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Pulmonary vasculitis identifies a heterogeneous group of diseases characterized by inflammation, damage and necrosis of the wall of pulmonary vessels. The most common approach to classify vasculitis is according to etiology, therefore dividing them into primary and secondary, with a further sub-classification of primary vasculitis based on the size of the affected vessels (large, medium, and small). Pulmonary involvement is frequently observed in patients with systemic vasculitis and radiological presentation is not pathognomonic, but may vary between diseases. The main findings using high-resolution computed tomography (HRCT) include small vessel wall thickening, nodular lesions, cavitary lesions, reticular opacities, ground-glass opacities (GGO), consolidations, interlobular septal thickening, tracheobronchial stenosis, and aneurysmal dilatation of pulmonary arteries, with or without pleural effusion. Radiological diagnosis alone is difficult since signs and symptoms of lung vessel involvement are often non-specific and might overlap with other conditions such as infections, connective tissue diseases and neoplasms. Therefore, the aim of this review is to describe the most common radiological features of lung involvement in pulmonary vasculitis so that, alongside detailed clinical history and laboratory tests, a prompt diagnosis can be performed. [ABSTRACT FROM AUTHOR]

We study the Bellman equation in the Wasserstein space arising in the study of mean field control problems, namely stochastic optimal control problems for McKean-Vlasov diffusion processes. Using the standard notion of viscosity solution à la Crandall-Lions extended to our Wasserstein setting, we prove a comparison result under general conditions on the drift and reward coefficients, which coupled with the dynamic programming principle, implies that the value function is the unique viscosity solution of the Master Bellman equation. This is the first uniqueness result in such a second-order context. The classical arguments used in the standard cases of equations in finite-dimensional spaces or in infinite-dimensional separable Hilbert spaces do not extend to the present framework, due to the awkward nature of the underlying Wasserstein space. The adopted strategy is based on finite-dimensional approximations of the value function obtained in terms of the related cooperative n-player game, and on the construction of a smooth gauge-type function, built starting from a regularization of a sharp estimate of the Wasserstein metric; such a gauge-type function is used to generate maxima/minima through a suitable extension of the Borwein-Preiss generalization of Ekeland's variational principle on the Wasserstein space. [ABSTRACT FROM AUTHOR]

Background: The identification of the electrical stimulation parameters for neuromodulation is a subject-specific and time-consuming procedure that presently mostly relies on the expertise of the user (e.g., clinician, experimenter, bioengineer). Since the parameters of stimulation change over time (due to displacement of electrodes, skin status, etc.), patients undergo recurrent, long calibration sessions, along with visits to the clinics, which are inefficient and expensive. To address this issue, we developed an automatized calibration system based on reinforcement learning (RL) allowing for accurate and efficient identification of the peripheral nerve stimulation parameters for somatosensory neuroprostheses. Methods: We developed an RL algorithm to automatically select neurostimulation parameters for restoring sensory feedback with transcutaneous electrical nerve stimulation (TENS). First, the algorithm was trained offline on a dataset comprising 49 subjects. Then, the neurostimulation was then integrated with a graphical user interface (GUI) to create an intuitive AI-based mapping platform enabling the user to autonomously perform the sensation characterization procedure. We assessed the algorithm against the performance of both experienced and naïve and of a brute force algorithm (BFA), on 15 nerves from five subjects. Then, we validated the AI-based platform on six neuropathic nerves affected by distal sensory loss. Results: Our automatized approach demonstrated the ability to find the optimal values of neurostimulation achieving reliable and comfortable elicited sensations. When compared to alternatives, RL outperformed the naïve and BFA, significantly decreasing the time for mapping and the number of delivered stimulation trains, while improving the overall quality. Furthermore, the RL algorithm showed performance comparable to trained experimenters. Finally, we exploited it successfully for eliciting sensory feedback in neuropathic patients. Conclusions: Our findings demonstrated that the AI-based platform based on a RL algorithm can automatically and efficiently calibrate parameters for somatosensory nerve stimulation. This holds promise to avoid experts’ employment in similar scenarios, thanks to the merging between AI and neurotech. Our RL algorithm has the potential to be used in other neuromodulation fields requiring a mapping process of the stimulation parameters. Trial registration: ClinicalTrial.gov (Identifier: NCT04217005) [ABSTRACT FROM AUTHOR]

Anterior segment optical coherence tomography (AS-OCT) allows the explore not only the anterior chamber but also the front part of the vitreous cavity. Our cross-sectional single-centre study investigated whether AS-OCT can distinguish between vitreous involvement due to vitreoretinal lymphoma (VRL) and vitritis in uveitis. We studied AS-OCT images from 28 patients (11 with biopsy-proven VRL and 17 with differential diagnosis uveitis) using publicly available radiomics software written in MATLAB. Patients were divided into two balanced groups: training and testing. Overall, 3260/3705 (88%) AS-OCT images met our defined quality criteria, making them eligible for analysis. We studied five different sets of grey-level samplings (16, 32, 64, 128, and 256 levels), finding that 128 grey levels performed the best. We selected the five most effective radiomic features ranked by the ability to predict the class (VRL or uveitis). We built a classification model using the xgboost python function; through our model, 87% of eyes were correctly diagnosed as VRL or uveitis, regardless of exam technique or lens status. Areas under the receiver operating characteristic curves (AUC) in the 128 grey-level model were 0.95 [CI 0.94, 0.96] and 0.84 for training and testing datasets, respectively. This preliminary retrospective study highlights how AS-OCT can support ophthalmologists when there is clinical suspicion of VRL. [ABSTRACT FROM AUTHOR]

For cosmetic industrial applications, polyurea microcapsules were formed by using hexamethylene diisocyanate biuret low viscosity (HDB‐LV) and three different amines: ethylenediamine (EDA), guanidine (GUA), and hexamethylenediamine (HMDA). Toluene droplets containing dissolved HDB‐LV were formed by an oil‐in‐water emulsion before being poured into a water phase containing the required excess of amine. The pH of the aqueous phase was fitted through time to calculate the kinetic constant k' and the diffusion constant DB through the polyurea shell when possible. At 60 °C, EDA and HMDA follow a pure kinetic regime, whereas GUA follows a combination of kinetic and diffusion regimes. The presented kinetic data shows that HDB‐LV is a promising nontoxic isocyanate for cosmetic encapsulation. [ABSTRACT FROM AUTHOR]

Lymphoproliferative lung diseases are a heterogeneous group of disorders characterized by primary or secondary involvement of the lung. Primary pulmonary lymphomas are the most common type, representing 0.5–1% of all primary malignancies of the lung. The radiological presentation is often heterogeneous and non-specific: consolidations, masses, and nodules are the most common findings, followed by ground-glass opacities and interstitial involvement, more common in secondary lung lymphomas. These findings usually show a prevalent perilymphatic spread along bronchovascular bundles, without a prevalence in the upper or lower lung lobes. An ancillary sign, such as a "halo sign", "reverse halo sign", air bronchogram, or CT angiogram sign, may be present and can help rule out a differential diagnosis. Since a wide spectrum of pulmonary parenchymal diseases may mimic lymphoma, a correct clinical evaluation and a multidisciplinary approach are mandatory. In this sense, despite High-Resolution Computer Tomography (HRCT) representing the gold standard, a tissue sample is needed for a certain and definitive diagnosis. Cryobiopsy is a relatively new technique that permits the obtaining of a larger amount of tissue without significant artifacts, and is less invasive and more precise than surgical biopsy. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to determine the frequency of detection of isthmoceles by ultrasound 6 months after caesarean section (CS) and which symptoms associated with isthmocele formation occur after CS. Subsequently, it was determined how often the ultrasound finding "isthmocele" coincided with the presence of complaints. Methods: A prospective multicentre cohort study was conducted with 546 patients from four obstetric centres in Berlin, who gave birth by primary or secondary CS from October 2019 to June 2020. 461 participants were questioned on symptoms 3 months after CS; 329 participants were included in the final follow-up 6 months after CS. The presence of isthmoceles was determined by transvaginal sonography (TVS) 6 months after CS, while symptoms were identified by questionnaire. Results: Of the 329 women, 146 (44.4%) displayed an isthmocele in the TVS. There was no statistically significant difference in the manifestation of symptoms between the two groups of women with and without isthmocele; however, when expressed on a scale from 1 to 10 the intensity of both scar pain and lower abdominal pain was significantly higher in the set of women that had shown to have developed an isthmocele (p = 0.014 and p = 0.031, respectively). Conclusion: The prevalence of isthmoceles 6 months after CS was 44.4%. Additionally, scar pain and lower abdominal pain were more pronounced when an isthmocele was also observed in the TVS. Trial registration: Trial registration number DRKS00024977. Date of registration 17.06.2021, retrospectively registered. [ABSTRACT FROM AUTHOR]

