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If you're near a school bus this week, chances are a state trooper isn't far away.
This week, troopers with the State Highway Patrol are looking to bring attention to motorists to pay closer attention when driving near a bus, in order to protect children getting on the bus in the morning or leaving the bus in the evening.
"We must ensure our children's safety as they travel to and from school," said Frank Perry, secretary of the Department of Public Safety, in a statement. "A child's life should never be put in danger just to save a minute or two during a daily commute. That's why we're going to make sure people know the law as well as the consequences of breaking it."
According to the state Department of Public Safety, on one day last year, 3,196 drivers committed moving violations at 2,299 bus stops.
"Children are now back at school, and just be careful in the early morning hours, and in the afternoon hours for buses stopped, picking up and discharging children," NCHP 1st Sgt. Robert Bowen said. "This week, Highway Patrol's going to be making a specialized effort across the state to follow school buses and be scene in and around school zones."
Bowen took over as the Highway Patrol first sergeant for Lenoir and Jones counties, replacing Charles Johnston, who retired from the position Aug. 2.
"I've worked as a trooper in Raleigh and over in Pitt County, in Greenville," said Bowen, who's been with the NCHP since 1992. "And I've been a sergeant in New Bern, Washington, Greenville, and then up at the Training Academy up in Raleigh. Though, mostly around here — mostly Down East since I came here in '99."
Wes Wolfe can be reached at 252-559-1075 and email@example.com. Follow him on Twitter @WolfeReports.


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Kohler K-2836-47 Almond Votive 18-1/2" Cast Iron Undermount Bathroom Sink
Item #:
Contact us for best available pricing on all Kohler!
We want to help make your remodel easy and affordable! Please call or chat during business hours using the links at the top of our site to take advantage of this special offer.
Offer Ends 6/5/2015
We still have product details, accessories, replacement parts and reviews below, scroll down to see them!
Technical Specs
|Specification Sheet
|Rough-In Guide
|Installation Guide
|Basin Depth
|Basin Length
|Basin Width
|Country Of Origin
|Drain Assembly Included
|Drain Connection
|Drain Placement
|Faucet Holes
|Faucet Included
|Installation Type
|Made in America
|Cast Iron
|Number Of Basins
|Sink Shape
Product Features:
- Specialty basin fulfills unique qualities for a distinct bathroom design
- Covered under Kohler's limited lifetime sink warranty
- Constructed of enameled cast-iron which combines strength, durability and insulation benefits
- Adds unique flair to your bathroom
- Striking hexagonal design highlighted by sleek installation
- Undermount installation delivers the classic look and feel to any bathroom
- Center drain location provides optimal draining capability
- All hardware needed for installation included
Product Technologies / Benefits:
- Undermount Sinks: Create a seamless counter-to-basin transition. Sleek styles and ease of cleaning are what makes these the preferred design choice.
- Enameled Cast-Iron: Kohler Enameled Cast-Iron combines the strength, durability, and insulation benefits of cast-iron with the scratch, chip, and burn resistance of a baked, powder coat finish and comes with an exceptional Lifetime Limited Warranty. These materials combined give the sink or tub the strength to last a lifetime of use. Another benefit is that Kohler Enameled Cast-Iron is available in a wide variety of specialty colors to truly customize your home.
Product Specifications:
- Overall Length: 20-3/16" (measured from the left outer rim to the right outer rim)
- Overall Width: 16-7/8" (measured from the back outer rim to the front outer rim)
- Height: 5-7/8" (measured from the bottom of sink to the top of the rim)
- Basin Width: 16-1/8" (measured from the back inner rim to the front inner rim)
- Basin Length: 18-7/16" (measured from the left inner rim to the right inner rim)
- Basin Depth: 3-7/8" (measured from the center of basin to the rim)
- Installation Type: Undermount
- Number of Faucet Holes: 0
- Drain Outlet Connection: 1-3/4"
Additional Kohler Links
- View Manufacturer Warranty
- Shop All Kohler Products
- Shop All Kohler Votive Collection Products
Our SKU: k-2836
This product is listed under the following manufacturer number(s):
- Almond*
- Basalt*
- Biscuit*
- Black Black*
- Black n Tan*
- Cane Sugar*
- Cashmere*
- Dune*
- Ember*
- Frost*
- Ice Grey*
- Innocent Blush*
- Iron Cobalt*
- Mexican Sand*
- Navy*
- Sandbar*
- Sea Salt*
- Skylight*
- Sunlight*
- Thunder Grey*
- Vapour Blue*
- Vapour Green*
- Vapour Indigo*
- Vapour Orange*
- Vapour Pink*
- White*
- Wild Rose*
*Denotes a finish or option that has been discontinued
Product Reviews
Rated 5 out of 5 by LillieOJ from Absolutely fabulous......but! I purchased 2 of these sinks for our Master Bathroom. They are absolutely fabulous, but Black was the only color I could buy that would go with my wild granite. I have 2 comments, the sinks are shallow, and black shows water spots (which I knew), but I literally have to wipe them down after each use. However, I don't regret buying them, because their uniqueness and beauty makes it worth it. I really love the 6 sided design.
Date published: 2014-02-03
Rated 5 out of 5 by vanilla707 from My Best Buy Ever! Unique Design with Superior Build Quality
Date published: 2013-12-27
Rated 5 out of 5 by vtk1 from Great Service First of all the picture of this sink did not do it justice! It is much prettier than the picture showed. The customer service is perfect. There was a problem with the expiration date on my credit card and when I called customer service they fixed it immediately. I actually ordered three sinks from Faucet Direct and all came very quickly. I was ready with my sinks before my contractor was! I would refer this company to anyone. Thanks Faucet Direct for making this part of my remodel as smooth as could be. I am sure I will be using you agin in the future. Vicky
Date published: 2013-09-04
Rated 5 out of 5 by alaskaann from Outstanding in style We had to pay a little more to have this 6 sided design cut in the counter top BUT it was so worth it. My husband and I are enjoying the double sinks in our master bath. It is so different and stylish.
Date published: 2013-03-27
Rated 4 out of 5 by CreativeStoneworks from Our customers were very happy with the unique quality, shape and color of this sink. With the color of the Diano Reale stone that they picked for their guest powder room, this sink was a great compliment. We had to finish the 6 corners by hand but that was minor. DXF file was accurate. We at Creative Stoneworks in Bellingham, Washington would recommend this sink.
Date published: 2010-05-10
Rated 5 out of 5 by MaryMartha from Like No Other We placed this in a rustic granite setting and we have everyone from the granite installers to the plumber raving how much they liked the style of this unique sink. We love it.
Date published: 2010-02-02
The Bold Look of Kohler is more than a slogan, it is a testament to the sight and focus of the Kohler company since the late 1800's. Kohler designs its plumbing fixtures and accessories for longevity and with a focus on pleasing your senses. Kohler's attributes make its plumbing and accessories a clear choice of quality for generations to come.
Kohler Votive Collection
The Votive Collection by Kohler features striking designs that are bold and eye-catching. Its geometric patterns make the Votive Collection an excellent choice for any bathroom.
