Optimal Measurement Time Research Articles

Randomised Assessment of Treatment using Panel Assay of Cardiac markers – Contemporary Biomarker Evaluation (RATPAC CBE)

To test the diagnostic accuracy for detecting an acute myocardial infarction (AMI) using highly sensitive troponin assays and a range of new cardiac biomarkers of plaque destabilisation, myocardial ischaemia and necrosis; to test the prognostic accuracy for detecting adverse cardiac events using highly sensitive troponin assays and this range of new cardiac biomarkers; and to estimate the cost-effectiveness of using highly sensitive troponin assays or this range of new cardiac biomarkers instead of an admission and 10- to 12-hour troponin measurement. Substudy of the point-of-care arm of the RATPAC (Randomised Assessment of Treatment using Panel Assay of Cardiac markers) trial. The emergency departments of six hospitals. Prospective admissions with chest pain and a non-diagnostic electrocardiogram randomised to point-of-care assessment or conventional management. Blood samples taken on admission and 90 minutes from admission for measurement of cardiac markers [cardiac troponin I (cTnI), myoglobin and creatine kinase MB isoenzyme (CK-MB)] by point-of-care testing. An additional blood sample was taken at admission and 90 minutes from admission for analysis of high-sensitivity cTnI (two methods) and cardiac troponin T (cTnT), myoglobin, heart-type fatty acid-binding protein (H-FABP), copeptin and B-type natriuretic peptide (NTproBNP). 1. Diagnostic accuracy compared with the universal definition of myocardial infarction utilising laboratory measurements of cardiac troponin performed at the participating sites together with measurements performed in a core laboratory. 2. Ability of biomarker measurements to predict major adverse cardiac events (death, non-fatal AMI, emergency revascularisation or hospitalisation for myocardial ischaemia) at 3 months' follow-up. 3. Comparison of incremental cost per quality-adjusted life-year (QALY) of different biomarker measurement strategies for the diagnosis of myocardial infarction. Samples were available from 850 out of 1132 patients enrolled in the study. Measurement of admission myoglobin [area under the curve (AUC) 0.76] and CK-MB (AUC 0.84) was diagnostically inferior and did not add to the diagnostic efficiency of cTnI (AUC 0.90-0.94) or cTnT (AUC 0.92) measurement on admission. Simultaneous measurement of H-FABP and cTnT or cTnI did improve admission diagnostic sensitivity to 0.78-0.92, but only to the same level as that achieved with troponin measured on admission and at 90 minutes from admission (0.78-0.95). Copeptin (AUC 0.62) and NTproBNP (AUC 0.85) measured on admission were not useful as diagnostic markers. As a prognostic marker, troponin measured on admission using a high-sensitivity assay (AUC 0.73-0.83) was equivalent to NTproBNP measurement (AUC 0.77) on admission, but superior to copeptin measurement (AUC 0.58). From modelling, 10-hour troponin measurement is likely to be cost-effective compared with rapid rule-out strategies only if a £30,000 per QALY threshold is used and patients can be discharged as soon as a negative result is available. The measurement of high-sensitivity cardiac troponin is the best single marker in patients presenting with chest pain. Additional measurements of myoglobin or CK-MB are not clinically effective or cost-effective. The optimal timing for measurement of cardiac troponin remains to be defined. Copeptin measurement is not recommended. H-FABP requires further investigation before it can be recommended for simultaneous measurement with high-sensitivity troponin in patients with acute chest pain. ISRCTN37823923. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 15. See the HTA programme website for further project information.

Systolic Blood Pressure and Mortality in Patients on Hemodialysis

Hypertension is extremely common in patients with end-stage renal disease who are receiving hemodialysis, and cardiovascular disease remains the leading cause of death in these patients. However, optimal blood pressure management strategies in this high-risk population are still controversial. This review first discusses the complex association of systolic blood pressure with clinical outcomes in patients on hemodialysis, with a focus on several recent studies. Next, it updates the reader on issues related to optimal timing and methods of blood pressure measurement, appropriate blood pressure targets, and pharmacologic and nonpharmacologic hypertension treatment strategies for patients on hemodialysis.

