text:
Manchester United summer signing Alexander Buttner has been describing the force of the Sir Alex Ferguson hairdryer treatment.
The 23-year-old moved to Old Trafford from Eredivisie club Vitesse Arnhem in a move that was met with some surprised at the time, but Buttner made a terrific debut to his United career by scoring in a 4-0 win over Wigan Athletic.
He was speaking to Dutch magazine Voetbal International when he gave some surprisingly open quotes about Ferguson's famed blasts of anger at players not carrying out his orders accordingly.
According to Buttner, the Scot is indiscriminate when it comes to handing out dressing downs to his stars, with reputation meaning nothing if his instructions aren't being carried out to the letter.
The young left-back also claims that the level of fury spouted by the Red Devils boss was unheard of in his native country.
"I've never seen anyone so angry as he can be. It is something that would be unprecedented in the Netherlands, I swear," he said, as translated by Sport Witness.
"And what is so special is against whom he rages, everybody without distinction. It matters to him not a jot whether it's Rooney, Scholes or Nani. If he does not like it, he flips it full on.
"Especially if you're in the game, doing something wrong because you are tired. There he really hates it."
It is unusual for Manchester United players to give such detailed accounts of Ferguson's behaviour in the dressing room and it would not be unreasonable for someone to suggest he may frown upon such an interview.
Major Old Trafford stars have fallen foul of Ferguson's anger, such as David Beckham or Jaap Stam, and learned that his wroth can lead to a quick exit.


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I saw that episode also!! The other Teams member did not like Mirna I was so suprised. Charla was her cute self.As for the final 3 I am not suprised. They all raced the game well. Glad to see 2 all female teams in the final 3 but I will be rooting for Danielle & Eric all the way.
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NASHVILLE (March 7, 2009) - For most of the 2008-09 season, much had been written and said about ETSU's "Big Three" of senior guard Courtney Pigram (Memphis), senior forward Kevin Tiggs (Flint, Mich.) and junior guard Mike Smith (Vandalia, Mo.).
But on Saturday in the finals of the Atlantic Sun Conference Championships at Allen Arena, it was the Buccaneers "Big 10" that truly made the difference. While Smith posted a double-double with 22 points and 12 rebounds to go with 21 points from Tiggs, the ETSU bench combined to provide 22 points and 12 rebounds in an absolutely dominating 85-68 win over Jacksonville.
With the win, ETSU (23-10) secures a bid to the 2009 NCAA Tournament, marking the eighth time in school history that the Buccaneers have made their way to March Madness. The Bucs are the 16th different team to win the A-Sun title and first new winner since Belmont took the championship in 2006.
"I'm just extremely happy for all 10 guys on our team because this just doesn't happen every year. It's something really special," said ETSU head coach Murry Bartow, who has now guided the Bucs to the NCAAs twice in his six seasons at the helm. "Mike Smith, Kevin Tiggs and Courtney Pigram were fantastic as usual, but the difference today was the entire team and the efforts we got from our bench."
Dominance in the paint and on the glass highlighted the first half for ETSU, along with a quick scoring start for Tiggs. The Bucs held a 22-17 advantage on the boards, outscoring the Dolphins 24-8 in the paint and enjoying a 14-0 edge in second chance points. Meanwhile, Tiggs scored 13 of ETSU's first 23 points, staking the Bucs to a 23-11 lead with just over 11 minutes left in the half.
From there, Tiggs got in foul trouble after picking up his third violation of the game with 6:12 left before the intermission. The score was 32-18 at the time, and despite Tiggs' departure ETSU still pushed the lead out to 43-28 at the break.
In the first half, Tiggs was joined by Smith with 13 points to lead the way, but despite the fact senior guard Courtney Pigram (Memphis) scored just 1 point, it was the supporting cast of freshman forward Isiah Brown (Miami, Fla.), sophomore forward Tommy Hubbard (Boston), sophomore guard Micah Williams (Manchester) and senior forward Greg Hamlin (Flint, Mich.) that combined for 16 points and 12 rebounds off the bench.
The second half opened with another ETSU run, as a 3-pointer by Pigram to open the half ignited an 11-2 run for the Buccaneers and made the score 54-30 with 16:19 left in the game. Jacksonville tried to answer with a 4-0 spurt of its own, but ultimately ETSU would lead by 30 at 69-39 with 9:05 left in the game.
Jacksonville ultimately rallied to outscore the Bucs 29-16 over the final nine minutes, but at that point it was simply too late for the Dolphins to recover.
For the game, ETSU shot 47 percent from the floor and outrebounded the Dolphins 40-34, forcing 15 turnovers on seven steals. Meanwhile, the Bucs' defense held JU to 39 percent shooting and just 68 points on the night.
Along with Smith and Tiggs, Williams finished with a career high 16 points, and Hubbard finished with six points and seven rebounds, while Brown pitched in nine points and five rebounds. Pigram, Smith and Tiggs made all-tournament team, with Tiggs earning MVP honors.
For JU, Ben Smith scored a game high 29, while Ayron Hardy and Evan Jefferson pitched in 11 each.
The Bucs will now await word on who they will play in the NCAA Tournament, as Selection Sunday is scheduled for next Sunday, March 15.


text: Some of you long time B/D fans know that I originally started the magazine in 1996 while growing up in the suburbs of Northern Virginia. Although there is a lot of talented artists in the region I wouldn't say that the local community is very supportive of underground magazines, the arts, or creativity in general. Most people are wrapped up in the politics of D.C. and could care less about art. So it was a a great surprise to get a call from Northern Virginia Community College (NOVA) asking me to come to my hometown and give a talk about B/D. Needless to say I jumped at the chance.I've always wanted to go back to where it all started in hopes of inspiring the next wave of Viriginia artists to give the middle finger to mediocrity and make things happen. Not only are the fine folks at NOVA flying out yours truly but they have an entire week of events including a public mural program, workshops on stenciling and wheatpasting, and a batch of other talks to get your creative juices flowing. This event is completely free and open to the public. If you're in the Washington D.C., Virginia, Maryland area come by and say hello. It should be a good time!


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Willow draping stories like waterfalls through the air
Chestnuts throwing daggers
Dripping perfume sap and resin
Broken limbs and torn ligaments
Ripped shoulders across the forest
Open, wounded, left
Littered medicine on neighbors lawns
Left for mulch and compost
Never taken for flu, tea, fire, scars
I scoop the drips from the branch
and dot it carefully on my daughter's incision
she says "thank you"
and I say "thank you"
to all the trees with giant scars
and take home the abandon medicine
for my chest.
Longing to create more meaningful nature practices? Called into the Forest to learn the Medicine of the Tree Nation?
Struggling to put into practice all those notions of Self-Care? Need real tools to help you put YOU first? Longing for a woman's voice to remind you how beautiful and powerful you are?


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Take a look at some of our specialties on the left.
No two businesses are alike; the more specialized your industry, the more specialized your digital development needs. Our passion is to work closely with our clients to gain a deep understanding of their operation; this has given us significant experience in several specific industries.
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text:
Athlete of the Week
Kevin Kordik
Johnsburg, Senior
The Skyhawks third baseman-pitcher had a huge hand in their two victories as the Skyhawks were 2-2 for the week.
In Tuesday's 8-1 victory over Cary-Grove, Kordik was 2 for 4 with a grand slam and five RBIs. The grand slam came late to seal the outcome for the Skyhawks.
On Saturday, Kordik made one of his best starts of the season in a 7-1 win against Antioch. Kordik struck out 10, allowed one hit and issued no walks during that game.
Kordik also was 3 for 4 with an RBI in Wednesday's 4-2 loss to Harvard and was 1 for 2 in Thursday's 8-1 loss to Huntley.
Ideal for closing: Harvard coach Donnie Nolen felt the last two seasons that Matt Piechocki has been his No. 1 pitcher, but this year he is using Piechocki in a different role, as closer.
Nolen feels his starting pitching is strong with junior Peyton Schneider and sophomores Johnny Peterson, Reiss Bielski and Logan Streit. That allows Piechocki to man the right field position until late in a game when he often closes.
"His bat is pretty good, so I keep him in the lineup," Nolen said. "He can throw every day and he enjoys it. I said, 'OK, I'll put that to use.' "
Nolen said the main thing with Piechocki is he will come in throwing strikes.
"I had him in Little League when he moved here at 11 and he would always throw strikes," Nolen said. "He seems perfect for closer. It really helps the ballclub a lot."
Piechocki has a 1.40 ERA and an 0-1 record with one save.
Hampshire to honor teachers: Hampshire's home game on Wednesday, May 7 will hold a special importance as each player will ask a teacher to wear his jersey and the teachers will be recognized before the game. It is a program Whip-Purs coach John Sarna started as an assistant at Jacobs and brought to Hampshire.
The Whips will do it as part of Teacher Appreciation Week, which is observed around the nation from May 5-9.
