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AAPS PharmSciTech Mar 2011Over the lifecycle of an orally inhaled product (OIP), multi-stage cascade impactor (CI) measurements are used for different purposes and to address different questions....
Over the lifecycle of an orally inhaled product (OIP), multi-stage cascade impactor (CI) measurements are used for different purposes and to address different questions. Full-resolution CIs can provide important information during product development and are widely used but are time- and resource-intensive, highly variable, and suboptimal for OIP quality control (QC) testing. By contrast, Efficient Data Analysis (EDA) combined with Abbreviated Impactor Measurement (AIM) systems pertinent either for QC and-possibly-for adult Human Respiratory Tract (pHRT) has been introduced for OIP performance assessment during and post-development. This article summarizes available evidence and discusses a strategy for using either abbreviated or full-resolution CI systems depending on the purpose of the measurement, such that adequate, accurate, and efficient testing of aerodynamic particle size distribution (APSD) of OIPs can be achieved throughout the lifecycle of a product. Under these proposals, a comprehensive testing program should initially be conducted by full-resolution CI in OIP development to ascertain the product's APSD. Subsequently, correlations should be established from the selected AIM CIs to the corresponding full-resolution system, ideally developing specifications common to both techniques. In the commercial phase, it should be possible to release product using AIM/EDA, keeping the full-resolution CI for investigations, change control, and trouble-shooting, thus optimizing resources for APSD characterization throughout the product lifecycle. If an in vitro-in vivo relationship is established and clinically relevant sizes are known, an AIM-pHRT could serve as a quick indicator that clinically relevant fractions have not changed and also, in the management of post-approval changes.
Topics: Administration, Inhalation; Adult; Equipment Design; Humans; Materials Testing; Nebulizers and Vaporizers; Particle Size; Pharmaceutical Preparations; Quality Control; Respiratory System; Respiratory System Agents; Technology, Pharmaceutical; Weights and Measures
PubMed: 21286882
DOI: 10.1208/s12249-011-9590-5 -
Journal of the Air & Waste Management... Aug 2023The authors present protocols for making fast, accurate, 3D velocity measurements in the stacks of coal-fired power plants. The measurements are traceable to...
The authors present protocols for making fast, accurate, 3D velocity measurements in the stacks of coal-fired power plants. The measurements are traceable to internationally-recognized standards; therefore, they provide a rigorous basis for measuring and/or regulating the emissions from stacks. The authors used novel, five-hole, hemispherical, differential-pressure probes optimized for non-nulling (no-probe rotation) measurements. The probes resist plugging from ash and water droplets. Integrating the differential pressures for only 5 seconds determined the axial velocity with an expanded relative uncertainty () ≤ 2% of the axial velocity at the probe's location, the flow's pitch (α) and yaw (β) angles with expanded uncertainties = = 1 °, and the static pressure with () = 0.1% of the static pressure. This accuracy was achieved 1) by calibrating each probe in a wind tunnel at 130, strategically-chosen values of (, ) spanning the conditions found in the majority of stacks (|| ≤ 20 °; || ≤ 40 °; 4.5 m/s ≤ ≤27 m/s), and 2) by using a long-forgotten definition of the pseudo-dynamic pressure that scales with the dynamic pressure. The resulting calibration functions span the probe-diameter Reynolds number range from 7,600 to 45,000.: The continuous emissions monitoring systems (CEMS) that measure the flue gas flow rate in coal-fired power plant smokestacks are calibrated (at least) annually by a velocity profiling method. The stack axial velocity profile is measured by traversing S-type pitot probes (or one of the other EPA-sanctioned pitot probes) across two orthogonal, diametric chords in the stack cross-section. The average area-weighted axial velocity calculated from the pitot traverse quantifies the accuracy of the CEMS flow monitor. Therefore, the flow measurement accuracy of coal-fired power plants greenhouse gas (GHG) emissions depends on the accuracy of pitot probe velocity measurements. Coal-fired power plants overwhelmingly calibrate CEMS flow monitors using S-type pitot probes. Almost always, stack testers measure the velocity without rotating or nulling the probe (i.e., the non-nulling method). These 1D non-nulling velocity measurements take significantly less time than the corresponding 2D nulling measurements (or 3D nulling measurements for other probe types). However, the accuracy of the 1D non-nulling velocity measurements made using S-type probes depends on the pitch and yaw angles of the flow. Measured axial velocities are accurate at pitch and yaw angles near zero, but the accuracy degrades at larger pitch and yaw angles.The authors developed a 5-hole hemispherical pitot probe that accurately measures the velocity vector in coal-fired smokestacks without needing to rotate or null the probe. This non-nulling, 3D probe is designed with large diameter pressure ports to prevent water droplets (or particulates) from obstructing its pressure ports when applied in stack flow measurement applications. This manuscript presents a wind tunnel calibration procedure to determine the non-nulling calibration curves for 1) dynamic pressure; 2) pitch angle; 3) yaw angle; and 4) static pressure. These calibration curves are used to determine axial velocities from 6 m/s to 27 m/s, yaw angles between ±40°, and pitch angles between ±20°. The uncertainties at the 95% confidence limit for axial velocity, yaw angle, and pitch angle are 2% (or less), 1°, and 1°, respectively. Therefore, in contrast to existing EPA-sanctioned probes, the non-nulling hemispherical probe provides fast, low uncertainty velocity measurements independent of the pitch and yaw angles of the stack flow.
