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Balloon valvuloplasty and surgical aortic valvotomy have been the treatment mainstays for congenital aortic stenosis in children. Choice of intervention often differs depending upon centre bias with limited relevant, comparative literature.
This study aims to provide an unbiased, contemporary matched comparison of these balloon and surgical approaches.
Retrospective analysis of patients with congenital aortic valve stenosis who underwent balloon valvuloplasty (Queensland Children’s Hospital, Brisbane) or surgical valvotomy (Royal Children’s Hospital, Melbourne) between 2005 and 2016. Patients were excluded if pre-intervention assessment indicated ineligibility to either group. Propensity score matching was performed based on age, weight, and valve morphology.
Sixty-five balloon patients and seventy-seven surgical patients were included. Overall, the groups were well matched with 18 neonates/25 infants in the balloon group and 17 neonates/28 infants in the surgical group. Median age at balloon was 92 days (range 2 days – 18.8 years) compared to 167 days (range 0 days – 18.1 years) for surgery (rank-sum p = 0.08). Mean follow-up was 5.3 years. There was one late balloon death and two early surgical deaths due to left ventricular failure. There was no significant difference in freedom from reintervention at latest follow-up (69% in the balloon group and 70% in the surgical group, p = 1.0).
Contemporary analysis of balloon aortic valvuloplasty and surgical aortic valvotomy shows no difference in overall reintervention rates in the medium term. Balloon valvuloplasty performs well across all age groups, achieving delay or avoidance of surgical intervention.
Creativity appears to be an important part of cognitive capacities and problem solving. Creativity is one’s ability to generate ideas that are novel, surprising, and compelling (Kaufman and Sternberg, 2010). This chapter will focus on the creative-cognitive approach, which seeks to further understand how human minds produce creative ideas.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
This study describes a procedural blank assessment of the ultraviolet photochemical oxidation (UV oxidation) method that is used to measure carbon isotopes of dissolved organic carbon (DOC) at the National Ocean Sciences Accelerator Mass Spectrometry Facility (NOSAMS). A retrospective compilation of Fm and δ13C results for secondary standards (OX-II, glycine) between 2009 and 2018 indicated that a revised blank correction was required to bring results in line with accepted values. The application of a best-fit mass-balance correction yielded a procedural blank of 22.0 ± 6.0 µg C with Fm of 0.30 ± 0.20 and δ13C of –32.0 ± 3.0‰ for this period, which was notably higher and more variable than previously reported. Changes to the procedure, specifically elimination of higher organic carbon reagents and improved sample and reactor handling, reduced the blank to 11.0 ± 2.75 µg C, with Fm of 0.14 ± 0.10 and δ13C of –31.0 ± 5.5‰. A thorough determination of the entire sample processing blank is required to ensure accurate isotopic compositions of seawater DOC using the UV oxidation method. Additional efforts are needed to further reduce the procedural blank so that smaller DOC samples can be analyzed, and to increase sample throughput.
The utility and efficacy of bolus dose vasopressors in hemodynamically unstable patients is well-established in the fields of general anesthesia and obstetrics. However, in the prehospital setting, minimal evidence for bolus dose vasopressor use exists and is primarily limited to critical care transport use. Hypotensive episodes, whether traumatic, peri-intubation-related, or septic, increase patient mortality. The purpose of this study is to assess the efficacy and adverse events associated with prehospital bolus dose epinephrine use in non-cardiac arrest, hypotensive patients treated by a single, high-volume, ground-based Emergency Medical Services (EMS) agency.
This is a retrospective, observational study of all non-cardiac arrest EMS patients treated for hypotension using bolus dose epinephrine from September 12, 2018 through September 12, 2019. Inclusion criteria for treatment with bolus dose epinephrine required a systolic blood pressure (SBP) measurement <90mmHg. A dose of 20mcg every two minutes, as needed, was allowed per protocol. The primary data source was the EMS electronic medical record.
Forty-two patients were treated under the protocol with a median (IQR) initial SBP immediately prior to treatment of 78mmHg (65-86) and a median (IQR) initial mean arterial pressure (MAP) of 58mmHg (50-66). The post-bolus SBP and MAP increased to 93mmHg (75-111) and 69mmHg (59-83), respectively. The two most common patient presentations requiring protocol use were altered mental status (55%) and respiratory failure (31%). Over one-half of the patients treated required both advanced airway management (62%) and multiple bolus doses of vasopressor support (55%). A single episode of transient severe hypertension (SBP>180mmHg) occurred, but there were no episodes of unstable tachyarrhythmia or cardiac arrest while en route or upon arrival to the receiving hospitals.
