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Nine Nelson Bay Marlins will line up for Black Diamond AFL in Saturday's representative fixture against Sydney.
The Bay's Jeremy Eddy, Todd Thornton and Luke Price will be part of the BDAFL men's team looking to make it five wins in a row against Sydney AFL during Saturday's representative round on the Central Coast.
Marlins Sophie Balcombe, Lauren Cooper, Pippa Smyth, Jemma Astley, Kate Holland and Lisa Steane will be part of the women's team looking for their first win against Sydney.
After making their debut against AFL Canberra in 2016, this year's Black Diamond women's team will come up against an equally strong AFL Sydney side.
"The squad performed very well last year before going down to AFL Canberra," Black Diamond women's coach Simon Berry said.
"With a further 12 months experience I am expecting another good performance against a good AFL Sydney team."
BDAFL's strength is in their midfield.
Steane, Alison Parkin and Audrey Gillingham are expected to win many possessions and give the forward's plenty of opportunities.
Smyth and Bec Ives will have a big job in the ruck to ensure the midfield gets first use of the football.
AFL Sydney's team will be talented given that they are made up of players who are members of the AFL NSW/ACT women's academy.
BDAFL's men will have a tough task extending their representative round results to five in a row, a fact not lost on coach Chris Bishop.
"Sydney AFL is regarded as the pinnacle league in the state and whoever pulls on the jumper for them will be a good player," he said.
Bishop expected the match would likely be decided in the middle of the ground.
All teams in the regular Black Diamond AFL competition have the bye this weekend.
The women's representative team will play first on Saturday, May 20.
Kick off at Adelaide St Oval, Killarney Vale, is noon.
The game will be live streamed by BarTV.
The men's representative game will be played at Adelaide St Oval from 2.15pm.
The game will also be live streamed by BarTV.


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French course - Basic Level
Speak French in 3 short months at LINGO.
This French course helps participants build a good foundation in the French language. It is especially suitable for people who have no knowledge of French.
Upon finishing the course, the participant will be equipped with a strong foundation in French. They will be able to understand simple conversations on a variety of topics.
Number of Lessons: 12 Lessons per module

Duration of Basic Module Completion: 18 hours

Mode of teaching: Interaction, Reading & Writing, Role Play
We also offer French private tuition and Customized French Corporate language training
Course Outline
The following will be covered in this basic French course:
- - French phonetics
- - Sentence structures
- - Everyday useful phrases
- - Verbs: present tense conjugation
- - Basic comprehension skills (through passage reading, dialogue and questions)
- - A new set of vocabulary to be taught each session
- - Introduction to the French society & culture, country, famous artists
- - Each session includes audio/video to develop listening techniques
Why LINGO?
- - Registered with the Ministry of Education
- - Learn a new language in just 3 months
- - All materials have been developed by native professionals
- - Small classes to enable students to participate and ask questions
- - All LINGO's instructors are native speakers, dedicated, qualified and experienced to help you optimize your learning experience
- - Minutes from Bugis MRT (Opposite Shaw Towers)
- - A Certificate will be issued upon completion
Seats are limited so book your seat now to avoid disappointment!
Call Fern now at 66648105
|Course name:
|French course - Basic Level
|Tuition fee, Administrative fee, Course material
87 Beach Road #02-02
Chye Sing Building Singapore 189695
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Quick Facts
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Main OfficeLingo School of Knowledge
87 Beach Road #02-02
Chye Sing Building
Singapore 189695
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subset: commoncrawl


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Comments about BELLA
September 10, 2014 6:17 am
by herbmeister from Tomball, TX Proud owner of Herbie
Thanks Bella's mom
Your kind words meant so very much to me. I will forever miss my Herbie. I know he would have loved to go hunting with Bella when he was young and healthy. Give Bella and extra hug and kiss for me today.
June 4, 2014 2:42 pm
by chunkymonkey from sacramento, CA Proud owner of Macy and Bailey
What a sweet little pup you are. We hope you get lots of extra play time and an extra treat today.
June 4, 2014 11:59 am
by cpn2jxp from Tobyhanna, PA Proud owner of Sabrett
Hi Bella
Your name rings true. Just beautiful! I would be putting little bows in your hair LOL It does sound like you lead a exciting life. My girl will be 15 in December so the excitement has died down a bit. We love your pictures with our favorite being you on the desk. Doxies are the the pups EVER!! Wishing you many happy healthy years with your family!!
June 4, 2014 7:25 am
by herbmeister from Tomball, TX Proud owner of Herbie
Hello Bella
I feel so honored to be the first to Welcome you and Congratulate you as DOTD. You are so very pretty and Mom and I enjoyed looking at all of your pictures. To bad you live so far away. Looks like your life if full of adventure. Enjoy your new day of fame. Best to you and your family and wishing all loads of love, good health and long life.
Only regisistered users may leave comments. Registering is fast and free! Register now or sign in if you have registered in the past.


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Lighting Upgrades: A Guide for Facility Managers
Green Lights lighting specialist Damon Wood takes you step-by-step through upgrading a lighting system, in either a retrofit or complete redesign scenario, for the purpose of increasing both energy efficiency and productivity. This guide is designed for use by anyone who needs to understand the principles of lighting and light's impact on conservation, productivity and safety. Readers will find valuable discussion of lighting quality, upgrade strategies, applications, technologies, economics, maintenance, project implementation and methods for assessing specific opportunities. This fully illustrated guide addresses these issues in lay terms and in an easy-to-understand, logical style.
Please visit Help Page for Questions
regarding ISBN / ISBN-10 / ISBN10, ISBN-13 / ISBN13, EAN / EAN-13, and Amazon
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Copyright © 2003-2014 AllDiscountBooks.net All rights reserved.


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Game 13 Quick Recap: OAK 5 NYY 2/
Early runs, no big hits with RISP, pitcher stung by one bad inning. Lather, rinse, repeat. Nathan Eovaldi was the victim of the one bad inning and the lack of offensive support last night. His body of work wasn't bad (6 IP, 3 ER, 7 K), but he gave up 3 runs on 2 doubles, 2 singles, and a sac fly by the first 5 batters of the 4th inning and that was all it took to set him up for the loss.
The offense didn't get completely shut out. Didi Gregorius staked the Yankees to an early lead with a solo home run in the bottom of the 2nd. But they didn't score again until the bottom of the 8th and that was on another solo shot by Carlos Beltran. In between it was a whole lot of nothing.
That home run would have meant a realistic chance at a tie or walk-off win in the 9th had it not been for Branden Pinder in the top half of the inning. He loaded the bases on 11 pitches (2 singles, walk) and Khris Davis cashed in with a 2-run single up the middle. 4-run lead heading into the final 2 innings might as well be a 4,000 run lead against this pathetic Yankee offense.
I haven't been watching a lot of the recent games because I've been participating in Milwaukee Beer Week, but it sounds like that's been for the best. Not a lot of fun to be had watching this team right now.
Game Notes:
- RISPFail Count: 2-49. It's gone from funny to sad to back to funny now.
- Didi was the only Yankee with multiple hits last night. He also struck out twice and got charged with an error.
- Aaron Hicks went 0-3 to drop his batting line even lower. He also threw a laser to home plate to finish an inning-ending double play in the 4th.
- Mark Teixeira went 0-4 with 2 strikeouts. Don't look now, but his average is down to .182.
- Scoreless innings for Kirby Yates and Ivan Nova in relief.


text: It was quite strange, I felt, that the two Grand Final coaches squared-off against each other in round one of the following season, only this time for two different clubs. Surely this has never happened before in rugby league? It was also odd that I wanted Des and his scummy dogs to get hammered only months after he guided our Club to the premiership. Oh well, there's always round 8 for that!


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Unused / unissued material - no paperwork - dates unclear or unknown
Location unknown - presumably Germany.
Various shots of Nazi scientists watching and preparing tests for what looks like the V2 flying bomb. Several of the tests fail and the bombs explode in close proximity to the test sites. One rocket falls off the launch pad and explodes where it stood. Firemen spray the remains of the rocket with hoses and foam. German officers inspect the wreckage.
N.B. This material is scratched and fairly dupey. It may have been used in 46/37 - MD.
This clip currently has no date range.
However, as surmised by the cataloguer, I too think this is the V-2 rocket. That would enable the piece to be safely dated as being from between 1942 and 1945.
The location is highly likely to be Peenemunde, Germany, where the V-2 rockets were all tested.


