text:
Tip off at 1:30, Crisler Center
Lets get it done today guys.
I'm still adapting to the fact this is relevant to my life.
i would find this more credible if it was about Tom Crean
I did not make this headline up
if Hail and Unite gets us on this list I will support it
further adventures in Jed York justifying the unjustifiable
national title buys you a lot of time
Only you can get away with that.
It's the same old story. Boy finds girl, boy loses girl, girl finds boy, boy forgets girl, boy remembers girl, girls dies in a tragic blimp accident over the Orange Bowl on New Year's Day.
We need some payback for last years game
If you're doing nothing, how do you know when you're finished?
Michigan Stadium:
The hole that Yost dug, Crisler paid for, Canham carpeted, Schembechler filled and Dave Brandon emptied


text:
International News Archive - October 26, 2010
A powerful earthquake that hit 48 miles west of South Pagai in the Mentawai islands late Monday touched off a tsunami that wiped out the coastal Indonesian village of Betu Monga, where many residents are missing and feared dead, officials said on Tuesday.
Word of the Day
- Large; stout; burly.
The word 'bowerly' is an alteration of 'burly'.

subset: commoncrawl


text:
Image: Dylan Thomas' Boathouse
the Shelf Festival of Words is
well established as one of the major events in Sheffield
and the region's cultural calendar. The festival has grown into one of the
largest, most popular and exciting events in the North of England attracting
some of the best known names in literature and the media. The festival offers a
wide range of events for audiences of all ages including readings, workshops,
storytelling, exhibitions, talks, walks, poetry and much more.
The Showroom is delighted to work in
collaboration with Off the Shelf, presenting an exciting and
extensive programme of guest speakers and film screenings
Callingall out-of-towners! The Sheffield Culture Consortium
need your help:
Do you live outside of Sheffield and intend to buy a ticket for
this year's Off The Shelf festival? We're interested in encouraging more
people like you to come to Sheffield and experience the fantastic festivals,
cultural venues and events on offer here.
Therefore, we would like to find out about you and what you
think about Off The Shelf. We'd be really thrilled if you could take part
in a short online survey, conducted in accordance with Market Research Society
guidelines, to tell us about how we can improve on your visitor experience in
the future.
If you complete the survey you'll also have a chance to win a
£10 book token kindly donated by Off The Shelf, so all you have to do is follow
the link to the survey here (it should only take you 10mins to complete)
All your responses will of course be treated confidentially.
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Latest Steinmetz Pink Diamond Stories
2011-06-10 07:10:00
VANCOUVER, June 10, 2011 /PRNewswire/ - Rockwell Diamonds Inc.
2005-07-10 07:59:26
By Mike Collett-White LONDON (Reuters) - "Diamonds," a new exhibition in London, boasts an impressive carat count and some of the world's most glittering gems, but protests over the treatment of African bushmen by mining giant De Beers exposed some flaws.
Word of the Day
- A bereavement by loss of parents or children; the state of being orbate; orbation.
The word 'orbity' ultimately comes from a Latin word meaning 'bereaved'.


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i don't think so...we understand the matter differently..for me, as a chessplayer, you can only say that you have solve it if you were able to see the key move and presicely calculated all collateral variations arising from it.
and i guess you did not able to solve it coz you suggested 1.Kb2?
What a strangely rigid definition of 'solve' - I guess once you make a mistake it is impossible to solve it, even when you give the correct key and all variations. :)
.....and i guess bigdoggproblem had problem understanding what i posted.
what i said:
"for me, as a chessplayer, you can only say that you have solve it if you were able to see the key move and presicely calculated all collateral variations arising from it."
bigdoggproblem said:
I guess once you make a mistake it is impossible to solve it, even when you give the correct key and all variations. :)
I'm sad becoz he did not understand the line "precisely calculated all collateral variations".. How can you make a mistake if you are precise in your calculations huh???!!!!
I put it into an engine. Analysis says "#-3 (Mate in 3)"All the suggested variations to get out of it fail.
Looks like I will have to go a tad more slowly.
Let's start with: "give" and "calculate" don't mean the same thing. :)
So you are saying that we are supposed to calculate ALL the possible moves to "solve" a puzzle ?
Example : mate in one.
You did not "solve" it if you didn't see the five mating moves, and the fact that 1.Qb3 draws, according to your definition.
i guess you have to read and understand thoroughly what i have posted.. what i meant "calculate all the colateral variations".. these are the variations you have to calculate after you have given the key move..in order to prove that you have comppletely solved a puzzle, you have to analyze all variations that would arise depending on black's reply..
Which one, precisely, is not given in #19 ?
Yikes...moving on...
- not #19, but your comment in #11 which suggests 1.Kb2??? which according to you can give mate more reliable..the key move you suggested is wrong, thus follows the variations as well.
Her plan is to post a comment every one or two days so her topic comes in the "Most Recent Posts" section at different times of the day, hoping that she gets more viewers. Ignore it.
- well, honestly i dont have such plans in mind..i posted this puzzle to challenge evryone who viewed it if they can solve it,..and that is all. i dont consider it as an honor that this may be included every week as "most recent posts", i would rather prefer to achieve a higher rating by playing chess in this site to prove something- and that I call honor.
If I follow your reasoning :
1-None gave the full lines in the same post, except Irontiger.
2-Irontiger got the puzzle wrong at first.
3-Thus, the puzzle is not solved.
Do you see a problem ? No ?
1-None has managed to create a fire, except Gronk the cavesman who put together the idea of silex from Hurk the stone carver and the idea of hitting from Durk the hunter.
2-Gronk the cavesman failed when he first tried clay instead of silex.
3-Thus, fire has not being invented yet.
Now I understand Sharrocks (#32) was true, and I will follow is advice. It was a pretty puzzle, but your trolling ruins it all.
there were more variations in it..tnx for liking it.
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Sean "Diddy" Combs is being treated for injuries he sustained during a minor car accident in Beverly Hills, Calif.
Sean "Diddy" Combs is being treated for injuries he sustained during a minor car accident in Beverly Hills, Calif.
