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On April 6, 2009, a strong earthquake (6.1 Mw) struck the city of L’Aquila, which was severely damaged as well as many neighboring towns. After this event, a digital model of the region affected by the earthquake was built and a large amount of data was collected and made available. This allowed us to obtain a very detailed dataset that accurately describes a typical historic city in central Italy. Building on this work, we propose a study that employs machine learning (ML) tools to predict damage to buildings after the 2009 earthquake. The used dataset, in its original form, contains 21 features, in addition to the target variable which is the level of damage. We are able to differentiate between light, moderate and heavy damage with an accuracy of 59%, by using the Random Forest (RF) algorithm. The level of accuracy remains almost stable using only the 12 features selected by the Boruta algorithm. In both cases, the RF tool showed an excellent ability to distinguish between moderate-heavy and light damage: around the 3% of the buildings classified as seriously damaged were labeled by the algorithm as minor damage.

SUMMARY In this paper, we simulate the earthquake that hit the city of L’Aquila on 2009 April 6 using SPEED (SPectral Elements in Elastodynamics with Discontinuous Galerkin), an open-source code able to simulate the propagation of seismic waves in complex 3-D domains. Our model includes an accurate 3-D reconstruction of the Quaternary deposits, according to the most up-to-date data obtained from the Microzonation studies in Central Italy and a detailed model of the topography incorporated using a newly developed tool. The sensitivity of our results with respect to different kinematic seismic sources is investigated. The results obtained are in good agreement with the recordings at the available seismic stations at epicentral distances within a range of 20 km. Finally, a blind source prediction scenario application shows that a reasonably good agreement between simulations and recordings can be obtained by simulating stochastic rupture realizations with basic input data. These results, although limited to nine simulated scenarios, demonstrate that it is possible to obtain a satisfactory reconstruction of a ground shaking scenario employing a stochastic source constrained on a limited amount of ex-ante information. A similar approach can be used to model future and past earthquakes for which little or no information is typically available, with potential relevant implications for seismic risk assessment.

Pressure retarded osmosis (PRO) power plants generate power from mixing of saltwater and freshwater by means of membrane systems. In this paper we present a model which describes the complete power station, suitable to optimize the power station both with respect to system parameters and in operating conditions. Special attention is dedicated to the flow model of the “core” membrane unit. It considers the relevant water and salt flows in the system. It also accounts for irreversible losses in the flow across the membrane as well as through the membrane unit, and in the surrounding pump-turbine system. The model represents a compromise between needed complexity (including the most relevant chemo-physics) and simplicity to allow rapid simulations which is an important prerequisit for optimisation. Finally, we optimise numerically, i.e., the net power output (per membrane area) with respect to geometric parameters, membrane parameters as well as operational parameters such as the applied pressure settings during operation.

IntroductionItaly has been one of the most affected countries by Covid-19 pandemic. Our University General Hospital, Policlinico of “Tor Vergata” (PTV) in Rome, has become a Covid Hub in order to manage the spread of the epidemic. Thus, our Psychiatric Emergency Service (PES)’s access has been partially limited. Direct indicators of PES activity, as admission rates, can be useful for evaluating the psychological impact of Covid epidemic.ObjectivesTo assess psychiatric admittance rates to PES of PTV before and during Covid-19 global pandemic.MethodsData from our PES register have been obtained and analyzed. We compared all the psychiatric access during the trimester March – May 2019 and 2020. All patients have been characterized according to clinical features.ResultsA marked reduction of the number of patients presenting to PES has been observed (76 patients) in the 57-day period (March 11–May 04, 2020) of lockdown compared to the same period in 2019 (266 patients). The cutback was visible for all diagnostic groups, except for “Borderline Personality Disorder” diagnosis which have slightly increased. On the other hand, hospitalization rates in our psychiatric inpatients unit remained steady.ConclusionsAlthough larger study are needed to understand the mental consequences of the lockdown experience, people’s fear of potential infection might explain our results. Interestingly, personality disorder patients represent an exception to it, suggesting the importance of the clinical characteristics of fearless, engagement in dangerous behavior and detachment from reality. These findings might be helpful to improve psychosocial crisis interventions during the pandemic.

