Desktop 3D printed anatomic models for minimally invasive direct coronary artery bypass.

BACKGROUND: Three-dimensional (3D) printing technology has impacted many clinical applications across medicine. However, 3D printing for Minimally Invasive Direct Coronary Artery Bypass (MIDCAB) has not yet been reported in the peer-reviewed literature. The current observational cohort study aimed to evaluate the impact of half scaled (50% scale) 3D printed (3DP) anatomic models in the pre-procedural planning of MIDCAB. METHODS: Retrospective analysis included 12 patients who underwent MIDCAB using 50% scale 3D printing between March and July 2020 (10 males, 2 females). Distances measured from CT scans and 3DP anatomic models were correlated with Operating Room (OR) measurements. The measurements were compared statistically using Tukey's test. The correspondence between the predicted (3DP & CT) and observed best InterCostal Space (ICS) in the OR was recorded. Likert surveys from the 3D printing registry were provided to the surgeon to assess the utility of the model. The OR time saved by planning the procedure using 3DP anatomic models was estimated subjectively by the cardiothoracic surgeon. RESULTS: All 12 patients were successfully grafted. The 3DP model predicted the optimal ICS in all cases (100%). The distances measured on the 3DP model corresponded well to the distances measured in the OR. The measurements were significantly different between the CT and 3DP (p < 0.05) as well as CT and OR (p < 0.05) groups, but not between the 3DP and OR group. The Likert responses suggested high clinical utility of 3D printing. The mean subjectively estimated OR time saved was 40 min. CONCLUSION: The 50% scaled 3DP anatomic models demonstrated high utility for MIDCAB and saved OR time while being resource efficient. The subjective benefits over routine care that used 3D visualization for surgical planning warrants further investigation.

Dapagliflozin and Empagliflozin in Paediatric Indications: A Systematic Review.

INTRODUCTION: In adults, sodium-glucose cotransporter type 2 inhibitors have revolutionised the treatment of type 2 diabetes mellitus, heart failure, and chronic kidney disease. OBJECTIVE: We aimed to review information on compassionate use, clinical pharmacology, efficacy, and safety of dapagliflozin and empagliflozin in children. METHODS: We conducted a systematic review of published clinical trials, case reports, and observational studies in Medline, Excerpta Medica, and Web of Science databases from inception to September 2023. For the two randomised controlled trials on type 2 diabetes mellitus (T2DM), we implemented a meta-analysis on the primary outcome (mean difference in glycosylated haemoglobin [HbA1c] between intervention and placebo groups). Review Manager (RevMan), version 5.4.1, was used for this purpose. RESULTS: Thirty-five articles (nine case reports, ten case series, one prospective non-controlled trial, four controlled randomised trials, two surveys, six pharmacokinetic studies, and three pharmacovigilance studies) were selected, in which 415 children were exposed to either dapagliflozin or empagliflozin: 189 diabetic patients (mean age 14.7 ± 2.9 years), 32 children with glycogen storage disease type Ib (GSD Ib), glucose-6-phosphatase catalytic subunit 3 (G6PC3) deficiency, or severe congenital neutropenia type 4 (8.5 ± 5.1 years), 47 children with kidney disease or heart failure (11.2 ± 6.1 years), 84 patients in pharmacokinetic studies (15.1 ± 2.3 years), and 63 patients in toxicological series. The effect of dapagliflozin and empagliflozin in T2DM was demonstrated by HbA1c reduction in two randomised trials among a total of 177 adolescents, with a mean HbA1c difference of -0.82% (95% confidence interval -1.34 to -0.29) as compared to placebo (no heterogeneity, I2 = 0%). Dosage ranged between 5 and 20 mg (mean 11.4 ± 3.7) once daily for dapagliflozin and between 5 and 25 mg (mean 15.4 ± 7.4) once daily for empagliflozin. Among the paediatric cases of GSD Ib, empagliflozin 0.1-1.3 mg/kg/day improved neutropenia, infections, and gastrointestinal health. Dapagliflozin (mean dosage 6.9 ± 5.2 mg once daily) was well-tolerated in children with chronic kidney disease and heart failure. Side effects were generally mild, the most frequent being hypoglycaemia in children with GSD Ib (33% of patients) or T2DM (14% of patients) on concomitant hypoglycaemic drugs. Diabetic ketoacidosis is rare in children. CONCLUSION: Early evidence suggests that dapagliflozin and empagliflozin are well tolerated in children. A clinical pharmacology rationale currently exists only for adolescents with diabetes mellitus. PROSPERO REGISTRATION NUMBER: CRD42023438162.

