1,288 research outputs found

    Optimizing the spatial configuration of a seven-talker speech display

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    Proceedings of the 9th International Conference on Auditory Display (ICAD), Boston, MA, July 7-9, 2003.Although there is substantial evidence that performance in multitalker listening tasks can be improved by spatially separating the apparent locations of the competing talkers, very little effort has been made to determine the best locations and presentation levels for the talkers in a multichannel speech display. In this experiment, a call-sign based color and number identification task was used to evaluate the effectiveness of three different spatial configurations and two different level normalization schemes in a sevenchannel binaural speech display. When only two spatially-adjacent channels of the seven-channel system were active, overall performance was substantially better with a geometrically-spaced spatial configuration (with far-field talkers at -90 , -30 , -10 , 0 , +10 , +30 , and +90 azimuth) or a hybrid near-far configuration (with far-field talkers at -90 , -30 , 0 , +30 , and +90 azimuth and near-field talkers at 90 ) than with a more conventional linearlyspaced configuration (with far-field talkers at -90 , -60 , -30 , 0 , +30 , +60 , and +90 azimuth). When all seven channels were active, performance was generally better with a ``better-ear'' normalization scheme that equalized the levels of the talkers in the more intense ear than with a default normalization scheme that equalized the levels of the talkers at the center of the head. The best overall performance in the seven-talker task occurred when the hybrid near-far spatial configuration was combined with the better-ear normalization scheme. This combination resulted in a 20% increase in the number of correct identifications relative to the baseline condition with linearly-spaced talker locations and no level normalization. Although this is a relatively modest improvement, it should be noted that it could be achieved at little or no cost simply by reconfiguring the HRTFs used in a multitalker speech display

    The alpha-1A adrenergic receptor agonist A61603 reduces cardiac polyunsaturated fatty acid and endocannabinoid metabolites associated with inflammation in vivo

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    Alpha-1-adrenergic receptors (α1-ARs) are G-protein coupled receptors (GPCRs) with three highly homologous subtypes (α1A, α1B, and α1D). Of these three subtypes, only the α1A and α1B are expressed in the heart. Multiple pre-clinical models of heart injury demonstrate cardioprotective roles for the α1A. Non-selective α1-AR activation promotes glycolysis in the heart, but the functional α1-AR subtype and broader metabolic effects have not been studied

    Flying by Ear: Blind Flight with a Music-Based Artificial Horizon

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    Two experiments were conducted in actual flight operations to evaluate an audio artificial horizon display that imposed aircraft attitude information on pilot-selected music. The first experiment examined a pilot's ability to identify, with vision obscured, a change in aircraft roll or pitch, with and without the audio artificial horizon display. The results suggest that the audio horizon display improves the accuracy of attitude identification overall, but differentially affects response time across conditions. In the second experiment, subject pilots performed recoveries from displaced aircraft attitudes using either standard visual instruments, or, with vision obscured, the audio artificial horizon display. The results suggest that subjects were able to maneuver the aircraft to within its safety envelope. Overall, pilots were able to benefit from the display, suggesting that such a display could help to improve overall safety in general aviation

    Alpha-1–Adrenergic Receptors in Heart Failure: The Adaptive Arm of the Cardiac Response to Chronic Catecholamine Stimulation

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    Alpha-1-adrenergic receptors are G-protein coupled receptors (GPCRs) activated by catecholamines. The alpha-1A and alpha-1B subtypes are expressed in mouse and human myocardium, whereas the alpha-1D protein is found only in coronary arteries. There are far fewer alpha-1-ARs than beta-ARs in the non-failing heart, but their abundance is maintained or increased in the setting of heart failure, which is characterized by pronounced chronic elevation of catecholamines and b□eta-AR dysfunction. Decades of evidence from gain- and loss-of-function studies in isolated cardiac myocytes and numerous animal models demonstrate important adaptive functions for cardiac alpha-1-ARs, to include physiological hypertrophy, positive inotropy, ischemic preconditioning, and protection from cell death. Clinical trial data indicate that blocking alpha-1-ARs is associated with incident heart failure in patients with hypertension. Collectively, these findings suggest that alpha-1-AR activation might mitigate the well-recognized toxic effects of beta-ARs in the hyperadrenergic setting of chronic heart failure. Thus, exogenous cardioselective activation of alpha-1-ARs might represent a novel and viable approach to the treatment of heart failure

    Alpha-1-adrenergic receptors: Targets for agonist drugs to treat heart failure

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    Evidence from cell, animal, and human studies demonstrates that α1-adrenergic receptors mediate adaptive and protective effects in the heart. These effects may be particularly important in chronic heart failure, when catecholamine levels are elevated and β-adrenergic receptors are down regulated and dysfunctional. This review summarizes these data and proposes that selectively activating α1-adrenergic receptors in the heart may represent a novel and effective way to treat heart failure

    Performance of random forests and logic regression methods using mini-exome sequence data

