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Background In the phase III KEYNOTE-189 study (NCT02578680), pembrolizumab plus pemetrexed and platinum-based chemotherapy (pemetrexed–platinum) significantly improved overall survival (OS) and progression-free survival (PFS) in patients with previously untreated metastatic nonsquamous non-small-cell lung cancer (NSCLC) versus placebo plus pemetrexed–platinum. We report updated efficacy outcomes from the protocol-specified final analysis, including outcomes in patients who crossed over to pembrolizumab from pemetrexed–platinum and in patients who completed 35 cycles (∼2 years) of pembrolizumab. Patients and methods Eligible patients were randomized 2 : 1 to receive pembrolizumab 200 mg (n = 410) or placebo (n = 206) every 3 weeks (for up to 35 cycles, ∼2 years) plus four cycles of pemetrexed (500 mg/m2) and investigators’ choice of cisplatin (75 mg/m2) or carboplatin (area under the curve 5 mg·min/ml) every 3 weeks, followed by pemetrexed until progression. Patients assigned to placebo plus pemetrexed–platinum could cross over to pembrolizumab upon progression if eligibility criteria were met. The primary endpoints were OS and PFS. Results After a median follow-up of 31.0 months, pembrolizumab plus pemetrexed–platinum continued to improve OS [hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.46-0.69] and PFS (HR, 0.49; 95% CI, 0.41-0.59) over placebo plus pemetrexed–platinum regardless of programmed death-ligand 1 expression. Objective response rate (ORR) (48.3% versus 19.9%) and time to second/subsequent tumor progression on next-line treatment (PFS2; HR, 0.50; 95% CI, 0.41-0.61) were improved in patients who received pembrolizumab plus pemetrexed–platinum. Eighty-four patients (40.8%) from the placebo plus pemetrexed–platinum group crossed over to pembrolizumab on-study. Grade 3-5 adverse events occurred in 72.1% of patients receiving pembrolizumab plus pemetrexed–platinum and 66.8% of patients receiving placebo plus pemetrexed–platinum. Fifty-six patients completed 35 cycles (∼2 years) of pembrolizumab; ORR was 85.7% and 53 (94.6%) were alive at data cut-off. Conclusions Pembrolizumab plus pemetrexed–platinum continued to show improved efficacy outcomes compared with placebo plus pemetrexed–platinum, with manageable toxicity. These findings support first-line pembrolizumab plus pemetrexed–platinum in patients with previously untreated metastatic nonsquamous NSCLC.

Tin halide perovskites (THPs) have been established as a lower-toxicity alternative to lead halide perovskites. In spite of the increasing interest, the behavior of photoexcited charges has not been well understood in this class of materials. We here investigate the behavior of excess electrons in a series of tin halide perovskites by employing advanced electronic-structure calculations. We first focus on CsSnBr3 and show that electron localization is favorable in this compound and that bipolaronic states are the most stable form of self-trapped electrons. We then extend the analysis to CsSnI3, CsSnCl3, MASnBr3, FASnBr3, and DMASnBr3 and show that electron bipolarons are stable in all these compounds, thus indicating that strong electron localization is recurrent in THPs.

Tin alloying is a promising strategy to reduce lead content in metal halide perovskites solar cells and to modulate the perovskite band gap. Mixed tin–lead perovskites have shown photovoltaic efficiencies approaching those of lead perovskites and improved long-term stability compared to that of pure tin perovskites. We here demonstrate that the recent success of mixed perovskites lies in a composition-dependent struggle between tin and iodine chemistry at the material’s surface. Tin oxidation, which plagues tin perovskite-based devices with low efficiency and thermodynamic instability, is hindered in mixed MAPb0.5Sn0.5I3by the competition with oxidation of iodine-related defects, the latter being generally favored by both thermodynamics and kinetics. Tin oxidation can be promoted, however, under Sn-poor conditions. When Sn is alloyed to Pb in low concentrations, it acts as a dopant and Sn(IV) is promptly formed on the perovskite surface.

Harmonic generation mechanisms are of great interest in nanoscience and nanotechnology, since they allow generating visible light by using near-infrared radiation, which is particularly suitable for its countless applications in bionanophotonics and optoelectronics. In this context, multilayer metal−dielectric nanocavities are widely used for light confinement and waveguiding at the nanoscale. They exhibit intense and localized resonances that can be conveniently tuned in the near-infrared and are therefore ideal for enhancing nonlinear effects in this spectral range. In this work, we experimentally investigate the nonlinear emission properties of multilayer metal−dielectric nanocavities. By engineering their absorption efficiency and exploiting their intrinsic interface-induced symmetry breaking, we achieve an almost 2 orders of magnitude higher second-harmonic generation efficiency compared to gold nanostructures featuring the same geometry and optical resonant behavior. In particular, while both the third-order nonlinear susceptibility and conversion efficiency are comparable with those of the Au nanoresonators, we estimate a second-order nonlinear susceptibility of the order of 1 pm/V, which is comparable with that of typical nonlinear crystals. We envision that our system, which combines the advantages of both plasmonic and dielectric materials, might enable the realization of composite and multifunctional nanosystems for the efficient manipulation of nonlinear optical processes at the nanoscale.

The Pastena cave is located in central Italy and its best-preserved sector is Grotticella W2, which is dated radiometrically to the Early-Middle Bronze Age. The aim of this paper is to explore human diet, animal husbandry, and plant management analyzing the findings there discovered. Carbon and nitrogen stable isotope analysis have been carried out on 40 charred seeds, 6 faunal remains and 4 human specimens, investigating the whole bio-archaeological samples available. To the best of our knowledge, this is one of the first papers presenting stable isotope analysis on carpological remains dated to the Italian Early-Middle Bronze Age. The obtained results are consistent with a diet based on terrestrial protein, mainly on plants and secondly on meat and animal products. The data suggest that plants, especially broad beans, were partially subjected to human management, while livestock was managed through different husbandry strategies. The cooperation between archaeological studies and molecular analysis allows us to contribute to clarify the economic strategies for a Central Italian community in a scenario that is still poor in published data.

