Oxidative Syntheses of N,N-Dialkylhydroxylamines.

Despite the wide utility of hydroxylamines in organic synthesis, relatively few are commercially available, and there is a need for direct, efficient, and selective methods for their synthesis. Herein, we report two complementary methods to accomplish direct oxidation of secondary amines using UHP as an oxidant. The first method uses 2,2,2-trifluoroethanol (TFE) and a large excess of amine. Isolation of hydroxylamine products is enabled by selective salt formation, and recovery of excess amine is demonstrated. The second method uses hexafluoroacetone as an additive and is highlighted by the 1:1 stoichiometry between the oxidant and amine.

COVID-19 Case Investigation and Contact Tracing Programs and Practice: Snapshots From the Field.

Between Fall 2020 and Spring 2021, the Association of State and Territorial Health Officials conducted 2 rapid queries to collect information from the field regarding the status of COVID-19 case investigation and contact tracing (CI/CT) programs and practice. These short surveys were distributed to senior deputies in state and territorial health agencies, yielding a response rate of 45.8% (November 2020) and 40.7% (April 2021). Findings indicated that CI/CT staff roles and assigned functions varied across jurisdictions, as did staffing levels/capacity, approaches for linking individuals to social supports, and program changes that were planned or underway. Agency-reported staffing levels/capacity and programmatic challenges changed over time, highlighting the dynamic nature of CI/CT program practice and implementation. While findings from the surveys cannot be generalized to the national level, they provide critical insights from the field on CI/CT program implementation, challenges, and changes in response to the evolving COVID-19 epidemic in the United States.

The utility of ICG fluorescence for sentinel lymph node identification in head and neck melanoma.

PURPOSE: Perform an evidence-based review to determine the utility of indocyanine green fluorescence (ICG) to detect sentinel lymph nodes (SLN) in patients with head and neck melanoma compared to blue dye or radiocolloid injection (RI). MATERIALS AND METHODS: A systematic review of the literature was performed to identify patients with head and neck melanoma managed with ICG fluorescence. PubMed, Embase, and Cochrane Library databases were searched. Included studies were assessed for level of evidence. Patient demographics and data on SLN identification were determined. RESULTS: Twenty-two studies encompassing 399 patients (75% male, 25% female, average age 57.1 years) met inclusion criteria. Publications comprised of two case reports, four retrospective case series, twelve cohort studies, and four clinical trials. Most common site of melanoma was scalp/temple/forehead (35%), cheek/midface (22%), and ear (17%) with an average Breslow thickness of 3.32 mm. SLN was identified in 80.7% (n = 201/249) of patients using ICG-RI, 85.2% (n = 75/88) using RI alone, and 63.4% (n = 52/82) using blue dye-RI. CONCLUSIONS: ICG-99mTc-nanocolloid hybrid tracer may be a superior alternative to blue dye + adiocolloid and has theoretical advantages compared to RI alone. Additional prospective randomized controlled trials are needed to further compare these methods and obtain data on false negative rates, operating room time, and cost effectiveness to fully elucidate the utility of ICG-99mTc-nanocolloid over current methods used for SLN identification in this patient population.

Acute epiglottitis: Analysis of U.S. mortality trends from 1979 to 2017.

PURPOSE: Evaluate trends in mortality due to acute epiglottitis before and after adoption of Haemophilus influenza Type b vaccination (Hib) in pediatric and adult populations. MATERIALS AND METHODS: Patients who died from acute epiglottis from 1979 to 2017 identified using National Vital Statistics System. Mortality rates calculated using age-adjusted US census data expressed in rate per 100,000 individuals. Trends analyzed using the National Cancer Institute Joinpoint Regression Program (version 4.7.0; Bethesda, Maryland). RESULTS: 1187 epiglottitis-related deaths were identified over thirty-nine years. Total deaths decreased from 65 in 1979 to 15 in 2017. Adult deaths accounted for 63.5% and decreased from 0.015 per 100,000 individuals (24 deaths) in 1979 to 0.006 per 100,000 individuals (14 deaths) in 2017. Best fitting log-liner regression model showed APC of -3.5% (95% CI, -4.2 to -2.7%) from 1979 to 2017. Pediatric and adolescent deaths accounted for 443 (37.3%) deaths, decreasing from 0.064 per 100,000 individuals (41 deaths) in 1979 to 0.001 per 100,000 individuals (1 death) in 2017. APC was -11.1% (95% CI, -13.8% to -8.3%) in 1979 to 1990; 46.5% (95% CI, -16.6% to 157.3%) in 1990 to 1993; -61.6% (95% CI, -88% to 23%) in 1993 to 1996; and 1.1% (95% CI, -2.4% to 4.7%) in 1996 to 2017. CONCLUSIONS: Mortality from acute epiglottitis decreased after widespread adoption of Hib vaccination in the US. Adults are now more likely than children to die of acute epiglottitis. Further research including multi-institutional cohort studies must be done to elucidate causative factors contributing to remaining cases of mortality.

