Gaussian Processes for Hearing Threshold Estimation Using Auditory Brainstem Responses.

The Auditory Brainstem Response (ABR) plays an important role in diagnosing and managing hearing loss, but can be challenging and time-consuming to measure. Test times are especially long when multiple ABR measurements are needed, e.g., when estimating hearing threshold at a range of frequencies. While many detection methods have been developed to reduce ABR test times, the majority were designed to detect the ABR at a single stimulus level and do not consider correlations in ABR waveforms across levels. These correlations hold valuable information, and can be exploited for more efficient hearing threshold estimation. This was achieved in the current work using a Gaussian Process (GP), i.e., a Bayesian approach for non-linear regression. The function to estimate with the GP was the ABR's amplitude across stimulus levels, from which hearing threshold was ultimately inferred. Active learning rules were also designed to automatically adjust the stimulus level and efficiently locate hearing threshold. Simulation results show test time reductions of up to  âˆ¼ 50% for the GP compared to a sequentially applied Hotelling's T2 test, which does not consider correlations across ABR waveforms. A case study was also included to briefly assess the GP approach in ABR data from an adult volunteer.

Objective measures for detecting the auditory brainstem response: comparisons of specificity, sensitivity and detection time.

OBJECTIVE: To evaluate and compare the specificity, sensitivity and detection time of various time-domain and multi-band frequency domain methods when detecting the auditory brainstem response (ABR). DESIGN: Simulations and subject recorded data were used to assess and compare the performance of the Hotelling's T2 test (applied in either time or frequency domain), two versions of the modified q-sample uniform scores test and both the Fsp and Fmp, which were evaluated using both conventional F-distributions with assumed degrees of freedom and a bootstrap approach. STUDY SAMPLE: Data consisted of click-evoked ABRs and recordings of EEG background activity from 12 to 17 normal hearing adults, respectively. RESULTS: An overall advantage in sensitivity and detection time was demonstrated for the Hotelling's T2 test. The false-positive rates (FPRs) of the Fsp and Fmp were also closer to the nominal alpha-level when evaluating statistical significance using the bootstrap approach, as opposed to using conventional F-distributions. The FPRs of the remaining methods were slightly higher than expected. CONCLUSIONS: In this work, Hotelling's T2 outperformed the alternative methods for automatically detecting ABRs. Its promise as a sensitive and efficient detection method should now be tested in a larger clinical study.

The greater susceptibility of North Ronaldsay sheep compared with Cambridge sheep to copper-induced oxidative stress, mitochondrial damage and hepatic stellate cell activation.

Sheep of the semi-feral North Ronaldsay (copper-sensitive) and domesticated Cambridge (copper-tolerant) breeds were compared in respect of pathological changes and protein expression in the liver as a result of excessive dietary copper. Acute mitochondrial damage and hepatic stellate cell (HSC) activation with collagen synthesis occurred in response to moderate copper overload in North Ronaldsay but not in Cambridge sheep. Mitochondrial degradative changes occurred either as ballooning degeneration and rupture with subsequent autophagic degradation or as mitochondrial matrical condensation (pyknosis). In North Ronaldsay sheep prolonged exposure to copper produced mitochondrial hyperplasia and hypertrophy, and nuclear damage with necrosis. Cytosolic isocitrate dehydrogenase (IDH), an enzyme responsive to oxidative stress, was induced in the liver of Cambridge sheep receiving a Cu-supplemented diet but was undetectable in the non-supplemented control sheep. Conversely, IDH was detected at similar levels in both control and copper-supplemented North Ronaldsay sheep, indicating a lower threshold response, and an enhanced susceptibility, to oxidative stress. "Upregulation" of mitochondrial thioredoxin-dependent peroxidase reductase (antioxidant protein-1) in the hepatic cytosol of the North Ronaldsay (but not Cambridge) sheep affirmed the increased susceptibility of the mitochondria to Cu-induced oxidative stress in this breed. Likewise the upregulation of cathepsin-D indicated increased lysosomal activity and HSC activation. The findings may be relevant to copper toxicosis in human infants.

National, state and urban-area vaccination-coverage levels among children aged 19-35 months, United States, 1999.

