1,552 research outputs found
Are "EIT Waves" Fast-Mode MHD Waves?
We examine the nature of large-scale, coronal, propagating wave fronts (``EIT
waves'') and find they are incongruous with solutions using fast-mode MHD
plane-wave theory. Specifically, we consider the following properties:
non-dispersive single pulse manifestions, observed velocities below the local
Alfven speed, and different pulses which travel at any number of constant
velocities, rather than at the ``predicted'' fast-mode speed. We discuss the
possibility of a soliton-like explanation for these phenomena, and show how it
is consistent with the above-mentioned aspects.Comment: to be published in the Astrophysical Journa
Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access program
Background: The Italian Renal Cell Cancer Early Access Program was an expanded access program that allowed access to nivolumab, for patients (pts) with metastatic renal cell carcinoma (mRCC) prior to regulatory approval. Methods: Pts with previously treated advanced or mRCC were eligible to receive nivolumab 3 mg/kg every 2 weeks. Pts included in the analysis had received ≥1 dose of nivolumab and were monitored for drug-related adverse events (drAEs) using CTCAE v.4.0. Immune-related (ir) AEs were defined as AEs displaying a certain, likely or possible correlation with immunotherapy (cutaneous, endocrine, hepatic, gastro-intestinal and pulmonary). The association between overall survival (OS) and irAEs was assessed, and associations between variables were evaluated with a logistic regression model. Results: A total of 389 pts were enrolled between July 2015 and April 2016. Overall, the objective response rate was 23.1%. At a median follow-up of 12 months, the median progression-free survival was 4.5 months (95% CI 3.7-6.2) and the 12-month overall survival rate was 63%. Any grade and grade 3-4 drAEs were reported in 124 (32%) and 27 (7%) of pts, respectively, and there were no treatment-related deaths. Any grade irAEs occurred in 76 (20%) of patients, 8% cutaneous, 4% endocrine, 2% hepatic, 5% gastro-intestinal and 1% pulmonary. Of the 22 drAEs inducing treatment discontinuation, 10 (45%) were irAEs. Pts with drAEs had a significantly longer survival than those without drAEs (median OS 22.5 versus 16.4 months, p = 0.01). Pts with irAEs versus without irAEs had a more significant survival benefit (median OS not reached versus 16.8 months, p = 0.002), confirmed at the landmark analysis at 6 weeks. The occurrence of irAEs displayed a strong association with OS in univariable (HR 0.48, p = 0.003) and multivariable (HR 0.57, p = 0.02) analysis. Conclusions: The appearance of irAEs strongly correlates with survival benefit in a real-life population of mRCC pts treated with nivolumab
Multiscale Bone Remodelling with Spatial P Systems
Many biological phenomena are inherently multiscale, i.e. they are
characterized by interactions involving different spatial and temporal scales
simultaneously. Though several approaches have been proposed to provide
"multilayer" models, only Complex Automata, derived from Cellular Automata,
naturally embed spatial information and realize multiscaling with
well-established inter-scale integration schemas. Spatial P systems, a variant
of P systems in which a more geometric concept of space has been added, have
several characteristics in common with Cellular Automata. We propose such a
formalism as a basis to rephrase the Complex Automata multiscaling approach
and, in this perspective, provide a 2-scale Spatial P system describing bone
remodelling. The proposed model not only results to be highly faithful and
expressive in a multiscale scenario, but also highlights the need of a deep and
formal expressiveness study involving Complex Automata, Spatial P systems and
other promising multiscale approaches, such as our shape-based one already
resulted to be highly faithful.Comment: In Proceedings MeCBIC 2010, arXiv:1011.005
Self-consistent description of nuclear compressional modes
Isoscalar monopole and dipole compressional modes are computed for a variety
of closed-shell nuclei in a relativistic random-phase approximation to three
different parametrizations of the Walecka model with scalar self-interactions.
Particular emphasis is placed on the role of self-consistency which by itself,
and with little else, guarantees the decoupling of the spurious
isoscalar-dipole strength from the physical response and the conservation of
the vector current. A powerful new relation is introduced to quantify the
violation of the vector current in terms of various ground-state form-factors.
