Improving evoked response audiometry

Normative studies were carried out with 8 adult subjects whose averaged evoked responses to auditory stimuli were scored visually and by a number of differently defined quantitative methods (machine scoring). In order to compare different scoring methods a common signal-to-noise ratio measure was introduced based on a model where noise is distributed normally and signal is additive. Visual and machine scoring proved to be approximately equally sensitive, but the latter lends itself to a superior testing procedure which takes only one-third as long for equivalent results and is not contaminated by subjective error. The authors believe that the greatest promise for improving evoked response audiometry lies in the exploration of the new techniques proposed earlier. Progress in proving out one of these techniques, fast periodic stimulation, is reported.     

Re-examining the relationship between audiometric profile and tinnitus pitch

Abstract

Objective: We explored the relationship between audiogram shape and tinnitus pitch to answer questions arising from neurophysiological models of tinnitus: ‘Is the dominant tinnitus pitch associated with the edge of hearing loss?’ and ‘Is such a relationship more robust in people with narrow tinnitus bandwidth or steep sloping hearing loss?’ Design: A broken-stick fitting objectively quantified slope, degree and edge of hearing loss up to 16 kHz. Tinnitus pitch was characterized up to 12 kHz. We used correlation and multiple regression analyses for examining relationships with many potentially predictive audiometric variables. Study Sample: 67 people with chronic bilateral tinnitus (43 men and 24 women, aged from 22 to 81 years). Results: In this ample of 67 subjects correlation failed to reveal any relationship between the tinnitus pitch and the edge frequency. The tinnitus pitch generally fell within the area of hearing loss. The pitch of the tinnitus in a subset of subjects with a narrow tinnitus bandwidth (n = 23) was associated with the audiometric edge. Conclusions: Our findings concerning subjects with narrow tinnitus bandwidth suggest that this can be used as an a priori inclusion criterion. A large group of such subjects should be tested to confirm these results.

Sumario

Objetivo: Exploramos la relación entre la forma del audiograma y el tono del acufeno para responder a preguntas provenientes de modelos neurofisiológicos del acúfeno: ‘Es el tono dominante del acúfeno asociado con el borde de la hipoacusia?’y ‘Será tal relación más robusta en personas con un acúfeno de banda angosta o con una hipoacusia de caída abrupta?’ Diseño: Una pendiente tipo “palo roto” objetivamente cuantificada, con severidad y borde de la hipoacusia hasta 16 kHz. El tono del acúfeno fue caracterizado hasta 12 kHz. Utilizamos un análisis de correlación y regresión múltiple para examinar la relación con muchas de las variables potencialmente predictivas. Muestra del estudio: 67 personas con acúfeno bilateral crónico (43 hombres y 24 mujeres con edades entre 22 y 81 años). Resultados: En esta amplia muestra de 67 sujetos, la correlación no demostró ninguna relación entre el acúfeno y el borde de la frecuencia. El tono del acúfeno generalmente cayó dentro del área de la hipoacusia. En un subgrupo de sujetos, que tenían un acúfeno de banda angosta (n=23), si hubo asociación con el borde audiométrico. Conclusiones: Nuestros hallazgos que corresponden a los sujetos con un acúfeno de banda angosta, sugieren que esto puede ser utilizado a priori como un criterio de inclusión. Un grupo grande de sujetos debe ser examinado para confirmar estos resultados.     

Components of variance

Components of variance have a long history and find application in all areas of scientific investigation. This review introduces components of variance and their importance firstly by examples on blood pressure, proteomic data, breath analysers and esophageal pH monitoring devices. We then present an intuitive geometric representation of analysis of variance and explain how the components of variance can be estimated from the analysis of variance table. We conclude by suggesting practice points for studies which incorporate components of variance, and recommend commonly used statistical software to undertake such analysis.     

The Mammallan Intervertebral Disc. Composition of the Nucleus Pulposus of Whales During Development and Aging

The composition of the nucleus from 25 intervertebral discs of sperm and fin whales of different fetal developmental stages and postnatal ages is reported. Early stages in the nucleus intrauterine life (one quarter to one half development) show drastic changes in the proportion of galactosamine and glucosamine. The collagen content of the dry fetal nucleus is higher than the hexosamine content in early stages although it rapidly decreases to a plateau in specimens of one half to full term development. Afterward, in the postnatal nucleus and during aging, the amount of hexosamine greater than that of collagen on a dry weight basis; furthermore, both remain invariant, although irregular changes in the proportion of galactosamine and glucosamine are observed.

