Two classes of active transcription sites and their roles in developmental regulation.

The expression of genes encoding powerful developmental regulators is exquisitely controlled, often at multiple levels. Here, we investigate developmental expression of three conserved genes, Caenorhabditis elegans mpk-1, lag-1, and lag-3/sel-8, which encode homologs of ERK/MAPK and core components of the Notch-dependent transcription complex, respectively. We use single-molecule FISH (smFISH) and MATLAB to visualize and quantify nuclear nascent transcripts and cytoplasmic mRNAs as a function of position along the germline developmental axis. Using differentially labeled probes, one spanning an exceptionally long first intron and the other spanning exons, we identify two classes of active transcription sites (ATS). The iATS class, for "incomplete" ATS, harbors only partial nascent transcripts; the cATS class, for "complete" ATS, harbors full-length nascent transcripts. Remarkably, the frequencies of iATS and cATS are patterned along the germline axis. For example, most mpk-1 ATS are iATS in hermaphrodite germline stem cells, but most are cATS in differentiating stem cell daughters. Thus, mpk-1 ATS class frequencies switch in a graded manner as stem cell daughters begin differentiation. Importantly, the patterns of ATS class frequency are gene-, stage-, and sex-specific, and cATS frequency strongly correlates with transcriptional output. Although the molecular mechanism underlying ATS classes is not understood, their primary difference is the extent of transcriptional progression. To generate only partial nascent transcripts in iATS, progression must be slowed, paused, or aborted midway through the gene. We propose that regulation of ATS class can be a critical mode of developmental gene regulation.

The Current State of Combined Pediatric Anesthesiology-Critical Care Practice: A Survey of Dual-Trained Practitioners in the United States.

BACKGROUND: Combined practice in pediatric anesthesiology (PA) and pediatric critical care medicine (PCCM) was historically common but has declined markedly with time. The reasons for this temporal shift are unclear, but existing evidence suggests that length of training is a barrier to contemporary trainees. Among current practitioners, restriction in dual-specialty practice also occurs, for reasons that are unknown at present. We sought to describe the demographics of this population, investigate their perceptions about the field, and consider factors that lead to attrition. METHODS: We conducted a cross-sectional, observational study of physicians in the United States with a combined practice in PA and PCCM. The survey was distributed electronically and anonymously to the distribution list of the Pediatric Anesthesia Leadership Council (PALC) of the Society for Pediatric Anesthesia (SPA), directing the recipients to forward the link to their faculty meeting our inclusion criteria. Attending-level respondents (n = 62) completed an anonymous, 40-question multidomain survey. RESULTS: Forty-seven men and 15 women, with a median age of 51, completed the survey. Major leadership positions are held by 44%, and 55% are externally funded investigators. A minority (26%) have given up one or both specialties, citing time constraints and politics as the dominant reasons. Duration of training was cited as the major barrier to entry by 77%. Increasing age and faculty rank and lack of a comparably trained institutional colleague were associated with attrition from dual-specialty practice. The majority (88%) reported that they would do it all again. CONCLUSIONS: The current cohort of pediatric anesthesiologist-intensivists in the United States is a small but accomplished group of physicians. Efforts to train, recruit, and retain such providers must address systematic barriers to completion of the requisite training and continued practice.

Operations and outcomes of a Hospital-wide Emergency Airway Response Team (HEART) in a quaternary academic children's hospital.

BACKGROUND: To improve pediatric airway management outside of the operating room, a Hospital-wide Emergency Airway Response Team (HEART) program composed of anesthesiology, otorhinolaryngology, and respiratory therapy clinicians was developed. AIMS: To report processes and outcomes of HEART activations in a quaternary academic children's hospital. METHODS: A retrospective observational cohort study between January 2017 and December 2019. Local airway emergency database was reviewed for HEART activations. Additional safety data was obtained from patients' electronic health records. PRIMARY OUTCOME: Adverse airway outcomes, either adverse tracheal intubation-associated events or oxygen desaturation (SpO2 <80%). We compared airway management by primary teams before HEART arrival and by HEART after arrival. RESULTS: Of 96 HEART activations, 36 were from neonatal intensive care unit, 35 from pediatric and cardiac intensive care units, 14 from emergency department, and 11 from inpatient wards. 56 (62%) children had airway anomalies and 41/96 (43%) were invasively ventilated. Median HEART arrival time was 5 min (interquartile range, 3-5). 56/96 (58%) required insertion of an advanced airway (supra/extra-glottic airway, endotracheal tube, tracheostomy tube). HEART succeeded in establishing a definitive airway in 53/56 (94%). Adverse airway outcomes were more common before (56/96, 58%) versus after HEART arrival (28/96, 29%; absolute risk difference 29%; 95% confidence interval 16, 41%; p < .001). Oxygen desaturation occurred more frequently before (46/96, 48%) versus after HEART arrival (24/96, 25%; absolute risk difference 23%; 95% confidence interval 11, 35%; p = .02). Cardiac arrests were more common before (9/96, 9%) versus after HEART arrival (3/96, 3%). Multiple (≥3) intubation attempts were more frequent before (14/42, 33%) versus after HEART arrival (9/46, 20%; absolute risk difference -14%; 95% confidence interval -32, 5%; p = .15). CONCLUSIONS: A multidisciplinary emergency airway response team plays an important role in pediatric airway management outside of the operating room. Adverse airway outcomes were more frequent before compared to after HEART arrival.

