Natural history of epilepsy in argininosuccinic aciduria provides new insights into pathophysiology: A retrospective international study

OBJECTIVE: Argininosuccinate lyase (ASL) is integral to the urea cycle, which enables nitrogen wasting and biosynthesis of arginine, a precursor of nitric oxide. Inherited ASL deficiency causes argininosuccinic aciduria, the second most common urea cycle defect and an inherited model of systemic nitric oxide deficiency. Patients present with developmental delay, epilepsy, and movement disorder. Here we aim to characterize epilepsy, a common and neurodebilitating comorbidity in argininosuccinic aciduria. METHODS: We conducted a retrospective study in seven tertiary metabolic centers in the UK, Italy, and Canada from 2020 to 2022, to assess the phenotype of epilepsy in argininosuccinic aciduria and correlate it with clinical, biochemical, radiological, and electroencephalographic data. RESULTS: Thirty-seven patients, 1-31 years of age, were included. Twenty-two patients (60%) presented with epilepsy. The median age at epilepsy onset was 24 months. Generalized tonic-clonic and focal seizures were most common in early-onset patients, whereas atypical absences were predominant in late-onset patients. Seventeen patients (77%) required antiseizure medications and six (27%) had pharmacoresistant epilepsy. Patients with epilepsy presented with a severe neurodebilitating disease with higher rates of speech delay (p = .04) and autism spectrum disorders (p = .01) and more frequent arginine supplementation (p = .01) compared to patients without epilepsy. Neonatal seizures were not associated with a higher risk of developing epilepsy. Biomarkers of ureagenesis did not differ between epileptic and non-epileptic patients. Epilepsy onset in early infancy (p = .05) and electroencephalographic background asymmetry (p = .0007) were significant predictors of partially controlled or refractory epilepsy. SIGNIFICANCE: Epilepsy in argininosuccinic aciduria is frequent, polymorphic, and associated with more frequent neurodevelopmental comorbidities. We identified prognostic factors for pharmacoresistance in epilepsy. This study does not support defective ureagenesis as prominent in the pathophysiology of epilepsy but suggests a role of central dopamine deficiency. A role of arginine in epileptogenesis was not supported and warrants further studies to assess the potential arginine neurotoxicity in argininosuccinic aciduria

Incidence rates of progressive childhood encephalopathy in Oslo, Norway: a population based study

<p>Abstract</p> <p>Background</p> <p>Progressive encephalopathy (PE) in children is a heterogeneous group of diseases mainly composed of metabolic diseases, but it consists also of neurodegenerative disorders where neither metabolic nor other causes are found. We wanted to estimate the incidence rate and aetiology of PE, as well as the age of onset of the disease.</p> <p>Methods</p> <p>We included PE cases born between 1985 and 2003, living in Oslo, and registered the number presenting annually between 1985 and 2004. Person-years at risk between 0 and 15 years were based on the number of live births during the observation period which was divided into four 5-year intervals. We calculated incidence rates according to age at onset which was classified as neonatal (0–4 weeks), infantile (1–12 months), late infantile (1–5 years), and juvenile (6–12 years).</p> <p>Results</p> <p>We found 84 PE cases representing 28 diagnoses among 1,305,997 person years, giving an incidence rate of 6.43 per 100,000 person years. The age-specific incidence rates per 100,000 were: 79.89 (<1 year), 8.64 (1–2 years), 1.90 (2–5 years), and 0.65 (>5 years). 66% (55/84) of the cases were metabolic, 32% (27/54) were neurodegenerative, and 2% (2/84) had HIV encephalopathy. 71% (60/84) of the cases presented at < 1 year, 24% (20/84) were late infantile presentations, and 5% (4/84) were juvenile presentations. Neonatal onset was more common in the metabolic (46%) (25/55) compared to the neurodegenerative group (7%) (2/27). 20% (17/84) of all cases were classified as unspecified neurodegenerative disease.</p> <p>Conclusion</p> <p>The overall incidence rate of PE was 6.43 per 100,000 person years. There was a strong reduction in incidence rates with increasing age. Two-thirds of the cases were metabolic, of which almost half presented in the neonatal period.</p

Search for Charged Higgs Bosons in e+e- Collisions at \sqrt{s} = 189 GeV

A search for pair-produced charged Higgs bosons is performed with the L3 detector at LEP using data collected at a centre-of-mass energy of 188.6 GeV, corresponding to an integrated luminosity of 176.4 pb^-1. Higgs decays into a charm and a strange quark or into a tau lepton and its associated neutrino are considered. The observed events are consistent with the expectations from Standard Model background processes. A lower limit of 65.5 GeV on the charged Higgs mass is derived at 95 % confidence level, independent of the decay branching ratio Br(H^{+/-} -> tau nu)

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Search for Kaluza-Klein Graviton Emission in ppˉp\bar{p} Collisions at s=1.8\sqrt{s}=1.8 TeV using the Missing Energy Signature

We report on a search for direct Kaluza-Klein graviton production in a data sample of 84 ${pb}^{-1}$ of \ppb collisions at $\sqrt{s}$ = 1.8 TeV, recorded by the Collider Detector at Fermilab. We investigate the final state of large missing transverse energy and one or two high energy jets. We compare the data with the predictions from a $3+1+n$-dimensional Kaluza-Klein scenario in which gravity becomes strong at the TeV scale. At 95% confidence level (C.L.) for $n$=2, 4, and 6 we exclude an effective Planck scale below 1.0, 0.77, and 0.71 TeV, respectively.Comment: Submitted to PRL, 7 pages 4 figures/Revision includes 5 figure

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Measurement of the average time-integrated mixing probability of b-flavored hadrons produced at the Tevatron

We have measured the number of like-sign (LS) and opposite-sign (OS) lepton pairs arising from double semileptonic decays of $b$ and $\bar{b}$-hadrons, pair-produced at the Fermilab Tevatron collider. The data samples were collected with the Collider Detector at Fermilab (CDF) during the 1992-1995 collider run by triggering on the existence of $\mu \mu$ and $e \mu$ candidates in an event. The observed ratio of LS to OS dileptons leads to a measurement of the average time-integrated mixing probability of all produced $b$-flavored hadrons which decay weakly, $\bar{\chi} = 0.152 \pm 0.007$ (stat.) $\pm 0.011$ (syst.), that is significantly larger than the world average $\bar{\chi} = 0.118 \pm 0.005$.Comment: 47 pages, 10 figures, 15 tables Submitted to Phys. Rev.

Search for R-parity-violating supersymmetry in events with four or more leptons in sqrt(s) =7 TeV pp collisions with the ATLAS detector

A search for new phenomena in final states with four or more leptons (electrons or muons) is presented. The analysis is based on 4.7 fb−1 of $\sqrt{s}=7\;\mathrm{TeV}$ proton-proton collisions delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in two signal regions: one that requires moderate values of missing transverse momentum and another that requires large effective mass. The results are interpreted in a simplified model of R-parity-violating supersymmetry in which a 95% CL exclusion region is set for charged wino masses up to 540 GeV. In an R-parity-violating MSUGRA/CMSSM model, values of m 1/2 up to 820 GeV are excluded for 10 < tan β < 40