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Health Sciences Complex
Events at STAR
- Need space for an event? Visit our Event Planning page to start the process!
Getting Involved
Letter to the Editor - News Journal
"Let's all hail STAR Campus program. There is a treasure in our community of which many are unaware. It is the STAR Campus at the University of Delaware in Newark. I recently went to physical therapy for a back problem. I was more than impressed with this facility and staff. The physical therapists are extremely knowledgeable, caring and observant. They are working with top-notch students. UD ranks No. 2 in the nation for its Physical Therapy program. They have access to the latest and most innovative equipment. Kudos to Dr. Kathleen Matt, dean and visionary of this gem."-- Janet McNamara, Newark, DE
Virtual Tour: STAR Campus
The University of Delaware's Science, Technology and Advanced Research Campus is the center of innovation, leading cutting-edge research in areas such as health science, cyber security, alternative energy and infrastructure.
'Modular' lab spaces planned for STAR Campus
Delaware Technology Park will create a 10,000-square-foot wet lab on the University of Delaware's Science, Technology and Advanced Research Campus for small, start-up companies officials hope will grow in the space and relocate elsewhere in the region, eventually creating jobs for Delawareans and contributing to the economy. Read More >>
SevOne to hire 200 workers, largely in Delaware
Employees will be hired to work at its 50,000-square-foot space at the University of Delaware's growing Science, Technology and Advanced Research campus. Read More >>
About the Health Sciences Complex
The University of Delaware has set the stage for the Science, Technology and Advanced Research Campus (STAR Campus) to be a center of innovation that will continue to evolve over the next half a century. The site's activities and tenants focus on science, technology, engineering and clinical practice in areas ranging from biomedicine and biotechnology to alternative energy and environmental sustainability.
In 2014, the Health Sciences Complex opened on the STAR Campus, and UD's College of Health Sciences is the first tenant to occupy the renovated building, not only providing the front door to the site but also setting the stage for the campus as a vibrant healthy community by design. The facility is fostering community connections, interprofessional training of healthcare professionals, and collaborative research between faculty and clinicians.
The first building houses the Nurse Managed Health Center and the Delaware Physical Therapy Clinic, both of which are open to the public. In addition, the facility contains high-tech meeting spaces and state-of-the-art core labs for research and education in areas including muscle performance, gait analysis, anatomy, pediatric mobility, cardiovascular disease, biochemical and biomarker analysis, and orthopedic rehabilitation. The site is also home to the Delaware Rehabilitation Institute and the Delaware Health Sciences Alliance.
Tenant space will be available at an annex for companies whose areas of business complement the mission of UD's College of
Health Sciences.
Need space for an event? Visit our Event Planning page to start the process!


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Dreadnought-Class Production Line (Spoilers?)
View Single Post
July 30 2013, 09:22 PM
Re: Dreadnought-Class Production Line (Spoilers?)
The only thing wrong with the Enterprise at all during her escape from the Vengeance was her warp drive was not 100% operational due to one coolant feed being sabotaged.
Classically, though, when main power is reduced, the entire performance of the ship suffers.
Vengeance's phasers reacted as though the shields weren't even there at all, not just blowing up but fully vapourising entire sections of the Enterprise's hull
The curious thing, just as you say, is that we never saw what shields are supposed to accomplish in this version of the 2250s-60s. In STXI, after arrival at Vulcan, raised shields do not prevent hull damage from a minor collision; the rest of shield action there is against Nero's reputedly exceptionally penetrating weapons.
Perhaps what we see is normal ship-to-ship combat for the era?
In such a case, one would expect ships to be defended with other things in addition to shields. Close-in active defenses, perhaps? In STXI, Robau and George Kirk tried to use such against Nero's missiles, almost but not quite successfully - and Sulu then demonstrated how easily a modern starship can shoot down missiles
that are not coming towards her
. Perhaps that was the key - Pike knew he couldn't defend against weapons coming directly at him, with no wingman to divert Nero's fire, and Kirk in ST:ID had no prayer of shooting down the whatevers that Marcus was firing, but could have defended a third party from these very same weapons?
Timo Saloniemi
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Jimena Patricia
Update on Jimena PatriciaJimena is married, has completed primary school and is 32 years old. She is a very responsible woman. Unfortunately, her mother is currently in a bad state of health due to which they are incurring various expenses for medicine, the hospital etc. Her mother left her in charge of her goods and other responsibilities within which Jimena is canceling debts due to her mother's poor health. This is why she needs money, since one of her cows died and she needs the milk production to continue generating income to be able to cover her debts. She wants to overcome the difficulties that they are facing.
Previous Loan DetailsSra. Jimena breeds cattle. She has 3 years of experience in the business. She used to live in Spain and with a lot of hard work she came back to Bolivia to build her own house. Now she wants to expand her livestock farm in order to have a better income. What with the expenses she had and what she... More from Jimena Patricia's previous loan »
Additional Information
About CIDRECIDRE is a Bolivian microfinance institution with a strong social commitment to the community. It works to provide quality financial services to rural and peri-urban borrowers, focusing primarily on agricultural loans for dairy farmers and micro-enterprises. CIDRE targets segments of the population that have not traditionally had access to credit, and invests in much-needed community development projects. It is currently working with coca farmers in the Chapare region to replace coca with less controversial crops. Get more involved by joining the Friends of CIDRE lending team.
Concurrent and Successive Loans
Our Field Partners often work with borrowers over a series of loans as the borrowers build credit, take out bigger loans, and expand their businesses. In order to make it easier for our Field Partners to post loans for borrowers who have been listed on Kiva before, we allow them to post successive and concurrent loans for their Kiva borrowers. This means that our Field Partners are able to post a borrower's second, third, etc., loan on Kiva without having to re-enter all of the borrower's information.
This borrower has been listed on Kiva before, so you'll see an updated loan description, as well as excerpts of the original descriptions from earlier loans. Most borrowers take out loans consecutively, meaning that they receive a second loan after having repaid the first. However, sometimes our Field Partners give out concurrent loans, allowing borrowers to take out one primary loan and a secondary "add-on" loan along with it. These "add-on" loans are typically smaller than the borrower's primary loan and serve a different purpose. Because Field Partners can now post loans as successive and concurrent loans, you will be able to track borrower progress over time and see the various ways a borrower is working with our Field Partners through funds from Kiva's lenders.
About Bolivia
133View loans »
US Dollars
Success!! The loan was 100% repaid
- Repayment Term
- 15 months (Additional Information)
- Repayment Schedule
- Monthly
- Pre-Disbursed:
- Sep 28, 2012
- Listed
- Nov 5, 2012
- Currency Exchange Loss:
- Ended:
- Dec 17, 2013


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Heads up! A newer version of this product is out!
Criteria Comments Rating
- Reception and call quality No comments
- Display Beautiful, bright display. Awesome for viewing pics/video that you take.
- Battery life No comments
- Camera No comments
- Ease of use No comments
- Design and form factor No comments
- Portability (size / weight) It's a little big, still getting used to that. Everyone who I've shown the phone to has commented on how big it is.
- Media support Cyanogen mod is awesome. I wish all Android phones would come with it.
- Durability No comments
- Ecosystem (apps, accessories, etc.) No comments
Detailed review
I bought this phone on an impulse when a friend of mine offered me his invitation. I'm coming from an HTC One M7, which I really really liked. The phone is wicked fast, it makes my HTC feel sluggish, and it had no problems switching between apps quickly. I've read reviews about how it's too big to use with one hand, I disagree. It's definitely big, but it's manageable. Cyanogen mod is pretty awesome. I read a lot of reviews that talked about how extremely customizable it is, which is true, but you'll have to pay for more themes and icon packs if you really want them. There are TONS of options though, I'm still discovering more ways to customize the experience (my favorite so far is being able to have custom colors for specific apps for your blinking notification light). I haven't experienced the camera too much, but it takes some good pictures, and the 1080/4k video is absolutely beautiful. Cyanogen's camera app is also really lightweight and intuitive. Also, so far I've had extremely fast 4G LTE service (on AT&T). I 100% recommend the phone, it's too cheap to pass up, and it has amazing performance.
good review!
