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Genes Jan 2024Population-based biobanking is an essential element of medical research that has grown substantially over the last two decades, and many countries are currently pursuing... (Review)
Review
Population-based biobanking is an essential element of medical research that has grown substantially over the last two decades, and many countries are currently pursuing large national biobanking initiatives. The rise of individual biobanks is paralleled by various networking activities in the field at both the national and international level, such as BBMRI-ERIC in the EU. A significant contribution to population-based biobanking comes from large cohort studies and national repositories, including the United Kingdom Biobank (UKBB), the CONSTANCES project in France, the German National Cohort (NAKO), LifeLines in the Netherlands, FinnGen in Finland, and the All of Us project in the U.S. At the same time, hospital-based biobanking has also gained importance in medical research. We describe some of the scientific questions that can be addressed particularly well by the use of population-based biobanks, including the discovery and calibration of biomarkers and the identification of molecular correlates of health parameters and disease states. Despite the tremendous progress made so far, some major challenges to population-based biobanking still remain, including the need to develop strategies for the long-term sustainability of biobanks, the handling of incidental findings, and the linkage of sample-related and sample-derived data to other relevant resources.
Topics: Humans; Biological Specimen Banks; Population Health; Biomedical Research; Calibration; Finland
PubMed: 38254956
DOI: 10.3390/genes15010066 -
Journal of Pharmaceutical Sciences Apr 2024To ensure the quality, safety and efficacy of medicinal products, it is necessary to develop and execute appropriate manufacturing process and product control... (Review)
Review
To ensure the quality, safety and efficacy of medicinal products, it is necessary to develop and execute appropriate manufacturing process and product control strategies. Traditionally, product control strategies have focused on testing known quality attributes with limits derived from levels administered in preclinical and clinical studies with an associated statistical analysis to account for variability. However, not all quality attributes have impact to the patient and those with the potential to impact safety and efficacy may not be significant when dosed at patient-centric levels. Therefore, achieving patient-centricity is understanding patient relevance, which is defined as the level of impact that a quality attribute could have on safety and efficacy within the potential exposure range. A patient-centric quality standard (PCQS) is therefore a set of patient relevant attributes and their associated acceptance ranges to which a drug product should conform within the expected patient exposure range. This manuscript describes historical perspectives details the way to create and leverage a PCQS in a variety of pharmaceutical product modalities.
Topics: Humans; Reference Standards; Patient-Centered Care
PubMed: 38280722
DOI: 10.1016/j.xphs.2024.01.006 -
Foot (Edinburgh, Scotland) Jun 2024Plantar pressure measurement systems are routinely used in sports and health applications to assess locomotion. The purpose of this review is to describe and critically... (Review)
Review Comparative Study
Plantar pressure measurement systems are routinely used in sports and health applications to assess locomotion. The purpose of this review is to describe and critically discuss: (a) applications of the pressure measurement systems in sport and healthcare, (b) testing protocols and considerations for clinical gait analysis, (c) clinical recommendations for interpreting plantar pressure data, (d) calibration procedures and their accuracy, and (e) the future of pressure sensor data analysis. Rigid pressure platforms are typically used to measure plantar pressures for the assessment of foot function during standing and walking, particularly when barefoot, and are the most accurate for measuring plantar pressures. For reliable data, two step protocol prior to contacting the pressure plate is recommended. In-shoe systems are most suitable for measuring plantar pressures in the field during daily living or dynamic sporting movements as they are often wireless and can measure multiple steps. They are the most suitable equipment to assess the effects of footwear and orthotics on plantar pressures. However, they typically have lower spatial resolution and sampling frequency than platform systems. Users of pressure measurement systems need to consider the suitability of the calibration procedures for their chosen application when selecting and using a pressure measurement system. For some applications, a bespoke calibration procedure is required to improve validity and reliability of the pressure measurement system. The testing machines that are commonly used for dynamic calibration of pressure measurement systems frequently have loading rates of less than even those found in walking, so the development of testing protocols that truly measure the loading rates found in many sporting movements are required. There is clear potential for AI techniques to assist in the analysis and interpretation of plantar pressure data to enable the more complete use of pressure system data in clinical diagnoses and monitoring.
