Natural clusters of tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND): new findings from the TOSCA TAND research project.

BACKGROUND: Tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND) have unique, individual patterns that pose significant challenges for diagnosis, psycho-education, and intervention planning. A recent study suggested that it may be feasible to use TAND Checklist data and data-driven methods to generate natural TAND clusters. However, the study had a small sample size and data from only two countries. Here, we investigated the replicability of identifying natural TAND clusters from a larger and more diverse sample from the TOSCA study. METHODS: As part of the TOSCA international TSC registry study, this embedded research project collected TAND Checklist data from individuals with TSC. Correlation coefficients were calculated for TAND variables to generate a correlation matrix. Hierarchical cluster and factor analysis methods were used for data reduction and identification of natural TAND clusters. RESULTS: A total of 85 individuals with TSC (female:male, 40:45) from 7 countries were enrolled. Cluster analysis grouped the TAND variables into 6 clusters: a scholastic cluster (reading, writing, spelling, mathematics, visuo-spatial difficulties, disorientation), a hyperactive/impulsive cluster (hyperactivity, impulsivity, self-injurious behavior), a mood/anxiety cluster (anxiety, depressed mood, sleep difficulties, shyness), a neuropsychological cluster (attention/concentration difficulties, memory, attention, dual/multi-tasking, executive skills deficits), a dysregulated behavior cluster (mood swings, aggressive outbursts, temper tantrums), and an autism spectrum disorder (ASD)-like cluster (delayed language, poor eye contact, repetitive behaviors, unusual use of language, inflexibility, difficulties associated with eating). The natural clusters mapped reasonably well onto the six-factor solution generated. Comparison between cluster and factor solutions from this study and the earlier feasibility study showed significant similarity, particularly in cluster solutions. CONCLUSIONS: Results from this TOSCA research project in an independent international data set showed that the combination of cluster analysis and factor analysis may be able to identify clinically meaningful natural TAND clusters. Findings were remarkably similar to those identified in the earlier feasibility study, supporting the potential robustness of these natural TAND clusters. Further steps should include examination of larger samples, investigation of internal consistency, and evaluation of the robustness of the proposed natural clusters

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar

Search for the Zγ decay mode of new high-mass resonances in pp collisions at √s = 13 TeV with the ATLAS detector

This letter presents a search for narrow, high-mass resonances in the Zγ final state with the Z boson decaying into a pair of electrons or muons. The √s = 13 TeV pp collision data were recorded by the ATLAS detector at the CERN Large Hadron Collider and have an integrated luminosity of 140 fb−1. The data are found to be in agreement with the Standard Model background expectation. Upper limits are set on the resonance production cross section times the decay branching ratio into Zγ. For spin-0 resonances produced via gluon–gluon fusion, the observed limits at 95% confidence level vary between 65.5 fb and 0.6 fb, while for spin-2 resonances produced via gluon–gluon fusion (or quark–antiquark initial states) limits vary between 77.4 (76.1) fb and 0.6 (0.5) fb, for the mass range from 220 GeV to 3400 GeV

Search for single vector-like B quark production and decay via B → bH(b¯b) in pp collisions at √s = 13 TeV with the ATLAS detector

A search is presented for single production of a vector-like B quark decaying into a Standard Model b-quark and a Standard Model Higgs boson, which decays into a b¯b pair. The search is carried out in 139 fb−1 of √s = 13 TeV proton-proton collision data collected by the ATLAS detector at the LHC between 2015 and 2018. No significant deviation from the Standard Model background prediction is observed, and mass-dependent exclusion limits at the 95% confidence level are set on the resonance production cross-section in several theoretical scenarios determined by the couplings cW, cZ and cH between the B quark and the Standard Model W, Z and Higgs bosons, respectively. For a vector-like B occurring as an isospin singlet, the search excludes values of cW greater than 0.45 for a B resonance mass (mB) between 1.0 and 1.2 TeV. For 1.2 TeV < mB < 2.0 TeV, cW values larger than 0.50–0.65 are excluded. If the B occurs as part of a (B, Y) doublet, the smallest excluded cZ coupling values range between 0.3 and 0.5 across the investigated resonance mass range 1.0 TeV < mB < 2.0 TeV

Search for single production of vector-like T quarks decaying into Ht or Zt in pp collisions at s√ = 13 TeV with the ATLAS detector