A spokeswoman for the 42-year-old rapper-producer says he hurt his neck, ribs and collarbone in the crash Wednesday on Sunset Boulevard near the Beverly Hills Hotel.
Combs was a passenger in a Cadillac Escalade when a Lexus sedan made a left turn and collided with it. A police lieutenant said Combs complained of pain but he was not taken to a hospital at the time.
Publicist Keesha Johnson said Thursday that doctors are now treating Combs, and he is grateful for the outpouring of fan support following the accident.
- Narcotics dog hospitalized after ingesting meth
- It's no easy task, but contract extension for Seahawks QB Russell Wilson will get done
- 5 Seahawks takeaways from the NFL League Meetings
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Report Clears Fla. Police Chief of All Allegations; Union Expected Investigation
Orlando Sentinel (Florida)
A report released Tuesday night dismissed allegations that police Chief Clarence Bass was untruthful with the City Council and fosters an environment of intimidation and favoritism as "emotional and personal feelings."
John McCollister, the investigator hired by the city to write the report, said he was convinced that while the chief "can be gruff and impatient," there is no evidence to substantiate any wrongdoing or justify his firing.
"When it comes to proving allegations against the chief, the investigator echoes the words of the late actress Clara Peller, who in the famous television commercial asked: 'Where's the beef?' " McCollister wrote.
Bass, who has managed the department of 11 full-time officers and five reserve officers for 11 years, did not answer any questions after the report was given.
An attorney for the police union said the report was "short on details."
"This is not what we expected," said Lawrence Collins, the union's attorney. "For some reason we expected an investigation. The [union] does not manufacture issues. There are real problems in the management of the Police Department."
Others in the audience questioned why there wasn't a further probe into some issues such as why the chief did not take action sooner after he was alerted that one officer made racial slurs on the job. That officer was demoted after the issue was raised publicly by the union.
McCollister issued 14 recommendations for the city to consider including, "Live in the present, not in the past" and "Let the chief and his staff do their jobs." He also urged the creation of a citizens advisory board, ombudsman and suggested that the city's paid staff and elected officials be prohibited from talking to the media.
McCollister, who listed his experience as a federal arbitrator and state special master who has conducted more than 600 hearings, refused to answer questions from citizens or reporters about his report.
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text:
"emerald impress for Elis Mum"
Description from franny: for Elis Mum - eg. brass chain around back of neck attached to stone tubes at either side of front, then brass rectangles (I'd prefer barrels) & completed with stone pumkins strung across the front! Voila! a necklace in cross section - (the rest is chain options as min. 8 frames required!) Hey, there's an idea - lengths of varieties of chain interspersed with the stones!
- "Beach Glass": on
"This is a great combo of blue for the beach. I can almost smell the…" read »
- "Bird's Eye": on
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"I love the clean feel of this combo of blues! Nice!…" read »
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|16" strand
|½ strand (loose)
|16" strand
|½ strand (loose)
Read the comments (or add your own)
Franny-That sounds gorgeous!!
It does and I love the green of this jasper!
Franny, this is beautful! I love all the different textures of the chains, and the jasper is awsome! I especially like the idea of chain and stones draping in front. Fabulous!
This is the coolest combination – love this particular green with the copper, and the play among textures. This went right into my favorites.
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1 review, 0 user ratings
Wrecking Crew, The by Jay Seaver
No Mercy by Jack Sommersby
Girl Like Her, A by Peter Sobczynski
Honest Liar, An by Jay Seaver
Heist, The by Jack Sommersby
Fade to White by Jay Seaver
I Was a Teenage Superhero Sidekick by Jay Seaver
Rustlers' Rhapsody by Jack Sommersby
Slap Shot 2: Breaking the Ice by Jack Sommersby
Noah, The by Jay Seaver
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SxSW 2015 Interview: LANDFILL HARMONIC director Brad Allgood
DVD/Blu-Ray Reviews For 3/23: "I Am The Wrath Of God! Who Else Is With Me?"
Films I Neglected To Review: It Must Be The Shoes
SxSW 2015 Interview: BRAND A SECOND COMING director Ondi Timoner
SxSW 2015 Interview: THE INVITATION director Karyn Kusama
SxSW 2015 Interview: WESTERN directors Bill & Turner Ross
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"A 'Transamerica' precursor, with the expected flaws."
USA 12-Sep-1997 (R) DVD: 25-Jan-2000UK 10-Apr-1998 (15) DVD: 02-May-2001Australia N/A (MA)
Directed by
Richard Spence
Written by
Tony Marchant
Steven Mackintosh
Rupert Graves
Miriam Margolyes
Saskia Reeves
Charlotte Coleman


text:
P-Mation #41: A-Door-Able
Blue boy meets his lovely neighbor!4.45 / 5.00 8,231 Views
Otherworld - Quiet Luke
in da othawurld4.44 / 5.00 4,429 Views
Joe vs the Environment
In collaboration with Earth Hour 2015 and Pocoyo4.11 / 5.00 2,230 Views
There will be cake.
Not bad
It was very short but it had violent bloody brains. Wouldnt mind seeing somthing like this in Half-Life. I wouldnt mind owning Half-Life either.
That was simple and yet entertaining, I give it 10 and 5.
keep it up. Alex
"God told me to say it"
thank God
That was a freaking smart Idea you got there!
Too bad you have to play the game to understand this joke...
how convenient
simplicity made the movie, I'll rate 5


text:
Page 1
Nelfinavir and Lamivudine Pharmacokinetics During the First
Two Weeks of Life
Mark Mirochnick, MD,* Karin Nielsen-Saines, MD, MPH,† Jose Henrique Pilotto, MD, PhD,‡
Jorge Pinto, MD, DSc,§ Valdilea Gonc ¸alves Veloso, MD,¶ Steven Rossi, PhD,? Jack Moye, MD,**
Yvonne Bryson, MD,† Lynne Mofenson, MD,†† Margaret Camarca, RN, MPH,‡‡ D. Heather Watts, MD,††
and NICHD HPTN 040/PACTG 1043 PROTOCOL Team
Background: There are no previous data describing nelfinavir and lami-
vudine pharmacokinetics in neonates treated with weight-band dosing
Design: Pharmacokinetic study of nelfinavir and lamivudine pharmacoki-
netics in infants during the first 2 weeks of life treated with weight-band
dosing regimens.