These preliminary data suggest that the administration of bolus dose epinephrine may be effective at rapidly augmenting hypotension in the prehospital setting with a minimal incidence of adverse events. Paramedic use of bolus dose epinephrine successfully increased SBP and MAP without clinically significant side effects. Prospective studies with larger sample sizes are needed to further investigate the effects of prehospital bolus dose epinephrine on patient morbidity and mortality.
UK Biobank is a well-characterised cohort of over 500 000 participants including genetics, environmental data and imaging. An online mental health questionnaire was designed for UK Biobank participants to expand its potential.
Describe the development, implementation and results of this questionnaire.
An expert working group designed the questionnaire, using established measures where possible, and consulting a patient group. Operational criteria were agreed for defining likely disorder and risk states, including lifetime depression, mania/hypomania, generalised anxiety disorder, unusual experiences and self-harm, and current post-traumatic stress and hazardous/harmful alcohol use.
A total of 157 366 completed online questionnaires were available by August 2017. Participants were aged 45–82 (53% were ≥65 years) and 57% women. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status. Lifetime depression was a common finding, with 24% (37 434) of participants meeting criteria and current hazardous/harmful alcohol use criteria were met by 21% (32 602), whereas other criteria were met by less than 8% of the participants. There was extensive comorbidity among the syndromes. Mental disorders were associated with a high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The UK Biobank questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed because of selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
Radnor Lake State Natural Area in Nashville, TN, has cedar glades that contain the endangered perennial herb wild dill [Perideridia americana (Nutt. ex DC.) Rchb.] and the invasive shrub Amur honeysuckle [Lonicera maackii (Rupr.) Herder]. This research examined whether L. maackii treatment in the Radnor Lake State Natural Area cedar glades is followed by an increase in P. americana plants. A grid of 60 adjacent 2 m by 4 m plots was placed in five cedar glades to encompass the P. americana population. With great care to protect P. americana, the annual treatment for L. maackii was to pull plants ≤1-m tall from the ground; and to cut stems >1-m tall and then treat the stumps with glyphosate. The t-tests of means for the log natural of the number of plants in the 60 plots (significance level of P-value = 0.05) were used to compare pretreatment L. maackii and P. americana counts with posttreatment counts in 2018 and P. americana counts at leaf out and flowering in 2018. The L. maackii population was significantly smaller (P-value < 0.001) in 2018 than pretreatment at all five sites. When pretreatment in 2014 and 2015 was compared with posttreatment in 2018 for the P. americana populations, the increases were significant at the Cheek, Harris 2, Hideaway, and Norfleet sites, but the increase at East Hall Farm was not significant. White-tailed deer (Odocoileus virginianus Zimmermann) trampling was the explanation given for the decreases in P. americana from leaf out to flowering at all five sites in 2018. Browsing was evident only at Hideaway, which had a greater loss for P. americana from leaf out to flowering in 2018 than the combined losses for the Cheek, East Hall Farm, Harris 2, and Norfleet sites. The research informed the creation of adaptive management decisions regarding monitoring and treatment of the invasive species L. maackii for an endangered species.
Good education requires student experiences that deliver lessons about practice as well as theory and that encourage students to work for the public good—especially in the operation of democratic institutions (Dewey 1923; Dewy 1938). We report on an evaluation of the pedagogical value of a research project involving 23 colleges and universities across the country. Faculty trained and supervised students who observed polling places in the 2016 General Election. Our findings indicate that this was a valuable learning experience in both the short and long terms. Students found their experiences to be valuable and reported learning generally and specifically related to course material. Postelection, they also felt more knowledgeable about election science topics, voting behavior, and research methods. Students reported interest in participating in similar research in the future, would recommend other students to do so, and expressed interest in more learning and research about the topics central to their experience. Our results suggest that participants appreciated the importance of elections and their study. Collectively, the participating students are engaged and efficacious—essential qualities of citizens in a democracy.
UK Biobank is a well-characterised cohort of over 500 000 participants that offers unique opportunities to investigate multiple diseases and risk factors.
An online mental health questionnaire completed by UK Biobank participants was expected to expand the potential for research into mental disorders.
An expert working group designed the questionnaire, using established measures where possible, and consulting with a patient group regarding acceptability. Case definitions were defined using operational criteria for lifetime depression, mania, anxiety disorder, psychotic-like experiences and self-harm, as well as current post-traumatic stress and alcohol use disorders.