Source Localization of Normal Variants Seen on EEG.

PURPOSE: The EEG is an essential neurological diagnostic tool. EEG abnormalities can guide diagnosis and management of epilepsy. There are also distinctive EEG waveforms that are seen in healthy individuals. It is critical not to misinterpret these as abnormal. To emphasize the importance of these waveforms, we analyzed different normal variants via the source localization technology. METHODS: This is a retrospective analysis of EEGs performed at the Duke University Hospital between June 2014 and Dec 2019. We selected samples of vertex waves, Mu, lambda, POSTS, wickets, and sleep spindles for analysis. EEG were imported to Curry 8 (Compumedics) to calculate the dipole and current density. The averaged head model from the Montreal Neurological Institute database was used for reconstruction. RESULTS: Thirty-four patient EEG samples were selected including five vertex, six Mu, four wicket, seven lambda, five POSTS, and seven spindles. Results from source localization showed that vertex waves are localized in the frontocentral area, whereas spindles in the deep midline central region. Mu were identified in the ipsilateral somatosensory cortex. Lambda and POSTS, on the other hand, had maximum results over the bilateral occipital region and wickets in the ipsilateral temporal lobe. CONCLUSIONS: Our results confirm and expand previous hypotheses. This allows us to speculate on the origin of these normal EEG variants. Although this study is limited by small sample size, lack of high-density EEG, and patient-specific MRI, our analysis provides an easily replicable three-dimensional visualization of these waveforms.

Rapid desensitization through immunoadsorption during cardiopulmonary bypass. A novel method to facilitate human leukocyte antigen incompatible heart transplantation.

BACKGROUND: Anti-human leukocyte antigen (HLA)-antibody production represents a major barrier to heart transplantation, limiting recipient compatibility with potential donors and increasing the risk of complications with poor waiting-list outcomes. Currently there is no consensus to when desensitization should take place, and through what mechanism, meaning that sensitized patients must wait for a compatible donor for many months, if not years. We aimed to determine if intraoperative immunoadsorption could provide a potential desensitization methodology. METHODS: Anti-HLA antibody-containing whole blood was added to a Cardiopulmonary bypass (CPB) circuit set up to mimic a 20 kg patient undergoing heart transplantation. Plasma was separated and diverted to a standalone, secondary immunoadsorption system, with antibody-depleted plasma returned to the CPB circuit. Samples for anti-HLA antibody definition were taken at baseline, when combined with the CPB prime (on bypass), and then every 20 min for the duration of treatment (total 180 min). RESULTS: A reduction in individual allele median fluorescence intensity (MFI) to below clinically relevant levels (<1000 MFI), and in the majority of cases below the lower positive detection limit (<500 MFI), even in alleles with a baseline MFI >4000 was demonstrated. Reduction occurred in all cases within 120 min, demonstrating efficacy in a time period usual for heart transplantation. Flowcytometric crossmatching of suitable pseudo-donor lymphocytes demonstrated a change from T cell and B cell positive channel shifts to negative, demonstrating a reduction in binding capacity. CONCLUSIONS: Intraoperative immunoadsorption in an ex vivo setting demonstrates clinically relevant reductions in anti-HLA antibodies within the normal timeframe for heart transplantation. This method represents a potential desensitization technique that could enable sensitized children to accept a donor organ earlier, even in the presence of donor-specific anti-HLA antibodies.

MIB-derived odor management based upon hydraulic regulation in small drinking water reservoirs: Principle and application.