This paper deals with a family of stochastic control problems in Hilbert spaces which arises in many engineering/economic/financial applications (in particular the ones featuring boundary control and control of delay equations with delay in the control) and for which it is difficult to apply the dynamic programming approach due to the unboundedness of the control operator and to the lack of regularity of the underlying transition semigroup. We introduce a specific concept of partial derivative, designed for this situation, and we develop a method to prove that the associated HJB equation has a solution with enough regularity to find optimal controls in feedback form. [ABSTRACT FROM AUTHOR]

Altered or atypical functional connectivity as measured with functional magnetic resonance imaging (fMRI) is a hallmark feature of brain connectopathy in psychiatric, developmental, and neurological disorders. However, the biological underpinnings and etiopathological significance of this phenomenon remain unclear. The recent development of MRI-based techniques for mapping brain function in rodents provides a powerful platform to uncover the determinants of functional (dys)connectivity, whether they are genetic mutations, environmental risk factors, or specific cellular and circuit dysfunctions. Here, we summarize the recent contribution of rodent fMRI toward a deeper understanding of network dysconnectivity in developmental and psychiatric disorders. We highlight substantial correspondences in the spatiotemporal organization of rodent and human fMRI networks, supporting the translational relevance of this approach. We then show how this research platform might help us comprehend the importance of connectional heterogeneity in complex brain disorders and causally relate multiscale pathogenic contributors to functional dysconnectivity patterns. Finally, we explore how perturbational techniques can be used to dissect the fundamental aspects of fMRI coupling and reveal the causal contribution of neuromodulatory systems to macroscale network activity, as well as its altered dynamics in brain diseases. These examples outline how rodent functional imaging is poised to advance our understanding of the bases and determinants of human functional dysconnectivity. [ABSTRACT FROM AUTHOR]

In this paper we show that several classes of languages from computational complexity theory, such as EXPTIME , can be characterized in a continuous manner by using only polynomial differential equations. This characterization applies not only to languages, but also to classes of functions, such as the classes defining the Grzegorczyk hierarchy, which implies an analog characterization of the class of elementary computable functions and the class of primitive recursive functions. [ABSTRACT FROM AUTHOR]

Gene transfer agents (GTAs) are prophage-like entities found in many bacterial genomes that cannot propagate themselves and instead package approximately 5 to 15 kbp fragments of the host genome that can then be transferred to related recipient cells. Although suggested to facilitate horizontal gene transfer (HGT) in the wild, no clear physiological role for GTAs has been elucidated. Here, we demonstrate that the α-proteobacterium Caulobacter crescentus produces bona fide GTAs. The production of Caulobacter GTAs is tightly regulated by a newly identified transcription factor, RogA, that represses gafYZ, the direct activators of GTA synthesis. Cells lacking rogA or expressing gafYZ produce GTAs harboring approximately 8.3 kbp fragment of the genome that can, after cell lysis, be transferred into recipient cells. Notably, we find that GTAs promote the survival of Caulobacter in stationary phase and following DNA damage by providing recipient cells a template for homologous recombination-based repair. This function may be broadly conserved in other GTA-producing organisms and explain the prevalence of this unusual HGT mechanism. The model organism Caulobacter crescentus is found to produce a prophage-like gene transfer agent that mediates survival to stationary phase and DNA damaging conditions by providing genomic DNA from donor cells for recombination-based repair in recipient cells. [ABSTRACT FROM AUTHOR]

COVID-19, the infectious disease caused by SARS-CoV-2, has spread on a pandemic scale. The viral infection can evolve asymptomatically or can generate severe symptoms, influenced by the presence of comorbidities. Lymphopenia based on the severity of symptoms in patients affected with COVID-19 is frequent. However, the profiles of CD4+ and CD8+ T cells regarding cytotoxicity and antiviral factor expression have not yet been completely elucidated in acute SARS-CoV-2 infections. The purpose of this study was to evaluate the phenotypic and functional profile of T lymphocytes in patients with moderate and severe/critical COVID-19. During the pandemic period, we analyzed a cohort of 62 confirmed patients with SARS-CoV-2 (22 moderate cases and 40 severe/critical cases). Notwithstanding lymphopenia, we observed an increase in the expression of CD28, a co-stimulator molecule, and activation markers (CD38 and HLA-DR) in T lymphocytes as well as an increase in the frequency of CD4+ T cells, CD8+ T cells, and NK cells that express the immunological checkpoint protein PD-1 in patients with a severe/critical condition compared to healthy controls. Regarding the cytotoxic profile of peripheral blood mononuclear cells, an increase in the response of CD4+ T cells was already observed at the baseline level and scarcely changed upon PMA and Ionomycin stimulation. Meanwhile, CD8+ T lymphocytes decreased the cytotoxic response, evidencing a profile of exhaustion in patients with severe COVID-19. As observed by t-SNE, there were CD4+ T-cytotoxic and CD8+ T with low granzyme production, evidencing their dysfunction in severe/critical conditions. In addition, purified CD8+ T lymphocytes from patients with severe COVID-19 showed increased constitutive expression of differentially expressed genes associated with the caspase pathway, inflammasome, and antiviral factors, and, curiously, had reduced expression of TNF-α. The cytotoxic profile of CD4+ T cells may compensate for the dysfunction/exhaustion of TCD8+ in acute SARS-CoV-2 infection. These findings may provide an understanding of the interplay of cytotoxicity between CD4+ T cells and CD8+ T cells in the severity of acute COVID-19 infection. [ABSTRACT FROM AUTHOR]

To investigate the role of combined systemic and local chemotherapy in improving the survival of patients with vitreoretinal lymphoma (VRL). Patients with VRL consecutively seen from 2006 to 2020 were retrospectively reviewed; data on the presence and time of central nervous system (CNS) involvement and treatment regimen (systemic, local or combined chemotherapy) were collected. Overall survival (OS) and progression-free survival (PFS) were calculated for each group. Forty-three eyes of 22 subjects with histology-proven VRL were included. Mean time of survival was 64.8 months (SE±10.8). Twelve patients (57%) presented CNS involvement, which was significantly associated with progression (r = 0.48, P =.03) and death (r = 0.56, P =.009). The isolated primary VRL group had a 5-year OS of 80%. Combined systemic and local chemotherapy reduced the risk of death by 82% (hazard ratio 0.18[0.04– 0.85]) in the entire cohort. Combined systemic and local chemotherapy significantly improved OS but not PFS of patients affected by VRL. [ABSTRACT FROM AUTHOR]

