A Survey on Metamorphic Testing

A test oracle determines whether a test execution reveals a fault, often by comparing the observed program output to the expected output. This is not always practical, for example when a program's input-output relation is complex and difficult to capture formally. Metamorphic testing provides an alternative, where correctness is not determined by checking an individual concrete output, but by applying a transformation to a test input and observing how the program output “morphs” into a different one as a result. Since the introduction of such metamorphic relations in 1998, many contributions on metamorphic testing have been made, and the technique has seen successful applications in a variety of domains, ranging from web services to computer graphics. This article provides a comprehensive survey on metamorphic testing: It summarises the research results and application areas, and analyses common practice in empirical studies of metamorphic testing as well as the main open challenges

Moving on up: Second-Line Agents as Initial Treatment for Newly-Diagnosed Patients with Chronic Phase CML

The treatment of chronic myelogenous leukemia (CML) was revolutionized by the development of imatinib mesylate, a small molecule inhibitor of several protein tyrosine kinases, including the ABL1 protein tyrosine kinase. The current second generation of FDA-approved ABL tyrosine kinase inhibitors, dasatinib and nilotinib, are more potent inhibitors of BCR-ABL1 kinase in vitro. Originally approved for the treatment of patients who were refractory to or intolerant of imatinib, dasatinib and nilotinib are now also FDA approved in the first-line setting. The choice of tyrosine kinase inhibitor (ie, standard or high dose imatinib, dasatinib, nilotinib) to use for initial therapy in chronic-phase CML (CML-CP) will not always be obvious. Therapy selection will depend on both clinical and molecular factors, which we will discuss in this review

Sensitivity analysis in optimized parametric curve fitting

Purpose – Curve fitting from unordered noisy point samples is needed for surface reconstruction in many applications -- In the literature, several approaches have been proposed to solve this problem -- However, previous works lack formal characterization of the curve fitting problem and assessment on the effect of several parameters (i.e. scalars that remain constant in the optimization problem), such as control points number (m), curve degree (b), knot vector composition (U), norm degree (k), and point sample size (r) on the optimized curve reconstruction measured by a penalty function (f) -- The paper aims to discuss these issues -- Design/methodology/approach - A numerical sensitivity analysis of the effect of m, b, k and r on f and a characterization of the fitting procedure from the mathematical viewpoint are performed -- Also, the spectral (frequency) analysis of the derivative of the angle of the fitted curve with respect to u as a means to detect spurious curls and peaks is explored -- Findings - It is more effective to find optimum values for m than k or b in order to obtain good results because the topological faithfulness of the resulting curve strongly depends on m -- Furthermore, when an exaggerate number of control points is used the resulting curve presents spurious curls and peaks -- The authors were able to detect the presence of such spurious features with spectral analysis -- Also, the authors found that the method for curve fitting is robust to significant decimation of the point sample -- Research limitations/implications - The authors have addressed important voids of previous works in this field -- The authors determined, among the curve fitting parameters m, b and k, which of them influenced the most the results and how -- Also, the authors performed a characterization of the curve fitting problem from the optimization perspective -- And finally, the authors devised a method to detect spurious features in the fitting curve -- Practical implications – This paper provides a methodology to select the important tuning parameters in a formal manner -- Originality/value - Up to the best of the knowledge, no previous work has been conducted in the formal mathematical evaluation of the sensitivity of the goodness of the curve fit with respect to different possible tuning parameters (curve degree, number of control points, norm degree, etc.

Variability in concentrations of potentially toxic elements in urban parks from six European cities

Use of a harmonised sampling regime has allowed comparison of concentrations of copper, chromium, nickel, lead and zinc in six urban parks located in different European cities differing markedly in their climate and industrial history. Wide concentrations ranges were found for copper, lead and zinc at most sites, but for chromium and nickel a wide range was only seen in the Italian park, where levels were also considerably greater than in other soils. As might be expected, the soils from older cities with a legacy of heavy manufacturing industry (Glasgow, Torino) were richest in potentially toxic elements (PTEs); soils from Ljubljana, Sevilla and Uppsala had intermediate metal contents, and soils from the most recently established park, in the least industrialised city (Aveiro), displayed lowest concentrations. When principal component analysis was applied to the data, associations were revealed between pH and organic carbon content; and between all five PTEs. When pH and organic carbon content were excluded from the PCA, a distinction became clear between copper, lead and zinc (the "urban" metals) on the one hand, and chromium and nickel on the other. Similar results were obtained for the surface (0-10 cm depth) and sub-surface (10-20 cm depth) samples. Comparisons with target or limit concentrations were limited by the existence of different legislation in different countries and the fact that few guidelines deal specifically with public-access urban soils intended for recreational use

Birth elicits a conserved neuroendocrine response with implications for perinatal osmoregulation and neuronal cell death

