Precision Goals Research Articles

Polarimeters and energy spectrometers for the ILC Beam Delivery System

Any future high energy e+e− linear collider aims at precision measurements of Standard Model quantities as well as of new, not yet discovered phenomena. In order to pursue this physics programme, excellent detectors at the interaction region have to be complemented by beam diagnostics of unprecedented precision. This article gives an overview of current plans and issues for polarimeters and energy spectrometers at the International Linear Collider, which have been designed to fulfill the precision goals at a large range of beam energies from 45.6 GeV at the Z0 pole up to 250 GeV or, as an upgrade, up to 500 GeV.

Cosmic microwave background power spectrum estimation with non-circular beam and incomplete sky coverage

Over the last decade, measurements of the cosmic microwave background (CMB) anisotropy have spearheaded the remarkable transition of cosmology into a precision science. However, addressing the systematic effects in the increasingly sensitive, high-resolution, ‘full’ sky measurements from different CMB experiments poses a stiff challenge. The analysis techniques must not only be computationally fast to contend with the huge size of the data, but the higher sensitivity also limits the simplifying assumptions which can then be invoked to achieve the desired speed without compromising the final precision goals. While maximum likelihood is desirable, the enormous computational cost makes the suboptimal method of power spectrum estimation using pseudo-Cl unavoidable for high-resolution data. The debiasing of the pseudo-Cl needs account for non-circular beams, together with non-uniform sky coverage. We provide a (semi)analytic framework to estimate bias in the power spectrum due to the effect of beam non-circularity and non-uniform sky coverage, including incomplete/masked sky maps and scan strategy. The approach is perturbative in the distortion of the beam from non-circularity, allowing for rapid computations when the beam is mildly non-circular. We advocate that it is computationally advantageous to employ ‘soft’ azimuthally apodized masks whose spherical harmonic transform die down fast with m. We numerically implement our method for non-rotating beams. We present preliminary estimates of the computational cost to evaluate the bias for the upcoming CMB anisotropy probes (lmax∼ 3000), with angular resolution comparable to the Planck surveyor mission. We further show that this implementation and estimate are applicable for rotating beams on equal declination scans, and can possibly be extended to simple approximations to other scan strategies.

Concise CIO based precession-nutation formulations

Context.The IAU 2000/2006 precession-nutation models have precision goals measured in microarcseconds. To reach this level of performance has required series containing terms at over 1300 frequencies and involving several thousand amplitude coefficients. There are many astronomical applications for which such precision is not required and the associated heavy computations are wasteful. This justifies developing smaller models that achieve adequate precision with greatly reduced computing costs.

Assessment of the practicability and analytical performance of a point-of-care affinity chromatography haemoglobin A1c analyser for use in the non-laboratory setting

Haemoglobin A(1c) (HbA(1c)) is a pivotal pathology test used around the world for the long-term management of patients with diabetes. Point-of-care testing (POCT) provides a convenient means for conducting HbA(1c) testing outside the laboratory. The practicability and analytical performance of the Micromat II POCT HbA(1c) analyser (Bio-Rad Laboratories, USA), which has affinity chromatography as its methods principle, was evaluated in Australia and compared with the DCA 2000 POCT device (Bayer Australia) and a laboratory-based high-performance liquid chromatography (HPLC) method. Overall between-day imprecision over 10 days was 1.9% for the laboratory HPLC method, 2.2% for the DCA 2000 and 7.0% for the Micromat II. In a second study over the same time period, the Micromat II's imprecision was 6.4%. The mean difference between the Micromat II and the laboratory method in a patient comparison (n = 100) was -0.25% (lower and upper limits of agreement -1.79 to 1.30). The imprecision obtained with the Micromat II was inferior to both the DCA 2000 and laboratory methods and did not meet current internationally accepted precision goals for this analyte. The Micromat II's poor imprecision can be explained by the high degree of technical expertise needed to perform the test; its use by non-laboratory health professionals such as nurses and Aboriginal health workers in rural and remote Australia cannot be recommended.

