Typical Goal Research Articles

Bevacizumab Advanced Melanoma (BEAM) Was a Positive Trial

TO THE EDITOR: Bevacizumab Advanced Melanoma (BEAM) by Kim et al was a randomized phase II trial. Cannistra clarified the differences between a phase III trial and a randomized phase II trial in 2009. “Unlike the randomized phase III study, the type I error of a randomized phase II trial is typically high, in the range of 10% to 20%, to keep patient numbers reasonable . . . The typical goal of performing a randomized comparison phase II trial is not to obtain definitive efficacy information, but to identify promising experimental regimens that have a high likelihood of success in the phase III setting.” The BEAM trial showed improvements in response rates, progression-free survival, and overall survival at all time points, with a similar degree of improvement to that seen in other solid tumors in which bevacizumab was added to chemotherapy. The hazard rate for improvement in overall survival at the last time point, 0.79, is the same rate of improvement seen with bevacizumab with the same chemotherapy that led the US Food and Drug Administration to approve bevacizumab for lung cancer. The BEAM trial produced strong evidence that a phase III trial would likely be successful. The statistical design for the BEAM trial was written in 2007, and the desire to keep the patient numbers reasonable together with the desire to use a more traditional type one error of 5% probably led to the hypothesis that the experimental arm would have a 50% improvement in progression-free survival, from 4 to 6 months, despite the fact that rate of improvement has almost never been reported with the addition of bevacizumab to chemotherapy. Because the statistical design of the trial was too ambitious in both the hypothesized improvement and the type one error (P value) sought, “the study did not meet the primary objective.” Our interpretation of the results of the BEAM might be moot if the results of a phase III trial were expected soon. Although there was enthusiasm among both the trial investigators and Genentech personnel in July 2009 for quickly starting a phase III trial, the merger of Genentech into Roche that year led to a change in corporate priorities away from a phase III trial in melanoma. Now with the approval of ipilimumab and vemurafenib, a first-line trial of chemotherapy with bevacizumab would be neither appropriate nor feasible. The BEAM trial was positive, and it will remain our best evidence of the efficacy of antiangiogenic therapy in metastatic melanoma for the near future. Other antivascular endothelial growth factor–targeted agents are being studied for melanoma, and we hope to soon see both phase II and phase III trials of bevacizumab with the new agents that are now our first-line therapy for metastatic melanoma.

Testing restorable systems: formal definition and heuristic solution based on river formation dynamics

Abstract Given a finite state machine denoting the specification of a system, finding some short interaction sequences capable of reaching some/all states or transitions of this machine is a typical goal in testing methods. If these sequences are applied to an implementation under test , then equivalent states or transitions would be reached and observed in the implementation—provided that the implementation were actually defined as the specification. We study the problem of finding such sequences in the case where configurations previously traversed can be saved and restored (at some cost). In general, this feature enables sequences to reach the required parts of the machine in less time, because some repetitions can be avoided. However, we show that finding optimal sequences in this case is an NP-hard problem. We propose an heuristic method to approximately solve this problem based on an evolutionary computation approach, in particular river formation dynamics (RFD). Given finite state machine specifications and sets of states/transitions to be reached, we apply RFD to construct testing plans reaching these configurations. Experimental results show that being able to load previously traversed states generally reduces the time needed to cover the target configurations.

CAN SECRET INTERVENTION BE COMPATIBLE WITH A NON‐PROFITMAKING CENTRAL BANK AND A FUNDAMENTAL‐CONSISTENT TARGET?

The coexistence of secret intervention operations and “the signaling channel” (Mussa. The Role of Official Intervention, 1981) seems confusing. Vitale ( Journal of International Economics, 49, 1999, 245–267) resolves this puzzle by employing an asymmetric information framework and an assumption of a fundamental‐inconsistent target for the exchange rate. Ferré and Manzano ( International Journal of Finance and Economics, 14, 2009, 378–393) follow Vitale's microstructure framework and argue that the central banks' profitability motivation offers a rationale for their secret intervention even under a target consistent with the fundamentals. However, that the authority uses its superior information to obtain speculative profits through secret intervention in the market is not a typical goal for central banks. To theoretically explain the opaqueness in non‐profitmaking central banks' exchange rate policies, we employ a model of a central bank's optimization by considering that no bank really knows the exact fundamental rate and they take into account the possible bad consequences of announcing the intervention. We also show that, in passing the bank's private information to market participants, a bank's announcement of the intervention size is equivalent to revealing its target rate. (JEL E58, F39)

