convicts who escaped from prison van
Even more than 24 hours after their escape,
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rolex perpetual datejust replica, managed to escape from the van transporting them to a correctional facility in Las Cruces. Wednesday. Thursday. The video was from a hotel lobby."In almost every case that you have a set of circumstances like this, it is not a matter of a lack of policies, a lack of systems, a lack of structure,
replica rolex datejust 2," said Gregg Marcantel, the state corrections secretary.State officials also waited several more hours after the discovery to alert the public that the men who a corrections spokeswoman said should be considered "armed and dangerous" were on the loose.They still hadn't been apprehended by early Friday. that the effort had concluded and the convicts were still at large.Cruz, 32,
replica value of a rolex oyster perpetual datejust, was convicted in 2007 for killing a man over drugs in Raton in northern New Mexico. Clah, 29, was convicted in Farmington in 2009 of armed robbery and assault with intent to commit a violent felony on a peace officer."Pretty hard to miss," Marcantel said.At a news conference Thursday in Santa Fe, Marcantel maintained that his department's policies weren't to blame in the case. He also said investigators were trying to determine if the escape was planned or spontaneous."This must be investigated as something more organized," he said. "We can't just assume an opportunity (presented itself)."The escape comes several months after Corrections Department officials warned of dangerously low staffing levels at prison facilities across the state and said low wages made it difficult to retain staffers.
Arson at Brussels criminology institute
BRUSSELS Belgium's criminal forensics laboratory was set alight in the early hours of Monday in an attack that prosecutors said was more likely linked to organized crime than terrorism.
Five people were detained near the National Institute of Criminology in Brussels over the fire which caused an explosion but no casualties but were later released.
"It was arson, deliberate arson, at the laboratory of the federal police,
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When asked whether the attack could be terrorism she said: "It is a path we are looking down,
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"We are thinking more of deliberate arson by organized crime. We have no indications that it was terrorism."
Belgium has been on high alert since Islamist attacks over the past year. and went into the wing of the building where the laboratories are located,
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More details about how the fire was started were not yet known, as investigators needed to wait until the building was declared safe to enter.
The institute is linked to the Belgian ministry of justice and carries out forensic investigations in criminal cases,
rolex perpetual oyster datejust replica, its director said.
Black preschoolers more likely to be suspended
public schools even as tiny preschoolers.
The racial disparities in American education, from access to high level classes and experienced teachers to discipline, were highlighted in a report released Friday by the Education Department's civil rights arm.
Black children represent about 18 percent of children in preschool programs in schools, but they make up almost half of the preschoolers who are suspended more than once, the report said. Six percent of the nation's districts with preschools reported suspending at least one preschool child.
Advocates long have said get tough suspension and arrest policies in schools have contributed to a "school to prison" pipeline that snags minority students,
old rolex oyster perpetual datejust fake, but much of the emphasis has been on middle school and high school policies. This was the first time the department reported data on preschool discipline.
Earlier this year, the Obama administration issued guidance encouraging schools to abandon what it described as overly zealous discipline policies that send students to court instead of the principal's office. But even before the announcement, school districts have been adjusting policies that disproportionately affect minority students.
Overall, the data show that black students of all ages are suspended and expelled at a rate that's three times higher than that of white children. Even as boys receive more than two thirds of suspensions, black girls are suspended at higher rates than girls of any other race or most boys.
The data doesn't explain why the disparities exist or why the students were suspended.
"It is clear that the United States has a great distance to go to meet our goal of providing opportunities for every student to succeed," Education Secretary Arne Duncan said in a statement.
"This critical report shows that racial disparities in school discipline policies are not only well documented among older students, but actually begin during preschool," Attorney General Eric Holder said. "Every data point represents a life impacted and a future potentially diverted or derailed. This administration is moving aggressively to disrupt the school to prison pipeline in order to ensure that all of our young people have equal educational opportunities."
Nationally, 1 million children were served in public preschool programs, with about 60 percent of districts offering preschool during the 2011 2012 school year, according to the data. The data show nearly 5,000 preschoolers were suspended once. At least 2,500 were suspended more than once.
Daniel Losen, director of the Center for Civil Rights Remedies for the Civil Rights Project at UCLA, said the findings are disturbing because the suspended preschoolers aren't likely presenting a danger, such as a teenager bringing a gun to school.