Results of an Aboriginal community-based renal disease management program incorporating point of care testing for urine albumin:creatinine ratio

There has been a significant increase in the burden of renal disease among Aboriginal Australians over the past 15 years. Urine albumin:creatinine ratio (ACR) is a well-established marker of microalbuminuria and can be conveniently performed on the DCA 2000 point-of-care testing (POCT) analyser (Bayer Australia; Melbourne, VIC, Australia) with an on-site result available in 7 min. The application of the urine ACR POCT for renal disease risk assessment was pioneered by our group in the Umoona Kidney Project. This article describes the results of the management arm of the Umoona Kidney Project, which used point-of-care urine ACR testing for the first time within a management framework to monitor albuminuria in patients at highest risk of renal disease. The article also examines the analytical quality of POCT results and overall community acceptance of the Umoona Kidney Project. Adults clinically assessed by Flinders Medical Centre renal specialists as being at greatest risk for renal disease were offered the ACE inhibitor (ACEI) perindopril on a voluntary basis. Selected renal markers, including POCT urine ACR (conducted on-site by Umoona's Aboriginal health worker team), plasma electrolytes, urea, creatinine, calculated glomerular filtration rate and blood pressure were measured six monthly. Regular quality control testing was undertaken to monitor the analytical performance of the POCT analyser. A culturally appropriate questionnaire was designed and implemented to assess community satisfaction with the project. In all, 231 patient management consultations were conducted over a two year period, with over 70% of patients having four or more (up to a maximum of eight) consultations; 35 patients (mean age 49.2 [+/-2.3] years, 54% males) participated voluntarily in the management arm. All were overtly hypertensive, hypertensive with other risk factors or had diabetes. The renal status of these patients was followed for a mean of 63 +/- 4.5 weeks. In total, 111 POCT urine ACR tests were performed for patient management (mean 3.2 tests per patient). There was no significant difference in POCT urine ACR in the study period with a median (and inter-quartile range) of 5.7 mg/mmol (1.2-15.2) pre-ACEI and 4.3 mg/mmol (1.3-16.7) post-ACEI treatment (p = 0.50, Wilcoxon signed ranks test). The calculated glomerular filtration rate altered from 110 to 118 mL/min (p = 0.019, paired t-test). There was no change in the group plasma potassium, urea and creatinine. Collectively these results indicate a stabilisation in renal function among the management group. Blood pressure (both lying and standing) fell significantly in the study period. The imprecision for urine ACR quality control POCT conducted during the management program was within nationally and internationally accepted precision goals for urine albumin, creatinine and ACR. Fifty community members completed the satisfaction questionnaire. Three-quarters of respondents felt there were no cultural barriers in providing a urine sample for urine ACR POCT. The management arm of the Umoona Kidney Project was effective in stabilising the renal function and improving the blood pressure of community members identified to be at greatest risk of kidney disease. POCT urine ACR testing can be utilised, not only for community risk assessment, but also for patient management. The Umoona Kidney Project was well accepted by the health service and community members.

Rigorous Methodology for the Design and Upgrade of Sensor Networks Using Cutsets

Traditional sensor network design for data-reconciliation-based monitoring systems consists of optimally placing sensors to satisfy predefined precision goals as well as residual precision and gross error robustness constraints to achieve minimum sensor network cost. One existing formulation of the cost optimal sensor network design is mixed integer nonlinear [Bagajewicz, M. AIChE J. 1997, 9, 2300.] which is solved using a tree search algorithm with some bounding properties. Although the tree search method guarantees global optimality, it fails to perform computationally well for medium size problems and fails altogether in large ones. Similar problems are found when using a MILP formulation [Bagajewicz, M.; Cabrera, E. AIChE J. 2001, 48, 2271.]. Other MINLP convex formulations [Chmielewski, D.; et al. Cost Optimal Retrofit of Sensor Networks with Loss Estimation Accuracy. Presented at the AIChE Annual Meeting, Dallas, TX, November, 1999. Chmielewski, D.; et al. AIChE J. 2002, 48, 1001.] have not been tested in large problems. Thus, the field has resorted to the use of genetic algorithms [Sen, S.; et al. Comput. Chem. Eng. 1998, 22, 385. Carnero, M.; et al. Ind. Eng. Chem. Res. 2001, 40, 5578. Carnero, M.; et al. Ind. Eng. Chem. Res. 2005, 44, 358.]. In this paper, we present an alternative sensor network design algorithm based on graph theory that guarantees global optimality and is faster than the existing tree searching approaches. The efficiency of the proposed algorithm, which is good for medium size problems, is illustrated.

THRESHOLD CORRECTIONS IN PRECISION LHC PHYSICS: QED⊗QCD

With an eye toward LHC processes in which theoretical precisions of 1% are desired, we introduce the theory of the simultaneous YFS resummation of QED and QCD to compute the size of the expected resummed soft radiative threshold effects in precision studies of heavy particle production at the LHC. Our results show that both QED and QCD soft threshold effects must be controlled to be on the conservative side to achieve such precision goals.