Topics: Humans; Pressure; Foot; Gait Analysis; Shoes; Calibration; Sports
PubMed: 38579518
DOI: 10.1016/j.foot.2024.102094 -
Environmental Science & Technology Sep 2023The effects and risks of microplastics correlate with three-dimensional (3D) properties, such as the volume and surface area of the biologically accessible fraction of...
The effects and risks of microplastics correlate with three-dimensional (3D) properties, such as the volume and surface area of the biologically accessible fraction of the diverse particle mixtures as they occur in nature. However, these 3D parameters are difficult to estimate because measurement methods for spectroscopic and visible light image analysis yield data in only two dimensions (2D). The best-existing 2D to 3D conversion models require calibration for each new set of particles, which is labor-intensive. Here we introduce a new model that does not require calibration and compare its performance with existing models, including calibration-based ones. For the evaluation, we developed a new method in which the volumes of environmentally relevant microplastic mixtures are estimated in one go instead of on a cumbersome particle-by-particle basis. With this, the new Barchiesi model can be seen as the most universal. The new model can be implemented in software used for the analysis of infrared spectroscopy and visual light image analysis data and is expected to increase the accuracy of risk assessments based on particle volumes and surface areas as toxicologically relevant metrics.
Topics: Microplastics; Plastics; Benchmarking; Calibration; Light
PubMed: 37683039
DOI: 10.1021/acs.est.3c03620 -
American Journal of Epidemiology Aug 2023Regression calibration is a popular approach for correcting biases in estimated regression parameters when exposure variables are measured with error. This approach...
Regression calibration is a popular approach for correcting biases in estimated regression parameters when exposure variables are measured with error. This approach involves building a calibration equation to estimate the value of the unknown true exposure given the error-prone measurement and other covariates. The estimated, or calibrated, exposure is then substituted for the unknown true exposure in the health outcome regression model. When used properly, regression calibration can greatly reduce the bias induced by exposure measurement error. Here, we first provide an overview of the statistical framework for regression calibration, specifically discussing how a special type of error, called Berkson error, arises in the estimated exposure. We then present practical issues to consider when applying regression calibration, including: 1) how to develop the calibration equation and which covariates to include; 2) valid ways to calculate standard errors of estimated regression coefficients; and 3) problems arising if one of the covariates in the calibration model is a mediator of the relationship between the exposure and outcome. Throughout, we provide illustrative examples using data from the Hispanic Community Health Study/Study of Latinos (United States, 2008-2011) and simulations. We conclude with recommendations for how to perform regression calibration.
Topics: Humans; Calibration; Regression Analysis; Bias; Public Health
PubMed: 37092245
DOI: 10.1093/aje/kwad098 -
Molecules (Basel, Switzerland) Mar 2024The process of blood coagulation, wherein circulating blood transforms into a clot in response to an internal or external injury, is a critical physiological mechanism.... (Review)
Review
The process of blood coagulation, wherein circulating blood transforms into a clot in response to an internal or external injury, is a critical physiological mechanism. Monitoring this coagulation process is vital to ensure that blood clotting neither occurs too rapidly nor too slowly. Anticoagulants, a category of medications designed to prevent and treat blood clots, require meticulous monitoring to optimise dosage, enhance clinical outcomes, and minimise adverse effects. This review article delves into the various stages of blood coagulation, explores commonly used anticoagulants and their targets within the coagulation enzyme system, and emphasises the electrochemical methods employed in anticoagulant testing. Electrochemical sensors for anticoagulant monitoring are categorised into two types. The first type focuses on assays measuring thrombin activity via electrochemical techniques. The second type involves modified electrode surfaces that either directly measure the redox behaviours of anticoagulants or monitor the responses of standard redox probes in the presence of these drugs. This review comprehensively lists different electrode compositions and their detection and quantification limits. Additionally, it discusses the potential of employing a universal calibration plot to replace individual drug-specific calibrations. The presented insights are anticipated to significantly contribute to the sensor community's efforts in this field.
