2,195 research outputs found
Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer
Background:We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose.Methods:Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using 99 Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry.Results:Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1±8.9 vs 31.3±12.9 mg (P=0.01). Both, AUC 24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P<0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P=0.03) in tumour specimens.Conclusion:Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies.Fil: Sarduy, M. R.. Medical-surgical Research Center; CubaFil: GarcĂa, I.. Centro de IngenierĂa GenĂ©tica y BiotecnologĂa; CubaFil: Coca, M. A.. Clinical Investigation Center; CubaFil: Perera, A.. Clinical Investigation Center; CubaFil: Torres, L. A.. Clinical Investigation Center; CubaFil: Valenzuela, C. M.. Centro de IngenierĂa GenĂ©tica y BiotecnologĂa; CubaFil: BaladrĂłn, I.. Centro de IngenierĂa GenĂ©tica y BiotecnologĂa; CubaFil: Solares, M.. Hospital Materno RamĂłn GonzĂĄlez Coro; CubaFil: Reyes, V.. Center For Genetic Engineering And Biotechnology Havana; CubaFil: HernĂĄndez, I.. Isotope Center; CubaFil: Perera, Y.. Centro de IngenierĂa GenĂ©tica y BiotecnologĂa; CubaFil: MartĂnez, Y. M.. Medical-surgical Research Center; CubaFil: Molina, L.. Medical-surgical Research Center; CubaFil: GonzĂĄlez, Y. M.. Medical-surgical Research Center; CubaFil: AncĂzar, J. A.. Centro de IngenierĂa GenĂ©tica y BiotecnologĂa; CubaFil: Prats, A.. Clinical Investigation Center; CubaFil: GonzĂĄlez, L.. Centro de IngenierĂa GenĂ©tica y BiotecnologĂa; CubaFil: CasacĂł, C. A.. Clinical Investigation Center; CubaFil: Acevedo, B. E.. Centro de IngenierĂa GenĂ©tica y BiotecnologĂa; CubaFil: LĂłpez Saura, P. A.. Centro de IngenierĂa GenĂ©tica y BiotecnologĂa; CubaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes; ArgentinaFil: GĂłmez, R.. Elea Laboratories; ArgentinaFil: Perea RodrĂguez, S. E.. Center For Genetic Engineering And Biotechnology Havana; Cuba. Centro de IngenierĂa GenĂ©tica y BiotecnologĂa; Cub
Relapse, cognitive reserve, and their relationship with cognition in first episode schizophrenia: a 3-year follow-up study
Schizophrenia is frequently characterized by the presence of multiple relapses. Cognitive impairments are core features of schizophrenia. Cognitive reserve (CR) is the ability of the brain to compensate for damage caused by pathologies such as psychotic illness. As cognition is related to CR, the study of the relationship between relapse, cognition and CR may broaden our understanding of the course of the disease. We aimed to determine whether relapse was associated with cognitive impairment, controlling for the effects of CR. Ninety-nine patients with a remitted first episode of schizophrenia or schizophreniform disorder were administered a set of neuropsychological tests to assess premorbid IQ, attention, processing speed, working memory, verbal and visual memory, executive functions and social cognition. They were followed up for 3 years (n=53) or until they relapsed (n=46). Personal and familial CR was estimated from a principal component analysis of the premorbid information gathered. Linear mixed-effects models were applied to analyse the effect of time and relapse on cognitive function, with CR as covariate. Patients who relapsed and had higher personal CR showed less deterioration in attention, whereas those with higher CR (personal and familial CR) who did not relapse showed better performance in processing speed and visual memory. Taken together, CR seems to ameliorate the negative effects of relapse on attention performance and shows a positive effect on processing speed and visual memory in those patients who did not relapse. Our results add evidence for the protective effect of CR over the course of the illness
Calibration of the Logarithmic-Periodic Dipole Antenna (LPDA) Radio Stations at the Pierre Auger Observatory using an Octocopter
An in-situ calibration of a logarithmic periodic dipole antenna with a
frequency coverage of 30 MHz to 80 MHz is performed. Such antennas are part of
a radio station system used for detection of cosmic ray induced air showers at
the Engineering Radio Array of the Pierre Auger Observatory, the so-called
Auger Engineering Radio Array (AERA). The directional and frequency
characteristics of the broadband antenna are investigated using a remotely
piloted aircraft (RPA) carrying a small transmitting antenna. The antenna
sensitivity is described by the vector effective length relating the measured
voltage with the electric-field components perpendicular to the incoming signal
direction. The horizontal and meridional components are determined with an
overall uncertainty of 7.4^{+0.9}_{-0.3} % and 10.3^{+2.8}_{-1.7} %
respectively. The measurement is used to correct a simulated response of the
frequency and directional response of the antenna. In addition, the influence
of the ground conductivity and permittivity on the antenna response is
simulated. Both have a negligible influence given the ground conditions
measured at the detector site. The overall uncertainties of the vector
effective length components result in an uncertainty of 8.8^{+2.1}_{-1.3} % in
the square root of the energy fluence for incoming signal directions with
zenith angles smaller than 60{\deg}.Comment: Published version. Updated online abstract only. Manuscript is
unchanged with respect to v2. 39 pages, 15 figures, 2 table
Multi-resolution anisotropy studies of ultrahigh-energy cosmic rays detected at the Pierre Auger Observatory
We report a multi-resolution search for anisotropies in the arrival
directions of cosmic rays detected at the Pierre Auger Observatory with local
zenith angles up to and energies in excess of 4 EeV ( eV). This search is conducted by measuring the angular power spectrum
and performing a needlet wavelet analysis in two independent energy ranges.