Comparative analysis of peak-detection techniques for comprehensive two-dimensional chromatography

Comprehensive two-dimensional gas chromatography (GC×GC) is a powerful technology for separating complex samples. The typical goal of GC×GC peak detection is to aggregate data points of analyte peaks based on their retention times and intensities. Two techniques commonly used for two-dimensional peak detection are the two-step algorithm and the watershed algorithm. A recent study [4] compared the performance of the two-step and watershed algorithms for GC×GC data with retention-time shifts in the second-column separations. In that analysis, the peak retention-time shifts were corrected while applying the two-step algorithm but the watershed algorithm was applied without shift correction. The results indicated that the watershed algorithm has a higher probability of erroneously splitting a single two-dimensional peak than the two-step approach. This paper reconsiders the analysis by comparing peak-detection performance for resolved peaks after correcting retention-time shifts for both the two-step and watershed algorithms. Simulations with wide-ranging conditions indicate that when shift correction is employed with both algorithms, the watershed algorithm detects resolved peaks with greater accuracy than the two-step method.

Stormwater BMP treatment performance variability for sediment and heavy metals

Performance-based stormwater best management practice (BMP) selection should match appropriate technologies with site water quality concerns and consider the ability to meet water quality standards. Empirically derived frequency analysis of effluent flow-weighted composite event mean concentrations (EMCs) for sites in the International BMP Database are presented for total suspended solids, and total and dissolved zinc and copper for dry detention basins, retention basins, wetland basins, media filters, grassed swales, bioretention, and permeable pavement. Performance characterization amongst BMPs using the probability plots is also compared to typical percent removal type assessment. No single device emerges as providing the best treatment across all water quality parameters considered. Detention basins provide the least water quality protection amongst all devices, and will not likely satisfy the typical goal of 75% TSS removal. Retention ponds can meet the 75% objective only when median percent removal is considered, but effluent TSS EMCs are approximately twice the level as compared to bioretention cells and grassed swales for the majority of events. Most BMPs are able to meet US EPA marine water quality discharge criteria for zinc, and many are able to meet the more stringent ANZECC threshold for 95% species protection. Copper is problematic for all BMPs with respect to water quality criteria. Resurfacing with permeable pavement could prevent up to 2/3 of the contaminant concentrations from typical urban source areas.

Automated Test-Form Generation

In automated test assembly (ATA), the methodology of mixed-integer programming is used to select test items from an item bank to meet the specifications for a desired test form and optimize its measurement accuracy. The same methodology can be used to automate the formatting of the set of selected items into the actual test form. Three different cases are discussed: (i) computerized test forms in which the items are presented on a screen one at a time and only their optimal order has to be determined; (ii) paper forms in which the items need to be ordered and paginated and the typical goal is to minimize paper use; and (iii) published test forms with the same requirements but a more sophisticated layout (e.g., double-column print). For each case, a menu of possible test-form specifications is identified, and it is shown how they can be modeled as linear constraints using 0–1 decision variables. The methodology is demonstrated using two empirical examples. Test development is a comprehensive process involving the typical stages of itembank design, item writing, field testing, and calibration, as well as test assembly and test-form generation. Guidelines for the various activities in these stages can be found, for instance, in Downing and Haladyna (2006) and Schmeiser and Welch (2006). Any step to automation of these stages is welcome, especially when it leads to optimization of the results and reduction of the amount of work. An area where such automation has made important progress lately is test assembly. Automated test assembly (ATA) involves the selection of the items for one or more test forms from an item bank subject to sets of content and statistical specifications while optimizing their measurement properties. The automation has become possible through the application of the methodology of mixed-integer programming (MIP). The core of the application consists of the definition of 0‐1 decision variables for the selection of the items, the modeling of the test specifications as a set of constraints with an objective function that is linear in the variables, and the use of a software package with an MIP solver to find the optimal solution, which is the combination of 0s and 1s for the variables for the items that identifies the optimal set in the bank. The use of MIP is extensively reviewed for a wide variety of test assembly problems in van der Linden (2005, chaps. 1‐9). In addition, introductions to ATA and a few worked examples can be found in Cor, Alves, and Gierl (2008, 2009). For readers not familiar with the methodology, a brief example is given in the Appendix. The same methodology can be used to design item banks and manage the process of item writing. The process then involves the definition of a design space for the items (i.e., the Cartesian product of all relevant item attributes) and the introduction

