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Runhaar, E. A.; Neijt, J. P.; Holthuis, J. J. M.; Vos, D.
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2 Citations
The bioavailability of two altretamine preparations was studied in a randomized cross-over design. The two preparations were compared with a third in a parallel design. Dissolution differences between the preparations were observed, which could give rise to differences in bioavailability caused by the extensive first-pass effect of altretamine. Thein vivo data showed a trend to differences in bioavailability.
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Kılıç, B.; Özden, T.; Toptan, S.; Özilhan, S.
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9 Citations
A specific and sensitive liquid chromatography-electrospray ionization tandem mass spectrometry method was developed for the determination of zolmitriptan and N-desmethylzolmitriptan in human plasma. The analytes and the internal standard (IS) paroxetine were extracted by liquid–liquid extraction with a mixture of saturated ethyl acetate:dichloromethane (4:1) and were separated using an isocratic mobile phase on a XTerra RP18 column. The mobile phase used was acetonitrile: 5 mM ammonium acetate: formic acid (50:50:0.053, v/v/v). Zolmitriptan and N-desmethylzolmitriptan in a range of 0.25–20 ng mL−1 were easily quantified. The validated method can be applied to pharmacokinetic and bioequivalence studies.
Yi, Hong Jae; Oh, Ju-Hee; Lee, Young-Joo
3 Citations
Hwang-Ryun-Hae-Dok-Tang (HT; a standardized herbal formula consisting of extracts from Coptidis Rhizoma, Scutellariae Radix, Phellodendri Cortex, and Gardeniae Fructus) was reported to modulate a function of multidrug resistance associated protein 2 (Mrp2) in vitro. The aim of this study was to assess the in vivo pharmacokinetic interactions between HT and phenolsulfonphthalein (PSP), a typical model Mrp2 substrate eliminated via bile through Mrp2 in rats. Rats received intravenous PSP (0.8 mg/kg) followed by either a single oral dose of HT (0.42 g/kg) or multiple oral doses of HT (0.42 g/kg for 7 days). The effect of HT treatment was also investigated at a steady-state after intravenous PSP infusion. In contrast to previous in vitro results, in this study, we found that the HT-treated and control groups did not show any significant difference in the plasma PSP concentration and pharmacokinetic parameters, including area under the plasma concentration-time curve (AUC; control: 118 ± 19, single dose: 116 ± 40, and multiple dose: 137 ± 4, in mg/(min·mL)) and biliary clearance (control: 3.15 ± 0.69, single dose: 2.59 ± 1.11, and multiple dose: 2.53 ± 0.65, in mL/(min·kg)). However, cyclosporine A (5 mg/kg, an inhibitor of Mrp2) significantly decreased the AUC and biliary clearance of PSP. The steady-state plasma concentration and biliary clearance of PSP-were also similar between the groups. Taken together, our results suggest that HT may not be affected by Mrp2-mediated herb-drug interaction in vivo.
Xu, Xu Steven; Dunne, Adrian; Kimko, Holly; Nandy, Partha; Vermeulen, An
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17 Citations
The objectives of the simulation study were to evaluate the impact of BQL data on pharmacokinetic (PK) parameter estimates when the incidence of BQL data is low (e.g. ≤10%), and to compare the performance of commonly used modeling methods for handling BQL data such as data exclusion (M1) and likelihood-based method (M3). Simulations were performed by adapting the method of a recent publication by Ahn et al. (J Phamacokinet Pharmacodyn 35(4):401–421, 2008). The BQL data in the terminal elimination phase were created at frequencies of 1, 2.5, 5, 7.5, and 10% based on a one- and a two-compartment model. The impact of BQL data on model parameter estimates was evaluated based on bias and imprecision. The simulations demonstrated that for the one-compartment model, the impact of ignoring the low percentages of BQL data (≤10%) in the elimination phase was minimal. For the two-compartment model, when the BQL incidence was less than 5%, omission of the BQL data generally did not inflate the bias in the fixed-effect parameters, whereas more pronounced bias in the estimates of inter-individual variability (IIV) was observed. The BQL data in the elimination phase had the greatest impact on the volume of distribution estimate of the peripheral compartment of the two-compartment model. The M3 method generally provided better parameter estimates for both PK models than the M1 method. However, the advantages of the M3 over the M1 method varied depending on different BQL censoring levels, PK models and parameters. As the BQL percentages decreased, the relative gain of the M3 method based on more complex likelihood approaches diminished when compared to the M1 method. Therefore, it is important to balance the trade-off between model complexity and relative gain in model improvement when the incidence of BQL data is low. Understanding the model structure and the distribution of BQL data (percentage and location of BQL data) allows selection of an appropriate and effective modeling approach for handling low percentages of BQL data.
Lee, Joo Hyun; Oh, Jung Mi; Lee, Myung Gull
Male Sprague-Dawley rats deprived of water for 72 h (a rat model of dehydration) showed no change in protein expression of the hepatic microsomal cytochrome P450 (CYP) 1A2, 2B1/2, 2C11, or 3A1/2, but an increase in protein expression (3-fold) and mRNA level (2.6-fold) of CYP2E1. Glucose feeding instead of food normalized CYP2E1 protein expression during dehydration. Here, we review how dehydration can change the pharmacokinetics of drugs reported in the literature via changing CYP isozyme levels. We also discuss how dehydration changes the pharmacokinetics of drugs that are metabolized via renal DHP-I, or are mainly excreted in the urine and bile, and form conjugates.
Johansson, Carl-Christer; Gennemark, Peter; Artursson, Per; Äbelö, Angela; Ashton, Michael; Jansson-Löfmark, Rasmus
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7 Citations
Enantioselective pharmacokinetics and absorption of eflornithine in the rat was investigated using population pharmacokinetic modeling and a modified deconvolution method. Bidirectional permeability of l- and d-eflornithine was investigated in Caco-2 cells. The rat was administered racemic eflornithine hydrochloride as a single oral dose [40–3,000 mg/kg bodyweight (BW)] or intravenously (IV) (100–2,700 mg/kg BW infused over 60–400 min). Serial arterial blood samples were collected and l- and d-eflornithine were quantitated with a previously published chiral bioanalysis method. The D:L concentration ratio was determined in rat faeces. Intravenous l-and d-eflornithine plasma concentration–time data was analyzed using population pharmacokinetic modeling and described with a 3-compartment pharmacokinetic model with saturable binding to one of the peripheral compartments. Oral plasma concentration–time data was analyzed using a modified deconvolution method accounting for nonlinearities in the eflornithine pharmacokinetics. Clearance was similar for both enantiomers (3.36 and 3.09 mL/min). Oral bioavailability was estimated by deconvolution at 30 and 59 % for l- and d-eflornithine. The D:L concentration ratio in feces was 0.49 and the Caco-2 cell permeability was similar for both enantiomers (6–10 × 10−8 cm/s) with no evident involvement of active transport or efflux. The results presented here suggest that the difference in the bioavailability between eflornithine enantiomers is caused by a stereoselective difference in extent rather than rate of absorption. The presented modified deconvolution method made it possible to account for the non-linear component in the suggested three-compartment pharmacokinetic model thus rapidly estimating eflornithine oral bioavailability.
Mehrotra, Nitin; Sabarinath, Sreedharan; Suryawanshi, Satyendra; Raj, Kanwal; Gupta, Ram Chandra
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4 Citations
The herbal medicament derived from the lipid soluble fraction obtained from Curcuma longa L. (Zingiberaceae) has shown potential neuroprotective activity in disorders like stroke. HM has been standardized with three biomarkers: ar-turmerone, α/β-turmerone and curlone, major bisabolane sesquiterpenes of turmeric oil. Development of a biaonalytical method for these sesquiterpenes was initiated to characterize its preclinical pharmacokinetics in rabbits to accelerate its development as a potential candidate for vascular complications. Since, the compounds are structurally and chemically very similar, gradient elution was utilized on a C-18 reversed phase column with a mobile phase comprising of acetonitrile and deionised water. The UV detector was set at wavelengths 240 and 270 nm. The sample clean-up was performed by protein precipitation with acetonitrile. The method was reasonably sensitive with limits of quantitation (LOQ) of 0.098 μg mL−1 in plasma for all the analytes. Accuracy and precision were within the acceptable limits, as indicated by relative standard deviation (% RSD) varying from 1.3 to 13.6% and bias values ranging from −5.5 to 10.3%, respectively. Moreover, the analytes were stable in plasma even after three freeze-thaw cycles. The method was applied to generate preliminary pharmacokinetics of turmeric oil in rabbits after intravenous administration.
Yang, Si H.; Lee, Joo H.; Lee, Dae Y.; Lee, Myung G.; Lyuk, Koon C.; Kim, So H.
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Docetaxel is a P-glycoprotein (P-gp) substrate and metabolized via cytochrome P450 (CYP) 3A subfamily in rats. Morin is an inhibitor of both CYPs and P-gp. Hence, the effects of morin on the intravenous and oral pharmacokinetics of docetaxel were investigated using 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumor rats (DMBA rats) as an animal model of human breast cancer. Docetaxel was administered intravenously (4 mg/kg) and orally (20 mg/kg) without and with morin (15 mg/kg) in DMBA rats. After the intravenous administration of docetaxel in control and DMBA rats with and without morin, the values of non-renal clearance and area under the plasma concentration-time (AUC) for docetaxel were comparable. Morin did not increase AUC or the absolute oral bioavailability (F) for docetaxel after the oral administration of docetaxel in control and DMBA rats with and without morin. The inhibition of hepatic and intestinal metabolism of docetaxel by morin and/or DMBA and the effect of intestinal P-gp inhibition by morin on the pharmacokinetics of docetaxel did not seem to be considerable in DMBA-induced mammary tumor rats.
Duan, Jingze; Dang, Yang; Meng, Houjun; Wang, Huizhen; Ma, Ping; Li, Guowen; Wu, Tao; Xie, Yan
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5 Citations
Pharmacokinetic properties of isorhamnetin, quercetin, and kaempferol in three different total flavones of Hippophae rhamnoides (TFH) preparations were compared after oral administration to beagle dogs by a UPLC–MS method. The pharmacokinetic results showed that Cmax of isorhamnetin and quercetin in TFH solid dispersion (TFH-SD) and TFH self-emulsifying (TFH-SE) preparations was significantly enhanced than that in TFH preparations (p < 0.05). The AUCs of isorhamnetin and quercetin in TFH-SD were 5.9- and 3.1-fold higher than that of TFH, while the AUCs of isorhamnetin and quercetin in TFH-SE were 3.4- and 2.4-fold higher than that of TFH. These findings suggested that the oral bioavailability of isorhamnetin and quercetin in beagle dogs can be significantly increased in TFH-SD and TFH-SE preparations compared to TFH preparations, which was helpful to explore the new forms for oral administration TFH and explain their in vivo processes.