Nasal Analysis of Classic Animated Movie Villains versus Hero Counterparts.

Opposing facial features between animated villains and heroes have historically been used to demonstrate contrasting morality between characters, and this could have an impact on how humans view someone as good or evil in everyday life. Studies have been done investigating classic dermatologic features of villainous characters. This principle can be applied to nasal features as well. A search for "top animated characters" was performed. Characters were chosen from American Film Institute's "The Top Tens," Rolling Stone's "25 Best Pixar Movie Characters," and Screenrant's "The 30 Best Animated Movie Characters of All Time." Twenty villains and twenty hero counterparts from respective films were chosen. Classic nasal features were analyzed. Twenty villains (14 male, 6 female) and 20 heroes (12 male, 8 female) were analyzed. Sixteen villains (80%) had greater than normal nasal frontal angle versus 18 heroes (90%). Thirteen villains (65%) had an acute nasolabial angle versus two heroes (10%). Two villains (10%) had excess columellar show versus seven heroes (35%). Seven villains (35%) and one hero (5%) had a dorsal hump. Twelve villains (60%) had an overprojected chin versus three heroes (15%). Villains in pre-2000s films more frequently had a dorsal hump, overprojected chin, ptotic tip, pollybeak deformity, and bulbous tip. Heroes in pre-2000s films more frequently had an overrotated tip. Villains and heroes commonly have a greater than normal nasofrontal angle. Villains more commonly have an acute nasolabial angle, underrotated tip, overprojected chin, dorsal hump, and pollybeak deformity. Heroes more commonly have a large nasolabial angle and overrotated tip. Further research in conjunction with psychologists is required to obtain concrete data on how this affects whether an individual in real life is seen as good or evil, and the impact this has on interactions in society, including in the medical field.

COVID-19 Case Investigation and Contact Tracing: Early Lessons Learned and Future Opportunities.

CONTEXT: Case investigation and contact tracing are fundamental public health strategies for controlling and preventing the spread of infectious diseases. Although the principles behind these strategies are not new, the capacity and operational requirements needed to support disease investigation during the SARS-CoV-2 (COVID-19) pandemic are unprecedented. This article analyzes the implementation of case investigation and contact tracing in controlling COVID-19 transmission during the early stages of the US pandemic response (January 20 through August 31, 2020). PROGRAM IMPLEMENTATION: Governmental public health agencies mobilized to expand case investigation and contact tracing programs in the early months of the pandemic. In doing so, they encountered a range of challenges that included rapidly scaling up the workforce; developing and subsequently revising guidance and protocols specific to COVID-19 as more was learned about the virus over time; defining job functions; encouraging public acceptance of and participation in case investigation and contact tracing; and assessing the utility of these activities during both the containment and mitigation phases of outbreak response. COVID-19 case investigation and contact tracing programs presented an array of opportunities for health departments to innovate, especially around technology to support public health efforts, as well as opportunities to address health equity and advance community resilience. CONCLUSION: Lessons learned from disease intervention specialists, guidance and resources from federal agencies and national partners, and peer-to-peer exchange of promising practices can support jurisdictions encountering early implementation challenges. Further research is needed to assess COVID-19 case investigation and contact tracing program models and innovations, as well as strategies for implementing these activities during containment and mitigation phases.

Annulation of Oxime-Ether Tethered Donor-Acceptor Cyclopropanes.

