A Hybrid Drift Diffusion Model: Derivation, Weak Steady State Solutions and Simulations

In this paper we derive a new hybrid model for drift di usion equations. This model provides a description of the quantum phenomena in the parts of the device where they are relevant, and degenerates to a semiclassical model where quantum e ects are negligible, so that the system can be considered classically. The study of quantum correction to the equation of state of an electron gas in a semiconductor with the assumption of localized quantum e ects leads to a further condition on the classical-quantum interface. Moreover, we prove the existence of weak solutions for our hybrid model. Finally, we present numerical results for di erent devices, by means of Colsys software

Beneficio e gradimento correlati all'utilizzo delle protesi impiantabili per via ossea.

L’udito è considerato una delle funzioni più importanti per quanto concerne la sfera comunicativa dell’essere umano. Il deficit uditivo interferisce in maniera rilevante sulla condotta di vita del soggetto affetto, limitando la partecipazione alle attività sociali, compromettendo le relazioni e le frequentazioni dell’individuo. Nel bambino l’ipoacusia è capace di inficiare l’apprendimento del linguaggio, interferendo con il corretto sviluppo delle abilità cognitive e comunicative. La perdita uditiva è considerata dall’OMS un problema di salute pubblica di estrema rilevanza, in quanto capace di insidiare, secondo molteplici fattori, l’integrità fisica e psicosociale dell’individuo. La ricerca scientifica ha permesso lo sviluppo di tecniche chirurgiche e strumenti capaci di rivoluzionare l’approccio terapeutico relativamente questo tipo di disturbo, garantendo nel tempo una gestione sempre più accurata e efficace della patologia. Un ambito che desta sempre più interesse all’interno della pratica ORL è quello che riguarda la conduzione per via ossea, lo studio di questo fenomeno ha permesso infatti l’ideazione di dispositivi capaci di sfruttare tale via nella trasmissione dello stimolo acustico, ripristinando un soddisfacente profilo uditivo nei soggetti ipoacusici. Il progresso tecnologico e l’approfondimento delle conoscenze circa i dispositivi per via ossea ha determinato un consistente miglioramento delle performance uditive raggiungibili tramite la protesizzazione. Tra i presidi protesici a disposizione, il sistema BAHA è risultato particolarmente utile ed efficace nel trattamento di quelle condizioni patologiche in cui l’approccio terapeutico tradizionale non ha apportato un beneficio soddisfacente. Questa tesi ha voluto, oltre che fornire un’adeguata visione di insieme delle protesi impiantabili per via ossea, documentare la loro utilità e il gradimento, descrivendo la casistica della Unità Operativa di Otorinolaringoiatria, Foniatria e Audiologia Universitaria della Azienda Ospedaliera Universitaria Pisana. Da questo studio è emerso un alto tasso di soddisfazione nei pazienti protesizzati, inoltre la stima del risultato protesico in diversi gruppi diagnostici ha permesso di definire e approfondire le variabili che possono incidere sul successo dell’amplificazione tramite BAHA. La costante integrazione delle conoscenze circa la conduzione per via ossea e l’attenta valutazione dei risultati legati alla protesizzazione è fondamentale nella realizzazione di una soluzione terapeutica sempre più soddisfacente non solo in termini audiologici ma anche di qualità di vita dell’individuo

Digital for Heritage and Museums: Design-Driven Changes and Challenges

In the recent decade, cultural institutions have increasingly embraced digital technologies as key resources for accomplishing their mission and innovating their cultural activities. In the present work, we attempt to disentangle through a design-driven and multidisciplinary approach the challenges brought by digital transformation in the cultural heritage sector. A diversified research team has thus been involved to include scholars with different backgrounds around the common phenomenon of investigation of Digital (Cultural) Heritage, under the Design Think Thank project. The Introduction is followed by a Methodological section, which outlines the approach to select and review case studies from the exploratory literature for producing a state-of-the-art report and delineates the methodology to map the main user behaviours and needs in the digital experience of CH throughout the value chain. The research team identified three relevant and major themes for the investigation which are addressed in the Literature Review Section through the lenses of design research and practices; simultaneously, design knowledge emerges to have an agency in the transformation. The following section tries to triangulate the results from the literature review, and the mapping of users and stakeholders throughout the cultural institutions value chain, to track and highlight their role and interest in changing heritage panorama. The contribution of the present work wishes to consolidate the results gathered in the first phases of the TT, providing the design community of academics and practitioners with a theoretical contribution about digital changes and challenges of heritage and museums based on a design perspective