Quality specifications in thyroid diseases

Background: Laboratory tests to support the diagnosis and management of thyroid diseases have undergone significant changes with the introduction of highly sensitive assays for thyroid stimulating hormone (TSH) and free T4 and T3 concentrations in plasma. Given the importance of these measurements, quality specifications are needed to ensure accurate results. Goals for precision and accuracy are available based on known intraindividual and interindividual biological variation. Methods: Results of external quality assurance (EQA) schemes are sufficient to document precision goals but survey materials are not commutable for use in determining bias or detect the presence of unusual antibodies on a case-by-case basis. Because TSH concentrations are inversely related to free T4, this physiologic relationship can be exploited for quality assurance purposes. Results: Significant discordance between this relationship can be caused by subclinical and potentially unrecognized disease, dysequilibrium caused by recent therapy, the presence of abnormal binding proteins or protein binding competitor drugs, and antibody interferences such as human antimouse antibody (HAMA) or rheumatoid factor. Conclusion: A mechanism to automatically track discordances for subsequent follow and investigation can be an effective part of a quality assurance program for thyroid hormone measurements.

Optimization of β-Quantification Methods for High-Throughput Applications

Risk of cardiovascular disease is assessed, in part, by laboratory measurement of the concentrations of several lipoproteins. beta-Quantification is a method of lipoprotein measurement that uses ultracentrifugation to partially separate lipoprotein classes. Although beta-quantification is used largely in clinical and basic research, methods have not been described to allow the analysis of a large number of small-volume specimens with a short turnaround time. We report two variations of the traditional 5-mL method used by the Lipid Research Clinics Program that overcome these shortcomings. Two lower-volume modifications of the traditional 5-mL beta-quantification method were developed. The methods used either 1 or 0.23 mL of specimen and required substantially less time for analysis (20 and 6 h, respectively) than the 5-mL method (2.5 days). The goal was to develop ultracentrifugation methods such that the concentration of cholesterol in the bottom fraction, from which LDL-cholesterol concentration is calculated, agreed with the 5-mL method. Fresh serum specimens (n = 45) were analyzed by the three methods to determine comparability of the methods based on the recovery of cholesterol in the bottom fraction after ultracentrifugation. To evaluate intrarun precision, replicate specimens (n = 17) were analyzed in a single run for each method. This experiment also evaluated how quickly the fractions would remix after separation by ultracentrifugation. For the 1-mL method, accuracy of the measurement of LDL- and HDL-cholesterol concentrations and the interrun precision were established by analysis of frozen serum specimens provided by the CDC, which established target values for the pools using reference methods. No clinically significant differences in cholesterol concentrations in the bottom fraction were observed for the 1- and 0.23-mL methods, which had mean biases of 0.8% and 1.5% relative to the 5-mL method, respectively. Intra- and interrun variability was acceptable for each method, e.g., <1.8% for cholesterol in the bottom fraction. Ultracentrifuged specimens were stable for at least 4 h with no evidence of contamination of cholesterol in the bottom fraction. For comparison specimens provided by the CDC, the 1-mL method met the accuracy and precision goals of the National Cholesterol Education Program for the measurement of HDL- and LDL-cholesterol concentrations (goals: total error <13% and <12%, respectively), with total errors of 6.45% and 5.43%, respectively. Both the 1- and 0.23-mL beta-quantification methods are suitable substitutes for the traditional 5-mL method for use in clinical and basic research for the determination of LDL-cholesterol concentration. Both methods provide much higher throughput and require substantially less specimen volume. The 0.23-mL method can be performed in 1 day, but it is slightly less precise than the 1-mL method. In our laboratory setting, as many as 80 specimens are routinely processed per day using the 1-mL method.

The use of track registration detectors to reconstruct contemporary and historical airborne radon ( 222RN) and radon progeny concentrations for radon-lung cancer epidemiologic study