The musty odorant (2-methylisoborneol, MIB) is prevalent in source water reservoirs and has become one of the major challenges for drinking water quality. This study proposes an approach to control the growth of MIB-producing cyanobacteria in a small reservoir based on hydraulic regulation, according to the results of long-term field investigations, laboratory culture experiments, model construction, and field application. Field investigations found that longer hydraulic retention time (HRT) is a factor that triggers MIB episodes. The culture study revealed that the maximum cell density, growth rate of MIB-producing Planktothricoides raciborskii, and MIB concentration are determined by the HRT (R2= 0.94, p-value < 0.001) and can be minimized by decreasing the HRT to less than 10 d. On this basis, an HRT regulation model was constructed and validated by field investigation, and critical HRT values were evaluated for 14 cyanobacteria genera. By decreasing the HRT to 5.4 ± 0.8 d, which is lower than the critical value of 7.5 ∼ 15.0 d, an MIB episode was successfully terminated in ZXD Reservoir in 2021. The results suggest that the proposed principle can provide a scientific basis for HRT regulation, which has been proved to be effective and feasible. This approach avoids negative impacts on water quality, does not require extra investment in engineering infrastructure, and in some cases may be applied readily by changing existing operational procedures. Therefore, HRT-based regulation is a promising strategy targeting MIB control and possibly for other cyanobacterial-derived water quality problems in small reservoirs.

Evaluating Ultrasonicator Performance for Cyanobacteria Management at Freshwater Sources.

Algal blooms consisting of potentially toxic cyanobacteria are a growing source water management challenge faced by water utilities globally. Commercially available sonication devices are designed to mitigate this challenge by targeting cyanobacteria-specific cellular features and aim to inhibit cyanobacterial growth within water bodies. There is limited available literature evaluating this technology; therefore, a sonication trial was conducted in a drinking water reservoir within regional Victoria, Australia across an 18-month period using one device. The trial reservoir, referred to as Reservoir C, is the final reservoir in a local network of reservoirs managed by a regional water utility. Sonicator efficacy was evaluated through qualitative and quantitative analysis of algal and cyanobacterial trends within Reservoir C and surrounding reservoirs using field data collected across three years preceding the trial and during the 18-month duration of the trial. Qualitative assessment revealed a slight increase in eukaryotic algal growth within Reservoir C following device installation, which is likely due to local environmental factors such as rainfall-driven nutrient influx. Post-sonication quantities of cyanobacteria remained relatively consistent, which may indicate that the device was able to counteract favorable phytoplankton growth conditions. Qualitative assessments also revealed minimal prevalence variations of the dominant cyanobacterial species within the reservoir following trial initiation. Since the dominant species were potential toxin producers, there is no strong evidence that sonication altered Reservoir C's water risk profiles during this trial. Statistical analysis of samples collected within the reservoir and from the intake pipe to the associated treatment plant supported qualitative observations and revealed a significant elevation in eukaryotic algal cell counts during bloom and non-bloom periods post-installation. Corresponding cyanobacteria biovolumes and cell counts revealed that no significant changes occurred, excluding a significant decrease in bloom season cell counts measured within the treatment plant intake pipe and a significant increase in non-bloom season biovolumes and cell counts as measured within the reservoir. One technical disruption occurred during the trial; however, this had no notable impacts on cyanobacterial prevalence. Acknowledging the limitations of the experimental conditions, data and observations from this trial indicate there is no strong evidence that sonication significantly reduced cyanobacteria occurrence within Reservoir C.

Baseline Characteristics of Pediatric Patients With Heart Failure Due to Systemic Left Ventricular Systolic Dysfunction in the PANORAMA-HF Trial.

BACKGROUND: Sacubitril/valsartan has been approved for the management of heart failure (HF) with reduced ejection fraction in adults. PANORAMA-HF trial (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF) investigated its effects on clinical outcomes in pediatric patients with HF. METHODS: PANORAMA-HF is a multicenter, Phase II/III study using an adaptive, seamless, 2-part design. The study aimed to evaluate the pharmacokinetics and pharmacodynamics of single doses of sacubitril/valsartan (Part 1), and the efficacy and safety of sacubitril/valsartan versus enalapril administered twice daily for 52 weeks (Part 2) in pediatric patients with HF due to left ventricular systolic dysfunction with biventricular heart physiology. An innovative trial design using a novel global rank assessment of severity was employed. For analysis, eligible patients were stratified into 3 age groups (Group 1, 6 to <18 years; Group 2a, 2 to <6 years; and Group 3a, 1 month to <2 years) and functional classification (New York Heart Association/Ross class I/II and III/IV). RESULTS: We report the key demographic, baseline, and clinical characteristics of 375 pediatric patients randomized to receive the study medication. The mean age for patients in Groups 1, 2a, and 3a was 12.2, 3.2, and 1.3 years, respectively. About 70% of patients had a prior HF hospitalization, 85% had New York Heart Association/Ross class I/II HF, and ≈8% were angiotensin-converting enzyme inhibitor/angiotensin receptor blocker naïve. CONCLUSIONS: Compared to other pediatric HF studies, PANORAMA-HF recruited a relatively homogeneous pediatric HF population across 3 age groups, enabling a more robust evaluation of pharmacokinetics/pharmacodynamics and efficacy/safety of sacubitril/valsartan. Most patients had mildly symptomatic HF at baseline. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02678312.

