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Incremental prediction of aggression from callous–unemotional (CU) traits is well established, but cross-cultural replication and studies of young children are needed. Little is understood about the contribution of CU traits in children who are already aggressive. We addressed these issues in prospective studies in the United Kingdom and Colombia. In a UK epidemiological cohort, CU traits and aggression were assessed at age 3.5 years, and aggression at 5.0 years by mothers (N = 687) and partners (N = 397). In a Colombian general population sample, CU traits were assessed at age 3.5 years and aggression at 3.5 and 5.0 years by mother report (N = 220). Analyses consistently showed prediction of age-5.0 aggression by age-3.5 CU traits controlling for age-3.5 aggression. Associations between age-3.5 CU traits and age-5.0 aggression were moderated by aggression at 3.5 years, with UK interaction terms, same informant, β = .07 p = .014 cross-informant, β = .14 p = .002, and in Colombia, β = .09 p = .128. The interactions arose from stronger associations between CU traits and later aggression in those already aggressive. Our findings with preschoolers replicated across culturally diverse settings imply a major role for CU traits in the maintenance and amplification of already established aggression, and cast doubt on their contribution to its origins.
Infants with moderate-to-severe CHD frequently undergo cardiopulmonary bypass surgery in childhood. Morbidity and mortality are highest in those who develop post-operative low cardiac output syndrome. Vasoactive and inotropic medications are mainstays of treatment for these children, despite limited evidence supporting their use.
To help inform clinical practice, as well as the conduct of future trials, we performed a systematic review of existing literature on inotropes and vasoactives in children after cardiac surgery using the PubMed and EMBASE databases. We included studies from 2000 to 2020, and the patient population was defined as birth – 18 years of age. Two reviewers independently reviewed studies to determine final eligibility.
The final analysis included 37 papers. Collectively, selected studies reported on 12 different vasoactive and inotropic medications in 2856 children. Overall evidence supporting the use of these drugs in children after cardiopulmonary bypass was limited. The majority of studies were small with 30/37 (81%) enrolling less than 100 patients, 29/37 (78%) were not randomised, and safety and efficacy endpoints differed widely, limiting the ability to combine data for meta-analyses.
Vasoactive and inotropic support remain critical parts of post-operative care for children after cardiopulmonary bypass surgery. There is a paucity of data for the selection and dosing of vasoactives and inotropes for these patients. Despite the knowledge gaps that remain, numerous recent innovations create opportunities to rethink the conduct of clinical trials in this high-risk population.
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.
Analysis of human remains and a copper band found in the center of a Late Archaic (ca. 5000–3000 cal BP) shell ring demonstrate an exchange network between the Great Lakes and the coastal southeast United States. Similarities in mortuary practices suggest that the movement of objects between these two regions was more direct and unmediated than archaeologists previously assumed based on “down-the-line” models of exchange. These findings challenge prevalent notions that view preagricultural Native American communities as relatively isolated from one another and suggest instead that wide social networks spanned much of North America thousands of years before the advent of domestication.
Preferential dissolution of the biogenic carbonate polymorph aragonite promotes preservational bias in shelly marine faunas. While field studies have documented the impact of preferential aragonite dissolution on fossil molluscan diversity, its impact on regional and global biodiversity metrics is debated. Epicontinental seas are especially prone to conditions that both promote and inhibit preferential dissolution, which may result in spatially extensive zones with variable preservation. Here we present a multifaceted evaluation of aragonite dissolution within the Late Cretaceous Western Interior Seaway of North America. Occurrence data of mollusks from two time intervals (Cenomanian/Turonian boundary, early Campanian) are plotted on new high-resolution paleogeographies to assess aragonite preservation within the seaway. Fossil occurrences, diversity estimates, and sampling probabilities for calcitic and aragonitic fauna were compared in zones defined by depth and distance from the seaway margins. Apparent range sizes, which could be influenced by differential preservation potential of aragonite between separate localities, were also compared. Our results are consistent with exacerbated aragonite dissolution within specific depth zones for both time slices, with aragonitic bivalves additionally showing a statistically significant decrease in range size compared with calcitic fauna within carbonate-dominated Cenomanian–Turonian strata. However, we are unable to conclusively show that aragonite dissolution impacted diversity estimates. Therefore, while aragonite dissolution is likely to have affected the preservation of fauna in specific localities, time averaging and instantaneous preservation events preserve regional biodiversity. Our results suggest that the spatial expression of taphonomic biases should be an important consideration for paleontologists working on paleobiogeographic problems.