"Almost none of these kids are kids that wouldn't be better off with some support from educators," Losen said. "Just kicking them out of school is denying them access to educational opportunity at such a young age. Then,
fake datejust rolex oyster perpetual, as they come in for kindergarten, they are just that much less prepared."
Losen said it's appropriate to discipline a 4 year old,
fake the oyster perpetual datejust, but a more appropriate response might be moving them to a different educational setting with additional services.
"Most preschool kids want to be in school," Losen said. "Kids just don't understand why they can't go to school."
Judith Browne Dianis, co director of the Advancement Project, a think tank that specializes in social issues affecting minority communities, said the findings didn't surprise her.
"I think most people would be shocked that those numbers would be true in preschool, because we think of 4 and 5 years olds as being innocent," she said. "But we do know that schools are using zero tolerance policies for our youngest also, that while we think our children need a head start, schools are kicking them out instead."
Kimbrelle Lewis, principal of Raleigh Bartlett Meadows Elementary School in Memphis, said she's never suspended a child in her school's preschool program and would only consider it in an "extreme circumstance." She said her district provides behavior specialists and other services to children with discipline problems so strategies can be worked out with teachers and parents if preschoolers need additional support.
If there are racial disparities among preschoolers disciplined, "I do think it's something to look at. I think it's a conversation to have," said Lewis,
rolex datejust lady fake, who served on a committee with the National Association of Elementary School Principals looking at issues affecting younger school children.
Dennis Van Roekel, the president of the National Education Association teachers' union, said in a statement that the findings show that "too many children don't have equitable access to experienced and fully licensed teachers."
"The inequities detailed in this report have been caused, at least in part, by policies that disregard the professionalism of teaching and create a revolving door of under prepared and under supported novices who leave before they've reached the levels of mastery required to truly make a difference," Van Roekel said.
Chocolate layer cake with chocolate mousse icing recipe,
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Preheat oven to 180C (160C fan forced). Grease and line 2 x 20 cm deep round cake pans.
In a bowl, sift cocoa, flour and combine with sugar, bicarbonate of soda and baking powder in the bowl of an electric mixer. Mix on low to combine.
In a large jug,
fake rolex perpetual datejust, combine eggs, water, buttermilk, melted butter and vanilla essence. With the mixer on low gradually pour in the liquid ingredients and continue to beat for 2 minutes.
Divide the mixture evenly between the 2 cake pans and bake for 50 55 minutes or until cooked when tested. Allow to cool for 10 minutes in the pans.
To make the chocolate mousse icing,
rolex oyster perpetual datejust cost replica, beat butter in a bowl with an electric mixer until light and fluffy, add chocolate and continue to beat for 2 minutes.
In another bowl beat cream and caster sugar until soft peaks form. Add cream to the chocolate mixture and beat for a further 2 minutes.
Turn the cakes out and allow to cool completely. Using a serrated knife, trim the top of the cakes and then cut each cake evenly into 2 layers. Divide the chocolate mousse icing evenly between the layers and top of the cake. Sprinkle with cocoa powder.
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This recipe is also great for cupcakes,
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For best results use the icing at room temperature as soon as it has been made. Icing can be refrigerated or frozen for later use. Allow it to come back to room temperature and beat again until smooth.
Bird Flu Season Hits Asia
It's winter in the northern hemisphere flu season for people and birds. Sure enough, bird flu has recently flared up in eight countries in Asia and the Middle East.
The World Health Organization fears that with a few mutations, the bird flu virus H5N1, could touch off the next global flu pandemic. But WHO Director General Margaret Chan says the world is years away from controlling it.
No country has done more to control bird flu than Vietnam. Mass vaccination of poultry often door to door and educational programs down to the commune and village level have paid off. Vietnam had no reports of bird flu in 2006.
At the Viet Doan Commune,
rolex oyster perpetual datejust value replica, not far from Hanoi,
fake rolex lady datejust, several hundred farmers and their families crowded into a community hall to hear about preventive measures. Singers entertained them with traditional music, and the farmers watched skits that showed the importance of washing hands and cleaning poultry cages. Posters and banners drove the messages home.
Still, the battle isn't won, especially this time of year.
"This is the season that everybody's concerned about," says Don Douglas, a consultant with Abt Associates, based in Hanoi. "Everybody holds their breath in the avian flu community with each passing flu season."
And this month, bird flu did come back in Vietnam. So far in January, there have been at least eight large outbreaks, all in the Mekong Delta in the south.
