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Ticiana De Francesco,1,2 Tsontcho Ianchulev,3 Douglas J Rhee,4 Ronald C Gentile,3,5 Louis R Pasquale,3 Iqbal Ike K Ahmed1,6,7 1John A. Moran Eye Center, University of Utah, Salt Lake City, UT, USA; 2Clinica de Olhos De Francesco, Fortaleza, Brazil; 3Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 4Department of Ophthalmology and Visual Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA; 5NYU Long Island School of Medicine, Department of Ophthalmology, Mineola, NY, USA; 6Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Canada; 7Prism Eye Institute, Mississauga, CanadaCorrespondence: Ticiana De Francesco, Tel +55 85 32192425, Email ticianadefrancesco@gmail.comAbstract: To review the latest surgical advances and evolving clinical use of scleral bio-tissue for reinforcement in the eye and review the published literature on novel surgical applications of scleral allograft bio-tissue. Conventional surgical procedures for scleral reinforcement using homologous scleral allograft have been traditionally ab-externo interventions comprising of anterior or posterior reinforcement of the sclera for clinical indications such as trauma, scleromalacia, glaucoma drainage device coverage, scleral perforation, buckle repair as well as posterior reinforcement for pathologic myopia and staphyloma. There have been a few novel ab-interno uses of scleral bio-tissue for reinforcement in both retina and glaucoma. Over the last decade, there has been an increase in peer-reviewed publications on scleral reinforcement, reflecting more interest in its clinical applications. With favorable biological and biomechanical properties, scleral allograft may be an ideal substrate for an array of new applications and surgical uses.Keywords: sclera, allograft, biotissue, glaucoma

Ticiana De Francesco,1– 3 Iqbal Ike K Ahmed3,4 1Clinica de Olhos De Francesco, Fortaleza, Brazil; 2Hospital de Olhos Leiria de Andrade (HOLA), Fortaleza, Brazil; 3John A. Moran Eye Center, University of Utah, Salt Lake City, UT, USA; 4Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON, CanadaCorrespondence: Ticiana De Francesco, 499 Barao de Aracati, Fortaleza, Brazil, Tel +55 85 3219-24-25, Email ticianadefrancesco@gmail.comAbstract: Microinvasive glaucoma surgery (MIGS) has emerged as a safer method to lower IOP with minimal impact on patient quality of life compared to traditional glaucoma surgeries. With the advent of MIGS, there has been a renewed interest in exploring the suprachoroidal route. MIGS targeting the suprachoroidal space allow for a safe reduction in IOP while sparing conjunctiva and allowing “blebless” surgery, thus avoiding bleb-related complications. This article aims to review the rationale behind the suprachoroidal MIGS procedures and the literature surrounding the efficacy and safety of a novel suprachoroidal device, the MINIject. The available literature has shown promising IOP lowering results with the MINIject implant with a potentially safer and less invasive approach than traditional glaucoma surgeries.Keywords: suprachoroidal space, microinvasive glaucoma surgery, glaucoma

