Over the last three years, Cox Associates has achieved breakthrough results in projects completed in each of its practice areas.  In addition, we've been awarded a number of patents in areas related to our practice.  To view summaries of our activities or to read about our patents, click on the link below for the appropriate discipline.

Customer Data Mining Services
Network Design and Optimization
Health and Safety Risk Analysis
Applied Statistics

Cox Associates inducted into Edelman Academy  

In May, 2006, Cox Associates was greatly honored to be inducted into the Franz Edelman Academy of the Institute for Operations Research and Management Science (INFORMS), an honor bestowed annually to a handful of companies in recognition of innovation and achievement in the practice of operations research and the management sciences. Cox Associates and their client the Animal Health Institute (AHI) were selected for this honor in recognition of their development and application of new operations research models and methods to help quantify human health impacts of animal antibiotics using currently available science and data.

New Book On Quantitative Health Risk Assessment Methods

In November, 2005, Dr. Tony Cox’s new book Quantitative Health Risk Analysis Methods: Modeling the Human Health Impacts of Antibiotics Used in Food Animals was published by Springer.  This book provides practical methods for quantifying and comparing uncertain health risks using available information, despite real-world limitations and gaps in scientific knowledge and relevant exposure and dose-response data.  The methods are developed and illustrated in detail for the often-controversial field of antimicrobial risk assessment.  For more on the book, see:  http://www.springer.com/sgw/cda/frontpage/0,11855,4-40517-22-50492725-0,00.html.

How To Improve Qualitative Assessment?

Many qualitative risk rating systems have been proposed that use ordered labels such as “High”, “Medium”, and “Low” to rate the components of risks (e.g., release potential, exposure potential, response probability, and consequence severity) and that then assign an overall qualitative rating to risk based on these component ratings.  In July, 2004, applied mathematics research at Cox Associates identified some of the inherent limitations of any such system, proving that, under natural conditions, qualitative risk assessment necessarily makes rating reversal errors (by assigning higher qualitative labels to quantitatively smaller risks) and can produce high qualitative risk ratings even for very small risks.  The value of information (VOI) from a qualitative risk assessment can be zero in many practical cases, because the intrinsic high error rate of such systems makes their results untrustworthy.  However, augmenting or replacing purely qualitative ratings with simple, robust quantitative variables and rating functions usually resolves these problems, even when the inputs are only imprecisely known.

How Should Combat Plans Be Updated as Situations Change?

In 2004, Cox Associates helped Systems View (www.systemsview.com) create and deliver to the US Air Force a new set of dynamic hierarchical planning and decision algorithms for adaptively allocating aircraft to bases and missions – and then intelligently re-allocating them as new information becomes available.  The new adaptive planning algorithms help combat planners hedge their bets against risks while exploiting newly perceived opportunities and defending against new threats from intelligent adversaries who are also dynamically re-planning.  These planning algorithms, based on a combination of artificial intelligence techniques and mathematical optimization heuristics, have potential applications in many settings where limited resources must be allocated among multiple regions over time while both the current situation in different locations and intelligence about them are evolving.

 A Simpler Approach To Dynamic Risk Management

In April, 2004, Cox Associates researchers completed an internal R&D effort to develop a computationally practical, radically simplified approach to making effective current planning decisions – e.g., about inventory, capacity additions, or infrastructure investments – when the future is highly uncertain, e.g., due to uncertain future demands, technology options, costs, and competition.  Development and computational implementation of the new approach, led by Dr. Djangir Babayev of Cox Associates, is based on the insight that using a detailed simulation model to generate random samples of future scenarios and then solving for the best current action for each scenario using commercial-quality deterministic solvers can, when combined with risk analysis methods, identify the best current action to take while hedging against realistic uncertainties about which future scenarios will turn out to be true.  Unlike earlier scenario-based and stochastic optimization approaches, the new one does not require prior identification of the scenarios to be considered (they are generated via simulation and may be hard to envision or anticipate intuitively), has nice mathematical properties (guaranteeing that approximately optimal current actions and contingency plans will be discovered with high probability), and is computationally much less demanding (since it exploits sampling to overcome the need for explicit combinatorial optimization.)   The new approach has the potential to allow existing deterministic solvers for complex planning problems to be re-used to solve new versions of the problems in which future uncertainties are taken into account.  This capability will be featured in future planning software tools from Cox Associates to allow our customers to optimize current decisions while hedging against future risks.

