text:
Page 1
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Mar. 2006, p. 874–879
Copyright © 2006, American Society for Microbiology. All Rights Reserved.
Vol. 50, No. 3
Pharmacokinetics of Telbivudine following Oral Administration of
Escalating Single and Multiple Doses in Patients with Chronic
Hepatitis B Virus Infection: Pharmacodynamic Implications
Xiao-Jian Zhou,1* Seng-Gee Lim,2Deborah M. Lloyd,1George C. Chao,1
Nathaniel A. Brown,1and Ching-Lung Lai3
Idenix Pharmaceuticals Inc., 60 Hampshire Street, Cambridge, Massachusetts 021391; National University Hospital,
5 Lower Kent Ridge Road, Singapore 119074, Singapore2; and Division of Hepatology, University of Hong Kong,
Queen Mary Hospital, 102 Pok Fu Lam Road, Pok Fu Lam, Hong Kong, China3
Received 11 July 2005/Returned for modification 1 September 2005/Accepted 8 December 2005
The pharmacokinetics of telbivudine were evaluated in adult patients with chronic hepatitis B virus (HBV)
infection following once-daily oral administration at escalating doses of 25, 50, 100, 200, 400, and 800 mg/day for 4
weeks. Telbivudine was rapidly absorbed after oral administration, with the median times Tmaxto the maximum
plasma concentration (Cmax) ranging from 0.8 to 3.0 h postdosing across cohorts. Single-dose and steady-state
maximum Cmaxs and the areas under the plasma concentration-time curve from time zero to time t (AUC0–ts)
increased proportionally with dose. At steady-state, the values of Cmaxand AUC0–twere higher than those obtained
after the administration of a single dose, indicative of a slight accumulation, with the ratios of the steady-state value
to the value after the administration of a single dose ranging from 1.14 to 1.49 for Cmaxand from 1.40 to 1.70 for
the substantial steady-state trough plasma levels observed in the groups receiving doses of 100 to 800 mg were
clearly indicative of the presence of a second slower elimination phase, with the mean estimated half-lives ranging
maximum-effect modeling established a quantitative relationship between a reduction in serum HBV DNA levels
and parameters of drug exposure, in particular, the steady-state Cmaxand AUC0–t. In summary, this study showed
that telbivudine exhibits dose-proportional plasma pharmacokinetics with sustained steady-state drug exposure
and exposure-related antiviral activity, supporting the need for further clinical studies by use of a once-daily
regimen in patients with chronic HBV infection.
Telbivudine (?-L-2?-deoxythymidine) is an L-configured nucle-
oside with potent and specific activities against hepatitis B virus
(HBV) and other hepadnaviruses and no appreciable activity
against human immunodeficiency virus or other viruses (3). The
in vitro median effective concentration of telbivudine for reducing
extracellular DNA levels in HBV-expressing hepatoma cell line
2.2.15 was 0.19 ?M (?0.05 ?g/ml). In woodchucks chronically
infected with woodchuck HBV, up to 28 days of telbivudine treat-
ment produced consistent, multilog reductions in circulating se-
rum woodchuck HBV DNA levels (3).
In vitro toxicological assessments produced no adverse
findings (1–3). The 50% cytotoxic concentration of telbivu-
dine in 2.2.15 cells was ?2,00 ?M (?500 ?g/ml), indicating
that it has an excellent therapeutic index in cell culture (3).
Other in vitro results suggested that telbivudine is unlikely
to be associated with hematologic or mitochondrial toxici-
ties, peripheral neuropathy, or myopathy (3). Mutagenic test
results were negative (1).
Acute and subchronic toxicology studies did not identify any
preclinical safety issues for telbivudine. In acute and sub-
chronic (28-day) toxicity studies conducted with rats and mon-
keys with daily doses up to 2,000 mg/kg of body weight, no
treatment-related clinical abnormalities were observed (1, 2).
Preclinical pharmacological studies conducted with cyno-
molgus monkeys following the administration of oral and in-
travenous doses showed that telbivudine was well absorbed,
with an oral bioavailability of 68% (4). Renal clearance appeared
to be the major pathway of telbivudine elimination (4). Prelimi-
nary results from a mass balance study with rats and14C-labeled
telbivudine indicated no major plasma or urine metabolite
(unpublished data).
The encouraging preclinical anti-HBV activity and favorable
safety profile of telbivudine prompted a phase I/II study with
patients with chronic HBV infection. The objectives were to
evaluate the safety, pharmacokinetics, and antiviral activity of
telbivudine administered orally at escalating doses starting at
25 mg/day for 4 weeks. Clinical efficacy and safety results have
recently been reported in more detail elsewhere (6). This re-
port provides a detailed pharmacokinetic analysis of telbivu-
dine and elaborates the pharmacodynamic relationships with
implications for telbivudine dose selection in subsequent phase
IIb (7) and phase III clinical safety and efficacy trials.
Study population. Patients meeting the following inclusion criteria were eli-
gible for the study: age of 18 years or older; documented chronic HBV infection,
as determined by the presence of serum HBsAg for ?6 months; serum HBeAg
positivity for ?1 month; a serum HBV DNA level of ?107copies/ml; and a
serum alanine aminotransferase level less than five times the upper limit of
normal. Written informed consent was obtained from all patients. Major exclu-
sion criteria included pregnancy or breast-feeding; coinfection with hepatitis C
* Corresponding author. Mailing address: Idenix Pharmaceuticals
Inc., 60 Hampshire Street, Cambridge, MA 02139. Phone: (617) 995-
9805. Fax: (617) 995-9801. E-mail: email@example.com.
Page 2
virus, hepatitis D virus, or human immunodeficiency virus; any previous treat-
ment with a nucleoside analog or any other drug treatment for HBV in the year
before the baseline; treatment with immunomodulatory agents or corticosteroids
within 6 months before the baseline; decompensated liver disease; hepatocellular
carcinoma; a history of other clinically important diseases and current abuse of
alcohol or illicit drugs. The trial was conducted at the Queen Mary Hospital in
Hong Kong and the National University Hospital in Singapore. The trial was
approved by the ethics committees of both centers. The first patient was re-
cruited on 20 July 2000, and last patient completed the trial on 5 July 2002.
Study design. This was a phase I/II, double-blind, placebo-controlled, dose-
escalation trial for evaluation of the safety, pharmacokinetics, and anti-HBV activity
of telbivudine administered once daily for 4 weeks at escalating doses of 25, 50, 100,
200, 400, and 800 mg, with a 12-week follow-up period. Seven patients who were
randomly assigned to receive telbivudine or matching placebo at a 6:1 ratio were
enrolled in each dosing cohort. Telbivudine 25-mg tablets were used in the 25- to
200-mg cohorts; 100-mg tablets were given to the 400-mg cohorts; and 200-mg
tablets were administered to the 800-mg cohort. All telbivudine tablets were formu-
lated for immediate release. The study drug was taken orally once daily in the
morning. There was no restriction regarding food intake.
Fourteen to 7 days prior to the baseline (the time of administration of the first
dose), patients underwent a screening evaluation that included a medical history,
a physical examination, and clinical laboratory measurements (HBV DNA level,
serum chemistry, hematology, and urinalysis). Clinical laboratory measurements
were repeated at the baseline and were monitored weekly during the study.
Blood sample collection. An intensive pharmacokinetic evaluation was con-
ducted over a period of 8 h after the first dose and on any day between weeks 2
and 4 (steady state). The selection of the blood sampling duration was largely
dictated by the outpatient nature of the study and consideration of the conve-
nience of the participants. Blood samples (5 ml at each time point) were drawn
into heparin-containing Vacutainer tubes immediately prior to and after dosing
at 0.5, 1, 2, 3, 4, 6, and 8 h. Plasma was obtained by centrifugation and was stored
at ?20°C until analysis. Serum samples for viral load measurement were ob-
tained at the baseline, weekly through week 8, and thereafter every other week
through week 16.
Blood sample analyses. For plasma samples from the 25- to 400-mg dose
cohorts, plasma concentrations of telbivudine were assessed by a validated high-
performance liquid chromatographic (HPLC) method with UV detection.
Briefly, 50 ?l of internal standard (?-L-2?-deoxyadenosine [LdA] at 40 ?g/ml)
and 6 ?l of thymidine phosphorylase (EC 18.104.22.168; ?1 unit/?l; Sigma Chemical
Co., St. Louis, Mo.) were added to 200 ?l of calibration standards (0.1 to 100
?g/ml), quality controls (QC; 0.1 to 80 ?g/ml), and unknown plasma samples.
The mixture was vortexed thoroughly and incubated at 37°C for 1 h to digest any
endogenous thymidine that may interfere with the telbivudine assay. After incu-
bation, acetonitrile (1.5 ml) was added to precipitate protein. The samples were
centrifuged, and the supernatant was recovered and evaporated to dryness. Prior
to chromatographic analysis, dry residues were reconstituted with 150 ?l of
mobile phase (20 mM phosphate buffer containing 2% [vol/vol] acetonitrile) and
centrifuged. The resulting supernatant was transferred into HPLC injection vials.
Reverse-phase chromatography was performed with 50-?l aliquots on a Novapak
C18column (3.9 by 150 mm; 4-?m pore size; Waters, Milford, Mass.). Elution
was carried out isocratically at 1 ml/min. Under these conditions, the retention
times were approximately 4.9 and 7.7 min for telbivudine and LdA, respectively.
Telbivudine and LdA were monitored at 267 nm. This assay was characterized by
a lower limit of quantitation of 0.1 ?g/ml, intra- and interday precisions (coef-
ficients of variation [CVs]) from 1.1 to 10.6%, and accuracies (percent deviation)
from ?3.3 to 6.1%, based on the results for the QC samples.
Plasma samples from the 800-mg cohort were analyzed by a validated HPLC
method with mass-spectrometry (MS)-MS detection. In this assay, the sample
preparation procedure was similar to that for the HPLC with UV detection
method described above. However, because of the high sensitivity of MS-MS
detection, a much smaller sample volume (100 ?l) was used. Reverse-phase
chromatography was performed on a TSK-GEL Amide-80 column (4.6 by 150
mm; 5 ?m pore size; Tosoh Bioscience, Montgomeryville, Pa.). Elution was
carried out isocratically at 1 ml/min with a mobile phase of 90:10 (vol/vol)
methanol–25 mM ammonium formate (pH 3.5). Under these conditions, the
retention times were approximately 1.68 and 1.73 min for telbivudine and LdA,
respectively. Telbivudine and LdA were monitored by using a PE Sciex API 3000
MS-MS mass analyzer at mass transitions of 243.0 to 127.1 m/z and 252.0 to 136.0
m/z, respectively. The mass analyzer was operated under the positive mode by
using atmospheric pressure chemical ionization. This assay has a lower limit of
quantitation of 0.01 ?g/ml, with a calibration curve range from 0.01 to 5 ?g/ml.
The intra- and interday precisions (CVs) and accuracies (percent deviation) were
from 2.3 to 5.6% and ?4.2 to 1.4%, respectively, based on the results for QC
samples with concentrations ranging from 0.03 to 4 ?g/ml. Both bioanalytical
methods were validated to their respective specifications without further cross-
Serum HBV DNA was quantitated by using the COBAS AMPLICOR PCR
assay (Roche Diagnostics, Branchburg, N.J.), which has a quantitation limit of
400 genome copies/ml).
Pharmacokinetic and pharmacodynamic analyses. The plasma concentration-
time data for telbivudine obtained after the first dose and at steady state were
analyzed by model-independent and compartmental modeling approaches by
using Kinetica (version 4.3; Thermo Electron Corporation, Waltham, Mass.).
The maximum plasma drug concentration (Cmax) and the time to Cmax(Tmax)
were obtained directly from the plasma concentration-time profiles. The area
under the plasma concentration-time curve from time zero to time t (AUC0–t),
where t is the time that the concentration was last measurable in a sample, was
calculated according to the linear trapezoidal rule. The half-life (t1/2) observed
over the 8-h sampling period was calculated as 0.693/?, where ? is the slope of the
linear portion of the natural log-transformed post-peak plasma drug concentra-
tion-time curve estimated by linear regression. Potential drug accumulation was
assessed by determination of the ratio of the steady-state value to the first-dose
value (accumulation factor) of Cmaxand AUC0–t.
To characterize the true terminal elimination phase, a compartmental mod-
eling analysis was applied to individual steady-state plasma concentration-versus-
time data for patients with measurable predose trough levels (100- to 800-mg
doses). Because of the lack of samples during the terminal phase, steady-state
predose plasma levels were "flipped over" and considered 24-h datum points. A
two-compartment open model with first-order input and first-order elimination,
parameterized into microconstants (absorption rate constant [Ka] and intercom-
partment rate constants [k12and k21]) and the volume of the central compart-
ment (V1), was fitted to the data. The estimated microconstants were then used
to calculate the elimination rate constant (?) and the terminal-phase half-life
(t1/2?; which is equal to 0.693/?).
The principal parameters underlying plasma drug exposure, including Cmax
and AUC0–t, were assessed for dose proportionality after the first dose and at
steady state in the 25- to 800-mg daily dose range by using the following power
model: Yij? a ? Djb? eij, where Djis the dose at level j; Yijis the pharmaco-
kinetic parameter for subject i at dose level j; a and b are the mean intercept and
slope, respectively; and eijis the residual error for subject i at dose level j. For