Measurement of Glutathionylated Haemoglobin by MALDI-ToF Mass Spectrometry as a Biomarker of Oxidative Stress in Heavy Smokers and in Occupational Obese Subjects

Glutathionyl-haemoglobin (Hb-SSG) is a minor form of haemoglobin characterized by the presence of a disulfide bond between the β-93 cysteine residue and the thiol group of glutathione. Hb-SSG is naturally present in the erythrocytes at levels comparable to those of glycated haemoglobin and can be measured by MALDI mass spectrometry on very small samples of erythrocytes from peripheral blood. Since Hb-SSG has been recognized as a sensitive biomarker of oxidative stress in several degenerative diseases (diabetes, hyperlipidemia, kidney disease) and in healthy workers exposed to glutathione-depleting toxic agents such as butadiene, we have measured for the first time the levels of Hb-SSG in two groups: healthy heavy cigarette smokers and overweight-obese

An overview of molecular mechanisms in fabry disease

Fabry disease (FD) (OMIM #301500) is a rare genetic lysosomal storage disorder (LSD). LSDs are characterized by inappropriate lipid accumulation in lysosomes due to specific enzyme deficiencies. In FD, the defective enzyme is alpha-galactosidase A (alpha-Gal A), which is due to a mutation in the GLA gene on the X chromosome. The enzyme deficiency leads to a continuous deposition of neutral glycosphingolipids (globotriaosylceramide) in the lysosomes of numerous tissues and organs, including endothelial cells, smooth muscle cells, corneal epithelial cells, renal glomeruli and tubules, cardiac muscle and ganglion cells of the nervous system. This condition leads to progressive organ failure and premature death. The increasing understanding of FD, and LSD in general, has led in recent years to the introduction of enzyme replacement therapy (ERT), which aims to slow, if not halt, the progression of the metabolic disorder. In this review, we provide an overview of the main features of FD, focusing on its molecular mechanism and the role of biomarkers

589 External validation of the increased wall thickness score for the diagnosis of cardiac amyloidosis

Abstract Aims This study aimed to validate the increased wall thickness (IWT) score, a multiparametric echocardiographic score to facilitate diagnosis of cardiac amyloidosis (CA), in an independent population of patients with increased LV wall thickness suspicious for CA. Methods and results Between January 2019 and December 2020, 152 consecutive patients with increased LV wall thickness suspicious for CA were included. For all patient, the multiparametric echocardiographic score (IWT score) was calculated. To validate the diagnostic accuracy of an IWT score ≥8 to predict the diagnosis of CA, sensibility (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), and predictive accuracy (PA) were calculated. Among the 152 patients included in the study, 50 (33%) were diagnosed as CA, 25 (16%) had severe aortic stenosis, 25 (16%) had hypertensive remodelling, and 52 (34%) had hypertrophic cardiomyopathy. Among the 50 and 102 patients with and without CA, 19 (38%) and 1 (1%) showed an IWT score ≥8, respectively. Overall, the diagnostic accuracy of an IWT score ≥8 for the diagnosis of CA in our population was the following: Se 38% (95% CI: 25–53%); Sp 99% (95% CI: 95–100%); PPV 95% (95% CI: 72–99%); NPV 77% (95% CI: 73–80%); PA 79% (95% CI: 72–85%). Conclusions This study reports the first external validation of the IWT score for the diagnosis of CA in patients with increased LV wall thickness. A score ≥8 showed a high Sp, PPV and PA, suggesting that the IWT score can be used to identify CA patients in those with increased LV wall thickness

Elevated gonadotropin levels are associated with increased biomarker risk of Alzheimer's disease in midlife women