Pediatric Airway Management in COVID-19 Patients: Consensus Guidelines From the Society for Pediatric Anesthesia's Pediatric Difficult Intubation Collaborative and the Canadian Pediatric Anesthesia Society.

The severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]) pandemic has challenged medical systems and clinicians globally to unforeseen levels. Rapid spread of COVID-19 has forced clinicians to care for patients with a highly contagious disease without evidence-based guidelines. Using a virtual modified nominal group technique, the Pediatric Difficult Intubation Collaborative (PeDI-C), which currently includes 35 hospitals from 6 countries, generated consensus guidelines on airway management in pediatric anesthesia based on expert opinion and early data about the disease. PeDI-C identified overarching goals during care, including minimizing aerosolized respiratory secretions, minimizing the number of clinicians in contact with a patient, and recognizing that undiagnosed asymptomatic patients may shed the virus and infect health care workers. Recommendations include administering anxiolytic medications, intravenous anesthetic inductions, tracheal intubation using video laryngoscopes and cuffed tracheal tubes, use of in-line suction catheters, and modifying workflow to recover patients from anesthesia in the operating room. Importantly, PeDI-C recommends that anesthesiologists consider using appropriate personal protective equipment when performing aerosol-generating medical procedures in asymptomatic children, in addition to known or suspected children with COVID-19. Airway procedures should be done in negative pressure rooms when available. Adequate time should be allowed for operating room cleaning and air filtration between surgical cases. Research using rigorous study designs is urgently needed to inform safe practices during the COVID-19 pandemic. Until further information is available, PeDI-C advises that clinicians consider these guidelines to enhance the safety of health care workers during airway management when performing aerosol-generating medical procedures. These guidelines have been endorsed by the Society for Pediatric Anesthesia and the Canadian Pediatric Anesthesia Society.

East/West Visiting Scholars in Pediatric Anesthesia Program (ViSiPAP): Developing tomorrow's pediatric anesthesia leaders.

Promoting and retaining junior faculty are major challenges for many medical schools. High clinical workloads often limit time for scholarly projects and academic development, especially in anesthesiology. To address this, we created the East/West Visiting Scholars in Pediatric Anesthesia Program (ViSiPAP). The program's goal is to help "jumpstart" academic careers by providing opportunities for national exposure and recognition through invited lectures and collaborative opportunities. East/West ViSiPAP benefits the participating scholars, the home and hosting anesthesia departments, and pediatric anesthesia fellowship training programs. By fostering a sense of well-being and inclusion in the pediatric anesthesia community, East/West ViSiPAP has the potential to increase job satisfaction, help faculty attain promotion, and reduce attrition. Faculty and trainees are exposed to new expertise and role models. Moreover, ViSiPAP provides opportunities for women and underrepresented in medicine faculty. This program can help develop today's junior faculty into tomorrow's leaders in pediatric anesthesia. We advocate for expanding the concept of ViSiPAP to other institutions in academic medicine.

Videolaryngoscopy versus Fiber-optic Intubation through a Supraglottic Airway in Children with a Difficult Airway: An Analysis from the Multicenter Pediatric Difficult Intubation Registry.

