study protocol for a randomized controlled trial

Background For treating deep caries lesions, selective or stepwise (one- and two-step) incomplete excavation seems advantageous compared with complete caries removal. However, current evidence regarding the success, as defined by not requiring any retreatments, or survival of teeth after different excavations is insufficient for definitive recommendation, especially when treating deciduous teeth. Moreover, restoration integrity has not been comparatively analyzed longitudinally, and neither patients’, dentists’ or parents’ preferences nor the clinical long-term costs emanating from both initial and retreatments have been reported yet. Methods/Design The planned study is a prospective multicenter, two-arm parallel group, randomized controlled clinical trial comparing selective and stepwise excavation in deciduous molars with deep, active caries lesions without pulpal symptoms. We will recruit 300 children aged between three and nine-years-old with a minimum of one such molar. Patients participating in another study, or those with systemic diseases, disabilities or known allergies to used materials as well patients with teeth expected to exfoliate within the next 18 months will be excluded. After inclusion, sequence generation will be performed. Initial treatment will follow dental routine. During excavation, leathery, moist and reasonably soft dentin will be left in proximity to the pulp followed by adhesive restoration of the cavity. Afterwards, patients’, dentists’ and parents’ subjective assessment of the treatment will be recorded using visual analogue or Likert scales. Re-examination will be performed after six months, and only then teeth will be allocated to one of the two interventions. Selectively excavated teeth will not be treated further, whilst for stepwise caries removal, a second excavation will be performed until only hard dentin remains. Clinical re-evaluations will be performed after 12, 24 and 36 months. Restorations will be reassessed using modified Ryge criteria. Objectively or subjectively required retreatments will determine success and survival. Retreatments will be evaluated both subjectively and regarding generated costs. Discussion Based on the results of the trial, decision-making for treating deep caries lesions in deciduous molars based on multiple criteria should be feasible

Early volumetric changes of hippocampus and medial prefrontal cortex following medial temporal lobe resection

Previous studies have shown that cognitive demands and physical exercise stimulate adult neurogenesis in the dentate gyrus and hippocampus. Recent observations in healthy humans and patients with mild cognitive impairment moreover suggest that training-induced increases in hippocampal volume may be associated with improved memory performance. The corresponding plasticity processes in hippocampal volume may occur on timescales of months to years. For patients with focal lesions in this region, previous functional imaging studies suggest that increased recruitment of the contralateral hippocampus and extratemporal regions may be an important part of the reorganization of episodic memory. However, it is currently unclear whether focal damage to the medial temporal lobe (MTL) induces gray matter (GM) volume changes in the intact contralateral hippocampus and in connected network regions on a shorter timescale. We therefore investigated whether unilateral resection of the MTL, including the hippocampus, induces measurable volumetric changes in the contralateral hippocampus and in the default mode network (DMN). We recruited 31 patients with unilateral left (N = 19) or right (N = 12) hippocampal sclerosis undergoing MTL resection for treatment of drug-resistant epilepsy. Structural MRI was acquired immediately before and 3 months after surgery. Longitudinal voxel-based morphometry (VBM) analysis revealed a significant increase of right hippocampal volume following resection of the left anterior MTL. Furthermore, this patient group showed GM volume increases in the DMN. These results demonstrate significant structural plasticity of the contralateral hippocampus, even in patients with a long-standing unilateral hippocampal dysfunction and structural reorganization processes extending to distant, but functionally connected brain regions

A physical model for the origin of the diffuse cosmic infrared background

We present a physical model for origin of the cosmic diffuse infrared background (CDIRB). By utilizing the observed stellar mass function and its evolution as input to a semi-empirical model of galaxy formation, we isolate the physics driving diffuse IR emission. The model includes contributions from three primary sources of IR emission: steady-state star formation owing to isolated disk galaxies, interaction-driven bursts of star formation owing to close encounters and mergers, and obscured active galactic nuclei (AGN). We find that most of the CDIRB is produced by equal contributions from objects at z=0.5-1 and z>1, as suggested by recent observations. Of those sources, the vast majority of the emission originates in systems with low to moderate IR luminosities (L_{IR}<10^{12} $L_sun); the most luminous objects contribute significant flux only at high-redshifts (z>2). All star formation in ongoing mergers accounts for <10% of the total at all wavelengths and redshifts, while emission directly attributable to the interaction-driven burst itself accounts for <5%. We furthermore find that obscured AGN contribute <1-2% of the CDIRB at all wavelengths and redshifts, with a strong upper limit of less than 4% of the total emission. Finally, since electron-positron pair production interactions with the CDIRB represent the primary source of opacity to very high energy (VHE: E_\gamma > 1 TeV) \gamma-rays, the model provides predictions for the optical depth of the Universe to the most energetic photons. We find that these predictions agree with observations of high-energy cutoffs at TeV energies in nearby blazars, and suggest that while the Universe is extremely optically thick at >10 TeV, the next generation of VHE \gamma-ray telescopes can reasonably expect detections from out to 50-150 Mpc.Comment: 14 pages, 13 figures, submitted to MNRA

Prognostic Factors Affecting Outcome after Allogeneic Transplantation for Hematological Malignancies from Unrelated Donors: Results from a Randomized Trial