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Without the help of our sponsors we would not be able to to hold such professional events. Sponsorship options range from an individual fence, through to a series of competitions. Take a look at some of our current sponsors below and if you would like to support us through sponsorship, please contact Alice Lissaman. Details of packages available
Thanks to those who support the Cottesmore Pony Club through their generous sponsorship – please use these businesses and let them know you are from the Cottesmore Hunt Pony Club
Ruddle Merz www.ruddlemerz.co.uk
The authoritative voice on business rates. One of the UKs most experienced ratings advisors.
Gates Garden Centre www.gatesnurseries.co.uk
Garden centre,tea room,gift and homeware,furniture,BBQ and water features.
Alex McIntyre Architects www.alexmcintyrearchitects.co.uk
Alex McIntyre Architects specialise in conservation and sensitive contemporary
architecture. Projects range from major alterations to listed buildings through to the designof a bespoke family home.
NFU Stamford www.nfumutal.co.uk/branches/stamford
NFU Stamford offers home,vehicle and business insurance as well as pensions andinvestments.
Langham Engineering Precision Ltd www.langhamengineering.co.uk
Langham Engineering is a long established family run business supplying high quality
engineering services.
Sturgess Hyundai www.sturgessgroup.co.uk/Hyundai
Sturgess Hyundai are experts in Leicester selling the entire range of new Hyundai cars
and a wide range of used Hyundai cars.
Barnsdale Lodge Hotel and Rutland Retreats www.barnsdalelodge.co.uk/rutlandretreats.co.uk
Barnsdale Lodge Hotel is situated on the north shore of Rutland Water in the heart ofRutland. Rutland Retreats is a brand new concept in lifestyle and a wonderful investment.
Sturgess Landrover www.sturgessgroup.co.uk/landrover
Sturgess Landrover in Leicester are an approved Landrover dealer with exceptionalcustomer service and a loyal customer base.
Mallard Jewellers www.mallardjewellers.co.uk
Mallard Jewellers specialise in new and pre owned jewellery.
Oakham Tyre Company www.oakhamtyres.co.uk
OakhamTyre Company is a family run buisness established in 1967. "Where safety andservice is our number 1 priority."
Cavells Country www.cavellscountry.co.uk
Cavells Country offer a fine selection of the finest country clothing,footwear andaccessories. With top brands like Barbour,Schoffell Country,Dubarry and RM Williams andmany others.
Weatherbys Bank www.weatherbysbank.co.uk
Weatherbys bank is a traditional family owned private bank.We are a fully accredited bank
offering all the services of a modern financial institution yet with the attention to detail youwould expect from a traditional family business.
Bullimores Sand and Gravel www.bullimores.net
'Celebrating 15 years of excellence, Amanet provides a wide
range of technology solutions and services for businesses, homes and
schools. From a complete range of IT support services, server based
network systems, mobile ICT suites, to whole house automation. Combined
with our online shop with 30,000 products at your fingertips every
aspect of your IT is provided for. URL: www.amanet.co.uk
Many thanks to Sturgess Motor group, sponsors of the Combined Training held at Stone Lodge, Marefield and also to Tim, Sarah and Ned Hercock for allowing us to invade their lovely home!
Thanks to NFU for their continued generous support and congratulations to the Tet team
Many thanks to Alex McIntyre architects – the winners receive their lovely rosettes
Also thanks to;
Xoaam equestrian, Wrights Concrete, Holly Campbell at Marefield Farm, Strutt and Parker, Furleys and Ruddle Merz for their sponsorship of the Junior One Day event at Fill Top Farm


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The Discrete Interval Sampler is a stainless steel chamber attached to a reel via a length of LDPE tubing. The reel has a pressure attachment for pressurising and venting the chamber. Pressure is applied using a high-pressure hand pump.
The chamber is pressurised initially which forces a check-ball valve at the bottom downwards, preventing water from entering. When the sampler is at the desired depth, the attachment on the reel can be switched to the vent the internal pressure allowing the chamber to be filled by the hydrostatic pressure around it. At the top of the chamber there is a polypropylene check-ball that floats and closes the valve when water fills the chamber preventing sample from coming in contact with the tubing. This provides a high quality VOC sample as organic compounds will not be lost via adsorption onto the LDPE tubing.


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I PAID too much for my first house, a tiny two-bedroom, one-bath bungalow that needed a lot of work, because of its prime location in a fashionable suburb. Two years later, a couple who saw more value in the address than I did gave me $10,000 above what I had paid.
That house came to mind often at the wheel of the 1996 Range Rover 4.0 SE from Land Rover North America. Throughout a weeklong test drive, people would ask the price and then exclaim, "That costs more than a house!" Indeed, the Range Rover's base price of $55,625 roughly matched what I paid for my first home in Michigan some 12 years ago, and a fancier version, the 4.6 HSE, costs nearly what I sold it for.
With the Range Rover, as with my house, worth is in the eye of the buyer.
The Range Rover has a long and proud tradition. Permanent four-wheel drive has been standard since 1948, and some technological features, like an adjustable air suspension, set it apart from other sport utility vehicles. Its off-road prowess is routinely demonstrated in competitive treks across the Sahara and through the Central American rain forest. And it serves as a modern-day carriage for the House of Windsor.
Its price has put the Range Rover in a class by itself. The 4.6 HSE, outfitted with a bigger engine and huge 18-inch tires, goes for $62,625. (The two Range Rovers occupy a neighborhood that Lexus recently invaded with its LX 450, which is nearly as pricey.)
The Range Rover's appearance has moved more into the mainstream. After 25 years of wearing the same boxy shape, the vehicle recently received a complete makeover. The new design, introduced in the United States a year ago, retains traditional Range Rover styling cues like the no-nonsense horizontal grille, but the lines are softer. The old design -- which was carried over for '95 as the "Range Rover County Classic" -- is no longer available.Continue reading the main story
Inside, the Range Rover is outfitted with leather seats and tasteful touches of genuine burled walnut on the doors, dash and center console. It comes with more standard amenities than many luxury cars, including individual climate controls for the driver and passenger, heated eight-way-adjustable power seats and a six-CD changer with an 11-speaker audio system. With the memory settings, two drivers can position the seats and mirrors to their liking from outside the car, and even set the brightness of the instrument lighting to their taste. The latest revamping included door beams for protection in side-impact crashes.
The Range Rover has its charming, and sometimes irritating, eccentricities. The toggle switches for the windows, set on the center console, seem backward to Americans: the front switches operate the rear windows, and vice versa. Likewise, the side-view mirrors adjust in a nonintuitive manner. And the turn signal emits a clip-clop sound like the hoofs of carriage horses.
Other noises -- and there are many -- are less enchanting. When you turn off the ignition, an annoying chime immediately sounds to remind you to remove the keys. The same chime weighs in when you insert the key to start the car.
The horn blared a couple times as I accidentally set off the hypersensitive theft alarm. (The remote entry control can be used to "super-lock" the vehicle. If a window is broken, the engine will not start and a motion sensor inside prevents the doors from being opened.)
Behind the steering wheel, I had a commanding sense of the road as I looked forward from my lofty perch. But a serious blind spot, made more pronounced by the rear-seat headrests, requires extreme caution and constant monitoring of the mirrors. Otherwise, driving the Range Rover is quite easy and not much different from operating any other sport utility.
Seats -- two buckets in front and a rear seat that can accommodate three and folds down in a 60/40 split -- are extremely comfortable. Headroom is good in the back, but tall drivers complained that their heads rubbed the roof in the front.
The rear seats can be folded flat to add to the cargo-carrying capability. No space is lost to the spare tire, which is housed under the floor of the roomy cargo bay. Access to the cargo area through the traditionally designed tailgate, which folds down, is difficult for short people. To load groceries, I had to pop open the upper glass portion and lift the bags over the unopened tailgate.
The Range Rover is powered by a 4-liter V8 engine rated at 190 horsepower, but it is no speed demon, with acceleration from 0 to 60 miles an hour at something over 10 seconds, about the same as the six-cylinder Lexus. (The 4.6-liter HSE knocks 2 seconds off that time.) Still, acceleration was adequate for around-town driving. The beefy four-wheel, four-channel anti-lock brakes confidently stop the 5,000-pound vehicle.
Fuel stops come frequently, with a rating of 13 miles a gallon in town and 17 on the highway. But my mileage over several hundred miles of highway, city and off-road driving was about 14 m.p.g. Because the Range Rover is classified as a truck, it is not subject to the Federal gas-guzzler tax.
The V8's torque -- the force that gets a vehicle moving -- makes the Range Rover ideal for off-road driving. It's too bad only about 3 percent of owners use their vehicles this way; they are missing the real fun.
In addition to its full-time four-wheel drive, the Range Rover has a low gear range, engaged by using the shifter in the center console. Diagrams of hills indicate the best gears for climbing and descending.
The Range Rover handily lumbered over the washboard trails of an abandoned railroad bed covered with snow, without tossing the passengers about too severely. It squeezed through the narrow muddy passages of a forsaken gravel pit, past the rusted skeleton of a snowmobile.
Adding to the Range Rover's off-road prowess is an electronic air suspension. By pressing a button on the dash, the vehicle's height can be raised a couple of inches above the standard minimum setting of 8.4 inches of ground clearance, for plowing through deep water and snowbanks. Or it can be lowered to make exit easier and handling better on twisty roads.
In the final analysis, it's impossible to ignore the issue of price. In either the 4.0 or 4.6 versions, the Range Rover is pleasant and comfortable to drive on a daily basis, and it is loads of fun off-road. But other sport utilities can provide comfort and off-roading capability at half the price. Few, however, have the Range Rover's cachet, and sales regularly set records as more and more people seem willing to pay the premium.
There's probably one parked in the driveway of my old house.
INSIDE TRACK: The Range Rover treats you royally. But is it worth a king's ransom?Continue reading the main story


