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Wild Australian Bushrangers
Bushrangers!'Bail Up' Escape from Cockatoo Island
During the 1820s, the number of bushrangers roaming around New South Wales, was so great that the government passed an act called the Bushranger Act, which gave police and soldiers almost unlimited powers to capture, search and ultimately hang, those convicted of 'bushranging' crimes. Economically, times were tough and this combined with the use of harsh punishment methods, was probably responsible for the outpouring of public sympathy and the rise of the mythical, romantic, bushranger folk hero. Some bushrangers, were violent, nasty and dangerous however and others were from marginalised groups, or were political rebels. Here are just a few:
John Caesar, was Australia's first bushranger. He was a convict from the First Fleet and a huge, dark, giant of a man of west Indian descent, who had initially fled to England, to avoid becoming a plantation slave . He was then transported from England, for stealing 240 shillings and sent to New South Wales for 7 years. In 1789, he escaped into the bush with a musket and began stealing food. A year later he was speared by Aboriginals and he moved back closer to the settlement. He was then captured and sent to the infamous, Norfolk Island and fathered a daughter there with Ann Power. Not long after leaving Norfolk Island for Port Jackson, he ran off into the bush again. Governor Hunter, put a price on his head of five gallons of rum, which would go to the man who captured him. A settler named John Wimbow shot him dead near liberty Plains (Strathfield).
Jack Donahoe
Also known as, The Wild Colonial Boy, after the famous folk ballad written about him, Jack Donahoe (1806 30), was born in Dublin and transported to New South Wales in 1823 for the 'intent to commit a felony'. Donahoe was a 'flaxen' haired, 'blue' eyed, Irish rebel who is admired for his defiance and bravery. On arrival in New South Wales, he had been assigned to a chain gang, but absconded with two other Irish men and began robbing bullock drays on the Windsor Road. The three men were caught and twice sentenced to death. The two other men hung, but Donahoe managed to escape and got together a gang and went on a crime spree, bailing up travelers on roads from Bathurst to Yass. Donahoe, became famous for constantly eluding the police and for brazenly riding into Sydney Town to have a ginger beer. He was caught however, when one of his gang turned informer. Donahoe, was gunned down at Bringelly, near Campbelltown, as he urged the police on using 'insulting and indecent epithets'.
(Sir) Thomas Mitchell drew a post mortem drawing of Donahoe' head and shoulders, which is now in the Mitchell Library. Also within weeks of his death a tradesman began making clay pipes which resembled Donahoe's head, complete with bullet hole.
Jack Donohoe
wanted Dead or AliveMatthew Brady
Credit: Archives Office of Tasmania
Matthew Brady, (1799 1826) was transported on the Juliana for the crime of stealing a basket and Hermes birkin bags fake some butter, bacon, sugar and rice. He was sent to van Diemen's land (Tasmania) and replica birkin handbags became a constant absconder. As punishment, he received around 350 lashes in four years. He was then sentenced to Macquarie Harbour, but escaped with 13 other desperate convicts, in a whale boat in 1824. For two years, the gang roamed the bush, aided by settlers, who were former convicts. A Reward was offered by Governor Arthur, replica hermes handbags outlet to anyone who could deliver Brady to the law. Brady responded with a cheeky note fastened to the door of an Inn:
"It has caused Matthew Brady much concern that such a person known as Sir George Arthur is at large. Twenty Gallons of Rum will be given to any persons that will deliver this person to me."
The reward for Brady was raised to 300 guineas and Brady was captured.
Brady was known as the "Gentleman Bushranger", as he only used violence in fashion cheap hermes handbags self defence and never harmed a women. His cell in Hobart, as he waited to stand trail was filled with flowers and cakes sent by female sympathisers and the crowd that watched him hang on May 26, cried and cheered him on. A lookout is named after him, in Tasmania, called Brady's lookout, with views over the Tamar River
Captain ThunderboltFred Ward, who is known as 'Captain Thunderbolt', was born in Windsor, in New South Wales, in 1836 and was the son of a convict. He was working as a drover and horse breaker when sentenced to Cockatoo Island for horse stealing. He was then, conditionally released from the island and was working as a horse breaker in Mudgee, but then returned to Cockatoo Island for various offences. Ward, escaped from the island and went to live with his half Aboriginal wife and their children on the Culgoa River near Bourke. He then, adopted the name 'Captain Thunderbolt' and began an almost 7 year crime spree. During this time, Ward was shot in the knee during a gunfight, when spotted by troopers (this helped the identification of his body later). Another time a constable held a pistol to his head and said 'you are my prisoner'. Thunderbolt laughed and galloped off into the bush. He met his end however in Uralla, New South Wales during a gunfight with a trooper.
Bushrangers!'Bail Up' Escape from Cockatoo Island
During the 1820s, the number of bushrangers roaming around New South Wales, was so great that the government passed an act called the Bushranger Act, which gave police and soldiers almost unlimited powers to capture, search and ultimately hang, those convicted of 'bushranging' crimes. Economically, times were tough and this combined with the use of harsh punishment methods, was probably responsible for the outpouring of public sympathy and the rise of the mythical, romantic, bushranger folk hero. Some bushrangers, were violent, nasty and dangerous however and others were from marginalised groups, or were political rebels. Here are just a few:
John Caesar, was Australia's first bushranger. He was a convict from the First Fleet and a huge, dark, giant of a man of west Indian descent, who had initially fled to England, to avoid becoming a plantation slave . He was then transported from England, for stealing 240 shillings and sent to New South Wales for 7 years. In 1789, he escaped into the bush with a musket and began stealing food. A year later he was speared by Aboriginals and he moved back closer to the settlement. He was then captured and sent to the infamous, Norfolk Island and fathered a daughter there with Ann Power. Not long after leaving Norfolk Island for Port Jackson, he ran off into the bush again. Governor Hunter, put a price on his head of five gallons of rum, which would go to the man who captured him. A settler named John Wimbow shot him dead near liberty Plains (Strathfield).
Jack Donahoe
Also known as, The Wild Colonial Boy, after the famous folk ballad written about him, Jack Donahoe (1806 30), was born in Dublin and transported to New South Wales in 1823 for the 'intent to commit a felony'. Donahoe was a 'flaxen' haired, 'blue' eyed, Irish rebel who is admired for his defiance and bravery. On arrival in New South Wales, he had been assigned to a chain gang, but absconded with two other Irish men and began robbing bullock drays on the Windsor Road. The three men were caught and twice sentenced to death. The two other men hung, but Donahoe managed to escape and got together a gang and went on a crime spree, bailing up travelers on roads from Bathurst to Yass. Donahoe, became famous for constantly eluding the police and for brazenly riding into Sydney Town to have a ginger beer. He was caught however, when one of his gang turned informer. Donahoe, was gunned down at Bringelly, near Campbelltown, as he urged the police on using 'insulting and indecent epithets'.
(Sir) Thomas Mitchell drew a post mortem drawing of Donahoe' head and shoulders, which is now in the Mitchell Library. Also within weeks of his death a tradesman began making clay pipes which resembled Donahoe's head, complete with bullet hole.
Jack Donohoe
wanted Dead or AliveMatthew Brady
Credit: Archives Office of Tasmania
Matthew Brady, (1799 1826) was transported on the Juliana for the crime of stealing a basket and Hermes birkin bags fake some butter, bacon, sugar and rice. He was sent to van Diemen's land (Tasmania) and replica birkin handbags became a constant absconder. As punishment, he received around 350 lashes in four years. He was then sentenced to Macquarie Harbour, but escaped with 13 other desperate convicts, in a whale boat in 1824. For two years, the gang roamed the bush, aided by settlers, who were former convicts. A Reward was offered by Governor Arthur, replica hermes handbags outlet to anyone who could deliver Brady to the law. Brady responded with a cheeky note fastened to the door of an Inn:
"It has caused Matthew Brady much concern that such a person known as Sir George Arthur is at large. Twenty Gallons of Rum will be given to any persons that will deliver this person to me."
The reward for Brady was raised to 300 guineas and Brady was captured.
Brady was known as the "Gentleman Bushranger", as he only used violence in fashion cheap hermes handbags self defence and never harmed a women. His cell in Hobart, as he waited to stand trail was filled with flowers and cakes sent by female sympathisers and the crowd that watched him hang on May 26, cried and cheered him on. A lookout is named after him, in Tasmania, called Brady's lookout, with views over the Tamar River
Captain ThunderboltFred Ward, who is known as 'Captain Thunderbolt', was born in Windsor, in New South Wales, in 1836 and was the son of a convict. He was working as a drover and horse breaker when sentenced to Cockatoo Island for horse stealing. He was then, conditionally released from the island and was working as a horse breaker in Mudgee, but then returned to Cockatoo Island for various offences. Ward, escaped from the island and went to live with his half Aboriginal wife and their children on the Culgoa River near Bourke. He then, adopted the name 'Captain Thunderbolt' and began an almost 7 year crime spree. During this time, Ward was shot in the knee during a gunfight, when spotted by troopers (this helped the identification of his body later). Another time a constable held a pistol to his head and said 'you are my prisoner'. Thunderbolt laughed and galloped off into the bush. He met his end however in Uralla, New South Wales during a gunfight with a trooper.