Transcriptomic analysis of tomato genotypes contrasting for stigma position suggests that stigma insertion occurred by the disruption of a process that finds a parallel in Arabidopsis gynoecium development. Domestication of cultivated tomato (Solanum lycopersicum L.) included the transition from allogamy to autogamy that occurred through the loss of self-incompatibilty and the retraction of the stigma within the antheridial cone. Although the inserted stigma is an established phenotype in modern tomatoes, an exserted stigma is still present in several landraces or vintage varieties. Moreover, exsertion of the stigma is a frequent response to high temperature stress and, being a cause of reduced fertility, a trait of increasing importance. Few QTLs for stigma position have been described and only one of the underlying genes identified. To gain insights on genes involved in stigma position in tomato, a bulk RNA sequencing (RNA-Seq) approach was adopted, using two groups of contrasting genotypes. Phenotypic analysis confirmed the extent and the stability of stigma position in the selected genotypes, whereas they were highly heterogeneous for other reproductive and productive traits. The RNA-Seq analysis yielded 801 differentially expressed genes (DEGs), 566 up-regulated and 235 down-regulated in the genotypes with exserted stigma. Validation by quantitative PCR indicated a high reliability of the RNA-Seq data. Up-regulated DEGs were enriched for genes involved in the cell wall metabolism, lipid transport, auxin response and flavonoid biosynthesis. Down-regulated DEGs were enriched for genes involved in translation. Validation of selected genes on pistil tissue of the 26 single genotypes revealed that differences between bulks could both be due to a general trend of the bulk or to the behaviour of single genotypes. Novel candidate genes potentially involved in the control of stigma position in tomato are discussed.

International audience; The martensitic transformation is a fundamental physical phenomenon at the origin of important industrial applications. However, the underlying microscopic mechanism, which is of critical importance to explain the outstanding mechanical properties of martensitic materials, is still not fully understood. This is because for most martensitic materials the transformation is a fast process that makes in situ studies extremely challenging. Noble solids krypton and xenon undergo a progressive pressure-induced face-centered cubic (fcc) to hexagonal close-packed (hcp) martensitic transition with a very wide coexistence domain. Here, we took advantage of this unique feature to study the detailed transformation progress at the atomic level by employing in situ x-ray diffraction and absorption spectroscopy. We evidenced a four-stage pathway and suggest that the lattice mismatch between the fcc and hcp forms plays a key role in the generation of strain. We also determined precisely the effect of the transformation on the compression behavior of these materials.

High-energy, long gamma-ray bursts (GRBs) can be generated by the core collapse of massive stars at the end of their lives. When they happen in the close-by universe they can be exceptionally bright, as seen from the Earth in the case of the recent, giant, long-lasting GRB221009A. GRB221009A was produced by a collapsing star with a redshift of 0.152: this event was observed by many gamma-ray space experiments, which also detected an extraordinary long gamma-ray afterglow. The exceptionally large fluence of the prompt emission of about 0.013 erg cm−2 illuminated a large geographical region centered on India and including Europe and Asia. We report in this paper the observation of sudden electron flux changes correlated with GRB221009A and measured by the HEPP-L charged particle detector on board the China Seismo-Electromagnetic Satellite, which was orbiting over Europe at the time of the GRB event. The time structure of the observed electron flux closely matches the very distinctive time dependence of the photon flux associated with the main part of the emission at around 13:20 UTC on 2022 October 9. To test the origin of these signals, we set up a simplified simulation of one HEPP-L subdetector: the results of this analysis suggest that the signals observed are mostly due to electrons created within the aluminum collimator surrounding the silicon detector, providing real-time monitoring of the very intense photon fluxes. We discuss the implications of this observation for existing and forthcoming particle detectors on low Earth orbits.

Caves are one of the most conservative environments on Earth, where archaeological, anthropological, climatic and tectonic data can be well-preserved. Here, we present the results of a multidisciplinary method that allowed us to recognize, for the first time in this area, the interaction between Late Pleistocene to Anthropocene neotectonic and archaeological evolutionary stages of a cave of the Apennines (La Sassa cave), that encompass also its surroundings (Volsci Range and Pontina Plain). Both structural and 3D survey highlighted a step-wise shape of the cave due to normal fault steps that allowed the localized formation of concretions also enveloping archaeological layers. Sixteen 14C ages on fauna and human bones and thousands of archaeological finds provided chronological constraints of faulting in the Late Pleistocene and possibly also after the Middle Bronze Age. In the frame of a region that was not previously recognized as tectonically active, the structural evidence is relevant for understanding the speleogenesis of the cave from the Late Pleistocene and its human occupation. Burial and ritual activities in the cave from the Copper Age to the Middle Bronze Age have been recognized with implications on possible settlement pattern schemes with the La Sassa cave as a “persistent place” in the prehistoric human landscape. The analyses of the ceramic style in a regional framework also suggests the presence of a cultural boundary near La Sassa, which becomes highly osmotic just after the beginning of the Middle Bronze Age. The La Sassa findings provide as well implications for the seismic hazard assessment in a region inhabited by about 0.4 million people.

UK Biobank (UKB) is a key contributor in mental health genome-wide association studies (GWAS) but only ~31% of participants completed the Mental Health Questionnaire (“MHQ responders”). We predicted generalized anxiety disorder (GAD), posttraumatic stress disorder (PTSD), and major depression symptoms using elastic net regression in the ~69% of UKB participants lacking MHQ data (“MHQ non-responders”; NTraining=50%; NTest=50%), maximizing the informative sample for these traits. MHQ responders were more likely to be female, from higher socioeconomic positions, and less anxious than non-responders. Genetic correlation of GAD and PTSD between MHQ responders and non-responders ranged from 0.636-1.08; both were predicted by polygenic scores generated from independent cohorts. In meta-analyses of GAD (N=489,579) and PTSD (N=497,803), we discovered many novel genomic risk loci (13 for GAD and 40 for PTSD). Transcriptomic analyses converged on altered regulation of prenatal dorsolateral prefrontal cortex in these disorders.