practical reasons, the model presented above is log10linearized as follows:
log(Yij) ? a ? b ? log(Dj) ? eij, and fitted by using the GLM (general linear
models) procedure in SAS software (version 8.0; SAS Institute Inc., Cary, N.C.).
A dose-proportional relationship is concluded if the 95% confidence interval of
the estimated mean slope (b) includes unity.
The relationship between telbivudine antiviral activity (pharmacodynamics)
and plasma exposure was explored by using the following Emaxmodel: E ?
Emax? PK/(EPK50? PK), where E and Emaxare the observed and the maximum
antiviral effects, respectively, measured as the viral load reduction (the HBV
DNA level on a log10scale) at the end of treatment (week 4); PK represents the
pharmacokinetic parameters of exposure, i.e., single-dose and steady-state Cmax
and AUC0–t; and EPK50is the value of the pharmacokinetic parameter that
produces 50% of Emax. Nonlinear regression was performed by using the NLIN
procedure in SAS software.
Patient characteristics and disposition. All patients enrolled
were Asian and were primarily of Chinese ethnicity. The treat-
ment groups were comparable with respect to demographics and
baseline serum HBV DNA levels. Table 1 summarizes the pa-
tients' demographics and baseline HBV-related data. Forty-two
of the 43 patients (36 patients receiving active treatment and 7
patients receiving placebo) completed the 4-week treatment and
the 12-week follow-up periods. One subject randomized to the
placebo in the 200-mg cohort withdrew from the study for per-
sonal convenience reasons unrelated to the study treatment. One
patient in the 400-mg telbivudine cohort completed the study but
was considered noncompliant by the investigator.
Plasma pharmacokinetics. The plasma pharmacokinetics of
telbivudine were investigated over an 8-h period on day 1 and
on any day between weeks 2 and 4 inclusive. Pharmacokinetic
Page 3
data from 35 telbivudine-treated patients were evaluated (Ta-
ble 2); the data for the pharmacokinetic parameters for the
noncompliant subject in the 400-mg cohort were estimated
(Table 2 footnotes) but are not included in the cohort sum-
mary statistics. Figure 1 shows the mean plasma telbivudine
concentration-time profiles obtained after single (day 1) and
repeated (steady-state) daily doses of 25 to 800 mg in HBV-
infected patients. Following oral dosing, telbivudine was rap-
idly absorbed, with peak plasma levels reached between 0.8
and 3.0 h (median values) across all dose cohorts on day 1 and
at steady state. Over the dose range of 25 to 800 mg/day
studied, in which the twofold dose increments imply an antic-
ipated doubling factor of 2.0 between adjacent doses with re-
spect to exposure, the mean Cmaxincreased from 0.20 to 3.97
?g/ml (mean doubling factor, 1.9 ? 0.4) on day 1 and from 0.22
to 5.46 ?g/ml (doubling factor, 1.9 ? 0.4) at steady state, and
the mean AUC0–tincreased from 0.51 to 20.94 ?g · h/ml (dou-
bling factor, 2.1 ? 0.5) on day 1 and from 0.75 to 29.73 ?g ·
h/ml (doubling factor, 2.1 ? 0.4) at steady state. The pharma-
cokinetic dose proportionality of telbivudine was ascertained
by statistical analyses of log-transformed parameters and dose.
The model estimates of the slope were close to unity in all
cases: 0.91 (95% confidence interval, 0.81 to 1.01) and 0.93
(95% confidence interval, 0.84 to 1.02) for day 1 and steady-
state Cmax, respectively, and 1.08 (95% confidence interval,
0.96 to 1.20) and 1.03 (95% confidence interval, 0.93 to 1.14)
for day 1 and steady-state AUC0–t, respectively. The telbivu-
dine Cmaxand AUC0–twere greater at steady state than after
a single dose. The mean ratios of the individual paired values
at steady state to the values after administration of a single
dose (accumulation factor) ranged from 1.14 to 1.49 for Cmax
and from 1.40 to 1.70 for AUC0–t. The detailed pharmacoki-
netic parameter data for each dose cohort are presented in
Table 2.
After peak plasma levels were achieved, the disposition of
telbivudine was essentially monophasic over the 8-h sampling
FIG. 1. Mean (SD) single-dose (day 1) and steady-state (week 2 to 4) plasma concentration-time profiles of telbivudine in HBV-infected patients
following oral administration of escalating doses at 25, 50, 100, 200, 400, and 800 mg.
TABLE 1. Patient characteristics at baselinea
Value at the following telbivudine dose (mg):
2550 100 200400800Total
No. of subjects
Age (yr)b
Gender (% male)
Wt (kg)b
Serum HBV DNAb
(log10no. of copies/ml)
Serum ALTc(IU/ml)d
7666666 36
30.9 ? 9.8
68.0 ? 13.4
8.3 ? 1.2
31.7 ? 7.5
72.5 ? 17.2
9.9 ? 1.1
32.0 ? 8.4
63.3 ? 17.2
8.8 ? 0.8
38.7 ? 11.6
59.4 ? 17.2
9.0 ? 1.1
29.4 ? 7.8
62.6 ? 9.1
7.9 ? 0.8
32.5 ? 10.0
63.6 ? 8.5
8.2 ? (0.6)
41.8 ? 16.5
66.3 ? 9.9
8.7 ? 1.3
34.3 ? 10.9
64.6 ? 13.4
8.8 ? 1.1
33 (27–78)68 (22–75)30 (24–139)63 (21–163)81 (20–169)126 (22–545)52 (31–243)58 (20–545)
aAll patients were Asian and seropositive for HBsAg and HBeAg.
bValues are presented as means ? SDs.
cALT, alanine aminotransferase.
dValues are presented as medians (ranges).
Page 4
period. This initial distribution-elimination phase had an esti-
mated t1/2that ranged from 2.5 to 5.0 h after the first dose and
at steady state across all doses. The presence of a second
slower elimination phase was evidenced by the substantial
steady-state predose plasma levels, which ranged from 0.15 to
2.65 ?g/ml (cohort mean values) for doses ?100 mg (Table 2).
To approximate the half-life of the unobserved second elim-
ination phase (t1/2?), a two-compartment model with first-or-
der input and first-order elimination was fitted to individual
steady-state plasma concentration-time data from the 100- to
800-mg dose cohorts, with the predose data "flipped over" and
considered the 24-h datum points. Mean ? standard error
(SE) model estimates were 68.3 ? 8.3 liters for V1, 0.492 ?
0.083 h?1for Ka, 0.361 ? 0.075 h?1for k12, and 0.052 ? 0.039
h?1for k21, respectively. The mean estimated t1/2?ranged from
29.5 to 41.3 h (Table 2). The mean ? standard deviation (SD)
model-predicted day 1 and steady-state AUCs from 0 to 8 h
were 2.89 ? 0.84 and 4.07 ? 0.67 ?g · h/ml, respectively, for the
100-mg dose; 5.48 ? 1.48 and 6.49 ? 1.39 ?g · h/ml, respec-
tively, for the 200-mg dose; 10.35 ? 5.64 and 12.93 ? 5.68 ?g
· h/ml, respectively, for the 400-mg dose, and 19.40 ? 7.06 and
29.89 ? 9.24 ?g · h/ml, respectively, for the 800-mg dose. The
model-predicted AUCs were therefore in excellent agreement
with the observed data presented in Table 2, indicating the ad-
equacy of the modeling analysis. At steady state, the AUC
from 0 to 8 h represented approximately 60% of the AUC over
the dosing interval (24 h).
Pharmacokinetic-pharmacodynamic relationship. An Emax
model was used to delineate the relationship between patient
serum HBV DNA reduction data (log10scale) at the end of 4
weeks of treatment, a measure of the pharmacodynamic effect
of telbivudine, and pharmacokinetic parameters of drug expo-
sure, i.e., Cmaxand AUC0–t, obtained on day 1 and at steady
state. The Emaxmodel fitted the dose-response data well, in
particular, the steady-state Cmaxand AUC0–t, with better pre-
cision for model estimates. As summarized in Table 3, model
estimates for Emaxranging from 3.20 to 3.44 log10were con-
sistent for all four pharmacokinetic parameters examined; es-
timates of the values of the pharmacokinetic parameters re-
quired to produce 50% of Emaxwere 0.06 and 0.12 ?g/ml for
the day 1 and steady-state Cmax, respectively, and 0.13 and 0.41
?g · h/ml for the day 1 and steady-state AUC0–t, respec-
tively. The steady-state plasma exposures required to pro-
duce a 3-log10or 99.9% reduction in the serum HBV DNA
level at week 4 were predicted to be as low as 0.78 ?g/ml for
Cmaxand 3.36 ?g · h/ml for AUC0–t, comparable to the
exposures achieved by a dose of 100 mg/day (Table 2). As
depicted in Fig. 2, while a more profound virologic response
was achieved with higher plasma drug exposure in patients
receiving higher telbivudine doses, consistent with its dose-
proportional pharmacokinetics, a nearly maximal viral load
reduction was obtained with plasma exposures corresponding
to telbivudine doses in the 400- to 800-mg range.
This dose-escalation study evaluated the safety, pharmacoki-
netics, and antiviral activity of telbivudine in HBV-infected pa-
tients during 4 weeks of oral, once-daily treatment. The results of
studies of the safety and antiviral activity of telbivudine, detailed
elsewhere (6), demonstrated that telbivudine is well tolerated
TABLE 2. Values of pharmacokinetic parameters for telbivudine on day 1 (first dose) and at steady state (weeks 2 to 4) following once-daily
oral administration of escalating doses from 25 to 800 mg in HBV-infected patientsj
AUC0–t(?g · h/ml)
Day 1SSh
Day 1SSRatioc
Day 1SSDay 1 SS
0.20 (0.08)
0.27 (0.07)
0.61 (0.21)
0.99 (0.31)
1.80 (0.44)
3.97 (1.01)
0.22 (0.08)
0.35 (0.08)
0.82 (0.24)
1.24 (0.30)
2.73 (0.96)
5.46 (1.64)
1.14 (NAi)
1.31 (0.14)
1.38 (0.27)
1.32 (0.36)
1.49 (0.31)
1.41 (0.42)
0.56 (0.33)
0.98 (0.38)
2.91 (0.88)
5.02 (1.47)
9.05 (3.02)
20.94 (3.47)
0.75 (0.31)
1.60 (0.49)
4.14 (1.05)
6.67 (1.47)
13.42 (6.22)
29.73 (10.35)
1.70 (0.26)
1.45 (0.17)
1.40 (0.40)
1.44 (0.33)
1.43 (0.48)
0.8 (0.5–1.1)
1.5 (1.0–3.0)
3.0 (0.4–4.0)
2.9 (1.9–3.0)
3.0 (0.4–3.0)
2.5 (1.9–4.0)
1.0 (1.0–1.9)
1.9 (1.0–3.0)
2.1 (1.2–4.0)
1.9 (1.9–2.9)
1.9 (1.9–3.0)
1.5 (0.0–3.9)
3.5 (0.9)
3.1 (1.3)
3.0 (0.8)
3.1 (1.4)
2.5 (0.5)
4.8 (1.6)
5.0 (2.2)
3.0 (0.4)
3.6 (0.6)
3.5 (0.9)
3.9 (1.0)
4.8 (1.3)
0.15 (0.05)
0.15 (0.06)
0.35 (0.38)
2.65 (2.01)
41.3 (8.4)
29.5 (9.1)
31.5 (14.8)
31.5 (10.9)
an ? 2 on day 1 (means [SEs] are shown), and n ? 4 at steady state for the 25-mg group; n ? 6 for all other doses except for the 400-mg group, where n is equal
to 5.
bOne subject in the 400-mg group was not compliant. The day 1 and steady-state pharmacokinetic parameters for this subject were 3.00 and 2.25 ?g/ml, respectively,
for Cmax, and 16.24 and 12.55 ?g · h/ml, respectively, for AUC0–t. Tmaxwas 1.9 h on both occasions.
cMean ratio of individual paired values at steady state to the values on day 1 for all cohorts except the 25-mg cohort, for which the ratio of the cohort mean values
is presented.
dTwo subjects in the 800-mg group took a dose within 12 h of the steady-state intensive pharmacokinetic dose, resulting in higher than expected predose levels. The
mean ? SD of the trough concentration (Ctrough) was 0.88 ? 0.59 ?g/ml when the data for these two subjects are excluded.
eMedian (range).
fCalculated from the observed log-linear portion of the post-peak concentration-time curve up to 8 h, not the terminal-phase t1/2.
gEstimated t1/2?from modeling analysis, approximating the terminal-phase half-life.
hSS, steady state.
iNA, not available.
jData are means (SDs) unless indicated otherwise.
TABLE 3. Emaxmodel analysis for pharmacokinetic-
pharmacodynamic relationshipa
EstimateP EstimateP
Day 1
Steady state
Day 1
Steady state
3.33 ? 0.20
3.44 ? 0.17
0.06 ? 0.03
0.12 ? 0.04
3.20 ? 0.17
3.36 ? 0.16
0.13 ? 0.09
0.41 ? 0.14
aModel estimates for Emaxand EPK50are means ? SEs.
Page 5
without clinically significant adverse events throughout treatment
and across all dose levels from 25 to 800 mg/day. Compared to
placebo, there were no significant changes in hematologic values
and there were no significant abnormalities in clinical laboratory
data throughout the trial. Clinical adverse events were all mild,
and there was no apparent dose-related or treatment-related pat-
tern in the incidence of adverse events (6). A profound, dose-
related virologic response was observed with all doses tested, with
serum HBV DNA reductions of 3.5 to 4.0 log10achieved with
doses of 400 to 800 mg/day by the end of 4 weeks of treatment.
The pharmacokinetics of telbivudine were evaluated over a
period of 8 h in this first clinical trial conducted with HBV-
infected patients. While this sampling interval proved to be
inadequate for a full pharmacokinetic characterization of tel-
bivudine, it did capture essential pharmacokinetic parameters,
such as Cmax, Tmax, and a significant portion of AUC (approxi-
mately 60%, based on model-predicted steady-state exposure),
therefore allowing assessment of the dose proportionality and the
dose-response relationship. The study results indicated that tel-
bivudine is rapidly absorbed after oral dosing, with Cmaxreached
within 1 to 3 h. Pharmacokinetic parameters of drug exposure,
including Cmaxand AUC0–t, are dose proportional over the dose
range studied. While the absolute oral bioavailability of telbivu-
dine remains unknown, the dose-proportional behavior of telbi-
vudine plasma kinetics indicates consistent absorption of the drug
with no restriction on food intake. A food-effect study later
showed that a high-calorie, high-fat meal had no effect on the
pharmacokinetics of telbivudine (unpublished data).
Over the 8-h period, telbivudine exhibits an apparent single-
phase decline, with a short observed t1/2. This phase later
proved to represent an early distribution-elimination phase, as
the presence of a second, slower elimination phase was evi-
denced by the substantial steady-state levels of telbivudine that
remained measurable 24 h after dosing (predose trough levels;
Fig. 1 and Table 2) in cohorts receiving ?100 mg/day. A mod-
eling approach was used to characterize this unobserved sec-
ond elimination phase by flipping the steady-state predose data
over to 24 h. Although the lack of datum points between 8 and
24 h prevents the model from generating high-precision esti-
FIG. 2. Plots of serum HBV DNA reduction at week 4 versus single-dose and steady-state telbivudine pharmacokinetic parameters underlying
plasma exposure (Cmaxand AUC0–t). Solid and dashed lines, the Emaxmodel-predicted response curves and associated 95% confidence intervals,
respectively. The symbols represent the dose groups.


