Significance Finding that pan-tolerance derives from defects in carbohydrate regulation connects stress-mediated lesions with metabolic change, identifies a stable type of tolerance, and demonstrates a widely shared death response. Manipulation of the response should improve antimicrobial efficacy, preserve beneficial bacteria during antimicrobial use, and protect industrial bacteria from toxic products. Mutations in many genes can interfere with stress-mediated metabolism; thus, mutation to pan-tolerance could be a high-probability event. Finding that selection of tolerance to one lethal stressor confers tolerance to many, if not all, indicates that massive disinfectant consumption potentially undermines antimicrobial efficacy and immune defenses against pathogenic bacteria. Since pan-tolerance is hidden from current surveillance of resistance, the work indicates a need for facile methods to measure tolerance.

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Objectives: Management of spontaneous pneumomediastinum in the pediatric population is highly variable. There are limited data on the use of diagnostic tests and the need for admission. Our objectives were to characterize the management of pediatric spontaneous pneumomediastinum, determine the diagnostic yield of advanced imaging, and describe the patients' outcomes.Methods: This is a retrospective cohort study of all patients presenting to a single tertiary pediatric emergency department between January 2008 and February 2015 diagnosed with pneumomediastinum. Patients were identified using 2 complementary strategies: International Classification of Diseases, Ninth Revision billing codes and a keyword search of the hospital radiology database. Results:We identified 183 patients with spontaneous pneumomediastinum.The mean age was 12.8 ± 4.8 years. Diagnosis was established by chest radiograph (CXR) in 165 (90%) patients, chest computed tomography in 15 (8%), neck imaging in 2 (1%), and abdominal imaging in 1. After diagnosis, many patients underwent additional studies: repeat CXR (99, 54%), chest computed tomography (53, 29%), esophagram (45, 25%), and laryngoscopy (15, 8%). Seventy-eight percent of patients (n = 142) were admitted with a median length of stay of 27 hours (18.4-45.6 hours). Six patients returned to the emergency department within 96 hours for persistent chest pain; 2 were admitted, and 1 was found to have worsening pneumomediastinum on CXR. We performed a secondary analysis on 3 key subgroups: primary spontaneous pneumomediastinum (64, 35%), secondary gastrointestinalassociated pneumomediastinum (31, 17%), and secondary respiratoryassociated pneumomediastinum (88, 48%). No patients in the study received an invasive intervention for pneumomediastinum. In all patients, further studies did not yield additional diagnostic information.Conclusions: Our data suggest that patients with spontaneous pneumomediastinum who are clinically well appearing can be managed conservatively with clinical observation, avoiding exposure to radiation and invasive procedures.

Widespread antimicrobial resistance encourages repurposing/refining of non-antimicrobial drugs for antimicrobial indications. Gallium nitrate (GaNt), an FDA-approved medication for cancer-related hypercalcemia, recently showed good activity against several clinically significant bacteria. However, the mechanism of GaNt antibacterial action is still poorly understood. In the present work, resistant and tolerant mutants of Escherichia coli were sought via multiple rounds of killing by GaNt. Multi-round-enrichment yielded no resistant mutant; whole-genome sequencing of one representative GaNt-tolerant mutant uncovered mutations in three genes (evgS, arpA, kdpD) potentially linked to protection from GaNt-mediated killing. Subsequent genetic analysis ruled out a role for arpA and kdpD, but two gain-of-function mutations in evgS conferred tolerance. The evgS mutation-mediated GaNt tolerance depended on EvgS to EvgA phosphor-transfer; EvgA-mediated up-regulation of GadE. YdeO, and SarfA also contributed to tolerance, the latter two likely through their regulation of GadE. GaNt-mediated killing of wild-type cells correlated with increased intracellular ROS accumulation that was abolished by the evgS-tolerant mutation. Moreover, GaNt-mediated killing was mitigated by dimethyl sulfoxide, and the evgS-tolerant mutation upregulated genes encoding enzymes involved in ROS detoxification and in the glyoxylate shunt of the TCA cycle. Collectively, these findings indicate that GaNt kills bacteria through elevation of ROS; gain-of-function mutations in evgS confer tolerance by constitutively activating the EvgA-YdeO/GadE cascade of acid-resistance pathways and by preventing GaNt-stimulated ROS accumulation by upregulating ROS detoxification and shifting TCA cycle carbon flux. The striking lethal activity of GaNt suggests that clinical use of the agent may not quickly lead to resistance.

