Establishing the phenotypic spectrum of ZTTK syndrome by analysis of 52 individuals with variants in SON

Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome, an intellectual disability syndrome first described in 2016, is caused by heterozygous loss-of-function variants in SON. Its encoded protein promotes pre-mRNA splicing of many genes essential for development. Whereas individual phenotypic traits have previously been linked to erroneous splicing of SON target genes, the phenotypic spectrum and the pathogenicity of missense variants have not been further evaluated. We present the phenotypic abnormalities in 52 individuals, including 17 individuals who have not been reported before. In total, loss-of-function variants were detected in 49 individuals (de novo in 47, inheritance unknown in 2), and in 3, a missense variant was observed (2 de novo, 1 inheritance unknown). Phenotypic abnormalities, systematically collected and analyzed in Human Phenotype Ontology, were found in all organ systems. Significant inter-individual phenotypic variability was observed, even in individuals with the same recurrent variant (n = 13). SON haploinsufficiency was previously shown to lead to downregulation of downstream genes, contributing to specific phenotypic features. Similar functional analysis for one missense variant, however, suggests a different mechanism than for heterozygous loss-of-function. Although small in numbers and while pathogenicity of these variants is not certain, these data allow for speculation whether de novo missense variants cause ZTTK syndrome via another mechanism, or a separate overlapping syndrome. In conclusion, heterozygous loss-of-function variants in SON define a recognizable syndrome, ZTTK, associated with a broad, severe phenotypic spectrum, characterized by a large inter-individual variability. These observations provide essential information for affected individuals, parents, and healthcare professionals to ensure appropriate clinical management

Prevalence and correlates of smoking among urban adult men in Bangladesh: slum versus non-slum comparison

Khan MH, Khan A, Krämer A, Mori M. Prevalence and correlates of smoking among urban adult men in Bangladesh: slum versus non-slum comparison. BMC Public Health. 2009;9(1):149.Background: Smoking is one of the leading causes of premature death particularly in developing countries. The prevalence of smoking is high among the general male population in Bangladesh. Unfortunately smoking information including correlates of smoking in the cities especially in the urban slums is very scarce, although urbanization is rapid in Bangladesh and slums are growing quickly in its major cities. Therefore this study reported prevalences of cigarette and bidi smoking and their correlates separately by urban slums and non-slums in Bangladesh. Methods: We used secondary data which was collected by the 2006 Urban Health Survey. The data were representative for the urban areas in Bangladesh. Both slums and non-slums located in the six City Corporations were considered. Slums in the cities were identified by two steps, first by using the satellite images and secondly by ground truthing. At the next stage, several clusters of households were selected by using proportional sampling. Then from each of the selected clusters, about 25 households were randomly selected. Information of a total of 12,155 adult men, aged 15 59 years, was analyzed by stratifying them into slum (= 6,488) and non-slum (= 5,667) groups. Simple frequency, bivariable and multivariable logistic regression analyses were performed using SPSS. Results: Overall smoking prevalence for the total sample was 53.6% with significantly higher prevalences among men in slums (59.8%) than non-slums (46.4%). Respondents living in slums reported a significantly (P < 0.001) higher prevalence of smoking cigarettes (53.3%) as compared to those living in non-slums (44.6%). A similar pattern was found for bidis (slums = 11.4% and non-slums = 3.2%, P < 0.001). Multivariable logistic regression revealed significantly higher odds ratio (OR) of smoking cigarettes (OR = 1.12, 95% CI = 1.03-1.22), bidis (OR = 1.90, 95% CI = 1.58-2.29) and any of the two (OR = 1.23, 95% CI = 1.13-1.34) among men living in slums as compared to those living in non-slums when controlled for age, division, education, marital status, religion, birth place and types of work. Division, education and types of work were the common significant correlates for both cigarette and bidi smoking in slums and non-slums by multivariable logistic regressions. Other significant correlates of smoking cigarettes were marital status (both areas), birth place (slums), and religion (non-slums). Similarly significant factors for smoking bidis were age (both areas), marital status (slums), religion (non-slums), and birth place (both areas). Conclusion: The men living in the urban slums reported higher rates of smoking cigarettes and bidis as compared to men living in the urban non-slums. Some of the significant correlates of smoking e. g. education and division should be considered for prevention activities. Our findings clearly underscore the necessity of interventions and preventions by policy makers, public health experts and other stakeholders in slums because smoking was more prevalent in the slum communities with detrimental health sequelae