Methods: Intensive 12-hour pharmacokinetic profiles were performed
between either days 4–7 or days 10–14 of life in 26 Brazilian infants.
Results: Pharmacokinetic data were obtained from 26 infants who received
median (range) per kg doses of 58.8 (48.4–79.0) mg/kg for nelfinavir and
2.0 (1.5–3.2) mg/kg for lamivudine. Median nelfinavir 12-hour AUC
(AUC0-12) was 25.5 (1.7–183.5) ?g*h/mL and median 12-hour concen-
tration (C12h) was 1.09 (?0.04–14.44) ?g/mL. AUC0–12 was less than
15 ?g*h/mL (the 10% for adults) in 12 infants (46%). Median lamivudine
AUC0–12 was 7.8 (2.7–15.6) ?g*h/mL and median C12h was 0.23
(?0.04–0.74) ?g/mL.
Conclusions: Lamivudine pharmacokinetic parameters observed in this
study were consistent with those seen in other studies of neonates. While
median nelfinavir AUC and C12h in these neonates were above the
exposure targets, interindividual variability in nelfinavir exposure was
large and nelfinavir exposure failed to meet the exposure targets in 46% of
Key Words: nelfinavir, lamivudine, pharmacokinetics, newborns
(Pediatr Infect Dis J 2011;30: 769–772)
during pregnancy and labor and to the neonate after birth. How-
ever, if the mother does not receive treatment during pregnancy,
the optimal composition and duration of postnatal neonatal anti-
retroviral prophylaxis is unknown. The number of antiretrovirals
with formulations suitable for use in neonates and with adequate
neonatal safety and pharmacokinetic data is limited, especially
among the protease inhibitors. Previous studies of nelfinavir phar-
macokinetics in the first weeks of life demonstrated low nelfinavir
exposure in a significant number of infants even with nelfinavir
doses of 40 to 45 mg/kg twice a day.1,2
Recent antiretroviral dosing guidelines for low resource
settings have recommended treatment with weight-band dosing
regimens rather than individual dose calculations using weight or
body surface area. There have been few previous studies describ-
ing antiretroviral exposure with weight-band dosing in the first weeks
of life. The goal of the current study was to describe the pharmaco-
kinetics of nelfinavir and lamivudine during the first 2 weeks of life
with use of weight-band dosing regimens. The nelfinavir regimen was
designed to provide 50 to 75 mg/kg per dose.
other-to-child HIV transmission can be dramatically reduced
with the administration of antiretroviral agents to the mother
NICHD/HPTN 040/IMPAACT P1043 is a recently com-
pleted trial in Brazil, Argentina, South Africa, and the United
States that compared the efficacy of 3 infant regimens (6 weeks of
zidovudine alone, 2 weeks of nelfinavir/lamivudine plus 6 weeks
of zidovudine or 3 doses nevirapine in the first week plus 6 weeks
of zidovudine) in preventing mother-to-child HIV transmission in
infants whose mothers receive no ARV therapy during pregnancy.
Infants in the nelfinavir arm received zidovudine (10 mg/mL
syrup), lamivudine (10 mg/mL syrup), and nelfinavir (50 mg/g
powder) twice a day according to the following weight-based
dosing regimen: zidovudine 12 mg if birth weight ?2000 g, 8 mg
if birth weight ?2000 g; lamivudine 6 mg if birth weight ?2000 g, 4
mg if birth weight ?2000 g; nelfinavir 200 mg if birth weight
?3000 g, 150 mg if birth weight between 2001 and 2999 g, 100
mg if birth weight ?2000 g. Eligible infants were less than 48
hours old at the time of enrollment and were born to mothers who
were identified as HIV-positive but received no antiretroviral
therapy during the pregnancy. Their mothers may have received
oral or intravenous ZDV during labor. Exclusion criteria included
gestational age less than 32 weeks, birth weight less than 1500 g,
presence of life-threatening conditions, inability to take oral med-
ication and administration to the mother of any ARV during labor,
and delivery other than ZDV. Local institutional review boards
approved the protocol at all participating sites, and signed in-
formed consent was obtained from the mothers of all subjects prior
to participation.
Two of the sites participating in the study (Hospital Geral de
Nova Iguac ¸u, Nova Iguac ¸u, Brazil; Federal Universidade of Minas
Accepted for publication March 24, 2011.
From the *Department of Pediatrics, Boston University School of Medicine,
Boston, MA; †Department of Pediatrics, David Geffen School of Medicine
at UCLA, Los Angeles, CA; ‡Infectious Diseases Department, Hospital
Geral de Nova Iguaçu, Nova Iguaçu and Laboratório de AIDS e Imunologia
Molecular/FIOCRUZ, Rio de Janeiro, Brazil; §Division of Immunology,
Department of Pediatrics, Universidade Federal de Minas Gerais, Belo
Horizonte, Brazil; ¶Instituto de Pesquias Clinica Evandro Chagas/Fiocruz
Institute, Rio de Janeiro, Brazil; ?Department of Pediatrics, University of
California, San Diego School of Medicine and Skaggs School of Phar-
macy & Pharmaceutical Sciences; **National Children's Study, NICHD,
NIH, DHHS, Bethesda, MD; ††Adolescent, and Maternal AIDS Branch,
NICHD, NIH, DHHS, Bethesda, MD; ‡‡Clinical Trials Area, Westat
Inc, Rockville, MD.
Supported by NICHD Contract HHSN267200800001C (NICHD Control N01-
HD-8-0001) and by the Eunice Kennedy Shriver National Institute of Child
Health and Human Development (contract NO1-HD33345), and co-spon-
sored by the HIV Prevention Trials Network (HPTN) and the International
Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Group.
