Progetto di controllori di volo mediante l'uso delle Guardian Maps.

Questo lavoro di tesi utilizza il metodo delle Guardian Maps per trattare la stabilità robusta di famiglie di sistemi lineari dipendenti da parametri. Si tratta di una tecnica di sintesi che affronta il problema in due passi successivi. Il primo consiste nel tradurre i requisiti richiesti da un dato sistema dinamico in vincoli sulla posizione dei poli in ciclo chiuso; il secondo consente di selezionare i guadagni del controllore affinché questi requisiti siano soddisfatti. La metodologia si basa sull’utilizzo di polinomi reali a coefficienti reali, costruiti con particolari tecniche, a partire dalla matrice di stato del sistema. La procedura illustrata permette anche di ottenere uno scheduling del controllore secondo un parametro, estendendo le prestazioni determinate in un certo punto di progetto ad un opportuno intervallo, il quale viene determinato sfruttando ancora le Maps. Gli algoritmi descritti nella prima parte del lavoro ed implementati in Matlab, sono corredati da semplici esempi e da applicazioni tratte dalla dinamica del volo, con riferimento a due velivoli per i quali vengono descritti dettagliatamente i modelli utilizzati. Partendo dalla configurazione “base”, determinata tramite l’uso delle Guardian Maps, nella seconda parte della tesi si propone un procedimento che mira ad ottimizzarla, minimizzando una funzione obiettivo scalare legata all’energia dei comandi richiesta per soddisfare i requisiti di progetto. Sono impostati e confrontati diversi metodi di ottimizzazione, che sfruttano sia semplici strumenti di ricerca del minimo, che i più complessi algoritmi genetici. Questa condizione di ottimo è il punto di partenza per la sintesi del controllore di volo, i cui risultati sono presentati ed analizzati nella parte finale del lavoro

Former heroin-dependent alcohol use disorder patients. prevalence, addiction history and clinical features

Aims: To examine the prevalence of former heroin dependence (FHA) in Alcohol Use Disorder (AUD) patients; to compare the clinical characteristics of FHA-AUD patients versus AUD patients without any past use of heroin at alcohol treatment entry; to document the heroin dependence history of FHA-AUD patients, and review treatment strategies for this group. Methods: Retrospective case review of 448 consecutive AUD patients. Results: The annual entry of FHA-AUD showed stability over the study period of 3 years overall 60/ 448 (13.3%). FHA-AUD patients showed higher concomitant use of cocaine, benzodiazepines, cannabis and hallucinogens than other heroin addicts. They consumed higher amounts of alcohol at the beginning of their alcohol dependence history, and reached a high maximum level of alcohol consumption, than other AUD patients, and tended to have more physical disorders. The most important signals of FHA-AUD were polyabuse and older age at the time of presentation. FHA-AUD patients tended to have had a severe pattern of heroin dependence associated with inadequate agonist opiate treatment. Conclusions: The prevalence of FHA-AUD patients is not negligible. This may relate to previous inadequate treatment of heroin addiction contributing to the development of severe AUD. For these patients we propose a reconsideration of ‘soft’ (low dose) agonist opiate treatment

A case of drug abuse

Methadone maintenance is one of the well-known harm reduction strategies for public health intervention in heroin addiction. The significance of methadone treatment in preventing needle sharing, which in turn reduces the risk of HIV and HCV transmission among injectors, has been demonstrated. Methadone maintenance is also considered gathering site where heroin addicts can effectively acquire knowledge on harm reduction and drug rehabilitation. We report a case of a 34-years-old patient with a history of heroin abuse. Therapy with methadone was essential for an adequate management of the case. The article describe difficulties and complexities of heroin abuse management and the therapeutic role of methadone

Can Ropinirole Modulate Reinforcing Subjective Effects of Cocaine in Humans?