Burger, David M.; Meenhorst, Pieter L.; Beijnen, Jos H.
8 Citations
In this paper aspects of the clinical pharmacokinetics of the antiretroviral agents zidovudine, didanosine and zalcitabine are reviewed. Special attention is paid to possibly altered pharmacokinetics in special circumstances, such as hepatic and renal dysfunction, pregnancy, stage of disease,etc. The dideoxynucleoside antiretroviral agents have some clinical pharmacokinetic properties in common (rapid absorption and elimination), but substantial differences exist in their degree of absorption, metabolism and penetration into the cerebrospinal fluid. All agents display wide interpatient variability in pharmacokinetic parameters. The relevance of therapeutic drug monitoring of antiretroviral agents is also discussed.
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August 29 is the big day. That's when the Dallas Streetcars will roll into the Bishop Arts District. The sleek vehicles already are a familiar sight in North Oak Cliff, and the extension ushers in a new era for one of the region's most popular entertainment and shopping district – adding an extra dose of cool to a neighborhood that's already got plenty of it.
The area has become popular for good reason: it's one of the best collections of unique boutiques, bistros and shops in Texas. It's not exactly a secret, as the bustling sidewalks (and parking hassles) attest. Not only will the streetcar provide the most convenient access to Bishop Arts, it's also a fitting addition to the urban environment. After all, the neighborhood originally sprung up around the streetcar lines of the early 20th century. [link to previous article]
The streetcar is the fruition of years of planning – going back to December 2010, when the Federal Transit Administration awarded the initial $23 million Transportation Investment Generating Economic Recovery (TIGER) grant that got the ball rolling. An additional $3 million in federal stimulus dollars was later granted to the project. DART reallocated $22 million in local funds to the streetcar project. In January 2013, NCTCOG approved reallocating $31 million in state funds to the project.
The Dallas Streetcar has been an important regional partnership between DART, the City of Dallas and the North Central Texas Council of Governments (NCTCOG). DART oversaw the construction and will operate the service under contract to the city.
Service begins at 9:30 a.m. each day — about the time things begin to stir around Bishop Arts — and the cars run until midnight, making connections with the final DART Rail trains at Union Station. Trains operate every 20 minutes, seven days a week, and the service is free.

subset: commoncrawl


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Spring has danced in to my life...not on little dainty pink ballerina flowered feet, but a thundering righteous horde of roustabout roses, whooping wisteria, screaming star jasmine, irate iris, oozing orange blossoms...the fragrance fills the night so full that my back patio resembles a very expensive olfactory house of ill … Read More


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Bank of India
BOI Recruitment 2016
Specialists Officer Posts
Last Date: 8th March 2016
Last Date: 8th March 2016
Shared By: WWW.GovtJobsPortal.IN
Latest Government jobs opportunities under Bank of India Department for various govt jobs of posts in India. Bank of India Recruitment official notification in which they are inviting all Indian candidates to apply for Specialists Officer Posts. Through their official notice they said that all eligible Indian candidates can apply online application for the 77 posts of Specialists Officer Posts through Online Process.
For more information related to Educational Qualification, Age criteria and other Eligibility required under this latest govt jobs for BOI Recruitment 2016 process read the below article carefully. Also must read the official advertisement in detail before applying.
Organization Name: Bank of India
Profile Name: Specialists Posts.
No. of Vacancies: 77
Post-Wise Details:
Chartered Accountant : 20 Posts
Risk Analysts : 04 Posts
Law Officer : 05 Posts
Information Technology : 42 Posts
Technical Officer (Premises) : 02 Posts
Technical Officer (Appraisal) : 04 Posts
Educational Eligibility: Candidate should have done Graduation in Required discipline from a recognized University. Check official Advertisement for complete detail.
Age Bond: Candidates should have their age between 21 to 35 years (FOR CA) & 25 to 35 years.
Selection Process: For this process for govt jobs of Specialists officer posts under BOI Recruitment 2016 the criteria of selection will be based on Written Test & Interview.
Application Fee: Rs 600/- For General/OBC
Rs 100/- For PWD/ST/SC
Process for Applying: Candidates have to submit the dully filled application form online through their official website on or before 8th March 2016. You can check the details from the given link below.
Starting Date to Apply Online: 23rd February 2016
Last Date to Apply Online: 8th March 2016
For Full Detail CLICK HERE
For Full Detail CLICK HERE
To Apply Now CLICK HERE


text:
02:28 Lyrics Feelin' Lucky
Woke up this morning
Rain pouring down
Slept in my car
On the wrong side of town
Gas tank's on empty
My job's on the line
Bossman said this is my last time
But I'm feelin' lucky
The clock on the dash
Said quarter past eight
Boss said 'don't come to work
If you're gonna be late'
So I drove to the store
I gave you a call
Spent twenty bucks
On the Powerball
'Cause I'm feelin' lucky
You kissed me last night
You whispered my name
You held me so tight
Said I was your man
So I'm feelin' lucky
Twenty- to- one horse
I bet it all
Feel so good
No worries at all
And I'm gonna win
That Powerball
'Cause I'm feelin' lucky
I'm feelin' lucky
02:15 Lyrics He's Got Nothin'
What's the matter with a girl like that?
She's got everything
The boy's got nothin'
What's the matter with a girl like that?
She's got everything
The boy's got nothin'
She lets him tell her how to wear her hair
She lets him tell her what clothes to wear
He's got nothin'
The boy's got nothin'
*Repeat Chorus
She turns her back on her friends at school
They all say she's acting like a fool
He's got nothin'
The boy's got nothin'
Mama's scared that she'll run away
Daddy says there'll be hell to pay
He's got nothin'
That boy's got nothin'
*Repeat Chorus
She said "The things that you don't see
Those are the things that mean the world to me
He's got everything
And you don't know nothin'
He's got everything
And you don't know nothin'"
*Repeat Chorus
(tag) She said "You don't know nothin!"
02:29 Lyrics Beach Town
You never see the sun come up
You never watch the sun go down
Not when you live in a beach town
In a beach town
You stumble out of bed by noon
You're drunk by three
You sleep away the afternoon
To keep the nighttime free
So you can dance by the light of the moon
In a beach town
You fall in love over Sunday brunch
Break up Monday after lunch
Wake up in somebody else's arms
Tuesday morning in a beach town
Livin's easy 'til the money's gone
You don't know where it went
On a barstool drinkin' all alone
Down to your last cent
That's just life in a beach town
In a beach town
03:40 Lyrics Fishermen (Singin' on the Water)
All day long water's all I see
Deep in the night the stars watch over me
Feel the rhythm and the rockin' of the waves
I'm homeward bound to the ones I love
Chorus: He..y Ho...o Fishermen singin' on the water
Hey...y Ho....o Fishermen singin' on the water
Seagulls spinnin' in circles overhead
Fish are jumpin' from their warm salty beds
See my home rise from the sea
My heart opens up brings this song out of me
Feel the comfort of dry sand on my feet
Run up the shore, fall down to my knees
Stretch my arms out across the land
Give a big kiss to the warm salty sand
03:27 Lyrics Sweet Relief
I'm lookin' for some sweet relief
Sit by the water, give my soul some peace
Turn my face to the warm, warm sun
Let my spirit run
I'm lookin' for some comfort there
Breathe deep, feel the air
Deep inside of me ..... oh, oh sweet relief
Bridge: And I can feel you there
Feel your warm breath touch my hair
Oh, Oh sweet relief
I'm lookin' for some company
Come and sit by me
We'll just let it be
Oh, oh sweet relief
And we won't say a word
Just listen to the bird's
Sweet melody
Oh, oh sweet relief
Finish: I'm lookin for some sweet relief
Sit by the water, give my soul some peace
Deep inside of me
Oh, oh sweet relief
03:16 Lyrics The Hawk
The patience of a hawk
In the blueness of the sky
We hurry far below
Time is passing by
So many things undone
So much left to do
While the hawk just circles 'round
And the sky just stays blue
The hawk holds the world
In the circle of its eye
Does what it was born to do
And it was born to fly
We question every little thing
Never knowing what is true
While the hawk just circles 'round
And the sky just stays blue
Why do we run like water
Searching for the sea?
Why do I never find
What's waiting there for me?
We only have a moment
We're only passing through
The hawk just circles 'round
And the sky just stays blue
03:31 Lyrics Flights of Angels
May your soul rise up to greet the sun
May your chains of troubles come undone
May your fears and sorrows melt away
May you rise in peace and joy that day
Chorus: You are gone away, you are gone
May flights of Angels sing you home
You are gone away, you are gone
May flights of Angels sing you home
Tears of sorrow fall helpless to the ground
Those left behind are gathered all around
They mourn the loss but celebrate your life
They know that Angels guide you in your flight
02:59 Lyrics Storm's A'comin'
Refrain: Storm's a comin'
Gone are the skies of blue
Storm's a comin'
What are we gonna do
We didn't pay attention
To all the blue skies we had
Now the storm clouds are gathrin'
And it's startin' to look bad
It's starin' to rain now
I can feel it runnin' down my face
Storm's a comin'
We gotta get out of this place
We got all the warnin's
We didn't pay 'em no mind
Now we better start runnin'
Runnin' for our lives
02:10 Lyrics Write Me a Letter
Six mailboxes standing in a line
Mailman stopped at every box but mine
Won't you write me a letter?