Several prognostic factors for the outcome after allogeneic hematopoietic stem-cell transplant (HSCT) from matched unrelated donors have been postulated from registry data; however, data from randomized trials are lacking. We present analyses on the effects of patient-related, donor-related, and treatment-related prognostic factors on acute GVHD (aGVHD), chronic GVHD (cGVHD), relapse, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS) in a randomized, multicenter, open-label, phase III trial comparing standard graft-versus-host-disease (GVHD) prophylaxis with and without pretransplantation ATG-Fresenius (ATG-F) in 201 adult patients receiving myeloablative conditioning before HSCT from HLA-A, HLA-B antigen, HLA-DRB1, HLA-DQB1 allele matched unrelated donors. High-resolution testing (allele) of HLA-A, HLA-B, and HLA-C were obtained after study closure, and the impact of an HLA 10/10 4-digit mismatch on outcome and on the treatment effect of ATG-F versus control investigated. Advanced disease was a negative factor for relapse, DFS, and OS. Donor age ≥40 adversely affected the risk of aGVHD III-IV, extensive cGVHD, and OS. Younger donors are to be preferred in unrelated donor transplantation. Advanced disease patients need special precautions to improve outcome. The degree of mismatch had no major influence on the positive effect of ATG-F on the reduction of aGVHD and cGVHD

Gamma-ray flaring activity from the gravitationally lensed blazar PKS 1830-211 observed by Fermi LAT

The Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope routinely detects the highly dust-absorbed, reddened, and MeV-peaked flat spectrum radio quasar PKS 1830-211 (z=2.507). Its apparent isotropic gamma-ray luminosity (E>100 MeV) averaged over $\sim$ 3 years of observations and peaking on 2010 October 14/15 at 2.9 X 10^{50} erg s^{-1}, makes it among the brightest high-redshift Fermi blazars. No published model with a single lens can account for all of the observed characteristics of this complex system. Based on radio observations, one expects time delayed variability to follow about 25 days after a primary flare, with flux about a factor 1.5 less. Two large gamma-ray flares of PKS 1830-211 have been detected by the LAT in the considered period and no substantial evidence for such a delayed activity was found. This allows us to place a lower limit of about 6 on the gamma rays flux ratio between the two lensed images. Swift XRT observations from a dedicated Target of Opportunity program indicate a hard spectrum and with no significant correlation of X-ray flux with the gamma-ray variability. The spectral energy distribution can be modeled with inverse Compton scattering of thermal photons from the dusty torus. The implications of the LAT data in terms of variability, the lack of evident delayed flare events, and different radio and gamma-ray flux ratios are discussed. Microlensing effects, absorption, size and location of the emitting regions, the complex mass distribution of the system, an energy-dependent inner structure of the source, and flux suppression by the lens galaxy for one image path may be considered as hypotheses for understanding our results.Comment: 14 pages, 6 figures, 2 tables. Accepted by the The Astrophysical Journal. Corresponding authors: S. Ciprini (ASI ASDC & INAF OAR, Rome, Italy), S. Buson (INAF Padova & Univ. of Padova, Padova, Italy), J. Finke (NRL, Washington, DC, USA), F. D'Ammando (INAF IRA, Bologna, Italy

Search for Doubly-Charged Higgs Boson Production at HERA

A search for the single production of doubly-charged Higgs bosons H^{\pm \pm} in ep collisions is presented. The signal is searched for via the Higgs decays into a high mass pair of same charge leptons, one of them being an electron. The analysis uses up to 118 pb^{-1} of ep data collected by the H1 experiment at HERA. No evidence for doubly-charged Higgs production is observed and mass dependent upper limits are derived on the Yukawa couplings h_{el} of the Higgs boson to an electron-lepton pair. Assuming that the doubly-charged Higgs only decays into an electron and a muon via a coupling of electromagnetic strength h_{e \mu} = \sqrt{4 \pi \alpha_{em}} = 0.3, a lower limit of 141 GeV on the H^{\pm\pm} mass is obtained at the 95% confidence level. For a doubly-charged Higgs decaying only into an electron and a tau and a coupling h_{e\tau} = 0.3, masses below 112 GeV are ruled out.Comment: 15 pages, 3 figures, 1 tabl

Multifrequency Studies of the Peculiar Quasar 4C +21.35 During the 2010 Flaring Activity

The discovery of Very High Energy (VHE; E > 100 GeV) γ-ray emission from 4C +21.35 (PKS 1222+216) by MAGIC on 2010 June 17, triggered by the high activity detected by the Fermi Large Area Telescope (LAT) in high energy (HE) γ-rays, poses intriguing questions on the location of the γ-ray emitting region in this flat spectrum radio quasar (FSRQ). We present multifrequency data of 4C +21.35 collected from radio to VHE during 2010 for investigating the properties of this source and discussing a possible emission model. The first hint of detection at VHE was observed by MAGIC on 2010 May 3, soon after a γ-ray flaring activity detected by Fermi-LAT and peaking on April 29. The same emission mechanism may therefore be responsible for both the HE and VHE emission during the 2010 flaring episodes. Two optical peaks were detected on 2010 April 20 and June 30, close in time but not simultaneous with the two γ-ray peaks, while no clear correlation was observed between the X-ray and γ-ray emission. An increasing flux density was observed in radio and mm bands from the beginning of 2009, in accordance with the increasing γ-ray activity observed by Fermi-LAT, and peaking on 2011 January 27 at 230 GHz. We model the spectral energy distributions (SEDs) of 4C +21.35 for the two periods of the VHE detection and a quiescent state with a one-zone model considering the emission from a very compact region outside the broad line region. The three SEDs could be fit with a combination of synchrotron self-Compton and external Compton emission of seed photons from a dust torus, changing only the electron distribution parameters among the SEDs. The fit of the optical/UV part of the spectrum for 2010 April 29 seems to favor an inner disk radius of 3 gravitational radii, a value expected for a maximally prograde rotating Kerr black hole