Warranty Info
Kohler Lifetime Limited Warranty Kohler Co. warrants its faucets to be leak and drip free during normal residential use for as long as the original purchaser owns his/her home.* If the faucet should leak or drip during normal use, Kohler will, free of charge, mail to the purchaser the cartridge necessary to put the faucet in good working condition. Kohler also warrants all other aspects of the faucet, except gold finish, to be free of defects in material and workmanship during normal residential use for as long as the original purchaser owns his/her own home. If a defect is found in normal residential use, Kohler Co. will (at its election) repair, provide a replacement part or product, or make appropriate adjustment. Damage to a product caused by accident, misuse, or abuse is not covered by this warranty. Proof of purchase (original sales receipt) must be provided to Kohler with all warranty claims. Kohler Co. is not responsible for labor charges, installation, or other consequential costs. In no event shall the responsibility of Kohler exceed the purchase price of the faucet. To obtain warranty service, contact Kohler Co. either through your Dealer or Plumbing Contractor or by calling 1-800-4-KOHLER or by writing: Kohler Co., Attn.: Customer Service Dept. Kohler, WI 53044, USA Please be sure to proide all pertinent information regarding your claim, including a complete description of the problem, the product, model number, color, finish, and the date the product was purchased. Also include the name of your contractor or distributor and your original invoice. TO THE EXTENT PERMITTED BY LAW, KOHLER DISCLAIMS ALL OTHER IMPLIED WARRANTIES INCLUDING THAT OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE . KOHLER CO. ALSO DISCLAIMS ANY LIABILITY FOR SPECIAL, INCIDENTAL, OR CONSEQUENTIAL DAMAGES. Some states do not allow limitations of how long an implied warranty lasts or the exclusion or limitation of special, incidental or consequential damages, so these limitations and exclusions may not apply to you. This warranty gives the consumer specific legal rights. You may also have other rights that vary from state to state. This warranty is to the original purchaser only, and excludes product damage due to installation error, product abuse, or product misuse, whether performed by a contractor, service company, or the consumer. This is our exclusive written warranty. *Trend faucets, MasterShower Tower, gold finish, accessories, fixture related items (as designated in the Kohler Faucets Price Book), and faucets used in commercial settings continue to be covered by Kohler's one-year limited warranty.6/98 COPYRIGHT © 1998 BY KOHLER CO. (SEE BELOW) All Kohler Plumbing Fixtures, Faucets and Fittings carry Kohler's Limited One-Year Warranty Unless Otherwise Noted. Limited One-Year Warranty Kohler® plumbing fixtures, faucets and fittings are warranted to be free of defects in material and workmanship for one year from date of installation. Kohler Co. will at its election repair, replace or make appropriate adjustment where Kohler Co. inspection discloses any such defects occurring in normal usage within one year after installation. Kohler Co. is not responsible for removal or installation costs. To obtain warranty service, contact Kohler Co. either through your Dealer or Plumbing Contractor or calling 1-800-4-KOHLER or by writing: Kohler Co., Attn: Customer Service Department Kohler, Wisconsin 53044 U.S.A. IMPLIED WARRANTIES INCLUDING THAT OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE ARE EXPRESSLY LIMITED IN DURATION TO THE DURATION OF THIS WARRANTY. KOHLER CO. DISCLAIMS ANY LIABILITY FOR SPECIAL, INCIDENTAL OR CONSEQUENTIAL DAMAGES. Some states do not allow limitations on how long an implied warranty lasts, or the exclusion or limitation of special, incidental or consequential damages so these limitations and exclusions may not apply to you. This warranty gives you specific legal rights. You may also have other rights which vary from state to state. This is our exclusive written warranty. Notes: There may be variation in color fidelity between catalog images and actual plumbing fixtures. Kohler Co. reserves the right to make changes in product characteristics, packaging or availability at any time with out notice. COPYRIGHT © 1989, 1990, 1997, 1998 BY KOHLER CO. Kohler Standby Generators Go to the following link to find a service center near you: http://www.kohlergenerators.com/sales-service/contact-sales

subset: commoncrawl


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The Holiday Inn Express® Hotel & Suites Arcadia is a hotel conveniently located a mile east of the downtown area, making it easy for you to get to meetings, whether they're at the hospital, the county courthouse or DeSoto Next Generation Solar Energy Center. Our Arcadia hotel also offers a boardroom if you need to host a small meeting or make a sales pitch, and our business center is open 24 hours.
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Applications for admission are accepted year round for the fall or spring semesters. Students may enter the program as a Master's degree student, a certificate student, or as someone who simply wants to take a course for their own professional development (non-degree student). Upper-level UMBC undergraduates can take advantage of the accelerated BS/MS option to get a head-start on an advanced degree.
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Results 10,181 to 10,200 of 27221
It's best to think of, and play, The Witcher series as primarily interactive fiction, albeit very violent and hands on interactive fiction. The intent of CDPR in both games is to tell a story through a game, not to make a game with a story, which is what the overwhelming majority of games do. The Witcher 2 achieves it to a far greater degree, to the point where I'd say it's the best and most important example of interactive narrative since Psychonauts in how it links it's narrative and it's mechanics. But The Witcher is still an excellent game where you can frequently see the roots that germinated into it's sublime successor.
I actually bought the game on the strength of the demo, so didn't have that much of a problem with the intro and first chapter, but it's fair to say that it's first two acts are much slower than the rest of the game. That's a trademark of CDPR though, they like to mess with gaming convention in order to work on better presenting scale and narrative scope. It's a slow start, but slow by design, and when you get to the middle of the game you know that it was the right choice as far as the whole is concerned.
The sex things-on the whole it's clearly pretty weak throughout the game, and I say that as a huge fan of the series. It's a classic example of a game projecting it's "maturity" by turning the inhabitants of a world into the attendees of a nihilistic fuck fest. At times I'd even say it was misogynistic. The Second game, to my relief, more or less neuters the sex entirely and actually becomes one of the best examples how to do sex in games-sparingly, with character, for a purpose, but incidental and unobtrusive. Contrast that with the Witcher where it is more a case of-every woman wants it, because..maturity?, every fucking where you look.
However if you pay attention to what's being said you don't have to have sex with anyone, ever, in either game. The example you give-there are two dialogue choices for you to make in the run up, in which time Triss talks about feeling like a teenager again, old feelings for Geralt coming flooding back. You are given the chance to give either a bluff or nervous "Yeah great, time to get going!" choice after both, or probe into those things she's saying. Where, in the bedroom, are conversations like that going to go with an old lover in a video game? Or, to be honest, the majority of media?
It's contrived and cliched certainly but to me at least I could still see what was coming a mile off when I first played the game, despite knowing nothing of the back-story or fiction.
The sad fact applies that in the first Witcher anything more than a compliment in a dialogue choice with a woman is basically a sexual overture, and it's disgusting frankly.
HOWEVER the tact and sensibility with which they dealt with other mature issues such as coming of age, racism, politics, relationships, war and morality, even gender actually, led me to give them the benefit of the doubt in the hope that their approach to sexuality was just a horrible accident or case of experimentation gone wrong. Turns out, if W2 is anything to buy, that's all it was.
But where the sexuality is a sledgehammer the majority of the rest of the game is subtle, rich, and markedly different if you give it the chance, like a good book. It's rare a classic novel achieves it's status on the basis of the first four chapters, it's about what it does as a whole, and that very much applies to The Witcher, it is, in spite of looking a bit creaky, still a BIG, ambitious and impressive game, very much a PC game. It's not about moment to moment thrills-although it's not bad on that when you get into Vizimia anyway-so it requires patience, but much like a good book give it time and you won't regret it. If you give ti time you will find a world which has been crafted to explore whilst also allowing for narrative propulsion. It's a game which is about places and people and lore, about the social tensions of towns and rural communities, the spaces both physical and cultural between them, and the way that war and politics brings it all together and threatens to dwarf them utterly. I studied Medieval Europe at University and I have never played a game which better recognises and portrays the rise of early modern ideals and existential forces pitted against folklore and tradition, which is what is really at the heart of this game. That probably sounds very ott but fuck it, it's what I got form it.
When making The Wire David Simon said he wanted to make a show that demanded hours of people's time to understand, and that he didn't care about who that alienated The Witcher is obviously nowhere near as impressive an accomplishment as said series but I think the intent was the same. It doesn't care if you don't want to give it time, but you'll be very glad if you did, because it's approach simply allows for experiences other games can't give without being similallry self-consciously challenging to get into.
To make it a more palatable experience visually there are some good texture mods
There is another mod, The full combat rebalance which make the combat a lot more challenging and akin to that of the Witcher 2 (requires patience, effort and tactical sense but with the pay off of dominating opponents if you do it properly, dying very quickly if not) not as advanced and well implemented as in the Witcher 2 but certainly done well enough for it to make a second play through satisfyingly different and more challenging. Better game play, but quite a bit harder.
There are many fine books on The Witcher in your local library (no there aren't).
Thank you.
Last edited by sonson; 01-12-2012 at 12:50 PM.
I finally got around playing Dishono(u)red. I have to say, after the first two missions, I'm a bit disappointed with it for now. Sure, the options presented to me to approach the missions are wide and escaping the Overseers by posessing a dog is awesome as heck but... I don't know. I'm not impressed with it. Maybe I'll give it a few more hours
I'm currently installing the Borderland 2 season pass (its 25% off at greenmangaming)
Gonna resume Borderlands 2 shenanigans hopefully this eve and for many eves to come!
Screenname is Tom4j on steam and i'm Level 35 true vault hunter. Feel free to add me!
In other news, spent an hour in the snail to trapdoor simulator that is Legend of Grimrock, and having a blast!