Write me a letter
Write me a letter
Stick it in the U.S. Mail
Got off the Work Farm
Tryin' to be good
Found a little shack
In the middle of the woods
*Repeat Chorus
Don't need a dime bag
Don't need a pound
Don't send nothin'
Bring the police around
*Repeat Chorus
Maybe just a postcard
Drop me a line
Ask me how I'm doin'
Well, I'm doin' fine
*Repeat Chorus
Stuck out in the boonies
Livin' all alone
Don't even have the money
For a flip telephone
*Repeat Chorus
Write me a letter
Show me that you care
Write me a letter
Tell me you'll be here
*Repeat Chorus
02:39 Lyrics Shaky Rock Shoes
Shaky little Maggie got a rock in her shoe
Hurts so bad she don't know what to do
Walkin' along on her shaky rock shoes
Shake it little Maggie, shake it 'til the rock come loose
Chorus: Shake it Maggie shake it
Shake it Maggie, shake it
Shake it little Maggie, shake it 'til the rock come loose
Little Maggie walkin' down the railroad tracks
Goin' clickety click clackety clack
Takin' those tracks goin' two by two
Rockin' along on her shaky rock shoes
Shake it little Maggie, shake it 'til the rock come loose
Little Maggie sittin' in a tall Oak tree
Goin' tweedley dum, tweedley dee
All the birdies start singin' too
Rockin' that limb with her shake rock shoes
Shake it little Maggie, shake it 'til the rock come loose
03:09 Lyrics I Sing to the Flowers
In the morning when I wake up, I walk along for hours
And I sing to the trees and I sing to the flowers
Feel the warmth of the sunshine as it rests upon my shoulders
And I'm living each moment as I am getting older
Refrain: La, la,la,la,la,la,la,la,la,la,la,la,la x 2
See the birds on the wing as I walk along below them
Say good morning to the people I meet, though I don't know them
It's the joy in my life and blissful awakening
Every moment is a gift, no for granted should be taken
And the song that you sing, that's the way people hear you
And the smiles that you bring, that's the way people feel you
It's the joy and the laughter as it rests upon your shoulder
And no matter your age, you will never feel any older
Finish: In the morning in the sunshine, I walk along for hours
And I sing to the trees and I sing to the flowers
03:24 Lyrics Purple Hair
She has purple hair
He has dirty nails
He smells like diesel fuel
She comes from money
Their love's a mystery
To friends and family
But he doesn't really care
And she thinks it's funny
She went to MIT
He works offshore
They own a house
Outside of Corpus
They don't have kids
Don't go to church
They sleep in late
On Sunday morning
Entwined in their own world
Like braided hair
Wrapped in a lover's bed
Where nothing matters
She loves him
And he loves her
They whisper to themselves
Between the kisses
She sips a glass of wine
He drinks Corona
She sits behind the wheel
Of his old white van
He's resting in the back
They'll be home by sunrise
He strapped the Norton down
And went to sleep
His trophy's on the dash
Another week behind them
He loves to ride that bike
In the Texas wind
They'll be back to work
Come Monday morning
She turns the music up
And smiles
And drives her lover home
02:27 Lyrics One More Cup of Coffee
One more cup of coffee
One more kiss goodbye
One more wave
One more glance at a blue sky
Turn the corner from the driveway
Stop at the light
Pull out into the traffic
And begin the commuter fight
Someone on a cell phone
Sending texts to an old friend
Veers into your lane
Brings your whole world to an end
Brings your whole world to an end
Refain: It won't happen to me
I can handle doing both
What's the harm in staying busy
Driving's such a bore
One more silent victim
One more big mistake
One more life is ended
Just another busy day
Just another busy day
One more cup of coffee
One more kiss ..........
- Nikki Hedrick/ Beachcomber Magazine 30A
" "Lucky Mud is from the deeper side of Folk Music. The couple have a soulful connection that is palpable." -EARBUZZ "
Having spent almost 7 years under the Nashville spell in the years of transition from the Country Music tradition of story telling through lyric to the current trend of songwriting by committee, Mike and Maggie McKinney returned to their Florida roots disillusioned with music. Michael McKinney became a well-respected author with a starred review in Publishers Weekly and accolades across the country for his first novel, 'A Thousand Bridges.'
But the love for songwriting still haunted them. Through a magical moment of clarity at the Kerrville Folk Festival in the Nineties, the realization struck them that Nashville had become the "Business of Music," not the music itself. That's when Maggie and Mike became Lucky Mud. Their reformation became their musical salvation. The love of a beautifully written lyric paired with a melody that fits the words so seamlessly that they cannot be separated without mournful loss. The ability to reach out and touch an audience with a voice that comforts or stings. A voice that amuses or inspires.
Words have power and a great melody enhances that power. That's "Mud Music." Their love of a great song has taken them on journeys throughout the world. Their original music has taken them from the Legendary Linenhall in Castlebar, Ireland, to Campbell's Pub on the wild coast of County Mayo in the West and throughout Connemara. From the island of Sark, in the Tidy Bowl blue English Channel, to the bridge-bound streets of Newcastle Upon Tyne in Northern England and Bandera, Texas, (yes, it is another country) to the beautiful hills of Nova Scotia and New Brunswick in Canada. Lucky Mud has shared their Florida swamp roots 'Mud born' music. Lucky Mud has opened for and shared stages with both the infamous and famous musicians currently touring today. From the legendary songwriter Eric Taylor to the irreverent Grant Peeples. From the mesmerizing talents of California folk-duo Paul Kamm and Eleanore MacDonald to the sultry-voiced Sally Spring. Too many incredible voices singing out in the wilderness of satellite radio channels and independent music sources to name, but all equally blessed with the true gift of storytelling.
Too honest for Nashville. Too gifted to compromise by writing songs-by-committee. The music, and nothing but the music, matters.


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In the long, bitter campaign fight between Barack Obama and Hillary Rodham Clinton, few states witnessed as much rancor as Nevada.
The state's 2008 Democratic caucus, scheduled early in the race to boost its influence, yielded a federal lawsuit, a fight between labor unions, charges of voter intimidation and accusations of prejudice, among other bricks that were heaved between the battling candidates and their backers — including a livid President Clinton.
Fittingly, the contest ended in a split decision, with Hillary Clinton winning the popular vote and Obama claiming the most nominating delegates to the Democratic National Convention.
Against that contentious backdrop, Clinton will return to Nevada on Tuesday to host the latest in a series of small-scale appearances undertaken since she formally announced her second presidential bid last month.
She will also test the relations frayed by that fratricidal 2008 contest.
Much of the acrimony involved Las Vegas' Culinary Union, the state's largest and most powerful labor organization. With 60,000 members at the time, many of them Democratic-leaning and politically active, the organization's endorsement was highly sought by the party's large field of hopefuls, who spent months courting union members and their leadership.
Obama ended up winning the official endorsement, a boost after Clinton's surprise victory in the New Hampshire primary. (Nevada is slotted as the third contest on the nominating calendar, after the Iowa caucuses and New Hampshire primary.) But the decision led to a split within Democratic ranks and hostilities that many have not forgotten.
"We have members who remember the caucuses vividly and talk about them almost like a civil war battle," said Yvanna Cancela, political director of the Culinary Union's Local 226, which represents the workers who service Las Vegas' life-blood tourist and gambling industries. "But I think enough time has passed where we can move on from the 2008 caucus."
Under the system, delegates were allotted on the basis of voting in party-sanctioned gatherings, or caucuses, held throughout the state.
Two days after the union formally endorsed Obama, lawyers for the Nevada State Education Assn. filed a federal lawsuit challenging the voting system. The timing of the teachers union suit — long after the rules had been established by the national Democratic Party — and the involvement of several Clinton supporters turned the legal fight into a proxy battle between the rival candidates.
Clinton's allies objected to polling sites at several casinos on the Las Vegas Strip, placed there in an effort to allow shift workers to participate in the caucuses, which were held during daylight hours on a Saturday.
D. Taylor, then head of Local 226, denounced the suit as "despicable" and "disgusting" and a deliberate effort to disenfranchise women, minorities and working people. Clinton distanced herself from the lawsuit, saying it was up to the courts and the state Democratic Party to hash out, but suggested it had merit.
Her husband was more vocal, angrily asserting the job-site balloting would unfairly give more weight to the votes of casino workers — a group that is heavily Latino — and he accused the Culinary Union of strong-arming members to back Obama.
Obama's allies fired back with a Spanish-language radio ad that accused a "shameless" Hillary Clinton of trying to repress the Latino vote. "Vote for a president who respects us and respects our right to vote," the spot urged in support of then-Sen. Obama.
In the end, a judge upheld the casino sites and Clinton won not only the popular vote but seven of the nine caucuses held on the Las Vegas Strip, thanks in part to vigorous campaigning by Bill Clinton and their daughter, Chelsea.
"It's not too often that you have the former president of the United States greet you as go into your caucus or have Chelsea Clinton leaflet you," Taylor told the Las Vegas Sun at the time. "It was a full onslaught of Clinton, and I congratulate her. She won."
In a recent interview at the Culinary Union headquarters, in an industrial area just off the Strip, Taylor said there were no lingering hard feelings.
"Politics is a tough, rough-and-tumble sport," said Taylor, now head of the union's national parent organization, Unite Here. "Just like any competitive thing, at the end of the day you recognize and respect each other and then move on."
That said, the Culinary Union is in no hurry to endorse a candidate for 2016. Its focus, according to Taylor, is on the current legislative session in Carson City, where state lawmakers are debating a number of bills that could weaken the influence of organized labor.
He and his members, Taylor said, want to take time to consider the presidential field once it is set. "Whenever I go to Baskin-Robbins, I don't know exactly what I'm going to order," he said. "I like to see the choices."
Former Maryland Gov. Martin O'Malley, who is considering a bid for the Democratic nomination, visited the Culinary Union headquarters in September during a midterm election swing on behalf of Nevada Democrats. Independent Sen. Bernie Sanders of Vermont, who entered the Democratic race on Thursday, held a town-hall-style meeting at the union headquarters in March.
Taylor and the Culinary Union leadership have yet to hear from the Democratic front-runner or her husband.
A Clinton spokeswoman, state campaign director Emmy Ruiz, said the candidate "will work to earn every vote" in Nevada, "including the Culinary Workers Union Local 226."
Twitter: @markzbarabak


text: June 9, 2014 at 6:04 AM Mount Rainier accident: Stop blaming climbers for costs Posted by Letters Coordinator A photo provided by the National Park Service shows Liberty Ridge and the Carbon Glacier, with a helicopter at top right. (National Park Service) Like many in the climbing community, I was sad to see the recent Rainier climbing accident, and proud of the rangers, guide service and community response ["Liberty Ridge is risky, deadly Mount Rainier route," Local News, June 2]. One thing I hope to address is the knee-jerk reaction that I almost always see online after any such accident: Climbers (or their survivors) should be sent a More Comments | More in Climbing | Topics: climbing, Mount Rainier, National Park Service


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It was the last time when we saw on how you can update with the latest Gingerbread 2.3.5 version of firmware which is XXJVT version. Now, in this article we will see about on how you can root the phone so that then you can easily update with the Gingerbread 2.3.5 based custom ROMs which we will see very soon at androidadvices.com. Again we would like to really apologize for the delay caused in bringing this article and in future we will ensure that as soon as the firmware update article comes the subsequent article will be of the rooting.
