In a sensitive cochlea, the basilar membrane response to transient excitation of any kind--normal acoustic or artificial intracochlear excitation--consists of not only a primary impulse but also a coda of delayed secondary responses with varying amplitudes but similar spectral content around the characteristic frequency of the measurement location. The coda, sometimes referred to as echoes or ringing, has been described as a form of local, short term memory which may influence the ability of the auditory system to detect gaps in an acoustic stimulus such as speech. Depending on the individual cochlea, the temporal gap between the primary impulse and the following coda ranges from once to thrice the group delay of the primary impulse (the group delay of the primary impulse is on the order of a few hundred microseconds). The coda is physiologically vulnerable, disappearing when the cochlea is compromised even slightly. The multicomponent sensitive response is not yet completely understood. We use a physiologically-based, mathematical model to investigate (i) the generation of the primary impulse response and the dependence of the group delay on the various stimulation methods, (ii) the effect of spatial perturbations in the properties of mechanically sensitive ion channels on the generation and separation of delayed secondary responses. The model suggests that the presence of the secondary responses depends on the wavenumber content of a perturbation and the activity level of the cochlea. In addition, the model shows that the varying temporal gaps between adjacent coda seen in experiments depend on the individual profiles of perturbations. Implications for non-invasive cochlear diagnosis are also discussed.
Introduction: Diagnostic testing is common in the emergency department. The value of some testing is questionable. The purpose of this study was to assess how varying levels of benefit, risk, and costs influenced an individual’s desire to have diagnostic testing.
Methods: A survey through Amazon Mechanical Turk presented hypothetical clinical situations: low risk chest pain and minor traumatic brain injury. Each scenario included three given variables (benefit, risk, and cost), that was independently randomly varied over four possible values (0.1%, 1%, 5%, 10% for benefit and risk and $0, $100, $500, and $1000 for the individual’s personal cost for receiving the test). Benefit was defined as the probability of finding the target disease (traumatic intracranial hemorrhage or acute coronary syndrome).
Results: A total of 1000 unique respondents completed the survey. Increasing benefit from 0.1% to 10%, the percent of respondents who accepted a diagnostic test went from 28.4% to 53.1%. [OR: 3.42 (2.57-4.54)] As risk increased from 0.1% to 10%, this number decreased from 52.5% to 28.5%. [OR: 0.33 (0.25-0.44)] Increasing cost from $0 to $1000 had the greatest change of those accepting the test from 61.1% to 21.4%, respectively. [OR: 0.15 (0.11-0.2)]
Conclusions: The desire for testing was strongly sensitive to the benefits, risks and costs. Many participants wanted a test when there was no added cost, regardless of benefit or risk levels, but far fewer elected to receive the test as cost increased incrementally. This suggests that out of pocket costs may deter patients from undergoing diagnostic testing with low potential benefit.
The Social Environment refers to characteristics of the people and institutions in a census tract, including: 1)
Religious organizations (churches and places of worship); and 2) Voter turnout for the 2012 Presidential Election. Coverage for all data: 10-county Detroit-Warren-Ann Arbor Combined Statistical Area.
Active living resources include spaces and organizations that facilitate physical activity, including 1) park land, 2) recreation areas (including parks, golf courses, amusement parks, beaches and other recreational landmarks); and 3) recreation centers (including gyms, dancing instruction, martial arts instruction, bowling centers, yoga instruction, sports clubs, fitness programs, golf course, pilates instruction, personal trainers, swimming pools, skating rinks, etc.)
Coverage for all data: 10-county Detroit-Warren-Ann Arbor Combined Statistical Area.
The food environment is: 1) The physical presence of food that affects a person’s diet; 2) A person’s proximity to food store locations; 3) The distribution of food stores, food service, and any physical entity by which food may be obtained; or 4) A connected system that allows access to food. (Source: https://www.cdc.gov/healthyplaces/healthtopics/healthyfood/general.htm) Data included here concern: 1) Food access; and 2) Liquor access. Spatial Coverage for most data: 10-county Detroit-Warren-Ann Arbor Combined Statistical Area, Michigan, USA. See exception for grocery store data below.
The rapid activation of the mechanistic target of rapamycin complex-1 (mTORC1) by growth factors is increased by extracellular amino acids through yet-undefined mechanisms of amino acid transfer into endolysosomes. Because the endocytic process of macropinocytosis concentrates extracellular solutes into endolysosomes and is increased in cells stimulated by growth factors or tumor-promoting phorbol esters, we analyzed its role in amino acid–dependent activation of mTORC1. Here, we show that growth factor-dependent activation of mTORC1 by amino acids, but not glucose, requires macropinocytosis. In murine bone marrow–derived macrophages and murine embryonic fibroblasts stimulated with their cognate growth factors or with phorbol myristate acetate, activation of mTORC1 required an Akt-independent vesicular pathway of amino acid delivery into endolysosomes, mediated by the actin cytoskeleton. Macropinocytosis delivered small, fluorescent fluid-phase solutes into endolysosomes sufficiently fast to explain growth factor–mediated signaling by amino acids. Therefore, the amino acid–laden macropinosome is an essential and discrete unit of growth factor receptor signaling to mTORC1