For the isoscalar-dipole mode two distinct regions are clearly identified: (i)
a high-energy component that is sensitive to the size of the nucleus and scales
with the compressibility of the model and (ii) a low-energy component that is
insensitivity to the nuclear compressibility. A fairly good description of both
compressional modes is obtained by using a ``soft'' parametrization having a
compression modulus of K=224 MeV.Comment: 28 pages and 10 figures; submitted to PR
Isoscalar dipole coherence at low energies and forbidden E1 strength
In 16O and 40Ca an isoscalar, low-energy dipole transition (IS-LED)
exhausting approximately 4% of the isoscalar dipole (ISD) energy-weighted sum
rule is experimentally known, but conspicuously absent from recent theoretical
investigations of ISD strength. The IS-LED mode coincides with the so-called
isospin-forbidden E1 transition. We report that for N=Z nuclei up to 100Sn the
fully self-consistent Random-Phase-Approximation with finite-range forces,
phenomenological and realistic, yields a collective IS-LED mode, typically
overestimating its excitation energy, but correctly describing its IS strength
and electroexcitation form factor. The presence of E1 strength is solely due to
the Coulomb interaction between the protons and the resulting isospin-symmetry
breaking. The smallness of its value is related to the form of the transition
density, due to translational invariance. The calculated values of E1 and ISD
strength carried by the IS-LED depend on the effective interaction used.
Attention is drawn to the possibility that in N-not-equal-Z nuclei this
distinct mode of IS surface vibration can develop as such or mix strongly with
skin modes and thus influence the pygmy dipole strength as well as the ISD
strength function. In general, theoretical models currently in use may be unfit
to predict its precise position and strength, if at all its existence.Comment: 9 pages, 6 figures, EPJA submitte
Idiopathic epilepsies with seizures precipitated by fever and SCN1A abnormalities.
Epilepsia. 2007 Sep;48(9):1678-85. Epub 2007 Jun 11.
Idiopathic epilepsies with seizures precipitated by fever and SCN1A abnormalities.
Marini C, Mei D, Temudo T, Ferrari AR, Buti D, Dravet C, Dias AI, Moreira A, Calado E, Seri S, Neville B, Narbona J, Reid E, Michelucci R, Sicca F, Cross HJ, Guerrini R.
SourceEpilepsy, Neurophysiology and Neurogenetic Unit, Institute of Child Neurology and Psychiatry, IRCCS Stella Maris Foundation, Calambrone, Pisa, Italy.
Abstract
PURPOSE: SCN1A is the most clinically relevant epilepsy gene, most mutations lead to severe myoclonic epilepsy of infancy (SMEI) and generalized epilepsy with febrile seizures plus (GEFS+). We studied 132 patients with epilepsy syndromes with seizures precipitated by fever, and performed phenotype-genotype correlations with SCN1A alterations.
METHODS: We included patients with SMEI including borderline SMEI (SMEB), GEFS+, febrile seizures (FS), or other seizure types precipitated by fever. We performed a clinical and genetic study focusing on SCN1A, using dHPLC, gene sequencing, and MLPA to detect genomic deletions/duplications on SMEI/SMEB patients.
RESULTS: We classified patients as: SMEI/SMEB = 55; GEFS+= 26; and other phenotypes = 51. SCN1A analysis by dHPLC/sequencing revealed 40 mutations in 37 SMEI/SMEB (67%) and 3 GEFS+ (11.5%) probands. MLPA showed genomic deletions in 2 of 18 SMEI/SMEB. Most mutations were de novo (82%). SMEB patients carrying mutations (8) were more likely to have missense mutations (62.5%), conversely SMEI patients (31) had more truncating, splice site or genomic alterations (64.5%). SMEI/SMEB with truncating, splice site or genomic alterations had a significantly earlier age of onset of FS compared to those with missense mutations and without mutations (p = 0.00007, ANOVA test). None of the remaining patients with seizures precipitated by fever carried SCN1A mutations.
