Study of PI3K/Akt signaling pathway as potential molecular target for T-cell acute lymphoblastic leukemia (T-ALL) treatment: pan-inhibition of PI3K catalitic isoforms as better therapeutic approach

Class I phosphatidylinositol 3-kinases (PI3Ks) are heterodimeric lipid kinases consisting of a regulatory subunit and one of four catalytic subunits (p110α, p110β, p110γ or p110δ). p110γ/p110δ PI3Ks are highly enriched in leukocytes. In general, PI3Ks regulate a variety of cellular processes including cell proliferation, survival and metabolism, by generating the second messenger phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3). Their activity is tightly regulated by the phosphatase and tensin homolog (PTEN) lipid phosphatase. PI3Ks are widely implicated in human cancers, and in particular are upregulated in T-cell acute lymphoblastic leukemia (T-ALL), mainly due to loss of PTEN function. These observations lend compelling weight to the application of PI3K inhibitors in the therapy of T-ALL. At present different compounds which target single or multiple PI3K isoforms have entered clinical trials. In the present research, it has been analyzed the therapeutic potential of the pan-PI3K inhibitor BKM120, an orally bioavailable 2,6-dimorpholino pyrimidine derivative, which has entered clinical trials for solid tumors, on both T-ALL cell lines and patient samples. BKM120 treatment resulted in cell cycle arrest and apoptosis, being cytotoxic to a panel of T-ALL cell lines and patient T-lymphoblasts. Remarkably, BKM120 synergized with chemotherapeutic agents currently used for treating T-ALL patients. BKM120 efficacy was confirmed in in vivo studies to a subcutaneous xenotransplant model of human T-ALL. Because it is still unclear which agents among isoform-specific or pan inhibitors can achieve the greater efficacy, further analyses have been conducted to investigate the effects of PI3K inhibition, in order to elucidate the mechanisms responsible for the proliferative impairment of T-ALL. Overall, these results indicated that BKM120 may be an efficient treatment for T-ALLs that have aberrant up-regulation of the PI3K signaling pathway and strongly support clinical application of pan-class I PI3K rather than single-isoform inhibitors in T-ALL treatment.

Assimilation of Meteosat Second Generation (MSG) satellite data in a regional numerical weather prediction model using a one-dimensional variational approach

The quality of temperature and humidity retrievals from the infrared SEVIRI sensors on the geostationary Meteosat Second Generation (MSG) satellites is assessed by means of a one dimensional variational algorithm. The study is performed with the aim of improving the spatial and temporal resolution of available observations to feed analysis systems designed for high resolution regional scale numerical weather prediction (NWP) models. The non-hydrostatic forecast model COSMO (COnsortium for Small scale MOdelling) in the ARPA-SIM operational configuration is used to provide background fields. Only clear sky observations over sea are processed. An optimised 1D–VAR set-up comprising of the two water vapour and the three window channels is selected. It maximises the reduction of errors in the model backgrounds while ensuring ease of operational implementation through accurate bias correction procedures and correct radiative transfer simulations. The 1D–VAR retrieval quality is firstly quantified in relative terms employing statistics to estimate the reduction in the background model errors. Additionally the absolute retrieval accuracy is assessed comparing the analysis with independent radiosonde and satellite observations. The inclusion of satellite data brings a substantial reduction in the warm and dry biases present in the forecast model. Moreover it is shown that the retrieval profiles generated by the 1D–VAR are well correlated with the radiosonde measurements. Subsequently the 1D–VAR technique is applied to two three–dimensional case–studies: a false alarm case–study occurred in Friuli–Venezia–Giulia on the 8th of July 2004 and a heavy precipitation case occurred in Emilia–Romagna region between 9th and 12th of April 2005. The impact of satellite data for these two events is evaluated in terms of increments in the integrated water vapour and saturation water vapour over the column, in the 2 meters temperature and specific humidity and in the surface temperature. To improve the 1D–VAR technique a method to calculate flow–dependent model error covariance matrices is also assessed. The approach employs members from an ensemble forecast system generated by perturbing physical parameterisation schemes inside the model. The improved set–up applied to the case of 8th of July 2004 shows a substantial neutral impact.