Valentina Perrone,1 Chiara Veronesi,1 Melania Dovizio,1 Domenica Daniela Ancona,2 Margherita Andretta,3 Fausto Bartolini,4 Arturo Cavaliere,5 Alessandro Chinellato,6 Andrea Ciaccia,7 Mariarosaria Cillo,8 Adele De Francesco,9 Nicola Enieri,6 Fulvio Ferrante,10 Simona Gentile,11 Cataldo Procacci,2 Loredana Ubertazzo,12 Adriano Vercellone,13 Domenico Lucatelli,14 Michela Procaccini,14 Luca Degli Esposti1 1CliCon S.r.l., Società Benefit-Health, Economics & Outcomes Research, Bologna, Italy; 2Dipartimento Farmaceutico, ASL BAT, Andria, Italy; 3UOC Assistenza Farmaceutica Territoriale, Azienda ULSS 8 Berica, Vicenza, Italy; 4Dipartimento Farmaceutico, USL Umbria 2, Terni, Italy; 5Farmaceutica Aziendale, ASL Viterbo, Viterbo, Italy; 6Unità Operativa Farmacia Ospedaliera, ULSS 3 Serenissima, Mestre, Italy; 7ASL Foggia, Foggia, Italy; 8Dipartimento Farmaceutico, ASL Salerno, Salerno, Italy; 9Azienda Ospedaliero-Universitaria “Mater Domini”, Catanzaro, Italy; 10ASL Frosinone, Frosinone, Italy; 11Direzione Generale per la Salute, Campobasso, Italy; 12ASL Roma 4, Civitavecchia, Roma, Italy; 13ASL Napoli 3 sud, Napoli, Italy; 14Angelini Pharma, Roma, ItalyCorrespondence: Valentina Perrone, CliCon S.r.l., Società Benefit-Health, Economics & Outcomes Research, Via Murri 9, Bologna, 40137, Italy, Tel +39 3450316494, Email valentina.perrone@clicon.itPurpose: A retrospective analysis was conducted to estimate the number of patients with focal epilepsy and drug-resistant epilepsy (DRE) and their characteristics, the therapeutic patterns, the consumption of health resources in a real-world Italian setting.Patients and Methods: A retrospective study was carried out on the administrative databases of a sample of Italian Health Departments, covering approximately 8.7 million health-assisted individuals. All adult patients with at least one hospitalization for focal epilepsy and an electroencephalogram (between 01/2010 and 12/2019), and at least one prescription of antiseizure medication (ASM) (between 01/2011 and 12/2018) were included in the study. Patients with at least two treatment failures and treated with a subsequent ASM were considered DRE.Results: Overall, 1897 patients with focal epilepsy (mean age 56 years, 47% male) were identified, of which 485 (25.6%) with DRE (mean age 53 years, 43% male). Among patients with focal epilepsy and DRE, respectively, 48% and 54% had essential hypertension, 23.4% and 26.6% had cardiovascular disease, and 46.3% and 62.1% had peptic ulcer/prescription of gastric secretion inhibitors. During follow-up, patients with focal epilepsy maintained first-line treatment for 53.9 months; among these, 52% passed to the second-line, and 485 (25.6% of the total) began third-line treatment. In patients with focal epilepsy, the mean cost was € 4448 (of which € 1410 were epilepsy-related), and in DRE patients total expenditures averages € 5825 (of which € 2165 were epilepsy-related). In both patients with focal epilepsy and DRE, hospitalizations represented the most impacting item of expenditure.Conclusion: The present analysis conducted in a setting of Italian clinical practice has shown that 25% of patients with focal epilepsy were resistant to antiepileptic treatments. Furthermore, these results showed that health-care costs for the management of epileptic patients were mainly accountable for the costs related to the disease-management and to hospitalizations.Keywords: epilepsy, real-world evidence, clinical practice, pharmacoutilization, healthcare resource consumption

Marco Bellone,1 Lorenzo Pradelli,1 Stefano Molica,2 Adele Emanuela De Francesco,3 Daniela Ghislieri,4 Emanuele Guardalben,5 Antonietta Caputo4 1Department of Health Economics and Outcome Research, AdRes Health Economics and Outcomes Research, Turin, Italy; 2Dipartimento Onco-ematologico, Azienda Ospedaliera Pugliese-Ciaccio, Catanzaro, Italy; 3Hospital Pharmacy, Mater Domini Azienda Ospedaliero Universitaria, Catanzaro, Italy; 4Market Access Department, Roche SpA, Monza, Italy; 5Medical Department, Roche SpA, Monza, ItalyCorrespondence: Marco BelloneAdRes Health Economics and Outcomes Research, 17 Via Vittorio Alfieri, Turin 10121, ItalyTel +39 011 765-1239Email m.bellone@adreshe.comObjective: To assess the cost-effectiveness of obinutuzumab (O-chemo) in comparison to rituximab (R-chemo) in patients with untreated advanced follicular lymphoma (FL) at intermediate or high risk from an Italian National Health Service (NHS) perspective.Methods: A previously developed four-state Markov model was adapted to estimate lifetime clinical outcomes and costs of Italian patients with advanced FL and an FL international predictive index score ≥ 2 in treatment with O-chemo and R-chemo. Life expectancy was derived from the GALLIUM and PRIMA clinical trials. Progression-free survival (PFS), early progressive disease (PD), and treatment duration were extrapolated by fitting parametric distributions to empirical data in GALLIUM and late PD to data in PRIMA. Expected survival was weighed by published utilities. Costs updated to 2020 Euros and health gains occurring after the first year were discounted at an annual 3% rate. Probabilistic sensitivity analysis (PSA) was carried out.Results: O-chemo was associated with an incremental survival increase (0.97 life-years [LYs]), even when weighted for quality (0.88 quality-adjusted LYs [QALYs]), and incremental costs (around € 15,000), driven by longer treatment during PFS state relative to R-chemo. The incremental cost-effectiveness ratio and incremental cost-utility ratio are both widely accepted by the Italian NHS (around € 15,500/LY and € 17,000/QALY gained, respectively). PSA simulations confirmed the robustness of results given sensible variations in assumptions.Conclusion: O-chemo has superior clinical efficacy compared to rituximab, and should be considered a cost-effective option in first-line treatment of patients with advanced FL at intermediate or high risk in Italy. Incremental cost-effectiveness ratios are below the threshold considered affordable by developed countries.Keywords: economic evaluation, oncology, FLIPI score, ICER, PFS, QALY