Achalasia is a very rare disease characterized by the lack of motor coordination in various phases of contraction-relaxation of esophageal muscles. The aim of the study is to determine the correlation between esophageal achalasia and oral diseases.Thirteen esophageal achalasia patients were assessed for the presence of any potential oral symptoms through a questionnaire. 5 volunteered to be included in the study. The oral health status of these 5 patients was assessed by a clinical oral examination. The oral health status of the included cases was compared to the oral health status data from a published observational study on healthy individuals belonging to the same (Italian) population.Our results show that the number of periodontal pockets with Probing Pocket Dept4 mm is significantly increased, compared to the average of the Italian population; the Bleeding On Probing (BOP) is not related to the Plaque Control Record (PCR); so we can say that the value of periodontal index is not correlated with the value of oral hygiene index.Considering the limitations of a research based on small numbers, it nevertheless seems advisable to assert that there is a correlation between esophageal achalasia and periodontal disease.

In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M o˙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87's spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded. © 2021. The Author(s). Published by the American Astronomical Society..

SUMMARY The purpose of this laboratory study was to compare the two-body wear resistance of different restorative materials commonly used for the indirect restoration of posterior teeth. The tested materials, based on ceramic (Imagine Press X, IPS e.max CAD, Milled Celtra Duo, Glaze-Fired Celtra Duo, Vita Mark II) and composite (Enamel Plus HRi, Enamel Plus HRi Bio-Function, Filtek Supreme XTE, Lava Ultimate), were compared with the wear properties of a type III gold alloy (Aurocast 8). Flat samples were prepared with a 6-mm thickness (n=10). Composite samples were tested after a heat polymerization cycle. All samples were exposed to a two-body wear test in a dual axis chewing simulator performing over 120,000 loading cycles. The opposing abrader cusps were fabricated from yttria-stabilized tetragonal zirconia polycrystal. The vertical substance loss (mm) and the volume loss (mm3) were recorded, as was the wear of the antagonist cusp (mm). Mean values were analyzed by one-way analysis of variance. Significant differences among materials were detected. The heat-cured resin-based composite material Enamel Plus Bio-Function and the type III gold alloy demonstrated similar mean values for wear depth and volumetric loss.

The aim of this study was to compare both the elastic modulus (EM) and the flexural strength (FS) of two materials used in dental prosthesis, namely polymethylmethacrylate (PMMA) and polymethylmethacrylate reinforced with graphene (G-PMMA).Twenty rectangular samples were manufactured by a milling machine and divided into two groups (n= 10/group): Group 1, PMMA; Group 2, G-PMMA. The specimens were subjected to a three-point bending test conducted in the elastic range to evaluate EM. A similar test was protracted until fracture to evaluate FS. Data on EM and FS were statistically analyzed with independent-samples t-test in order to compare the two groups. A scanning electron microscope (SEM) (5.00 kx and 1.00 kx magnification) was used to evaluate the morphology of sample's fracture.Compared to PMMA samples, each G-PMMA sample showed significantly higher values of FS (p0.001) and EM (p0.001). SEM images analysis showed an inhomogeneous fracture morphology in G-PMMA samples.The results show that G-PMMA is a promising material to be used for prosthetic purposes. This is demonstrated by a significant increase in both peak load and bending stiffness, resulting from the bending test performed on G-PMMA samples. Furthermore, the latter exhibit greater homogeneity in their mechanical behavior, supporting the potential value of this material in dental prosthesis.

SUMMARY The purpose of the present in vitro study was to compare the two-body wear resistance of a type 3 gold alloy (Aurocast8), two lithium disilicate glass ceramics (IPS e.max CAD and IPS e.max Press), a heat-pressed feldspathic porcelain (Cerabien ZR Press), an yttria-stabilized tetragonal zirconia polycrystal ceramic (Katana Zirconia ML), and three heat-cured composite resins (Ceram.X Universal, Enamel Plus Function, and Enamel Plus HRi) opposing antagonistic cusps made out of the same restorative materials. Ten 6-mm-thick samples and 10 cusp-shaped abraders were manufactured with each test material (n=10) according to standard laboratory procedures. All sample/antagonist pairs made out of the same material were subjected to a two-body wear test in a dual-axis chewing simulator for up to 120,000 loading cycles. The total vertical wear (mm) and the total volumetric loss (mm3) for each sample/antagonist pair were calculated. Data were statistically analyzed using one-way analysis of variance tests. The total vertical wear for the gold alloy was not significantly different compared to Ceram.X Universal, Enamel Plus Function, IPS e.max CAD, and Cerabien ZR Press. Significantly increased wear values were observed for Enamel Plus HRi and IPS e.max Press. The lowest values for total vertical wear and volumetric loss were recorded on the monolithic zirconia.

Transcriptomic analysis of tomato genotypes contrasting for stigma position suggests that stigma insertion occurred by the disruption of a process that finds a parallel in Arabidopsis gynoecium development. Domestication of cultivated tomato (Solanum lycopersicum L.) included the transition from allogamy to autogamy that occurred through the loss of self-incompatibilty and the retraction of the stigma within the antheridial cone. Although the inserted stigma is an established phenotype in modern tomatoes, an exserted stigma is still present in several landraces or vintage varieties. Moreover, exsertion of the stigma is a frequent response to high temperature stress and, being a cause of reduced fertility, a trait of increasing importance. Few QTLs for stigma position have been described and only one of the underlying genes identified. To gain insights on genes involved in stigma position in tomato, a bulk RNA sequencing (RNA-Seq) approach was adopted, using two groups of contrasting genotypes. Phenotypic analysis confirmed the extent and the stability of stigma position in the selected genotypes, whereas they were highly heterogeneous for other reproductive and productive traits. The RNA-Seq analysis yielded 801 differentially expressed genes (DEGs), 566 up-regulated and 235 down-regulated in the genotypes with exserted stigma. Validation by quantitative PCR indicated a high reliability of the RNA-Seq data. Up-regulated DEGs were enriched for genes involved in the cell wall metabolism, lipid transport, auxin response and flavonoid biosynthesis. Down-regulated DEGs were enriched for genes involved in translation. Validation of selected genes on pistil tissue of the 26 single genotypes revealed that differences between bulks could both be due to a general trend of the bulk or to the behaviour of single genotypes. Novel candidate genes potentially involved in the control of stigma position in tomato are discussed.

