208 research outputs found
Surfactants, nanomedicines and nanocarriers: a critical evaluation on clinical trials
Advances, perspectives and innovation in drug delivery have increased in recent years; however, there is limited information available regarding the actual presence of surfactants, nanomed-icines and nanocarriers in investigational medicinal products submitted as part of a request for authorization of clinical trials, particularly for those authorized in the European Economic Area. We retrieve, analyze and report data available at the Clinical Trial Office of the Italian Medicines Agency (AIFA), increasing the transparency and availability of relevant information. An analysis of quality documentation submitted along with clinical trials authorized by the AIFA in 2018 was carried out, focusing on the key terms “surfactant”, “nanomedicine” and “nanocarrier”. Results suggest potential indications and inputs for further reflection and actions for regulators to actively and safely drive innovation from a regulatory perspective and to transpose upcoming evolution of clinical trials within a strong regulatory framework
Massively parallel computing on an organic molecular layer
Current computers operate at enormous speeds of ~10^13 bits/s, but their
principle of sequential logic operation has remained unchanged since the 1950s.
Though our brain is much slower on a per-neuron base (~10^3 firings/s), it is
capable of remarkable decision-making based on the collective operations of
millions of neurons at a time in ever-evolving neural circuitry. Here we use
molecular switches to build an assembly where each molecule communicates-like
neurons-with many neighbors simultaneously. The assembly's ability to
reconfigure itself spontaneously for a new problem allows us to realize
conventional computing constructs like logic gates and Voronoi decompositions,
as well as to reproduce two natural phenomena: heat diffusion and the mutation
of normal cells to cancer cells. This is a shift from the current static
computing paradigm of serial bit-processing to a regime in which a large number
of bits are processed in parallel in dynamically changing hardware.Comment: 25 pages, 6 figure
Photoionization Dynamics of the Tetraoxo Complexes OsO4 and RuO4
The photoionization dynamics of OsO4 and RuO4, chosen as model systems of small-size mononuclear heavy-metal complexes, has been theoretically studied by the time-dependent density functional theory (TDDFT). Accurate experimental measurements of photoionization dynamics as a benchmarking test for the theory are reported for the photoelectron asymmetry parameters of outer valence ionizations of OsO4, measured in the 17-90 eV photon energy range. The theoretical results are in good agreement with the available experimental data. The observed dynamical behavior of partial cross sections and asymmetry parameters has been related to both the coupling to the continuum of discrete excited states, giving strong modulations in the photon energy dependency, and the atomic composition of the initial ionized states, which determines the rate of decay of ionization probability for increasing excitation energies. Overall, an extensive analysis of the photoionization dynamics for valence and core orbitals is presented, showing good agreement with all the available experimental data. This provides confidence for the validity of the TDDFT approach in describing photoionization of heavy transition element compounds, with the perspective of being used for larger systems. Further experimental work is suggested for RuO4 to gather evidence of the sensitivity of the theoretical method to the nature of the metal atom
Valutazione della bontà educativa dei casi clinici di ECCE, il programma di formazione a distanza (FAD) basato sulle evidenze destinato ai medici italiani
OBIETTIVO. Valutare la qualit\ue0 dei percorsi clinici di un programma FAD destinato a tutti i medici italiani
verificando le loro propriet\ue0 psicometriche. METODI. AIFA ha lanciato un programma nazionale di sostegno
dell\u2019informazione indipendente tramite la distribuzione gratuita ai medici di Clinical Evidence (CE). Sulla base
dei contenuti di CE \ue8 stato sviluppato un programma FAD all\u2019interno del sistema di Educazione Continua in
Medicina (ECM) dal nome ECCE, anch\u2019esso gratuito. I medici hanno accesso a CE online e ai relativi percorsi
clinici. Superandoli il medico ottiene i crediti ECM. Nel corso del 2006 \ue8 stata valutata la qualit\ue0 di un
campione di venti percorsi, su un totale di 120. La valutazione formale della qualit\ue0 dei 20 casi selezionati \ue8
avvenuta attraverso le seguenti dimensioni psicometriche:
Giudizio generale sui percorsi da parte degli utilizzatori (face validity);
Valutazione dei contenuti da parte di clinici esperti (content validity);
Valutazione della attendibilit\ue0 del test attraverso un criterio di consistenza interna (internal reliability); Difficolt\ue0 degli items;
Capacit\ue0 del test di rilevare una modificazione della conoscenza (responsiveness).
RISULTATI: Alcune migliaia di utenti hanno partecipato alla valutazione fornendo esiti contrastanti: mentre la
face e content validity sono state valutate positivamente dagli utilizzatori e dai clinici esperti, altri parametri come l\u2019internal reliability e la difficolt\ue0 degli items hanno mostrato grande variabilit\ue0 tra i percorsi. Sette casi mostrano un valore di alpha complessivo inferiore a 0.50 (soglia minima di affidabilit\ue0). I casi si sono dimostrati nel complesso medio-facili. Facendo riferimento solo alle proprie conoscenze i partecipanti rispondevano correttamente a circa a met\ue0 delle domande. La lettura delle fonti era associata a un miglioramento della performance (miglioramento prima-dopo statisticamente significativo, p<0.05 per 19/20 percorsi).