We consider the infusion of a diluted suspension of nanoparticles (NPs) into poroelastic brain tissue, in view of relevant biomedical applications such as intratumoral thermotherapy. Indeed, the high impact of the related pathologies motivates the development of advanced therapeutic approaches, whose design also benefits from theoretical models. This study provides an analytical expression for the time-dependent NPs concentration during the infusion into poroelastic brain tissue, which also accounts for particle binding onto cells (by recalling relevant results from the colloid filtration theory). Our model is computationally inexpensive and, compared to fully numerical approaches, permits to explicitly elucidate the role of the involved physical aspects (tissue poroelasticity, infusion parameters, NPs physico-chemical properties, NP-tissue interactions underlying binding). We also present illustrative results based on parameters taken from the literature, by considering clinically relevant ranges for the infusion parameters. Moreover, we thoroughly assess the model working assumptions besides discussing its limitations. While not laying any claims of generality, our model can be used to support the development of more ambitious numerical approaches, towards the preliminary design of novel therapies based on NPs infusion into brain tissue.

Concentrations of 3alpha-reduced neuroactive steroids are altered in depression and normalize after antidepressant pharmacotherapy with selective serotonin re-uptake inhibitors (SSRIs). We investigated the impact of mirtazapine on the activity of a key neurosteroidogenic enzyme, the 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD), and on the levels of neuroactive steroids in relation to clinical response. A total of 23 drug-free in-patients suffering from a major depressive episode (DSM-IV criteria) underwent 5-week treatment with mirtazapine (45 mg/day). Plasma samples were taken weekly at 0800 and quantified for neuroactive steroids by means of combined gas chromatography/mass spectrometry analysis. Enzyme activity was determined by assessment of steroid conversion rates. Irrespective of clinical outcome, there were significant increases in 3alpha,5alpha-tetrahydroprogesterone, 3alpha,5beta-tetrahydroprogesterone, 5alpha-dihydroprogesterone, and 5beta-dihydroprogesterone after mirtazapine treatment, whereas 3beta,5alpha-tetrahydroprogesterone levels were significantly decreased. In vitro investigations demonstrated a dose-dependent inhibitory effect of mirtazapine on the activity of the microsomal 3alpha-HSD in the oxidative direction (conversion of 3alpha,5alpha-tetrahydroprogesterone to 5alpha-dihydroprogesterone). Mirtazapine affects neuroactive steroid composition similarly as do SSRIs. The inhibition of the oxidative pathway catalyzed by the microsomal 3alpha-HSD is compatible with an enhanced formation of 3alpha-reduced neuroactive steroids. However, the changes in neuroactive steroid concentrations more likely reflect direct pharmacological effects of this antidepressant rather than clinical improvement in general.

We study a magnetic-nanoparticle-mediated hyperthermia treatment by considering both the nanofluid infusion and the subsequent thermal activation of the infused nanoparticles. Our study aims at providing a quantitative framework, which is currently missing, for the design of hyperthermia treatments. In more detail, we consider a heterogeneous spherical tumor, and we obtain a simplified analytical expression for the nanoparticles concentration profile during the infusion. We then exploit such an expression in order to compute the steady-state temperature profile achieved through the heating step. Despite the simplifications introduced to enable the analytical derivations, we account for many physically relevant aspects including tissue heterogeneity, poroelasticity, blood perfusion, and nanoparticles absorption onto tissue. Moreover, our approach permits to elucidate the effects on the final temperature profile of the following control parameters: infusion duration and flow rate, nanoparticles concentration in the nanofluid, magnetic field intensity and frequency. We present illustrative numerical results, based on parameters values taken from experimental studies, which are consistent with previous numerical investigations and current hyperthermia approaches. In particular, we obtain optimal working curves which could be effectively used for planning real procedures. While not laying any claims of generality, this work takes a preliminary yet quantitative step toward the design of hyperthermia treatments.