Utility and Costs During the Initial Year of 3D Printing in an Academic Hospital.

OBJECTIVE: There is a paucity of utility and cost data regarding the launch of 3D printing in a hospital. The objective of this project is to benchmark utility and costs for radiology-based in-hospital 3D printing of anatomic models in a single, adult academic hospital. METHODS: All consecutive patients for whom 3D printed anatomic models were requested during the first year of operation were included. All 3D printing activities were documented by the 3D printing faculty and referring specialists. For patients who underwent a procedure informed by 3D printing, clinical utility was determined by the specialist who requested the model. A new metric for utility termed Anatomic Model Utility Points with range 0 (lowest utility) to 500 (highest utility) was derived from the specialist answers to Likert statements. Costs expressed in United States dollars were tallied from all 3D printing human resources and overhead. Total costs, focused costs, and outsourced costs were estimated. The specialist estimated the procedure room time saved from the 3D printed model. The time saved was converted to dollars using hospital procedure room costs. RESULTS: The 78 patients referred for 3D printed anatomic models included 11 clinical indications. For the 68 patients who had a procedure, the anatomic model utility points had an overall mean (SD) of 312 (57) per patient (range, 200-450 points). The total operation cost was $213,450. The total cost, focused costs, and outsourced costs were $2,737, $2,180, and $2,467 per model, respectively. Estimated procedure time saved had a mean (SD) of 29.9 (12.1) min (range, 0-60 min). The hospital procedure room cost per minute was $97 (theoretical $2,900 per patient saved with model). DISCUSSION: Utility and cost benchmarks for anatomic models 3D printed in a hospital can inform health care budgets. Realizing pecuniary benefit from the procedure time saved requires future research.

Exploring the Possible Impact of Echocardiographic Diastolic Function Parameters on Outcome in Paediatric Dilated Cardiomyopathy.

Diastolic dysfunction is an important determinant for prognosis and survival in several paediatric heart diseases. We aimed to explore its possible impact on outcome in children with dilated cardiomyopathy. From 2006 to 2016, children less than 18 years old with dilated cardiomyopathy were retrospectively enrolled. Echocardiographic diastolic function parameters and child outcomes were analysed. Of 43 children aged 0.2 to 16.1 years old referred with dilated cardiomyopathy, 8 patients required cardiac transplant or mechanical assist devices (18%), 24 had persistently abnormal left ventricular function and/or dilatation (56%) and 11 patients recovered (26%). There was no significant difference in mitral velocities on Tissue Doppler Imaging, mitral valve inflow velocities, isovolumic relaxation time, left atrial area z-score and mitral lateral E/e' ratios between patients with recovery and patients with disease progression or persistently abnormal ventricular function and/or dilation. This is the first study on childhood dilated cardiomyopathy to address individual echocardiographic diastolic function parameters and their association to recovery. In this study, echocardiographic parameters for diastolic function did not predict recovery.

Pediatric heart transplantation following donation after circulatory death, distant procurement, and ex-situ perfusion.