text:
The President's claim that Cedar Falls residents can get a gig for less than many Americans pay for premium cable is untrue. His statement that the Cedar Falls Utility network is 100 times faster than the average American Internet connection is, at best, a misleading and contradictory exaggeration, and at worst, absolutely false.
Last week, President Obama said "we're going to change" — i.e., preempt through federal fiat — state laws that prohibit their municipalities from owning broadband networks. (See embedded YouTube video at 14:00.) The White House supported his preemption plan with this "fact sheet" and a blog post listing "five things you need to know" about the President's announcement. The problem is, several of the "facts" and other things the White House wants you to know are false, misleading, or contradictory.

subset: commoncrawl


text:
View Product
The #17 Lightweight Chiseling Blade by X-ACTO is a precision chiseling tool, meant to handle lightweight woods and like materials. The chisel has a straight, razor sharp blade with a thin profile – perfect for removing fine layers and performing detail work on delicate craft material.
The X-ACTO #17 Lightweight Chiseling Blade is designed to work with the following materials:
X-ACTO blades are designed to allow you to make the careful and detailed cuts you need time and time again. Our blades are created with care and exceptional craftsmanship, producing a cutting edge that stays sharp. An X-ACTO quality blade is always ready when you need it.
The original X-ACTO knife has been praised for more than 50 years as the standard for precision. Attaining this level of precision, accuracy and reliability starts with supreme quality craftsmanship. X-ACTO knife blades are crafted with sharpened carbon steel for a reliable cut and a strong blade. X-ACTO knife blades fit with most X-ACTO knife models.
The Designer Series Circle Cutter can trace or cut perfect circles up to 5 7/8 inches. It is ideal for scrapbooking, paper crafts, labels, hangtags, and more. The easy to adjust knob makes changing sizes a breeze. And with its built-in storage compartment for extra blades, it's the perfect tool to have around!


text:
Yangon, Burma
Yangon, Burma News
Local news for Yangon, Burma continually updated from thousands of sources on the web.
The Irrawaddy: Privatization of transmitter site stirs passions in Parliament - Zue Zue
12 hrs ago | Burmanet | Comment?
Over 10,000 people infected dengue fever in Myanmar so far this year
Yesterday | Xinhuanet | Comment?
Mizzima: Gay subject of documentary warns of continuing rights violations in Myanmar - Author
Friday Jun 26 | Burmanet | Comment?
Myanmar Times: NLD seeks help from civil society on electoral rolls - Lun Min Mang
Friday Jun 26 | Burmanet | Comment?
Burmese disappointed but unshaken after constitution change vote fails
Friday Jun 26 | Asian Correspondent | Comment?
Myanmar, Thailand destroy nearly $1 bn in seized drugs
Friday Jun 26 | Channelnewsasia.com | Comment?
American Terrorism: Plain and Simple
terrorism 187
15 Horribly Disappointing Facts About Music
Are Warning Labels Needed on Soda?
News 62
Democratic Voice of Burma: Activists seek bail at Tharawaddy court hearing - Naw Noreen
Thursday Jun 25 | Burmanet | Comment?
The Irrawaddy: Citing nonpartisan duty, election chief says...
Thursday Jun 25 | Burmanet | Comment?
Deal watch: Silversea to offer free airfare to Asia
Thursday Jun 25 | USA Today | Comment?
Yangon film festival pays tribute to Czech visionary Vaclav Havel
Thursday Jun 25 | Asian Correspondent | Comment?
Myanmar's parliament blocks changes to constitution
Thursday Jun 25 | The Beaumont Enterp... | Comment?
Myanmar's parliament blocks changes to constitution
Thursday Jun 25 | SFGate | Comment?
Myanmar players to contest in Thailand Karate event
Wednesday Jun 24 | Xinhuanet | Comment?
Myanmar minister promises minimum wages by June-end
Wednesday Jun 24 | Fibre2Fashion | Comment?
Thai Buddhists to help Myanmar anti-Muslim set up radio station
Wednesday Jun 24 | The Peninsula | 6
20 sentenced in Myanmar for trafficking boat people
Wednesday Jun 24 | Bangkok Post | Comment?
The Irrawaddy: LGBT activist in spotlight at human rights film fest - Aung Thet Htwe
Wednesday Jun 24 | Burmanet | Comment?
Trending Now
Yangon, Burma News, Events & Info
Loading ...
Updated: Mon Jun 29, 2015 02:44 pm
Copyright © 2015 Topix LLC


text:
Original recipe yields 24 servings
Amount per serving ({{servings}} total)
Based on a 2,000 calorie diet
Ready In
Just like Mom used to make (almost)! Some things to keep in mind, make sure the loaf is sealed (or the filling spills out) and make sure the dough isn't rolled too thinly. The taste is awesome.
This is exactly what I was looking for! Absolutely delicious, just like I used to eat in Hungary growing up. Now, it's my turn to pass this heavenly tradition on to my boys. My only problem w...
In Polish, this is Strucla z makiem i orzechami wloskimi: Diós-mákos beigli in Hungarian. This is just like my Polish Grandmother makes. She would sprinkle some poppy seeds on the top and her's ...


text:
- News
- Premium
- Lifestyle
- Tech
- Communities
- Video
- Multimedia
- More
Eurozone inflation slips back again in December
Published on Jan 7, 2014 6:12 PM
BRUSSELS (AFP) - Eurozone inflation slipped to 0.8 per cent in December from 0.9 per cent in November, official figures showed on Tuesday.
In December 2012, inflation in the 17-member eurozone ran at 2.2 per cent but it fell steadily, hitting a four-year low of 0.7 per cent in October against a background of concern that deflation was on the prowl.
The Eurostat statistics agency said the largest gains in December prices were seen in food, alcoholic drinks and tobacco which rose 1.8 per cent after an increase of 1.6 per cent in November.
Energy prices were flat after falling 1.1 per cent in November while services were up 1.0 per cent compared with 1.4 per cent.
To continue reading, log in if you are a subscriber
Enjoy 2 weeks of unlimited digital access to The Straits Times. Get your free access now!