The nation's 40 million ducks are mostly to blame. Ducks can spread the virus without showing symptoms. And a moratorium on duck hatchings didn't work. Neither did orders to keep ducks penned up and out of rice paddies, where traditionally the birds are used to fertilize the rice, and to clean up leftover grain after harvests.
"Rice production and duck raising have gone hand in hand for hundreds of years," says Dr. Juan Lubroth, the lead bird flu expert of the United Nations' Food and Agriculture Organization.
These ancient practices are hard to change, especially when they run counter to farmers' economic interests. Lubroth says the ban on duck roaming made some farmers cover up the fact that their flocks were on the loose. Because the ducks weren't registered, they didn't get vaccinated against bird flu.
"What has happened with the ban," Lubroth says, "is those ducks are, let's say, 'underground,' are not vaccinated and thus are not protected. And that's where we have seen the outbreaks of late."
But a much bigger problem is growing in Indonesia. Last year, Indonesia surpassed Vietnam in the number of humans who have died from bird flu: 62.
But Lubroth predicts Indonesia won't be able to stop people from keeping backyard poultry.
"It will still continue to occur, even though there is a ban," he says. "So it's better for it in some ways to be out in the open and have positive measures, such as improving hygiene, awareness, veterinary inspection at the markets, vaccines delivered to the villages or urban areas where these backyard chickens are being raised."
Implementing such measures is a daunting task especially in a country like Indonesia that is sprawled among 13,000 islands and three time zones.
So Keiji Fukuda,
buy rolex oyster perpetual datejust fake, the WHO's global flu coordinator, says there may be one useful aspect of continuing outbreaks of bird flu, at least among poultry. They keep people motivated when prevention measures become an endless daily grind.
"I think that the presence of avian influenza outbreaks has been an important spur," Fukuda says. "If there's a silver lining, that's it, I guess."
The Vietnamese don't need a spur.
"Avian influenza is a very big concern of my family," says Nguyen Van Tikh, who has a prosperous farm with more than 1,000 chickens and ducks in Bac Ninh Province in northern Vietnam. "We invest quite a lot of capital in our poultry. And avian influenza is happening every year in the world."P>
It's also a big concern for Bui Quang Anh, the chief animal health officer in Vietnam's Ministry of Agriculture and Rural Development.
Even before the latest outbreaks, Anh was worried about prevention fatigue. His concern is peaking right now, in the weeks leading up to the lunar new year celebrations called Tet in mid February. That's when many Vietnamese travel to ancestral villages, often carrying cages of live chickens to prepare the traditional Tet banquets; it's a good way to spread bird flu.
"In the Tet holidays, it's not so easy to control the live chickens," Bui says. "There's a lot of transportation of chickens. Before the Tet holiday,
datejust rolex oyster perpetual fake, we implement very serious vaccination programs."
based Tahoe Resources faces lawsuit over violence at Guatemala mine
Vancouver based Tahoe Resources faces lawsuit over violence at Guatemala mineDerrick Penner, Vancouver SunA group of men wounded last year during a protest outside a Guatemala mine is suing the Vancouver based mining company, Tahoe Resources Inc., in British Columbia Supreme Court.
Mark van ManenA group of men wounded last year during a protest outside a Guatemala mine is suing the Vancouver based mining company, Tahoe Resources Inc., in British Columbia Supreme Court arguing it should be held liable for the alleged violent action against them. for events that occurred at operations outside of Canada, but it follows from three suits against Toronto based Hudbay Minerals, which were accepted to proceed to trial by an Ontario Superior Court Judge last year, also related to alleged violent incidents in Guatemala.
Together, the suits are part of increasing efforts of non government organizations seeking greater accountability from Canadian mining companies operating abroad.
"The plaintiffs feel like they've not got justice for what happened to them (in Guatemala)," said Matt Eisenbrandt, legal director for the Canadian Centre for International Justice.
The seven men named in a notice of civil claim allege they were shot at close range during a peaceful protest on a public road outside Tahoe's Escobal silver mine east of Guatemala City on the evening of April 27, 2013, in what they argue was a planned act of intimidation by the company's security guards.
The mine's security manager, Alberto Rotondo,
oyster rolex perpetual datejust fake, was arrested and faces criminal charges of obstruction of justice, causing injury and mistreatment of a minor, Eisenbrandt said.
However, while that case is underway, the plaintiffs believe Tahoe should also be held accountable. Eisenbrandt said Canada's formal institutions that regulate Canadian companies abroad are too weak to do the job, so they are seeking damages in a Canadian court.
