Efficacy And Tolerability Of Vigabatrin In West Syndrome [avaliaçao Da Eficácia E Tolerabilidade Da Vigabatrina Na Síndrome De West]

West syndrome (WS) is a severe epileptic encephalopathy of childhood, characterized by spasms, developmental deterioration and hipsarhythymia. Objective: To evaluate the safety and efficacy of vigabatrin (VGB) in the treatment of WS. Method: We evaluated every patient diagnosed with WS seen at the pediatric epilepsy clinic and exposed to VGB. Patients were interviewed according to a semistructured questionnaire and we analyzed gender, age, etiology (cryptogenic or symptomatic), associated diseases, age of seizure onset, neuroimaging findings, EEG prior and after VGB, use of other antiepileptic drugs, time for seizure control, electroretinogram, visual complaints, adverse events and family history of epilepsy. Results: Twenty-three patients were evaluated, 16 boys, ages ranging from 1.25 years to 11.5 years (mean=5y3m). Sixteen (69.5%) patients were seizure free, five (22%) had partial seizure control and in two (8.5%) there was no improvement. Only one patient presented gabaergic retinopathy. Six (26%) patients presented adverse events: somnolence, aggressivity or retinopathy. Patients with seizure onset after 6 months of age presented better results after VGB introduction (p0.05). After VGB, no patient presented hipsarrhythymia and 50% had a normal EEG. Conclusion: Although VGB may be associated with serious adverse events such as gabaergic retinopathy, our results show that it should be considered in the treatment of WS.632 B469473Appleton, R.E., West syndrome: Long-term prognosis and social aspects (2001) Brain Dev, 23, pp. 688-691Mitchell, W.G., Shah, N.S., Vigabatrin for infantile spasms (2002) Pediatr Neurol, 27, pp. 161-164Wallace, S.J., Newer antiepileptic drugs: Advantages and disadvantages (2001) Brain & Dev, 23, pp. 277-283Harding, G.F., Wild, J.M., Robertson, K.A., Rietbrock, S., Martinez, C., Separating the retinal electrophysiologic effects of vigabatrin: Treatment versus field loss (2000) Neurology, 55, pp. 347-352McDonagh, J., Stephen, L.J., Dolan, F.M., Peripheral retinal dysfunction in patients taking vigabatrin (2003) Neurology, 61, pp. 1690-1694Chiron, C., Dulac, O., Luna, D., Vigabatrin in infantile spasms (1990) Lancet, 335, pp. 363-364Chiron, C., Dulac, O., Beaumont, D., Palacios, L., Pajot, N., Mumford, J., Therapeutic trial of vigabatrin in refractory infantile spasms (1991) J Child Neurol, (SUPPL. 2), pp. S52-S59Rotta, N.T., Silva, A.R., Ohlweiler, L., Riesgo, R., Vigabatrin in the treatment of epilepsy in patients with West syndrome and tuberous sclerosis (2003) Arq Neuropsiquiatr, 61, pp. 988-990Curatolo, P., Seri, S., Verdecchia, M., Bombardieri, R., Infantile spasms in tuberous sclerosis complex (2001) Brain Dev, 23, pp. 502-507Elterman, R.D., Shields, W.D., Mansdield, K.A., Nakagawa, J., Randomized trial of vigabatrin in patients with infantile spasms (2001) Neurology, 57, pp. 1416-1421Riikonen, R.S., Steroids or vigabatrin in the treatment of infantile spasms? (2000) Pediatr Neurol, 23, pp. 403-408Antoniuk, S.A., Bruck, I., Spessatto, A., West syndrome: Clinical and electroencephalographic follow up of 70 patients and response to its treatment with adrenocorticotropic hormone, prednisone, vigabatrin, nitrazepam and valproate (2000) Arq Neuropsiquiatr, 58, pp. 683-690Fejerman, N., Cersosimo, R., Caraballo, R., Vigabatrin as a first-choice drug in the treatment of West syndrome (2000) J Child Neurol, 