Guidelines to determine the optimal variables for the MTC measurement by noise analysis

In this paper guidelines will be given in order to determine the required measurement time for a specified precision of the Moderator Temperature Coefficient (MTC) estimate by noise analysis. Until now the discussion of the precision of the MTC estimate was neglected. We will study the relation between the precision, the coherence, the amount of temperature sensors and the measurement time. Based on this relation guidelines to determine the optimal measurement time will be given. Simulations in MATLAB will be used to verify the theoretical analysis. Realistic values for the different influencing variables for a specific measurement setup will be given by use of the analysis of a measurement at a Nuclear Power Plant in Belgium.

Methodological aspects of determining soil particle‐size distribution using the laser diffraction method

AbstractThis paper presents the influence of selected methodological aspects on the results of particle‐size distribution (PSD) as measured by the laser diffraction method (LDM). The investigations were carried out using the Mastersizer 2000 with Hydro MU attachment (Malvern Ltd., UK). It was found that for the investigated soils: (1) optimal speed of pump and stirrer was 2500 rpm, (2) optimal measurement time was ≈ 1 min, (3) there are two, practically equivalent methods for soil‐sample dispersion: chemical (with the use of a solution of sodium hexametaphosphate) or physical (by means of ultrasound application for 4 min at a maximum power of 35W), (4) one must not use the chemical and physical dispersing methods simultaneously, because this can lead to aggregation (not dispersion) of soil particles, (5) the Fraunhofer theory (physical models) can be used to convert scattered‐light data to PSD. In the case of the Mie theory, the best results were obtained for a refractive index (RI) in the range of 1.5–1.6 and an absorption index (AI) of 1.0. It was also found that most of the discussed parameters depend on design of the measuring device and on the type and volume of the investigated suspensions. It is necessary, therefore, to explain how the data was obtained every time and to specify the details in the methodological part of the paper.

Optimizing active and passive calibration of optical tweezers

To obtain quantitative information from optical trapping experiments it is essential toperform a precise force calibration. Therefore, sources of noise should be pinpointed andeliminated. Fourier analysis is routinely used to calibrate optical trapping assaysbecause it is excellent for pinpointing high frequency noise. In addition, Allanvariance analysis is particularly useful for quantifying low frequency noise and forpredicting the optimal measurement time. We show how to use Allan variance incombination with Fourier analysis for optimal calibration and noise reduction in opticaltrapping assays. The methods are applied to passive assays, utilizing the thermalmotion of a trapped particle, and to active assays where the bead is harmonicallydriven. The active method must be applied in assays where, for example, theviscoelastic properties of the medium or the size or shape of the trapped object areunknown. For measurement times shorter than the optimal calibration time thenoise is larger in active than in the passive assays. For times equal to or longerthan the optimal measurement time, though, the noise on passive and activeassays is identical. As an example, we show how to quantify the influence onmeasurement noise of bead size and chamber geometry in active and passive assays.

Antimüllerian hormone as a predictor of controlled ovarian hyperstimulation outcome: comparison of two commercial immunoassay kits

This study was performed to compare antimüllerian hormone (AMH) levels measured by two commercially available AMH measuring kits currently available, and to evaluate the AMH levels as predictor of controlled ovarian hyperstimulation (COH) outcome using the two different kits. The two assays for AMH measurement provide similar results, and serum AMH levels measured by the two kits both could be used as COH outcome predictors with similar reference values.

Anti-Mullerian hormone dynamics during controlled ovarian hyperstimulation and optimal timing of measurement for outcome prediction

Anti-Müllerian hormone (AMH) has been suggested as a marker of ovarian reserve and predictor of ovarian response to controlled ovarian hyperstimulation (COH). Several studies have demonstrated AMH changes during follicular and luteal phases during COH, but not after human chorionic gonadotrophin (hCG) administration. The objectives of this study were to investigate changes in AMH levels during the entire COH cycle and to clarify the regulatory mechanism of AMH secretion. In addition, we analyzed the COH outcome parameters to determine the optimal timing for AMH measurement to predict outcome. The study included 74 women who underwent in vitro fertilization (IVF) cycles with a GnRH agonist or antagonist protocol. Serum AMH and inhibin B levels were measured at baseline, Day 5 of stimulation (d5), day of hCG administration (dhCG), day of oocyte retrieval (dOPU) and 14 days after oocyte retrieval (dPO14). Follicular fluid (FF) from dominant follicles upon oocyte retrieval were also analyzed for AMH and inhibin B concentrations. AMH levels were analyzed for changes during the cycle and for correlations with COH outcome parameters. Serum AMH levels decreased progressively during COH until dhCG, then increased on dOPU and further increased on dPO14. Serum and FF AMH levels and dynamic changes were not different between the GnRH agonist and antagonist cycles. Serum AMH levels on every sample day and the FF AMH levels were significantly correlated with outcomes of COH, such as dose of gonadotrophins used, estradiol level on dhCG and number of retrieved oocytes; the strength of the relationship was highest for baseline AMH. The results of the present study suggest that changes in the hormonal milieu during stimulation and after the LH surge may affect AMH secretion. Serum AMH levels during COH are good markers to predict ovarian response, but the baseline serum level seems to be the most predictive marker.