Epidemiologic studies that investigate the relationship between radon and lung cancer require accurate estimates for the long-term average concentrations of radon progeny in dwellings. Year-to-year and home-to-home variations of radon in domestic environments pose serious difficulties for reconstructing an individual's long-term radon-related exposure. The use of contemporary radon gas concentrations as a surrogate for radon-related dose introduces additional uncertainty in dose assessment. Studies of glass exposed in radon chambers and in a home show that radon progeny deposited on, and implanted in, glass hold promise for reconstructing past radon concentrations in a variety of atmospheres. We developed an inexpensive track registration detector for the Iowa Radon Lung Cancer Study (IRLCS) that simultaneously measures contemporary airborne radon concentrations, surface deposited alpha activity density, and implanted 210Po activity density. The implanted activity is used to reconstruct the cumulative radon and radon progeny exposure from the age of the glass and the ratios of the contemporary deposited activiteis to airborne radon gas activity. We placed over 2500 of these detectors in more than 1000 homes and retrieved 97% of them after a one-year exposure period. A preliminary analysis of the 1280 detectors that have undergone quality assurance review shows that the modules are meeting their accuracy and precision goals (10%). There is good correlation (r 2∼0.5) between the total radon exposure estimated from contemporary radon gas measurements and historical average reconstructed from the implanted 210Po surface activity. The linear regression slope of the airborne radon exposure to implanted activity is the same as the room model slope based on typical room parameters. This correlation improves (r 2∼0.7) when the deposited surface activity measurements are added to the linear regression. Thus, track-registration detectors can contribute to accurate radon-related dose assessment in epidemiologic studies. Additional work is planned to incorporate the deposited activities in a more sophisticated reconstruction model.

An application of mathematical programming to sample allocation

The problem of sample allocation in multipurpose surveys is complicated by the fact that an efficient allocation for some estimates may be inefficient for others. There may also be precision goals that must be met for certain estimates plus constraints on costs and minimum sample sizes for strata to permit variance estimation. These requirements lead to formulating the allocation problem as one of mathematical programming with an objective function and constraints that are nonlinear in the sample size target variables. We discuss a flexible approach for a two-stage sample allocation that uses multicriteria optimization programming. Software was developed to permit survey designers to easily explore alternative problem formulations and to compare the resulting allocations. The method is illustrated using a business establishment survey that estimates the costs to employers of providing wages and benefits to employees and the percentages of employees that receive certain benefits. © 1997 Elsevier Science B.V.

Development and manufacture of collimators for gamma ray imaging

We report the development of very fine collimator slit patterns for gamma ray imaging. Astronomical objects emitting gamma rays cannot be imaged in a classical way. However, it is possible to measure Fourier components of the images by observing gamma ray sources through pairs of patterns of fine slits placed at a mutual distance of several meters. The finest pattern should have slit 50 μm wide at a pitch of 100 μm. To achieve high contrast images, the slit geometry must meet high precision goals. The absolute slit position accuracy must be on the order of a few micrometers within an area of 130 mm × 130 mm. The slit patterns have been realized by stacking logn thin blades separated by small spacers. The application of flexible spacers and precision reference frames results in a high pitch accuracy. The spacer design was optimized using finite-element analysis. The spacers were made via a multistep precision etching technique. Measurements on the full-size slit patterns show low slit position errors.

Intraindividual variation of glycohemoglobin: implications for interpretation and analytical goals

Intraindividual variation (CVi) for glycohemoglobin (GHb) was estimated from serial measurements in patients with diabetes in either stable or variable clinical control. GHb determinations were performed by an affinity column procedure with an analytical imprecision of 4.9% (weighted average; GHb 8.2-14.7%). Within the groups of patients, both a short- (28-32 days) and long-term (approximately 85 days) sampling protocol was used. The derived CVi for each category was 4.2% (n = 16, stable, short-term), 7.1% (n = 23, stable, long-term), 5.1% (n = 13, variable, short-term), and 9.8% (n = 21, variable, long-term). The mean GHb within each category was similar (approximately 11%), and there was no statistically significant difference in GHb values between categories. The results establish that the CVi for GHb is affected by both clinical control and the sampling time interval. These findings have important implications for the estimation of significant differences between serial GHb measurements and the setting of appropriate analytical precision goals.

1992 Clinical Chemistry Forum: Accuracy, precision goals and medical relevance. Proceedings

1992 Clinical Chemistry Forum: Accuracy, precision goals and medical relevance. Proceedings

Analytical performance goals for measuring prostate-specific antigen

We have assessed the feasibility of using fixed-limit criteria based on medical relevance and biological variation for evaluating the analytical performance of the prostate-specific antigen (PSA) test. The estimated within-subject variation of serum PSA is on the order of 10-20% at clinical decision points. The calculated performance goals of 5-10% CV are attainable with current immunoassay technology and agree with precision goals based on clinical experience and the current clinical use of the test. However, new clinical applications of PSA may require a degree of analytical performance that current methods may not be able to provide. The PSA model demonstrates the need for biologically based fixed-limit criteria for all tumor-marker tests.