0 people find this review helpful
Comments (3) subscribe to this review's comments
Hi themezzilla, I'm looking to buy oneplus phone, as I checked in google I found you have brough mobile. I dont have friends who brought oneplus to get invite. Can you please invite me to buy this mobile or if you have any other option, please suggest.
please can you send me an invite id really like to get my hands on this phone my name sikho langeni
Possible to get an invite for the OnePlusOne phone ?


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So, one of our mares came in with ringworm on her side. We've been grooming her everyday, so it just appeared yesterday. The hair was falling out around it today. Don't really know where she got it, but I washed and bleached all our brushes today to try and not cross-contaminate.
We've been putting Clotrimazole 1% anti-fungal cream on it. Would anything else be needed to supplement it, or do we just wait until it runs its course for the next couple weeks?
My yearling is turned out with the mare. They don't touch or scratch each other, as the mare usually chases away the yearling if she gets too close. Should I be concerned about separating them to prevent the ringworm spreading, or will they be okay as long as they don't share the same brushes?


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FLSmidth : Interim Report for FLSmidth & Co. A/S 1 January - 31 March 2013 Company Announcement to the Danish Financial Supervisory Authority No. 08-2013, 17 May 2013 The Board of Directors and the Group Management of FLSmidth & Co. A/S have today reviewed and approved the Interim Report for 1 January to 31 March 2013. The Interim Report has been presented in accordance with IAS 34 and additional Danish information requirements regarding interim reporting of listed companies. No review or auditing of the interim report has taken place. The Interim Report is accessible at FLSmidth's website: http://www.flsmidth.com/reports The main conclusions of the Interim Report are: Q1 is seasonally weak, and 2013 is no exception. Revenue increased 17% versus Q1 2012 whereas order intake was down 22%. Fewer large orders were signed in Q1, while unannounced orders were stable. Guidance for 2013 is maintained, however skewed towards the lower end due to increased customer hesitation, market uncertainty and a certain lack of efficiency. Corrective actions are being developed and will in parallel with initiatives from the new CEO be communicated in connection with the Q2 report. The earlier announced share buyback programme will be initiated now. Financial results in Q1 2013 The order intake decreased 22% to DKK 5,027m (Q1 2012: DKK 6,421m) The order backlog decreased 3% to DKK 28,583m (end of 2012: DKK 29,451m) Revenue increased 17% to DKK 5,651m (Q1 2012: DKK 4,829m) Earnings before amortisation and impairment of intangible assets (EBITA) decreased 38% to DKK 254m (Q1 2012: DKK 408m), corresponding to an EBITA margin of 4.5% (Q1 2012: 8.4%) Earnings before interest and tax (EBIT) decreased 51% to DKK 166m (Q1 2012: DKK 341m), corresponding to an EBIT margin of 2.9% (Q1 2012: 7.1%) The profit for the period decreased 86% to DKK 34m (Q1 2012: DKK 241m) Cash flow from operating activities amounted to DKK -466m (Q1 2012: DKK -117m) Net interest-bearing debt (excl. Cembrit) amounted to DKK -3,883m (end of 2012: DKK -3,183m) Working capital (excl. Cembrit) amounted to DKK 2,335m (end of 2012: DKK 1,629m). Return on capital employed (ROCE) declined to 17% in Q1 2013 (Q1 2012: 23%) Guidance for 2013 FLSmidth & Co. A/S maintains expectations of consolidated revenue of DKK 27-30bn (2012: DKK 25bn) and an EBITA margin of 8-10% (2012: 10.1%). Market uncertainty and customer hesitation has increased in recent months, which is expected to have an adverse impact on order intake and revenue in the remainder of the year, although tender activity remains high and the service activities show no signs of weakness. As a consequence, the guidance for 2013 is now skewed towards the lower end. Corrective actions are being developed and will in parallel with initiatives from the new CEO be communicated in connection with the Q2 report. The margin guidance includes costs of a one-off nature of around DKK -200m for the Group in 2013 (2012: DKK -225m). Cash flow from investing activities (including acquisitions but excluding disposals) is expected to amount to the level of DKK -1bn in 2013 (2012: DKK -3,6bn). The effective tax rate is now expected to be 36% in 2013 (2012: 34%) due to withholding tax in Chile related to the integration of Ludowici (previous expectation 32-34%). Return on Capital Employed (ROCE) is expected to be approximately 15% in 2013 (2012: 19%). The four divisions are expected to see the following developments in 2013: Expected revenue Customer Services DKK 8-10bn Material HandlingDKK 4-6bn Mineral Processing DKK 10-12bn Cement DKK 5-7bn Expected EBITA margin Customer Services 13-15% Material Handling > 0% Mineral Processing8-10% Cement 6-8% Please address any questions to this announcement to Mr Thomas Schulz, Group CEO, telephone +45 36 18 18 00. An investor & press meeting and telephone conference regarding the Interim Report will be held today at 11:00 hours CET at the company's headquarters. For further details please visit www.flsmidth.com. http://www.flsmidth.com/en-US/News+and+Press/News/2013/Invitation+to+Investor+Meeting+Q1+2013 FLSmidth & Co. A/S Corporate Communications & Investor Relations 1st Quarter Report 2013 ------------------------------------------------------------------------------ This announcement is distributed by Thomson Reuters on behalf of Thomson Reuters clients. The owner of this announcement warrants that: (i) the releases contained herein are protected by copyright and other applicable laws; and (ii) they are solely responsible for the content, accuracy and originality of the information contained therein. Source: FLSmidth via Thomson Reuters ONE HUG#1702815
FLSmidth : Interim Report for FLSmidth & Co. A/S 1 January - 31 March 2013
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I think ddd bagged enough zuglets to make himself a strap.
The Watch Appreciation Thread (Reviews and Photos of Men's Timepieces by Rolex, Patek Philippe, Breitling, JLC etc...) - Page 1983
Styles mentioned in this thread:
What a sneaky little bastard the zuglet can be. It has now officially invaded the watch appreciation thread. LOL
Warning: Spoiler! (Click to show)
Extremely light and comfortable. Both are very light and the design of their straps are extremely well executed.
I'm pretty sure I've posted them all at one time or another, but I currently own the following.
PP 5711, PP 5167, AP 15300, Rolex 1680 Red, Rolex 116520A50B7859., Rolex 16610LV, Rolex 16710, and Omega 357350..
- Posts: 85
- Joined: 7/2010
- Select All Posts By This User
Not a fan of either. To me its like looking at half a Nautilus or half a RO. To me they are designs that only work well on an integrated bracelet. YMMV, but I find Nautiluses and RO's on straps very undesirable. Wishing you luck with whatever you decide.
Thanks, Dino. While I get that the RO bracelet is a very iconic part of the watch, I find that RG ROC on brown croc to be a real stunner. It's one of the few ROs I've ever seen in person, and it haunts me.
BTW, looks like the Entourage movie is going to feature a ton of APs. Looks like a ROC on Eric and a Diver on Drama.
+1 Same here. I miss having new episodes to watch so I can't wait for the movie to be released.
As for ROs or Nautiluses, while I like them in RG, they would have to be on a bracelet or I'd stick with steel. I don't like the little end pieces that attach to the leather strap. I have tried on a RO in RG on a bracelet and its a beautiful watch in rose. However, it gets very, very $$$$$ when its in all gold including the bracelet. Wishing you luck on your next watch adventure.
Styles mentioned in this thread:
- IWC Portuguese Automatic Steel Blue Mens Watch IW500107No reviews yet.


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- 15Promote
Art Print
Fetchby Awkwardyeti
Collect your choice of gallery quality Giclée, or fine art prints custom trimmed by hand in a variety of sizes with a white border for framing.
A boy so bored and feeling unimaginative, holds a tennis ball and gazes at his own reflection. Without looking up, he has no idea that there's a fantastic awkward dragon just waiting to play. I made this while experiencing a creative block, it was a slap in my own face - as in, "just look up, you fool!"


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- Age / Gender:
- 29, Male
- Location:
- Fayetteville, AR
- Joined:
- 8/23/07
- All Stats >
I like things. There are also some things that I dislike. Me speak'um nice english.