John Liu,1,2 Ticiana De Francesco,1,2 Matthew Schlenker,1,2 Iqbal Ike Ahmed1,2 1Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Ontario, Canada; 2Prism Eye Institute, Oakville, Ontario, CanadaCorrespondence: Iqbal Ike Ahmed Tel +1 (905) 456-3937Email ike.research@prismeye.caAbstract: The Icare HOME (TA022, Icare Oy, Vanda, Finland) is rebound tonometer recently approved by the US Food and Drug Administration in March 2017 designed for self-measurement of intraocular pressure (IOP). IOP remains a major modifiable risk factor for glaucoma progression; however, IOP measurements typically occur through single office measurements on Goldmann applanation tonometry (GAT) and do not always reveal the complete picture of patient’s IOP patterns and daily fluctuations, which are important for accurate diagnosis and evaluation. Numerous studies have now compared the efficacy of the Icare HOME to that of GAT. The objective of this article is to review the existing literature surrounding the Icare HOME tonometer and its efficacy as a self-tonometer in comparison to GAT. The available literature has shown promising results in its accuracy of measuring IOP but suggests cautious usage in patients with central corneal thicknesses or IOP ranges that are outside of a certain range. This article will also provide details and example cases for when the Icare HOME may be most clinically useful.Keywords: Icare HOME, Icare, self-tonometry, glaucoma

We review recent inelastic neutron scattering experiments aimed at investigating still open issues in the microscopic dynamics of liquids. It is shown that the interpretation of experimental results is put on solid ground by the application of modern methods of analysis and lineshape modelling which ensure the fulfillment of fundamental physical properties that the spectra must obey. This last condition becomes crucial to avoid overinterpretations of the genuine information conveyed by scattering data, especially when studying weak signals in the dynamic structure factor. Moreover, we highlight the different roles that neutron data presently play compared to molecular dynamics simulations depending on the nature of the sample, including the case of quantum liquids. In particular, we show how neutron measurements remain an indispensable benchmark in assessing the present capabilities of classical and quantum simulation methods. We also mention the potential of statistical methods, such as Bayesian inference, when applied to neutron data analysis and the opportunity they provide in establishing the spectral features without arbitrary assumptions on the model lineshape.

Within a project co-funded by the Italian Ministry of Foreign Affairs, the final aim of which is to develop a WSN for smart monitoring of pesticides on agricultural land, the Italian and Serbian researchers have developed a hardware section of an electronic nose for pesticides. Since there are no specialized sensors which can smell the presence or absence of pesticides in the air, the electronic nose has been designed starting from an array of commercial gas sensors developed for other environmental applications. These sensors have a great advantage as they are COTS components. A measurement bench for testing the performance of the system has also been developed. Experimental tests have been conducted and the results have demonstrated the appropriateness of the idea. A test for calibration has been designed, as well, and it will be performed in the near future.