15, pp. 161-165Appleton, R.E., Peters, A.C., Mumford, J.P., Shaw, D.E., Randomised, placebo-controlled study of vigabatrin as first-line treatment of infantile spasms (1999) Epilepsia, 40, pp. 1627-1633Granstrom, M.I., Gaily, E., Liukkonen, E., Treatment of infantile spasms of a population-based study with vigabatrin as the first drug for spasms (1999) Epilepsia, 40, pp. 950-957Cossette, P., Riviello, J.J., Carmant, L., ACTH versus vigabatrin therapy in infantile spasms: A retrospective study (1999) Neurology, 52, pp. 1691-1694Villeneuve, N., Soufflet, C., Plouin, P., Chiron, C., Dulac, O., Treatment of infantile spasms with vigabatrin as first-line therapy and in monoteraphy: Apropos of 70 infants (1998) Arch Pediatr, 5, pp. 731-738Wohlrab, G., Boltshauser, E., Schmitt, B., Vigabatrin as a first-line drug in West syndrome: Clinical and electroencephalographic outcome (1998) Neuropediatrics, 29, pp. 133-136Vigevano, F., Cilio, M.R., Vigabatrin versus ACTH as first-line treatment for infantile spasms: A randomized, prospective study (1997) Epilepsia, 38, pp. 1270-1274Arndt, C.F., Derambure, P., Defoort-Dhellemmes, S., Hache, J.C., Outer retinal dysfunction in patients with vigabatrin (1990) Neurology, 52, pp. 1201-1205Krauss, G.L., Johnson, M.A., Miller, N.R., Vigabatrin-associated retinal cone system dysfunction: Electroretinogram and ophthalmologic findings (1998) Neurology, 50, pp. 614-618Banin, E., Shalev, R.S., Obolensky, A., Neis, R., Chowers, I., Gross-Tsur, V., Retinal function abnormalities in patients treated with vigabatrin (2003) Arch Ophthalmol, 121, pp. 811-816Harding, G.F., Wild, J.M., Robertson, K.A., Electro-oculography, electroretinography, visual evoked potentials, and multifocal electroretinography in patients with vigabatrin-attributed visual field constriction (2000) Epilepsia, 41, pp. 1420-1431Malmgren, K., Ben-Menachem, E., Frisen, L., Vigabatrin visual toxicity: Evolution and dose dependence (2001) Epilepsia, 42, pp. 609-615Hardus, P., Verduin, W.M., Engelsman, M., Visual field loss associated with vigabatrin: Quantification and relation to dosage (2001) Epilepsia, 42, pp. 262-267Jensen, H., Sjo, O., Uldall, P., Vigabatrin and retinal changes (2002) Doc Ophthalmol, 104, pp. 171-180Schmitz, B., Schmidt, T., Jokiel, B., Pfeiffer, S., Tiel-Wilck, K., Ruther, K., Visual field constriction in epilepsy patients treated with vigabatrin and other antiepileptic drugs: A prospective study (2002) J Neurol, 249, pp. 469-475Capovilla, G., Beccaria, F., Montagnini, A., Short-term nonhormonal and nonsteroid treatment in West syndrome (2003) Epilepsia, 44, pp. 1085-1088Koul, R., Chacko, A., Ganesh, A., Bulusu, S., Al Riyami, K., Vigabatrin associated retinal dysfunction in children with epilepsy (2001) Arch Dis Child, 85, pp. 469-473Schmidt, T., Ruther, K., Jokiel, B., Pfeiffer, S., Tiel-Wilck, Schmitz, B., Is visual field constriction in patients treated with vigabatrin reversible? (2002) J Neurol, 249, pp. 1066-1071Giordano, L., Valseriati, D., Vignoli, A., Morescalchi, F., Gandolfo, E., Another case of reversibility of visual-field defect induced by vigabatrin monotherapy: Is young age a favorable factor? (2000) Neurol Sci, 21, pp. 185-186Versino, M., Veggiotti, P., Reversibility of vigabatrin-induced visual-field defect (1999) The Lancet, 354, p. 486Vanhatalo, S., Alen, R., Riikonen, R., Reversed visual field constrictions in children after vigabatrin withdrawal - True retinal recovery or improved test performance only? (2001) Seizure, 10, pp. 508-51