User Statshot
- Community Stats
Level 12 Blank Slate
Garbage Whistle
Ranked as Safety Patrol
Contact Info / Websites
Latest News
So, I got banned from the BBS for seven fucking days because I accidentally posted on a thread that was 'soft locked' by Bigbadron. I couldn't find info about 'soft locks' on any of the help pages or the new user forum post, so I think that I should not have been banned. Also, I think a week is a little harsh. I almost feel like I want to just delete my account completely. I've never posted anything hateful or racist or homophobic, and I try to be helpful, but I get banned because some megalomaniac has control issues. Fuck it.


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Cognitive Training to Enhance VA Work Program Outcomes
This study is ongoing, but not recruiting participants.
VA Connecticut Healthcare System
Information provided by (Responsible Party):
VA Connecticut Healthcare System
ClinicalTrials.gov Identifier:
First received: January 24, 2009
Last updated: December 22, 2014
Last verified: September 2012
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
No Study Results Posted on ClinicalTrials.gov for this Study
|Study Status:
|This study is ongoing, but not recruiting participants.
|Estimated Study Completion Date:
|December 2015
|Estimated Primary Completion Date:
|December 2015 (Final data collection date for primary outcome measure)


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mils & fils
after stacy left we watched everybody loves raymond. i sooo identified with last night's episode. i identify with poor debra more than you know. my mother in law is just like ray's mom. it's almost scary. so i totally understood when debra had a hard time calling her "mom". jon says "that will never happen with you and my mom huh?" no way. i just couldn't do it. i have a hard time now because i don't know what to call his parents. their 1st names feel weird because i'm not their buddy, and mr. & mrs. feels too formal. i can't wait to have kids. then i can just call them gramma & grandpa. now i just get in their line of vision when i have to talk to them and avoid at all costs having to call them from across a room. advice to all engaged couples: get it down now what you're going to call your in laws before it gets awkward. you can't switch to something cutesy years into it. it's just weird. i really liked the idea of mil & fil. for mother in law & father in law. but we're too far into it for that now.
Monthly Archives: April 2002
mils & fils after stacy left we watched everybody…
mils & fils
our 1st official dinner guest last night stacy ca…
our 1st official dinner guest
last night stacy came over for dinner. aside from our house warming, she's our 1st official dinner guest. we broke out the candles & ate in the dining room instead of the bistro table. stacy & i met in the new members class when i was joining covenant presbyterian. jon was a member there and that's where we got married. and it turns out she's from columbia, sc where i grew up. we've been friends ever since. we get together at least once a month for a dinner and last night it was at my house. jon grilled us up some steaks and we had a good time giving stacy a presentation about the food network. we couldn't believe she doesn't watch it. we love that channel.
fun things i love the website jenny pointed out w…
fun things
i love the website jenny pointed out where you can build yourself in legos. so cute.
beauty product update i'm in love with this new stuff i found. i'm not sure if it's a new product or just new to me. it's john frieda's beach blonde. it smells yummy like coconut and makes your hair thick like how it feels when you're at the beach and you don't wash the ocean water out of your hair.
3 obsessions
the other day on bob & sheri they were talking about people's 3 obsessions. that if you think about it everyone has 3 things that they think about a lot or obsess over. these are not priorities like your family etc. and they're usually pretty silly. i think they are right. i was thinking about mine and they are: the mail, beauty products (including lotions, cosmetics, hair products), and lip balm. let me explain. the mail: i have to check it. if jon checks it he sorts through it and decides what's junk and tosses it. this might mean i could miss out on a great sale somewhere or a cool catalog to leaf through. or he'll check it and leave it somewhere and i won't get to see it for days. drives me nuts. don't know why. beauty products: i have them all. or at least it feels like it. i'm such a sucker. i'll totally buy new hair stuff when i have no less than 34,097 bottles, jars etc of hair stuff in my drawer or under the sink already with approximately 1 inch of product left in them. i don't know why i don't just throw it out or better yet, use it all before buying a new thing. lip balm: this isn't included in the beauty products section because it's not about buying new lip balm, it's about having it handy. i have a tube in literally every room in the house where i hang out. i have 2 tubes in my purse, 1 in my car, 1 on my desk at work. you get the idea. i never wear something without pockets unless i know i can get to my lip balm. my mother in law even gave me this tiny beaded ivory purse that was just big enough to hold a tube for our wedding. it's a sickness i tell ya.
i love power tools this was a good weekend in a l…
i love power tools
this was a good weekend in a laid back homeowner sort of way. saturday husband and i slept in a little then headed out to qdoba for lunch. we stopped in to dean & deluca for some bread then went on a mad search for maggie moo's ice cream. it was really good. it was funny though, jon and i were the only people in there that didn't have a huge amount of children with them.
we finally made it to lowe's (which was our goal when we set out). we had to buy some weed killer and a sprayer to kill these carpenter bees which have taken over our storage building. i've never seen anything like it. these crazy bees actually drill into the wood. they've practically hollowed out our fence & gate & have drilled tons of holes in our storage building. they leave little piles of sawdust everywhere. it's just so weird. anyway, we finally get home and start working on the yard. we'd borrowed a blower, weed wacker and hedge trimmer from my mom. you don't realize how much stuff you need when you buy a house. it seems like with each project we realize what we're lacking in the tool department. we had a big time with the tools. it was fun weilding all that lawn power. i even mowed the lawn. you'd realize what a big deal that is if you knew how girly i am.
we went in once it got too dark to work and watched trading spaces. we weren't crazy about doug's blue room but the homeowner was so that's good. and the episode with the half naked chick picture was nuts. i agree with rachel about paige going on and on about how hot the girl was in the picture. let it go paige. and at first i thought it was all set up with them, but she seemed really surprised. they must have cleared it with the husband though. but how creepy to see doug rooting around in her panty drawer!
jon had to work in the morning so i cleaned the house. when he got home it was more yardwork for us. we bought the house from a lady who never worked in the yard so it's taking us a while just to get it looking decent. we returned our tools to my mom and ended up hanging out there til 9 pm. i'm sleepy this morning from going to bed so late. that daylight savings makes you forget that even though it's light out it's really late.
victim it's finally happened. my poor little com…
it's finally happened. my poor little computer has been hit with a virus. it's a sneaky one too. i've run norton anti virus and it doesn't find anything. this virus came from my friend stacey's 85 yr old grandfather who got hit with it. he sent it to her and she sent it to me and of course i opened the attachment because it's from her and BAM. so now our master email address (that we don't even use) is sending these random emails to everyone in the free world (some people we don't even know) and these emails are totally nonsensical. it's like it pulls random info and just sends it out. most of them seem to be about gambling which is weird. all of pop's (stacey's grandad) emails were in french. and now it's mucked up our desktop where all the icons scoot around the screen and won't let you click on them. i'm not equipped to deal with this! i don't know what to do!
friday five thanks to heather 1. What are your h…
friday five thanks to heather
1. What are your hobbies? painting, scrapbooking, reading, making hand drawn note cards, crochet, just about anything crafty. and since we've bought a house i have 2 new hobbies: gardening & decorating (remodeling).
2. Do you collect anything? If so, what? matchbooks from restaurants & magnets from each state, major city, and/or theme park or tourist trap we visit. i'm also obsessed with stationary & pens so i collect those things too.
3. Is there a hobby you're interested in, but just don't have the time/money to do? all of my current hobbies. i'd love to have more time to do them. i'd also like to learn how to lay tile & create tile mosaics
4. Have you ever turned a hobby into a moneymaking opportunity? i've sold some ceramic pieces i've painted and i turned my mini obsession with kitchen tools into a part time job when i started selling pampered chef.
5. Besides web-related stuff (burbs, rings, etc.), what clubs do you belong to? none. not even anything web related. if i don't have enough time to do my regular hobbies, how am i going to have time for clubs & meetings?
missed it by this much i finally broke down yeste…
missed it by this much
i finally broke down yesterday afternoon and went to belk to stock up on clinique. i was desperately low on my yellow moisterizer and i had run out of touch base (creamy eye shadow). so i thought i might be able to sneak in under the wire with the free gift but i apparently missed it. the nice lady at the counter told me the schedule for free gifts for all our major stores at south park so now i'm set. but the next free gift isn't until august and i couldn't wait that long for moisterizer so i had to go plunk down a nice chunk of change. i only splurge on clinique once or twice a year and their products last for a long time so i feel justified. i bought my moisterizer, the clarifying lotion #2, and two of the new touch tint for eyes (lilac frost and blue pearl). fun shimmery shadows. i have a feeling the touch tint will be replacing the touch base, but you never know. i also managed to talk the sales lady into hooking me up with a free gift of sorts. she put together a bunch of samples and a cosmetic tray so it still feels like i got a free giftie.