CONCLUSIONI: L\u2019importante eterogeneit\ue0 tra percorsi dimostrerebbe come differenti casi possono analizzare
in maniera molto disomogenea il domino conoscenza evidence-based derivata dai contenuti di CE
A novel free-electron laser single-pulse Wollaston polarimeter for magneto-dynamical studies
Here, we report on the conceptual design, the hardware realization, and the first experimental results of a novel and compact x-ray polarimeter capable of a single-pulse linear polarization angle detection in the extreme ultraviolet photon energy range. The polarimeter is tested by performing time resolved pump-probe experiments on a Ni80Fe20 Permalloy film at the M-2,M-3 Ni edge at an externally seeded free-electron laser source. Comparison with similar experiments reported in the literature shows the advantages of our approach also in view of future experiments
Regional actorness and interregional relations:ASEAN, the EU and Mercosur
The European Union (EU) has a long tradition of interregional dialogue mechanisms with other regional organisations and is using these relations to project its own model of institutionalised actorness. This is partly motivated by the emerging actorness of the EU itself, which benefits from fostering capable regional counterparts in other parts of the world. This article advances the argument that actorness, which we conceptualise in terms of institutions, recognition and identity, is a relational concept, dependent on context and perception. Taking the Association of Southeast Asian Nations (ASEAN) and the Common Market of the South (Mercosur) and their relations with the EU as case studies, this article demonstrates that the actorness capabilities of all three organisations have been enhanced as result of ASEAN-EU and Mercosur-EU relations. However, there are clear limits to the development of the three components of regional actorness and to the interregional relations themselves. These limits stem both from the type of interregionalism at play and from the different regional models the actors incorporate. While there is evidence of institutional enhancement in ASEAN and Mercosur, these formal changes have been grafted on top of firmly entrenched normative underpinnings. Within the regional organisations, interactions with the EU generate centrifugal forces concerning the model to pursue, thus limiting their institutional cohesion and capacity. In addition, group-to-group relations have reinforced ASEAN and Mercosur identities in contrast to the EU. The formation of such differences has narrowed the scope of EU interregionalism despite the initial success of improved regional actorness
Modeling of negative Poisson’s ratio (auxetic) crystalline cellulose Iβ
Energy minimizations for unstretched and stretched cellulose models using an all-atom empirical force field (Molecular Mechanics) have been performed to investigate the mechanism for auxetic (negative Poisson’s ratio) response in crystalline cellulose Iβ from kraft cooked Norway spruce. An initial investigation to identify an appropriate force field led to a study of the structure and elastic constants from models employing the CVFF force field. Negative values of on-axis Poisson’s ratios nu31 and nu13 in the x1-x3 plane containing the chain direction (x3) were realized in energy minimizations employing a stress perpendicular to the hydrogen-bonded cellobiose sheets to simulate swelling in this direction due to the kraft cooking process. Energy minimizations of structural evolution due to stretching along the x3 chain direction of the ‘swollen’ (kraft cooked) model identified chain rotation about the chain axis combined with inextensible secondary bonds as the most likely mechanism for auxetic response
Small tumor necrosis factor receptor biologics inhibit the tumor necrosis factor-p38 signalling axis and inflammation
Anti-TNF therapy has improved the treatment of inflammatory disease but can predispose to infection and malignancy. Here the authors show an anti-TNF biologic peptide that functionally and selectively targets the TNF-p38 pathway in multiple models of inflammation
Evaluation of the public health impacts of traffic congestion: a health risk assessment
Background: Traffic congestion is a significant issue in urban areas in the United States and around the world. Previous analyses have estimated the economic costs of congestion, related to fuel and time wasted, but few have quantified the public health impacts or determined how these impacts compare in magnitude to the economic costs. Moreover, the relative magnitudes of economic and public health impacts of congestion would be expected to vary significantly across urban areas, as a function of road infrastructure, population density, and atmospheric conditions influencing pollutant formation, but this variability has not been explored. Methods: In this study, we evaluate the public health impacts of ambient exposures to fine particulate matter (PM2.5) concentrations associated with a business-as-usual scenario of predicted traffic congestion. We evaluate 83 individual urban areas using traffic demand models to estimate the degree of congestion in each area from 2000 to 2030. We link traffic volume and speed data with the MOBILE6 model to characterize emissions of PM2.5 and particle precursors attributable to congestion, and we use a source-receptor matrix to evaluate the impact of these emissions on ambient PM2.5 concentrations. Marginal concentration changes are related to a concentration-response function for mortality, with a value of statistical life approach used to monetize the impacts. Results: We estimate that the monetized value of PM2.5-related mortality attributable to congestion in these 83 cities in 2000 was approximately 60 billion. In future years, the economic impacts grow (to over 13 billion in 2020 before increasing to $17 billion in 2030, given increasing population and congestion but lower emissions per vehicle. Across cities and years, the public health impacts range from more than an order of magnitude less to in excess of the economic impacts. Conclusions: Our analyses indicate that the public health impacts of congestion may be significant enough in magnitude, at least in some urban areas, to be considered in future evaluations of the benefits of policies to mitigate congestion
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