Halting the hallmarks: a cellular automaton model of early cancer growth inhibition

Cancer treatment is a fragmented and varied process, as “cancer” is really hundreds of different diseases. The “hallmarks of cancer” proposed by Hanahan and Weinberg (Cell 100(1):57–70, 2000) are a framework for viewing cancer within a common set of underlying principles—ten properties that are common to almost all cancers, allowing them to grow uncontrollably and ravage the body. We used a cellular automaton model of tumour growth paired with lattice Boltzmann methods modelling oxygen flow to simulate combination drugs targeted at knocking out pairs of hallmarks. We found that knocking out some pairs of cancer-enabling hallmarks did not prevent tumour formation, while other pairs significantly prevent tumour growth (\(p=0.0004\) using Wilcoxon signed-rank adjusted with the Bonferroni correction for multiple comparisons). This is not what would be expected from models of knocking out the hallmarks individually, as many pairs did not have an additive effect but had either no statistically significant effect or a multiplicative one. We propose that targeting certain pairs of cancer hallmarks, specifically cancers ability to induce blood vessel development paired with another cancer hallmark, could prove an effective cancer treatment option.     

The design of a collision avoidance system for use by Pilots operating on the airport ramp and in taxiway areas

Ground collisions have serious implications from both a safety and a commercial perspective. This paper reports on human computer interaction (HCI) research related to the advancement of a collision avoidance system, for use by Pilots operating on the airport ramp and in taxiway areas. Primarily, this paper focuses on the key findings of this research and the emerging HCI design solution.     

Measuring team skills in crime scene investigation: exploring ad hoc teams

The purpose of this study was to measure the team skills of operational crime scene examiners (CSEs). The techniques used were based on established methods and helped to gain a greater understanding of the domain of forensic investigation. The research begins with a hierarchical task analysis and then adapts pre-established methods for measuring the performance of CSEs in four UK Police Forces. The process supports comparison between prescribed methods of 'good practice' and real world practice. This has allowed the identification of the distributed skills and tasks of the CSE. Using Annett et al.'s HTA(T), crime scene examination can be categorised and the communications and coordination structures occurring between teams investigating a burglary considered. This makes it possible to generalise the method to situations involving ad hoc teams.     

What is the best method of surgical training?: A report of America's leading senior surgeons

OBJECTIVES: To characterize the career choices and developments made by leading senior surgeons in this country and to examine hypothetically whether application of a short tracking program would have hindered their career decisions. DESIGN: A survey pertaining to each surgeon's career, decisions, and opinions concerning surgical training. SETTING AND PARTICIPANTS: Senior surgeons of regional and national surgical societies. MAIN OUTCOME MEASURE: Survey responses. RESULTS: A total of 352 surveys (41.4%) were received. Respondents answered that the most common reasons for choosing a specialty were role models or mentors (56%), research (51%), and available patient population (23%). The 2 most common stages in a career at which the respondents became interested in a specialty, or an area of expertise, were at the junior residency level (when the specialty was chosen) and at the assistant professor level (when a more specific topic within the specialty was chosen). The most common stage at which the group believed they acquired their expertise was also at the assistant professor level. Seventy-one percent of respondents believed broad training was superior to a short tracking system, although none had participated in shortened surgical training. CONCLUSIONS: Most leading senior surgeons in this country still believe that broad surgical training is superior and should be maintained. Because career specialties in this surveyed group were generally chosen in early residency, a hypothetical application of the short tracking system would have still allowed for these important decisions to be made. Also, it seems likely that specialty and career development would not have been hindered because "expertization" mostly occurred after training was completed. Regardless of training method, a role model or mentor seems most important in career choices and developments.     

Solid-state 2H NMR study of methyl-d3-cobalamin

A solid-state 2H NMR study of methyl-d3-cobalamin has been performed as a function of temperature to provide information concerning the character and energetics of the motion performed by this unique bioorganometallic methyl group. Analysis of the 2H NMR line shape indicates that the methyl group undergoes rapid three-fold rotation, and that the Co-C-2H angle lies between 105.9 and 109.5 degrees. Determination of the spin-lattice relaxation times T1 shows that the relaxation is anisotropic, consistent with a "jumping" motion of the methyl group rather than rotational diffusion. This also provides the activation energy to methyl jumps as 8.3 +/- 1.3 kJ/mol. It is proposed that this energetic barrier may be a useful probe of changes in the electronic character of the Co-C bond that accompany the biological role of this molecule in such enzymes as methionine synthase.     

Frequency analysis of river water quality using integrated urban wastewater models

In recent years integrated models have been developed to simulate the entire urban wastewater system, including urban drainage systems, wastewater treatment plants, and receiving waterbodies. This paper uses such an integrated urban wastewater model to analyze the frequency of receiving water quality in an urban wastewater system with the aim of assessing the overall system performance during rainfall events. The receiving water quality is represented by two indicators: event mean dissolved oxygen (DO) concentration and event mean ammonium concentration. The compliance probability of the water quality indicators satisfying a specific threshold is used to represent the system performance, and is derived using the rainfall events from a series of 10 years' rainfall data. A strong correlation between the depth of each rainfall event and the associated volume of combined sewer overflow (CSO) discharges is revealed for the case study catchment, while there is a low correlation between the intensity/duration of the rainfall event and the volume of the CSO discharges. The frequency analysis results obtained suggest that the event mean DO and ammonium concentrations have very different characteristics in terms of compliance probabilities at two discharging points for CSO and wastewater treatment plant effluent, respectively. In general, the simulation results provide an understanding of the performance of the integrated urban wastewater system and can provide useful information to support water quality management.     

Sustainable Disposal of Domestic Sanitary Waste

The study presented is an example of the assessment of the relative sustainability of either option for disposal of domestic sanitary waste, either via the toilet or via the solid waste route. This required an evaluation of the total (social, economic, environmental, and technical) benefit/cost of implementing and adopting the alternative routes and an assessment of public responsiveness to encouragement to change sanitary waste disposal practices. It illustrates how, even for an apparently straightforward either/or question, the assessment of relative sustainability is complex and the amount of data needed to quantify sustainability indicators is prodigious. The study also provides an appraisal of the effectiveness of public campaigns to reduce waterborne disposal. Important information regarding public attitude and behavior in relation to wastewater systems has been acquired and lessons for ways of encouraging behavioral change to more sustainable ways of living have been gleaned.     

Formal verification of conflict detection algorithms

Safety assessment of new air traffic management systems is a main issue for civil aviation authorities. Standard techniques such as testing and simulation have serious limitations in new systems that are significantly more autonomous than the older ones. In this paper, we present an innovative approach for establishing the correctness of conflict detection systems. Fundamental to our approach is the concept of trajectory, and how we represent a continuous physical trajectory by a continuous path in the x-y plane constrained by physical laws and operational requirements. From the model of trajectories, we extract, and formally prove, high-level properties that can serve as a framework to analyze conflict scenarios. We use the AILS (Airborne Information for Lateral Spacing) alerting algorithm as a case study of our approach. Published online: 19 November 2002