Contingent screening for down syndrome is an efficient alternative to non-disclosure sequential screening

Objective To present a first and second trimester Down syndrome screening strategy, whereby second-trimester marker determination is contingent on the first-trimester results. Unlike non-disclosure sequential screening (the Integrated test), which requires all women to have markers in both trimesters, this allows a large proportion of the women to complete screening in the first trimester. Methods Two first-trimester risk cut-offs defined three types of results: positive and referred for early diagnosis; negative with screening complete; and intermediate, needing second-trimester markers. Multivariate Gaussian modelling with Monte Carlo simulation was used to estimate the false-positive rate for a fixed 85% detection rate. The false-positive rate was evaluated for various early detection rates and early test completion rates. Model parameters were taken from the SURUSS trial. Results Completion of screening in the first trimester for 75% of women resulted in a 30% early detection rate and a 55% second trimester detected rate (net 85%) with a false-positive rate only 0.1% above that achievable by the Integrated test. The screen-positive rate was 0.1% in the first trimester and 4.7% for those continuing to be tested in the second trimester. If the early detection rate were to be increased to 45% or the early completion rate were to be increased to 80%, there would be a further 0.1% increase in the false-positive rate. Conclusion Contingent screening can achieve results comparable with the Integrated test but with earlier completion of screening for most women. Both strategies need to be evaluated in large-scale prospective studies particularly in relation to psychological impact and practicability.

Three-stage contingent screening for down syndrome

Objective To demonstrate the potential value of three-stage sequential screening for Down syndrome. Methods Protocols were considered in which maternal serum pregnancy associated plasma protein-A (PAPP-A) and free -human chorionic gonadotropin (hCG) measurements were taken on all women in the first trimester. Those women with very low Down syndrome risks were screened negative at that stage and nuchal translucency (NT) was measured on the remainder and the risk reassessed. Those with very low risk were then screened negative and those with very high risk were offered early diagnostic testing. Those with intermediate risks received second-trimester maternal serum -fetoprotein, free -hCG, unconjugated estriol and inhibin-A. Risk was then reassessed and those with high risk were offered diagnosis. Detection rates and false-positive rates were estimated by multivariate Gaussian modelling using Monte-Carlo simulation. Results The modelling suggests that, with full adherence to a three-stage policy, overall detection rates of nearly 90% and false-positive rates below 2.0% can be achieved. Approximately two-thirds of pregnancies are screened on the basis of first-trimester biochemistry alone, five out of six women complete their screening in the first trimester, and the first-trimester detection rate is over 60%. Conclusion Three-stage contingent sequential screening is potentially highly effective for Down syndrome screening. The acceptability of this protocol and its performance in practice, should be tested in prospective studies. Copyright © 2006 John Wiley & Sons, Ltd.

Sequential cost-reimbursement rules

This paper studies cost-sharing rules under dynamic adverse selection. We present a typical principal-agent model with two periods, set up in Laffont and Tirole's (1986) canonical regulation environment. At first, when the contract is signed, the firm has prior uncertainty about its efficiency parameter. In the second period, the firm learns its efficiency and chooses the level of cost-reducing effort. The optimal mechanism sequentially screens the firm's types and achieves a higher level of welfare than its static counterpart. The contract is indirectly implemented by a sequence of transfers, consisting of a fixed advance payment based on the reported cost estimate, and an ex-post compensation linear in cost performance.

An integrated framework for combining gist vision with object segregation categorisation and recognition

There are roughly two processing systems: (1) very fast gist vision of entire scenes, completely bottom-up and data driven, and (2) Focus-of-Attention (FoA) with sequential screening of specific image regions and objects. The latter system has to be sequential because unnormalised input objects must be matched against normalised templates of canonical object views stored in memory, which involves dynamic routing of features in the visual pathways.

Land of the rising soy an internationalization plan for nutre to the Japanese Soy milk market

The present work project studies the next step in the internationalization process of Shoyce, the soy milk products brand of Nutre. In order to select the best target market in the Asia-Pacific for Nutre to export, a sequential screening process was developed using two complementary approaches: preliminary country screening and country ranking, followed by an in-depth analysis of the country ranking first. The analysis revealed Japan as the most attractive country for Shoyce’s international expansion. Potential entry modes in the Japanese soy milk market were then evaluated, whereby direct exporting via a local distributor was found to be the most appropriate.

