Improving Mechanical Circulatory Support Outcomes in Failing Bidirectional Glenn Physiology.

There remains high morbidity and mortality with mechanical circulatory support (MCS) in failing bidirectional Glenn (BDG) physiology. We performed a retrospective analysis of children with BDG physiology supported with MCS before and after 2018. Fourteen patients met inclusion criteria (median age 1.5 years, weight 9 kg). Prior to 2018 (n = 7), with variable anticoagulation and strategies including pulsatile VAD, continuous flow VAD, and extracorporeal membrane oxygenation (ECMO), 3 (43%) of patients were transplanted with a total of 536 patient-days of support (median 59 days). Major hemocompatability-related adverse event (MHRAE) rate was 63 per 100 patient-months. After 2018 (n = 7), using a staged support strategy (ECMO to pulsatile VAD) and bivalirudin anticoagulation, 5 (71%) patients were transplanted with a total of 1260 patient-days of support (median 188 days) and MHRAE rate of 24 per 100 patient-months. Despite challenging physiology, we have observed improved survival and reduced MHRAE despite longer support duration.

Contemporary outcomes of pediatric cardiac transplantation with a positive retrospective crossmatch.

BACKGROUND: A positive crossmatch (+ XM) has traditionally been associated with adverse outcomes following pediatric heart transplantation. However, more recent studies suggest that favorable intermediate-term outcomes may be achieved despite a + XM. This study's hypothesis is that children with a + XM have similar long-term survival, but higher rate of complications such as rejection, coronary allograft vasculopathy (CAV), and infection, compared to patients with a negative (-) XM. METHODS: The Pediatric Heart Transplant Society Registry (PHTS) database was queried from 2010-2021 for all patients <18 years of age with a known XM. Baseline demographics were compared between + XM and - XM groups using appropriate parametric and non-parametric group comparisons. Cox Proportional Hazards Modeling was used to identify risk factors for post-transplant graft loss, rejection, and CAV. RESULTS: Of 4599 pediatric heart transplants during the study period, XM results were available for 3914 (85%), of which 373 (9.5%) had a + XM. Univariate analysis showed lower 10-year survival for patients with + XM (HR = 1.3, p = .04). Multivariate analyses revealed no significant difference in 10-year survival in the 2 groups; however, time to first rejection (p = .0001) remained significantly shorter in the + XM group. CONCLUSIONS: Pediatric patients transplanted across a + XM experience earlier rejection; however, after multivariate adjustment, + XM is not independently associated with intermediate-term graft loss. The risk of heart transplantation against a + XM must be balanced with the ongoing risk of waitlist mortality.

Pediatric heart transplant waiting times in the United States since the 2016 allocation policy change.

We describe waiting times for pediatric heart transplant (HT) candidates after the 2016 revision to the US allocation policy. The OPTN database was queried for pediatric HT candidates listed between 7/2016 and 4/2019. Of the 1789 included candidates, 65% underwent HT, 14% died/deteriorated, 8% were removed for improvement, and 13% were still waiting at the end of follow-up. Most candidates were status 1A at HT (81%). Median wait times differ substantially by listing status, blood type, and recipient weight. The likelihood of HT was lower in candidates <25 kg and in those with blood type O; The <25 kg, blood type O subgroup experiences longer wait times and higher wait list mortality. For status 1A candidates, median wait times were 108 days (≤25 kg, blood type O), 80 days (≤25 kg, non-O), 47 days (>25 kg, O), and 24 days (>25 kg, non-O). We found that centers with more selective organ acceptance practices, based on a lower median Pediatric Heart Donor Assessment Tool (PH-DAT) score for completed transplants, experience longer status 1A wait times for their listed patients. These data can be used to counsel families and to select appropriate advanced heart failure therapies to support patients to transplant.

Health Help-Seeking Behaviour in Spiritual Healing Practice: Records from the Panacea Society's Healing Department, 1924-1997.

Why people seek help is a question shared by both health psychologists and scholars of spiritual healing. This overlap, however, has gone unexplored. This article shows convergence between health help-seeking behaviours in spiritual healing and secular professional health services. It does so by drawing on the archival records from the Panacea Society in Bedford, England, which began an international healing ministry by post-amassing over 120,000 correspondents from 93 different countries. Archives from the Panacea Society's Healing Department containing records of the self-reported effects of the prescribed water-taking healing ritual were used to investigate variables related to help-seeking for health problems through spiritual healing. A sample of over 10% of the available records (n = 7192) contained data from 40,627 letters written over a 73-year period from 48 different countries. In line with research from health psychology, and specifically the Health Belief Model, findings showed that those who were older, female, and receiving perceived benefits from treatment were more likely to engage in help-seeking.