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Junior High School 45 John S Roberts
New York, NY 10035
About This School
In 2011, Junior High School 45 John S Roberts had 11 students for every full-time equivalent teacher. The New York average is 13 students per full-time equivalent teacher.
Student Ethnicity (2011)
Students (2011)
Students Per Teacher (2011)
Female/Male (2011)
Subsidized Lunch (2011)
Grade 7 Math Performance
Junior High School 45 John S Roberts Reviews
What I liked about going to this school
I Graduated from P.S. 45 John S. Roberts J.H.S. in 1967. I found the teachers there very encouraging and helpful. They helped me graduate in spite of my home family problems. If they didn't take me under their wings I probably be dead and never had the experience of graduating college. I know the times from then too now may have changed a little but, a great teacher can change the lives of many of the future.
I Graduated from JHS45 in 2009. I had some of the best teachers from Ms. Dakin to Mr. Vernola to Mr. Diaz and Ms. Clee and Ms. Williams etc. I loved swimming there every chance I got. I was in fact on the swim team with Ms. Maggie and Mr. Melendez. Even though I was some-what of a handful Ms. Brice always believed in me having the potential to become the beautiful and mature young lady that I am today. So Thank You Ms. Alvarez for inviting me into your school I had a ball! =)
I graduated from JHS45 in 65. I had the best teachers of all my school years. JHS45 had so much to offer. The only school with an olympic size pool, biggest kitchen for cooking class I had ever seen. So much to offer that even the school's evening center was enjoyed by all the community. Would like to know how I can get a copy of the 65 year book. Thank you


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3710 US Hwy 15-501 N
Carthage, NC 27376
Across from Fair Grounds in Carthage
Thursday (show)
Monday 8:00am - 6:30pm
Tuesday 8:00am - 6:30pm
Wednesday 8:00am - 6:30pm
Thursday 8:00am - 6:30pm
Friday 8:00am - 6:30pm
Saturday 8:00am - 4:00pm
Sunday closed (hide)
Across from Fair Grounds in Carthage
Billboard - The latest coupons and news on this business!
Rental Department
Old-fashioned service.
|MON 8:00am - 6:30pm
|TUE 8:00am - 6:30pm
|WED 8:00am - 6:30pm
|THURS 8:00am - 6:30pm
|FRI 8:00am - 6:30pm
|SAT 8:00am - 4:00pm
|SUN closed
Category: Pets and Pet Supplies|Plumbing Equipment and Supplies|Garden Equipment and Supplies|Agricultural Equipment and Supplies
Service Area: Serving: Carthage NC, Moore County Areawide NC (Metro), Chatham County NC, Cumberland County NC, Harnett County NC, Hoke County NC, Lee County NC, Montgomery County NC, Moore County NC, Randolph County NC, Richmond County NC, Scotland County NC
Product: Lawn Mowers, Garden Tools, Garden Decor, Potting Soil, Garden Chemicals, Garden Centers, Seeds, Sprinklers, Compost, Planters
Buying Options: Garden Equipment Rental
Product: Agricultural Seed, Feed, Livestock Equipment, Fertilizing Equipment, Dusting and Spraying Equipment, Farm Equipment
Buying Options: Agricultural Equipment Rental
Product: Pet Food, Pet Toys, Pet Carriers, Pet Sanitation, Pet Health Care Products, Pet Treats, Kennel Equipment, Diamond, Eukanuba, Frontline Plus, Iams, Taste of the Wild
Product: Plumbing Fittings, Plumbing Pipes, Plumbing Valves
Specialty: Commercial Plumbing Fixtures, Industrial Plumbing Fixtures
our GO-TO store
by Cajun Farmer , 06/20/2013
The folks at the feed store are always super knowledgeable and NEVER too busy to take the time to answer a question or help with a project. This is the way a store SHOULD be run!
Owner of Horseshoe Poultry Farm
by Nowell Brown , 07/22/2010
Great place to shop for farm and garden supplies... Been shopping there for 30 yrs.


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Bus bombing, rocket strikes shatter illusion of security in Tel Aviv: Report
A Wednesday bus bombing in central Tel Aviv and a handful of Hamas-fired rocket strikes on Israel's largest city in the past week has reinforced a new belief within the regime that no one within the occupied territories is safe any longer, a US daily reports. "Stress throughout Israel's population has surged and that's likely to continue even if the cease-fire holds," said a Los Angeles Times report from Tel Aviv on Thursday, citing Israeli "mental health experts."
According to the report, although some Israelis try "desperately" to cope with the reality that rockets fired by the Hamas resistance movement can now reach any area under control of the Tel Aviv regime and "maintain the illusion of normality and sense of control," trauma expert Yehudit Bar Hai says, "Others avoid taking showers, fearful they couldn't react fast enough in a rocket attack. Others have slept on porches, believing that being that much closer to a shelter made them safer."The report further adds that repeated trips to air raid shelters, sometimes two or three times a night, "have left many Israelis short on sleep." "Between the sirens, bombings and a 4 a.m. attack that really shook my house, I'm so tired my body feels like it's night right now," said Orly Gal, executive director of Natal trauma center for victims of "terrorist" attacks. "But we're getting by on adrenaline. Everyone's a bit cranky, but what can you do?" Although Israelis welcomed the news of Wednesday's cease-fire, many expressed pessimism about how long it would hold, given the poor record of such agreements in past years. Meanwhile, the report adds, Israeli police forces stepped up security in Tel Aviv after the noontime bombing, which occurred as the bus rounded a corner near the ministries for justice and military affairs. Buses were noticeably empty as word spread, however. Tel Aviv has long enjoyed a reputation as a party town somewhat insulated from the airborne attacks seen in areas of Israel closer to the Gaza Strip, the daily further underlined. Despite the hope that the ceasefire will halt rocket strikes, the report notes that some Israeli analysts believe that the Palestinian weapons will "only increase in range and accuracy over time." "They're learning and making progress," said Meir Elran, an analyst with the Institute for National Security Studies, a think tank. "Some of their people are innovative and entrepreneurial." MFB/HJL/MA


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Absolute Stunner
By Pradhyum Shetkar on 02 Oct 2012 | Views: 5443
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Ex-showroom Price: 7.44 to 10.41 lacs (Delhi)
|Detailed review :
Renault Scala is definitely 2012's best C-segment sedan in India. The Scala is an absolute stunner with its grand size and chrome finish on the grille and rear of the car. Even if we keep beautiful looks aside, it is impressive thanks to the luxury,safety and performance it delivers. Scala is available in 4 different variants: 2 in diesel and 2 in petrol.But the variant that impressed most is the fully loaded top-end model RxZ(diesel). A 1.5 litre engine that develops 86PS of power @ 3750rpm and an impressive torque of 200Nm @ 2000rpm and the 5-speed manual transmission makes it a good highway cruiser. The best thing about this car are its features.Features like push to start and steering mounted controls bring more convenience to its owner.Interiors quality is upmarket and feels luxurious while legroom is great for all passengers. With 490 litres of boot space, it has no other match in the Indian market.For safety of passengers, the RxZ has front passenger and driver airbags,ABS with EBD,automatic speed sensing door locks,anti-theft system with alarm. At a price tag of Rs 9,51,730 (ex-showroom Mumbai), it's the best C-class sedan money can buy.
|Purchased as :
By: Anubhav on Ford 2013 EcoSport ,on 15 Jan 2015
Rating: 4.25 out of 5
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The only reason I would ever scan a tranny is to post it on line. I don't know why anyone would take the quality of a slide and routinely degrade it thru the limits of d*&%$@l technology. The quality of the projected image was always disappointing, too. My 35mm's get viewed directly in an old Pana-Vue Bi-lens viewer. It's like being there looking right at the scene. Medium format gets put on a light table and viewed thru a magnifying visor.