IntroductionIn preclinical studies, menopausal elevations in pituitary gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), trigger Alzheimer's disease (AD) pathology and synaptic loss in female animals. Herein, we took a translational approach to test whether gonadotropin elevations are linked to AD pathophysiology in women.MethodsWe examined 191 women ages 40–65 years, carrying risk factors for late-onset AD, including 45 premenopausal, 67 perimenopausal, and 79 postmenopausal participants with clinical, laboratory, cognitive exams, and volumetric MRI scans. Half of the cohort completed 11C-Pittsburgh Compound B (PiB) amyloid-β (Aβ) PET scans. Associations between serum FSH, LH and biomarkers were examined using voxel-based analysis, overall and stratified by menopause status. Associations with region-of-interest (ROI) hippocampal volume, plasma estradiol levels, APOE-4 status, and cognition were assessed in sensitivity analyses.ResultsFSH levels were positively associated with Aβ load in frontal cortex (multivariable adjusted P ≤ 0.05, corrected for family wise type error, FWE), an effect that was driven by the postmenopausal group (multivariable adjusted PFWE ≤ 0.044). LH levels were also associated with Aβ load in frontal cortex, which did not survive multivariable adjustment. FSH and LH were negatively associated with gray matter volume (GMV) in frontal cortex, overall and in each menopausal group (multivariable adjusted PFWE ≤ 0.040), and FSH was marginally associated with ROI hippocampal volume (multivariable adjusted P = 0.058). Associations were independent of age, clinical confounders, menopause type, hormone therapy status, history of depression, APOE-4 status, and regional effects of estradiol. There were no significant associations with cognitive scores.DiscussionIncreasing serum gonadotropin levels, especially FSH, are associated with higher Aβ load and lower GMV in some AD-vulnerable regions of midlife women at risk for AD. These findings are consistent with preclinical work and provide exploratory hormonal targets for precision medicine strategies for AD risk reduction

Multimodality Imaging in Cardiomyopathies with Hypertrophic Phenotypes

Multimodality imaging is a comprehensive strategy to investigate left ventricular hypertrophy (LVH), providing morphologic, functional, and often clinical information to clinicians. Hypertrophic cardiomyopathy (HCM) is defined by an increased LV wall thickness not only explainable by abnormal loading conditions. In the context of HCM, multimodality imaging, by different imaging techniques, such as echocardiography, cardiac magnetic resonance, cardiac computer tomography, and cardiac nuclear imaging, provides essential information for diagnosis, sudden cardiac death stratification, and management. Furthermore, it is essential to uncover the specific cause of HCM, such as Fabry disease and cardiac amyloidosis, which can benefit of specific treatments. This review aims to elucidate the current role of multimodality imaging in adult patients with HCM

Clinical and dopaminergic imaging characteristics of the FARPRESTO cohort of trial-ready idiopathic rapid eye movement sleep behavior patients

Introduction: Idiopathic/isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is considered the prodromal stage of alpha-synucleinopathies. Thus, iRBD patients are the ideal target for disease-modifying therapy. The risk FActoRs PREdictive of phenoconversion in iRBD Italian STudy (FARPRESTO) is an ongoing Italian database aimed at identifying risk factors of phenoconversion, and eventually to ease clinical trial enrollment of well-characterized subjects.Methods: Polysomnography-confirmed iRBD patients were retrospectively and prospectively enrolled. Baseline harmonized clinical and nigrostriatal functioning data were collected at baseline. Nigrostriatal functioning was evaluated by dopamine transporter-single-photon emission computed tomography (DaT-SPECT) and categorized with visual semi-quantification. Longitudinal data were evaluated to assess phenoconversion. Cox regressions were applied to calculate hazard ratios.Results: 365 patients were enrolled, and 289 patients with follow-up (age 67.7 & PLUSMN; 7.3 years, 237 males, mean follow-up 40 & PLUSMN; 37 months) were included in this study. At follow-up, 97 iRBD patients (33.6%) phenoconverted to an overt synucleinopathy. Older age, motor and cognitive impairment, constipation, urinary and sexual dysfunction, depression, and visual semi-quantification of nigrostriatal functioning predicted phenoconversion. The remaining 268 patients are in follow-up within the FARPRESTO project.Conclusions: Clinical data (older age, motor and cognitive impairment, constipation, urinary and sexual dysfunction, depression) predicted phenoconversion in this multicenter, longitudinal, observational study. A standardized visual approach for semi-quantification of DaT-SPECT is proposed as a practical risk factor for phenoconversion in iRBD patients. Of note, non-converted and newly diagnosed iRBD patients, who represent a trial-ready cohort for upcoming disease-modification trials, are currently being enrolled and followed in the FARPRESTO study. New data are expected to allow better risk characterization