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CCM imeua na imetesa watu wengi sana. ushahidi ni huu!!!!
Discussion in 'Jukwaa la Siasa' started by Mcheza Karate, Nov 13, 2011.
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This introduction to car accident claims gives you the big picture, the view from 30,000 feet.
Let's get started.
Car Accident Statistics
Unfortunately, car accidents are a common part of modern life.
Estimates of the number of car accidents in the United States each year range from 6 million to over 10 million. Using the larger figure, which comes from the U.S. Census Bureau, the average is almost 30,000 accidents daily.
Although this figure has been coming down, In 2010, according to the National Highway Traffic Safety Administration's (NHTSA), there were still 32,788 traffic fatalities. And, more than 2 million more drivers, passengers and pedestrians were injured by car accidents.
Car accidents frequently result in car accident claims, an estimated 3,000,000 each year.
Statistically, you will make a car accident claim every 15 to 17 years.
Settle Your Claim Yourself exists to assist you when it is your turn to make car accident claims.
Although it may surprise you to hear a car accident lawyer such as me say this, I am convinced you can settle your own routine car accident claims if you want to. I believe you can recover full value for your claims without hiring a lawyer. All you need is some information about the car accident claims process and you are in the right place to get it.
Car Accident Claims Legal Concepts
Traditionally, car accident claims have been based on a fault system. The driver who causes an accident pays for the harm done.
Technically, fault claims arising out of car accidents are "negligence" claims.
Negligence essentially means carelessness. It means that someone did not comply with the duty the law imposes on all drivers to use "reasonable care" when driving.
When someone violates the duty of reasonable care and causes harm, they are considered negligent and they are responsible for the harm they cause.
While most states have a fault system for car accident injury claims, there are currently 12 states that have a no-fault system. The no-fault states are Florida, Hawaii, Kansas, Kentucky, Massachusetts, Michigan, Minnesota, New Jersey, New York, North Dakota, Pennsylvania and Utah.
In no-fault states, your insurance company pays your medical bills and lost income, but you cannot recover for pain and suffering.
Actually, even in no-fault states, you can file a lawsuit against the at-fault driver, and recover pain and suffering damages, if your case exceeds a certain "threshold." Thresholds vary from no-fault state to no-fault state but normally involve having medical bills in excess of a certain amount or suffering a "serious injury," which is defined in the state's laws.
Curiously, even in no-fault states, fault still determines who pays for property damage caused by a car accident.
Car Accident Liability
In fault states, the first question that must be answered is "who caused the accident?" Or, stated more correctly, "was anyone negligent?"
Generally, those who are negligent and cause accidents are responsible for the resulting damages.
However, there are defenses to negligence claims.
Four states (and D.C.) have a defense called contributory negligence.
Contributory negligence is a complete and total defense to a negligence claim. So, if someone else was the primary cause of an accident, but you were partly to blame for causing it, in contributory negligence states – Alabama, North Carolina, Maryland and Virginia (as well as the District of Columbia) – your contributory negligence completely defeats your claim against the primarily negligent driver. Pretty harsh, huh?
The other states have one of several forms of comparative negligence. Because there are different forms of comparative negligence, be sure to check the law of the state where your car accident happened to get the details.
Generally, though, under a comparative negligence system, your degree of negligence reduces your claim against the more negligent driver by the percentage of your fault. For example, if you were 25% responsible for causing an accident, your claim against the driver who was primarily responsible would be reduced by 25% on account of your contribution to causing the accident.
What I have discussed so far, in car accident lingo, is called the "liability" issue. Here's the "bottom line": If there is no liability, there is no car accident claim that you can make against another driver (although you may be entitled to benefits under your own car accident policy).
Car Accident Damages
If there is liability, the next question is "what harm did the careless conduct cause?" In the language of car accident claims, this question is called the damages question.
See, you are already becoming fluent in car accident-speak. The first car accident claims issue is "liability" and the second issue is "damages."
There are basically two types of car accident damage claims.
One is a claim for damage to your property, mainly your vehicle. These are commonly called property damage, or "P.D.," claims.
The other type of claim seeks compensation for injuries incurred in the accident. Some insurance companies call these personal injury or "P.I." claims. Other companies call them bodily injury or "B.I." claims.
Basically, your claim for injuries (P.I. or B.I.) entitles you to compensation for two things: financial losses and non-financial losses.
Financial losses include the medical bills you incurred, any loss of income and any other financial losses directly caused by the car accident. In insurance-speak, these financial losses are called "special damages," or "specials."
Non-financial losses, or "general damages," are often referred to as "pain and suffering." While physical pain and mental anguish are part of what is included in these non-financial losses, there are other elements of general damages including such things as inconvenience, loss of enjoyment of life and any negative effects on your marriage (which is called "loss of consortium").
If liability exists, you can recover the special damages and general damages resulting from your car accident. If you received a permanent injury that will cause future damages, you can recover those too.
The Car Accident Settlement Process
Most car accident claims are settled without a court trial. In fact, most are settled without courts being involved at all.
Most often, car accident claims are settled by an agreement between the claimant (that's you) and the insurance company responsible for paying damages.
Yes, although your claim is against the at-fault driver, in the overwhelming number of cases, that other driver had car insurance so you end up dealing with the negligent driver's insurance company, not the driver herself. In practice, the insurance company makes all decisions concerning the claim and, up to their policy limit, pays any damages their policyholder owes.
While there are exceptions to these general rules, this is how settlements are usually reached.
Shortly after the accident, car damage claims are resolved. You are entitled to the lower of these two: the cost of repairing your vehicle or your vehicle's actual cash value. So, if it would cost $10,000 to repair your vehicle which is only worth $7,500, your vehicle is considered a "total loss" and you are entitled to receive its value. You are also probably entitled to a rental vehicle while yours is being repaired or until you are paid for your totaled vehicle.
Later, after you recover from your injuries, you can make a car accident injury claim.
Normally, injury claims are initiated by you sending a letter, alternately called a "settlement letter" or a "demand letter," to the responsible insurance company.
In the letter, you document what caused the collision, to prove liability, and you document your losses, to prove damages. Based on the evidence, you make a "demand" for a specified amount that you will accept as compensation for your injuries and damages.
This "demand" usually leads to back-and-forth settlement negotiations with the insurance company. With solid documentation and reasonable negotiation skills, this process will lead you to a car accident settlement.
Car Accident Lawsuits
Sometimes, the negotiations with the insurance company do not produce a settlement. The usual reasons a settlement cannot be made is that you and the insurance company disagree over who caused the accident (liability) or over the amount you are entitled to receive as compensation (damages).
Although there are infrequently-used alternatives, such as mediation and arbitration, the usual alternative if you cannot settle with the insurance company is a car accident lawsuit.
I believe that you can effectively represent yourself in a lawsuit against the driver who caused your accident if that case is in small claims court. In small claims court, formal court procedures are simplified, as are the rules of evidence. One of the guiding principles behind small claims courts is that citizens should be able to represent themselves without a lawyer.
Small claims courts have limits on the maximum amount you can recover, and the limits vary from state to state. The range is a low of $1,500 in Kentucky to a maximum of $25,000 in some jurisdictions in Tennessee. Five thousand dollars ($5,000) is a common limit.
Car Accident Lawyers
As you know, I believe that you can settle routine car accident claims yourself, without a lawyer, provided only that you take the time to learn car accident claims basics. The fact that you are reading this article shows that you are willing to spend the time.
However, at any point in the process of settling your car accident claims, you may decide to hire a car accident lawyer.
For example, if there is a dispute over liability that will be fought out in regular civil court where technical rules of procedure and evidence apply (not small claims court), you should hire a lawyer. Or, if the amount in dispute is too much to risk losing, you should hire a lawyer to protect you.
Traditionally, lawyers charge a "contingent fee." This means that the legal fee is contingent on you recovering money damages for your injuries. If there is no recovery, you owe no fee. If there is a recovery, you owe a percentage of it, usually 1/3, as a legal fee. You may also be responsible for paying out-of-pocket expenses such as court costs.
After You Settle Or Receive A Judgment
After your claim is resolved, either through an out-of-court settlement or a trial in court which results in a "judgment" in your favor, you are not done. There are details to be taken care of.
If you settled with the insurance company, you must sign a Release of your right to make any further claim against the at-fault driver arising out of this accident. That's what a settlement is, an exchange. The insurance company pays you money damages and, in return, you waive (release) your right to make any further claims against the at-fault driver.
There may also be claims against the amount you recovered.
For example, you may have unpaid medical bills. There may also be claims against your recovery from those who paid your medical bills, such as Medicare or your health insurance company. These claims are called liens or subrogation claims. There are technical differences between liens and subrogation claims, but the practical effect of both is that claims are being made against your recovery, and you must deal with them.
Don't pay more on these claims that you are required to pay.
Final Thoughts About Car Accident Claims
It doesn't sound complicated, does it?
Sure, there are details that are not covered in this introduction to car accident claims, but you can find discussions of those details elsewhere at Settle Your Claim Yourself.