Biomarkers of Acute Kidney Injury

ESPITE more than half a century of investigation,acute kidney injury (AKI) remains a major healthcareissue in medicine today. Reported to occur in 1–32% of allhospital admissions and 10–90% of intensive care unit ad-missions, the wide variation reflects different criteria used todefineAKI.However,independentofdefinition,adiagnosisof AKI is consistently associated with an increase in bothshort- and long-term morbidity and mortality. Even themildest forms of AKI are independently associated with in-creased early as well as long-term mortality, the risk increas-ing as severity of renal injury increases.

Quantifying Noise in Optical Tweezers by Allan Variance

Much effort is put into minimizing noise in optical tweezers experiments because noise and drift can mask fundamental behaviours of, e.g., single molecule assays. Various initiatives have been taken to reduce or eliminate noise but it has been difficult to quantify their effect. We propose to use Allan variance as a simple and efficient method to quantify noise in optical tweezers setups.We apply the method to determine the optimal measurement time, frequency, and detection scheme, and quantify the effect of acoustic noise in the lab. The method can also be used on-the-fly for determining optimal parameters of running experiments.

Time-Dependent Phenomena in the Potential Response of Ion-Selective Electrodes Treated by the Nernst−Planck−Poisson Model. Part 2: Transmembrane Processes and Detection Limit

The detection limit of ion-selective electrodes (ISEs) is of great interest because of the many possible practical applications of ISEs in trace analysis. Existing theoretical interpretations of the detection limit of ISEs are restricted by severe assumptions such as steady-state and electroneutrality, which hamper theorizing on this problem. For this reason, the Nernst-Planck-Poisson (NPP) equations are used to predict and visualize the detection limit variability under nonequilibrium conditions. For the first time, the NPP model is applied to the so-called inverse problem: finding the optimal measurement time and inner solution concentration for lowering the detection limit.

Aldosterone to Renin Ratio (ARR) in Clinical use, with Reference to the Primary Care Setting: ARR to Whom, When, How, What for?

Compelling evidence indicates that primary aldosteronism (PA) is the most frequent cause of secondary hypertension, with an estimated prevalence ranging from 10 to 15% in the population referred to specialist hypertension units. In clinical practice, the aldosterone to renin ratio (ARR) is the cornerstone of population screening, although difficulties in methodology and thus in defining precise cut-off values still represent an area of uncertainty. In hypertensive subjects, the elevated ARR is a marker of inappropriately high aldosterone secretion for the degree of renin-angiotensin system activation, and often is the only index capable of distinguish normokalemic PA from essential hypertension. On the basis of such a high prevalence, it is unclear whether ARR measurement should be reserved for selected subgroups of patients, or extended to all hypertensive subjects in the population as a whole. In unselected, normotensive populations elevated aldosterone levels and elevated ARR have recently been reported as predisposing factors to the subsequent development of hypertension, raising the question of the optimal timing for ARR measurement, especially in those with a family history of hypertension in primary care. In a large proportion of patients presenting elevated ARR the diagnosis of PA is formally ruled out by confirmatory/ exclusion testing, although the clinical relevance of “inappropriate aldosterone secretion” in these patients remains unclear. May it serve as a predictor of the usefulness of mineralocorticoid receptor antagonist treatment? These and related questions will be examined in this review, particularly given clearly unsatisfactory levels of BP control even in the populations of Western countries.