Society For Risk Analysis Best Paper Award, 2003

In December of 2003, a paper on " Bayesian Monte Carlo uncertainty analysis of human health risks from animal antimicrobial use in a dynamic model of emerging resistance", by Drs. Tony Cox and Doug Popken of Cox Associates, received a Society for Risk Analysis Best Paper Award at the Society for Risk Analysis Annual Conference, Baltimore, MD. December 7-10, 2003 (http://www.birenheide.com/sra/2003AM/program/singlesession.php3?sessid=M21&order=2#2). This paper presented the results of a statistical uncertainty analysis of a simulation model showing how allowing for realistic uncertainties in model parameters leads to the conclusion that a long record of past use of an animal drug (virginiamycin) without substantial endemic of human resistance implies that the underlying parameter values in the model must be such that future emergence of an epidemic of resistance is extremely unlikely.

Nonlinear Breakdown of Hematopoiesis

In September of 2003, Cox Associates delivered to the American Chemistry Council a new biomathematical simulation model of the effects of mixtures of volatile organic compounds (including benezene) on hematotoxicity and cancer risk.  This model integrates an MVK-type stochastic two-stage model of carcinogenesis with a detailed pharmacodynamic model of hematopoietic stem cell kinetics in the presence of hematotoxic cell-killing.  A dramatic and unexpected finding is that the simulated hematopoietic system exhibits catastrophic failure modes, leading to an abrupt transition from relatively low cancer risks to relatively high ones, as any of three exposure parameters – dose rate (ppm-hours per day of exposure) or days per week of exposure or number of weeks of exposure – passes a threshold (whose value depends on the remaining two exposure parameters).  Such bifurcation of risk as a function of exposure parameters has potentially profound consequences for how exposure-reponse data should be summarized and analyzed.  It implies that traditional dose-response relations (e.g., with ppm-years on the x-axis and probability of cancer on the y-axis) contain inherent ambiguities, as the aggregate exposure can correspond to risks that differ by an order of magnitude depending on the detailed time pattern of dosing.  (http://www.birenheide.com/sra/2003AM/program/singlesession.php3?sessid=WRT2&order=3#3 )

Risk Assessment And The Future Of Animal Antibiotics

In September of 2003, Tony Cox presented an invited talk on the future of antibiotic use at the Seventh Discover Conference on Food Animal Agriculture (http://www.adsa.org/discover/7thDISCOVERProg4-8-03_files/INTERPRETIVE%20SUMMARIES/Cox%20abstract.htm). This talk introduced the Rapid Risk Rating Technique (RRRT) and applied it to show that (a)  Human health risks from continued use of common animal antibiotics such as macrolides are typically on the order of less than 1 excess case per year; and (b)  Human health benefits from continued use of common animal antibiotics are typically on the order of more than 1000 cases per year prevented.  If these calculations are even approximately correct, then current regulatory concerns and efforts to restrict animal antibiotic use may, paradoxically, cause much more human health harm than they could possibly prevent, increasing the need to use human antibiotics and hastening the development of resistance.  This highlights the importance of using sound, data-driven, quantitative risk assessment, rather than qualitative concerns and good intentions, to inform public policy.

Selected Recent Papers and Presentations

Cox LA Jr. and D Babayev.  Networked facilities expansion problem.  International Journal of Information Technology and Decision-Making 2006, June; 5(2), in press. http://www.worldscinet.com/ijitdm/ijitdm.shtml

Cox LA Jr. Universality of J-Shaped and U-Shaped dose-response relations as emergent properties of stochastic transition systems.  Nonlinearity in Biology, Toxicology and Medicine 2006 3(3), in press.

Cox LA Jr, Wong C.  State transition model for customer relationship management.  Direct Marketing Association Analytics.  April, 2006, in press.

Bier V, Cox LA Jr.  Probabilistic Risk Analysis for Engineered Systems, in Advances in Decision Analysis. W. Edwards, D. von Winterfeldt and R. Miles, Eds. Cambridge University Press, 2006, in press.

Cox LA Jr. Health Risk Analysis for Risk Management Decision-Making. Advances in Decision Analysis. W. Edwards, D. von Winterfeldt and R. Miles, Eds. Cambridge University Press, 2006, in press.

Cox LA Jr., Popken DA. Quantifying potential human health impacts of animal antibiotic use:  Enrofloxacin  and macrolides in chickens.  Risk Analysis 2006 26(1), forthcoming.

