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Common Sense Oncology (CSO) prioritises treatments providing meaningful benefits for people with cancer. Here, we describe CSO principles aimed at improving the design, analysis, and reporting of randomised, controlled, phase 3 clinical trials evaluating cancer treatments. These principles include: (1) control treatment should be the best current standard of care; (2) the preferred primary endpoint is overall survival or a validated surrogate; (3) an absolute measure of benefit should be provided, such as the difference between groups in median overall survival times or the proportion of surviving patients at a prespecified time; (4) health-related quality of life should be at least a secondary endpoint; (5) toxicity should be described objectively without subjective language diminishing its importance; (6) trials should be designed to show or rule out clinically meaningful differences in outcomes, rather than a statistically significant difference alone; (7) censoring should be detailed, and sensitivity analyses done to determine its possible effects; (8) experimental treatments known to improve overall survival at later disease stages should be offered and funded for patients progressing in the control group; and (9) reports of trials should include a lay-language summary. We include checklists to guide compliance with these principles. By encouraging adherence, CSO aims to ensure that clinical trials yield results that are scientifically robust and meaningful to patients.

We discuss the application of virtual elements to linear elasticity problems, for both the compressible and the nearly incompressible case. Virtual elements are very close to mimetic finite differences (see, for linear elasticity, [L. Beirão da Veiga, M2AN Math. Model. Numer. Anal., 44 (2010), pp. 231-250]) and in particular to higher order mimetic finite differences. As such, they share the good features of being able to represent in an exact way certain physical properties (conservation, incompressibility, etc.) and of being applicable in very general geometries. The advantage of virtual elements is the ductility that easily allows high order accuracy and high order continuity.

The present review paper has several objectives. Its primary aim is to give an idea of the general features of virtual element methods (VEMs), which were introduced about a decade ago in the field of numerical methods for partial differential equations, in order to allow decompositions of the computational domain into polygons or polyhedra of a very general shape. Nonetheless, the paper is also addressed to readers who have already heard (and possibly read) about VEMs and are interested in gaining more precise information, in particular concerning their application in specific subfields such as ${C}^1$ -approximations of plate bending problems or approximations to problems in solid and fluid mechanics.

We provide a framework for the analysis of a large class of discontinuous methods for second-order elliptic problems. It allows for the understanding and comparison of most of the discontinuous Galerkin methods that have been proposed over the past three decades for the numerical treatment of elliptic problems.

Background Proper wound healing after regenerative surgical procedures is an essential issue for clinical success. Guided tissue regeneration (GTR) and application of enamel matrix derivatives (EMD) are common means to regenerate periodontal tissues. Both methods bear considerable advantages due to their special characteristics, but also go along with certain disadvantages. Today, there is no consensus in the literature whether GTR or EMD show better results regarding early wound healing, which is considered a crucial stage in periodontal regeneration. Therefore, the aim of the present systematic review was to compare the early wound healing after regenerative periodontal surgery with either EMD or GTR treatment. Methods An electronic literature search in PubMed was performed to identify randomized clinical trials (RCTs) or clinical trials (CTs) comparing regenerative surgery employing EMD and/or GTR in patients with chronic periodontitis. Among the finally included studies, a qualitative and quantitative data extraction regarding early wound healing parameters was performed. Primary outcome parameters were early wound healing index (EWH), flap dehiscence, membrane exposure, suppuration and abscess formation during the first 6 weeks. As secondary parameters, swelling and allergic reactions were assessed. Results Seven studies reporting 220 intrabony periodontal defects in 199 patients were analysed. Flap dehiscence was observed in two studies in 12% of the GTR treated sites and in 10.3% of those treated with EMD. Membrane exposure was evaluated in five studies and was registered in the 28.8% of the defects, while no dehiscence was reported on the EMD group. Swelling was reported only in one study in 8/16 GTR sites and 7/16 EMD sites. Due to considerable heterogeneity of parameters no meta-analysis was possible. Conclusions Due to considerable heterogeneity of the published studies a clear beneficial effect of the EMD on the early wound healing outcomes after surgical treatment of periodontal intrabony defects cannot be confirmed. Standardized RCT studies are needed in order to allow for proper comparison of early wound healing after both types of surgical approaches.

State-of-the-art physics experiments require high-resolution, low-noise, and low-threshold detectors to achieve competitive scientific results. However, experimental environments invariably introduce sources of noise, such as electrical interference or microphonics. The sources of this environmental noise can often be monitored by adding specially designed “auxiliary devices” (e.g. microphones, accelerometers, seismometers, magnetometers, and antennae). A model can then be constructed to predict the detector noise based on the auxiliary device information, which can then be subtracted from the true detector signal. Here, we present a multivariate noise cancellation algorithm which can be used in a variety of settings to improve the performance of detectors using multiple auxiliary devices. To validate this approach, we apply it to simulated data to remove noise due to electromagnetic interference and microphonic vibrations. We then employ the algorithm to a cryogenic light detector in the laboratory and show an improvement in the detector performance. Finally, we motivate the use of nonlinear terms to better model vibrational contributions to the noise in thermal detectors. We show a further improvement in the performance of a particular channel of the CUORE detector when using the nonlinear algorithm in combination with optimal filtering techniques.