Online education in a hurry: Delivering pediatric graduate medical education during COVID-19.

In the setting of the coronavirus disease 2019 (COVID-19) pandemic, an emergency hospital-wide eWork policy was enacted at Boston Children's Hospital on March 16, 2020. The number of clinicians on campus was restricted to only essential personnel, guidelines limited clinical care delivery to solely non-elective patients, and strict maximums were placed on the numbers of people allowed to congregate in the same physical space. With this abrupt transition to social distancing and electronic communication, the established approach to educating graduate medical trainees became obsolete overnight. Anticipating significant impact on trainee and faculty professional and personal lives, the importance of adaptive teaching strategies was evident. This document details one approach to redesigning the clinical learning system including a description of the learners and environment, the pedagogical principles that guided the approach, and technological tools used in implementation. Additionally, available literature pertinent to this topic is explored, assessment of the work to date is presented, and suggestions are provided regarding future directions related to online graduate medical education.

Sporadic Genetic Connectivity among Small Insular Populations of the Rare Geoendemic Plant Caulanthus amplexicaulis var. barbarae (Santa Barbara Jewelflower).

Globally, a small number of plants have adapted to terrestrial outcroppings of serpentine geology, which are characterized by soils with low levels of essential mineral nutrients (N, P, K, Ca, Mo) and toxic levels of heavy metals (Ni, Cr, Co). Paradoxically, many of these plants are restricted to this harsh environment. Caulanthus ampexlicaulis var. barbarae (Brassicaceae) is a rare annual plant that is strictly endemic to a small set of isolated serpentine outcrops in the coastal mountains of central California. The goals of the work presented here were to 1) determine the patterns of genetic connectivity among all known populations of C. ampexlicaulis var. barbarae, and 2) estimate contemporary effective population sizes (Ne), to inform ongoing genomic analyses of the evolutionary history of this taxon, and to provide a foundation upon which to model its future evolutionary potential and long-term viability in a changing environment. Eleven populations of this taxon were sampled, and population-genetic parameters were estimated using 11 nuclear microsatellite markers. Contemporary effective population sizes were estimated using multiple methods and found to be strikingly small (typically Ne < 10). Further, our data showed that a substantial component of genetic connectivity of this taxon is not at equilibrium, and instead showed sporadic gene flow. Several lines of evidence indicate that gene flow between isolated populations is maintained through long-distance seed dispersal (e.g., >1 km), possibly via zoochory.

Portable Automation of Static Chamber Sample Collection for Quantifying Soil Gas Flux.

Quantification of soil gas flux using the static chamber method is labor intensive. The number of chambers that can be sampled is limited by the spacing between chambers and the availability of trained research technicians. An automated system for collecting gas samples from chambers in the field would eliminate the need for personnel to return to the chamber during a flux measurement period and would allow a single technician to sample multiple chambers simultaneously. This study describes hamber utomated ampling quipment (Flux) to collect and store chamber headspace gas samples at assigned time points for the measurement of soil gas flux. The FluxCASE design and operation is described, and the accuracy and precision of the FluxCASE system is evaluated. In laboratory measurements of nitrous oxide (NO), carbon dioxide (CO), and methane (CH) concentrations of a standardized gas mixture, coefficients of variation associated with automated and manual sample collection were comparable, indicating no loss of precision. In the field, soil gas fluxes measured from FluxCASEs were in agreement with manual sampling for both NO and CO. Slopes of regression equations were 1.01 for CO and 0.97 for NO. The 95% confidence limits of the slopes of the regression lines included the value of one, indicating no bias. Additionally, an expense analysis found a cost recovery ranging from 0.6 to 2.2 yr. Implementing the FluxCASE system is an alternative to improve the efficiency of the static chamber method for measuring soil gas flux while maintaining the accuracy and precision of manual sampling.

The new subversive geranium: some notes on the management of additional troubles in maximum security prisons.

In this paper, we revisit King and McDermott's 1990 article on the social construction of 'control problem' prisoners and their management in high security prisons, in the light of our recent research on the location and building of trust in contemporary high security prisons. We examine how religious and race identities are now deeply implicated in the construction of risk, and we describe the procedures for and some of the consequences of managing the new risks of radicalization and extremist violence in prison. The analysis is based on observations and interviews with staff and prisoners in two main and two supplementary maximum-security prisons in England and Wales.

Plant diversity predicts beta but not alpha diversity of soil microbes across grasslands worldwide.