"Few other professionals touch as many people as teachers do," Sarna said. "The Teacher Appreciation Game is a good time to learn about the contributions educators make to our community every day. We recognize we are role models. That brings satisfaction. It also brings responsibility. We strive to take it to the next step."
The event will be sponsored by Buffalo Wild Wings and Hoosier Bat Company, which will have a personalized, laser-engraved wood bat for every teacher.
This Week's Top Games
Grayslake Central vs. Johnsburg
4:30 p.m., Tuesday and Thursday
• Grayslake Central won the FVC Fox Division in 2010, 2011 and 2012 and wants to get back to the top. If Johnsburg wants to contend, it needs to prove worthy right away in division games. They play at Johnsburg on Tuesday and at Grayslake on Thursday.
Huntley vs. Jacobs
4:30 p.m., Tuesday and Thursday
• Huntley is a defending co-champion in the FVC Valley and Jacobs looks like a serious contender. The two teams play at Jacobs on Tuesday and at Huntley on Thursday.
Baseball insider: Johnsburg's Kordik player of week
Athlete of the Week


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Joined: 20 Jan 2013
Posts: 8
Posted: Mon 21 Jan 2013, 21:03
Post subject:
Puppy livecd doesn't boot (black screen)
I'm hoping someone can help me out here. Puppy works quite well on my laptop (except for some reason I can't get the movie player to work, but I'll get that sorted another time. . . =)) but on my netbook (Lenovo Ideapad S110), it seems like I can't get Puppy to work at all.
When I boot it up with the cd, all the usual messages show, but when it comes to the part where the desktop is supposed to appear, all I get is a black screen. I've tried Slacko and Precise, the latest versions.
Should I try using an older version? If so, what would be the best?
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Posts: 5056
Location: Everybody knows this is nowhere...
Posted: Mon 21 Jan 2013, 22:07
Post subject:
First of all -- welcome, as we say, to the Kennels! We hope you'll hang around.
At the black screen, hold down CTRL and ALT simultaneously, then press <-BKSP once.
This should get you to a prompt:
Make the prompt look like this:
# xorgwizard
then press [ENTER]. You should (if these really new Pups are like the rest of 'em) see a DOS-like screen that lets you manually configure things. (You will not be using a mouse here! Arrow keys and [ENTER] are your new best friends.) Try Xvesa first (the 'vesa' button on the first screen). Having completed the wizard, you'll find yourself at the:
This time, make it look like this:
# xwin
and press [ENTER].
If the colors are all off, or it's full of fuzz, or it's something that twiddling resolution won't fix -- CTRL+ALT+BKSP, and reenter the wizard. This time you have a decision to make.
If your computer uses discrete graphics, and you know what they are (eg ATi or nVIDIA) then pick the middle ("Choose") button and select the relevant driver. IIRC there are two for nVIDIA and the one that has always been full of bugs is noted as such. There are three or four for ATi. Try each one in turn, till you find the one that works -- I don't know for your laptop which it is (hey, at least I'm honest about it!).
If your laptop does not have (and never did) a sticker on it for ATi or nVIDIA, then you probably have Intel graphics. Choose the leftmost button (something like "Xorg" or "Continue") and follow the prompts, with one exception -- DO NOT CLICK "TEST"! The "test" button has always been wonky with me -- sometimes it will do the right thing, more often it just messes things up. Best, then, to avoid it.
Hope that helps, and if it doesn't, we're here to answer more questions
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Joined: 20 Jan 2013
Posts: 8
Posted: Tue 22 Jan 2013, 09:00
Post subject:
Thanks for replying!
Unfortunately, nothing happened when tried to start the wizard. Also kinda scary, there was an ominous beeping sound when I used the ctrl and alt on the right U^_^
I suppose I'll have to check out the older versions? or whatever is gonna work for a generic intel card
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Joined: 29 Jan 2006
Posts: 4353
Location: Sydney Australia
Posted: Tue 22 Jan 2013, 09:20
Post subject:
Try >>> DpupExprimo5X327
23-Feb-2012 15:36 150M
Should be a goer....chris.
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Joined: 20 Jan 2013
Posts: 8
Posted: Wed 23 Jan 2013, 20:56
Post subject:
thanks! I've been checking out the other puplets but I've never come across this one.
It seems to be working, and I was psyched that it came with Enlightenment, which is my favorite WM. Unfortunately, when I switched to it xorg crashed after a few seconds. . . gonna try to configure it later, but so far using vesa makes it crash as well
Oh well.
So based on the name, I'm assuming this is compatible with Debian Squeeze?
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Joined: 05 Sep 2011
Posts: 2420
Location: Germany
Posted: Wed 23 Jan 2013, 21:17
Post subject:
If it (any puppy) doesn't boot into X desktop, try boot option
LazY Puppy
RSH's DNA
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Posts: 5056
Location: Everybody knows this is nowhere...
Posted: Wed 23 Jan 2013, 21:37
Post subject:
...or, at the "hashtag" prompt (
), type
and press [ENTER]. That *should* get you to a good old-fashioned text-mode video setup wizard.
At the end of xorgwizard, you'll find yourself at the hashtag. Type
and press [ENTER] and you should be up. If it dies again, go back to xorgwizard. (If it dies but doesn't put you back to the hashtag, hold down CTRL+ALT and press BKSP. That
get you back!)
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Joined: 20 Jan 2013
Posts: 8
Posted: Thu 24 Jan 2013, 18:18
Post subject:
Configuring xorg was easy. . . getting X to STAY up was the problem =))) I click on one thing in E17 and down it goes. I tried a few settings but nothing comes of it
(( Looks like I'm stuck with JWM or other minimalistic WMs U^_^ Macpup isn't really my style, even if it does use E17.
Haha, I guess it's my netbook . . all the distributions I've wanted to run on it (Puppy, Tiny Core) always had trouble with the graphics
Oh well, Puppy without the WM that I want is better than no Puppy at all
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Joined: 22 Nov 2010
Posts: 5056
Location: Everybody knows this is nowhere...
Posted: Thu 24 Jan 2013, 21:05
Post subject:
Did some research for your problem. What you have sounded to me like a driver incompatibility, and I was right.
The problem is (basically) primarily one of corporate politics combined with Puppy tending to orient itself for somewhat older setups. Your computer is (in the Puppy view of things) rather new, and so Puppy doesn't like your graphics. Plus...
Intel (from what I understand) is not willing to release anything other than "development versions" (beta releases) of their graphics drivers for Linux use. I came across a reference on Arch Linux to a community driver via XFree86 (the organization that develops the X Window System) but there's going to be some work involved in making that functional for you, and I'm not an expert enough at it, to tell you how to do it.
If you want to go that route, please PM our resident drivers guru,
. I would, after referencing this thread, tell him that you're trying to get graphics drivers working for MacPup (make sure he knows which version), with an Intel GMA3150 driver setup. Tell him that I think
this driver
will work for you, if he can help you make it work.
On the other hand, it occurs to me that you could see if XorgWizard contains the "intel" driver -- try that first, then if it fails, talk to tempestuous at that point -- at least, that's my suggestion.
I wish you plenty of luck in either case.
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Joined: 20 Jan 2013
Posts: 8
Posted: Sat 26 Jan 2013, 09:31
Post subject:
Thank you! I really appreciate you clearing this up for me
Seems like my netbook just isn't as Linux-friendly as I'd've liked it to be. This isn't the only distribution that has had trouble with it, so I guess I know what to stay away from next time I go shopping. Haha, I was beginning to think that the main problem existed between the keyboard and chair. . .
Anyway, I really appreciate you and everyone else's help. Seems like Puppy just isn't for my netbook. . . well, for now. I don't really have enough time to be working on getting it to work, as I use to for school every day.
Oh well, it's not all bad. Puppy works great on my bigger laptop anyway XD
Also, for the record. . . I was able to use the Lucid Puppy live cd so I rejoiced for a second and then--no wifi
Alas. And apparently getting it up would involve compiling a driver, which I am so not ready for
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Joined: 11 Oct 2009
Posts: 11564
Location: S.C. USA
Posted: Sat 26 Jan 2013, 12:57
Post subject:
There are additional wifi drivers for Lucid Puppy here:
The things they do not tell you, are usually the clue to solving the problem.
When I was a kid I wanted to be older.... This is not what I expected
(any iso installer)
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Joined: 20 Jan 2006
Posts: 6750
Location: hobart
Posted: Mon 28 Jan 2013, 06:16
Post subject:
if you have the dreaded linux-unfriendly poulsbo graphics you may want to check the slacko-5.4-pae & upup-precise-3.7.2 threads.
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Posts: 8
Posted: Mon 28 Jan 2013, 22:39
Post subject:
Fortunately, I don't think I do. . . just a generic intel card (which is keeping me from running Slacko)
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Joined: 20 Jan 2013
Posts: 8
Posted: Mon 28 Jan 2013, 22:42
Post subject:
bigpup wrote:
There are additional wifi drivers for Lucid Puppy here:
Ah, unfortunately I can't even follow the first tip--I can't just disable the encryption. I'm not the one paying for the wifi, so I can't mess it. Instructions seem a bit intimidating, but I'll try it if nothing else works. Thanks.
