scholarly journals Assessing Biomarker Stability and Assay Performance Parameters for the Use of Biomarkers in Mental Disorders; A Study of Early Stage Biomarker Assay Method Development

2021 ◽  
Author(s):  
Mike jentsch ◽  
Barry van de Strate ◽  
Marjolein Meddens ◽  
Marcus Meddens ◽  
Robert Schoevers
Keyword(s):  
Body Fluid ◽  
Method Development ◽  
Early Stage ◽  
A Priori ◽  
Assay Development ◽  
Assay Method ◽  
Assay Performance ◽  
Starting Point ◽  
Fit For Purpose ◽  
Almost All

Abstract Within the field of psychiatry the development of biomarker based assay methods is relatively young. Recent efforts focused on combining several biomarkers within a panel to increase discriminative power. However, most biomarker panels have failed to advance to the stage of clinical application. An important prerequisite is a proper sampling and storage procedure, based on a priori identified stability properties of all biomarker/body fluid combinations present in the panel. Second, is the performance requisites of the assays in use, such as Enzyme-Linked Immunosorbent Assays (ELISA), in order to assure reliable results within and between runs. In this study, we analyzed 24 biomarker assays in 32 biomarker/body fluid combinations. Each biomarker body fluid combination was tested for stability and assay performance. We found hampering stability in almost all cases expect three biomarkers in urine and three in serum. Variability in biomarker stability either indicates decreased biomarker stability or issues in assay performance. This study indicates that basic biomarker/body fluid combination stability provides a good starting point for biomarker panel assay development. However, assay performance plays an important role in the correct interpretation of those results. Along the way of assay development, other quality assurance parameters might be implemented focused on a fit for purpose principle ultimately providing reliable data necessary for diagnostical method implementation.

THE FRENCH FOUNDATIONS OF HUTTON’S THEORY OF THE EARTH, PART TWO: HUTTON’S DEBTS TO ROUELLE

2021 ◽  
Vol 40 (2) ◽  
pp. 332-364
Author(s):  
GREGORY F.W. TODD
Keyword(s):  
Eighteenth Century ◽  
A Priori ◽  
Chemistry Teachers ◽  
History Of Geology ◽  
Starting Point ◽  
History Of ◽  
Degree Of Confidence ◽  
New Interpretation ◽  
Almost All ◽  
High Degree

This contribution, in two parts, addresses a long-standing problem in the history of geology: Was the geological theory of James Hutton derived inductively from observations and scientific knowledge, or was it derived a priori as a speculative system? Hutton’s own writings do little to clarify the question, and the conflict in interpretations has remained at an impasse. This contribution proposes to resolve that conflict by focusing on the two years Hutton spent as a young man studying chemistry in Paris. I argue that Hutton studied with one of the great chemistry teachers of the eighteenth century, Guillaume-François Rouelle, and that Rouelle’s teachings provided the foundations of Hutton’s geological theory. Part One of this contribution reviewed evidence that Hutton was a student of Rouelle’s, and concluded with a high degree of confidence, but less than certainty, that Hutton did study with Rouelle. In this Part Two, it is argued that Hutton adopted almost all the geological ideas found in Rouelle’s lectures. This Part Two also proposes a reconstruction of the development of Hutton’s cyclical model of Earth strata, taken as the starting point of his broader theory, to show that it developed from observations and inductions, and his study with Rouelle, and was not developed as an a priori system. That conclusion will require a new interpretation of Hutton’s theory, which should now be understood as part of a continuum of geological knowledge developing during the eighteenth century.