Topics: Coal; Calibration; Power Plants; Environmental Monitoring
PubMed: 37506216
DOI: 10.1080/10962247.2023.2218827 -
PLoS Biology Jun 2019Both basic and translational research are continuously evolving, but the principles that underpin research integrity remain constant. These include rational,...
Both basic and translational research are continuously evolving, but the principles that underpin research integrity remain constant. These include rational, hypothesis-driven, and adequately planned and controlled science, which is carried out openly, honestly, and ethically. An important component of this should be minimising experimental irreproducibility. Biological systems, in particular, are inherently variable due to the nature of cells and tissues, as well as the complex molecules within them. As a result, it is important to understand and identify sources of variability and to strive to minimise their influence. In many instances, the application of metrology (the science of measurement) can play an important role in ensuring good quality research, even within biological systems that aren't always amenable to many of the metrological concepts applied in other fields. Here, we introduce the basic concepts of metrology in relation to biological systems and promote the application of these principles to help avoid potentially costly mistakes in both basic and translational research. We also call on funders to encourage the uptake of metrological principles, as well as provide funding and support for later engagement with regulatory bodies.
Topics: Animals; Bias; Biology; Humans; Reference Standards; Reproducibility of Results; Research Design; Translational Research, Biomedical; Weights and Measures
PubMed: 31220076
DOI: 10.1371/journal.pbio.3000338 -
Journal of Vascular Surgery. Venous and... Sep 2020
Topics: Australasia; COVID-19; Consensus; Humans; India; Latin America; Lymphatic Diseases; Pandemics; Patients; Radiology, Interventional; SARS-CoV-2; Triage; United States; Veins; Weights and Measures
PubMed: 32426221
DOI: 10.1016/j.jvsv.2020.05.003 -
European Journal of Applied Physiology Jan 2004Participation in at least 30 min of moderate intensity activity on most days is assumed to confer health benefits. This study accordingly determined whether the more...
Participation in at least 30 min of moderate intensity activity on most days is assumed to confer health benefits. This study accordingly determined whether the more vigorous household and garden tasks (sweeping, window cleaning, vacuuming and lawn mowing) are performed by middle-aged men at a moderate intensity of 3-6 metabolic equivalents (METs) in the laboratory and at home. Measured energy expenditure during self-perceived moderate-paced walking was used as a marker of exercise intensity. Energy expenditure was also predicted via indirect methods. Thirty-six males [ X (SD): 40.0 (3.3) years; 179.5 (6.9) cm; 83.4 (14.0) kg] were measured for resting metabolic rate (RMR) and oxygen consumption ( VO(2)) during the five activities using the Douglas bag method. Heart rate, respiratory frequency, CSA (Computer Science Applications) movement counts, Borg scale ratings of perceived exertion and Quetelet's index were also recorded as potential predictors of exercise intensity. Except for vacuuming in the laboratory, which was not significantly different from 3.0 METs ( P=0.98), the MET means in the laboratory and home were all significantly greater than 3.0 ( P=0.006). The sweeping and vacuuming MET means were significantly higher ( P<0.001) at home than in the laboratory, whereas the converse applied for window cleaning and lawn mowing. Measured RMR was significantly lower ( P<0.001) than the 1-MET constant. Estimating METs by fitting random intercept regression models to the data resulted in standard deviations for the "leave-one-out" prediction errors (predicted-measured) of 0.4 and 0.5 METs for the laboratory and home equations, respectively. While the means indicate that all the activities were performed at a moderate intensity, there was great inter-individual variability in energy expenditure. The laboratory and home-based equations predicted with correct classification rates of 89% and 88%, respectively, whether energy expenditure was <3.0 or >/=3.0 METs.
Topics: Activities of Daily Living; Adult; Basal Metabolism; Body Mass Index; Energy Metabolism; Exercise; Forecasting; Heart Rate; Humans; Male; Oxygen Consumption; Task Performance and Analysis; Weights and Measures
PubMed: 12955520
DOI: 10.1007/s00421-003-0932-1 -
Journal of Biomedicine & Biotechnology 2007
Topics: Biosensing Techniques; Crystallization; Microchemistry; Nanoparticles; Weights and Measures
PubMed: 18528530
DOI: 10.1155/2007/82752 -
Respiratory Care Sep 2013
Topics: Female; Heating; Humans; Humidity; Male; Respiratory Therapy; Tracheostomy; Weights and Measures
PubMed: 23981591
DOI: 10.4187/respcare.02761 -
Critical Care (London, England) Mar 2021Pulmonary artery thermodilution is the clinical reference method for cardiac output monitoring. Because both continuous and intermittent pulmonary artery thermodilution... (Meta-Analysis)
Meta-Analysis
Agreement between continuous and intermittent pulmonary artery thermodilution for cardiac output measurement in perioperative and intensive care medicine: a systematic review and meta-analysis.