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What we know and don't know
But it's unclear how Gray, who was arrested on a weapons charge April 12, suffered a severe spinal cord injury that led to his death seven days later.
Here are the big questions surrounding this controversial case:
What we know: Gray was arrested on a weapons charge in a high crime area of Baltimore known for drugs. He "gave up without the use of force," Baltimore Deputy Police Commissioner Jerry Rodriguez said last week.
An officer apparently took his Taser out and was prepared to use it on Gray, but he never deployed it, Rodriguez said. And none of the six officers involved in the arrest described using force against the 25 year old.
"And when Mr. Gray was taken out of that van, he could not talk, and he could not breathe," according to Rodriguez.
Police have said Gray was not buckled in with a seat belt during the ride to a booking center.
What we don't know: It's unknown what caused the spinal cord injury that led to his death a week after the arrest, and it's also unknown what, if anything, happened inside the van.
What can be seen on the released video
What we know: Segments of cell replica hermes handbags outlet phone video shot from two different positions appear to begin after Gray has been arrested and show officers dragging Hermes birkin bags fake Gray, who is fashion cheap hermes handbags handcuffed, to a van. He can be heard screaming.
"He was dragged a bit," said Baltimore Mayor Stephanie Rawlings Blake, "but then you see him using his legs to get into the van, so he was able bodied when he was in the van. And we know that when he was finally taken out of the van, he was unresponsive."
One woman who recorded a video of the arrest said she knew Gray.
"When I ran up the street and seen him, the first thing I asked him was he OK because I heard him screaming," the woman replica birkin handbags said. "He didn't never say yes or no, he just said 'I can't breathe' and just was yelling."
Rawlings Blake and Deputy Police Commissioner Kevin Davis have said the arresting officers should have asked for medical attention immediately after Gray asked for it.
But it's unclear how Gray, who was arrested on a weapons charge April 12, suffered a severe spinal cord injury that led to his death seven days later.
Here are the big questions surrounding this controversial case:
What we know: Gray was arrested on a weapons charge in a high crime area of Baltimore known for drugs. He "gave up without the use of force," Baltimore Deputy Police Commissioner Jerry Rodriguez said last week.
An officer apparently took his Taser out and was prepared to use it on Gray, but he never deployed it, Rodriguez said. And none of the six officers involved in the arrest described using force against the 25 year old.
"And when Mr. Gray was taken out of that van, he could not talk, and he could not breathe," according to Rodriguez.
Police have said Gray was not buckled in with a seat belt during the ride to a booking center.
What we don't know: It's unknown what caused the spinal cord injury that led to his death a week after the arrest, and it's also unknown what, if anything, happened inside the van.
What can be seen on the released video
What we know: Segments of cell replica hermes handbags outlet phone video shot from two different positions appear to begin after Gray has been arrested and show officers dragging Hermes birkin bags fake Gray, who is fashion cheap hermes handbags handcuffed, to a van. He can be heard screaming.
"He was dragged a bit," said Baltimore Mayor Stephanie Rawlings Blake, "but then you see him using his legs to get into the van, so he was able bodied when he was in the van. And we know that when he was finally taken out of the van, he was unresponsive."
One woman who recorded a video of the arrest said she knew Gray.
"When I ran up the street and seen him, the first thing I asked him was he OK because I heard him screaming," the woman replica birkin handbags said. "He didn't never say yes or no, he just said 'I can't breathe' and just was yelling."
Rawlings Blake and Deputy Police Commissioner Kevin Davis have said the arresting officers should have asked for medical attention immediately after Gray asked for it.
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William Devin Howell kept body of woman in his murder mobile van for weeks and slept with it
Cellmate claims serial killer admitted slaughtering seven and slept holding corpse fake hermes brown belt whosale he called 'baby' for weeks in his 'murder mobile' van
William Devin Howell, 45, a drifter with a lengthy criminal record, charged with six additional killings and is already serving time for manslaughterThe bodies of all seven victims were found at separate intervals beginning in 2007 in a wooded area behind a strip mall in New Britain, ConnecticutVictims disappeared in 2003 when Howell was working odd jobs in stateHave been identified as: JoyvalineMartinez, 24, of East Hartford; Diane replica Hermes belts france Cusack, 53, of New Britain; Mary Jane Menard, 40, of New Britain; Melanie Ruth Camilini, 29, of Seymour; Marilyn Gonzalez, 26, of Waterbury; Danny Lee Whistnant, 44, of New Britain; and Nilsa Arizmendi, 33, of WethersfieldHe sexually assaulted some of the women and sex tapes were found in vanIf convicted, Howell would become one of state's most prolific serial killersBy
A drifter accused of being a serial killer told fellow inmates he killed seven people in Connecticut in 2003, including a woman whose body he kept for two weeks in a van he called the 'murder mobile'.
William Devin Howell, 45, told a cellmate 'there was a monster inside of him that just came out' and called himself a 'sick ripper',according to an arrest warrant released in New Britain on Friday.
He said if he wasn't caught, he was going to go cross country and kill others, it said.
Scroll down for video
The document was released after Howell was arraigned in New Britain Superior Court on multiple murder charges related to six of the killings.
A judge set bail at $10million, but Howell already was serving a 15 year prison sentence for manslaughter for killing one of the seven victims.
Howell told a cellmate the first person he killed was a woman he raped in his van, the warrant said.
Howell told the fellow inmate he kept the woman's body wrapped up in hermes belt price replica his van because it was too cold outside to bury her, the warrant said.
He also said he cut off the tips of her fingers, dismantled her bottom jaw and disposed of the body parts in Virginia, it said.
He told his cellmate he slept next to the woman's body in the van, calling her his 'baby', according to the warrant
Marilyn Gonzalez (left) of Waterbury, Connecticut, andDanny Lee Whistnan (right) were also victims of Howell
All seven victims disappeared in 2003, when Howell was mowing lawns and working other odd jobs in central Connecticut.
They were identified as: Joyvaline Martinez, 24, of East Hartford; Diane Cusack, 53, of New Britain; Mary Jane Menard, 40, of New Britain; Melanie Ruth Camilini, 29, of Seymour; Marilyn Gonzalez, 26, of Waterbury; Danny Lee Whistnant, 44, of New Britain; and Nilsa Arizmendi, 33, of Wethersfield.
Police said in the arrest warrant that Howell sexually assaulted three of the women he killed.
Many relatives of the victims attended the proceeding, and several cried after Howell was brought into the courtroom in an orange prison jumpsuit, shackled on his arms and legs.
Howell did not speak or enter any pleas and the case was continued to October 28.
His lawyer urged the public to remember Howell imitation hermes mens belt is innocent until proved guilty.
Martinez's sister, Sandra Martinez, said: 'Today we had to face a monster.
'I didn't think this day would ever come, but thanks to all the hard work that was put into it they were able to catch him, and I hope he never gets out of jail and he rots,' she told WFSB TV.
The bodies of all seven victims were found in a wooded area behind a strip mall in New Britain.
'Let's remember each of these victims and their families,' police Chief James Wardwell said after the court hearing.
'Each victim was loved and cherished.
'They were people from our communities and in no way deserved the violence that ended their lives.'
The wooded area where the bodies were found is about 12 miles southwest of Hartford in Connecticut
If convicted of the killings, Howell would be one of the most prolific serial killers in Connecticut history.
Cellmate claims serial killer admitted slaughtering seven and slept holding corpse fake hermes brown belt whosale he called 'baby' for weeks in his 'murder mobile' van
William Devin Howell, 45, a drifter with a lengthy criminal record, charged with six additional killings and is already serving time for manslaughterThe bodies of all seven victims were found at separate intervals beginning in 2007 in a wooded area behind a strip mall in New Britain, ConnecticutVictims disappeared in 2003 when Howell was working odd jobs in stateHave been identified as: JoyvalineMartinez, 24, of East Hartford; Diane replica Hermes belts france Cusack, 53, of New Britain; Mary Jane Menard, 40, of New Britain; Melanie Ruth Camilini, 29, of Seymour; Marilyn Gonzalez, 26, of Waterbury; Danny Lee Whistnant, 44, of New Britain; and Nilsa Arizmendi, 33, of WethersfieldHe sexually assaulted some of the women and sex tapes were found in vanIf convicted, Howell would become one of state's most prolific serial killersBy
A drifter accused of being a serial killer told fellow inmates he killed seven people in Connecticut in 2003, including a woman whose body he kept for two weeks in a van he called the 'murder mobile'.
William Devin Howell, 45, told a cellmate 'there was a monster inside of him that just came out' and called himself a 'sick ripper',according to an arrest warrant released in New Britain on Friday.
He said if he wasn't caught, he was going to go cross country and kill others, it said.
Scroll down for video
The document was released after Howell was arraigned in New Britain Superior Court on multiple murder charges related to six of the killings.
A judge set bail at $10million, but Howell already was serving a 15 year prison sentence for manslaughter for killing one of the seven victims.
Howell told a cellmate the first person he killed was a woman he raped in his van, the warrant said.
Howell told the fellow inmate he kept the woman's body wrapped up in hermes belt price replica his van because it was too cold outside to bury her, the warrant said.
He also said he cut off the tips of her fingers, dismantled her bottom jaw and disposed of the body parts in Virginia, it said.