A sensitivity analysis of the step-temperature technique for measurement of local tissue blood perfusion

The step-temperature technique is a thermal technique that uses a small thermistor probe for measuring blood perfusion of tissue. The blood perfusion is derived from temperature and power measurements using equations that describe heat transfer in the integrated probe/tissue system. A numerical experiment is used to analyse the theoretical error caused by the assumptions used in the technique. The effects of the bead parameters, tissue parameters and measurement parameters are investigated. The study results are in accordance with experimental phenomena described previously. An optimal measurement time window is found to be 4 – 10 s, dependent mainly on the thermal conductivity and blood perfusion of tissue measured. This research will lead to reduce perfusion measurement errors.

Mechanical and electroconductive properties of spatially distributed double stranded DNA arrays on Au (111)

Conductive AFM was used to investigate electroconductivity through 10 nm long double stranded DNA molecules in mixed monolayers of thioalkylated-DNA and mercaptohexanol (MCH) on Au (111) surface. The distribution of DNA molecules on the surface was analyzed by tapping mode AFM. Measurements performed in lift mode confirmed that the DNA molecules protrude from the surface rather than lie horizontally adsorbed on the interface. The optimal conductivity measurement time, which is shorter than the mechanical relaxation time of oligonucleotide duplexes, was determined. It was concluded that oligonucleotide duplexes have a resistance of the order of ~ 2 Ω ⁎m at 1 V.

Serum anti-Müllerian hormone and inhibin B concentrations in early follicular phase as predictors of poor ovarian response and outcomes of controlled ovarian hyperstimulation

Recently, anti-Müllerian hormone (AMH) and inhibin B have been suggested as ovarian reserve markers and predictors of ovarian response to controlled ovarian hyperstimulation (COH) in assisted reproduction cycles. However, optimal timing of measurement and cut-off levels for prediction of poor responses are still unclear. The objectives of this study were to investigate the usefulness of early follicular AMH and inhibin B levels as predictors of poor responses and to determine optimal timing of measurement and cut-off levels.

Canopy Temperature Depression Sampling to Assess Grain Yield and Genotypic Differentiation in Winter Wheat

Canopy temperature depression (CTD = air temperature [Ta] – canopy temperature [Tc]) has been used to estimate crop yield and to rank genotypes for tolerance to heat and drought, but when to measure CTD for breeding selection has seldom been addressed. Our objectives were to evaluate the suitability of CTD for the Texas High Plains environment and to determine optimal measurement times in relation to growth stage, time of day, and weather. Three years of CTD and weather data were used to assess regression models of grain yield in three wheat (Triticum aestivum L.) lines. Under dryland agriculture, long‐term mean CTD at noon and yield were correlated in 2000 and 2001. The relation of short‐term CTD readings to grain yield was highly variable. Poor correlation was associated with days of low solar irradiance, high wind speed, and rain events. Genotype effects on CTD were detected for all hours of day and night. Genotype × hour interaction was insignificant at night, suggesting that nighttime measurements may provide more stable conditions for CTD comparison among genotypes. In general, tree regression assessed grain yield from short‐term CTD measurements better than linear regression and suggested that the best times to measure CTD were 0900, 1300, and 1800 h. Tree regression models provided a heuristic interpretation of crop water status under different scenarios of soil water availability.

Optimum experimental designs for dynamic systems in the presence of correlated errors

The problem of determining an optimal measurement time schedule for identification of unknown parameters in multiresponse systems when correlations between observations occur is considered. The measurement process is performed by collecting data at discrete time instants from several outputs. An observation plan is proposed based on a scalar measure of the Fisher information matrix as the design criterion quantifying the accuracy of parameter estimators. A numerical procedure is proposed to determine approximations of optimum designs in the case of correlated measurement errors. The approach is illustrated with an example of the multi-output system of equations describing a chemical kinetic reaction.

The Optimal Timing of BNP Measurement after Exercise

The Optimal Timing of BNP Measurement after Exercise

Measurement of intra-abdominal pressure in intensive care units in the United Kingdom: a national postal questionnaire study

To explore the attitudes of intensivists in the UK to intra-abdominal pressure (IAP) measurement and abdominal compartment syndrome (ACS) and to determine current practice. A postal questionnaire study addressed to the lead clinician in the intensive care unit was sent to hospitals in the UK with a general surgical service. Completed questionnaires were received from 137 of the 207 hospitals surveyed (66.2% response rate). Only 1.5% of the respondents (n=2) had no prior knowledge of intra-abdominal hypertension and ACS. IAP had been measured on some occasion by 75.9% (n=104) of the respondents, always by the intravesical route. Among those intensive care units that measured IAP, in 93.2% (n=97) it was only measured when there was a suspicion of the development of ACS; 3.8% of units (n=4) measured IAP on all patients who had undergone an emergency laparotomy, and 2.9% (n=3) measured IAP only in those who had undergone emergency laparotomy associated with massive fluid resuscitation. There was major disparity in the frequency of IAP measurement and when to recommend abdominal decompression. Despite widespread awareness of IAH and the ACS, many intensive care units never measure the IAP. When it is measured, the intravesical route is used exclusively. No consensus exists on optimal timing of measurement or when decompressive laparotomy should be performed.