157 366 completed online questionnaires were available by August 2017. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status than the general population across a range of indicators. Thirty-five per cent (55 750) of participants had at least one defined syndrome, of which lifetime depression was the most common at 24% (37 434). There was extensive comorbidity among the syndromes. Mental disorders were associated with high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed owing to selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
Declaration of interest
G.B. received grants from the National Institute for Health Research during the study; and support from Illumina Ltd. and the European Commission outside the submitted work. B.C. received grants from the Scottish Executive Chief Scientist Office and from The Dr Mortimer and Theresa Sackler Foundation during the study. C.S. received grants from the Medical Research Council and Wellcome Trust during the study, and is the Chief Scientist for UK Biobank. M.H. received grants from the Innovative Medicines Initiative via the RADAR-CNS programme and personal fees as an expert witness outside the submitted work.
Direct ink writing of silicone elastomers enables printing with precise control of porosity and mechanical properties of ordered cellular solids, suitable for shock absorption and stress mitigation applications. With the ability to manipulate structure and feedstock stiffness, the design space becomes challenging to parse to obtain a solution producing a desired mechanical response. Here, we derive an analytical design approach for a specific architecture. Results from finite element simulations and quasi-static mechanical tests of two different parallel strand architectures were analyzed to understand the structure-property relationships under uniaxial compression. Combining effective stiffness-density scaling with least squares optimization of the stress responses yielded general response curves parameterized by resin modulus and strand spacing. An analytical expression of these curves serves as a reduced order model, which, when optimized, provides a rapid design capability for filament-based 3D printed structures. As a demonstration, the optimal design of a face-centered tetragonal architecture is computed that satisfies prescribed minimum and maximum load constraints.
OBJECTIVES/SPECIFIC AIMS: Platelets govern signal-dependent inflammatory responses by leukocytes. Although dysregulated inflammation is common in older adults, platelet-leukocyte signaling events and downstream inflammatory gene synthesis in aging is not known. METHODS/STUDY POPULATION: Highly-purified platelets and monocytes were isolated from healthy older (age>60, n=27) and younger (age<45, n=36) adults and incubated together in autologous and nonautologous conditions. Inflammatory gene synthesis by monocytes, basally and in the presence of activated platelets, was examined. Next-generation RNA-sequencing allowed for unbiased profiling of the platelet transcriptome in older and younger adults. Differentially expressed candidates in aged platelets were validated and recombinant granzyme A (in the presence and absence of TLR4 and Caspase-1 inhibition) identified putative ligands controlling inflammatory gene synthesis. RESULTS/ANTICIPATED RESULTS: In unstimulated or activated conditions, monocyte chemoattractant protein 1 (MCP-1) and interleukin-8 (IL-8) synthesis by monocytes alone did not differ between older and younger adults. However, in the presence of autologous activated platelets, monocytes from older adults synthesized significantly greater MCP-1 (867.150 vs. 216.36 ng/mL, p<0.0001) and IL-8 (41.5 vs. 9.2 ng/mL, p<0.0001) than younger adults. Nonautologous, or switch experiments, demonstrated that aged platelets were sufficient for upregulating MCP-1 and IL-8 synthesis by monocytes. Surprisingly, classic platelet proteins known to signal to monocytes and induce MCP-1 synthesis (p-selectin, RANTES, and PF4) were not increased in platelets from older adults. Using RNA-seq followed by validation via RT-PCR and immunoblot, we identified candidate platelet molecules increased in aging that mediate platelet-monocyte signaling and pro-inflammatory gene synthesis. We confirmed that granzyme A (GrmA), a serine protease not previously identified in platelets, is present in human platelets at the mRNA and protein level. GrmA is secreted by activated platelets in signal-dependent fashion. Moreover, GrmA in platelets is significantly increased in aging (~9-fold vs. younger adults). Blocking GrmA inhibited MCP-1 and IL-8 synthesis in older adults. Finally, we uncovered that platelet GrmA signaling to monocytes is regulated through TLR4 and Caspase-1. DISCUSSION/SIGNIFICANCE OF IMPACT: Human aging is associated with reprogramming of the platelet transcriptome. A previously unrecognized protein in platelets, GrmA, is increased in aging and causes increased MCP-1 and IL-8 gene synthesis by target monocytes in a TLR4 and Caspase-1 dependent mechanism. Increased platelet GrmA in aging may contribute to injurious inflammatory responses common in older adults.