BACKGROUND: The success rates and related complications of various techniques for intubation in children with difficult airways remain unknown. The primary aim of this study is to compare the success rates of fiber-optic intubation via supraglottic airway to videolaryngoscopy in children with difficult airways. Our secondary aim is to compare the complication rates of these techniques. METHODS: Observational data were collected from 14 sites after management of difficult pediatric airways. Patient age, intubation technique, success per attempt, use of continuous ventilation, and complications were recorded for each case. First-attempt success and complications were compared in subjects managed with fiber-optic intubation via supraglottic airway and videolaryngoscopy. RESULTS: Fiber-optic intubation via supraglottic airway and videolaryngoscopy had similar first-attempt success rates (67 of 114, 59% vs. 404 of 786, 51%; odds ratio 1.35; 95% CI, 0.91 to 2.00; P = 0.16). In subjects less than 1 yr old, fiber-optic intubation via supraglottic airway was more successful on the first attempt than videolaryngoscopy (19 of 35, 54% vs. 79 of 220, 36%; odds ratio, 2.12; 95% CI, 1.04 to 4.31; P = 0.042). Complication rates were similar in the two groups (20 vs. 13%; P = 0.096). The incidence of hypoxemia was lower when continuous ventilation through the supraglottic airway was used throughout the fiber-optic intubation attempt. CONCLUSIONS: In this nonrandomized study, first-attempt success rates were similar for fiber-optic intubation via supraglottic airway and videolaryngoscopy. Fiber-optic intubation via supraglottic airway is associated with higher first-attempt success than videolaryngoscopy in infants with difficult airways. Continuous ventilation through the supraglottic airway during fiber-optic intubation attempts may lower the incidence of hypoxemia.

Social dimensions of science-humanitarian collaboration: lessons from Padang, Sumatra, Indonesia.

This paper contains a critical exploration of the social dimensions of the science-humanitarian relationship. Drawing on literature on the social role of science and on the social dimensions of humanitarian practice, it analyses a science-humanitarian partnership for disaster risk reduction (DRR) in Padang, Sumatra, Indonesia, an area threatened by tsunamigenic earthquakes. The paper draws on findings from case study research that was conducted between 2010 and 2011. The case study illustrates the social processes that enabled and hindered collaboration between the two spheres, including the informal partnership of local people and scientists that led to the co-production of earthquake and tsunami DRR and limited organisational capacity and support in relation to knowledge exchange. The paper reflects on the implications of these findings for science-humanitarian partnering in general, and it assesses the value of using a social dimensions approach to understand scientific and humanitarian dialogue.

Effect of transfusion guidelines on postoperative transfusion in children undergoing craniofacial reconstruction surgery.

OBJECTIVE: To assess the effect of implementation of population-specific postoperative management guidelines on postoperative transfusion in children undergoing cranial vault reconstruction surgery. DESIGN: Retrospective observational study with historical controls. SETTING: Single, large, academic tertiary pediatric hospital. PATIENTS: : Children aged 6 months to 17 yrs undergoing fronto-orbital advancement or posterior cranial vault reconstruction surgery enrolled in our craniofacial surgery perioperative registry from April 14, 2008 to September 7, 2011. INTERVENTION: Postoperative management guidelines for children undergoing cranial vault reconstruction surgery were implemented on December 1, 2009. These management guidelines included projected surgical drain output as well as specific transfusion thresholds for packed red blood cells and hemostatic blood products. MEASUREMENTS AND MAIN RESULTS: We queried our craniofacial surgery perioperative registry for children who underwent cranial vault reconstruction to assess transfusion practices before and after the implementation of the postoperative guidelines. Subjects were divided into a preguideline cohort and a postguideline cohort. Perioperative demographic data and postoperative transfusion data were compared between the two groups. The registry query returned data on 59 procedures in the preguideline cohort and 58 procedures in the postguideline cohort. The immediate postoperative hematocrit and the postoperative blood loss through surgical drains were not statistically different in the two groups. The prevalence of postoperative transfusion of any blood product was significantly less in the postguideline cohort (17% vs. 42%, p = .003). Most of the transfusion reduction was achieved through a reduction in fresh frozen plasma transfusion (5% vs. 25%, p = .002). CONCLUSIONS: In this observational study, the implementation of postoperative management guidelines was associated with a 60% reduction in postoperative transfusion. The use of transfusion thresholds is a simple, inexpensive, and effective strategy for transfusion reduction and should be a first-line approach to perioperative transfusion reduction in this population.

Modelling and quantifying tomorrow's risks from natural hazards.

Understanding and modelling future risks from natural hazards is becoming increasingly crucial as the climate changes, human population grows, asset wealth accumulates, and societies become more urbanised and interconnected. This need is recognised by the 2015-2030 Sendai Framework for Disaster Risk Reduction, which emphasises the importance of preparing for the disasters that our world may face tomorrow through strategies/policies that aim to minimise uncontrolled development in hazardous areas. While the vast majority of natural-hazard risk-assessment frameworks have so far focused on static impacts associated with current conditions and/or are influenced by historical context, some authors have sought to provide decision makers with risk-quantification approaches that can be used to cultivate a sustainable future. This Review documents these latter efforts, explicitly examining work that has modelled and quantified the individual components that comprise tomorrow's risk, i.e., future natural hazards affected by climate change, future exposure (e.g., in terms of population, land use, and the built environment), and the evolving physical vulnerabilities of the world's infrastructure. We end with a discussion on the challenges faced by modellers in determining the risks that tomorrow's world may face from natural hazards, and the constraints these place on the decision-making abilities of relevant stakeholders.