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Scenic Vista Wall Art
This scenic artwork is a best seller! It is hand painted oil that has been done on crackled canvas. The canvas has been stretched and mounted on a hardback. Sides are painted black. Due to the handcrafted nature of this artwork, each piece may have subtle differences.


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After over 250 hours in the studio, a successful Kickstarter campaign, and input from professionals and artists, we have something we're ready to show the world.
The Pretty Unknown – DEBUT ALBUM is here! Get your copy today.
Just $15 plus shipping.
TEN, all-original tracks that move from pop love songs to dark, moody, jazz creations, up-tempo funk, and even a couple slow ballads. There's something in there for everyone.
Kickstarters – you'll be receiving your loot here shortly!
Also available on CDBABY!
(and just a few days for iTunes, Amazon and more)
Produced, Recorded & Mixed by Tom Gordon for Inspired Amateur Productions at Imirage Sound Lab, Sparks, NV.
Mastered by Scott Hull at Masterdisk, NYC
2nd engineers: Alan Griffith and Timmy Chatwood.
Thanks to Dr. Lawrence Davis, Imirage Sound Lab.


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Social customer relationship management (CRM) empowers companies to influence their customers and strengthen customer relationships. Social CRM strategies are sustainable only when all stakeholders participate across the social media lifecycle.
In an article published at TMCnet.com, Infosys expert – Nishith Gupta, discusses how stakeholders can contribute to sustainable social CRM:
Published with the permission of TMCnet.com
Nishith Gupta, Associate Consultant, Oracle practice, Infosys Limited
Nishith is a process and domain consulting expert for next generation CRM solutions. He has rich experience in campaign management, customer retention, and customer qualification. Nishith is involved in Infosys Social CRM Center of Excellence. He can be reached at
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It has been a doubt-ridden challenge to use a social medium as an assessment-driven learning journal. Blogging my learning in past years I developed conversational habits: casual language, asking and answering questions, and commenting at other blogs. It was a struggle to maintain these yet also follow academic style while completing tasks that were not designed for conversation. Harder again were tasks suggesting conceptual depth to be written with shallow volume.
This post is the final requirement for my "OLJ for INF206". First it will evaluate how I met learning objectives of the subject with particular reference to three OLJ task posts; then it will reflect on INF206 and critique my development as a social networker and information professional.
Social networking technologies (SNT)
In "Ask me about pins" my critical examination of the functionality of Pinterest focussed on evaluating its usefulness for two of the alleged benefits of social networking technologies: collaboration and engagement with users. Linking to the boards I created and which a fellow student helped populate with contributors; I identified that Pinterest has limited value for collaboration. Its lack of direct interpersonal communication features (ie other than commenting upon a pin) means that except through external communications one cannot volunteer to a board, nor moderate contributions.
Through another board I had been exploring evaluation strategies, identifying that the number of repins, likes and comments was an overt way to see whether an organisation's pinning has engaged with its community. Whether library pinning can be shown to be effective at sending significant traffic to library websites or catalogues awaits evidence that libraries are yet to provide. I reported two examples of libraries who had engaged with pinners from their communities by providing a topic.
Beyond the topic, my Pinterest post demonstrates an understanding of social networking technologies which I tried to apply in all my posts: networking through "link love" (Crosby, 2010, p. 72). When mentioning the fellow student with whom I experimented at collaborative pinning, I linked to her own post. I believe that selective use of HTML links to connect with other people is the foundation of online social networks. It is not enough to rely on social network sites' built in linking features.
Participatory library – concepts, theory and practice
350 words to critique ASU LibraryChannels against "4Cs" (content creation, conversation, community and collaboration) can only barely touch these four of the plethora of themes bandied about with "Library 2.0". Aside from brevity, it was difficult to critique against conceptual standards that ASU Libraries did not overtly state to be their objectives. None of their channels declared any two-way intentions: In Youtube and Twitter they stated only an intention to broadcast news and information and made no overall purpose statements at all in Facebook. Sometimes one-way communication is more suitable to purpose than two-way. For example: when parties are not in equivalent positions with respect to knowledge or goals.
While Mathews (2009) stated that it is the social part of social software that is most crucial; and in many respects I agree, the realm of "social" interaction is more diverse than conversation. Speech itself is a social medium, yet sometimes conversation is neither the best means nor appropriate goal of speech. Therefore perhaps it is no great failure to effectively present one-way communication even where intereactive features are available.
In my dissenting view, many concepts theories and practices were misappropriated under the 2.0 hype. For just one example, I believe that the cycle of communication to discover, provide, evaluate, and improve against customer needs (Casey & Savastinuk, 2006) is actually a pre-existing fundamental standard of librarianship.
Issue – SNissue
My 5 key points on social media policy tried to convey my understanding that:
- Policies form at the intersection of institutional objectives, legal regulations, social mores and individual freedoms.
- Specific behavioural guidance is best given through guidelines and training that differentiate between legal and contractual obligations.
- And, some areas of activity (such as use of third-party tools in education) raise issues that have not yet had all wrinkles ironed out in either policy or guideline.
Again 350 words (nor yet three times that if I try to twist the aforementioned posts into this learning objective) will barely touch a sliver of the social, cultural, educational, ethical or technical management issues that exist and evolve in computer mediated social networking. However this post did refer to a selection of other policies relevant to such issues that ought to be reviewed to make clear their application in the context of social media behaviours.
INF206 and becoming a SNIP
INF206 introduced me to fellow students and provided opportunities to discuss issues at the intersection of social network sites and information practice. I am grateful to the students who explored new tools with me; and those who, through comments within the Facebook group, between our blogs and in one-to-one discussions through Skype, Google + Hangout, Second Life and email, engaged with me in deeper, critical discussion. I look forward to seeing ongoing stimulation from them through our social network sites, and hope my own sharing will be useful to them.
Experience with social networking sites (SNS) may help develop three main information professional (IP) capacities: to liaise within SNS; to advise clients regarding SNS as information media; and to use (ie organise, search, or publish within) SNS as information media. However in each of these, the skills of a social networking information professional (SNIP) are the same as if they were offline, with technological twists.
In liaison one must make connections that suit the goal; and nurture those connections into constructive relationships. During this subject I practiced SNS versions of collegial relationship activities: from initiating and accepting connections in follows and friendships; through stimulating and taking up discussions to cross-channel collaborative experiments; and even some Second Life tutoring.
As a new experiment, I found out how to build an RSS feed from a Twitter search string. With such techniques I have been following Mathews' (2006), Burkhardt's (2010), and Schrier's (2011) advice to listen to my local community for potential patrons and opportunities to engage in conversation. In a professional capacity I think it still common conversational strategies that I apply in institutionally relevant contexts.
As an introvert (ie, not shyness, but rather a preference for fewer, deeper connections) I find that my offline and online social behaviours are similar. I make very few status updates, and enjoy making and receiving comments that dig deeper into interesting topics. I listen long (usually) and make heavy use of silence, drafts, my delete and backspace keys; but find the most versatile tool usually turns out to be questioning, occasionally lubricated with compassion.
Information service
Through the class Facebook group, an article Dale shared prompted me to explore my perspective on advising clients about social sources. Bringing that out here:
Where I see our job as information practitioners is: not to try to characterise any medium as more, or less, suspicious than another medium; but to understand how much credibility or authority or authenticity is important in any particular context–and teach how to check for and convey to the appropriate degree. In some situations it will also be important to identify and produce expressions of objective truth – and if we work in areas where a certain value of truth is important, then we need to know how to check for that.
I probably have this attitude because I do not trust any source at all. Somewhere along the way every single type of source has proven unreliable, so I find it safest to question. Not least, academic and peer-reviewed work. Thoroughness is rare, and apparently for many people rarely necessary – until it is.
Using SNS as information media
Having learned my habits of using informal language and genuine, image-filled content from advocates such as King (n.d), I am not surprised that these are qualities Landis' (2010, p. 79) labels best practice. I was less certain that my less casual sense of humour would qualify, so it was particularly rewarding to have amused Dale, fellow student, (Smith, 2012). Similarly, I take Tim Tyrell-Smith's (2012) thoughtful appreciation of my own take on his advice as validation of my conversational practices.
Mathews (2009) advice to "be yourself" recommends that on the job, librarians communicate as individuals rather than as "faceless, institutional" entities. I had recently added my real face to the nom-de-pixel through which I had already successfully blended personal and professional activity in SNS, but this journal provided excuses to begin writing under my real name, so I feel more prepared to do so in a professional role.