"At the end of the day, what the plaintiffs are looking for is a judgment from a Canadian court that Tahoe is responsible for what they suffered," said Eisenbrandt, who is part of the legal team that put the claim together.
The Guatemalan men's claim was filed by Vancouver lawyer Joe Fiorante of the firm Camp, Fiorante, Matthews, Mogerman. They are represented in Guatemala by the Guatemalan Centre for Legal, Environmental and Social Action.
Tahoe could not be reached for comment Wednesday but in a statement last year disputed the circumstances of the incident, alleging in return that men armed with machetes were approaching the gate at shift change in a hostile act and were turned back by security guards using tear gas and rubber bullets.
However, in the notice of claim, the plaintiffs allege that Rotondo carried out a campaign to undermine and intimidate local opposition to the Escobal project, and further that the security manager, a retired Peruvian Navy Captain, had planned a show of force to do just that on the date in question.
In the claim,
sell rolex oyster perpetual datejust fake, the men allege they were shot with buckshot and rubber bullets and suffered injuries to their faces, legs and backs.
Adolfo Garcia was shot in the back while retreating, with the projectile lodging near his spine, the statement of claim says. Luis Monroy was shot in the face, ultimately losing his sense of smell, the document says.
The suit alleges that the shooting constituted battery for which Tahoe should be considered vicariously liable.
Further, it alleges Tahoe had committed to operate under principles of corporate social responsibility to respect human rights, so it had a duty of care to make sure that its employees and contractors abided by those principles and was negligent for failing to do so. court will agree to hear it.
However, Pierre Gratton, CEO of the Mining Association of Canada, said historically courts have ruled that they don't have jurisdiction over such cases, thought that view is now evolving.
"The general principle of industry, and not just (mining companies), is for justice to be served appropriately, it should be heard in the country where the offence, if there was an offence,
fake rolex datejust 2, took place," Gratton said.
He added that Canada is in the process of reviewing its existing regulatory process at the Extractive Sector Corporate Social Responsibility Counsellor's office in the Trade and Development Canada department.
The counsellor's role is to investigate and mediate grievances between Canadian companies and communities affected by extractive industries. The criticism against that process, Eisenbrandt said,
oyster perpetual rolex datejust replica, is that it is voluntary and companies don't have to comply with it.
Gratton said the Mining Association has lobbied the federal government to make participation in the first stage of the CSR counselling process mandatory, which involves investigating and establishing whether grievances are legitimate.
"Companies shouldn't be able to walk away from it," he said.
Within the NGO community, however, the view is that the government isn't interested in strengthening accountability for Canadian companies operating abroad, which is why they are turning to the courts, according to Jennifer Moore, Mining Watch Canada's coordinator for Latin America.
Articles about Van Gogh,
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ARTICLES BY DATECALIFORNIA LOCALGregory White Smith dies at 62; co wrote Jackson Pollock biographyApril 12, 2014 By Elaine Woo, Los Angeles TimesGregory White Smith, a Harvard trained lawyer, businessman,
fake rolex datejust watch, philanthropist and Pulitzer Prize winning biographer who raised hackles in the art world with an intensely psychological examination of the life and work of Jackson Pollock, has died. He was 62. Naifeh and Smith won the Pulitzer Prize in biography for "Jackson Pollock: An American Saga," which was published in 1990 and spurred the 2000 movie "Pollock" starring Ed Harris.Norton Simon brings late Van Gogh self portrait to CaliforniaAugust 1, 2012 By Jori FinkelRight now, the most famous Van Gogh painting in a California museum happens to be one of his sunniest: The Getty owns an exuberant field of irises that the artist painted in 1889 as a sort of postcard for his arrival at a bucolic looking asylum in Saint Rmy de Provence, France. But this winter, the Norton Simon Museum in Pasadena, home to seven other Van Gogh paintings,
fake oyster rolex perpetual datejust, will exhibit a darker work from the same year that is celebrated for different reasons. 25 'In the Land of Snow: Buddhist Art of the Himalayas' Pasadena's Norton Simon Museum is well known for having the most impressive collection of European Old Master and early Modern paintings in Los Angeles. Less familiar is the museum's exceptional Indian, Nepalese and Tibetan art. This show will chronicle the movement of Buddhism from India to the Himalayas more than a thousand years ago, bringing numerous important loans together with superlative examples of painting, sculpture, ritual and decorative arts from the Simon's own collection.Museum talks on Caravaggio's cameras,
fake oyster perpetual datejust, Van Gogh's paints and moreDecember 28, 2012 By Jori FinkelDid Caravaggio use optical devices essentially transforming his studio into a giant camera obscura to make his paintings? Pegged to their big exhibitions this winter, the Los Angeles County Museum of Art, Getty and the Norton Simon have organized a range of talks with guest scholars and scholar scientists, and a LACMA lecture next week promises to address that question head on. Jerry is a sensitive man. DAVID JOHNSON Los AngelesThe mystery of the discolored Van GoghsIt's hard to imagine some of Vincent van Gogh's signature works without the vibrant strokes of yellow that brightened the sky in "Starry Night" and drenched his sunflowers in color. But the yellow hues in some of his paintings have mysteriously turned to brown and now a team of European scientists has figured out why. Using sophisticated X ray machines, they discovered the chemical reaction to blame one never before observed in paint.