Tranny's should be viewed directly with transmitted light. They really come alive, and nothing can compare.
I have often thought of co-opting the optics of a DLT TV, as those are essentially slide projectors. Too many projects on the list, though.


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To demonstrate the use of risk-benefit analysis for comparing multiple competing interventions in the absence of randomized trials, we applied this approach to the evaluation of five anticoagulants to prevent thrombosis in patients undergoing orthopedic surgery.
Using a cost-effectiveness approach from a clinical perspective (i.e. risk benefit analysis) we compared thromboprophylaxis with warfarin, low molecular weight heparin, unfractionated heparin, fondaparinux or ximelagatran in patients undergoing major orthopedic surgery, with sub-analyses according to surgery type. Proportions and variances of events defining risk (major bleeding) and benefit (thrombosis averted) were obtained through a meta-analysis and used to define beta distributions. Monte Carlo simulations were conducted and used to calculate incremental risks, benefits, and risk-benefit ratios. Finally, net clinical benefit was calculated for all replications across a range of risk-benefit acceptability thresholds, with a reference range obtained by estimating the case fatality rate - ratio of thrombosis to bleeding.
The analysis showed that compared to placebo ximelagatran was superior to other options but final results were influenced by type of surgery, since ximelagatran was superior in total knee replacement but not in total hip replacement.
Using simulation and economic techniques we demonstrate a method that allows comparing multiple competing interventions in the absence of randomized trials with multiple arms by determining the option with the best risk-benefit profile. It can be helpful in clinical decision making since it incorporates risk, benefit, and personal risk acceptance.
Keywords:Risk-Benefit Analysis; Decision Making; Meta-Analysis; Methods; Monte Carlo Method; Risk; indirect comparison
In daily clinical practice clinicians are frequently presented with multiple competing treatment alternatives for the same clinical situation. In general it is accepted that when comparing several therapeutic alternatives the best evidence is derived from randomized trials. However, randomized trials are usually conducted comparing only two (or seldom three) options because inclusion of more treatment groups would require prohibitively large sample sizes and substantial increases in research costs and as a consequence, studies comparing all available treatment options at the same time are usually lacking.
Some notions should be noted regarding clinical decisions. First, if two or more equally effective alternatives are available for a disease the preferred one should be that conveying the lesser risk. Conversely, if all alternatives have equal risk, clinicians should opt for the most beneficial. Second, an alternative is usually not chosen if the risk associated with it outweighs the expected benefit [1]. The decision of using a specific option ultimately represents a personal choice and depends on the decision maker's perception of the associated benefits and risks with the potential caveat that such perception depends on factors such as the clinician's experience, knowledge, and expertise. Furthermore, when multiple alternatives exist for the same situation, the risks and benefits associated with each alternative should be pondered before deciding for a particular option.
Risks and benefits from medical interventions should be assessed together because their occurrence is inter-related and ideally, several factors should be considered in the decision process including: the expected clinical benefits and risks for each alternative, the uncertainty of these parameters, and the clinician's personal preference regarding the trade-off between benefits and risks [1,2]. A problem with this framework is that simultaneously incorporating all of the aforementioned factors for each available option in the decision process while at the same time considering all available evidence is practically difficult and not straightforward. Furthermore, since there are variations in personal preference for the trade-off between risks and benefits, comparative risk-benefit summaries should be presented throughout a range of trade-off values.
There has been an increasing interest in methods for jointly assessing risk and benefit and some work has been done in this area [3-7]. Proposed approaches to evaluate benefit and risk include using the number needed to treat and the number needed to harm [4,5,8]. These estimations are generally used independently and they are seldom combined in a risk-benefit ratio. Major problems with this approach are: a) the risk-benefit ratio is difficult to interpret and extrapolate outside the trial generating the information, and b) assessing uncertainty of a ratio is difficult because estimation of confidence intervals is problematic [9-11]. Additionally, besides being conceptually difficult to interpret, these approaches have the disadvantage of not allowing a comparison between multiple agents when these are available for the same indication. Methods using meta-analytical techniques have been developed to indirectly compare interventions that have not been directly compared; however, these methods involve a comparison of effect sizes (e.g. odds ratios) and result in estimates with wide confidence intervals which are difficult to interpret and do not provide a conjoint assessment of benefits and risks [12,13]. A possible way to solve some of the aforementioned problems that takes advantage of the Bayesian framework is the use of modeling techniques that allow introducing a term of uncertainty around a parameter estimate using strategies such as Monte Carlo simulation or non-parametric bootstrapping [11,14-16]. In 2004 Lynd and O'Brien proposed an interesting approach to this problem [2]. Their method used a cost-effectiveness approach similar to the one used in the health economics literature [17] and involves the estimation of the joint density of incremental risk and incremental benefit using probabilistic simulation, which is then plotted in a risk-benefit plane analogous to the cost-benefit plane used in economics (Figure 1)[18]; then a risk-benefit acceptability curve (RBAC) is created. This curve shows the proportion of net risk-beneficial interventions at a given threshold for risk acceptance and is analogous to the cost-effectiveness acceptability curve [19]. A limitation of this method is that each curve compares only two interventions and, although multiple curves can be superimposed in a single plot, this will only inform the probability for each intervention of being risk-beneficial but it would not allow determining which one has the best risk-benefit profile.
Figure 1. Risk-benefit plane showing a hypothetical conjoint risk-benefit analysis. In this hypothetical example, each point represents a joint risk-benefit observation calculated from a replication obtained from the Monte Carlo simulation. The percentage of the observations lying below the risk-benefit acceptability threshold (solid line) represents the probability of the intervention being net-beneficial for that specific threshold. It can be noted that a higher value of the threshold (i.e. a higher risk acceptance) will result in a higher probability of the intervention being net risk-beneficial.
Herein we elaborate on an extension of the method proposed by Lynd and O'Brien [2] in order to compare multiple competing interventions. We use information obtained from a meta-analysis of the literature to estimate the clinical risk (i.e. the "clinical cost") and benefit of each intervention together with an estimation of their corresponding uncertainties and, given that the optimal cutoff value for the tradeoff between risks and benefits is usually not known, we present the information through a range of tradeoff values which allows incorporating personal preference for risk acceptance. Finally, we incorporate a reference tradeoff value based on the clinical relevance of risk and benefit.
It is well known that major orthopedic surgery, including total knee or hip arthroplasty, is associated with an increased risk of venous thromboembolic disease (VTE) -comprising deep vein thrombosis and pulmonary embolism- that might be as high as 85% and that anticoagulants decrease this risk but also result in increased bleeding events [20]. Given the high case-fatality rate of major bleeding avoiding an excess bleeding risk is as important as achieving a good preventive effect. In addition, anticoagulants have very few side effects other than hemorrhage and thus their risk and benefit can be readily defined. Several anticoagulant drugs are available for this indication but they all differ in their efficacy and safety and therefore, in order to define the best intervention the ideal study should include 5 or 6 arms making it unfeasible. We used a risk-benefit analysis framework as outlined in the following sections to compare five different anticoagulants for the prevention of VTE in patients undergoing major orthopedic surgery.
Estimation of risks and benefits
While measuring the clinical benefit derived from an intervention is usually straightforward, defining the risk can be more problematic. Risk should be defined by an intervention-derived adverse event. Ideally, the intervention should have only one or very few adverse effects, of which the most frequent should be used to define the clinical cost. Alternatively, a composite endpoint can be used to incorporate different adverse events into a single outcome measure (e.g. mortality due to all causes or permanent disability). Since the risk and the benefit are defined by clinical events, it is necessary to know the proportion of patients experiencing such events. This can be obtained from a systematic review and meta-analysis of published evidence, which if properly conducted should provide a relatively unbiased summary of the available information [21].