Purpose: This study aimed to compare the acute effects of uphill repeated sprinting "with long recovery" (RS) and uphill intermittent running (IR) training on heart rate (HR) and blood lactate (BL) responses. Methods: Thirteen young male soccer players randomly performed in two separate occasions, on a slope (10 %), an RS and an IR session. RS consisted of three sets of eight maximal uphill 20-m sprints with long (90 s) recovery between sprints, and 8 min passive rest between sets, whereas IR consisted of 24 repetitions of 22-m sub-maximal (95 % of maximum speed achieved in an incremental test) uphill runs interspersed by a 15-s downhill walking recovery, lasting for a total duration of 8 min. Results: The mean HR, expressed as the percentage of HRMAX, was significantly higher in IR than in RS (86.1 ± 3.1 vs. 77.0 ± 4.5 %, respectively, p < 0.05). Conversely, BL measured after 3 min was significantly higher in RS (5.9 ± 1.1 mmol L-1) than in IR (2.9 ± 1.2 mmol L-1, p < 0.05). Conclusions: The differences found between RS and IR may be attributed to the different work/recovery ratios and speed characteristics. Therefore, uphill IR seems more suitable when the target is to tax the aerobic system, while RS may be more suitable when the focus is on stimulating the speed without increasing the metabolic demand. © 2014 Springer-Verlag Italia.

Besides their binding to cognate intracellular receptors gonadal steroids may also act as functional antagonists at the 5-HT3 receptor. A structure-activity relationship for the actions of a variety of steroids at the 5-HT3 receptor was elaborated that differed considerably from that known for GABA(A) receptors. Steroids appear to interact allosterically with ligand-gated ion channels at the receptor membrane interface. The functional antagonism of gonadal steroids at the 5-HT3 receptor may play a role for the development and course of nausea during pregnancy and of psychiatric disorders. Moreover, we could demonstrate that 3alpha-reduced neuroactive steroids concurrently modulate the GABA(A) receptor and regulate gene expression via the progesterone receptor after intracellular oxidation. Animal studies showed that progesterone is converted rapidly into GABAergic neuroactive steroids in vivo. Progesterone reduces locomotor activity in a dose dependent fashion in male Wister rats. Moreover, progesterone and 3alpha,5alpha-tetrahydroprogesterone produce a benzodiazepine-like sleep EEG profile in rats and humans. In addition, there is a dysequilibrium of such 3alpha-reduced neuroactive steroids during major depression which is corrected by successful treatment with antidepressants. Neuroactive steroids may further be involved in the treatment of depression and anxiety with antidepressants in patients during ethanol withdrawal. First studies in patients with panic disorder suggest that neuroactive steroids may also play a pivotal role in human anxiety. The genomic and non-genomic effects of steroids in the brain contribute to the pathophysiology of psychiatric disorders and the mechanisms of action of antidepressants. Neuroactive steroids affect a broad spectrum of behavioral functions through their unique molecular properties and may constitute a yet unexploited class of drugs.

We studied the effect of brain and spinal cord injury induced by fluid-percussion on the local synthesis of neurosteroids as measured by a gas-chromatographic/mass-spectrometric method. In the nervous system of sham operated rats i.v. infusion of pregnenolone (PREGN)-sulfate results in a 2-4 fold increase in PREGN, progesterone (PROG), 5alpha-dehydroprogesterone (5alpha-DHP) and 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha5alpha-THP, allopregnanolone) concentrations, as compared to vehicle treated rats. When PREGN-sulfate was infused 1, 3 or 7 days after brain or spinal cord injury it was observed a large time-dependent increase of PROG, 5alpha-DHP and 3alpha5alpha-THP levels in the peri-focal but not in the focal site. This increase in neurosteroids content may be due essentially to the glial cells hyperplasia in the peri-focal area and to an activation of the pathways involved in the metabolism of PREGN-sulfate to PROG, 5alpha-DHP and 3alpha5alpha-THP.

We study a hybrid model linking the quantum hydrodynamics equation with classical hydrodynamics deriving the transmission conditions between the two PDE systems modeling the quantum and the classical dynamics. These conditions are derived under the assumption of constant scaled temperature and assuming a current jump across the interface between the classical and the quantum region. In Section 2.2 we shall give a heuristic and physically plausible explanation of this assumption. Because of this fact we produce not a weak solution on the whole device domain, but a piecewise smooth solution.

