Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome

Purpose: Pathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features have been described for 11 patients with (likely) pathogenic SETD1B sequence variants. This study aims to further delineate the spectrum of the SETD1B-related syndrome based on characterizing an expanded patient cohort. Methods: We perform an in-depth clinical characterization of a cohort of 36 unpublished individuals with SETD1B sequence variants, describing their molecular and phenotypic spectrum. Selected variants were functionally tested using in vitro and genome-wide methylation assays. Results: Our data present evidence for a loss-of-function mechanism of SETD1B variants, resulting in a core clinical phenotype of global developmental delay, language delay including regression, intellectual disability, autism and other behavioral issues, and variable epilepsy phenotypes. Developmental delay appeared to precede seizure onset, suggesting SETD1B dysfunction impacts physiological neurodevelopment even in the absence of epileptic activity. Males are significantly overrepresented and more severely affected, and we speculate that sex-linked traits could affect susceptibility to penetrance and the clinical spectrum of SETD1B variants. Conclusion: Insights from this extensive cohort will facilitate the counseling regarding the molecular and phenotypic landscape of newly diagnosed patients with the SETD1B-related syndrome

Measurement of vector boson production cross sections and their ratios using pp collisions at √s = 13.6 TeV with the ATLAS detector

Abstract available from publisher's website

Searches for exclusive Higgs boson decays into D⁎γ and Z boson decays into D0γ and Ks0γ in pp collisions at √s = 13 TeV with the ATLAS detector

Searches for exclusive decays of the Higgs boson into D⁎γ and of the Z boson into D0γ and Ks0γ can probe flavour-violating Higgs boson and Z boson couplings to light quarks. Searches for these decays are performed with a pp collision data sample corresponding to an integrated luminosity of 136.3 fb−1 collected at s=13TeV between 2016–2018 with the ATLAS detector at the CERN Large Hadron Collider. In the D⁎γ and D0γ channels, the observed (expected) 95% confidence-level upper limits on the respective branching fractions are B(H→D⁎γ)<1.0(1.2)×10−3, B(Z→D0γ)<4.0(3.4)×10−6, while the corresponding results in the Ks0γ channel are B(Z→Ks0γ)<3.1(3.0)×10−6

Beam-induced backgrounds measured in the ATLAS detector during local gas injection into the LHC beam vacuum

Inelastic beam-gas collisions at the Large Hadron Collider (LHC), within a few hundred metres of the ATLAS experiment, are known to give the dominant contribution to beam backgrounds. These are monitored by ATLAS with a dedicated Beam Conditions Monitor (BCM) and with the rate of fake jets in the calorimeters. These two methods are complementary since the BCM probes backgrounds just around the beam pipe while fake jets are observed at radii of up to several metres. In order to quantify the correlation between the residual gas density in the LHC beam vacuum and the experimental backgrounds recorded by ATLAS, several dedicated tests were performed during LHC Run 2. Local pressure bumps, with a gas density several orders of magnitude higher than during normal operation, were introduced at different locations. The changes of beam-related backgrounds, seen in ATLAS, are correlated with the local pressure variation. In addition the rates of beam-gas events are estimated from the pressure measurements and pressure bump profiles obtained from calculations. Using these rates, the efficiency of the ATLAS beam background monitors to detect beam-gas events is derived as a function of distance from the interaction point. These efficiencies and characteristic distributions of fake jets from the beam backgrounds are found to be in good agreement with results of beam-gas simulations performed with theFluka Monte Carlo programme

Options for Regional Integration in Southern Africa

The Southern African Development Community (SADC) had at its inception a strong anti-apartheid political orientation. From 1992, economic cooperation has been based on 'efficiency, economy and competitiveness'. In 1996 SADC Protocol on Trade Co-operation for the creation of a Free Trade Area (FTA) was agreed and the ratification process is almost complete. Realisation of the full benefits of the FTA requires rule-based system institutional arrangements. The institutional reform that could deliver a workable FTA is demanding. Moreover, the FTA, or more accurately the 'intended' FTA, requires the application of strict rules of origin to succeed. Given the weak administrative capacity of the member countries, it is likely that the 'intended' FTA would, in practice, operate like a Customs Union with the Common External Tariff based on the lowest tariff rates prevailing for each commodity amongst member states (CUmin). Against the forces moving for regional economic integration, there are power forces from the international community leading towards unilateral freer trade, and ultimately Free Trade (FT). These circumstances provide a rich background for exploring the options for regional integration

Are transnational tobacco companies' market access strategies linked to economic development models? A case study of South Korea.

Transnational tobacco companies (TTCs) have used varied strategies to access previously closed markets. Using TTCs' efforts to enter the South Korean market from the late 1980s as a case study, this article asks whether there are common patterns in these strategies that relate to the broader economic development models adopted by targeted countries. An analytical review of the existing literature on TTCs' efforts to access emerging markets was conducted to develop hypotheses relating TTCs' strategies to countries' economic development models. A case study of Korea was then undertaken based on analysis of internal tobacco industry documents. Findings were consistent with the hypothesis that TTCs' strategies in Korea were linked to Korea's export-oriented economic development model and its hostile attitude towards foreign investment. A fuller understanding of TTCs' strategies for expansion globally can be derived by locating them within the economic development models of specific countries or regions. Of foremost importance is the need for governments to carefully balance economic and public health policies when considering liberalisation

Automatic tracking of the intersection of a laser and electron beam

For the Compton Polarimeter experiment at the Stanford Linear Accelerator the crossing point of a laser beam and an electron beam must be kept accurate and stable. An electronic system is described for the automatic tracking and correcting of the beam crossing. A remote CCD camera, relatively insensitive to electromagnetic disturbance, records small displacements of the pulsed laser beam. Video signals are analyzed at a remote station, the amount of drift from a selected reference point determined and the appropriate correction commands sent to the motorized mirror deflecting the laser beam. A description of the system, its performance and the test results are presented. 2 refs., 4 figs