text:
You are a fan of insta wolfenstein ? Come to discover the best forums insta wolfenstein on the internet and share your experience with a community fan of insta wolfenstein . You can also build a forum insta wolfenstein and create your online discussion.
A forum for the ET server FUNBOY (BEGINNER).
#wolfenstein, enemy, territory, clan, jaymod, server, [fby], venom, panzer
Official UcE Wolfenstein Enemy Territory forum page


text:
Diario de Cuba, Havana, 7 June 2015 – Over 40 Ladies in White and some 27 activists were arrested this Sunday, the ninth of repressive operations in Havana, according to dissidents.
Among those arrested were the musician Gorki Aguila, the director of Estado de Sats, Antonio Rodiles, photographer Claudio Fuentes and artist Tania Bruguera, who has already been released, according to the activist Ailer Gonzalez.
Other Ladies in White and opponents were arrested on leaving their homes, or forced to remain in them, according to the dissident Martha Beatriz Roque. Continue reading


text:
The world's most eligible wizard is taken, sorry girls, you're going to have to settle for the ginger, Rupert Grint, as he's the only single dude from the Harry Potter franchise.
Daniel Radcliffe is dating...a muggle. No seriously, he's dating a non-famous person. Radcliffe was spotted walking hand in hand in New York City with a brunette who has been identified as Rosanne Coker.
Coker and Radcliffe, both 22, met when she worked as a production assistant on "Harry Potter and the Half-Blood Prince" in 2007. They have since worked together on the last two HP films, as well as "The Woman in Black" a new horror film Radcliffe is starring in next year.
While the two are trying to keep things hush-hush, the girls dad, Malcolm Coker, reportedly spilled details about their relationship to the UK's Daily Mail. Did he really need a paycheck that bad? Who whores out your daughters relationship to one of the biggest UK tabloids?
"Rosanne has worked on the last three "Harry Potter" films, so she and Daniel have known each other quite a long time. But they have been going out for just over a year now. I have met Daniel and he is a lovely guy. I'm just really happy for Rosanne, and as long as she is happy that is all that matters to me," says Malcolm.
Thanks Dad! He literally hit all the relationship bullet points. How they met? Check. How long they've dated? Check. Does Dad like Daniel? Check.
Anyways, the couple have a bi-continental relationship. Daniel spends most of his time in NYC while he appears on Broadway in "How to Succeed in Business Without Really Trying," and Coker lives with her parents in Surrey, England.
Though when you boyfriend makes $25 million per Harry Potter film, pretty sure he's picking up a tab on all those British Airways miles.
Coker's dad continues, "They have a lot of fun together and at their age, what more could you ask? Who knows where it is going to lead?" And then after he spills all those details he also adds, "I don't want to say too much really as they would really prefer to keep things quiet."
Father Coker also adds that the fame for Daniel Radcliffe is sometimes too much, "I don't think anyone realizes how much he gets pestered. I have been out for a meal with him and it just gets embarrassing. He feels awkward about it."
Just last month, Radcliffe hinted at his relationship but didn't reveal his girlfriends name, "I've got a girlfriend at the moment, who I am very much in love with. So you know, we'll see where that goes."
He also told GQ in May, "I now have a girlfriend I've been going out with for eight months."
Let it be known, Daniel Radcliffe is off the market. Just ask his girlfriend's dad.


text:
Upload Photo
Mustang and Shelby Showdown at Levittown Ford
The Mustang and Shelby Club of Long Island held its annual "Mustang Showdown" at Levittown Ford on Hempstead Turnpike on July 28 for Mustang, Shelby and other classic-car enthusiasts to show off their prized autos. Levittown Ford also donated a portion of the proceeds from the show to the Wounded Warrior Project to help disabled U.S. veterans. Here is a gallery of some of the vehicles on display.
Weird, clever Long Island license plates In the Garage: Long Islanders' classic rides Consumer Reports: These 30 cars burn too much oil 28 best and worst car brands in 2015 21 best and worst cars for fuel efficiency in 2015 26 worst used cars to buy in 2015 Kelly Blue Book's 10 coolest cars under $18G 15 hot new cars, trucks and SUVs of 2016 30 best used cars to buy in 2015


text:
Leaving the skins on the peaches for the purée makes for a beautifully pink swirl in this refreshing summer dessert.
These pancakes are lighter than those in your standard stack: slender and slightly crisp on the outside, light and lacy with assertive raspberry flavor. The raspberries are blended into the milk before being added to the battera solution to having pockmarks of berry flavor only here and there. You'll want a mile-high pile.
Yogurt gets used in two ways in this simple dinner party-worthy chicken dish: as a tenderizing marinade and mixed with the pan juices to create a rich sauce for serving.
It's make-ahead. It's impressive. And it won't break the bank.
Ask your butcher for a whole leg, which will include part of the sirloin.
Squeezing the liquid out of the zucchini is the secret to crisp fritters. (The potato helps, too.)
You don't need an ice-cream maker to serve cool, creamy scoops. All you need is a bowl to make semifreddo happen.
Creamy dreamy salad dressings are easier than you might think.
Why spend a ton of money on this specialty health product when you can make it at home?
This homemade yogurt works well as a dairy-free alternative. We prefer making our own coconut milk over using canned—the flavor is much more fresh. To reuse the pressed coconut, dry it out in a low oven until no longer moist, then use in baked goods or sprinkle over yogurt.


text:
Latest: Study Finds Assessment of Age Based on Physical Development to be Inaccurate
Latest: The Role of Free Light Chains in the Diagnosis of Monoclonal Gammopathies
Latest: It's T-Time for Refractometers
Latest: Nanoparticle Characterization Seminar Attendees Impressed by Malvern Instruments' Expert ...
Latest: Top Tips for LC-MS Sample Preparation
Latest: Markes International Launches Analytical Chemistry Awareness Campaign
Latest: Huber Kältemaschinenbau Presents New E-grade "Explore" for Process Development at ACHEMA ...
The Role of Free Light Chains in the Diagnosis of Monoclonal Gammopathies
Webinar Highlights: Analytical Methods for Semi-Targeted Screening of Pharmaceuticals and Illicit D...
It's T-Time for Refractometers
Analytik Jena Donates Analytical Measuring Technology to a Ukrainian University in Need
A Guide to the Most Common Pumps – and Which One is Right for You!
Top Tips for LC-MS Sample Preparation
Immunoassay Platform Convergence: From ELISA to Multiplex Immunoassays with the Help of ...
Peptide Separations Using Reverse Phase RediSep® Columns
Measuring Mitochondrial Function and Glycolytic Flux in 3D Cell Cultures
Estimation of the Refractive Index of Monocrystalline Sapphire by Polarization Measuremen...
Automated, Intelligent Sample Preparation: Integration of the ESI prepFAST Auto-Dilution ...
Discriminating Mycobacterial Strains by LC and Multivariate Analysis
Clinical Chemistry Analyzers
Next Generation Sequencing
Hematology Analyzers
Microplate Readers
Water Purification
PCR Technology
Allergies 2015
08 Jul 2015-09 Jul 2015
AACC (American Association fo...
26 Jul 2015-30 Jul 2015
Neuroscience 2015
17 Oct 2015-21 Oct 2015
12 Dec 2015-16 Dec 2015
28 October 2013
Hear about the current major bottleneck for biofuel use worldwide: degradation of biofuels in storage conditions. Dr. Cavalcanti discusses the causes of biodiesel and ethanol degradation in storage tanks and transportation, such as oxidation due to climatic conditions, and how his team investigates this phenomenon using a wide range of analytical and physical techniques. Learn how the research conducted at the National Institute of Technology will have real practical applications for biofuel markets around the world. SelectScience Interview for 'Science in Brazil' Special Feature.