So, before you proceed with the procedure to root your phone you will now have to ensure that the firmware in your Samsung Galaxy S GT I9000 is the XXJVT 2.3.5 and nothing else. Please note that if you continue to still proceed with this procedure to root your phone then you may face issues like phone not turning On etc. Just in case if you are not sure of the version on which version the phone is updated to then you can have a check the same. All you need to do is to just go to the path in your phone that is Settings > About Phone > Firmware Version where you will find the version of Android OS where it will show XXJVT 2.3.5.
So, for all those who wanted to know in short about what is the rooting and what rooting is all about along with the advantages as well as disadvantages then we will guide you on the same. For your simplicity we have broken this article into two different pages, on this page we will see on what is the rooting, advantages and disadvantages of rooting followed by the instructions on how you can root the phone with a simple to follow tutorial which is there in the next page.
What is Rooting?
Rooting is basically a technique wherein if a phone is rooted then it lets third party applications as well as the user to access the system level files which otherwise are not provided with the access so that the required amount of customizations can be made with the System which are generally done by the custom ROM installations. Let's check out on what are the advantages and disadvantages of the rooting.
Advantages of Rooting:
- First and Foremost, rooting allows the customizations like it allows the installation of Custom ROMs in the phone.
- Allows you to convert file systems from the laggy RFS to the speedy EXT4,
- Allows you to remove the system apps which come by default with the phone,
- Allows you to apply host of other customizations
Sometimes, the procedure to root the phone is bit lengthy, so you are required to follow the instructions carefully or else you may end up bricking up the phone.
Rooting voids the warranty, though it can be reclaimed by updating with the default factory firmware on unlocked phones which doesn't come with the boot loader lock.
Procedure to Reclaim Warranty or Revoke Root Access:
Just in case if you have rooted your phone on XXJVT 2.3.5 Firmware and now you wish to un root / Revoke the root access of the device, all you need to do is to just follow the procedure to again apply the update of XXJVT 2.3.5. Please note that in this process you need to disable any Voodoo lag fixes if applied from the recovery mode or else it will brick your phone.
Note: We should not be held responsible or liable in any manner if anything wrong happens with your device, though which is a very unlikely if you follow the instructions which are mentioned in the article.
So, let's proceed to the next step where we will see on how you can apply this root to your Samsung Galaxy S GT I9000 phone.
131 Comments
Thank you for your website.
Can I upgrade my Samsung Galaxy S GT-I9000T operating system?
the XXJVT 2.3.5 Rooting Packagelink in not working :/
to downlink dont work :/
hi when i put my phone in download mode and connect to pc with odin already open nothing happens and my pc makes the device not connect sound, the usb connection does work normally though for file transfer etc. Please hlep
are you using the FTP Server?
this is weird my samsung galaxy s gt i9000 is running android 2.3.6 on xxjvt.is this something i should worry about?
when i put my phone into recovery mode it doesnt show up in odin, but it deos wen the phone is on….. please help
I got a secondhand I9000, and I'm a total newbie concerning rooting and custom ROM of smart-phone.
Here's the "about phone" page of my GT-I9000 phone:
Firmware version: 2.3.6
Baseband version: I9000XXJVT
Build number: GINGERBREAD.XWJVW
Now I'd like to root my phone, but I couldn't find any tutorial or tools to root the XXJVT running Gingerbread (2.3.6)…any help/suggestions?
Thanks in advance,
Hi, I'm not very techie, but I did try to follow your instructions above. I got it so far as all drivers installed with the ID:COM block as yellow, but when i click PDA, and got the extracted file from my desktop, the phone closed suddenly and I can't turn it on anymore. The symbol on the phone is: an exclamation mark in a triangle between a mobile phone and computer icons. Help!
What should I do now? I tried doing the recovery after Force Close Error after Rooting, but it won't budge. I removed the battery and turned on the phone, but I still get the same icons. Help, please?
Brother, i cant downlioad the rooting package from the link. an error message appears everytime i click the link. can you help me with this one as i want to try the new custom rom.
Thanks brother
The download link is still not working. Can you please fix it?
How to convert RFS to EXT4?. . .or how to speed up my phone after rooting my phone?
i have an error message while i try to root. its a image with a exclamation mark place between a phone and a pc. please help thanks
if i root my samsung g i900 XXJVT with this update will my applications/games/contacts be lost?
Hi Neal,
Successfully upgrade. Thanks a lot.
How can I include Chinese interface/ writing method into the current firmware?
Thanks a lot!
Neal how can unzip a file which is already unzipped????
why is it zipped as a rar
Can I upgrade my Samsung Galaxy GT-I9000 firmware version 2.3.3 directly into android 4.0???
Neal, download link is dead to me. I don't know if the same to everyone else. The link for the http://downloads.androidadvices.com/S/SamsungGALAXY_S_GTI9000_XXJVT_2.3.5.zip also dead
I couldn't download it
download link is not working at the moment please fix this issue.
I am on 2.3.5 JVk have rooted as described above but wifi and auto rotate not working. how do you unroot and will this sort out the issues?
I am using samsung galaxy S GT-I9003. Can I root it on Gingerbread 2.3.5 XXJVT?
Hi… I recently updated my galaxy s.. But after the update, I am not able to access internet on my phone. After updating, i could easily access internet for 2 days. But after 2 days, the internet connection is not being detected. I have the APN's also. My operator is Vodafone India.
Hi Neal ,I had rooted my galaxy i9000,after installing gingerbread 2.3.5XXJVT firmware.Every thing was working perfectly but suddenly got problem with market application.Market is not opening with a massage \connection time out try again\.Kindly help.
hai ! neel ! i have one doubt ! plz help me !
imy mob is Galaxy GT-I9000 with XXJVS, Gingerbread-XXJVS .. can i root using XXJVT 2.3.5 Rooting Package ?
Hello i have successfully rooted my SGS i9000 but i am having one problem is that there are some changes that i find quite odd.
The option button color is different from the others, and there is no color in top navigation bar its completely black.
Original Image : http://i960.photobucket.com/albums/ae87/jeetdholakia/Original.png
After the update : http://i960.photobucket.com/albums/ae87/jeetdholakia/shot_000003.png
so is it due to change in version because i have not seen such a change.
thank alot … another device of my friend equipped with gignerbread .
neal u made lot of ppl day … with powerful gingerbread .
and rooting done without any error as always .
Thanks a lot for your useful advices & beautifull site. I used this Rooting Method and it was Great.
Hey neal, Im using Galaxy S Gt-9003, when i got the phone the internet was really fast for first 2 days… amazing speed … but i dont know what happened after that its dead slow now… pls help me out.
how do i root my sam g s i9000 gingerb 2.3.2 so i can upgrade to ics
My phone is having a problem since I have updated it with Gingerbread 2.3.4,also problem remains the same after i upgarde XXJVT 2.3.5.
It randomly force close the process "Com.android.phone" and my phone stop working for 5-6 seconds
This issue is just killing me, Please Help
also posted same on 24th Oct.
Hi Neal
When im starting up my phone i can't connect to my 3g internet.
Can you please tel me whats going on?
hi neal,
can the above procedure be used for samsung galaxy s GT-I9003??
Hi, Neal. Thank you for these useful instructions. I have a question. I rooted my phone to install Titanium Backup months ago, but yesterday I updated my firmware. Do I need to root it again? And if so, do I need to uninstall Titanium before doing that? And what about the Super User that is already on my phone? Thanks a million.
not able to download the rooting package
Hi there
i have rooted my galaxy s i9000 with gingerbread n after that my cell is unable to be on …just blinking on the screen galaxy s….what to do
hi…in rooting process Odin is stuck in "setup connection"…..help
Is there any alternet way to reach out to Neel
any mail ID or chat..
how can we do voodoo lag fix after rooting this?
Please advise ..
My phone is having a problem since I have updated it with Gingerbread 2.3.4,also problem remains the same after i upgarde XXJVT 2.3.5.
It randomly force close the process "Com.android.phone" and my phone stop working for 5-6 seconds
This issue is just killing me, Please Help
I believe I'll need to apply the factory PIT file and ROM!
Hi Neal,
Here's what happened after applied root. My phone will reboot loops… When it's start on the screen [Galaxy S GT-I9000M] and then swtch to another screen [Galaxy S GT-I9000] and black screen for a second and loop back…
How can I remove that root?
Pls help anybody?
Or do you have another flash for my model (i9000m) or recommendation of what to do ?
Thanks Neal
Thank you Neal. I'm new to this rooting… Can you please help on how to go back to the factory default?
I tryed to root my Samsung Galaxy I9000M with Gingerbread 2.3.3 from your instruction http://downloads.androidadvices.com/S/Samsung_GALAXY_S_XXJVT_RootingPackage.rar
and now I got reboot loop.
Can anybody help me?
Thanks So much
I just flashed my i9000 but there is no (ΕΛΛΗΝΙΚΑ) Greek language to the input languages for SMS!can i do something?
the rooting zip file XXJVT 2.3.5 gets downloaded as a rar file. please check as i cannot unzip a file which is already unzipped.
i have been trying to do it since yesterday.
Hi Neal
I am not able to download the rooting zip file XXJVT 2.3.5. It gets downloaded as a Rar file which is not recognized / windows fails to open it.
Plz help
When I downloaded from the "XXJVT 2.3.5 Rooting Package" Link, I am only getting Samsung_GALAXY_S_XXJVT_RootingPackage.rar". Not as mentioned here. Please check and advise. So I am not able to proceed to root my galaxy s I9000.
Does rooting helps me get rid of the enforced PIN lock if I have the company's email on my device ?
thank you brother.
Thank you Neal for this article. Rooted successfully. Can I install Cyanogen MOD 7.1 Custom ROM Firmware as I have XXJVT.
when ever i am rooting my samsung galaxy s GT I-9000 my phone start up sound is not working.
Many Thanks to androidadvices.com for there tips,advices for all adroid devices. Its really helpful for us, as we are now just in transition mode from all time user friendly NOKIA to ANDROID DEVICES.
