76 research outputs found
Targeted resequencing identifies genes with recurrent variation in cerebral palsy
A growing body of evidence points to a considerable and heterogeneous genetic aetiology of cerebral palsy (CP). To identify recurrently variant CP genes, we designed a custom gene panel of 112 candidate genes. We tested 366 clinically unselected singleton cases with CP, including 271 cases not previously examined using next-generation sequencing technologies. Overall, 5.2% of the naĂŻve cases (14/271) harboured a genetic variant of clinical significance in a known disease gene, with a further 4.8% of individuals (13/271) having a variant in a candidate gene classified as intolerant to variation. In the aggregate cohort of individuals from this study and our previous genomic investigations, six recurrently hit genes contributed at least 4% of disease burden to CP: COL4A1, TUBA1A, AGAP1, L1CAM, MAOB and KIF1A. Significance of Rare VAriants (SORVA) burden analysis identified four genes with a genome-wide significant burden of variants, AGAP1, ERLIN1, ZDHHC9 and PROC, of which we functionally assessed AGAP1 using a zebrafish model. Our investigations reinforce that CP is a heterogeneous neurodevelopmental disorder with known as well as novel genetic determinants.C. L. van Eyk, M. A. Corbett, M. S. B. Frank, D. L. Webber, M. Newman, J. G. Berry, K. Harper, B. P. Haines, G. McMichael, J. A. Woenig, A. H. MacLennan, and J. Gec
Human Rights and the Pink Tide in Latin America : Which Rights Matter?
Latin America witnessed the election of ânew Leftâ governments in the early 21 st century that, in different ways, sought to open a debate about alternatives to paradigms of neoliberal development. What has this meant for the way that human rights are understood and for patterns of human rights compliance? Using qualitative and quantitative evidence, this article discusses how human rights are imagined and the compliance records of new Left governments through the lens of the three âgenerationsâ of human rights â political and civil, social and economic, and cultural and environmental rights. The authors draw in particular on evidence from Andean countries and the Southern Cone. While basic civil and individual liberties are still far from guaranteed, especially in the Andean region, new Left countries show better overall performances in relation to socio-economic rights compared to the past and to other Latin American countries. All new Left governments also demonstrate an increasing interest in âthird generationâ (cultural and environmental) rights, though this is especially marked in the Andean Left. The authors discuss the tensions around interpretations and categories of human rights, reflect on the stagnation of first generation rights and note the difficulties associated with translating second and third generation rights into policy
Measurement of the branching fraction
The branching fraction is measured in a data sample
corresponding to 0.41 of integrated luminosity collected with the LHCb
detector at the LHC. This channel is sensitive to the penguin contributions
affecting the sin2 measurement from The
time-integrated branching fraction is measured to be . This is the most precise measurement to
date
Measurement of the CP-violating phase \phi s in Bs->J/\psi\pi+\pi- decays
Measurement of the mixing-induced CP-violating phase phi_s in Bs decays is of
prime importance in probing new physics. Here 7421 +/- 105 signal events from
the dominantly CP-odd final state J/\psi pi+ pi- are selected in 1/fb of pp
collision data collected at sqrt{s} = 7 TeV with the LHCb detector. A
time-dependent fit to the data yields a value of
phi_s=-0.019^{+0.173+0.004}_{-0.174-0.003} rad, consistent with the Standard
Model expectation. No evidence of direct CP violation is found.Comment: 15 pages, 10 figures; minor revisions on May 23, 201
Absolute luminosity measurements with the LHCb detector at the LHC
Absolute luminosity measurements are of general interest for colliding-beam
experiments at storage rings. These measurements are necessary to determine the
absolute cross-sections of reaction processes and are valuable to quantify the
performance of the accelerator. Using data taken in 2010, LHCb has applied two
methods to determine the absolute scale of its luminosity measurements for
proton-proton collisions at the LHC with a centre-of-mass energy of 7 TeV. In
addition to the classic "van der Meer scan" method a novel technique has been
developed which makes use of direct imaging of the individual beams using
beam-gas and beam-beam interactions. This beam imaging method is made possible
by the high resolution of the LHCb vertex detector and the close proximity of
the detector to the beams, and allows beam parameters such as positions, angles
