Pseudo-fivefold diffraction symmetries in tetrahedral packing.

We review the way in which atomic tetrahedra composed of metallic elements pack naturally into fused icosahedra. Orthorhombic, hexagonal, and cubic intermetallic crystals based on this packing are all shown to be united in having pseudo-fivefold rotational diffraction symmetry. A unified geometric model involving the 600-cell is presented: the model accounts for the observed pseudo-fivefold symmetries among the different Bravais lattice types. The model accounts for vertex-, edge-, polygon-, and cell-centered fused-icosahedral clusters. Vertex-centered and edge-centered types correspond to the well-known pseudo-fivefold symmetries in Ih and D5h quasicrystalline approximants. The concept of a tetrahedrally-packed reciprocal space cluster is introduced, the vectors between sites in this cluster corresponding to the principal diffraction peaks of fused-icosahedrally-packed crystals. This reciprocal-space cluster is a direct result of the pseudosymmetry and, just as the real-space clusters, can be rationalized by the 600-cell. The reciprocal space cluster provides insights for the Jones model of metal stability. For tetrahedrally-packed crystals, Jones zone faces prove to be pseudosymmetric with one another. Lower and upper electron per atom bounds calculated for this pseudosymmetry-based Jones model are shown to accord with the observed electron counts for a variety of Group 10-12 tetrahedrally-packed structures, among which are the four known Cu/Cd intermetallic compounds: CdCu2, Cd3Cu4, Cu5Cd8, and Cu3Cd10. The rationale behind the Jones lower and upper bounds is reviewed. The crystal structure of Zn11Au15Cd23, an example of a 1:1 MacKay cubic quasicrystalline approximant based solely on Groups 10-12 elements is presented. This compound crystallizes in Im3 (space group no. 204) with a = 13.842(2) Å. The structure was solved with R1 = 3.53 %, I > 2σ; = 5.33 %, all data with 1282/0/38 data/restraints/parameters.

COVID-19 Radiology Preparedness, Challenges & Opportunities: Responses From 18 Countries.

PURPOSE: Radiology departments around the world have been faced with the challenge to adapt, and recover to the COVID-19 pandemic. This study is part of a worldwide survey of radiologists' responses to COVID-19 in 18 different countries in Africa, Asia, Europe, and Latin America. The purpose of this study is to analyze the changes made in international radiology departments and practices in response to the pandemic. METHODS: The 18-item survey was sent via email from April to May 2020 to radiologists in Africa, Asia, Europe, and Latin America to assess their response to COVID-19. Our survey included questions regarding imaging, workforce adjustments, testing availability, staff and patient safety, research and education, and infrastructure availability. RESULTS: Twenty-eight survey responses were reviewed. Of the 28 respondents, 42.9% have shortages of infrastructure and 78.6% responded that COVID-19 testing was available. Regarding the use of Chest CT in COVID-19 patients, 28.6% respondents used Chest CT as screening for COVID-19. For staff safety, interventions included encouraging use of masks in patient encounters, social distancing and PPE training. To cope with their education and research mission, radiology departments are doing online lectures, reducing the number of residents in rotations, and postponing any non-urgent activities. CONCLUSION: In conclusion, there are disparities in infrastructure, research, and educational initiatives during COVID-19 which also provides opportunity for the global radiology community to work together on these issues.

Should Radiology Residency Interviews Remain Virtual? Results of a Multi-institutional Survey Inform the Debate.

RATIONALE AND OBJECTIVES: The recent completion of the inaugural virtual interview season has triggered calls for the permanency of virtual interviews in the radiology resident selection process. We designed a study to assess the inaugural 2020-2021 virtual interview season and inform the anticipated debate on the future of radiology residency interviews. MATERIALS AND METHODS: Forty-four and 39-question survey instruments developed for program directors (PDs) and applicants, respectively, were distributed through the Radiology Residency Education Research Alliance to measure the demographics, experiences with technology, attitudes toward the virtual interview season and attitudes about proposed changes to the interview process. Comparisons were made between demographics and survey queries. RESULTS: PD and applicant response rates were 74% (25/34) and 45% (84/186), respectively. Eighty percent (20/25) of PDs and 76% (64/84) of applicants described the virtual interview season as excellent or very good. Sixty percent of PDs agreed or strongly agreed with the statement "The benefits of the virtual interview season outweighed the drawbacks," while 24% disagreed or strongly disagreed, and 16% were neutral. Among applicants, 80% agreed or strongly agreed, 10% disagreed or strongly disagreed, and 10% were neutral toward the same statement. Ninety-two percent of PDs noted that their rank order list performed the same or better than in years prior. Both PDs and applicants identified applicant equity and wellness as major benefits of virtual interviews, while identifying over-application and interview hoarding as significant detriments. CONCLUSION: The virtual interview provides an adequate substitute for the conventional in-person residency interview, with real and perceived benefits to applicant wellness, equity, and financial well-being. The downsides of virtual interviews, namely over-application and interview hoarding, have workable solutions.