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.
Salmonella enterica serovar Wangata (S. Wangata) is an important cause of endemic salmonellosis in Australia, with human infections occurring from undefined sources. This investigation sought to examine possible environmental and zoonotic sources for human infections with S. Wangata in north-eastern New South Wales (NSW), Australia. The investigation adopted a One Health approach and was comprised of three complimentary components: a case–control study examining human risk factors; environmental and animal sampling; and genomic analysis of human, animal and environmental isolates. Forty-eight human S. Wangata cases were interviewed during a 6-month period from November 2016 to April 2017, together with 55 Salmonella Typhimurium (S. Typhimurium) controls and 130 neighbourhood controls. Indirect contact with bats/flying foxes (S. Typhimurium controls (adjusted odds ratio (aOR) 2.63, 95% confidence interval (CI) 1.06–6.48)) (neighbourhood controls (aOR 8.33, 95% CI 2.58–26.83)), wild frogs (aOR 3.65, 95% CI 1.32–10.07) and wild birds (aOR 6.93, 95% CI 2.29–21.00) were statistically associated with illness in multivariable analyses. S. Wangata was detected in dog faeces, wildlife scats and a compost specimen collected from the outdoor environments of cases’ residences. In addition, S. Wangata was detected in the faeces of wild birds and sea turtles in the investigation area. Genomic analysis revealed that S. Wangata isolates were relatively clonal. Our findings suggest that S. Wangata is present in the environment and may have a reservoir in wildlife populations in north-eastern NSW. Further investigation is required to better understand the occurrence of Salmonella in wildlife groups and to identify possible transmission pathways for human infections.
OBJECTIVES/SPECIFIC AIMS: o To review the community’s recommendations on how to rebuild trust in the Flint community. o To review effective community engagement strategies utilized with the Flint Special Projects for project conceptualization, participant recruitment, data analysis, project oversight, and dissemination. METHODS/STUDY POPULATION: The study population includes nearly two hundred residents representing seniors, youth and diverse ethnicities recruited to participate in eleven focus group meetings. The population also represents the general public who attended informational meetings in Flint, Michigan to learn about the crisis and allow residents to voice their opinions and concerns during the onset of the crisis. The project is a mixed methods community based participatory research effort that utilized community decision making in all phases of the effort such as pre-conception, implementation, dissemination and advocacy to encourage the community’s recommendations are adopted at policy and institutional responsiveness levels. It includes three community engaged research efforts: (project 1) A qualitative analysis of community sentiment provided during 17 recorded legislative, media and community events, and (projects 2-3) two mixed methods efforts utilizing purposive sampling of stakeholders whose voice may not have been heard. RESULTS/ANTICIPATED RESULTS: The project presents a qualitative analysis of the community’s voice during the onset of the man-made disaster when the community first became aware of the emergency manager’s plans to switch the water source. It also reflects current perspectives of community voice since the projects are scheduled to end late February 2019. Findings from a trust measure administered to nearly two hundred residents will be presented, along with a qualitative analysis of focus group findings among segments of the population (seniors, youth, and diverse ethnicities) who may have been left out of narratives on the water crisis. Finally, the project will compare empowerment and resiliency approaches being utilized in Flint, Michigan to recover from the disaster with other approaches grounded in literature and theory. DISCUSSION/SIGNIFICANCE OF IMPACT: Communities of color often experience social determinants of health which negatively impact their health, well-being and human rights. Some Flint citizens are experiencing negative health consequences (i.e., rashes, brain and behavioral sequelle, fertility, etc.) as a result of the disaster, and are uncertain of health outcomes in the future. This is the first project to rigorously document and analyze levels of trust and mistrust in the city of Flint since the water disaster occurred. The qualitative research will guide future clinical research that will benefit this traumatized community experiencing high levels of mistrust (i.e., government, elected officials, etc.). The community engaged methodology involved residents and study participants in all phases of the project including project oversight, validating and analyzing data, and dissemination. This methodology will contribute to existing literature and theory on community based participatory research, community engaged research, team science and citizen science. The approaches empowered a call to action among residents, for example, seniors who attended two senior focus group sessions shared “they are hopeful and have a purpose,” resulting in the creation of a council (with officers) at their housing complex to advocate for the well-being of seniors during the recovery process. Recruitment methodologies were extremely successful due to resident level trust in community leaders and community partner organizations. Finally, the project’s examination of approaches encouraging empowerment and resiliency will provide lessons learned for other communities challenged with crisis.