text:
What is the seat width and depth? What is the seat height from the floor?
I consider this chair one of the best purchases I ever made. It is comfortable, sturdy, the price for the quality of the chair was excellent. The delivery time was less than 3 days. Way to Go!!!!!!...
Aragon Captain's Guest Arm Chair with Casters
Make a classic style statement in any office space with this heirloom quality mahogany guest arm chair. This stylish, rolling arm chair features hand-applied brass nail head trim and a robust mahogany finish for a traditional, elegant look.
ITEM#: 14605588The Aragon Opusoft Captain's Guest Arm Chair has a hand-applied Brass Nail Head trim. A Rich Mahogany Finish makes this the perfect chair for the Executive Office. Use this heirloom quality mahogany guest arm chair to give your office a touch of class. The legs of the chair are fitted with hooded casters for easy maneuverability around your workspace. The chair is crafted using metal, wood, foam and Opusoft vinyl, which give it a mix of durability, comfort and convenience.
Click here to view additional information about model A107 (Black).
Click here to view additional information about Model A108 (Burgundy).
- Materials: Wood, Metal, Foam, Opusoft Vinyl
- Colors: Black, Burgundy
- Classic Traditional styling
- Hand-applied individual brass nail head trim
- Rich Mahogany Wood Finish
- Sturdy Hardwood Frame
- No Sag Spring Seat
- Hooded Casters
- Model: A1zx
- Weight capacity: 250 pounds
- Seat dimensions: 22 inches wide x 21 inches deep
- Seat height: 18.5 inches high
- Dimensions: 24 inches wide x 26 inches deep x 31 inches high
Assembly Required
Please note: orders of 4 or more chairs will ship with a freight carrier, and are not traceable via UPS. Please allow 10 days before contacting Overstock.com regarding any freight carrier shipping concerns.
|Classic Traditional
|Brass Mahogany Wood
|Visitor Chairs
|Mahogany Finish
|Chair Back Height
|Black Red
|Furniture Pattern
|Seat Style
|Weight Capacity
|Up to 250 lbs.
|See description
|6 year Manufacturer
|See description
|Model Number
Customer Reviews
- Disclosures & Guidelines
- Filter By:
- Most Helpful
- Most Recent
I consider this chair one of the best purchases I ever made. It is comfortable, sturdy, the price for the quality of the chair was excellent. The delivery time was less than 3 days. Way to Go!!!!!!Read More
Desk Chair
Easy to assemble, and looks great. Just hope the fabric holds up.Read More
Roll up to the table
Love these chairs. The Oxford Blood color is sophisticated. The height of the chairs is perfect for our table and very comfortable. I had been shopping for chairs on casters for almost a year at local furniture stores without finding anything I liked. These exceeded my expectations.Read More
Terrific buy!
I purchased 4 of the crimson color chairs to go around our poker table. They look amazing. They are sturdy and comfortable. I'm extremely happy with the purchase.Read More
Aragon Captains Chair
Excellent chair.have probably bought at least 12 in the last couple years for offices.Read More
Great Chairs
Purchased two of these chairs for my elderly parents. Searched around my city for this type of chair and could only come up with very large kitchenette type chairs that were easily more than twice as expensive. These don't take up a lot of space but are certainly large enough to be comfortable to sit in and easy to roll. We purchased for use in an assisted living facility. Some elderly people cannot manage to scoot a dining room chair away from a table. These chairs provide comfort and move easily. Very satisfied.Read More
GOOD LOOKING CHAIR. COLOR IS JUST AS PICTURED. A TAD HARD TO PUT TOGETHER BY YOURSELF. SCREW HOLES WERE A LITTLE OFF. WILL TIP BACKWARD IF YOU LEAN ON THE BACK WITHOUT SOMEONE SITTING IN IT. A TAD SHORT FOR AN OFFICE DESK, BUT LOOKS RICH. VERY STURDY, ROLLS WELL ON FLOOR AND CARPET.Read More
nice but low
this is an otherwise great chair. but one review i read, from a man who was 6'1" suggested that it was low, which i thought would be perfect for me as i am 5'4". it is great for my height but, since i wanted to use it as a desk chair, it's too low to actually write with w/out a seat cushion. i also plan to put carpet down b/c the wheels do leave slight marks on the hard wood in my apartment. other than that, i really like it.Read More
Great club chairs, easy to assemble.
The chairs were received quickly. They were are darker red tone as promised. Very easy to assemble. I put three together in less than 30 minutes. All the tools needed were provided. I am completely satisfied with my purchase of these chairs. The size was as advertised, same with the color. The pricing was a value. I'm pleased.Read More
guest chair
The chair is well worth the money. I put it together in less than four minutes, as per instructions.Read More
Questions & Answers
Hello michaeljstrom, this item features seat dimensions approximately 22 inches wide x 21 inches deep x 18.5 inches high. Thank you for shopping with us.
Why did you choose this product?
Yes. Black .
I choose this chair because it looks comfortable, it has casters , a back and arms. This is just what I need for my new computer chair. Also the reviews were very good!!!!
style price need
because you needed more money from me.
What is the height of the top of the chair arm measured from the floor? Need to know if it will clear underneath of our current table.
Hello rjbasmtm, we appreciate your inquiry. The highest point of the arm from the floor is 26 inches. We hope this information has been helpful. Thank you for shopping with us. Have a great day!
This chair looks like it would be good for what I need, but do the wheels lock in place?
Hello, theresela66, Hope your day is going well. Unfortunately no,the wheels don't lock in place. Please let us know if you have any further question.
Shopping Tips & Inspiration
How to Create a Homework Zone
How to Create a Homework Zone from Overstock.com. Follow these tips and design a study area where children will want to work and learn.
Features of an Office Chair
Features of an Office Chair from Overstock.com. Our guides provide customers with information about office chairs and advice about our many brand-name products.
Decorate Your Office Right
Decorate Your Office Right from Overstock.com. Here's how to create a comfortable and soothing workspace that also fosters efficiency.
Office Feng Shui
Office Feng Shui from Overstock.com. Using the ancient principles of feng shui, you can make your office an inviting and producitve place to work.
Office Supplies Buying Guide
Office Supplies Buying Guide from Overstock.com. Our buying guides provide customers with detailed information about office supplies, answers to common questions and buying tips for our many brand-name products.
Discount Office Supplies Checklist
Discount Office Supplies Checklist from Overstock.com. Our guides provide customers with information about discount office supplies and advice about our many brand-name products.
Top 5 Essential Office Supplies
Top 5 Essential Office Supplies from Overstock.com. Our guides provide customers with the top 5 essential office supplies and advice about our many brand-name products.
How to Save Money Shopping Online
How to Save Money Shopping Online from Overstock.com. Shop online and save when you follow these tips.
Living Frugally--Adding Savings to Your Lifestyle
Living Frugally: Adding Savings to Your Lifestyle from Overstock.com. Our guides provide customers with information about living frugally and advice about our many brand-name products.
Top 5 Reasons to Drive a Hybrid Car
Top 5 Reasons to Drive a Hybrid Car from Overstock.com. Our guides provide customers with information about hybrid cars and advice about our many brand-name products.
Shipping & Returns
Usually leaves our warehouse in 1-2 business days. *
Standard Return Policy:
Items must be returned in new or unused condition and contain all original materials included with the shipment. More Details
FINAL SALE EXCLUSION: Items marked as FINAL SALE are not returnable unless the problem you experience is the result of our error.
This item cannot be shipped to Alaska or Hawaii. More details
Shipping Information:
Our standard shipping method is ground shipping. We also offer expedited shipping for most items. Your final
shipping cost and estimated delivery timeframe will be available at checkout.
Standard shipping details
Expedited shipping details
* For your protection, all orders are screened for security purposes. If your order is selected for review, our Loss Prevention Team may contact you by phone or email. There may be a two business day delay to process your order.
** Most Oversize orders are delivered within 1-4 weeks. Some orders may take 6 weeks to be delivered.


text:
1010381 English Conversation for Tourism and Hotel - at the travel agent
- published: 24 Nov 2011
- views: 36011
- author: กล้า ตรั่นวัน
Many of us fall into a vacation rut – by which I mean that we go to the same destinations year after year: Jamaica and Aruba, London and Paris, San Francisco and Hawaii. How about trying new locales, new cultures, new lifestyles, new...The Wichita Eagle 2014-02-16
Tourism Dunedin is to be disestablished and its work absorbed by a new Dunedin City Council in-house marketing agency that will promote the city's business, education and...Otago Daily Times 2014-01-29
Dunedin, 29 January 2014 �" The Dunedin City Council is establishing an in-house City marketing agency to align the city's promotional activities across key sectors and...Scoop 2014-01-29
"The People's Republic of China Tourism Law" will officially come into effect on October 1, 2013. As "10.1" is coming, the provincial tourism service quality supervision...noodls 2013-09-27
The Independent
London Evening Standard
Like World News?
(Source: Atlantic Canada Opportunities Agency ) October 03, 2014 - Charlottetown, PEI - Atlantic Canada Opportunities Agency The Honourable Gail Shea, Minister of Fisheries and Oceans, on behalf of the Honourable Rob Moore, Minister of State (Atlantic Canada Opportunities Agency), and PEI Minister of Tourism and Culture Robert Henderson today announced combined funding of...noodls 2014-10-03
Friday, August 29, 2014 5:44pm LARA CERRI | Times The Pinellas County Tourist Development Council made the right call this month when it rejected the idea of converting the county's public tourism agency into a private-public partnership. When a successful leader is wooed away, it can be tempting to push for radical change. But the Pinellas County Tourist Development Council...Tampabay.com 2014-08-29
A TRAVEL group has endorsed the candidacy of former Tourism Secretary and Sen. Richard Gordon, saying the industry can count on him to further promote and give dynamism to tourism. Founding chairman of the Network of Independent Travel Agencies Robert Lim Joseph said Gordon exemplifies a leadership that brings results as shown in his past achievements as senator, local...Journal Online 2013-04-05
(Source: Government of Nova Scotia) Good Jobs A Step Closer for Windsor The province issued a tender for office space today, Feb. 8, taking another step to bring good jobs to Windsor and locating provincial departments and agencies in communities throughout Nova Scotia. A tender for office space to house the Nova Scotia Tourism Agency is posted on the government procurement...noodls 2013-02-08
MONTRÉAL, July 28, 2014 /CNW Telbec/ - Tourisme Montréal is proud to announce that it has chosen the integrated advertising agency, lg2, to represent its brand. The rigorous selection process, which occurred in spring 2014, was undertaken in two stages—an open call for nominations, which lead to a shortlist of three agencies, each of whom were subsequently asked to analyze a...Canada Newswire 2014-07-28
JAMAL THALJITampa Bay Times Wednesday, August 20, 2014 1:31pm CLEARWATER — There was no debate at today's Pinellas Tourist Development Council meeting about whether the county tourism agency should switch to a public-private model that would let it spend bed tax dollars without the accountability of a government agency. Related News/Archive That's not going to happen. There was...Tampabay.com 2014-08-20
(Source: Atlantic Canada Opportunities Agency ) September 12, 2014 - Cardigan, PEI - Atlantic Canada Opportunities Agency Page Content The Honourable Gail Shea, Minister of Fisheries and Oceans, on behalf of the Honourable Rob Moore, Minister of State (Atlantic Canada Opportunities Agency), and PEI Tourism and Culture Minister Robert Henderson today announced a combined...noodls 2014-09-12


text:
Cadillac Escalade Problem Report
Cadillac Escalade Speedometer or Other Instrument Panel Gauge May Work Erratically
(34 reports)
The speedometer or other instrument panel gauge may begin to work erratically at times. Our technicians tell us that the instrument cluster must be sent to a repair facility to correct this fault. The warranty has been extended on some of these units to 7 years or 70,000 miles.
The whole instrument panel would go out and when it came back on the gauges would be moving back and forth. I took it to dealership they said they reset the panel. It worked for a few days then went out and has not came back on. I have not clue how fast I'm going or how much gas is in the tank. - Visitor
13 people like this
I had this problem and GM refused to fix because I had over 50K miles. I had to pay out of my packet to have this problem repaired. I am not upset because some defective parts were installed but they refused to have it fixed. Never will buy GM. They must understand its their problem passed on to a customer - Visitor
8 people like this
Whole cluster randomly shuts off for awhile then comes back on then shuts off. - Visitor
5 people like this
Dashborad instrument oanel is erractic. Goes out completely then comes back on. - Visitor
4 people like this
INSTRUMENT PANEL IS DEAD AND DOES NOT ACTIVATE UNTIL DRIVING FROM 2 TO 10 MILES; THEN COMES ON; HAD TO CHANGE THROTTLE BODY ASSEMBLY; BUT AFTERWARDS; INSTRUMENT PANEL GAUGE STILL ERRATIC AT 197000 MILES - MikesCady
3 people like this
speedometer started working erratic and not at all sometimes cadillac shop found bad cluster an replaced,it - Visitor
2 people like this
Same issue - Visitor
Tachometer stopped working. Too much money to fix. - Visitor
The RPM gauge works sometimes. Sometimes it sticks and does not move. - maxxman
oil gauge is read upside down - Visitor
Speedo needle eratic and then stopped working altogether. Bought speedo servo kit and replaced all instrument cluster servos. Re-installed. - Visitor
All gauges are not working correctly - Visitor
Speedometer pegged, doesn't work at all! Needle as far as it can go ! - Visitor
instrumentation panel goes out, then comes back on - sometimes 6-10 times when driving. checked fuses, they were ok. - Visitor
Australian zip codes only have 4 digits, so there is obviously a problem with your website. Speedo went berserk. Someone had tried to fix the cluster before and damaged the printed circuit wiring. Fixed the damage, and replaced all the servos while I was at it. - Visitor
All my gages are messing up going beyond zero - Visitor
Related Items:
The speedometer or other instrument panel gauge may begin to work erratically at times. Our te...
all other gauges work. Some thing other than gauge?
Is it safe to assume that the fuel gauge is defective if it reads erratically but the digital r...
The A/C works and blows cold air, then switches to hot air. If I stop and turn the car off, the...


