129 research outputs found
Lipoprotein(a) Genotype Influences the Clinical Diagnosis of Familial Hypercholesterolemia
Background Evidence suggests that LPA risk genotypes are a possible contributor to the clinical diagnosis of familial hypercholesterolemia (FH). This study aimed at determining the prevalence of LPA risk variants in adult individuals with FH enrolled in the Italian LIPIGEN (Lipid Transport Disorders Italian Genetic Network) study, with (FH/M+) or without (FH/M-) a causative genetic variant. Methods and ResultsAn lp(a) [lipoprotein(a)] genetic score was calculated by summing the number risk-increasing alleles inherited at rs3798220 and rs10455872 variants. Overall, in the 4.6% of 1695 patients with clinically diagnosed FH, the phenotype was not explained by a monogenic or polygenic cause but by genotype associated with high lp(a) levels. Among 765 subjects with FH/M- and 930 subjects with FH/M+, 133 (17.4%) and 95 (10.2%) were characterized by 1 copy of either rs10455872 or rs3798220 or 2 copies of either rs10455872 or rs3798220 (lp(a) score >= 1). Subjects with FH/M- also had lower mean levels of pretreatment low-density lipoprotein cholesterol than individuals with FH/M+ (t test for difference in means between FH/M- and FH/M+ groups <0.0001); however, subjects with FH/M- and lp(a) score >= 1 had higher mean (SD) pretreatment low-density lipoprotein cholesterol levels (223.47 [50.40] mg/dL) compared with subjects with FH/M- and lp(a) score=0 (219.38 [54.54] mg/dL for), although not statistically significant. The adjustment of low-density lipoprotein cholesterol levels based on lp(a) concentration reduced from 68% to 42% the proportion of subjects with low-density lipoprotein cholesterol level >= 190 mg/dL (or from 68% to 50%, considering a more conservative formula). ConclusionsOur study supports the importance of measuring lp(a) to perform the diagnosis of FH appropriately and to exclude that the observed phenotype is driven by elevated levels of lp(a) before performing the genetic test for FH
Expanding the toolbox of metabolically stable lipid prodrug strategies
Nucleoside- and nucleotide-based therapeutics are indispensable treatment options for patients suffering from malignant and viral diseases. These agents are most commonly administered to patients as prodrugs to maximize bioavailability and efficacy. While the literature provides a practical prodrug playbook to facilitate the delivery of nucleoside and nucleotide therapeutics, small context-dependent amendments to these popular prodrug strategies can drive dramatic improvements in pharmacokinetic (PK) profiles. Herein we offer a brief overview of current prodrug strategies, as well as a case study involving the fine-tuning of lipid prodrugs of acyclic nucleoside phosphonate tenofovir (TFV), an approved nucleotide HIV reverse transcriptase inhibitor (NtRTI) and the cornerstone of combination antiretroviral therapy (cART). Installation of novel lipid terminal motifs significantly reduced fatty acid hepatic ω-oxidation while maintaining potent antiviral activity. This work contributes important insights to the expanding repertoire of lipid prodrug strategies in general, but particularly for the delivery and distribution of acyclic nucleoside phosphonates
Evaluating the effects of entry regulations and firing costs on international income differences
Charged jet cross sections and properties in proton-proton collisions at root s=7 TeV
The differential charged jet cross sections, jet fragmentation distributions, and jet shapes are measured in minimum bias proton-proton collisions at center-of-mass energy root s = 7 TeV using the ALICE detector at the LHC. Jets are reconstructed from charged particle momenta in the midrapidity region using the sequential recombination k(T) and anti-k(T) as well as the SISCone jet finding algorithms with several resolution parameters in the range R = 0.2-0.6. Differential jet production cross sections measured with the three jet finders are in agreement in the transverse momentum (p(T)) interval 20 ) of the reconstructed jet p(T). The fragmentation of leading jets with R = 0.4 using scaled p(T) spectra of the jet constituents is studied. The measurements are compared to model calculations from event generators (PYTHIA, PHOJET, HERWIG). The measured radial density distributions and distributions are well described by the PYTHIA model (tune Perugia-2011). The fragmentation distributions are better described by HERWIG.Peer reviewe
Centrality dependence of inclusive J/ψ production in p-Pb collisions at s N N = 5.02 TeV
We present a measurement of inclusive J/psi production in p-Pb collisions at root S-NN = 5.02 TeV as a function of the centrality of the collision, as estimated from the energy deposited in the Zero Degree Calorimeters. The measurement is performed with the ALICE detector down to zero transverse momentum, p(T), in the backward (-4.46 < y(cms) < -2.96) and forward (2.03 < y(cms) < 3.53) rapidity intervals in the dimuon decay channel and in the mid-rapidity region (-1.37 < y(cms) < 0.43) in the dielectron decay channel. The backward and forward rapidity intervals correspond to the Pb-going and p-going direction, respectively. The p(T)-differential J/psi production cross section at backward and forward rapidity is measured for several centrality classes, together with the corresponding average p(T) and p(T)(2) values. The nuclear modification factor is presented as a function of centrality for the three rapidity intervals, and as a function of p(T) for several centrality classes at backward and forward rapidity. At mid-and forward rapidity, the J/psi yield is suppressed up to 40% compared to that in pp interactions scaled by the number of binary collisions. The degree of suppression increases towards central p-Pb collisions at forward rapidity, and with decreasing p(T) of the J/psi. At backward rapidity, the nuclear modification factor is compatible with unity within the total uncertainties, with an increasing trend from peripheral to central p-Pb collisions