He told his cellmate he slept next to the woman's body in the van, calling her his 'baby', according to the warrant
Marilyn Gonzalez (left) of Waterbury, Connecticut, andDanny Lee Whistnan (right) were also victims of Howell
All seven victims disappeared in 2003, when Howell was mowing lawns and working other odd jobs in central Connecticut.
They were identified as: Joyvaline Martinez, 24, of East Hartford; Diane Cusack, 53, of New Britain; Mary Jane Menard, 40, of New Britain; Melanie Ruth Camilini, 29, of Seymour; Marilyn Gonzalez, 26, of Waterbury; Danny Lee Whistnant, 44, of New Britain; and Nilsa Arizmendi, 33, of Wethersfield.
Police said in the arrest warrant that Howell sexually assaulted three of the women he killed.
Many relatives of the victims attended the proceeding, and several cried after Howell was brought into the courtroom in an orange prison jumpsuit, shackled on his arms and legs.
Howell did not speak or enter any pleas and the case was continued to October 28.
His lawyer urged the public to remember Howell imitation hermes mens belt is innocent until proved guilty.
Martinez's sister, Sandra Martinez, said: 'Today we had to face a monster.
'I didn't think this day would ever come, but thanks to all the hard work that was put into it they were able to catch him, and I hope he never gets out of jail and he rots,' she told WFSB TV.
The bodies of all seven victims were found in a wooded area behind a strip mall in New Britain.
'Let's remember each of these victims and their families,' police Chief James Wardwell said after the court hearing.
'Each victim was loved and cherished.
'They were people from our communities and in no way deserved the violence that ended their lives.'
The wooded area where the bodies were found is about 12 miles southwest of Hartford in Connecticut
If convicted of the killings, Howell would be one of the most prolific serial killers in Connecticut history.
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Will new Caddy feature New York style
The Sleuth can't help wondering what Antoine de la Mothe Cadillac, who founded Detroit in 1701, would think about the Cadillac brand's plan to move its headquarters out of the city in 2015 and establish a base camp in New York City. Apparently Johan De Nysschen, who recently became Cadillac's head honcho, thinks the division will achieve a more global perspective if it's located in the city that never sleeps (specifically, Manhattan's trendy Soho district) that will help it move more metal. It's from there that Cadillac will announce a number of new models, including a redesigned SRX tall wagon, the ultra luxury CT6 sedan and a replacement for the ELR coupe that uses the same plug in electric powertrain as the Chevrolet Volt. Your Trenchcoated Spymaster also hears that De Nysschen is planning a new Cadillac roadster based on the Ciel concept car that debuted in 2011.
Next Tucson will look more like the Santa Fe: Hyundai knows a good thing when it sells one and the Korea based automaker is selling plenty of its Santa Fe sport utility vehicles. Hoping to trade on the vehicle's popularity, The Sleuth understands that the 2016 Hyundai Tucson will look a lot like the Santa Fe when it shows up in mid 2015. From what The Sleuth has been told, the Tucson will become a bit larger than the current version and will feature a squared off Santa Fe like nose. Overall, it seems, the compact tall wagon will adopt a more conservative shape, which is where Hyundai's design "language" appears to he heading, Hermes belt replica france if the new 2015 Genesis and Sonata sedans are any indication.
Panamera's progress: The Sleuth has picked up some intel concerning Porsche's new luxury Panamera hatchback sedan that's due out in a couple of years. As he suspected, the car's controversial body shape fake hermes mens belt will undergo significant beautification that should add to its appeal. The Panamera will replica Hermes belts france also use Porsche's new front engine architecture that, along with more aluminum and composite materials, will help it drop at least 100 kilograms over the current structure. The platform will also be used by Bentley (it and Porsche are part of Volkswagen) when it builds the next generation Continental coupe. There will be new gas engine choices for the more svelte Panamera in addition to a returning hybrid edition.
Engine start stop systems might save a bit of gas, but they come at a cost: The technology that shuts off a car's engine at stoplights or in stop and go traffic and then immediately fires it back up again when the brake pedal is released, is cropping up on many new cars these days as a way to save gas. But according to what The Sneakster is hearing, stop start is not popular with buyers who don't like the shudders that can be felt throughout their vehicles each time the system does its thing. In addition, there are reports that the frequent off on cycling is shortening the life of the lead acid batteries. Automakers are apparently aware of the latter problem and are considering the introduction of energy storing ultracapacitors that would ease the draw on the batteries. As for the rough restarts, perhaps a mandatory switch that turns start stop systems off is in order. However, the Spy Guy hears that VW's brass has once again set its sights on a replacement luxury model. Apparently, the success of Hyundai Equus and Kia K900 upscale sedans has led to plans to revive the Phaeton if that's what it will be called sometime in the next three years, but after the next generation VW Passat sedan and Touareg tall wagon have been launched. Under consideration is a range of new engines, including a turbocharged V 6 plus V 8 and 12 cylinder powerplants.
Warren Buffett's majority stake purchase of the Van Tuyl Group: The man nicknamed the "Oracle of Omaha" for his savvy investment strategies now controls North America's largest privately owned auto dealership group, with 78 stores in its roster. Collectively, Van imitation hermes mens belt Tuyl sells nearly a quarter of a million cars a year and generates close to $8 billion US in revenues. Buffet will rename his purchase Berkshire Hathaway Automotive (BH is the name of his holding company). Conclusion? If Buffett is buying up dealerships, he expects demand for new vehicles to remain strong for some time to come.
No Porsche plans for a sub Boxster roadster: Apparently the speculation about Porsche building a lighter, lower cost roadster (it was even supposed to be called the 718, after a 1960s Porsche racing car) was just that. Company CEO Detlev von Patten ruled out that Porsche had any interest in, or plans for, producing such a vehicle. He further stated that if fans of the brand are seeking an affordable Porsche, they should consider purchasing a pre owned Boxster through one of the company's dealers. Ouch.
The Sleuth can't help wondering what Antoine de la Mothe Cadillac, who founded Detroit in 1701, would think about the Cadillac brand's plan to move its headquarters out of the city in 2015 and establish a base camp in New York City. Apparently Johan De Nysschen, who recently became Cadillac's head honcho, thinks the division will achieve a more global perspective if it's located in the city that never sleeps (specifically, Manhattan's trendy Soho district) that will help it move more metal. It's from there that Cadillac will announce a number of new models, including a redesigned SRX tall wagon, the ultra luxury CT6 sedan and a replacement for the ELR coupe that uses the same plug in electric powertrain as the Chevrolet Volt. Your Trenchcoated Spymaster also hears that De Nysschen is planning a new Cadillac roadster based on the Ciel concept car that debuted in 2011.
Next Tucson will look more like the Santa Fe: Hyundai knows a good thing when it sells one and the Korea based automaker is selling plenty of its Santa Fe sport utility vehicles. Hoping to trade on the vehicle's popularity, The Sleuth understands that the 2016 Hyundai Tucson will look a lot like the Santa Fe when it shows up in mid 2015. From what The Sleuth has been told, the Tucson will become a bit larger than the current version and will feature a squared off Santa Fe like nose. Overall, it seems, the compact tall wagon will adopt a more conservative shape, which is where Hyundai's design "language" appears to he heading, Hermes belt replica france if the new 2015 Genesis and Sonata sedans are any indication.
Panamera's progress: The Sleuth has picked up some intel concerning Porsche's new luxury Panamera hatchback sedan that's due out in a couple of years. As he suspected, the car's controversial body shape fake hermes mens belt will undergo significant beautification that should add to its appeal. The Panamera will replica Hermes belts france also use Porsche's new front engine architecture that, along with more aluminum and composite materials, will help it drop at least 100 kilograms over the current structure. The platform will also be used by Bentley (it and Porsche are part of Volkswagen) when it builds the next generation Continental coupe. There will be new gas engine choices for the more svelte Panamera in addition to a returning hybrid edition.
Engine start stop systems might save a bit of gas, but they come at a cost: The technology that shuts off a car's engine at stoplights or in stop and go traffic and then immediately fires it back up again when the brake pedal is released, is cropping up on many new cars these days as a way to save gas. But according to what The Sneakster is hearing, stop start is not popular with buyers who don't like the shudders that can be felt throughout their vehicles each time the system does its thing. In addition, there are reports that the frequent off on cycling is shortening the life of the lead acid batteries. Automakers are apparently aware of the latter problem and are considering the introduction of energy storing ultracapacitors that would ease the draw on the batteries. As for the rough restarts, perhaps a mandatory switch that turns start stop systems off is in order. However, the Spy Guy hears that VW's brass has once again set its sights on a replacement luxury model. Apparently, the success of Hyundai Equus and Kia K900 upscale sedans has led to plans to revive the Phaeton if that's what it will be called sometime in the next three years, but after the next generation VW Passat sedan and Touareg tall wagon have been launched. Under consideration is a range of new engines, including a turbocharged V 6 plus V 8 and 12 cylinder powerplants.
Warren Buffett's majority stake purchase of the Van Tuyl Group: The man nicknamed the "Oracle of Omaha" for his savvy investment strategies now controls North America's largest privately owned auto dealership group, with 78 stores in its roster. Collectively, Van imitation hermes mens belt Tuyl sells nearly a quarter of a million cars a year and generates close to $8 billion US in revenues. Buffet will rename his purchase Berkshire Hathaway Automotive (BH is the name of his holding company). Conclusion? If Buffett is buying up dealerships, he expects demand for new vehicles to remain strong for some time to come.