Issue/problem The increase of vaccine hesitancy is leading to decrease vaccination coverage. In Italy, a new vaccination law was approved in July 2017 to contrast the spread of preventable infections. 10 vaccines became mandatory for children and unaccompanied foreign minors aged 0-16 and provided for free according to the national immunization schedule for each birth cohort. Being vaccinated is now required to attend schools and kindergartens even if a ban for students aged 0-6 or a fine for the other are previewed. Description of the problem According to the law, in Lazio Region, a web platform was realized in May 2018 in order to permit schools to update the list of their pupils. Medical doctors from LHAs had to evaluate continuously the updated lists, verifying the vaccination status of each student in order to approve their enrolment at schools or to recall parents providing counseling about vaccination. Results From August 2018 to March 2019 schools settled in the area of LHA Roma 1 registered 121.687 pupils (among those 105.720 pupils were also resident in the area of LHA Roma 1). After a preliminary check within data already present in the regional vaccination registry, around 30 healthcare operators, from the 6 healthcare districts of LHA Roma 1, were widely involved in order to evaluate pupils’ vaccination status. The number of evaluations decreases in the same period from 19.634 to 4921, but 4908 out of these 4921 were pupils not found in the regional vaccination registry, probably for errors in the registration of personal data such as the fiscal code. Some students’ families received vaccination counseling. Lessons The web platform realization was an innovative way to monitor vaccination status: it facilitates a further collaboration among schools and LHAs in order to guarantee health in community and to increase awareness about vaccinations and their benefits. A great involvement of schools and healthcare operators was observed. Key messages Although some problems such as pupils not found in the regional vaccination registry persist, the way of working in a collaborative way addressing community troubles is clearly traced. Technology and information systems help community services in monitoring and improving health outcomes. Their use has to be improved and promoted.

Alveolar ridge augmentation procedures allow restoring jaw defects due to teeth extractions, periodontal diseases, trauma, or outcomes from a previous surgery. This case report describes a patient suffering from Fibrous Dysplasia of the right upper maxilla surgically reconstructed by fibula free flap. In 2003, four dental implants were placed in the 1.2, 1.3, 1.5, and 1.6 areas. Twelve years later, the onset of peri-implantitis led to the failure of osseointegration with consequent thinning of the fibula flap. To avoid the risk of fracture and to restore the bone volumes necessary for a new implant-prosthetic rehabilitation, we used heterologous biomaterials in combination with a non-reabsorbable membrane, according to the Guided Bone Regeneration (GBR) technique. GBR was performed using the Equimatrix® natural bone mineral matrix, Cytoplast™ Ti-150, a non-reabsorbable titanium-reinforced membrane, and four fastening screws to pin the membrane. After six months, the membrane was removed and two Zimmer® implants 3.7×13 mm were placed in the 1.1 and 1.2 areas. A fixed implant-supported prosthesis with a custom-milled titanium bar screwed to the implants was made. Computed tomography (CT) six months after GBR showed a good bone regeneration of 1.5 cm mesiodistal (MD), 1.8 cm buccopalatal (BP), and 2.8 cm in height. The main difficulty of this clinical case concerns the low predictability of success of GBR on a maxillary reconstructed area with a free fibula flap: there is no previous evidence in the literature. Clinical and radiographic exams nowadays show that there is no macroscopic bone reabsorption; however, further research is needed to obtain more information.

Silicon-vacancy (SiV) color centers in diamond offer novel possibilities to probe light-matter interaction in nano-quantum optics and provide a scalable quantum system suitable for single-photon emission. However, their effective count-rate is still limited by non-radiative decay channels, radiation at wide angles and total internal reflection at the diamond interface. Recently optical antennas have been utilized in order to modify light-matter interaction at the nanoscale. Acting as resonators, they are able to increase the spontaneous emission rate of quantum emitters by several orders of magnitude in a broad spectral range. Because coupling a quantum emitter to a nano-antenna requires close proximity between the two systems, we implant Si ions on very thin diamond membranes that provide the required dimension for near-field interaction in a controlled manner and investigate the optical properties of SiV color centers in such diamond membranes. We consider gold nano-cones as nano-antennas, fabricated by focused electron beam induced deposition (EBID), followed by sputtering and focused ion beam (FIB) milling. The finite-difference time-domain (FDTD) calculations show that gold nano-cones can provide more than four orders of magnitude enhancement in the Purcell factor with an antenna efficiency (AE) of 80%.

The aim of this prospective cohort study was to evaluate how the radiation technique can affect crestal bone loss and the implant survival rate in head and neck cancer patients treated with radiotherapy. In this study, the type of radiotherapy treatment, i.e. three-dimensional conformal radiotherapy (3D-CRT) or intensity modulated radiation therapy (IMRT), was the predictor variable. The primary outcome variable was crestal bone loss, recorded at implant placement and after 3, 6, 12, and 24 months. A descriptive analysis and ANOVA test were performed; significance was set at P0.05. Thirty-two patients were enrolled and a total of 113 dental implants placed in irradiated residual bone. There was no statistically significant difference in crestal bone loss levels between the groups at any of the intervals (P0.05), except after 6 months (P=0.028). The cumulative dental implant survival rate was 94.7%. After 24 months, the mean marginal bone loss was 0.83±0.12mm in the 3D-CRT group and 0.74±0.15mm in the IMRT group (P=0.179). The data suggest that the different radiation techniques did not affect the outcomes of implant-supported prosthetic rehabilitation, as related to crestal bone loss and implant survival. However, long-term follow-up studies are necessary to evaluate the real influence of the radiotherapy technique on dental implants.

