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Short-lived α-decaying nuclei "northeast" of Pb208 in the chart of nuclides were studied using the reaction Ca48+Am243 with the decay station TASISpec at TASCA, GSI Darmstadt. Decay energies and times from pile-up events were extracted with a tailor-made pulse-shape analysis routine and specific α-decay chains were identified in a correlation analysis. Decay chains starting with the even-even Ra220 and its odd-A neighbors, Fr219, and Ra221,219, with a focus on the Ra219→Rn215 decay, were studied by means of α-γ spectroscopy. A revised α-decay scheme of Ra219 is proposed, including a new decay branch from a previously not considered isomeric state at 17 keV excitation energy. Conclusions on nuclear structure are drawn from the experimental data, aided by Geant4 simulations and a discussion on theoretical calculations.

Short-lived α-decaying nuclei "northeast" of Pb208 in the chart of nuclides were studied using the reaction Ca48+Am243 with the decay station TASISpec at TASCA, GSI Darmstadt. Decay energies and times from pile-up events were extracted with a tailor-made pulse-shape analysis routine and specific α-decay chains were identified in a correlation analysis. Decay chains starting with the even-even Ra220 and its odd-A neighbors, Fr219, and Ra221,219, with a focus on the Ra219→Rn215 decay, were studied by means of α-γ spectroscopy. A revised α-decay scheme of Ra219 is proposed, including a new decay branch from a previously not considered isomeric state at 17 keV excitation energy. Conclusions on nuclear structure are drawn from the experimental data, aided by Geant4 simulations and a discussion on theoretical calculations.

A multi-step Coulomb excitation measurement with the GRETINA and CHICO2 detector arrays was carried out with a 430-MeV beam of the neutron-rich 110Ru (t1/2=12 s) isotope produced at the CARIBU facility. This represents the first successful measurement following the post-acceleration of an unstable isotope of a refractory element. The reduced transition probabilities obtained for levels near the ground state provide strong evidence for a triaxial shape; a conclusion confirmed by comparisons with the results of beyond-mean-field and triaxial rotor model calculations.

Products of the fusion-evaporation reaction 48Ca + 243Am were studied with the TASISpec set-up at the gas-filled separator TASCA at the GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt, Germany. Amongst the detected thirty correlated α-decay chains associated with the production of element Z=115, two recoil-α-fission and five recoil-α-α-fission events were observed. The latter five chains are similar to four such events reported from experiments performed at the Dubna gas-filled separator, and three such events reported from an experiment at the Berkeley gas-filled separator. The four chains observed at the Dubna gas-filled separator were assigned to start from the 2n-evaporation channel 289115 due to the fact that these recoil-α-α-fission events were observed only at low excitation energies. Contrary to this interpretation, we suggest that some of these recoil-α-α-fission decay chains, as well as some of the recoil-α-α-fission and recoil-α-fission decay chains reported from Berkeley and in this article, start from the 3n-evaporation channel 288115.

Produced in the reaction 48Ca+243Am, thirty correlated α-decay chains were observed in an experiment conducted at the GSI Helmholzzentrum für Schwerionenforschung, Darmstadt, Germany. The decay chains are basically consistent with previous findings and are considered to originate from isotopes of element 115 with mass numbers 287, 288, and 289. A set-up aiming specifically for high-resolution charged particle and photon coincidence spectroscopy was placed behind the gas-filled separator TASCA. For the first time, γ rays as well as X-ray candidates were observed in prompt coincidence with the α-decay chains of element 115.

We investigated decays of ^{51,52,53}K at the ISOLDE Decay Station at CERN in order to understand the mechanism of the β-delayed neutron-emission (βn) process. The experiment quantified neutron and γ-ray emission paths for each precursor. We used this information to test the hypothesis, first formulated by Bohr in 1939, that neutrons in the βn process originate from the structureless "compound nucleus." The data are consistent with this postulate for most of the observed decay paths. The agreement, however, is surprising because the compound-nucleus stage should not be achieved in the studied β decay due to insufficient excitation energy and level densities in the neutron emitter. In the ^{53}K βn decay, we found a preferential population of the first excited state in ^{52}Ca that contradicted Bohr's hypothesis. The latter was interpreted as evidence for direct neutron emission sensitive to the structure of the neutron-unbound state. We propose that the observed nonstatistical neutron emission proceeds through the coupling with nearby doorway states that have large neutron-emission probabilities. The appearance of "compound-nucleus" decay is caused by the aggregated small contributions of multiple doorway states at higher excitation energy.