Optimal timing for postprandial glucose measurement in pregnant women with diabetes and a non-diabetic pregnant population evaluated by the Continuous Glucose Monitoring System (CGMS®)

Using the Continuous Glucose Monitoring System (CGMS; Medtronic Minimed) for a group of pregnant women with and without glucose intolerance, we attempted to answer the following questions: (1) when does the physiological peak of postprandial glucose occur?; (2) do non-diabetic pregnant women and pregnant women with diabetes have different postprandial glucose profiles?; and (3) what is the optimal time for postprandial glucose measurement rated according to clinical outcome? We included 53 pregnant women in our study. Based on the criteria of the German Diabetes Association (fasting, 5.0 mmol/L; 1-h, 10.0 mmol/L; 2-h, 8.6 mmol/L) we included 13 women with gestational diabetes, four with type 1 diabetes and 36 non-diabetic pregnant (NDP) women. Gestational and type 1 diabetics were classed as one group: pregnancy complicated by diabetes (PCD). Patients with carbohydrate intolerance underwent dietary counseling in accordance with the recommendations of the American Diabetes Association. Patients received a CGMS for use over 72 h. This was calibrated seven times a day with an Accu-Check. The pre- and postprandial glucose levels were documented at 15-min intervals for 3 h from the beginning of each meal. The postprandial data from the three meals were added. The group was divided according to three clinical outcome parameters: mode of delivery, birth weight percentile, and diabetes-associated complications. Statistically significant differences between groups were found for body mass index, fetal birth weight and oral glucose tolerance test. No significant differences were found for age, parity and gestational age, mode of delivery, and diabetes-associated complications. The sensor provided similar numbers of measurements in both groups (278+/-43 vs. 298+/-73, P = 0.507). The postprandial glucose peak was reached after 82+/-18 min in the non-diabetics vs. 74+/-23 min in the PCD group (not significant). Postprandial glucose values were normally slightly higher in PCD (not significant). We added the postprandial glucose values at each time interval for the three meals for each day. For the sum, there was a significant difference between the measurements at 120 min and at 135 min postprandial (P < 0.05). Dividing the group by clinical outcome showed a significant difference between the postprandial time intervals of 75 min and 105 min (P < 0.05). In addition, the time interval was different from 60 min to 135 min for the mode of delivery and birth weight percentile (P < 0.05). The 120-min interval is too long and has a lower correlation to clinical outcome parameters than earlier measurements. Our findings show that the optimal time for testing is between 45 and 120 min postprandial. Based on our practical experience and dietary recommendations, we would prefer a 60-min interval, because patients can calculate this more easily and can have more freedom to eat the recommended number of snacks.

Model selection and optimal sampling in high-throughput experimentation.

The practical difficulties encountered in analyzing the kinetics of new reactions are considered from the viewpoint of the capabilities of state-of-the-art high-throughput systems. There are three problems. The first problem is that of model selection, i.e., choosing the correct reaction rate law. The second problem is how to obtain good estimates of the reaction parameters using only a small number of samples once a kinetic model is selected. The third problem is how to perform both functions using just one small set of measurements. To solve the first problem, we present an optimal sampling protocol to choose the correct kinetic model for a given reaction, based on T-optimal design. This protocol is then tested for the case of second-order and pseudo-first-order reactions using both experiments and computer simulations. To solve the second problem, we derive the information function for second-order reactions and use this function to find the optimal sampling points for estimating the kinetic constants. The third problem is further complicated by the fact that the optimal measurement times for determining the correct kinetic model differ from those needed to obtain good estimates of the kinetic constants. To solve this problem, we propose a Pareto optimal approach that can be tuned to give the set of best possible solutions for the two criteria. One important advantage of this approach is that it enables the integration of a priori knowledge into the workflow.