Ultra-wideband and lightweight electromagnetic polarization converter based on multiresonant metasurface

Abstract Polarization-control devices have attracted considerable interest, however, most of the polarization converters operating at lower frequencies have a heavy design and narrow bandwidth which limits their practical applications. Here we report a simple design of an ultra-wideband and lightweight polarization converter for applications in the S- and C-bands. The proposed converter is designed based on a metasurface structure with the dielectric layer modified to hollow structure to obtain a lightweight design even working at such low frequency. Theoretical analysis and simulation results indicate that the converter can convert the orthogonal polarization transformation of reflected wave. Furthermore, the measurement results show good agreement with the simulation results. The proposed polarization converter can achieve a polarization conversion ratio above 90% in an ultra-wide frequency range from 2 to 8.45 GHz due to multi-resonance modes. These performances are going beyond state of the art in terms of bandwidth and lightweight design, thus it can be applied in various applications in the operating bands

Symptom prevalence, bother, and treatment satisfaction in men with lower urinary tract symptoms in Southeast Asia: a multinational, cross-sectional survey

Purpose: The overall objective of the survey was to systematically examine patients’ perspectives on lower urinary tract symptoms (LUTS) and their treatment in Southeast Asia. Methods: A multinational cross-sectional survey involving adult men seeking consultation at urology outpatient clinics because of LUTS in Southeast Asia was conducted using convenience sampling. Self-reported prevalence, bother, treatment and treatment satisfaction of selected LUTS including urgency, nocturia, slow stream, and post-micturition dribble were evaluated. Results: In total, 1535 eligible patients were enrolled in the survey. A majority of respondents were aged 56–75 years, not employed, and had not undergone prostate operation before. Overall, the self-reported prevalence of nocturia was 88% (95% CI 86–90%), slow stream 61% (95% CI 59–63%), post micturition dribble 55% (95% CI 52–58%), and urgency 52% (95% CI 49–55%). There were marked differences in the country specific prevalence of LUTS complaints. Frequently, symptoms coexisted and were combined with nocturia. More than half of patients felt at least some degree of bother from their symptoms: 61% for urgency, 57% for nocturia, 58% for slow stream, and 60% for post-micturition dribble. Before seeing the present urologists, nearly half of patients have received some form of prescribed treatment and more than 80% of patients indicated they would like to receive treatment. Conclusion: Men who sought urologist care for LUTS often presented with multiple symptoms. Nocturia emerged as the most common symptom amongst the four core symptoms studied

PF-06463922, an ALK/ROS1 Inhibitor, Overcomes Resistance to First and Second Generation ALK Inhibitors in Preclinical Models

SummaryWe report the preclinical evaluation of PF-06463922, a potent and brain-penetrant ALK/ROS1 inhibitor. Compared with other clinically available ALK inhibitors, PF-06463922 displayed superior potency against all known clinically acquired ALK mutations, including the highly resistant G1202R mutant. Furthermore, PF-06463922 treatment led to regression of EML4-ALK-driven brain metastases, leading to prolonged mouse survival, in a superior manner. Finally, PF-06463922 demonstrated high selectivity and safety margins in a variety of preclinical studies. These results suggest that PF-06463922 will be highly effective for the treatment of patients with ALK-driven lung cancers, including those who relapsed on clinically available ALK inhibitors because of secondary ALK kinase domain mutations and/or brain metastases

Discovery of <i>N</i>‑((3<i>R</i>,4<i>R</i>)‑4-Fluoro-1-(6-((3-methoxy-1-methyl‑1<i>H</i>‑pyrazol-4-yl)amino)-9-methyl‑9<i>H</i>‑purin-2-yl)pyrrolidine-3-yl)acrylamide (PF-06747775) through Structure-Based Drug Design: A High Affinity Irreversible Inhibitor Targeting Oncogenic EGFR Mutants with Selectivity over Wild-Type EGFR

Mutant epidermal growth factor receptor (EGFR) is a major driver of non-small-cell lung cancer (NSCLC). Marketed first generation inhibitors, such as erlotinib, effect a transient beneficial response in EGFR mutant NSCLC patients before resistance mechanisms render these inhibitors ineffective. Secondary oncogenic EGFR mutations account for approximately 50% of relapses, the most common being the gatekeeper T790M substitution that renders existing therapies ineffective. The discovery of PF-06459988 (<b>1</b>), an irreversible pyrrolopyrimidine inhibitor of EGFR T790M mutants, was recently disclosed. Herein, we describe our continued efforts to achieve potency across EGFR oncogenic mutations and improved kinome selectivity, resulting in the discovery of clinical candidate PF-06747775 (<b>21</b>), which provides potent EGFR activity against the four common mutants (exon 19 deletion (Del), L858R, and double mutants T790M/L858R and T790M/Del), selectivity over wild-type EGFR, and desirable ADME properties. Compound <b>21</b> is currently being evaluated in phase-I clinical trials of mutant EGFR driven NSCLC