Reprints: Mark Mirochnick, MD, Boston Medical Center, 771 Albany Street–
Dowling 4N, Room 4111, Boston, MA 02118. E-mail: firstname.lastname@example.com.
Supplemental digital content is available for this article. Direct URL citations
appear in the printed text and are provided in the HTML and PDF versions
of this article on the journal's Web site (www.pidj.com).
Copyright © 2011 by Lippincott Williams & Wilkins
DOI: 10.1097/INF.0b013e3182242950
The Pediatric Infectious Disease Journal • Volume 30, Number 9, September 2011
www.pidj.com | 769
Page 2
Gerais, Belo Horizonte, Brazil) elected to participate in a substudy
of nelfinavir and lamivudine pharmacokinetics. A separate in-
formed consent was obtained for participation in this substudy.
Twenty-six infants were enrolled in the pharmacokinetic
substudy. They were started on nelfinavir and lamivudine
within 48 hours of birth and were studied between either days
4–7 or days 10–14 of life. On the study day, plasma samples
were collected prior to a morning dose and at 1, 2, 4, 8, and 12
hours after the dose.
Nelfinavir and lamivudine plasma concentrations were mea-
sured by validated HPLC assays with a lower limit of quantitation
of 0.04 ?g/mL for each, as previously described.1Pharmacokinetic
calculations were performed using WinNonlin (Pharsight Corpo-
ration, Mountain View, CA) and Excel (Microsoft Corporation,
Redmond, WA). The nelfinavir exposure targets were 12-hour
AUC (AUC0-12) more than 15 ?g*h/mL (the 10th percentile for
adults) and 12-hour concentration (C12h) ?0.8 ?g/mL (the stan-
dard trough concentration target used in therapeutic drug monitor-
ing programs). Demographic and pharmacokinetic parameters are
presented as medians (range).
Twenty-six infants (9 females, 17 males) were studied, 14 at
age 4–7 days and 12 at age 10–14 days. Their median (range) birth
weight was 3105 (1775–3900) g and their median gestational age
was 39 (34–42) weeks. They were born to mothers with a median
age of 25 (15–42) years, a median HIV viral load of 8622
(224–538,773) copies/mL, and a median CD4 cell count of 704
(143–1711) cells/mm3. Fourteen infants received nelfinavir doses
of 200 mg, 11 received 150 mg, and 1 received 100 mg. The
median per kilogram nelfinavir dose was 58.8 (48.4–79.0) mg/kg.
Twenty-five infants received lamivudine doses of 6 mg and 1
received doses of 4 mg. The median per kilogram lamivudine dose
was 2.0 (1.5–3.2) mg/kg.
Nelfinavir concentration-time plots for the infants studied at
Digital Content 1 and 2, http://links.lww.com/INF/A879. The nelfinavir
pharmacokinetic parameters are presented in Table 1. No nelfina-
vir pharmacokinetic parameter differed between infants studied on
days 4–7 versus days 10–14. For the combined population at both
time points, median nelfinavir AUC0–12 was 25.5 (1.7–183.5)
?g*h/mL and median C12h was 1.09 (?0.04–14.44) ?g/mL.
AUC0–12 was less than 15 ?g*h/mL (the 10% percentile for
adults) in 12 infants (46%). C12h was less than 0.8 ?g/mL (the
standard nelfinavir therapeutic drug monitoring trough concentra-
tion target) in 12 infants (46%) and was less than 0.05 ?g/mL (10
times the upper limit for nelfinavir IC50 of wild-type HIV) in 2
infants (8%). Nelfinavir t1/2 was not calculated as many of the
nelfinavir concentration-time plots demonstrated flat or erratic
profiles for which there were insufficient data points to determine
a terminal elimination half-life.
Plasma sample volumes from one subject were inadequate
to perform the lamivudine assay, so lamivudine pharmacokinetic
data are available for 25 subjects. Lamivudine concentration-time
plots are presented in Figs., Supplemental Digital Content 3 and 4,
http://links.lww.com/INF/A879, and the lamivudine pharmacoki-
netic parameters are presented in Table 2. Lamivudine t1/2 was
longer in infants studied on day 4 to 7 compared with day 10 to 14
(P ? 0.04). No other lamivudine pharmacokinetic parameter
differed between infants studied on days 4 to 7 versus days 10 to
14. For the combined population at both time points, median
lamivudine AUC0–12 was 7.8 (2.7–15.6) ?g*h/mL and median
C12h was 0.23 (?0.04–0.74) ?g/mL. Lamivudine C12h exceeded
the assay lower limit of quantitation of 0.04 ?g/mL for 22 of 25
subjects (88%).
Our study is the first to describe nelfinavir and lamivudine
pharmacokinetics in infants during the first 2 weeks of life treated
with weight-band dosing regimens. Weight-band dosing was cho-
sen to facilitate study implementation across sites, to simplify drug
administration to enrolled infants, and to make the results more
easily transferable to a variety of settings once the optimum
regimen was determined. Weight or age band dosing of antiretro-
virals is currently recommended by the WHO for use in low
resource settings.3Nelfinavir was chosen as the protease inhibitor
used in the study because at the time of initiation of the protocol
it was the only protease inhibitor available in a formulation
suitable for use in neonates. Although liquid formulation lopinavir/
ritonavir is now available, there are no lopinavir pharmacokinetic
data from infants in the first 2 weeks of life.4In addition, recent
reports of life-threatening toxicities in premature infants receiving
lopinavir/ritonavir have led to a warning against its use in term
infants younger than 2 weeks postnatal age and in premature
infants younger than 42 weeks postmenstrual age.5
Previous studies of nelfinavir pharmacokinetics in neonates
have shown significant differences compared with older infants,
children, and adults. Nelfinavir apparent oral clearance has been
shown to be highly variable and to decrease with age, with
nelfinavir clearance 2 to 3 times higher in children aged 2 to 13
years than in adults and further increased in children below age 2
years.6–9The current recommended dose of nelfinavir in children
aged 2 to 13 years is 45 to 55 mg/kg twice a day; there is no
approved dose for children under age 2. Previous studies in
for Infants Studied at Ages 4–7 Days, 10–14 Days, and
Both Groups Combined
Lamivudine Pharmacokinetic Parameters
4–7 Days
(n ? 13)
10–14 Days
(n ? 12)
(n ? 25)
t max (h)
Cmax (ug/mL)
C12 h (ug/mL)
Cl/F (L/h/kg)
2.8 (1–4)
1.08 (0.38–2.01)
0.31 (bql–0.74)
7.0 (2.9–15.6)
2.5 (1–4)
1.27 (0.38–2.17)
0.22 (bql–0.62)
7.9 (2.7–14.0)
2.5 (1–4)
1.24 (0.38–2.17)
0.23 (bql–0.74)
7.8 (2.7–15.6)
0.27 (0.11–0.70)
5.3 (3.3–10.5)
0.27 (0.14–0.74)
3.9 (3.1–6.3)*
0.27 (0.11–0.74)
4.7 (3.1–10.5)
Data presented as medians (ranges).