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    Machine learning approaches are an attractive option for analyzing large-scale data to detect genetic variants that contribute to variation of a quantitative trait, without requiring specific distributional assumptions. We evaluate two machine learning methods, random forests and logic regression, and compare them to standard simple univariate linear regression, using the Genetic Analysis Workshop 17 mini-exome data. We also apply these methods after collapsing multiple rare variants within genes and within gene pathways. Linear regression and the random forest method performed better when rare variants were collapsed based on genes or gene pathways than when each variant was analyzed separately. Logic regression performed better when rare variants were collapsed based on genes rather than on pathways

    County and Demographic Differences in Drug Arrests and Controlled Substance Use in Maine

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    . Introduction: The Diversion Alert Program (DAP) was established to curb misuse of drugs and help identify people who may need treatment for substance use disorder (SUD). Law enforcement compiled arrest data into a database accessible by health care providers. Our objectives were to identify regional and demographic differences in drug use and misuse in Maine. Methods: All arrests (N = 11 234) reported to the DAP from 2013 to 2018 were examined by county and arrestee demographics, and classified into families (opioids, stimulants, sedatives). The Drug Enforcement Administration’s Automation of Reports and Consolidated Orders System (ARCOS) tracks the distribution of controlled pharmaceuticals (Schedule II-III). Opioids were converted to oral morphine milligram equivalents (MMEs). County and zip-code maps were constructed. Results: The most arrests per capita occurred in Androscoggin, Knox, and Cumberland Counties. Opioids were the most common drug class in arrests in all counties except Aroostook County, where stimulants were most common. Medical distribution of opioids varied. Although buprenorphine doubled, many prescription opioids (eg, hydrocodone, fentanyl, oxymorphone) exhibited large (\u3e 50%) reductions in distribution. Methadone was the predominant opioid statewide (56.4% of total MMEs), although there were sizable differences between regions (Presque Isle = 8.6%, Bangor = 78.9%). Amphetamine distribution increased by 67.9%. Discussion: The DAP, a unique pharmacoepidemiological resource, revealed a 6-fold difference in drug arrests by county. Regional differences in methadone may be due to heterogeneities in methadone clinic distribution. Conclusions: The decrease in most prescription opioids, but increase in prescription stimulants, may warrant continued monitoring to improve public health

    Frequent and specific immunity to the embryonal stem cell–associated antigen SOX2 in patients with monoclonal gammopathy

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    Specific targets of cellular immunity in human premalignancy are largely unknown. Monoclonal gammopathy of undetermined significance (MGUS) represents a precursor lesion to myeloma (MM). We show that antigenic targets of spontaneous immunity in MGUS differ from MM. MGUS patients frequently mount a humoral and cellular immune response against SOX2, a gene critical for self-renewal in embryonal stem cells. Intranuclear expression of SOX2 marks the clonogenic CD138− compartment in MGUS. SOX2 expression is also detected in a proportion of CD138+ cells in MM patients. However, these patients lack anti-SOX2 immunity. Cellular immunity to SOX2 inhibits the clonogenic growth of MGUS cells in vitro. Detection of anti-SOX2 T cells predicts favorable clinical outcome in patients with asymptomatic plasmaproliferative disorders. Harnessing immunity to antigens expressed by tumor progenitor cells may be critical for prevention and therapy of human cancer

    Observations of bromine monoxide transport in the Arctic sustained on aerosol particles

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    The return of sunlight in the polar spring leads to the production of reactive halogen species from the surface snowpack, significantly altering the chemical composition of the Arctic near-surface atmosphere and the fate of long-range transported pollutants, including mercury. Recent work has shown the initial production of reactive bromine at the Arctic surface snowpack; however, we have limited knowledge of the vertical extent of this chemistry, as well as the lifetime and possible transport of reactive bromine aloft. Here, we present bromine monoxide (BrO) and aerosol particle measurements obtained during the March 2012 BRomine Ozone Mercury EXperiment (BROMEX) near Utqiaġvik (Barrow), AK. The airborne differential optical absorption spectroscopy (DOAS) measurements provided an unprecedented level of spatial resolution, over 2 orders of magnitude greater than satellite observations and with vertical resolution unable to be achieved by satellite methods, for BrO in the Arctic. This novel method provided quantitative identification of a BrO plume, between 500 m and 1 km aloft, moving at the speed of the air mass. Concurrent aerosol particle measurements suggest that this lofted reactive bromine plume was transported and maintained at elevated levels through heterogeneous reactions on colocated supermicron aerosol particles, independent of surface snowpack bromine chemistry. This chemical transport mechanism explains the large spatial extents often observed for reactive bromine chemistry, which impacts atmospheric composition and pollutant fate across the Arctic region, beyond areas of initial snowpack halogen production. The possibility of BrO enhancements disconnected from the surface potentially contributes to sustaining BrO in the free troposphere and must also be considered in the interpretation of satellite BrO column observations, particularly in the context of the rapidly changing Arctic sea ice and snowpack
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