Studio controllato sull'effetto di un elemento protesico a sbalzo a livello di impianti dentali singoli. Analisi delle variazioni del livello osseo marginale e della profondità di sondaggio ad 1 anno.

Scopo: scopo del presente lavoro è stato quello di valutare il riassorbimento osseo marginale (BL) e la profondità di sondaggio (PPD) intorno ad impianti singoli supportanti ricostruzioni parziali di due elementi, uno dei quali costituito da un elemento a sbalzo. Materiali e metodo: pazienti riabilitati tra il 2012 ed il 2013 mediante un impianto singolo (Straumann SLA, Standard Plus) supportante un ricostruzione protesica parziale di due elementi, di cui uno a sbalzo, sono stati reclutati (gruppo test). Un gruppo controllo è stato formato selezionando un numero uguale di soggetti che avevano ricevuto impianti singoli e corone singole nello stesso periodo di tempo ed in siti comparabili. Quando possibile, un approccio split-mouth è stato applicato. Al momento della finalizzazione protesica è stata effettuata una lastra endo-orale utilizzando un centratore. Dopo il primo anno si follow-up è stata eseguita una seconda lastra e registrata la profondità di sondaggio. Sono state calcolati i valori medi della perdita ossea (BL) avvenuta nel corso del primo anno di follow-up, del livello radiografico della cresta ossea al follow-up (BLevT12), e del PPD al follow-up Gruppo test e gruppo controllo sono stati confrontati utilizzando l'unpaired t-test. Sono stati inoltre calcolati i valori medi di questi stessi parametri a livello dell'interfaccia implantare adiacente all'elemento a sbalzo e quella opposta. Questi due gruppi sono stati confrontati per mezzo del paired t-test. Risultati: dei 19 pazienti test selezionati al baseline, 17 erano ancora presenti al follow-up. Nel gruppo test come nel gruppo controllo, solo piccole variazioni medie del livello osseo marginale sono state registrate (0.3-0.4mm), senza alcuna differenza tra i gruppi (p>0.05). Al livello del solo gruppo test, il confronto di BL, BLevT12 e PPDT12 a livello dell'interfaccia implantare adiacente il cantilever e quella opposta non ha rilevato differenze significative (p>0.05). Conclusioni: nei limiti del presente lavoro, la presenza di un elemento protesico a sbalzo in caso di ricostruzioni protesiche parziali fisse supportate da un impianto singolo non sembra causare una perdita ossea marginale o una profondità di sondaggio piu' elevate dopo il primo anno di carico rispetto ad impianti singoli supportanti corone singole

Nanosecond-level time synchronization of autonomous radio detector stations for extensive air showers

To exploit the full potential of radio measurements of cosmic-ray air showers at MHz frequencies, a detector timing synchronization within 1 ns is needed. Large distributed radio detector arrays such as the Auger Engineering Radio Array (AERA) rely on timing via the Global Positioning System (GPS) for the synchronization of individual detector station clocks. Unfortunately, GPS timing is expected to have an accuracy no better than about 5 ns. In practice, in particular in AERA, the GPS clocks exhibit drifts on the order of tens of ns. We developed a technique to correct for the GPS drifts, and an independent method is used to cross-check that indeed we reach a nanosecond-scale timing accuracy by this correction. First, we operate a ``beacon transmitter'' which emits defined sine waves detected by AERA antennas recorded within the physics data. The relative phasing of these sine waves can be used to correct for GPS clock drifts. In addition to this, we observe radio pulses emitted by commercial airplanes, the position of which we determine in real time from Automatic Dependent Surveillance Broadcasts intercepted with a software-defined radio. From the known source location and the measured arrival times of the pulses we determine relative timing offsets between radio detector stations. We demonstrate with a combined analysis that the two methods give a consistent timing calibration with an accuracy of 2 ns or better. Consequently, the beacon method alone can be used in the future to continuously determine and correct for GPS clock drifts in each individual event measured by AERA. <P /