The ventricular assist device is being increasingly used as a “bridge-to-transplant” option in children with heart failure who have failed medical management. Care for this medically complex population must be optimised, including through concomitant pharmacotherapy. Pharmacokinetic/pharmacodynamic alterations affecting pharmacotherapy are increasingly discovered in children supported with extracorporeal membrane oxygenation, another form of mechanical circulatory support. Similarities between extracorporeal membrane oxygenation and ventricular assist devices support the hypothesis that similar alterations may exist in ventricular assist device-supported patients. We conducted a literature review to assess the current data available on pharmacokinetics/pharmacodynamics in children with ventricular assist devices. We found two adult and no paediatric pharmacokinetic/pharmacodynamic studies in ventricular assist device-supported patients. While mechanisms may be partially extrapolated from children supported with extracorporeal membrane oxygenation, dedicated investigation of the paediatric ventricular assist device population is crucial given the inherent differences between the two forms of mechanical circulatory support, and pathophysiology that is unique to these patients. Commonly used drugs such as anticoagulants and antibiotics have narrow therapeutic windows with devastating consequences if under-dosed or over-dosed. Clinical studies are urgently needed to improve outcomes and maximise the potential of ventricular assist devices in this vulnerable population.
OBJECTIVES/SPECIFIC AIMS: The purpose of this study was to characterize the pharmacokinetics of phosphatidylethanol (PEth) 16:0/20:4 homolog in uncoagulated, human blood samples taken from 18 participants in a clinical laboratory setting after consumption of 2 doses of ethanol. METHODS/STUDY POPULATION: Male and female participants received either 0.4 or 0.8 g/kg oral doses of ethanol during a 15-minute period. Blood samples were collected before and throughout 6 hours immediately after alcohol administration, then after 2, 4, 7, 11, and 14 days of administration day. PEth 16:0/20:4 levels were quantified by liquid mass spectrometry. Breath ethanol concentrations were measure concurrently with each blood collection during the administration day, as well as transdermal ethanol concentrations monitored constantly before, during and after ethanol administration day. RESULTS/ANTICIPATED RESULTS: (1) Single doses of 0.4 and 0.8 g ethanol/kg produced proportional increases in BrAC and PEth 16:0/20:4 levels; (2) the increase of Peth 16:0/20:4 from base line to Cmax was less than either PEth 16:0/18:1 or PEth 16:0/18:2 during the 6-hour period after ethanol administration; (3) the mean rate of formation of PEth 16:0/20:4 was lower than those of the other 2 homologs; (4) the mean half-life of PEth 16:0/20:4 was 2.18 days, which was shorter than that of either PEth 16:0/18:1 and PEth 16:0/18:2, which were 6.80 and 6.62, respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: The results of this study further confirm that PEth homologs are a sensitive biomarker for ethanol consumption. The measurement of three PEth homologs appears to provide additional information about the level and time frame of drinking.