@sonson I'll give witcher another chance off the back of yourand others rps'ers commentary. Those mods should help bribe my eyes to forgive my brain.I'm failing to writing a blog, specifically about playing games the wrong way
- Join Date
- Jun 2011
- Posts
- 781
Damn i'm 100x better at Chivalry on small player servers, because my FPS is above 15 even during fights. Seriously there's so much detail (frames) lost at low FPS. I can't even score a stab on a moving target at 10 fps.
Is Chivalry really that unoptimised or something? Man, I heard more complaints about the frames in this game than the Dark Souls port
It's the first game by a ragtag crew of random people scattered throughout the world that have only ever met each other IRL once in their life. Which makes it's excellent gameplay all that much more impressive. But yeah, tech issues every freaking where. And the server browser is freaking horrible.
It's built on UE3 though so as far as performance goes it shouldn't be too hard to tweak, I imagine.
- Join Date
- Jun 2011
- Posts
- 781
My system is old, admittedly, but the performance is really really bad even with fairly modest settings.
Are you playing with in-game VSync on? That setting alone outright crippled the performance.
- Join Date
- Feb 2012
- Location
- Stockton-on-Tees, UK
- Posts
- 2,695
This week I have played 30 hours of Fallen Enchantress. I feel sympathy for anyone who had to review this game. Even after 30 hours I don't feel really qualified to say whether it's good or not.Irrelevant on further examination of the rest of the thread.
I know I meet my mom everyday and all but it seems a bit strange that I can't send any letters to Mom in Animal Crossing. She's so nice to me
- Join Date
- Jun 2011
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- 1,018
- Join Date
- May 2012
- Location
- Texas
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- 180
Knocking out some items from my backlog that I started and never finished, like Hard Reset, 1000 Amps, Amnesia, Waveform, and English Country Tune All good games that I started and then never completed due to distractions.
Hard Reset gets better the more I play it, but that's will a clear understanding of what it is and what it isn't. It's very much a Doom clone, in that it's just firefight upon firefight, with little room for exposition. I'm really coming to enjoy the weapons though. There's a lot of room for trying out the various combinations of weapons for specific enemy types. It felt cheap at first, until I figured out that they game really wants you to switch up your weapons and use the environment. Play the game by just strafing and shooting, you'll die in a hurry.
Amnesia is, well, fantastic. No doubt about it. The only reason I've taken a break from it was frustration with some puzzles, and it's an emotionally draining game. Very tense, as you all know. So I need a break from it from time to time.
I really like 1000 Amps too, but I don't know that I'll finish it. It's a flash-based platformer, and it's very polished. But I simply HATE platformers with a keyboard. How you make a platformer these days without controller support is beyond my pea-brain. I respect the game's design, and the puzzles are unique and fun. But it just sucks platforming with a keyboard. Maybe I should look into one of those keyboard-to-mouse mapping programs...
Hope to spend more time in Chivalry, Vindictus, and The Secret World too, but who knows if I'll get there. Work projects interfere...
Oh, and if anyone is interested in playing through the Portal 2 co-op game, let me know. I missed that originally and want to go back and check it out.
Thanks agentorange, Casimir Effect and sonson for the replies. It looks like I should be soon past the boring part, so I will endure some more.
Rock, Paper, Shotgonne - Come join us. We have LOOT!
The Onward March of Bundles - filling your backlog since 1911
Stalk my Steam profile, or follow my fight against the backlog on HowLongToBeat.
"You take the Klingon's detached hand"
I do find it a very overhyped game by some people, so I'm with you on that. But I can kind of see where they're coming from. Where it fails as a game it could be said to make up as a unique experience. It does things other RPGs are scared to do.
For example, without giving anything away there's a quest to solve a murder which involves collecting clues and interviewing people. There's a number of witnesses and at any point, even when you have all the clues, you can accuse them. In a Bioware game (as the RPG standard example) when you find the 'extra' piece of evidence a magical new conversation option appears that makes everything better. In The Witcher there is no new option and if you accuse the wrong person you could piss them off, making them unreceptive for the rest of the game. So just because the option is there, doesn't mean you should take it; you're encouraged to read the info you've collected rather than let the game do it for you.
Stuff like that is what makes it stand out. And to some people that elevates the game to a whole new level, forgiving many of its sins like I do with Planescape Torment or FarCry 2, for example. And like I'm sure most other people do with their favourite games.
ETA: Syndicate is like the anti-Spec Ops: The Line
Last edited by F. Lynx Pardinus; 02-12-2012 at 07:00 AM.
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- Jun 2011
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- 2,069
So I finally gave Planetside 2 a go. As expected, it's basically Battlefield 2142: Meh edition.
- the art style in this game is seriously crap, everything looks like GI Joe
- the performance is pretty horrible despite the fact that the game looks surprisingly unimpressive, especially the textures in "hard to reach" places(hint: they're not hard to reach WITH A JETPACK)
- speaking of jetpack, when you make a soldier you're instantly pushed a) into a class, b) into a squad, and c) into an (almost) certain death in the current meatgrinder. Nice
- glitches, glitches everywhere
- The class division is weird, some classes seem weirdly OP/exceedingly useful(engineers, medics) and some mostly useless(Light assault - yay, jetpack, so you can surprise one enemy by jumping on a roof and then get instantly waxed by 20 of his buddies; or infiltrator with a sniper rifle that doesn't kill enemies even with a headshot)
- unlocks seem to fall into two categories: must-have(more health, etc.) and a lot, LOT of crap you'll never buy because what's the point, really(most weapons which all have almost identical stats, scopes, etc.)
The gameplay as mentioned is a meatgrinder. And sure there can be a lot of players at once, but it doesn't really automatically make the game better, it just makes it a bigger meatgrinder. I really see no difference between three people spamming grenades down a corridor on a Titan and thirty people standing on a hill taking potshots at enemies on the walkways. I had one situation just like this, where we took an enemy base by literally doing just that; for an hour it was hill vs. base(or house vs. base, or a slightly different hill vs. base) where no progress has been made, millions of rounds were fired, and when we finally managed to capture the damn thing it was the most unimpressive victory in my gaming career. It literally seemed as if the enemy simply got bored and just let us have it because jesus, a whole hour of spam(hour I've been there. Might've actually been longer).
Yeah, the map is huge, but you'll never see or use 90% of it. Sunderers(Because Galaxies fly, and there's ridiculous oversaturation of AA in the game) get conveniently placed next to every base, so all the buffer areas/midfield(to use a T:A term) never gets fought over. The map really could be simply cut into pieces of facility + some surrounding terrain and for 99% time you're playing it wouldn't make a slightest bit of difference.
But then it would quite literally be BF2142: Meh Edition. Minus Titans. And aircraft that you can actually fly for more than thirty seconds. And with better art style. And with better weapon selection. And...
I'm starting to get impressed with Dishono(u)red. That Golden Cat mission was great. I just figured causing an 'unfortunate accident' with the steamer is much more satisfying than breaking the door down and slicing the twin's throat.
I'm currently playing Hotline Miami, Torchlight 2, Endless Space and Cargo Commander.Support Fruitbat Factory to play the best Japanese indie games in English. Our games 100% Orange Juice and War of Human Tanks are on Greenlight.
Though I kind of liked my eventual approach as well: I blinked across the outer balconies, opened the door behind him, stabbed him through the spine and was gone before the hooker even realised anything had happened.
That's the only mission where I eliminated the targets lethally. Because I just can't stand Pendleton. Also because I wanted the contents of that safe.
I've just finished the mission where you encounter the assassins, and I did a lot more running away in that one because they don't have those annoying alarms. If a guard activates the alarm in one of the mission areas, you're pretty much screwed. But running and hiding is so much more tense than quickloading whenever you're discovered, so I wish I had done it more often.
Last edited by LTK; 02-12-2012 at 08:40 AM.


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text:
Chiang-Shan Ray Li MD PhD
Associate Professor of Psychiatry and of Neurobiology
Departments & Organizations
Yale Combined Program in the Biological and Biomedical Sciences (BBS): Neuroscience
Office of Student ResearchInterdepartmental Neuroscience ProgramNeurobiologyPsychiatry: Connecticut Mental Health Center; Substance Abuse Research; Obsessive Compulsive Disorder Research Clinic; Specialized Center of Research (SCOR) on Sex and Gender Factors Affecting Women's Health
Research Interests
Systems neuroscience; Psychophysics; Neural imaging; Cognitive control; Addiction; Psychostimulant; Alcohol; Anxiety disorders more...