Your tip & advice had helped us a lot.
Warm Rgds
I have SAMSUNG GALAXY S which came with 2.2 version, can i update it to 2.3.5 GinjerBread Version of Android OS.
In your article yo mentioned "So, before you proceed with the procedure to root your phone you will now have to ensure that the firmware in your Samsung Galaxy S GT I9000 is the XXJVT 2.3.5 and nothing else"
So i wanted to ask that rooting and upgarding from 2.2 to 2.3.5 is the same thing or two different thing.
hmmm are u going to give custom update for galaxy s i9000 (sc-02b) ntt docomo model of SGS i9000 .. i can't update my unit with ur custom rom, when i try to update it with ur rom the IMEI is gone and all the network signals are also gone..
i'd really appreaciate it if u can provide update/rooting for sc-02b models.. thanks guys…
why is it zipped as a rar
I have successfully rooted my i9000 following your instructions, well there was the second com i.d. port which was RED & flashed Falied, but still the handset was rooted successfully.
Off lately after 1 month suddenly I am not able to send or receive sms from a particular number.. can you help me fix this issue ?
Also very often I am getting force close messages. Please help I am in mess.
Ajay More
HYE Neal my wifi is not working for this i change the version to 2.3.5 but still not working
but please how to unroot him i tried all my best but not working andd not open too


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Tag Archives: tattooing
Do Tattoos Make You Look More Fit?
Do my tattoos make me look more fit, or fit at all? Gosh, I hope so. Look over here at my guns—er, arms—and not at the middle age gut I'm fighting to suck in. In a study of 6528 undergraduates … Continue reading
Posted in Anthropology, Christopher Lynn, Evolution and Psychology Tagged Alabama, Alabama football, Alabama tattoos, BMI, Cassie Medeiros, costly honest signaling, football, Haley Dillon, human canvas hypothesis, Inking of Immunity, intercollegiate athletes, Mackenzie Manns, Mandy Guitar, piercing, Rachael Carmen, Roll Tide, tattooing, upping-the-ante hypothesis, WEIRD Comments Off on Do Tattoos Make You Look More Fit?
Malu is Like a Golden Ticket (Pt. 3)
Please consider contributing supporting the Inking of Immunity 2018 field season at Experiment.com/InkingImmunity. We had worried when the study started that we would have difficulty juggling multiple tattoo sessions with only two researchers because we only took along one bioimpedance analyzer … Continue reading
Posted in Anthropology, Biological Anthropology, Christopher Lynn Tagged American Samoa, cortisol, immunoglobulin A, Inking of Immunity, Off Da Rock Tattoos, Samoan Tattoo Song, tatau, tattooing Comments Off on Malu is Like a Golden Ticket (Pt. 3)
Is tattooing a costly honest signal of fitness?
Last year I published a book chapter synthesizing an evolutionary perspective on tattooing for our Evolution Education in the American South volume and concluded by wondering whether athletes, specifically football players, get tattoos more than the average person (Lynn & … Continue reading
Posted in Anthropology, Biological Anthropology, Christopher Lynn Tagged AJ McCarron, costly honest signaling, Crimson Tide, Inking of Immunity, Jesse Williams, Reuben Foster, tattooing Comments Off on Is tattooing a costly honest signal of fitness?
Of "Toxic" Tattooed Lymph Nodes and Public Relations
I was heartened this week by conversations with visiting ALLELE lecturer Nina Jablonski, one of the world's foremost experts on skin biology and evolution. I was glad to see that she discussed tattooing in her 2006 book Skin: A Natural … Continue reading
Posted in Anthropology, Biological Anthropology, Christopher Lynn, Columnists, Evolution & Pop Culture, Evolution in Media Tagged cultural impacts on health, Ines Schreiver, media, neuroanthropology, Nina Jablonski, skin, tattoo pigments, tattooing, tattoos, toxicity Comments Off on Of "Toxic" Tattooed Lymph Nodes and Public Relations
#2016Highlights Month-by-Month: Part 1
Though the end of 2016 was miserable, most of the year was awesome, and it's important that we have a little perspective. At my house, we have a dinner ritual called "Good Thing/Bad Thing" or GTBT. We each take turns … Continue reading
Posted in American Anthropological Association, American Association of Physical Anthropologists, Anthropology, Biological Anthropology, Biological Anthropology Section of AAA, Christopher Lynn, Conferences, Evolution Conference, Human Biology Association Tagged African Village in America, Alabama Natural History Museum, Alabama-Greece Initiative, Alexander Georgiev, ALLELE, American Journal of Human Biology, American Samoa, Austin Lawrence, Becky Burch, Bill Bomar, Bob Olin, Caitlin Schrein, Charlotte Wegryznowski, Darwin Day, David Herdrich, Dean Falk, Human Biology Association, immune response, Julienne Rutherford, Lee Berger, Lee McCorkle, Luaheng Han, Marc Kissel, Mary Schweitzer, Michaela Howells, SEEPS, Tatiana Summers, tattooing, Vaia Touna, Zika Comments Off on #2016Highlights Month-by-Month: Part 1
Sabbatical is Here!
Have I started relaxing yet? Everyone asks me this. Do y'all not know me? We just arrived at my in-laws for the holiday, & I'm already thinking about how to fill my days. I don't relax well. But I am … Continue reading
Posted in American Association of Physical Anthropologists, Anthropology, Biological Anthropology, Christopher Lynn, Education, Evolution & Pop Culture, Evolution Outreach, Human Biology Association, Sabbatical, Southeastern Evolutionary Perspectives Society Tagged American Samoa, Big Red Earth, Costa Rica, Dustin Eirdosh, Erik Peterson, EvoKids, Evolution Education in the American South, Greg Batchelder, HBERG, immune response, Michael Muehlenbein, Michaela Howells, SEEPS, Signaling theory, Susan Hanisch, tattooing, Tisa's Tattoo Festival, Transcendental Medication, UA in Oxford, Zika Comments Off on Sabbatical is Here!
Tattooing Primes the Immune System
…But First, a Test of the "Rap Guide to Evolution"… A few weeks ago I presented a poster at the Human Biology Association annual scientific meeting about the roles of emotions in learning about evolution via a performance of Baba … Continue reading
"Human Canvas" & "Upping-the-Ante" Hypotheses for the Evolutionary Significance of Tattooing
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HBES 2012 Roundup 3: Kissing Petri Dishes & Staring at Gross Things to Get all Hot & Bothered
The highlight of Saturday's talks was my slowly growing consciousness of this new theoretical paradigm called the "behavioral immune system" that I've written about in the past & will write about again in the future but the scope (& name) … Continue reading


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The modern quarterback must be cunning. The position requires a player who can forsake the deliberative comforts of the huddle to stand above center, scan the opposing defensive formation, and, like Napoleon, whose theory of battle was on s'engage, et puis on voit (you enter the fray, and then you see what to do), make rapid play-calling decisions. Omaha. Hut. Snap. Touchdown passes are fine, but in today's game the desideratum is a quarterback who possesses the accuracy to minimize turnovers, and the presence of mind to avoid being sacked. Meanwhile, in response to the public dismay over long-term effects of football-related concussions, the league has swathed the quarterback in a crinoline of new rules of the game, which make it more difficult for pass rushers to legally hit him—advantages that further enhance the aristocratic primacy of the position. It is the most important role in American team sports.
Given how crucial the quarterback is to his team's success, and given the months of immersive preparation that every team's scouts, personnel men, and coaches devote to the annual draft, in April, you'd think that N.F.L. teams would be unerring evaluators of promising college quarterbacks. But that is not the case. Of the four N.F.L. quarterbacks who will lead their teams into this weekend's conference championship games, only one, Peyton Manning, of the Denver Broncos, was a first-round draft choice. The San Francisco 49ers' Colin Kaepernick was taken in the second round. The Seattle Seahawks chose Russell Wilson in the third round. And the New England Patriots' Tom Brady, whom many inside the sport consider the finest quarterback of his time because he wins with marginally gifted receivers, was, famously, a low-sixth-round choice. Brady embodies the N.F.L. truism that forecasting talent, though always necessary, is often futile.
This year, as many as four college quarterbacks may be chosen among the first ten picks of the draft. N.F.L. front-office men are currently spending their days inside locked, windowless war rooms, reviewing sheaves of scouting reports and loops of game film as they parse the risk parity of Louisville's Teddy Bridgewater, debate how well Texas A. & M.'s Johnny (Football) Manziel will survive the big-time hits and the big-city nights, predict if and when Central Florida's Blake Bortles's throwing will win him enough attention to out-Google his oft-searched girlfriend, and analyze whether Fresno State's Derek Carr is a keeper or more like his brother, the fizzled former No. 1 over-all choice David Carr. As these draft teams labor, they'll keep in mind picks like the Falcons' second-round selection in 1991. After seeing their rookie attempt a total of four unsuccessful passes that year, Atlanta traded Brett Favre to Green Bay. The draft specialists also keep in mind J. P. Losman.
"Remember J. P. Losman?" the former Raiders quarterback Rich Gannon, now a CBS broadcaster, asked. "He was a first-round pick for Buffalo out of Tulane [in 2004]. You take Tom Brady, Peyton Manning, and J. P. Losman out to the park in shorts for a workout, and all of us would take J. P. Losman. He was faster, had a bigger arm, and he'd blow you away in the workout. But from the shoulders up, how good is he?"
"Manning doesn't throw the ball as well as he did. He's coming off neck surgery," Gannon continued. "How's he breaking everybody's records? The game has slowed down for him. He sees what other people don't see." Losman, meanwhile, has been "on the street," as N.F.L. personnel men say, since 2011.
What does it take to succeed as an N.F.L. quarterback? Not so long ago, football was a more freewheeling sport, and quarterbacking statistics reflected it. In the nineteen-seventies, when quarterbacks were urged to think of the passing game in high-reward, "vertical" terms, a fifty-per-cent passing-completion rate was the acceptable standard. Today, when short crossing patterns—in effect, thrown running plays—are a crucial feature of the game, every team craves a sixty-per-cent passer. (Nine of the twelve most accurate passers in N.F.L. history are active.)
"Comparing quarterbacks twenty years ago with quarterbacks today is like comparing a Cadillac twenty years ago to a Cadillac of today," the retired N.F.L. head coach Dick Vermeil said. "They just do it better today." (Vermeil's quarterback in 1999, when he led the St. Louis Rams to a Super Bowl victory, was that modern progenitor Kurt Warner, a career 65.5 per-cent passer—tied with Manning for the fourth best in N.F.L. history.)