To demonstrate the use of the methods proposed herein we use data from a previously conducted meta-analysis evaluating the use of anticoagulants for prophylaxis of VTE in patients undergoing major orthopedic surgery [22]. We included randomized controlled trials evaluating short-term (< 15 days) administration of anticoagulants for VTE prophylaxis in patients undergoing total hip or knee arthroplasty. The main benefit outcome was the proportion of major VTE (proximal deep vein thrombosis, pulmonary embolism or death) assessed by previously validated criteria [23]. The risk was assessed by estimating the proportion of major bleeding using a standard definition [24]. The search included MEDLINE, EMBASE, The Cochrane Library and also grey literature and was included studies published between 1980 and 2005. Details on the search strategy are available from the authors upon request.
The retrieved references were evaluated for inclusion independently by 2 reviewers and discrepancies were resolved by consensus. Data was abstracted by one reviewer and independently verified by a second reviewer. Quality of the studies was assessed using the criteria proposed by Jadad [25] and allocation concealment was evaluated according to the definition proposed by Schulz and Grimes [26]. A meta-analysis of proportions was conducted to obtain pooled estimates of proportions and their variances using a fixed or random effects model as described in Appendix 1. To determine the appropriate statistical model to be used, heterogeneity of the proportions across individual studies was calculated using a χ2 statistic for a k × 2 table, considering as statistically significant a p < 0.1. Individual subgroup and sensitivity analyses were planned a priori for type of surgery, adequacy of allocation concealment, source of funding, quality score, blinded outcome adjudication, timing of initiation of anticoagulation and type of analysis. Publication bias was explored plotting point estimates versus precision, or alternatively sample size. All the analyses were done using Excel XP version (Microsoft Corp., Redmond WA) with the statistical add-in software package Analyse-it release 1.7 (Analyse-it Software, Leeds UK).
Estimation of uncertainty, joint risk-benefit and risk-benefit analysis
To determine the risk-benefit profile of a therapeutic option it is necessary to determine the difference in the risk (i.e. the incremental risk or ΔR), the difference in the benefit (i.e. the incremental benefit or ΔB), and the ratio of both (i.e. the incremental risk-benefit ratio or IRBR) that such option has compared to a reference, usually placebo or the standard of treatment. The IRBR is analogous to the incremental cost-effectiveness ratio (ICER) and it can be defined as ΔR/ΔB (i.e. the ratio of the difference in risk to the difference in benefit between two competing treatments) representing a joint risk-benefit measure which can be plotted in a risk-benefit plane (Figure 1). An intervention will be dominant if it provides more benefit with less risk, and it will be dominated if it provides less benefit with more risk. Problem arises when interventions provide an increase in benefit with an associated increase in risk. In such cases the choice will depend on the decision maker's willingness-to-accept the risk. This is called the risk-benefit acceptability threshold (RBAT) and is represented by the slope of a line crossing the origin of the risk-benefit plane (Figure 1).
The use of the IRBR poses the problem of evaluating the uncertainty around the joint distribution. Uncertainty should be presented to avoid the ambiguity supposed by the use of the ratio alone [11]. Under the Bayesian framework proposed by Lynd and O'Brien, ΔR and ΔB are treated as random variables whose values lie over a specific distribution function, [2]. Since probabilities are limited by 0 and 1, their distribution is better expressed using the beta distribution which is defined on the interval (0, 1) and is frequently used as a prior distribution in Bayesian analysis. It is a continuous probability distribution with the probability density function defined by parameters α and β, where α is the expected number of subjects that will experience an event and β is the expected number of subjects that will not experience an event. In the case of Lynd and O'Brien, they used data from a single study to conduct further analysis, thus limiting the number of interventions evaluated to those included in the study used to obtain the information. However, the model can also be parameterized using the information derived from a systematic review and meta-analysis of the literature to estimate the probability of a patient experiencing an event, with the advantage of providing a more pragmatic estimate if the meta-analysis is well conducted.
We conducted risk-benefit analyses for each competing anticoagulant. Analyses were conducted from a clinical perspective and the analytic horizon was short since studies explored the occurrence of the clinical outcomes (VTE and bleeding) within 30 days of surgery, and therefore no discounting was considered. Using the method of moments [27] we calculated the α and β parameters of a beta distribution using the information obtained from the meta-analysis. Then the α and β values were used to parameterize a second order Monte Carlo simulation with 1,000 replications, each one representing a repeat estimation of the pooled proportion from the distribution previously defined. The simulations were done using Microsoft Excel 2002 (Microsoft Corp., Seattle WA) and CrystalBall 7·1 (Decisioneering Inc. Denver CO) software. Using the results of the Monte Carlo simulation, we calculated the percentage of the replications lying below a range of values for the RBAT. These values can be plotted in a risk-benefit acceptability curve, representing the probability of the intervention being risk-beneficial for a range of RBAT values. Although curves can be superimposed, they will only show the probability of each intervention being risk beneficial but will not inform which has the best risk-benefit profile.
Calculation of the net clinical benefit and indirect comparison of multiple treatment options
Unfortunately, the mathematical properties of the IRBR yield some limitations: when the difference in effectiveness (or benefit) is small the confidence bounds may become too wide which makes it difficult to estimate the uncertainty of the ratio [28]. In economic analyses the use of the net monetary benefit has been proposed as an alternative to overcome the problems with the ICER [28]. Using a similar approach we calculated the net clinical benefit (NCB) which is analogous to the net monetary benefit and is a way to assign a clinical value to the increment in clinical benefit that is obtained from the new treatment, subtracting from this the increment in the risk derived from such treatment. If the NCB is positive it means that the risk of achieving an additional benefit is less than the value of the benefit achieved. If the NCB is negative then the treatment should not be accepted since the risk exceeds the value of the benefit achieved [29].
Using the probabilistic framework proposed by Lynd and O'Brien [2], we assumed that a treatment would be risk-beneficial if the IRBR is less than the RBAT represented by the linear expression
where ΔR denotes the differential risk, ΔB the differential benefit, and ρ is the RBAT. The inequality can be re-arranged as
or alternatively
with variance equal to
where NCB represents the net clinical benefit and for NCB to be positive ρΔB has to be greater than ΔR.
Taking advantage of this approach we extended Lynd and O'Brien's [2] method in order to compare multiple agents by evaluating which anticoagulant(s) result(s) in a greater clinical benefit when the risk associated with the intervention has been accounted for.
Using this approach we used data from the Monte Carlo simulations to calculate the NCBj for each j individual simulation trial using the equation
where ΔRj is the incremental risk and ΔBj is the incremental benefit obtained in the j individual simulation trial. The variance can be used to estimate 95 percent confidence limits if we assume a normal distribution of the data, or alternatively in order to avoid an assumption of normality we can estimate these limits using the values for the 2.5 and 97.5 percentiles of the values obtained from the simulation.
The NCBj was calculated for each simulation trial across a range of ρ values for each of the five anticoagulant agents included in the systematic review and for placebo. For each trial and each value of ρ we determined which anticoagulant had the highest NCBj. We then calculated for each agent and value of ρ the proportion of trials in which such agent had the highest NCBj. This proportion represents the probability that each anticoagulant had of achieving the highest net clinical benefit across a range of ρvalues. The results were then plotted in a net clinical benefit probability curve which shows which of the competing treatment alternatives is/are most likely to have the best risk-benefit profile at a given RBAT value.
Determination of a reference RBAT
Since the ideal RBAT is usually not known this analytic approach allows incorporating clinicians' personal risk acceptance in the decision process. However, the optimal RBAT depends on the relative weigh of the risk versus the benefit. However, determining the weighs can be problematic particularly if the outcomes of risk and benefit are surrogate markers. In the latter case, determining an outcome common to both risk- and benefit-defining events is necessary. In this work we obtained pooled estimates of the case fatality rates for both VTE and major bleeding and their 95% confidence intervals using the approach shown in appendix I. Finally, we calculated the case fatality rate ratio of VTE versus bleeding. These ratio indicates the relative importance of VTE to bleeding, in other words it informs how lethal is a thrombotic event compared to a bleeding event. To obtain the 95% CI for each ratio, a Monte Carlo simulation was conducted using 1,000 replications of the case fatality rates and ratios were calculated for each replication and the 2.5th and 97.5th percentile values of the replications were used to define the 95% confidence interval.
