Identifying quantitative operation principles in metabolic pathways: a systematic method for searching feasible enzyme activity patterns leading to cellular adaptive responses

Background: Optimization methods allow designing changes in a system so that specific goals are attained. These techniques are fundamental for metabolic engineering. However, they are not directly applicable for investigating the evolution of metabolic adaptation to environmental changes. Although biological systems have evolved by natural selection and result in well-adapted systems, we can hardly expect that actual metabolic processes are at the theoretical optimum that could result from an optimization analysis. More likely, natural systems are to be found in a feasible region compatible with global physiological requirements. Results: We first present a new method for globally optimizing nonlinear models of metabolic pathways that are based on the Generalized Mass Action (GMA) representation. The optimization task is posed as a nonconvex nonlinear programming (NLP) problem that is solved by an outer- approximation algorithm. This method relies on solving iteratively reduced NLP slave subproblems and mixed-integer linear programming (MILP) master problems that provide valid upper and lower bounds, respectively, on the global solution to the original NLP. The capabilities of this method are illustrated through its application to the anaerobic fermentation pathway in Saccharomyces cerevisiae. We next introduce a method to identify the feasibility parametric regions that allow a system to meet a set of physiological constraints that can be represented in mathematical terms through algebraic equations. This technique is based on applying the outer-approximation based algorithm iteratively over a reduced search space in order to identify regions that contain feasible solutions to the problem and discard others in which no feasible solution exists. As an example, we characterize the feasible enzyme activity changes that are compatible with an appropriate adaptive response of yeast Saccharomyces cerevisiae to heat shock Conclusion: Our results show the utility of the suggested approach for investigating the evolution of adaptive responses to environmental changes. The proposed method can be used in other important applications such as the evaluation of parameter changes that are compatible with health and disease states.

A Quantitative method for the characterization of lytic metastases of the bone from radiographic images

The aim of our study was to assess the diagnostic usefulness of the gray level parameters to distinguish osteolytic lesions using radiological images. Materials and Methods: A retrospective study was carried out. A total of 76 skeletal radiographs of osteolytic metastases and 67 radiographs of multiple myeloma were used. The cases were classified into nonflat (MM1 and OL1) and flat bones (MM2 and OL2). These radiological images were analyzed by using a computerized method. The parameters calculated were mean, standard deviation, and coefficient of variation (MGL, SDGL, and CVGL) based on gray level histogram analysis of a region-of-interest.Diagnostic utility was quantified bymeasurement of parameters on osteolyticmetastases andmultiplemyeloma, yielding quantification of area under the receiver operating characteristic (ROC) curve (AUC). Results: Flat bone groups (MM2 and OL2) showed significant differences in mean values of MGL ( = 0.048) and SDGL ( = 0.003). Their corresponding values of AUC were 0.758 for MGL and 0.883 for SDGL in flat bones. In nonflat bones these gray level parameters do not show diagnostic ability. Conclusion: The gray level parametersMGL and SDGL show a good discriminatory diagnostic ability to distinguish between multiple myeloma and lytic metastases in flat bones.

The use of mixed methods research in the behavioral sciences field

Mixed methods research involves the combined use of quantitative and qualitative methods in the same research study, and it is becoming increasingly important in several scientific areas. The aim of this paper is to review and compare through a mixed methods multiple-case study the application of this methodology in three reputable behavioural science journals: the Journal of Organizational Behavior, Addictive Behaviors and Psicothema. A quantitative analysis was carried out to review all the papers published in these journals during the period 2003-2008 and classify them into two blocks: theoretical and empirical, with the latter being further subdivided into three subtypes (quantitative, qualitative and mixed). A qualitative analysis determined the main characteristics of the mixed methods studies identified, in order to describe in more detail the ways in which the two methods are combined based on their purpose, priority, implementation and research design. From the journals selected, a total of 1.958 articles were analysed, the majority of which corresponded to empirical studies, with only a small number referring to research that used mixed methods. Nonetheless, mixed methods research does appear in all the behavioural science journals studied within the period selected, showing a range of designs, where the sequential equal weight mixed methods research design seems to stand out.

Implementing a Cancer Fast-track programme between primary and specialised care in Catalonia(Spain): amixed methods study

BACKGROUND: The Cancer Fast-track Programme's aim was to reduce the time that elapsed between well-founded suspicion of breast, colorectal and lung cancer and the start of initial treatment in Catalonia (Spain). We sought to analyse its implementation and overall effectiveness. METHODS: A quantitative analysis of the programme was performed using data generated by the hospitals on the basis of seven fast-track monitoring indicators for the period 2006-2009. In addition, we conducted a qualitative study, based on 83 semistructured interviews with primary and specialised health professionals and health administrators, to obtain their perception of the programme's implementation. RESULTS: About half of all new patients with breast, lung or colorectal cancer were diagnosed via the fast track, though the cancer detection rate declined across the period. Mean time from detection of suspected cancer in primary care to start of initial treatment was 32 days for breast, 30 for colorectal and 37 for lung cancer (2009). Professionals associated with the implementation of the programme showed that general practitioners faced with suspicion of cancer had changed their conduct with the aim of preventing lags. Furthermore, hospitals were found to have pursued three specific implementation strategies (top-down, consensus-based and participatory), which made for the cohesion and sustainability of the circuits. CONCLUSION: The programme has contributed to speeding up diagnostic assessment and treatment of patients with suspicion of cancer, and to clarifying the patient pathway between primary and specialised care.