The signal feature of today's offensive coördinators is that they draw from the entire tactical history of the sport to build their game plans. They are modificationists, and as a result, Vermeil estimates, the offensive-call volume is four times what it was twenty-five years ago. A contemporary quarterback can adjust the entire look of his offense from play to play, putting more pressure on the opposing defense—so long as he is capable of mastering the eclectic trove of calls. "Everybody wants to change personnel on every play, but not everybody is Peyton Manning," Tom Moore, a retired N.F.L. passing impresario, said. Moore was the Colts' offensive coördinator for the duration of Manning's career there.
A generation ago, a young quarterback was expected to apprentice for a season or two on the sidelines before assuming control of a team. "The older-style West Coast quarterbacks took longer to develop, perhaps because they hadn't played in a [high-tech] offense at earlier levels, and because top college quarterbacks were inevitably drafted by poor teams," the retired Bills coach Marv Levy said. Jim Plunkett, Dan Pastorini, and Archie Manning were all drafted in 1971 by lousy franchises. For them, Levy noted, "it wasn't a matter of succeeding; it was a matter of surviving." Today, quarterbacks who are drafted in the first round cost enough money against the salary cap that they are usually expected to lead their teams right away. Most do have the advantage of having played in pro-style passing offenses in college. Still, as significant as the position of quarterback is, football remains fundamentally a team game. Even a superior quarterback can't expect to thrive if the players around him, and the offensive coördinator's preferred style of play, don't complement his skills. The second-year Colts quarterback Andrew Luck is a fine player, but part of the reason he became successful so quickly is that he joined a talented team.
For all the promise that Luck, Kaepernick, and Wilson have demonstrated in reaching the N.F.L. playoffs, the sustained excellence of Brady and Manning is very rare. Consider Mark Sanchez. After being selected by the Jets in the first round of the 2009 draft, Sanchez and a team of fine veteran players went to consecutive A.F.C. championship games—and had a 3-2 record against Brady's Patriots. In 2010, Sanchez led N.F.L. quarterbacks with six game-winning drives. The next two seasons, however, he regressed, throwing an alarming flurry of interceptions and becoming the butt of an infamous N.F.L. collision. He missed the entire 2013 season owing to a preseason shoulder injury that required surgery. At the moment, he is a career fifty-five-per-cent passer, with sixty-eight touchdown passes and sixty-nine interceptions. That portfolio is sufficiently modest that the Jets could cut him.
Yet several former players and coaches think that N.F.L. teams in need of a quarterback ought to consider signing Sanchez instead of drafting one of those enticing collegians. "So many times, quarterbacks are the victim of the team they play on," Vermeil told me. "Sanchez took his team to the playoffs. That means he can do it again. Sometimes it takes moving to another place for a guy like him."
"The fans have beat the hell out of him. Other teams have beat the hell out of him. The quarterback's not the only one at fault," Vermeil said. "He takes most of the blame, but normally there's an accumulation of reasons. Coming out of college, everybody thought he was a fine player. We all saw it."
After leaving the Colts, Tom Moore was hired as an offensive consultant by the Jets, in 2011. The time he spent with Sanchez at the team's facility left him with a favorable impression of the then twenty-four-year-old passer's strength of arm, recall, and personality. "I did like him, and always will like him," Moore told me. "He started out hot. He slipped a little, and then he got injured. I think he is a special talent. You have to do it quick, and he can. He works hard…. Archie Manning was as fine a quarterback as ever went down the pike, and he never went to a playoff game. Not a good quarterback—a great one. Lot of it has to do with the team."
Gannon, the former Raiders quarterback, also worked with Sanchez as an off-season consultant. He found much to admire in Sanchez's athletic abilities, but like many of the Jets talent evaluators I came to know while writing a book about the team, Gannon questioned Sanchez's ability to make winning decisions under pressure. The Sanchez I knew was a compelling person, but he was young—and he seemed young; from the first, Brady and Manning were old football souls. Gannon attributes part of Sanchez's erratic play to the lack of continuity in New York, where he had to adjust to a stream of new receivers, as well as three different offensive coördinators. Brady has played only for offensive coördinators who were promoted through the Patriots system. Similarly, Manning, the Saints' Drew Brees, and Aaron Rodgers, of the Green Bay Packers, have thrived by playing within one scheme throughout their careers. Sanchez has had to start anew three times. "It's French to Spanish to Greek," Gannon said. "Too hard."
Gannon has reason to be sympathetic to Sanchez's plight: his own experience as a player found him cycling through a series of coaches and systems in Minnesota, Washington, and, finally, Kansas City. "Only after seven years did I finally learn how to break down an opponent," he said. He signed with Oakland in 1999, where, at the age of thirty-four, he suddenly became a Pro Bowl quarterback.
Another late-to-flourish quarterback was Jim Plunkett. Like Sanchez, Plunkett grew up in California, in a Hispanic family. He played college football to acclaim in his home state, winning the 1970 Heisman Trophy, and then came east as a young man. He joined the Patriots, whose yielding offensive line and frequent reliance on option running plays is at least partially to blame for Plunkett's brutal succession of injuries. But, like Sanchez, Plunkett was tough. Six weeks after a surgery to place a pin in his left shoulder, Plunkett played again and was hit so hard the pin popped out of the bone. New England eventually traded him to San Francisco; the 49ers soon released him. "I was very depressed," Plunkett told Sports Illustrated's Rick Telander. But then, in 1978, Plunkett became a Raider, and after two years of reserve duty, at thirty-three, he led the team to the Super Bowl and was named M.V.P. Given their luck with withershins quarterbacks, Sanchez might soon be Oakland's man.
Tom Flores, Plunkett's former head coach with the Raiders and a quarterback specialist, is one who thinks Sanchez can thrive. "Did all of a sudden Sanchez become a bad quarterback? No." Flores said. "Jim Plunkett had some of that [adversity]. He didn't resurface until ten years later. Why that happens is not easy to say."
Plunkett was a political-science major at Stanford and a particularly introspective football player—the sort of person who lingered on his interceptions rather than on his touchdowns. Sanchez is more optimistic by nature. But watching him founder across the 2011 and 2012 seasons, he seemed to me to have lost the fluid intuition for his position that all the best players exude. And now he has been absent from the game for a year. Most of the books that offer deep insight into football are not really football books, and Sanchez's struggles bring to mind a passage from John Williams's great novel of the West, "Butcher's Crossing," in which a skilled buffalo hunter who has been away from the prairie describes the uncertainty he feels as he sets off on a new expedition: "I just have to get the feel of the land again. I've been watching too close, trying too hard to remember."
Manning and Brady both missed seasons because of serious injuries and then returned with their intuitions for a white-lined, hundred-yard range completely intact. But as we watch them face one another in Denver this weekend, we should appreciate that they are the rarest of athletes. As Dick Vermeil came to understand during his long career, most quarterbacks are built of so many ambiguous, conflicting features that even expert eyes have difficulty seeing them clearly.
As a young man, Vermeil was Plunkett's quarterback coach at Stanford. "When I coached Plunkett, they were thinking of making him a linebacker." Vermeil recalled, almost fifty years later. "I read a lot of war books now that I'm retired. The thing I notice is nobody can predict who will win the Medal of Honor. It's never who they think. They're cut from different sizes and shapes and environments. Quarterbacks are the same way. Who could predict Kurt Warner would do what he did? I couldn't, and I signed him. Kurt Warner was better on game days under pressure. How do you predict that?"
Nicholas Dawidoff's most recent article for the magazine, "Quarterback Shuffle," was published in September, 2012, and he is the author of the book "Collision Low Crossers."
Above: Mark Sanchez on August 9, 2013, in Detroit, Michigan. Photograph by Leon Halip/Getty.


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We propose a design route for the next generation of nitride alloys via a concept of multicomponent alloying based on self-organization on the nanoscale via a formation of metastable intermediate products during the spinodal decomposition. We predict theoretically and demonstrate experimentally that quasi-ternary (TiCrAl)N alloys decompose spinodally into (TiCr)N and (CrAl)N-rich nanometer sized regions. The spinodal decomposition results in age hardening, while the presence of Cr within the AlN phase delays the formation of a detrimental wurtzite phase leading to a substantial improvement of thermal stability compared to the quasi-binary (TiAl)N or (CrAl)N alloys.
Funding Agencies|SSF||Swedish Research Council||Gran Gustafsson Foundation for Research in Natural Sciences and Medicine||
This licentiate thesis reports experimental and theoretical work on the high temperature mechanical properties and the thermal stability of cubic (c)-(Ti-Cr-Al)1-N1 coatings. It is demonstrated that it is possible to tailor and improve the properties of hard nitride coatings by different degrees of multicomponent alloying. When Cr is added to Ti-Al-N the coatings exhibit age hardening up to 1000 ºC which is higher compared to what is observed for Ti-Al-N. In addition, the coatings show a less pronounced hardness decrease when hexagonal (h)-Al-N is formed compared to Ti-Al-N. The improved thermal stability is discussed in terms of a lowered coherency stress and a lowered enthalpy of mixing due to the addition of Cr. When Ti is added to Cr-Al-N the formation and growth of the detrimental h-Al-N phase is suppressed and delayed improving the mechanical properties. This is discussed in terms of kinetic effects where the Ti atoms obstruct the Al diffusion and consequently the growth of h-Al-N precipitates. The microstructure evolution investigated at different stages of spinodal decomposition, coarsening and phase transformations are correlated to the thermal responses and the mechanical hardness of the coatings. Upon annealing up to 1400 ºC the coatings decompose into c-TiN, bcc-Cr and h-AlN. The decomposition takes place via several intermediate phases, c-CrAlN, c-TiCrN and hexagonal (β)-Cr2N.
The oxidation resistance of (Tix-Cry-Al60)1-N1 is also investigated and presented for different x/y ratios. The results show that it is possible to generate coatings with both excellent mechanical properties and oxidation resistance improving the functionality in the working temperature range of 850-1100 ºC of for example cutting tools.
