We tested the hypothesis that plasma neurofilament light chain (NfL) identifies asymptomatic carriers of familial frontotemporal lobar degeneration (FTLD)-causing mutations at risk of disease ...progression.
Baseline plasma NfL concentrations were measured with single-molecule array in original (n = 277) and validation (n = 297) cohorts.
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mutation carriers and noncarriers from the same families were classified by disease severity (asymptomatic, prodromal, and full phenotype) using the CDR Dementia Staging Instrument plus behavior and language domains from the National Alzheimer's Disease Coordinating Center FTLD module (CDR+NACC-FTLD). Linear mixed-effect models related NfL to clinical variables.
In both cohorts, baseline NfL was higher in asymptomatic mutation carriers who showed phenoconversion or disease progression compared to nonprogressors (original: 11.4 ± 7 pg/mL vs 6.7 ± 5 pg/mL,
= 0.002; validation: 14.1 ± 12 pg/mL vs 8.7 ± 6 pg/mL,
= 0.035). Plasma NfL discriminated symptomatic from asymptomatic mutation carriers or those with prodromal disease (original cutoff: 13.6 pg/mL, 87.5% sensitivity, 82.7% specificity; validation cutoff: 19.8 pg/mL, 87.4% sensitivity, 84.3% specificity). Higher baseline NfL correlated with worse longitudinal CDR+NACC-FTLD sum of boxes scores, neuropsychological function, and atrophy, regardless of genotype or disease severity, including asymptomatic mutation carriers.
Plasma NfL identifies asymptomatic carriers of FTLD-causing mutations at short-term risk of disease progression and is a potential tool to select participants for prevention clinical trials.
ClinicalTrials.gov Identifier: NCT02372773 and NCT02365922.
This study provides Class I evidence that in carriers of FTLD-causing mutations, elevation of plasma NfL predicts short-term risk of clinical progression.
Unlike familial Alzheimer's disease, we have been unable to accurately predict symptom onset in presymptomatic familial frontotemporal dementia (f-FTD) mutation carriers, which is a major hurdle to ...designing disease prevention trials. We developed multimodal models for f-FTD disease progression and estimated clinical trial sample sizes in C9orf72, GRN and MAPT mutation carriers. Models included longitudinal clinical and neuropsychological scores, regional brain volumes and plasma neurofilament light chain (NfL) in 796 carriers and 412 noncarrier controls. We found that the temporal ordering of clinical and biomarker progression differed by genotype. In prevention-trial simulations using model-based patient selection, atrophy and NfL were the best endpoints, whereas clinical measures were potential endpoints in early symptomatic trials. f-FTD prevention trials are feasible but will likely require global recruitment efforts. These disease progression models will facilitate the planning of f-FTD clinical trials, including the selection of optimal endpoints and enrollment criteria to maximize power to detect treatment effects.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Inclusive transverse momentum spectra of eta mesons have been measured within p(T)=2-10 GeV/c at midrapidity by the PHENIX experiment in Au+Au collisions at root s(NN) = 200 GeV. In central Au+Au the ...eta yields are significantly suppressed compared to peripheral Au+Au, d+Au, and p+p yields scaled by the corresponding number of nucleon-nucleon collisions. The magnitude, centrality, and p(T) dependence of the suppression is common, within errors, for eta and pi(0). The ratio of eta to pi(0) spectra at high p(T) amounts to 0.40 < R-eta/pi(0)< 0.48 for the three systems, in agreement with the world average measured in hadronic and nuclear reactions and, at large scaled momentum, in e(+)e(-) collisions.
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The anisotropy parameter (v(2)), the second harmonic of the azimuthal particle distribution, has been measured with the PHENIX detector in Au+Au collisions at roots(NN)=200 GeV for identified and ...inclusive charged particle production at central rapidities (eta<0.35) with respect to the reaction plane defined at high rapidities (eta=3-4 ). We observe that the v(2) of mesons falls below that of (anti)baryons for p(T)>2 GeV/c, in marked contrast to the predictions of a hydrodynamical model. A quark-coalescence model is also investigated.
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The PHENIX experiment has measured midrapidity transverse momentum spectra (0.4<p(T)<4.0 GeV/c) of single electrons as a function of centrality in Au+Au collisions at roots(NN) = 200 GeV. ...Contributions from photon conversions and Dalitz decays of light neutral mesons are measured by introducing a thin (1.7% X-0) converter into the PHENIX acceptance and are statistically removed. The subtracted nonphotonic electron spectra are primarily due to the semileptonic decays of hadrons containing heavy quarks, mainly charm at lower p(T). For all centralities, the charm production cross section is found to scale with the nuclear overlap function, T-AA. For minimum-bias collisions the charm cross section per binary collision is N-c (c) over bar/T-AA=622+/-57(stat)+/-160(syst) mub.
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The invariant differential cross section for inclusive neutral-pion production in p+p collisions at roots=200 GeV has been measured at midrapidity (eta<0.35) over the range 1<p(T)less than or similar ...to14 GeV/c by the PHENIX experiment at the Relativistic Heavy Ion Collider. Predictions of next-to-leading order perturbative QCD calculations are consistent with these measurements. The precision of our result is sufficient to differentiate between prevailing gluon-to-pion fragmentation functions.
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Transverse single-spin asymmetries to probe the transverse-spin structure of the proton have been measured for neutral pions and nonidentified charged hadrons from polarized proton-proton collisions ...at midrapidity and root s = 200 GeV. The data cover a transverse momentum (pT) range 1.0-5.0 GeV/c for neutral pions and 0.5-5.0 GeV/c for charged hadrons, at a Feynman-x value of approximately zero. The asymmetries seen in this previously unexplored kinematic region are consistent with zero within errors of a few percent. In addition, the inclusive charged hadron cross section at midrapidity from 0.5 < P-T < 7.0 GeV/c is presented and compared to next-to-leading order perturbative QCD ( pQCD) calculations. Successful description of the unpolarized cross section above similar to 2 GeV/c suggests that pQCD is applicable in the interpretation of the asymmetry results in the relevant kinematic range.
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Bose-Einstein correlations of identically charged pion pairs were measured by the PHENIX experiment at midrapidity in Au+Au collisions at roots(NN)=200 GeV. The Bertsch-Pratt radius parameters were ...determined as a function of the transverse momentum of the pair and as a function of the centrality of the collision. Using the standard core-halo partial Coulomb fits, and a new parametrization which constrains the Coulomb fraction as determined from the unlike-sign pion correlation, the ratio R-out/R-side is within 0.8-1.1 for 0.25<<k(T)><1.2 GeV/c. The centrality dependence of all radii is well described by a linear scaling in N-part(1/3), and R-out/R-side for <k(T)>similar to0.45 GeV/c is approximately constant at unity as a function of centrality.
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We report on the yield of protons and antiprotons, as a function of centrality and transverse momentum, in Au+Au collisions at rootS(NN)=200 GeV measured at midrapidity by the PHENIX experiment at ...the BNL Relativistic Heavy Ion Collider. In central collisions at intermediate transverse momenta (1.5<p(T)<4.5 GeV/c) a significant fraction of all produced particles are protons and antiprotons. They show a centrality-scaling behavior different from that of pions. The (p) over bar/pi and p/pi ratios are enhanced compared to peripheral Au+Au, p+p, and e(+)e(-) collisions. This enhancement is limited to p(T)<5 GeV/c as deduced from the ratio of charged hadrons to pi(0) measured in the range 1.5<p(T)<9 GeV/c.
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