115 research outputs found
The role of the CNTNAP2 gene in the development of autism spectrum disorder
Autism spectrum disorder (ASD) is a neurodevelopmental disorder in which genetic and environmental factors interact in its development. Research suggests that the contactin associated protein 2 (CNTNAP2) gene may play a role in ASD pathophysiology, yet more studies involving human participants and animal models of autism are needed. One such model may be the use of prenatal valproic acid (VPA) model to induce autism-like behaviors in offspring rats. The aim of this study was twofold: (1) to examine the association of the CNTNAP2 gene rs2710102 variant with ASD in children; and (2) to examine the effect of prenatal exposure to VPA on Cntnap2 gene expression in the rat brain. The study included 167 children of European ancestryâ81 diagnosed with ASD (20 girls, 61 boys; age 4.9 ± 1.4 years) and 86 controls (44 girls, 42 boys; 5.1 ± 1.2 years). In vivo experiments were conducted in 80 rats (40 with the VPA model of autism), with Cntnap2 gene expression analysis in the amygdala, hippocampus, prefrontal cortex, and cerebellum. Results demonstrated that the frequency of the CNTNAP2 gene rs2710102 GG genotype was significantly higher in children with ASD when compared with controls (33.3 vs 19.8%; OR=2.03, 95%CI [1.004, 4.102], p = 0.035), although, potentially due to bias in cohort selection, in the ASD children this polymorphism did not meet Hardy-Weinberg expectations (Ï2 =5.40, p = 0.02). In addition, Cntnap2 gene expression was significantly lower (p < 0.01) in the amygdala and hippocampus of VPA rats when compared with controls, regardless of sex. These results support previous research and provide evidence for the CNTNAP2 gene as a risk factor for ASD
Ibrutinib in the Treatment of Refractory Chronic Lymphocytic Leukemia
Background & Aims. This paper presents the results of the observational study of ibrutinib in patients with chronic lymphocytic leukemia (CLL), conducted in SP Botkin Municipal Clinical Hospital. The main objective was the analysis of complications of ibrutinib and identification of factors, influencing the dosage regimen; the secondary objective was the estimation of the total response to treatment, event-free and overall survival.
Materials & Methods. The study included 96 patients with CLL with indications for ibrutinib therapy. The median age was 64,9 years (range 32â91 years), the study population consisted of 69 (72 %) men and 27 (28 %) women. The condition of 25 (26 %) patients according to the ECOG scale was of > 3 points. The disease of stage C were diagnosed in 36 (37 %) patients . Deletion of 17p/TP53 mutations were detected in 29 (33 %) of 87 patients. Seventy patients had refractory CLL. The median of the number of the lines of the previous therapy was 3 (range 1â9). Adverse events were assessed in accordance with the CTCAE criteria, version 4.0; the bleeding severity was evaluated using ITP-specific bleeding score; hematological complications were classified according to the recommendations of IWCLL-2008.
Results. Ibrutinib was administered at a dosage of 420 mg per day daily until progression or intolerable toxicity. The median duration of ibrutinib therapy was 10.3 months. Ibrutinib was shown to have moderate toxicity, mostly of grade I or II. The bleeding was the most frequent complication. Of the hematological complications, thrombocytopenia was the most common (35 %); neutropenia grade III) developed in 26 % of patients. The treatment response was assessed in 92 patients. The overall response to treatment was 89 %. Complete remission, partial remission and partial remission with lymphocytosis were achieved in 4 (4 %), 57 (62 %), and 21 (23 %) patients, respectively. The event-free survival and overall survival by the month 10 was 90 % and 91 %, respectively. For this observation period, ECOG status and the number of the lines of therapy prior to ibrutinib had the prognostic value.
Conclusion. Ibrutinib was shown to have high efficiency in relapsed/refractory forms of CLL. The nature of the ibrutinib toxicity is fundamentally different from that of the conventional chemotherapy. The frequency of ibrutinib therapy complications and patientsâ non-compliance depends on the intensity of the previous treatment of CLL. Despite a short observation period, it can be concluded that ibrutinib had the greatest impact on the patientâs quality of life when administered for the first relapse. The low toxicity of ibrutinib is likely to allow the combination with other antitumor agents
The HITRAN2020 molecular spectroscopic database
The HITRAN database is a compilation of molecular spectroscopic parameters. It was established in the early 1970s and is used by various computer codes to predict and simulate the transmission and emission of light in gaseous media (with an emphasis on terrestrial and planetary atmospheres). The HITRAN compilation is composed of five major components: the line-by-line spectroscopic parameters required for high-resolution radiative-transfer codes, experimental infrared absorption cross-sections (for molecules where it is not yet feasible for representation in a line-by-line form), collision-induced absorption data, aerosol indices of refraction, and general tables (including partition sums) that apply globally to the data. This paper describes the contents of the 2020 quadrennial edition of HITRAN. The HITRAN2020 edition takes advantage of recent experimental and theoretical data that were meticulously validated, in particular, against laboratory and atmospheric spectra. The new edition replaces the previous HITRAN edition of 2016 (including its updates during the intervening years). All five components of HITRAN have undergone major updates. In particular, the extent of the updates in the HITRAN2020 edition range from updating a few lines of specific molecules to complete replacements of the lists, and also the introduction of additional isotopologues and new (to HITRAN) molecules: SO, CH3F, GeH4, CS2, CH3I and NF3. Many new vibrational bands were added, extending the spectral coverage and completeness of the line lists. Also, the accuracy of the parameters for major atmospheric absorbers has been increased substantially, often featuring sub-percent uncertainties. Broadening parameters associated with the ambient pressure of water vapor were introduced to HITRAN for the first time and are now available for several molecules. The HITRAN2020 edition continues to take advantage of the relational structure and efficient interface available at www.hitran.org and the HITRAN Application Programming Interface (HAPI). The functionality of both tools has been extended for the new edition