Medically relevant laboratory-performance goals: a listing of the complexities and a call for action

This 1992 Clinical Chemistry Forum asks if accuracy and precision goals for the laboratory can be specified by reference to medical requirements, which are a function of the total laboratory testing process as well as the needs of patients, clinicians, and societal institutions. Furthermore, medical decisions and decisions about medical requirements must be made in situations of uncertainty and thus are subject to predictable cognitive errors. The interaction of all these factors must be considered by patients, laboratorians, and clinicians to identify practical and effective performance goals. Pathologists and clinical chemists are uniquely trained to identify thoughtful clinicians who are knowledgeable in quantitative judgment to participate in this goal-setting endeavor. It is time for these parties to accumulate the available data and engage in the synthesis of effective performance goals.

6.1.2.4 Analytical Goals for Accuracy and Precision of Plasma Creatinine Determinations Evaluated by Reference Method Measurements

Using approaches based on "medical needs" and biological variation, goals for analytical accuracy were assessed to 0.072-0.15 expressed as relative deviations, and goals for analytical precision were estimated to 0.022-0.14 expressed as relative standard deviations. A representative clinical method was evaluated using a reference method. On this basis, it is concluded that accuracy goals are fulfilled at high but not at low levels, and that precision goals are met according to medical needs but not with respect to biological variation.

Evaluation of stat and routine turnaround times as a component of laboratory quality.

Quality assurance has been an essential part of clinical laboratory operations for more than two decades. Analytic precision and accuracy goals have been established, and laboratory performance is monitored periodically. For a laboratory test to be useful, it must be available in a timely manner. Expedience of result reporting has not, however, been routinely included among measures of laboratory quality. The authors evaluated stat and routine turnaround times for 42,414 requests on 24 clinical analytes over a 14-day period with the use of a personal computer. Median turnaround time is 1.70 times faster for stat than for routine tests. When examined by shift, average turnaround time is considerably faster for tests ordered stat than for tests ordered routinely during the day and evening shifts, when the work load is the greatest. The authors are now examining turnaround time as an indicator of quality laboratory performance and efficiency. Computer systems in many clinical laboratories already have the sophistication necessary to perform turnaround time analysis. The authors recommend that clinical laboratories begin to include timeliness of stat and routine result reporting as part of their quality assurance programs. Laboratories may also wish to investigate the usefulness of stat requests during slower shifts because these requests may interrupt the normal flow of specimens without expediting result reporting.

Testing cholesterol accuracy. Performance of several common laboratory instruments.

The national emphasis on assessing coronary risk by cholesterol testing mandates that analytical determinations be as accurate and precise as is medically necessary. One goal of the National Cholesterol Education Program is to improve the quality of laboratory tests. Currently, 5% limits of imprecision and 5% of bias vs the nationally accepted Abell-Kendall reference method is recommended, with a goal of reducing these limits to 3% by 1992. Clinicians must be aware of how the cholesterol values are obtained, and especially whether the laboratory's method meets the performance goals. We assayed patients' serum samples for cholesterol using several commercially available, routinely used enzymatic methods and by the Abell-Kendall reference method. Precision of these methods was also assessed using serum-based controls. All instruments were operated precisely according to the manufacturers' instructions. Performance was objectively judged based on the National Cholesterol Education Program goals and on medically allowable total error. In all cases, the DuPont aca, the Kodak Ektachem, the Hitachi 737, and the Cobas FARA determined cholesterol levels acceptably. The precision and accuracy goals of 3% are achievable by these methods.

Testing Cholesterol Accuracy

The national emphasis on assessing coronary risk by cholesterol testing mandates that analytical determinations be as accurate and precise as is medically necessary. One goal of the National Cholesterol Education Program is to improve the quality of laboratory tests. Currently, 5% limits of imprecision and 5% of bias vs the nationally accepted Abell-Kendall reference method is recommended, with a goal of reducing these limits to 3% by 1992. Clinicians must be aware of how the cholesterol values are obtained, and especially whether the laboratory's method meets the performance goals. We assayed patients' serum samples for cholesterol using several commercially available, routinely used enzymatic methods and by the Abell-Kendall reference method. Precision of these methods was also assessed using serum-based controls. All instruments were operated precisely according to the manufacturers' instructions. Performance was objectively judged based on the National Cholesterol Education Program goals and on medically allowable total error. In all cases, the DuPont aca, the Kodak Ektachem, the Hitachi 737, and the Cobas FARA determined cholesterol levels acceptably. The precision and accuracy goals of 3% are achievable by these methods. (<i>JAMA</i>1988;260:2552-2557)