Inflammasomes are intracellular protein complexes that promote an inflammatory host defense in response to pathogens and damaged or neoplastic tissues and are implicated in inflammatory disorders and therapeutic-induced toxicity. We investigated the mechanisms of activation for inflammasomes nucleated by NOD-like receptor (NLR) protiens. A screen of a small-molecule library revealed that several tyrosine kinase inhibitors (TKIs)-including those that are clinically approved (such as imatinib and crizotinib) or are in clinical trials (such as masitinib)-activated the NLRP3 inflammasome. Furthermore, imatinib and masitinib caused lysosomal swelling and damage independently of their kinase target, leading to cathepsin-mediated destabilization of myeloid cell membranes and, ultimately, cell lysis that was accompanied by potassium (K + ) efflux, which activated NLRP3. This effect was specific to primary myeloid cells (such as peripheral blood mononuclear cells and mouse bone marrow-derived dendritic cells) and did not occur in other primary cell types or various cell lines. TKI-induced lytic cell death and NLRP3 activation, but not lysosomal damage, were prevented by stabilizing cell membranes. Our findings reveal a potential immunological off-target of some TKIs that may contribute to their clinical efficacy or to their adverse effects.

Purpose: Clinical fellows, those training to become subspecialists in a program certified by the Accreditation Council for Graduate Medical Education, supervise residents on inpatient subspecialty rotations. Unlike for supervising residents or for faculty, there is a paucity of literature describing fellows' supervision of residents. The aim of this study was to understand residents' and fellows' perception of successful supervision of residents by fellows on inpatient subspecialty rotations to inform the development of curricula to support fellows as supervisors., Method: Using grounded theory methodology, the authors held focus groups in May 2020 of pediatric residents and pediatric subspecialty fellows at Boston Children's Hospital, Boston, Massachusetts. Focus groups were conducted until thematic saturation was achieved. Deidentified transcripts were independently coded by 2 authors. The author team consolidated the codes into themes and developed an interpretive model for fellows' successful supervision of residents. Key results were confirmed via member checking., Results: The authors conducted 4 resident focus groups, composed of 16 pediatric residents, and 4 fellow focus groups, composed of 13 pediatric subspecialty fellows. Participants perceived that fellows who provided successful resident supervision advanced residents' professional growth and supported residents' development along 5 "bridges": (1) generalist to subspecialist, (2) trainee to autonomous practitioner, (3) individual to member of the interprofessional team, (4) emerging physician to patient-facing care provider, and (5) newcomer to engaged clinical learner. Fellows can further residents' growth in these areas by demonstrating approachability, empathy, appreciation, and kindness., Conclusions: As newcomers on inpatient subspecialty rotations, residents engage in legitimate peripheral participation. Fellows who are successful supervisors move residents toward full participation in their profession via the bridge model. The fellow-resident dynamic carries advantages of near-peer learning. Fellows can harness their role, subspecialty knowledge, and familiarity with the training environment to enhance resident supervision., (Copyright © 2022 by the Association of American Medical Colleges.)

The NLRP3 inflammasome is an important player in innate immunity and pathogenic inflammation. Numerous studies have implicated it in sensing endogenous danger signals, yet the precise mechanisms remain unknown. Here, we review the current knowledge on the organismal and cellular metabolic triggers engaging NLRP3, and the mechanisms involved in integrating the diverse signals., (Copyright © 2021. Published by Elsevier Ltd.)