Optimisation of a real-time multi-period truck dispatching system in mining operations

In recent years, there has been considerable research on optimisation of long-term and short-term open pit mine plans to maximise the net present value of a given mining project. The typical goal of truck allocation models in the literature is either minimisation of the number of trucks required to pursue the production target for a given operational period or maximisation of the production based on the available trucks and shovels. With this framework, there is no guarantee of meeting the main goal of a mining project, which is maximisation of the net present value. The objective of this research is to develop a linear programming model for truck allocation, and to utilise it in conjunction with the existing mixed integer programming model for short and long-term mine planning. We test a linear programming model and run it with a mixed integer-programming model concurrently and interactively for solving truck allocation problem. The proposed approach of truck allocation overcomes the shortcomings of the existing models by taking into account economic parameters, multi time periods and the uncertainty of load and travel times and ore grades. We provide a case study of McLaughlin gold mine to show the implementation of our model.

Restoration of alpine spoil heaps: Successional rates predict vegetation recovery in 50 years

Human disturbances in the alpine region can have long-lasting ecosystem effects because biological recovery in harsh environments proceeds slowly. As a by-product of the exploitation of hydroelectricity, surplus masses from tunnel excavations are deposited as spoil heaps in the alpine landscape. The typical management goal for such spoil heaps is that their species composition converges towards that of their undisturbed surroundings. At present we lack knowledge of the rate as well as the direction of these successions. We examined the species composition of five alpine spoil heaps in western Norway at two points in time, after 6–16, and 24–34 years of succession, with regard to vegetation cover, species richness, species composition and soil conditions. We also compared the vegetation of spoil heaps with that of their surroundings. After ca. 30 years, bryophyte and lichen cover and species richness were similar to those of their surroundings, while cover of vascular plants and species richness recovered more slowly. The vegetation development of spoil heaps appears safe-site limited rather than dispersal limited. Topsoil development was slow, but some accumulation of organic matter was observed. The species composition followed a successional trajectory in direction of the vegetation of the surroundings. Estimated linear successional rates indicate that 35–48 years are needed from construction of spoil heaps till a species composition more or less similar to their surroundings has been reached. However, these estimates are likely to be over-optimistic because successional rates tend to decrease with time. Based on our results we propose three changes to the current spoil-heap construction practice that will improve their restoration: (1) to increase surface unevenness, by which the number of safe sites will increase and germination and establishment success will be enhanced; (2) to increase substrate variability, by adding more of fine-grained materials more species will establish in shorter time; and (3) to use seed from local sources or to let the spoil heaps regenerate naturally.

Terrestrial Quadstatic Interferometric Radar Observations of Mars

A new technique for resolving the ambiguity inherent in delay-Doppler radar observations of Mars has been developed and implemented using a suite of data collected during 2001, 2003, and 2005 oppositions. New recording systems, processing techniques, and, most importantly, the addition of a fourth receiving telescope allow for the high-resolution mapping of Mars' radar properties. In this paper, we develop a maximum likelihood method to probabilistically estimate the contributions to the received radar signal from the ambiguous resolution cells. Our delay-Doppler interferometric radar observations are designed to map the radar properties of Mars surface while disregarding the historically typical goal of measuring topography, instead using Mars' topography as <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">a priori</i> knowledge. Example data from the September 27, 2003 observation over Mars' southern highlands, including Ma'adim Vallis and Gusev Crater, and the June 7, 2001 observation crossing Terra Meridiani are presented to demonstrate the effectiveness of the technique. Analysis of these observations predicted a root-mean-square (rms) roughness, or slopes, for the Mars Exploration Rover (MER) Spirit landing site of 1.80° ± 0.75°. Similarly, analysis of the Gusev Crater landing site of MER Opportunity predicted rms slopes of 1.1° ± 0.1°. Both predictions were validated by analysis of <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">in situ</i> rover images.