No Porsche plans for a sub Boxster roadster: Apparently the speculation about Porsche building a lighter, lower cost roadster (it was even supposed to be called the 718, after a 1960s Porsche racing car) was just that. Company CEO Detlev von Patten ruled out that Porsche had any interest in, or plans for, producing such a vehicle. He further stated that if fans of the brand are seeking an affordable Porsche, they should consider purchasing a pre owned Boxster through one of the company's dealers. Ouch.
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Virgil van Dijk 'happy' at Southampton but remains ambitious
Virgil van Dijk says he is happy at Southampton but harbours ambitions like every other professional player in football.
The Netherlands international has been linked with Manchester City and Chelsea during next month's transfer window.
However, the 25 year old remains coy over his immediate plans, telling The Times: "Southampton is a very good club for me, it is an amazing place fashion cheap hermes handbags to be and I am happy to be part of the success.
"Every player in the world has ambitions. I have ambitions like everyone else. I want to get the maximum out of myself as a player.
Saints boss Claude Puel is keen to keep Van Dijk at the club
"I can improve in every aspect and that takes time. That takes games. That takes playing at the highest level and with the national team.
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A Treehouse Man Cave in DallasA view inside a treehouse built by Pete Nelson for Bobby and Marty Page in Malakoff, Texas, March 14, 2014.
Vernon Bryant/The Dallas Morning News
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It is the 4x4's ability to provide a safe journey that is comfortable while being practical that has contributed to the growing popularity of 4x4s and has made for increased interest and availability of 4x4 clubs. These tours utilise modern satellite navigation systems along with sophisticated mobile communications devices. The 4x4s available today are a far cry from the expensive and cumbersome transports that, while useful in their time, certainly did not represent the pure fun and enjoyment of today's vehicles.
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vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation
Patients who filled a prescription for a standard dose non vitamin K antagonist oral anticoagulant (novel oral anticoagulants, NOACs) were excluded. To control for baseline differences in the population, a propensity score for receipt of either of the four treatment alternatives was calculated to apply an inverse probability treatment weight.
InterventionInitiated anticoagulant treatment (dabigatran 110 mg, rivaroxaban 15 mg, apixaban 2.5 mg, and warfarin).
Main outcome measuresPatients were followed in the registries from onset of treatment for the primary effectiveness outcome of ischaemic stroke/systemic embolism and for the principal safety outcome of any bleeding events.
ResultsAmong 55644 patients with atrial fibrillation who met inclusion criteria, the cohort was distributed according to treatment: apixaban n=4400; dabigatran n=8875; rivaroxaban n=3476; warfarin n=38893. The overall mean age was 73.9 (SD 12.7), ranging from a mean of 71.0 (warfarin) to 83.9 (apixaban). During one year of follow up, apixaban was associated with higher (weighted) event rate of ischaemic stroke/systemic embolism (4.8%), while dabigatran, rivaroxaban, and warfarin had event rates of 3.3%, 3.5%, and 3.7%, respectively. In the comparison between a non vitamin K antagonist oral anticoagulant and warfarin in the inverse probability of treatment weighted analyses and investigation of the effectiveness outcome, the hazard ratios were 1.19 (95% confidence interval 0.95 to 1.49) for apixaban, 0.89 (0.77 to 1.03) for dabigatran, and 0.89 (0.69 to 1.16) for rivaroxaban. For the principal safety outcome versus warfarin, the hazard ratios were 0.96 (0.73 to 1.27) for apixaban, 0.80 (0.70 to 0.92) for dabigatran, and 1.06 (0.87 to 1.29) for rivaroxaban.
ConclusionIn this propensity weighted nationwide study of reduced dose non vitamin K antagonist oral anticoagulant regimens, apixaban 2.5 mg twice a day was associated with a trend towards higher rates of ischaemic stroke/systemic embolism compared with warfarin, while rivaroxaban 15 mg once a day and dabigatran 110 mg twice a day showed a trend towards lower thromboembolic rates. The results were not significantly different. Rates of bleeding (the principal safety outcome) were significantly lower for dabigatran, but not significantly different for apixaban and rivaroxaban compared with warfarin.
IntroductionAtrial fibrillation is associated with an increased risk of ischaemic stroke and mortality. During the past five years, large randomised trials have established that non vitamin K antagonist oral anticoagulants (novel oral anticoagulants, NOACs) have a similar efficacy to warfarin but have a superior safety profile, largely driven by a substantial reduction in associated risk of intracranial haemorrhage.1 These findings have subsequently changed guidelines to either include NOACs as an option for stroke prophylaxis2 or to recommend these agents as first choice of drug.3 The findings of clinical trials have been confirmed in various observational cohort studies based on data from clinical practice.4567
While meticulous dose adjustments are not required for NOACs as they are for warfarin, a clinical evaluation of appropriate (constant) dose is still necessary. Various degrees of renal function entails recommendations to offer these drugs in a reduced dosing regimen, but different cut off values for age, body weight, or interacting drugs also require consideration for appropriate dose selection.8 Indeed, both age and chronic kidney disease in patients with atrial fibrillation intensifies the risk of stroke and increases the risk of bleeding during antithrombotic treatment.9 Elderly patients with atrial fibrillation (such as those aged 80) and patients with impaired renal function were included in the landmark trials of NOACs, but these important subgroups comprised only a small proportion of the patient populations.
Nevertheless, contemporary guidelines suggest a reduced dosing regimen for dabigatran (110 mg twice a day) if patients are aged 80 or have an estimated glomerular filtration rate (eGFR) of 30 50 mL/min; rivaroxaban (15 mg once a day) if eGRF is 15 49 mL/min; apixaban (2.5 mg twice a day) if two of the three following criteria are present: age 80 or an eGRF 15 29 mL/min or body weight 60 kg; or edoxaban (30 mg once a day) if eGFR is 15 50 mL/min.10 While subgroup analyses including patients with varying degree of renal function showed comparable efficacy with warfarin,11 evidence on reduce dose regimens of non vitamin K antagonist oral anticoagulants from "real world" clinical practice is scarce. In response to this lack of evidence about reduce dose regimens for stroke prevention in atrial fibrillation, fake hermes brown belt whosale we conducted a nationwide cohort study to examine effectiveness and safety compared with warfarin. To ascertain appropriateness of prescribing, we particularly focused on subgroups of elderly patients and those with impaired renal function, given their potential "indication for dose reduction" when NOACs are used.
MethodsThis was an observational cohort study of a nationwide population of unselected patients with atrial fibrillation who had not previously taken an oral anticoagulant. Patients were identified from nationwide registries in Denmark.
Data sourcesIn Denmark, individuals are assigned a unique identification number allowing linkage on an individual level between databases. Study data were obtained from three nationwide administrative databases: the Danish national prescription registry, which holds information on purchase date, Anatomical Therapeutic Chemical (ATC) classification code, and package size for every prescription claim since 1994; the Danish civil registration system, which holds information on sex, date of birth, and vital and emigration status; and the Danish national patient register, which includes admission/discharge date, and discharge ICD (international classification of diseases) diagnosis codes for hospital admissions since 1977.
Patient populationEligible patients were identified as those with a first time prescription claim for an NOAC defined as: apixaban (introduced 10 December 2012), dabigatran (introduced 1 August 2011), or rivaroxaban (introduced 1 February 2012), as well as individuals who started warfarin treatment (since 1 August 2011) up to 28 February 2016. Patients who had taken any oral anticoagulant within the previous year were excluded to establish a naive cohort. All NOACs were restricted to reduced doses approved for stroke prevention in atrial fibrillation (in Europe) as follows: apixaban 2.5 mg, dabigatran 110 mg, and rivaroxaban 15 mg. To focus on non valvular atrial fibrillation, we excluded patients with previous hospital diagnoses indicating valvular atrial fibrillation (mitral stenosis or mechanical heart valves). We further excluded all those patients with an indication for oral anticoagulant treatment other than atrial fibrillation (history of pulmonary embolism, deep venous thrombosis, or recent hip/knee surgery). This allowed for an indirect identification of eligible patients with atrial fibrillation as all other reasons for initiation of an oral anticoagulation were ruled out. We therefore assumed that initiation of treatment indicated stroke prophylaxis for atrial fibrillation.
Patient involvementNo patients were involved in setting the research question or the outcome measures, nor were they involved in developing plans for recruitment, design, or implementation of the study. No patients were asked to advise on interpretation or writing up of results. There are no plans to disseminate the results of the research to study participants or the relevant patient community.