Objectives: To assess the characteristics of children hospitalized with complicated pneumonia at US children's hospitals and compare these characteristics with those of children hospitalized with community-acquired pneumonia (CAP)., Methods: We identified children hospitalized with complicated pneumonia (parapneumonic effusion, empyema, necrotizing pneumonia, or lung abscess) or CAP across 34 hospitals between 2011 and 2019. We evaluated differences in patient characteristics, antibiotic selection, and outcomes between children with complicated pneumonia and CAP. We, also, assessed seasonal variability in the frequency of these 2 conditions and evaluated the prevalence of complicated pneumonia over the 9-year study period., Results: Compared with children hospitalized with CAP ( n = 75 702), children hospitalized with complicated pneumonia ( n = 6402) were older (a median age of 6.1 vs 3.4 years; P < .001), with 59.4% and 35.2% of patients ≥5 years of age, respectively. Patients with complicated pneumonia had higher rates of antibiotic therapy targeted against methicillin-resistant Staphylococcus aureus (46.3% vs 12.2%; P < .001) and Pseudomonas (8.6% vs 6.7%; P < .001), whereas differences in rates of coverage against mycoplasma were not clinically significant. Children with complicated pneumonia had a longer median hospital length of stay and higher rates of ICU admissions, mechanical ventilation, 30-day readmissions, and costs. Seasonal variation existed in both complicated pneumonia and CAP, with 42.7% and 46.0% of hospitalizations occurring during influenza season. The proportion of pneumonia hospitalizations due to complicated pneumonia increased over the study period (odds ratio 1.04, 95% confidence interval: 1.02-1.06)., Conclusions: Complicated pneumonia more frequently occurs in older children and accounts for higher rates of resource use, compared to CAP., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Objectives: A large portion of residency education occurs in inpatient teaching services without widely accepted consensus regarding the essential components that constitute a teaching service. We sought to generate consensus around this topic, with the goal of developing criteria programs that can be used when creating, redesigning, or evaluating teaching services., Methods: A list of potential components of teaching services was developed from a literature search, interviews, and focus groups. Eighteen pediatric medical education experts participated in a modified Delphi method, responding to a series of surveys rating the importance of the proposed components. Each iterative survey was amended on the basis of the results of the previous survey. A final survey evaluating the (1) effort and (2) impact of implementing components that had reached consensus as recommended was distributed., Results: Each survey had 100% panelist response. Five survey rounds were conducted. Fourteen attending physician characteristics and 7 system characteristics reached consensus as essential components of a teaching service. An additional 25 items reached consensus as recommended. When evaluating the effort and impact of these items, the implementation of attending characteristics was perceived as requiring less effort than system characteristics but as having similar impact., Conclusions: Consensus on the essential and recommended components of a resident teaching service was achieved by using the modified Delphi method. Although the items that reached consensus as essential are similar to those proposed by the Accreditation Council for Graduate Medical Education, those that reached consensus as recommended are less commonly discussed and should be strongly considered by institutions., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Radioactive ^{129}Sb, which can be treated as a proton plus semimagic ^{128}Sn core within the particle-core coupling scheme, was studied by Coulomb excitation. Reduced electric quadrupole transition probabilities, B(E2), for the 2^{+}⊗πg&#95;{7/2} multiplet members and candidate πd&#95;{5/2} state were measured. The results indicate that the total electric quadrupole strength of ^{129}Sb is a factor of 1.39(11) larger than the ^{128}Sn core, which is in stark contrast to the expectations of the empirically successful particle-core coupling scheme. Shell-model calculations performed with two different sets of nucleon-nucleon interactions suggest that this enhanced collectivity is due to constructive quadrupole coherence in the wave functions stemming from the proton-neutron residual interactions, where adding one nucleon to a core near a double-shell closure can have a pronounced effect. The enhanced electric quadrupole strength is an early signal of the emerging nuclear collectivity that becomes dominant away from the shell closure.

Background: Increasing census and work compression on the pediatric inpatient hematologic malignancy (IHM) service yielded resident dissatisfaction, impaired learning, and decreased perceived quality of patient care. This study aimed to evaluate the impact of a service redesign on resident perceptions of (a) the educational value of the rotation and (b) the safety of patient care. As a secondary objective, we evaluated the impact on the time of day of patient discharge., Procedure: A bundled intervention on the IHM service was instituted, including decreased patient volumes, intentional patient assignment, intentional faculty selection, and increased weekend staffing. We distributed an annual survey to end-of-the-year junior residents. We compared responses from residents who experienced the redesign (2017) with residents whose experience predated the redesign (2016). We compared the time of day of patient discharge before and after the redesign., Results: Survey completion rates were 70% (28/40) in 2016 and 57% (29/51) in 2017. Redesign residents rated their educational experience and perceived ability to care for patients on the nights and weekends significantly higher than previous residents. Redesign residents reported that their clinical education was compromised by excessive service less frequently than previous residents (24% vs 82%, P < 0.001). The time of day of patient discharge after the redesign was 35 minutes earlier than before the redesign (4:06 pm vs 4:41 pm, P = 0.01, 95% CI = -63, -6)., Conclusions: A redesign initiative of an oncology service led to improved resident perceptions of the educational value of the rotation and ability to provide safe care to patients, along with earlier discharge times., (© 2019 Wiley Periodicals, Inc.)