To date, the treatment of patients affected by head and neck squamous cell carcinoma (HNSCC) is highly challenging for clinicians. Possible therapies are surgical resection of the tumor mass, radiotherapy, chemotherapy or, more often, a combined treatment that inevitably affects both normal and tumor cells. Consequently, patients' anatomy and functions become reduced or altered. Nowadays the functional restoration is significantly improved thanks to the innovation in prosthetic rehabilitation and in radiotherapy. The current IMRT (Intensity Modulated Radiation Therapy) allows planning adequate treatments evaluating different tissues' involvement and radiation dosage. It is possible to define the most suitable sites for implant insertion, using data provided by dose-volume histogram (DVH). This study aims to illustrate the idea of obtaining a unique CT image by blending radiation-planning CT and Cone Beam CT.Five patients among 54 candidates were selected for this study. Selection criteria were: good general health (PS0-1), age between 18 and 72 years, absence of metastatic disease or local recurrence, disease-free interval of at least 18 months. Radiation planning CT scan and maxillo-facial CT Cone Beam of every patient were overlapped and merged. Only one CT for every evaluated patient was obtained in order to plan the most suitable areas for implant placement.The placement of 10 implants in 5 patients was programmed using the explained method. Patients (all male) were aged between 48 and 72 years old, with a median age of 64.4 years. In every case of this study, a modification of the initial program of implant placement was necessary. The new imaging method we are proposing was able to provide information about radiation isodoses received in the planned osseointegrated implants' positions.This new method allows operators to correct their own therapy plans and choices, customizing the treatment plan on the actual condition of the patient. Moreover, it makes all the rehabilitation process safer and can reduce the risk of failure, side effects and inconveniences for the patients.

In this paper the seismic response of a multi-storey reinforced concrete (RC) building base isolated by lead rubber bearings (LRBs) is compared with the seismic response of the same structure base isolated by an innovative seismic isolator which we called high damping hybrid seismic isolator (HDHSI). The study is performed in the context of passive structural control and seismic base isolation technique for the earthquake resistance of RC buildings. This novel high damping hybrid seismic isolator (HDHSI) is obtained by the assembly in series of a lead rubber bearing (LRB) and a friction slider (FS) characterized by a high friction coefficient. The base isolation system is realized by elastomeric materials and steel-teflon bearings. The nonlinear behavior of the composite devices is investigated by reporting a detailed analysis of the hysteretic cycles of the isolators. The purpose of the analysis is to highlight the features offered by the proposed HDHSI base isolation system compared to the traditional LRB base isolation system in the seismic protection of structures. Nonlinear dynamic analyses are performed for base isolated multi-storey RC structures. In the analysis the inputs of different seismic events are adopted which can be considered as extreme events in terms of peak ground acceleration and in terms of frequency content. The seismic records are related to seismic events obtained by suitably amplifying the El Centro earthquake. They are characterized by their high values of the peak ground acceleration. Another seismic event considered in the analysis is the Erzincan earthquake which is characterized by high energetic content at low frequencies. Accordingly, the seismic events adopted in the analysis are characterized by anomalous values of intensity and frequency content. A nonlinear dynamic analysis is illustrated for a multi-storey RC building base isolated by the proposed HDHSI system compared with the traditional LRB base isolation system. The time history of the base shear and the time history of the base displacement of the superstructure are illustrated for the different analyzed seismic events. The benefits of the presented composite HDHSI base isolation system are shown to be appropriate in conferring a suitable seismic protection to multi-storey RC buildings even under extreme seismic events.

Titanium dioxide (TiO2) is a well-known biocompatible material with important applications in many fields of biomedicine. Here we show our results on the development of a new TiO2 based sol-gel system that can act as negative tone resist for both ultraviolet (UV) and electron beam (EB) lithographies. The system allows the direct patterning of high resolution structures (down to 40nm). Moreover, it allows the preparation of nanopatterned nanoporous TiO2 simply by changing the conditions of resist development. The presented system can be used as functional tool for the systematic investigation of cell behavior with respect to a complex topographic texture of the substrate (cell guidance). TiO2 structures of different dimensions, geometries and nanoporosity, whose size ranges from a few hundred to a few tens nanometer, are obtained after UV and/or EB lithography. The adhesion of different cell lines, i.e., human osteosarcoma (HOS) and neuroblastoma (N2A), on the patterns is assessed and our results show that cells have a preference for TiO2 patterns with respect to glass. Display Omitted A new formula directly patternable nanoporous TiO2 resist is presented.The gel is sensitive to both UV and electron beam exposure.The system can be prepared with smooth and porous morphology.Complex structures with different geometries and morphologies can be achieved.The system can be used in cell guidance experiments.

Droplets with colloidal biological suspensions evaporating on substrates with defined wetting properties generate confined environments for initiating aggregation and self-assembly processes. We describe smart micro- and nanostructured surfaces, optimized for probing single droplets and residues by synchrotron radiation micro- and nanobeam diffraction techniques. Applications are presented for Ac-IVD and β-amyloid (1–42) peptides capable of forming cross-β sheet structures. Complementary synchrotron radiation FTIR microspectroscopy addresses secondary structure formation. The high synchrotron radiation source brilliance enables fast raster-scan experiments.

The excitation of plasmonic Fano resonances leads to a dual advantage in nano-photonics, in terms of local field enhancement and far-field spectral selectivity. Nevertheless, a remarkable challenge related to the hybridization between bright and dark plasmonic modes, i.e. between the two elements cooperating to the Fano resonance generation, consists in the sub-wavelength activation of dark modes via near-field channel. In this regard, strongly coupled plasmonic nano-assemblies are ideal systems providing a highly efficient way towards their excitation. Here, we analyze two trimer nano-architectures supporting respectively electric and magnetic Fano resonances. The different approaches employed for describing the two systems highlighted the role that the near-field coupling and the LSPs de-phasing separately play in the Fano hybridization phenomena.