Second-trimester soft markers: relation to first-trimester nuchal translucency in unaffected pregnancies

Objective Genetic sonography following first-trimester combined screening appears to increase substantially detection rates for Down syndrome but it relies on the unproved assumption of independence between these tests. In this study we aimed to investigate the relationship between first-trimester nuchal translucency (NT) and a series of second-trimester soft markers and structural defects in unaffected pregnancies. Methods NT measurement in the first trimester was followed by second-trimester scan (18 to 23 + 6 weeks) including examination for three categorical markers (intracardiac echogenic foci, hyperechogenic bowel and structural defects) and measurement of nasal bone length, nuchal-fold thickness, femur length, humerus length, renal pelvis diameter and prenasal thickness. All continuous variables were expressed in multiples of the median (MoM) for gestation and correlation coefficients between log-transformed NT and second-trimester variables were calculated. In addition, frequencies of soft markers and structural defects in cases with increased NT were compared to those with normal NT, using MoM cut-offs. Results In a dataset of 1970 cases, NT was significantly correlated (P < 0.05) with all second-trimester continuous variables, the correlation being strongest for nuchal-fold thickness (r = 0.10). There was a higher frequency of cases with second-trimester nuchal-fold thickness above the 97.5th centile (10.7 vs. 2.2%) and hyperechogenic bowel (2.4 vs. 0.1%) in cases with increased NT. Conclusions Straightforward reassessment of risk using likelihood ratios derived from the second-trimester genetic sonogram might lead to inaccurate estimates. Multivariate models using continuous second-trimester variables might be preferable in sequential screening strategies. Copyright. 2012 ISUOG. Published by John Wiley & Sons, Ltd.

Emulation of random output simulators

Computer models, or simulators, are widely used in a range of scientific fields to aid understanding of the processes involved and make predictions. Such simulators are often computationally demanding and are thus not amenable to statistical analysis. Emulators provide a statistical approximation, or surrogate, for the simulators accounting for the additional approximation uncertainty. This thesis develops a novel sequential screening method to reduce the set of simulator variables considered during emulation. This screening method is shown to require fewer simulator evaluations than existing approaches. Utilising the lower dimensional active variable set simplifies subsequent emulation analysis. For random output, or stochastic, simulators the output dispersion, and thus variance, is typically a function of the inputs. This work extends the emulator framework to account for such heteroscedasticity by constructing two new heteroscedastic Gaussian process representations and proposes an experimental design technique to optimally learn the model parameters. The design criterion is an extension of Fisher information to heteroscedastic variance models. Replicated observations are efficiently handled in both the design and model inference stages. Through a series of simulation experiments on both synthetic and real world simulators, the emulators inferred on optimal designs with replicated observations are shown to outperform equivalent models inferred on space-filling replicate-free designs in terms of both model parameter uncertainty and predictive variance.

An optimal design for screening trials

Yao, Begg, and Livingston (1996, Biometrics 52, 992-1001) considered the optimal group size for testing a series of potentially therapeutic agents to identify a promising one as soon as possible for given error rates. The number of patients to be tested with each agent was fixed as the group size. We consider a sequential design that allows early acceptance and rejection, and we provide an optimal strategy to minimize the sample sizes (patients) required using Markov decision processes. The minimization is under the constraints of the two types (false positive and false negative) of error probabilities, with the Lagrangian multipliers corresponding to the cost parameters for the two types of errors. Numerical studies indicate that there can be a substantial reduction in the number of patients required.

Random sequential multilayer deposition of different‐sized k mers on a one dimensional infinite substrate

Kinetics of random sequential, irreversible multilayer deposition of macromolecules of two different sizes on a one dimensional infinite lattice is analyzed at the mean field level. A formal solution for the corresponding rate equation is obtained. The Jamming limits and the distribution of gaps of exact sizes are discussed. In the absence of screening, the jamming limits are shown to be the same for all the layers. A detailed analysis for the components differing by one monomer unit is presented. The small and large time behaviors and the dependence of the individual jamming limits of the k mers and (k−1) mers on k and the rate parameters are analyzed.

Auditory brainstem response in term and preterm infants with neonatal complications: the importance of the sequential evaluation

Introduction Literature data are not conclusive as to the influence of neonatal complications in the maturational process of the auditory system observed by auditory brainstem response (ABR) in infants at term and preterm. Objectives Check the real influence of the neonatal complications in infants by the sequential auditory evaluation. Methods Historical cohort study in a tertiary referral center. A total of 114 neonates met inclusion criteria: treatment at the Universal Neonatal Hearing Screening Program of the local hospital; at least one risk indicator for hearing loss; presence in both evaluations (the first one after hospital discharge from the neonatal unit and the second one at 6 months old); all latencies in ABR and transient otoacoustic emissions present in both ears. Results The complications that most influenced the ABR findings were Apgar scores less than 6 at 5 minutes, gestational age, intensive care unit stay, peri-intraventricular hemorrhage, and mechanical ventilation. Conclusion Sequential auditory evaluation is necessary in premature and term newborns with risk indicators for hearing loss to correctly identify injuries in the auditory pathway.