carbon, [1] expanded graphite (EG), carbon nanotubes (CNTs), and graphene), dielectric loss materials (ZnO [2] and BaTiO 3), and magnetic loss materials (MFe 2 O 4 , [3] Fe, Co, Ni, and their alloys [4,5]) are generally included. Among them, ferrite materials are widely used as EAMs because of their abundant raw materials, low cost, easy preparation, nontoxicity, and good chemical stability. [3,6] However, their low permittivity and large density render them too thick and heavy to be used in light and thin electronic devices. Besides, EG consisting of sheet-like graphite as an EAM has also attracted much attention. Its excellent properties (low cost, low density, large conductivity, large specific surface area, good antioxidation ability, and big shape anisotropy [6,7]) make it a superb host for nanoparticles. [8] Nevertheless, studies have demonstrated that EG solely used as an EAM hardly meets the high demand of broadband EAMs due to its single conductivity loss and poor impedance matching. Layered C/ferrite nanoparticle array (NPA) and expanded graphite (EG)/C/MFe 2 O 4 (M = Fe, Co, Ni, Zn) NPA heterostructures are synthesized via a simple sodium salt-template method. An array of well-distributed ferrite nanoparticles supported by layered carbon grows simultaneously on the EG surface from metal-oleate complexes. Some dynamic factors are systematically optimized to well adjust the size, content, and morphology of the heterostructures. The heterostructures show good soft magnetic nature with the M s decreasing in the following order: EG/C/γ-Fe 2 O 3 > EG/C/CoFe 2 O 4 > EG/C/NiFe 2 O 4 > EG/C/ZnFe 2 O 4. As microwave absorbers, these heterostructures of EG/C/MFe 2 O 4 NPA exhibit significantly enhanced electromagnetic-wave absorbing capabilities (EWACs) compared with pure EG, EG/γ-Fe 2 O 3 NPA heterostructure, and other C-based composites. Hereinto, EG/C/CoFe 2 O 4 NPA heterostructures exhibit the optimal EWAC with a minimal reflection loss of −49.85 dB at 13.9 GHz and a 1.3 mm coating thickness. The frequency range of 99% absorption is over 2.0-17.0 GHz and the corresponding thickness is 1.10-8.0 mm. The excellent microwave absorption relies on cooperation of double dielectric relaxations, natural resonance, eddy current loss, high attenuation, and appropriate impedance matching. Therefore, layered heterostructures of EG/C/MFe 2 O 4 NPA are promising electromagnetic wave absorbers for practical application.

A sequential multiple assignment randomized trial (SMART) facilitates the comparison of multiple adaptive treatment strategies (ATSs) simultaneously. Previous studies have established a framework to test the homogeneity of multiple ATSs by a global Wald test through inverse probability weighting. SMARTs are generally lengthier than classical clinical trials due to the sequential nature of treatment randomization in multiple stages. Thus, it would be beneficial to add interim analyses allowing for an early stop if overwhelming efficacy is observed. We introduce group sequential methods to SMARTs to facilitate interim monitoring based on the multivariate chi-square distribution. Simulation studies demonstrate that the proposed interim monitoring in SMART (IM-SMART) maintains the desired type I error and power with reduced expected sample size compared to the classical SMART. Finally, we illustrate our method by reanalyzing a SMART assessing the effects of cognitive behavioral and physical therapies in patients with knee osteoarthritis and comorbid subsyndromal depressive symptoms.

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