Laparoscopic sleeve gastrectomy (LSG) is the most performed surgical procedure worldwide. Long-term outcomes report that up to 30% of patients require revisional surgery and re-sleeve gastrectomy (rLSG) is one of the revisional procedures available. The aim was to update the outcomes of a cohort of rLSG at 52 months. This study reports the 52-month follow-up of a cohort of 19 patients previously published after 24-month follow-up. Sixteen patients completed the follow-up. Nine patients complained of GERD symptoms after 36 months. Five patients were converted to laparoscopic RYGB. Two patients were converted to a laparoscopic BPD-DS for weight regain 4 patients are asymptomatic with stable weight. On the basis of our disappointing results, it can be said that rLSG is not currently offered as revisional procedure in both centers.

We present details regarding the modeling of light-nanomatter interaction in terahertz plasmonic nanocavities.

Lip and palate cleft represent one of the most frequently occurring congenital deformity, which includes dental anomalies, such as variation in tooth number and position. In case of hypodontia implant-prosthetic rehabilitation offers significant advantages in terms of function, aesthetics and quality of life and bone graft is usually needed. Secondary bone grafting, generally performed in the mixed dentition phase (years 8-11) seems to be the most successful method to allow for rehabilitation. It's often necessary to perform a tertiary bone grafting in adult age in order to achieve better bone quantity and quality before implant placement. Aim of this retrospective study was to evaluate the aesthetic perception that patients had of themselves comparing dental implants placed in tertiary grafted alveolar cleft sites with a previous secondary grafting to only secondary grafting. Between 2009 and 2012, fourteen alveolar cleft were treated with implant rehabilitation and eleven of them received tertiary bone grafting six months prior to implant placement. All patients were questioned to give a score from 1 to 10 their aesthetic satisfaction of their smile before and after implant rehabilitation and during pre-surgery provisional rehabilitation. At the end of their prosthesis rehabilitation patients who received tertiary bone grafting resulted more satisfied than those who had secondary bone grafting only (9.5 vs 8).

Resume Introduction Determiner des facteurs predictifs de bonne reponse au crosslinking (CXL) dans la prise en charge du keratocone evolutif. Patients et methodes Cinquante-quatre yeux de 41 patients ont beneficie d’un CXL entre juin 2011 et decembre 2012 pour keratocone evolutif. Un examen clinique ophtalmologique avec une topographie corneenne (Orbscan ® ) est realise a 1, 3, 6 mois, 1 an en postoperatoire et compare a l’examen preoperatoire. Resultats A un an, le CXL permet une amelioration significative de la meilleure acuite visuelle corrigee (MAVC) (0,16 ± 0,21 LogMar en preoperatoire versus 0,09 ± 0,16 LogMar a 1 an, p = 0,007), une stabilite de l’astigmatisme refractif (AR) ( p = 0,69), une amelioration significative de l’astigmatisme irregulier topographique des 3 mm centraux ( p = 0,04), et une stabilite du Kmax (48,4 D ± 4,1 en preoperatoire versus 48,5 D ± 4,1 a 1 an, p = 0,46). Les facteurs predictifs d’amelioration postoperatoire de MAVC sont, en preoperatoire, une MAVC faible, un AR eleve et un keratocone evolue. Les facteurs predictifs de stabilite du Kmax postoperatoire sont un keratocone preoperatoire peu evolue, et principalement localise dans les 3 mm centraux. Conclusion Cette etude retrospective confirme l’interet et l’efficacite du CXL dans la prise en charge therapeutique d’un keratocone evolutif, tant sur le plan refractif que topographique. La localisation du cone ou son excentricite semble etre un facteur expliquant la variabilite des resultats bibliographiques d’efficacite du CXL. La severite du cone apparait dans cette etude comme etant un facteur predictif de mauvaise reponse topographique au CXL, mais devant etre pondere par la localisation preferentielle du cone (3 ou 5 mm centraux).

Display Omitted An approach for the fabrication of hybrid nanostructures has been proposed.ZnO flowers have been grown selectively on the top of gold nanopillars.Raman analysis have shown that ZnO presents a wurtzite structure.Such systems could find application in photocatalysis or energy harvesting. We fabricated flower-like shaped ZnO nanorods on the apexes of hollow gold nanopillars by Focused Ion Beam lithography and hydrothermal growth. The hollow nanopillar geometry was defined on a photoresist by ion-beam induced inversion and subsequently metalized. Then the bottom section of the pillars was protected by a second resist coating, exposing only the nanopillar tips for hydrothermal growth of ZnO. The wurtzite crystalline structure of the ZnO nanorods that composes the flowers was confirmed by Raman spectroscopy. Such novel 3D hybrid metal semiconductor nanostructures are promising materials for catalysis and energy harvesting.

SUMMARY The aim of this study was to assess the flexural strength, flexural elastic modulus and Vickers microhardness of three resin composites prepared at room temperature or cured after one or repeated preheating cycles to a temperature of 39°C. Three resin composites were evaluated: Enamel Plus HFO (Micerium), Opallis (FGM), and Ceram X Duo (Dentsply DeTrey). For each trial, one group of specimens of each material was fabricated under ambient laboratory conditions, whereas in the other groups, the composites were cured after 1, 10, 20, 30, or 40 preheating cycles to a temperature of 39°C in a preheating device. Ten rectangular prismatic specimens (25 × 2 × 2 mm) were prepared for each group (N=180; n=10) and subjected to a three-point bending test for flexural strength and flexural modulus evaluation. Vickers microhardness was assessed on 10 cylindrical specimens from each group (N=180; n=10). Statistical analysis showed that, regardless of the material, the number of heating cycles was not a significant factor and was unable to influence the three mechanical properties tested. However, a significant main effect of the employed material on the marginal means of the three dependent variables was detected.