BACKGROUND: Limited availability of suitable donor hearts remains a challenge to pediatric heart transplantation, contributing to waitlist mortality. Controlled donation after circulatory death (DCD) has demonstrated success in adults. Early series of pediatric DCD heart transplantation using cold storage alone reported significant early mortality. We report a collaboration between 2 centers in the United Kingdom, combining expertise in adult DCD organ retrieval and pediatric transplantation. METHODS: This retrospective series comprises 6 children (4 male, all >20 kg) undergoing DCD heart transplantation at Great Ormond Street Hospital between 1 February and 30 September 2020, following retrieval with direct procurement and perfusion using portable normothermic machine perfusion by the Royal Papworth Hospital service. Baseline characteristics and 1-year follow-up were compared to 9 children who underwent donation after brain death (DBD) transplants contemporaneously. RESULTS: Mean DCD donor age was 24.67 years and mean DCD recipient age was 13.83 years. Mean functional warm ischemic time was 28.5 minutes and ex-situ heart perfusion time was 280 minutes. Median ICU and hospital stay were 9 and 17 days, respectively. All children survived to 1-year post-transplant. Survival and ICU and hospital stay were similar between the DCD and DBD cohorts. Performing DCD transplants resulted in a 66.7% increase in transplants for children >20 kg at GOSH during the study. CONCLUSIONS: This series demonstrates that DCD heart transplant can be performed safely with excellent short-term survival in children. Although the cohort is small, there was no significant difference in major outcomes compared to a DBD cohort.

Visualizing dynamic data with heat triangles.

In this paper, an overview-based interactive visualization for temporally long dynamic data sequences is described. To reach this goal, each data object at a certain time point can be mapped to a number value based on a given property. Among others, a property is application-dependent and can be number of vertices, number of edges, average degree, density, number of self-loops, degree (maximum and total), or edge weight (minimum, maximum, and total) for dynamic graph data, but it can as well be the number of ball contacts in a football match, or the time-dependent visual attention paid to a stimulus in an eye tracking study. To achieve an overview over time, an aggregation strategy based on either the mean, minimum, or maximum of two values is applied. This temporal value aggregation generates a triangular shape with an overview of the entire data sequence as the peak. The color coding can be adjusted, forming visual patterns that can be rapidly explored for certain data features over time, supporting comparison tasks between the properties. The usefulness of the approach is illustrated by means of applying it to dynamic graphs generated from US domestic flight data as well as to dynamic Covid-19 infections on country levels.

Dynamic graph exploration by interactively linked node-link diagrams and matrix visualizations.

The visualization of dynamic graphs is a challenging task owing to the various properties of the underlying relational data and the additional time-varying property. For sparse and small graphs, the most efficient approach to such visualization is node-link diagrams, whereas for dense graphs with attached data, adjacency matrices might be the better choice. Because graphs can contain both properties, being globally sparse and locally dense, a combination of several visual metaphors as well as static and dynamic visualizations is beneficial. In this paper, a visually and algorithmically scalable approach that provides views and perspectives on graphs as interactively linked node-link and adjacency matrix visualizations is described. As the novelty of this technique, insights such as clusters or anomalies from one or several combined views can be used to influence the layout or reordering of the other views. Moreover, the importance of nodes and node groups can be detected, computed, and visualized by considering several layout and reordering properties in combination as well as different edge properties for the same set of nodes. As an additional feature set, an automatic identification of groups, clusters, and outliers is provided over time, and based on the visual outcome of the node-link and matrix visualizations, the repertoire of the supported layout and matrix reordering techniques is extended, and more interaction techniques are provided when considering the dynamics of the graph data. Finally, a small user experiment was conducted to investigate the usability of the proposed approach. The usefulness of the proposed tool is illustrated by applying it to a graph dataset, such as e co-authorships, co-citations, and a Comprehensible Perl Archive Network distribution.

Silk-Cellulose Acetate Biocomposite Materials Regenerated from Ionic Liquid.

The novel use of ionic liquid as a solvent for biodegradable and natural organic biomaterials has increasingly sparked interest in the biomedical field. As compared to more volatile traditional solvents that rapidly degrade the protein molecular weight, the capability of polysaccharides and proteins to dissolve seamlessly in ionic liquid and form fine and tunable biomaterials after regeneration is the key interest of this study. Here, a blended system consisting of Bombyx Mori silk fibroin protein and a cellulose derivative, cellulose acetate (CA), in the ionic liquid 1-ethyl-3-methylimidazolium acetate (EMIMAc) was regenerated and underwent characterization to understand the structure and physical properties of the films. The change in the morphology of the biocomposites (by scanning electron microscope, SEM) and their secondary structure analysis (by Fourier-transform infrared spectroscopy, FTIR) showed that the samples underwent a wavering conformational change on a microscopic level, resulting in strong interactions and changes in their crystalline structures such as the CA crystalline and silk beta-pleated sheets once the different ratios were applied. Differential scanning calorimetry (DSC) results demonstrated that strong molecular interactions were generated between CA and silk chains, providing the blended films lower glass transitions than those of the pure silk or cellulose acetate. All films that were blended had higher thermal stability than the pure cellulose acetate sample but presented gradual changes amongst the changing of ratios, as demonstrated by thermogravimetric analysis (TGA). This study provides the basis for the comprehension of the protein-polysaccharide composites for various biomedical applications.