Innovative Homogeneous and Heterogeneous Systems for Electrochemically Generated Luminescence Investigations: Towards One-Dimensional ECL

My research PhD work is focused on the Electrochemically Generated Luminescence (ECL) investigation of several different homogeneous and heterogeneous systems. ECL is a redox induced emission, a process whereby species, generated at electrodes, undergo a high-energy electron transfer reaction to form excited states that emit light. Since its first application, the ECL technique has become a very powerful analytical tool and has widely been used in biosensor transduction. ECL presents an intrinsically low noise and high sensitivity; moreover, the electrochemical generation of the excited state prevents scattering of the light source: for all these characteristics, it is an elective technique for ultrasensitive immunoassay detection. The majority of ECL systems involve species in solution where the emission occurs in the diffusion layer near to the electrode surface. However, over the past few years, an intense research has been focused on the ECL generated from species constrained on the electrode surface. The aim of my work is to study the behavior of ECL-generating molecular systems upon the progressive increase of their spatial constraints, that is, passing from isolated species in solution, to fluorophores embedded within a polymeric film and, finally, to patterned surfaces bearing “one-dimensional” emitting spots. In order to describe these trends, I use different “dimensions” to indicate the different classes of compounds. My thesis was mostly developed in the electrochemistry group of Bologna with the supervision of Prof Francesco Paolucci and Dr Massimo Marcaccio. With their help and also thanks to their long experience in the molecular and supramolecular ECL fields and in the surface investigations using scanning probe microscopy techniques, I was able to obtain the results herein described. Moreover, during my research work, I have established a new collaboration with the group of Nanobiotechnology of Prof. Robert Forster (Dublin City University) where I spent a research period. Prof. Forster has a broad experience in the biomedical field, especially he focuses his research on film surfaces biosensor based on the ECL transduction. This thesis can be divided into three sections described as follows: (i) in the fist section, homogeneous molecular and supramolecular ECL-active systems, either organic or inorganic species (i.e., corannulene, dendrimers and iridium metal complex), are described. Driving force for this kind of studies includes the search for new luminophores that display on one hand higher ECL efficiencies and on the other simple mechanisms for modulating intensity and energy of their emission in view of their effective use in bioconjugation applications. (ii) in the second section, the investigation of some heterogeneous ECL systems is reported. Redox polymers comprising inorganic luminophores were described. In such a context, a new conducting platform, based on carbon nanotubes, was developed aimed to accomplish both the binding of a biological molecule and its electronic wiring to the electrode. This is an essential step for the ECL application in the field of biosensors. (iii) in the third section, different patterns were produced on the electrode surface using a Scanning Electrochemical Microscopy. I developed a new methods for locally functionalizing an inert surface and reacting this surface with a luminescent probe. In this way, I successfully obtained a locally ECL active platform for multi-array application.

Photo- and redox-active supramolecular systems containing metal complexes

The aim of this Ph.D. project has been the photophysical and photochemical characterization of new photo- and redox-active supramolecular systems. In particular we studied two different classes of compounds: metal complexes and dendrimers. Two different families of bis-cyclometalated neutral Ir(III) complexes are presented and their photophysical properties are discussed. The first family of complexes contains two 2-phenylpyridyl (ppy) or 2-(4,6-difluorophenyl)pyridyl (F2ppy) cyclometalated ligands and an ancillary ligand constituted by a phenol-oxazoline (phox), which can be substituted in the third position with a fluorine group (Fphox). In the second part of this study, we present another family of bis-cyclometalated Ir(III) complexes in which the ancillary ligand could be a chiral or an achiral bis-oxazoline (box). We report on their structural, electrochemical, photophysical, and photochemical properties. Complexes containing phox and Fphox ancillary ligands show blue luminescence with very high quantum yield, while complexes with box ligands do not show particularly interesting photophysical properties. Surprisingly these complexes give an unexpected photoreaction when irradiated with UV light in presence of dioxygen. This photoreaction originates a stable, strong blue emitting and particularly interesting photoproduct. Three successive generations of a family of polyethyleneglycol (PEG)-coated Pd(II) tetrabenzoporphyrin (PdTBP)-based dendritic nanoprobes are presented, and their ability to sensitize singlet oxygen and inflict cellular photodamage are discussed. It was found that the size of the dendrimer has practically no effect on the singlet oxygen sensitization efficiency, that approximate the unity, in spite of the strong attenuation of the triplet quenching rate with an increase in the dendrimer generation. Nevertheless, when compared against a commonly used singlet oxygen sensitizer, as Photofrin, the phosphorescent probes were found to be non-phototoxic. The lack of phototoxicity is presumably due to the inability of PEGylated probes to associate with cell surfaces and/or penetrate cellular membranes. The results suggest that protected phosphorescent probes can be safely used for oxygen measurements in biological systems in vivo. A new family of two photoswitchable (G0(Azo) and G1(Azo)) dendrimers with an azobenzene core, two cyclam units as coordination sites for metal ions, and luminescent naphthalene units at the periphery have been characterized and their coordination abilities have been studied. Because of their proximity, the various functional groups of the dendrimer may interact, so that the properties of the dendrimers are different from those exhibited by the separated functional units. Both the naphthalene fluorescence and the azobenzene photoisomerization can be observed in the dendrimer, but it has been shown that (i) the fluorescent excited state of the naphthalene units is substantially quenched by excimer and exciplex formation and by energy transfer to the azobenzene units, and (ii) in the latter case the fluorescence quenching is accompanied by the photosensitized isomerization of the trans → cis, and, with higher efficiency, the cis → trans reaction. Complexation of these dendrimers, both trans and cis isomers, with Zn(II) ions shows that complexes of 1:1 and 2:1 metal per dendrimer stoichiometry are formed showing different photophysical and photochemical properties compared to the corresponding free ligands. Practically unitary efficiency of the sensitized isomerization of trans → cis and cis → trans reaction is observed, as well as a slight increase in the naphthalene monomer emission. These results are consistent with the coordination of the cyclam amine units with Zn(II), which prevents exciplex formation. No indication of a concomitant coordination of both cyclam to a single metal ion has been obtained both for trans and cis isomer.