bql indicates below quantitation limit of assay of 0.04 ?g/mL.
*P ? 0.05 compared to 4–7 days.
Infants Studied at Ages 4–7 Days, 10–14 Days, and
Both Groups Combined
Nelfinavir Pharmacokinetic Parameters for
4–7 Days
(n ? 14)
10–14 Days
(n ? 12)
(n ? 26)
t max (h)
Cmax (ug/mL) 2.07 (0.42–17.25) 2.86 (0.26–4.19) 2.60 (0.26–17.25)
C12 h (ug/mL) 0.81 (0.18–14.44) 1.33 (bql–4.06)
Cl/F (L/h/kg)3.1 (0.3–15.1)
3 (0–8)4 (1–12) 4 (0–12)
1.09 (bql–14.44)
25.5 (1.7–183.5)20.7 (3.4–183.5)25.5 (1.7–41.7)
2.7 (1.3–35.3)2.7 (0.3–35.3)
Data presented as medians (ranges).
bql indicates below quantitation limit of assay of 0.04 ?g/mL.
Mirochnick et al
The Pediatric Infectious Disease Journal • Volume 30, Number 9, September 2011
© 2011 Lippincott Williams & Wilkins
770 | www.pidj.com
Page 3
neonates have shown high variability and inadequate nelfinavir
concentrations with doses up to 40 to 45 mg/kg twice a day.1,2
In the present study, we used a weight-based nelfinavir
dosing regimen that provided a median nelfinavir dose of 58.8
mg/kg twice a day. The per kilogram nelfinavir doses ranged from
18% below the median dose to 34% above and are presented
graphically in Figure 1. While the median AUC and Cmin in our
subjects exceeded the pharmacokinetic targets, interpatient vari-
ability was very large, with AUC varying from 1.7 to 183.5
?g*h/mL. Nearly half (46%) of individual subjects failed to meet
the AUC or Cmin target. Figure 1 suggests that AUC did not vary
with per kg dose administered and that although the per kg doses
were greater than those used in previous studies, interpatient
variability increased as well, resulting in larger maximum expo-
sures while a significant proportion of subjects remained below the
pharmacokinetic target. A recent population analysis of nelfinavir
pharmacokinetics in a large group of infants and children sug-
gested that in those less than 2 months nelfinavir doses of 40
mg/kg twice a day were not adequate and that 50 to 60 mg/kg 3
times a day should be studied.10The large amount of interpatient
variability in nelfinavir exposure observed in our subjects suggests
that a further increase in nelfinavir dosing might result in high and
potentially toxic nelfinavir concentrations in some infants along
with suboptimal concentrations in others. If nelfinavir is to be used
to treat HIV infected neonates during the first weeks of life,
therapeutic drug monitoring should be encouraged to ensure ade-
quate but not excessive nelfinavir exposure.
Lamivudine elimination was prolonged in these neonates
studied during the first week of life compared with older infants
and children, consistent with previous studies.11,12Lamivudine is
primarily renally eliminated, and its elimination increases during
the first weeks and months of life in parallel with postnatal
maturation of renal function.12,13Current dosing recommendations
for lamivudine are 2 mg/kg twice a day during the first 4 weeks of
life and 4 mg/kg twice a day after age 4 weeks. The weight-band
dosing regimen used in the current study resulted in a median dose
of 2 mg/kg, with a range of 1.5 to 3.2 mg/kg. Although there is no
target lamivudine concentration for the prevention of HIV infec-
tion, lamivudine AUC values were in the same range as those
previously observed in prior studies of neonatal and pediatric
patients, and trough lamivudine concentrations in nearly all sub-
jects exceeded the range of lamivudine IC50 in wild-type HIV
(0.0006–0.021 ?g/mL).14
Mother-to-child HIV transmission can be reduced to less
than 1% with the use of maternal combination antiretroviral
therapy during pregnancy and infant formula feeding. The results
of the parent protocol of this study demonstrated that when
HIV-infected pregnant women do not receive combination antiret-
roviral therapy prior to delivery, treating infants with 6 weeks of
ZDV plus either daily lamivudine/nelfinavir for 2 weeks or 3 doses
of nevirapine during the first week of life will reduce intrapartum
HIV transmission by roughly 50%.15We have previously reported
that nevirapine concentrations with the 3-dose weight-band regi-
men remain above our prophylactic target of 100 ng/mL through
the first 10 days of life but well less than the 3000 ng/mL trough
concentration target used in HIV infected patients receiving nevi-
rapine as part of combination treatment regimens.16As we report
in this article, the weight-band nelfinavir regimen resulted in
nelfinavir trough concentrations ?0.8 ?g/mL, the standard nelfi-
navir trough concentration target for treating HIV infection in
nearly half of our subjects, although nearly all had nelfinavir
trough concentration more than 0.05 ?g/mL (10 times the upper
limit of nelfinavir IC50 for wild-type HIV). Although there are no
data establishing definitive target concentrations for antiretrovirals
used for prevention of HIV infection, the equivalent efficacy of
2 hour AUC (ug
0 1020 30 4050 6070 80
12 Hour Dose (mg/kg)12 Hour Dose (mg/kg)
FIGURE 1. Scatter plots of nelfinavir AUC versus dose size (normalized to 12 hour dosing) from PACTG 0531(open trian-
gles) and current study (open squares). Dashed line represents AUC target of 15 ?g*h/mL.