Both analyses are complementary since the angular power spectrum achieves a
better performance in identifying large-scale patterns while the needlet
wavelet analysis, considering the parameters used in this work, presents a
higher efficiency in detecting smaller-scale anisotropies, potentially
providing directional information on any observed anisotropies. No deviation
from isotropy is observed on any angular scale in the energy range between 4
and 8 EeV. Above 8 EeV, an indication for a dipole moment is captured; while no
other deviation from isotropy is observed for moments beyond the dipole one.
The corresponding -values obtained after accounting for searches blindly
performed at several angular scales, are in the case of
the angular power spectrum, and in the case of the needlet
analysis. While these results are consistent with previous reports making use
of the same data set, they provide extensions of the previous works through the
thorough scans of the angular scales.Comment: Published version. Added journal reference and DOI. Added Report
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Ultrahigh-energy neutrino follow-up of Gravitational Wave events GW150914 and GW151226 with the Pierre Auger Observatory
On September 14, 2015 the Advanced LIGO detectors observed their first
gravitational-wave (GW) transient GW150914. This was followed by a second GW
event observed on December 26, 2015. Both events were inferred to have arisen
from the merger of black holes in binary systems. Such a system may emit
neutrinos if there are magnetic fields and disk debris remaining from the
formation of the two black holes. With the surface detector array of the Pierre
Auger Observatory we can search for neutrinos with energy above 100 PeV from
point-like sources across the sky with equatorial declination from about -65
deg. to +60 deg., and in particular from a fraction of the 90% confidence-level
(CL) inferred positions in the sky of GW150914 and GW151226. A targeted search
for highly-inclined extensive air showers, produced either by interactions of
downward-going neutrinos of all flavors in the atmosphere or by the decays of
tau leptons originating from tau-neutrino interactions in the Earth's crust
(Earth-skimming neutrinos), yielded no candidates in the Auger data collected
within s around or 1 day after the coordinated universal time (UTC)
of GW150914 and GW151226, as well as in the same search periods relative to the
UTC time of the GW candidate event LVT151012. From the non-observation we
constrain the amount of energy radiated in ultrahigh-energy neutrinos from such
remarkable events.Comment: Published version. Added journal reference and DOI. Added Report
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Azimuthal asymmetry in the risetime of the surface detector signals of the Pierre Auger Observatory
The azimuthal asymmetry in the risetime of signals in Auger surface detector
stations is a source of information on shower development. The azimuthal
asymmetry is due to a combination of the longitudinal evolution of the shower
and geometrical effects related to the angles of incidence of the particles
into the detectors. The magnitude of the effect depends upon the zenith angle
and state of development of the shower and thus provides a novel observable,
, sensitive to the mass composition of cosmic rays
above eV. By comparing measurements with predictions from
shower simulations, we find for both of our adopted models of hadronic physics
(QGSJETII-04 and EPOS-LHC) an indication that the mean cosmic-ray mass
increases slowly with energy, as has been inferred from other studies. However,
the mass estimates are dependent on the shower model and on the range of
distance from the shower core selected. Thus the method has uncovered further
deficiencies in our understanding of shower modelling that must be resolved
before the mass composition can be inferred from .Comment: Replaced with published version. Added journal reference and DO
Supporting Spartina: Interdisciplinary Perspective Shows Spartina As A Distinct Solid Genus
In 2014, a DNA-based phylogenetic study confirming the paraphyly of the grass subtribe Sporobolinae proposed the creation of a large monophyletic genus Sporobolus, including (among others) species previously included in the genera Spartina, Calamovilfa, and Sporobolus. Spartina species have contributed substantially (and continue contributing) to our knowledge in multiple disciplines, including ecology, evolutionary biology, molecular biology, biogeography, experimental ecology, biological invasions, environmental management, restoration ecology, history, economics, and sociology. There is no rationale so compelling to subsume the name Spartina as a subgenus that could rival the striking, global iconic history and use of the name Spartina for over 200 yr. We do not agree with the subjective arguments underlying the proposal to change Spartina to Sporobolus. We understand the importance of both the objective phylogenetic insights and of the subjective formalized nomenclature and hope that by opening this debate we will encourage positive feedback that will strengthen taxonomic decisions with an interdisciplinary perspective. We consider that the strongly distinct, monophyletic clade Spartina should simply and efficiently be treated as the genus Spartina
Evidence for a mixed mass composition at the `ankle' in the cosmic-ray spectrum
We report a first measurement for ultra-high energy cosmic rays of the
correlation between the depth of shower maximum and the signal in the water
Cherenkov stations of air-showers registered simultaneously by the fluorescence
and the surface detectors of the Pierre Auger Observatory. Such a correlation
measurement is a unique feature of a hybrid air-shower observatory with
sensitivity to both the electromagnetic and muonic components. It allows an
accurate determination of the spread of primary masses in the cosmic-ray flux.
Up till now, constraints on the spread of primary masses have been dominated by
systematic uncertainties. The present correlation measurement is not affected
by systematics in the measurement of the depth of shower maximum or the signal
in the water Cherenkov stations. The analysis relies on general characteristics
of air showers and is thus robust also with respect to uncertainties in
hadronic event generators. The observed correlation in the energy range around
the `ankle' at differs significantly from
expectations for pure primary cosmic-ray compositions. A light composition made
up of proton and helium only is equally inconsistent with observations. The
data are explained well by a mixed composition including nuclei with mass . Scenarios such as the proton dip model, with almost pure compositions, are
thus disfavoured as the sole explanation of the ultrahigh-energy cosmic-ray
flux at Earth.Comment: Published version. Added journal reference and DOI. Added Report
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