Optical Design for Automatic Identification and Portable Systems

This thesis proposes design methods and test tools, for optical systems, which may be used in an industrial environment, where not only precision and reliability but also ease of use is important. The approach to the problem has been conceived to be as general as possible, although in the present work, the design of a portable device for automatic identification applications has been studied, because this doctorate has been funded by Datalogic Scanning Group s.r.l., a world-class producer of barcode readers. The main functional components of the complete device are: electro-optical imaging, illumination and pattern generator systems. For what concerns the electro-optical imaging system, a characterization tool and an analysis one has been developed to check if the desired performance of the system has been achieved. Moreover, two design tools for optimizing the imaging system have been implemented. The first optimizes just the core of the system, the optical part, improving its performance ignoring all other contributions and generating a good starting point for the optimization of the whole complex system. The second tool optimizes the system taking into account its behavior with a model as near as possible to reality including optics, electronics and detection. For what concerns the illumination and the pattern generator systems, two tools have been implemented. The first allows the design of free-form lenses described by an arbitrary analytical function exited by an incoherent source and is able to provide custom illumination conditions for all kind of applications. The second tool consists of a new method to design Diffractive Optical Elements excited by a coherent source for large pattern angles using the Iterative Fourier Transform Algorithm. Validation of the design tools has been obtained, whenever possible, comparing the performance of the designed systems with those of fabricated prototypes. In other cases simulations have been used.

Innovative architecture of on-board and on-ground radio systems for space communication

The radio communication system is one of the most critical system of the overall satellite platform: it often represents the only way of communication, between a spacecraft and the Ground Segment or among a constellation of satellites. This thesis focuses on specific innovative architectures for on-board and on-ground radio systems. In particular, this work is an integral part of a space program started in 2004 at the University of Bologna, Forlì campus, which led to the completion of the microsatellite ALMASat-1, successfully launched on-board the VEGA maiden flight. The success of this program led to the development of a second microsatellite, named ALMASat-EO, a three-axis stabilized microsatellite able to capture images of the Earth surface. Therefore, the first objective of this study was focused on the investigation of an innovative, efficient and low cost architecture for on-board radio communication systems. The TT&C system and the high data rate transmitter for images downlink design and realization are thoroughly described in this work, together with the development of the embedded hardware and the adopted antenna systems. Moreover, considering the increasing interest in the development of constellations of microsatellite, in particular those flying in close formations, a careful analysis has been carried out for the development of innovative communication protocols for inter-satellite links. Furthermore, in order to investigate the system aspects of space communications, a study has been carried out at ESOC having as objective the design, implementation and test of two experimental devices for the enhancement of the ESA GS. Thus, a significant portion of this thesis is dedicated to the description of the results of a method for improving the phase stability of GS radio frequency equipments by means of real-time phase compensation and a new way to perform two antennas arraying tracking using already existing ESA tracking stations facilities.