Highlights From the Annual Meeting of the American Epilepsy Society 2022

With more than 6000 attendees between in-person and virtual offerings, the American Epilepsy Society Meeting 2022 in Nashville, felt as busy as in prepandemic times. An ever-growing number of physicians, scientists, and allied health professionals gathered to learn a variety of topics about epilepsy. The program was carefully tailored to meet the needs of professionals with different interests and career stages. This article summarizes the different symposia presented at the meeting. Basic science lectures addressed the primary elements of seizure generation and pathophysiology of epilepsy in different disease states. Scientists congregated to learn about anti-seizure medications, mechanisms of action, and new tools to treat epilepsy including surgery and neurostimulation. Some symposia were also dedicated to discuss epilepsy comorbidities and practical issues regarding epilepsy care. An increasing number of patient advocates discussing their stories were intertwined within scientific activities. Many smaller group sessions targeted more specific topics to encourage member participation, including Special Interest Groups, Investigator, and Skills Workshops. Special lectures included the renown Hoyer and Lombroso, an ILAE/IBE joint session, a spotlight on the impact of Dobbs v. Jackson on reproductive health in epilepsy, and a joint session with the NAEC on coding and reimbursement policies. The hot topics symposium was focused on traumatic brain injury and post-traumatic epilepsy. A balanced collaboration with the industry allowed presentations of the latest pharmaceutical and engineering advances in satellite symposia

Measurement of quarkonium production cross sections in pp collisions at root s=13 TeV

Differential production cross sections of prompt J/psi and psi(2S) charmonium and Upsilon(nS) (n = 1, 2, 3) bottomonium states are measured in proton-proton collisions at root s = 13 TeV, with data collected by the CMS detector at the LHC, corresponding to an integrated luminosity of 2.3 fb(-1) for the J/psi and 2.7 fb(-1) for the other mesons. The five quarkonium states are reconstructed in the dimuon decay channel, for dimuon rapidity vertical bar y vertical bar <1.2. The double-differential cross sections for each state are measured as a function of y and transverse momentum, and compared to theoretical expectations. In addition, ratios are presented of cross sections for prompt psi(2S) to J/psi, Upsilon(2S) to Upsilon(1S), and Upsilon(3S) to Upsilon(1S) production. (C) 2018 The Author(s). Published by Elsevier B.V.Peer reviewe

Search for new long-lived particles at root s=13 TeV

A search for long-lived particles was performed with data corresponding to an integrated luminosity of 2.6 fb(-1) collected at a center-of-mass energy of 13 TeV by the CMS experiment in 2015. The analysis exploits two customized topological trigger algorithms, and uses the multiplicity of displaced jets to search for the presence of a signal decay occurring at distances between 1 and 1000 mm. The results can be interpreted in a variety of different models. For pair-produced long-lived particles decaying to two b quarks and two leptons with equal decay rates between lepton flavors, cross sections larger than 2.5 fb are excluded for proper decay lengths between 70-100 mm for a long-lived particle mass of 1130 GeV at 95% confidence. For a specific model of pair-produced, long-lived top squarks with R-parity violating decays to a b quark and a lepton, masses below 550-1130 GeV are excluded at 95% confidence for equal branching fractions between lepton flavors, depending on the squark decay length. This mass bound is the most stringent to date for top squark proper decay lengths greater than 3 mm. (C) 2018 The Author(s). Published by Elsevier B.V.Peer reviewe

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI