bluuebunny/crossref_metadata_2025 huggingface dataset:
A Cross-Sectional Study of the Clinical Metrics of Functional Status Tools in Pediatric Critical Illness
Authors: Ong Chengsi , Lee Jan Hau , Yang Liying , Wong Judith J. M. , Leow Melvin K. S. , Puthucheary Zudin A.
Published: April 2021

OBJECTIVES:

To determine the clinical metrics of functional assessments in pediatric critical illness survivors.

DESIGN:

Cross-sectional observational study.

SETTING:

PICU follow-up clinic.

PATIENTS:

Forty-four PICU survivors 6–12 months post PICU stay, and 52 healthy controls 0–18 years old.

INTERVENTIONS:

Nil.

MEASUREMENTS AND MAIN RESULTS:

Function was assessed using the Pediatric Quality of Life Inventory 4.0 generic scales and infant scales, the Pediatric Evaluation of Disability Inventory–Computer Adaptive Test, and the Functional Status Scale. Muscle strength was assessed by hand grip strength in children greater than or equal to 6 years. Clinical metrics assessed included floor and ceiling effects, known-group, and convergent validity. Floor and ceiling effects were present if the participants achieving the worst or best scores exceeded 15%, respectively. Known-group validity was assessed by comparing scores between those with and without complex chronic conditions and abnormal versus good baseline function. Convergent validity was assessed using partial correlation between two tools. Functional Status Scale and Pediatric Quality of Life Inventory physical domain scores showed significant ceiling effects in PICU survivors (69.2% and 15.4%, respectively, achieved the highest possible score). Functional scores were not significantly different between children with or without complex chronic conditions or children with good versus abnormal baseline function. In healthy children, Pediatric Quality of Life Inventory physical correlated moderately with hand grip strength (partial r = 0.66; p < 0.001), whereas Pediatric Quality of Life Inventory psychosocial correlated moderately with Pediatric Evaluation of Disability Inventory–Computer Adaptive Test social/cognitive score (partial r = 0.53; p < 0.001). In PICU survivors, only Pediatric Quality of Life Inventory physical and Pediatric Evaluation of Disability Inventory–Computer Adaptive Test mobility scores were correlated (partial r = 0.55; p < 0.001).

CONCLUSIONS:

PICU functional assessment tools have varying clinical metrics. Considering ceiling effects, Pediatric Evaluation of Disability Inventory–Computer Adaptive Test may be more suitable in survivors than Functional Status Scale. Differences in scores between children with or without complex chronic conditions, and with or without baseline functional impairment, were not observed. Functional assessments likely require a combination of tools to measure the spectrum of pediatric critical illness and recovery.
Pertussis Infants Needing Mechanical Ventilation and Extracorporeal Membrane Oxygenation: Single-Center Retrospective Series in Vietnam
Authors: Tuan Ta Anh , Xoay Tran Dang , Nakajima Noriko , Nakagawa Satoshi , Phuc Phan Huu , Hung Dau Viet , Dung Nguyen Trong , Dong Ngo Tien , Dung Tran Ba , Thuy Phung Thi Bich , Hai Le Thanh , Dien Tran Minh
Published: April 2021

Objectives:

Pertussis is an infectious disease that causes epidemics and outbreaks and is associated with a high mortality rate, especially in infants, in both developed and developing countries. We aimed to characterize infants with pertussis with respiratory failure and shock and investigated the factors related to mortality.

Design:

A retrospective, observational study conducted between January 2015 and October 2020.

Setting:

This study was conducted at the Vietnam National Children’s Hospital, which is a government hospital that serves as a tertiary care center in Hanoi, Vietnam.

Patients:

Children who fulfilled the following inclusion criteria were included: 1) admitted to the PICU, 2) less than 16 years old, 3) pertussis confirmed by real-time polymerase chain reaction, and 4) treated with mechanical ventilation due to respiratory failure and shock.

Interventions:

None.

Measurement and Main Results:

Seventy-three mechanically ventilated children (40 boys; median age, 56 d), whereas 19 patients received extracorporeal membrane oxygenation support. Twenty-six patients (36%) died including 12 who received extracorporeal membrane oxygenation. Those who received extracorporeal membrane oxygenation support had higher leukocyte counts upon admission and were more frequently diagnosed with pulmonary hypertension and stage 3 acute kidney injury. Compared with survivors, nonsurvivors showed increased heart rates, leukocyte and neutrophil counts, and lower systolic and diastolic blood pressure at admission. Increased Vasoactive-Inotropic Score, stage 3 acute kidney injury, fluid overload, the use of renal replacement therapy, and extracorporeal membrane oxygenation use were prevalent among nonsurvivors.

Conclusions:

In this study, around one third of mechanically ventilated patients with pertussis died. Those who received extracorporeal membrane oxygenation had higher leukocyte counts, a higher prevalence of pulmonary hypertension, and advanced stages of acute kidney injury. Higher Vasoactive-Inotropic Score and advanced stages of acute kidney injury were associated with a greater risk of mortality.
Cardiopulmonary Bypass–Induced Inflammation and Myocardial Ischemia and Reperfusion Injury Stimulates Accumulation of Soluble MER*
Authors: Becker Amanda C. , Lantz Connor W. , Forbess Joseph M. , Epting Conrad L. , Thorp Edward B.
Published: April 2021

Objectives:

Soluble MER has emerged as a potential biomarker for delayed resolution of inflammation after myocardial injury and a therapeutic target to reduce cardiac-related morbidity and mortality in adults. The significance of soluble MER in pediatric populations, however, is unclear. We sought to investigate if soluble MER concentrations change in response to myocardial ischemia and reperfusion injury in pediatric patients. In parallel, we also sought to investigate for correlations between the change in soluble MER concentration and specific patient, bypass, and postoperative data.

Design:

We quantified the change in plasma soluble MER concentration post- compared with precardiopulmonary bypass for each patient in a cohort of pediatric patients. Linear regression, correlation coefficients, and t tests were used to compare innate patient characteristics (i.e., sex, age, cyanotic vs acyanotic cardiac lesion), cardiac bypass data (i.e., total cardiac bypass time, total aortic cross-clamp time, perioperative steroid administration), and postcardiac bypass data (total postoperative ventilator days, total postoperative vasoactive medication days, and total postoperative ICU days) with change in soluble MER concentrations.

Setting:

Whole blood samples were obtained intraoperatively at a single tertiary care children’s hospital from April to October 2019.

Subjects:

Our patient cohort included 24 pediatric patients ages ranging from birth to 19 years old with both cyanotic and acyanotic cardiac lesions.

Interventions:

Retrospective analyses of pediatric blood specimens, as well as patient, bypass, and postoperative data, were performed.

Measurements and Main Results:

We observed a statistically significant increase in soluble MER concentration post cardiac bypass in 17 of 24 patients (71%).

Conclusions:

Soluble MER concentrations increase with cardiopulmonary bypass–induced inflammation and myocardial ischemia and reperfusion injury in pediatric patients. The utility of soluble MER as a clinical biomarker to identify pediatric patients at risk for exacerbated postoperative outcomes after bypass-induced myocardial ischemia and reperfusion injury requires further investigation.
Late presentation for HIV impairs immunological but not virological response to antiretroviral treatment
Authors: Rava Marta , Bisbal Otilia , Domínguez-Domínguez Lourdes , Aleman Ma Remedios , Rivero María , Antela Antonio , Estrada Vicente , Ribera Esteban , Muñoz Adolfo , Iribarren José-Antonio , Moreno Santiago , Rubio Rafael , Jarrín Inmaculada
Published: April 2021

Objectives:

The aim of this study was to examine the impact of late presentation (CD4+ cell count <350 cells/μl or an AIDS-defining event) on effectiveness and safety of initial antiretroviral therapy (ART) and to evaluate whether treatment response depends on first-line ART regimen in late presenters.

Design:

ART-naive adults from the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) starting triple ART between 2010 and 2018.

Methods:

We used multivariable models to assess differences in viral suppression (viral load <50 copies/ml), immunological response (change in CD4+ cell count, CD4% (>29%) and CD4/CD8 normalization (>0.4 and >1) multiple T-cell marker recovery (MTMR): CD4+ cell count more than 500 cells/μl and CD4% >29% and CD4/CD8 >1), and treatment discontinuation due to adverse events (TDAE) at 48 weeks from ART initiation.

Results:

Out of 8002 participants, 48.7% were late presenters. Of them, 45.8% initiated ART with a NNRTI- (mostly TDF/FTC/EFV), 33.9% with a protease inhibitor (mostly TDF/FTC+boosted DRV) and 20.3% with an INI-based regimen (mostly ABC/3TC/DTG). At 48 weeks, late presenters had similar viral suppression, but worse immunological response, than non-late presenters with no difference on TDAE. Late presenters initiating with NNRTI-based regimens were more likely to achieve viral suppression than those starting with INI-based, due to the higher chance of achieving viral suppression observed with TDF/FTC/RPV compared to ABC/3TC/DTG. Initial treatment with NNRTI or protease inhibitor based showed similar immunological response than the INI-based regimens, which showed lower rates of TDAE than NNRTI- and protease inhibitor based regimens.

Conclusion:

Despite safety and effectiveness of initial ART in terms of viral suppression, late presenters may not experience complete immunological response. In late presenters, effectiveness and safety depends on both the class and the specific first-line ART regimen.
HIV disease duration, but not active brain infection, predicts cortical amyloid beta deposition
Authors: Morgello Susan , Cortes Etty P. , Gensler Gary , Meloni Gregory , Jacobs Michelle M. , Murray Jacinta , Borukov Valeriy , Crary John F.
Published: April 2021

Objective:

Abnormal deposition of the antimicrobial peptide amyloid beta (Aβ) is a characteristic of Alzheimer's disease. The objective of this study was to elucidate risk factors for brain Aβ in a cohort enriched for HIV and other neurotropic pathogens.

Design:

Cross-sectional cohort study.

Methods:

We examined autopsy brains of 257 donors with a mean age of 52.8 years; 62% were men; and 194 were HIV+ and 63 HIV−. Hyperphosphorylated tau (p-tau) and Aβ were identified in frontal and temporal regions by immunohistochemistry. APOE genotyping was performed. Clinical and neuropathological predictors for Aβ were identified in univariate analyses, and then tested in multivariate regressions.

Results:

Cortical Aβ was identified in 32% of the sample, and active brain infection in 27%. Increased odds of Aβ were seen with increasing age and having an APOE ε4 allele; for the overall sample, HIV+ status was protective and brain infection was not a predictor. Within the HIV+ population, predictors for Aβ were duration of HIV disease and APOE alleles, but not age. When HIV disease duration and other HIV parameters were introduced into models for the entire sample, HIV disease duration was equivalent to age as a predictor of Aβ.

Conclusion:

We hypothesize that dual aspects of immune suppression and stimulation in HIV, and beneficial survivor effects in older HIV+ individuals, account for HIV+ status decreasing, and HIV duration increasing, odds of Aβ. Importantly, with HIV, disease duration replaces age as an independent risk for Aβ, suggesting HIV-associated accelerated brain senescence.
Antiretroviral therapy administration reduces neuroinflammation without restoring brain-derived neurotrophic factor signaling in alcohol-administered simian immunodeficiency virus-infected macaques
Authors: Maxi John K. , Foret Brittany L. , Amedee Angela M. , McDaniel Lee S. , Nelson Steve , Simon Liz , Edwards Scott , Molina Patricia E.
Published: April 2021

Objective:

The present study examined interactions between simian immunodeficiency virus (SIV), chronic binge alcohol (CBA), and antiretroviral therapy (ART) on growth factor signaling, neuroinflammatory markers, viral loads (VL), and CD4+ cell counts.

Design:

Adult male rhesus macaques were administered CBA (13–14 g ethanol (EtOH)/kg per week) or sucrose (SUC) 3 months prior to SIVmac251 infection until the study endpoint. At viral setpoint, a subset of CBA/SIV+ and SUC/SIV+ macaques were randomized to receive daily ART (9-[2-Phosphonyl-methoxypropyly]adenine [PMPA] 20 mg/kg, 2’,3’-dideoxy-5-fluoro-3’-thiacytidine (FTC), 30 mg/kg). Frontal cortex (FC) and basal ganglia (BG) were collected for gene and protein expression.

Methods:

Relationships between brain and plasma VL or CD4+ cell counts were determined using linear regression. Effects of SIV, CBA, and ART on markers of neuroinflammation and brain-derived neurotrophic factor (BDNF) signaling were determined by ANOVA and linear regression.

Results:

SIV increased FC and BG neuroinflammatory and glial cell gene expression (CX3CR1, B2M), and reduced FC protein kinase B phosphorylation. CBA decreased FC and BG tropomyosin receptor kinase B (TrkB) phosphorylation, and increased full-length TrkB (TrkB-FL) and SLC1A3 expression in FC and BG, respectively. ART suppressed plasma and brain VL, reduced neuroinflammatory gene expression in FC (IBA1, CX3CR1, and GFAP), and BG (CD74 and CD11ß), and did not restore FC or BG BDNF signaling deficits.

Conclusions:

Results show ART-mediated reduction in VL and neuroinflammatory gene expression, irrespective of CBA administration. ART did not attenuate SIV- and CBA-mediated BDNF signaling deficits, suggesting these deficits, despite effective neuroinflammation suppression, may explain CBA- and SIV-associated neurocognitive deficits. Therapeutics targeting growth factor signaling may be important adjuvants in treating HIV-associated neurocognitive decline.
Prevalence and association with birth outcomes of low vitamin D levels among pregnant women living with HIV
Authors: Bergløv Anne , Moseholm Ellen , Katzenstein Terese L. , Johansen Isik S. , Storgaard Merete , Pedersen Gitte , Weis Nina
Published: April 2021

Objectives:

To evaluate the prevalence of low vitamin D levels among well treated pregnant women living with HIV (WLWH) on combination antiretroviral therapy in Denmark, to identify risk factors of low vitamin D levels, and to assess the association between vitamin D status and birth outcomes.

Design:

Nationwide cohort study.

Methods:

All WLWH in Denmark giving birth from 2000 to 2018 with a vitamin D measurement during pregnancy were identified. Risk factors for low vitamin D (deficiency or insufficiency) were assessed using log-binomial regression models, both univariate and adjusted for maternal and HIV factors. The association between vitamin D status and birth outcomes was assessed using linear regression models for continuous outcomes and log-binomial models for binary outcomes.

Results:

Among 208 WLWH, the prevalence of vitamin D deficiency was 13%, insufficiency 34%, and sufficiency 53%. Being of African origin (RR 2.68, P = 0.01), Asian origin (RR 3.38, P = < 0.01), or having HIV RNA levels more than 50 copies/ml (RR 1.43, P = 0.04) was associated with an increased risk of low vitamin D level. WLWH with vitamin D deficiency had an increased risk of preterm birth (RR 2.66, P = 0.03) and giving birth to small for gestational age (SGA) children (RR 6.83, P = 0.02) compared with WLWH with sufficient vitamin D level.

Conclusion:

Low vitamin D level was prevalent among well treated pregnant WLWH in Denmark, especially among women of African or Asian origin, and women with detectable viral loads. Vitamin D deficiency was associated with an increased risk of preterm birth and SGA.
Image Quality and Detection of Small Focal Liver Lesions in Diffusion-Weighted Imaging
Authors: Saake Marc , Seuß Hannes , Riexinger Andreas , Bickelhaupt Sebastian , Hammon Matthias , Uder Michael , Laun Frederik B.
Published: April 2021

Objectives

The aim of this study was to compare intraindividual diffusion-weighted imaging (DWI) of the liver acquired with free breathing (FB) versus navigator triggering (NT) for assessing small focal liver lesions (FLLs) in noncirrhotic patients.

Materials and Methods

Patients with known or suspected multiple FLLs were prospectively included, and spin-echo echo-planar DWI with NT and FB acquisition was performed (b-values, 50 and 800 s/mm2 [b50 and b800]). NT and FB DWI sequences with similar acquisitions times were used. Liver and lesion signal-to-noise ratios were measured at b800. The DWI scans were analyzed independently by 2 readers. Liver edge delineation, presence of stair-step artifacts, vessel sharpness, severity of cardiac motion artifacts, overall image quality, and lesion conspicuity were rated with 5-point Likert scales. Small and large FLLs (ie, <1 cm or ≥1 cm) were rated separately for lesion conspicuity. The FLL detectability was estimated by comparing the number of lesions visible with FB to those visible with NT.

Results

Forty-three patients were included in the study. The FB acquisition performed better in terms of severity of cardiac motion artifacts. The NT performed better in terms of liver edge delineation and vessel sharpness. Little difference was found for stair-step artifact, overall image quality, and conspicuity of large FLL, whereas the conspicuity of small FLL was better for NT. For small FLL, both readers found more lesions with NT in 11 cases at b800. For large FLL, this effect was much less pronounced (1 case at b800 reported by 1 of the readers). The mean liver and lesion signal-to-noise ratios were 16.8/41.5 and 19.8/38.4 for NT/FB, respectively.

Conclusions

Small FLL detection is better with NT. Large FLL detection by FB and NT is similarly good. We conclude that NT should be used.
A Real-World Clinical Implementation of Automated Processing Using Intelligent Work Aid for Rapid Reformation at the Orbitomeatal Line in Head Computed Tomography
Authors: Nishii Tatsuya , Okuyama Shun , Horinouchi Hiroki , Chikuda Ryo , Kamei Eisuke , Higuchi Satoshi , Ohta Yasutoshi , Fukuda Tetsuya
Published: April 2021

Objectives

The aim was to investigate the time savings and plane accuracy of multivendor head computed tomography (CT) using the intelligent work aid with automatic reformatting of the axial head image at the orbitomeatal line.

Materials and Methods

We retrospectively reviewed 781 head CTs (median, 70 years; 441 men) collected by CT systems from 3 vendors. In addition to the orbitomeatal line image reformatted by a CT specialist as a reference, we obtained the fully automated orbitomeatal line image using the intelligent work aid. We calculated the offset angle from the reference of the automatically reformatted image. We defined the large offset angle groups as those with an offset angle greater than 3 degrees. Multivariate logistic regression was used to determine the independent factors for the large offset angle groups. We compared the postprocessing times measured using the intelligent work aid or by a CT specialist.

Results

With the intelligent work aid, 99.7% of CTs were automatically reformatted to the orbitomeatal line without error. Furthermore, 88.1% of CTs were within the 3 degrees' offset angle when compared with the reference produced by a CT specialist. The median offset angle from the reference was 1.41 degrees. Multivariate analysis showed that the offset angle of the positioning plane was an independent factor (odds ratio, 1.045; P = 0.005) for predicting the large offset angle group. Furthermore, this technique was 4 times faster (6.4 ± 0.7 seconds) than a CT specialist (25.6 ± 6.4 seconds).

Conclusions

The intelligent work aid can generate a fast and precise head CT image aligned at the orbitomeatal line, even in real-world clinical CTs. However, precise positioning remains essential.
Evaluation of Iterative Denoising 3-Dimensional T2-Weighted Turbo Spin Echo for the Diagnosis of Deep Infiltrating Endometriosis
Authors: Florin Marie , Vaussy Alexis , Macron Laurent , Bazot Marc , Stemmer Alto , Pinar Ugo , Jarboui Lamia
Published: April 2021

Objectives

The primary end point of this study was to evaluate the image quality and reliability of a highly accelerated 3-dimensional T2 turbo spin echo (3D-T2-TSE) sequence with prototype iterative denoising (ID) reconstruction compared with conventional 2D T2 sequences for the diagnosis of deep infiltrating endometriosis (DIE). The secondary end point was to demonstrate the 3D-T2-TSE sequence image quality improvement using ID reconstruction.

Material and Methods

Patients were prospectively enrolled to our institution for pelvis magnetic resonance imaging because of a suspicion of endometriosis over a 4-month period. Both conventional 2D-T2 (sagittal, axial, coronal T2 oblique to the cervix) and 3D-T2-TSE sequences were performed with a scan time of 7 minutes 43 seconds and 4 minutes 58 seconds, respectively. Reconstructions with prototype ID (3D-T2-denoised) and without prototype ID (3D-T2) were generated inline at the end of the acquisition. Two radiologists independently evaluated the image quality of 3D-T2, 3D-T2-denoised, and 2D-T2 sequences. Diagnosis confidence of DIE was evaluated for both 3D-T2-denoised and 2D-T2 sequences. Intraobserver and interobserver agreements were calculated using Cohen κ coefficient.

Results

Ninety female patients were included. Both readers found that the ID algorithm significantly improved the image quality and decreased the artifacts of 3D-T2-denoised compared with 3D-T2 sequences (P < 0.001). A significant image quality improvement was found by 1 radiologist for 3D-T2-denoised compared with 2D-T2 sequences (P = 0.002), whereas the other reader evidenced no significant difference. The interobserver agreement of 3D-T2-denoised and 2D-T2 sequences was 0.84 (0.73–0.95) and 0.78 (0.65–0.9), respectively, for the diagnosis of DIE. Intraobserver agreement for readers 1 and 2 was 0.86 (0.79–1) and 0.83 (0.76–1), respectively. For all localization of DIE, interobserver and intraobserver agreements were either almost perfect or substantial for both 3D-T2-denoised and 2D-T2 sequences.

Conclusions

Three-dimensional T2-denoised imaging is a promising tool to replace conventional 2D-T2 sequences, offering a significant scan time reduction without compromising image quality or diagnosis information for the assessment of DIE.
Rapid Cycle Deliberate Practice Versus Traditional Simulation for Training Extracorporeal Membrane Oxygenation Specialists in Circuit Air Emergency Management
Authors: Swinger Nathan , Hocutt Gail , Medsker Brock H. , Gray Brian W. , Abulebda Kamal
Published: April 2021

Introduction

Extracorporeal membrane oxygenation (ECMO) is a highly complex therapy used to support critically ill patients. Simulation-based training of ECMO specialists in the management of ECMO emergencies has been described in the literature, but optimal methods are not currently established. The objective of this study was to compare rapid cycle deliberate practice (RCDP) simulation versus traditional simulation (TS) with reflective debriefing for training ECMO specialists in the management of arterial air emergencies.

Methods

A prospective, randomized, pre-post interventional design was used to compare the impact of RCDP training with that of TS training on ECMO specialist performance during a simulated ECMO circuit emergency. Participants were divided into 2 training groups—RCDP and TS. Each participant completed a simulated arterial air emergency scenario before training, immediately after training, and again 3 months later. The primary outcome was the time required by individual participants to complete critical clinical actions.

Results

Twenty-four ECMO specialists completed the study. Immediately after the training, the RCDP group had faster times to dissociate the patient from the ECMO circuit (11-seconds RCDP vs. 16-seconds TS, P = 0.03) and times to re-establish ECMO support (59-seconds RCDP vs. 82.5-seconds TS, P = 0.01). Follow-up testing at 3 months showed persistence in faster times to re-establish ECMO support in the RCDP group (114-seconds RCDP vs. 199-seconds TS, P = 0.01).

Conclusions

Rapid cycle deliberate practice simulation provides a superior curriculum and method of training ECMO specialists in the management of arterial air emergencies in comparison with traditional simulation.
Evaluating Nontechnical Skills in US Emergency Departments Using Simulation
Authors: Meguerdichian David A. , Huancahuari Nadia , Pozner Charles N. , Eyre Andrew , Schuur Jeremiah , Yule Steven
Published: April 2021

Introduction

Nontechnical skills (NTS) in medicine are the “cognitive, social, and personal resource skills that complement technical skills contributing to safe and efficient care.” We aimed to (1) evaluate the validity and reliability of a 12-element United Kingdom emergency medicine (EM) NTS assessment tool in the context of United States (US) EM practice and (2) identify behaviors unique to US clinical practice.

Methods

This was a mixed methods study conducted in 2 phases, following Kane's validity framework. The intended use of the NTS tool is to provide formative assessment of US EM physicians (EPs) from a video of simulated clinical encounters. In phase I, a focus group assessed the appropriateness of each aspect of the tool in the context of US EM practice by reviewing and identifying the NTS of an EP in a simulated clinical scenario. In phase II, EPs (N = 208) attending a national EM conference evaluated an EP's behaviors in 1 of 2 video simulations. Reliability in the form of internal consistency was calculated using Cronbach α. All participants suggested exemplar behaviors for the 12 elements in the context of their own clinical practice and generated new assessment elements.

Results

Internal consistency was acceptable (α > 0.7) for all categories, except teamwork and cooperation. Participants proposed 4 novel behavioral elements and suggested US exemplar behaviors for all 12 original elements.

Conclusions

This tool can be used to assess US EP's NTS for the purpose of formative assessment. Refinement of exemplar behaviors and inclusion of novel US-specific elements may optimize usability.
Rapid Cycle Deliberate Practice Improves Retention of Pediatric Resuscitation Skills Compared With Postsimulation Debriefing
Authors: Won Sharon K. , Doughty Cara B. , Young Ann L. , Welch-Horan T. Bram , Rus Marideth C. , Camp Elizabeth A. , Lemke Daniel S.
Published: April 2021

Introduction

Rapid cycle deliberate practice (RCDP) for teaching team-based resuscitation is associated with similar improvements in immediate performance as compared with postsimulation debriefing (PSD). Limited studies compare skill retention between these 2 modalities. Our objective was to compare retention of team leader performance in residents trained with RCDP versus PSD.

Methods

This was a cluster-randomized trial comparing RCDP and PSD from January 2018 to April 2019. Pediatric and emergency medicine residents participated in simulation-based pediatric resuscitation education, and teams were randomized to undergo either RCDP or PSD. Each participant's team leader performance was assessed 1 to 12 months after training via a simulated cardiac arrest. The primary outcome was time to defibrillation. Secondary outcomes included overall team leader performance and time to chest compressions.

Results

Thirty-two residents (90.6% pediatrics, 9.4% emergency medicine) met inclusion criteria (16 RCDP, 16 PSD). Of the 32 residents, 40% returned in 1 to 3 months, 25% 3 to 6 months, 16% 6 to 9 months, and 19% 10 to 12 months. Participants in RCDP had more than 5 times the odds of achieving defibrillation versus those in the PSD group (odds ratio = 5.57, 95% confidence interval = 1.13–27.52, P = 0.04). The RCDP group had a higher mean Resident Team Leader Evaluation score (0.54 ± 0.19) than the PSD group (0.34 ± 0.16, P < 0.001).