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Joined: 20 Jan 2013
Posts: 8
Posted: Sat 02 Feb 2013, 09:11
Post subject:
cthisbear wrote:
Try >>> DpupExprimo5X327
23-Feb-2012 15:36 150M
Should be a goer....chris.
Seems to work, though not with E17. JWM seems to be working crash-free though, which is enough for me.
I guess this one is built with Debian Squeeze? I don't mind that it's an old version, but I'm hoping it's well-supported? That's what worries me the most about the Puppy derivatives, actually.
I was hoping to stay with one of the main puppy releases (Lucid or Slacko) but beggars can't be choosers. Thanks
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MOLECULAR GENETICS OF MENTAL DISORDERS Release Date: March 6, 1998 RFA: MH-98-010 P.T. National Institute of Mental Health Letter of Intent Receipt Date: April 14, 1998 Application Receipt Date: May 19, 1998 PURPOSE The purpose of this Request for Applications (RFA) is to solicit applications for multidisciplinary, collaborative research projects that employ state-of-the-art diagnostic procedures and analytic methods to (1) collect and clinically characterize a large pedigree sample of adequate statistical power for identifying genomic regions which may harbor loci conferring susceptibility to schizophrenia, bipolar disorder, or early-onset recurrent unipolar depression, and (2) conduct a whole-genome scan to establish the chromosomal localization of such loci. Data and biological materials collected and produced in projects funded under this RFA will augment existing resources distributed by the National Institute of Mental Health (NIMH) for genetic analyses by the wider scientific community. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Molecular Genetics of Mental Disorders, is related to many priority areas. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-512-1800). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign, for-profit and non-profit organizations, public and private organizations such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as principal investigators. The collection of clinically well-characterized samples of sufficient size for linkage analyses and for linkage disequilibrium mapping studies in genetically isolated populations may be facilitated by the establishment of international consortia. Full collaborations between American scientists and scientists at international institutions are encouraged, when scientifically appropriate. In these cases, awards may be made to international institutions or to domestic applications that include international components. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) research project grant (R01) or the collaborative R01 research project grant for clinical studies of mental disorders. The multi-institutional cooperative research project grant (R10) mechanism will no longer be accepted by NIMH, as indicated in a notice in the NIH Guide for Grants and Contracts, Vol 26, No. 40, December 19, 1997 and available on the World Wide Web at https://grants.nih.gov/grants/guide/notice-files/not97-242.html. Further information on the collaborative R01 research project grant may be found in a program announcement entitled, þCollaborative R01s for Clinical Studies of Mental Disordersþ in the December 19, 1997 issue of the NIH Guide on the Web at https://grants.nih.gov/grants/guide/pa-files/PAR-98-017.html. FUNDS AVAILABLE This RFA is a one-time solicitation. It is anticipated that $4.8 million (including direct and indirect costs) will be available for this initiative in Fiscal Year 1998, during which it is anticipated that 10 to 12 awards will be made. Additional funding for new awards will be made available in Fiscal Year 1999. Awards pursuant to this RFA are contingent upon the availability of funds for this purpose. The amount of funding for this initiative may be increased if a large number of highly meritorious applications are received and if funds are available. Only applications that are found to be of the highest scientific merit will be considered for funding and not all of the funding will be spent if there are not enough highly meritorious applications. Funding in future years will be subject to the availability of funds. The total project period for an application submitted in response to this RFA may not exceed four years. Investigators who submit an individual R01 application requesting direct costs of $500,000 or more for any one year, and investigators as a group who submit a collaborative R01 application requesting an overall total direct cost budget of $500,000 or more for any one year, are strongly encouraged to consult with the program staff listed under INQUIRIES. The earliest anticipated award date is September 30, 1998. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of an award also will vary. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. Awards will be administered under PHS grants policy as stated in the PHS Grants Policy Statement. Future unsolicited competing continuation applications will compete will all investigator-initiated applications, and will be reviewed according to the customary peer review procedures. All awards will be issued and managed by NIMH. RESEARCH OBJECTIVES Background Much of current biomedical research is based upon the expectation that understanding the genetic basis of disease will revolutionize diagnosis, treatment, and prevention. Defining and understanding the role of genetic factors will also ultimately allow the non- genetic, environmental contributions to illness to be more clearly identified and understood. While tremendous advances have occurred in mapping and cloning genes for rare diseases that follow predictable Mendelian patterns in families, the discovery of genes that influence susceptibility to more common human conditions like mental disorders has proceeded much more slowly. Considerable research has been conducted to investigate the familial bases of schizophrenia and mood disorders. Data from family, twin and adoption studies spanning six decades have consistently supported the involvement of genetic factors in the familial transmission of these disorders, but conclusive identification and replication of a chromosomal region that harbors a susceptibility locus has not been forthcoming. Several molecular genetic studies produced sizeable lod scores linking bipolar disorder to the X chromosome. However, methodologic criticisms have been raised about many of the earlier studies, and multiple failures to replicate have occurred. In one case additional analyses of the same pedigrees with DNA markers in Xq28 led to a diminution of linkage evidence in this region. Linkage to chromosomal region 11p was found in the Amish, but the lod score was diminished to non-significance by additional analyses in the same pedigrees. Recent studies have collectively implicated a chromosomal region of over 80 Megabases (Mb) that spans most of both arms of chromosome 18. Convincingly replication of linkages to these or other genomic regions has not occurred. An association between trinucleotide repeat expansions and bipolar disorder was reported, but has not been followed by identification of a specific expanded gene. The history of linkage studies in schizophrenia is marked by comparable difficulties. Significant evidence for 5q linkage in several pedigrees was not replicated in other samples, and a combined re-analysis of several data sets excluded a susceptibility locus from this region. Chromosomal regions 6p and 8p have each been implicated twice. However, post-hoc analyses of over 700 families contributed by 14 research groups worldwide failed to find more than suggestive evidence of linkage to either 6p or 8p. Additional studies have failed to convincingly replicate linkages to these or other genomic regions. Weak associations between schizophrenia and different candidate genes have not been convincingly replicated in large samples. An association between trinucleotide repeat expansions and schizophrenia was reported, but has not been followed by identification of a specific expanded gene. In several family studies probands were subdivided according to age-of-onset and/or history of recurrent depression; greatest risk was to relatives of early-onset, recurrent depressive probands. Consequently, depression appears more familial when probands are chosen on the basis of an early-onset recurrent illness. A recent segregation analysis of early-onset recurrent depression yielded some evidence of a major gene effect. Reported associations between unipolar depression and two candidate genes have not been replicated in other samples. No molecular genetic studies have focused exclusively on the early-onset recurrent variant. In summary, the modes of inheritance of schizophrenia and mood disorders are complex and likely involve environmental factors and multiple genes in interaction. It is clear that single major genes do not account for their familial aggregation in most pedigrees. The number of susceptibility loci involved and the recurrence risk ratios conferred by each, the extent of locus heterogeneity, the role of gene-environment interaction, and the degree of epistatic interaction remain unknown. A similar lack of knowledge exists for early onset recurrent depression, which is likely to be the most heritable variant of depressive illness. Molecular genetic studies of schizophrenia and bipolar disorder have implicated several chromosomal regions that may harbor susceptibility loci, but the magnitude of the statistical evidence and the failure to convincingly replicate demonstrate that these are clearly not confirmed, convincing findings. Inconsistent results may reflect the influence of small relative gene effects, locus heterogeneity, false-positive results, or a lack of power in small samples. Insufficient data exist to strongly implicate a genomic region as containing a susceptibility locus for early onset recurrent depression. New technologies have been developed for rapid high-throughput genotyping, and dense maps of polymorphisms are widely available. Automated methods for the discovery and scoring of simple, bi- allelic polymorphisms (termed single nucleotide polymorphisms, or SNPs) currently being developed will lead to the generation of a dense map of thousands of new markers across the genome and will permit the rapid and efficient cataloging of human DNA sequence variation. These developments will complement the three major analytic methods that have proved successful for the discovery of Mendelian disease genes: localization to a chromosomal region of several Mb by linkage analysis of family data, followed by fine genetic mapping; analysis of haplotypes for linkage disequilibrium mapping; and direct detection of an increased prevalence of a functional variant in affected individuals, through association analysis. Dramatic progress in genetic analytic methods and technologies will facilitate gene discovery in the study of mental disorders. However, it seems clear that ultimate success will require new large-scale data collection efforts to obtain samples of sufficient size that have high power for the detection of susceptibility loci of small relative effect. Such large-scale data collection efforts by a single principal investigator, or by self-selected teams of principal investigators working in collaboration, will permit the application of uniform methods for data acquisition, diagnosis, and comprehensive, state-of-the-art clinical characterization on a scale unprecedented in the molecular genetic studies of these disorders. Whole-genome analyses conducted in such data sets will have tremendous potential for identifying chromosomal regions that harbor susceptibility loci. Such achievements will set the stage for a new era in the genetic analysis of mental disorders, in which research efforts will dramatically shift from initial localization to gene identification. Objective and Scope The molecular and statistical tools that