Research into the gut microbiota of human infants is necessary in order to better understand how inter-species interactions and ecological succession shape the diversity of the gut microbiota, and in turn, how the specific composition of the gut microbiota impacts on host health both during infancy and in later years. Blastocystis is a ubiquitous intestinal protist that has been linked to a number of intestinal and extra-intestinal diseases. However, emerging data show that asymptomatic carriage is common and that Blastocystis is prevalent in the healthy adult gut microbiota. Nonetheless, little is known about the prevalence and diversity of this microorganism in the healthy infant gut, including when and how individuals become colonized by Blastocystis. Here, we surveyed the prevalence and diversity of Blastocystis in an infant population (n = 59) from an industrialized country (Ireland) using Blastocystis-specific primers at three or more time-points up to 24 months old. Only three infants were positive for Blastocystis (prevalence = 5%) and this was only noted for samples collected at month 24. This rate is comparatively low relative to previously reported prevalence rates in the contemporaneous adult population. These data suggest that infants in Westernized countries that are successfully colonized by Blastocystis most likely acquire this microorganism via horizontal transfer.
We analyze Sun-as-a-star observations spanning over solar cycles 22 – 24 from the ground-based network BiSON and solar cycles 23 – 24 collected by the space-based VIRGO and GOLF instruments on board the SoHO satellite. Using simultaneous observations from all three instruments, our analysis suggests that the structural and magnetic changes responsible for modifying the frequencies remained comparable between cycle 23 and cycle 24 but differ from cycle 22. Thus we infer that the magnetic layer of the Sun has become thinner since the beginning of cycle 23 and continues during the current cycle.
Using continuous observations for 22 years from ground-based network GONG and space-borne instruments MDI onboard SoHO and HMI onboard SDO, we report both global and local properties of the convection zone and their variations with time.
While a long history of experimental data shows that aerial thermal images can reveal a wide range of both surface and subsurface archaeological features, technological hurdles have largely prevented more widespread use of this promising prospecting method. However, recent advances in the sophistication of thermal cameras, the reliability of commercial drones, and the growing power of photogrammetric software packages are revolutionizing archaeologists' ability to collect, process, and analyze aerial thermal imagery. This paper provides an overview of the theory behind aerial thermography in archaeology, as well as a discussion of an emerging set of methods developed by the authors for undertaking successful surveys. Summarizing investigations at archaeological sites in North America, the Mediterranean, and the Near East, our results illustrate some contexts in which aerial thermography is very effective, as well as cases in which ground cover, soil composition, or the depth and character of archaeological features present challenges. In addition, we highlight novel approaches for filtering out noise caused by vegetation, as well as methods for improving feature visibility using radiometric thermal imagery.
Background: Stroke patients of lower socioeconomic status have worse outcomes. It remains poorly understood whether this is due to illness severity or personal or health system barriers. We explored the experiences of stroke patients with financial barriers in a qualitative descriptive pilot study, seeking to capture perceived challenges that interfere with their poststroke health and recovery. Methods: We interviewed six adults with a history of stroke and financial barriers in Alberta, Canada, inquiring about their: (1) experiences after stroke; (2) experience of financial barriers; (3) perceived reasons for financial barriers; (4) health consequences of financial barriers; and (5) mechanisms for coping with financial barriers. Two reviewers analyzed data using inductive thematic analysis. Results: The participants developed new or worsened financial circumstances as a consequence of stroke-related disability. Poststroke impairments and financial barriers took a toll on their mental health. They struggled to access several aspects of long-term poststroke care, including allied health professional services, medications, and proper nutrition. They described opportunity costs and tradeoffs when accessing health services. In several cases, they were unaware of health resources available to them and were hesitant to disclose their struggles to their physicians and even their families. Conclusion: Some patients with financial barriers perceive challenges to accessing various aspects of poststroke care. They may have inadequate knowledge of resources available to them and may not disclose their concerns to their health care team. This suggests that providers themselves might consider asking stroke patients about financial barriers to optimize their long-term poststroke care.
The aim of this study was to describe previously unrecognised or under-recognised adverse events associated with Melody® valve implantation.
In rare diseases and conditions, it is typically not feasible to conduct large-scale safety trials before drug or device approval. Therefore, post-market surveillance mechanisms are necessary to detect rare but potentially serious adverse events.
