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1.
The purpose of this investigation was to characterize noise levels in spaces designated as “effective quiet” areas on a U.S. Navy aircraft carrier. Noise dosimetry samples were collected in 15 designated spaces, representing 15 noise measurements, while at-sea during airwing carrier qualifications. Equivalent sound level (Leq) measurements were collected during flight operations (Leq (flt ops)), non-flight operations (Leq (non-flt ops)), and over 24-hr periods (Leq (24-hr)). These data were compared to the 70 dBA American Conference of Governmental Industrial Hygienists (ACGIH®) Threshold Limit Value (TLV®) for “effective quiet” areas intended for temporary threshold shift recovery when personnel live and work in a potentially noise hazardous environment for periods greater than 24?hr. The monitored areas were selected based on personnel occupancy/use during off-duty time periods. Areas were classified by either (1) leisure areas that included mess (eating areas), gyms, lounges, an internet cafe, and the fantail social area or (2) berthing (sleeping) areas. The Leq measurements in decibels “A” weighted (dBA) were compared to determine significant differences between Leq (flt ops), Leq (non-flt ops), and Leq (24-hr) and were compared between leisure area and berthing area. Measured noise levels according to time period ranged as follows: (1) Leq (24-hr): 70.8–105.4 dBA; (2) Leq (flt ops): 70–101.2 dBA; and (3) Leq (non-flt ops): 39.4–104.6 dBA. All area measurements over the 24-hr period and during flight operations and 46.7% of the areas during the non-flight operation time period exceeded the “effective quiet” 70 dBA ACGIH TLV. Mean Leqs were 15 dBA higher during flight operations compared to non-flight operations in “effective quiet” areas (p?=?0.001). The Leqs in leisure areas were significantly higher than berthing areas by approximately 21 dBA during non-flight operation periods (p?=?0.001). Results suggest noise levels in “effective quiet” areas frequented by aircraft carrier personnel during off-duty hours when at-sea may inhibit auditory recovery from occupational noise exposures that occur on-duty.  相似文献   
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Ticagrelor is a cornerstone of modern antithrombotic therapy alongside aspirin in patients with acute coronary syndrome and after percutaneous coronary intervention. Adverse effects such as bleeding and dyspnea have been associated with premature ticagrelor discontinuation, which may limit any potential advantage of ticagrelor over clopidogrel. The randomized trials of ticagrelor captured adverse events, offering the opportunity to more precisely quantify these effects across studies. Therefore, a meta-analysis of 4 randomized clinical trials of ticagrelor conducted between January 2007 and June 2017 was performed to quantify the incidence and causes of premature ticagrelor discontinuation. Among 66,870 patients followed for a median 18 months, premature ticagrelor discontinuation was seen in 25%; bleeding was the most common cause of discontinuation followed by dyspnea. Versus the comparators, the relative risk of dyspnea-related discontinuation during follow-up was 6.4-fold higher, the relative risk of bleeding was 3.2-fold higher, and the relative risk of discontinuation due to any adverse event was 59% higher for patients receiving ticagrelor. Understanding these potential barriers to adherence to ticagrelor is crucial for informed patient-physician decision making and can inform future efforts to improve ticagrelor adherence. This review discusses the incidence, causes, and biological mechanisms of ticagrelor-related adverse effects and offers strategies to improve adherence to ticagrelor.  相似文献   
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Phenylketonuria (PKU), an inborn error of phenylalanine metabolism, has been shown to be a risk factor for tardive dyskinesia (TD). In male psychiatric patients there was a significant relationship between TD and measures of plasma phenylalanine following ingestion of a standardized phenylalanine dose that was indicative of higher brain availability of phenylalanine in patients with TD. In addition, a medical food formulation consisting of branched chain amino acids, which compete with phenylalanine for transport across the blood-brain barrier, has been demonstrated to be an efficacious treatment for TD. Cumulatively these findings suggested that TD was related to phenylalanine metabolism and thus that sequence variants in the gene for phenylalanine hydroxylase (PAH), the rate-limiting enzyme in the catabolism of phenylalanine, could be associated with TD susceptibility. Genetic screening of PAH in a group of 123 psychiatric patients revealed ten sequence polymorphisms and two mutations, but none appeared to be a significant risk factor for TD.  相似文献   
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BACKGROUND: Few data are currently available investigating neurosteroids (NS) in Alzheimer's disease (AD). The NS allopregnanolone may be decreased in serum and plasma in patients with AD, but it is unclear if allopregnanolone is also reduced in brain. Because a number of NS exhibit neuroprotective effects and impact cognitive performance in rodent models, these molecules may be relevant to the pathophysiology of neurodegenerative disorders. We therefore investigated prefrontal cortex (PFC) NS levels in AD. METHODS: Neurosteroid levels (allopregnanolone, pregnenolone, dehydroepiandrosterone [DHEA]) were determined in postmortem PFC in 14 male subjects with AD and 15 cognitively intact male control subjects by gas chromatography/mass spectrometry preceded by high-performance liquid chromatography purification. RESULTS: Subjects with AD exhibit significant reductions in allopregnanolone compared with cognitively intact control subjects (median levels = 2.50 ng/g vs. 5.59 ng/g, respectively; p = .02). Allopregnanolone levels are inversely correlated with neuropathological disease stage (Braak), r = -.49, p = .007. Median DHEA levels are elevated in subjects with AD (p = .01). CONCLUSIONS: Subjects with AD demonstrate significant reductions in PFC allopregnanolone levels, a finding that may be relevant to neuropathological disease stage severity. Neurosteroids may have utility as candidate biomarkers in AD.  相似文献   
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