will greatly facilitate gene discovery for complex human diseases like mental disorders are just beginning to emerge. Such tools undoubtedly will require clinically well-characterized samples of adequate statistical power for the detection of genes that exert a small relative effect. Therefore, NIMH seeks the new collection of large samples, in which probands and their relatives are clinically characterized through the application of state-of-the-art diagnostic methods and comprehensive assessments of psychopathology. Data collection may occur within the context of a linkage study in an outbred population, or a linkage disequilibrium mapping study in a genetically isolated population. Application of rapid and highly cost-effective genotyping will permit initial scans to identify chromosomal regions that harbor disease susceptibility genes. It is expected that data and biological materials collected and produced in projects funded under this RFA will augment existing resources distributed by NIMH for genetic analyses by the wider scientific community. Positional cloning, in which a gene is identified and cloned by virtue of its subchromosomal location in the genome rather than by using knowledge of its biochemistry, has become increasingly straightforward but remains a formidable, multi-step task. Genetic mapping of affected families with polymorphic markers spanning the genome permits localization of the putative disease genes to a candidate region, often in the range of 2 to 5 Mb. Such intervals are physically mapped with overlapping DNA clones, which usually serve as substrates to identify genes (transcripts). Subsequently, the genes are examined for large-scale sequence mutations in affected individuals. Cloning susceptibility genes for common, complex diseases like mental disorders, in which there is not a perfect correspondence between phenotype and genotype, presents additional difficulties not encountered when mapping simple Mendelian traits. Given such complexities, the focus of molecular and statistical analyses supported under this RFA will be limited to the goal of initial chromosomal localization. This will represent a significant achievement, and set the stage for future positional cloning efforts. Principal investigators, or self-selected teams of principal investigators, are generally expected to focus their application on schizophrenia, bipolar disorder, or early-onset recurrent unipolar depression. Recruitment efforts may be consolidated, and a commensurate time and cost savings expected, if a principal investigator proposes to collect and analyze data for more than one disorder. In such cases, review and award criteria will consider the feasibility of large-scale data collection and analysis of each disorder. Regardless of the scope of the project, it is expected that applications will include a multidisciplinary team comprised of clinicians, diagnosticians, molecular geneticists, and statistical geneticists. It is expected that the first three years of the project will be focused predominantly on pedigree ascertainment and phenotypic assessment, with genetic analyses being conducted in the final year. Each of the following areas are expected to be comprehensively addressed in the application. 1) Pedigree Structure Applications are solicited for the collection of family data that can be analyzed using the methods that have proved successful for the mapping of Mendelian disease genes. These methods require ascertainment of: (1) extended pedigrees in genetically isolated populations, for linkage disequilibrium mapping studies; or (2) small nuclear or extended pedigrees consisting of affected sibling pairs (ASPs) or of multiple affected individuals, for linkage analyses. Data collection from affected individuals and two parents for family-based association analyses is strongly encouraged, but only when such a configuration occurs within a pedigree containing an ASP or multiple affected individuals. Collection of pedigrees for family-based association analyses in which diagnostic data and biological materials can be collected only from an affected individual and his two parents will not be supported by this RFA. Applicants must adequately justify the proposed sample size targets for a three-year data collection period as being both feasible and sufficient for the chromosomal localization of susceptibility genes for the disorder under investigation, given the proposed analytic method. 2) Structured Diagnostic Criteria The application of standardized and structured diagnostic criteria is essential to the accurate phenotyping of subjects for genetic analyses of mental disorders. While the use of operational diagnostic criteria has undeniably improved the reliability of psychiatric diagnoses, the validity of any such category is indeterminate. Most importantly, it is still unclear which, if any, diagnostic system offers the phenotypic definitions that correlate most highly with underlying genotypes. In this sense, there is no clear indication as to which diagnostic system (e.g., the revised third (DSM-III-R) or fourth (DSM-IV) editions of the American Psychiatric Associationþs Diagnostic and Statistical Manual for Mental Disorders, Research Diagnostic Criteria (RDC), International Classification of Diseases (ICD)) should be employed. On the other hand, efforts to replicate results and combine data across different samples may be hampered if diagnostic criteria for pedigree recruitment are widely variable. Consequently, the definition of þaffectedþ status when defining ASPs or when specifying a minimum number of affected individuals in projects supported under this RFA, for the purpose of pedigree ascertainment, is expected to follow DSM-IV criteria. This will permit pooling of these data with existing NIMH resources and will provide some uniformity, but does not in any way preclude the use of other diagnostic systems and criteria in establishing diagnoses in probands and relatives. In fact, where scientifically appropriate, investigators are encouraged to use the full range of diagnostic definitions under multiple systems when making phenotypic assessments. Given that it is unclear which diagnostic system offers the phenotypic definitions that correlate most highly with underlying genotypes, it is essential that it be possible to establish diagnoses in multiple diagnostic systems. Such a polydiagnostic approach requires recording clinical information accurately and in sufficient detail to allow different definitions of an illness to be applied. The comprehensive phenotypic information collected in projects funded under this RFA (see below) is expected to permit the establishment of diagnoses within a multitude of systems, according to different criteria sets. In addition, such information may form the basis for future approaches to phenotyping after susceptibility genes are discovered. Most importantly, the definition of þaffectedþ for the purpose of ascertainment should be limited exclusively to core phenotypes (schizophrenia, bipolar disorder, or early-onset recurrent unipolar depression), which are diagnosed with greater reliability than broadened illness definitions (so-called þspectrumþ phenotypes). Such a focus is expected to decrease misclassification and diagnostic error while maximizing genetic homogeneity. For example, an applicant proposing to collect 500 ASPs to identify genes that confer susceptibility to schizophrenia will assure that both siblings in each ASP are diagnosed with DSM-IV schizophrenia. Other diagnostic systems, criteria sets, and phenotypes may be used to classify subjects as affected in the analyses conducted; however, each ascertained pedigree will have either multiple affected individuals and/or an ASP in which affected status reflects a DSM-IV diagnosis of a core phenotype. While there is no DSM-IV criterion for þearly onsetþ recurrent depression, the applicant will clearly specify the age-cutoff for onset that was uniformly applied. 3) Comprehensive Phenotypic Assessment Minimization of phenotypic error and imprecision, especially that which contributes to false-positive diagnoses of affected status, requires the careful application of state-of-the-art diagnostic techniques. This is expected to include the comprehensive synthesis of information systematically collected from structured or semi- structured diagnostic interviews of high reliability, medical records, and multiple family informants. Applicants should fully document their procedures for establishing such a final "best estimate" lifetime psychiatric diagnosis. Establishment of a highly reliable psychiatric diagnosis is facilitated by the use of a structured or semi-structured diagnostic interview. Applicants shall use one of the self-report interviews currently available and ready for use at the time the project is to begin. It is expected that the project does not include percentage effort or costs for the development or modification of existing instruments. One such set of instruments is the Diagnostic Interview for Genetic Studies (DIGS) and the Family Interview for Genetic Studies (FIGS) that were developed for the NIMH Human Genetics Initiative. Blank forms and training and code manuals are available via the Web at http://zork.wustl.edu/nimh/digs/newpage11.htm. While their use is not required, applicants who choose not to use them must clearly document the reliability and adequacy of their instruments for assessing a comprehensive range of clinical psychopathology. The structured interview utilized by the investigator must be sufficiently broad to incorporate the criterion sets for diagnosing major mental disorders in multiple systems. This is important to permit creation of the broadest possible dataset for genetic research on mental disorders, ensure maximum comparability with other data sets, and to permit comparisons to older studies using different criterion sets. While it is not required that investigators establish diagnoses in systems (e.g., ICD, RDC, DSM- III-R) other than DSM-IV, sufficient clinical data must be collected to allow diagnostic determinations in multiple systems. Currently, there is an imperfect correlation between a phenotype established according to any psychiatric diagnostic criteria set and an underlying genotype. The future discovery of susceptibility genes for mental disorders may significantly change current diagnostic criteria. Consequently, phenotypic assessments are expected to include not only a psychiatric diagnosis but also determination of a comprehensive range of clinical psychopathology. The diagnostic interview utilized by the applicant is expected to a broad range of psychopathology that may form the basis for future studies that correlate phenotypic characteristics, and not exclusively existing diagnostic categories, to underlying genotypes. It is expected that the principal investigator will demonstrate high diagnostic reliability among raters and/or collaborating sites when employing the diagnostic interview of choice. It is strongly encouraged that this be demonstrated prior to award. If this is not feasible, training exercises and limited reliability studies are expected to occur and be completed during the projectþs first month or two. Most importantly, such efforts must not delay the commencement of large-scale data recruitment efforts. 