Systematic review, estimation of risks, benefits, and case fatality rates
The search of the literature identified 1,583 potentially relevant citations of which 203 were fully assessed and 55 were included in the final review. These references are included in additional file 1. The reasons for exclusion and a flow diagram of the review are shown in the supplementary figure S1 included in additional file 1. The characteristics of the 55 included studies are shown in supplementary tables S1 and S2 included in additional file 1. We included studies evaluating, low molecular weight heparin (LMWH), unfractionated heparin (UFH), warfarin, fondaparinux, and ximelagatran, and placebo. The included studies comprised 123 intervention arms 2 of which were excluded. One study included a danaparoid arm in addition to the tinzaparin and dalteparin arms; the other study included an indomethacin arm together with a nadroparin and a placebo arms. In total 121 patient groups enrolling 42,131 patients were included in the review. Of these, 24,630 underwent total hip replacement, 13,318 underwent total knee replacement, 2,001 underwent surgery for hip fracture, and in 2,182 the type of surgery was not specified. Of the total number of patients enrolled in all the studies, 34,209 (81.2%) were evaluable for major VTE and 40,975 (97.3%) for major bleeding. The methodological characteristics of the studies are shown in the supplementary table S2 included in additional file 1. In general the methodological quality of the reports was acceptable. Allocation concealment was appropriate in approximately two thirds of the studies. The majority of the studies were funded by the pharmaceutical industry, and most of them used a blinded process to adjudicate outcomes. Only about one half of the studies used a similar definition for major bleeding events.
Additional file 1. Supplementary information of the systematic review. This file contains the following information regarding the systematic review: flow diagram showing the progress of the systematic review (figure), characteristics of the studies included in the systematic review (table), methodological characteristics of the studies included in the systematic review (table), and references of the studies included in the systematic review.
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The pooled estimates of VTE and bleeding for all studies are shown in table 1. The pooled estimates were obtained using a random effects model. The drugs resulting in the highest and lowest proportion of major VTE were UFH and fondaparinux, respectively whereas those resulting in the highest and lowest proportion of bleeding were fondaparinux and warfarin, respectively. Sensitivity analyses showed that only the type of surgery influenced the occurrence of outcomes and therefore 2 separate analyses for patients undergoing total hip and total knee replacement were conducted. The random effects pooled estimates of the proportion of fatal events (case fatality rates) of major VTE and major bleeding were 1.391% (95% CI 0.892, 2.162) and 3.557% (95% CI 3.203, 3.911), respectively. Finally, the case fatality rate-ratio of major VTE with respect to major bleeding was 0.391 (95% CI 0.158, 1.579). In other words, in these studies on average, a major VTE was less lethal than a major bleeding event.
Table 1. Pooled estimates of proportions for risk and benefit outcomes in studies evaluating the use of anticoagulant prophylaxis for venous thromboembolism in orthopedic surgery
Estimation of uncertainty and risk-benefit analysis
The information on risks and benefits obtained from the systematic review was used to parameterize Monte Carlo simulations. The results of the simulations were used to calculate the incremental benefits and risks for all anticoagulants which were subsequently used to construct risk-benefit planes. (Figures 2A-E). The proportion of paired observations lying below the risk-benefit acceptability threshold -represented by a dashed line in Figure 2- was calculated across a range of values and plotted in risk-benefit acceptability curves for each agent that were overlapped in a single plot (Figure 3A). Separate analyses were conducted for patients undergoing total hip or knee replacement (Figures 3B and 3C). These curves represent the probability that an agent has of being net-beneficial relative to placebo across a range of values for the risk-benefit acceptability threshold. In all analyses, as expected all options had high probabilities of being net-beneficial compared to placebo (Proportion > 0.8 with an RBAT = 0.391). The probabilities did not differ in subgroup analyses according to surgery type (total hip or knee replacement). However, as can be seen in Figure 3, the risk-benefit acceptability curves do not allow a comparison of all options at the same time. Thus, in order to compare all agents we calculated the NCB for each one of the 1000 simulations and subsequently we calculated for each agent the proportion of the simulated trials in which each agent had the highest NCB across a range of RBAT values. Results were plotted as probabilities in net clinical benefit probability curves (Figures 4A-C). These curves show which drug(s) has(have) the highest probability of having the highest net clinical benefit (and this the best risk-benefit profile) at a given value of the RBAT. As depicted in Figure 4A, ximelagatran was the agent with the highest probability (87.8%) of having the best net-clinical benefit when considering all patients, but subgroup analyses showed that this difference was mainly driven by the total knee replacement population (Figure 4C) in which the probability was 85.2% for ximelagatran, and that in the case of total hip replacement patients, the choice between warfarin or ximelagatran would be probably indifferent with probabilities of obtaining the highest net clinical benefit of 48.6% and 36.7%, respectively. It can be seen that the agents vary in their probability of having the best risk-benefit profile as the value of risk acceptance (RBAT) changes. Finally, because the optimal RBAT is not known, a reference value was calculated based on 'hard' outcomes. The clinical relevance of VTE relative to that of major bleeding was estimated using the values of the case fatality rate-ratios. These ratios and their 95% CI were then plotted in the curves to provide an estimate of the approximate level of risk acceptance (RBAT) that should be considered. The ratios were indicated in the curves as the vertical dashed line with the 95% CI indicated by the shaded area.
Figure 2. Risk-benefit planes showing the joint incremental risk and benefit of anticoagulants used for venous thromboembolism prophylaxis in orthopedic surgery. The figure shows separate analyses for patients receiving ximelagatran (A), low molecular weight heparin (B), Unfractionated heparin (C), warfarin (D) and fondaparinux (E). The dashed line corresponds to the reference value for the risk benefit acceptability threshold.
Figure 3. Risk-benefit acceptability curves for anticoagulants used for venous thromboembolism prophylaxis in orthopedic surgery compared to placebo for all patients (A), total hip replacement patients (B) and total knee replacement patients (C). The curves show for each anticoagulant the probability of being net risk-beneficial compared to placebo across different risk-benefit acceptability thresholds which reflect the willingness to accept the risk of major bleeding episodes. The reference value is shown as the vertical dashed line with the 95% confidence interval shown as the shadowed area. Note that these curves do not allow a comparison of all agents simultaneously and do not inform the option with the best risk-benefit profile.
Figure 4. Net clinical benefit probability curves for anticoagulants used in the prevention of venous thromboembolism in all patients undergoing orthopedic surgery (A), total hip replacement (B) and total knee replacement (C). The curves plot the probability that each drug has of providing the highest net clinical benefit -and consequently having the best risk-benefit profile- for each value of the risk-benefit acceptability threshold. The reference value is shown as the vertical dashed line with the 95% confidence interval shown as the shadowed area. Note that the probabilities change at different values of risk acceptance and that at each value the probabilities add up to one.
The present study demonstrates the use of risk-benefit analysis to perform indirect comparisons of multiple competing interventions. We believe that this approach might help to guide clinical decisions in areas where tension between risk and benefit exist and there are multiple therapeutic options. This approach provides a way to indirectly compare several interventions in the absence of randomized trials involving multiple arms.
This method assumes that the use of certain therapy has a clinical risk, something particularly important when potentially harmful therapies are used. Clinicians opt for these options because the expected benefit outweighs the risk; however, choosing the best therapeutic option can be difficult when the rates of major complications (risk) or clinical effectiveness (benefits) from different options vary. Furthermore, clinicians' willingness-to-accept the risks might differ depending on a number of issues. If for a clinical situation there are numerous therapeutic options it is unlikely that all options will be compared in a randomized trial usually because of sample size and research cost constraints. The approach described herein takes advantage of the risk-benefit analysis framework and provides a way to indirectly compare several interventions in order to determine the one with the best risk-benefit profile using information available from randomized trials to estimate costs and benefits.
Using the proposed approach we conducted an indirect comparison of five common anticoagulant drugs used to prevent the development of thrombotic complications in patients undergoing major orthopedic surgery. This intervention is particularly suited to exemplify this approach given that anticoagulants are associated with bleeding episodes as their major (and almost only) complication and with a palpable benefit, namely prevention of thrombosis. Furthermore, they are usually given for a short period of time which facilitates defining the time horizon for the study. The analysis showed that compared to placebo, all agents are likely risk-beneficial (Figures 3A-C), a finding that is not surprising. The problem is then choosing the one(s) with the best risk-benefit profile. By calculating the net clinical benefit for each anticoagulant at a particular value of the RBAT it can be easily determined the probability of obtaining the highest net clinical benefit for each competing anticoagulant at that particular RBAT value. These probabilities are then calculated for a range of RBAT values and used to create a net clinical benefit probability curve (Figures 4A-C). Furthermore, since the ultimate clinical consequences of major bleeding and venous thromboembolic events might be different (i.e. their associated mortality), we incorporated in the analysis a reference range of RBAT values derived from the case fatality rate-ratios of thrombosis and bleeding. The final plots then incorporate the key elements of a decision, namely risk, benefit, willingness to accept the risk and their uncertainties.