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The neurotransmitter dopamine (DA) modulates executive functions, learning, and emotional processing, all of which are impaired in individuals with autism spectrum disorders (ASDs). Our previous findings suggest a role for dopamine-related genes in families with only affected males.
We examined two additional genes which affect DA function, the DRD2 and PPP1R1B (DARPP-32) genes, in a cohort of 112 male-only affected sib-pair families. Selected polymorphisms spanning these genes were genotyped and both family-based and population-based tests were carried out for association analysis. General discriminant analysis was used to examine the gene-gene interactions in predicting autism susceptibility.
There was a significantly increased frequency of the DRD2 rs1800498TT genotype (P=0.007) in affected males compared to the comparison group, apparently due to over-transmission of the T allele (P=0.0003). The frequency of the PPP1R1B rs1495099CC genotype in affected males was also higher than that in the comparison group (P=0.002) due to preferential transmission of the C allele from parents to affected children (P=0.0009). Alleles rs1800498T and rs1495099C were associated with more severe problems in social interaction (P=0.0002 and P=0.0016, respectively) and communication (P=0.0004 and P=0.0046), and increased stereotypic behaviours (P=0.0021 and P=0.00072). General discriminant analysis found that the DRD2 and PPP1R1B genes additively predicted ASDs (P=0.00011; Canonical R=0.26) and explain ~7% of the variance in our families. All findings remained significant following corrections for multiple testing.
Our findings support a role for the DRD2 and PPP1R1B genes in conferring risk for autism in families with only affected males and show an additive effect of these genes towards prediction of affected status in our families.
Autism spectrum disorders (ASDs) are characterized by repetitive behaviours and interests, as well as deficiencies in communication and social interaction. They are believed to be complex, polygenic disorders predominantly characterized by multifactorial inheritance [1], although Zhao et al. [2] (2007) suggested that Mendelian inheritance may apply to autism risk in a subgroup of families with affected males. To address the significant genetic heterogeneity and phenotypic variation seen among affected individuals, which has confounded the conclusive identification of candidate genes for the majority of cases, we have been testing genes for evidence of association with specific ASD endophenotypes in an effort to identify a subgroup within the ASD population whose members share an underlying pathophysiology.
Abnormalities in neurotransmitter pathways can account for the deficits seen in persons with ASDs. In contrast to the attention which has been directed to the study of genes involved in the glutamate [3], GABA [3] and serotonin pathways [1], genes related to the synthesis, function and metabolism of dopamine (DA) have received little attention [4].
We have argued [5] that genes in the dopaminergic (DAergic) pathway are excellent candidates based on their affect on ASD behaviours. DA modulates motor functions [6], cognitive processes (including executive functions [7] and learning [8]), and emotional regulation [9] - all of which are abnormal in individuals with autism [10-13]. DA also plays a role in social interactions [14] and the pathophysiology of stereotypies [15]; impairments in social interaction and the presence of increased stereotypies are core features of autism. Furthermore, there is decreased DAergic activity in the medial prefrontal cortex (PFC) in children with autism [16], and increased levels of the major metabolite of DA, homovanillic acid (HVA), in cerebrospinal fluid from affected children compared to controls [17], indicating altered DAergic function in these individuals.
Based on our earlier findings on the dopamine β-hydroxylase (DBH) gene, which encodes the enzyme that converts DA to norepinephrine, in mothers from male-only affected sib-pair families [18], we have pursued a comprehensive study of DA-related genes in mothers and sons with ASDs. Since our initial study with DBH, in which we found an increased frequency of the 19-bp deletion in mothers from male-only affected sib-pair families [18], we identified a 3-marker risk haplotype in the dopamine D1 receptor (DRD1) gene [5] in our family cohort having only affected sons. Here we report our findings on two other genes affecting DA levels and function, the dopamine D2 receptor (DRD2) and protein phosphatase 1, regulatory subunit 1B (PPP1R1B) genes, and results of tests for gene-gene interactions.
The DRD2 gene comprises eight exons [19] and maps to 11q22-q23 [20]. It encodes the dopamine D2 receptor which, in addition to its role in postsynaptic neurons, acts as an autoreceptor mediating DA synthesis [21] and neurotransmission [22] in DAergic neurons. The dopamine D2 receptor is involved in the DAergic modulation of executive functions [23], reversal learning [24] and emotional processing [25]. Drd2−/− mice have abnormal gait similar to that of individuals with Parkinson disease [26], and the administration of antipsychotic medications (e.g., risperidone, a dopamine D2 receptor antagonist) has proven efficacious in treating symptoms associated with ASDs [27].
The PPP1R1B gene, located at chromosome 17q12 and comprising 7 exons ( http://www.ncbi.nlm.nih.gov; GeneID 84152), encodes DARPP-32, which is expressed in dopaminoceptive (DAceptive) neurons [28] and mediates the effects of both D1 and D2 dopamine receptor classes [29]. For example, dopamine D2 receptor antagonist-induced catalepsy in rats is attenuated in Ppp1r1b−/− mice [30] and knockout mice are impaired in reversal learning [31]. Genetic [32,33] and immunoblot [34] studies showed an association of PPP1R1B with altered PFC DARPP-32 protein levels in schizophrenia and bipolar disorder, two conditions for which DA dysfunction is evident and which exhibit comorbidity with autism [35].
There are two previous studies which examined the DRD2 gene as a candidate gene for autism. The first [36] reported an increased frequency of the TaqI A1 allele in persons with autism (N=33) compared to controls (N=314), whereas the second [37] found no evidence for transmission disequilibrium of an intragenic microsatellite in 39 affected sib-pair families. No association studies have examined the role of PPP1R1B as a candidate gene for ASDs.
Based on our hypothesis that DA-related genes are important in male-only affected sib-pair families [18], we examined four markers at the DRD2 locus that are commonly used to investigate possible associations between DAergic function and behavioural abnormalities [38], and three polymorphisms at the PPP1R1B locus to determine whether there was an association of these DA-related genes with autism.
The 112 affected sib-pair families and the comparison group (N=443) were previously described [5]. Briefly, the study group included 28 families from Canada [18], 5 from the South Carolina Autism Project [39], and 79 families obtained through the Autism Genetic Resource Exchange (AGRE) in the United States [40]. All families have two or more children with either autism or an ASD, including Asperger syndrome and pervasive developmental disorder (PDD) variants. This study was approved by the Queen's University Research Ethics Board and written informed consent was obtained from parents of all participating families from Canada and South Carolina, and through AGRE [40].
All 443 samples from the comparison group (bloodspots from anonymous newborns taken for the purpose of PKU testing and made available from the Ontario Ministry of Health) were available for the study of the PPP1R1B locus. Two hundred and fifty-three comparison group samples were used for the DRD2 gene studies. There were no significant differences in the allele frequencies for DRD2 (P=0.57–0.93) and PPP1R1B (P=0.28–0.91) markers in males and females from the respective comparison cohorts and thus our comparison cohorts included both males and females. Although comprehensive information regarding psychiatric and behavioural disorders is not available for the comparison group, we do not expect the prevalence of ASDs in this comparison group to be greater than that in the general population, or approximately 1/110 [41].
Four polymorphisms (rs1799732 Ins/Del, rs1079597 G/A, rs1800498 T/C and rs1800497 C/T) were studied at the DRD2 locus (Figure (Figure1).1). The DRD2 gene contains four haplotype blocks [Haploview 4.1; available at http://hapmap.ncbi.nlm.nih.gov] [42]. Three of the blocks are small (<4kb) and one block is 20kb in size. One of four polymorphisms used in this study, rs1079597, is part of the HapMap dataset. both this SNP and and rs1800498 are located within the larger haplotype block and were examined in previous studies of other neuropsychiatric disorders. Primer sequences, PCR and digestion conditions are shown in Table Table1.1. All PCR reactions were carried out using 5ng of template DNA; digestion products were separated on either 2% (rs1079597, rs1800498 and rs1800497) or 2.5% (rs1799732) agarose gels and visualized using ethidium bromide and UV illumination. In order to minimize genotyping errors, DNAs from affected individuals and family members were randomly arranged on 96-well plates, and all results were independently scored and tabulated by two persons.