Certain neuroactive steroids modulate ligand-gated ion channels via non-genomic mechanisms. Especially 3alpha-reduced pregnane steroids are potent positive allosteric modulators of the GABA type A-receptor. During major depression there is a dysequilibrium of 3alpha-reduced neuroactive steroids, which is corrected by clinically effective pharmacological treatment. To investigate whether these alterations are a general principle of successful antidepressant treatment we studied the impact of non-pharmacological treatment options on neuroactive steroid concentrations during major depression. Neither partial sleep deprivation, transcranial magnetic stimulation nor electroconvulsive therapy affected neuroactive steroid levels irrespectively of the response to these treatments. These studies suggest that the changes in neuroactive steroids observed after antidepressant pharmacotherapy more likely reflect distinct pharmacological properties of antidepressants rather than the clinical response. In patients with panic disorder changes in neuroactive steroid composition have been observed opposite of those seen in depression. These changes may represent counterregulatory mechanisms against the occurrence of spontaneous panic attacks. However, during experimental panic induction with either cholecystokinin-tetrapeptide or sodium lactate there was a pronounced decline in the concentrations of 3alpha-reduced neuroactive steroids in patients with panic disorder, which might result in a decreased GABAergic tone. In contrast, no changes in neuroactive steroid concentrations could be observed in healthy controls with the exception of 3alpha, 5alpha-tetrahydrodeoxycorticosterone, allotetrahydrodeoxycorticosterone. The modulation of GABA type A-receptors by neuroactive steroids might contribute to the pathophysiology of depression and anxiety disorders and might offer new targets for the development of novel anxiolytic compounds.

The neuroactive steroid 3alpha, 5alpha-tetrahydroprogesterone is the most potent endogenous positive modulator of gamma-amino-butyric acid (GABA)(A) receptors. There is evidence for a relation between neuroactive steroids and seizure susceptibility.To evaluate the putative role of counteregulator neuroactive steroids in the occurrence of seizures in patients with tuberous sclerosis.Plasma concentrations of the enantiomers 3alpha, 5alpha- and 3alpha, 5beta-tetrahydroprogesterone (3alpha(s)-THP), which are positive modulators of GABA(A) receptors, were measured in 18 patients, along with their endogenous functional antagonists 3beta, 5alpha- and 3beta, 5beta-THP (3beta(s)-THP), to assess their possible modification compared with control subjects. Neuroactive steroids were assayed using a highly sensitive and specific gas chromatographic/mass spectrometric method.In the tuberous sclerosis patients with poorly controlled seizures, there was a significantly lower 3alpha(s)/3beta(s)-THP ratio than in seizure-free patients or control subjects.The reduced 3alpha(s)/3beta(s)-THP ratio may decrease GABAergic tone, contributing to the appearance of seizures in tuberous sclerosis patients with epilepsy.

The levels of the neuroactive steroids allopregnanolone (THP) and 5alpha-dihydroprogesterone (DHP) were quantified in the plasma of 11 (group 1) and in the liquor of 12 (group 2) Parkinson's disease (PD) patients using a gas-chromatographic/mass-spectrometric method. When compared with controls, both groups showed a significant decrease in DHP and THP concentrations. These decreases could be a useful marker of PD. Moreover, in view of the importance of GABA-ergic transmission to substantia nigra (SN) neurons and GABA-ergic modulation exerted by the two neuroactive steroids, our data indicate a global dysregulation of the SN GABA-ergic system in PD patients. Moreover, a lack of neuroprotective factors (i. e., GDNF, BDNF), promoted by DHP, may contribute to dopaminergic cell death.

There is evidence for a differential alteration in the concentrations of 3 alpha-reduced neuroactive steroids in major depression. Because it has been suggested that fluoxetine may shift the activity of the 3 alpha-hydroxysteroid oxidoreductase towards the reductive direction, treatment of major depression may be accompanied by a further increase in plasma 3 alpha, 5 alpha-tetrahydrodeoxycorticosterone (THDOC) concentration. We studied eight male depressed patients before and after treatment with fluoxetine and compared them to healthy age-matched control subjects. Blood samples were quantified for 3 alpha, 5 alpha-tetrahydroprogesterone, 3 alpha,5 beta-tetrahydroprogesterone (THP) and THDOC by means of a highly sensitive combined gas chromatography/mass spectrometry analysis. Compared to control subjects, concentrations of THDOC were higher in depressed patients and decreased after fluoxetine treatment. In contrast, THP concentrations were lower in depressed patients and increased after fluoxetine treatment. Our results give further evidence for a disequilibrium of 3 alpha-reduced neuroactive steroids in major depression, which is normalized by treatment with fluoxetine.