Conclusions

This study shows significant differences in subsequent performance in the team leader trained with RCDP and suggests that RCDP may improve retention of pediatric resuscitation skills compared with PSD. Future studies should focus on best applications for RCDP with attention to knowledge and skill decay.
Simulation in Upper and Lower Limb Trauma Skill Acquisition
Authors: Heskin Leonie , Galvin Rose , Traynor Oscar , Simms Ciaran
Published: April 2021

Summary Statement

This review aimed to explore the published evidence with regard to the types and composition of both full- and part-task trainers to teach surgeons extremity exploration procedures in limb trauma management. Studies were included if they reported the development and/or validation of synthetic or virtual task trainers. Studies were evaluated to determine their derivation, usability, and clinical utility.

A total of 638 citations were identified and 63 satisfied the inclusion criteria. Twenty-five articles addressed simulator validation and 36 addressed level of learning achieved with simulator engagement. Two studies described a dedicated limb simulator. Simulators were developed to repair limb structures including skin (n = 15), tendon (n = 7), nerve (n = 1), fascia (n = 1), muscle (n = 1), vascular (n = 24), and bone (n = 11). Considerations such as material fidelity, learning outcomes, cost or reusability, validity, and effectiveness are inconsistently reported. Future studies should address design standards for the effective production of synthetic or virtual simulators for limb trauma management.
Q-Methodology
Authors: Klein Barbie A.
Published: April 2021

Summary Statement

Learner perceptions of simulation can be challenging to assess and are usually limited to qualitative strategies. Q-methodology is an exploratory, systematic research technique that combines quantitative and qualitative procedures to measure differences in subjectivity. This article briefly reviews Q-methodology, provides an example of how it could be applied to assess the affective domain of simulation-based learning, and discusses implications for the use of Q-methodology in future simulation scholarship.
Computational Simulation Is a Vital Resource for Navigating the COVID-19 Pandemic
Authors: Page Andrew , Diallo Saikou Y. , Wildman Wesley J. , Hodulik George , Weisel Eric W. , Gondal Neha , Voas David
Published: April 2021

Introduction

COVID-19 has prompted the extensive use of computational models to understand the trajectory of the pandemic. This article surveys the kinds of dynamic simulation models that have been used as decision support tools and to forecast the potential impacts of nonpharmaceutical interventions (NPIs). We developed the Values in Viral Dispersion model, which emphasizes the role of human factors and social networks in viral spread and presents scenarios to guide policy responses.

Methods

An agent-based model of COVID-19 was developed with individual agents able to move between 3 states (susceptible, infectious, or recovered), with each agent placed in 1 of 7 social network types and assigned a propensity to comply with NPIs (quarantine, contact tracing, and physical distancing). A series of policy questions were tested to illustrate the impact of social networks and NPI compliance on viral spread among (1) populations, (2) specific at-risk subgroups, and (3) individual trajectories.

Results

Simulation outcomes showed large impacts of physical distancing policies on number of infections, with substantial modification by type of social network and level of compliance. In addition, outcomes on metrics that sought to maximize those never infected (or recovered) and minimize infections and deaths showed significantly different epidemic trajectories by social network type and among higher or lower at-risk age cohorts.

Conclusions

Although dynamic simulation models have important limitations, which are discussed, these decision support tools should be a key resource for navigating the ongoing impacts of the COVID-19 pandemic and can help local and national decision makers determine where, when, and how to invest resources.
Structure, function and parallel evolution of the bivalve byssus, with insights from proteomes and the zebra mussel genome
Authors: McCartney Michael A.
Published: April 2021

The byssus is a structure unique to bivalves. Byssal threads composed of many proteins extend like tendons from muscle cells, ending in adhesive pads that attach underwater. Crucial to settlement and metamorphosis, larvae of virtually all species are byssate. By contrast, in adults, the byssus is scattered throughout bivalves, where it has had profound effects on morphological evolution and been key to adaptive radiations of epifaunal species. I compare byssus structure and proteins in blue mussels (Mytilus), by far the best characterized, to zebra mussels (Dreissena polymorpha), in which several byssal proteins have been isolated and sequenced. By mapping the adult byssus onto a recent phylogenomic tree, I confirm its independent evolution in these and other lineages, likely parallelisms with common origins in development. While the byssus is superficially similar inDreissenaandMytilus, in finer detail it is not, and byssal proteins are dramatically different. I used the chromosome-scaleD. polymorphagenome we recently assembled to search for byssal genes and found 37 byssal loci on 10 of the 16 chromosomes. Most byssal genes are in small families, with several amino acid substitutions between paralogs. Byssal proteins of zebra mussels and related quagga mussels (D. rostriformis) are divergent, suggesting rapid evolution typical of proteins with repetitive low complexity domains. Opportunities abound for proteomic and genomic work to further our understanding of this textbook example of a marine natural material. A priority should be invasive bivalves, given the role of byssal attachment in the spread of, and ecological and economic damage caused by zebra mussels, quagga mussels and others.