Topics: Blood Coagulation; Anticoagulants; Biological Assay; Calibration; Thrombin
PubMed: 38611733
DOI: 10.3390/molecules29071453 -
Nutrients Jul 2023Anorexia nervosa is associated with a significant risk of morbidity and mortality. In clinical practice, health risk is assessed and estimated using routinely collected...
UNLABELLED
Anorexia nervosa is associated with a significant risk of morbidity and mortality. In clinical practice, health risk is assessed and estimated using routinely collected laboratory data. This study will develop a risk score using clinically relevant laboratory parameters. The related question is how to estimate the health risk associated with underweight using body weight, height and age.
METHODS
We used routinely collected laboratory parameters from a total of 4087 patients. The risk score was calculated on the basis of electrolytes, blood count, transaminases and LDH. The nine parameters used were summed as zlog-transformed values. Where appropriate, the scales were inverted so that high values represented higher risk. For statistical prediction of the risk score, weight/height and age reference values from the WHO, the CDC (Center of Disease Control) and representative studies of German children and adults (KIGGS and NNS) were used.
RESULTS
The score calculated from nine laboratory parameters already shows a convincing relationship with BMI. Among the weight measures used for height and age, the z-score from the CDC reference population emerged as the best estimate, explaining 34% of the variance in health risk measured by the laboratory score. The percentile rank for each age-specific median weight from the KIGGS/NNS still explained more than 31% of the variance. In contrast, percentiles explained less variance than BMI without age correction.
CONCLUSIONS
The score we used from routine laboratory parameters appears to be an appropriate measure for assessing the health risk associated with underweight, as measured by the quality of the association with BMI. For estimating health risk based on weight, height and age alone, z-scores and percentages of age-specific median weight, as opposed to percentiles, are appropriate parameters. However, the study also shows that existing age-specific BMI reference values do not represent risk optimally. Improved statistical estimation methods would be desirable.
Topics: Child; Adult; Humans; Body Mass Index; Thinness; Risk Factors; Reference Values; Body Height; Body Weight
PubMed: 37513680
DOI: 10.3390/nu15143262 -
JACC. Cardiovascular Imaging Dec 2023Myocardial deformation by echocardiographic strain imaging is a key measurement in cardiology, providing valuable diagnostic and prognostic information. Reference ranges...
BACKGROUND
Myocardial deformation by echocardiographic strain imaging is a key measurement in cardiology, providing valuable diagnostic and prognostic information. Reference ranges for strain should be established from large healthy populations with minimal methodologic biases and variability.
OBJECTIVES
The aim of this study was to establish echocardiographic reference ranges, including lower normal limits of global strains for all 4 cardiac chambers, by guideline-directed dedicated views from a large healthy population and to evaluate the influence of subject-specific characteristics on strain.
METHODS
In total, 1,329 healthy participants from HUNT4Echo, the echocardiographic substudy of the 4th wave of the Trøndelag Health Study, were included. Echocardiographic recordings specific for each chamber were optimized according to current recommendations. Two experienced sonographers recorded all echocardiograms using GE HealthCare Vivid E95 scanners. Analyses were performed by experts using GE HealthCare EchoPAC.
RESULTS
The reference ranges for left ventricular (LV) global longitudinal strain and right ventricular free-wall strain were -24% to -16% and -35% to -17%, respectively. Correspondingly, left atrial (LA) and right atrial (RA) reservoir strains were 17% to 49% and 17% to 59%. All strains showed lower absolute values with higher age, except for LA and RA contractile strains, which were higher. The feasibility for strain was overall good (LV 96%, right ventricular 83%, LA 94%, and RA 87%). All chamber-specific strains were associated with age, and LV strain was associated with sex.