The polysaccharides from the fetal tissue are more polydisperse and undersulfated than those isolated from postnatal specimens. The major polysaccharides of the whale nucleus are CS-4SO₄, CS-6SO₄, and KS. The fetal nucleus also contains CS. The distribution of CS-4SO₄ and CS-6SO₄ in the cartilage plates is the reverse of that observed in the nucleus pulposus. Characteristic of both anatomic structures is a decrease of CS during fetal development.

The proteoglycan fraction of the postnatal nucleus (PG-L) was found to contain polysaccharide peptides. Similar fractions from fetal specimens contained no polysaccharide peptides. The polydispersity of the proteoglycans in the fetal nucleus appears to be regulated by the amount of a cystine-containing proteoglycan fraction (Fraction F) sensitive to disulfide reducing reagents. Such a correlation was not observed in preparations from postnatal specimens.     

Cross-talk between the complement system and endothelial cells in physiologic conditions and in vascular diseases

The endothelial layer represents a continuous physical barrier that controls coagulation and allows selective passage of soluble molecules and circulating cells across the vessel wall into the tissue. The functional activity of the endothelial cells may be influenced by their interaction with components of the complement system. In this review we shall discuss the complex interplay that can be established between the endothelium and complement proteins or activation products. Endothelial cells may also secrete several complement components which contribute to the circulating pool. This process can be regulated by cytokines and other pro-inflammatory stimuli. In addition, complement activation products stimulate endothelial cells to acquire a pro-inflammatory and pro-coagulant status. Expression of regulatory molecules on the cell surface provides protection against an undesired attack by complement activation products. Unrestricted complement activation under pathological conditions may lead to structural and functional changes of the endothelium resulting in vascular disease.     

Early Components of the Averaged Electroencephalic Response to Monaural and Binaural Stimulation

Early components of the averaged electroencephalic response were recorded in 11 subjects from C_z-A₁, C_z-A₂, C₃-A₁, and C₄-A₂. The early components were examined in response to stimulation of either the left, right, or both ears with 40 dB SL clicks at a rate of 4/sec in awake subjects. Peak latency and peak-to-peak amplitude measures failed to discriminate between stimulus conditions. Left minus right difference scores obtained for each subject showed no consistent relationship to the ear stimulated     

夹竹桃花脂溶性成分提取工艺优化及其生物活性分析

目的 研究夹竹桃花脂溶性成分的提取工艺、组成成分及生物活性。方法 利用Box-Behnken响应面法优化提取工艺，GC-MS分析组成成分，滤纸片扩散法和二倍连续梯度稀释法分析抑菌活性，并测定抗氧化活性。结果 最佳提取工艺为索氏提取4 h，连续提取4次，料液比1∶ 15，得率9.16%，比优化前提高了13.09%。脂溶性成分含有烷烃类、醛类和酯类等30种化合物，具有还原能力和清除DPPH自由基、羟自由基、超氧自由基的能力，对枯草芽孢杆菌、金黄色葡萄球菌、大肠埃希菌和铜绿假单胞菌的最小抑菌浓度分别为1.22，1.72，0.75，1.96 g·L^–1，最小杀菌浓度分别为2.34，2.84，1.88，3.32 g·L^–1。结论 脂溶性成分最佳提取工艺得率为9.16%，以烷烃类、醛类、酯类为主，具有一定的抗氧化和抑菌活性，可为夹竹桃资源的开发利用提供参考。     

Utilizing quantitative certificate of analysis data to assess the amount of excipient lot-to-lot variability sampled during drug product development

Understanding variability in excipient physico-chemical properties is becoming an important aspect of Quality-by-Design drug product development. However, present experimental methods have only been able to study a few physico-chemical properties for a few excipient lots due to time, cost, and sample gathering considerations. An alternative analysis method is proposed here that shows how quantitative physico-chemical property data reported in vendor certificates of analysis can evaluate excipient lot-to-lot variability in a comprehensive and low cost manner. Microcrystalline cellulose, spray-dried lactose, and magnesium stearate were selected as commonly-used excipients for this demonstration. The proposed analysis method offers drug product developers several advantages over present experimental methods, including the ability to: (1) examine excipient products for manufacturing site and/or year-to-year variations, (2) quantify a domain of prior experience for each excipient by determining the percentage of excipient lots contained within a multi-dimensional ellipsoid described by the excipient lots used during drug product development, and (3) rationally select excipient lots from the vendors inventory to maximize the domain of prior experience throughout the drug development process. For cases where certificate of analysis data may contain insufficient information, drug product developers and excipient vendors should work together to identify more appropriate datasets for analysis.