This paper describes a search for the single production of an up-type vector-like quark (T) decaying as T → Ht or T → Zt. The search utilises a dataset of pp collisions at s√ = 13 TeV collected with the ATLAS detector during the 2015–2018 data-taking period of the Large Hadron Collider, corresponding to an integrated luminosity of 139 fb−1. Data are analysed in final states containing a single lepton with multiple jets and b-jets. The presence of boosted heavy resonances in the event is exploited to discriminate the signal from the Standard Model background. No significant excess above the Standard Model expectation is observed, and 95% CL upper limits are set on the production cross section of T quarks in different decay channels. The results are interpreted in several benchmark scenarios to set limits on the mass and universal coupling strength (κ) of the vector-like quark. For singlet T quarks, κ values above 0.53 are excluded for all masses below 2.3 TeV. At a mass of 1.6 TeV, κ values as low as 0.35 are excluded. For T quarks in the doublet scenario, where the production cross section is much lower, κ values above 0.72 are excluded for all masses below 1.7 TeV, and this exclusion is extended to κ above 0.55 for low masses around 1.0 TeV

Search for excited τ-leptons and leptoquarks in the final state with τ-leptons and jets in pp collisions at s√ = 13 TeV with the ATLAS detector

A search is reported for excited τ-leptons and leptoquarks in events with two hadronically decaying τ-leptons and two or more jets. The search uses proton-proton (pp) collision data at s√ = 13 TeV recorded by the ATLAS experiment during the Run 2 of the Large Hadron Collider in 2015–2018. The total integrated luminosity is 139 fb−1. The excited τ-lepton is assumed to be produced and to decay via a four-fermion contact interaction into an ordinary τ-lepton and a quark-antiquark pair. The leptoquarks are assumed to be produced in pairs via the strong interaction, and each leptoquark is assumed to couple to a charm or lighter quark and a τ-lepton. No excess over the background prediction is observed. Excited τ-leptons with masses below 2.8 TeV are excluded at 95% CL in scenarios with the contact interaction scale Λ set to 10 TeV. At the extreme limit of model validity where Λ is set equal to the excited τ-lepton mass, excited τ-leptons with masses below 4.6 TeV are excluded. Leptoquarks with masses below 1.3 TeV are excluded at 95% CL if their branching ratio to a charm quark and a τ-lepton equals 1. The analysis does not exploit flavour-tagging in the signal region

Measurement of the cross-sections of the electroweak and total production of a Zγ pair in association with two jets in pp collisions at √s = 13 TeV with the ATLAS detector

This Letter presents the measurement of the fiducial and differential cross-sections of the electroweak production of a Zγ pair in association with two jets. The analysis uses 140 fb−1 of LHC proton–proton collision data taken at √s = 13 TeV recorded by the ATLAS detector during the years 2015–2018. Events with a Z boson candidate decaying into either an e+e− or μ+μ− pair, a photon and two jets are selected. The electroweak component is extracted by requiring a large dijet invariant mass and by using the information about the centrality of the system and is measured with an observed and expected significance well above five standard deviations. The fiducial pp → Zγ jj cross-section for the electroweak production is measured to be 3.6 ± 0.5 fb. The total fiducial cross-section that also includes contributions where the jets arise from strong interactions is measured to be 16.8+2.0 −1.8 fb. The results are consistent with the Standard Model predictions. Differential cross-sections are also measured using the same events and are compared with parton-shower Monte Carlo simulations. Good agreement is observed between data and predictions

Search for light long-lived neutral particles that decay to collimated pairs of leptons or light hadrons in pp collisions at s√ = 13 TeV with the ATLAS detector

A search for light long-lived neutral particles with masses in the O(MeV–GeV) range is presented. The analysis targets the production of long-lived dark photons in the decay of a Higgs boson produced via gluon–gluon fusion or in association with a W boson. Events that contain displaced collimated Standard Model fermions reconstructed in the calorimeter or muon spectrometer are selected in 139 fb−1 of s√ = 13 TeV pp collision data collected by the ATLAS detector at the LHC. Background estimates for contributions from Standard Model processes and instrumental effects are extracted from data. The observed event yields are consistent with the expected background. Exclusion limits are reported on the production cross-section times branching fraction as a function of the mean proper decay length cτ of the dark photon, or as a function of the dark-photon mass and kinetic mixing parameter that quantifies the coupling between the Standard Model and potential hidden (dark) sectors. A Higgs boson branching fraction above 1% is excluded at 95% CL for a Higgs boson decaying into two dark photons for dark-photon mean proper decay lengths between 10 mm and 250 mm and dark photons with masses between 0.4 GeV and 2 GeV