Background: Midline Tremor is defined as an isolated or combined tremor that affects the neck, trunk, jaw, tongue, and/or voice and could be part of Essential Tremor (ET), or dystonic tremor. The clinical efficacy of deep brain stimulation for Midline Tremor has been rarely reported. The Ventral Intermediate Nucleus and Globus Pallidus Internus are the preferred targets, but with variable outcomes. Thalamic Ventral-Oralis (VO) complex and Zona Incerta (ZI) are emerging targets for tremor control in various etiologies.To report on neuroradiological, neurophysiological targeting and long-term efficacy of thalamic Ventral-Oralis complex and Zona Incerta deep brain stimulation in Midline Tremor.Three patients (two males and one female) with Midline Tremor in dystonic syndromes were recruited for this open-label study. Clinical, surgical, neurophysiological intraoperative testing and long-term follow-up data are reported.Intraoperative testing and reconstruction of volume of tissue activated confirmed the position of the electrodes in the area stimulated between the thalamic Ventral-Oralis complex and Zona Incerta in all patients.All three patients showed optimal control of both tremor and dystonic features at short-term (6 months) and long-term follow-up (up to 6 years). No adverse events occurred.In the syndromes of Midline Tremor of various origins, the best target for DBS might be difficult to identify. Our results showed that thalamic Ventral-Oralis complex/Zona Incerta may be a viable and safe option even in specific forms of tremor with axial distribution.Objective: Midline Tremor is defined as an isolated or combined tremor that affects the neck, trunk, jaw, tongue, and/or voice and could be part of Essential Tremor (ET), or dystonic tremor. The clinical efficacy of deep brain stimulation for Midline Tremor has been rarely reported. The Ventral Intermediate Nucleus and Globus Pallidus Internus are the preferred targets, but with variable outcomes. Thalamic Ventral-Oralis (VO) complex and Zona Incerta (ZI) are emerging targets for tremor control in various etiologies.To report on neuroradiological, neurophysiological targeting and long-term efficacy of thalamic Ventral-Oralis complex and Zona Incerta deep brain stimulation in Midline Tremor.Three patients (two males and one female) with Midline Tremor in dystonic syndromes were recruited for this open-label study. Clinical, surgical, neurophysiological intraoperative testing and long-term follow-up data are reported.Intraoperative testing and reconstruction of volume of tissue activated confirmed the position of the electrodes in the area stimulated between the thalamic Ventral-Oralis complex and Zona Incerta in all patients.All three patients showed optimal control of both tremor and dystonic features at short-term (6 months) and long-term follow-up (up to 6 years). No adverse events occurred.In the syndromes of Midline Tremor of various origins, the best target for DBS might be difficult to identify. Our results showed that thalamic Ventral-Oralis complex/Zona Incerta may be a viable and safe option even in specific forms of tremor with axial distribution.Methods: Midline Tremor is defined as an isolated or combined tremor that affects the neck, trunk, jaw, tongue, and/or voice and could be part of Essential Tremor (ET), or dystonic tremor. The clinical efficacy of deep brain stimulation for Midline Tremor has been rarely reported. The Ventral Intermediate Nucleus and Globus Pallidus Internus are the preferred targets, but with variable outcomes. Thalamic Ventral-Oralis (VO) complex and Zona Incerta (ZI) are emerging targets for tremor control in various etiologies.To report on neuroradiological, neurophysiological targeting and long-term efficacy of thalamic Ventral-Oralis complex and Zona Incerta deep brain stimulation in Midline Tremor.Three patients (two males and one female) with Midline Tremor in dystonic syndromes were recruited for this open-label study. Clinical, surgical, neurophysiological intraoperative testing and long-term follow-up data are reported.Intraoperative testing and reconstruction of volume of tissue activated confirmed the position of the electrodes in the area stimulated between the thalamic Ventral-Oralis complex and Zona Incerta in all patients.All three patients showed optimal control of both tremor and dystonic features at short-term (6 months) and long-term follow-up (up to 6 years). No adverse events occurred.In the syndromes of Midline Tremor of various origins, the best target for DBS might be difficult to identify. Our results showed that thalamic Ventral-Oralis complex/Zona Incerta may be a viable and safe option even in specific forms of tremor with axial distribution.Results: Midline Tremor is defined as an isolated or combined tremor that affects the neck, trunk, jaw, tongue, and/or voice and could be part of Essential Tremor (ET), or dystonic tremor. The clinical efficacy of deep brain stimulation for Midline Tremor has been rarely reported. The Ventral Intermediate Nucleus and Globus Pallidus Internus are the preferred targets, but with variable outcomes. Thalamic Ventral-Oralis (VO) complex and Zona Incerta (ZI) are emerging targets for tremor control in various etiologies.To report on neuroradiological, neurophysiological targeting and long-term efficacy of thalamic Ventral-Oralis complex and Zona Incerta deep brain stimulation in Midline Tremor.Three patients (two males and one female) with Midline Tremor in dystonic syndromes were recruited for this open-label study. Clinical, surgical, neurophysiological intraoperative testing and long-term follow-up data are reported.Intraoperative testing and reconstruction of volume of tissue activated confirmed the position of the electrodes in the area stimulated between the thalamic Ventral-Oralis complex and Zona Incerta in all patients.All three patients showed optimal control of both tremor and dystonic features at short-term (6 months) and long-term follow-up (up to 6 years). No adverse events occurred.In the syndromes of Midline Tremor of various origins, the best target for DBS might be difficult to identify. Our results showed that thalamic Ventral-Oralis complex/Zona Incerta may be a viable and safe option even in specific forms of tremor with axial distribution.Conclusion: Midline Tremor is defined as an isolated or combined tremor that affects the neck, trunk, jaw, tongue, and/or voice and could be part of Essential Tremor (ET), or dystonic tremor. The clinical efficacy of deep brain stimulation for Midline Tremor has been rarely reported. The Ventral Intermediate Nucleus and Globus Pallidus Internus are the preferred targets, but with variable outcomes. Thalamic Ventral-Oralis (VO) complex and Zona Incerta (ZI) are emerging targets for tremor control in various etiologies.To report on neuroradiological, neurophysiological targeting and long-term efficacy of thalamic Ventral-Oralis complex and Zona Incerta deep brain stimulation in Midline Tremor.Three patients (two males and one female) with Midline Tremor in dystonic syndromes were recruited for this open-label study. Clinical, surgical, neurophysiological intraoperative testing and long-term follow-up data are reported.Intraoperative testing and reconstruction of volume of tissue activated confirmed the position of the electrodes in the area stimulated between the thalamic Ventral-Oralis complex and Zona Incerta in all patients.All three patients showed optimal control of both tremor and dystonic features at short-term (6 months) and long-term follow-up (up to 6 years). No adverse events occurred.In the syndromes of Midline Tremor of various origins, the best target for DBS might be difficult to identify. Our results showed that thalamic Ventral-Oralis complex/Zona Incerta may be a viable and safe option even in specific forms of tremor with axial distribution. [ABSTRACT FROM AUTHOR]

To identify the best transfer learning approach for the identification of the most frequent abnormalities on chest radiographs (CXRs), we used embeddings extracted from pretrained convolutional neural networks (CNNs). An explainable AI (XAI) model was applied to interpret black-box model predictions and assess its performance. Seven CNNs were trained on CheXpert. Three transfer learning approaches were thereafter applied to a local dataset. The classification results were ensembled using simple and entropy-weighted averaging. We applied Grad-CAM (an XAI model) to produce a saliency map. Grad-CAM maps were compared to manually extracted regions of interest, and the training time was recorded. The best transfer learning model was that which used image embeddings and random forest with simple averaging, with an average AUC of 0.856. Grad-CAM maps showed that the models focused on specific features of each CXR. CNNs pretrained on a large public dataset of medical images can be exploited as feature extractors for tasks of interest. The extracted image embeddings contain relevant information that can be used to train an additional classifier with satisfactory performance on an independent dataset, demonstrating it to be the optimal transfer learning strategy and overcoming the need for large private datasets, extensive computational resources, and long training times. [ABSTRACT FROM AUTHOR]