We reviewed the United States Food and Drug Administration’s Manufacturer and User Facility Device Experience (MAUDE) database and conducted a structured literature review to evaluate adverse events associated with on- and off-label Melody® valve implantation. Adverse events were compared with those described in the prospective Investigational Device Exemption and Post-Market Approval Melody® transcatheter pulmonary valve trials.
We identified 631 adverse events associated with “on-label” Melody® valve implants and 84 adverse events associated with “off-label” implants. The most frequent “on-label” adverse events were similar to those described in the prospective trials including stent fracture (n=210) and endocarditis (n=104). Previously unrecognised or under-recognised adverse events included stent fragment embolisation (n=5), device erosion (n=4), immediate post-implant severe valvar insufficiency (n=2), and late coronary compression (n=2 cases at 5 days and 3 months after implantation). Under-recognised adverse events associated with off-label implantation included early valve failure due to insufficiency when implanted in the tricuspid position (n=7) and embolisation with percutaneous implantation in the mitral position (n=5).
Post-market passive surveillance does not demonstrate a high frequency of previously unrecognised serious adverse events with “on-label” Melody® valve implantation. Further study is needed to evaluate safety of “off-label” uses.
The objective is to determine the nature of the unseen companion of the single-lined spectroscopic binary, WR 148 (= WN7h+?). The absence of companion lines supports a compact companion (cc) scenario. The lack of hard X-rays favours a non-compact companion scenario. Is WR 148 a commonplace WR+OB binary or a rare WR+cc binary?
This study examines the interplay between individual and social–developmental factors in the development of positive functioning, substance use problems, and mental health problems. This interplay is nested within positive and negative developmental cascades that span childhood, adolescence, the transition to adulthood, and adulthood. Data are drawn from the Seattle Social Development Project, a gender-balanced, ethnically diverse community sample of 808 participants interviewed 12 times from ages 10 to 33. Path modeling showed short- and long-term cascading effects of positive social environments, family history of depression, and substance-using social environments throughout development. Positive family social environments set a template for future partner social environment interaction and had positive influences on proximal individual functioning, both in the next developmental period and long term. Family history of depression adversely affected mental health functioning throughout adulthood. Family substance use began a cascade of substance-specific social environments across development, which was the pathway through which increasing severity of substance use problems flowed. The model also indicated that adolescent, but not adult, individual functioning influenced selection into positive social environments, and significant cross-domain effects were found in which substance-using social environments affected subsequent mental health.
The aim of the study was to evaluate the trends in respiratory syncytial virus-related hospitalisations and associated outcomes in children with haemodynamically significant heart disease in the United States of America.
The Kids’ Inpatient Databases (1997–2012) were used to estimate the incidence of respiratory syncytial virus hospitalisation among children ⩽24 months with or without haemodynamically significant heart disease. Weighted multivariable logistic regression and chi-square tests were used to evaluate the trends over time and factors associated with hospitalisation, comparing eras before and after publication of the 2003 American Academy of Pediatrics palivizumab immunoprophylaxis guidelines. Secondary outcomes included in-hospital mortality, morbidity, length of stay, and cost.
Overall, 549,265 respiratory syncytial virus-related hospitalisations were evaluated, including 2518 (0.5%) in children with haemodynamically significant heart disease. The incidence of respiratory syncytial virus hospitalisation in children with haemodynamically significant heart disease decreased by 36% when comparing pre- and post-palivizumab guideline eras versus an 8% decline in children without haemodynamically significant heart disease (p<0.001). Children with haemodynamically significant heart disease had higher rates of respiratory syncytial virus-associated mortality (4.9 versus 0.1%, p<0.001) and morbidity (31.5 versus 3.5%, p<0.001) and longer hospital length of stay (17.9 versus 3.9 days, p<0.001) compared with children without haemodynamically significant heart disease. The mean cost of respiratory syncytial virus hospitalisation in 2009 was $58,166 (95% CI:$46,017, $70,315).
These data provide stakeholders with a means to evaluate the cost–utility of various immunoprophylaxis strategies.