The orbital underpinnings of the electron localization function (ELF), devised by Becke and Edgecombe, are explored in terms of an interpretation of the dominant term in this expression, ρ-5/3∑ i |∇ψ i |2. High ∑ i |∇ψ i |2 implies large electronic kinetic energy and electron delocalization. It is shown how this arises in practice through the population of noded wave functions. Such an approach provides an attractive way with which to view electron localization in systems that obey the Hund localization condition, hypervalent and electron-deficient molecules, and metals and insulators. ELF is shown to provide a description of the term “electron localization” that is highly self-consistent when interpreted in terms of nodes and also consistent with many of the present uses of the term.

We present a trajectory-based method with which to learn information about the qualitative role that solvent molecules play in dynamic simulations of reactions that occur in solution. A spatial grid is superimposed on the system being simulated, and average fluxes of solvent molecules between cells on the grid are calculated along reactive trajectories. The average solvent fluxes form a much smaller set of variables and provide a much simpler description of the reaction under study than the full list of atomic positions and momenta. The feasibility and utility of the method are demonstrated by producing reduced descriptions of the mechanisms of the dissociation reaction of NaCl in water and of the rearrangement of the alanine dipeptide in water. Comparisons between our method and other possible data reduction techniques are discussed.

Density functional calculations were performed on 1,1‘,5,5‘-tetramethyl-6,6‘-dioxo-3,3‘-biverdazyl diradical (BVD) and BVD[CuI(PL3)]2 complexes (L = H, Me, OH, OMe, F) in order to investigate how Cu chelation affects the singlet−triplet splitting of the verdazyl system. It was found that donating ligands on Cu destabilize the singlet ground state. Size was also found to play a role, as smaller ligands allow for closer Cu−verdazyl contacts. Although a triplet ground state was not obtained for any of the molecules examined, a very small splitting of 40 cm-1 was calculated for the phosphine complex.

A lattice gas simulation of water between a hydrophobic plate and a hydrophilic plate (a Janus interface) shows large fluctuations in the number of liquid cells in contact with the hydrophobic plate, and a power spectrum similar to the experimental results that Zhang, Zhu, and Granick found [X. Y. Zhang, Y. X. Zhu, and S. Granick, Science 295, 663 (2002)] when measuring viscous response in a Janus system. Study of the spatial Fourier modes of the liquid-vapor interface suggests that interface fluctuations with length scales between approximately 1.5 and 20 nm cause the effects observed in the simulation.

This cohort study assesses whether removal of a warning against use of cephalosporins in the electronic health record (EHR) of patients with penicillin allergy was associated with changes in the dispensing or administration of cephalosporins.

RATIONALE: Adults and adolescents with severe asthma who completed the SIROCCO (48 weeks) and CALIMA (56 weeks) Phase III benralizumab trials entered the safety extension BORA (NCT02258542) study. Benralizumab's continued safety and efficacy in the first year of BORA (Year 2 of treatment) have been reported (Lancet Respir Med 2019;7:46-59). We present outcomes for 2 years of benralizumab treatment for BORA adolescent patients. METHODS: SIROCCO/CALIMA study patients who received benralizumab 30 mg every 4 weeks (p-Q4W) or every 8 weeks (p-Q8W) continued their regimens in BORA (108 weeks). Placebo (p-pbo) patients were rerandomized 1:1 to benralizumab Q4W or Q8W. Primary outcome was safety. Secondary outcomes included annual asthma exacerbation rate and change from baseline in prebronchodilator forced expiratory volume in 1 second (pre-FEV 1). RESULTS: This analysis included 86 adolescents, 61 receiving Q8W and 25 receiving Q4W. Of those, 69 completed treatment (51 Q8W patients). Safety profile was consistent with previous studies (treatment-emergent adverse events [TEAEs]: Q8W: 74% [45/61], Q4W: 68% [17/25]; TEAEs leading to death or discontinuation: Q8W: none, Q4W: none [death] and 4% [1/25] [discontinuation]; serious adverse events: Q8W: 7% [4/61], Q4W: 8% [2/25]). Efficacy was consistent with previous BORA findings. With Q8W, 69% (42/61) remained exacerbation-free (p-pbo/Q8W: 62% [18/29], p-Q8W/Q8W: 75% [24/32]). Pre-FEV 1 mean change (SD) at Week 108 vs. BORA baseline were 0.327 L (0.452) (p-pbo/Q8W) and 0.323 L (0.558) (p-Q8W/Q8W). CONCLUSIONS: Safety and efficacy profiles in this 2 year extension study, representing up to 3 years of benralizumab treatment in adolescents, were consistent with previous findings.