text:
Lisbon Book Fair
The open-air book fair in Edward VII Park (Parque Eduardo VII) has been a popular event on Lisbon's calendar since the 1930s. It offers visitors wonderful browsing opportunities through the dusty covers of old books, to new reads and comic books.
Venue: Edward VII Park
Date: 28 May to 14 June 2015
Website: www.feiradolivrodelisboa.pt


text:
Filmlinc DailyRSS
Film Comment's Essential Cinema: "Nebraska"
As the year draws to a close, Film Comment is celebrating the best movies of 2013. In the third of 15 pieces from their Essential Cinema supplement, they take on NYFF51 Main Slate selection film Nebraska by Alexander Payne.
Film Comment's Essential Cinema: "Her"
As the year draws to a close, Film Comment is celebrating the best movies of 2013. In the second of 15 pieces from their Essential Cinema supplement, they take on NYFF51 Closing Night film Her by Spike Jonze.
Film Comment Magazine's Best of 2013 Lists Revealed
Joel and Ethan Coen's Inside Llewyn Davis, Steve McQueen's 12 Years a Slave, and Richard Linklater's Before Midnight take the top three spots on the magazine's list of the top 50 films released in 2013, and Philippe Garrel's Jealousy tops the list of undistributed films.
Film Comment's Essential Cinema: "12 Years a Slave"
As the year draws to a close, Film Comment is celebrating the best movies of 2013 in a number of ways. Earlier today, they revealed their highly anticipated end-of-year lists and, over the next few weeks, they'll be putting online 15 pieces from their Essential Cinema supplement. First up is Steve McQueen's awards-buzzed 12 Years a Slave...
Tracing Love's Path in 'About Time' and 'Le Week-End'
A member of this year's NYFF Critics Academy, Graham Winfrey caught Richard Curtis' About Time at the New York Film Festival last month. The film, about a 21 year-old who uses his ability of time travel to pursue a girlfriend, is now in theaters.
NYFF51: It's A Love Thing
[NYFF Critics Academy member Mark E Lukenbill looks back at the 51st festival and explores the "aching highs" and "melancholic lows" of love in three of the festival's films, Her, Blue Is the Warmest Color and Only Lovers Left Alive.]
NYFF51 Video: Scorsese, Vampires, and "Nebraska"
Do you miss the 51st New York Film Festival as much as we do? Hopefully these videos will help! Martin Scorsese, Jim Jarmusch, Tilda Swinton, Alexander Payne, Bruce Dern, June Squibb, and Will Forte were just some of the people who stopped by to make NYFF51 so special...
NYFF51 Photos: "Blue," "Dazed and Confused," "Only Lovers," and "Her"
Even in its final days, the 51st New York Film Festival was rolling out the premieres and special events. Here's one last batch of photos of the directors and stars who made these nights so special!
NYFF51 Debut "When Evening Falls On Bucharest Or Metabolism" Heads to U.S. Theaters
Corneliu Porumboiu's recent New York Film Festival debut When Evening Falls On Bucharest or Metabolism is headed for U.S. theaters in early 2014.
Arnaud Desplechin's "Jimmy P" Heads from NYFF51 to U.S. Theaters
New York Film Festival debut Jimmy P.: Psychotherapy of a Plains Indian is headed for a U.S. theatrical release in early 2014 courtesy of IFC Films.


text:
The White Olive Reviews
- Info
- |
- Rates
- |
- Map & Directions
- |
- Reviews
- |
- Facilities
Reviews & Ratings Explained
The rating percentage is calculated from customers who booked within the last 12 months.
All ratings and reviews are based on the feedback and opinions of the customers who submitted them and do not express the opinions of Hostelworld.com. This way, you get an up-to-the-minute opinion of just how good a hostel really is.
Read our review guidelines »
We couldn't believe our luck when we stumbled upon this place! It really was a little slice of heaven. The beautiful scenery, friendly pets and Andrew who looked after us all made it the most perfect stay!
- Novice Nomad
- alicerampling3393
- England
- Mixed Group, 25-30
- (2 reviews)


text:
Alex Boone
6-7/315 Ohio State
5.16 Senior
Pros: Has nice size and strength. Has decent feet, and shows nice technique in pass protection. Stays square and gets good position on defenders. A good downhill blocker that has nice mobility and can block on the second level. Has a nice mean streak.
Cons: Lacks good feet and really struggles against speedy edge rushers because he's not quick into his stance. Will miss some assignments. Needs to improve his hand placement, and may have a tendency to hold at the next level. Doesn't always lock onto defender in the ground game.
Overview: Boone has been a bit overhyped throughout his career. He's never been a great left tackle, but was just effective most of his time. He's routinely struggled with athletic edge rushers. But he's a good fit in a zone blocking scheme, and if makes the move to the right side, his issues in pass protection won't be as big concerns. Had some off-field concerns stemming from a drinking incident after the season. Also interesting that he was listed at 310 at OSU, but came to the Combine after 325, but seemingly dropped that excess weight for his pro day.
NFL Forecast: Move him to the right side in a zone blocking scheme, and he could be a good tackle. He's a bit like Jon Runyan or Jon Jansen in that regard, because his greatest upside lies as a run blocker. If he continues to improve his technique and strength, then he'll be capable taking on the bigger left ends, but will likely always have issues against smaller, athletic speed rushers. But as he refines his technique, particularly his hand use, he has the makings of being a top run blocker. He's never going to really dominate guys, but will certainly clear holes for guys in the zone blocking scheme. He should make a solid starter in that scheme, and I don't think the off-field concerns will be too much of an issue from keeping him from reaching his potential.
ATL Forecast: Boone would be a near ideal candidate to take over the Falcons right tackle spot. He's probably not ready to start immediately, as he still needs work in pass protection and would struggle against some of the better LDEs in the NFC if he was thrown to the wolves too early. But by his second year, he should be refined enough to start. He'd be a better long-term answer at RT than Clabo, but they are similar players, although Boone is more natural playing outside than him. He could be a nice bookend to Baker for years to come and would be a similar player to Jon Runyan here in Atlanta, although may not be as dominant a run blocker as Runyan has been throughout his career. But the potential is there.
Value: Boone is a solid third or fourth round pick for a team trying to develop a run-blocking right tackle.
Alex Boone, OT, Ohio State
Scouting Reports of centers, guards, and offensive tackles in the 2009 NFL Draft.
1 post • Page 1 of 1
- Pudge
- Purveyor of Truth & Justice
- Posts: 26397
- Joined: Thu Dec 23, 2004 1:03 pm
- Location: North Carolina
- Contact:
Alex Boone, OT, Ohio State
"Vincere scis, Hannibal, victoria uti nescis" -- Maharbal, 216 B.C.E.
1 post • Page 1 of 1
Who is online
Users browsing this forum: No registered users and 1 guest


text:
Monday, July 06, 2015
1 comments
Well during the holiday weekend we had to change all plans. We were cooking out on Saturday and Sunday, bu the storms moved in and we did not get to. We fixed a meal Saturday tat we had not planned. On Sunday we make the ribs in the oven as ... Read more
Saturday, July 04, 2015
1 comments
Well Friday Hubby was off and we had an appointment with his workman's comp attorney and then an appointment with his IRA financial manager. We try to get with each a couple f times a year. So far all is well on both fronts , He ten tk me to... Read more
Thursday, July 02, 2015
0 comments
Well yesterday was a bust as far a my plans. I was headed out to work in another shop and got caught behind apparently a serious or messy accident. I sat in non moving traffic for over an hour. I worked on my grocery list. read the newspaper... Read more
Wednesday, July 01, 2015
1 comments
Well I got up early and headed out to work on one of my locations. I spent about 3 hours cleaning, rearranging and adding new merchandiise. I was hoping to make it home before the storm hit. i left and got about 2 miles down the road when the... Read more
Monday, June 29, 2015
3 comments
Well I am off early to gt as much done as possible before the storms hit about 1:30 or 2 according to the weatherman. I have a lot to get done if possible I hope to get one of my shops completed today but if not will have to go back tomorrow. ... Read more
Sunday, June 28, 2015
2 comments
Well we were at the market yesterday and today. It has been sohot and humid it was miserable. We sat there and I started inn one are and cleaned and priced for my shops. I purchased quite a lot while I was working and stored it in boxes. We... Read more
Friday, June 26, 2015
1 comments
I was trying to get all my errands run before the storms hit. Miss Coco is really out of food so a trip to PetSmart was in order. Through all our trials with her allergies and other problems we are down to Grain free Blue Buffalo with no c... Read more
Thursday, June 25, 2015
0 comments
Well I had a busy day. It was Miss Coco's spa day so across town we went. I stop at a couple of places looking for merchandise. I had a cup of pepperjack crawfish soup and a scoop (small) of tuna salad. Then off to a store that was having a ... Read more
Wednesday, June 24, 2015
2 comments
I am taking a day for myself. I am going to make a pot of gumbo as I have fresh veggies . I will put some in the freezer for later use. We are scheduled to have another round of storms later today. I am so ready for these to be over, Th... Read more
Tuesday, June 23, 2015
2 comments
Monday was hot. I was to met Hubby at the dealership to leave his truck for a scheduled maintenance checkup. It was almost a 100 degrees when I got there. We left and Hubby wanted to stop and get a salad at his favorite barbeque place so we d... Read more
Sunday, June 21, 2015
0 comments
Well are hot again today. Hubby was trying to keep going today but I could tell it was taking a toll. I old him no business no need to stay. We closed up at 2 and we admitted that the heat was making him sick. We went to a store to get him S... Read more
Saturday, June 20, 2015
2 comments
We the actual temperature where we were was 102. I walked down to the end of our section and it was so hot. On the way back to our shop I was feeling really bad. There is a vendor about half way that makes and sells outdoor furniture. I sat ... Read more
Friday, June 19, 2015
2 comments
We need a break from the intense heat. We do not need storms, but just plain old steady rain. We are dry and the fire danger is great and we are having outbreaks of small fires. So far they have been able to control, but not good as it gets ... Read more
Thursday, June 18, 2015
2 comments
Well I got up early and watched the news and whether The temps were using fast. 2 to 3 degrees every 30 to 45 minutes. I got myself ready and told Miss Coco we were going. Got her to the groomers I took my car in for service and they were... Read more
Wednesday, June 17, 2015
1 comments
Well, it has been really hot and humid in our area. The heat is reaching a 100 and the heat index is higher. My ac is working hard as our house is older. We have insulated but it is not that air tight. We have not replaced the windows and pr... Read more


text:
Travis Rice is officially a "baller" now. Showing up to a movie that is all about you in a Rolls Royce with a hot model and walking the red carpet in NYC is pretty "baller" methinks.
It looks like the place was packed and that everyone was dressed nice and a few big names like Justin Timberlake even showed up. John Jackson really looked like a toolbox in his horrible blue suit and top hat and a lotta guys were wearing Yankee hats for some reason, but most people looked nice.
I've gotta say, I wish I was there for it. How 'bout you? Too bro brah for ya, or did it look fun?
ham bone
Lack of the recognition of the Harry and Lloyd reference deems you the first hammer pulled out of the toolbox.
Jordan S
Side note on the Jackson outfit, When in Aspen, Lloyd goes to where "the water flow's like wine", Check out the title of the chapter in the DVD at 54:30…. hmmm makes ya wonder
the girl with T.Rice is an organic chef in Jackson! not a model, but is still super hot anyway
tit dirt
john jackson's 'buddy' is his brother eric… also a pro snowboarder
Yep, Baller. Don't think that's a model tho, check out the tattoos, I think it's just his lady-friend.
Reno Local
Rolls Royce = Classy.
Someone didn't get that John Jackson and his buddy showed up as Harry and Lloyd from the Dumb And Dumber owl benefit scene.
-1 for lack of pop culture recognition
You don't watch movies other than ski movies… Do you? There is this magical little one from the 90's called "Dumb and Dumber". Let me tell you about a scene; the two protagonist show up to a ritzy Aspen party in suits that have no style at all. Those suits are similar to the ones that John Jackson and his buddy are wearing…
John Jackson looked awesome wadda ya talkin about