The Pediatric Infectious Disease Journal • Volume 30, Number 9, September 2011Nelfinavir and Lamivudine
© 2011 Lippincott Williams & Wilkins
www.pidj.com | 771
Page 4
these regimens in reducing intrapartum HIV transmission when
used in combination with zidovudine suggests that HIV infection
can be prevented with antiretroviral concentrations lower than
those used in treatment of HIV infected individuals.
The authors thank the patients and their families who
enrolled in this trial. In addition to the authors, members of the
NICHD/HPTN 040/PACTG 1043 protocol team include the fol-
lowing: Belo Horizonte- Federal University of Minas Gerais:
Flavia Faleiro Ferreira, Fabiana Kakehasi. Hospital Geral de
Nova Iguac ¸u: Jorge Eurico Ribeiro. Oswaldo Cruz Foundation,
Rio de Janeiro (FIOCRUZ): Francisco Inacio Bastos, Beatriz
Grinsztejn, Ronaldo Ismerio, Mariza Morgado, Marilia Santini de
Oliveira, Vale ´ria Ribeiro. Westat, Inc.: Emmanuel Aluko, Jim
Bethel, Yolanda Bertucci, Patty Chen, Barbara Driver, Ruby
Duston, Adriana Ferreira, Priya Guyadeen, Sarah Howell, Mar-
sha Johnson, Naomi Leshabane, Lilya Meyerson, Rita Patel,
Georgine Price, Susan Raitt, Eunice Yu. NICHD: Jennifer Read,
George Siberry. Other protocol team members included Ruth
Dickover from the University of CA-Davis, and Elizabeth Smith
and Sheryl Zwerski from the National Institute of Allergy and
Infectious Diseases, Diane Holland from the University of CA-San
Diego Pediatric Pharmacology Laboratory. Pharmaceutical sup-
port and representatives included Marita McDonough from
Boehringer-Ingelheim Pharmaceuticals, Inc. and Helen Watson
from GlaxoSmithKline.
1. Mirochnick M, Stek A, Acevedo M, et al. Safety and pharmacokinetics of
nelfinavir coadministered with zidovudine and lamivudine in infants during
the first 6 weeks of life. J Acquir Immune Defic Syndr. 2005;39:189–194.
2. Rongkavilit C, van Heeswijk RP, Limpongsanurak S, et al. Dose-escalating
study of the safety and pharmacokinetics of nelfinavir in HIV-exposed
neonates. J Acquir Immune Defic Syndr. 2002;29:455–463.
3. WHO Paediatric Antiretroviral Working Group. Preferred antiretroviral
medicines for treating and preventing HIV infection in younger children.
2007; http://www.who.int/hiv/pub/paediatric/ARV_WG_meeting_report_
may2008.pdf. Accessed June 12, 2008.
4. Chadwick EG, Capparelli EV, Yogev R, et al. Pharmacokinetics, safety and
efficacy of lopinavir/ritonavir in infants less than 6 months of age: 24 week
results. AIDS. 2008;22:249–255.
5. FDA. Safety alert-Kaletra (lopinavir/ritonavir): Label Change - Serious
Health Problems in Premature Babies. Available at: http://www.fda.gov/
ucm246167.htm. Accessed March 8, 2011.
6. Capparelli EV, Sullivan JL, Mofenson L, et al. Pharmacokinetics of
nelfinavir in human immunodeficiency virus-infected infants. Pediatr Infect
Dis J. 2001;20:746–751.
7. Krogstad P, Wiznia A, Luzuriaga K, et al. Treatment of human immuno-
deficiency virus 1-infected infants and children with the protease inhibitor
nelfinavir mesylate. Clin Infect Dis. 1999;28:1109–1118.
8. Litalien C, Faye A, Compagnucci A, et al. Pharmacokinetics of nelfinavir
and its active metabolite, hydroxy-tert-butylamide, in infants perinatally
infected with human immunodeficiency virus type 1. Pediatr Infect Dis J.
9. Payen S, Faye A, Compagnucci A, et al. Bayesian parameter estimates of
nelfinavir and its active metabolite, hydroxy-tert-butylamide, in infants
perinatally infected with human immunodeficiency virus type 1. Antimicrob
Agents Chemother. 2005;49:525–535.
10. Hirt D, Urien S, Jullien V, et al. Age-related effects on nelfinavir and M8
pharmacokinetics: a population study with 182 children. Antimicrob Agents
Chemother. 2006;50:910–916.
11. Moodley D, Pillay K, Naidoo K, et al. Pharmacokinetics of zidovudine and
lamivudine in neonates following coadministration of oral doses every 12
hours. J Clinic Pharmacol. 2001;41:732–741.
12. Tremoulet AH, Capparelli EV, Patel P, et al. Population pharmacokinetics
of lamivudine in human immunodeficiency virus-exposed and -infected
infants. Antimicrob Agents Chemother. 2007;51:4297–4302.
13. Heald AE, Hsyu PH, Yuen GJ, et al. Pharmacokinetics of lamivudine in
human immunodeficiency virus-infected patients with renal dysfunction.
Antimicrob Agents Chemother. 1996;40:1514–1519.
14. Coates JA, Cammack N, Jenkinson HJ, et al. (-)-2?-deoxy-3?-thiacytidine is
a potent, highly selective inhibitor of human immunodeficiency virus type
1 and type 2 replication in vitro. Antimicrob Agents Chemother. 1992;36:
15. Nielsen-Saines K, Watts H, Gonc ¸alves Veloso V, et al. Phase III Random-
ized Trial of the Safety and Efficacy of 3 Neonatal ARV Regimens for
Prevention of Intrapartum HIV-1 Transmission: NICHD HPTN 040/
PACTG 1043. Paper presented at: 18th Conference on Retroviruses and
Opportunistic Infections; March 2, 2011; Boston, MA. Abstract 124LB.