In this study we evaluated, by means of the “cocaine rush visual analog scale,” the impact of ropinirole on the expected rush induced by cocaine in a group of heroin addicts abusing cocaine; the self-reported reaction to the rush blockade (if any) on cocaine consumption, and the correlations between this self-reported reaction and individual, clinical, and therapeutic parameters. Nineteen cocaine abuser heroin-dependent patients entered the study. Their experienced cocaine rush was 61.31 ± 32.1% of the maximum effect previously experienced. Compared with their previous rush intensity 16 patients experienced significantly lower intensity, 3 the same intensity, and none a higher intensity. In particular, two patients experienced a complete blockade of rush and reported a reduced use of cocaine. Fourteen patients experienced a partial blockade of cocaine rush; of these, nine reported they had reduced their use of cocaine. Ropinirole does diminish the subjective intensity of an expected cocaine rush, so interfering with the dynamics of reward, while supporting its possible use in the treatment of cocaine dependence

Antioxidant support to ameliorate the oxaliplatin-dependent microglial alteration: morphological and molecular study

Oxaliplatin is a third-generation chemotherapy drug mainly used for colorectal cancer treatment. However, it is also known to trigger neuropathy whose underlying neurobiological mechanisms are still under investigation and currently available treatments show limited efficacy. It is now established that neurons are not the only cell type involved in chronic pain and that glial cells, mainly microglia and astrocytes, are implicated in the initiation and maintenance of neuropathy. Among all the pathogenetic factors involved in neuropathic pain, an oxaliplatin- dependent oxidative stress plays a predominant role. In our study, the antioxidant properties of magnesium (Mg), manganese (Mn) and zinc (Zn) salts were evaluated in order to counteract microglial activation induced by oxaliplatin. The antioxidant efficacy of these metals was evaluated by means of molecular and morphological assays on the BV-2 microglial cell line. Our data clearly show that Mg, Mn and Zn salts are able to prevent oxaliplatin-dependent microglial alterations by reducing both oxidative and endoplasmic reticulum stress

Hybrid transcatheter left ventricular reconstruction for the treatment of ischemic cardiomyopathy

Left ventricular (LV) enlargement is a mechanical adaptation to accommodate LV systolic inefficiency following an acute damage or a progressive functional deterioration, which fails to correct the decline of stroke volume in the long term, leading to progressive heart failure (HF). Surgical ventricular reconstruction (SVR) is a treatment for patients with severe ischemic HF aiming to restore LV efficiency by volume reduction and LV re-shaping. Recently, a new minimally-invasive hybrid technique for ventricular reconstruction has been developed by means of the Revivent (TM) system (BioVentrix Inc., San Ramon, CA, USA). The device for ventricular reconstruction consists of anchor pairs that enable plication of the anterior and free wall LV scar against the right ventricular (RV) septal scar of anteroseptal infarctions to decrease cardiac volume without ventriculotomy in a beating-heart minimally-invasive procedure, consisting of a transjugular and left thoracotomy approach. Patients with severe (Grade 4) functional mitral regurgitation (FMR) or with previous cardiac surgery procedures were excluded. Outcome of the reconstruction procedure: from 2012 until 2019, it has been applied to 203 patients, with 5 (2.5%) in-hospital deaths. LV volume reduction varied according to experience gained along years: LV end-systolic volume index decreased from baseline 43% (post-market registry) vs. 27% (CE-mark study); left ventricular ejection fraction (LVEF) increased from baseline 25% (post-market registry) vs. 16% (CE-mark study). Clinical status (NYHA class, HF questionnaire, 6-minute walking test) improved significantly compared to baseline, and re-hospitalization rate was only 13% at 6-month follow-up (60% of patients in NYHA =3). FMR grade decreased at follow-up in 63%, while it was unchanged in 37% of patients. The hybrid ventricular reconstruction (HVR) seems a promising treatment for HF patients who may benefit from LV volume reduction, with reasonable mortality and good results at follow-up. A baseline less severe clinical profile was not associated to better outcome at follow-up, which makes the procedure feasible in patients with very large ventricles and depressed ejection fraction (EF). LV reshaping has no detrimental effect on FMR, that may, on the contrary, benefit owing to less papillary muscle displacement, partial recovery of torsion dynamics and of myofibers re-orientation. A controlled study on top of optimal medical treatment is warranted to confirm its role in the management of HF patients