text:
The Top 10 In Action Sports
01Brick By Brick: Camping Lego Style
02Booze and Bikes: 14 Tours That Let Combine Two of the Best Things in the World
03Who Needs Hollywood? These Incredible Videos Were All Filmed on the Simplest Cameras
04Sam Pilgrim vs. The World: The Champion Aiming To Reclaim His Crown In A New Era Of Biking
05Eccentric Adventures Episode 2: Britain's Most Brutal Illegal Event is All About Cheese
06A Journey Into Darkness: We Went Mountain Biking in the Abandoned Mines of Slovenia
07After the Apocalypse: Inside The World's Most Breathtaking Ghost Towns
08Debate: Let's Stop Hating On Parents Who Want To Raise Adventurous Kids
09Guns, Roses, And Eating Insects: Adventure Cycling in Vietnam
10From Intense Trails to Intensive Care: Dicing with Death In a Mountain Biking Paradise
KICKSTART (Trailer)
A Motocross video by motoXcinema - 17,130 views
PreOrder the DVD and enter to win a new GoPro Camera!!
TransWorld Motocross Magazine presents KICKSTART, starring Nate Adams, Justin Barcia, Ryan Dungey, Tarah Gieger, Josh Grant, Jason Lawrence, Chad Reed and James Stewart. With footage shot in Florida, Delaware, California, North Carolina, New Jersey, Pennsylvania, Michigan and Maryland, KICKSTART is the first TWMX movie shot and edited entirely by the magazines editorial staff.
What Do You Think?
Get the best of Mpora straight to your inbox


text:
Gunmetal Black Ep 01
episode 14.26 / 5.00 5,028 Views
Lucina's First Day
A look at the first day of Lucina in Super Smash4.23 / 5.00 16,387 Views
BATMAN v SUPERMAN final showdown
SPOILERS!!4.19 / 5.00 14,703 Views
the ending sucked
no offense, but I'm REEEEEEEEEEEEEEEEEEEEEEEEEEEEEEAAAALL LLLLLLLLLLLYYYYY tired of hearing that. but everything else is a-ok. 4/5
Ignore what SteeLRaTnl said, i thought it was very good, and definatly didn't deserve a 0, the action was a little slow but not a problem, the first kill was completely unexpected, overall 8/10, not perfect but very good.
i really liked but i dont thinq paper boxes stop bullets, anyway i really enjoy it. it has great quality and everything. if only they made a decent game like the krinkles one.
The boxes have................METAL INSIDE THEM YES, METAL now lets not talk about this strange cover up for lazyness wait what?
After so long
It's finally here.
The kills were amazing. Kudo's for DJTrickyM, he sure knows how to make custom wounds.
But what i neglected to see was you own backrounds. I mean at firest they were just plain rooms but they were custom! xD
But later on, it was plain backrounds made by krinkels, which is ok, but show's some sort of lazyness.
But threwout it all, i really enjoyed it.
9/10 5/5
I can't draw epic backgrounds oh and now you've brought that up I just relised i fucking forgot to customize them.
*slaps face* :(
very nice
cool animations, but the end was somewhat too abrubt.
if i might give you a hint: the protagonist hops so much that it looks like he has a limp or something
and STeeLRaTnl, 0 improvement doesnt mean you have to give it a 0. this was a good animation!
He's not hopping, He's jumping thats my style.
Oh and steelratnl is just a faggot.


text:
Learning is important because it boosts confidence, is enjoyable and provides happiness, leads to a better quality of life and helps boost personal development. Learning is about more than economic success, but is also about the way that it can influence a person's life in positive ways such as happiness.Know More
Learning is the key to achieving a person's full potential. Human beings are uniquely adapted to learn and can learn throughout their lifespan. For people, learning does not stop after high school, college or graduate school. People who continue to learn are able to transform their lives and become more successful at home, more successful with their families, more successful at work and more successful within their local community.
Learning does not happen through isolation, and there are many factors that can either boost learning or hinder learning. A person's motivation and their preferred learning style can be a help or a hindrance to their ability to learn. A person's external factors, such as their obligations and demands, can also be a help or a hindrance. There are several key factors that affect people's learning behavior and these include people's resources, their image of learning, the rewards associated with the learning activity, the availability of information about learning opportunities, the availability of appropriate learning environments and the climate in which learning takes place.Learn more about Social Sciences
It is important to use primary and secondary data to test researcher bias and to gather enough information to fully explore a topic. Primary research is any data that is gathered by the researcher. This includes observations, interviews and anything else that is learned during the data collection process. In historical research, primary data is first hand accounts of events and occurrences, and original documents.Full Answer >
Mothers are important because they help in a child's social and emotional development according to Psych Central. The role of a mother has changed over the past couple of generations, but there are still vital tasks that a mother must carry out. One thing that has not changed is that mothers give birth to children who one day grow up to become contributing members of society.Full Answer >
Respecting people is important in relating to others. By respecting others and their properties, the world becomes a safer place. Respect is one of the virtues that distinguishes humans from animals.Full Answer >
Punctuality is important because it is polite to be on time. Being late to an appointment or event is simply rude. Lateness leaves a bad impression.Full Answer >


text:
Volkswagen Beetle TDI Problem Report
Volkswagen Beetle TDI Correct Maintenance of Timing Belt
(6 reports)
To ensure longevity of the engine, our technicians recommend to follow the maintenance schedule for the timing belt.
Related Items:
do most shops replace all of the needed components when changing the timing belt: water pump,...
What is the recommended mileage for replacement of the timing chain.Thanks Patty
Just turns over and tries to start but won't.
I was only doing 40mph and the belt didn't break. the engine will turn over but the time belt w...
The car has 283,000 miles and the engine runs strong. I keep getting the code PO116. Put in a new oem sensor. Still getting the code yet my scanner shows the coolant temp at 30 degrees when it's 190? New Thermostat didn't help!
Car has 283,000 and runs strong. Did the timing belt and new water pump about 7,000 miles ago....


text: Charming and intimate. Peaceful and quiet. Upon rising in the morning, we walked about 25 meters to take a dip in the pool and listen to the surf. What a great way to wake up!! The salt water pool is divided in two sections: shallow for the little kids and up to chest deep for adults. Plenty of poolside lounges... More


text:
1997 BMW 540i Q&A
1997 BMW 540i Question: Car is leaking coolant and it drains quick from rear of engine and bellhousing.
I can't find the heater hoses on first glance. Is that where they are? - wagesdf
Answer 1
Hi. The most common coolant leaks that we see on this engine are from the valley pan (aluminum plate w/ plastic cover on top of the engine block under the intake manifold) and/or the coolant tubes (2 aluminum tubes that run from the back of the water pump to the crossover tube on the back of the engine that attaches to each cylinder head. When those items leak, the coolant tends to run off of the back of the block and streams down the bellhousing. The way to verify this is to remove the top engine cover and use a flashlight to look under the intake manifold at the front and rear of the engine. A cooling system pressure test will also pinpoint the leak if there is any question as to the source of it. If the top of the engine is wet, you will need to remove the intake and replace the valley pan, the seals for the tubes and either remove and replace the water pump gaskets (good time to replace the pump and t-stat), or the crossover tube gaskets where they seal to the back of the heads (depending on which side of the engine you choose to remove the tubes from). You should also re-seal the PCV cover at the back of the intake manifold at the same time and change the thermostat housing assembly. The coolant sensor on the housing will leak internally and push coolant through the wires back to the Eng. control module. This is very common and when it happens, it is very expensive because the DME (ECM) is about $1400 (you can't just install a used module without also replaceing the EWS, and ignition lock cylinder and the used parts must be from the same car and can be difficult to source). I would be happy to visually inspect the leak and provide a complete estimate for the repair also. Good luck! James Wallace EuroAsian Garage Seatac, WA 206.246.3886 www.euroasiangarage.com - Jamesw
Related Content
1. stevieray1
2. pushrod
3. globalhelper
4. csubak30
5. ziptie12


text:
Don't throw Away Those Old Christmas Lights, They Can Be Recycled!
As many people gather up the Holiday decorations for the season, many will find that string or strings of lights that no longer work, but don't throw them in the garbage.
As many people gather up the Holiday decorations for the season, many will find that string or strings of lights that no longer work, but don't throw them in the garbage.
What's in a name? That's a question Santa Claus himself should be asking when looking at who's been naughty and nice this year.
If you had to guess, what do you think a former Rocket Scientist does in his spare time? If you guessed design Ugly Christmas Sweaters you are correct!
Ever wonder how the next generation is going to turn out? Well, it looks like they're shaping up to be a pretty kickass bunch -- at least, if their names are any indication.
Now that we rolled with our full belly out of the Thanksgiving Holiday, our attention has turned to the other ones coming up fast. Here are a few new releases you can put on your shopping list for the music fan in your life.
I have never heard of this in my life, but obviously some people will fall for this. Yes Thanksgiving is over, but some people still cook turkeys for other Holidays.
Here it is a new trend on the horizon for ladies....dying your armpit hair. If you decide to go natural you might as well show it off right?
For Vikings fans it seems the surge in how well they are playing has come a little to late,with ticket sales slumping at their temporary home of TCF Stadium.
This year we are not putting up a Christmas tree or decorations around the house, and in a way I feel like my neighbors will wonder what is wrong with us?
Who doesn't or didn't love the show "Friends?" To this day I still watch re-runs and let out more than a chuckle or two.
With this being the busiest travel weekend all year, many people are packing up the car or headed to the airport to celebrate with friends and family. But, don't leave your house vulnerable.
It is a very Thankful week with the holiday and some great new releases this week from some big artists!


text:
Filter Results
Featured Events
- Cardinals tickets
- Chargers tickets
- CONCACAF Gold Cup tickets
- Cowboys tickets
- Cubs tickets
- International Champions Cup tickets
- Mexico National Soccer tickets
- MLB All Star Game tickets
- MLB Home Run Derby tickets
- Notre Dame tickets
- Packers tickets
- Red Sox tickets
- SF Giants tickets
- US Open Tennis tickets
- WWE - World Wrestling Entertainment tickets
Calgary Roughnecks Ticket & Seating Information
Calgary Roughnecks tickets are now on sale at Vividseats.com. Pick a date and pick up some cheap Calgary Roughnecks tickets to catch the incredible action that this sport offers. Vividseats.com offers a massive selection of sports tickets with premium seating throughout the year, including super deals on Calgary Roughnecks tickets. Act now and pick up your Calgary Roughnecks tickets before they sell out. Order your Calgary Roughnecks tickets today with our reliable internet server.