Genetic gains in physic nut using selection indexes

The objective of this work was to estimate genetic gains in physic nut (Jatropha curcas) using selection indexes and to establish the best selection strategy for the species. Direct and indirect selection was carried out using different selection indexes, totalizing 14 strategies. One hundred and seventy five families from the active germplasm bank of Embrapa Agroenergy, Brasília, Brazil, were analyzed in a randomized complete block design with two replicates. The evaluated traits were: grain yield; seeds per fruit; endosperm/seed ratio; seed weight, length, width, and thickness; branches per plant at 0.5, 1.0, and 1.5 m; plant height; stem diameter; canopy projection on rows and between lines; canopy volume; juvenility (days to the first flowering); and height of the first inflorescence. Evaluations were done during the second year of cultivation. The use of selection indexes is relevant to maximize the genetic gains in physic nut, favoring a better distribution of desirable traits. The multiplicative and restrictive indexes are considered the most promising for selection

Systematic study of flow vector decorrelation in sNN=5.02\mathbf{\sqrt{\textit{s}_{_{\bf NN}}}=5.02} TeV Pb--Pb collisions

Measurements of the $p_{\rm T}$-dependent flow vector fluctuations in Pb--Pb collisions at $\sqrt{s_{_{\rm NN}}} = 5.02~\mathrm{TeV}$ using azimuthal correlations with the ALICE experiment at the LHC are presented. A four-particle correlation approach [1] is used to quantify the effects of flow angle and magnitude fluctuations separately. This paper extends previous studies to additional centrality intervals and provides measurements of the $p_{\rm T}$-dependent flow vector fluctuations at $\sqrt{s_{_{\rm NN}}} = 5.02~\mathrm{TeV}$ with two-particle correlations. Significant $p_{\rm T}$-dependent fluctuations of the $\vec{V}_{2}$ flow vector in Pb--Pb collisions are found across different centrality ranges, with the largest fluctuations of up to $\sim$15% being present in the 5% most central collisions. In parallel, no evidence of significant $p_{\rm T}$-dependent fluctuations of $\vec{V}_{3}$ or $\vec{V}_{4}$ is found. Additionally, evidence of flow angle and magnitude fluctuations is observed with more than $5\sigma$ significance in central collisions. These observations in Pb--Pb collisions indicate where the classical picture of hydrodynamic modeling with a common symmetry plane breaks down. This has implications for hard probes at high $p_{\rm T}$, which might be biased by $p_{\rm T}$-dependent flow angle fluctuations of at least 23% in central collisions. Given the presented results, existing theoretical models should be re-examined to improve our understanding of initial conditions, quark--gluon plasma (QGP) properties, and the dynamic evolution of the created system.Measurements of the pT-dependent flow vector fluctuations in Pb–Pb collisions at sNN=5.02TeV using azimuthal correlations with the ALICE experiment at the Large Hadron Collider are presented. A four-particle correlation approach [ALICE Collaboration, Phys. Rev. C 107, L051901 (2023)] is used to quantify the effects of flow angle and magnitude fluctuations separately. This paper extends previous studies to additional centrality intervals and provides measurements of the pT-dependent flow vector fluctuations at sNN=5.02TeV with two-particle correlations. Significant pT-dependent fluctuations of the V⃗2 flow vector in Pb–Pb collisions are found across different centrality ranges, with the largest fluctuations of up to ∼15% being present in the 5% most central collisions. In parallel, no evidence of significant pT-dependent fluctuations of V⃗3 or V⃗4 is found. Additionally, evidence of flow angle and magnitude fluctuations is observed with more than 5σ significance in central collisions. These observations in Pb–Pb collisions indicate where the classical picture of hydrodynamic modeling with a common symmetry plane breaks down. This has implications for hard probes at high pT, which might be biased by pT-dependent flow angle fluctuations of at least 23% in central collisions. Given the presented results, existing theoretical models should be reexamined to improve our understanding of initial conditions, quark–gluon plasma properties, and the dynamic evolution of the created system.Measurements of the $p_{\rm T}$-dependent flow vector fluctuations in Pb-Pb collisions at $\sqrt{s_{_{\rm NN}}} = 5.02~\mathrm{TeV}$ using azimuthal correlations with the ALICE experiment at the LHC are presented. A four-particle correlation approach [1] is used to quantify the effects of flow angle and magnitude fluctuations separately. This paper extends previous studies to additional centrality intervals and provides measurements of the $p_{\rm T}$-dependent flow vector fluctuations at $\sqrt{s_{_{\rm NN}}} = 5.02~\mathrm{TeV}$ with two-particle correlations. Significant $p_{\rm T}$-dependent fluctuations of the $\vec{V}_{2}$ flow vector in Pb-Pb collisions are found across different centrality ranges, with the largest fluctuations of up to $\sim$15% being present in the 5% most central collisions. In parallel, no evidence of significant $p_{\rm T}$-dependent fluctuations of $\vec{V}_{3}$ or $\vec{V}_{4}$ is found. Additionally, evidence of flow angle and magnitude fluctuations is observed with more than $5\sigma$ significance in central collisions. These observations in Pb-Pb collisions indicate where the classical picture of hydrodynamic modeling with a common symmetry plane breaks down. This has implications for hard probes at high $p_{\rm T}$, which might be biased by $p_{\rm T}$-dependent flow angle fluctuations of at least 23% in central collisions. Given the presented results, existing theoretical models should be re-examined to improve our understanding of initial conditions, quark--gluon plasma (QGP) properties, and the dynamic evolution of the created system