Long-standing clinical findings report a dramatic surge of vasopressin in umbilical cord blood of the human neonate, but the neural underpinnings and function(s) of this phenomenon remain obscure. We studied neural activation in perinatal mice and rats, and found that birth triggers activation of the suprachiasmatic, supraoptic, and paraventricular nuclei of the hypothalamus. This was seen whether mice were born vaginally or via Cesarean section (C-section), and when birth timing was experimentally manipulated. Neuronal phenotyping showed that the activated neurons were predominantly vasopressinergic, and vasopressin mRNA increased fivefold in the hypothalamus during the 2–3 days before birth. Copeptin, a surrogate marker of vasopressin, was elevated 30-to 50-fold in plasma of perinatal mice, with higher levels after a vaginal than a C-section birth. We also found an acute decrease in plasma osmolality after a vaginal, but not C-section birth, suggesting that the difference in vasopressin release between birth modes is functionally meaningful. When vasopressin was administered centrally to newborns, we found an ~ 50% reduction in neuronal cell death in specific brain areas. Collectively, our results identify a conserved neuroendocrine response to birth that is sensitive to birth mode, and influences peripheral physiology and neurodevelopment.Fil: Hoffiz, Yarely C.. Georgia State University; Estados UnidosFil: Castillo Ruiz, Alexandra. Georgia State University; Estados UnidosFil: Hall, Megan A. L.. Georgia State University; Estados UnidosFil: Hite, Taylor A.. Georgia State University; Estados UnidosFil: Gray, Jennifer M.. Georgia State University; Estados UnidosFil: Cisternas, Carla Daniela. Georgia State University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Cortes, Laura R.. Georgia State University; Estados UnidosFil: Jacobs, Andrew J.. Georgia State University; Estados UnidosFil: Forger, Nancy G.. Georgia State University; Estados Unido

Association between PTPN1 polymorphisms and obesity-related phenotypes in European adolescents: influence of physical activity

Background: To study the associations of Protein Tyrosine Phosphatase-N1 (PTPN1) polymorphisms with obesity-related phenotypes in European adolescents, and the influence of physical activity on these relationships. Methods: Five polymorphisms of PTPN1 were genotyped in 1057 European adolescents (12–18 years old). We measured several phenotypes related to obesity, such as adiposity markers, and biochemical and clinical parameters. Physical activity was objectively measured by accelerometry. Results: The T, A, T, T and G alleles of the rs6067472, rs10485614, rs2143511, rs6020608 and rs968701 polymorphisms, respectively, were associated with lower levels of obesity-related phenotypes (i.e., body mass index, body fat percentage, hip circumference, fat mass index, systolic blood pressure and leptin) in European adolescents. In addition, the TATTG haplotype was associated with lower body fat percentage and fat mass index compared to the AACCA haplotype. Finally, when physical activity levels were considered, alleles of the rs6067472, rs2143511, rs6020608 and rs968701 polymorphisms were only associated with lower adiposity in active adolescents. Conclusions: PTPN1 polymorphisms were associated with adiposity in European adolescents. Specifically, alleles of these polymorphisms were associated with lower adiposity only in physically active adolescents. Therefore, meeting the recommendations of daily physical activity may reduce obesity risk by modulating the genetic predisposition to obesity. Impact: - Using gene-phenotype and gene*environment analyses, we detected associations between polymorphisms of the Protein Tyrosine Phosphatase-N1 (PTPN1) gene and obesity-related phenotypes, suggesting a mechanism that can be modulated by physical activity. - This study shows that genetic variability of PTPN1 is associated with adiposity, while physical activity seems to modulate the genetic predisposition. - This brings insights about the mechanisms by which physical activity positively influences obesity

Estimation of the real population and its impact on the utilisation of healthcare services in Mediterranean resort regions: an ecological study

BACKGROUND: The demographic structure has a significant influence on the use of healthcare services, as does the size of the population denominators. Very few studies have been published on methods for estimating the real population such as tourist resorts. The lack of information about these problems means there is a corresponding lack of information about the behaviour of populational denominators (the floating population or tourist load) and the effect of this on the use of healthcare services. The objectives of the study were: a) To determine the Municipal Solid Waste (MSW) ratio, per person per day, among populations of known size; b) to estimate, by means of this ratio, the real population in an area where tourist numbers are very significant; and c) to determine the impact on the utilisation of hospital emergency healthcare services of the registered population, in comparison to the non-resident population, in two areas where tourist numbers are very significant. METHODS: An ecological study design was employed. We analysed the Healthcare Districts of the Costa del Sol and the island of Menorca. Both are Spanish territories in the Mediterranean region. RESULTS: In the two areas analysed, the correlation coefficient between the MSW ratio and admissions to hospital emergency departments exceeded 0.9, with p < 0.001. On the basis of MSW generation ratios, obtained for a control zone and also measured in neighbouring countries, we estimated the real population. For the summer months, when tourist activity is greatest and demand for emergency healthcare at hospitals is highest, this value was found to be double that of the registered population. CONCLUSION: The MSW indicator, which is both ecological and indirect, can be used to estimate the real population in areas where population levels vary significantly during the year. This parameter is of interest in planning and dimensioning the provision of healthcare services