- Ph.D., California Institute of Technology, 06/1996
- M.D., National Taiwan University, 1989
Selected Publications
- Li C-SR, Ide JS, Zhang S, Hu S, Chao HH, Zaborszky L (2014) Resting state functional connectivity of the basal nucleus of Meynert in humans. NeuroImage 97:321-32.
- Farr OM, Hu S, Matuskey D, Zhang S, , Abdelghany O, Li C-SR (2014). The effects of methylphenidate on cerebral activations to salient stimuli in healthy adults. Exp Clin Neuropsychopharmacol. 22(2):154-65.
- Luo X, Zhang S, Hu S, Bednarski SR, Erdman E, Farr O, Hong K-I, Sinha R, Mazure CM, Li C-SR (2013) Error processing and gender shared and specific neural predictors of relapse in cocaine dependence. Brain 136: 1231-1244.


text:
GasBuddy Blog
The long-term dependability of three-year-old models has improved year-over-year, according to the J.D. Power and Associates 2013 U.S. Vehicle Dependability Study.The study, now in its 24th year, measures problems experienced during the past 12 months by original owners of three-year-old vehicles (those that were introduced for the 2010 model year). Overall dependability is determined by the number of problems experienced per 100 vehicles (PP100), with a lower score reflecting higher quality.In 2013, the dependability of models that were new or substantially redesigned for the 2010 model year averages 116 PP100, compared with 133 PP100 for models that were unchanged from the 2009 model-year--also referred to as carryover...
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text:
Speculation in commodities markets is in part to blame for the steady rise in U.S. gasoline prices, a petroleum trade group official said.Motor group AAA reports U.S. drivers paid, on average, $3.75 for a gallon of regular unleaded gasoline Tuesday, up 15 cents compared to the same time last week.A series of refinery outages, a switch to more expensive summer blends of gasoline and higher oil prices are also behind the price increase.Mark Griffin, president of the Michigan Petroleum Association, told the Detroit Free Press that spring price fluctuations are normal but usually not this early."This year it seems to be a couple of weeks early," he said. "And what drives most of it is speculation; the oil markets start speculating that the demand is going to come and that drives (price
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text: Growing Stronger in Christ is a 172-page book by Dr. Robert Jeffress. Dr. Jeffress wrote this book for you to help nurture your relationship with the Lord. Your grasp of His Word. Your connection with Him — and others. And how all of these important things work together to transform your everyday life. It's highly practical. It's honest and straightforward. In this day of chaos, turmoil, unrest — politically, spiritually, financially, and relationally — this book is meant to be a respite...filled with practical encouragement for your life and Biblical hope.


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Emacs Org-Mode
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Mariners Inn alumni Minister David P. Smith speaks about his involvement with the PRIDE Club.
Mariners Inn serves as an anchor for those struggling to navigate the treacherous waters of homelessness and substance abuse by providing professional and compassionate residential substance abuse treatment for homeless men, and providing youth, adults, and families within our community the highest quality prevention and intervention programs.
Letters from our consumers


text:
Statins (Cholesterol-Lowering Drugs)
News about Statins (Cholesterol-Lowering Drugs), including commentary and archival articles published in The New York Times.
Chronology of Coverage
Nov. 18, 2014
Study reported at annual American Heart Assn meeting finds cholesterol-lowering drug ezetimibe, or Zetia, can protect people from heart attacks and strokes; shows drug is alternative for millions of people who cannot tolerate statins or do not respond to them sufficiently. MORE
Aug. 16, 2014
Op-Ed article by Profs David S Fedson and Steven M Opal supports World Health Organization's endorsement of experimental drug use to combat Ebola outbreak in Africa; submits that statins and similar drugs used to treat patients with cardiovascular disease and diabetes may be useful in treating Ebola; holds that while use of statins presents risks, evidence suggests their efficacy for treating outbreaks of range of acute illnesses. MORE
Jul. 31, 2014
Statins, the widely used cholesterol-lowering drugs, may have a role in surgical wound healing, a new analysis suggests. MORE
Jul. 28, 2014
Cholesterol-lowering statin drugs are associated with a lower risk of Barrett's esophagus, a precancerous condition that can sometimes lead to esophageal cancer, a new study has found. MORE
Nov. 26, 2013
Critics of revised cholesterol treatment guidelines note that researchers ignored large bodies of data in favor of randomized clinical trials, adding that their efforts were severely underfunded and that they did not open results to public debate before issuing guidelines. MORE
Nov. 21, 2013
Letter from John G Harold, president, American College of Cardiology, and Mariell Jessup, president, American Heart Assn, comments on Nov 18 article on flaws found in online risk calculator for cholesterol. MORE
Nov. 19, 2013
Editorial notes potential flaws in a new online risk calculator for heart attack or stroke that may put tens of millions of healthy individuals on cholesterol-lowering statin drugs unnecessarily; urges patients who need treatment to wait until heart organizations, who released calculator, reassess its possible flaws and decide how best to fix it. MORE
Nov. 18, 2013
Deep flaws are discovered in online calculator meant to help doctors assess risks and treatment options in light of sweeping new guidelines for lowering cholesterol, potentially causing doctors to mistakenly determine that millions more people are candidates for statin drugs; revelation is major embarrassment for the American Heart Association and the American College of Cardiology, which provided the guidelines. MORE
Nov. 15, 2013
New guidelines governing use of cholesterol-lowering medicines represent huge change for doctors and a vast number of patients, but impact on drug industry is expected to be less tumultuous, largely due to relatively unprofitable status of generic statin drugs; changes do cast into doubt future of new class of cholesterol-lowering drugs known as PCSK9 inhibitors, which had been highly anticipated on Wall Street. MORE
Nov. 14, 2013
New guidelines released by American College of Cardiology and American Heart Assn advise that doctors should not put most people on cholesterol-lowering medications like statins based on cholesterol levels alone; guidelines represent surprising change from decades of protocol on preventing heart disease and stroke. MORE
Nov. 14, 2013
Op-Ed article by author John D Abramson and cardiologist Rita F Redberg criticizes recommendation by American Heart Assn and American College of Cardiology that millions of Americans should immediately start taking statins; holds recommendation is consequence of simply expanding the definition of who should take drugs and who will benefit the pharmaceutical industry more than anyone else. MORE
Nov. 13, 2013
Nation's leading heart organizations release new guidelines fundamentally reshaping use of cholesterol-lowering statin medicines; patients on statins will no longer need to lower cholesterol levels to specific numerical targets, but will simply take right dose; previously, emphasis on lowering cholesterol levels by specific amounts meant patients not hitting target levels with statins alone were often prescribed additional drugs. MORE
Oct. 2, 2013
A new study suggests statins may have a beneficial side effect: reducing gum inflammation, which is a known risk factor for plaque buildup in arteries. MORE
Sep. 25, 2013
In one of the largest studies ever done on the subject, researchers have found that taking statins, the widely used cholesterol-lowering drugs, is associated with an increased risk for cataracts. MORE
May. 6, 2013
A new study suggests that men with prostate cancer who take statins may have a lower risk of dying from the disease than those who do not. MORE
Nov. 6, 2012
Use of experimental drugs in trials reduced so-called bad cholesterol by about 40 to 70 percent in a matter of weeks, equivalent to the reduction achieved by the most effective statins like Lipitor; pharmaceutical companies are racing to bring drugs to market. MORE
Mar. 27, 2012
Science Q&A on whether the rate of death from heart attacks in the United States been going down in the years since people have been taking statins. MORE
Mar. 6, 2012
Dr Mary A Whooley study published online in The Journal of Clinical Psychiatry finds that the use of statin drugs to lower cholesterol in people with stable coronary artery disease is associated with a significantly reduced risk for depression. MORE
Feb. 29, 2012
Food and Drug Administration is adding new safety alerts to the prescribing information for statins, the cholesterol-reducing medications that are among the most widely prescribed drugs in the world; officials cite rare risks of memory loss, diabetes and muscle pain for the warnings, but say drugs are still extremely beneficial and safe. MORE
Dec. 20, 2011
Study published in the The Journal of Infectious Diseases finds that statins, commonly prescribed for the prevention of cardiovascular disease, also appear to reduce the risk for death in patients hospitalized with the flu; study is co-authored by Dr Ann R Thomas of the Oregon Public Health Division. MORE
There are no additional abstracts to display.
Ask Well: Statins and Your Sex Life
The science on statins and sexual function is inconclusive, but it does appear that taking a statin can affect a person's sex life, in both positive and negative ways.