Inclusive photon production at forward rapidities in proton\u2013proton collisions at 1a s = 0.9, 2.76 and 7 TeV
The multiplicity and pseudorapidity distribu- tions of inclusive photons have been measured at forward rapidities (2.3 < \u3b7 < 3.9) in proton\u2013proton collisions at three center-of-mass energies, 1as = 0.9, 2.76 and 7 TeV using the ALICE detector. It is observed that the increase in the average photon multiplicity as a function of beam energy is compatible with both a logarithmic and a power-law dependence. The relative increase in average photon multi- plicity produced in inelastic pp collisions at 2.76 and 7 TeV center-of-mass energies with respect to 0.9 TeV are 37.2 \ub1 0.3% (stat) \ub1 8.8% (sys) and 61.2 \ub1 0.3% (stat) \ub1 7.6% (sys), respectively. The photon multiplicity distributions for all center-of-mass energies are well described by negative binomial distributions. The multiplicity distributions are also presented in terms of KNO variables. The results are com- pared to model predictions, which are found in general to underestimate the data at large photon multiplicities, in par- ticular at the highest center-of-mass energy. Limiting frag- mentation behavior of photons has been explored with the data, but is not observed in the measured pseudorapidity range
Production of Σ(1385)± and Ξ(1530)0 in proton–proton collisions at √s = 7 TeV
The production of the strange and double-strange baryon resonances (Σ(1385)±, Ξ(1530)0) has been measured at mid-rapidity (|y| <0.5) in proton–proton collisions at s√ = 7 TeV with the ALICE detector at the LHC. Transverse momentum spectra for inelastic collisions are compared to QCD-inspired models, which in general underpredict the data. A search for the ϕ(1860) pentaquark, decaying in the Ξπ channel, has been carried out but no evidence is seen
Measurement of charged jet suppression in Pb-Pb collisions at = 2.76 TeV
A measurement of the transverse momentum spectra of jets in Pb-Pb collisions at √sNN = 2.76TeV is reported. Jets are reconstructed from charged particles using the anti-k T jet algorithm with jet resolution parameters R of 0.2 and 0.3 in pseudo-rapidity |η| < 0.5. The transverse momentum p T of charged particles is measured down to 0.15 GeV/c which gives access to the low p T fragments of the jet. Jets found in heavy-ion collisions are corrected event-by-event for average background density and on an inclusive basis (via unfolding) for residual background fluctuations and detector effects. A strong suppression of jet production in central events with respect to peripheral events is observed. The suppression is found to be similar to the suppression of charged hadrons, which suggests that substantial energy is radiated at angles larger than the jet resolution parameter R = 0.3 considered in the analysis. The fragmentation bias introduced by selecting jets with a high p T leading particle, which rejects jets with a soft fragmentation pattern, has a similar effect on the jet yield for central and peripheral events. The ratio of jet spectra with R = 0.2 and R = 0.3 is found to be similar in Pb-Pb and simulated PYTHIA pp events, indicating no strong broadening of the radial jet structure in the reconstructed jets with R < 0.3
Multiplicity dependence of jet-like two-particle correlation structures in p-Pb collisions at 1asNN=5.02 TeV
Two-particle angular correlations between unidentified charged trigger and associated particles are measured by the ALICE detector in p\u2013Pb collisions at a nucleon\u2013nucleon centre-of-mass energy of 5.02 TeV. The transverse-momentum range 0.7 < pT,assoc < pT,trig < 5.0 GeV/c is examined, to include correlations induced by jets originating from low momentum-transfer scatterings (minijets). The correlations expressed as associated yield per trigger particle are obtained in the pseudorapidity range |\u3b7| < 0.9. The near-side long-range pseudorapidity correlations observed in high-multiplicity p\u2013Pb collisions are subtracted from both near-side short-range and away-side correlations in order to remove the non-jet-like components. The yields in the jet-like peaks are found to be invariant with event multiplicity with the exception of events with low multiplicity. This invariance is consistent with the particles being produced via the incoherent fragmentation of multiple parton\u2013parton scatterings, while the yield related to the previously observed ridge structures is not jet-related. The number of uncorrelated sources of particle production is found to increase linearly with multiplicity, suggesting no saturation of the number of multi-parton interactions even in the highest multiplicity p\u2013Pb collisions. Further, the number scales only in the intermediate multiplicity region with the number of binary nucleon\u2013nucleon collisions estimated with a Glauber Monte-Carlo simulation
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