Deliverable D2:Consolidation of needs of the european wasten management agencies and the regulator of the consortium: Work Package 1, Site-specific and palaeo environmental data. Modelling sequential biosphere systems under climate change for radioactive waste disposal. (BIOCLIM)

The nature of long-lived radioactive wastes is that they present a radiological hazard over a period of time that is extremely long compared with the timescale over which the engineered protection systems and institutional management of a disposal, or long-term storage, facility can be guaranteed. Safety assessments for potential deep repositories need to be able to provide indicators of safety performance over time periods of hundreds of thousands of years. On such timescales, it is generally assumed that radionuclides may be slowly released from the containment system, migrating via geosphere pathways until they reach the accessible environment. Hence, there is a need to study the evolution of the environment external to the disposal system and the ways in which this might impact on its long-term radiological safety performance, for example in terms of influences on the migration and accumulation of radionuclides

Deliverable D3: Global climatic features over the next million years and recommendation for specific situations to be considered. Work Package 2, Simulation of the future evolution of the biosphere system using the hierarchical strategy. Modelling Sequential Biosphere Systems under Climate Change for Radioactive Waste Disposal (BIOCLIM)

The BIOCLIM project aims at assessing the possible long-term impacts of climate change on the safety of waste repositories in deep formations using climate simulations of the long-term climate in various European areas. One of the objectives of the project is to develop two strategies for representing sequential climatic changes to the geosphere-biosphere system for different sites over Europe, addressing the time scale of one million years. The results of this work will be interpreted in terms of global or regional changes of climate and of vegetation. The first strategy (hierarchical strategy) will use the full hierarchy of existing climate models (a climate model is a numerical simplified representation of the climate system behaviour and evolution). Simple models (LLN 2-D NH and threshold models; see the description here after) will simulate the overall long-term evolution of the global climate. Their results will then be used as inputs to more complex models (LMD climate models possibly coupled with vegetation models, either SECHIBA or ORCHIDE) and finally climate and vegetation cover will be determined for specific sites at specific times. A second strategy (integrated strategy) will consist in building an integrated climate model, which represents most of the physical mechanisms for studying long-term climatic variations. The results will then be interpreted on a regional scale. This deliverable is the first step of the hierarchical strategy. The purpose of this deliverable is to identify and justify some specific climatic situations amongst different long-term simulations that are of interest for assessing the safety of radioactive waste repository sites and that will be further studied with GCMs (General Circulation Model)

Deliverable D4/5: Global climatic characteristics, including vegetation and seasonal cycles over Europe, for snapshots over the next 200,000 years. Work Package 2, Simulation of the future evolution of the biosphere system using the hierarchical strategy. Modelling Sequential Biosphere Systems under Climate Change for Radioactive Waste Disposal (BIOCLIM)

The aim of the BIOCLIM project is to develop and present techniques that can be used to develop self-consistent patterns of possible future climate changes over the next million years (climate scenarios), and to demonstrate how these climate scenarios can be used in assessments of the long-term safety of nuclear waste repository sites. Within the project, two strategies are implemented to predict climate change. The first is the hierarchical strategy, in which a hierarchy of climate models is used to investigate the evolution of climate over the period of interest. These models vary from very simple 2-D and threshold models, which simulate interactions between only a few aspects of the earth system, through general circulation models (GCMs) and vegetation models, which simulate in great detail the dynamics and physics of the atmosphere, ocean, and biosphere, to regional models, which focus in particular on the European region and the specific areas of interest. The second strategy is the integrated strategy, in which intermediate complexity climate models are developed, and used to consecutively simulate the development of the earth system over many millennia. Although these models are relatively simple compared to a GCM, they are more advanced than 2D models, and do include physical descriptions of the biosphere, cryosphere, atmosphere and ocean. This deliverable, D4/5, focuses on the hierarchical strategy, and in particular the GCM and vegetation model simulation of possible future climates. Deliverable D3 documented the first step in this strategy. The Louvain-la-Neuve 2-D climate model (LLN-2D) was used to estimate (among other variables) annual mean temperatures and ice volume in the Northern Hemisphere over the next 1 million years. It was driven by the calculated evolution of orbital parameters, and plausible scenarios of CO2 concentration. From the results, 3 future time periods within the next 200,000 years were identified as being extreme, that is either significantly warmer or cooler than the present. The next stage in the hierarchical strategy was to use a GCM and biosphere model, to simulate in more detail these extreme time periods