The long and winding road to inhaled TB therapy: not only the bug’s fault

Not all of the issues impacting the success of tuberculosis (TB) treatment arise from pathogen-related disease characteristics. Nowadays, there is an increasing awareness that antibiotic treatment is not the only answer to the TB problem, promoting the search for alternative administration strategies and host-directed therapies. Among all the administration routes, being the lungs the main TB focus, inhalation is conceptually a logical solution to enhance treatment effectiveness and compliance. Nevertheless, research efforts and funding are almost entirely conveyed to conventional approaches. This review will critically evaluate the reasons constraining research in this field, providing some future perspectives. The most recent advances in inhalation approaches for TB will be discussed, either at the preclinical or clinical phase, illustrating the risk of failure and chances of success.     

Energy performance of an exhibition hall in a life cycle perspective: embodied energy,operational energy and retrofit strategies

Nowadays, the focus on the building energy consumption in the use phase prevails over an interest concerning the energy impacts linked to all the other phases of the construction process. However, reducing operational energy could lead to shifting the impacts from one stage to another. Thus, combining the study of strategies improving energy efficiency in the use phase with a life cycle approach is crucial. Exhibition halls are peculiar buildings from the geometry, construction and use points of view, rarely addressed in energy and life cycle energy analysis studies. Therefore, in this paper, a representative hall of the Milan Trade Fair is taken as a case study. A building energy simulation model is firstly calibrated in order to derive the operational energy for climatisation. The operational energy appears artificially low due to the short use period during the year. When compared with the calculated embodied energy of the envelope and structure, it is found that 57 years would be needed to balance energy spent in the construction and in the use phase. Further, some retrofit interventions are proposed and analyzed. Insulation interventions are not attractive from the economic payback time point of view. However, when the embodied energy of the retrofit interventions is compared with the energy savings in the use phase, interesting energy payback times are obtained. Therefore, this study puts in evidence on the importance of adopting a life cycle perspective, especially for buildings with low-intensity use. Eventually, the critical issues of the life cycle energy analysis are deeply discussed.     

Gene regulatory networks reconstruction from time series datasets using genetic programming: a comparison between tree-based and graph-based approaches

Genetic programming researchers have shown a growing interest in the study of gene regulatory networks in the last few years. Our team has also contributed to the field, by defining two systems for the automatic reverse engineering of gene regulatory networks called GRNGen and GeNet. In this paper, we revise this work by describing in detail the two approaches and empirically comparing them. The results we report, and in particular the fact that GeNet can be used on large networks while GRNGen cannot, encourage us to pursue the study of GeNet in the future. We conclude the paper by discussing the main research directions that we are planning to investigate to improve GeNet.     

Dynamic test planning: a study in an industrial context

Testing accounts for a relevant part of the production cost of complex or critical software systems. Nevertheless, time and resources budgeted to testing are often underestimated with respect to the target quality goals. Test managers need engineering methods to perform appropriate choices in spending testing resources, so as to maximize the outcome. We present a method to dynamically allocate testing resources to software components minimizing the estimated number of residual defects and/or the estimated residual defect density. We discuss the application to a real-world critical system in the homeland security domain. We describe a support tool aimed at easing industrial technology transfer by hiding to practitioners the mathematical details of the method application.     

A comparison of two sampling methods for global sensitivity analysis

We compare the convergence properties of two different quasi-random sampling designs – Sobol?s quasi-Monte Carlo, and Latin supercube sampling in variance-based global sensitivity analysis. We use the non-monotonic V-function of Sobol? as base case-study, and compare the performance of both sampling strategies at increasing sample size and dimensionality against analytical values. The results indicate that in almost all cases investigated here, the Sobol? design performs better. This, coupled with the fact that effective Latin supercube sampling requires a priori knowledge of the interaction properties of the function, leads us to recommend Sobol? sampling in most practical cases.     

Operator precedence and the visibly pushdown property

Floyd?s operator precedence grammars and languages (FG, FL) are a classical subclass of deterministic context-free (DCF) grammars and languages. We prove that several recently introduced language families motivated by the needs of model checking and of specifying XML-like languages are proper subsets of FL. The main cases considered include visibly pushdown languages (VPL) and balanced languages (BALAN), which are characterized by restricted precedence relations. FL have all the closure properties available for regular languages and generally viewed as necessary for application to model checking: reversal, prefixing and suffixing, concatenation, Kleene star, and boolean operations. All but the last results are new, and some require complex proofs, due to the necessary changes of syntax structure. Thus FL are the largest known subfamily of DCF having the same closure properties as VPL. FG, unlike VPL grammars, which are intended for abstract syntax modelling, are structurally adequate to specify real programming languages.     

A comprehensive meta-analysis on evidence of Mediterranean diet and cardiovascular disease: Are individual components equal?

Many studies have reported that higher adherence to Mediterranean diet may decrease cardiovascular disease (CVD) incidence and mortality. We performed a meta-analysis to explore the association in prospective studies and randomized control trials (RCTs) between Mediterranean diet adherence and CVD incidence and mortality. The PubMed database was searched up to June 2014. A total of 17 studies were extracted and 11 qualified for the quantitative analysis. Individuals in the highest quantile of adherence to the diet had lower incidence [relative risk (RR): 0.76, 95% confidence intervals (CI): 0.68, 0.83] and mortality (RR: 0.76, 95% CI: 0.68, 0.83) from CVD compared to those least adherent. A significant reduction of risk was found also for coronary heart disease (CHD) (RR: 0.72, 95% CI: 0.60, 0.86), myocardial infarction (MI) (RR: 0.67; 95% CI: 0.54, 0.83), and stroke (RR: 0.76; 95% CI: 0.60, 0.96) incidence. Pooled analyses of individual components of the diet revealed that the protective effects of the diet appear to be most attributable to olive oil, fruits, vegetables, and legumes. An average reduced risk of 40% for the aforementioned outcomes has been retrieved when pooling results of RCTs. A Mediterranean dietary pattern is associated with lower risks of CVD incidence and mortality, including CHD and MI. The relative effects of specific food groups should be further investigated.     

Evaluation of log‐of‐power extremum seeking control for wind turbines using large eddy simulations

The extremum seeking control (ESC) algorithm has been proposed to determine operating parameters that maximize power production below rated wind speeds (region II). This is usually done by measuring the turbine's power signal to determine optimal values for parameters of the control law or actuator settings. This paper shows that the standard ESC with power feedback is quite sensitive to variations in mean wind speed, with long convergence time at low wind speeds and aggressive transient response, possibly unstable, at high wind speeds. The paper also evaluates the performance, as measured by the dynamic and steady state response, of the ESC with feedback of the logarithm of the power signal (LP‐ESC). Large eddy simulations (LES) demonstrate that the LP‐ESC, calibrated at a given wind speed, exhibits consistent robust performance at all wind speeds in a typical region II. The LP‐ESC is able to achieve the optimal set‐point within a prescribed settling time, despite variations in the mean wind speed, turbulence, and shear. The LES have been conducted using realistic wind input profiles with shear and turbulence. The ESC and LP‐ESC are implemented in the LES without assuming the availability of analytical gradients.