This article is part of the Theo Murphy meeting issue ‘Molluscan genomics: broad insights and future directions for a neglected phylum’.
Whole-genome re-sequencing data to infer historical demography and speciation processes in land snails: the study of twoCandidulasister species
Authors: Chueca Luis J. , Schell Tilman , Pfenninger Markus
Published: April 2021

Despite the global biodiversity of terrestrial gastropods and their ecological and economic importance, the genomic basis of ecological adaptation and speciation in land snail taxa is still largely unknown. Here, we combined whole-genome re-sequencing with population genomics to evaluate the historical demography and the speciation process of two closely related species of land snails from western Europe,Candidula unifasciataandC. rugosiuscula. Historical demographic analysis indicated fluctuations in the size of ancestral populations, probably driven by Pleistocene climatic fluctuations. Although the current population distributions of both species do not overlap, our approximate Bayesian computation model selection approach on several speciation scenarios suggested that gene flow has occurred throughout the divergence process until recently. Positively selected genes diverging early in the process were associated with intragenomic and cyto-nuclear incompatibilities, respectively, potentially fostering reproductive isolation as well as ecological divergence. Our results suggested that the speciation between species entails complex processes involving both gene flow and ecological speciation, and that further research based on whole-genome data can provide valuable understanding on species divergence.

This article is part of the Theo Murphy meeting issue ‘Molluscan genomics: broad insights and future directions for a neglected phylum’.
MolluscDB: a genome and transcriptome database for molluscs
Authors: Caurcel Carlos , Laetsch Dominik R. , Challis Richard , Kumar Sujai , Gharbi Karim , Blaxter Mark
Published: April 2021

As sequencing becomes more accessible and affordable, the analysis of genomic and transcriptomic data has become a cornerstone of many research initiatives. Communities with a focus on particular taxa or ecosystems need solutions capable of aggregating genomic resources and serving them in a standardized and analysis-friendly manner. Taxon-focussed resources can be more flexible in addressing the needs of a research community than can universal or general databases. Here, we present MolluscDB, a genome and transcriptome database for molluscs. MolluscDB offers a rich ecosystem of tools, including an Ensembl browser, a BLAST server for homology searches and an HTTP server from which any dataset present in the database can be downloaded. To demonstrate the utility of the database and verify the quality of its data, we imported data from assembled genomes and transcriptomes of 22 species, estimated the phylogeny of Mollusca using single-copy orthologues, explored patterns of gene family size change and interrogated the data for biomineralization-associated enzymes and shell matrix proteins. MolluscDB provides an easy-to-use and openly accessible data resource for the research community.

This article is part of the Theo Murphy meeting issue ‘Molluscan genomics: broad insights and future directions for a neglected phylum’.
Examining adaptive evolution of immune activity: opportunities provided by gastropods in the age of ‘omics’
Authors: Seppälä Otto , Çetin Cansu , Cereghetti Teo , Feulner Philine G. D. , Adema Coen M.
Published: April 2021

Parasites threaten all free-living organisms, including molluscs. Understanding the evolution of immune defence traits in natural host populations is crucial for predicting their long-term performance under continuous infection risk. Adaptive trait evolution requires that traits are subject to selection (i.e. contribute to organismal fitness) and that they are heritable. Despite broad interest in the evolutionary ecology of immune activity in animals, the understanding of selection on and evolutionary potential of immune defence traits is far from comprehensive. For instance, empirical observations are only rarely in line with theoretical predictions of immune activity being subject to stabilizing selection. This discrepancy may be because ecoimmunological studies can typically cover only a fraction of the complexity of an animal immune system. Similarly, molecular immunology/immunogenetics studies provide a mechanistic understanding of immunity, but neglect variation that arises from natural genetic differences among individuals and from environmental conditions. Here, we review the current literature on natural selection on and evolutionary potential of immune traits in animals, signal how merging ecological immunology and genomics will strengthen evolutionary ecological research on immunity, and indicate research opportunities for molluscan gastropods for which well-established ecological understanding and/or ‘immune-omics’ resources are already available.

This article is part of the Theo Murphy meeting issue ‘Molluscan genomics: broad insights and future directions for a neglected phylum’.
Molluscan mitochondrial genomes break the rules
Authors: Ghiselli Fabrizio , Gomes-dos-Santos André , Adema Coen M. , Lopes-Lima Manuel , Sharbrough Joel , Boore Jeffrey L.
Published: April 2021

The first animal mitochondrial genomes to be sequenced were of several vertebrates and model organisms, and the consistency of genomic features found has led to a ‘textbook description’. However, a more broad phylogenetic sampling of complete animal mitochondrial genomes has found many cases where these features do not exist, and the phylum Mollusca is especially replete with these exceptions. The characterization of full mollusc mitogenomes required considerable effort involving challenging molecular biology, but has created an enormous catalogue of surprising deviations from that textbook description, including wide variation in size, radical genome rearrangements, gene duplications and losses, the introduction of novel genes, and a complex system of inheritance dubbed ‘doubly uniparental inheritance’. Here, we review the extraordinary variation in architecture, molecular functioning and intergenerational transmission of molluscan mitochondrial genomes. Such features represent a great potential for the discovery of biological history, processes and functions that are novel for animal mitochondrial genomes. This provides a model system for studying the evolution and the manifold roles that mitochondria play in organismal physiology, and many ways that the study of mitochondrial genomes are useful for phylogeny and population biology.

