Current research on tiltrotor noise predominantly concentrates on configurations with high disk loading and Reynolds numbers, leaving smaller aircraft setups underexplored. This study investigates aeroacoustic and aerodynamic trends resulting from rotor-wing interaction at low disk loading (<100 N/m2) and Reynolds number (Re < 100 000). The experimental setup comprises an anechoic chamber housing a two-blade rotor, flat and National Advisory Committee for Aeronautics 0012 airfoil wings, an ATI mini 40 load cell for aerodynamic data acquisition, and microphones positioned at the rotor height and installed on a rotation stage for acoustic data capture and directivity check.
View Article and Find Full Text PDFDiamond Blackfan Anemia (DBA) is a rare macrocytic red blood cell aplasia that usually presents within the first year of life. The vast majority of patients carry a mutation in one of approximately 20 genes that results in ribosomal insufficiency with the most significant clinical manifestations being anemia and a predisposition to cancers. Nemo-like Kinase (NLK) is hyperactivated in the erythroid progenitors of DBA patients and inhibition of this kinase improves erythropoiesis, but how NLK contributes to the pathogenesis of the disease is unknown.
View Article and Find Full Text PDFCharacterizing changes in the higher order structure (HOS) of monoclonal antibodies upon stressed conditions is critical to gaining a better understanding of the product and process. One single biophysical approach may not be best suited to assess HOS comprehensively; thus, the synergy from multiple, complementary approaches improves characterization accuracy and resolution. In this study, we employed two mass spectrometry (MS )-based footprinting techniques, namely, fast photochemical oxidation of proteins (FPOP)-MS and hydrogen-deuterium exchange (HDX)-MS, supported by dynamic light scattering (DLS), differential scanning calorimetry (DSC), circular dichroism (CD), and nuclear magnetic resonance (NMR) to study changes to the HOS of a mAb upon thermal stress.
View Article and Find Full Text PDFLaryngoscope Investig Otolaryngol
October 2023
Objectives: Review of the current and relevant literature to develop a list of evidence-based recommendations that can be implemented in head and neck surgical practices. To provide rationale for the multiple aspects of comprehensive care for head and neck surgical patients. To improve postsurgical outcomes for head and neck surgical patients.
View Article and Find Full Text PDFOpportunities exist to leverage mobile phones to replace or supplement in-person supervision of lay counselors. However, contextual variables, such as network connectivity and provider preferences, must be considered. Using an iterative and mixed methods approach, we co-developed implementation guidelines to support the implementation of mobile phone supervision with lay counselors and supervisors delivering a culturally adapted trauma-focused cognitive behavioral therapy in Western Kenya.
View Article and Find Full Text PDFNovel furoxan/coumarin hybrids were synthesized, and pharmacologic studies showed that the compounds displayed potent antiproliferation activities via downregulating both the phosphatidylinositide 3-kinase (PI3K) pathway and the mitogen-activated protein kinase (MAPK) pathway. To investigate the preclinical pharmacokinetic (PK) properties of three candidate compounds (CY-14S-4A83, CY-16S-4A43, and CY-16S-4A93), liquid chromatography, in tandem with the mass spectrometry LC-MS/MS method, was developed and validated for the simultaneous determination of these compounds. The absorption, distribution, metabolism, and excretion (ADME) properties were investigated in in vitro studies and in rats.
View Article and Find Full Text PDFEarly neuropathology mechanisms in neurodevelopmental disorders are partially understood because routine anatomical magnetic resonance imaging (MRI) cannot detect subtle brain microstructural changes in vivo during postnatal development. Therefore, we investigated the potential value of magnetic resonance elastography (MRE) and diffusion tensor imaging (DTI) in a rat model of neurodevelopmental disorder induced by maternal immune activation. We studied 12 offspring of mothers injected with polyriboinosinic-polyribocytidylic acid (poly (I:C), 4 mg/kg) on gestational day 15, plus 8 controls.
View Article and Find Full Text PDFDiamond-Blackfan anemia (DBA) is a ribosomopathy that is characterized by macrocytic anemia, congenital malformations, and early onset during childhood. Genetic studies have demonstrated that most patients carry mutations in one of the 20 related genes, most of which encode ribosomal proteins (RP). Treatment of DBA includes corticosteroid therapy, chronic red blood cell transfusion, and other forms of immunosuppression.
View Article and Find Full Text PDFCPT Pharmacometrics Syst Pharmacol
January 2023
Objective: To identify differences in inpatient otolaryngology consultations and interventions for patients based on COVID-19.
Methods: Records were reviewed for all patients for whom otolaryngology was consulted at a high-volume tertiary care hospital from April 30, 2020 to October 1, 2020. Demographic information, length of stay, COVID-19 status, indication for consultation, and otolaryngology interventions were recorded.
