Mechanisms of synaptic depression triggered by metabotropic glutamate receptors

Abstract.: Glutamate, by activation of metabotropic receptors (mGluRs), can lead to a reduction of synaptic efficacy at many synapses. These forms of synaptic plasticity are referred to as long-term depression (mGluR-LTD). We will distinguish between mGluR-LTD induced by pre- or postsynaptic receptors and mGluR-LTD induced by the locus of the expression mechanism of the synaptic depression. We will also review recent evidence that mGluR-mediated responses themselves are subject to depression, which may constitute a form of metaplasticit

Il gioco della logica tra uso del linguaggio e costruzione della scienza.

E tanto più intendo tanto più ignoro, motto di Tommaso Campanella, può servire a spiegare, bene, le virgolette messe attorno alla parola: gioco, ed il suo carattere, ambiguo e contraddittorio, essendo tutto ciò vero tanto nello uso del linguaggio, quanto nella costruzione della scienza. Quanto segue si dipana in alcuni meandri della filosofia analitica, a partire dal positivismo logico, dove molto forte è l’accanirsi contro la metafisica. A riguardo, avendo presente l’uso rinnovato del termine, fatto da giovani filosofi contemporanei, corre il dovere di precisare la sua validità, se significa andare oltre le cose fisiche, con le assunzioni necessarie per pensare e fare scienza. Al contrario, validissimo è il rigetto della metafisica, quando questa voglia dire, come nella tradizione della storia del pensiero, rifarsi a principi primi indiscutibili ed assoluti. Rudolf Carnap e Karl Raimund Popper sono i maggiori esponenti delle scuole filosofiche, prese in esame. La trattazione collega linguaggio e costruzione della scienza, perché una concezione moderna descrive la scienza come un linguaggio, capace di leggere la realtà fisica, dove la complessità della analisi cresce al crescere della complessità della modellazione adottata. Infatti oltre a muoversi liberamente nello spazio, parametrizzato con righe, colonne e pile, è spesso necessario muoversi congiuntamente nel tempo e/o nel cosiddetto spazio delle scale, entrambi parametrizzati con pioli e montanti, a seconda che si permanga ad un dato livello, oppure si passi da un livello ad un altro. Da altra parte, un esempio musicale dà il segno della complessità: le cinque note pentatoniche (la si do re mi fa sol) permettono 720 permutazioni, mentre le dodici note (mettendo insieme i tasti bianchi e neri del pianoforte) permettono 479.001.600 permutazioni e, anche limitandosi alle ventiquattro scale armoniche, maggiori e minori (sulle sette note del clavicembalo ben temperato), il numero di permutazioni è 120.960. In questo contesto, il superamento della empiria fa passare dalla capacità di verificazione alla sola possibilità di falsificazione, dove è possibile dire quello che è errato, ma non è possibile certificare quello che è esatto. Infatti la verità è sempre provvisoria e precaria, valida fino ad una possibile smentita, più o meno prossima, e le costruzioni tecniche, sociali, economiche e politiche sono, sempre e solo, governate dal dubbio ed altrettanto precarie e provvisorie. Infine con un salto notevole di contenuto, ma affatto estraneo alla vita ed alle concezioni dei pensatori (qui già citati e/o citati nel seguito), è davvero difficile, soprattutto in questi tempi così tanto travagliati, separare il parlare alto di ricerca scientifica e tecnologica, nonché di storia della scienza e della tecnica, e di epistemologia, dai casi della vita quotidiana, vari e diversi. Di fronte a tutti questi è davvero difficile scegliere la strada migliore, in ogni caso, ben sapendo come occorra, sempre ed ovunque, il coraggio e lo impegno e talvolta anche la ribellione

Cost-effectiveness analysis of alectinib versus crizotinib in first-line treatment of anaplastic lymphoma kinase-positive advanced non-small cell lung cancer:

In the randomized, active-controlled, multicenter Phase III open-label ALEX trial, alectinib showed superior efficacy and lower toxicity compared with crizotinib in the primary treatment of anaplastic lymphoma kinase-positive non-small cell lung cancer (ALK-positive NSCLC). The aim of this economic evaluation was to assess the cost-utility of alectinib versus crizotinib from the perspective of the Italian National Health Service (INHS). A partitioned survival model with three health states (progression-free, post-progression, and death) was used. The clinical data (progression-free survival, overall survival and time to progression) was based on the ALEX trial. Utility values were derived from EQ-5D scores evaluated in the ALEX trial and literature. Costs included drug treatments, progression-free, post-progression and supportive care. Direct medical costs and benefits (quality-adjusted life-years, QALYs) were discounted at a 3.0% annual rate. Uncertainty was assessed using deterministic and probabilistic sensitivity analyses. Treatment with alectinib versus crizotinib led to a gain of 2.82 life-years, 1.86 QALYs, and incremental costs of €58,276, resulting in an incremental cost-utility ratio of €31,353 per QALY. The deterministic analysis showed that the most critical parameters in the model were the cost of post-progression and utility scores. From the probabilistic sensitivity analysis, alectinib had a 64.5% probability of being cost-effective at a willingness-to-pay threshold of €40,000 per QALY. Compared with crizotinib, alectinib increased the length of the progression-free state and the QALYs. The incremental overall cost increase was reflective of longer treatment durations in the progression-free state. Compared with crizotinib, alectinib can be considered a valid cost-utility option in the treatment of naive patients with ALK-positive NSCLC