Intraoperative anti-A/B immunoadsorption is associated with significantly reduced blood product utilization with similar outcomes in pediatric ABO-incompatible heart transplantation.

BACKGROUND: Intraoperative anti-A/B immunoadsorption (ABO-IA) was recently introduced for ABO-incompatible heart transplantation. Here we report the first case series of patients transplanted with ABO-IA, and compare outcomes with those undergoing plasma exchange facilitated ABO-incompatible heart transplantation (ABO-PE). METHODS: Data were retrospectively analysed on all ABO-incompatible heart transplants undertaken at a single centre between January 1, 2000 and June 1, 2020. Data included all routine laboratory tests, demographics and pre-operative characteristics, intraoperative details and post-operative outcomes. Primary outcome measures were volume of blood product transfusions, maximum post-transplant isohaemagglutinin titres, occurrence of rejection and graft survival. Secondary outcome measures were length of intensive care and hospital stay. Demographic and survival data were also obtained for ABO-compatible transplants during the same time period for comparison. RESULTS: Thirty-seven patients underwent ABO-incompatible heart transplantation, with 27 (73%) using ABO-PE and 10 (27%) using ABO-IA. ABO-IA patients were significantly older than ABO-PE patients (p < 0.001) and the total volume of blood products transfused during the hospital admission was significantly lower (164 [126-212] ml/kg vs 323 [268-379] ml/kg, p < 0.001). No significant differences were noted between methods in either pre or post-transplant maximum isohaemagglutinin titres, incidence of rejection, length of intensive care or total hospital stay. Survival comparison showed no significant difference between antibody reduction methods, or indeed ABO-compatible transplants (p = 0.6). CONCLUSIONS: This novel technique appears to allow a significantly older population than typical to undergo ABO-incompatible heart transplantation, as well as significantly reducing blood product utilization. Furthermore, intraoperative anti-A/B immunoadsorption does not demonstrate increased early post-transplant isohaemagglutinin accumulation or rates of rejection compared to ABO-PE. Early survival is equivalent between ABO-IA, ABO-PE and ABO-compatible heart transplantation.

Isolation and expansion of thymus-derived regulatory T cells for use in pediatric heart transplant patients.

Regulatory T-cells (Tregs) are a subset of T cells generated in the thymus with intrinsic immunosuppressive properties. Phase I clinical trials have shown safety and feasibility of Treg infusion to promote immune tolerance and new studies are ongoing to evaluate their efficacy. During heart transplantation, thymic tissue is routinely discarded providing an attractive source of Tregs. In this study, we developed a GMP-compatible protocol for expanding sorted thymus-derived CD3+ CD4+ CD25+ CD127- (Tregs) as well as CD3+ CD4+ CD25+ CD127- CD45RA+ (RA+ Tregs) cells. We aimed to understand whether thymic RA+ Tregs can be isolated and expanded offering an advantage in terms of stability as it has been previously shown for circulating adult CD45RA+ Tregs. We show that both Tregs and RA+ Tregs could be expanded in large numbers and the presence of rapamycin is essential to inhibit the growth of IFN-γ producing cells. High levels of FOXP3, CTLA4, and CD25 expression, demethylation of the FOXP3 promoter, and high suppressive ability were found with no differences between Tregs and RA+ Tregs. After freezing and thawing, all Treg preparations maintained their suppressive ability, stability, as well as CD25 and FOXP3 expression. The number of thymic Tregs that could be isolated with our protocol, their fold expansion, and functional characteristics allow the clinical application of this cell population to promote tolerance in pediatric heart transplant patients.

Identification of MIB producers and odor risk assessment using routine data: A case study of an estuary drinking water reservoir.