Bioanalytical method development and validation of simultaneous analysis of telmisartan and hydrochlorthiazide in human plasma using LC-MS/MS

2016 ◽  
Vol 5 (03) ◽  
pp. 4862 ◽  
Author(s):  
Mathew George* ◽  
Lincy Joseph ◽  
Arpit Kumar Jain ◽  
Anju V.
Keyword(s):  
Human Plasma ◽  
Retention Time ◽  
High Performance ◽  
Method Development ◽  
Matrix Effects ◽  
Solid Phase ◽  
Internal Standard ◽  
Assay Method ◽  
Buffer System ◽  
Internal Standards

A simple, sensitive, rapid and economic high performance thin layer chromatographic method and a mass spectroscopic assay method has been developed for the quantification of telmisartan and hydrochlorthiazide combination in human plasma. The internal standards and analytes were extracted from human plasma by solid-phase extraction with HLB Oasis1cc (30mg) catridges. The scanning and optimization for the samples are done using methanol: water (50:50). The samples were chromatographed using reverse phase chromatography with C-18 column of different manufacturers like Ascentis C18 (150×4. 6, 5µ) using the buffer system Acetonitrile: Buffer (80:20%v/v) which consist of 2±0. 1Mm ammonium format at a flow rate of 0. 7ml/min at a column oven temperature 35±10c. The internal standard used was hydrochlorthiazide13c1, d2 and telmisartand3. The extraction techniques include conditioning, loading, washing and elution, drying followed by reconstitution of the dried samples. The volume injected was 10µl with the retention time of 3-4 min for telmisartan, 1-2 min for hydrochlorthiazide and for the internal standards the retention time was 3-4 min for telmisartand3 and 1-2 min for hydrochlorthiazide c13d2. The rinsing solution was Acetonitrile: HPLC grade water in the ratio (50:50). The above developed method was validated using various parameters like selectivity and sensitivity, accuracy and precision, matrix effects, % recovery and various stability studies. The method was proved to be sensitive, accurate, precise and reproducible. The preparation showed high recovery for the quantitative determination of telmisartan and hydrochlorthiazide in human plasma.

scholarly journals Analytical and physiological validation of an enzyme immunoassay to measure oxytocin in dog, wolf, and human urine samples

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
G. Wirobski ◽  
F. S. Schaebs ◽  
F. Range ◽  
S. Marshall-Pescini ◽  
T. Deschner
Keyword(s):  
Enzyme Immunoassay ◽  
Human Urine ◽  
Extraction Efficiency ◽  
Urine Samples ◽  
Antibody Specificity ◽  
Analytical Validation ◽  
Human Urine Samples ◽  
Assay Performance ◽  
Fit For Purpose ◽  
Commercial Enzyme Immunoassay

AbstractOxytocin (OT) promotes pro-sociality, bonding, and cooperation in a variety of species. Measuring oxytocin metabolite (OTM) concentrations in urine or saliva provides intriguing opportunities to study human and animal behaviour with minimal disturbance. However, a thorough validation of analytical methods and an assessment of the physiological significance of these measures are essential. We conducted an analytical validation of a commercial Enzyme Immunoassay (EIA; Arbor OT assay kit) to measure OTM concentrations in dog, wolf, and human urine samples. To test the assay’s ability to detect changes in OTM concentrations, we administered oxytocin intranasally to 14 dogs. Assay performance with regard to parallelism was acceptable. Assay accuracy and extraction efficiency for dog and wolf samples were comparable to a previously validated assay (Enzo OT assay kit) but variation was smaller for human samples. Binding sensitivity and antibody specificity were better in the Arbor assay. Average OTM concentrations were more than twice as high as in comparable samples measured with the Enzo assay, highlighting a lack of comparability of absolute values between different assays. Changes in OTM concentrations after intranasal treatment were detected reliably. The Arbor assay met requirements of a “fit-for-purpose” validation with improvement of several parameters compared to the Enzo assay.

scholarly journals Toxicity Induced by Cytokines, Glucose, and Lipids Increase Apoptosis and Hamper Insulin Secretion in the 1.1E7 Beta Cell-Line

2021 ◽  
Vol 22 (5) ◽  
pp. 2559
Author(s):  
Antonia Diaz-Ganete ◽  
Aranzazu Quiroga-de-Castro ◽  
Rosa M. Mateos ◽  
Francisco Medina ◽  
Carmen Segundo ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Cell Line ◽  
High Glucose ◽  
Secretory Pathway ◽  
Early Stage ◽  
Hybrid Cell ◽  
Basic Research ◽  
Stress Markers ◽  
Beta Cell Line ◽  
Starting Point

