Two-particle correlations with
K
S
0
,
Λ
/
Λ
¯
, and charged hadrons as trigger particles in the transverse momentum range
8
<
p
T
,
trig
<
16
GeV/
c
, and associated charged particles within
1
<
p
...T
,
assoc
<
8
GeV/
c
, are studied at midrapidity in pp and central Pb–Pb collisions at a centre-of-mass energy per nucleon–nucleon collision
s
NN
=
5.02
TeV with the ALICE detector at the LHC. After subtracting the contributions of the flow background, the per-trigger yields are extracted on both the near and away sides, and the ratio in Pb–Pb collisions with respect to pp collisions (
I
AA
) is computed. The per-trigger yield in Pb–Pb collisions on the away side is strongly suppressed to the level of
I
AA
≈
0.6
for
p
T
,
assoc
>
3
GeV/
c
as expected from strong in-medium energy loss, while an enhancement develops at low
p
T
,
assoc
on both the near and away sides, reaching
I
AA
≈
1.8
and 2.7 respectively. These findings are in good agreement with previous ALICE measurements from two-particle correlations triggered by neutral pions (
π
0
–h) and charged hadrons (h–h) in Pb–Pb collisions at
s
NN
=
2.76
TeV. Moreover, the correlations with
K
S
0
mesons and
Λ
/
Λ
¯
baryons as trigger particles are compared to those of inclusive charged hadrons. The results are compared with the predictions of Monte Carlo models.
Objective
To characterize the dose‐related pharmacokinetics of the immunosuppressant agent sirolimus (formerly rapamycin) in kidney transplant patients by use of two‐stage and nonlinear mixed‐effect ...model population methods.
Methods
Patients (n = 36) from three centers (Germany, the United Kingdom, and Sweden) who received steady‐state oral doses of cyclosporine (ciclosporin) were assessed after single oral administration of sirolimus at doses of 3, 5, 10, and 15 mg/m2. Plasma and whole blood sirolimus samples were analyzed by a high‐performance liquid chromatographic/mass spectrophotometric method. Simultaneous fitting used biexponential functions with intercept/slope or clearance/volume terms, as well as first‐order absorption (ka) and a lag‐time.
Results
The nonlinear mixed‐effect model method (P‐Pharm) provided a better characterization of sirolimus kinetics, especially for the absorption and distribution phases where fewer data were available per patient. Sirolimus distribution between whole blood and plasma was concentration‐independent, with a mean blood/plasma ratio (coefficient of variation) of 30.9 (48.5%). Elimination was not influenced by dose, as shown by estimates of the terminal half‐life of 63 hours (27.5%) and apparent oral blood clearance of 8.9 L/hr (38.2%). Sirolimus distribution parameters were influenced by body weight and surface area. Sirolimus was rapidly absorbed, as shown by the absorption lag‐time of 0.27 hour (35.1%), and ka of 2.77 hr−1 (48.4%). The concomitant administration of sirolimus and cyclosporine did not reveal any pharmacokinetic interaction.
Conclusion
This report provides an initial population pharmacokinetics of sirolimus in kidney transplant recipients receiving cyclosporine concurrently. Sirolimus blood and plasma pharmacokinetics were biexponential and linear for doses from 3 to 15 mg/m2. No pharmacokinetic interaction was found between sirolimus and cyclosporine.
Clinical Pharmacology & Therapeutics (1997) 61, 416–428; doi:
The inclusive production cross sections at forward rapidity of Formula: see text, Formula: see text, Formula: see text(1S) and Formula: see text(2S) are measured in Formula: see text collisions at ...Formula: see text with the ALICE detector at the LHC. The analysis is based on a data sample corresponding to an integrated luminosity of 1.35 pbFormula: see text. Quarkonia are reconstructed in the dimuon-decay channel and the signal yields are evaluated by fitting the Formula: see text invariant mass distributions. The differential production cross sections are measured as a function of the transverse momentum Formula: see text and rapidity Formula: see text, over the ranges Formula: see text GeV/c for Formula: see text, Formula: see text GeV/c for all other resonances and for Formula: see text. The measured cross sections integrated over Formula: see text and Formula: see text, and assuming unpolarized quarkonia, are: Formula: see text Formula: see textb, Formula: see text Formula: see textb, Formula: see text nb and Formula: see text nb, where the first uncertainty is statistical and the second one is systematic. The results are compared to measurements performed by other LHC experiments and to theoretical models.