This study will provide an overview and a description of the most promising alternatives to conventional thermal treatments for juice stabilization, as well as a review of the literature data on fruit and vegetable juice processing in terms of three key parameters in juice production, which are microbial reduction, enzyme inactivation, and nutrient-compound retention. The alternatives taken into consideration in this work can be divided, according to the action mechanism upon which these are based, in non-conventional thermal treatments, among which microwave heating (MWH) and ohmic heating (OH), and non-thermal treatments, among which electrical treatments, i.e., pulsed electric fields (PEF), high-pressure processing (HPP), radiation treatments such as ultraviolet light (UVL) and high-intensity pulsed light (PL), and sonication (HIUS) treatment, and inert-gas treatments, i.e., the pressure change technology (PCT) and supercritical carbon dioxide (SC-CO2) treatments. For each technology, a list of the main critical process parameters (CPP), advantages (PROS), and disadvantages (CONS) will be provided. In addition, for the non-thermal technologies, a summary of the most relevant published result of their application on fruit and vegetable juices will be presented. On top of that, a comparison of typical specific working energy costs for the main effective and considered technologies will be reported in terms of KJ per kilograms of processed product. [ABSTRACT FROM AUTHOR]

To evaluate the efficacy of Rituximab (RTX) therapy in patients affected by Vogt-Koyanagi-Harada (VKH) disease poorly controlled by traditional immunosuppressive treatment. Retrospective case series of recurrent VKH uveitis treated with intravenous RTX between January 2019 and November 2020. All patients were treated with intravenous RTX and underwent complete ophthalmic examination, best-corrected visual acuity (BCVA), fundus photography, subfoveal choroidal thickness (SFCT) measurement on enhanced depth imaging optical-coherence tomography (EDI-OCT), fluorescein, and indocyanine green angiography. Five patients were included. All patients received at least 3 RTX infusions. Mean BCVA improved from 20/32 Snellen equivalent at baseline before RTX treatment to 20/28 Snellen equivalent (p =.008). Mean SFCT on EDI-OCT showed a reduction from 564.4 µm(SD = 176.2) to 280.0 µm(SD = 140.4) (p =.015). Follow-up ranged from 12 to 21 months, with a mean of 18.2 ± 3.7 months. In these case series, RTX was effective in VHK disease poorly controlled by traditional immunosuppressive treatment. [ABSTRACT FROM AUTHOR]

We analyze the effectiveness of the first six months of vaccination campaign against SARS-CoV-2 in Italy by using a computational epidemic model which takes into account demographic, mobility, vaccines data, as well as estimates of the introduction and spreading of the more transmissible Alpha variant. We consider six sub-national regions and study the effect of vaccines in terms of number of averted deaths, infections, and reduction in the Infection Fatality Rate (IFR) with respect to counterfactual scenarios with the actual non-pharmaceuticals interventions but no vaccine administration. Furthermore, we compare the effectiveness in counterfactual scenarios with different vaccines allocation strategies and vaccination rates. Our results show that, as of 2021/07/05, vaccines averted 29, 350 (IQR: [16, 454–42, 826]) deaths and 4, 256, 332 (IQR: [1, 675, 564–6, 980, 070]) infections and a new pandemic wave in the country. During the same period, they achieved a −22.2% (IQR: [−31.4%; −13.9%]) IFR reduction. We show that a campaign that would have strictly prioritized age groups at higher risk of dying from COVID-19, besides frontline workers and the fragile population, would have implied additional benefits both in terms of avoided fatalities and reduction in the IFR. Strategies targeting the most active age groups would have prevented a higher number of infections but would have been associated with more deaths. Finally, we study the effects of different vaccination intake scenarios by rescaling the number of available doses in the time period under study to those administered in other countries of reference. The modeling framework can be applied to other countries to provide a mechanistic characterization of vaccination campaigns worldwide. Author summary: We propose a realistic epidemic model to study the first six months of the COVID-19 vaccination campaign in Italy. The model is applied to six subnational territories and is informed with a wealth of data describing demographics, the impact of non-pharmaceutical interventions (NPIs) on contacts patterns, vaccines administration, and the spread of the Alpha variant. The results highlight the critical beneficial effects of the vaccination campaign. As of 2021/07/05 vaccines averted 29K+ deaths, 4.5M+ infections, and a new pandemic wave in the country with respect to a baseline without vaccines but the same NPIs. Through counterfactual scenarios, we show that a strict vaccine prioritization by age would have avoided additional fatalities while prioritizing the most socially active part of the population would have led to a smaller number of infections but more deaths. Our framework provides the anatomy of the vaccination rollout and its effects on the COVID-19 Pandemic in Italy. Furthermore, it can be used to provide a characterization of vaccination campaigns in other countries. [ABSTRACT FROM AUTHOR]

High-frequency (HF) radio-frequency identification (RFIDs) tags can be combined to electrodes coated with semiconducting thin-films to produce low-cost and disposable sensors with wireless capabilities. Mobile phone applications generally use near-field connection (NFC) to read chip digital information, providing discrete information from the device. To obtain a continuous analogic reading, more sophisticated equipment such as spectrum analyzers are needed. In the present article, we describe a method to obtain the frequency response spectrum of RFID tags using synchronous detection via a lock-in amplifier. The tags were coupled to interdigitated electrodes coated with semiconducting metal oxides (SMOs) to produce UV-sensors and with semiconducting polymer polyaniline (Pani) as chemically responsive wireless devices for the proof-of-concept of the developed method. [ABSTRACT FROM AUTHOR]

This study introduces a robust method for analyzing the geochemical behavior of chemical species in river catchment water. It focuses on isometric log-ratio coordinates obtained from a sequential partition method that successively maximizes the explained variance in the data set. Robust orthonormal coordinates are created based on hierarchical clustering and robust estimation of the variation matrix. Applying this to the water chemistry of Italy's Arno and Tiber basins, the research reveals the associations of variables in data structure and processes across varying geological and climatic conditions. The method uncovers key contrasting geochemical processes and suggests that the behavior of simple balances characterized by lower variances (i.e., Ca 2 + / HCO 3 − and Na + / Cl −) are mainly influenced by random fluctuations with no differences between classical or robust methods. However, when balances describe more complex geochemical processes resulting in frequency distributions affected by the presence of bimodality or outliers, significant differences among the two approaches emerge, compromising the data interpretation. The proposed metodology offers more insights into the investigation of catchment geochemistry's resilience to hydroclimatic changes, marking a significant step in understanding large-scale environmental dynamics. [Display omitted] • Implemented robust procedure to calculate principal balances • Debate oriented on the role of the variance for robust balances • Robust balances as monitoring indices of geochemical variability in Mediterranean river basins • Catchment geochemical resilience to hydro-climatic changes assessed by robust balances. [ABSTRACT FROM AUTHOR]