Coatings are vital to protect and to increase the productivity of cutting tools in high speed and dry cutting applications. During the cutting operation the temperature may exceed 1000 ºC it is therefore necessary that the coatings withstand high temperatures. A lot of development and research has been carried out during the last 30 years on finding new coating material systems providing enhanced properties such as adhesion, hardness and oxidation resistance at elevated temperatures. This thesis is based on multicomponent alloying of quaternary transition metal nitride hard coatings with a main focus on Ti-Cr-Al-N coatings. Many different coatings and compositions have been deposited using an industrial scale cathodic arc evaporation deposition system. All deposited coatings contain Al as this element is known to increase the hardness and the oxidation resistance of nitride coatings. The deterioration of the hardness in Al-containing nitride coatings is generally attributed to the transformation of cubic Al-N into hexagonal Al-N and the consequent domain coherency relaxation. This thesis investigates these phenomena on an atomic level providing a deeper understanding of and a way to engineer improved hard nitride coatings. The essence of this thesis is that by adding a third metal to a ternary nitride material system, for example one of the most frequently used Ti-Al-N, it is possible to tune and engineer the thermal stability of the cubic structure and the coherency strain which in turn affects the hardness and the oxidation resistance. The key point is that new intermediate phases in the decomposition process are generated so that the eventual detrimental phases are suppressed and delayed. More specifically, when Cr is added to the Ti-Al-N material system the coatings exhibit an age hardening process up to 1000 ºC caused by spinodal decomposition into coherent TiCr- and AlCr-rich cubic Ti-Cr-Al-N domains. This means that the unstable cubic Ti-Cr-Al-N phase decomposes via yet another unstable cubic Cr-Al-N phase before the detrimental hexagonal transformation of AlN takes place. The hardness is therefore retained up to a higher temperature compared to Ti-Al-N coatings.
By utilizing multicomponent alloying through addition of Ti to Cr-Al-N coatings the hardness is retained after annealing up to 1100 ºC. This is a dramatic improvement compared to Cr-Al-N coatings. Here the Ti addition promotes the competitive spinodal decomposition into TiCr- and Al-enriched domains suppressing the detrimental hexagonal AlN formation.
To investigate the effect of multicomponent alloying for other material systems with different mixing free energies and atomic sizes, Zr-containing, Zr-Cr-Al-N and Zr-Ti-Al-N, quaternary nitride coatings have also been deposited. For high Al- and high Zr-containing coatings the cubic solid solution structure is disrupted into a mix of nano-crystalline hexagonal and cubic phases with significantly lower hardness. The results show that the structure and hardness of these coatings are sensitive to the composition and in order to optimize the hardness and thermal stability the composition has to be fine-tuned. Altogether it is shown that through multicomponent alloying and through the control of the coherency strain it is possible to enhance the hardness and the oxidation resistance compared to the ternary system which may lead to new improved functional hard coatings.
The performance of modern hard coating materials puts high demands on properties such as hardness, thermal stability and oxidation resistance. These properties not only depend on the chemical composition, but also on the structure of the material on a nanoscale. This kind of nanostructuring will change during use and can be both beneficial and detrimental as materials grown under non-equilibrium conditions transforms under heat treatment or pressure into other structures with significantly different properties. This thesis aims to reveal the physics behind the processes of phase stability and transformations and how this can be utilized to improve on the properties of this class of alloys. This has been achieved through the application of various methods of first-principles calculations and analysis of the results on the basis of thermodynamics and electronic structure theory.
Within multicomponent transition metal aluminum nitride alloys (TMAlN) a number of studies have been carried out and presented here on ways of improving high temperature stability and hardness. Most (TMAl)N and TMN prefer a cubic B1 structure while AlN is stable in a hexagonal B4 phase, but for the purposes of hard coatings the metastable cubic B1 AlN phase, isostructural with the TMN phase is desired. It will be shown how the introduction of additional alloying components, such as Cr, into (TiAl)N changes the thermodynamic stability of phases so that new intermediary and metastable phases are formed during decomposition. In the case of such a (CrAl)N phase it is shown to have greater thermodynamic stability in the cubic phase than the pure AlN, resulting in improved high temperature hardness. Also, the importance of treating not just the binodal decomposition through the formation energy relative to end products but also the impact of spinodal decomposition from its second derivative due to the topology of formation energy surfaces is emphasized in the thesis. The impact of pressure on the AlN phase has also been studied through the calculation of a P-T diagram of AlN as part of a (TiAl)N alloy.
During the study of chemical alloying of TM components into AlN the alloying of low concentrations of these TM were treated in great detail. What is generally referred to as the AlN phase in decomposition is not entirely pure and can be expected to contain traces of any alloying components, such as Ti and Cr or whatever other metals may be present. Low concentration alloying of Cr, on the order of 5-10% is also shown to be stable with regard to isostructural decomposition. Detailed analysis of the effect of Ti and Cr impurities in AlN has been carried out along with a systematic search of AlN alloyed with small amounts of other TM components. The impact of these impurities on the electronic structure and thermodynamic properties is analyzed and the general trends will be explained through the occupation of impurity states by d-like electrons.
Theoretical treatment of such impurities is not straightforward however. AlN is an s-p semiconductor with a wide band gap while TM impurities generate states of a d-like nature situated inside the band gap. Such localized impurity states are expected to give rise to magnetic effects due to spin dependent exchange, in addition strong correlation effects might have to be taken into account. For that reason the use of hybrid functionals with orbital corrections according to the mHSE+Vw scheme, developed specifically for this class of materials, has been used and shown to influence the results during calculation of impurities of Ti and Cr.
In nanocomposite multilayered structures, composed of very thin layers of one material sandwiched between slabs of another, such as layers of SiN between TiN or ZrN, the material properties are greatly affected by the interfaces. In addition to the thermodynamic effects and lattice strains of the interfaces one also has to consider the atomic vibrational motion in the interface structure. Hence, dynamical stability of these thin multilayers is of great importance. As part of this thesis, results on the thermodynamic and dynamical stability of both TiN-SiN layers and ZrN-SiN will be presented. It will be shown that due to considerable dynamical instability in the interface structure of monolayered B1 SiN sandwiched between isostructural layers of B1 ZrN along (111) interfaces this structure cannot be expected to grow, instead preferring the stable (001) direction of growth.


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Hello Ladies!
Today I have a vibrant polish for you, Ulraviolet By Pop Beauty's Nail Glam. I came across this beauty in an Ulta in Virginia Beach, where I will be living shortly! :p
This is my very first polish from Pop Beauty and I really think the name Ultraviolet really describes it perfectly! It's a bright violet creme that really pops out against my skintone! I really enjoyed the formula, and two were needed. I was VERY happy with this polish! :)
Isn't it pretty? :D I got Ultraviolet and an Ulta, but Pop Beauty's entire line can be purchased can be purchased at www.popbeauty.co.uk for $9-$10/bottle
Essie all in one base coat/ Sally Hansen Insta-Dri topcoat (I needed a break from Seche Vite)


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That's it, I'm calling it early: this is officially the "summer of surveillance." Especially with the latest news that due to this surveillance, not one, but two, separate companies announced they were shutting down their encrypted email services (including the one that Edward Snowden was using) this week.
"If you knew what I know about email, you might not use it either," said the owner of one of those companies, Lavabit.
This statement, paradoxically, both misses the point and hints at the right course of action.
Because there are two separate – yet often entangled – ideologies in our discourse about the surveillance state: The first is the individualistic conception of cyber-hygiene: how *you *should behave to secure your own communications, protect your *own *data, and avoid your own tracking. The second is the notion of tech-centric solutionism (a term popularized by Evgeny Morozov): what tech hack, device, or app can I turn to for a quick fix to my privacy troubles?
The problem is that focusing on one or both of these approaches distracts from the much-needed political reform and societal pushback necessary to dig up a surveillance state at its root.
To be sure, personal protections are important. There are some easy plug-ins and simple behavioral changes people can make. And there's no shortage of articles and how-to guides tips for securing privacy, with headlines promising "Five ways to stop the NSA from spying on you."__ __Through means such as end-to-end encryption, software for anonymized web surfing, and removing device's batteries, why, you too, can enjoy secure communications. But if we really want to attempt to thwart the NSA's spying, well, you'll need to brush up on your computer science skills and take a deep dive into cryptographic techniques.
Here's the thing, though: We shouldn't resolve ourselves to a life where cyber-hygiene and an obsession with technological solutions fools us into thinking we've somehow preserved our privacy.
This might be sufficient if, say, we're trying to prevent a boss or partner from snooping. But it's always going to be a losing battle when going against a panoptic titan whose methods are wide-reaching, constantly evolving, and classified. Just look at the fates of Lavabit and Silent Circle, the two email services that shuttered last week. Despite no subpoenas, warrants, security letters, "or anything else by any government", Silent Circle admitted "we see the writing on the wall."
It's a telling sign when one company is bullied – and the other preemptively so – into going against the prevailing instinct of developing yet another technological fix that provides the desired protections. (It's also a telling sign that Obama explicitly endorses solutionism. He said in his speech Friday that people can turn to tech if they don't like government snooping: "I mean, there may be some technological fixes that provide another layer of assurance.")
The fundamental belief in technology's ability to "fix" everything ignores the fact that not everything needs to be fixed in the first place. And it gives birth to questions such as what if Trayvon Martin wore Google Glass? Sure, technology could help – but such questions (and answers!) miss the larger social and cultural context that needs to be addressed here.
In fact, taking the tech-centric route can lead to even more severe, unintended consequences. There's a feedback loop between solutionist tendencies and the growth of a surveillance state: The rapid spread and use of technologies ironically laid the very foundation for it to engulf more and more aspects of our lives. Governments around the world must be saying a prayer of thanks because most of us willingly carry, at all times, a location tracker, listening bug, camera, internet hunter-gatherer, and more in the form of a smartphone.
Except for the most cybersecurity-savvy among us (and even then not if services like Lavabit and Silent Circle continue to wane), trying to outsmart and outrun the government's data-hungry tendrils will only leave people ensnared. This is especially true when it comes to those who do not have the privilege – knowledge, ability, or wealth – to protect their privacy.
Being a "techie" often blinds us to the plight of the majority – who, for one reason or another, don't know they're targets for tracking or simply can't avoid being one. For many, the actions necessary to set up encryption or even abandon certain services are not feasible. Privacy should not become a luxury for an elite tech-savvy few; it matters far too much. Yet without structural reform those who lack cyber-privilege are often left exposed and tracked.
And even if we do take the steps to have good data practices, we're likely to run up against a precarious catch-22 where many common techniques to protect privacy can be met with legal recourse – as security expert Ashkan Soltani pointed out here in WIRED. Just using encryption can land you on NSA's list of suspicious people.