CONCLUSIONS
Reference ranges of strain for all cardiac chambers were established based on guideline-directed chamber-specific recordings. Age and sex were the most important factors influencing reference ranges and should be considered when using strain echocardiography.
Topics: Humans; Reference Values; Global Longitudinal Strain; Predictive Value of Tests; Echocardiography; Heart Atria; Ventricular Function, Left
PubMed: 37921718
DOI: 10.1016/j.jcmg.2023.08.011 -
Physiological Reports Sep 2023The cardiovascular system is primarily controlled by the autonomic nervous system, and any changes in sympathetic or parasympathetic activity also have an impact on... (Review)
Review
The cardiovascular system is primarily controlled by the autonomic nervous system, and any changes in sympathetic or parasympathetic activity also have an impact on myocardial activity. Heart rate variability (HRV) is a readily available metric used to assess heart rate control by the autonomic nervous system. HRV can provide information about neural (parasympathetic, sympathetic, reflex) and humoral (hormones, thermoregulation) control of myocardial activity. Because there are no relevant reference values for HRV parameters in rats in the scientific literature, all experimental results are only interpreted on the basis of changes from currently measured control or baseline HRV values, which are, however, significantly different in individual studies. Considering the significant variability of published HRV data, the present study focused primarily on comparing control or baseline HRV values under different conditions in in vivo experiments involving rats. The aim of the study was therefore to assess whether there are differences in the starting values before the experiment itself.
Topics: Male; Animals; Rats; Heart Rate; Autonomic Nervous System; Body Temperature Regulation; Myocardium; Reference Values
PubMed: 37735345
DOI: 10.14814/phy2.15827 -
Scientific Reports Sep 2023There is direct evidence of risks at moderate and high levels of radiation dose for highly radiogenic cancers such as leukaemia and thyroid cancer. For many cancer...
There is direct evidence of risks at moderate and high levels of radiation dose for highly radiogenic cancers such as leukaemia and thyroid cancer. For many cancer sites, however, it is necessary to assess risks via extrapolation from groups exposed at moderate and high levels of dose, about which there are substantial uncertainties. Crucial to the resolution of this area of uncertainty is the modelling of the dose-response relationship and the importance of both systematic and random dosimetric errors for analyses in the various exposed groups. It is well recognised that measurement error can alter substantially the shape of this relationship and hence the derived population risk estimates. Particular attention has been devoted to the issue of shared errors, common in many datasets, and particularly important in occupational settings. We propose a modification of the regression calibration method which is particularly suited to studies in which there is a substantial amount of shared error, and in which there may also be curvature in the true dose response. This method can be used in settings where there is a mixture of Berkson and classical error. In fits to synthetic datasets in which there is substantial upward curvature in the true dose response, and varying (and sometimes substantial) amounts of classical and Berkson error, we show that the coverage probabilities of all methods for the linear coefficient [Formula: see text] are near the desired level, irrespective of the magnitudes of assumed Berkson and classical error, whether shared or unshared. However, the coverage probabilities for the quadratic coefficient [Formula: see text] are generally too low for the unadjusted and regression calibration methods, particularly for larger magnitudes of the Berkson error, whether this is shared or unshared. In contrast Monte Carlo maximum likelihood yields coverage probabilities for [Formula: see text] that are uniformly too high. The extended regression calibration method yields coverage probabilities that are too low when shared and unshared Berkson errors are both large, although otherwise it performs well, and coverage is generally better than these other three methods. A notable feature is that for all methods apart from extended regression calibration the estimates of the quadratic coefficient [Formula: see text] are substantially upwardly biased.
Topics: Humans; Calibration; Generalization, Psychological; Thyroid Neoplasms; Leukemia; Monte Carlo Method
PubMed: 37704705
DOI: 10.1038/s41598-023-42283-y