We deal with an infinite horizon, infinite dimensional stochastic optimal control problem arising in the study of economic growth in time-space. Such a problem has been the object of various papers in deterministic cases when the possible presence of stochastic disturbances is ignored (see, e.g., [P. Brito, The Dynamics of Growth and Distribution in a Spatially Heterogeneous World, working paper 2004/14, ISEG-Lisbon School of Economics and Management, University of Lisbon, 2004], [R. Boucekkine, C. Camacho, and G. Fabbri, J. Econom. Theory, 148 (2013), pp. 2719--2736], [G. Fabbri, J. Econom. Theory, 162 (2016), pp. 114--136], and [R. Boucekkine, G. Fabbri, S. Federico, and F. Gozzi, J. Econom. Geography, 19 (2019), pp. 1287--1318]). Here we propose and solve a stochastic generalization of such models where the stochastic term, in line with the standard stochastic economic growth models (see, e.g., the books [A. G. Malliaris and W. A. Brock, Stochastic Methods in Economics and Finance, Advanced Textbooks in Economics 17, North Holland, 1982, Chapter 3] and [H. Morimoto, Stochastic Control and Mathematical Modeling: Applications in Economics, Cambridge Books, 2010, Chapter 9]), is a multiplicative one, driven by a cylindrical Wiener process. The problem is studied using the dynamic programming approach. We find an explicit solution of the associated HJB equation, use a verification type result to prove that such a solution is the value function, and find the optimal feedback strategies. Finally, we use this result to study the asymptotic behavior of the optimal trajectories. [ABSTRACT FROM AUTHOR]

We consider the life-cycle optimal portfolio choice problem faced by an agent receiving labor income and allocating her wealth to risky assets and a riskless bond subject to a borrowing constraint. In this paper, to reflect a realistic economic setting, we propose a model where the dynamics of the labor income has two main features. First, labor income adjusts slowly to financial market shocks, a feature already considered in Biffis et al. (2015). Second, the labor income y i of an agent i is benchmarked against the labor incomes of a population y n ≔ (y 1 , y 2 , ... , y n) of n agents with comparable tasks and/or ranks. This last feature has not been considered yet in the literature and is faced taking the limit when n → + ∞ so that the problem falls into the family of optimal control of infinite-dimensional McKean–Vlasov Dynamics, which is a completely new and challenging research field. We study the problem in a simplified case where, adding a suitable new variable, we are able to find explicitly the solution of the associated HJB equation and find the optimal feedback controls. The techniques are a careful and nontrivial extension of the ones introduced in the previous papers of Biffis et al. (2015, 0000). [ABSTRACT FROM AUTHOR]

The promise of efficacious vaccines against SARS-CoV-2 is fulfilled and vaccination campaigns have started worldwide. However, the fight against the pandemic is far from over. Here, we propose an age-structured compartmental model to study the interplay of disease transmission, vaccines rollout, and behavioural dynamics. We investigate, via in-silico simulations, individual and societal behavioural changes, possibly induced by the start of the vaccination campaigns, and manifested as a relaxation in the adoption of non-pharmaceutical interventions. We explore different vaccination rollout speeds, prioritization strategies, vaccine efficacy, as well as multiple behavioural responses. We apply our model to six countries worldwide (Egypt, Peru, Serbia, Ukraine, Canada, and Italy), selected to sample diverse socio-demographic and socio-economic contexts. To isolate the effects of age-structures and contacts patterns from the particular pandemic history of each location, we first study the model considering the same hypothetical initial epidemic scenario in all countries. We then calibrate the model using real epidemiological and mobility data for the different countries. Our findings suggest that early relaxation of safe behaviours can jeopardize the benefits brought by the vaccine in the short term: a fast vaccine distribution and policies aimed at keeping high compliance of individual safe behaviours are key to mitigate disease resurgence. Author summary: The start of vaccination campaigns is a decisive turning point in the global effort against COVID-19. Nonetheless, at least in the short and medium-term, vaccine availability and the logistical issues associated with an unprecedented mass vaccination suggest that non-pharmaceutical interventions will still play an important role in virus containment. Here, we propose an epidemic model to study the possible effects induced by a relaxation of COVID-safe behaviours in response to the vaccine rollout. Individuals may see this milestone as the end of the emergency and thus give up preventive measures potentially exposing themselves to higher infection risk. We explore the interplay between such behavioural changes and different population pyramids, contact patterns, epidemic conditions, vaccine allocation strategies, rollout speed, and vaccine efficacy. We show that early relaxation of COVID-safe behaviours can jeopardize and even nullify the benefit brought by the vaccine in the short and medium-term. Our results indicate that a high level of compliance to NPIs during vaccines rollout is crucial to avoid hindering the gigantic effort of the vaccination campaigns. [ABSTRACT FROM AUTHOR]

We correct assumption (4.6) in Theorem 4.1 in [F. Gozzi and F. Masiero, SIAM J. Control Optim., 55 (2017), pp. 2981-3012], and we consequently change the proof of Theorem 4.1. We correct the proof of Lemma 5.4 in [F. Gozzi and F. Masiero, SIAM J. Control Optim., 55 (2017), pp. 2981-3012]. Moreover, throughout the paper, starting from formulas (3.13) and (3.14), we notice that the current cost of the control problem cannot depend on the state for the results of the paper to work. This change in the current cost must be made in the paper [F. Gozzi and F. Masiero, SIAM J. Control Optim., 55 (2017), pp. 3013-3038], too. [ABSTRACT FROM AUTHOR]

Severely molar-incisor hypomineralization (MIH)–affected teeth are prone to develop early posteruptive enamel breakdown (PEB) and caries. A novel conservative interim approach for the prevention of this complication is presented. A 6-year-old boy with strong hypersensitivity and extensive brown opacities in the partially erupted mandibular permanent first molars (PFMs) was diagnosed with MIH. Constant hygiene and dietary counseling were followed by the application of luted orthodontic bands and glass ionomer sealants to protect PFMs from caries and PEB until the complete eruption of the teeth. After 36 months, the PFMs were completely erupted, with no caries and PEB, and the cooperation of the child increased. Temporary strategies are useful to preserve MIH-affected PFMs. With the methodology described, the hypersensitivity decreased and the patient reached a good degree of cooperation, making possible definitive rehabilitative considerations. [ABSTRACT FROM AUTHOR]

John Aitchison revolutionised in 1982 our way of approaching geochemical data focusing on their relative nature. In this perspective, the investigation of single variables is meaningless due to the entangled structure that links all the parts of a composition. Starting from that time, several developments have characterized the debate within the scientific community, both from the applied and the theoretical point of view. The consequence was that the number of papers where compositional data are consistently and coherently managed increased exponentially. The exploratory phase of compositional data is a very important step in data analysis and modeling. It not only helps to clarify the available sample data structure but also determines the base to develop models to predict time and space changes. Real chemical data along the course of the river Tevere (Tiber) (Italy) and its tributaries are taken to illustrate how compositional techniques help explore compositions and detect patterns and outliers in the data. [Display omitted] • Explorative statistics as a fundamental step of data analysis • Choice of the sample space for compositional data • Investigating the source of compositional variability and outliers • Combining compositional and non-compositional information • Identifying discriminant compositional indices [ABSTRACT FROM AUTHOR]

This work aimed to systematically abate in batch mode organic pollutants from raw dairy wastewater (DW) with high values of chemical oxygen demand (COD, ∼10.3 g L−1), total organic carbon (TOC, ∼2.4 g L−1), and total nitrogen (TN, ∼0.28 g L−1) by using the Poterioochromonas malhamensis algae strains. In this regard, variables such as fractions of DW (40–100%, v/v), mineral nutritional inoculum addition (0–100%, w/v) and CO 2 -enriched air (2–8%) were proposed to address a study in optimizing conditions with new insights on algae production. As controlled photobioreactors (PBR), a set of tubular PBRs and a pair of flat-plate PBRs (FP-PBR) surrounded by fluorescent lamps and pumped by CO 2 -enriched air at a flow rate of 1.4 L min− 1 per litre were used. A Box-Behnken design (BBD) for algal growing was applied using the set of tubular PBRs to get a better reduction in TOC, TN and COD, defining an optimized condition. On the best tubular PBRs-based outcome and including a holed baffles system for hydrodynamically providing a flashing light state, 9-day kinetic experiments based on a pair of FP-PBRs were performed to provide more insights on how to enhance the algal yield and COD, TN and TOC reduction. A biomass yield rate of 1.1 g L−1 per day was attained using FP-PBRs, being comparatively 10% better than tubular PBRs. Additionally, the organic pollution abatement in DW was highly significant, with a decrease of about 98%, 95%, and 92% in COD, TN and TOC, respectively, besides changing the initial bacteria diversity to another less harmful one. • Optimized combination of dairy wastewater, inoculum, and CO 2 has improved algal yield. • High removals of total organic carbon and nitrogen were attained by the algae P. malhamensis. • Inoculum supplementation was applied to reduce organic matter in an eco-friendly context. • Algal yield and pollution reduction improvement were attained using flat-plate photobioreactors. • Eco-friendly results were attained using P. malhamensis algae with changes in the biodiversity. [ABSTRACT FROM AUTHOR]