April 3, 2015, Friday
MORE ON STATINS (CHOLESTEROL-LOWERING DRUGS) AND: Statins (Cholesterol-Lowering Drugs) , Sex
Tests of Cholesterol Drugs Offer Hope of Reducing Heart Attacks and Strokes
Researchers cautioned, however, that the studies were small and meant to assess whether the drugs safely lowered cholesterol, not whether they staved off heart attacks.
March 16, 2015, Monday
MORE ON STATINS (CHOLESTEROL-LOWERING DRUGS) AND: Cholesterol , Cleveland Clinic , Los Angeles (Calif) , San Diego (Calif) , New England Journal of Medicine , Heart , Stroke , Drugs (Pharmaceuticals) , Amgen Inc , Regeneron Pharmaceuticals Inc , Sanofi SA , Statins (Cholesterol-Lowering Drugs) , Nissen, Steven E
Study Finds Alternative to Anti-Cholesterol Drug
The finding, which showed that the drug ezetimibe lowers LDL cholesterol, can help millions who cannot tolerate statins or do not respond to them sufficiently.
November 18, 2014, Tuesday
MORE ON STATINS (CHOLESTEROL-LOWERING DRUGS) AND: Cholesterol , Heart , Stroke , Zetia (Drug) , Statins (Cholesterol-Lowering Drugs) , American Heart Assn , Califf, Robert M
Can Statins Help Treat Ebola?
Experimental treatments are in short supply, but affordable and widely available drugs may work.
August 16, 2014, Saturday
MORE ON STATINS (CHOLESTEROL-LOWERING DRUGS) AND: Ebola Virus , Statins (Cholesterol-Lowering Drugs) , Epidemics , Africa , Drugs (Pharmaceuticals) , ZMapp (Drug)
Statins Don't Require Routine Liver Tests
There is no need for people on statins to have a test for the sole purpose of monitoring liver function.
August 11, 2014, Monday
MORE ON STATINS (CHOLESTEROL-LOWERING DRUGS) AND: Russo, Mark W , Hepatology (Journal) , Liver , Statins (Cholesterol-Lowering Drugs)
Statins May Speed Wound Healing
Statins, the widely used cholesterol-lowering drugs, may have a role in surgical wound healing, a new analysis suggests.
July 31, 2014, Thursday
MORE ON STATINS (CHOLESTEROL-LOWERING DRUGS) AND: Annals of Thoracic Surgery, The (Journal) , Surgery and Surgeons , Statins (Cholesterol-Lowering Drugs)
Statins Tied to Lower Risk of Barrett's Esophagus
Cholesterol-lowering statin drugs are associated with a lower risk of Barrett's esophagus, a precancerous condition that can sometimes lead to esophageal cancer, a new study has found.
July 28, 2014, Monday
MORE ON STATINS (CHOLESTEROL-LOWERING DRUGS) AND: Cholesterol , Drugs (Pharmaceuticals) , Esophageal Cancer , Statins (Cholesterol-Lowering Drugs) , El-Serag, Hashem B , Gastroenterology (Journal)
3 Things to Know About Niacin and Heart Health
New studies are adding to concerns about the safety and effectiveness of niacin, a popular drug for the prevention of cardiovascular disease.
July 16, 2014, Wednesday
MORE ON STATINS (CHOLESTEROL-LOWERING DRUGS) AND: Krumholz, Harlan M , New England Journal of Medicine , National Institutes of Health , Medicine and Health , Heart , Statins (Cholesterol-Lowering Drugs) , Niacin , Stroke , Cholesterol
A New Women's Issue: Statins
An increasingly vocal group of cardiologists argue that many women are taking the cholesterol-lowering medications unnecessarily.
May 5, 2014, Monday
MORE ON STATINS (CHOLESTEROL-LOWERING DRUGS) AND: Medicine and Health , Heart , Women and Girls , Statins (Cholesterol-Lowering Drugs) , Cholesterol
Do Statins Change Our Eating Habits?
Are statins giving people license to eat? A 12-year study has found that people who use statins gradually increase their intake of fat and calories.
May 1, 2014, Thursday
MORE ON STATINS (CHOLESTEROL-LOWERING DRUGS) AND: Weight , Statins (Cholesterol-Lowering Drugs) , Cholesterol
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text:
Author Affiliations: Stanford Prevention Research Center, Department of Medicine, and Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California (Dr Ioannidis); and Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece (Drs Ioannidis and Panagiotou).
Context Many biomarkers are proposed in highly cited studies as determinants of disease risk, prognosis, or response to treatment, but few eventually transform clinical practice.
Objective To examine whether the magnitude of the effect sizes of biomarkers proposed in highly cited studies is accurate or overestimated.
Data Sources We searched ISI Web of Science and MEDLINE until December 2010.
Study Selection We included biomarker studies that had a relative risk presented in their abstract. Eligible articles were those that had received more than 400 citations in the ISI Web of Science and that had been published in any of 24 highly cited biomedical journals. We also searched MEDLINE for subsequent meta-analyses on the same associations (same biomarker and same outcome).
Data Extraction In the highly cited studies, data extraction was focused on the disease/outcome, biomarker under study, and first reported relative risk in the abstract. From each meta-analysis, we extracted the overall relative risk and the relative risk in the largest study. Data extraction was performed independently by 2 investigators.
Results We evaluated 35 highly cited associations. For 30 of the 35 (86%), the highly cited studies had a stronger effect estimate than the largest study; for 3 the largest study was also the highly cited study; and only twice was the effect size estimate stronger in the largest than in the highly cited study. For 29 of the 35 (83%) highly cited studies, the corresponding meta-analysis found a smaller effect estimate. Only 15 of the associations were nominally statistically significant based on the largest studies, and of those only 7 had a relative risk point estimate greater than 1.37.
Conclusion Highly cited biomarker studies often report larger effect estimates for postulated associations than are reported in subsequent meta-analyses evaluating the same associations.
Many new biomarkers are continuously proposed1- 3 as potential determinants of disease risk, prognosis, or response to treatment. The plethora of statistically significant associations4,5 increases expectations for improvements in risk appraisal.6 However, many markers get evaluated only in 1 or a few studies.7 Among those evaluated more extensively, few reach clinical practice.8
This translational attrition requires better study. Are the effect sizes proposed in the literature accurate or overestimated?9 It is interesting to address this question in particular for biomarker studies that are highly cited. Many of these risk factors are also evaluated in meta-analyses10 that allow overviews of the evidence. However, some meta-analyses may suffer bias from selective reporting, especially among small data sets11- 13; then large studies may provide more unbiased evidence.
Here, we examined biomarkers that had been evaluated in at least 1 highly cited study and for which at least 1 meta-analysis had been performed for that same association. We aimed to compare the effect size of these associations in the most highly cited studies vs what was observed in the largest studies and the corresponding meta-analyses.
We considered biomarkers that had a relative risk (RR) estimate presented numerically in the abstract of an article that had received more than 400 citations in ISI Web of Science until December 2010. The threshold of 400 citations was decided a priori, to target approximately the top 3% of biomarker studies published in influential journals. Of those, we focused further on biomarkers with published meta-analyses on the same association. Eligible RR metrics included risk ratios, odds ratios, and hazard ratios. Log odds scores were excluded.
We considered all markers of disease risk, prognosis, or treatment response representing body fluid, tissue, or imaging measurements. We did not consider demographic, anthropometric, social, environmental, psychological, and behavioral factors unless represented by a fluid, tissue, or imaging measurement. We did not consider associations with other markers and nonclinical outcomes.
Meta-analyses were eligible if they had addressed the same association (same marker, same outcome) as the one highlighted in the abstract of the highly cited study. When several eligible RR estimates appeared in the abstract of the highly cited study, we selected the one presented first.
Screening citation counts for all biomarker studies is extremely difficult because there are probably more than 100 000 studies published to date. Instead, we focused our searches on 24 nonreview biomedical journals that receive very high numbers of citations (per 2009 Journal Citation Reports) and that may publish on new biomarkers. These journals are (in decreasing total citations) Nature, PNAS, Science, New England Journal of Medicine, Cell, Lancet, Circulation, Cancer Research, Blood, Journal of Immunology, JAMA, Journal of Clinical Oncology, Journal of Clinical Investigation, Neurology, BMJ, Nature Genetics, Journal of Experimental Medicine, Journal of Clinical Endocrinology and Metabolism, Journal of the American College of Cardiology, Cancer, Gastroenterology, Clinical Cancer Research, Pediatrics, and Journal of the National Cancer Institute (JNCI).