Pietro Castellan,1 Michele Marchioni,2 Roberto Castellucci,1 Piergustavo De Francesco,2 Romina Iantorno,1 Luigi Schips,1,2 Luca Cindolo1 1Department of Urology, ASL02 Abruzzo, Chieti, Italy; 2Department of Urology, University “G. d’Annunzio”, Chieti, Italy Abstract: In recent years, therapeutic advances, together with new medication sequences and combinations, have improved outcomes for prostate cancer. For a long time, androgen deprivation therapy (ADT) has been the standard of care for newly diagnosed, metastatic prostate cancer, first as a standalone therapy and then in combination with taxane-based regimens. More recently, the addition of abiraterone acetate to ADT to achieve complete androgen blockade has proven beneficial for the treatment of metastatic hormone-resistant prostate cancer and metastatic hormone-sensitive prostate cancer (mHSPC). In this review, we summarize recent findings on the early use of abiraterone in mHSPC and discuss survival benefits as reported in clinical trials. On the basis of existing data, abiraterone in combination with ADT could be considered a new standard of care for patients affected by mHSPC. Keywords: prostate cancer, metastatic hormone-sensitive prostate cancer, androgen receptor, hormonal therapy, abiraterone acetate, prostate castration naïve

The control of sound propagation in materials via the design of their elastic properties is an exciting task at the forefront of Condensed Matter. It becomes especially compelling at terahertz frequencies, where phonons are the primary conveyors of heat flow. Despite the increasing focus on this goal, this field of research is still in its infancy; To achieve a few advances in this field, we performed several Inelastic X-Ray Scattering (IXS) measurements on elementary systems as dilute suspensions of nanoparticles (NPs) in liquids. We found that nanoparticles can effectively impact the sound propagation of the hosting liquid. We also explored the possibility of shaping terahertz sound propagation in a liquid upon confinement on quasi-unidimensional cavities. These results are here reviewed and discussed, and future research directions are finally outlined.

PurposePilot study to evaluate adverse events and intraocular pressure (IOP)-lowering of a novel, noninvasive glaucoma procedure, femtosecond laser, image-guided, high-precision trabeculotomy (FLIGHT).DesignProspective, nonrandomized, single-center, interventional, single-arm clinical trial.ParticipantsEighteen eyes from 12 patients with open-angle glaucoma.MethodsEighteen eyes from 12 patients underwent FLIGHT, creating a single channel measuring 500-μm wide by 200-μm high through the trabecular meshwork and into Schlemm's canal. Adverse events, IOP, and other parameters were evaluated out to 24 months.Main outcome measuresOutcomes were the rates and types of adverse events and the rate of postprocedure best-corrected visual acuity loss (≥ 2 lines) compared with baseline. Efficacy outcomes were reduction in mean intraocular pressure (IOP) with respect to baseline and the percentage of eyes with a ≥ 20% reduction in IOP.ResultsEighteen eyes from 12 patients were enrolled in the study; 11 patients (17 eyes) returned at 24 months. There were no serious adverse events related to the laser treatment. Well-defined channels were clearly visible at 24 months by gonioscopy and anterior segment OCT, with no evidence of closure. At 24 months, the mean IOP was reduced by 34.6% from 22.3 ± 5.5 to 14.5 ± 2.6 mmHg (P < 5e-5), with an average of 2.0 ± 1.2 hypotensive medications compared with 2.2 ± 1.1 at baseline (P = 0.22). Fourteen out of the 17 study eyes (82.3%) achieved a ≥ 20% reduction in IOP at 24 months when compared with baseline.ConclusionThe FLIGHT system demonstrated a favorable safety profile in this initial pilot study, with no device-related serious adverse events. The channels appeared patent at 24 months, indicating medium-term durability.Financial disclosuresProprietary or commercial disclosure may be found after the references.

The production of low alcohol beer (LAB) with a full and well-balanced flavour is still now a complex challenge because of the different flavour profile they have compared to regular beers. In this study, a brown ale beer was used to obtain a low alcohol beer by osmotic distillation in a small pilot plant. Beer-diluted carbonated solutions were used as strippers and were taken under flux of CO2 in order to contrast loss of volatiles from beer during the process. A forced carbonation was applied on LAB to avoid the foam collapse. Furthermore, hop extract and pectin solution were added to LAB to improve the overall taste and body. Results highlighted an improvement into retention of volatiles probably due to the use of carbonated solutions such as strippers. The forced carbonation and the addition of pectins ensured both a higher concentration of dissolved CO2 and a higher stability of foam in LAB. The antioxidant activity of beer remained unchanged. The sensory analysis highlighted differences among low alcohol beer and original one. The addition of hop extract and pectin solution to LAB better maintained hop and fruity-citrus notes during tasting, compared with the original beer.