Active inductor-based ultra-wideband low noise amplifier for rejection of wireless LAN interference

This paper presents a low noise amplifier (LNA) for the ultra-wideband (UWB) application in the range 3.1–10.6 GHz based on active inductor topology. The LNA is designed to provide a flat gain and to reject wireless local area networking interference at 5–6 GHz band. An active inductor based on the feedback resistor topology is proposed in this work and integrated with the LNA. The use of an active inductor instead of a conventional CMOS spiral inductor provides advantages over the area, quality factor, and inductance. The active inductor provides a relatively uniform inductance at 5–6 GHz and is used to design an on-chip notch filter circuit, which achieves a maximum attenuation of 45 dB at the center frequency of ~5.6 GHz. The LNA is designed and processed in the standard 0.18 mm CMOS technology. The simulated LNA exhibits the gain of 20 dB and a noise figure of less than 3.7 dB in the non-interfering bands. The input (S11) and output return losses (S22) are less than –10 and –12 dB, respectively, in the allocated UWB frequency spectrum, and amplifier occupies a chip area of 0.54 µm2. The proposed LNA has a superior flat gain, excellent interference rejection, minimum return losses, and a low noise figure in the intended operation band. This LNA finds important application in the radiofrequency front-end devices for UWB application

Analysis of Noisy 2D Angiographic Images for Improved Blood Flow Rate Quantification in Dialysis Access

Measurement of access blood flow rate pre- and post-angioplasty is a marker of interventional success and confirmation of dialysis access function restoration during endovascular procedures. In this paper, we discuss the effects of noise on indicator-dilution curves at various acquisition and flow conditions and investigate the methods to minimize such errors through the use of noise reducing techniques. It was found that for peak to peak algorithm using gamma variate curve fit, the overall mean accuracy of all simulated conditions was 23% above measured flow, while for cross-correlation algorithm using mean filter method the overall mean accuracy was 18% above measured flow. The mean quantification accuracy based on all measured flow conditions was considered best at 3 F/s- which correlate to conditions for minimum radiation risk. The results of this study will be useful to understand the impact of noise on accuracy and for selecting optimum methods and acquisition parameters to improve computational accuracy while aiming for minimum radiation dose

Targeting Cell Cycle Progression in HER2+ Breast Cancer: An Emerging Treatment Opportunity

The development of HER2-targeted therapies has dramatically improved patient survival and patient management and increased the quality of life in the HER2+ breast cancer patient population. Due to the activation of compensatory pathways, patients eventually suffer from resistance to HER2-directed therapies and develop a more aggressive disease phenotype. One of these mechanisms is the crosstalk between ER and HER2 signaling, especially the CDK4/6-Cyclin D-Rb signaling axis that is commonly active and has received attention for its potential role in regulating tumor progression. CDK 4/6 inhibitors interfere with the binding of cell-cycle-dependent kinases (CDKs) with their cognate partner cyclins, and forestall the progression of the cell cycle by preventing Rb phosphorylation and E2F release that consequentially leads to cancer cell senescence. CDK 4/6 inhibitors, namely, palbociclib, ribociclib, and abemaciclib, in combination with anti-estrogen therapies, have shown impressive outcomes in hormonal receptor-positive (HR+) disease and have received approval for this disease context. As an extension of this concept, preclinical/clinical studies incorporating CDK 4/6 inhibitors with HER2-targeted drugs have been evaluated and have shown potency in limiting tumor progression, restoring therapeutic sensitivity, and may improving the management of the disease. Currently, several clinical trials are examining the synergistic effects of CDK 4/6 inhibitors with optimized HER2-directed therapies for the (ER+/-) HER2+ population in the metastatic setting. In this review, we aim to interrogate the burden of HER2+ disease in light of recent treatment progress in the field and examine the clinical benefit of CDK 4/6 inhibitors as a replacement for traditional chemotherapy to improve outcomes in HER2+ breast cancer

Percutaneous-Reinforced Osteoplasty: A Review of Emerging Treatment Strategies for Bone Interventions

Percutaneous-reinforced osteoplasty is currently being investigated as a possible therapeutic procedure for fracture stabilization in high-risk patients, primarily in patients with bone metastases or osteoporosis. For these patients, a percutaneous approach, if structurally sound, can provide a viable method for treating bone fractures without the physiologic stress of anesthesia and open surgery. However, the low strength of fixation is a common limitation that requires further refinement in scaffold design and selection of materials, and may potentially benefit from tissue-engineering-based regenerative approaches. Scaffolds that have tissue regenerative properties and low inflammatory response promote rapid healing at the fracture site and are ideal for percutaneous applications. On the other hand, preclinical mechanical tests of fracture-repaired specimens provide key information on restoration strength and long-term stability and enable further design optimization. This review presents an overview of percutaneous-reinforced osteoplasty, emerging treatment strategies for bone repair, and basic concepts of in vitro mechanical characterization

Systematic Design Methodology of a Wideband Multibit Continuous-Time Delta-Sigma Modulator

