scholarly journals Importance of between and within Subject Variability in Extracellular Vesicle Abundance and Cargo when Performing Biomarker Analyses

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 485
Author(s):  
Lauren A. Newman ◽  
Alia Fahmy ◽  
Michael J. Sorich ◽  
Oliver G. Best ◽  
Andrew Rowland ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Drug Exposure ◽  
Extracellular Vesicle ◽  
The Novel ◽  
Protein Markers ◽  
Diurnal Variability ◽  
Normal Ranges ◽  
Sampling Protocols ◽  
Subject Variability ◽  
Within Subject Variability

Small extracellular vesicles (sEV) have emerged as a potential rich source of biomarkers in human blood and present the intriguing potential for a ‘liquid biopsy’ to track disease and the effectiveness of interventions. Recently, we have further demonstrated the potential for EV derived biomarkers to account for variability in drug exposure. This study sought to evaluate the variability in abundance and cargo of global and liver-specific circulating sEV, within (diurnal) and between individuals in a cohort of healthy subjects (n = 10). We present normal ranges for EV concentration and size and expression of generic EV protein markers and the liver-specific asialoglycoprotein receptor 1 (ASGR1) in samples collected in the morning and afternoon. EV abundance and cargo was generally not affected by fasting, except CD9 which exhibited a statistically significant increase (p = 0.018). Diurnal variability was observed in the expression of CD81 and ASGR1, which significantly decreased (p = 0.011) and increased (p = 0.009), respectively. These results have potential implications for study sampling protocols and normalisation of biomarker data when considering the expression of sEV derived cargo as a biomarker strategy. Specifically, the novel finding that liver-specific EVs exhibit diurnal variability in healthy subjects should have broad implications in the study of drug metabolism and development of minimally invasive biomarkers for liver disease.

Population pharmacokinetic analysis of abiraterone acetate in healthy volunteers and chemotherapy-naive and chemotherapy-pretreated metastatic castration-resistant prostate cancer patients.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 58-58
Author(s):  
Kim Stuyckens ◽  
Fred Saad ◽  
Steven Xu ◽  
Charles J. Ryan ◽  
Matthew R. Smith ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Food Intake ◽  
Healthy Subjects ◽  
Abiraterone Acetate ◽  
Population Pharmacokinetic ◽  
Castration Resistant Prostate Cancer ◽  
Prior Chemotherapy ◽  
Castration Resistant ◽  
Subject Variability ◽  
Within Subject Variability

58 Background: Abiraterone acetate (AA) is an effective therapy for patients with metastatic castration-resistant prostate cancer (mCRPC). AA is metabolized to abiraterone, an androgen biosynthesis inhibitor. We performed population pharmacokinetic (PK) analyses to estimate PK parameters after a 1,000 mg/d oral dose of AA in patients with mCRPC with and without prior chemotherapy and after a one-time 1,000 mg dose in healthy volunteers, to determine consistency between groups. Methods: Studies included in analysis: COU-AA-302 (pre-chemotherapy mCRPC); COU-AA-301 and COU-AA-006 (post-docetaxel mCRPC); and COU-AA-008, COU-AA-009, and COU-AA-014 (healthy subjects). A total of 4,627 plasma concentrations from 360 subjects were analyzed using nonlinear mixed-effects modeling. Results: A two-compartment model with three-transit compartments following sequential zero-first order kinetics was used to characterize the systemic absorption of abiraterone. Absorption-related parameters were affected by food intake. Abiraterone PK was characterized by an extensive apparent clearance, which was lower in patients with mCRPC (1505 L/h) compared with healthy subjects (2240 L/h), and by large apparent central (5630 L) and peripheral volumes of distribution (17,400 L). PK of abiraterone was similar in chemotherapy-naïve and chemotherapy-pretreated patients and was characterized by a relatively high between- and within-subject variability (eg, between-subject coefficient of variation [CV%] for relative bioavailability in the clinical studies was 61.1% and the CV% for within-subject variability was 71.3%). No factors other than food intake and patient-healthy volunteer status impacted PK. Conclusions: Based on this population PK model, the recommended 1,000 mg/d dose of AA results in similar abiraterone exposure for patients with mCRPC regardless of prior chemotherapy status. The food effect on absorption-related parameters in this analysis confirms current dosing instructions for AA. Clinical trial information: NCT00638690, NCT00887198.