Quantum Correlations in Field Theory and Integrable Systems

In this thesis we will investigate some properties of one-dimensional quantum systems. From a theoretical point of view quantum models in one dimension are particularly interesting because they are strongly interacting, since particles cannot avoid each other in their motion, and you we can never ignore collisions. Yet, integrable models often generate new and non-trivial solutions, which could not be found perturbatively. In this dissertation we shall focus on two important aspects of integrable one- dimensional models: Their entanglement properties at equilibrium and their dynamical correlators after a quantum quench. The first part of the thesis will be therefore devoted to the study of the entanglement entropy in one- dimensional integrable systems, with a special focus on the XYZ spin-1/2 chain, which, in addition to being integrable, is also an interacting model. We will derive its Renyi entropies in the thermodynamic limit and its behaviour in different phases and for different values of the mass-gap will be analysed. In the second part of the thesis we will instead study the dynamics of correlators after a quantum quench , which represent a powerful tool to measure how perturbations and signals propagate through a quantum chain. The emphasis will be on the Transverse Field Ising Chain and the O(3) non-linear sigma model, which will be both studied by means of a semi-classical approach. Moreover in the last chapter we will demonstrate a general result about the dynamics of correlation functions of local observables after a quantum quench in integrable systems. In particular we will show that if there are not long-range interactions in the final Hamiltonian, then the dynamics of the model (non equal- time correlations) is described by the same statistical ensemble that describes its statical properties (equal-time correlations).

Modeling and simulations of some anisotropic soft-matter systems: from biaxial to chiral materials

We have modeled various soft-matter systems with molecular dynamics (MD) simulations. The first topic concerns liquid crystal (LC) biaxial nematic (Nb) phases, that can be possibly used in fast displays. We have investigated the phase organization of biaxial Gay-Berne (GB) mesogens, considering the effects of the orientation, strength and position of a molecular dipole. We have observed that for systems with a central dipole, nematic biaxial phases disappear when increasing dipole strength, while for systems characterized by an offset dipole, the Nb phase is stabilized at very low temperatures. In a second project, in view of their increasing importance as nanomaterials in LC phases, we are developing a DNA coarse-grained (CG) model, in which sugar and phosphate groups are represented with Lennard-Jones spheres, while bases with GB ellipsoids. We have obtained shape, position and orientation parameters for each bead, to best reproduce the atomistic structure of a B-DNA helix. Starting from atomistic simulations results, we have completed a first parametrization of the force field terms, accounting for bonded (bonds, angles and dihedrals) and non-bonded interactions (H-bond and stacking). We are currently validating the model, by investigating stability and melting temperature of various sequences. Finally, in a third project, we aim to explain the mechanism of enantiomeric discrimination due to the presence of a chiral helix of poly(gamma-benzyl L-glutamate) (PBLG), in solution of dimethylformamide (DMF), interacting with chiral or pro-chiral molecules (in our case heptyl butyrate, HEP), after tuning properly an atomistic force field (AMBER). We have observed that DMF and HEP molecules solvate uniformly the PBLG helix, but the pro-chiral solute is on average found closer to the helix with respect to the DMF. The solvent presents a faster isotropic diffusion, twice as HEP, also indicating a stronger interaction of the solute with the helix.

Antipodal random sequences with prescribed second-order statistics: application to Compressive Sensing and UWB system based on DS-CDMA

It is usual to hear a strange short sentence: «Random is better than...». Why is randomness a good solution to a certain engineering problem? There are many possible answers, and all of them are related to the considered topic. In this thesis I will discuss about two crucial topics that take advantage by randomizing some waveforms involved in signals manipulations. In particular, advantages are guaranteed by shaping the second order statistic of antipodal sequences involved in an intermediate signal processing stages. The first topic is in the area of analog-to-digital conversion, and it is named Compressive Sensing (CS). CS is a novel paradigm in signal processing that tries to merge signal acquisition and compression at the same time. Consequently it allows to direct acquire a signal in a compressed form. In this thesis, after an ample description of the CS methodology and its related architectures, I will present a new approach that tries to achieve high compression by design the second order statistics of a set of additional waveforms involved in the signal acquisition/compression stage. The second topic addressed in this thesis is in the area of communication system, in particular I focused the attention on ultra-wideband (UWB) systems. An option to produce and decode UWB signals is direct-sequence spreading with multiple access based on code division (DS-CDMA). Focusing on this methodology, I will address the coexistence of a DS-CDMA system with a narrowband interferer. To do so, I minimize the joint effect of both multiple access (MAI) and narrowband (NBI) interference on a simple matched filter receiver. I will show that, when spreading sequence statistical properties are suitably designed, performance improvements are possible with respect to a system exploiting chaos-based sequences minimizing MAI only.