Aboveground-belowground interactions exert critical controls on the composition and function of terrestrial ecosystems, yet the fundamental relationships between plant diversity and soil microbial diversity remain elusive. Theory predicts predominantly positive associations but tests within single sites have shown variable relationships, and associations between plant and microbial diversity across broad spatial scales remain largely unexplored. We compared the diversity of plant, bacterial, archaeal and fungal communities in one hundred and forty-five 1 m(2) plots across 25 temperate grassland sites from four continents. Across sites, the plant alpha diversity patterns were poorly related to those observed for any soil microbial group. However, plant beta diversity (compositional dissimilarity between sites) was significantly correlated with the beta diversity of bacterial and fungal communities, even after controlling for environmental factors. Thus, across a global range of temperate grasslands, plant diversity can predict patterns in the composition of soil microbial communities, but not patterns in alpha diversity.

Impact of a positive crossmatch on pediatric heart transplant outcomes.

BACKGROUND: Pediatric heart transplant (HT) candidates experience high waitlist mortality due to a limited donor pool that is constrained in part by anti-HLA sensitization. We evaluated the impact of CDC and Flow donor-specific crossmatch (XM) results on pediatric HT outcomes. METHODS: All pediatric HTs between 1999 and 2019 in the OPTN database were included. Donor-specific XM results were sub-categorized based on CDC and Flow results. Primary outcomes were treated rejection in the first year and time to death or allograft loss. Propensity scores were utilized to adjust for differences in baseline characteristics. RESULTS: A total of 4,695 pediatric HT patients with T-cell XM data were included. After propensity score adjustment, a positive T-cell CDC-XM was associated with 2 times higher odds of treated rejection (OR 2.29 (1.56, 3.37)) and shorter time to death/allograft loss (HR 1.50 (1.19, 1.88)) compared to a negative Flow-XM. HT recipients who were Flow-XM positive with negative/unknown CDC-XM did not have higher odds of rejection or shorter time to death/allograft loss. An isolated positive B-cell XM was also not associated with worse outcomes. Over the study period XM testing shifted from CDC- to Flow-based assays. CONCLUSIONS: A positive donor-specific T-cell CDC-XM was associated with rejection and death/allograft loss following pediatric HT. This association was not observed with a positive T-cell Flow-XM or B-cell XM result alone. The shift away from performing the CDC-XM may result in loss of important prognostic information unless the clinical relevance of quantitative Flow-XM results on heart transplant outcomes is systematically studied.

Dual Magnetic Particle Imaging and Akaluc Bioluminescence Imaging for Tracking Cancer Cell Metastasis.

Magnetic particle imaging (MPI) provides hotspot tracking and direct quantification of superparamagnetic iron oxide nanoparticle (SPIO)-labelled cells. Bioluminescence imaging (BLI) with the luciferase reporter gene Akaluc can provide complementary information on cell viability. Thus, we explored combining these technologies to provide a more holistic view of cancer cell fate in mice. Akaluc-expressing 4T1Br5 cells were labelled with the SPIO Synomag-D and injected into the mammary fat pads (MFP) of four nude mice. BLI was performed on days 0, 6 and 13, and MPI was performed on days 1, 8 and 14. Ex vivo histology and fluorescence microscopy of MFP and a potential metastatic site was conducted. The BLI signal in the MFP increased significantly from day 0 to day 13 (p < 0.05), mirroring tumor growth. The MPI signal significantly decreased from day 1 to day 14 (p < 0.05) due to SPIO dilution in proliferating cells. Both modalities detected secondary metastases; however, they were visualized in different anatomical regions. Akaluc BLI complemented MPI cell tracking, allowing for longitudinal measures of cell viability and sensitive detection of distant metastases at different locations. We predict this multimodal imaging approach will help to evaluate novel therapeutics and give a better understanding of metastatic mechanisms.

A comparative genomic map for Caulanthus amplexicaulis and related species (Brassicaceae).

Adaptation to environment is the cornerstone of ecological genetics. The subject of this study is a wild relative of the sequenced and annotated model plant species, Arabidopsis thaliana. Caulanthus amplexicaulis var. barbarae lives on serpentine soils, known for high concentrations of heavy metals and low concentrations of essential plant macronutrients, and provides a compelling example of an organism's adaptation to environment. We constructed an F(2) linkage map, using a cross to the nonserpentine sister taxon, C. amplexicaulis var. amplexicaulis. C. amplexicaulis is a member of a highly diverse set of taxa (within the tribe Thelypodieae), described here as the 'Streptanthoid Complex' that are adapted to a broad range of environments, yet share a common n = 14 chromosome number and likely arose by a recent radiation. The linkage map consists of 97 polymorphic microsatellite markers, and 40 exon-primed intron-crossing markers based on A. thaliana exon sequences and Brassica ESTs. The map covers 14 linkage groups and has a total length of 1513 cM. Both the patterns of marker segregation and the comparative map indicate that C. amplexicaulis is a diploid organism with a compact genome. All exon-primed intron-crossing markers, and an unexpectedly large number of microsatellite markers (83%), had significant similarity to the A. thaliana genome, facilitating the development of a comparative genome map. As a proof of principle, we used the comparative map to identify candidate genes underlying differences in sepal colour between the two parent taxa. We demonstrate that the genomic tools developed here will be portable throughout the Streptanthoid Complex.

