1,721,026 research outputs found
Klinische impact van geslachtshormonen gemeten met massaspectrometrie
No full textSex steroids are mainly synthesized in the reproductive organs and the adrenal glands. Sex steroid levels are regulated by the hypothalamic-pituitary-gonadal axis, via a classical feedback system. Testosterone (T) represents the main androgen and estradiol (E2) the main estrogen. Androgens can be aromatized into estrogens by the aromatase enzyme. This key enzyme in the biosynthesis of estrogens is highly expressed in adipose tissue.
In circulation, sex steroids are bound to sex hormone-binding globulin (SHBG) and albumin with a high and low affinity respectively. Only a small fraction circulates in a non-protein bound or free form. According to the ‘free hormone hypothesis’, the free fraction is responsible for the biological activity of sex steroids, as only the free hormone can enter the cell and can activate its nuclear receptor.
In routine clinical practice, total T and total E2 concentrations are most often measured by immunoassays. These assays are not standardized for low concentrations, such as T levels in women and E2 levels in men, resulting in inaccurate measurements in this clinically important low range. To measure low total T and E2 levels accurately, liquid or gas chromatography-tandem mass spectrometry (LC-MS/MS or GC-MS/MS) is the method of choice. Furthermore, free T and E2 levels are currently calculated from total T and E2, SHBG and albumin levels. Inevitably, these calculations rely on accurate measurements of total sex steroid levels.
In this project, we studied the clinical correlates of mass-spectrometry measured sex steroids. In the first part of this project, we performed the clinical validation of a new LC-MS/MS method to measure estrogens (E2 and estrone), which was recently developed in the clinical laboratory of the University Hospitals. With this highly sensitive method, we can measure estrogen concentrations in patients with low to very low levels, such as adolescents, postmenopausal women and men, including men treated with anti-androgens.
Furthermore, concentrations of sex steroids and SHBG change considerably in ageing and disease. From the third decade, male testosterone levels decrease by 0.4-2% per year, together with a rise in SHBG, which results in a greater rate of decline of free T compared to total T. However, to date, it is not clear if total T or free T levels are more important in assessing the androgen status in ageing men.
Moreover, in epidemiologic research, low SHBG and low testosterone levels have been identified as risk factors for the development of the metabolic syndrome. It is however unclear if BMI, insulin resistance or body composition mediate this risk.
In the second part of this project, we used the framework of the European Male Ageing Study (EMAS). In this large European cohort, 3369 healthy men between 40-79 years from 8 European countries participated. The main research question in EMAS is to investigate the association between age-related hormonal changes and a broad range of health outcomes in elderly men.
In a first paper, we showed that low total T is a risk factor for developing metabolic syndrome, independently of BMI, insulin resistance or body composition. On the other hand, E2 levels do not contribute to this risk, but a lower aromatization of T into E2 can be protective for developing metabolic syndrome.
In a second paper, we found that men with low free T, but normal total T, have more androgen deficiency-related symptoms than men with normal total T and free T. Moreover, symptoms were not different in men with low total T, but normal free T. We thus provide strong evidence that not only total, but also free T levels are important in the diagnostic workup of men with hypogonadal symptoms.
In women, high androgen levels have a negative impact on the menstrual cycle and fertility. In the third part of the project, we investigated the role of androgens and SHBG in diagnosing and classifying women with subfertility and oligomenorrhea. We showed that also in these women, free T is the most sensitive marker for identifying women with hormonal, ovarian and metabolic disturbances.
In conclusion, we studied the clinical correlates of mass-spectrometry measured sex steroids in several patient groups and diseases in which precise measurements of sex steroid levels in the low range are important and determine further clinical management. In men and postmenopausal women, we can now perform precise measurements of estradiol and estrone. We showed that low total T and low free T are risk factors for metabolic syndrome, whereas estradiol is not. We also proved that free T is important in the diagnostic workup of androgen deficiency in men. Furthermore, free T proved to be a sensitive marker in evaluating androgen excess in women.status: Publishe
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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