Nonlinear constrained and saturated control of power electronics and electromechanical systems

Power electronic converters are extensively adopted for the solution of timely issues, such as power quality improvement in industrial plants, energy management in hybrid electrical systems, and control of electrical generators for renewables. Beside nonlinearity, this systems are typically characterized by hard constraints on the control inputs, and sometimes the state variables. In this respect, control laws able to handle input saturation are crucial to formally characterize the systems stability and performance properties. From a practical viewpoint, a proper saturation management allows to extend the systems transient and steady-state operating ranges, improving their reliability and availability. The main topic of this thesis concern saturated control methodologies, based on modern approaches, applied to power electronics and electromechanical systems. The pursued objective is to provide formal results under any saturation scenario, overcoming the drawbacks of the classic solution commonly applied to cope with saturation of power converters, and enhancing performance. For this purpose two main approaches are exploited and extended to deal with power electronic applications: modern anti-windup strategies, providing formal results and systematic design rules for the anti-windup compensator, devoted to handle control saturation, and “one step” saturated feedback design techniques, relying on a suitable characterization of the saturation nonlinearity and less conservative extensions of standard absolute stability theory results. The first part of the thesis is devoted to present and develop a novel general anti-windup scheme, which is then specifically applied to a class of power converters adopted for power quality enhancement in industrial plants. In the second part a polytopic differential inclusion representation of saturation nonlinearity is presented and extended to deal with a class of multiple input power converters, used to manage hybrid electrical energy sources. The third part regards adaptive observers design for robust estimation of the parameters required for high performance control of power systems.

Model predictive control in thermal management of multiprocessor systems-on-chip

MultiProcessor Systems-on-Chip (MPSoC) are the core of nowadays and next generation computing platforms. Their relevance in the global market continuously increase, occupying an important role both in everydaylife products (e.g. smartphones, tablets, laptops, cars) and in strategical market sectors as aviation, defense, robotics, medicine. Despite of the incredible performance improvements in the recent years processors manufacturers have had to deal with issues, commonly called “Walls”, that have hindered the processors development. After the famous “Power Wall”, that limited the maximum frequency of a single core and marked the birth of the modern multiprocessors system-on-chip, the “Thermal Wall” and the “Utilization Wall” are the actual key limiter for performance improvements. The former concerns the damaging effects of the high temperature on the chip caused by the large power densities dissipation, whereas the second refers to the impossibility of fully exploiting the computing power of the processor due to the limitations on power and temperature budgets. In this thesis we faced these challenges by developing efficient and reliable solutions able to maximize performance while limiting the maximum temperature below a fixed critical threshold and saving energy. This has been possible by exploiting the Model Predictive Controller (MPC) paradigm that solves an optimization problem subject to constraints in order to find the optimal control decisions for the future interval. A fully-distributedMPC-based thermal controller with a far lower complexity respect to a centralized one has been developed. The control feasibility and interesting properties for the simplification of the control design has been proved by studying a partial differential equation thermal model. Finally, the controller has been efficiently included in more complex control schemes able to minimize energy consumption and deal with mixed-criticalities tasks

Characterization of optical transduction-based molecular systems and nanoparticles for the development of chemical sensors

With the increasing importance that nanotechnologies have in everyday life, it is not difficult to realize that also a single molecule, if properly designed, can be a device able to perform useful functions: such a chemical species is called chemosensor, that is a molecule of abiotic origin that signals the presence of matter or energy. Signal transduction is the mechanism by which an interaction of a sensor with an analyte yields a measurable form of energy. When dealing with the design of a chemosensor, we need to take into account a “communication requirement” between its three component: the receptor unit, responsible for the selective analyte binding, the spacer, which controls the geometry of the system and modulates the electronic interaction between the receptor and the signalling unit, whose physico-chemical properties change upon complexation. A luminescent chemosensor communicates a variation of the physico-chemical properties of the receptor unit with a luminescence output signal. This thesis work consists in the characterization of new molecular and nanoparticle-based system which can be used as sensitive materials for the construction of new optical transduction devices able to provide information about the concentration of analytes in solution. In particular two direction were taken. The first is to continue in the development of new chemosensors, that is the first step for the construction of reliable and efficient devices, and in particular the work will be focused on chemosensors for metal ions for biomedical and environmental applications. The second is to study more efficient and complex organized systems, such as derivatized silica nanoparticles. These system can potentially have higher sensitivity than molecular systems, and present many advantages, like the possibility to be ratiometric, higher Stokes shifts and lower signal-to-noise ratio.