and widths to be determined. The results of the two methods have comparable
precision and are in good agreement. Combining the two methods, an overall
precision of 3.5% in the absolute luminosity determination is reached. The
techniques used to transport the absolute luminosity calibration to the full
2010 data-taking period are presented.Comment: 48 pages, 19 figures. Results unchanged, improved clarity of Table 6,
9 and 10 and corresponding explanation in the tex
Measurement of the ratio of branching fractions BR(B0 -> K*0 gamma)/BR(Bs0 -> phi gamma) and the direct CP asymmetry in B0 -> K*0 gamma
The ratio of branching fractions of the radiative B decays B0 -> K*0 gamma
and Bs0 phi gamma has been measured using an integrated luminosity of 1.0 fb-1
of pp collision data collected by the LHCb experiment at a centre-of-mass
energy of sqrt(s)=7 TeV. The value obtained is BR(B0 -> K*0 gamma)/BR(Bs0 ->
phi gamma) = 1.23 +/- 0.06(stat.) +/- 0.04(syst.) +/- 0.10(fs/fd), where the
first uncertainty is statistical, the second is the experimental systematic
uncertainty and the third is associated with the ratio of fragmentation
fractions fs/fd. Using the world average value for BR(B0 -> K*0 gamma), the
branching fraction BR(Bs0 -> phi gamma) is measured to be (3.5 +/- 0.4) x
10^{-5}.
The direct CP asymmetry in B0 -> K*0 gamma decays has also been measured with
the same data and found to be A(CP)(B0 -> K*0 gamma) = (0.8 +/- 1.7(stat.) +/-
0.9(syst.))%.
Both measurements are the most precise to date and are in agreement with the
previous experimental results and theoretical expectations.Comment: 21 pages, 3 figues, 4 table
Absolute luminosity measurements with the LHCb detector at the LHC
Absolute luminosity measurements are of general interest for colliding-beam
experiments at storage rings. These measurements are necessary to determine the
absolute cross-sections of reaction processes and are valuable to quantify the
performance of the accelerator. Using data taken in 2010, LHCb has applied two
methods to determine the absolute scale of its luminosity measurements for
proton-proton collisions at the LHC with a centre-of-mass energy of 7 TeV. In
addition to the classic "van der Meer scan" method a novel technique has been
developed which makes use of direct imaging of the individual beams using
beam-gas and beam-beam interactions. This beam imaging method is made possible
by the high resolution of the LHCb vertex detector and the close proximity of
the detector to the beams, and allows beam parameters such as positions, angles
and widths to be determined. The results of the two methods have comparable
precision and are in good agreement. Combining the two methods, an overall
precision of 3.5% in the absolute luminosity determination is reached. The
techniques used to transport the absolute luminosity calibration to the full
2010 data-taking period are presented.Comment: 48 pages, 19 figures. Results unchanged, improved clarity of Table 6,
9 and 10 and corresponding explanation in the tex
Absolute luminosity measurements with the LHCb detector at the LHC
Absolute luminosity measurements are of general interest for colliding-beam
experiments at storage rings. These measurements are necessary to determine the
absolute cross-sections of reaction processes and are valuable to quantify the
performance of the accelerator. Using data taken in 2010, LHCb has applied two
methods to determine the absolute scale of its luminosity measurements for
proton-proton collisions at the LHC with a centre-of-mass energy of 7 TeV. In
addition to the classic "van der Meer scan" method a novel technique has been
developed which makes use of direct imaging of the individual beams using
beam-gas and beam-beam interactions. This beam imaging method is made possible
by the high resolution of the LHCb vertex detector and the close proximity of
the detector to the beams, and allows beam parameters such as positions, angles
and widths to be determined. The results of the two methods have comparable
precision and are in good agreement. Combining the two methods, an overall
precision of 3.5% in the absolute luminosity determination is reached. The
techniques used to transport the absolute luminosity calibration to the full
2010 data-taking period are presented.Comment: 48 pages, 19 figures. Results unchanged, improved clarity of Table 6,
9 and 10 and corresponding explanation in the tex
First observation of the decay and a measurement of the ratio of branching fractions
The first observation of the decay using
data collected by the LHCb detector at a centre-of-mass energy of 7 TeV,
corresponding to an integrated luminosity of 36 pb, is reported. A
signal of events is obtained and the absence of signal is
rejected with a statistical significance of more than nine standard deviations.