[The model project "newborn auditory screening" in the Upper Palatinate: high process and result quality of an interdisciplinary concept]

BACKGROUND: In May 2003, a newborn auditory screening program was initiated in the Upper Palatinate. METHODS: Sequential OAE- and BERA-screening was conducted in all hospitals with obstetric facilities. The Screening Center at the Public Health Authority was responsible for the coordination of the screening process, completeness of participation, the follow-up of all subjects with a positive screening test and the quality of instrumental screening. RESULTS: A total of 96% of 17,469 newborns were screened. The referral rate at discharge was 1.6% (0.4% for bilateral positive findings). For 97% of the positive screening results, a definite diagnosis to confirm or exclude hearing loss was achieved; for 43% only after intervention by the Screening Center. Fifteen children with profound bilateral hearing impairment were identified of whom eight were only detected by the intervention of the Screening Center. CONCLUSION: The effective structures established in the Upper Palatinate provide a standard for the quality of neonatal auditory screening achievable in Germany.

The performance of human papillomavirus high-risk DNA testing in the screening and diagnostic settings.

OBJECTIVE: We sought to evaluate the performance of the human papillomavirus high-risk DNA test in patients 30 years and older. MATERIALS AND METHODS: Screening (n=835) and diagnosis (n=518) groups were defined based on prior Papanicolaou smear results as part of a clinical trial for cervical cancer detection. We compared the Hybrid Capture II (HCII) test result with the worst histologic report. We used cervical intraepithelial neoplasia (CIN) 2/3 or worse as the reference of disease. We calculated sensitivities, specificities, positive and negative likelihood ratios (LR+ and LR-), receiver operating characteristic (ROC) curves, and areas under the ROC curves for the HCII test. We also considered alternative strategies, including Papanicolaou smear, a combination of Papanicolaou smear and the HCII test, a sequence of Papanicolaou smear followed by the HCII test, and a sequence of the HCII test followed by Papanicolaou smear. RESULTS: For the screening group, the sensitivity was 0.69 and the specificity was 0.93; the area under the ROC curve was 0.81. The LR+ and LR- were 10.24 and 0.34, respectively. For the diagnosis group, the sensitivity was 0.88 and the specificity was 0.78; the area under the ROC curve was 0.83. The LR+ and LR- were 4.06 and 0.14, respectively. Sequential testing showed little or no improvement over the combination testing. CONCLUSIONS: The HCII test in the screening group had a greater LR+ for the detection of CIN 2/3 or worse. HCII testing may be an additional screening tool for cervical cancer in women 30 years and older.

Australia: new screening method for cold tolerance during the reproducitve stage in rice

Low temperature, particularly during the reproductive stage of the development of rice, limits productivity in the Riverina region of New South Wales (NSW). This study primarily examined genotypic differences in cold damage that are associated with low temperature during reproductive development. Results from experiments in temperature-controlled rooms and the cold water facility were combined with four years of field experiments, which used natural exposure to low temperature to examine the response of over 50 cultivars from diverse origins. Plants were exposed to day/night air temperatures of 27°/13°C in temperature-controlled rooms and to a constant temperature of 19°C in the cold water facility. Low temperature treatments were imposed from panicle initiation (PI) to 50% heading. In field experiments several techniques were used to increase the likelihood of inducing cold damage such as sequential sowing dates (five to eight sowing dates each year), shallow water depths (5cm) and high nitrogen rates (e.g. 300kgN ha-1). Several cultivars were identified that were more cold tolerant than Australia’s commercial cultivars.

An efficient screening method for computer experiments

Computer simulators of real-world processes are often computationally expensive and require many inputs. The problem of the computational expense can be handled using emulation technology; however, highly multidimensional input spaces may require more simulator runs to train and validate the emulator. We aim to reduce the dimensionality of the problem by screening the simulators inputs for nonlinear effects on the output rather than distinguishing between negligible and active effects. Our proposed method is built upon the elementary effects (EE) method for screening and uses a threshold value to separate the inputs with linear and nonlinear effects. The technique is simple to implement and acts in a sequential way to keep the number of simulator runs down to a minimum, while identifying the inputs that have nonlinear effects. The algorithm is applied on a set of simulated examples and a rabies disease simulator where we observe run savings ranging between 28% and 63% compared with the batch EE method. Supplementary materials for this article are available online.