Polynomial Time Algorithms for Ratio Regions and a Variant of Normalized Cut

In partitioning, clustering, and grouping problems, a typical goal is to group together similar objects, or pixels in the case of image processing. At the same time, another goal is to have each group distinctly dissimilar from the rest and possibly to have the group size fairly large. These goals are often combined as a ratio optimization problem. One example of such a problem is a variant of the normalized cut problem, another is the ratio regions problem. We devise here the first polynomial time algorithms solving optimally the ratio region problem and the variant of normalized cut, as well as a few other ratio problems. The algorithms are efficient and combinatorial, in contrast with nonlinear continuous approaches used in the image segmentation literature, which often employ spectral techniques. Such techniques deliver solutions in real numbers which are not feasible to the discrete partitioning problem. Furthermore, these continuous approaches are computationally expensive compared to the algorithms proposed here. The algorithms presented here use as a subroutine a minimum s,t-cut procedure on a related graph which is of polynomial size. The output consists of the optimal solution to the respective ratio problem, as well as a sequence of nested solutions with respect to any relative weighting of the objectives of the numerator and denominator.

Bayesian testing of many hypotheses × many genes: A study of sleep apnea

Substantial statistical research has recently been devoted to the analysis of large-scale microarray experiments which provide a measure of the simultaneous expression of thousands of genes in a particular condition. A typical goal is the comparison of gene expression between two conditions (e.g., diseased vs. nondiseased) to detect genes which show differential expression. Classical hypothesis testing procedures have been applied to this problem and more recent work has employed sophisticated models that allow for the sharing of information across genes. However, many recent gene expression studies have an experimental design with several conditions that requires an even more involved hypothesis testing approach. In this paper, we use a hierarchical Bayesian model to address the situation where there are many hypotheses that must be simultaneously tested for each gene. In addition to having many hypotheses within each gene, our analysis also addresses the more typical multiple comparison issue of testing many genes simultaneously. We illustrate our approach with an application to a study of genes involved in obstructive sleep apnea in humans.

A Pareto optimal design approach for simultaneous control of thinning and springback in stamping processes

One of the most relevant research issues in automotive field is focused on the reduction of stamped parts weight also increasing their strength. In this way, a strong research effort is developed on high strength steels which are widely utilized and they require a proper springback control. Springback reduction in sheet metal forming is a typical goal to be pursued which is conflicting with thinning reduction for instance. Thus, such problems can be considered as multi-objective ones characterized by conflicting objectives. What is more, nowadays, a great interest would be focused on the availability of a cluster of possible optimal solutions instead of a single one, particularly in an industrial environment. In this paper, integration between numerical simulations, response surface methodology and Pareto optimal solutions search techniques was applied in order to design a DP 600 U-channel shape stamping operation. In particular the friction conditions and blank holder force were optimized as design variables in order to accomplish two different objectives: reduce excessive thinning and avoid excessive geometrical distortions due to springback occurrence.

Policy futures markets with multiple goals

Previous work in monetary policy futures markets under a single policy goal have shown this approach to be effective at eliminating the circularity problem inherent with private-sector targeting strategies. We extend this monetary policy setting framework to a typical multiple goal policy objective: inflation and output stabilization. We also demonstrate how the prices in policy futures markets can help resolve debates over important policy questions.

Results reported from two clinical trials of a real-ear system within a hearing aid

Results reported from two clinical trials of a real-ear system within a hearing aid

Effects of problem frame and gender on principals’ decision making

Research indicates people’s decisions can sometimes be influenced by seemingly trivial differences in the framing (i.e., wording) of alternative options. The tendency to prefer risk averse options when framed positively and risky options when framed negatively is known as the framing effect. The current study examined the susceptibility of school principals to the framing effect. Additionally, analytical and intuitive decision styles, the degree to which one’s typical goal is to maximize (rather than satisfice), gender, and years of experience as a principal were measured to assess whether they are predictive of principals’ choices, and to test whether they moderate the effects of framing on choice. Seventy-one principals completed six decision problems (framed either positively or negatively) and instruments assessing decision style, typical decision goal, gender, and experience. Analyses demonstrated that principals are influenced by framing. Although the positively and negatively framed versions of the decision problems were objectively identical, negative framing resulted in more risky choices. Additionally, regardless of frame, men made more risky choices than women. There was no evidence that experience, decision style, or the degree to which one’s typical decision goal was to maximize, decreased framing effects. Several potential debiasing strategies are described, and limitations are noted.