Updated measurements of exclusive J/Ï and Ï(2S) production cross-sections in pp collisions at âs = 7 TeV
The differential cross-section as a function of rapidity has been measured for the exclusive production of J/Ï and Ï(2S) mesons in protonâproton collisions at âs = 7 TeV, using data collected by the LHCb experiment, corresponding to an integrated luminosity of 930 pbâ1. The cross-sections times branching fractions to two muons having pseudorapidities between 2.0 and 4.5 are measured to be where the first uncertainty is statistical and the second is systematic. The measurements agree with next-to-leading order QCD predictions as well as with models that include saturation effects
Observation of Two New Excited Îb0 States Decaying to Îb0 K-Ï+
Two narrow resonant states are observed in the Îb0K-Ï+ mass spectrum using a data sample of proton-proton collisions at a center-of-mass energy of 13 TeV, collected by the LHCb experiment and corresponding to an integrated luminosity of 6 fb-1. The minimal quark content of the Îb0K-Ï+ system indicates that these are excited Îb0 baryons. The masses of the Îb(6327)0 and Îb(6333)0 states are m[Îb(6327)0]=6327.28-0.21+0.23±0.12±0.24 and m[Îb(6333)0]=6332.69-0.18+0.17±0.03±0.22 MeV, respectively, with a mass splitting of Îm=5.41-0.27+0.26±0.12 MeV, where the uncertainties are statistical, systematic, and due to the Îb0 mass measurement. The measured natural widths of these states are consistent with zero, with upper limits of Î[Îb(6327)0]<2.20(2.56) and Î[Îb(6333)0]<1.60(1.92) MeV at a 90% (95%) credibility level. The significance of the two-peak hypothesis is larger than nine (five) Gaussian standard deviations compared to the no-peak (one-peak) hypothesis. The masses, widths, and resonant structure of the new states are in good agreement with the expectations for a doublet of 1D Îb0 resonances
Studies of beauty baryon decays to D0phâ and Î+châ final states
Decays of beauty baryons to the D0phâ and Î+châ final states (where h indicates a pion or a kaon) are studied using a data sample of pp collisions, corresponding to an integrated luminosity of 1.0ââfbâ1, collected by the LHCb detector. The Cabibbo-suppressed decays Î0bâD0pKâ and Î0bâÎ+cKâ are observed, and their branching fractions are measured with respect to the decays Î0bâD0pÏâ and Î0bâÎ+cÏâ. In addition, the first observation is reported of the decay of the neutral beauty-strange baryon Î0b to the D0pKâ final state, and a measurement of the Î0b mass is performed. Evidence of the Î0bâÎ+cKâ decay is also reported
Measurement of the CKM angle using with decays
A model-dependent amplitude analysis of the decay is performed using proton-proton collision data
corresponding to an integrated luminosity of 3.0fb, recorded at
and by the LHCb experiment. The CP violation observables
and , sensitive to the CKM angle , are measured to
be \begin{eqnarray*} x_- &=& -0.15 \pm 0.14 \pm 0.03 \pm 0.01, y_- &=& 0.25 \pm
0.15 \pm 0.06 \pm 0.01, x_+ &=& 0.05 \pm 0.24 \pm 0.04 \pm 0.01, y_+ &=&
-0.65^{+0.24}_{-0.23} \pm 0.08 \pm 0.01, \end{eqnarray*} where the first
uncertainties are statistical, the second systematic and the third arise from
the uncertainty on the amplitude model. These
are the most precise measurements of these observables. They correspond to
and , where is
the magnitude of the ratio of the suppressed and favoured decay amplitudes, in a mass region of around the
mass and for an absolute value of the cosine of the decay
angle larger than .Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2016-007.htm
Search for the and decays with the LHCb detector
A search is performed for the as yet unobserved baryonic and
decays with 3 of proton-proton collision data recorded by the LHCb
experiment. The decay is used as a
normalisation channel. No significant signal is observed for the decay. An upper limit is found on the
branching fraction of } at 90\% confidence level. Evidence is seen for
the presence of the decay at the level of
significance, with a branching fraction }.Comment: 22 pages, 6 figures. v2 is published version (very minor revisions
Search for dark photons produced in 13 TeV collisions
Searches are performed for both promptlike and long-lived dark photons,
A
0
, produced in proton-proton
collisions at a center-of-mass energy of 13 TeV, using
A
0
â
Ό
ĂŸ
Ό
â
decays and a data sample corresponding
to an integrated luminosity of
1
.
6
fb
â
1
collected with the LHCb detector. The promptlike
A
0
search covers
the mass range from near the dimuon threshold up to 70 GeV, while the long-lived
A
0
search is restricted to
the low-mass region
214
<m
Ă°
A
0
Ă
<
350
MeV. No evidence for a signal is found, and 90% confidence
level exclusion limits are placed on the
Îł
â
A
0
kinetic-mixing strength. The constraints placed on promptlike
dark photons are the most stringent to date for the mass range
10
.
6
<m
Ă°
A
0
Ă
<
70
GeV, and are
comparable to the best existing limits for
m
Ă°
A
0
Ă
<
0
.
5
GeV. The search for long-lived dark photons is the
first to achieve sensitivity using a displaced-vertex signature
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