Study of flavor dependence of the baryon-to-meson ratio in proton-proton collisions at s=13\sqrt{s} = 13 TeV

International audienceThe production cross sections of ${\rm D^0}$ and $\Lambda^+_{\rm c}$ hadrons originating from beauty-hadron decays (i.e. non-prompt) were measured for the first time at midrapidity ($|y|<0.5$) by the ALICE Collaboration in proton-proton collisions at a center-of-mass energy $\sqrt{s}=13$ TeV. They are described within uncertainties by perturbative QCD calculations employing the fragmentation fractions of beauty quarks to baryons measured at forward rapidity by the LHCb Collaboration. The ${\rm b\overline{b}}$ production cross section per unit of rapidity at midrapidity, estimated from these measurements, is ${\rm d}\sigma_{\rm b\overline{b}}/{\rm d}y|_{|y|<0.5} = 83.1 \pm 3.5 (\mathrm{stat.}) \pm 5.4(\mathrm{syst.}) ^{+12.3}_{-3.2} (\mathrm{extrap.})\,\mu$b. The baryon-to-meson ratios are computed to investigate the hadronization mechanism of beauty quarks. The non-prompt $\Lambda^+_{\rm c}/{\rm D^0}$ production ratio has a similar trend to the one measured for the promptly produced charmed particles and to the p$/\pi^+$ and $\Lambda/{\rm K^0_S}$ ratios, suggesting a similar baryon-formation mechanism among light, strange, charm, and beauty hadrons. The $p_{\rm T}$-integrated non-prompt $\Lambda_{\rm c}/{\rm D^0}$ ratio is found to be significantly higher than the one measured in e$^+$e$^-$ collisions

Investigation of <math><mrow><msup><mi>K</mi><mo>+</mo></msup><msup><mi>K</mi><mo>−</mo></msup></mrow></math> interactions via femtoscopy in Pb-Pb collisions at <math><mrow><msqrt><msub><mi>s</mi><mrow><mi>N</mi><mi>N</mi></mrow></msub></msqrt><mo>=</mo><mn>2.76</mn></mrow></math> TeV at the CERN Large Hadron Collider