Ascertainment of outcome measures and comorbidityWe used the Danish national patient register to follow included patients from onset of treatment until 30 April 2016 for the occurrence of a combined endpoint of "ischaemic hermes belt price replica stroke or systemic embolism" and ischaemic stroke separately. All cause mortality was included as a single endpoint because oral anticoagulants significantly reduce the risk of stroke and death compared with control or placebo,12 while NOACs significantly reduce all cause mortality compared with warfarin.13 Safety outcomes were recorded as haemorrhagic stroke and major and gastrointestinal bleeding and reported in a combined endpoint as "any bleeding" and specific for haemorrhagic stroke. Major bleeding was defined as bleeding with anaemia, haemothorax, haematuria, epistaxis, and bleeding in the eye (see table A in appendix 1). We used ICD 10 (international classification of diseases, 10th revision) to identify outcomes. The coding accuracy of the selected outcomes has previously been validated and found sufficiently accurate for epidemiological research.1415
For quantifying thromboembolic risk, we combined comorbidity information into the CHA2DS2 VASc score16; similarly, to assess the risk of bleeding we calculated the HAS BLED score (table B in appendix 2).17
Within each NOAC agent, there are differences in criteria for recommendation of a reduced dose; nevertheless, elderly people and those with renal impairment are subgroups of patients who require special attention regarding choice of NOAC and dose.18 Therefore, we analysed these subgroups as having a potential "indication for dose reduction." We identified those with adult polycystic kidney disease, chronic glomerulonephritis, chronic tubulointestinal nephropathy, diabetic nephropathy, non end stage chronic kidney disease, hypertensive nephropathy, and nephropathy of unknown aetiology and categorised them as having chronic kidney disease (table A in appendix 1). While we did not have access to individual eGFR or creatinine clearance directly at the time of treatment initiation, a reasonable clinical assumption is that the aforementioned diseases would affect the renal function to such an extent that it could confer a clinical recommendation to reduce the dose of any NOAC.
Statistical analysesCharacteristics of the study population were reported as percentages, means (standard deviation), or medians (interquartile range). Person years of follow up were calculated from the date of first prescription claim to the occurrence of first endpoint, death, emigration, or end of follow up, whichever came first. Incidence rates were calculated as number of events divided by person time. To determine the risk of outcomes among NOAC users compared with warfarin (reference) users, we calculated cause specific hazard ratios using Cox regression models. Failure curves were used to depict how risks of events evolved over time. Specifically, we used the Aalen Johansen estimator to calculate absolute risk of events taking into account the competing risk of death16 and the Kaplan Meier estimator hermes belts Knockoff for all cause mortality. To allow an unbiased comparison across different treatment regimens, we applied an inverse probability of treatment weighted approach. This is particularly suitable when there are several treatment alternatives in this case, dabigatran, apixaban, rivaroxaban, and warfarin.1920 The weights were derived to obtain estimates representing population average treatment effects with optimal balance between the treatment populations21 by using generalised boosted models based on 10000 regression trees as done previously.4 The underlying propensity models included age (continuous); binary indicators for sex and hospital diagnosis of atrial fibrillation, ischaemic stroke, vascular disease, ischaemic heart disease, hypertension, diabetes, cancer, chronic obstructive lung disease, heart failure or left ventricular dysfunction, recent prescription of aspirin, blockers, non steroidal anti inflammatory drugs, statins, loop and non loop diuretics, amiodarone, dronedarone, vasodilators, calcium channel blockers, and verapamil; and the CHA2DS2 VASc and HAS BLED scores included as continuous variables.
The examined treatment regimens should be contrasted on comparable populations and any patient must have positive probability for any treatment (positivity Hermes belts replica paris assumption), hence substantial overlap between the propensities for each treatment should be present. In agreement with best methodological practice, this was assessed by graphical inspection of the weight distributions (appendix 2).22 Additionally, we evaluated balance between treatment populations by standardised differences of all baseline covariates, using a threshold of 0.1 to indicate imbalance.23
Sensitivity analysesTo further explore the potential for bias from baseline differences and the propensity of receiving treatment with an NOAC, we performed sensitivity analyses using an ordinary crude and Cox multivariate adjusted analysis to compare the results obtained from the weighted analyses. We also performed a sensitivity analysis using standardised morbidity ratio24 weights to address the (hypothetical) casual situation of all patients receiving warfarin treatment rather than an NOAC.
To allow for a thorough prognostic evaluation and given the divergence of age across oral anticoagulant exposure groups, we supplemented the main analysis by a sensitivity analysis stratified on age category for instance, age 80. While not all of these patients would have renal deficiencies severe enough to acquire a diagnosis, advanced age significantly affects renal function2526; thus, assessment of comparative effectiveness and safety between NOAC and warfarin in these age groups is of clinical value given the age dependency on renal function (opting for reduce dose NOAC regimen). We also conducted a sensitivity analysis restricted to patients with a hospital diagnosis of atrial fibrillation to increase likelihood of treatment indication. Finally, as the introduction of each NOAC could have influenced patient selection, we repeated the main analysis confined to the time period where all three NOACs were available in Denmark that is, from 12 December 2012, when apixaban (latest market drug) was available in Denmark.
The analyses were performed with Stata version 14 (StataCorp) and R version 3.1.1 (R Foundation for Statistical Computing). A two sided P
ResultsWe identified 88141 patients in the study period who were eligible for inclusion by either fillinga prescription for low dose regimen NOAC or warfarin (only 2.5 mg available in Denmark). After we excluded reasons for oral anticoagulant treatment other than atrial fibrillation (n=31852) and previous use of phenprocoumon within the past year for unknown reasons (n=645), we identified a study population (n=55644) of patients who had not been taking oral anticoagulants within the previous year and who were starting treatment with either reduced dose NOAC or warfarin (fig A in appendix 3).
The study population was distributed by type of oral anticoagulant: 69.9% received warfarin, 7.9% apixaban, 15.9% dabigatran, and 6.3% rivaroxaban. The population average time of follow up (with respect to all cause mortality) was 2.3 years, with the apixaban group having the shortest mean follow up of one year. The study population age varied markedly across exposure to each drug for example, the average age for apixaban users was 83.9, while for warfarin the average age was 71.0 (table 1). Patients treated with either apixaban or rivaroxaban had a higher prevalence of renal diseases (9.5% and 9.1%, respectively) than patients treated with dabigatran (3.9%) or warfarin (8.3%). In general, the patients treated with apixaban had more comorbidities such as heart failure, previous thromboembolism, diabetes, and presence of vascular diseases. Therefore, the estimated risk of stroke, as summarised by the mean CHA2DS2 VASc score, was highest in patients treated with apixaban (4.3), and slightly lower for dabigatran (3.8) and rivaroxaban (3.6), and lowest for warfarin treated patients (3.0). A similar pattern (but with less pronounced differences) for risk of bleeding, as summarised by the mean HASBLED score, was observed with an overall population average score of 2.4.
Table 1 Characteristics of patients with atrial fibrillation who had not previously received oral anticoagulant by treatment groups. Values are numbers (percentages) unless stated otherwise
View this table:View popupView inline
With inverse probability of treatment weight to account for baseline differences, the standardised differences were less than 0.09 (compared with 1.01 before imposing estimated weights). Comparisons of individual propensity score distributions showed sufficient overlap, and suggest that application of the weights of inverse probability of treatment, resulted in a cohort in which the distribution of variables were comparable between treatment groups; hence comparisons between treatment groups were feasible (appendix 2).
Patients who filled a prescription for a standard dose non vitamin K antagonist oral anticoagulant (novel oral anticoagulants, NOACs) were excluded. To control for baseline differences in the population, a propensity score for receipt of either of the four treatment alternatives was calculated to apply an inverse probability treatment weight.
InterventionInitiated anticoagulant treatment (dabigatran 110 mg, rivaroxaban 15 mg, apixaban 2.5 mg, and warfarin).
Main outcome measuresPatients were followed in the registries from onset of treatment for the primary effectiveness outcome of ischaemic stroke/systemic embolism and for the principal safety outcome of any bleeding events.
ResultsAmong 55644 patients with atrial fibrillation who met inclusion criteria, the cohort was distributed according to treatment: apixaban n=4400; dabigatran n=8875; rivaroxaban n=3476; warfarin n=38893. The overall mean age was 73.9 (SD 12.7), ranging from a mean of 71.0 (warfarin) to 83.9 (apixaban). During one year of follow up, apixaban was associated with higher (weighted) event rate of ischaemic stroke/systemic embolism (4.8%), while dabigatran, rivaroxaban, and warfarin had event rates of 3.3%, 3.5%, and 3.7%, respectively. In the comparison between a non vitamin K antagonist oral anticoagulant and warfarin in the inverse probability of treatment weighted analyses and investigation of the effectiveness outcome, the hazard ratios were 1.19 (95% confidence interval 0.95 to 1.49) for apixaban, 0.89 (0.77 to 1.03) for dabigatran, and 0.89 (0.69 to 1.16) for rivaroxaban. For the principal safety outcome versus warfarin, the hazard ratios were 0.96 (0.73 to 1.27) for apixaban, 0.80 (0.70 to 0.92) for dabigatran, and 1.06 (0.87 to 1.29) for rivaroxaban.
ConclusionIn this propensity weighted nationwide study of reduced dose non vitamin K antagonist oral anticoagulant regimens, apixaban 2.5 mg twice a day was associated with a trend towards higher rates of ischaemic stroke/systemic embolism compared with warfarin, while rivaroxaban 15 mg once a day and dabigatran 110 mg twice a day showed a trend towards lower thromboembolic rates. The results were not significantly different. Rates of bleeding (the principal safety outcome) were significantly lower for dabigatran, but not significantly different for apixaban and rivaroxaban compared with warfarin.