Silicon Photonics Integrated Circuits for Flexible Optical Systems

This dissertation deals with the design and the characterization of novel reconfigurable silicon-on-insulator (SOI) devices to filter and route optical signals on-chip. Design is carried out through circuit simulations based on basic circuit elements (Building Blocks, BBs) in order to prove the feasibility of an approach allowing to move the design of Photonic Integrated Circuits (PICs) toward the system level. CMOS compatibility and large integration scale make SOI one of the most promising material to realize PICs. The concepts of generic foundry and BB based circuit simulations for the design are emerging as a solution to reduce the costs and increase the circuit complexity. To validate the BB based approach, the development of some of the most important BBs is performed first. A novel tunable coupler is also presented and it is demonstrated to be a valuable alternative to the known solutions. Two novel multi-element PICs are then analysed: a narrow linewidth single mode resonator and a passband filter with widely tunable bandwidth. Extensive circuit simulations are carried out to determine their performance, taking into account fabrication tolerances. The first PIC is based on two Grating Assisted Couplers in a ring resonator (RR) configuration. It is shown that a trade-off between performance, resonance bandwidth and device footprint has to be performed. The device could be employed to realize reconfigurable add-drop de/multiplexers. Sensitivity with respect to fabrication tolerances and spurious effects is however observed. The second PIC is based on an unbalanced Mach-Zehnder interferometer loaded with two RRs. Overall good performance and robustness to fabrication tolerances and nonlinear effects have confirmed its applicability for the realization of flexible optical systems. Simulated and measured devices behaviour is shown to be in agreement thus demonstrating the viability of a BB based approach to the design of complex PICs.

Mental states monitoring through passive Brain-Computer Interface systems

The monitoring of cognitive functions aims at gaining information about the current cognitive state of the user by decoding brain signals. In recent years, this approach allowed to acquire valuable information about the cognitive aspects regarding the interaction of humans with external world. From this consideration, researchers started to consider passive application of brain–computer interface (BCI) in order to provide a novel input modality for technical systems solely based on brain activity. The objective of this thesis is to demonstrate how the passive Brain Computer Interfaces (BCIs) applications can be used to assess the mental states of the users, in order to improve the human machine interaction. Two main studies has been proposed. The first one allows to investigate whatever the Event Related Potentials (ERPs) morphological variations can be used to predict the users’ mental states (e.g. attentional resources, mental workload) during different reactive BCI tasks (e.g. P300-based BCIs), and if these information can predict the subjects’ performance in performing the tasks. In the second study, a passive BCI system able to online estimate the mental workload of the user by relying on the combination of the EEG and the ECG biosignals has been proposed. The latter study has been performed by simulating an operative scenario, in which the occurrence of errors or lack of performance could have significant consequences. The results showed that the proposed system is able to estimate online the mental workload of the subjects discriminating three different difficulty level of the tasks ensuring a high reliability.

Medical Malpractice in Public Healthcare Systems: An Empirical Investigation of Scheduled Damages

In the last decades, medical malpractice has been framed as one of the most critical issues for healthcare providers and health policy, holding a central role on both the policy agenda and public debate. The Law and Economics literature has devoted much attention to medical malpractice and to the investigation of the impact of malpractice reforms. Nonetheless, some reforms have been much less empirically studied as in the case of schedules, and their effects remain highly debated. The present work seeks to contribute to the study of medical malpractice and of schedules of noneconomic damages in a civil law country with a public national health system, using Italy as case study. Besides considering schedules and exploiting a quasi-experimental setting, the novelty of our contribution consists in the inclusion of the performance of the judiciary (measured as courts’ civil backlog) in the empirical analysis. The empirical analysis is twofold. First, it investigates how limiting compensations for pain and suffering through schedules impacts on the malpractice insurance market in terms of presence of private insurers and of premiums applied. Second, it examines whether, and to what extent, healthcare providers react to the implementation of this policy in terms of both levels and composition of the medical treatments offered. Our findings show that the introduction of schedules increases the presence of insurers only in inefficient courts, while it does not produce significant effects on paid premiums. Judicial inefficiency is attractive to insurers for average values of schedules penetration of the market, with an increasing positive impact of inefficiency as the territorial coverage of schedules increases. Moreover, the implementation of schedules tends to reduce the use of defensive practices on the part of clinicians, but the magnitude of this impact is ultimately determined by the actual degree of backlog of the court implementing schedules.