BACKGROUND: Assessment of vaccination coverage is an important component of the U.S. vaccination program and is primarily measured by the National Immunization Survey (NIS). METHODS: The 1999 NIS is a nationally representative sample of children aged 19 to 35 months, verified by provider records, that is conducted to obtain estimates of vaccination coverage rates. Coverage estimates are calculated for the nation, states, and selected urban areas for recommended vaccines and selected vaccine series. RESULTS: Coverage estimates are presented by a variety of demographic and healthcare-related factors: overall, by poverty status, race/ethnicity, selected milestone ages, participation in WIC, level of urbanicity, provider participation in VFC, and by provider facility type. In 1999, national coverage estimates were high for most vaccines and among most demographic groups. State and urban-area level estimates varied.

Assessment of nutritional, clinical, and immunologic status of HIV-infected, inner-city patients with multiple risk factors.

OBJECTIVE: To evaluate the nutritional, clinical, and immunologic factors associated with human immunodeficiency virus (HIV)-infected, inner-city patients with multiple risk factors. DESIGN: Prospective cross-sectional nutrition evaluation of patients with HIV infection. SETTING: Patients were interviewed at the outpatient clinic at Mt Sinai Medical Center, New York City, NY. SUBJECTS: Our subjects were men and women older than 18 years of age and at all stages of HIV infection (n = 56). OUTCOME MEASURES: Anthropometric measurements, history of weight changes (maintenance of preillness body weight or decrease from preillness weight status), 3-day food records, and clinical laboratory tests. STATISTICAL ANALYSES: Tests were used to compare patients who were at a stable weight with patients who had lost weight with regard to the anthropometric, dietary, and clinical variables. Spearman's rank correlation coefficient and chi 2 tests were applied to examine correlations between pairs and differences in proportions, respectively. RESULTS: Patients were classified into groups according to whether they were at a stable weight (n = 25) or had lost weight (n = 31). All anthropometric measurements, CD4 lymphocytes, and CD8 lymphocytes were significantly lower in the patients who had lost weight. No differences were observed between the groups for absolute lymphocyte count or transferrin, hemoglobin, and albumin levels. The mean energy intake of the 56 patients was 74% of the Recommended Dietary Allowance (RDA). Forty-seven patients (84%) took vitamin and/or mineral supplements within a range of 2% to 50,000% of the RDA. No significant positive correlations were observed between nutrient intake, CD4 cells, and absolute lymphocyte count. CONCLUSIONS/APPLICATIONS: All anthropometric measurements, CD4 lymphocytes, and CD8 lymphocytes were notably lower in patients with weight loss. The mean energy intake of the subjects was only 74% of the RDA. Megadoses of vitamin supplements were taken by a large number of patients, but no significant positive effects were observed for absolute lymphocyte count and CD4 cells. Although supplementation of micronutrients may influence the progression of HIV infection, a balanced, nutritious diet may be more beneficial in maintaining or improving the physiologic status of the patients. However, members of a high-risk population may benefit less from HIV-related social services and food or nutrition resources. With the growing number of injection-drug users in the acquired immunodeficiency syndrome population, it will be essential to develop comprehensive strategies to address the interconnected needs for medical and nutrition care. Ensuring that patients have adequate meals during an extended course of treatment in the outpatient clinic or that dietitians have meals available in group settings or through home-delivery service may be the most appropriate nutrition intervention in these high-risk patients.

Effects of lipids on the activity of ferrochelatase.

Removal of lipids from submitochondrial particles or detergent-solubilized mitochondrial preparations of rat liver resulted in a 90% loss of ferrochelatase (protochemeferro-lyase, EC 4.99.1.1) activity. The addition of either a fatty acid or phospholipid restored enzyme activity; the extent of reactivation being correlated with the degree of unsaturation of the fatty acid or acyl chain and independent of the polar head group of the phospholipid, Arrhenius plots of the ferrochelatase activities of submitochondrial particles and detergent-solubilized mitochondrial preparations showed transition temperatures of 37 and 28.5 degrees C, respectively. Ferrochelatase of submitochondrial particles or detergent-solubilized preparations had an absolute requirement for Ca2+. The ferrous salt of oxalic acid, a Ca2+ chelator, was a very poor substrate for these preparations. In contrast, ferrochelatase activities of fatty acid- or lipid-supplemented acetone extracts of these preparations were not dependent on the presence of Ca2+ and ferrous oxalate served as substrate for these extracts.20