Three polymorphisms (rs1495099 G/C, rs907094 T/C and rs3764352 A/G) were examined in the PPP1R1B gene (Figure (Figure2).2). These variants were chosen from the NCBI dbSNP Build 121 database from the Human Genome Project (available at http://www.ncbi.nlm.nih.gov/SNP/snp_summary.cgi) based on the following criteria: the markers span the PPP1R1B locus, they have minor allele frequencies (MAFs) of approximately 20%, and alleles at rs907094 and rs3764352 are associated with changes in DARPP-32 mRNA expression and measures of cognitive performance [32]. The PPP1R1B locus has a single haplotype block which includes rs907094 and rs3764352 as haplotype-tagged SNPs (htSNPs). PCR reactions were carried out using 5ng of template DNA and amplicons were digested using conditions shown in Table Table1.1. All digestion products were separated on 2% agarose gels and visualized using ethidium bromide and UV illumination. In order to minimize genotyping errors, DNAs from affected individuals and family members were randomly arranged on 96-well plates, and all results were independently scored and tabulated by two persons.
Prior to carrying out analyses, Mendelian errors were checked in the family cohort using the FBAT program, v1.5.5 [44]. DRD2 marker data on five families and PPP1R1B marker data on two families were excluded from the analyses due to identified Mendelian errors. Single gene analyses were performed as previously described [5]. To avoid allele and genotype frequency distortion from using related individuals in case–control comparisons, one affected individual was selected at random from each family using SPSS v14.0 (SPSS, Chicago, IL) with the same cohort of randomly chosen individuals used for single marker allele and genotype frequency comparisons for all polymorphisms as well as general discriminant analyses. Family-based association tests (FBAT), including quantitative disequilibrium tests (QTDT), were done using FBAT v1.5.5. Because FBAT v1.5.5 can accommodate multiple affected individuals from each family, all affected individuals including those used for case–control comparisons, were included for FBAT and QTDT analyses. The domains, 'reciprocal social interaction', 'communication' and 'repetitive stereotyped behaviours' used for QTDT analyses were derived from the total scores from the 'Qualitative Abnormalities in Reciprocal Social Interaction' (A1 to A4), 'Qualitative Abnormalities in Communication' (B1, B2(V), B3(V) and B4) and 'Restricted, Repetitive, and Stereotyped Patterns of Behaviour' (C1 to C4) subdomains in the ADI-R diagnostic algorithm [45].
General Discriminant Analysis (GDA) was used to evaluate the predictive value of our single gene findings in discriminating between individuals with and without autism, as well as to test for evidence of interaction effects between genes. Genotypes were coded as categorical variables and GDA was performed using Statistica 9.1 [Statsoft, Tulsa, OK, USA].
The contribution of a single gene to autism susceptibility is predicted to be relatively small and thus difficult to detect statistically. Although corrections for multiple testing must be made in genetic association studies, Bonferroni correction is thought to be too stringent, with a high risk for rejecting true significant findings. The false discovery rate (FDR) approach [46] is a compromise between not correcting for multiple comparisons, which is too lax, and Bonferroni adjustments, which are too strict. FDR has two methods, the Benjamini and Hochberg (BH) method and the Benjamini and Liu method (BL) [46]. The BH method is appropriate for correcting for both independent and positively-dependent comparisons [47], and thus is appropriate for genetic studies using polymorphisms.
FDR corrections were performed separately for single gene case–control and family-based comparisons, as well as GDA findings, using an initial FDR threshold of 0.050.
High r2 measures of linkage disequilibrium (LD) were observed between DRD2 polymorphisms rs1079597 and rs1800497, with no LD between rs1799732 and rs1079597 and rs1800497 (Figure (Figure1).1). R-squared measures between PPP1R1B markers showed high LD (r2>0.9) between rs907094 and rs3764352, and lower LD between rs1495099 and rs907094 and rs3764352 (Figure (Figure22).
All four markers of DRD2 were in HWE in the comparison and family cohorts with the exception of rs1799732 and rs1800498 in affected males (P=0.009 and P=0.012, respectively); all markers were in HWE in the parents from these families. As shown in Table Table2,2, there was an increased frequency of the rs1800498 TT genotype (P=0.007) in affected males (43.4% versus 28.7% in the comparison group), which remained significant following FDR correction. No significant differences in genotype frequencies of the other three markers were seen between cases and the comparison group (P=0.32–0.51) (Table (Table2).2). Separate analyses using the extended-transmission disequilibrium test (ETDT) showed that significant over-transmission of the rs1800498 T allele was not from mothers (21 transmitted, 11 untransmitted; χ2=3.125, df=1, P=0.077) but was from fathers (26 transmitted, 12 untransmitted; χ2=5.158, df=1, P=0.023) to affected sons. No differences in rs1800498 T allele or rs1800498 TT genotype frequencies were found between mothers (P=0.69 and P=0.26, respectively) or fathers (P=0.90 and P=0.65, respectively) and the comparison group (data not shown).
All three PPP1R1B markers were in HWE in the comparison group; none were in HWE in the cohort of affected individuals (P=0.008, P=0.033 and P=0.033, respectively), although all markers were in HWE in the parents (data not shown). As shown in Table Table2,2, the rs1495099 CC (P=0.002), rs907094 CC (P=0.028) and rs3764352 GG (P=0.025) genotype frequencies were increased in affected males (22.0%, 14.5% and 14.5%, respectively) relative to the comparison group (9.9%, 6.9% and 6.7%, respectively). Findings on alleles of these polymorphisms were similar, with the minor allele frequencies of all three markers, rs1495099 C, rs907094 C and rs3764352 G, being increased in the affected males relative to the comparison group (P=0.001, P=0.014 and P=0.021, respectively, all remained significant following FDR correction; data not shown).
Because we hypothesize that maternal effects including genetic factors may contribute to autism susceptibility in some autism families [18], we compared frequencies of rs1495099 C alleles and rs1495099 CC genotypes between mothers (33.2% and 12.7%, respectively) and the comparison group (28.7% and 9.9%, respectively) but found no significant differences (P=0.19 and P=0.39, respectively; data not shown).
FBAT showed that the DRD2 rs1800498 T allele was over-transmitted to affected males (P=0.0003; significant following FDR correction), while no evidence of preferential allele transmission was found for the other three markers (P=0.16–0.94) (Table (Table3).3). The rs1799732 Ins - rs1079597 G - rs1800498 T - rs1800497 C (Ins-G-T-C) haplotype, consisting of the major alleles for all four markers, was over-transmitted to affected males but with a P-value (P=0.0009; data not shown) slightly higher than that observed with rs1800498 T alone (P=0.0003). It should be noted that the additive model was used in FBAT for polymorphisms at the DRD2 locus because of the increased CT and TT genotype frequencies found for rs1800498.
For PPP1R1B, a recessive model was used in FBAT because of the increased frequency of rs1495099 CC, rs907094 CC and rs3764352 GG genotypes found in affected individuals compared to the comparison cohort. Family-based association analyses and FDR-based corrections showed significant over-transmission of rs1495099 C (P=0.00092) but not of rs907094 C (P=0.11) or rs3764352 G (P=0.09) (Table (Table3).3). The rs1495099 C - rs907094 C - rs3764352 G (C-C-G) haplotype was not significantly over-transmitted to affected males (P=0.031; not significant following FDR correction; data not shown) compared to that of rs1495099 C alone (P=0.00092).
We next used quantitative transmission disequilibrium tests (QTDT) to determine whether the extent of impairment in the core behaviours was more pronounced in affected males with the risk allele. The DRD2 rs1800498 T allele was associated with more severe impairments in reciprocal social interaction (P=0.0002), verbal communication (P=0.0004), and repetitive and stereotyped behaviours (P=0.0021); these findings remained significant following corrections for multiple comparisons.
The PPP1R1B rs1495099 C allele was associated with higher ADI-R domain scores (more severe problems) in affected males for social interaction (P=0.0016), nonverbal communication (P=0.0046), and stereotyped behaviours (P=0.00072) (Table (Table4),4), with strong evidence for association shown by multivariate QTDT between rs1495099 C and the combined effect of all three ADI-R subdomains (P=0.00042; data not shown). All findings were significant following FDR-based corrections.