Outcomes of cardiac transplantation in highly sensitized pediatric patients.

Despite aggressive immunosuppressive therapy, pediatric orthotopic heart transplant (OHT) candidates with elevated pre-transplant panel reactive antibody (PRA) carry an increased risk of rejection and early graft failure following transplantation. This study has aimed to more specifically evaluate the outcomes of transplant candidates stratified by PRA values. Records of pediatric patients listed for OHT between April 2004 and July 2008 were reviewed (n = 101). Survival analysis was performed comparing patients with PRA < 25 to those with PRA > 25, as well as patients with PRA < 80 and PRA > 80. Patients with PRA > 25 had decreased survival compared with those with PRA < 25 after listing (P = 0.004). There was an even greater difference in survival between patients with PRA > 80 and those with PRA < 80 (P = 0.002). Similar analyses for the patients who underwent successful transplantation showed no significant difference in post-transplant survival between patients with a pre-transplant PRA > 25 and those with PRA < 25 (P = 0.23). A difference approaching significance was noted for patients with PRA > 80 compared with PRA < 80 (P = 0.066). Patients with significantly elevated pre-transplant PRAs at the time of listing have a significantly worse outcome compared to those with moderately increased PRA values or non-sensitized patients. Further study is necessary to guide physician and family treatment decisions at the time of listing.

Patients with single-ventricle physiology: prognostic implications of stress testing.

This study used a retrospective analysis of adults with single-ventricle physiology to ascertain the predictive power of cardiopulmonary stress-testing parameters in determining patients at increased risk of suffering from adverse clinical outcomes. We found that the specific parameters of percent of maximum predicted heart rate achieved and maximum oxygen consumption were significantly correlated with adverse clinical outcomes in patients with single-ventricle congenital heart disease.

Current evaluation and management of plastic bronchitis in the pediatric population.

OBJECTIVE: To describe a multidisciplinary approach for the treatment of plastic bronchitis (PB) in children. METHODS: Retrospective chart review of children with PB between 1997 and 2017. Data regarding clinical presentation, diagnosis, management, and outcomes were analyzed. RESULTS: Of 34 patients presenting with PB, 24 had single ventricle (SV) heart disease, 9 had pulmonary disease, and one had no underlying disease. Median (IQR: interquartile range) age at the time of PB diagnosis was 5.5 years (IQR: 9.0). Presenting symptoms included cough productive of casts (n = 27, 79%), wheezing (n = 5, 15%), dyspnea (n = 18, 53%), hypoxia (n = 31, 91%), and respiratory failure (n = 9, 26%). Diagnosis was made based on clinical evaluation, bronchoscopy findings, and/or pathology of casts. Treatment methods included bronchoscopy for cast removal (25% of SV patients, 91% of non-SV patients), chest physiotherapy (SV: 92%, non-SV: 45%), albuterol (SV: 79%, non-SV: 73%), inhaled steroids (SV: 75%, non-SV: 18%), nebulized hypertonic saline (SV: 29%, non-SV: 9%), nebulized heparin (SV: 8%, non-SV: 55%), nebulized tissue plasminogen activator (tPA; SV: 33%, non-SV: 9%), inhaled Dornase Alfa (SV: 54%, non-SV: 9%), antibiotics (SV: 46%, non-SV: 45%), systemic steroids (SV: 13%, non-SV: 45%), and lymphatic embolization (SV: 8%, non-SV: 45%). Of SV patients, 11 had no recurrence, 5 underwent heart transplantation, one awaits transplant, and 3 died due to cardiac disease. Three patients with respiratory disease had recurrent PB and one died from MRSA pneumonia. CONCLUSION: PB is a highly morbid disease with limited treatment options. Bronchoscopy and chest physiotherapy for airway clearance are among the most-utilized therapies.

Integrating the underlying structure of stochasticity into community ecology.

