Dysfunction of the Heteromeric KV7.3/KV7.5 Potassium Channel is Associated with Autism Spectrum Disorders

Heterozygous mutations in the KCNQ3 gene on chromosome 8q24 encoding the voltage-gated potassium channel KV7.3 subunit have previously been associated with rolandic epilepsy and idiopathic generalized epilepsy (IGE) including benign neonatal convulsions. We identified a de novo t(3;8) (q21;q24) translocation truncating KCNQ3 in a boy with childhood autism. In addition, we identified a c.1720C > T [p.P574S] nucleotide change in three unrelated individuals with childhood autism and no history of convulsions. This nucleotide change was previously reported in patients with rolandic epilepsy or IGE and has now been annotated as a very rare SNP (rs74582884) in dbSNP. The p.P574S KV7.3 variant significantly reduced potassium current amplitude in Xenopus laevis oocytes when co-expressed with KV7.5 but not with KV7.2 or KV7.4. The nucleotide change did not affect trafficking of heteromeric mutant KV7.3/2, KV7.3/4, or KV7.3/5 channels in HEK 293 cells or primary rat hippocampal neurons. Our results suggest that dysfunction of the heteromeric KV7.3/5 channel is implicated in the pathogenesis of some forms of autism spectrum disorders, epilepsy, and possibly other psychiatric disorders and therefore, KCNQ3 and KCNQ5 are suggested as candidate genes for these disorders

Cohort profile: the 100 million Brazilian cohort

The creation of The 100 Million Brazilian Cohort was motivated by the availability of high quality but dispersed social and health databases in Brazil and the need to integrate data and evaluate the impact of policies aiming to improve the social determinants of health (e.g. social protection policies) on health outcomes, overall and in subgroups of interest in a dynamic cohort. • The baseline of The 100 Million Brazilian Cohort comprises 131 697 800 low-income individuals in 35 358 415 families from 2011 to 2018. The Cohort population is mostly composed of children and young adults, with a higher proportion of females than the general Brazilian population, who identify themselves as Brown and live in the urban area of the country. • Exposure to social protection and the follow-up of individuals are obtained through: (i) deterministic linkage using the Social Identification Number (NIS) to link the Cohort baseline to social protection programmes and to periodically renewed socioeconomic information in Cadatro U ́ nico datasets; and/or (ii) non-deterministic linkage using the CIDACS-RL non-deterministic linkage tool, to link the Cohort baseline to administrative health care datasets such as mortality (Mortality Information System, SIM), disease notification (Information System for Notifiable Diseases, SINAN), birth information (Live Birth Information System, SINASC) and nutrition status (Food and Nutrition Surveillance System, SISVAN). • So far, studies have used The 100 Million Brazilian Cohort to investigate the socioeconomic and demographic determinants of leprosy, leprosy treatment outcomes and low birthweight and to evaluate the impact of the Bolsa Familia Programme (BFP) on leprosy and child mortality. Other studies are now being conducted that are of utmost relevance to the health inequalities of Brazil and many low- and middle-income countries, and many research opportunities are being opened up with the linkage of a range of health outcomes

Evaluation of night-time aerosols measurements and lunar irradiance models in the frame of the first multi-instrument nocturnal intercomparison campaign