Lest we forget, these power dynamics aren't distributed evenly, either. Those of under-represented class, gender, race, and other minorities – who by birth or circumstance don't have the benefit of a social network of influencers – are often the first to fall.
The Snowden leaks have led to renewed, even frantic, interest in finding the best ways to protect privacy and resist the government's blanket monitoring and collecting of our data. A recent Pew Research poll shows, for the first time, that more people are concerned about the status of their civil liberties than about threats from terrorism.
Concern. It's a great start, but preserving democratic freedoms and fighting the government's spy-machine will mean focusing and turning concern into actionable change. It will require "coordinated dissent" from individuals, advocacy groups, and, yes, technology companies. Smart people like Ron Wyden (D-Oregon) warn that our inaction opens the door for such surveillance to become an irreversible and regrettable part of our society, but the hard truth is that citizens need to muster incredible will to demand or enact sorely needed privacy protections.
But the task of defending privacy from surveillance shouldn't fall to a tech-savvy or solutionist few. And even then, as Michael Phillips pointed out in The New Yorker, the few dissenters "are painted as a rogue's gallery of hackers, leakers, spies, and traitors."
The task of defending privacy from surveillance should be taken up by all citizens, together. As Mark Hagerott and Daniel Sarewitz argued in Slate, "[O]ne of society's most powerful narratives of democratic struggle – the myth of the individual who rebels against social and political conformity – has been rendered implausible by the development of pervasive security technology." It's time to change that narrative so that the notion of a "democratic" struggle in our time isn't always equated with a solely technological one.
Editor: Sonal Chokshi @smc90


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Combination Chemotherapy With or Without Bone Marrow or Stem Cell Transplantation in Treating Men With Untreated Germ Cell Tumors
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
|ClinicalTrials.gov Identifier: NCT00002596
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : June 26, 2013
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not known whether combining chemotherapy with bone marrow or peripheral stem cell transplantation is more effective than combination chemotherapy alone in treating men with germ cell tumors.
PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without bone marrow or peripheral stem cell transplantation in treating men with previously untreated germ cell tumors.
|Condition or disease
|Childhood Germ Cell Tumor Extragonadal Germ Cell Tumor Testicular Germ Cell Tumor
|Biological: bleomycin sulfate Biological: filgrastim Drug: carboplatin Drug: cisplatin Drug: cyclophosphamide Drug: etoposide Procedure: autologous bone marrow transplantation Procedure: bone marrow ablation with stem cell support Procedure: conventional surgery Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy
|Phase 3
- Compare the efficacy of bleomycin, etoposide, and cisplatin (BEP) with or without high-dose carboplatin, etoposide, and cyclophosphamide plus autologous bone marrow or peripheral blood stem cell transplantation in male patients with poor- or intermediate-risk germ cell tumors.
- Compare the toxicity of these regimens in these patients.
- Compare prospectively the prognosis in terms of the rate of decline of the serum tumor markers, human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP), in patients treated with these regimens.
- Correlate hCG and AFP with complete response and survival in patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center and risk status (poor vs intermediate). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive bleomycin IV on days 1, 8, and 15 and etoposide (VP-16) IV over 30-60 minutes and cisplatin (CDDP) IV over 30-60 minutes on days 1-5 (BEP). Filgrastim (G-CSF) is administered subcutaneously (SC) on days 7-16 or until blood counts recover. Treatment continues every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. G-CSF is discontinued 24 hours before initiating subsequent courses of chemotherapy, and withheld on days of bleomycin administration.
- Arm II: Patients receive 2 courses of BEP and G-CSF as in arm I. Patients who have no marrow involvement with tumor undergo harvest of autologous bone marrow before the first or second course of BEP. Patients who have bone marrow involvement with tumor undergo harvest of G-CSF-mobilized autologous peripheral blood stem cells (PBSC) on days 17-21 of the first and/or second courses of BEP. When blood counts recover, patients receive high-dose intensification comprising carboplatin IV over 1 hour, VP-16 IV over 30-60 minutes, and cyclophosphamide IV over 1 hour on days -5 to -3. Autologous bone marrow or PBSC are reinfused over 15-20 minutes on day 0. G-CSF is administered SC beginning 24 hours after transplantation and continuing until blood counts recover. Beginning 1-3 weeks after hospital discharge for the first transplantation and after recovery from any toxic effects, patients with a Karnofsky performance status of 70-100% receive a second course of high-dose intensification plus a second bone marrow or PBSC transplantation in the absence of disease progression or unacceptable toxicity.
Patients on both arms with brain metastases at presentation undergo radiotherapy and/or surgery concurrently with BEP, if medically indicated.
Patients with normal alpha fetoprotein (AFP) and human chorionic gonadotropin (hCG) tumor marker levels after completion of treatment on arm I or II undergo surgical resection of all residual masses. Patients who have no residual malignant tumor or undergo complete resection of only a mature teratoma receive no further therapy. Patients on arm I who undergo complete resection of residual malignant tumor receive 2 additional courses of VP-16 and CDDP without bleomycin. Patients on arm II who undergo complete resection of residual malignant tumor receive no additional chemotherapy. Patients with an unresectable residual malignant tumor receive additional therapy at the discretion of the treating physician. Patients with residual tumor marker (AFP and hCG) positivity after treatment on arm I or II undergo resection of residual masses if tumor marker values fall to normal by marker half-life.
PROJECTED ACCRUAL: A total of 270 patients (135 per treatment arm) will be accrued for this study within 4.4 years.
|Study Type :
|Interventional (Clinical Trial)
|Estimated Enrollment :
|270 participants
|Primary Purpose:
|Official Title:
|Study Start Date :
|September 1994
|Actual Study Completion Date :
|July 2006
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:
|12 Years and older (Child, Adult, Older Adult)
|Sexes Eligible for Study:
|Accepts Healthy Volunteers:
Histologically proven poor-risk, nonseminoma germ cell tumor
Must meet 1 of the following 3 conditions:
Testis or retroperitoneal primary site without visceral metastasis but with any of the following tumor marker values:
- Lactic dehydrogenase (LDH) greater than 10 times upper limit of normal (ULN)
- Human chorionic gonadotropin (hCG) greater than 50,000 IU/L
- Alpha-fetoprotein (AFP) greater than 10,000 ng/mL
Testis or retroperitoneal primary site with 1 or more nonpulmonary visceral metastases (regardless of tumor marker values), including the following:
- Bone
- Brain
- Liver
- Other nonpulmonary viscera (e.g., skin, spleen)
- Mediastinal primary site, regardless of presence/absence of visceral metastasis or tumor marker values OR
Histologically proven intermediate-risk, nonseminoma germ cell tumor
Testis or retroperitoneal primary site with no visceral metastasis (except lung), and with any of the following tumor marker values:
- LDH 3-10 times ULN
- hCG 5,000-50,000 IU/L
- AFP 1,000-10,000 ng/mL OR
Histologically proven intermediate-risk, seminoma germ cell tumor with 1 or more nonpulmonary visceral metastases (regardless of tumor marker values or primary site), including the following:
- Bone
- Brain
- Liver
- Other nonpulmonary visceral metastasis (e.g., skin, spleen)
- Histologic confirmation may be delayed, at the discretion of the protocol chairman, until after initiation of study therapy for patients with a testicular mass and elevated AFP or hCG if medical circumstances warrant immediate treatment
- Measurable or evaluable disease
- Concurrent registration on protocol MSKCC-89076 (SWOG-9345) for tumor biology studies required
- 12 and over
- Male
Performance status:
- Not specified
Life expectancy:
- Not specified
- WBC at least 3,000/mm^3
- Platelet count at least 100,000/mm^3
- See Disease Characteristics
- Creatinine no greater than ULN* OR
- Creatinine clearance greater than 50 mL/min* NOTE: * Abnormal levels due to ureteral obstruction by tumor allowed at the discretion of the protocol chairman
- HIV negative
- No other concurrent malignancy except nonmelanomatous skin cancer
Biologic therapy:
- Not specified
- No prior chemotherapy
- No other concurrent chemotherapy
Endocrine therapy:
- Not specified
- At least 30 days since prior radiotherapy except for brain metastases or documented disease progression
- Recovered from the toxic effects of any prior radiotherapy
- Recovered from the effects of any recent surgery
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00002596
Show 153 Study Locations
|Study Chair:
|Robert J. Motzer, MD
|Memorial Sloan Kettering Cancer Center
|Study Chair:
|Patrick J. Loehrer, MD
|Indiana University Melvin and Bren Simon Cancer Center
|Study Chair:
|Kim A. Margolin, MD
|City of Hope Comprehensive Cancer Center
|Study Chair:
|Eric J. Small, MD
|University of California, San Francisco
Publications of Results:
|ClinicalTrials.gov Identifier:
|NCT00002596 History of Changes
|Other Study ID Numbers:
CDR0000063820 ( Registry Identifier: PDQ (Physician Data Query) )
|First Posted:
|January 27, 2003 Key Record Dates
|Last Update Posted:
|June 26, 2013
|Last Verified:
|October 2003
stage II malignant testicular germ cell tumor
stage III malignant testicular germ cell tumor
testicular seminoma
testicular embryonal carcinoma
testicular choriocarcinoma
testicular teratoma
testicular yolk sac tumor
testicular embryonal carcinoma and teratoma
testicular embryonal carcinoma and teratoma with seminoma
testicular embryonal carcinoma and yolk sac tumor
testicular embryonal carcinoma and yolk sac tumor with seminoma
testicular embryonal carcinoma and seminoma
testicular yolk sac tumor and teratoma
testicular yolk sac tumor and teratoma with seminoma
testicular choriocarcinoma and yolk sac tumor
testicular choriocarcinoma and embryonal carcinoma
testicular choriocarcinoma and teratoma
testicular choriocarcinoma and seminoma
extragonadal germ cell tumor
childhood teratoma
childhood malignant testicular germ cell tumor
childhood extragonadal germ cell tumor
Neoplasms, Germ Cell and Embryonal
Testicular Neoplasms
Neoplasms by Histologic Type
Endocrine Gland Neoplasms
Neoplasms by Site
Genital Neoplasms, Male
Urogenital Neoplasms
Genital Diseases, Male
Endocrine System Diseases
Testicular Diseases
Gonadal Disorders
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antibiotics, Antineoplastic