There is evidence from animal studies that fluoxetine may enhance the concentrations of neuroactive steroids. Therefore, the authors investigated whether clinically effective treatment with antidepressants may alter the concentrations of neuroactive steroids in patients suffering from a major depressive episode.In the first study, eight drug-naive outpatients with major depression were studied during treatment with fluoxetine. In a complementary study, 11 inpatients with major depression were studied during a severe depressive episode and after recovery following treatment with different antidepressants. Plasma samples were quantified for neuroactive steroids by means of a highly sensitive and specific combined gas chromatography/mass spectrometry analysis.During depression, there was a significant decrease in 3 alpha, 5 alpha-tetrahydroprogesterone (3 alpha, 5 alpha-THP) and 3 alpha, 5 beta-THP concentrations, both of which are positive modulators of the gamma-aminobutyric acidA receptor, and a concomitant increase in 3 beta, 5 alpha-THP levels. This dysequilibrium of neuroactive steroids could be corrected by treatment with different antidepressants.These results provide the first clinical evidence of a possible role of neuroactive steroids in successful antidepressant therapy.

Recent research in rats and humans has shown that exogenous progesterone evokes a sleep profile similar to that induced by agonistic modulators of gamma-aminobutyric acid(A) receptors, such as benzodiazepines. This finding suggests the involvement of the neuroactive metabolite of progesterone, allopregnanolone. In the vehicle-controlled study reported here, we assessed the sleep effects of two doses of allopregnanolone (7.5 and 15 mg/kg), mixed with oil, administered intraperitoneally at light onset in 8 rats. The electroencephalogram (EEG) and electromyogram were recorded during the first 6 postinjection hr. Compared with vehicle, both doses of allopregnanolone reduced the latency to non-rapid eye movement sleep (non-REMS) and 15 mg/kg allopregnanolone significantly increased the time spent in pre-REMS, an intermediate state between non-REMS and REMS. Furthermore, allopregnanolone dose-dependently influenced EEG activity during non-REMS and REMS. In non-REMS, EEG activity was decreased in the lower frequencies (or =7 Hz) and enhanced in the frequencies ofor =13 Hz. In REMS, allopregnanolone enhanced high-frequency EEG activity (or =17 Hz). The effects were most pronounced during the first postinjection hours and gradually diminished thereafter. Analysis of the plasma and brain concentrations of allopregnanolone in 45 rats revealed long-lasting increases, which reached maximal levels during the first postinjection hour. The sleep effects of allopregnanolone are very similar to those elicited by larger doses of progesterone, which produce comparable brain levels of allopregnanolone. These data indicate that the steroid allopregnanolone has benzodiazepine-like effects on sleep.

Osmotic-driven plant movements are widely recognized as impressive examples of energy efficiency and low power consumption. These aspects motivate the interest in developing an original biomimetic concept of new actuators based on the osmotic principle exploited by plants. This study takes a preliminary step in this direction, by modelling the dynamic behaviour of two exemplificative yet relevant implementations of an osmotic actuator concept. In more detail, the considered implementations differ from each other in the way actuation energy storage is achieved (through a piston displacement in the former case, through membrane bulging in the latter). The dynamic problem is analytically solved for both cases; scaling laws for the actuation figures of merit (namely characteristic time, maximum force, maximum power, power density, cumulated work and energy density) as a function of model parameters are obtained for the bulging implementation. Starting from such performance indicators, a preliminary dimensioning of the envisaged osmotic actuator is exemplified, based on design targets/constraints (such as characteristic time and/or maximum force). Moreover, model assumptions and limitations are discussed towards effective prototypical development and experimental testing. Nonetheless, this study takes the first step towards the design of new actuators based on the natural osmotic principle, which holds potential for disruptive innovation in many fields, including biorobotics and ICT solutions.