Stochasticity is a core component of ecology, as it underlies key processes that structure and create variability in nature. Despite its fundamental importance in ecological systems, the concept is often treated as synonymous with unpredictability in community ecology, and studies tend to focus on single forms of stochasticity rather than taking a more holistic view. This has led to multiple narratives for how stochasticity mediates community dynamics. Here, we present a framework that describes how different forms of stochasticity (notably demographic and environmental stochasticity) combine to provide underlying and predictable structure in diverse communities. This framework builds on the deep ecological understanding of stochastic processes acting at individual and population levels and in modules of a few interacting species. We support our framework with a mathematical model that we use to synthesize key literature, demonstrating that stochasticity is more than simple uncertainty. Rather, stochasticity has profound and predictable effects on community dynamics that are critical for understanding how diversity is maintained. We propose next steps that ecologists might use to explore the role of stochasticity for structuring communities in theoretical and empirical systems, and thereby enhance our understanding of community dynamics.

An experimental investigation of conformational fluctuations in proteins G and L.

The B1 domains of streptococcal proteins G and L are structurally similar, but they have different sequences and they fold differently. We have measured their NMR spectra at variable temperature using a range of concentrations of denaturant. Many residues have curved amide proton temperature dependence, indicating that they significantly populate alternative, locally unfolded conformations. The results, therefore, provide a view of the locations of low-lying, locally unfolded conformations. They indicate approximately 4-6 local minima for each protein, all within ca. 2.5 kcal/mol of the native state, implying a locally rough energy landscape. Comparison with folding data for these proteins shows that folding involves most molecules traversing a similar path, once a transition state containing a beta hairpin has been formed, thereby defining a well-populated pathway down the folding funnel. The hairpin that directs the folding pathway differs for the two proteins and remains the most stable part of the folded protein.

Identification of the Core Set of Carbon-Associated Genes in a Bioenergy Grassland Soil.

Despite the central role of soil microbial communities in global carbon (C) cycling, little is known about soil microbial community structure and even less about their metabolic pathways. Efforts to characterize soil communities often focus on identifying differences in gene content across environmental gradients, but an alternative question is what genes are similar in soils. These genes may indicate critical species or potential functions that are required in all soils. Here we identified the "core" set of C cycling sequences widely present in multiple soil metagenomes from a fertilized prairie (FP). Of 226,887 sequences associated with known enzymes involved in the synthesis, metabolism, and transport of carbohydrates, 843 were identified to be consistently prevalent across four replicate soil metagenomes. This core metagenome was functionally and taxonomically diverse, representing five enzyme classes and 99 enzyme families within the CAZy database. Though it only comprised 0.4% of all CAZy-associated genes identified in FP metagenomes, the core was found to be comprised of functions similar to those within cumulative soils. The FP CAZy-associated core sequences were present in multiple publicly available soil metagenomes and most similar to soils sharing geographic proximity. In soil ecosystems, where high diversity remains a key challenge for metagenomic investigations, these core genes represent a subset of critical functions necessary for carbohydrate metabolism, which can be targeted to evaluate important C fluxes in these and other similar soils.

Divergent responses of viral and bacterial communities in the gut microbiome to dietary disturbances in mice.

To improve our understanding of the stability of mammalian intestinal communities, we characterized the responses of both bacterial and viral communities in murine fecal samples to dietary changes between high- and low-fat (LF) diets. Targeted DNA extraction methods for bacteria, virus-like particles and induced prophages were used to generate bacterial and viral metagenomes as well as 16S ribosomal RNA amplicons. Gut microbiome communities from two cohorts of C57BL/6 mice were characterized in a 6-week diet perturbation study in response to high fiber, LF and high-refined sugar, milkfat (MF) diets. The resulting metagenomes from induced bacterial prophages and extracellular viruses showed significant overlap, supporting a largely temperate viral lifestyle within these gut microbiomes. The resistance of baseline communities to dietary disturbances was evaluated, and we observed contrasting responses of baseline LF and MF bacterial and viral communities. In contrast to baseline LF viral communities and bacterial communities in both diet treatments, baseline MF viral communities were sensitive to dietary disturbances as reflected in their non-recovery during the washout period. The contrasting responses of bacterial and viral communities suggest that these communities can respond to perturbations independently of each other and highlight the potentially unique role of viruses in gut health.

Comment on "Worldwide evidence of a unimodal relationship between productivity and plant species richness".

Fraser et al. (Reports, 17 July 2015, p. 302) report a unimodal relationship between productivity and species richness at regional and global scales, which they contrast with the results of Adler et al. (Reports, 23 September 2011, p. 1750). However, both data sets, when analyzed correctly, show clearly and consistently that productivity is a poor predictor of local species richness.