A simple and rapid UHPLC-MS/MS method for the quantitation of the dual aurora kinase A/B inhibitor SCH-1473759 in murine plasma.

The Aurora kinase family facilitates cell division through various processes and is overexpressed in a wide variety of human cancers, leading to aneuploidy. For that reason, these enzymes are currently targets of a rising class of anticancer drugs, with some molecules already in therapeutic use. In this study, a new UHPLC-MS/MS method was developed and validated to quantitate a new pan Aurora kinase inhibitor still in preclinical development, SCH-1473759. This bioanalytical method employed a liquid-liquid extraction from plasma using ethyl acetate before evaporation. Calibration range encompassed 0.5-2500ng/mL. The inter- and intra-day accuracy and precision were assessed over five quality control levels; all within limits required by the FDA guidelines. Assay applicability was demonstrated in a first-in-animals study with oral administration, where the maximum plasma concentration (34ng/mL) occurred at 1h, the half-life (1h) was consistent with a previous IV study, and oral bioavailability was poor (F=0.002).

Population pharmacokinetic analyses of the effect of carboplatin pretreatment on olaparib in recurrent or refractory women's cancers.

PURPOSE: Combining olaparib with carboplatin was recently shown to be active in both BRCA and non-BRCA mutant cancers in a recent phase I/Ib combination trial. The optimal drug sequence recommended was carboplatin 1-day before olaparib. However, carboplatin pre-treatment induced a ~50% faster olaparib clearance. METHODS: To further explore this drug interaction, a population pharmacokinetic (PK) model was designed that included a lag time parameter, a second absorption compartment from tablet formulation, a single distribution/elimination compartment, and covariance among the clearance and volume parameters. RESULTS: Clearance (6.8 L/h) and volume (33 L) estimates were comparable with literature. The only significant covariate was the presence of carboplatin on olaparib clearance, consistent with published noncompartmental PK and in vitro data. CONCLUSIONS: Simulations predicted lower steady-state peak/trough olaparib exposure through 24-36 h post carboplatin pre-treatment, but this effect was lost by day 2 and thus no dose adjustment is recommended.

Safety and Clinical Activity of the Programmed Death-Ligand 1 Inhibitor Durvalumab in Combination With Poly (ADP-Ribose) Polymerase Inhibitor Olaparib or Vascular Endothelial Growth Factor Receptor 1-3 Inhibitor Cediranib in Women's Cancers: A Dose-Escalation, Phase I Study.

Purpose Data suggest that DNA damage by poly (ADP-ribose) polymerase inhibition and/or reduced vascular endothelial growth factor signaling by vascular endothelial growth factor receptor inhibition may complement antitumor activity of immune checkpoint blockade. We hypothesize the programmed death-ligand 1 (PD-L1) inhibitor, durvalumab, olaparib, or cediranib combinations are tolerable and active in recurrent women's cancers. Patients and Methods This phase I study tested durvalumab doublets in parallel 3 + 3 dose escalations. Durvalumab was administered at 10 mg/kg every 2 weeks or 1,500 mg every 4 weeks with either olaparib tablets twice daily or cediranib on two schedules. The primary end point was the recommended phase II dose (RP2D). Response rate and pharmacokinetic analysis were secondary end points. Results Between June 2015 and May 2016, 26 women were enrolled. The RP2D was durvalumab 1,500 mg every 4 weeks with olaparib 300 mg twice a day, or cediranib 20 mg, 5 days on/2 days off. No dose-limiting toxicity was recorded with durvalumab plus olaparib. The cediranib intermittent schedule (n = 6) was examined because of recurrent grade 2 and non-dose-limiting toxicity grade 3 and 4 adverse events (AEs) on the daily schedule (n = 8). Treatment-emergent AEs included hypertension (two of eight), diarrhea (two of eight), pulmonary embolism (two of eight), pulmonary hypertension (one of eight), and lymphopenia (one of eight). Durvalumab plus intermittent cediranib grade 3 and 4 AEs were hypertension (one of six) and fatigue (one of six). Exposure to durvalumab increased cediranib area under the curve and maximum plasma concentration on the daily, but not intermittent, schedules. Two partial responses (≥15 months and ≥ 11 months) and eight stable diseases ≥ 4 months (median, 8 months [4 to 14.5 months]) were seen in patients who received durvalumab plus olaparib, yielding an 83% disease control rate. Six partial responses (≥ 5 to ≥ 8 months) and three stable diseases ≥ 4 months (4 to ≥ 8 months) were seen in 12 evaluable patients who received durvalumab plus cediranib, for a 50% response rate and a 75% disease control rate. Response to therapy was independent of PD-L1 expression. Conclusion To our knowledge, this is the first reported anti-PD-L1 plus olaparib or cediranib combination therapy. The RP2Ds of durvalumab plus olaparib and durvalumab plus intermittent cediranib are tolerable and active. Phase II studies with biomarker evaluation are ongoing.