Basic research on types 1 and 2 diabetes mellitus require early stage studies using beta cells or cell lines, ideally of human origin and with preserved insulin secretion in response to glucose. The 1.1E7 cells are a hybrid cell line resulting from the electrofusion of dispersed human islets and PANC-1 cells, capable of secreting insulin in response to glucose, but their survival and function under toxic conditions remains untested. This characterization is the purpose of the present study. We treated these cells with a cytokine mix, high glucose, palmitate, and the latter two combined. Under these conditions, we measured cell viability and apoptosis (MTT, Caspase Glo and TUNEL assays, as well as caspase-8 and -9 levels by Western blotting), endoplasmic reticulum stress markers (EIF2AK3, HSPA4, EIF2a, and HSPA5) by real-time PCR, and insulin secretion with a glucose challenge. All of these stimuli (i) induce apoptosis and ER stress markers expression, (ii) reduce mRNA amounts of 2–5 components of genes involved in the insulin secretory pathway, and (iii) abrogate the insulin release capability of 1.1E7 cells in response to glucose. The most pronounced effects were observed with cytokines and with palmitate and high glucose combined. This characterization may well serve as the starting point for those choosing this cell line for future basic research on certain aspects of diabetes.

Characteristics and attitudes of family planners in Khartoum, Sudan

1982 ◽  
Vol 14 (1) ◽  
pp. 7-16 ◽  
Author(s):  
M. A. Khalifa
Keyword(s):  
Family Planning ◽  
Birth Control ◽  
Early Stage ◽  
Significant Proportion ◽  
Large Family ◽  
Capital City ◽  
Age Group ◽  
African Countries ◽  
The Mean ◽  
Almost All

SummaryIn a survey of 1475 urban Moslem wives in the age group 15–49 living in the capital city of the Sudan, knowledge of birth control was reported by almost all respondents while a significant proportion had used contraception at least once. The mean age of the users was 32·8 years, their duration of marriage was 15·1 years and their mean number of surviving children was 4·6. Those who had never used contraception had a higher mean age, a longer duration of marriage and more surviving children. Most of the users had an urban residential background and belonged to the high socioeconomic class. They held favourable attitudes to family planning. Although they thought that having a large family (more than five children) was not desirable, their mean preferred family size was no different from that of the never users.The results indicate that contraception is used for the purpose of spacing births rather than limiting their ultimate number. At this early stage of contraceptive adoption in Sudan, the characteristics of the pioneer acceptors are similar to those observed in other African countries.

Känslans platser. Topikerna för pathos i Aristoteles Retoriken

2018 ◽  
Vol 22 (78) ◽  
pp. 63-74
Author(s):  
Janne Lindqvist
Keyword(s):  
Significant Part ◽  
Starting Point ◽  
The Common ◽  
Almost All

Our understanding of Aristotle’s Rhetoric is still incomplete and distorted. This is especially true concerning his analysis of the specific topics of pathos that make up a significant part of the second book of the text. Even though this part of the text is almost twice as long as the analysis of the common topics, the discussion has attracted surprisingly small scholarly interest, at least as viewed as an example of a list of topics, as the researchers that have aspired to an understanding of “the topics” as such have almost all ignored this part of the text. The purpose of this essay is to lay out the grounds for such a study. The result of the essay is firstly a distinction between two kinds of specific topics, here somewhat ponderously labeled schematic and concrete specific topics. With these as a starting point it is possible to make a further distinction between three general specific topics here named subject, stimulus and agent. These three schematic topics could, it is finally suggested, be as useful in the 21:st century as they were in an Athens of the 4th century BCE

Stability Indicating Assay Method Development and Validation of Simultaneous Estimation of Chlorzoxazone, Diclofenac Sodium and Paracetamol in Bulk Drug and Tablet by RP-HPLC

2021 ◽  
pp. 5024-5028
Author(s):  
Krutika Patel ◽  
Sudheer Kumar Verriboina ◽  
S.G. Vasantharaju
Keyword(s):  
Method Development ◽  
Diclofenac Sodium ◽  
Potassium Dihydrogen Phosphate ◽  
Hplc Method ◽  
Assay Method ◽  
Simultaneous Estimation ◽  
Dihydrogen Phosphate ◽  
Stability Indicating ◽  
Rp Hplc ◽  
Bulk Drug