Cox LA Jr.  Some limitations of a proposed linear model for antimicrobial risk management.  Risk Analysis. 2005 Dec; 25(6): 1327-1332.

http://www.blackwell-synergy.com/doi/abs/10.1111/j.1539-6924.2005.00703.x

Cox LA, Babayev D. Optimization under uncertainty via random sampling of scenarios II.  Applied and Computational Mathematics, 2005;4(1): 20-28

Cox LA Jr., VanSickle JJ, Popken DA, Sahu R.  Optimal tracking and testing of US and Canadian herds for BSE:  A Value-of-Information (VoI) approach.  Risk Analysis, 2005;  25(4): 827-840.  http://www.blackwell-synergy.com/doi/abs/10.1111/j.1539-6924.2005.00648.x

Cox LA Jr, Babayev D, Huber W..  Some limitations of qualitative risk rating systems.  Risk Analysis, 2005 Jun;25(3):651-62

 http://www.blackwell-synergy.com/doi/abs/10.1111/j.1539-6924.2005.00615.x

Ricci PF, MacDonald TR, Cox LA Jr. Precautionary decision making: Analysis and results. Int. J. Risk Assessment and Management, 2005 6(2-4):237-270.

Cox LA Jr. Potential human health benefits of antibiotics used in food animals:  A case study of virginiamycin.  Environment International, 2005 May;31(4): 549-563.  doi:10.1016/j.envint.2004.10.012  

Cox LA Jr, Ricci PF..   Causation in risk assessment and management: Models, inference, biases, and a microbial risk-benefit case study. Environ Int. 2005 Apr;31(3):377-97.

Cox, LA Jr. Predicting and optimizing customer behaviors.  Chapter 12 in A. Labbi (Ed.), Handbook of Integrated Risk Management for E-Business:  Measuring, Modeling, and Managing Risk.  J. Ross Publishng.  February, 2005.  http://www.jrosspub.com/Engine/Shopping/catalog.asp?store=12&category=351&item=2813

Popken, DA and LA Cox.  A simulation-optimization approach to air warfare planning.  Journal of Defense Modeling and Simulation, 1(3), 127-140.  December, 2004., http://www.scs.org/pubs/jdms/vol1number3/Popken.pdf

Cox, LA Jr.  BSE Update.  Invited presentation, R-CALF Annual National Convention.  January 19, 2005  Red Lion Hotel, Denver CO.

http://www.lmaweb.com/infonewspast.html , http://www.hpj.com/bsetimeline.cfm

Cox, LA Jr.  Dynamics of u-shaped and n-shaped dose-response in a simple model of cytotoxicity-mediated carcinogenesis.  Poster presented at the Fourth Annual International Conference on Hormesis:  Implications for Toxicology, Medicine, and Risk Assessment.  University of Massachusetts at Amherst.  Amherst, MA, June 8, 2005.   http://belleonline.com/BellePrelim_2005.pdf

Cox LA Jr., Approaches to Antimicrobial Risk Analysis in Food Safety Decision Making in Poultry Medicine.  Invited talk, 2005 AAAP/AVMA Annual Meeting.  Minneapolis Convention Center.  July 17^th, 2005. http://www.aaap.info/annlmtg/m2005/Symposium%20AAAP%202005.pdf

Cox LA Jr., Modeling Lung Carcinogenesis 1:  Genotoxic and epigenetic events in two-stage clonal expansion (TSCE) models.  Invited presentation, Philip Morris Research Laboratories Symposium on Genotoxic and Epigenetic Tumorigenesis. Crown Plaza Hotel.  Cologne, Germany. November 14-16, 2005

Cox LA Jr., Modeling Lung Carcinogenesis 2:  Toward a biologically based model of smoking and lung cancer .  Invited presentation, Philip Morris Research Laboratories Symposium on Genotoxic and Epigenetic Tomorigenesis. Crown Plaza Hotel.  Cologne, Germany. November 14-16, 2005

Cox LA Jr., What Fraction of Disease Can be Prevented by Removing Specific Exposures?  Presentation at the Society for Risk Analysis (SRA) Annual Meeting.  Orlando, Florida.  December 4-7^th, 2005. http://birenheide.com/sra/2005AM/program/singlesession.php3?sessid=M4

Risk analysis and public health – How to get from good intentions to good results: Animal antibiotics and other examples.  Invited talk, Café Scientifique.  Denver Colorado.  January 17^th, 2006.  http://cafescicolorado.org/Cox.htm#topic