IntroductionAtrial fibrillation is associated with an increased risk of ischaemic stroke and mortality. During the past five years, large randomised trials have established that non vitamin K antagonist oral anticoagulants (novel oral anticoagulants, NOACs) have a similar efficacy to warfarin but have a superior safety profile, largely driven by a substantial reduction in associated risk of intracranial haemorrhage.1 These findings have subsequently changed guidelines to either include NOACs as an option for stroke prophylaxis2 or to recommend these agents as first choice of drug.3 The findings of clinical trials have been confirmed in various observational cohort studies based on data from clinical practice.4567
While meticulous dose adjustments are not required for NOACs as they are for warfarin, a clinical evaluation of appropriate (constant) dose is still necessary. Various degrees of renal function entails recommendations to offer these drugs in a reduced dosing regimen, but different cut off values for age, body weight, or interacting drugs also require consideration for appropriate dose selection.8 Indeed, both age and chronic kidney disease in patients with atrial fibrillation intensifies the risk of stroke and increases the risk of bleeding during antithrombotic treatment.9 Elderly patients with atrial fibrillation (such as those aged 80) and patients with impaired renal function were included in the landmark trials of NOACs, but these important subgroups comprised only a small proportion of the patient populations.
Nevertheless, contemporary guidelines suggest a reduced dosing regimen for dabigatran (110 mg twice a day) if patients are aged 80 or have an estimated glomerular filtration rate (eGFR) of 30 50 mL/min; rivaroxaban (15 mg once a day) if eGRF is 15 49 mL/min; apixaban (2.5 mg twice a day) if two of the three following criteria are present: age 80 or an eGRF 15 29 mL/min or body weight 60 kg; or edoxaban (30 mg once a day) if eGFR is 15 50 mL/min.10 While subgroup analyses including patients with varying degree of renal function showed comparable efficacy with warfarin,11 evidence on reduce dose regimens of non vitamin K antagonist oral anticoagulants from "real world" clinical practice is scarce. In response to this lack of evidence about reduce dose regimens for stroke prevention in atrial fibrillation, fake hermes brown belt whosale we conducted a nationwide cohort study to examine effectiveness and safety compared with warfarin. To ascertain appropriateness of prescribing, we particularly focused on subgroups of elderly patients and those with impaired renal function, given their potential "indication for dose reduction" when NOACs are used.
MethodsThis was an observational cohort study of a nationwide population of unselected patients with atrial fibrillation who had not previously taken an oral anticoagulant. Patients were identified from nationwide registries in Denmark.
Data sourcesIn Denmark, individuals are assigned a unique identification number allowing linkage on an individual level between databases. Study data were obtained from three nationwide administrative databases: the Danish national prescription registry, which holds information on purchase date, Anatomical Therapeutic Chemical (ATC) classification code, and package size for every prescription claim since 1994; the Danish civil registration system, which holds information on sex, date of birth, and vital and emigration status; and the Danish national patient register, which includes admission/discharge date, and discharge ICD (international classification of diseases) diagnosis codes for hospital admissions since 1977.
Patient populationEligible patients were identified as those with a first time prescription claim for an NOAC defined as: apixaban (introduced 10 December 2012), dabigatran (introduced 1 August 2011), or rivaroxaban (introduced 1 February 2012), as well as individuals who started warfarin treatment (since 1 August 2011) up to 28 February 2016. Patients who had taken any oral anticoagulant within the previous year were excluded to establish a naive cohort. All NOACs were restricted to reduced doses approved for stroke prevention in atrial fibrillation (in Europe) as follows: apixaban 2.5 mg, dabigatran 110 mg, and rivaroxaban 15 mg. To focus on non valvular atrial fibrillation, we excluded patients with previous hospital diagnoses indicating valvular atrial fibrillation (mitral stenosis or mechanical heart valves). We further excluded all those patients with an indication for oral anticoagulant treatment other than atrial fibrillation (history of pulmonary embolism, deep venous thrombosis, or recent hip/knee surgery). This allowed for an indirect identification of eligible patients with atrial fibrillation as all other reasons for initiation of an oral anticoagulation were ruled out. We therefore assumed that initiation of treatment indicated stroke prophylaxis for atrial fibrillation.
Patient involvementNo patients were involved in setting the research question or the outcome measures, nor were they involved in developing plans for recruitment, design, or implementation of the study. No patients were asked to advise on interpretation or writing up of results. There are no plans to disseminate the results of the research to study participants or the relevant patient community.
Ascertainment of outcome measures and comorbidityWe used the Danish national patient register to follow included patients from onset of treatment until 30 April 2016 for the occurrence of a combined endpoint of "ischaemic hermes belt price replica stroke or systemic embolism" and ischaemic stroke separately. All cause mortality was included as a single endpoint because oral anticoagulants significantly reduce the risk of stroke and death compared with control or placebo,12 while NOACs significantly reduce all cause mortality compared with warfarin.13 Safety outcomes were recorded as haemorrhagic stroke and major and gastrointestinal bleeding and reported in a combined endpoint as "any bleeding" and specific for haemorrhagic stroke. Major bleeding was defined as bleeding with anaemia, haemothorax, haematuria, epistaxis, and bleeding in the eye (see table A in appendix 1). We used ICD 10 (international classification of diseases, 10th revision) to identify outcomes. The coding accuracy of the selected outcomes has previously been validated and found sufficiently accurate for epidemiological research.1415
For quantifying thromboembolic risk, we combined comorbidity information into the CHA2DS2 VASc score16; similarly, to assess the risk of bleeding we calculated the HAS BLED score (table B in appendix 2).17
Within each NOAC agent, there are differences in criteria for recommendation of a reduced dose; nevertheless, elderly people and those with renal impairment are subgroups of patients who require special attention regarding choice of NOAC and dose.18 Therefore, we analysed these subgroups as having a potential "indication for dose reduction." We identified those with adult polycystic kidney disease, chronic glomerulonephritis, chronic tubulointestinal nephropathy, diabetic nephropathy, non end stage chronic kidney disease, hypertensive nephropathy, and nephropathy of unknown aetiology and categorised them as having chronic kidney disease (table A in appendix 1). While we did not have access to individual eGFR or creatinine clearance directly at the time of treatment initiation, a reasonable clinical assumption is that the aforementioned diseases would affect the renal function to such an extent that it could confer a clinical recommendation to reduce the dose of any NOAC.
Statistical analysesCharacteristics of the study population were reported as percentages, means (standard deviation), or medians (interquartile range). Person years of follow up were calculated from the date of first prescription claim to the occurrence of first endpoint, death, emigration, or end of follow up, whichever came first. Incidence rates were calculated as number of events divided by person time. To determine the risk of outcomes among NOAC users compared with warfarin (reference) users, we calculated cause specific hazard ratios using Cox regression models. Failure curves were used to depict how risks of events evolved over time. Specifically, we used the Aalen Johansen estimator to calculate absolute risk of events taking into account the competing risk of death16 and the Kaplan Meier estimator hermes belts Knockoff for all cause mortality. To allow an unbiased comparison across different treatment regimens, we applied an inverse probability of treatment weighted approach. This is particularly suitable when there are several treatment alternatives in this case, dabigatran, apixaban, rivaroxaban, and warfarin.1920 The weights were derived to obtain estimates representing population average treatment effects with optimal balance between the treatment populations21 by using generalised boosted models based on 10000 regression trees as done previously.4 The underlying propensity models included age (continuous); binary indicators for sex and hospital diagnosis of atrial fibrillation, ischaemic stroke, vascular disease, ischaemic heart disease, hypertension, diabetes, cancer, chronic obstructive lung disease, heart failure or left ventricular dysfunction, recent prescription of aspirin, blockers, non steroidal anti inflammatory drugs, statins, loop and non loop diuretics, amiodarone, dronedarone, vasodilators, calcium channel blockers, and verapamil; and the CHA2DS2 VASc and HAS BLED scores included as continuous variables.
The examined treatment regimens should be contrasted on comparable populations and any patient must have positive probability for any treatment (positivity Hermes belts replica paris assumption), hence substantial overlap between the propensities for each treatment should be present. In agreement with best methodological practice, this was assessed by graphical inspection of the weight distributions (appendix 2).22 Additionally, we evaluated balance between treatment populations by standardised differences of all baseline covariates, using a threshold of 0.1 to indicate imbalance.23
Sensitivity analysesTo further explore the potential for bias from baseline differences and the propensity of receiving treatment with an NOAC, we performed sensitivity analyses using an ordinary crude and Cox multivariate adjusted analysis to compare the results obtained from the weighted analyses. We also performed a sensitivity analysis using standardised morbidity ratio24 weights to address the (hypothetical) casual situation of all patients receiving warfarin treatment rather than an NOAC.
To allow for a thorough prognostic evaluation and given the divergence of age across oral anticoagulant exposure groups, we supplemented the main analysis by a sensitivity analysis stratified on age category for instance, age 80. While not all of these patients would have renal deficiencies severe enough to acquire a diagnosis, advanced age significantly affects renal function2526; thus, assessment of comparative effectiveness and safety between NOAC and warfarin in these age groups is of clinical value given the age dependency on renal function (opting for reduce dose NOAC regimen). We also conducted a sensitivity analysis restricted to patients with a hospital diagnosis of atrial fibrillation to increase likelihood of treatment indication. Finally, as the introduction of each NOAC could have influenced patient selection, we repeated the main analysis confined to the time period where all three NOACs were available in Denmark that is, from 12 December 2012, when apixaban (latest market drug) was available in Denmark.