Novel oxime-ether tethered cyclopropanes, when exposed to Yb(OTf)3 and heat, annulate to generate hydropyrrolo-oxazines products that can be taken to their respective pyrrolidines via hydrogenative N-O bond cleavage. The hydropyrrolo-oxazines are generated in a diastereoselective manner isolating the cis or trans product based on the temperature of the reaction. 20 examples of selective cis and trans hydropyrrolo-oxazines were generated in high yields by temperature control.

O-Isocyanates as Uncharged 1,3-Dipole Equivalents in [3+2] Cycloadditions.

1,3-Dipoles are commonly used in [3+2] cycloadditions, whereas isoelectronic uncharged dipole variants remain underdeveloped. In contrast to conventional 1,3-dipoles, uncharged dipole equivalents form zwitterionic cycloadducts, which can be exploited to build further molecular complexity. In this work, the first cycloadditions of oxygen-substituted isocyanates (O-isocyanates) were studied experimentally and by DFT calculations. This unique cycloaddition strategy provides access to a novel class of heterocycle aza-oxonium ylides through intramolecular and intermolecular cycloadditions with alkenes. This allowed a systematic study of the reactivity of the transient aza-oxonium ylide intermediate, which can undergo N-O bond cleavage followed by nitrene C-H insertion, and the formation of ß-lactams or isoxazolidinones upon varying the structure of the alkene or O-isocyanate reagents.

Toddlers prefer to help familiar people.

Young children's willingness to spontaneously help others is the subject of a large body of research investigating the ontogeny of moral behavior and thought. A developing debate centers around the extent to which social factors influence the desire to help. Familiarity with the person needing help is one such factor that varies across many studies but has not been systematically investigated. In Experiment 1, we show that toddlers were significantly more likely to assist a person on an out-of-reach clothespin task when they had previously become familiar with that person. Moreover, and in contrast to previous work, we found that becoming familiar with a person increases helpfulness only toward that person and does not transfer to an unknown person. We further demonstrate, in Experiment 2A, that children were equally likely to approach and take a sticker from an experimenter with whom they were familiar or unfamiliar-thereby ruling out wariness of strangers as the key driver for familiarity effects in Experiment 1. Moreover, in Experiment 2B, we show that children were more likely to help the previously unfamiliar partner (from Experiment 2A) after the partner gave the child the sticker. We conclude that familiarity is an ecologically important social influencer of toddler helping behavior.

Influenza Antiviral Shortages Reported by State and Territorial Public Health Officials, 2022-2023.

This study provides survey results from state and territorial public health preparedness directors regarding antiviral shortages during the 2022-2023 respiratory viral season.

Biomarkers in Pediatric Cardiac Critical Care.

OBJECTIVES: In this review, we discuss the physiology, pathophysiology, and clinical role of troponin, lactate, and B-type natriuretic peptide in the assessment and management of children with critical cardiac disease. DATA SOURCE: MEDLINE, PubMed. CONCLUSION: Lactate, troponin, and B-type natriuretic peptide continue to be valuable biomarkers in the assessment and management of critically ill children with cardiac disease. However, the use of these markers as a single measurement is handicapped by the wide variety of clinical scenarios in which they may be increased. The overall trend may be more useful than any single level with a persistent or rising value of more importance than an elevated initial value.

A perivascular niche for brain tumor stem cells.

Cancers are believed to arise from cancer stem cells (CSCs), but it is not known if these cells remain dependent upon the niche microenvironments that regulate normal stem cells. We show that endothelial cells interact closely with self-renewing brain tumor cells and secrete factors that maintain these cells in a stem cell-like state. Increasing the number of endothelial cells or blood vessels in orthotopic brain tumor xenografts expanded the fraction of self-renewing cells and accelerated the initiation and growth of tumors. Conversely, depletion of blood vessels from xenografts ablated self-renewing cells from tumors and arrested tumor growth. We propose that brain CSCs are maintained within vascular niches that are important targets for therapeutic approaches.

Inter-professional in-situ simulated team and resuscitation training for patient safety: Description and impact of a programmatic approach.