Indonesian earthquake: earthquake risk from co-seismic stress.

Following the massive loss of life caused by the Sumatra-Andaman earthquake in Indonesia and its tsunami, the possibility of a triggered earthquake on the contiguous Sunda trench subduction zone is a real concern. We have calculated the distributions of co-seismic stress on this zone, as well as on the neighbouring, vertical strike-slip Sumatra fault, and find an increase in stress on both structures that significantly boosts the already considerable earthquake hazard posed by them. In particular, the increased potential for a large subduction-zone event in this region, with the concomitant risk of another tsunami, makes the need for a tsunami warning system in the Indian Ocean all the more urgent.

Seismology: earthquake risk on the Sunda trench.

On 28 March 2005 the Sunda megathrust in Indonesia ruptured again, producing another great earthquake three months after the previous one. The rupture was contiguous with that of the December 2004 Sumatra-Andaman earthquake, and is likely to have been sparked by local stress, although the triggering stresses at its hypocentre were very small - of the order of just 0.1 bar. Calculations show that stresses imposed by the second rupture have brought closer to failure the megathrust immediately to the south, under the Batu and Mentawai islands, and have expanded the area of increased stress on the Sumatra fault. Palaeoseismologic studies show that the Mentawai segment of the Sunda megathrust is well advanced in its seismic cycle and is therefore a good candidate for triggered failure.

Perioperative management of children undergoing craniofacial reconstruction surgery: a practice survey.

OBJECTIVE/AIMS: To assess current practices in the management of children undergoing craniofacial surgery and identify areas of significant practice variability with the intent to direct future research. BACKGROUND: The perioperative management of infants and children undergoing craniofacial reconstruction surgery can be challenging because of the routine occurrence of significant blood loss with associated morbidity. A variety of techniques have been described to improve the care for these children. It is presently unknown to what extent these practices are currently employed. METHODS: A web-based survey was sent to representatives from 102 institutions. One individual per institution was surveyed to prevent larger institutions from being over-represented in the results. RESULTS: Requests to complete the survey were sent to 102 institutions; 48 surveys were completed. The survey was composed of two parts: management of infants undergoing strip craniectomies, and management of children undergoing major craniofacial reconstruction. CONCLUSIONS: Significant variability exists in the management of children undergoing these procedures; further study is required to determine the optimal management strategies. Clinical trials assessing the utility of central venous pressure and other hemodynamic monitoring modalities would enable evidence-based decision-making for monitoring in these children. The development of institutional transfusion thresholds should be encouraged, as there exists a body of evidence supporting their efficacy and safety.

Fluoroscopic-assisted endobronchial intubation for single-lung ventilation in infants.

OBJECTIVE: Review our institutional experience with an alternative to fiberoptic-guided endobronchial intubation. AIM: The aim of this retrospective cohort study was to present our experience with the use of fluoroscopy to facilitate endobronchial lung isolation in infants undergoing thoracoscopic procedures. BACKGROUND: Anesthesiologists are more frequently being asked to anesthetize infants and small children for thoracoscopic surgery. Typically, endobronchial intubation or bronchial blockers are utilized to achieve lung isolation during these procedures. However, sometimes small and complicated anatomy can make this challenging. METHODS: Respective chart review over a 13-month period of infants undergoing thoracoscopic excision of congenital lung lesions at the Children's Hospital of Philadelphia. Rate of success in achieving lung isolation along with time of fluoroscopy exposure were recorded. RESULTS: Twenty infants had thoracoscopic lung surgery attempted during the period of the review. Lung isolation was successfully achieved in all of the patients. The average exposure to fluoroscopy was 83.7 s (range 20-320 s). CONCLUSIONS: Fluoroscopic aided lung isolation is a reliable and effective alternative method to the use of fiberoptic bronchoscope for endobronchial intubation in infants.

Dynamic earthquake triggering response tracks evolving unrest at Sierra Negra volcano, Galápagos Islands.

The propensity for dynamic earthquake triggering is thought to depend on the local stress state and amplitude of the stress perturbation. However, the nature of this dependency has not been confirmed within a single crustal volume. Here, we show that at Sierra Negra volcano, Galápagos Islands, the intensity of dynamically triggered earthquakes increased as inflation of a magma reservoir elevated the stress state. The perturbation of short-term seismicity within teleseismic surface waves also increased with peak dynamic strain. Following rapid coeruptive subsidence and reduction in stress and background seismicity rates, equivalent dynamic strains no longer triggered detectable seismicity. These findings offer direct constraints on the primary controls on dynamic triggering and suggest that the response to dynamic stresses may help constrain the evolution of volcanic unrest.