Gray Wolf (Canis lupus italicus) and Red Fox (Vulpes vulpes) Parasite Survey in Anthropized and Natural Areas of Central Italy

Simple Summary Studies on wild animal parasites are considered crucial for the adoption of effective strategies aimed at reducing the impact of these pathogens on evolving ecosystems. This study aimed to assess and compare gastrointestinal nematodes and protozoa and other parasites detectable with coprological analysis in free-ranging wolf and red fox populations living in natural and anthropized areas of Tuscany (Central Italy). This comparison allowed us to detect significant differences in the occurrence and frequency of some parasite taxa considering the same canid species in different environments (natural and anthropized) and the two canid species in the same environment. Data obtained in this study may indicate different parasite risks and different roles played by the wolf and the fox in the diffusion of specific parasite taxa in the environments considered herein. Gastrointestinal nematodes and protozoa and other parasite occurrences were evaluated in free-ranging wolf (Canis lupus italicus) and red fox (Vulpes vulpes) populations from natural and anthropized areas of Central Italy. Analyzed fecal samples were collected from 60 foxes and 40 wolves in the anthropized areas, and 41 foxes and 39 wolves in the natural areas. In foxes, hookworm infections (p < 0.0001) were more frequently recorded in the anthropized environment, while coccidia (p < 0.05) and Cryptosporidium spp. (p < 0.0001) were more frequent in the natural area. In wolves, a higher frequency of hookworms (p < 0.0001) was observed in natural areas, while coccidia were more common in the anthropized area (p < 0.05). Moreover, in the natural environment, trichuroid nematodes (p < 0.0001) were significantly more frequent in wolves than in foxes, while Cryptosporidium (p < 0.001) and Giardia duodenalis (p < 0.001) were more common in foxes. In the anthropic area, the occurrence of hookworms was found to be significantly higher in foxes (p < 0.0001), while trichuroid nematodes were more common in wolves (p < 0.0001). The obtained data are indicative of a different diffusion of specific parasite taxa in wolves and foxes living in the natural and/or anthropized environments examined herein

Alcohol-Induced Blood-Brain Barrier Impairment: An In Vitro Study

In recent years, alcohol abuse has dramatically grown with deleterious consequence for people’s health and, in turn, for health care costs. It has been demonstrated, in humans and animals, that alcohol intoxication induces neuroinflammation and neurodegeneration thus leading to brain impairments. Furthermore, it has been shown that alcohol consumption is able to impair the blood–brain barrier (BBB), but the molecular mechanisms underlining this detrimental effect have not been fully elucidated. For this reason, in this study we investigated the effects of alcohol exposure on a rat brain endothelial (RBE4) cell line, as an in vitro-validated model of brain microvascular endothelial cells. To assess whether alcohol caused a concentration-related response, the cells were treated at different times with increasing concentrations (10–1713 mM) of ethyl alcohol (EtOH). Microscopic and molecular techniques, such as cell viability assay, immunofluorescence and Western blotting, were used to examine the mechanisms involved in alcohol-induced brain endothelial cell alterations including tight junction distribution, apoptosis, and reactive oxygen species production. Our findings clearly demonstrate that alcohol causes the formation of gaps between cells by tight junction disassembly, triggered by the endoplasmic reticulum and oxidative stress, highlighted by GRP78 chaperone upregulation and increase in reactive oxygen species production, respectively. The results from this study shed light on the mechanisms underlying alcohol-induced blood–brain barrier dysfunction and a better understanding of these processes will allow us to take advantage of developing new therapeutic strategies in order to prevent the deleterious effects of alcohol