We searched for potentially eligible highly cited studies in ISI Web of Science (last update December 26, 2010) using the search risk ratio OR relative risk OR odds ratio OR hazard NOT random*. The last item aimed to exclude randomized trials, which use RRs predominantly for treatment effects rather than biomarker associations. When 2 or more highly cited articles from the same cohort or study were identified, we included only the one published earlier. To test the sensitivity of the search strategy, we also searched without any journal limits for articles published in 2002: 9326 items were retrieved for that calendar year alone, vs 696 with the search limited to the 24 selected journals; the journal-unlimited search yielded 12 eligible highly cited biomarker studies, 10 of which (83%) were from the 24 journals.
For each potentially eligible highly cited biomarker study, we searched PubMed (last update January 3, 2011) for meta-analyses of the selected association highlighted in the abstract of the highly cited study (same biomarker and outcome). The search used the biomarker name and synonyms, limited to publication type = "meta-analysis." Whenever multiple eligible meta-analyses existed, we identified whichever included the most studies. In each meta-analysis, we also identified the largest study (the one with greatest weight [smallest variance]).
For each highly cited study, we extracted information on journal, publication year, number of citations, and information on the selected RR: the biomarker of interest, condition/outcome implicated, sample size and number of outcome events, RR estimate, and corresponding exposure contrast.
For each meta-analysis, we extracted information on the journal; first author; total sample size and number of events; sample size and number of events in the largest study; the years of the published studies; summary RR estimate in the meta-analysis and 95% confidence interval (CI) by random effects14 (or fixed-effect calculations, if random effects were not presented at all); RR in the largest study and its 95% CI; RR in the index highly cited study and its 95% CI, as given in the meta-analysis; and type of RR and exposure contrast used in the meta-analysis. When RR estimates and CIs were only shown graphically in forest plots, we perused the corresponding primary study publications. If this remained unclear, we used the open-source software Engauge Digitizer (version 4.1) to extract numbers from the graphically presented information.
Biomarkers are sometimes tested independently, but their true clinical value is best appreciated when one can document whether they confer incremental information beyond what other variables and other biomarkers can provide. We examined all the evaluated highly cited studies and all the respective meta-analyses to record how many used unadjusted effects, how many provided adjusted effects adjusting for factors other than biomarkers, and how many adjusted also for other biomarkers.
Finally, we noted whether the RR estimate and 95% CI for the highly cited study as extracted from each meta-analysis were identical to those reported in the abstract of the highly cited study. Whenever not identical, we noted whether this was due to differences in exposure contrast, adjusting covariates, or sample size (a larger or smaller data set included in the meta-analysis than in the original highly cited publication). For comparison against the largest study and the meta-analysis results, we used for consistency the RR estimate of the highly cited study as reported in the meta-analysis. Whenever a meta-analysis did not include the highly cited study, it was not considered eligible, because it addressed potentially a different question than the highly cited study. However, we accepted as eligible those meta-analyses that (1) had replaced the highly cited study in their calculations with data from a larger data set that included the data from the highly cited study; (2) had excluded the highly cited study because of some technical issue (eg, Hardy-Weinberg violation in a genetic study), but the data addressed the same question; or (3) presented collaborative meta-analyses of individual participant data that did not have the raw data from the highly cited study even though it addressed the same question. In these 3 cases, for comparison against the largest study and meta-analysis result, we used the RR estimate of the highly cited study as reported in its original abstract. When the exposure contrast of categorical variables was different between the highly cited study and the corresponding meta-analysis, the RR was approximated for the same contrast as used in the meta-analysis, after converting exposure contrasts to standard deviation equivalents.
Data extraction was performed independently by 2 investigators. Discrepancies were discussed to reach consensus.
We compared the magnitude of the effect sizes (RRs) in the highly cited study against the meta-analysis and against the largest study using the same exposure contrast. Exposures were coined consistently to represent RR values greater than 1.00 in the highly cited study, eg, if a highly cited study gave an RR of 1.5 for above vs below median values of the biomarker, this was coined to become an RR of 0.67 for below vs above median values of the biomarker. We estimated for how many associations the RRs were in opposite direction, larger, more than twice as large, more than 4 times as large, or different beyond chance in the highly cited vs the largest study and in the highly cited study vs the meta-analysis. We also calculated the ratio of the RR estimates (relative relative risk [RRR]) and their 95% CIs. All analyses were conducted in Stata version 10.1 (Stata Corp, College Station, Texas). All P values are 2-tailed.
Among 14 025 articles, 377 had received more than 400 citations. Of those, we identified 113 highly cited biomarker studies that listed at least 1 RR for a biomarker in the abstract.
Of the 113 studies, 13 were meta-analyses by themselves and 100 were primary studies. We identified published systematic reviews (n = 44) that could potentially correspond to 61 of the 100 associations. On further scrutiny, 26 associations were excluded, because the RR in the abstract was possibly wrong and could not be identified in the full text of the highly cited article (n = 1), systematic reviews did not provide any summary estimate for the eligible association (n = 6), another highly cited study from the same population cohort had been published earlier (n = 1), the highly cited study addressed different risk factors (n = 6) or different outcomes (n = 3) or had a different design (n = 4) from the studies considered eligible for the meta-analysis, or no study-specific RRs could be retrieved from the meta-analysis (n = 5). Therefore, 35 highly cited studies15- 49 published between 1991 and 2006 remained eligible (Table 1). For each of 2 associations (C-reactive protein and coronary heart disease, Helicobacter pylori and gastric cancer) there were 3 eligible highly cited studies; thus, 31 independent meta-analyses50- 80 were considered.
The 35 eligible highly cited articles had received a median of 645 (interquartile range [IQR], 526-1054) citations vs 609 (IQR, 503-804) for the 65 excluded articles (P = .83). The median publication year of eligible articles was 1996 (IQR, 1995-2000) vs 1998 (IQR, 1995-2001) for those excluded (P = .07).
The highly cited biomarkers (Table 1) included genetic risk factors (n = 11 associations), blood proteins (n = 3), other blood biomarkers (n = 8), infectious agent biomarkers (n = 6), and others (n = 7). Cancer-related (n = 14) and cardiovascular-related (n = 12) outcomes predominated. The median sample size for the 35 highly cited studies was 518 (IQR, 218-1327), and median number of events was 197 (IQR, 103-504). The median RR was 2.50 (IQR, 1.70-4.08). Diverse exposure contrasts were involved (Table 1). The 35 studies were published in 10 different journals (New England Journal of Medicine, n = 13 studies; JAMA, n = 4; JNCI, n = 4; Nature, n = 3; Lancet, n = 3; other, n = 8).
Thirty-one of the 35 associations were statistically significant, while 4 were not (ACE deletion-insertion polymorphism and ischemic heart disease,29 penicillin resistance and pneumococcal pneumonia mortality,32 insulinlike growth factor 1 levels and breast cancer in postmenopausal women,40 and total estradiol levels and breast cancer43). In 3 of these 4, other statistically significant associations were also reported in the abstract of the same highly cited study.
Table 2 shows the characteristics of the meta-analyses corresponding to the eligible highly cited studies. These meta-analyses, published between 1998 and 2010, included a median of 24 (IQR, 12-42) primary studies. Five were meta-analyses of individual patient data.57,65,68,71,74 For 18 associations, the highly cited was published early (within the first 2 years in the accumulation of evidence), while in the other 17 it was published later (median, 6 years [IQR, 5-13] in the accumulation of evidence). The median reported sample size was 12 128 (IQR, 4267-30 650); median number of events was 4790 (IQR, 2862-10 451).
The median sample size of the largest studies was 1820 (IQR, 721-5457) and median number of events was 509 (IQR, 123-1121). In 3 cases (C-reactive protein levels and coronary heart disease,25 NS5A2209-2248 [amino acid sequence 2209 to 2248 of nonstructural protein 5A] and interferon response in hepatitis C virus infection,31 and bone mineral density and fracture37), the largest study was the highly cited one. Excluding these 3 cases, the median number of citations in the largest studies was only 79 (IQR, 34-159). The largest studies were published a median of 5 years (IQR, 2-8) after the highly cited study, but in 3 cases they were published before the highly cited studies.
For 15 of the 35 studies, the biomarker effect was assessed in unadjusted analyses, and in the other 20 it was adjusted for other variables; in 7 of these studies, the adjusting variables also included other biomarkers. Similarly, for the meta-analyses, adjustments for other variables occurred in 21 cases and 7 included also other biomarkers (eTable).