The Pierre Auger Cosmic Ray Observatory

The Pierre Auger Observatory, located on a vast, high plain in western Argentina, is the world's largest cosmic ray observatory. The objectives of the Observatory are to probe the origin and characteristics of cosmic rays above 1017 eV and to study the interactions of these, the most energetic particles observed in nature. The Auger design features an array of 1660 water Cherenkov particle detector stations spread over 3000 km2 overlooked by 24 air fluorescence telescopes. In addition, three high elevation fluorescence telescopes overlook a 23.5 km2, 61-detector infilled array with 750 m spacing. The Observatory has been in successful operation since completion in 2008 and has recorded data from an exposure exceeding 40,000 km2 sr yr. This paper describes the design and performance of the detectors, related subsystems and infrastructure that make up the Observatory

Measurement of the cosmic ray spectrum above 4 × 10<SUP>18</SUP> eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding 4×1018 eV is presented, which is based on the analysis of showers with zenith angles greater than 60° detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above 5.3×1018 eV, the ``ankle'', the flux can be described by a power law E-γ with index γ=2.70 ± 0.02 (stat) ± 0.1 (sys) followed by a smooth suppression region. For the energy (Es) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find Es=(5.12±0.25 (stat)+1.0-1.2 (sys))×1019 eV

Measurement of the muon production depths at the Pierre Auger Observatory

The muon content of extensive air showers is an observable sensitive to the primary composition and to the hadronic interaction properties. The Pierre Auger Observatory uses water-Cherenkov detectors to measure particle densities at the ground and therefore is sensitive to the muon content of air showers. We present here a method which allows us to estimate the muon production depths by exploiting the measurement of the muon arrival times at the ground recorded with the Surface Detector of the Pierre Auger Observatory. The analysis is performed in a large range of zenith angles, thanks to the capability of estimating and subtracting the electromagnetic component, and for energies between 1019.2 and 1020eV. <P /

Sorafenib blocks tumour growth, angiogenesis and metastatic potential in preclinical models of osteosarcoma through a mechanism potentially involving the inhibition of ERK1/2, MCL-1 and ezrin pathways

<p>Abstract</p> <p>Background</p> <p>Osteosarcoma (OS) is the most common primary bone tumour in children and young adults. Despite improved prognosis, metastatic or relapsed OS remains largely incurable and no significant improvement has been observed in the last 20 years. Therefore, the search for alternative agents in OS is mandatory.</p> <p>Results</p> <p>We investigated phospho-ERK 1/2, MCL-1, and phospho-Ezrin/Radixin/Moesin (P-ERM) as potential therapeutic targets in OS. Activation of these pathways was shown by immunohistochemistry in about 70% of cases and in all OS cell lines analyzed. Mutational analysis revealed no activating mutations in KRAS whereas BRAF gene was found to be mutated in 4/30 OS samples from patients. Based on these results we tested the multi-kinase inhibitor sorafenib (BAY 43-9006) in preclinical models of OS. Sorafenib inhibited OS cell line proliferation, induced apoptosis and downregulated P-ERK1/2, MCL-1, and P-ERM in a dose-dependent manner. The dephosphorylation of ERM was not due to ERK inhibition. The downregulation of MCL-1 led to an increase in apoptosis in OS cell lines. In chick embryo chorioallantoic membranes, OS supernatants induced angiogenesis, which was blocked by sorafenib and it was also shown that sorafenib reduced VEGF and MMP2 production. In addition, sorafenib treatment dramatically reduced tumour volume of OS xenografts and lung metastasis in SCID mice.</p> <p>Conclusion</p> <p>In conclusion, ERK1/2, MCL-1 and ERM pathways are shown to be active in OS. Sorafenib is able to inhibit their signal transduction, both <it>in vitro </it>and <it>in vivo</it>, displaying anti-tumoural activity, anti-angiogenic effects, and reducing metastatic colony formation in lungs. These data support the testing of sorafenib as a potential therapeutic option in metastatic or relapsed OS patients unresponsive to standard treatments.</p

Cosmic Rays from the Knee to the Highest Energies

This review summarizes recent developments in the understanding of high-energy cosmic rays. It focuses on galactic and presumably extragalactic particles in the energy range from the knee (10^15 eV) up to the highest energies observed (>10^20 eV). Emphasis is put on observational results, their interpretation, and the global picture of cosmic rays that has emerged during the last decade.Comment: Invited review, submitted to Progress in Particle and Nuclear Physic