text:
Driveline Single Piece 219 Axle Sprocket
Burris Hi Rev 2-Cycle Lubricants
AN5 Airframe Bolt, 5/16-24 Thread
Stainless Steel Safety Wire, 1 lb. Spool
Douglas 17mm Spindle Mount Aluminum Wheel 5.0" x 5" - Black
"Thanks for the help. Your customer service is always top notch." P.G. from Texas
Flanged metric bearing for Margay racing karts or any chassis utilizing an 8mm bore bearing with a 22mm o.d. Requires 2 per spindle.
Follow us on facebook
Pegasus Auto Racing Supplies2475 S 179th StNew Berlin WI 53146 USA
Order Toll Free: 1-800-688-6946 (US & Canada)
Local/International Order Line: 1-262-317-1234
Technical Questions: 1-262-317-1200
Fax Line: 262-317-1201
Email - General Questions: email@example.com
Email - Technical Product Questions: firstname.lastname@example.com
We do our best to ensure that the prices and descriptions shown on our website and in our printed catalog are accurate.However, we reserve the right to correct any errors that may occur.
Privacy Policy
© 2004 - 2015 Pegasus Auto Racing Supplies, Inc. - All rights reserved


text:
As hip-hop's influence has gone global over the years, it became natural for hip-hop to expand into media beyond music in its 40-year existence. The ...Read More
12 Best Hip-Hop Instagrams Of The Week
A high Michael Jordan, an asian version of baby Drake, and Swizz Beatz' adorable daughter were the highlights of Instagram this week. Add in ...Read More
16 Hip-Hop Moments Of The Week
This has gone by fast and you may have missed some of the biggest moments in hip-hop. That's why we're here. This week there's a ...Read More
5 Craziest Moments From The New Cam'ron Trailer (NSFW)
On October 1st, everybody's favorite Vine videographer, Cam'ron will be kickstarting a brand new web series. The series entitled 1st Of The Month will be starring ...Read More
Cam'ron Has A New Series Coming Soon
Cam'ron is taking his talents from Vine to YouTube. Killa is set to drop a new series called 1st Of The Month and judging from ...Read More
Here's Some Pictures Of Rappers Reppin' The American Flag
In honor of this American holiday, it's only right to show appreciation from the hip-hop community. Being that this day celebrates U.S laborers, XXL ...Read More
15 Rap Songs For Your Labor Day Weekend BBQ Playlist
Labor Day weekend is in many ways the last gasp of summer. Unlike the 4th of July, a holiday filled with possibility and hope, Labor ...Read More
Cam'ron Invites You To Harlem In "Welcome To My World"
Cam'ron may be teasing a bit, but the release of Ghetto Heaven Vol. 1 is approaching on October 1. Until then, the Dipset rapper gives ...Read More
Today In Hip-Hop: Charli Baltimore Turns 38
Flame-haired rapper, Charli Baltimore, turns 38 today. Although, she only released one album, 1999's Cold As Ice, Baltimore was a significant presence in the New York ...Read More
- 24 Rappers Who Don't Have Their Own Artists
- 26 Photos of Bad Boy Over the Years
- Here's a History of Scott Storch's Troubles
- Diddy's Been a Regular at the UCLA Campus the Past Few Months
- 9 Rappers Called Out by Their Exes
- Best Hip-Hop Instagrams of the Day
- 10 of Chris Brown's Emotional Moments Over Karrueche Tran
- 19 Rappers Who Performed in Africa
- Chris Brown's Major Meltdowns Over the Years
- 3 Rappers Who Saved Someone's Life
- 49 of the Most Recent Leaked Songs by Young Thug
- 5 Rap Videos Shot in Africa
- 11 Rappers Giving Lectures at Universities
- 29 Rappers Celebrate Their Mothers On Instagram
- Best Hip-Hop Instagrams of the Day


text:
A practical guide to minimal surgery for retinal detachment: Temporary tamponades with balloon and gases without drainage, buckling versus gases versus vitrectomy, reoperation, case presentations
Thieme, 2000 - Medical - 356 pages
From inside the book
27 pages matching coagulation in this book
Where's the rest of this book?
Results 1-3 of 27
What people are saying - Write a review
We haven't found any reviews in the usual places.
Balloon Buckle versus Pneumatic Retinopexy
2 other sections not shown
Common terms and phrases
additional balloon catheter balloon operation balloon procedure beneath cataract central artery cerclage Chapter clock hour coagulation complications conjunctiva cryopexy lesions diplopia drainage of subretinal expanding gas expanding-gas operation external buckling gas bubble technique gas injection gas operation gas tamponade giant tear group of breaks hole horseshoe tear inferior detachment intraocular gas bubble intraocular pressure Kreissig laser coagulation laser lesions lateral edges lattice degeneration lens light perception limbus Lincoff H loon macula ment minimal extraocular ml of fluid morbidity needle o'clock Ophthalmol ophthalmoscopy ora serrata parabulbar balloon pars plana patient perfluorocarbon gases pigmented pneumatic retinopexy position posterior edge posterior pole postoperative primary vitrectomy radial redetachment reoperation retina was reattached retinal break retinal detachment retrohyaloidal rotation scleral buckling segmental buckling small gas bubble sponge stylette subretinal fluid superior surgical failure sutures temporary balloon buckle tion treated treatment uncomplicated detachments undetected break visual acuity vitrectomy vitreous hemorrhage volume


text:
- Article
- About the Authors
- Metrics
- Comments
- Related Content
About the Authors
- Philip Salesses, Katja Schechtner, César A. Hidalgo
- The MIT Media Lab, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
- Katja Schechtner
- Mobility Department, Austrian Institute of Technology, Vienna, Austria
- Katja Schechtner
- Institute of Urban Design and Landscape Architecture, Vienna University of Technology, Vienna, Austria
- César A. Hidalgo
- Engineering Systems Division, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
- César A. Hidalgo
- Instituto de Sistemas Complejos de Valparaiso, Valparaiso, Chile
Corresponding Author
Email: firstname.lastname@example.com
Competing Interests
César A Hidalgo is a PLOS ONE Editorial Board member. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.
Author Contributions
Conceived and designed the experiments: CAH. Performed the experiments: PS. Analyzed the data: CAH PS. Contributed reagents/materials/analysis tools: CAH PS KS. Wrote the paper: CAH KS PS. Original Idea: CAH.


text:
Delhi water crisis worsens as Haryana cuts down supply
New Delhi: An unprecedented water crisis loomed large over the city today with neighbouring Haryana drastically cutting supply, leaving various treatment plants short of raw water and areas across Delhi parched.
Areas across the city have already been grappling with acute shortage of water and the situation may worsen further as production at water treatment plants has come down sharply due to shortage of raw water.
Top officials in the Delhi Government said most areas in the city will face severe water shortage and accused the neighbouring state of playing "foul" with Delhi on the water issue.
"People of Delhi are bound to face acute shortage of drinking water as Haryana has arbitrarily and drastically curtailed raw water supply," said a late night statement from Chief Minister`s office.
Considering the gravity of the situation, Chief Minister Sheila Dikshit have been trying to speak to her Haryana counterpart Bhupinder Singh Hooda but to no avail, sources said.
Expressing anger at Haryana cutting raw water, Chief Minister`s office said Delhi Government would take up the issue "at all levels" as Delhi is not just a city but the national capital.
"We are not asking for any favour. We want what is due to us," it said.
Officials said Chief Secretary P K Tripathi and DJB CEO Debashree Mukherjee have also been requesting top officials in Haryana government to release water to Delhi but so far no positive indication has come from the neighbouring state.
They said production of water in various treatment plants has come down by 45 million gallon per day (MGD) which would leave most people "thirsty" tomorrow.
"The residents of North, West, New Delhi and Walled city will have to face a very difficult situation in their localities," the statement from Dikshit`s office said.
"It is expected that around 25 lakh residents in Khayala, Patel Nagar, Mot Nagar, Kirti Nagar, Narela, Bawana Wazirabad, and old Delhi localities will be severely affected," it said.
The officials said around 40 lakh people in various areas of the city will face severe shortage of drinking water due to cut in supply by Haryana.
The production of water at Wazirabad treatment plant has gone down by 30 MGD while Haiderpur plant produced 15 MGD water less.
The current average demand of potable water in the city is around 1,100 mgd (million gallons per day) and currently Delhi Jal Board is supplying around 750 mgd water.
DJB officials said the water level at the Wazirabad pond has also come down sharply due to cut in supply by Haryana. Water treatment plants at Haiderpur, Wazirabad and Chandrawal rely on raw water supply from the Wazirabad pond.
Upset over Haryana not heeding to Delhi`s request for supply of more water, Dikshit on Tuesday had said that she would seek the Prime Minister`s intervention in finding an early solution to the Munak canal dispute with the neighbouring state.
The Munak canal was constructed by Haryana with financial assistance of around Rs 400 crore given by Delhi government on the condition that the national capital will be supplied 80 MGD water from it. But later, Haryana refused to supply the water to the city.
Chief Secretary Tripathi on Monday had asked his Haryana counterpart P K Chaudhery to release more water to Delhi to address the problem of water shortage but the latter turned down the request.
More from India
More from World
More from Sports
More from Entertaiment
- Dr Subhash Chandra Show: Is Corporate Social Responsibility nothing but a marketing gimmick?
- Journalist covering Vyapam scam dies in Madhya Pradesh
- Vyapam Scam: IMA president Sudhir Tiwari fears life threat
- Vyapam Scam: Mystery over journalist Akshay Singh's death continues
- The inside story of IC-814 hijacking
- Vyapam scam: MP medical college dean found dead in hotel, body sent for post-mortem
- Vyapam scam: Last rites of journalist Akshay Singh performed; MP CM assures of SIT probe
- Photographer captures International Space Station flying across moon
- Akshay Singh's death case: MP CM assures fair probe, lambasts Oppn over Vyapam scam
- Chile stun Argentina to win first Copa America crown


text:
Yesterday's loss was not only frustrating it was really boring. No flow, pure frustration, mixed with a touch of rage.
That might be overstated, but when the Pirates collapsed last year a huge hallmark was their complete inability to beat bad teams.
I guess playing up to good competition is a good attribute, the Pittsburgh Steelers won a Superbowl playing down to poor competition. In the playoffs all the competition is good.
The good news is that the next two games will be pitched by guys I have a feeling are gonna step up.
Francisco Liriano pitches tonight. If I wasn't so busy waiting for the other shoe to inevitably drop with him I'd say he has to be a top five Cy Young candidate. Not that I would ever say such a thing about a guy who struggles every time I praise him.
He sucks. He blows. He can't win.
Keeping the ball in the park, giving up few hits, striking out a ton. What more could you ask from the guy?
His last outing was dazzling, his outing before? Electrifying. He has put that poor first outing back from the break in the rear-view mirror and is just continuing on the path of greatness.
Four of his last five outings were 7+ innings, including that awesome complete game shutout.
He is throwing up a quality start in 67% of his outings and has an average gamescore of 61.7, well above the average of 50.
Most important the Pirates are playing .733 ball when Liriano pitches.
He's basically been unbeatable at home.
Liriano's sole matchup with the Rockies came in 2010, a loss, but not a nice outing.
That looks eerily similar to a typical Pirate pitcher's losing line.
It wasn't long ago that Jorge De La Rosa was rumored to be the top free agent target of the Pittsburgh Pirates.
Okay, maybe that was long ago.
Of course he signed with the Rockies, started out good but proceeded to pitch just 13 games in 2011 and 2012. Something that would have really hurt the Pirates. That's the risk with big money free agents though. The Pirates actually dodged quite the bullet.
But he's back now, and pitching fine. Of course the Pirates will face the Rockies top three. Why would this series be any different than every other series?
It appears De La Rosa has learned how to pitch a little bit instead of relying on raw stuff to blow past guys. Just about everything is lower than his career average. Hits, walks, strikeouts, homers, WHIP. All down.
He got his ass kicked against the Braves though. I mean, big time.
I'm not sure if it's circumstances or design but he has only thrown 100 or more pitches three times. He has gone eleven straight games without reaching the 100 pitch mark. That leads to some shorter outings. He has only gone seven innings four times. He hasn't gone more than that at all.
Because of that his quality start percentage is 59% and his gamescore is 52.9. The Rockies still play good ball when he is pitching though with a .636 winning percentage, but he only 5.7 IP per game.
Obviously then the key is to get that pitch count up and feast on that crappy bullpen. The Rockies bullpen ranks 23rd in ERA and 25th in WHIP. They've also pitched the fifth most innings in baseball, just 0.1 innings less than the Pirates.
As you can imagine De La Rosa can be tough on lefties, I'd definitely sit Doubleplay Garrett Jones tonight.
A little oddity for Jorge is that he actually pitches better at Coors Field than on the road.
De La Rosa has been nothing special, or nothing terrible, against the Buccos.
He has been pretty bad at PNC Park.
First Pitch: 7:05 PM EST
Where To Watch: Root Sports, MLB.TV, Root Sports (Colorado)