BACKGROUND
Pulmonary artery thermodilution is the clinical reference method for cardiac output monitoring. Because both continuous and intermittent pulmonary artery thermodilution are used in clinical practice it is important to know whether cardiac output measurements by the two methods are clinically interchangeable.
METHODS
We performed a systematic review and meta-analysis of clinical studies comparing cardiac output measurements assessed using continuous and intermittent pulmonary artery thermodilution in adult surgical and critically ill patients. 54 studies with 1522 patients were included in the analysis.
RESULTS
The heterogeneity across the studies was high. The overall random effects model-derived pooled estimate of the mean of the differences was 0.08 (95%-confidence interval 0.01 to 0.16) L/min with pooled 95%-limits of agreement of - 1.68 to 1.85 L/min and a pooled percentage error of 29.7 (95%-confidence interval 20.5 to 38.9)%.
CONCLUSION
The heterogeneity across clinical studies comparing continuous and intermittent pulmonary artery thermodilution in adult surgical and critically ill patients is high. The overall trueness/accuracy of continuous pulmonary artery thermodilution in comparison with intermittent pulmonary artery thermodilution is good (indicated by a pooled mean of the differences < 0.1 L/min). Pooled 95%-limits of agreement of - 1.68 to 1.85 L/min and a pooled percentage error of 29.7% suggest that continuous pulmonary artery thermodilution barely passes interchangeability criteria with intermittent pulmonary artery thermodilution. PROSPERO registration number CRD42020159730.
Topics: Cardiac Output; Humans; Monitoring, Physiologic; Pulmonary Artery; Reproducibility of Results; Thermodilution; Weights and Measures
PubMed: 33781307
DOI: 10.1186/s13054-021-03523-7 -
Critical Care (London, England) 2008Gastrointestinal dysfunction is an intuitively important, yet descriptively elusive component of the multiple organ dysfunction syndrome. Reintam and colleagues have...
Gastrointestinal dysfunction is an intuitively important, yet descriptively elusive component of the multiple organ dysfunction syndrome. Reintam and colleagues have attempted to quantify this dimension using a combination of intolerance of enteral feeding, and the development of intra-abdominal hypertension. While they show that both parameters are associated with an increased risk of death (and therefore that, in combination, the risk of death is even greater), they fall short in developing a novel descriptor of gastrointestinal dysfunction. Nonetheless, and even with its shortcomings, their effort is a welcome contribution to the surprisingly complex process of describing the morbidity of critical illness.
Topics: Critical Illness; Gastrointestinal Diseases; Humans; Weights and Measures
PubMed: 18828891
DOI: 10.1186/cc7001 -
The Journal of Clinical Endocrinology... Sep 2020The use of anogenital distance (AGD) in clinical and epidemiological settings is increasing; however, sex-specific reference data on AGD and data on longitudinal changes...
CONTEXT
The use of anogenital distance (AGD) in clinical and epidemiological settings is increasing; however, sex-specific reference data on AGD and data on longitudinal changes in AGD in children is scarce.
OBJECTIVE
To create age-, sex-, and method-related reference ranges of AGD in healthy boys and girls aged 0-24 months, to assess the age-related changes in AGD and to evaluate the 2 predominantly used methods of AGD measurement.
DESIGN
The International AGD consortium comprising 4 centers compiled data from 1 cross-sectional and 3 longitudinal cohort studies (clinicaltrials.gov [NCT02497209]).
SETTING
All data were collected from population-based studies, recruiting from 4 maternity or obstetric centers (United States, Cambridge [United Kingdom], Odense, and Copenhagen [Denmark]).
SUBJECTS
This study included a total of 3705 healthy, mainly Caucasian children aged 0-24 months on whom 7295 measurements were recorded.
MAIN OUTCOME MEASURES
AGDAS (ano-scrotal), AGDAF (ano-fourchette), AGDAP (ano-penile), AGDAC (ano-clitoral), AGD body size indices (weight, body mass index [BMI], body surface area, and length), and intra- and interobserver biases.
RESULTS
We created age-specific reference ranges by centers. We found that AGD increased from birth to 6 months of age and thereafter reached a plateau. Changes in AGD/BMI during the first year of life were minor (0-6% and 0-11% in boys and girls, respectively).
CONCLUSIONS
Reference ranges for AGD can be used in future epidemiological research and may be utilized clinically to evaluate prenatal androgen action in differences-in-sex-development patients. The increase in AGD during the first year of life was age-related, while AGD/BMI was fairly stable. The TIDES and Cambridge methods were equally reproducible.
Topics: Age Factors; Anal Canal; Body Weights and Measures; Cross-Sectional Studies; Female; Genitalia; Health; Humans; Infant; Infant, Newborn; Longitudinal Studies; Male; Reference Values; Sex Characteristics
PubMed: 32574349
DOI: 10.1210/clinem/dgaa393