An Oil Painting May Come Into Its Own As An Investment,
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Very rich people are not always clever or good at making money. Some have inherited or stolen everything they own. However, most wealthy people are pretty shrewd and many are entirely responsible for the fortunes that they have made and retained. It is therefore interesting to reflect on why so many ultra rich people invest in an oil painting.
Although major works by painters such as Rubens and Renoir are mostly owned by governments and nations there is nevertheless a healthy market for private collectors. Private individuals and some corporations with money to invest attend auctions either personally or through agents and pay very considerable sums to own a masterpiece. They understand the investment and aesthetic value of works that might grace a board room or private collection and at the same time constitute a growing asset.
It comes as a surprise to learn that artists can be shown to be statistically among the most highly paid professional people. They are more highly paid than, scientists doctors and lawyers. Jackson Pollock created a picture in 1948 that was sold in 2006 for $156.8 million. Statistically this would account for many works not sold at all but it throws light on the value of art works that succeed when compared with other manufactured products such as buttons or motor cars. Things of beauty are joys forever,
fake rolex oyster perpetual datejust value, and very much more expensive than ordinary objects.
When the son of a scientist once professed an interest in being an artist he was discouraged on the grounds that art was,
rolex lady datejust oyster perpetual replica, in the opinion of the father, for 'no brainers'. This anecdote illustrates a common social attitude towards artists, but also something important about artists.
The son in question gave up art and became a lawyer. Had he been a genuine artist he would have been compelled to follow his passion for better or worse. He might have produced a work worth millions because in some indefinable way it would have been infused with his passion for his work. In art, emotion and hard practicalities like money are inextricably entwined.
Art investments may be thought of as investments in rarity. An original oil painting is unique even though fakes might replicate every minute detail. The fake always remains a fake because it copies something that has its own identity. Ownership of an original oil painting is an excellent investment because it affords daily satisfaction, appreciates daily and has minimal maintenance costs.
As a medium oil is favored for several reasons over water colors,
gold rolex oyster perpetual datejust replica, acrylics and other mediums. It allows an artist to work slowly, adding textures and light that will endure without fading. It is said that one of Van Gogh's famous paintings survived a considerable time as the floor of a chicken coop before being recovered and returned to its pristine state.
A collector wishing to invest in an oil painting can now use the Internet to investigate the many opportunities that exist. At first it may be tempting to buy hand painted replicas of great works that are available. However, a better bet might be an original work by a new or little known artist. If it does please it will immediately serve the true purpose of art. If its creator becomes famous in the fullness of time it could also become fabulously valuable.