CONCLUSION: We obtained a frequency of 71%SCN1A abnormalities in SMEI/SMEB and of 11.5% in GEFS+ probands. MLPA complements DNA sequencing of SCN1A increasing the mutation detection rate. SMEI/SMEB with truncating, splice site or genomic alterations had a significantly earlier age of onset of FS. This study confirms the high sensitivity of SCN1A for SMEI/SMEB phenotypes
Worker remittances and the global preconditions of ‘smart development’
With the growing environmental crisis affecting our globe, ideas to weigh economic or social progress by the ‘energy input’ necessary to achieve it are increasingly gaining acceptance. This question is intriguing and is being dealt with by a growing number of studies, focusing on the environmental price of human progress. Even more intriguing, however, is the question of which factors of social organization contribute to a responsible use of the resources of our planet to achieve a given social result (‘smart development’). In this essay, we present the first systematic study on how migration – or rather, more concretely, received worker remittances per GDP – helps the nations of our globe to enjoy social and economic progress at a relatively small environmental price. We look at the effects of migration on the balance sheets of societal accounting, based on the ‘ecological price’ of the combined performance of democracy, economic growth, gender equality, human development, research and development, and social cohesion. Feminism in power, economic freedom, population density, the UNDP education index as well as the receipt of worker remittances all significantly contribute towards a ‘smart overall development’, while high military expenditures and a high world economic openness are a bottleneck for ‘smart overall development’
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The Dampening Effect of Iceberg Orders on Small Traders' Welfare
Iceberg orders, which allow traders to hide a portion of their order size, have become prevalent in many electronic limit order markets. This paper investigates, via a real options analysis, whether small traders, who have no use for submitting iceberg orders, are better off submitting their orders to fully transparent markets which have low depth, or to more liquid markets which do permit the placement of iceberg orders by large traders. Surprisingly, we find that in the context of our model, small traders are better off submitting to fully transparent markets in spite of them being less liquid
Effectiveness and safety of sofosbuvir‐based regimens plus an NS5A inhibitor for patients with HCV genotype 3 infection and cirrhosis: results of a multicenter real‐life cohort
[Abstract] Patients with HCV genotype 3 (GT3) infection and cirrhosis are currently the most difficult to cure. We report our experience with sofosbuvir+daclatasvir (SOF+DCV) or sofosbuvir/ledipasvir (SOF/LDV), with or without ribavirin (RBV) in clinical practice in this population. This was a multicenter observational study including cirrhotic patients infected by HCV GT3, treated with sofosbuvir plus an NS5A inhibitor (May 2014‐October 2015). In total, 208 patients were included: 98 (47%) treatment‐experienced, 42 (20%) decompensated and 55 (27%) MELD score >10. In 131 (63%), treatment was SOF+DCV and in 77 (37%), SOF/LDV. Overall, 86% received RBV. RBV addition and extension to 24 weeks was higher in the SOF/LDV group (95% vs 80%, P=.002 and 83% vs 72%, P=.044, respectively). A higher percentage of decompensated patients were treated with DCV than LDV (25% vs 12%, P=.013). Overall, SVR12 was 93.8% (195/208): 94% with SOF+DCV and 93.5% with SOF/LDV. SVR12 was achieved in 90.5% of decompensated patients. Eleven treatment failures: 10 relapses and one breakthrough. RBV addition did not improve SVR (RR: 1.08; P=.919). The single factor associated with failure to achieve SVR was platelet count <75×10E9/mL (RR: 3.50, P=.019). In patients with MELD <10, type of NS5A inhibitor did not impact on SVR12 (94% vs 97%; adjusted RR: 0.49). Thirteen patients (6.3%) had serious adverse events, including three deaths (1.4%) and one therapy discontinuation (0.5%), higher in decompensated patients (16.7% vs 3.6%, P<.006). In patients with GT3 infection and cirrhosis, SVR12 rates were high with both SOF+DCV and SOF/LDV, with few serious adverse events
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