The analyses were performed with Stata version 14 (StataCorp) and R version 3.1.1 (R Foundation for Statistical Computing). A two sided P
ResultsWe identified 88141 patients in the study period who were eligible for inclusion by either fillinga prescription for low dose regimen NOAC or warfarin (only 2.5 mg available in Denmark). After we excluded reasons for oral anticoagulant treatment other than atrial fibrillation (n=31852) and previous use of phenprocoumon within the past year for unknown reasons (n=645), we identified a study population (n=55644) of patients who had not been taking oral anticoagulants within the previous year and who were starting treatment with either reduced dose NOAC or warfarin (fig A in appendix 3).
The study population was distributed by type of oral anticoagulant: 69.9% received warfarin, 7.9% apixaban, 15.9% dabigatran, and 6.3% rivaroxaban. The population average time of follow up (with respect to all cause mortality) was 2.3 years, with the apixaban group having the shortest mean follow up of one year. The study population age varied markedly across exposure to each drug for example, the average age for apixaban users was 83.9, while for warfarin the average age was 71.0 (table 1). Patients treated with either apixaban or rivaroxaban had a higher prevalence of renal diseases (9.5% and 9.1%, respectively) than patients treated with dabigatran (3.9%) or warfarin (8.3%). In general, the patients treated with apixaban had more comorbidities such as heart failure, previous thromboembolism, diabetes, and presence of vascular diseases. Therefore, the estimated risk of stroke, as summarised by the mean CHA2DS2 VASc score, was highest in patients treated with apixaban (4.3), and slightly lower for dabigatran (3.8) and rivaroxaban (3.6), and lowest for warfarin treated patients (3.0). A similar pattern (but with less pronounced differences) for risk of bleeding, as summarised by the mean HASBLED score, was observed with an overall population average score of 2.4.
Table 1 Characteristics of patients with atrial fibrillation who had not previously received oral anticoagulant by treatment groups. Values are numbers (percentages) unless stated otherwise
View this table:View popupView inline
With inverse probability of treatment weight to account for baseline differences, the standardised differences were less than 0.09 (compared with 1.01 before imposing estimated weights). Comparisons of individual propensity score distributions showed sufficient overlap, and suggest that application of the weights of inverse probability of treatment, resulted in a cohort in which the distribution of variables were comparable between treatment groups; hence comparisons between treatment groups were feasible (appendix 2).
What Causes a Car to Stall While Driving
Engines don really want to run; it in their replica birkin handbags nature to just sit there as inert lumps of metal, until we add just the right ingredients, in just the right proportions as just the right times to make them run. If any one of those is off, even in the slightest, the engine will revert to its natural state as a 700 pound paperweight. There are literally thousands of reasons that this might happen; but if your engine just up and dies while driving, you can trace down a few of the likely causes according to when it does.
Modern cars will usually stall because of a sensor failure. All fake hermes bag of the sensors are important, but anything with "position" in the name is critical. The throttle , crankshaft and camshaft position sensors are three that your computer just can compensate for if they malfunction. Mass airflow sensors are important, especially at idle, because they tell the engine how much air is going in. If the MAF is dirty or malfunctioning, the computer will think there less air going in than there is. That could easily throw it into a "lean stall" before the oxygen sensors have a chance to tell the computer that things have gone awry. Manifold air pressure sensors are almost as important, and just as important in cars that don replica hermes handbags outlet have MAF sensors. But the TPS, CPS and MAF sensors are always primary suspects in stalling.
Believe it or not, idling is one of the hardest things an engine has to do. At idle, engines are more sensitive to even the slightest variation in air, fuel and spark delivery. Often, engines that stall only at idle do so because they getting either too much air, or not enough fuel. Leaking vacuum lines and intake induction parts are the classic suspects, but these days you have to account for exhaust gas recirculation valves stuck in the open position, and idle air control valves doing the same. An IAC valve is like a metered air leak that the engine uses at idle. If the IAC is stuck open, the engine gets more air than it should, and can stall at idle. As mentioned, sensor failures are always suspect, but these kinds of failures will generally manifest as problems at higher rpm as well.
Pressing the gas pedal means opening the main throttle plate, which introduces more air into the engine. The engine has to respond by delivering more fuel, and more aggressive spark timing to set it off. Massive vacuum leaks can cause stalling under acceleration, but more often the cause goes back to a failure in fuel delivery. That means a bad fuel pump or regulator, or a clogged fuel filter or injectors. Bad gas or gas contaminated with chemicals or water is another possible cause here. A weak ignition system or bad ignition timing will also cause stalling under acceleration. Check your ignition module, plug wires and spark fashion cheap hermes handbags plugs on a newer car. Owners of older cars with distributors should check for proper timing advance. Stalling under deceleration almost always goes back to either excess fuel or not enough air especially when accompanied by a backfire. Check that you IAC is opening, and isn clogged with carbon and debris.
Sudden stalling under cruise conditions is usually electrical in nature. Air and fuel failures will generally cause the vehicle to surge and drop off in power before stalling; electrical or sensor failures will kill an engine outright, even if it already at cruise speed. Two often overlooked causes are bad engine ground connections and overheating ignition coils. A failing coil will get very hot under consistent use. The hotter it gets, the more it resists electricity, and then the hotter it gets. If your vehicle runs fine for a few minutes, and then starts acting up while you going down the highway, check the ignition coil or coils. They shouldn sizzle when you put a drop of water on them. Fuel pressure failures will also cause stalling under cruise, but it usually more gradual like running out of gas. If you get sudden, random stalls under cruise, check the electrical system first.
Engines don really want to run; it in their replica birkin handbags nature to just sit there as inert lumps of metal, until we add just the right ingredients, in just the right proportions as just the right times to make them run. If any one of those is off, even in the slightest, the engine will revert to its natural state as a 700 pound paperweight. There are literally thousands of reasons that this might happen; but if your engine just up and dies while driving, you can trace down a few of the likely causes according to when it does.
Modern cars will usually stall because of a sensor failure. All fake hermes bag of the sensors are important, but anything with "position" in the name is critical. The throttle , crankshaft and camshaft position sensors are three that your computer just can compensate for if they malfunction. Mass airflow sensors are important, especially at idle, because they tell the engine how much air is going in. If the MAF is dirty or malfunctioning, the computer will think there less air going in than there is. That could easily throw it into a "lean stall" before the oxygen sensors have a chance to tell the computer that things have gone awry. Manifold air pressure sensors are almost as important, and just as important in cars that don replica hermes handbags outlet have MAF sensors. But the TPS, CPS and MAF sensors are always primary suspects in stalling.
Believe it or not, idling is one of the hardest things an engine has to do. At idle, engines are more sensitive to even the slightest variation in air, fuel and spark delivery. Often, engines that stall only at idle do so because they getting either too much air, or not enough fuel. Leaking vacuum lines and intake induction parts are the classic suspects, but these days you have to account for exhaust gas recirculation valves stuck in the open position, and idle air control valves doing the same. An IAC valve is like a metered air leak that the engine uses at idle. If the IAC is stuck open, the engine gets more air than it should, and can stall at idle. As mentioned, sensor failures are always suspect, but these kinds of failures will generally manifest as problems at higher rpm as well.
Pressing the gas pedal means opening the main throttle plate, which introduces more air into the engine. The engine has to respond by delivering more fuel, and more aggressive spark timing to set it off. Massive vacuum leaks can cause stalling under acceleration, but more often the cause goes back to a failure in fuel delivery. That means a bad fuel pump or regulator, or a clogged fuel filter or injectors. Bad gas or gas contaminated with chemicals or water is another possible cause here. A weak ignition system or bad ignition timing will also cause stalling under acceleration. Check your ignition module, plug wires and spark fashion cheap hermes handbags plugs on a newer car. Owners of older cars with distributors should check for proper timing advance. Stalling under deceleration almost always goes back to either excess fuel or not enough air especially when accompanied by a backfire. Check that you IAC is opening, and isn clogged with carbon and debris.
Sudden stalling under cruise conditions is usually electrical in nature. Air and fuel failures will generally cause the vehicle to surge and drop off in power before stalling; electrical or sensor failures will kill an engine outright, even if it already at cruise speed. Two often overlooked causes are bad engine ground connections and overheating ignition coils. A failing coil will get very hot under consistent use. The hotter it gets, the more it resists electricity, and then the hotter it gets. If your vehicle runs fine for a few minutes, and then starts acting up while you going down the highway, check the ignition coil or coils. They shouldn sizzle when you put a drop of water on them. Fuel pressure failures will also cause stalling under cruise, but it usually more gradual like running out of gas. If you get sudden, random stalls under cruise, check the electrical system first.
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William and Kate's inner circle
While politicians and foreign dignitaries were out in force at Westminster Abbey for the Royal wedding between Prince William and his bride Kate Middleton, the Duke and Duchess of Cambridge will have been most thrilled by those who had gathered in Statesmen's Aisle in the abbey's north transept to see them marry.
This was the space, overlooked by statues of Disraeli, Gladstone and Palmerstone, reserved for some of the couple's closest friends.
Also among them were long time friends of the Royal family, wealthy landowners and aristocrats who have known Prince William all his life, together with the mentors who helped him cope with his mother's death and saw his bride transformed from commoner to future Queen.
