Parameter dependence of acoustic mode quantities in an idealized model for shallow-water nonlinear internal wave ducts.

Nonlinear internal waves in shallow water have significant acoustic impacts and cause three-dimensional ducting effects, for example, energy trapping in a duct between curved wavefronts that propagates over long distances. A normal mode approach applied to a three-dimensional idealized parametric model [Lin, McMahon, Lynch, and Siegmann, J. Acoust. Soc. Am. 133(1), 37-49 (2013)] determines the dependence of such effects on parameters of the features. Specifically, an extension of mode number conservation leads to convenient analytical formulas for along-duct (angular) acoustic wavenumbers. The radial modes are classified into five types depending on geometric characteristics, resulting in five distinct formulas to obtain wavenumber approximations. Examples of their dependence on wavefront curvature and duct width, along with benchmark comparisons, demonstrate approximation accuracy over a broad range of physical values, even including situations where transitions in mode types occur with parameter changes. Horizontal-mode transmission loss contours found from approximate and numerically exact wavenumbers agree well in structure and location of intensity features. Cross-sectional plots show only small differences between pattern phases and amplitudes of the two calculations. The efficiency and accuracy of acoustic wavenumber and field approximations, in combination with the mode-type classifications, suggest their application to determining parameter sensitivity and also to other feature models.

Comparing the attitudes of physicians and non-physicians toward communicating a patient's BRCA1 mutation to a first-degree relative against a patient's wishes.

Although genetic testing can be vastly informative, it creates a dilemma if a patient does not want to disclose an abnormal genetic test to at-risk relatives. A sample of 200 participants from Nevada (100 physicians, 100 non-physicians) completed an 11-item questionnaire asking demographic information, familiarity with genetics and genetic testing, and opinions about a physician's role in a hypothetical case in which a patient does not wish to communicate her BRCA1 mutation to her sister. Although most respondents did not think the physician should notify the sister against the patient's wishes, more non-physicians (40%) than physicians (23%) contended that the physician should do so (p = 0.0119). Most respondents from both groups agreed that the physician should not have the legal duty to notify the sister, would not be morally justified in sharing genetic test results with the sister, but should have the right to notify a patient's relatives if the disease is "serious, preventable, and treatable." More non-physicians than physicians agreed that physicians should have an educational requirement on how to communicate genetic test results to patients and their family (88% vs 65%, p = 0.0002). Most physicians (70%) reported a familiarity/strong familiarity with genetic testing compared to non-physicians (33%; p < 0.0001). Future qualitative research should assess physicians' understanding of issues surrounding familial communication of genetic test results. Educational interventions to facilitate effective communication to patients and families are needed and welcomed by most physicians. Discrepancies between the attitudes of physicians and patients or the public need to be better understood and addressed.

Osimertinib in EGFR-Mutated Lung Cancer: A Review of the Existing and Emerging Clinical Data.

The use of epidermal growth factor receptor (EGFR) inhibitors such as osimertinib has improved outcomes and quality of life for patients with EGFR-mutated non-small cell lung cancer (NSCLC). Osimertinib has become the preferred EGFR tyrosine kinase inhibitor (TKIs) for patients with these mutations after demonstrating superior efficacy compared to first generation EGFR TKIs, such as erlotinib and gefitinib. More recently osimertinib has also shown to be beneficial in patients with resectable NSCLC harboring EGFR mutations irrespective of whether they received adjuvant chemotherapy or not. The drug is now FDA approved in this setting. With osimertinib being used more commonly in earlier stage and front-line settings, we are more likely to see patients who develop resistance to this drug. The aim of this review is to provide a comprehensive review of the data with osimertinib in EGFR mutation positive NSCLC, potential resistance mechanisms and an overview of key ongoing clinical trials.

Modeling the Kinetic Behavior of Reactive Oxygen Species with Cerium Dioxide Nanoparticles.

The world of medicinal therapies has been historically, and remains to be, dominated by the use of elegant organic molecular structures. Now, a novel medical treatment is emerging based on CeO2 nano-crystals that are discrete clusters of a few hundred atoms. This development is generating a great deal of exciting and promising research activity, as evidenced by this Special Issue of Biomolecules. In this paper, we provide both a steady-state and time-dependent mathematical description of a sequence of reactions: superoxide generation, superoxide dismutase, and hydrogen peroxide catalase and ceria regeneration. This sequence describes the reactive oxygen species (ROS); superoxide, O2-, molecular oxygen, O2, hydroxide ion OH- and hydrogen peroxide, H2O2, interacting with the Ce3+, and Ce4+ surface cations of nanoparticle ceria, CeO2. Particular emphasis is placed on the predicted time-dependent role of the Ce3+/Ce4+ ratio within the crystal. The net reaction is succinctly described as: H2O2 + 2O2- + 2H+ → 2H2O + 2O2. The chemical equations and mathematical treatment appears to align well with several critical in vivo observations such as; direct and specific superoxide dismutase (SOD), ROS control, catalytic regeneration, ceria self-regulation and self-limiting behavior. However, in contrast to experimental observations, the model predicts that the 4+ ceric ion state is the key SOD agent. Future work is suggested based on these calculations.