, retention and recently completed twin neuroimaging studies. In addition to the focal twins, longitudinal data were also collected from two parents and nontwin siblings. Our adolescent and young adult neuroimaging sample (N = 600) completed several previous behavioral and environmental assessments, beginning shortly after birth. The extensive phenotyping is meant to support a range of empirical investigations with potentially differing theoretical perspectives.
While echocardiographic parameters are used to quantify ventricular function in infants with single ventricle physiology, there are few data comparing these to invasive measurements. This study correlates echocardiographic measures of diastolic function with ventricular end-diastolic pressure in infants with single ventricle physiology prior to superior cavopulmonary anastomosis.
Data from 173 patients enrolled in the Pediatric Heart Network Infant Single Ventricle enalapril trial were analysed. Those with mixed ventricular types (n = 17) and one outlier (end-diastolic pressure = 32 mmHg) were excluded from the analysis, leaving a total sample size of 155 patients. Echocardiographic measurements were correlated to end-diastolic pressure using Spearman’s test.
Median age at echocardiogram was 4.6 (range 2.5–7.4) months. Median ventricular end-diastolic pressure was 7 (range 3–19) mmHg. Median time difference between the echocardiogram and catheterisation was 0 days (range −35 to 59 days). Examining the entire cohort of 155 patients, no echocardiographic diastolic function variable correlated with ventricular end-diastolic pressure. When the analysis was limited to the 86 patients who had similar sedation for both studies, the systolic:diastolic duration ratio had a significant but weak negative correlation with end-diastolic pressure (r = −0.3, p = 0.004). The remaining echocardiographic variables did not correlate with ventricular end-diastolic pressure.
In this cohort of infants with single ventricle physiology prior to superior cavopulmonary anastomosis, most conventional echocardiographic measures of diastolic function did not correlate with ventricular end-diastolic pressure at cardiac catheterisation. These limitations should be factored into the interpretation of quantitative echo data in this patient population.
This study identified underlying career orientation types of clinical research coordinators (CRCs) using cluster analysis. Select career (satisfaction, engagement, and planning) and competency-related (perceived competence) information was used to identify four distinct career orientation types.
A web-based survey was administered to CRCs employed in one of four research institutions affiliated with a National Institutes of Health-funded Clinical and Translational Research Award (CTSA) in the southeastern USA. Each respondent completed a survey containing questions about personal background, individual attributes, perceived professional competence, and career orientation.
The first CRC type (35.2%) possessed a positive, knowledge-seeking orientation, characterized by high career-related scores but a conservative assessment of perceived competence. The second CRC type (18.6%) represented an optimistic and confident career orientation reflected in moderate to high scores on each of the four identifying factors. The third CRC type (27.6%) reflected an inconsistent career orientation highlighted by lowered perceived competence. The final CRC type (18.6%) reflected a disengaged orientation characterized by negative responses to all career and competence factors.
Understanding the career orientation of CRCs can be helpful to institutional administrators and clinical investigators as they seek to support the professional development of CRCs through tailored training efforts or work-related supports. Knowledge of career orientation may also inform individual CRCs as they manage their personal career paths by assessing current levels of functioning, career-related strengths or weaknesses, and training needs.
Implementation of a novel experimental approach using a bright source of narrowband x-ray emission has enabled the production of a photoionized argon plasma of relevance to astrophysical modelling codes such as Cloudy. We present results showing that the photoionization parameter ζ = 4πF/ne generated using the VULCAN laser was ≈ 50 erg cm s−1, higher than those obtained previously with more powerful facilities. Comparison of our argon emission-line spectra in the 4.15 - 4.25 Å range at varying initial gas pressures with predictions from the Cloudy code and a simple time-dependent code are also presented. Finally we briefly discuss how this proof-of-principle experiment may be scaled to larger facilities such as ORION to produce the closest laboratory analogue to a photoionized plasma.
The pore structure of vapour deposited ASW is poorly understood, despite its importance to fundamental processes such as grain chemistry, cooling of star forming regions, and planet formation. We studied structural changes of vapour deposited D2O on intra-molecular to 30 nm length scales at temperatures ranging from 18 to 180 K and observed enhanced mobility from 100 to 150 K. An Arrhenius type model describes the loss of surface area and porosity with a common set of kinetic parameters. The low activation energy (428 K) is commensurate with van der Waals forces between nm-scale substructures in the ice. Our findings imply that water porosity will always change with time, even at low temperatures.