Table 3 shows comparatively the effect sizes in each highly cited study, meta-analysis, and largest study. Of note, in 23 of the 35 associations, there were some differences between the RR reported in the original highly cited study and how it was represented in the meta-analysis in terms of exposure contrast (n = 18), adjusting covariates (n = 9), and/or sample size (n = 7). However, the difference was equally likely to yield a smaller or larger estimate in the meta-analysis representation of the study results than in the original abstract of the highly cited study.
For 30 of the 35 associations (86%), the highly cited studies had a stronger effect estimate than the largest study, for 3 the largest and highly cited study coincided, and only twice was the effect estimate stronger in the largest than in the highly cited study (Figure). The RR estimate was in the opposite direction in the highly cited than in the largest study in 5 associations, and the increase was more than 2-fold greater in another 20 associations (more than 4-fold in 13 associations). Both early- and late-published highly cited studies showed more extreme results than those found in meta-analyses of these biomarkers (eFigure 1). Differences were beyond chance (RRR 95% CIs excluding 1.00) in 9 associations: 5 for which the highly cited study was published early (in the first 2 years of accumulation of published evidence) and 4 for which the highly cited study was published late. Of the 9 discrepancies, 3 involved highly cited studies for which the effect sizes had been adjusted for other variables.
Diagonal lines represent equal effects between the highly cited study and the largest study (A) or the meta-analysis (B), respectively. A, Not shown are 3 topics whereby the highly cited study was the same as the largest study. B, Meta-analyses may include the data from the highly cited studies, but the latter are usually small compared with the corresponding meta-analyses (median, 5%; interquartile range, 2%-12%, of the meta-analysis sample size).
For 29 of the 35 highly cited studies (83%), the corresponding meta-analysis found a smaller effect (Figure). The RR estimate was in the opposite direction in the highly cited than in the meta-analysis in 4 associations and the increase was more than 2-fold greater in another 14 associations (more than 4-fold in 7 associations). Both early- and late-published highly cited studies showed larger effects than those in meta-analyses (eFigure 2). Differences were beyond chance in 11 associations: 8 in which the highly cited study was published early (in the first 2 years of accumulation of published evidence) and 3 in which the highly cited study was published late. Of the 11 discrepancies, 6 involved highly cited studies where the effect estimates had been adjusted for other variables.
Only 15 associations were nominally statistically significant based on the largest studies and of those 7 had a point estimate RR greater than 1.37. Thirty-two of the 35 associations showed nominally statistically significant increased risk based on the meta-analyses and of those 18 had a point estimate RR greater than 1.37.
This empirical evaluation of 35 top-cited biomarker studies suggests that many of these highlighted associations are exaggerated. In some cases, these markers may have no predictive ability, if one trusts the subsequent replication record, in particular the results of the largest studies on the same associations. Less than half of these biomarkers have shown nominally significant results in the largest studies that have been conducted on them, and only 1 in 5 has shown an RR greater than 1.37. There are several true associations, but they correspond predominantly to small or modest effects with uncommon exceptions. Such effects, even if genuine, may have only incremental translational value for clinical use.
The results of highly cited studies were often in stark contrast against both the largest study on the same association and the corresponding meta-analysis. Occasionally, the contrast was more prominent against the largest study. Meta-analyses of risk factors may have more inflated effects themselves, because typically they include also the highly cited studies and they may suffer from publication and other selective reporting biases.106- 111 It is probably less common to see smaller effect sizes in large studies due to poorer quality of biomarker and outcome measurements in grand-scale investigations or different population characteristics.
Several reasons could explain false-positive and inflated results among the examined highly cited investigations.9,112 Many of these studies were relatively small and among the first to report on the association of interest. Discoveries made in small studies are prone to overestimate or underestimate the actual association.9 Interest in publishing major discoveries leads to selective reporting from chasing significance. Half of the highly cited studies were published early and this may also have given them a citation advantage (more time to accrue citations). However, half of the highly cited studies were not published early in the accumulation of evidence, and often these attractive articles were among the late-appearing studies on the question of interest. There are some cases where the highly cited studies were even published after the largest study in the field. More extreme estimates of associations can be seen in both early studies and late-appearing studies.
The potential exaggeration of effects was seen in almost all cases that we analyzed, but some exceptions may also occur. Even in those uncommon exceptions where the effect estimate was smaller in the highly cited study than in the meta-analysis, a similar mechanism of preference for attention-drawing results may have applied, but simply a "negative" result was felt to carry more notoriety. For example, in 1 occasion the highly cited study showed that penicillin resistance unexpectedly did not increase the risk of death from pneumococcal pneumonia,32 while the meta-analysis showed an increase in mortality.63 However, in the large majority, notoriety is associated with large rather than paradoxical null effects.
We should acknowledge that several of the highly cited biomarkers probably have genuine associations; a minority have even large effects, eg, the associations of gene loci such as CFH with age-related macular degeneration,18 prothrombin G2010A and venous thrombosis,49 and CYP2C9 and bleeding risk36; the associations of H pylori with gastric cancer and atrophic gastritis21- 23,38; or the association of NS5A mutations with interferon response.31 Nevertheless, even in these cases, highly cited studies described often optimistic effect estimates. Some of these biomarkers have started being used in clinical practice.113 Their cost-utility depends on their cost and on their discriminating ability.114,115 If discriminating ability is overestimated, markers may become overpriced. Biomarkers with large populations of potential users could cause major escalation of health care costs with limited benefits. Obviously, adopting markers with no discriminating ability would be even worse. Clinical biomarker use requires robust evidence and safeguards.3,116,117
Novel biomarkers that purport to assist in complex problems related to decisions about diagnosis and prognosis with relatively simple objective measures are often viewed oversimplistically as major advances. However, biomarkers may start having a potential clinical utility when it can be demonstrated that they can provide incremental information beyond already known predictors and any other known biomarkers.118 Regardless of such adjustments, the results of highly cited biomarker studies that appear in major journals are often substantially overestimated. This should lead to reinforcing healthy skepticism about interpreting this literature. This does not mean that no biomarkers of any use are possible to discover, but that the standards for claiming success should be higher. These standards should include not only prospective design, careful analysis plans, and meticulous reporting, but also extensive replication and validation of proposed biomarkers in large independent studies and assessment of their incremental ability. Until such studies are available, emphasis on single studies with highly promising results may be premature.
Some limitations should be discussed. First, we selected only highly cited studies that presented RRs in their abstracts. This removed subjectivity in selecting the most important RR estimate among the many presented in the full text of these articles. Moreover, many highly cited biomarker studies do not report RR estimates in their abstract and were thus excluded from our sample. It is unlikely, however, that the replication record of such biomarkers would be better. Second, we were able to retrieve meta-analyses corresponding to only a third of the highly cited primary studies. It is unlikely that biomarkers lacking a corresponding meta-analysis are enriched in successful replications. If anything, meta-analyses are more likely to conduct for biomarkers that had more and successful replications. Third, the results may not be directly extrapolated to studies of biomarkers that do not get much cited. Citation bias, the preference to cite extreme results, is described in diverse fields.119- 122 However, less-cited biomarkers are probably less influential in scientific circles and less likely to draw enough attention to become applied in practice. Finally, there is no consensus on what threshold characterizes a highly cited study. One can set also citation criteria that adjust for the time since publication to compare citations of articles published in very different years. However, we preferred to select articles that have clearly achieved cumulative recognition in the literature rather than those that may (or may not) achieve this in the future.
Merely because an article is highly cited does not indicate that the reason for citing it is that it is considered the best science. It is difficult to judge the quality of biomarker studies, mostly because reporting of methods in this literature has been largely elliptical to date.11,13,123 This further reinforces the notion that citing investigators pay more attention to reporting more extreme estimates rather than the robustness of the methods, which is often either intangible or difficult to compare between different studies. Readers should be cautious when authors cite single studies and not meta-analyses, and authors should be more careful in what they cite.
While we acknowledge these caveats, our study documents that results in highly cited biomarker studies often significantly overestimate the findings seen from meta-analyses. Evidence from multiple studies, in particular large investigations, is necessary to appreciate the discriminating ability of these emerging risk factors. Rapid clinical adoption in the absence of such evidence may lead to wasted resources.