Objective: To determine the role of the NLRP3 inflammasome by using the selective NLRP3 inhibitor MCC950 in patients with NLRP3 low penetrance variants and clinical symptoms suggestive for an autoinflammatory syndrome including central nervous system (CNS) involvement., Methods: Nineteen symptomatic patients with low penetrance NLRP3 variants (Q703K n = 17, V198M n = 2) recruited between 2011 and 2017 were included in this monocentric study. A functional inflammasome activation assay was performed in patients in comparison to healthy controls (HC), including the determination of interleukin-1beta (IL-1β), interleukin-6 (IL-6) and tumor-necrosis factor alpha (TNF-α) secretion in the presence of the NLRP3 selective small-molecule inhibitor MCC950. Detailed clinical features were assessed and anti-IL-1 treatment response was determined., Results: Peripheral blood mononuclear cells (PBMC) from patients with low penetrance NLRP3 variants displayed enhanced IL-1β levels following inflammasome activation compared to HC. Furthermore, IL-1β release was NLRP3-dependent as it was blocked by MCC950. The production of IL-6 and TNF-α was also increased in patients with low penetrance NLRP3 variants. Clinically, they presented with a heterogenous spectrum of neurological manifestations, while cranial nerve inflammation was the most common feature. Overall inflammasome activation did not correlate with disease severity. Eight of ten treated patients responded to anti IL-1 treatment, however a complete response was only documented in four patients., Conclusion: PBMC of several patients with NLRP3 low penetrance variants and CNS manifestation showed increased NLRP3-specific IL-1β release upon stimulation and elevated NLRP3-independent IL-6 and TNF-α levels as those were not suppressed by MCC950. Our data suggest that beside the possible causal involvement of the NLRP3 inflammasome additional, yet unidentified genetic or environmental factors may contribute to the multi-organ inflammation in our patients and explain the partial response to IL-1 targeting therapies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Inflammasomes activate the protease caspase-1, which cleaves interleukin-1β and interleukin-18 to generate the mature cytokines and controls their secretion and a form of inflammatory cell death called pyroptosis. By generating mice expressing enzymatically inactive caspase-1 C284A , we provide genetic evidence that caspase-1 protease activity is required for canonical IL-1 secretion, pyroptosis, and inflammasome-mediated immunity. In caspase-1-deficient cells, caspase-8 can be activated at the inflammasome. Using mice either lacking the pyroptosis effector gasdermin D (GSDMD) or expressing caspase-1 C284A , we found that GSDMD-dependent pyroptosis prevented caspase-8 activation at the inflammasome. In the absence of GSDMD-dependent pyroptosis, the inflammasome engaged a delayed, alternative form of lytic cell death that was accompanied by the release of large amounts of mature IL-1 and contributed to host protection. Features of this cell death modality distinguished it from apoptosis, suggesting it may represent a distinct form of pro-inflammatory regulated necrosis., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Silica (SiO₂) nanoparticles (NPs) usage includes, but is not limited to, industrial and biomedical applications. Toxic effects of SiO₂ NPs have been explored either in vitro or in vivo , assessing different surface modifications to reduce their harmful effects. Here, murine bone marrow-derived dendritic (BMDC) and a mouse model of mild allergic inflammation were used to study inflammasome activation and lung inflammation. Our results showed that SiO₂ plain NPs induced NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome activation, increasing interleukin (IL)-1β release in vitro , and, to a lesser extent, in vivo . In addition, SiO₂ plain NPs triggered a pulmonary inflammatory milieu in both non-sensitized (NS) and sensitized (S) mice, by inducing the expression of key inflammatory cytokines and chemokines. Electron microscopy showed that SiO₂ NPs were mostly localized in alveolar macrophages, within vesicles and/or in phagolysosomes. Both the in vitro and the in vivo effects of SiO NPs were attenuated by coating NPs with phosphonate or amino groups, whereas PEGylation, although it mitigated inflammasome activation in vitro , was not a successful coating strategy in vivo . These findings highlight that multiple assays are required to determine the effect of surface modifications in limiting NPs inflammatory potential. Taken together, these data are obtained by comparing in vitro and in vivo effects of SiO₂ NPs suggest the use of amino and phosphonate coating of silica NPs for commercial purposes and targeted applications, as they significantly reduce their proinflammatory potential., Competing Interests: The authors declare no conflict of interest.