OBJECTIVES/SPECIFIC AIMS: The central goal of this proposal is to characterize the mechanisms that mediate success or failure of immature intestinal barrier in necrotizing enterocilitis. METHODS/STUDY POPULATION: To do this, I will utilize stem cell derived human intestinal organoids (HIOs), an innovative model of the immature intestine, and a cohort of bacterial isolates collected from premature infants who developed NEC to interrogate the cause-effect relationship of these strains on maintenance of the intestinal barrier. I hypothesize that the epithelial response to bacterial colonization is strain-dependent and results in differences in inflammatory signaling that shape epithelial barrier function in the immature intestine. RESULTS/ANTICIPATED RESULTS: Preliminary data shows that colonization of HIOs with different bacteria leads to species-specific changes in barrier function, and some species selectively damage the epithelial barrier while others enhance epithelial barrier function. I have identified key inflammatory signals that serve as central drivers of intestinal barrier function. DISCUSSION/SIGNIFICANCE OF IMPACT: Characterization of this process is expected to substantially advance scientific understanding of early events in NEC pathogenesis and lead to new opportunities for targeted therapeutic intervention to accelerate barrier maturation or prevent hyperinflammatory reactivity in the neonatal intestine. The research proposed in this application represents an entirely novel approach to studying host-microbial interactions in the immature. Conceptually, this novel translational approach will help to define the pivotal role of colonizing bacteria in initiating epithelial inflammation in NEC patients.
OBJECTIVES/SPECIFIC AIMS: More men than women develop urinary stones and their prevalence alters in women with menopause suggesting a steroidal influence. In men the incidence of stones is highest during July and August suggesting that environmental factors such as Vitamin D (VitD), a steroid, may affect stone formation. Previous studies have found differences in the development of stones between men and women; however, the reasons for sex differences in stone formation and type remain unclear. METHODS/STUDY POPULATION: We examined VitD levels in men and women (n = 18,753) that had no diseases based on a lack of an ICD-9 or ICD-10 code in their electronic medical record. We found that normal, healthy women had significantly higher levels of sera VitD compared to men (p = 6x10-6). We then examined whether sex differences existed for key endpoints/data from the Mayo Clinic Urinary Stone Disease (USD) Registry, which has around 1,600 urinary stone patients that are well-phenotyped according to sex, age and stone type. RESULTS/ANTICIPATED RESULTS: Control women were found to have higher sera VitD levels than men, but the sex difference no longer exists in kidney stone disease patients. When we further separated by race, we found that differences in VitD levels reappeared; this suggests that race also plays a role in sera VitD variances. DISCUSSION/SIGNIFICANCE OF IMPACT: We are developing a disease severity score, which we will use to correlate to sera VitD levels in patients according to sex, age and race. Future analyses will take into account whether subjects had VitD and calcium supplementation. This project begins to explore the mechanism behind the sex differences known to exist in urinary stone disease, which is critically needed to provide improved diagnosis and therapy for this debilitating disease.
The second year of life is a period of nutritional vulnerability. We aimed to investigate the dietary patterns and nutrient intakes from 1 to 2 years of age during the 12-month follow-up period of the Growing Up Milk – Lite (GUMLi) trial. The GUMLi trial was a multi-centre, double-blinded, randomised controlled trial of 160 healthy 1-year-old children in Auckland, New Zealand and Brisbane, Australia. Dietary intakes were collected at baseline, 3, 6, 9 and 12 months post-randomisation, using a validated FFQ. Dietary patterns were identified using principal component analysis of the frequency of food item consumption per d. The effect of the intervention on dietary patterns and intake of eleven nutrients over the duration of the trial were investigated using random effects mixed models. A total of three dietary patterns were identified at baseline: ‘junk/snack foods’, ‘healthy/guideline foods’ and ‘breast milk/formula’. A significant group difference was observed in ‘breast milk/formula’ dietary pattern z scores at 12 months post-randomisation, where those in the GUMLi group loaded more positively on this pattern, suggesting more frequent consumption of breast milk. No difference was seen in the other two dietary patterns. Significant intervention effects were seen on nutrient intake between the GUMLi (intervention) and cows’ milk (control) groups, with lower protein and vitamin B12, and higher Fe, vitamin D, vitamin C and Zn intake in the GUMLi (intervention) group. The consumption of GUMLi did not affect dietary patterns, however, GUMLi participants had lower protein intake and higher Fe, vitamins D and C and Zn intake at 2 years of age.
The consumption of high-Ca, high-protein dairy foods (i.e. milk, cheese, yogurt) is advocated for bone health across the lifespan to reduce the risk of low-trauma fractures. However, to date, the anti-fracture efficacy of dairy food consumption has not been demonstrated in randomised controlled trials but inferred from cross-sectional and prospective studies. The anti-fracture efficacy of dairy food consumption is plausible, but testing this requires a robust study design to ensure outcomes are suitably answering this important public health question. The evidence of skeletal benefits of dairy food consumption is equivocal, not because it may not be efficacious but because the study design and execution are often inadequate. The key issues are compliance with dietary intervention, dropouts, sample sizes and most importantly lack of deficiency before intervention. Without careful appraisal of the design and execution of available studies, precarious interpretations of outcomes may be made from these poorly designed or executed studies, without consideration of how study design may be improved. Dairy food interventions in children are further hampered by heterogeneity in growth: in particular sex and maturity-related differences in the magnitude, timing, location and surface-specific site of bone accrual. Outcomes of studies combining children of different sexes and maturity status may be masked or exaggerated by these differences in growth, so inaccurate conclusions are drawn from results. Until these critical issues in study design are considered in future dairy food interventions, the anti-fracture efficacy of dairy food consumption may remain unknown and continue to be based on conjecture.