Background. The role of prolactin (PRL) on tissue injury and repair mechanisms in multiple sclerosis (MS) remains unclear. The aim of this work was to investigate the relationship between PRL plasma levels and brain damage as measured by magnetic resonance imaging (MRI).Methods. We employed a chemiluminescence immunoassay for measuring plasma levels of PRL. We used a 1.5 T scanner to acquire images and Jim 4.0 and SIENAX software to analyse them.Results. We included 106 women with relapsing remitting (RR) MS and stable disease in the last two months. There was no difference in PRL plasma levels between patients with and without gadolinium enhancement on MRI. PRL plasma levels correlated with white matter volume (WMV) (rho = 0.284,p=0.014) but not with grey matter volume (GMV). Moreover, PRL levels predicted changes in WMV (Beta: 984,p=0.034).Conclusions. Our data of a positive association between PRL serum levels and WMV support the role of PRL in promoting myelin repair as documented in animal models of demyelination. The lack of an increase of PRL in the presence of gadolinium enhancement, contrasts with the view considering this hormone as an immune-stimulating and detrimental factor in the inflammatory process associated with MS.

ZnO nanorods present great potential for application in optical, sensing and piezoelectric devices; thanks to their nanometric diameter and large surface area. In some of these applications a probing current must flow directly through the nanorods, requiring each nanorod to be directly connected to two electrodes. To attain this architecture a few solutions have been proposed in the past, mostly involving the use of complex and time-consuming procedures, but the large-scale production of such devices represents still a major challenge. We present here a new all-solution approach that allows the fabrication of extensive self-assembled, bi-dimensional networks of ZnO nanorods. Such networks can be easily produced on interdigitated electrodes with no need for any alignment, resulting directly in the formation of very robust devices. The entire process is fast, does not require any complex experimental apparatus and involves only the use of inexpensive and environmentally friendly chemical reagents. We demonstrate the potentiality of such networks in a gas sensing application, where these networks were able to detect NO2 at trace levels, at low temperatures, using UV-visible activation.

Modern implantology is based on the use of endosseous dental implants and on the study of osseointegration processes. The loss of marginal bone around a dental implant can be caused by many factors; the proper distribution of the masticatory loads is important and is closely dependent on the quality and quantity of bone tissue surrounding the implant. In fact, bone has the ability to adapt its microstructure, through processes of resorption and neoformation of new bone matrix, as a result of the mechanical stimuli that are generated during the chewing cycles. The purpose of this article is to redefine in a modern key and in light of current industrial and engineering technology, clinical and biomechanical concepts that characterize the monophasic implants, in order to assess proper use by evaluating the biomechanical differences with the biphasic implants.

Permanent maxillary canines are the second most frequently impacted teeth and the prevalence of this clinical condition is estimated to be 1-2% in the general population. The diagnosis of maxillary canine impaction should be based on both clinical and radiographic examinations. The aim of this study was to evaluate the presence of a correlation between the facial biotype and the inclination of the upper cusp axis. A correlation between the total radicular length of the lateral incisors was also evaluated, by comparing the side of impaction with the healthy side. Twenty three patients with a diagnosis of unilateral upper cusp impaction were recruited. For each patient, dental casts and radiographic material (panoramic radiographs and lateral cephalograms) were examined. Statistical analyses were done with Spearman's rank correlation coefficient or Spearman's rho (ρ). X-ray examinations demonstrated that canine impaction was associated to other dental anomalies (32% of the sample). The mean α angle measurements were 22.9° ± 4.1°, and mean values of the β angle were 34.7°± 4.0°. The mean distance "d" value was 14.6 mm ± 1.2 mm. The mean values of the angle between the upper cusp axis and the perpendicular-to-Fh plane were 20.8° ± 2.6°. Among the 23 subjects recruited, 5 showed values included in the range 25°-45° and 1 an inclination > 45°. The results obtained in the present study demonstrate a significant inverse correlation between the MM angle and the inclination of the upper cusp axis to the perpendicular-to-Fh plane.

The aim of this study is to present a clinical case of a full arch prosthetic rehabilitation on natural teeth, combining both digital work-flow and monolithic zirconia.Digital impression was taken with an intraoral optical scanner (CS3500, Carestream Dental, Atlanta, GA, USA). A prosthetic rehabilitation was realized on natural teeth using monolithic zirconia from 1.6 to 1.4 and from 2.7 to 2.4 frameworks, while in the aesthetic area (from 2.3 to 1.3), technicians left on the structure a 0.8 mm vestibular space for ceramic layering.The combination of digital impression technology and the use of the monolithic zirconia had demonstrated the delivery of the final prosthetic device in a quick time without the need to remodel functional or aesthetic areas. The digital work-flow combines intraoral optical impression techniques and CAD/CAM technology, in order to achieve a fully digital and successful way to deliver prosthetic restorations to patients, providing aesthetics and function in shorter intervals of time. The clinical outcome of this study was satisfactory but a long-term evaluation is needed.

the generation and the following collapse of a gas bubble in water is a highly efficient technique for capturing, trapping and delivering water dispersed nanoscale elements in a specific area of a substrate.

Background Conventional dentures in edentulous patients show some limitations due to the lack of retention, support and stability thus resulting in difficulty to chew. The modern implantology allows to use different implant overdentures and different attachment systems. The selection of the attachment by practitioners is mainly influenced by the clinical experience or technical preferences. Aims The aim of the present review is to provide an adequate background to the clinicians, in order to select the prosthetic attachments according to the current literature. The mechanical attachments have been compared to the magnetic devices, with the aim to guide the decision of the practitioners. Methods Articles topics selection was based on the use of magnetic attachments in dentistry and the comparison between them and mechanical connectors. The databases used were PubMed/MEDLINE, Google Scholar and ISI Web of Science. A critical evaluation of the selected paper has been made to choose the ones that matched the inclusion criteria. Results Nowadays, few studies have compared different attachments in a manner useful for clinical decision-making. The main problem limiting long-term durability of magnetic attachments in the oral fluid is the poor corrosion resistance of permanent magnets and the consequent leaching of cytotoxic ions. Conclusion Magnetic attachments in comparison with other attaching systems can be useful in patients with special needs, in patients with limited interocclusal space, or in patients with neuromuscular limitations, thanks to the automatic reseating properties. However, it’s important to highlight that the mechanical attachments still represent the best choice in common conditions requiring dental prostheses.