This article is part of the Theo Murphy meeting issue ‘Molluscan genomics: broad insights and future directions for a neglected phylum’.
Benchmarking Oxford Nanopore read assemblers for high-quality molluscan genomes
Authors: Sun Jin , Li Runsheng , Chen Chong , Sigwart Julia D. , Kocot Kevin M.
Published: April 2021

Choosing the optimum assembly approach is essential to achieving a high-quality genome assembly suitable for comparative and evolutionary genomic investigations. Significant recent progress in long-read sequencing technologies such as PacBio and Oxford Nanopore Technologies (ONT) has also brought about a large variety of assemblers. Although these have been extensively tested on model species such asHomo sapiensandDrosophila melanogaster, such benchmarking has not been done in Mollusca, which lacks widely adopted model species. Molluscan genomes are notoriously rich in repeats and are often highly heterozygous, making their assembly challenging. Here, we benchmarked 10 assemblers based on ONT raw reads from two published molluscan genomes of differing properties, the gastropodChrysomallon squamiferum(356.6 Mb, 1.59% heterozygosity) and the bivalveMytilus coruscus(1593 Mb, 1.94% heterozygosity). By optimizing the assembly pipeline, we greatly improved both genomes from previously published versions. Our results suggested that 40–50X of ONT reads are sufficient for high-quality genomes, with Flye being the recommended assembler for compact and less heterozygous genomes exemplified byC. squamiferum, while NextDenovo excelled for more repetitive and heterozygous molluscan genomes exemplified byM. coruscus. A phylogenomic analysis using the two updated genomes with 32 other published high-quality lophotrochozoan genomes resulted in maximum support across all nodes, and we show that improved genome quality also leads to more complete matrices for phylogenomic inferences. Our benchmarking will ensure efficiency in future assemblies for molluscs and perhaps also for other marine phyla with few genomes available.

This article is part of the Theo Murphy meeting issue ‘Molluscan genomics: broad insights and future directions for a neglected phylum’.
Molluscan phylogenomics requires strategically selected genomes
Authors: Sigwart Julia D. , Lindberg David R. , Chen Chong , Sun Jin
Published: April 2021

The extraordinary diversity in molluscan body plans, and the genomic mechanisms that enable it, remains one of the great questions of evolution. The eight distinct living taxonomic classes of molluscs are each unambiguously monophyletic; however, significant controversy remains about the phylogenetic relationships among those eight branches. Molluscs are the second-largest animal phylum, with over 100 000 living species with broad biological, economic and medical interest. To date, only around 53 genome assemblies have been accessioned to NCBI GenBank covering only four of the eight living molluscan classes. Furthermore, the molluscan taxa where partial or whole-genome assemblies are available are often aberrantly fast evolving or recently derived lineages. Characteristic adaptations provide interesting targets for whole-genome projects, in animals like the scaly-foot snail or octopus, but without basal-branching lineages for comparison, the context of recently derived features cannot be assessed. The currently available genomes also create a non-optimal set of taxa for resolving deeper phylogenetic branches: they are a small sample representing a large group, and those that are available come primarily from a rarefied pool. Thoughtful selection of taxa for future projects should focus on the blank areas of the molluscan tree, which are ripe with opportunities to delve into peculiarities of genome evolution, and reveal the biology and evolutionary history of molluscs.

This article is part of the Theo Murphy meeting issue ‘Molluscan genomics: broad insights and future directions for a neglected phylum’.
Sticky problems: extraction of nucleic acids from molluscs
Authors: Adema Coen M.
Published: April 2021

Traditional molecular methods and omics-techniques across molluscan taxonomy increasingly inform biology of Mollusca. Recovery of DNA and RNA for such studies is challenged by common biological properties of the highly diverse molluscs. Molluscan biomineralization, adhesive structures and mucus involve polyphenolic proteins and mucopolysaccharides that hinder DNA extraction or copurify to inhibit enzyme-catalysed molecular procedures. DNA extraction methods that employ the detergent hexadecyltrimethylammoniumbromide (CTAB) to remove these contaminants importantly facilitate molecular-level study of molluscs. Molluscan pigments may stain DNA samples and interfere with spectrophotometry, necessitating gel electrophoresis or fluorometry for accurate quantification. RNA can reliably be extracted but the ‘hidden break’ in 28S rRNA of molluscs (like most protostomes) causes 18S and 28S rRNA fragments to co-migrate electrophoretically. This challenges the standard quality control based on the ratio of 18S and 28S rRNA, developed for deuterostome animals. High-AT content in molluscan rRNA prevents the effective purification of polyadenylated mRNA. Awareness of these matters aids the continuous expansion of molecular malacology, enabling work also with museum specimens and next-generation sequencing, with the latter imposing unprecedented demands on DNA quality. Alternative methods to extract nucleic acids from molluscs are available from literature and, importantly, from communications with others who study the molecular biology of molluscs.

This article is part of the Theo Murphy meeting issue ‘Molluscan genomics: broad insights and future directions for a neglected phylum’.
Mobilizing molluscan models and genomes in biology
Authors: Davison Angus , Neiman Maurine
Published: April 2021

Molluscs are among the most ancient, diverse, and important of all animal taxa. Even so, no individual mollusc species has emerged as a broadly applied model system in biology. We here make the case that both perceptual and methodological barriers have played a role in the relative neglect of molluscs as research organisms. We then summarize the current application and potential of molluscs and their genomes to address important questions in animal biology, and the state of the field when it comes to the availability of resources such as genome assemblies, cell lines, and other key elements necessary to mobilising the development of molluscan model systems. We conclude by contending that a cohesive research community that works together to elevate multiple molluscan systems to ‘model’ status will create new opportunities in addressing basic and applied biological problems, including general features of animal evolution.

This article is part of the Theo Murphy meeting issue ‘Molluscan genomics: broad insights and future directions for a neglected phylum’.