Soldier operational performance is determined by their fitness, nutritional status, quality of rest/recovery, and remaining injury/illness free. Understanding large fluctuations in nutritional status during operations is critical to safeguarding health and well-being. There are limited data world-wide describing the effect of extreme climate change on nutrient profiles. This study investigated the effect of hot-dry deployments on vitamin D status (assessed from 25-hydroxyvitamin D (25(OH)D) concentration) of young, male, military volunteers. Two data sets are presented (pilot study, n 37; main study, n 98), examining serum 25(OH)D concentrations before and during 6-month summer operational deployments to Afghanistan (March to October/November). Body mass, percentage of body fat, dietary intake and serum 25(OH)D concentrations were measured. In addition, parathyroid hormone (PTH), adjusted Ca and albumin concentrations were measured in the main study to better understand 25(OH)D fluctuations. Body mass and fat mass (FM) losses were greater for early (pre- to mid-) deployment compared with late (mid- to post-) deployment (P<0·05). Dietary intake was well-maintained despite high rates of energy expenditure. A pronounced increase in 25(OH)D was observed between pre- (March) and mid-deployment (June) (pilot study: 51 (sd 20) v. 212 (sd 85) nmol/l, P<0·05; main study: 55 (sd 22) v. 167 (sd 71) nmol/l, P<0·05) and remained elevated post-deployment (October/November). In contrast, PTH was highest pre-deployment, decreasing thereafter (main study: 4·45 (sd 2·20) v. 3·79 (sd 1·50) pmol/l, P<0·05). The typical seasonal cycling of vitamin D appeared exaggerated in this active male population undertaking an arduous summer deployment. Further research is warranted, where such large seasonal vitamin D fluctuations may be detrimental to bone health in the longer-term.
The objective of this study was to investigate the impact of the most commonly cited factors that may have influenced infants’ gut microbiota profiles at one year of age: mode of delivery, breastfeeding duration and antibiotic exposure. Barcoded V3/V4 amplicons of bacterial 16S-rRNA gene were prepared from the stool samples of 52 healthy 1-year-old Australian children and sequenced using the Illumina MiSeq platform. Following the quality checks, the data were processed using the Quantitative Insights Into Microbial Ecology pipeline and analysed using the Calypso package for microbiome data analysis. The stool microbiota profiles of children still breastfed were significantly different from that of children weaned earlier (P<0.05), independent of the age of solid food introduction. Among children still breastfed, Veillonella spp. abundance was higher. Children no longer breastfed possessed a more ‘mature’ microbiota, with notable increases of Firmicutes. The microbiota profiles of the children could not be differentiated by delivery mode or antibiotic exposure. Further analysis based on children’s feeding patterns found children who were breastfed alongside solid food had significantly different microbiota profiles compared to that of children who were receiving both breastmilk and formula milk alongside solid food. This study provided evidence that breastfeeding continues to influence gut microbial community even at late infancy when these children are also consuming table foods. At this age, any impacts from mode of delivery or antibiotic exposure did not appear to be discernible imprints on the microbial community profiles of these healthy children.
We consider the effect of high rotation rates on two liquid layers that initially form concentric cylinders, centred on the axis of rotation. The configuration may be thought of as a fluid–fluid centrifuge. There are two types of perturbation to the interface that may be considered, an azimuthal perturbation around the circumference of the interface and a varicose perturbation in the axial direction along the length of the interface. It is the first of these types of perturbation that we consider here, and so the flow may be considered essentially two-dimensional, taking place in a circular domain. A linear stability analysis is carried out on a perturbation to the hydrostatic background state and a fourth-order Orr–Sommerfeld-like equation that governs the system is derived. We consider the dynamics of systems of stable and unstable configurations, inviscid and viscous fluids, immiscible fluid layers with surface tension and miscible fluid layers that may have some initial diffusion of density. In the most simple case of two layers of inviscid fluid separated by a sharp interface with no surface tension acting, we show that the effects of the curvature of the interface and the confinement of the system may be characterised by a modified Atwood number. The classical Atwood number is recovered in the limit of high azimuthal wavenumber, or the outer fluid layer being unconfined. Theoretical predictions are compared with numerical experiments and the agreement is shown to be good. We do not restrict our analysis to equal volume fluid layers and so our results also have applications in coating and lubrication problems in rapidly rotating systems and machinery.