The first multi-instrument nocturnal aerosol optical depth (AOD) intercom-parison campaign was held at the high-mountain Iza ̃na Observatory (Tener-ife, Spain) in June 2017, involving 2-minutes synchronous measurements fromtwo different types of lunar photometers (Cimel CE318-T and Moon Preci-sion Filter Radiometer, LunarPFR) and one stellar photometer. The Robotic Lunar Observatory (ROLO) model developed by the U.S. Geological Survey(USGS) was compared with the open-access ROLO Implementation for Moonphotometry Observation (RIMO) model. Results showed rather small differ-ences at Iza ̃na over a 2-month time period covering June and July, 2017(±0.01 in terms of AOD calculated by means of a day/night/day coherencetest analysis and±2 % in terms of lunar irradiance). The RIMO model hasbeen used in this field campaign to retrieve AOD from lunar photometricmeasurements. No evidence of significant differences with the Moon’s phase angle wasfound when comparing raw signals of the six Cimel photometers involved inthis field campaign.The raw signal comparison of the participating lunar photometers (Cimeland LunarPFR) performed at coincident wavelengths showed consistent mea-surements and AOD differences within their combined uncertainties at 870 nmand 675 nm. Slightly larger AOD deviations were observed at 500 nm, point-ing to some unexpected instrumental variations during the measurement pe-riod.Lunar irradiances retrieved using RIMO for phase angles varying between0◦and 75◦(full Moon to near quarter Moon) were compared to the irradi-ance variations retrieved by Cimel and LunarPFR photometers. Our resultsshowed a relative agreement within±3.5 % between the RIMO model andthe photometer-based lunar irradiances.The AOD retrieved by performing a Langley-plot calibration each nightshowed a remarkable agreement (better than 0.01) between the lunar pho-tometers. However, when applying the Lunar-Langley calibration using RIMO,AOD differences of up to 0.015 (0.040 for 500 nm) were found, with differ-ences increasing with the Moon’s phase angle. These differences are thoughtto be partly due to the uncertainties in the irradiance models, as well asinstrumental deficiencies yet to be fully understood.High AOD variability in stellar measurements was detected during thecampaign. Nevertheless, the observed AOD differences in the Cimel/stellarcomparison were within the expected combined uncertainties of these twophotometric techniques. Our results indicate that lunar photometry is amore reliable technique, especially for low aerosol loading conditions.The uncertainty analysis performed in this paper shows that the com-bined standard AOD uncertainty in lunar photometry is dependent on thecalibration technique (up to 0.014 for Langley-plot with illumination-basedcorrection, 0.012-0.022 for Lunar-Langley calibration, and up to 0.1 for the 2 Sun-Moon Gain Factor method). This analysis also corroborates that theuncertainty of the lunar irradiance model used for AOD calculation is withinthe 5-10 % expected range.This campaign has allowed us to quantify the important technical diffi-culties that still exist when routinely monitoring aerosol optical propertiesat night-time. The small AOD differences observed between the three typesof photometers involved in the campaign are only detectable under pristinesky conditions such as those found in this field campaign. Longer campaignsare necessary to understand the observed discrepancies between instrumentsas well as to provide more conclusive results about the uncertainty involvedin the lunar irradiance model

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Search for the standard model Higgs boson decaying to a bbˉb\bar{b} pair in events with no charged leptons and large missing transverse energy using the full CDF data set

We report on a search for the standard model Higgs boson produced in association with a vector boson in the full data set of proton-antiproton collisions at $\sqrt{s} = 1.96$ TeV recorded by the CDF II detector at the Tevatron, corresponding to an integrated luminosity of 9.45 fb$^{-1}$. We consider events having no identified charged lepton, a transverse energy imbalance, and two or three jets, of which at least one is consistent with originating from the decay of a $b$ quark. We place 95% credibility level upper limits on the production cross section times standard model branching fraction for several mass hypotheses between 90 and $150 \mathrm{GeV}/c^2$. For a Higgs boson mass of $125 \mathrm{GeV}/c^2$, the observed (expected) limit is 6.7 (3.6) times the standard model prediction.Comment: Accepted by Phys. Rev. Let

Search for the standard model Higgs boson decaying to a bb pair in events with one charged lepton and large missing transverse energy using the full CDF data set

We present a search for the standard model Higgs boson produced in association with a W boson in sqrt(s) = 1.96 TeV p-pbar collision data collected with the CDF II detector at the Tevatron corresponding to an integrated luminosity of 9.45 fb-1. In events consistent with the decay of the Higgs boson to a bottom-quark pair and the W boson to an electron or muon and a neutrino, we set 95% credibility level upper limits on the WH production cross section times the H->bb branching ratio as a function of Higgs boson mass. At a Higgs boson mass of 125 GeV/c2 we observe (expect) a limit of 4.9 (2.8) times the standard model value.Comment: Submitted to Phys. Rev. Lett (v2 contains clarifications suggested by PRL

Search for the standard model Higgs boson decaying to a bb pair in events with two oppositely-charged leptons using the full CDF data set

We present a search for the standard model Higgs boson produced in association with a Z boson in data collected with the CDF II detector at the Tevatron, corresponding to an integrated luminosity of 9.45/fb. In events consistent with the decay of the Higgs boson to a bottom-quark pair and the Z boson to electron or muon pairs, we set 95% credibility level upper limits on the ZH production cross section times the H -> bb branching ratio as a function of Higgs boson mass. At a Higgs boson mass of 125 GeV/c^2 we observe (expect) a limit of 7.1 (3.9) times the standard model value.Comment: To be submitted to Phys. Rev. Let