4) Computerized Database The creation and maintenance of a computerized database that includes a comprehensive array of clinical, family structure, diagnostic, and genotypic information is essential for rapid and efficient genetic analyses. Creation of such an electronic database is quite time-consuming and labor-intensive. Thus, it is expected that the applicant will have already developed, or have access to, such resources prior to the initiation of this project. Inclusion of a comprehensive range of information about psychopathology may be facilitated through the use of software that permits incorporation in an electronic database of all the information collected from a comprehensive structured interview. All of the data collected from the DIGS interview (but not the FIGS) may be input into such a database via a Windows 95 operating system graphical user interface. Software is available via the Web at http://zork.wustl.edu/nimh/digs/newpage11.htm. While the use of DIGS software is not required, applicants who choose not to use it must clearly document the existence and utility of a transparent graphical user interface through which data on a comprehensive array of clinical psychopathology data gathered through use of the diagnostic instrument they propose to use may be directly entered into an electronic database. The applicant must maintain a high- quality electronic database for data entry and analyses throughout the period of the funded project. It is expected that investigators shall establish electronic databases of all clinical, final best estimate diagnostic, and family structure information for wide dissemination to qualified investigators in the scientific community for use in genetic analyses, in accordance with a data sharing plan developed by the investigator (see below, section 7). The creation and validation of such datafiles are expected to occur prior to the genetic analyses conducted in the last year of the award. It is expected that the minimum data provided for each subject will include a unique subject and family identification number (ID), parental IDs, sex status, death status, ethnicity, age, twin status, final best estimate DSM-IV diagnosis, best estimate of the age at onset, and the comprehensive range of clinical information obtained from a structured interview. Data will be maintained without personal identifiers and thus are unlinked to their sources; such materials are "anonymous" samples. Creation and initial validation of such databases will signify that genetic analyses are to begin. Only at that time is it expected that DNA samples as extracted from cell lines (see below, section 5) will be required by investigators. It is also expected that genotyping data produced in projects funded under this RFA - including DNA marker names, allele sizes in base pairs and corresponding frequencies, and relative map distances - will be widely distributed to qualified investigators in the scientific community, according to the investigatorþs data sharing plan (see below, section 7). If requested by the investigator, NIMH will provide no-cost access to a data management facility; extensively documented electronic files ready for immediate genetic analysis will be created for use by the wider scientific community. Applicants may request funds to defray the costs of establishing databases with extensive documentation for wide distribution to the scientific community, with adequate justification. If another resource is utilized, it is expected that the adequacy, efficiency and cost of creating, maintaining, and documenting electronic databases as stipulated in their data sharing plan (see below, section 7) for dissemination to qualified investigators in the scientific community will be comparable to what could be achieved by using the resource to which NIMH provides no-cost access. 5) Lymphoblastoid Cell Lines and DNA Samples Creation of lymphoblastoid cell lines from blood samples establishes an infinitely renewable source of DNA for subsequent genetic analyses. In addition, these biological materials will be invaluable source for future studies that employ genetic maps of much higher density (e.g., those with SNPs as a basis) and that employ efficient technologies to study gene function and expression. Therefore, it is expected that permanent cell lines will be established for subjects studied in projects funded under this RFA. The creation of cell lines and extraction of DNA for genetic analyses requires provision of blood samples to a cell repository. It is expected that investigators shall obtain blood samples to establish cell lines and extract DNA samples for wide dissemination to qualified investigators in the scientific community for use in genetic analyses, in accordance with a data sharing plan developed by the investigator (see below, section 7). If requested by the investigator, NIMH will provide no-cost access to a cell repository; high-quality cell lines will be created upon receipt of blood samples, and DNA will be extracted and provided to applicants at no cost for their exclusive use in the quantities specified in their application. Applicants may request funds to defray the costs of establishing cell lines and extracting DNA for distribution to the wider scientific community, with adequate justification. If another repository is utilized, it is expected that the adequacy, efficiency and cost of the procedures for establishing cell lines and extracting DNA for wide dissemination to qualified investigators in the scientific community as stipulated in their data sharing plan will be comparable to what could be achieved by using the resource to which NIMH provides no-cost access. 6) Molecular and Statistical Genetic Analyses Identification and cloning of a disease susceptibility locus first requires chromosomal localization. Genetic analyses to be conducted in projects funded under this RFA will focus on genome-wide scans and statistical analyses to identify chromosomal regions that may harbor disease susceptibility loci. Fine mapping studies (including the saturation of regions of interest with multiple markers), gene sequencing, mutation analysis, and other steps in the positional cloning process will not be supported by this RFA. One resource currently available to applicants is the Center for Inherited Disease Research (CIDR), a centralized facility established to provide high-throughput genotyping and statistical genetics services for investigators seeking to identify genes that contribute to human disease. CIDR utilizes automated fluorescent microsatellite analysis using a standard marker set (Weber Screening Set 8), consisting of 387 primer pairs spaced approximately 10 CentiMorgans throughout the genome. Current capacity is approximately 120,000 genotypes per month. CIDR was established in 1996 as a joint effort of eight NIH Institutes, and is supported through a contract to Johns Hopkins University. CIDR is available to all investigators through competitive peer review by a chartered CIDR Access Committee (CAC). The CAC is a standing NIH committee comprised of scientists who have expertise in gene mapping and the genetic dissection of complex diseases. Projects are evaluated on the need for high throughput genotyping and the likelihood that genotyping will lead to successful mapping of genes contributing to that disease. Given that NIMH is one of the supporting NIH Institutes, research projects funded under this RFA are eligible for CIDRþs special introductory rate of no-cost genotyping. Further information about CIDR may be found on the World Wide Web at http://www.cidr.jhmi.edu. Submission deadlines for applications requesting CIDR access are November 1, March 1 and July 1. Applicants are expected to request access to CIDR. Applicants will not learn the outcome of the CAC evaluation in time to include an approval letter from the CAC in their application. Thus, investigators are expected to include in their application a scientific plan to accomplish a high throughput genome-wide scan at a centralized laboratory and statistical analyses, as well as budgeted genotyping and analysis costs. It is expected that the time frame and costs for their genomic scan and statistical analyses will be generally comparable to what could be achieved at CIDR or at academic or commercial facilities. A time frame for completion of a genome wide scan within one year, at a cost of $1 - $1.5 per genotype, appears reasonable. It is anticipated that technologies will improve and the rate of work and associated cost will change. 7) Data and Biological Materials Dissemination The sharing of materials, data, and software in a timely manner has been an essential element in the rapid progress that has been made in the genetic analysis of human diseases. PHS policy requires that investigators make unique research resources readily available for research purposes to qualified individuals within the scientific community when they have been published (PHS Grants Policy Statement in the July 12, 1996 issue of the NIH Guide to Grants and Contracts). Providing access to data collected in human genetic studies for qualified investigators in the wider scientific community has been a guiding principle of the NIMH Human Genetics Initiative, which funded data collection and genetic analysis for schizophrenia, bipolar disorder, and late-onset Alzheimer disease. Information for this Initiative is available on the Web at http://zork.wustl.edu/nimh/NIMH_initiative/NIMH_initiative_link.html. Data and materials collected and produced in projects funded by this RFA will be distributed to qualified scientific investigators in the wider research community, and will augment these existing resources. To address the joint interests of the government in the availability of, and access to, the results of publicly funded research and in the opportunity for economic development based on these results, NIMH requires applicants who respond to this RFA to develop and propose detailed plans for sharing the data and materials generated through the grant. It is expected that the information to be shared includes all clinical, diagnostic, and pedigree structure information, in addition to cell lines and DNA. For this purpose, it is the opinion of the NIH that dissemination of such data and materials via individual laboratories and Web sites is not sufficient, as it would force interested investigators to have to search several different data collections to make use of the results of this initiative. In addition, differences in protocols across projects for creating databases, establishing cell lines, and extracting DNA may make it impossible for researchers to combine information for integrated genetic analyses. It is preferable that data and materials generated in grants funded under this RFA should be placed in common, public cell repositories and databases that are widely accessible by investigators in the scientific community. The data management facility and cell repository supported by NIMH contractors are such resources. The NIMH Human Genetics Initiative employs procedures by which data and biological materials are widely disseminated to qualified investigators in the scientific community. These are described on the Web at http://zork.wustl.edu/nimh/NIMH_initiative/ NIMH%20Human%20Genetics%20Initiative%20Access%20Information.htm. It is preferable that the procedures for determining access and for disseminating data and materials are comparable to those currently employed in the NIMH Human Genetics Initiative. This is essential to pooling of data and materials collected and produced in grants funded under this RFA with existing resources widely distributed to the scientific community. It is expected that the investigatorþs data sharing plan will specify the following elements: (1) the creation of comprehensive and verified databases that contain all clinical, diagnostic, pedigree structure, and genotypic information collected and produced in the grant; (2) the establishment of cell lines, from which DNA will be extracted and stored, for all subjects studied from whom blood samples have been obtained; (3) mechanisms by which all databases and biological materials (DNA samples, cell lines) are widely distributed to qualified investigators in the scientific community; (4) a protocol and criteria for wide dissemination of these data and materials; (5) a timetable for distribution; and (6) an assurance that data and biological materials are disseminated in a manner comparable to existing protocols and procedures for distributing such data and materials in the NIMH Human Genetics Initiative. The Initial review group will comment on the proposed plan for sharing and data access. The plan will be considered part of the methodology for carrying out the research and, as such, the adequacy of the plan will be considered by NIMH staff in determining whether the grant shall be awarded. The sharing plan as approved, after negotiation with the applicant when necessary, will be a condition of the award. Evaluation of renewal applications will include assessment of the effectiveness of data and biological material release. After extensive discussion with mental health and human genetics researchers and advocacy members, the Genetics Workgroup of the National Advisory Mental Health Council (NAMHC) recommended that NIMH should draft a policy that provides for the sharing of genetic materials after a 12- to 18-month proprietary period. It was also recommended that this policy include all elements of the guidelines developed by the NIH and the Department of Energy (DOE) to address the special needs of genome research. These guidelines call for material and information from genome research to be made available within six months of the time the data or materials are collected, and are available on the Web at http://www.nhgri.nih.gov/Grant_info/Funding/Statements/data_release.html. Adherence with the time frame recommended by the NAMHCþs Genetics Workgroup is highly desirable. This is expected to result in all data being released to the scientific community by the end of the four-year award period, even if a competing renewal application is submitted. More rapid sharing is encouraged. Requests for exemptions or extensions will require compelling justification and will be fully evaluated through peer review and by program staff. 