We describe the case of Gefitinib-related bilateral corneal perforation. An 86-year-old female patient had bilateral painless and progressive vision loss due to neurotrophic corneal ulcer, following a 2-month treatment with Gefitinib, a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor for metastatic adenocarcinoma of the lung with confirmed EGFR gene mutation. She had no signs of ocular infection, inflammation, or lid problems to account for the development of corneal damage. Neurotrophic ulcer evolved into a frank perforation in one eye and an impending perforation on the other eye. EGFR inhibitors have been associated with dry eye, epithelial erosions, ulcerative keratitis, and corneal edema. However, to the best of our knowledge, this is the first case of bilateral severe corneal ulcer due to Gefitinib. The patient went on to have bilateral corneal graft surgery. This case aims to raise awareness among ophthalmologists and oncologists of the association between EGFR inhibitors, corneal neurotrophic ulcers, and possible evolution in corneal perforation. [ABSTRACT FROM AUTHOR]

Introdução: Pereskia grandifolia Haw. (Cactaceae), amplamente reconhecida pelo nome vernacular "ora-pronóbis", representa uma espécie endêmica da flora brasileira. Este vegetal tropical carrega uma rica tradição de aplicação na medicina tradicional, cujas propriedades terapêuticas têm sido valorizadas e utilizadas ao longo de séculos. As folhas têm sido tradicionalmente incorporadas na suplementação dietética e frequentemente consumidas sob a forma de infusões, resultantes de propriedades antioxidantes, antitumorais, anti-inflamatórias, hipolipemiantes, antidiabéticas e hipotensoras. Apesar do amplo potencial terapêutico a pesquisa que se debruça sobre a eficácia terapêutica dessa planta no tratamento de condições inflamatórias permanece limitada. A partir do uso popular e tradicional de P. grandifolia em doenças inflamatórias é importante aprofundar e ampliar as investigações quanto ao potencial agente anti-inflamatório de P. grandifolia. Objetivo: Dentro deste contexto, o presente estudo tem como propósito a avaliação da atividade anti-inflamatória e citotóxica in vitro em células cancerígenas, com a finalidade de aprofundar o conhecimento diversificado sobre esta espécie. Método: Para atingir este objetivo, procedeu-se à pulverização de folhas (100 g) e sua subsequente extração por infusão em 1 L de água fervente. O infuso resultante foi mantido em um frasco âmbar por um período de 5 horas. Após filtragem, o infuso foi tratado com etanol 95% na proporção de 1:3 (v/v) para precipitar proteínas e polissacarídeos. A fração solúvel em etanol foi concentrada por meio de um rotaevaporador e posteriormente liofilizada. A avaliação da atividade anti-inflamatória foi realizada por meio das técnicas de fagocitose e espraiamento, utilizando células de macrófagos da linhagem RAW 264. Para a avaliação da citotoxicidade, empregou-se o método de MTT com células de hepatocarcinoma HUH7. Ambas as linhagens celulares foram cultivadas sob condições de cultivo padronizadas, uma atmosfera contendo 4,5% de dióxido de carbono, e uma temperatura de 37°C. As análises de citotoxicidade envolveram concentrações de 100, 200, 400, 800 e 1600 Îg/ml, enquanto os ensaios anti-inflamatórios utilizaram concentrações de 200, 400 e 600 Îg/ml. Resultados: Na avaliação da atividade anti-inflamatória in vitro, o extrato demonstrou os seguintes resultados nas concentrações testadas de 200, 400 e 600 Îg/ml: 43,18%, 47,68% e 56,66% de inibição da fagocitose e 46,99%, 62,05% e 66,87% de inibição do espraiamento. No que diz respeito à análise de citotoxicidade, a determinação concentração de inibição média (IC50%) foi de 446 Îg/mL, 523,4 Îg/mL e 183,3 Îg/mL, respectivamente, nos tempos de 24, 48 e 72 horas. No ensaio de citotoxicidade, observou-se um impacto significativo na viabilidade e proliferação celular das células cancerígenas, indicando a ausência de toxicidade direta nas células testadas. Este achado sugere que P. grandifolia exerce um impacto notável na supressão da carcinogênese, além de se revelar um agente antiinflamatório Conclusão: O extrato de P. grandifolia demonstrou uma marcante atividade anti-inflamatória in vitro, acompanhada de um notável efeito citotóxico sobre as células de hepatocarcinoma. Os resultados obtidos permitem propor o extrato de "ora-pró-nobis" como um agente antiinflamatório e antitumoral seguro e eficaz, abrindo a perspectiva de emprego deste extrato vegetal em modelos de estudos pré-clínícos e translacionais. [ABSTRACT FROM AUTHOR]

We consider an infinite horizon portfolio problem with borrowing constraints, in which an agent receives labor income which adjusts to financial market shocks in a path dependent way. This path dependency is the novelty of the model and leads to an infinite dimensional stochastic optimal control problem. We solve the problem completely and find explicitly the optimal controls in feedback form. This is possible because we are able to find an explicit solution to the associated infinite dimensional HJB equation, even if state constraints are present. To the best of our knowledge, this is the first infinite dimensional generalization of Merton's optimal portfolio problem for which explicit solutions can be found. The explicit solution allows us to study the properties of optimal strategies and discuss their financial implications. [ABSTRACT FROM AUTHOR]

Renal infarction is a rare cause of abdominal pain whose diagnosis is often misunderstood or severely delayed. The difficulty in identifying this time-dependent condition greatly limits the possibilities of therapeutic intervention and determines the loss of renal parenchyma that could have been saved with prompt diagnosis. It is, therefore, essential to include renal infarction in the differential diagnosis in case of abdominal pain and to identify this pathology beforehand. We present a case of a 65-yearold male with atrial fibrillation in therapy with Edoxaban who was admitted to the hospital for acute onset of widespread abdominal pain with nausea, vomit, and a worsening of renal function according to the laboratory tests. An abdominal computed tomography with contrast confirmed the presence of a bilateral renal infarction. The patient developed chronic kidney disease and was discharged on anticoagulant therapy. The aim of this paper is, therefore, to increase physician awareness towards this condition, the best opportunity to diagnose early renal infarction and to establish acute and long-term therapy. [ABSTRACT FROM AUTHOR]