We used GDA to determine whether DA-related genes predict ASD susceptibility in affected males compared to the comparison group and to test for gene-gene interactions. Tests were performed based on our single gene findings for DRD2 and PPP1R1B from this study, and our previous findings with DRD1[5]. DRD2 rs1800498 genotypes and PPP1R1B rs1495099 genotypes each significantly contributed to prediction of ASDs in our families (P=0.0063 and P=0.00086, respectively), as well as when weighted and tested together (P=0.00011; Canonical R=0.26) (Table (Table5).5). We generated a classification matrix to determine the percent correct classification of individuals with and without autism based on DRD2 rs1800498 and PPP1R1B rs1495099 genotypes, and found that 97% of individuals from our comparison cohort and 13% of individuals with autism were correctly classified (the analysis was based on the a priori baseline frequency of 70% of individuals without autism and 30% of individuals with autism). Using the weighted scores to predict group membership, we found that 72% of control individuals and 64% of affected individuals were predicted correctly using DRD2 and PPP1R1B genotypes. However, while ~7% of the variance was explained with DRD2 rs1800498 and PPP1R1B rs1495099 genotypes, addition of our previously identified DRD1 rs265981–rs4532–rs686 haplotypes to the analyses did not result in a significant improvement in the overall canonical correlation (Canonical R=0.27).
Adding all possible two-way interactions between DRD2 rs1800498 and PPP1R1B rs1495099 genotypes, as well as comparisons between DRD1 rs265981–rs4532–rs686 haplotypes and DRD2 rs1800498 genotypes, and DRD1 rs265981–rs4532–rs686 haplotypes and PPP1R1B rs1495099 genotypes, we found no evidence for gene-gene interactions (P=0.35–0.75; data not shown).
Our model for the involvement of the DA pathway in determining some of the core deficits of ASDs is based on earlier results implicating the DBH gene as a maternal effect locus, and on our hypothesis that autism susceptibility is determined by a combination of fetal susceptibility genes and fetal gender as well as maternal effects including maternal genetic factors [18]. Following our findings with the DRD1 gene [5], and as part of our investigation to determine whether other DA-related genes are significant factors in the etiology of ASDs, we found evidence for association of the DRD2 and PPP1R1B genes with autism in affected males from multiple-incidence families.
We found an increased frequency of the DRD2 rs1800498 TT genotype (P=0.007) in affected males (43.4%) compared to the comparison group (28.7%) (Table (Table2),2), and the rs1800498 T allele was over-transmitted to affected children (P=0.0003) (Table (Table3).3). The rs1800498 risk allele was associated with more severe impairments in social interaction (P=0.0002), verbal communication (P=0.0004) and stereotyped behaviours (P=0.0021) in affected males (Table (Table4),4), and the rs1800498 TT genotype was associated with an increased risk for ASD with an OR of 1.9 [95% CI: 1.5–2.5]. In addition, we examined three polymorphisms at the PPP1R1B locus and identified the rs1495099 C allele as a recessive risk allele for susceptibility to ASDs in male-only affected sib-pair families. The CC genotype frequency was increased in affected males (22.0%) relative to the comparison group (9.9%, P=0.002), and family-based association tests using FBAT with a recessive model showed distorted allele transmission with over-transmission of this allele in families (P=0.00092) (Table (Table3).3). This allele was associated with greater impairments in social interaction (P=0.0016) and nonverbal communication (P=0.0046), and more severe stereotyped behaviours (P=0.00072), core features of ASDs. Finally, the rs1495099 CC genotype was associated with an increased risk for ASD with an OR of 2.6 [95% CI=1.9–3.6]. All findings were significant following FDR-based corrections for multiple comparisons.
Our findings at the DRD2 and PPP1R1B loci may reflect the functional effects of unidentified risk variants in LD with rs1800498 at DRD2 and rs1495099 at PPP1R1B. Functional analyses of these markers have not been reported but in silico analyses performed using PupaSuite [available at http://pupasuite.bioinfo.cipf.es/] [48] did not identify any putative functional role for these polymorphisms while analyses using FASTSNP [available at http:// http://fastsnp.ibms.sinica.edu.tw/pages/input_CandidateGeneSearch.jsp] [49] predicted a 'very low-to-low' effect for rs1800498 at DRD2 as an intronic enhancer and a 'very low-to-medium' effect for rs1495099 at PPP1R1B as a regulatory region/intronic enhancer. Meyer-Lindenberg et al. [32] (2007) identified a common 7-marker PPP1R1B haplotype that was associated with increased DARPP-32 mRNA expression and improved performance on measures of working memory and cognitive flexibility. This haplotype included the T and A alleles of rs907094 and rs3764352 respectively, while a haplotype containing the minor alleles at these loci (i.e. rs907094 C and rs3754352 G) was associated with decreased mRNA expression in post-mortem brain. Houlihan et al. [50] (2009) screened this 7-marker haplotype to test PPP1R1B as a genetic determinant of cognitive ageing and found that rs907094 C and rs3754352 G alleles were associated with decreased cognitive ability. However, our findings do not support an association of either rs907094 C or rs3764352 G with autism in our family cohort. Unfortunately, because rs1495099 was not included in these studies, its functional role is not known. With respect to the DRD2 locus, the rs1800498 polymorphism was found to be in low LD with rs1799732, a functional variant in the DRD2 promoter [51], in our comparison group and parents from families (Figure (Figure1).1). To investigate whether alleles from rs1799732 are contributing as a risk factor for autism susceptibility in our families, comparisons between family-based tests of rs1800498 and rs1799732 alleles considered separately (P=0.0003 and P=0.16, respectively), and haplotypes containing alleles from both rs1800498 and rs1799732, showed that the observed over-transmission in families is derived from rs1800498, and not because of the rs1799732 polymorphism (data not shown). However, only 31 families were informative for rs1799732 compared to 73 families for rs1800498, so we cannot determine from these findings whether alleles from the functional variant rs1799732 are contributing to autism susceptibility in our families. Another genetic variant at the DRD2 locus, rs1076560GT, has been associated with altered mRNA isoform expression [52,53] and differences in striatal post-synaptic D2 receptor abundance [54]. Bertolini et al. [53] (2009) found in control and schizophrenia cohorts (N=114 and N=91, respectively) that individuals heterozygous for the minor "T" allele perform worse in the N-back test of working memory but only at a high level of difficulty (2-back) compared to individuals homozygous for the major "G" allele while Zhang et al. [52] (2007) found using healthy subjects (N=117) that heterozygous individuals performed worse at higher attentional loads in the variable attentional control (VAC) task, and had increased activity as measured using BOLD fMRI in PFC and striatum compared to individuals homozygous for the major allele. However, the true contribution of this variant to DAergic function and cognition is unclear as no genotype effects of this polymorphism to overall working memory performance and fMRI activity were also reported [52,54]. Nevertheless, both rs1076560 and rs1079597 are in high LD in the HapMap CEU panel (r2>0.9) and are found in the same 20kb haplotype block as rs1800498. However, no information is available regarding LD between rs1076560 and rs1800498. It is of interest that low LD (r2<0.3) was found between rs1800498 and rs1079597 in our comparison group and parents from families (Figure (Figure1).1). Additional families informative at these DRD2 loci are needed to determine whether these functional variants or another functional polymorphism in LD with rs1800498 is responsible for the increased risk for autism. In addition, functional analyses and resequencing of both genes in affected individuals with this risk haplotype at DRD2 or the risk allele at PPP1R1B are required.
The QTDT results support an association of the DRD2 and PPP1R1B loci with autism (Table (Table4).4). A role for the DRD2 gene in autism susceptibility is suggested by the fact that antipsychotic medications, which prevent dopamine D2 receptor activation, improve the core symptoms of ASDs [55]. Postsynaptic D2 receptors and presynaptic D2 autoreceptors are involved in the DAergic modulation of cognitive and emotional processes that are impaired in individuals with autism [56,57]. Thus, functional polymorphisms which affect receptor availability (e.g. altered gene expression), either postsynaptically on DAceptive neurons or presynaptically on DAergic neurons, may contribute to the impairments found in individuals with autism.