Femtoscopic correlations of nonidentical charged kaons (K+K−) are studied in Pb-Pb collisions at a center-of-mass energy per nucleon-nucleon collision sNN=2.76 TeV by ALICE at the CERN Large Hadron Collider. One-dimensional K+K− correlation functions are analyzed in three centrality classes and eight intervals of particle-pair transverse momentum. The Lednický and Luboshitz interaction model used in the K+K− analysis includes the final-state Coulomb interactions between kaons and the final-state interaction through a0(980) and f0(980) resonances. The mass of f0(980) and coupling were extracted from the fit to K+K− correlation functions using the femtoscopic technique. The measured mass and width of the f0(980) resonance are consistent with other published measurements. The height of the ϕ(1020) meson peak present in the K+K− correlation function rapidly decreases with increasing source radius, qualitatively in agreement with an inverse volume dependence. A phenomenological fit to this trend suggests that the ϕ(1020) meson yield is dominated by particles produced directly from the hadronization of the system. The small fraction subsequently produced by final-state interactions could not be precisely quantified with data presented in this paper and will be assessed in future work.Femtoscopic correlations of non-identical charged kaons ($\rm K^+ K^-$) are studied in Pb$-$Pb collisions at a center-of-mass energy per nucleon$-$nucleon collision $\sqrt{s_{\mathrm{NN}}} =2.76$ TeV by ALICE at the LHC. One-dimensional $\rm K^+ K^-$ correlation functions are analyzed in three centrality classes and eight intervals of particle-pair transverse momentum. The Lednický and Luboshitz interaction model used in the $\rm K^+ K^-$ analysis includes the final-state Coulomb interactions between kaons and the final-state interaction through $a_{0}$(980) and $f_{0}$(980) resonances. The mass of $f_{0}$(980) and coupling were extracted from the fit to $\rm K^+ K^-$ correlation functions using the femtoscopic technique. The measured mass and width of the $f_{0}$(980) resonance are consistent with other published measurements. The height of the $\phi$(1020) meson peak present in the $\rm K^+ K^-$ correlation function rapidly decreases with increasing source radius, qualitatively in agreement with an inverse volume dependence. A phenomenological fit to this trend suggests that the $\phi$(1020) meson yield is dominated by particles produced directly from the hadronization of the system. The small fraction subsequently produced by final-state interactions could not be precisely quantified with data presented in this paper and will be assessed in future work

Data-driven precision determination of the material budget in ALICE

International audienceThe knowledge of the material budget with a high precision is fundamental for measurements of direct photon production using the photon conversion method due to its direct impact on the total systematic uncertainty. Moreover, it influences many aspects of the charged-particle reconstruction performance. In this article, two procedures to determine data-driven corrections to the material-budget description in ALICE simulation software are developed. One is based on the precise knowledge of the gas composition in the Time Projection Chamber. The other is based on the robustness of the ratio between the produced number of photons and charged particles, to a large extent due to the approximate isospin symmetry in the number of produced neutral and charged pions. Both methods are applied to ALICE data allowing for a reduction of the overall material budget systematic uncertainty from 4.5% down to 2.5%. Using these methods, a locally correct material budget is also achieved. The two proposed methods are generic and can be applied to any experiment in a similar fashion

First measurement of antideuteron number fluctuations at energies available at the Large Hadron Collider

The first measurement of event-by-event antideuteron number fluctuations in high energy heavy-ion collisions is presented. The measurements are carried out at midrapidity (|\eta| |η|<0.8) as a function of collision centrality in Pb-Pb collisions at sNN=5.02  TeV using the ALICE detector. A significant negative correlation between the produced antiprotons and antideuterons is observed in all collision centralities. The results are compared with a state-of-the-art coalescence calculation. While it describes the ratio of higher order cumulants of the antideuteron multiplicity distribution, it fails to describe quantitatively the magnitude of the correlation between antiproton and antideuteron production. On the other hand, thermal-statistical model calculations describe all the measured observables within uncertainties only for correlation volumes that are different with respect to those describing proton yields and a similar measurement of net-proton number fluctuations.The first measurement of event-by-event antideuteron number fluctuations in high energy heavy-ion collisions is presented. The measurements are carried out at midrapidity (|\eta| < 0.8$) as a function of collision centrality in Pb$-$Pb collisions at$\sqrt{s_{\rm NN}} = 5.02$ TeV using the ALICE detector. A significant negative correlation between the produced antiprotons and antideuterons is observed in all collision centralities. The results are compared with a state-of-the-art coalescence calculation. While it describes the ratio of higher order cumulants of the antideuteron multiplicity distribution, it fails to describe quantitatively the magnitude of the correlation between antiproton and antideuteron production. On the other hand, thermal-statistical model calculations describe all the measured observables within uncertainties only for correlation volumes that are different with respect to those describing proton yields and a similar measurement of net-proton number fluctuations