Whole-exome sequencing of two patients with idiopathic complex neurodevelopmental disorder (NDD) identified biallelic variants of unknown significance within FIBCD1, encoding an endocytic acetyl group-binding transmembrane receptor with no known function in the central nervous system. We found that FIBCD1 preferentially binds and endocytoses glycosaminoglycan (GAG) chondroitin sulphate-4S (CS-4S) and regulates GAG content of the brain extracellular matrix (ECM). In silico molecular simulation studies and GAG binding analyses of patient variants determined that such variants are loss-of-function by disrupting FIBCD1-CS-4S association.
View Article and Find Full Text PDFPierre-Robin sequence (PRS) patients frequently exhibit symptoms of airway obstruction due to multiple etiologies, predominantly from glossoptosis and tongue base obstruction. Rarely, these patients can have palatal mass and even rarer is one of neural origin. To date, there are few reports of heterotopic neural tissue causing airway obstruction in literature, and there are only two reports related to PRS.
View Article and Find Full Text PDFCutaneous adverse events (cAEs) from targeted antineoplastic agents and immune checkpoint inhibitors are common in children with cancer and may lead to dose reduction or cessation of critical oncologic treatment. Timely diagnosis and proper management of cAEs in pediatric oncology patients is essential to optimize ongoing cancer-directed therapy and improve quality of life. This systematic review of published studies summarizes dermatologic toxicities to targeted anticancer treatments and immune checkpoint inhibitors.
View Article and Find Full Text PDFPurpose: A population pharmacokinetic (PK) analysis of the anti-fibroblast growth factor receptor 2b antibody, bemarituzumab, was performed to evaluate the impact of covariates on the PK and assess whether dose adjustment is necessary for a future phase 3 trial.
Methods: Serum concentration data were obtained from three clinical trials, with 1552 bemarituzumab serum samples from 173 patients, and were analyzed using nonlinear mixed-effects modeling.
Results: A two-compartment model with parallel linear and nonlinear (Michaelis-Menten) elimination from the central compartment best described the bemarituzumab serum concentration data.
Objective: Patient-reported outcomes (PROs) are an integral part of treat-to-target approaches in managing rheumatoid arthritis (RA). In clinical practice, however, routine collection, documentation, and discussion of PROs with patients are highly variable. The RISE LC (Rheumatology Informatics System for Effectiveness Learning Collaborative) was established to develop and share best practices in PRO collection and use across adult rheumatology practices in the United States METHODS: The goals of the RISE LC were developed through site surveys and in-person meetings.
View Article and Find Full Text PDFThis report summarizes a totality-of-evidence approach supporting recommendation of a 320-mg total daily dose, either as 160-mg twice daily (BID) or 320-mg once daily (QD) for zanubrutinib in patients with mantle cell lymphoma. Data were derived from a phase 2 study in patients receiving 160-mg BID and a phase 1/2 study with similar response rates observed with 160-mg BID or 320-mg QD. Given the limited number of patients in the QD dose group, population pharmacokinetics and exposure-response analyses were employed to bridge the two regimens.
View Article and Find Full Text PDFThe risk of drug-induced liver injury (DILI) poses a major challenge for development of natural products derived from traditional Chinese medicines (NP-TCMs). It is urgent to find a new method for the safety assessment of the NP-TCMs. Recent study has reported an in vitro/in silico method to estimate the acceptable daily intake of hepatotoxic compounds using support vector machine (SVM) classifier and physiologically based pharmacokinetic (PBPK) modeling.
View Article and Find Full Text PDFZanubrutinib is a potent, second-generation Bruton's tyrosine kinase inhibitor that is currently being investigated in patients with B-cell malignancies and recently received accelerated approval in the United States for treatment of relapsed/refractory mantle cell lymphoma. The objective of this analysis was to develop a population pharmacokinetic (PK) model to characterize the PKs of zanubrutinib and identify the potential impact of intrinsic and extrinsic covariates on zanubrutinib PK. Data across nine clinical studies of patients with B-cell malignancies and data of healthy volunteers (HVs) were included in this analysis, at total daily doses ranging from 20 to 320 mg.
View Article and Find Full Text PDFSpine (Phila Pa 1976)
March 2021
Study Design: Single-center prospective non-randomized matched cohort comparison.
Objective: To compare elective lumbar spine surgery outcomes for cases triaged through a multidisciplinary spine pathway versus conventional referral processes.
Summary Of Background Data: Many health care systems have facilitated low back pain (LBP) guidelines into primary care practice by creating local or regional "pathways" with the goal of enhanced quality of care, improved patient satisfaction and optimal resource utilization, particularly for imaging and surgery.