Policy-makers and practitioners have a need to assess community resilience in disasters. Prior efforts conflated resilience with community functioning, combined resistance and recovery (the components of resilience), and relied on a static model for what is inherently a dynamic process. We sought to develop linked conceptual and computational models of community functioning and resilience after a disaster.
We developed a system dynamics computational model that predicts community functioning after a disaster. The computational model outputted the time course of community functioning before, during, and after a disaster, which was used to calculate resistance, recovery, and resilience for all US counties.
The conceptual model explicitly separated resilience from community functioning and identified all key components for each, which were translated into a system dynamics computational model with connections and feedbacks. The components were represented by publicly available measures at the county level. Baseline community functioning, resistance, recovery, and resilience evidenced a range of values and geographic clustering, consistent with hypotheses based on the disaster literature.
The work is transparent, motivates ongoing refinements, and identifies areas for improved measurements. After validation, such a model can be used to identify effective investments to enhance community resilience. (Disaster Med Public Health Preparedness. 2018;12:127–137)
Twin pairs discordant for disease may help elucidate the epigenetic mechanisms and causal environmental factors in disease development and progression. To obtain the numbers of pairs, especially monozygotic (MZ) twin pairs, necessary for in-depth studies while also allowing for replication, twin studies worldwide need to pool their resources. The Discordant Twin (DISCOTWIN) consortium was established for this goal. Here, we describe the DISCOTWIN Consortium and present an analysis of type 2 diabetes (T2D) data in nearly 35,000 twin pairs. Seven twin cohorts from Europe (Denmark, Finland, Norway, the Netherlands, Spain, Sweden, and the United Kingdom) and one from Australia investigated the rate of discordance for T2D in same-sex twin pairs aged 45 years and older. Data were available for 34,166 same-sex twin pairs, of which 13,970 were MZ, with T2D diagnosis based on self-reported diagnosis and medication use, fasting glucose and insulin measures, or medical records. The prevalence of T2D ranged from 2.6% to 12.3% across the cohorts depending on age, body mass index (BMI), and national diabetes prevalence. T2D discordance rate was lower for MZ (5.1%, range 2.9–11.2%) than for same-sex dizygotic (DZ) (8.0%, range 4.9–13.5%) pairs. Across DISCOTWIN, 720 discordant MZ pairs were identified. Except for the oldest of the Danish cohorts (mean age 79), heritability estimates based on contingency tables were moderate to high (0.47–0.77). From a meta-analysis of all data, the heritability was estimated at 72% (95% confidence interval 61–78%). This study demonstrated high T2D prevalence and high heritability for T2D liability across twin cohorts. Therefore, the number of discordant MZ pairs for T2D is limited. By combining national resources, the DISCOTWIN Consortium maximizes the number of discordant MZ pairs needed for in-depth genotyping, multi-omics, and phenotyping studies, which may provide unique insights into the pathways linking genes to the development of many diseases.
Nanoparticles have applications in a diverse range of products including medications, detergents, cosmetics, paint, sunscreen and electronics, with an economic worth projected to reach $2.5 trillion dollars in 2015. Research into the effects of manufactured nanomaterials on the environment, however, has failed to keep pace with the high volume of commercial production. Whereas a number of studies have examined the effects of nanoparticles on aquatic species, little work has focused on the way in which benthic marine species encounter, ingest and depurate these materials. The purpose of this study was to examine the ingestion and depuration of titania nanoparticles (anatase) by the blue mussel (Mytilus edulis) and the eastern oyster (Crassostrea virginica) during a spill scenario (an acute exposure to elevated concentrations). Bivalves were exposed to nanoparticles either incorporated into marine snow, an environmentally relevant medium for pollutants, or added directly to seawater at a concentration of 4.5 mg L−1 for 2 h. After feeding, the animals were transferred to filtered seawater and allowed to depurate. Faeces and tissues were collected at 0, 6, 24, 72 and 120 h, post-exposure, and analysed for concentrations of titanium by inductively coupled plasma-mass spectrometry. Results indicated that the capture and ingestion of titania nanoparticles by both species was not dependent on the method of delivery (incorporated into marine snow or freely suspended). Additionally, greater than 90% of the titania nanoparticles, on average, were eliminated from the tissues after 6 h, and only trace amounts remained after 72 h. These data demonstrate that mussels and oysters readily ingest titania nanoparticles, but rapidly depurate the material within hours of an acute exposure suggesting that little would be transferred to secondary consumers including humans. Further research is required to determine if other species of suspension-feeders handle titania nanoparticles in a manner similar to bivalves.