Higher-order correlations between different moments of two flow amplitudes in Pb−-Pb collisions at sNN=5.02\sqrt{s_{\rm NN}}=5.02 TeV

International audienceThe correlations between different moments of two flow amplitudes, extracted with the recently developed asymmetric cumulants, are measured in Pb$-$Pb collisions at $\sqrt{s_{\rm NN}} = 5.02$ TeV recorded by the ALICE detector at the LHC. The magnitudes of the measured observables show a dependence on the different moments as well as on the collision centrality, indicating the presence of non-linear response in all even moments up to the eighth. Furthermore, the higher-order asymmetric cumulants show different signatures than the symmetric and lower-order asymmetric cumulants. Comparisons with state-of-the-art event generators using two different parameterizations obtained from Bayesian optimization show differences between data and simulations in many of the studied observables, indicating a need for further tuning of the models behind those event generators. These results provide new and independent constraints on the initial conditions and transport properties of the system created in heavy-ion collisions

Measurement of the lifetime and Λ\Lambda separation energy of Λ3H^{3}_{\Lambda}\mathrm H

The most precise measurements to date of the $^{3}_{\Lambda}\mathrm H$ lifetime $\tau$ and $\Lambda$ separation energy ${\rm B}_{\Lambda}$ are obtained using the data sample of Pb-Pb collisions at $\sqrt{s_{\mathrm{NN}}}=$ 5.02 TeV collected by ALICE at the LHC. The $^{3}_{\Lambda}\mathrm H$ is reconstructed via its charged two-body mesonic decay channel ($^{3}_{\Lambda}\mathrm{H} \rightarrow$ $^3$He + $\pi^-$ and the charge-conjugate process). The measured values $\tau = [253 \pm 11 \text{ (stat.)} \pm 6 \text{ (syst.)}]$ ps and ${\rm B}_{\Lambda}= [72 \pm 63 \text{ (stat.)} \pm 36 \text{ (syst.)}]$ keV are compatible with predictions from effective field theories and conclusively confirm that the $^{3}_{\Lambda}\mathrm H$ is a weakly-bound system.The most precise measurements to date of the HΛ3 lifetime τ and Λ separation energy BΛ are obtained using the data sample of Pb-Pb collisions at sNN=5.02  TeV collected by ALICE at the LHC. The HΛ3 is reconstructed via its charged two-body mesonic decay channel (HΛ3→He3+π- and the charge-conjugate process). The measured values τ=[253±11(stat)±6(syst)]  ps and BΛ=[102±63(stat)±67(syst)]  keV are compatible with predictions from effective field theories and confirm that the HΛ3 structure is consistent with a weakly bound system.The most precise measurements to date of the $^{3}_{\Lambda}\mathrm H$ lifetime $\tau$ and $\Lambda$ separation energy ${\rm B}_{\Lambda}$ are obtained using the data sample of Pb-Pb collisions at $\sqrt{s_{\mathrm{NN}}}=$ 5.02 TeV collected by ALICE at the LHC. The $^{3}_{\Lambda}\mathrm H$ is reconstructed via its charged two-body mesonic decay channel ($^{3}_{\Lambda}\mathrm{H} \rightarrow$$^3$He + $\pi^-$ and the charge-conjugate process). The measured values $\tau = [253 \pm 11 \text{ (stat.)} \pm 6 \text{ (syst.)}]$ ps and ${\rm B}_{\Lambda}= [102 \pm 63 \text{ (stat.)} \pm 67 \text{ (syst.)}]$ keV are compatible with predictions from effective field theories and confirm that the $^{3}_{\Lambda}\mathrm H$ structure is consistent with a weakly-bound system