A simple, accurate, specific and stability-indicating RP-HPLC method was developed for simultaneous determination of chlorzoxazone, diclofenac sodium and paracetamol, using C18 Vydac Monomeric 120A (250 × 4.6mm, 5μ) at 40ºC. The mobile phase contains a mixture of 20mM potassium dihydrogen phosphate buffer (pH 6.2 adjusted with potassium hydroxide) and acetonitrile (30:70 v/v). The flow rate was 1ml/min and detection was carried out at 275nm using PDA detector. The retention time of paracetamol, chlorzoxazone and diclofenac sodium were 3.28mins, 13.27mins and 15.61mins respectively. The analytical curve was linear over a concentration range of 0.65- 6.5μg/ml for paracetamol, 1-10μg/ml for chlorzoxazone and 0.1-1μg/ml for diclofenac sodium. The drugs in bulk and tablet were subjected to acid and alkali hydrolysis, oxidation, thermal and photolytic degradation. This method can be successfully employed for simultaneous quantitative analysis of Chlorzoxazone, Diclofenac sodium and Paracetamol in bulk drug and tablet formulation.

scholarly journals Estimation of the mean normal measure from flat sections

2008 ◽  
Vol 40 (01) ◽  
pp. 31-48
Author(s):  
Markus Kiderlen
Keyword(s):  
A Priori ◽  
The Other ◽  
Consistent Estimator ◽  
Random Set ◽  
Normal Measure ◽  
Mild Assumption ◽  
The Mean ◽  
Vertical Sections ◽  
Almost All

We discuss the determination of the mean normal measure of a stationary random set Z ⊂ ℝ d by taking measurements at the intersections of Z with k-dimensional planes. We show that mean normal measures of sections with vertical planes determine the mean normal measure of Z if k ≥ 3 or if k = 2 and an additional mild assumption holds. The mean normal measures of finitely many flat sections are not sufficient for this purpose. On the other hand, a discrete mean normal measure can be verified (i.e. an a priori guess can be confirmed or discarded) using mean normal measures of intersections with m suitably chosen planes when m ≥ ⌊d / k⌋ + 1. This even holds for almost all m-tuples of k-dimensional planes are viable for verification. A consistent estimator for the mean normal measure of Z, based on stereological measurements in vertical sections, is also presented.

scholarly journals An historical framework for psychiatric nosology

2009 ◽  
Vol 39 (12) ◽  
pp. 1935-1941 ◽  
Author(s):  
K. S. Kendler
Keyword(s):  
Psychiatric Illness ◽  
Theoretical Orientation ◽  
A Priori ◽  
Early History ◽  
Top Down ◽  
Species Definition ◽  
Psychiatric Nosology ◽  
Bottom Up ◽  
Starting Point ◽  
History Of

This essay, which seeks to provide an historical framework for our efforts to develop a scientific psychiatric nosology, begins by reviewing the classificatory approaches that arose in the early history of biological taxonomy. Initial attempts at species definition used top-down approaches advocated by experts and based on a few essential features of the organism chosena priori. This approach was subsequently rejected on both conceptual and practical grounds and replaced by bottom-up approaches making use of a much wider array of features. Multiple parallels exist between the beginnings of biological taxonomy and psychiatric nosology. Like biological taxonomy, psychiatric nosology largely began with ‘expert’ classifications, typically influenced by a few essential features, articulated by one or more great 19th-century diagnosticians. Like biology, psychiatry is struggling toward more soundly based bottom-up approaches using diverse illness characteristics. The underemphasized historically contingent nature of our current psychiatric classification is illustrated by recounting the history of how ‘Schneiderian’ symptoms of schizophrenia entered into DSM-III. Given these historical contingencies, it is vital that our psychiatric nosologic enterprise be cumulative. This can be best achieved through a process of epistemic iteration. If we can develop a stable consensus in our theoretical orientation toward psychiatric illness, we can apply this approach, which has one crucial virtue. Regardless of the starting point, if each iteration (or revision) improves the performance of the nosology, the eventual success of the nosologic process, to optimally reflect the complex reality of psychiatric illness, is assured.

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