Identification of MIB(2-methylisoborneol)-producing cyanobacteria in source water has been a big challenge for reservoir authorities because it normally requires isolation of cyanobacteria strains. Here, a protocol based on Pearson's product moment correlation analysis combined with standardized data treatment and expert judgement was developed to sort out the MIB producer(s), mainly based on routine monitoring data from an estuary drinking water reservoir in the Yangtze River, China, and a risk model using quantile regressions was established to evaluate the risk of MIB occurrences. This reservoir has suffered from MIB problems in summer since 2011. Among 323 phytoplankton species, Planktothrix was judged to be the MIB producer in this reservoir because it exhibited the highest correlation coefficient (R = 0.60) as well as the lowest false positive-ratio (FP% = 0) and false-negative rate (FN% = 14). The low false-positive rate is particularly important, since MIB should not detected without detection of the producer. A high light extinction coefficient (k=5.57±2.48 m-1) attributed to high turbidity loading in the river water lowered the subsurface water light intensity, which could protect the low irradiance Planktothrix from excessive solar radiation, and allow them to grow throughout the summer. The risk model shows that the probability of suffering unacceptable MIB concentrations (>15 ng L-1) in water is as high as 90% if the cell density of Planktothrix is >609.0 cell mL-1, while the risk will be significantly reduced to 50% and 10% at cell densities of 37.5 cell mL-1 and 9.6 cell mL-1, respectively. The approach developed in this study, including the protocol for identification of potential producers and the risk model, could provide a reference case for the management of source water suffering from MIB problems using routine monitoring data.

T cell phenotype in paediatric heart transplant recipients.

Paediatric heart transplantation recipients suffer an increased incidence of infectious, autoimmune and allergic problems. The relative roles of thymus excision and immunosuppressive treatments in contributing to these sequelae are not clear. We compared the immunological phenotypes of 25 heart transplant recipients (Tx), 10 children who underwent thymus excision during non-transplantation cardiac surgery (TE) and 25 age range-matched controls, in two age bands: 1-9 and 10-16 years. Significant differences from controls were seen mainly in the younger age band with Tx showing lower CD3 and CD4 cell counts whilst TE showed lower CD8 cell counts. Naïve T cell and recent thymic emigrant proportions and counts were significantly lower than controls in both groups in the lower age band. T cell recombination excision circle (TREC) levels were lower than controls in both groups in both age bands. There were no differences in regulatory T cells, but in those undergoing thymus excision in infancy, their proportions were higher in TE than Tx, a possible direct effect of immunosuppression. T cell receptor V beta spectratyping showed fewer peaks in both groups than in controls (predominantly in the older age band). Thymus excision in infancy was associated with lower CD8 cell counts and higher proportions of Tregs in TE compared to Tx. These data are consistent with thymus excision, particularly in infancy, being the most important influence on immunological phenotype after heart transplantation.

The complication rate of intravascular ultrasound (IVUS) in a multicenter pediatric heart transplant population: A study of the international pediatric IVUS consortium.

BACKGROUND: Our purpose was to determine the complication rate from intravascular ultrasound (IVUS) in a large, multicenter cohort of pediatric heart transplant (PHT) patients. METHODS: We retrospectively reviewed all PHT who underwent IVUS at 5 institutions (2006-2014). Rates of major and minor complications were calculated. All adverse events (AE) were graded from 1 to 5 using a previously published AE severity scale. RESULTS: There were 1380 catheterizations in 505 patients and 32 AE (2.3%); 9 major (0.6%) and 23 AE (1.7%). The major AE attributed to IVUS were all coronary artery vasospasm (7). Major and minor AE rates directly related to IVUS were 0.5% and 0.7%, respectively. Minor AE possibly attributable to IVUS included excessive fluoroscopy (3) and transient ST segment changes (7). Of AE related to IVUS, only 3 were of moderate severity. The rest were ≤ minor in severity. There were no reports of coronary artery dissection or death. CONCLUSION: Most AE during routine PHT coronary evaluation with IVUS were minor and not directly related to the use of IVUS. The number of coronary related AE was similar to a registry-based report of coronary angiography alone. Efforts to minimize IVUS-related complications should be focused on preventing coronary artery vasospasm.