Corresponding Author: John P. A. Ioannidis, MD, DSc, Stanford Prevention Research Center, Stanford University School of Medicine, Stanford University, Medical School Office Bldg, Room X306, 251 Campus Dr, Stanford, CA 94305 (email@example.com).
Author Contributions: Dr Ioannidis had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Ioannidis.
Acquisition of data: Ioannidis, Panagiotou.
Analysis and interpretation of data: Ioannidis, Panagiotou.
Drafting of the manuscript: Ioannidis.
Critical revision of the manuscript for important intellectual content: Ioannidis, Panagiotou.
Statistical analysis: Ioannidis, Panagiotou.
Study supervision: Ioannidis.
Conflict of Interest Disclosures: Both authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
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|Introduction | Nikon AF Nikkor 20mm f/2.8D | Nikon AF Nikkor 28mm f/2.8D | Nikon AF Nikkor 35mm f/2D | Nikon AF Nikkor 85mm f/1.8D
With a DxOMark overall score of 19, the Nikon AF Nikkor 35mm f/2D is still a good lens, just like both the 20mm and 28mm lenses in the AF-D line that we previously analyzed in parts 1 & 2 of our "Oldies" review.
|Strong points
|Weak points
|Satisfactory sharpness
|Susceptible to vignetting (a classic problem for this kind of lens)
|A very bright lens
|Very little distortion
|Negligeable chromatic aberrations
|Very light (205g, just like the 28mm f/2.8D)
|Affordable (365 USD)
With a DxO Mark score of 27, the 35mm f/1.4G comes out significantly ahead of its predecessor.
The advantages of Nikon 35mm f/1.4G:
The advantages of the Nikon 35mm f/2.0D:
Strictly in terms of image quality, the youthful 35mm 1.4G unquestionably takes the lead. But again, it's important to keep the 35mm f/2.0D's many charms in mind— i.e., it gets pretty darned good results for an older lens that is both very light-weight and low in price.
Sony still needs to make more progress before it can justify the price difference between its lens and the Nikon 35mm f/2.0.
For those who aren't put off by manual focusing, the Samyang remains competitive in this lens category.
Finally, here's how the DX 35mm f/1.8G and our vintage Nikkor 35mm compare when mounted on a Nikon D90.
To provide photographers with a broader perspective about mobiles, lenses and cameras, here are links to articles, reviews, and analyses of photographic equipment produced by DxOMark, renown websites, magazines or blogs.
Here is a new series featuring the results of Pentax prime lenses mounted on the compatible camera with the best resolution thus far, the Pentax K5. (But as usual, you can consult DxOMark to see the results for these lenses when mounted on other compatible camera bodies, such as the Pentax K7 or Km.)
After looking at the Nikon AF-D series, DxOMark continues working its way through the history of photography by presenting the measurements for another "antique" lens, the Canon EF 20-35mm f/3.5-4.5 USM.


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After you've waited patiently to finally fit a ride in, and nothing throws a wrench in your fun like running out of water midway through a bike outing. The Camelbak Rogue is an excellent hydration pack for a quick road ride across town or a short spin on your local singletrack. The Rogue features an air mesh harness and air channel back panel to promote ventilation and keep the heat off your back and shoulders. The included 2L Antidote™ reservoir can be refilled on the fly via the quick-release flap on the front of the pack. Two external pockets store small items like keys, wallet, phone, or a packable layer. Stretch elastic side panels provide for expansion and twin compression straps shrink the pack down when empty. Reflective back strip with tab to clip on a blinker for early morning and evening safety.
Antidote™ Reservoir Features: 1/4 turn - easy open/close cap, lightweight fillport, center baffling and low-profile design, patented Big Bite™ Valve, HydroGuard™ technology, PureFlow™ tube, easy-to-clean wide-mouth opening
Key Pack Features: External fill, dual compression straps, overflow storage, reflectivity, and bike tool organizer pocket
Designed to Carry: Multi-tool, pump, spare tube, phone, wallet, keys
CamelBak® Got Your Bak™ Guarantee: If we built it, we'll Bak it™ with our lifetime guarantee.
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Comments about Camelbak Rogue Pack 2014:
First hydration pack after winding up with an empty water bottle too often.
Lots of room for tools, snacks, etc. Works well since I ride two different bikes.
Comfortable, hardly notice the weight. Easier to drink from on the trails.
Downside is having to suck water through the hose/mouthpiece. Compared to squeezing a huge gulp from a bottle, takes some getting used to.
Best Uses
Comments about Camelbak Rogue Pack 2014:
I've had trouble finding a bottle cage that would allow me to run two caged on my 2011 Redline Monocog 29'r, so I decided to give a hydration pack a try. No real gripes thus far.
The webbing and straps offer plenty of adjustability, and overall it's quite comfortable for the 2-3 hour rides I take it out on. It's plenty stable on my back, even without the chest strap. Water flow is excellent, and refilling isn't too bad (though I would hate to have to do it at anything other than a faucet.) Setting it up to dry has proven a bit more inconsistent than I'd like, but I'm getting the hang of it more and more with every use.
Storage-wise, there is plenty to work with. I am especially fond of the space between the bottom bag and the reservoir compartment itself, which I didn't even know existed at the time of purchase; very handy for larger items, such as granola bars, or a small pump.
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Comments about Camelbak Rogue Pack 2014:
i don"t like carrying things on my back but with this one i made an exception. i tried it before from a friend and got to say it's comfy, plus i get to carry tools, power bars, shock pump etc.. things you may need for a nice riding hiking day.
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Anne Frank: her life in words and pictures from the archives of the Anne Frank House
The scrapbook from a young girl who did not survive the Holocaust, showing pictures of Anne and her family during this terrible time.
The scrapbook from a young girl who did not survive the Holocaust, showing pictures of Anne and her family during this terrible time.
11 short stories about everyday problems of growing up
Jill goes along with the rest of the fifth-grade class in tormenting a classmate and then finds out what it's like when she, too, becomes a target.
After a plane crash, 13-year-old Brian spends 54 days in the Canadian wilderness, surviving with only the aid of a hatchet.
Georgina persuades her younger brother to help her in an elaborate scheme to get money by stealing a dog and then claiming the reward that the owners are bound to offer.
After his parents die, Jeffrey Lionel Magee's life becomes legendary, as he accomplishes athletic and other feats which awe his contemporaries.
Twelve-year-old Catherine just wants a normal life, which is near impossible when you have a brother with autism and a family that revolves around his disability. Catherine has to ask herself: What is normal, anyway?
Mibs Beaumont is turning 13, and discovers her "savvy"--a magical power unique to each member of her family--just as her father is injured in a terrible accident.
When their beloved Aunt Grace dies, Dan and Amy - along with other Cahill descendants - are faced with an unusual choice: inherit one million dollars or participate in a perilous treasure hunt.
An alley cat named Aldwyn passes himself off as a magical animal companion to a young wizard in training. Next thing they know, they are trying to save the kingdom!


text: Many students fear starting school, whether its starting a new school or the transition from one grade to the next. Students don't need any more stress than necessary when beginning school or switching to a different campus. I have compiled a list of apps that will reduce the stress and make school more enjoyable for all students who have an IOS device. Lets face it if our kids aren't happy we aren't happy. These applications can benefit parents too.


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|The Converse Chuck taylor All Star Pro Skate Shoe features a canvas upper, heavy-duty rubber outsole, rubber toe cap for added durability and protection, metal eyelets for quick and easy lacing, Converse logo at the side and is canvas-lined with lightly padded footbed for comfort, vulcanized construction for true board feel and flexibility.


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Situated just south of Orlando, our hotel's location is convenient to the area's best parks, restaurants and attractions, as well as many major businesses. Whether you're in town for business or pleasure, the Holiday Inn Express Hotel & Suites® Orlando South - Davenport is a great place to relax, have fun and get the job done.
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Our hotel is near Disney World, making it an ideal place to stay when you want to spend time with friends and family at the Magic Kingdom. We're also near parks like Universal Studios, Florida and SeaWorld Orlando, amazing golf courses and attractions like Bok Tower Gardens and Fantasy of Flight. If you're into sports and nature, you'll enjoy the expansive Lake Myrtle Sports Complex and the beauty of natural areas like Shingle Creek Regional Park, both of which are near our Davenport, FL hotel.
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Maroon 5 Lyrics
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Are you a MAROON 5 fan? Install for FREE this app with all the songs lyrics of your favourite band! All the lyrics of all of their albums are in this application for your android device. Go over them whenever or wherever you want while listening to their music!
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