BACKGROUND: Inter-professional teamwork is key for patient safety and team training is an effective strategy to improve patient outcome. In-situ simulation is a relatively new strategy with emerging efficacy, but best practices for the design, delivery and implementation have yet to be evaluated. Our aim is to describe and evaluate the implementation of an inter-professional in-situ simulated team and resuscitation training in a teaching hospital with a programmatic approach. METHODS: We designed and implemented a team and resuscitation training program according to Kern's six steps approach for curriculum development. General and specific needs assessments were conducted as independent cross-sectional surveys. Teamwork, technical skills and detection of latent safety threats were defined as specific objectives. Inter-professional in-situ simulation was used as educational strategy. The training was embedded within the workdays of participants and implemented in our highest acuity wards (emergency department, intensive care unit, intermediate care unit). Self-perceived impact and self-efficacy were sampled with an anonymous evaluation questionnaire after every simulated training session. Assessment of team performance was done with the team-based self-assessment tool TeamMonitor applying Van der Vleuten's conceptual framework of longitudinal evaluation after experienced real events. Latent safety threats were reported during training sessions and after experienced real events. RESULTS: The general and specific needs assessments clearly identified the problems, revealed specific training needs and assisted with stakeholder engagement. Ninety-five interdisciplinary staff members of the Children's Hospital participated in 20 in-situ simulated training sessions within 2 years. Participant feedback showed a high effect and acceptance of training with reference to self-perceived impact and self-efficacy. Thirty-five team members experiencing 8 real critical events assessed team performance with TeamMonitor. Team performance assessment with TeamMonitor was feasible and identified specific areas to target future team training sessions. Training sessions as well as experienced real events revealed important latent safety threats that directed system changes. CONCLUSIONS: The programmatic approach of Kern's six steps for curriculum development helped to overcome barriers of design, implementation and assessment of an in-situ team and resuscitation training program. This approach may help improve effectiveness and impact of an in-situ simulated training program.

Optimisation of simulated team training through the application of learning theories: a debate for a conceptual framework.

BACKGROUND: As a conceptual review, this paper will debate relevant learning theories to inform the development, design and delivery of an effective educational programme for simulated team training relevant to health professionals. DISCUSSION: Kolb's experiential learning theory is used as the main conceptual framework to define the sequence of activities. Dewey's theory of reflective thought and action, Jarvis modification of Kolb's learning cycle and Schön's reflection-on-action serve as a model to design scenarios for optimal concrete experience and debriefing for challenging participants' beliefs and habits. Bandura's theory of self-efficacy and newer socio-cultural learning models outline that for efficient team training, it is mandatory to introduce the social-cultural context of a team. SUMMARY: The ideal simulated team training programme needs a scenario for concrete experience, followed by a debriefing with a critical reflexive observation and abstract conceptualisation phase, and ending with a second scenario for active experimentation. Let them re-experiment to optimise the effect of a simulated training session. Challenge them to the edge: The scenario needs to challenge participants to generate failures and feelings of inadequacy to drive and motivate team members to critical reflect and learn. Not experience itself but the inadequacy and contradictions of habitual experience serve as basis for reflection. Facilitate critical reflection: Facilitators and group members must guide and motivate individual participants through the debriefing session, inciting and empowering learners to challenge their own beliefs and habits. To do this, learners need to feel psychological safe. Let the group talk and critical explore. Motivate with reality and context: Training with multidisciplinary team members, with different levels of expertise, acting in their usual environment (in-situ simulation) on physiological variables is mandatory to introduce cultural context and social conditions to the learning experience. Embedding in situ team training sessions into a teaching programme to enable repeated training and to assess regularly team performance is mandatory for a cultural change of sustained improvement of team performance and patient safety.

Intraosseous Hemangioma of the Zygomatic Bone with Multidisciplinary Approach to Surgical Resection and Orbital Reconstruction.