Objective: To assess whether implementation of age-dependent therapeutic targets for high hemoglobin A1c (HbA1c) changed clinicians’ ordering of diabetes medications for older adults. Background: In 2016, Kaiser Permanente Southern California (KPSC) changed the therapeutic targets for alerting clinicians about high HbA1c results in the electronic health record, KP HealthConnect (KPHC). Previously, all HbA1c results ≥7.0 percent were flagged as high in adult patients with diabetes. Starting in 2016, HbA1c therapeutic targets were relaxed to <7.5 percent for patients age 65 to 75, and to <8.0 percent for patients over age 75 to reduce treatment intensity and adverse events. Methods: This retrospective analysis used logistic regression models to calculate the change in odds of a medication change following an HbA1c result after age-dependent HbA1c flags were introduced. Results: The odds of medication change decreased among patients whose HbA1c targets were relaxed: Odds Ratio (OR) 0.72 (95 percent CI 0.67–0.76) for patients age 65–75 and HbA1c 7.0 percent–7.5 percent; OR 0.72 (95 percent CI 0.65–0.80) for patients over age 75 and HbA1c 7.0 percent–7.5 percent; and OR 0.67 (95 percent CI 0.61–0.75) for patients over age 75 and HbA1c 7.5 percent–8.0 percent. In the age and HbA1c ranges for which the alerts did not change, the odds of medication change generally increased or stayed the same. There was little evidence of medication de-intensification in any group. Conclusions: These findings suggest that the change in therapeutic targets was associated with a reduction in medication intensification among older adults with diabetes.

RATIONALE: Carboplatin is chemotherapy of choice for treatment of gynecologic malignancy. Patients received multiple course therapy have increase rate of hypersensitivity reaction (HSR) up to 27%. Switch to alternative regimens may shorten progression free survival (PFS) and overall survival (OS). Rapid desensitization has been used to provide safe reintroduction of carboplatin treatment. METHODS: Retrospective review of consecutive patients experienced carboplatin HSR who visit Allergy clinic, Ramathibodhi hospital from June 2010 to June 2020 were collected. Onco-Gynecology -Allergy multidisciplinary team workflow was established in 2016 to offer rapid access to skin test (ST). Patients who had initial negative carboplatin ST were follow and repeated ST until conversion to positive or completion of carboplatin treatment. Patient's demographic data, including disease status and severity of initial HSR to carboplatin were collected. RESULTS: Seventy-one patients were included. Mean age was 57.8 years (SD 9.93). Majority of patients (80.3%) were recurrent disease, mostly on second course of carboplatin. Mean carboplatin cycle before developing initial HSR was 15.35 (range 6-42, SD 6.211). One-third of patients (38.0%) had only mild cutaneous reaction, while 18.3% had anaphylactic shock. Skin test positive was found in 55 patients (77.5%). Of 16 patients with Initial negative ST results, 6 patients changed chemotherapy regimens, while all of 10 patients who continue the same regimen converted to positive result at a median of 2.1 cycles (range 1-4). CONCLUSIONS: Multidisciplinary team approach provided rapid accessibility to ST to carboplatin. Interestingly all patients were finally converted to positive result at a median of 2.1 cycles.