In this work, we aim to determine the main factors driving self-initiated behavioral changes during the seasonal flu. To this end, we designed and deployed a questionnaire via Influweb, a Web platform for participatory surveillance in Italy, during the 2017 − 18 and 2018 − 19 seasons. We collected 599 surveys completed by 434 users. The data provide socio-demographic information, level of concerns about the flu, past experience with illnesses, and the type of behavioral changes voluntarily implemented by each participant. We describe each response with a set of features and divide them in three target categories. These describe those that report i) no (26%), ii) only moderately (36%), iii) significant (38%) changes in behaviors. In these settings, we adopt machine learning algorithms to investigate the extent to which target variables can be predicted by looking only at the set of features. Notably, 66% of the samples in the category describing more significant changes in behaviors are correctly classified through Gradient Boosted Trees. Furthermore, we investigate the importance of each feature in the classification task and uncover complex relationships between individuals' characteristics and their attitude towards behavioral change. We find that intensity, recency of past illnesses, perceived susceptibility to and perceived severity of an infection are the most significant features in the classification task and are associated to significant changes in behaviors. Overall, the research contributes to the small set of empirical studies devoted to the data-driven characterization of behavioral changes induced by infectious diseases. Author summary: Human behavior and infectious diseases are linked by a feedback loop. While individuals might change their behavior as a response to an epidemic, such changes might influence the spreading itself. So far, our understanding and characterization of behavioral changes induced by diseases has been strongly limited by the lack of empirical data. As result, the vast majority of research has been focused on theoretical, what if, scenarios. In this work, we collected a unique dataset comprised of 599 surveys submitted by 434 users to the participatory surveillance platform Influweb over the 2017 − 18 and 2018 − 19 flu seasons. The data provide socio-demographic information, level of concerns about the flu, past experience with illnesses, and the type of self-initiated behavioral changes implemented by each participant. Our analysis, conducted adopting machine learning algorithms, show that both past experience of illness and personal beliefs about the disease are fundamental drivers of behavioral change. These findings are in good agreement with the constructs of the Health Belief Model and provide, to the best of our knowledge, the first data driven characterization of behavioral changes during the seasonal flu. [ABSTRACT FROM AUTHOR]

Granulomatous dermatitis (GD) is the most common among a variety of skin reactions that may occur in the varicella‐zoster virus (VZV) reactivation area. It is thought that the formation of granulomas may be the result of a delayed hypersensitivity reaction to viral envelope glycoproteins. Immune checkpoint inhibitors (ICIs), such as nivolumab stimulate T cells and promote hypersensitivity reactions, leading to the formation of granulomas in VZV wrapping proteins, thus triggering VZV‐GD. Few cases of the use of ICIs in patients diagnosed with VZV‐GD have been reported in the literature. Here, we report the clinical case of a patient with metastatic lung cancer which was treated with nivolumab who subsequently developed VZV‐GD. Accurate clinical diagnosis and prompt treatment with antiviral agents have resulted in a complete resolution of the clinical picture. Key points: Significant findings: Treatment with ICIs may result in VZV reactivation.Accurate differential diagnosis and early treatment led to the resolution of VZV‐GD. What this study adds: Few cases of ICI and VZV reactivation have been reported in the literature.Full and timely resolution of VZV‐GD allowed the continuation of ICI treatment. [ABSTRACT FROM AUTHOR]

Aging is a natural and progressive process, which affects aspects of the individual holistically. An organism aged under normal conditions may survive adequately. However, when subjected to toxicological, physical and emotional stress, among others, it may present difficulties in maintaining its homeostasis and leading to the onset of the hormone mechanism. Hormese is derived from the Greek "hormaein" which means "to excite". In its first definition was described as a biphasic behavior, that is, a biological ability that can be modified by low doses of a xenobiotic, but inhibited by high doses of it, it was proposed as an explanation for changes in homeostasis. One of the most well-accepted theories related to aging is free radical theory. In addition to free radicals other xenobiotics may be intrinsically correlated with senescence of nerve cells, such as drugs of abuse, medications of continuous use, toxins and drugs, among others. This article intends to scientifically present a systematic literature review, bringing the themes hormone, aging and toxicology correlated to the areas of health, toxicology and regulation, showing the fundamental misunderstanding in nature when evaluating responses only by observing the triad dose x response x exposure. During the first decades of the twentieth century this error was the result of multiple factors, including the conflict between homeopathy and traditional medicine, and the evaluations of the hormone dose responses are difficult to interpret, requiring more attention and abstraction compared to linear models, traditionally accepted by the majority of the scientific community. The concept of hormone helps researchers to better address the low dose response, showing that there is adaptability of the organisms and can open a new look on the onset of chronic degenerative diseases and generating paradigm breaks in this perspective. [ABSTRACT FROM AUTHOR]

We report on the unique self-assembling properties of one molybdacarborane (1) and two ruthenacarborane complexes (2 and 3) to spontaneously form nanoparticles alone or in combination with bovine serum albumin (BSA) in a 10:1 molar ratio (BSA:metallacarborane). The maverick behaviour of the metallacarboranes in aqueous media was investigated using several spectroscopic techniques, including nanoparticle tracking analysis, UV-Vis, fluorescence, Rayleigh light scattering and NMR spectroscopy, as well as MALDI-TOF mass spectrometry, from which a molecular picture of the nanoparticles was developed. The metallacarborane–albumin nanoparticles showed optimal stability in phosphate buffer (pH 7.4), retaining a mostly monomodal dispersion over 24 h, in contrast to the highly polydispersed nanoparticles of 1–3 alone. The three metallacarboranes were tested in vitro against the MCF-7 (breast carcinoma) cell line, using a BSA-free and a BSA-containing formulation. Surprisingly, the latter induced a significant increase in the cytotoxicity of 1, whereby it did not greatly affect the activity profile of 2 and 3. Finally, label-free confocal Raman imaging was applied to visualise the uptake of the metallacarboranes into single cells. The size of intracellular aggregates in the cytoplasm ranged from 300 nm to 5 μm. The discussed formulation concept is proposed as a new method to increase the bioactivity and the biological stability of poorly water-soluble (metalla)carboranes. [ABSTRACT FROM AUTHOR]

Studying the chemistry of surface waters and their resilience to compositional changes represents a global challenge to preserve them from human- and changing climate-induced modifications. River waters are sentinel parameters for all processes occurring in a river basin. This is particularly true for regional watersheds, which can include both natural- and anthropogenic-sourced solutes such as those present in the Tiber River basin, the biggest one in Central Italy. In this work, innovative applications of statistical methods are proposed, from the perspective of Compositional Data Analysis theory, in order to consider the geochemical riverine system as a whole and detect compositional changes throughout the catchment. Robust compositional biplots highlighted different sources of variability linked to geological (low variability) and anthropogenic origin (high variability) of the main compounds, thus identifying a hierarchy in the variance of the riverine geochemical processes. On a different scale, the innovative use of the robust Mahalanobis distance in an iterative way monitored spatial compositional shifts for single cases. The effectiveness of this method consists in minimising the influence of an individual anomalous point on the compositional centre and the covariance structure of the data highlighting when along the river a significant compositional shift occurs. The study provides powerful compositional tools for detecting potential contamination events or climate-induced modifications both at catchment and river scale. • Geochemistry of river waters investigated by Compositional Data Analysis. • Discovering different sources of variability in the water composition. • Compositional shifts detected through the robust Mahalanobis distance. • Revealing the hierarchy of the variance in complex riverine systems. [ABSTRACT FROM AUTHOR]

Gd2O3 and Y2O3 films, respectively, doped with Eu3+, Tb3+, and Tm3+ have been grown by the electron beam physical vapor codeposition technique on optically polished quartz substrates. The film samples have been doped at different concentrations by the corresponding rare-earth oxides. The concentration range explored is from 0.9% to 9.8% on 18 samples. For each film sample an extended characterization has been performed by thin film-x-ray diffraction, scanning electron microscopy, energy dispersion spectroscopy, cathodoluminescence spectroscopy, and color coordinate analysis. Y2O3 films display the most intense red-green-blue (RGB) emission and their film morphology and structure are more compact and crystalline with respect to Gd2O3 monoclinic films. Eu3+ and Tb3+ doped Y2O3 films grow oriented along the (222) direction. The ratios between the intensities of the electric dipole and magnetic dipole transitions have been also evaluated. The blue emission of Tm3+ doped Gd2O3 is lacking in the dopant concentration range from 1.6% to 7.6%, whereas it is present in Tm3+ doped Y2O3 films, at approximately the same dopant concentration range (1.9%–9.8%). Commission Internationale de l’Eclairage plot of the color coordinates of all the RGB film samples has been reported together with the RGB phosphor standard used in cathodic ray tube TV screens. [ABSTRACT FROM AUTHOR]