8) Quality Control The verification of family structure and updating of diagnostic and other clinical information is essential to the conduction of genetic analyses. Applicants are expected to maintain an electronic database of clinical, family structure, and diagnostic information that will be verified and updated throughout the project. Rigorous quality control procedures will permit the applicant to create up- to-date diagnostic and pedigree structure information. An essential element of the quality control procedure is to verify this family structure and diagnostic information. Final information - consisting of family structure information obtained after genotyping, updated final best estimate diagnostic data, and other updated clinical information - is expected to be included in the investigatorþs data sharing plan. In addition, high-quality cell lines and DNA are expected to be included in the investigatorþs data sharing plan. 9) Human Subjects Issues Proper safeguards are required to protect the welfare and rights of subjects who participate in genetic research. Subjects who participate in research projects funded under this RFA need to be fully informed that data collected from them will be rendered anonymous and will be distributed by NIMH to qualified scientific investigators in the wider research community. Subjects also need to be informed that some of these qualified investigators may have commercial interests. As a result of research supported under this RFA and of research subsequently conducted on these data, it is possible that enough information eventually might be developed to allow individuals to be identified and, consequently, become subject to any risk(s) that might arise as a result of that identification. Applicants should address any special human subjects issues that arise as a result of the proposed research. NIH is currently working to develop a model consent form for human genetic research, and this will be provided to applicants whose projects are funded under this RFA. This may then serve as a template that is subject to modification and/or approval by local institutional review boards. Post-Award Management During the course of the project period, while the original approved scope of work will be maintained, it is anticipated that technologies will improve and the rate of progress and focus of work supported by the grant(s) may change. Accordingly, it is expected that the principal investigator(s) will make many necessary adjustments in scientific direction to accommodate such changes. Most importantly, it is essential to the achievement of the study aims for recruitment to proceed as rapidly and efficiently as possible. Thus, principal investigators may need to be flexible in modifying recruitment strategies to assure that the targeted sample size is achieved within a three-year period. During the course of the award period, the principal investigators will be invited to meet with NIMH program staff in the Washington, D.C. area, to review scientific progress. Other scientists external to and knowledgeable about these studies may also be invited to participate. Budget requests should include travel funds for the principal investigator to meet annually in the Washington, D.C. area, should such meetings be advisable. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing research involving human subjects should read the "NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical Research," which have been published in the Federal Register of March 28, 1994 (FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, Volume 23, Number 11, March 18, 1994. Investigators also may obtain copies of the policy from the program staff listed under INQUIRIES, who may also provide additional relevant information. LETTER OF INTENT Prospective applicants are encouraged to discuss their research objectives with NIMH staff early in their planning process. Prospective applicants are asked to submit, by April 14, 1998, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the principal investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows NIMH staff to estimate the potential review workload and avoid conflicts of interest in the review. Investigators who submit an individual R01 application requesting direct costs of $500,000 or more for any one year, and investigators as a group who submit a collaborative R01 application requesting an overall total direct cost budget of $500,000 or more for any one year, are strongly encouraged to submit a letter of intent. The letter of intent is to be sent to: Dr. Steven O. Moldin Division of Basic and Clinical Neuroscience Research National Institute of Mental Health 5600 Fishers Lane, Room 10C-26 Rockville, MD 20857 Telephone: (301) 443-2037 FAX: (301) 443-9890 Email: firstname.lastname@example.com APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 5/95) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research or from the Division of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910; telephone (301) 710-0267; fax (301) 480-0525; email: firstname.lastname@example.com. The RFA label available in the PHS 398 (rev. 5/95) application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number, "Molecular Genetics of Mental Disorders: MH-98-010," must be typed in section 2 of the face page of the application form and the YES box marked. Applicants submitting a collaborative R01 application must follow the instructions and application procedures described in PAR-98-017, "Collaborative R01s for Clinical Studies of Mental Disorders," which appeared in the December 19, 1997 issue of the NIH Guide on the Web at https://grants.nih.gov/grants/guide/pa-files/PAR-98-017.html. In these cases, this program announcement title and number must also be typed in section 2 of the face page of the application form. Submit a signed, typewritten original of the application, including the Checklist, and four photocopies in one package to: CENTER FOR SCIENTIFIC REVIEW NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) At the time of submission, one additional copy of the application must be sent to: Dr. Steven O. Moldin Division of Basic and Clinical Neuroscience Research National Institute of Mental Health 5600 Fishers Lane, Room 10C-26 Rockville, MD 20857 Applications must be received by May 19, 1998. If an application is received after that date, it will be returned to the applicant without review. The Center for Scientific Review (CSR) will not accept any application in response to this RFA that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The CSR will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. The applicants should also ensure that their revised applications respond to the review criteria by which applications in response to this RFA will be evaluated. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by CSR and for responsiveness to this RFA by NIMH staff. Incomplete applications will be returned to the applicant without further consideration. If the application is not responsive to the RFA, NIH staff will contact the applicant to determine whether to return the application to the applicant or submit it for review in competition with unsolicited applications at the next review cycle. Those applications that are complete and responsive to this RFA will be evaluated for scientific and technical merit in accordance with the criteria stated below by an appropriate peer review group. As part of the initial merit review, all applications will receive a written critique and may undergo a process in which only those applications deemed to have the highest scientific merit will be discussed and assigned a priority score. All applications will receive a second level of review by the NIMH National Advisory Council. Review Criteria The criteria to be used in the evaluation of grant applications are listed below. To put those criteria in context the following information is contained in instructions to peer reviewers. The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. The reviewers will comment on the following aspects of the application in their written critiques in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of the criteria will be addressed and considered by the reviewers in assigning the overall score weighting them as appropriate for each application. Note that the application does not need to be strong in all categories to be judged likely to have a major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward. o Significance: Does this study specify the large-scale data collection effort needed to determine the chromosomal localization of genes that confer susceptibility to schizophrenia, bipolar disorder, or early-onset recurrent unipolar depression? Does the applicant propose to collect a new pedigree sample, and not one that has been previously studied? Is the scope of work for the molecular genetic studies focused exclusively on efforts to establish the chromosomal locations of susceptibility loci, and not focused on fine mapping, sequencing, or mutation analyses? o Approach: Are the conceptual framework, design, ascertainment strategy, assessment/ diagnostic procedures, and targeted sample size adequate, appropriate, and feasible to accomplish the specific aims of the project? Does the applicant have access to sufficient resources to obtain the targeted sample size? Is the sample size sufficient to identify chromosomal regions that harbor genes conferring susceptibility to the disorder under investigation? Does the applicant acknowledge potential problems in recruitment and consider alternatives? Is the scientific and technical merit of the proposed research sufficient to advance the objectives of the RFA? Is phenotyping being done in a highly reliable, rigorous and comprehensive fashion, permitting the establishment of diagnoses in multiple systems? Is the applicant collecting data on a broad range of psychopathology, which may form the basis for future studies that correlate phenotypic characteristics (and not just existing diagnoses) to underlying genotypes? Will genotyping be accomplished in a rapid and cost-effective fashion? o Innovation and originality: Does the project employ novel and creative concepts and approaches for large-scale pedigree