Optimal decay rate constant estimates from phased array data utilizing joint Bayesian analysis

Since their initial description, phased array coils have become increasingly popular due to their ease of customization for various applications. Numerous methods for combining data from individual channels have been proposed that attempt to optimize the SNR of the resultant images. One issue that has received comparatively little attention is how to apply these combination techniques to a series of images obtained from phased array coils that are then analyzed to produce quantitative estimates of tissue parameters. Herein, instead of the typical goal of maximizing the SNR in a single image, we are interested in maximizing the accuracy and precision of parameter estimates that are obtained from a series of such images. Our results demonstrate that a joint Bayesian analysis offers a “worry free” method for obtaining optimal parameter estimates from data generated by multiple coils (channels) from a single object (source). We also compare the properties of common channel combination techniques under different conditions to the results obtained from the joint Bayesian analysis. If the noise variance is constant for all channels, a sensitivity weighted average provides parameter estimates equivalent to the joint analysis. If both the noise variance and signal intensity are similar in all channels, a simple channel average gives an adequate result. However, if the noise variance differs between channels, an “ideal weighted” approach should be applied, where data are combined after weighting by the channel amplitude divided by the noise variance. Only this “ideal weighting” provides results similar to the automatic-weighting inherent in the joint Bayesian approach.

Multidimensional Potentials of Mean Force from Biased Experiments along a Single Coordinate

External biasing forces are often applied to enhance sampling in regions of phase space which would otherwise be rarely observed. While the typical goal of these experiments is to calculate the potential of mean force (PMF) along the biasing coordinate, here I present a method to construct PMFs in multiple dimensions and along arbitary alternative degrees of freedom. A protocol for multidimensional PMF reconstruction from nonequilibrium single-molecule pulling experiments is introduced and tested on a series of two-dimensional potential surfaces with varying levels of correlation. Reconstruction accuracy and convergence from several methods--this new protocol, equilibrium umbrella sampling, and free diffusion--are compared, and nonequilibrium pulling is found to be the most efficient. To facilitate the use of this method, the source code for this analysis is made freely available.

Editorial

Editorial

C³: Cross-Course Collaboration in a distance learning environment

A typical goal of the capstone course in an MBA programme is integrating prior coursework. Serendipitous scheduling of Strategic Management and an elective in Operations Strategy for a near-captive audience allowed the instructors to develop an innovative and tightly integrated conclusion to the MBA programme taught entirely in a distance-learning environment. The instructors faced two instructional challenges: 1) video conference technology has been less than optimal as compared with traditional delivery; and 2) programme integration and close coordination between the two courses were essential. Course assessment involved using mid- and post-semester surveys, two 'one-minute papers', and a post-semester focus group discussion.

On the shaping of the main lobe in wide-band arrays

This paper describes a method to obtain a wide-band beam pattern whose main lobe has the desired shape and, at the same time, the level of the side lobes is acceptable. The aim is to reproduce a main lobe profile as close as possible to the desired one through the synthesis of the array-weighting window. A typical goal is to obtain, in wide-band conditions, a flat-top shaped beam similar to the ones produced by specific narrow-band windows. To achieve this result, an optimization process based on simulated annealing is developed and applied under different operating conditions, including two wide-band beam pattern definitions and different values of the fractional bandwidth. Although the shape of the resulting main lobe is not as good as the one obtained in narrow-band conditions (the reasons for this drawback are given), it is shown that the adoption of windows synthesized by the proposed method is more suitable than the direct application of narrow-band windows in wide-band conditions. In addition to providing better performances, it is shown that the windows synthesized by the proposed method also result in greater robustness to random perturbations of weight values, which are unavoidable in real systems.