It can be argued that when analyzing and pooling information obtained from randomized trials, the use of proportions for comparison purposes -as opposed to effect sizes- supposes the loss of the randomization effect because groups are treated independently. Nevertheless, if properly conducted and reported, information derived from randomized trials has usually a high quality [30], and although we recognize that there might be a concern regarding the generalizability of the results from randomized trials, pooled estimates of event proportions will most likely approach reality as the population in the included studies increases. Although non-randomized studies could potentially also be used we prefer randomized trials which are less prone to bias. However, since a number of issues could influence meta-analysis results, systematic reviews should be methodologically sound and incorporate a priori all pertinent subgroup and sensitivity analyses, an evaluation of the homogeneity of outcomes' definitions used across different studies, and an assessment of study quality using validated scales [25,31]. This issue can be better appreciated in our study by analyzing the results for all patients and the subgroup analyses which showed that the risk-benefit profiles of the different anticoagulants were different in patients undergoing hip or knee replacement
Some conditions are necessary to conduct study using the approach proposed herein: First, outcomes used to measure risks and benefits must be defined similarly across studies. Incorporating studies using different outcome definitions would result in a heterogeneous result difficult to interpret. It is entirely possible that the results of the study example could be different if all and each one of the potential side effects of the drugs were incorporated in the analysis. Second, if clinically acceptable, risks and benefits should ideally be defined by a single outcome; if this is not possible then a composite outcome could be used, such as mortality. Third, events defining risks and benefits should be clinically relevant. Fourth, if the systematic review spans several years, it is particularly important to test for secular trends since outcome definitions might change over time as a result of new knowledge, which might affect the evaluation of older therapies still in use. In addition, changes in medical or surgical techniques or in health policy are likely to influence the results and therefore populations might not be similar. It can be appreciated that the systematic review must be stringently rigorous and adhere to standardized requirements such as the PRISMA (formerly QUOROM) statement and exploring heterogeneity becomes essential. A thorough sensitivity analysis should be conducted prior to incorporating the information into the Monte Carlo simulation, to assure to the maximum extent that studies include comparable populations. If these conditions are met, it can be argued that this approach provides a pragmatic panorama of the situation studied.
Our approach does not estimate effect sizes; instead it provides the clinician with information regarding the probability of having the best risk-benefit profile that certain intervention will have at a given value of risk acceptance. If risks and benefits can be measured in equivalent terms (e.g. deaths induced or prevented by the treatment), the preferred choice should be that conferring the highest probability of being beneficial at the chosen value for risk acceptance. However, if surrogate endpoints are used case fatality rates might be different and so will be the clinical relevance of costs and benefits relative to one another. Our method allows for an adjustment by changing the value of the RBAT to one that better suits the clinical situation being studied. Since the level of risk acceptance is pivotal to making the best choice, a reference value for the RBAT can be obtained from expert consensus or surveys, or by using case-fatality rate ratios. In any case a reference RBAT should be a guideline for the clinician to be applied on an individual basis.
It is important to note that randomized trials are usually powered to detect differences in benefit-defining events and inadequately powered to detect differences in risk and only some of them include risk-defining events in a composite outcome. In this regard, an advantage of our approach is that it allows larger sample sizes; hence more power to detect differences in less common, more clinically meaningful outcomes.
The potential limitations of our approach arise from three issues: 1) the fact that the information is obtained retrospectively from a systematic review and meta-analysis with their inherent caveats; 2) the methodological issues regarding the pooling of single proportions; and 3) the limitations regarding modeling techniques and their application to clinical risk-benefit ratio and incremental risk-benefit ratio analysis. With respect to the first point we considered that an ample sensitivity analysis should establish the robustness of the conclusions. If the conclusions are not robust, the conduction of a study using such information should probably be questioned.
In regard to the second point there are examples of the application of the proposed pooling techniques [32] and a major strength of this method is the fact that the estimates are the result of a comprehensive review and meta-analysis including all major studies. A potential problem with the weighting method of Laird and Mosteller is that it uses a normal approximation to proportions which might be problematic if the proportions are very small because they might not have a normal distribution anymore [33]. In a similar fashion, the statistical properties of a χ2 test to determine heterogeneity might be adversely affected when proportions are very small. If this is the case, robustness might be assessed by using alternate pooling methods or comparing fixed versus random approaches. Finally, although the modeling techniques used in this study are not commonly found in clinical medicine and their application to clinical decision making was described only very recently hey are frequent in the economic literature and have been well validated. Additionally, other concerns have been recently raised regarding the use of cost-effectiveness analysis (in our case risk-benefit analysis), namely the degree of discrepancy between probability-based and expectation-based methods, as well as non-transitivity in pair-wise comparisons [34,35]. These problems could potentially arise in economic studies and their potential effects on studies using the approach proposed herein deserves further evaluation. Finally, the performance of the present approach compared to other methods for indirect comparisons still remains to be tested.
Herein we demonstrate the application of risk-benefit analysis to conduct indirect comparisons of competing interventions using a Bayesian framework and incorporating the key elements of the decision process (rIsk, benefit, and willingness-to-accept the risk) and might prove to be a valuable aid in order to facilitate the implementation and practice of evidence-based medicine.
List of abbreviations
ICER: Incremental cost-effectiveness ratio; IRBR: Incremental risk-benefit ratio; LMWH: Low molecular weight heparin; NCB: Net clinical benefit; RBAC: Risk-benefit acceptability curve; RBAT: Risk-benefit acceptability threshold; UFH: Unfractionated heparin.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
AL-L participated in the conception, design, and development of the method, as well as in data collection, analysis, and drafting of the manuscript, MAR participated in the development of the method, as well as in data collection, analysis, and drafting of the manuscript, NJB participated in the development of the statistical methods and drafting of the manuscript, TR participated in the development of the statistical methods and drafting of the manuscript, PSW participated in data collection, analysis, and drafting of the manuscript, and DAC participated in the conception, design, and development of the method, as well as in analysis, and drafting of the manuscript. All authors read and approved the final manuscript.
Appendix 1
Methodology for the calculation of pooled estimates of proportions
For a collection of k studies, each i individual study giving a pi proportion
where xi is the number of events and ni the number of patients in the ith study; for i = 1 to k
If homogeneity holds, a estimate of the true probability is
with variance
The confidence interval can be calculated using the Wilson score method [36] as follows:
where z is the 1 - α/2 point of the standard Normal distribution, and q = 1 - p.
If the proportions are not homogeneous then a random effects estimator of the true proportion may be defined as
with variance
where the weights are defined as proposed by Laird and Mosteller [33]
where the mean proportion for the k collection of individual i studies is
and where the estimate of the variance of the proportions is
Acknowledgements and funding
Financial Support
During the conduction of this work Dr. Alejandro Lazo-Langner was supported by a Graduate Scholarship from Consejo Nacional de Ciencia y Tecnología (CONACyT), México, an International Fellowship awarded by the University of Ottawa and by Program Grant PRG 5513 of the Heart and Stroke Foundation of Ontario. Dr. Marc A. Rodger is supported by a Career Scientist Research award from the Heart and Stroke Foundation of Ontario. Dr. Philip S. Wells is supported by the Canada Research Chairs Program.
Role of the funding source
The funding bodies previously acknowledged had no role in any stage of this work as well as in the decision to submit for publication.
This paper was recognized with the University of Ottawa Epidemiology and Community Medicine Graduate Students' Association Research Recognition Award in March 2007. All authors have seen and approved the final version of the manuscript. No author has declared conflict of interests.
We are kindly indebted to the editor and reviewers of a previous version of the manuscript.
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