Coverage-based quality metric of mutation operators for test suite improvement

The choice of mutation operators is a fundamental aspect in mutation testing to guide the tester to an effective test suite. Designing a set of mutation operators is subject to a trade-off between effectiveness and computational cost: a larger mutation population might uncover more faults, but will take longer to analyse. With the aim of resolving this trade-off, several authors have defined an assortment of metrics to determine the most valuable operators. In this work, we extend an existing quality metric by incorporating an additional source of data and coverage information and therefore investigate the extent to which mutants that are often covered but rarely killed can improve the evaluation of mutation operators for the refinement of the test suite. As a case study, we analyse C++ class-level operators based on the new coverage-based quality metric to assess whether the original metric is enhanced. The results when selecting the best-valued operators show that this metric has great potential to help the tester in finding effective mutation operators. In comparison with the metric from which it is derived, the use of coverage data allows to reduce the number of mutants but often loses fewer test cases and, in addition, retains those that seem hard to design

Reverse Engineering Time Discrete Finite Dynamical Systems: A Feasible Undertaking?

With the advent of high-throughput profiling methods, interest in reverse engineering the structure and dynamics of biochemical networks is high. Recently an algorithm for reverse engineering of biochemical networks was developed by Laubenbacher and Stigler. It is a top-down approach using time discrete dynamical systems. One of its key steps includes the choice of a term order, a technicality imposed by the use of Gröbner-bases calculations. The aim of this paper is to identify minimal requirements on data sets to be used with this algorithm and to characterize optimal data sets. We found minimal requirements on a data set based on how many terms the functions to be reverse engineered display. Furthermore, we identified optimal data sets, which we characterized using a geometric property called “general position”. Moreover, we developed a constructive method to generate optimal data sets, provided a codimensional condition is fulfilled. In addition, we present a generalization of their algorithm that does not depend on the choice of a term order. For this method we derived a formula for the probability of finding the correct model, provided the data set used is optimal. We analyzed the asymptotic behavior of the probability formula for a growing number of variables n (i.e. interacting chemicals). Unfortunately, this formula converges to zero as fast as , where and . Therefore, even if an optimal data set is used and the restrictions in using term orders are overcome, the reverse engineering problem remains unfeasible, unless prodigious amounts of data are available. Such large data sets are experimentally impossible to generate with today's technologies

Memory consolidation in the cerebellar cortex

Several forms of learning, including classical conditioning of the eyeblink, depend upon the cerebellum. In examining mechanisms of eyeblink conditioning in rabbits, reversible inactivations of the control circuitry have begun to dissociate aspects of cerebellar cortical and nuclear function in memory consolidation. It was previously shown that post-training cerebellar cortical, but not nuclear, inactivations with the GABA(A) agonist muscimol prevented consolidation but these findings left open the question as to how final memory storage was partitioned across cortical and nuclear levels. Memory consolidation might be essentially cortical and directly disturbed by actions of the muscimol, or it might be nuclear, and sensitive to the raised excitability of the nuclear neurons following the loss of cortical inhibition. To resolve this question, we simultaneously inactivated cerebellar cortical lobule HVI and the anterior interpositus nucleus of rabbits during the post-training period, so protecting the nuclei from disinhibitory effects of cortical inactivation. Consolidation was impaired by these simultaneous inactivations. Because direct application of muscimol to the nuclei alone has no impact upon consolidation, we can conclude that post-training, consolidation processes and memory storage for eyeblink conditioning have critical cerebellar cortical components. The findings are consistent with a recent model that suggests the distribution of learning-related plasticity across cortical and nuclear levels is task-dependent. There can be transfer to nuclear or brainstem levels for control of high-frequency responses but learning with lower frequency response components, such as in eyeblink conditioning, remains mainly dependent upon cortical memory storage

Using fractional exhaled nitric oxide (FeNO) to diagnose steroid-responsive disease and guide asthma management in routine care

