Current strategies for quantification of estrogens in clinical research

Estrogens and their bioactive metabolites play key roles in regulating diverse processes in health and disease. In particular, estrogens and estrogenic metabolites have shown both protective and non-protective effects on disease pathobiology, implicating the importance of this steroid pathway in disease diagnostics and monitoring. All estrogens circulate in a wide range of concentrations, which in some patient cohorts can be extremely low. However, elevated levels of estradiol are reported in disease. For example, in pulmonary arterial hypertension (PAH) elevated levels have been reported in men and postmenopausal women. Conventional immunoassay techniques have come under scrutiny, with their selectivity, accuracy and precision coming into question. Analytical methodologies such as gas and liquid chromatography coupled to single and tandem mass spectrometric approaches (GC–MS, GC–MS/MS, LC–MS and LC–MS/MS) have been developed to quantify endogenous estrogens and in some cases their bioactive metabolites in biological fluids such as urine, serum, plasma and saliva. Liquid-liquid or solid-phase extraction approaches are favoured with derivatization remaining a necessity for detection in lower volumes of sample. The limits of quantitation of individual assays vary but are commonly in the range of 0.5–5 pg/mL for estrone and estradiol, with limits for their bioactive metabolites being higher. This review provides an overview of current approaches for measurement of unconjugated estrogens in biological matrices by MS, highlighting the advances in this field and the challenges remaining for routine use in the clinical and research environment

Trace analysis of environmental matrices by large-volume injection and liquid chromatography-mass spectrometry

The time-honored convention of concentrating aqueous samples by solid-phase extraction (SPE) is being challenged by the increasingly widespread use of large-volume injection (LVI) liquid chromatography–mass spectrometry (LC–MS) for the determination of traces of polar organic contaminants in environmental samples. Although different LVI approaches have been proposed over the last 40 years, the simplest and most popular way of performing LVI is known as single-column LVI (SC-LVI), in which a large-volume of an aqueous sample is directly injected into an analytical column. For the purposes of this critical review, LVI is defined as an injected sample volume that is ≥10% of the void volume of the analytical column. Compared with other techniques, SC-LVI is easier to set up, because it requires only small hardware modifications to existing autosamplers and, thus, it will be the main focus of this review. Although not new, SC-LVI is gaining acceptance and the approach is emerging as a technique that will render SPE nearly obsolete for many environmental applications.In this review, we discuss: the history and development of various forms of LVI; the critical factors that must be considered when creating and optimizing SC-LVI methods; and typical applications that demonstrate the range of environmental matrices to which LVI is applicable, for example drinking water, groundwater, and surface water including seawater and wastewater. Furthermore, we indicate direction and areas that must be addressed to fully delineate the limits of SC-LVI

Using the Bat: A Six Dimensional Mouse for Object Placement

Existing strategies for 6-D placement (i.e positioning and orienting) are briefly reviewed. An approach is presented that uses a 6-D variant on the conventional mouse, called the \u27bat\u27, because it is like a mouse that flies. This device encodes relative position, like the mouse, but delivers data in all six dimensions needed for object placement. The goal is to evaluate the bat to determine how well it is suited to placement operations, which are studied in the context of a hierarchically constructed scene. Two distinct parts of the placement operation, visualization and manipulation, are examined and the hardware and software environment designed as a test for the study are described. Manipulation with the bat, which is discussed in some detail, is judged to be successful

Analytical bias between species caused by matrix effects in quantitative analysis of a small-molecule pharmaceutical candidate in plasma

Background: Suppression or enhancement of MS ionization, particularly evident when electrospray is used as the source of ions, has been widely discussed. Methods: An assay for a small-molecule pharmaceutical in dog plasma between 1–300 ng/ml was validated with a mean bias across the calibration range of 5.0%. When the calibration sample matrix was substituted for human plasma, the mean bias across the range increased to 29.1%. A study of bias originating as a result of matrix effects, arising from endogenous glycerophosphocholine species, in plasma sources is discussed. Conclusion: A simple strategy to assess the potential of any unmitigated matrix effect to bias quantitative analysis by nonequivalent ionization induction or suppression is evaluate

Understanding the Associations among Social Vulnerabilities, Indigenous Peoples, and COVID-19 Cases within Canadian Health Regions

Indigenous Peoples are at an increased risk for infectious disease, including COVID-19, due to the historically embedded deleterious social determinants of health. Furthermore, structural limitations in Canadian federal government data contribute to the lack of comparative rates of COVID-19 between Indigenous and non-Indigenous people. To make visible Indigenous Peoples’ experiences in the public health discourse in the midst of COVID-19, this paper aims to answer the following interrelated research questions: (1) What are the associations of key social determinants of health and COVID-19 cases among Canadian health regions? and (2) How do these relationships relate to Indigenous communities? As both proximal and distal social determinants of health conjointly contribute to COVID-19 impacts on Indigenous health, this study used a unique dataset assembled from multiple sources to examine the associations among key social determinants of health characteristics and health with a focus on Indigenous Peoples. We highlight key social vulnerabilities that stem from systemic racism and that place Indigenous populations at increased risk for COVID-19. Many Indigenous health issues are rooted in the historical impacts of colonization, and partially invisible due to systemic federal underfunding in Indigenous communities. The Canadian government must invest in collecting accurate, reliable, and disaggregated data on COVID-19 case counts for Indigenous Peoples, as well as in improving Indigenous community infrastructure and services