collection? Does the applicant employ novel methods for integrating data from multiple sources to establish best estimate psychiatric diagnoses? Does the project foster new analytic approaches for identifying chromosomal regions of interest? o Investigator: Are the principal investigator and staff appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Is there a multidisciplinary research effort that includes representation of the scientists needed for large-scale data collection and genetic analysis (e.g., clinicians, diagnosticians, molecular geneticist, statistical geneticist, bioinformatics specialist)? o Scalability: What is the likelihood that the data collected in the project will be rapidly collected and available for analysis by a broad range of biomedical investigators? o Integration with other resources: Are the plans adequate to integrate the data and materials collected with those collected in the NIMH Human Genetics Initiative? Are comprehensive diagnostic assessment instruments and software currently available utilized in the project? Are DSM-IV criteria used to define a minimum number of affected individuals with the core phenotype, for the purpose of pedigree ascertainment? o Exportability and accessibility: Will the applicantþs data management plans permit creation of a highly efficient and organized electronic database? Will these plans facilitate the creation of databases containing final best estimate diagnostic data, family structure information, and clinical data, as well as the establishment of cell lines and DNA samples, that will be widely disseminated to qualified investigators in the scientific community? Will data provided to the data management facility and cell repository be in a highly exportable format that will permit rapid integration with comparable resources maintained by NIMH? Does the investigatorþs quality control plans assure that databases provided to the scientific community are accurate and up-to-date, and that cell lines and DNA samples are of high-quality? o Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed methods take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support? Does the applicant have access to sufficient clinical resources to obtain the targeted sample size? o Budget and duration: Are the proposed budget and duration appropriate in relation to the proposed research? Are the costs and time frames for molecular and statistical analyses generally comparable to those at CIDR and other high-throughput genotyping facilities? Are the costs, time frames, and abilities to widely distribute data and materials to qualified investigators in the scientific community for the cell repository and data management facility chosen by the applicant to create databases, establish cell lines, and extract DNA generally comparable to those that would be obtained by using existing NIMH resources? o Adequacy of plans to include both genders and minorities and their subgroups: Are both genders and minority groups represented, or is their exclusion scientifically justified? The initial review group will also examine the provisions for the protection of human and animal subjects, the safety of the research environment, and conformance with the NIH Guidelines for the Inclusion of Women and Minorities as Subjects in Clinical Research. The availability of special opportunities for furthering methods development through the use of unusual talent resources or environmental conditions in other countries which are not readily available in the United States, or which provide augmentation of existing U.S. resources, will be considered in the review. AWARD CRITERIA The earliest anticipated date of award is September 30, 1998. Subject to the availability of funds, and consonant with the priorities of this RFA, NIMH will provides funds for a project period not to exceed 4 years. Factors that will be used to make award decisions are as follows: o Quality of the proposed project, as determined by rigorous scientific peer review; o Feasibility of the proposed large-scale data collection effort, within a three-year time frame; o Cost effectiveness and rapidity of the proposed genotyping work and genetic analyses; o Adequacy of plan to assure that data and biological materials collected and produced in the project can be easily integrated with comparable data and materials collected in the NIMH Human Genetics Initiative; o Adequacy of plans to make all data and biological materials collected and produced as a result of the proposed research widely accessible in a timely manner to the biomedical research community; o Availability of funds. INQUIRIES Written, telephone, and e-mail inquiries concerning this RFA are strongly encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Dr. Steven O. Moldin Division of Basic and Clinical Neuroscience Research National Institute of Mental Health 5600 Fishers Lane, Room 10C-26 Rockville, MD 20857 Telephone: (301) 443-2037 FAX: (301) 443-9890 Email: firstname.lastname@example.com Direct inquiries regarding fiscal matters to: Ms. Diana S. Trunnell Grants Management Branch National Institute of Mental Health 5600 Fishers Lane, Room 7C-08 Rockville, MD 20857 Telephone: (301) 443-2805 FAX: (301) 443-6885 Email: email@example.com AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.242. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards will be administered under PHS grants policy as stated in the Public Health Service Grants Policy Statement (April 1, 1994). PHS strongly encourages all grant and contract recipients to provide a smoke-free workplace and promote the nonuse of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.
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I think back to February of 2009, long before the Abreu Fellows Program existed. I was still in school and visiting Boston for an audition and I distinctly remember telling my cousin and his wife that I wanted to combine my performing with some El Sistema-style educational endeavors. I told my them, if only there was a way I could learn the skills needed to do this. Perhaps I could use a grant-writing course. Maybe I could do a non-profit management seminar. I left Boston brainstorming about doing El Sistema.
Fast forward four months and Dr. Jose Antonio Abreu (pictured with me at the top of my blog), founder of El Sistema, had won the TED Prize. Subsequently the New England Conservatory announced, per Dr. Abreu's wish, a fellowship program to train gifted musicians and music educators in the El Sistema philosophy, non-profit management, community partnerships and music education. The fellowship even included a trip to Venezuela to study El Sistema up close. Of course, I applied and got a spot in the inaugural class of the Abreu Fellows Program. I called my cousins in Boston to tell them I was moving to their city to do exactly what I had told them I wanted to do not four months earlier.
After graduating from the Abreu Fellows Program in June 2010, the ten Abreu Fellows went about leading an El Sistema-style programs all over the USA. Of course, along with Al Meyers, I co-founded the Atlanta Music Project.
Growing up studying music helped me develop a strong work ethic from an early age, so I found myself quite at home with the busy and hectic schedule offered by the Abreu Fellows Program. It was an intense year, definitely the most I had worked in all my life...until the Atlanta Music Project came along. The joys of running a start-up non-profit include: picking between downtime and no sleep or no downtime and no sleep (I usually pick the former), missing all of March Madness, people asking me why I emailed them at 3:30am, and hoping the other person will pay for that business lunch.
Besides these annoying issues, I can say that I wouldn't trade places with anyone. It's fun as heck. The Atlanta Music Project is fulfilling its mission every day. To see our students developing their musical, social and emotional abilities right before my very eyes is mind boggling. No doubt, this combination of intense musical training and academic tutoring (done by our collaborator, the Atlanta After School All-Stars) is working.
Here are a few highlights on doing El Sistema in Atlanta:
Since moving to Atlanta, I've quickly learned that this is a Coca-Cola town. With its headquarters here in Atlanta, the world's biggest brand has its footprint all over the city, especially when its comes to supporting charitable efforts. The Atlanta Music Project is fortunate to have been awarded a grant from the Coca-Cola Company, which, with generous in-kind donations from our City Of Atlanta Office Of Cultural Affairs, enabled us to launch our program. In July 2010, Coca-Cola invited me to the National Black Arts Festival Gala. I got the chance to meet Atlanta's Mayor, Kasim Reed, for the first time.
|Meeting Mayor Kasim Reed for the first time.
Here I am at CNN studios just before doing a live interview with Ali Velshi about the Atlanta Music Project. You can watch a video of the CNN interview here.
|About to start a live interview with Ali Velshi on CNN.
Photo courtesy of Green Theory PR&Marketing.
|AMP Teaching Artists after Winter Performance
L to R: Dr. Jackie Pickett, Kristen Faust, John Bryant, Bryan Crumpler, Elizabeth Oladele, Jessica Sherer, Aisha Bowden, Dantes Rameau. Photo Courtesy of My True Vision Photography.
Hanging out with Wynton Marsalis after his Jazz At Lincoln Center performance at the Woodruff Arts Center. A big fan of El Sistema, Wynton has been to Venezuela, met Abreu and seen El Sistema for himself. The Atlanta Music Project students also got to meet him and watch his dress rehearsal.
|With Wynton Marsalis
|Atlanta Music Project students hang with their music mentors at the Atlanta Symphony Youth Orchestra Concert.
Below is a picture the AMP students performing as a choir during our Winter Performance at the Museum Bar. Our students are a joy to work with. However, some of them, as we expected, do have some behaviour issues. Not that I blame them, it's amazing to hear what some of them have already gone through at their age. But I'm around them so much that I'm privileged to be able to see all the sides of their personalities.
The instance that most caught my attention in these first months was seeing one of our students, who can come off as particularly hardened, backstage before going out to perform. Here was this kid, one of our bigger ones, who can be quite the bully and troublemaker, scared out of his/her mind to go out on stage to perform. I smiled and said to myself "that's the real him/her." I could see it in his/her face. Behind all that bravado was simply a young child: humbled, intimidated, unpolished, innocent and full of potential.
On doing El Sistema in Atlanta, I always keep in mind that, through music, we're developing the true side of our children.
|What it's all about. Led by choir director Aisha Bowden, AMP students perform during their Winter Performance.
Photo courtesy of My True Vision Photography.
Next AMP Concert:
If you're in Atlanta, be sure to come check out the Atlanta Music Project Teaching Artists in concert at the Gilbert House on Thursday March 31 at 6pm. More info here.


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Adam Levine is all smiles on the cover of Men's Health's March 2013 issue, hitting newsstands Friday (February 8).
Here is what the 33-year-old Maroon 5 singer had to share with the mag:
On turning to Yoga: "I have a hard time sitting still. I can be all over the map. Yoga has given me the ability to be more focused and make better decisions that come from a clear place. It's made me more successful. I love it and I don't know what I do without it."
On his style secrets: "I tend to go for clothes with a classic feel. But I also want them to have a story, a history, some meaning. I don't want to buy a T-shirt and then go out to lunch and see someone else wearing the same thing. I want my clothes to be unique. Not necessarily expensive, just one of a kind."