Many of the most sensitive physics experiments searching for rare events, like neutrinoless double beta ( 0 ν β β ) decay, coherent elastic neutrino nucleus scattering and dark matter interactions, rely on cryogenic macro-calorimeters operating at the mK-scale. Located underground at the Gran Sasso National Laboratory (LNGS), in central Italy, CUORE (Cryogenic Underground Observatory for Rare Events) is one of the leading experiments for the search of 0 ν β β decay, implementing the low-temperature calorimetric technology. We present a novel multi-device analysis to correlate environmental phenomena with the low-frequency noise of low-temperature calorimeters. Indeed, the correlation of marine and seismic data with data from a couple of CUORE detectors indicates that cryogenic detectors are sensitive not only to intense vibrations generated by earthquakes, but also to the much fainter vibrations induced by marine microseisms in the Mediterranean Sea due to the motion of sea waves. Proving that cryogenic macro-calorimeters are sensitive to such environmental sources of noise opens the possibility of studying their impact on the detectors physics-case sensitivity. Moreover, this study could pave the road for technology developments dedicated to the mitigation of the noise induced by marine microseisms, from which the entire community of cryogenic calorimeters can benefit.

PurposePanobinostat, an orally bioavailable pan-HDAC inhibitor, has demonstrated potent activity in multiple malignancies, including pediatric brain tumors such as DIPG, with increased activity against H3K27M mutant cell lines. Given limited evidence regarding the CNS penetration of panobinostat, we sought to characterize its BBB penetration in a murine model.MethodsPanobinostat 15 mg/kg was administered IV to 12 CD-1 female mice. At specified time points, mice were euthanized, blood samples were collected, and brains were removed. LC–MS was performed to quantify panobinostat concentrations. Cmax and AUC were estimated and correlated with previously published pharmacokinetic analyses and reports of IC-50 values in DIPG cell lines.ResultsMean panobinostat plasma concentrations (ng/mL) were 27.3 ± 2.5 at 1 h, 7.56 ± 1.8 at 2 h, 1.48 ± 0.56 at 4 h, and 2.33 ± 1.18 at 7 h. Mean panobinostat brain concentrations (ng/g) were 60.5 ± 6.1 at 1 h, 42.9 ± 5.4 at 2 h, 33.2 ± 6.1 at 4 h, and 28.1 ± 4.3 at 7 h. Brain-to-plasma ratio at 1 h was 2.22 and the brain to plasma AUC ratio was 2.63. Based on the published human pharmacokinetic data, the anticipated Cmax in humans is expected to be significantly higher than the IC-50 identified in DIPG models.ConclusionIt is expected that panobinostat would be effective in CNS tumors where the IC-50 is in the low nanomolar range. Thus, our data demonstrate panobinostat crosses the BBB and achieves concentrations above the IC-50 for DIPG and other brain tumors and should be explored further for clinical efficacy.

Carotenoid-based colouration plays an important role in sexual signaling in animals as an honest indicator of individual quality during mate choice and competitive interactions. However, few studies have examined how natural variation in weather conditions influences interannual variation in the expression of ornamentation, potentially through affecting the dietary availability of carotenoids. In this study, we examine variation in the expression of carotenoid-based plumage colouration in relation to temperature and rainfall during the pre-moulting and moulting period over 11 years in a population of American redstarts, Setophaga ruticilla, breeding in eastern Canada. We used reflectance spectrometry of tail feathers collected from male and female redstarts to relate feather colour with weather conditions the previous breeding season during the months over which redstarts are likely to moult (June-September). At a population level, birds expressed feathers with higher red chroma and lower brightness in years following high July rainfall and low August temperature. The pattern was stronger in males, but was generally consistent across ages and sexes. Analyses of feathers from repeatedly captured birds indicated that the above patterns could be explained by individual change in feather colour. We suggest that higher rainfall during the moulting period may increase insect abundance and the availability of dietary carotenoids. This is among the first studies to show effects of weather conditions on a sexual signalling trait, which may have important consequences for sexual selection, mate choice, and the reliability of putative signals.

This work is aimed at reconstructing the water-rock interaction processes controlling the geochemical characteristics of the shallow or relatively shallow groundwaters of the Pollino National Park, based on the data acquired for 105 water samples from local springs. Reaction path modeling of rock dissolution was carried out in a purely stoichiometric mode for the main lithotypes cropping out in the study area, that is, limestone, Mg-limestone, dolomite, serpentinite, Al-silicate fraction of calcschist, and carbonate fraction of calcschist. Reaction path modeling was carried out in a purely stoichiometric mode, considering the rocks of interest as materials of known stoichiometry and unknown thermodynamic properties. Calculations were carried out assuming a closed system for secondary solid phases whereas an open system was assumed for gases, O2(g) and CO2(g). Comparison of the results of geochemical modeling and the analytical data acquired for the groundwaters of the Pollino National Park shows that concentrations of major solutes, SiO2, Li, Al, and Fe of the different chemical types of waters, are explained by the dissolution of pertinent lithotypes. Moreover, the detected concentrations of Al, Cl, F, NO3, and SO4 are within the threshold values recommended by WHO.