Reflex Responses in Upper Limb Muscles to Cutaneous Stimuli

1993 ◽  
Vol 20 (04) ◽  
pp. 271-278 ◽  
Author(s):  
R. Chen
Keyword(s):  
Stimulus Intensity ◽  
Upper Limb ◽  
Healthy Subjects ◽  
Voluntary Contraction ◽  
Cutaneous Reflexes ◽  
Focal Lesions ◽  
Normal Ranges ◽  
Conduction Velocities ◽  
Limb Muscles ◽  
Biphasic Responses

ABSTRACT:Cutaneous reflexes in the upper limb were elicited by stimulating digital nerves and recorded by averaging rectified EMG from proximal and distal upper limb muscles during voluntary contraction. Distal muscles often showed a triphasic response: an inhibition with onset about 50 ms (Il) followed by a facilitation with onset about 60 ms (E2) followed by another inhibition with onset about 80 ms (12). Proximal muscles generally showed biphasic responses beginning with facilitation or inhibition with onset at about 40 ms. Normal ranges for the amplitude of these components were established from recordings on 22 arms of 11 healthy subjects. An attempt was made to determine the alterent fibers responsible for the various components by varying the stimulus intensity, by causing ischemic block of larger fibers and by estimating the afferent conduction velocities. The central pathways mediating these reflexes were examined by estimating central delays and by studying patients with focal lesions

Within-Subject Variability in Ingratiation as a Function of Self-Esteem and Time

2019 ◽  
Vol 18 (4) ◽  
pp. 216-226
Author(s):  
Katharina Schmitte ◽  
Bert Schreurs ◽  
Mien Segers ◽  
I. M. “Jim” Jawahar
Keyword(s):  
Individual Differences ◽  
Small Group ◽  
Self Esteem ◽  
Random Coefficient ◽  
Person Perspective ◽  
Authority Figure ◽  
Subject Variability ◽  
Over Time ◽  
Within Subject Variability

Abstract. Adopting a within-person perspective, we theorize why ingratiation use directed toward an authority figure increases over time and for whom. We posit that as the appraisal event draws closer, the salience of achieving good evaluations increases, leading to an increasing use of ingratiation. We further propose that the increase will be stronger for individuals with low relative to high self-esteem. Participants were 349 students enrolled in a small-group, tutor-led management course. Data were collected in three bi-weekly waves and analyzed using random coefficient modeling. Results show that ingratiation use increased as time to the evaluation decreased, and low self-esteem students ingratiated more as time progressed. We conclude that ingratiation use varies as a function of contextual and inter-individual differences.

Protein biomarkers in breast cancer-derived extracellular vesicles for use in liquid biopsies

2021 ◽  
Author(s):  
Dan Li ◽  
Wenjia Lai ◽  
Di Fan ◽  
Qiaojun Fang
Keyword(s):  
Breast Cancer ◽  
Early Diagnosis ◽  
Extracellular Vesicles ◽  
Liquid Biopsy ◽  
Breast Cancer Diagnosis ◽  
Extracellular Vesicle ◽  
Detection Methods ◽  
Protein Markers ◽  
Liquid Biopsies ◽  
Diagnosis And Prognosis

Breast cancer is the most common malignant disease in women worldwide. Early diagnosis and treatment can greatly improve the management of breast cancer. Liquid biopsies are becoming convenient detection methods for diagnosing and monitoring breast cancer due to their non-invasiveness and ability to provide real-time feedback. A range of liquid biopsy markers, including circulating tumor proteins, circulating tumor cells, and circulating tumor nucleic acids, have been implemented for breast cancer diagnosis and prognosis, with each having its own advantages and limitations. Circulating extracellular vesicles are messengers of intercellular communication that are packed with information from mother cells and are found in a wide variety of bodily fluids; thus, they are emerging as ideal candidates for liquid biopsy biomarkers. In this review, we summarize extracellular vesicle protein markers that can be potentially used for the early diagnosis and prognosis of breast cancer or determining its specific subtypes.

Head positioning control in a gravito-inertial field and in normal gravity

2004 ◽  
Vol 14 (4) ◽  
pp. 321-333
Author(s):  
Frédéric Sarès ◽  
Christophe Bourdin ◽  
Jean-Michel Prieur ◽  
Jean-Louis Vercher ◽  
Jean-Pierre Menu ◽  
...  
Keyword(s):  
Inertial Force ◽  
The Body ◽  
Body Axis ◽  
Positioning Control ◽  
Head Positioning ◽  
Subject Variability ◽  
Visual Frame ◽  
Vector Orientation ◽  
The Right ◽  
Within Subject Variability

The way in which the head is controlled in roll was investigated by dissociating the body axis and the gravito-inertial force orientation. Seated subjects (N = 8) were requested to align their head with their trunk, 30° to the left, 30° to the right or with the gravito-inertial vector, before, during (Per Rotation), after off-center rotation and on a tilted chair without rotation (Tilted). The gravito-inertial vector angle during rotation and the chair tilt angle were identical (17°). The subjects were either in total darkness or facing a visual frame that was fixed to the trunk. Both final error and within-subject variability of head positioning increased when the body axis and the gravito-inertial vector were dissociated (Per Rotation and Tilted). However, the behavior was different depending on whether the subjects were in the Tilted or Per Rotation conditions. The presentation of the visual frame reduced the within-subject variability and modified the perception of the gravito-inertial vector's orientation on the tilted chair. As head positioning with respect to the body and sensing of the gravito-inertial vector are modified when body axis and gravito-inertial vector orientation are dissociated, the observed decrease in performance while executing motor tasks in a gravito-inertial field may be at least in part attributed to the inaccurate sensing of head position.

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