ON OUTLIER DETECTION IN A PHOTOGRAMMETRIC MOBILE MAPPING DATASET

Various types of technology are used for Terrestrial Mobile Mapping (TMM) such as IMU, cameras, odometers, laser scanner etc., which are integrated in order to determine the attitude and the position of the vehicle in use, especially in the absence of GNSS signal i.e. in an urban canyon. The aim of this study is to use only photogrammetric measurements obtained with a low cost camera (with a reduced focal length and small frames) located on the vehicle, in order to improve the quality of TMM solution in the absence of a GNSS signal. It is essential to have good quality frames in order to solve this problem. In fact it is generally quite easy to extract a large number of common points between the frames (the so-called 'tie points'), but this does not necessarily imply the goodness of the matching quality, which might be uncorrected due to the presence of obstacles that may occlude the camera sight. The Authors used two different methods for solving the problem of the presence of outliers: RANSAC and the Forward Search. In this article the Authors show the results obtainable with good quality frames (frames without occlusions) and under difficult conditions that simulate better reality

Theory of single-charge exchange heavy-ion reactions

The theory of heavy-ion single-charge exchange reactions is reformulated. In momentum space, the reaction amplitude factorizes into a product of projectile and target transition form factors, folded with the nucleon-nucleon isovector interaction. The multipole structure of the transition form factors is studied in detail for Fermi-type non-spin-flip and Gamow-Teller-type spin-flip transitions, also serving to establish the connection to nuclear β decay. The reaction kernel is evaluated for central and rank-2 tensor interactions. Initial- and final-state ion-ion elastic interactions are accounted for by a distortion coefficient. Since the ion-ion interactions are dominated by the imaginary part of the optical potentials, the distortion coefficients can be evaluated in the strong absorption limit. For a Gaussian potential form factor, the distortion coefficient is evaluated in closed form, revealing the relation to the total reaction cross section. It is shown that at small momentum transfer distortion effects reduce to a simple scaling factor, allowing us to define a reduced forward-angle cross section which is given by nuclear matrix elements of β decay type. Thus we introduce new unit cross sections, as those traditionally used with light projectiles for spectroscopic purposes, for heavy-ion charge-exchange reactions. Results are discussed for τ ± excitations of 18 O and 40 Ca , respectively. Spectral distributions of nuclear-charge-changing transitions are obtained by self-consistent Hartree-Fock-Bogolubov (HFB) and quasiparticle random phase approximation (QRPA) theory and compared to spectroscopic data. The interplay of nuclear structure and reaction dynamics is illustrated for the single-charge exchange (SCE) reaction 18 O + 40 Ca → 18 F + 40 K at T lab = 270 MeV, by performing full-scale numerical calculations of the SCE cross section. We also show that the latter compare rather well with the results obtained within the strong absorption limit, thus confirming the possibility to factorize the forward-angle cross section into intrinsic nuclear transition dynamics and reaction dynamics.Programa Horizonte 2020 de la Unión Europea.654002Ministerio de Ciencia, Innovación y Universidades de España y Fondos FEDER. FIS2017- 88410-

Probing beta decay matrix elements through heavy ion charge exchange reactions

To access information on neutrinoless double beta decay (0νββ) nuclear matrix elements, it has been proposed by the NUMEN collaboration to exploit the analogies between double beta decay processes and double charge exchange (DCE) nuclear reactions, looking in particular at the conditions where the corresponding cross section can be factorized into nuclear reaction and nuclear structure terms. DCE reactions can be treated as a convolution of two correlated or uncorrelated single charge exchange (SCE) processes, resembling 0νββ and 2νββ, respectively. Thus it is important to model first SCE processes, to get a deeper insight into the possibility to factorize the corresponding cross section, so one can gain a better understanding of DCE cross section factorization. In this contribution, DCE reactions are discussed in terms of the convolution of two uncorrelated SCE processes, which should allow one to extract information on 2νββ nuclear matrix elements. These theoretical investigations are performed in close synergy with the experimental activity running at INFN-LNS within the NUMEN project

A Novel Muco-Gingival Approach for Immediate Implant Placement to Obtain Soft- and Hard-Tissue Augmentation

The aim of this article is to describe a novel approach combining muco-gingival, regenerative and prosthetics concepts for immediate implant insertion that overcomes the limits traditionally considered as contraindications for Type 1 flapless implant positioning, simultaneously obtaining soft- and hard-tissue augmentation. After pre-surgical CBCT evaluation, the surgical technique consisted in the execution of a lateral-approach coronally advanced envelope flap, with oblique submarginal interproximal incisions directed towards the flap’s center of rotation (the tooth to be extracted); after buccal-flap elevation, the atraumatic extraction of the tooth was performed. Following guided implant insertion, a mixture of biomaterial and autologous bone was placed, stabilized by a pericardium membrane and a connective-tissue graft sutured in the inner aspect of the buccal flap. The peri-implant soft tissues were conditioned with a provisional crown until the shape and position for the mucosal scallop to resemble the gingival margin of the adjacent corresponding tooth were obtained; then, the definitive screw-retained restoration was placed. Within the limitations of this case report, the proposed immediate implant placement approach combining CTG application and buccal bone regeneration showed the possibility of obtaining 1-year-follow-up implant success, stable bone level, good esthetic results and high patient satisfaction