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

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

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

Cytokine Induced Killer cells are effective against sarcoma cancer stem cells spared by chemotherapy and target therapy

Metastatic bone and soft tissue sarcomas often relapse after chemotherapy (CHT) and molecular targeted therapy (mTT), maintaining a severe prognosis. A subset of sarcoma cancer stem cells (sCSC) is hypothesized to resist conventional drugs and sustain disease relapses. We investigated the immunotherapy activity of cytokine induced killer cells (CIK) against autologous sCSC that survived CHT and mTT. The experimental platform included two aggressive bone and soft tissue sarcoma models: osteosarcoma (OS) and undifferentiated-pleomorphic sarcoma (UPS). To visualize putative sCSC we engineered patient-derived sarcoma cultures (2 OS and 3 UPS) with a lentiviral sCSC-detector wherein the promoter of stem-gene Oct4 controls the expression of eGFP. We visualized a fraction of sCSC (mean 24.2 +/- 5.2%) and confirmed their tumorigenicity in vivo. sCSC resulted relatively resistant to both CHT and mTT in vitro. Therapeutic doses of doxorubicin significantly enriched viable eGFP(+)sCSC in both OS (2.6 fold, n = 16) and UPS (2.3 fold, n = 29) compared to untreated controls. Treatment with sorafenib (for OS) and pazopanib (for UPS) also determined enrichment (1.3 fold) of viable eGFP(+)sCSC, even if less intense than what observed after CHT. Sarcoma cells surviving CHT and mTT were efficiently killed in vitro by autologous CIK even at minimal effector/target ratios (40:1 = 82%, 1:4 = 29%, n = 13). CIK immunotherapy did not spare sCSC that were killed as efficiently as whole sarcoma cell population. The relative chemo-resistance of sCSC and sensitivity to CIK immunotherapy was confirmed in vivo. Our findings support CIK as an innovative, clinically explorable, approach to eradicate chemo-resistant sCSC implicated in tumor relapse

High-Energy Cosmic Rays from Gamma-Ray Bursts

A model is proposed for the origin of cosmic rays (CRs) from ~10^14 eV to the highest energies, >10^20 eV. Gamma-Ray Bursts (GRBs) are assumed to inject CR protons and ions into the interstellar medium of star-forming galaxies--including the Milky Way--with a power law spectrum extending to a maximum energy ~10^20 eV. The CR spectrum near the knee is fit with CRs trapped in the Galactic halo that were accelerated and injected by an earlier Galactic GRB. These CRs diffuse in the disk and halo of the Galaxy due to gyroresonant pitch-angle scattering with MHD turbulence in the Galaxy's magnetic field. The preliminary (2001) KASCADE data through the knee of the CR spectrum are fit by a model with energy-dependent propagation of CR ions from a single Galactic GRB. Ultra-high energy CRs (UHECRs), with energies above the ankle are assumed to propagate rectilinearly with their spectrum modified by photo-pion, photo-pair, and expansion losses. We fit the measured UHECR spectrum assuming comoving luminosity densities of GRB sources consitent with possible star formation rate histories of the universe. For power-law CR proton injection p>2 this model implies that the nonthermal content in the GRB blast waves is hadronically dominated by a factor ~60-200. Calculations show that 100 TeV-100 PeV neutrinos could be detected several times per year from all GRBs in kilometer-scale neutrino detectors such as IceCube, for GRB blast-wave Doppler factors <~200. GLAST measurements of gamma-ray components and cutoffs will constrain the product of nonthermal baryon loading and radiative efficiency, limit the Doppler factor, and test this senario.Comment: 43 pages, 21 figures, to appear in Astropart. Phy