Acknowledgements We thank Robin Taylor for his informative thinking and publications on FeNO, which have helped to influence and direct the thinking of the authors. Funding Extraction of the real-life dataset was funded by Research in Real Life Limited, the analysis of the dataset and the writing of this manuscript were co-funded (50:50) by Research in Real Life Limited and Aerocrine.Peer reviewedPublisher PD

Genetic and acquired factors influencing the effectiveness and toxicity of drug therapy in osteoporosis

Introduction: Osteoporosis is a highly prevalent skeletal disorder characterized by compromised bone strength, usually related to decreased bone mass and microstructural alterations of bone tissue, predisposing a person to an increased risk of fracture. As other prevalent disorders, osteoporosis is the result of a complex interplay of genetic and acquired factors. Areas covered: We provide an update of recent studies aimed at identifying the clinical and genetic factors that influence the response to drugs used to treat osteoporosis, as well as those determining the risk of two intriguing adverse effects of antiresorptives: osteonecrosis of the jaw (ONJ) and atypical femoral fractures (AFF). Expert opinion: Several clinical factors have been suggested to increase the risk of a poor drug response, such as advanced age and frailty. Candidate gene studies suggest that some common polymorphisms of the Wnt pathway and farnesyl diphosphate synthase (FDPS), the target enzyme for bisphosphonates, also influence the response to antiresorptives. However, they await for replication in large independent cohorts of patients. Similarly, some genetic and acquired factors may influence the risk of ONJ and AFF. Preliminary data suggest that the risk of suffering these adverse effects may have a polygenic basis

Enhancement of Water Transport and Microstructural Changes Induced by High-Intesity Ultrasound Application on Orange Peel Drying

The main aim of this work was to evaluate the effect of high-intensity ultrasound (US) on the drying kinetics of orange peel as well as its influence on the microstructural changes induced during drying. Convective drying kinetics of orange peel slabs were carried out at a relative humidity of 26.5±0.9%, 40 °C and 1 m/s with (AIR+US) and without (AIR) ultrasound application. In order to identify the US effect on water transport, drying kinetics were analyzed by taking the diffusion theory into account. Fresh, AIR and AIR+US dried samples were analyzed using Cryo-Scanning Electron Microscopy. Results showed that the drying kinetics of orange peel were significantly improved by US application, which involved a significant (p<0.05) improvement of mass transfer coefficient and effective moisture diffusivity. The effects on mass transfer properties were confirmed with microstructural observations. In the cuticle surface of flavedo, the pores were obstructed by the spread of the waxy components, this fact evidencing US effects on the air solid interfaces. Furthermore, the cells of the albedo were disrupted by US, as it created large intercellular air spaces facilitating water transfer through the tissue.The authors would like to acknowledge the financial support of MICINN and CEE (European Regional Development Fund) from projects Ref. DPI2009-14549-C04-04, PSE-060000-2009-003, and FP6-2004-FOOD-23140 HIGHQ RTE.García Pérez, JV.; Ortuño Cases, C.; Puig Gómez, CA.; Cárcel Carrión, JA.; Pérez Munuera, IM. (2012). Enhancement of Water Transport and Microstructural Changes Induced by High-Intesity Ultrasound Application on Orange Peel Drying. Food and Bioprocess Technology. 5(6):2256-2265. https://doi.org/10.1007/s11947-011-0645-0S2256226556Alandes, L., Perez-Munuera, I., Llorca, E., Quiles, A., & Hernando, I. (2009). 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Information content and reward processing in the human striatum during performance of a declarative memory task

Negative feedback can signal poor performance, but it also provides information that can help learners reach the goal of task mastery. The primary aim of this study was to test the hypothesis that the amount of information provided by negative feedback during a paired-associate learning task influences feedback-related processing in the caudate nucleus. To do this, we manipulated the number of response options: With two options, positive and negative feedback provide equal amounts of information, whereas with four options, positive feedback provides more information than does negative feedback. We found that positive and negative feedback activated the caudate similarly when there were two response options. With four options, the caudate’s response to negative feedback was reduced. A secondary goal was to investigate the link between brain-based measures of feedback-related processing and behavioral indices of learning. Analysis of the posttest measures showed that trials with positive feedback were associated with higher posttest confidence ratings. Additionally, when positive feedback was delivered, caudate activity was greater for trials with high than with low posttest confidence. This experiment demonstrated the context sensitivity of feedback processing and provided evidence that feedback processing in the striatum can contribute to the strengthening of the representations available within declarative memory