The friends have remained low key throughout the couple's romance, but the jigsaw of who's who within the Duke and Duchess's inner circle can now be revealed.
THE GLOUCESTERSHIRE SET
Friends of the Prince's from his home county of Gloucestershire, who have been entertained at Highgrove, the Prince of Wales's country estate, were well represented.
Known fashion cheap hermes handbags as the "Glosse Posse", its most glamorous member is Arabella Musgrave, 28, said to have been a former flame of Prince William and once described as "the only woman who could make Kate Middleton" jealous.
Now head of PR at Gucci, Miss Musgrave met the Prince through friends at the Cirencester Park Polo Club, run by her father Major replica hermes handbags outlet Nick Musgrave, an old friend of the Prince of Wales.
A regular on the London party scene, until recently she dated James Tollemache.
Seated in front of Miss Musgrave is Lady Natasha Rufus Isaacs. Known as "Nats" to friends, she met Prince William while attending Westonbirt School, which is close to Highgrove.
Lady Natasha, 27, sat on Prince William's table at his "Out of Africa" themed 21st birthday at Windsor Castle. The daughter of the Marquess of Reading and older sister of Julian, Viscount Erleigh, she is also one of Prince Harry's best friends.
Lady Natasha runs the fashion label Beulah, selling clothes made by women who have escaped the sex trade in India, of which her grandfather was viceroy in the 1920s.
She dates Rupert Finch, a former boyfriend of the Duchess of Cambridge. Described as "affable" and "handsome", Mr Finch, 32, was a final year law student at St Andrews University when Kate arrived to study History of Art in 2001. The couple dated for less than a year. Some have suggested that Prince William "stole" his future bride from Mr Finch, but others insist that the relationship had run its course. He is now an employment lawyer in London.
Tom and Victoria Inskip "Skippy" and "Tor" to friends have known Princes William and Harry since childhood. Mr Inskip, 26, attended Eton with the Princes and helped to organise his stag party with Guy Pelly, the nightclub entrepreneur who was sat elsewhere in the abbey.
Miss Inskip, 27, who also attended Westonbirt, is the best friend of Prince William's first serious girlfriend Rose Farquhar. A Chelsea based estate agent, she is also friends with Prince Harry. The Inskips were regulars at "Club H", the nightclub William and Harry set up in the basement of Highgrove,
She has also been a fundraiser for Sentebale, the African charity set up by Prince Harry. Claire Inskip, their mother, is a sculptress.
Seated next to Mrs Inskip, is Jamie Murray Wells, an old Harrovian childhood friend of Prince William from replica birkin handbags Gloucestershire.
Mr Murray Wells, Hermes birkin bags fake 27, is the son of Simon Murray Wells, an investment analyst, and his wife Alison, who are close friends of the Inskips.
Mr Murray Wells is believed to be a multi millionaire after founding Glasses Direct selling cheap spectacles online during his final term at University of Bristol in 2004.
Renowned for his sense of humour, he once reportedly sent sheep into Specsavers stores in Newcastle upon Tyne to illustrate his belief that customers were being "fleeced".
In a prank in 2006, he and Mr Pelly, raided Westonbirt School in a hunt for girls (the school was empty at the time), with Mr Murray Wells falling from a wall and breaking his leg.
He showed loyalty to the Duchess during her brief split with Prince William in 2007, escorting her to nightclubs.
FRIENDS FROM SCHOOL AND UNIVERSITY DAYS
Seated beneath the statue of Benjamin Disraeli are Sir Henry and Lady Cheape. Sir Henry, a landowner educated at Harrow and Newcastle University, and distant cousin of the Prince, rented Balgove House to the couple during their third year at university, where their romance was allowed to flourish away from scrutiny.
At the other end of the row from Sir Henry and his wife, Louisa, is Will Matthews, another old Harrovian. Known to his friends as "Stan", he lives in Fulham, where many of the couple's set have their London bases.
Mr Matthews is an associate in the country house sales department at Knight Frank, the estate agents and close friends with Rory Penn (seated beside him with his wife Francesca Penn) and Sir Henry.
All three attended Newcastle University, together with James Meade, Prince William's closest friend who, with Thomas van Straubenzee, delivered a joint best man speech.
Mr Penn, 30, is a City fund manager and a descendant of Sir Claude George Bowes Lyon, 14th Earl of Strathmore and Kinghorne, the Queen Mother's father.
While politicians and foreign dignitaries were out in force at Westminster Abbey for the Royal wedding between Prince William and his bride Kate Middleton, the Duke and Duchess of Cambridge will have been most thrilled by those who had gathered in Statesmen's Aisle in the abbey's north transept to see them marry.
This was the space, overlooked by statues of Disraeli, Gladstone and Palmerstone, reserved for some of the couple's closest friends.
Also among them were long time friends of the Royal family, wealthy landowners and aristocrats who have known Prince William all his life, together with the mentors who helped him cope with his mother's death and saw his bride transformed from commoner to future Queen.
The friends have remained low key throughout the couple's romance, but the jigsaw of who's who within the Duke and Duchess's inner circle can now be revealed.
THE GLOUCESTERSHIRE SET
Friends of the Prince's from his home county of Gloucestershire, who have been entertained at Highgrove, the Prince of Wales's country estate, were well represented.
Known fashion cheap hermes handbags as the "Glosse Posse", its most glamorous member is Arabella Musgrave, 28, said to have been a former flame of Prince William and once described as "the only woman who could make Kate Middleton" jealous.
Now head of PR at Gucci, Miss Musgrave met the Prince through friends at the Cirencester Park Polo Club, run by her father Major replica hermes handbags outlet Nick Musgrave, an old friend of the Prince of Wales.
A regular on the London party scene, until recently she dated James Tollemache.
Seated in front of Miss Musgrave is Lady Natasha Rufus Isaacs. Known as "Nats" to friends, she met Prince William while attending Westonbirt School, which is close to Highgrove.
Lady Natasha, 27, sat on Prince William's table at his "Out of Africa" themed 21st birthday at Windsor Castle. The daughter of the Marquess of Reading and older sister of Julian, Viscount Erleigh, she is also one of Prince Harry's best friends.
Lady Natasha runs the fashion label Beulah, selling clothes made by women who have escaped the sex trade in India, of which her grandfather was viceroy in the 1920s.
She dates Rupert Finch, a former boyfriend of the Duchess of Cambridge. Described as "affable" and "handsome", Mr Finch, 32, was a final year law student at St Andrews University when Kate arrived to study History of Art in 2001. The couple dated for less than a year. Some have suggested that Prince William "stole" his future bride from Mr Finch, but others insist that the relationship had run its course. He is now an employment lawyer in London.
Tom and Victoria Inskip "Skippy" and "Tor" to friends have known Princes William and Harry since childhood. Mr Inskip, 26, attended Eton with the Princes and helped to organise his stag party with Guy Pelly, the nightclub entrepreneur who was sat elsewhere in the abbey.
Miss Inskip, 27, who also attended Westonbirt, is the best friend of Prince William's first serious girlfriend Rose Farquhar. A Chelsea based estate agent, she is also friends with Prince Harry. The Inskips were regulars at "Club H", the nightclub William and Harry set up in the basement of Highgrove,
She has also been a fundraiser for Sentebale, the African charity set up by Prince Harry. Claire Inskip, their mother, is a sculptress.
Seated next to Mrs Inskip, is Jamie Murray Wells, an old Harrovian childhood friend of Prince William from replica birkin handbags Gloucestershire.
Mr Murray Wells, Hermes birkin bags fake 27, is the son of Simon Murray Wells, an investment analyst, and his wife Alison, who are close friends of the Inskips.
Mr Murray Wells is believed to be a multi millionaire after founding Glasses Direct selling cheap spectacles online during his final term at University of Bristol in 2004.
Renowned for his sense of humour, he once reportedly sent sheep into Specsavers stores in Newcastle upon Tyne to illustrate his belief that customers were being "fleeced".
In a prank in 2006, he and Mr Pelly, raided Westonbirt School in a hunt for girls (the school was empty at the time), with Mr Murray Wells falling from a wall and breaking his leg.
He showed loyalty to the Duchess during her brief split with Prince William in 2007, escorting her to nightclubs.
FRIENDS FROM SCHOOL AND UNIVERSITY DAYS
Seated beneath the statue of Benjamin Disraeli are Sir Henry and Lady Cheape. Sir Henry, a landowner educated at Harrow and Newcastle University, and distant cousin of the Prince, rented Balgove House to the couple during their third year at university, where their romance was allowed to flourish away from scrutiny.
At the other end of the row from Sir Henry and his wife, Louisa, is Will Matthews, another old Harrovian. Known to his friends as "Stan", he lives in Fulham, where many of the couple's set have their London bases.
Mr Matthews is an associate in the country house sales department at Knight Frank, the estate agents and close friends with Rory Penn (seated beside him with his wife Francesca Penn) and Sir Henry.
All three attended Newcastle University, together with James Meade, Prince William's closest friend who, with Thomas van Straubenzee, delivered a joint best man speech.
Mr Penn, 30, is a City fund manager and a descendant of Sir Claude George Bowes Lyon, 14th Earl of Strathmore and Kinghorne, the Queen Mother's father.
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