The branching fraction is measured relative to
that of : , where the first uncertainty is statistical, the second systematic and
the third is due to the uncertainty on the ratio of the and
hadronisation fractions.Comment: 10 pages, 3 figures, submitted to Phys. Lett. B; ISSN 0370-269
Genomic and phenotypic characterization of 404 individuals with neurodevelopmental disorders caused by CTNNB1 variants
Purpose: Germline loss-of-function variants in CTNNB1 cause neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV; OMIM 615075) and are the most frequent, recurrent monogenic cause of cerebral palsy (CP). We investigated the range of clinical phenotypes owing to disruptions of CTNNB1 to determine the association between NEDSDV and CP. Methods: Genetic information from 404 individuals with collectively 392 pathogenic CTNNB1 variants were ascertained for the study. From these, detailed phenotypes for 52 previously unpublished individuals were collected and combined with 68 previously published individuals with comparable clinical information. The functional effects of selected CTNNB1 missense variants were assessed using TOPFlash assay. Results: The phenotypes associated with pathogenic CTNNB1 variants were similar. A diagnosis of CP was not significantly associated with any set of traits that defined a specific phenotypic subgroup, indicating that CP is not additional to NEDSDV. Two CTNNB1 missense variants were dominant negative regulators of WNT signaling, highlighting the utility of the TOPFlash assay to functionally assess variants. Conclusion: NEDSDV is a clinically homogeneous disorder irrespective of initial clinical diagnoses, including CP, or entry points for genetic testing.Sayaka Kayumi, Luis A. Perez-Jurado, MarĂa Palomares, Sneha Rangu, Sarah E. Sheppard, Wendy K. Chung, Michael C. Kruer, Mira Kharbanda, David J. Amor, George McGillivray, Julie S. Cohen, Sixto GarcĂa-MinaĂșr, Clare L. van Eyk, Kelly Harper, Lachlan A. Jolly, Dani L. Webber, Christopher P. Barnett, Fernando Santos-Simarro, Marta Pacio-MĂguez, Angela del Pozo, Somayeh Bakhtiari, Matthew Deardorff, Holly A. Dubbs, Kosuke Izumi, Katheryn Grand, Christopher Gray, Paul R. Mark, Elizabeth J. Bhoj, Dong Li, Xilma R. Ortiz-Gonzalez, Beth Keena, Elaine H. Zackai, Ethan M. Goldberg, Guiomar Perez de Nanclares, Arrate Pereda, Isabel Llano-Rivas, Ignacio Arroyo, MarĂa Angeles Fernandez-Cuesta, Christel Thauvin-Robinet, Laurence Faivre, Aurore Garde, Benoit Mazel, Ange-Line Bruel, Michael L. Tress, Eva Brilstra, Amena Smith Fine, Kylie E. Crompton, Alexander P.A. Stegmann, Margje Sinnema, Servi C.J. Stevens, Joost Nicolai, Gaetan Lesca, Laurence Lion-Francois, Damien Haye, Nicolas Chatron, Amelie Piton, Mathilde Nizon, Benjamin Cogne, Siddharth Srivastava, Jennifer Bassetti, Candace Muss, Karen W. Gripp, Rebecca A. Procopio, Francisca Millan, Michelle M. Morrow, Melissa Assaf, Andres Moreno-De-Luca, Shelagh Joss, Mark J. Hamilton, Marta Bertoli, Nicola Foulds, Shane McKee, Alastair H. MacLennan, Jozef Gecz, Mark A. Corbet
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