Osteosarcoma is an aggressive primary bone tumor composed of connective tissue cells directly producing osteoid and bone. Prosthetic rehabilitations in post-oncological patients after bone reconstruction are not substantially different than those of patients affected by severe atrophy of upper or lower jaw after bone reconstruction. The treatment for patients with a malignant neoplasia of the oral cavity requires multidisciplinary approach by a team of different specialists that follow the patient through the phases of diagnosis, therapy and oral rehabilitation. Reconstructive surgery of jaws using vascularized free flap allows a significant gain of tissues that enables a successful final prosthetic rehabilitation. In fact main prosthetics difficulties result from lack of hard and soft tissues in affected area. Reconstructed patients have a greater ease of care management.A 25-year-old Caucasian male was diagnosed with chondroblastic osteosarcoma of the pre-maxilla. The patient initially noticed the displacement of his maxillary incisors with progression into a definite swelling of the pre-maxillary a month later. Computerized Tomographic Scan and Radionuclide Bone Scan revealed the absence of both distant metastasis and regional nodal involvement. A biopsy and subsequent histopathology examination confirmed the lesion as being a chondroblastic type of osteosarcoma. The case study directed us to rehabilitate the patient by implant supported prosthesis consisting 3 different components: a titanium base screwed on implants, a titanium structure (primary structure) assembled on the base and a composite coatedstructure (secondary structure) that reproduced teeth and gum. At surgery, we proceeded placing 6 dental implants in 1.4, 1.3 1.2, 2.1, 2.2 and 2.4 positions. Contextually was performed a bone graft using particulate bone and collagen membranes.Prosthetic rehabilitation in Maxillofacial Osteosarcoma treatment is an hard challenge for prosthodontist due to anatomic conditions of this kind of patients. Dental implants play a crucialrole in the therapy of patients affected by malignancies in the head-and-neck region. The goal of implant rehabilitationis to improve the quality of life of these patients by allowing proper retention of removable prostheses and a reduction in the load placed on vulnerable soft tissues. Today prosthetically guided rehabilitation represents the main rehabilitation protocol in prosthodontics, especially in those oncological patients with relevant lost of tissues and modified anatomy.

Introduction The present study aimed to compare the long-term results of transanal haemorrhoidal dearterialisation (THD) with mucopexy and stapler haemorrhoidopexy (SH) in treatment of grade III and IV haemorrhoids. Methods One hundred and twenty-four patients with grade III and IV haemorrhoids were randomised to receive THD with mucopexy (n=63) or SH (n=61). A telephone interview with a structured questionnaire was performed at a median follow-up of 42 months. The primary outcome was the occurrence of recurrent prolapse. Patients, investigators and those assessing the outcomes were blinded to group assignment. Results Recurrence was present in 21 patients (16.9%). It occurred in 16 (25.4%) in the THD group and 5 (8.2%) in the SH group (p=0.021). A second surgical procedure was performed in eight patients (6.4%). Reoperation was open haemorrhoidectomy in seven cases and SH in one case. Five patients out of six in the THD group and both patients in the SH group requiring repeat surgery presented with grade IV haemorrhoids. No significant difference was found between the two groups with respect to symptom control. Patient satisfaction for the procedure was 73.0% after THD and 85.2% after SH (p=0.705). Postoperative pain, return to normal activities and complications were similar. Conclusions The recurrence rate after THD with mucopexy is significantly higher than after SH at long-term follow-up although results are similar with respect to symptom control and patient satisfaction. A definite risk of repeat surgery is present when both procedures are performed, especially for grade IV haemorrhoids.

Super-hydrophobic (SH) surfaces are bio-inspired, nanotechnology artifacts which feature a reduced friction coefficient whereby they can be used for a number of very practical applications including, on the medical side, the manipulation of biological solutions. These surfaces can be combined with bio-photonic devices to obtain an integrated lab-on-a-chip system where, on a first stage, the SH surface would vehicle or transport the analytes of interest into a small area and, on a second stage, the bio-sensors would permit, in that area, the detection of the solute with the resolution of a single molecule. This novel diagnostic modality offers realistic possibilities for the early detection of cancers. Nevertheless, as it stands, the device still suffers from the severe disadvantage that the exact final position of the solute, upon evaporation, is unpredictable, and thus the localization and recognition of few molecules would be impractical. Conventional SH surfaces typically comprise micro pillars combined to form a regular hexagonal motif. Here, the periodicity of those pillars was broken introducing artificial gradients of wettability over the surface. In doing so, some regions are rendered more hydrophilic than others and, on account of this, a solute would preferentially target these hydrophilic regions upon evaporation. In this work, such non regular geometries were realized and used to condense diluted Rhodamine solutions in a small area. Randomly distributed silver nano aggregates, conveniently positioned upon the micropillars, permitted the identification of few molecules using enhanced Fourier transform infrared spectroscopy (FTIR) spectroscopy.

In natural environments commonly appear periodic micro- and nano-structures exhibiting macroscopic properties different from the ones on the single elements. Typical examples are butterfly wings in optics, lotus leaves in fluidics or complex 3D neuronal networks in neuroscience and biology. Within this context, mimicking the intrinsic regularity exhibited by natural architectures can lead to unprecedented results addressing fundamental science but also intriguing challenges in technological applications. Here we will describe results we achieved by combining plasmonic nanostructures with nature-inspired superhydrophobic metamaterials. Then, we will try to extend this concept to the recent development of electronic devices with neuromorphic architectures for future computing.