Systematic design of a low power, wideband and multi-bit continuous-time delta-sigma modulator (CTDSM) is presented. The design methodology is illustrated with a 640 MS/s, 20 MHz signal bandwidth 4th order 2-bit CTDMS implemented in 0.18 µm CMOS technology. The implemented design achieves a peak SNDR of 65.7 dB and a high dynamic range of 70 dB while consuming only 19.7 mW from 1.8 V supply. The design achieves a FoM of 0.31 pJ/conv. Direct path compensation is employed for one clock excess loop delay compensation. In the feedforward topology, capacitive summation using the last opamp eliminates extra summation opamp

Patient-Derived Primary Cancer-Associated Fibroblasts Mediate Resistance to Anti-Angiogenic Drug in Ovarian Cancers

Ovarian cancers rank first in both aggressiveness and dismal prognosis among gynecological neoplasms. The poor outcome is explained by the fact that most patients present with late-stage disease and progress through the first line of treatment. Ovarian neoplasms, especially epithelial ovarian cancers, are diagnosed at advanced/metastatic stages, often with a high angiogenesis index, one of the hallmarks of ovarian cancers with rapid progression and poor outcome as resistance to anti-angiogenic therapy develops. Despite therapy, the metastatic progression of aggressive ovarian cancer is a spectacularly selective function of tumor cells aided and abetted by the immune, mesenchymal and angiogenic components of the tumor microenvironment (TME) that enforces several pro-metastatic event(s) via direct and indirect interactions with stromal immune cells, cancer-associated fibroblasts (CAFs), and vascular endothelial cells. Since transdifferentiation of tumor endothelium is one of the major sources of CAFs, we hypothesized that ovarian CAF plays a critical role in resisting anti-angiogenic effects via direct crosstalk with endothelium and hence plays a direct role in the development of resistance to anti-angiogenic drugs. To test the hypothesis, we set up a hybrid ex vivo model for co-culture comprising Patient-Derived ex vivo primary CAFs from ovarian tumor samples and human umbilical vein endothelial cells (HUVEC). Patient-Derived CAFs were characterized by the mRNA and protein expression of positive (SMA, S100A4, TE-7, FAP-A, CD90/THY1), negative (EpCAM, CK 8,18, CD31, CD44, CD45), functional (PDGFRA, TGFB1, TGFB2, TGFRA) and immunological markers (PD-L1, PD-L2, PD-1) associated with CAFs by qRT-PCR, flow cytometry, Western blot, and ICC. Data from our HUVEC-on-CAF ex vivo Hybrid Co-Culture (HyCC) study demonstrate the pro-angiogenic effect of Patient-Derived ovarian CAFs by virtue of their ability to resist the effect of anti-angiogenic drugs, thereby aiding the development of resistance to anti-angiogenic drugs. Ascertaining direct experimental proof of the role of CAFs in developing resistance to specific anti-angiogenic drugs will provide an opportunity to investigate new drugs for counteracting CAF resistance and "normalizing/re-educating" TME in aggressive ovarian cancers. Our data provide a unique experimental tool for the personalized testing of anti-angiogenic drugs, positively predicting the development of future resistance to anti-angiogenic drugs well before it is clinically encountered in patients

Factors Associated with Total Laryngectomy Utilization in Patients with cT4a Laryngeal Cancer

Background: Despite recommendations for upfront total laryngectomy (TL), many patients with cT4a laryngeal cancer (LC) instead undergo definitive chemoradiation, which is associated with inferior survival. Sociodemographic and oncologic characteristics associated with TL utilization in this population are understudied. Methods: This retrospective cohort study utilized hospital registry data from the National Cancer Database to analyze patients diagnosed with cT4a LC from 2004 to 2017. Patients were stratified by receipt of TL, and patient and facility characteristics were compared between the two groups. Logistic regression analyses and Cox proportional hazards methodology were performed to determine variables associated with receipt of TL and with overall survival (OS), respectively. OS was estimated using the Kaplan–Meier method and compared between treatment groups using log-rank testing. TL usage over time was assessed. Results: There were 11,149 patients identified. TL utilization increased from 36% in 2004 to 55% in 2017. Treatment at an academic/research program (OR 3.06) or integrated network cancer program (OR 1.50), male sex (OR 1.19), and Medicaid insurance (OR 1.31) were associated with increased likelihood of undergoing TL on multivariate analysis (MVA), whereas age > 61 (OR 0.81), Charlson–Deyo comorbidity score ≥ 3 (OR 0.74), and clinically positive regional nodes (OR 0.78 [cN1], OR 0.67 [cN2], OR 0.21 [cN3]) were associated with decreased likelihood. Those undergoing TL with post-operative radiotherapy (+/− chemotherapy) had better survival than those receiving chemoradiation (median OS 121 vs. 97 months; p = 0.003), and TL + PORT was associated with lower risk of death compared to chemoradiation on MVA (HR 0.72; p = 0.024). Conclusions: Usage of TL for cT4a LC is increasing over time but remains below 60%. Patients seeking care at academic/research centers are significantly more likely to undergo TL, highlighting the importance of decreasing barriers to accessing these centers. Increased focus should be placed on understanding and addressing the additional patient-, physician-, and system-level factors that lead to decreased utilization of surgery