Both obesity and chronic inflammation are often associated with insulin resistance and type 2 diabetes. The Zucker diabetic fatty (ZDF) rat (fa/fa) is an obese animal model frequently used in type 2 ...diabetes research. The current study determines whether chronic administration (from 5 weeks of age through 24 weeks of age) of salsalate, a salicylate with anti-inflammatory properties, would be effective in mitigating diabetes disease progression in ZDF rats. Although a trend existed for lower blood glucose in the salsalate-treated group, significant differences were obscured by high animal-level variability. However, even in the non-drug-treated group, not all ZDF rats became diabetic as expected. Therefore, animals were parsed into two groups, regardless of drug treatment: normoglycemic ZDF rats, which maintained blood glucose profiles identical to nondiabetic Zucker lean rats (ZLRs), and hyperglycemic ZDF rats, which exhibited progressive elevation in blood glucose. To ascertain the differences between ZDF rats that became hyperglycemic and those that did not, relevant physiological indices and expression levels of adiponectin, tumor necrosis factor-α, interleukin-6, and glucocorticoid-induced leucine zipper messenger RNAs in adipose tissue were measured at sacrifice. Plasma C-reactive protein concentrations and expression levels of cytokine and glucocorticoid-induced leucine zipper messenger RNAs suggested more prevalent chronic inflammation in hyperglycemic animals. Early elevation of the insulin-sensitizing adipokine, adiponectin, was present in both ZDF groups, with the rate of its age-related decline faster in hyperglycemic animals. The most marked difference between the two groups of ZDF animals was in insulin output. Although the two ZDF populations had very similar elevated plasma insulin concentrations for the first 10 weeks, after that time, plasma insulin decreased markedly in the animals that became hyperglycemic, whereas it remained high in the normoglycemic ZDF rats. Thus, hyperglycemic ZDF animals exhibit both insulin resistance and progressive beta cell failure, whereas normoglycemic ZDF rats exhibit a lesser degree of insulin resistance that does not progress to beta cell failure. In these respects, the normoglycemic ZDF rats appear to revert back to a phenotype that strongly resembles that of nondiabetic Zucker fatty rats from which they were derived.
The production of
π
±
,
K
±
,
K
S
0
,
K
∗
(
892
)
0
,
p
,
ϕ
(
1020
)
,
Λ
,
Ξ
-
,
Ω
-
, and their antiparticles was measured in inelastic proton–proton (pp) collisions at a center-of-mass energy of
s
...= 13 TeV at midrapidity (
|
y
|
<
0.5
) as a function of transverse momentum (
p
T
) using the ALICE detector at the CERN LHC. Furthermore, the single-particle
p
T
distributions of
K
S
0
,
Λ
, and
Λ
¯
in inelastic pp collisions at
s
=
7
TeV are reported here for the first time. The
p
T
distributions are studied at midrapidity within the transverse momentum range
0
≤
p
T
≤
20
GeV/
c
, depending on the particle species. The
p
T
spectra, integrated yields, and particle yield ratios are discussed as a function of collision energy and compared with measurements at lower
s
and with results from various general-purpose QCD-inspired Monte Carlo models. A hardening of the spectra at high
p
T
with increasing collision energy is observed, which is similar for all particle species under study. The transverse mass and
x
T
≡
2
p
T
/
s
scaling properties of hadron production are also studied. As the collision energy increases from
s
= 7–13 TeV, the yields of non- and single-strange hadrons normalized to the pion yields remain approximately constant as a function of
s
, while ratios for multi-strange hadrons indicate enhancements. The
p
T
-differential cross sections of
π
±
,
K
±
and
p
(
p
¯
) are compared with next-to-leading order perturbative QCD calculations, which are found to overestimate the cross sections for
π
±
and
p
(
p
¯
) at high
p
T
.
(ProQuest: ... denotes formulae and/or non-USASCII text omitted; see image) The ratios of yields of anti-baryons to baryons probes the mechanisms of baryon-number transport. Results for ..., ..., ... ...and ... in pp collisions at ..., measured with the ALICE detector at the LHC, are reported. Within the experimental uncertainties and ranges covered by our measurement, these ratios are independent of rapidity, transverse momentum and multiplicity for all measured energies. The results are compared to expectations from event generators, such as PYTHIA and HIJING/B, that are used to model the particle production in pp collisions. The energy dependence of ..., ..., ... and ..., reaching values compatible with unity for ..., complement the earlier ... measurement of ALICE. These dependencies can be described by exchanges with the Regge-trajectory intercept of ..., which are suppressed with increasing rapidity interval Δy. Any significant contribution of an exchange not suppressed at large Δy (reached at LHC energies) is disfavoured.
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