For more from Adam, visit MensHealth.com!
Also pictured: Adam graces the cover of 7 Hollywood's Icons issue along with Bella Heathcote, Ke$ha, Sophia Loren, David Gandy, Celine Dion, and Sigrid Agren.


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Sen. Cruz formally gives up Canadian citizenship
AUSTIN, Texas (AP) — Canada-born U.S. Sen. Ted Cruz has made good on a promise to renounce his birth country's citizenship, amid speculation he could make a run at the White House in 2016.
Spokeswoman Catherine Frazier said Cruz's action became official May 14 and that the Texas senator received written confirmation at his home in Houston on Tuesday. She said the Republican "is pleased to have the process finalized."
"Being a U.S. Senator representing Texas, it makes sense he should be only an American citizen," Frazier said in an email.
Cruz, 43, was born in Calgary, Alberta, in 1970, while his parents were working in the oil business there. His mother, Eleanor, is from the U.S., while his father, Rafael, is a Cuban who did not become a U.S. citizen until 2005.
Though he has been in office only about 18 months, Cruz helped lead last year's partial government shutdown and has become a conservative grass-roots champion.
Amid questions last year about his eligibility to be president should he decide to run, Cruz released his birth certificate to the Dallas Morning News — and said he was surprised to learn he was a dual Canadian-U.S. citizen.
Upon learning that he'd received it at birth, he promised to formally give it up. Months passed before Cruz hired an immigration attorney to help him with the process.
Frazier provided a copy of Cruz's Certificate of Renunciation, which certifies that Rafael Edward Cruz "has formally renounced Canadian citizenship and pursuant to the Citizenship Act will cease to be a citizen."
The U.S. Constitution says only a "natural born Citizen" may be president. Legal scholars, however, generally agree the description covers foreign-born children of U.S. parents.
Previous foreign-born Americans — notably Republicans John McCain and George Romney — have run for president with some mention, but no serious challenges, of their eligibility.
Some conservatives claimed President Barack Obama was born in Kenya and thus not eligible to be U.S. president. Obama is an American citizen; his father was Kenyan, his mother American.
Cruz, who has made frequent trips to Iowa, New Hampshire and South Carolina, the first three states to hold presidential contests, has refused to say if he plans to run for president.


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NASA: Solar Storm Nearly Causes Catastrophe on Earth
Scientists say the Earth narrowly missed a catastrophic solar storm in 2012. WSJ's Monika Vosough reports. (Photo: NASA)
This transcript has been automatically generated and may not be 100% accurate.
I ... this was the son then two thousand twelve when the scientists found that a catastrophic solar storm came very close to striking here ... on July twenty thirty two thousand twelve the sun and eastern asset class of plasma ... also known as Cromwell message actions icy and he's ... the of the most intense eruptions on the side ... nice to see in these propelled away from the sun at a speed of more than eighteen hundred miles per second ... the storm tore through ETFs are a bit but it missed the yet not by much though ... had the storm occurred only nine days area scientists now believe ... it would depend on our planet ... the sanctions have been analyzing the data at the sands and they concluded that the stock was one of the strong this in recorded history ... this is so scary actually need to and keep knocking style apps as a colorful CNBC like that cant that they would have a tremendous impact potentially knocking out power grids GPS and communications networks will buy ... according to a study by the National Academy of Sciences ... economic impact of such a blast could exceed two trillion dollars about twenty times more than the cost of the hurricane like Katrina ... unfortunately nesting this as ... I have enough data for scientists to make reliable predictions on when the next ... threatening Sunstone my happen ... for that piece that scientists would have to constantly monitor the sun from many different analysts ... project that has been too expensive to fund so far ...


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Megan Fox Gives Birth to Baby Boy
Aug 9, 2016 6:39 PM EDT
There's a new man in Megan Fox's life. The New Girl actress gave birth to her third son last week, E! reports. Journey River Green was born Aug. 4. It's the third child for Fox and Brian Austin Green, who also have sons Noah, 3, and Bodhi, 2. Journe… Read more


text: Job Discussion Forums :: View topic - Yet more anti-Euro nonsense from the BBC Get TEFL Certified & Start Your Adventure Today! Job Discussion Forums"The Internet's Meeting Place for ESL/EFL Students and Teachers from Around the World!" FAQ Search Memberlist Usergroups Register Profile Log in to check your private messages Log in Yet more anti-Euro nonsense from the BBC Goto page Previous 1, 2, 3 Job Discussion Forums Forum Index -> Current Events Forum View previous topic :: View next topic Author Message QaaolchouraJoined: 10 Oct 2008Posts: 539Location: 21 miles from the Syrian border Posted: Sat Jul 28, 2012 10:08 pm Post subject: Sashadroogie wrote: Make no mistake about it! The EU exists for the sole purpose of keeping Americans out of our TEFL schools. I knew it! It's all about keeping the Germans in, the Americans out, and the Russians down. Or something like that. (As you know, all us Yanks are all horrid with geography and politics.) ~Q Back to top SashadroogieJoined: 17 Apr 2007Posts: 11061Location: Moskva, The Workers' Paradise Posted: Sun Jul 29, 2012 9:04 am Post subject: Yip! All your dark suspicions were correct - as many posters have written on this very forum, the EU is really about keeping Americans and their corrupt bourgeois ways out of European classrooms. And protecting out kids from the resulting gun-related violence. But the Russians aren't down... merely waiting in the wings... Back to top sparksJoined: 20 Feb 2008Posts: 629 Posted: Tue Jul 31, 2012 2:36 am Post subject: Isn't all this talk of the ECB buying bonds similar to what the U.S. Fed. did a while ago with American banks? With the Euro countries though, they are painting it as a sign that the end is nigh, in the U.S. it is only being used as fodder for the campaigning. Back to top SashadroogieJoined: 17 Apr 2007Posts: 11061Location: Moskva, The Workers' Paradise Posted: Thu Aug 02, 2012 6:33 am Post subject: http://www.bbc.co.uk/news/world-us-canada-19089970 Gasp! Californian cities teeter on the abyss. Fears of dollar collapse fuelling social unrest. Possible break up of the US if California secedes. Click on our panic-mongering graphics to see totally made-up scenarios and learn how this might affect you! OK, so this is not what you'll read in the BBC article. But why not? Back to top SashadroogieJoined: 17 Apr 2007Posts: 11061Location: Moskva, The Workers' Paradise Posted: Sun Feb 03, 2013 6:12 am Post subject: Ho ho! Is the Sterling zone about to break up? Perhaps the rump-state that used to be UK will be joining the Eurozone in a couple of years? http://www.bbc.co.uk/news/business-21302776 Back to top scot47Joined: 10 Jan 2003Posts: 15323 Posted: Sun Feb 03, 2013 9:08 pm Post subject: The Stderling Zone ! Ah, nostalgia. I nremember when it covered more than a quarter of the Globe. Has anyone told the City of London that things have changed ? Have they noticed that the Empire has gone ? Back to top SashadroogieJoined: 17 Apr 2007Posts: 11061Location: Moskva, The Workers' Paradise Posted: Mon Feb 04, 2013 6:52 am Post subject: It was sold to the Americans so as to keep the Germans out. The Empire's very own 'open-door' policy, as described by Marxist historians. Back to top Display posts from previous: All Posts1 Day7 Days2 Weeks1 Month3 Months6 Months1 Year Oldest FirstNewest First Job Discussion Forums Forum Index -> Current Events Forum All times are GMTGoto page Previous 1, 2, 3 Page 3 of 3 Jump to: Select a forum Where to Begin----------------General DiscussionNewbie ForumCurrent Events ForumTechnology ForumOnline Teaching Forum Africa Forums----------------General Africa Forum Asia Forums----------------CambodiaChina (Job-related Posts Only)China (Off-Topic)Hong KongIndiaIndonesiaJapanMalaysiaPhilippinesSingaporeTaiwanThailandGeneral Asia ForumVietnam Caribbean Forums----------------General Caribbean Forum Europe Forums----------------Czech RepublicFranceGermanyGreeceItalyMacedonia and the BalkansPolandRomaniaRussia & C.I.S.SpainTurkeyUkraineUnited KingdomGeneral Europe Forum Latin America Forums----------------ArgentinaBrazilChileColombiaCosta RicaMexicoMexico (off-topic)PeruGeneral Latin America Forum The Middle East Forums----------------BahrainEgyptIsraelKuwaitOmanQatarSaudi ArabiaUnited Arab EmiratesGeneral Middle East Forum North America Forums----------------General North America Forum Oceania----------------Australia/New Zealand You cannot post new topics in this forumYou cannot reply to topics in this forumYou cannot edit your posts in this forumYou cannot delete your posts in this forumYou cannot vote in polls in this forum This page is maintained by the one and only Dave Sperling. Contact Dave's ESL Cafe Copyright © 2018 Dave Sperling. All Rights Reserved. Powered by phpBB © 2001, 2002 phpBB Group Teaching Jobs in China