The absorption of hydrogen by Pd wire samples has been studied at 299 K and in the H2 pressure range from 18 to 1800 mbar under both tensile stress and tensile stress under cold H2 plasma. Plasma is generated in a corona discharge regime by applying a dc high voltage between a Pd wire and a cylindrical counterelectrode. Positive and negative coronas have been performed. Three independent experimental quantities have been simultaneously measured: ratio x=nH/nPd, with n the number of atoms; ratio R/R0, with R the four-probe resistance of the wire and R0 the resistance when x=0; and ratio Δl/l0, with Δl the length change of the wire and l0 its length when x=0. From the thermodynamic analysis of data, the absorption standard chemical potential, Δμabs0, and the excess chemical potential, Δμexc, of hydrogen atoms in Pd have been obtained. At constant T, H2 pressure, and tensile stress, the x value under cold plasma is always higher. [ABSTRACT FROM AUTHOR]

Alcoholism is often associated with other forms of drug abuse, suggesting that innate predisposing factors may confer vulnerability to addiction to diverse substances. However, the neurobiological bases of these factors remain unknown. Here, we have used a combination of imaging, neurochemistry and behavioral techniques to investigate responses to the psychostimulant amphetamine in Marchigian Sardinian (msP) alcohol-preferring rats, a model of vulnerability to alcoholism. Specifically, we employed pharmacological magnetic resonance imaging to investigate the neural circuits engaged by amphetamine challenge, and to relate functional reactivity to neurochemical and behavioral responses. Moreover, we studied self-administration of cocaine in the msP rats. We found stronger functional responses in the extended amygdala, alongside with increased release of dopamine in the nucleus accumbens shell and augmented vertical locomotor activity compared with controls. Wistar and msP rats did not differ in operant cocaine self-administration under short access (2 hours) conditions, but msP rats exhibited a higher propensity to escalate drug intake following long access (6 hours). Our findings suggest that neurobiological and genetic mechanisms that convey vulnerability to excessive alcohol drinking also facilitate the transition from psychostimulants use to abuse. [ABSTRACT FROM AUTHOR]

Icosahedral carboranes in medicine are still an emerging class of compounds with potential beneficial applications in drug design. These highly hydrophobic clusters are potential “new keys for old locks” which open up an exciting field of research for well-known, but challenging important therapeutic substrates, as demonstrated by the numerous examples discussed in this review. [ABSTRACT FROM AUTHOR]

This trial (20010168) studied how body weight (BW) and body mass index (BMI) influenced the pharmacokinetics (PK) of anakinra. Subjects (n = 32) were assigned to four groups (n = 8) according to BW and BMI. Randomization was according to a four‐treatment, four‐period, four‐sequence crossover design. The four anakinra injections were 100, 150, and 300 mg s.c. and 100 mg i.v. Plasma samples were measured by enzyme‐linked immunosorbent assay and noncompartmental PK parameters estimated. BW demonstrated the following effects: after i.v. administration, significant effects (P < 0.05) were observed for exposure (area under the concentration–time curve from zero to infinity (AUC0–∞)), peak plasma concentration (Cmax), volume of distribution at steady state, and clearance; whereas after s.c. administration, significant effects (P < 0.05) were observed for Cmax, AUC0–∞, terminal half‐life, and estimated apparent clearance. Mean AUC was reduced 24% and 33% for heavier (BW ≥ 100 kg) vs. lighter subjects (BW ≤ 90 kg) after i.v. and s.c. administration, respectively. BMI increased clearance for heavier subjects. For example, mean (SD) plasma clearance of i.v. anakinra increased from 1.17 ± 0.29 to 1.62 ± 0.24 mL/minute/kg (P < 0.05) for larger (> 100 kg) obese (BMI > 36) vs. larger (> 100 kg) less obese (BMI < 35) subjects, respectively. Similarly, results following s.c. supported those after i.v. administration. Derived half‐lives increased with higher BW and higher BMI ranging from 3.63 hour for less obese, lighter‐weight subjects to 7.62 hour for obese, heavier‐weight subjects. Absolute bioavailability ranged from 80–92% and was unrelated to BW or BMI. Anakinra exposure is statistically significantly related to BW and to a lesser extent BMI. [ABSTRACT FROM AUTHOR]

Today, medicinal chemistry is still clearly dominated by organic chemistry, and commercially available boron-based drugs are rare. In contrast to hydrocarbons, boranes prefer the formation of polyhedral clusters via delocalized 3c2e bonds, such as polyhedral dicarba-closo-dodecaborane(12) (closo-C2B10H12). These clusters have remarkable biological stability, and the three isomers, 1,2- (ortho), 1,7- (meta), and 1,12-dicarba-closo-dodecaborane(12) (para), have attracted much interest due to their unique structural features. Furthermore, anionic nido clusters ([7,8-C2B9H11]2−), derived from the neutral icosahedral closo cluster 1,2-dicarba-closo-dodecaborane(12) by deboronation followed by deprotonation are suitable ligands for transition metals and offer the possibility to form metallacarboranes, for example via coordination through the upper pentagonal face of the cluster. The isolobal analogy between the cyclopentadienyl(–1) ligand (Cp−) and [C2B9H11]2− clusters (dicarbollide anion, Cb2−) is the motivation in using Cb2− as ligand for coordination to a metal center to design compounds for various applications. This review focuses on potential applications of half- and mixed-sandwich-type transition metal complexes in medicine. [ABSTRACT FROM AUTHOR]

Abstract In this paper we show that, via an extension of time, some metric structures naturally appear in both classical and quantum mechanics when both are formulated via path integrals. We calculate the various Ricci scalar and curvatures associated to these metrics and prove that they can be chosen to be zero in classical mechanics while this is not possible in quantum mechanics. Highlights • The discovery of a new role for time and its partner. • The discovery of a super-extension of time and its curvature. • The discovery that the curvature can be brought to zero in Classical Mechanics. [ABSTRACT FROM AUTHOR]

Abstract Light-emitting composites are materials that combine the light-emitting characteristic of phosphor materials with the solubility of conductive polymers. This paper has the purpose of showing an experimental study on electroluminescence in a light-emitting composite comprising PEDOT:PSS as the conductive polymer and Zn 2 SiO 4 :Mn as the phosphor material. The relationship between d.c. current and voltage, as well as luminance and voltage, of light-emitting devices were measured for different active layer thickness and different temperature conditions. Luminance was also measured during impedance spectroscopy experiments (a.c. characterization). It was observed that the electroluminescence in the studied light-emitting composite is a field effect mechanism, with turn-on electric field of (4.6 ± 0.2) kV/cm, and that the electroluminescence efficiency is independent of temperature. Additionally, it was observed that electroluminescence is strictly dependent on the drift current of charge carriers. Finally, a model was proposed to describe the electrical properties and luminance of the studied light-emitting composite. Highlights • Electroluminescence in the light-emitting composite is a field effect mechanism. • Electroluminescence is strictly dependent on the drift current of charge carriers. • A model was proposed to describe the luminance of the light-emitting composite. [ABSTRACT FROM AUTHOR]

In this paper we provide a characterization of the complexity class PSPACE by using a purely continuous model defined with polynomial ordinary differential equations. [ABSTRACT FROM AUTHOR]

In this paper we put forward some simple rules which can be used in order to pass from the quantum Moyal evolution operator to the classical one of Liouville without taking the limit of ħ → 0 . These rules involve the averaging over some auxiliary variables. [ABSTRACT FROM AUTHOR]