DARPP-32 mediates the downstream effects of dopamine receptor activation, and thus plays an important role in the modulation of DA-related processes which are abnormal in individuals with autism. Unlike dopamine receptors, which can be studied using systemic or local administration of ligands, DARPP-32 is found in the cytoplasm of DAceptive neurons and there are few studies which have examined its role in DA-modulated processes and behaviours. One such study by Hotte et al. [58] (2006) found that administration of D1 receptor antagonists in mice caused deficits in working memory which coincided with decreased levels of phosphorylated-DARPP-32 in the PFC. Deficiencies in working memory [59] and impairments in reversal learning [10] are found in individuals with autism. Both Drd2 −/− mice and Ppp1r1b −/− mice exhibit impairments in reversal learning compared to wild-type mice [31,60].
The role of DARPP-32 in mediating the DA-related changes to neuronal excitability necessary for memory and learning was shown in a study by Calabresi et al. [61] (2000). These authors were unable to induce long-term potentiation (LTP) and long-term depression (LTD), two forms of synaptic plasticity, in the striatum of Ppp1r1b −/− mice. DA has a role in synaptic plasticity in both the striatum [62] and amygdala [63], subcortical structures that are important for regulating emotional behaviours [64] and social interactions [65], and are implicated in the pathophysiology of repetitive behaviours [66].
Based on our findings in this study and our previous findings [5], single-gene analyses showed evidence for association of DRD1DRD2 and PPP1R1B with autism in male-only affected sib-pair families. We performed general discriminant analysis using Statistica v9.1 to predict ASD susceptibility in affected males, and to test for evidence of gene-gene interactions of DA-related genes and ASDs. We found that DRD2 rs1800498 genotypes and PPP1R1B rs1495099 genotypes significantly contributed to prediction of ASDs in our families when tested separately and together (P=0.0063–0.00011), which accounted for ~7% of the variance. These results were significant following corrections for multiple comparisons (Table (Table5).5). We also found that 97% of individuals from our comparison cohort and 13% of individuals with autism were correctly classified while 72% of control individuals and 64% of affected individuals were predicted correctly using a weighted additive combination of DRD2 and PPP1R1B genotypes. The inclusion of DRD1 rs265981–rs4532–rs686 haplotypes into the analysis did not significantly change our findings (data not shown), and we found no evidence for gene-gene interactions (data not shown).
Our findings suggest that single genes individually confer risk of autism susceptibility in our families and, although there was no evidence for gene-gene interactions between DA-related genes and autism susceptibility per se, we did find evidence that DRD2 and PPP1R1B together significantly contribute to ASD prediction. Thus, while both genes independently confer risk of autism susceptibility, there is a cumulative effect towards predicting whether an individual has the condition. Furthermore, based on our findings from GDA analysis we found an effect size of ~7%. While this effect size is small, it is comparable to those reported in similar studies [4]. These generally small effect sizes likely reflect the highly heterogeneous nature of ASDs.
The increased transmission of the DRD1 rs265981 C –rs4532 A –rs686 T (C-A-T) haplotype from mothers (P=0.029) [5], and of the DRD2 rs1800498 T allele from fathers (P=0.023), to affected sons suggests that imprinting effects of these genes are also important risk factors for ASDs. A role for imprinting has been proposed for several brain-related disorders, including autism [67]. There is evidence of imprinting of genes from neurotransmitter pathways implicated in ASDs such as the 5-hydroxytryptamine receptor 2A (HTR2A) gene in the serotoninergic pathway [68].
The dopamine D1 and D2 receptors are expressed in human placentae [69,70] and fetal brains [71,72]. Placental D1 and D2 receptors are involved in DA-mediated release of opioids [73] and lactogen [74] respectively, which are required for fetal development and growth . Both dopamine D1 and D2 receptors are involved in brain development. Dopamine D2 receptors expressed in fetal brain induce neurite outgrowth and axon elongation while dopamine D1 receptors inhibit neurite outgrowth in cortical neuron differentiation [75], with the opposite effects found in striatal neuron differentiation [76]. There is no evidence for the kind of parent-of-origin-specific DNA methylation at the DRD1 or DRD2 loci in either human placentae or fetal brains that is suggestive of imprinting [77]. Further, a review of the 'imprinted gene and parent-of-origin effect' database [available at http://igc.otago.ac.nz/home.html] [78] did not yield any evidence supporting imprinting at either locus. The possibility remains, however, that imprinting of these genes may occur during a very narrow developmental period or in a specific subpopulation of brain cells, as has been demonstrated for the Ube3a gene in mice [79]. It should be noted that the evidence presented for parent-of-origin effects in ASDs is based on three markers in the DRD1 gene and one marker in the DRD2 gene and thus, more polymorphisms need to be studied to confirm our findings.
Our results strongly support a role for the DRD2 and PPP1R1B genes in susceptibility to autism spectrum behaviours in males from affected sib-pair families in which there are only affected males, and especially those males where there are severe impairments in social interaction (DRD2 and PPP1R1B), verbal communication (DRD2), nonverbal communication (PPP1R1B) and stereotyped behaviours (DRD2 and PPP1R1B). Our results also support an additive effect of the DRD2 and PPP1R1B genes in predicting ASDs in our families. However, we recognize that large genome-wide association studies have not implicated these genes in autism susceptibility, but those studies did not analyse male-only affected sib-pair families separately from other families, and there is no information about the level of impairments in the core characteristics of ASDs. Further studies are needed using additional similar family cohorts and sequencing of the DRD2 and PPP1R1B genes in individuals with the risk alleles to identify functional polymorphisms that could be associated with the clinical findings in order to further develop our model for an association of DA-related gene function and susceptibility to ASD behaviours.
The authors declare they have no competing interests.
JJAH and JAH conceived and designed the study. JAH was a graduate student and this study is part of his PhD research. JAH and XL carried out the molecular analyses. MLH and AL manage the study subjects and phenotype data. ILC, RCM, CES, and MESL participated in the evaluation of the subjects. JAH, XL, and ILC performed the data analyses. JAH wrote the initial draft of the manuscript and all authors read and participated in the writing and approval of the final manuscript.
This work was supported by research grants from the Ontario Mental Health Foundation (OMHF; JJAH, PI), the Canadian Institutes for Health Research (CIHR; #43820, JJAH, PI) and the Canada Foundation for Innovation (#7939) to the Autism Spectrum Disorders Canadian-American Research Consortium (ASD-CARC) (JJAH, PI; http://www.asdcarc.com; http://www.AutismResearch.ca) and funded in part by a grant from the South Carolina Department of Disabilities and Special Needs (SCDDSN)(CES). This work was also supported by a research studentship from the OMHF to JAH. JAH was a trainee with the CIHR/Autism Speaks STIHR Interdisciplinary Inter-Institute Autism Spectrum Disorders Training Program (PI: JJAH) ( http://www.AutismTraining.ca). MESL is a Career Scholar supported by the Michael Smith Foundation for Health Research. The authors are very grateful to all the families who participated in this research and we gratefully acknowledge the resources provided by the Autism Genetic Resource Exchange (AGRE) Consortium and the participating AGRE families. AGRE is a program of Cure Autism Now and is supported, in part, by grant MH64547 from the National Institute of Mental Health to Daniel H. Geschwind (PI).
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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According to The Tracking Board Scarlett Johansson, the recent star of Marvel's Avengers is being chased to play a lead role in Universal's remake of Creature From The Black Lagoon. Although nothing is official – she does have our approval. Now the script or story itself? That's yet to be seen.
Creature From The Black Lagoon was the last of the classic Universal Monsters and unlike it's predecessors has not yet been remade in one form or another. With Universal eyeing to reboot all of it's classics we've been the most hesitant about this one. Stay tuned for more news as it's available!


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