Resolving the Sources of Plasma Glucose Excursions following a Glucose Tolerance Test in the Rat with Deuterated Water and [U-13C]Glucose

Sources of plasma glucose excursions (PGE) following a glucose tolerance test enriched with [U-13C]glucose and deuterated water were directly resolved by 13C and 2H Nuclear Magnetic Resonance spectroscopy analysis of plasma glucose and water enrichments in rat. Plasma water 2H-enrichment attained isotopic steady-state within 2–4 minutes following the load. The fraction of PGE derived from endogenous sources was determined from the ratio of plasma glucose position 2 and plasma water 2H-enrichments. The fractional gluconeogenic contributions to PGE were obtained from plasma glucose positions 2 and 5 2H-positional enrichment ratios and load contributions were estimated from plasma [U-13C]glucose enrichments. At 15 minutes, the load contributed 26±5% of PGE while 14±2% originated from gluconeogenesis in healthy control rats. Between 15 and 120 minutes, the load contribution fell whereas the gluconeogenic contribution remained constant. High-fat fed animals had significant higher 120-minute blood glucose (173±6 mg/dL vs. 139±10 mg/dL, p<0.05) and gluconeogenic contributions to PGE (59±5 mg/dL vs. 38±3 mg/dL, p<0.01) relative to standard chow-fed controls. In summary, the endogenous and load components of PGE can be resolved during a glucose tolerance test and these measurements revealed that plasma glucose synthesis via gluconeogenesis remained active during the period immediately following a glucose load. In rats that were placed on high-fat diet, the development of glucose intolerance was associated with a significantly higher gluconeogenic contribution to plasma glucose levels after the load

Time-trend and variations in the proportion of second-eye cataract surgery

<p>Abstract</p> <p>Background</p> <p>Despite recommendations for greater use of second-eye cataract surgery and the bilateral progression of the disease, there is a substantial proportion of unmet need for this treatment. Few studies have explored the factors associated with second-eye cataract surgery utilisation. The objective of our study was to estimate the proportion of second-eye cataract surgery, evaluate its time-trend, and explore differences in utilisation by patients' gender, age, and region of residence.</p> <p>Methods</p> <p>All senile cataract surgeries performed between 1999 and 2002 in the public health system of Catalonia (Spain) were obtained from the Minimum Data Set. The proportion of second-eye surgery from November 2000 to December 2002 was calculated. The time-trend of this proportion was characterised through linear regression models with the logarithmic transformation of time.</p> <p>Results</p> <p>The proportion of second-eye surgery was 30.0% and showed an increasing trend from 24.8% (95% Confidence Interval [CI] 21.6; 26.1) in November 2000 to 31.8% (95% CI 31.4; 33.6) in December 2002. This proportion was 1.9% (95% CI 0.9; 2.9) higher in women (p < 0.001) and held constant across time. Male patients aged less than 60 had the lowest proportion (22.6%; 95% CI 22.4; 22.9) and females between 70 and 79 had the highest proportion (27.4%; 95% CI 26.9; 27.9). The time-trend for the proportion of second-eye surgery in those aged over 80 years was greater than for younger ages, showing an increase of 9% at the end of the period for both males and females. Variations between regions decreased over time because regions with the lowest initial proportions of second-eye surgery (approximately 17%) showed a greater increase over the study period.</p> <p>Conclusion</p> <p>We predict greater utilization of second-eye surgery in patients aged 70 to 79 years and in women. A greater increase in the utilisation rates of second-eye surgery is expected in the regions with lower proportions and in older patients. The observed trend suggests that there will be a substantial proportion of unmet need for bilateral surgery.</p