Background: Intraosseous hemangiomas are rare benign tumors comprising fewer than 1% of all osseous tumors; even more uncommon are intraosseous hemangiomas of the zygomatic bone. This case reports a multidisciplinary approach for excision and reconstruction of an intraosseous hemangioma of the zygomatic bone in a 54-year-old female. Methods: Multidisciplinary approach with both otolaryngology head and neck surgery and oculofacial plastics and reconstructive surgery included right lateral canthotomy and right transconjunctival orbitotomy with en-bloc excision of the zygomatic arch, followed by reconstruction of the orbital rim, orbital floor, and eyelid with Medpor implant. Results: Final surgical pathology was consistent with intraosseous hemangioma of the zygomatic bone. At 4-month follow-up, the patient was healing well with good midface projection and without any visual deficits. Conclusions: A multidisciplinary coordinated case allowed us to meet the standard of maintaining cosmesis and function while undergoing resection of a rare tumor involving a key facial structure-the zygoma. Involvement of oculofacial plastics and reconstructive surgery service allowed for advanced eyelid reconstruction techniques to limit any functional impairment to our patient with deliberate choice of implant material for well-adhered, durable, and aesthetically optimal reconstruction of the right malar eminence, lateral orbital rim, and orbital floor defect. The postoperative result through the multidisciplinary approach was a near symmetrical facial reconstruction without any associated eyelid or globe abnormalities.

Establishing a paediatric critical care core quality measure set using a multistakeholder, consensus-driven process.

Introduction: Monitoring healthcare quality is challenging in paediatric critical care due to measure variability, data collection burden, and uncertainty regarding consumer and clinician priorities. Objective: We sought to establish a core quality measure set that (i) is meaningful to consumers and clinicians and (ii) promotes alignment of measure use and collection across paediatric critical care. Design: We conducted a multi-stakeholder Delphi study with embedded consumer prioritisation survey. The Delphi involved two surveys, followed by a consensus meeting. Triangulation methods were used to integrate survey findings prior tobefore the consensus meeting. In the consensus panel, broad agreement was reached on a core measure set, and recommendations were made for future measurement directions in paediatric critical care. Setting and participants: Australian and New Zealand paediatric critical care survivors (aged >18 years) and families were invited to rank measure priorities in an online survey distributed via social media and consumer groups. A concurrent Delphi study was undertaken with paediatric critical care clinicians, policy makers, and a consumer representative. Interventions: None. Main outcome measures: Priorities for quality measures. Results: Respondents to the consumer survey (n = 117) identified (i) nurse-patient ratios; (ii) visible patient goals; and (iii) long-term follow-up as their quality measure priorities. In the Delphi process, clinicians (Round 1 n = 191; Round 2 n = 117 [61% retention]; Round 3 n = 14) and a consumer representative reached broad agreement on a 51-item (61% of 83 initial measures) core measure set. Clinician priorities were (i) nurse-patient ratio; (ii) staff turnover; and (iii) long term-follow up. Measure feasibility was rated low due to a perceived lack of standardised case definitions or data collection burden. Five recommendations were generated. Conclusions: We defined a 51-item core measurement set for paediatric critical care, aligned with clinician and consumer priorities. Next steps are implementation and methodological evaluation in quality programs, and where appropriate, retirement of redundant measures.

Cope-Type Hydroamination of Vinylboronates.

Aminoboronic acid derivatives can serve as versatile synthetic intermediates and pharmacophores but remain difficult to synthesize. Herein we report a synthesis of the ß-aminoboronic acid motif via anti-Markovnikov hydroamination of vinylboronates. This reaction benefits from the activating effect of the boronate substituent and forms novel BON-containing heterocycles, oxazaborolidine zwitterions. A computational study is included to help determine the effects of alkene boron substitution. Derivatization reactions also support the synthetic utility of the oxazaborolidine adducts.

A redox-enabled strategy for intramolecular hydroamination.

Metal- or acid-catalyzed intramolecular hydroamination and Cope-type intramolecular hydroamination, a distinct concerted approach using hydroxylamines, typically suffer from significant synthetic limitations. Herein we report a process for intramolecular hydroamination that uses a redox-enabled strategy relying on efficient in situ generation of hydroxylamines by oxidation, followed by Cope-type hydroamination, then reduction of the resulting pyrrolidine N-oxide. The steps are performed sequentially in a single pot, no catalyst is required, the conditions are mild, the process is highly functional group tolerant, and no chromatography is generally required for isolation. A robustness screen and a gram-scale example further support the practicality of this approach.