16. Mirochnick M, Nielsen-Saines K, Pilotto JH, et al. Nevirapine concentra-
tions in newborns receiving an extended prophylactic regimen. J Acquir
Immune Defic Syndr. 2008;47:334–337.
Mirochnick et al
The Pediatric Infectious Disease Journal • Volume 30, Number 9, September 2011
© 2011 Lippincott Williams & Wilkins
772 | www.pidj.com


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- NSW - Sydney
Alder Park
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The City of Newcastle includes a collection of fantastic open spaces that the whole family can enjoy.
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Highlight: Ed Ruscha
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Elsworth Kelly
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sold for $577,750
at Sotheby's New York
Nov. 14, 2001


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A golden night for Chaz Yorkville
Chaz Yorkville recently captured the top International Residential Project Gold Nugget Award at the Pacific Coast Builders' Conference.
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Chaz Yorkville, the Toronto condominium being developed by 45 Charles Ltd. and Edenshaw Homes, recently captured the top International Residential Project Gold Nugget Award at the Pacific Coast Builders' Conference in San Francisco. There were more than 450 international entries.
Now under construction at Bloor and Yonge Sts., Chaz Yorkville's exterior by Page + Steele/IBI Group Architects impressed the judges with its courageous design. The sleek design of the 47-storey tower has recessed balconies. This allows the building skin to remain uncluttered while the 36th and 37th floors cantilever out from the south side. The building also looks like it's wearing a bow-tie due to a unique architectural addition.
This is the second international award the building has won. Last year, at the National Sales and Marketing Awards held in Orlando, it won four gold awards including International Community of the Year for its location, design, architecture and features.
The building amenities and features are intended to inspire residents to socialize with family and friends, says David McComb, president of Edenshaw Homes, as well as offer the latest social connectivity requirements including a high-tech gamers' room.
"The lobby will be like a living room with plenty of seating so people passing through or waiting for a taxi or friends will be inspired to mingle. There will be dining and bar areas with kitchens and serving areas for parties. Outside there will be space for entertaining with a courtyard, barbecue and outdoor fireplace. The Green Room will be a Zen-inspired space to relax," he says.
A business centre, second lobby for deliveries and 24-hour concierge provide professionalism for any business. Fitness areas include the latest equipment, rooms for yoga, and spa-like amenities such as massage chairs, hydro-massage beds and steam rooms. Even pets get their own spa for grooming. A car-sharing service is also available.
"However the pièce de résistance will be the Chaz Club, a resident's club on floors 36 and 37 that will have panoramic views, a bar, lounge and a private dining area for about 25 people," says McComb.
"While we have 15,000 square feet of amenities, we also have a broad range of suite sizes and designs," Jason Fane of 45 Charles Ltd. says "There are small studios to spacious three-bedrooms-plus-den suites and terraced penthouses with nine- to 14-foot ceilings. Prices range from mid-$300,000 to $1.5 million. Condo fees are about 49 cents per square foot.
"Our Petersen suites are unique and designed for a family with children. There are three bedrooms, 3.5 baths, soundproofed study and several doors and hallways that divide living areas from bedrooms for peace and quiet. They are about 2,230 square feet in size and will rival any Yorkville home with the advantage of not having any stairs," says Fane. There are also more affordable three-bedrooms suites in the 1,000 to 1,200 square foot range in the podium area of the building, Fane says.
Attention to detail in all suites includes plenty of closet space, six-foot tall medicine cabinets in the bathrooms and full-length mirrors. "We've included the features that every woman wants in a bathroom. In kitchens we have clever features such as storage in the backsplash – shelves behind sliding glass," he says. "Even small details such as illuminated light switches, lighting under floating vanities and extra electrical outlets will be appreciated." Such details designed by design Ciccone Simone Inc. of Toronto were featured on the Steven and Chris TV show.
With the Yorkville location of great shopping, restaurants, entertainment and cultural attractions, Chaz Yorkville will please residents inside and outside the building.
• For more information, go to chazyorkville.com.
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Arts & entertainment
78 results total, viewing 21 - 30
Marie Antoinette's life has been the inspiration for books, plays, films and speculation for many years, but a Wonderbound production always offers a new and original perspective on any topic. Artistic director Garrett Ammon has made a point … more
Sonya Ellingboe | 2/4/15
"The Color Red" is the theme for the latest show at the Depot Art Gallery, 2069 W. Powers Ave. — in Littleton's circa 1891 bright red Santa Fe Depot. The exhibit opened Feb. 4 and a public reception is planned from 4-6 p.m. on Feb. … more
Sonya Ellingboe | 2/4/15
Christopher Weed's 24-foot by 14-foot public art piece "Connected" was installed on Jan. 19 at 14th and Lamar. The piece represents the neighborhoods coming together to support the … more
By Clarke Reader | 2/4/15
For Tanya Long, history doesn't just lie in the pages of a book, it's all around us. "I grew up listening to the stories of my grandmother and my great grandmother living here, so I knew a lot of the people who lived here, or the 'old timers' … more
Crystal Anderson | 2/2/15
The Colorado Cowboy Gathering was held at the American Mountaineering Center in Golden last weekend. The gathering featured dozens of artists over three days, skilled in songwriting, poetry and … more
Photo by Amy Woodward | 1/28/15
Although there have been exhibits of beautifully illustrated and hand-bound books for hundreds of years, book art is a somewhat new concept for a show in the arts and fine crafts world. "Beyond Words: Contemporary Book Art" is a first for the … more
Sonya Ellingboe | 1/27/15
Adams County Historical Society is kicking off a membership drive this month. "People who invest in the museum, though membership and volunteering, or both, help to keep our doors open." said Cliff Lushbough, the Adams County Historical … more
Lou Ellen Bromley | 1/20/15
Millions of young girls would love to write and perform songs that reach an audience, but not everyone puts in the time and dedication that Amanda May does. The 13-year-old singer-songwriter from Parker released her first song on iTunes last … more
Chris Michlewicz | 1/19/15 | 1 comment
Time travel. There's hardly a more alluring fantasy in our pop culture, from the simplest depictions — children's cartoons, comic strips, romantic comedy films — to the "Interstellar'' kind that you need a physics degree to … more
Jocelyn Noveck, of the Associated Press | 1/17/15
"rePOPulated: contemporary perspectives on pop art" opens Jan. 22 in the Main Gallery at the Arvada Center and runs through March 29. At the same time, the Upper Gallery will host a collection of work by Phil Bender, Colorado's Pop master, … more
Sonya Ellingboe | 1/13/15
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SWIAEE Night at the Angel Stadium Baseball Park
- Sports & Fitness
- Angel Stadium, Anaheim CA
2013 Annual Chapter Reception at EXPO EXPO Houston
The Southwest Chapter of IAEE
Tuesday, December 10, 2013 from 5:00 PM to 6:30 PM (PST)
Join your friends and collegues at this fun event during EXPO EXPO!
IAEE and its Southwest Chapter promotes the unique value of exhibitions and other events that bring buyers and sellers together such as road shows, conferences with an exhibition component, and proprietary corporate exhibitions. IAEE is the principle resource for those who plan, produce and service the industry.. To learn more about the Chapter, please visit www.swiaee.com or contact the chapter administrator at firstname.lastname@example.com
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Iranian military pilots bow down
Saturday 24 April 2010
Members of Iran's air force pray during Friday prayers in Tehran yesterday.
The senior cleric and interim Friday Prayers leader Ayatollah Ahmad Jannati told Iranians that the US was "the only nuclear criminal in the world".
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- 4 April Fools' Day 2015: The best hoax news stories from around the internet
- 5 Gamers confess the worst things they've done in The Sims
Discover the Bajan Rhythm
Brilliant Barbados is an exciting promotion giving visitors to Barbados more than ever before. It's always a good time to visit Barbados.
Win a trip to Tobago for two
Discover Tobago with our competition for one lucky reader to have the chance to win a seven night self-catering holiday for two. Enter here.
How researchers are set to leave their marks on solving crime
The technology, which is now being trialled by West Yorkshire Police, could lead to the biggest change in forensic fingerprinting in its 100-year history.
Taking steps to tackle the housing crisis
Whatever the result of the forthcoming General Election, tackling Britain's housing crisis should be at the top of a new government's to-do list.
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Mob kills dozens of displaced Sudanese sheltered by UN
Gunmen posed as peaceful protesters before opening fire
Friday 18 April 2014
A mob of armed civilians pretending to be peaceful protesters delivering a petition to the United Nations in South Sudan forced their way into a UN base sheltering some 5,000 civilians and opened fire in the latest example of violence in a country that has seen months of fighting.
A UN source, speaking on condition of anonymity, said at least 48 people had been killed and 60 wounded in the attack on the base in Bor in northern Jonglei state, where there are Indian and South Korean UN peacekeepers.
Dozens of civilians were said to be wounded, but the exact number of people killed or wounded had not yet been confirmed. Two UN peacekeepers were wounded repelling the armed mob, he said.
The attackers forced their way into a camp in Bor where more than 5,000 ethnic Nuers have sought safety since fighting broke out in South Sudan in mid-December.
"The assailants, a mob of armed civilians, came to the base under the guise of peaceful demonstrators intending to present a petition ... The armed mob forced entry on to the site and opened fire on the internally displaced persons sheltering inside the base," said UN spokesman Stephane Dujarric, at UN headquarters in New York. Major Kuol Mayen Deng, of the South Sudanese military, said yesterday that Ugandan troops stationed in the region had been drafted in to protect the UN base at Bor.
Thousands of people have been killed and more than one million displaced since fighting erupted, triggered by a power struggle between President Salva Kiir and former Vice-President Riek Machar. The conflict in Africa's newest country took on a tribal dimension as Mr Kiir's Dinka supporters fought Mr Machar's Nuer tribesmen for control of strategic towns before a ceasefire was signed on 23 January.
Sporadic clashes between both sides after the ceasefire deal erupted into full-blown combat this week, when the rebels seized Bentiu, the capital of oil-producing Unity state. Bor has changed hands a number of times between the military and rebels.
The UN Secretary-General, Ban Ki-moon, strongly condemned the attack on a site where civilians are being protected by foreign peacekeepers. Mr Ban said any attack on UN soliders "constitutes a war crime".
Ateny Wek, South Sudan's presidential spokesman, said the government was still receiving information about the attack but called it a "very, very bad situation".
Samantha Power, the US Ambassador to the United Nations, condemned all recent attacks on civilians and the United Nations in South Sudan, saying "particularly egregious is [the] armed attack on an [UN] compound in Bor by a heavily armed group that used rocket-propelled grenades".
"All parties should regard [UN] sites as inviolable, and should afford protection to citizens sheltering at those locations," Ms Power added.
Perry Mansfield, who heads the aid group World Vision in South Sudan, said staff in the border town of Renk were caught in crossfire and could not safely access the UN base. "Renk was a stable place far from the conflict where parents could bring their children to safety while fighting continued. Now they are forced to run again," he said.
Earlier this week, Mr Ban said that up to one million Sudanese people faced potential famine-level hunger because of the fighting. The planting season is under way across the country but few are actively farming.
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text:
Part 5: Our Hall of Fame
BY Advocate Contributors
March 28 2012 2:00 AM ET
When "don't ask, don't tell" was finally repealed in 2011 and troops began serving openly, many thought of Army National Guard Lt. Dan Choi. For one thing, he'd already caused a ruckus when trying to reenlist.
Numerous soldiers had spoken out, groups had formed to fight for DADT repeal, but Choi knew how to make an impression, whether speaking at rallies or being arrested for handcuffing himself to the gates of the White House in protest. It began when he went on The Rachel Maddow Show in 2009 and came out.
"Only an unflinching commitment to improve the lives of others can determine the nature of one's service," Choi said after the military announced it would honorably discharge him 17 months later.
-Lucas Grindley
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