Brussels attacks suspect still at large as identity of second suicide bomber caught on CCTV remains mystery
Najim Laachraouiwas captured on CCTV at Brussels Airport with two suicide bombers, prosecutorFrederic Van Leeuw said. The suitcase he was wheeling through the terminal on a luggage trolley carried the largest explosive charge but did not go off and was deactivated by the army.Two more suitcases left at the address the trio were picked up from in a taxi were found to contain explosives, nails and screws, suggesting a far larger death toll was planned.Follow the latest live updates hereOne of the men has been identified asBrahim el Bakraoui, whose brother Khalid is reported to have blown himself up at Maalbeek Metro station,
replica van cleef and arpels alhambra turquoise necklace, while the name of the third man pictured on the left is unknown.Journalists fromDe TijdandEenVandaagsubsequently claimed the arrested man, who has not been identified,
replica van cleef and arpels mini alhambra necklace,was found at a pizza restaurant but the report has not been confirmed.A suspicious pizza order allegedly alerted police to Salah Abdeslam's wherabouts last week, while empty pizza boxes were also found littering hotel rooms used by the Paris attackers to prepare for November's massacres.Laachraoui isbelieved to be the only suspect remaining on the run following Tuesday's attacks, where brothersKhalid and Brahim el Bakraoui died in bombings at Brussels airport and Maalbeek Metro station.Under his alias Soufiane Kayal, the 25 year old had been wanted for months as a suspected bombmaker linked to the Paris attacks after his DNA was found alongside that of the terrorists who carried out the massacres at a safe house where traces of explosives and suicide belts were found.Laachraoui was picked up in Budapest by SalahAbdeslam, possibly making his way back from Syria,on 9 September alongsideMohamed Belkaid, the35 year old Algerian killed by police in Forest on 15 March.The net has been tightening on the remaining accomplices following Belkaid's death and Abdeslam's eventual arrest on Fridayand there was speculation that Tuesday's attacks were either an act of revenge or the fulfilment of plots Abdeslam claimed had already been hatched.The airport explosions,
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van cleef and arpels alhambra necklace replica,left at least 31 dead and 250 wounded.Click the Adblock/Adblock Plus icon, which is to the right of your address bar.On Adblock click "Don't run on pages on this domain".If you are Private Browsing in Firefox, "Tracking Protection" may cause the adblock notice to show. It can be temporarily disabled by clicking the "shield" icon in the address bar.
Association between thyroid autoantibodies and miscarriage and preterm birth
AbstractObjectives To evaluate the association between thyroid autoantibodies and miscarriage and preterm birth in women with normal thyroid function. To assess the effect of treatment with levothyroxine on pregnancy outcomes in this group of women.Data sources Medline, Embase, Cochrane Library, and SCISEARCH (inception 2011) without any language restrictions. We used a combination of key words to generate two subsets of citations, one indexing thyroid autoantibodies and the other indexing the outcomes of miscarriage and preterm birth.Study selection Studies that evaluated the association between thyroid autoantibodies and pregnancy outcomes were selected in a two stage process. Two reviewers selected studies that met the predefined and explicit criteria regarding population, tests, and outcomes.Data synthesis Odds ratios from individual studies were pooled separately for cohort and case control studies with the random effects model.Results 30 articles with 31 studies (19 cohort and 12 case control) involving 12126 women assessed the association between thyroid autoantibodies and miscarriage. Five studies with 12566 women evaluated the association with preterm birth. Of the 31 studies evaluating miscarriage, 28 showed a positive association between thyroid autoantibodies and miscarriage. Meta analysis of the cohort studies showed more than tripling in the odds of miscarriage with the presence of thyroid autoantibodies (odds ratio 3.90, 95% confidence interval 2.48 to 6.12; PConclusion The presence of maternal thyroid autoantibodies is strongly associated with miscarriage and preterm delivery. There is evidence that treatment with levothyroxine can attenuate the risks.IntroductionMiscarriage, the loss of a pregnancy before 24 weeks of gestation, affects up to one in five women who conceive, making it the commonest complication of pregnancy.1 Preterm birth, delivery of a baby between 24 and 37 completed weeks of gestation, occurs in 6 10% of pregnancies.2 Up to 85% of neonatal deaths are attributable to preterm birth (especially those delivered before 28 weeks). Of those who survive, around 10% have long term disability.3 The cost of preterm birth is 93m a year in the United Kingdom.3 This includes healthcare costs (including neonatal care), education, and costs to the parents.There is evidence that thyroid autoimmunity is an important risk factor for miscarriage and preterm birth.4 The presence of thyroid autoantibodies is relatively common in women of reproductive age. In an "unselected" population of women, the prevalence ranges from 6% to 20%,4 5 being even higher in women with a history of recurrent pregnancy loss, at around 17 33%,6 7 8 and in women with a history of subfertility, at around 10 31%.9 10 11 In the developed world,
van cleef and arpels necklace alhambra replica, thyroid autoimmunity is the main cause of hypothyroidism, which itself results in poor obstetric outcomes. Even in women with biochemically normal thyroid function, studies have reported an association between the presence of thyroid autoantibodies, particularly thyroid peroxidase antibodies and adverse pregnancy outcomes, including miscarriage, preterm birth, and adverse neurodevelopmental sequelae in children.12 13 The exact mechanisms of these associations are unknown, though two have been proposed. Firstly, the presence of thyroid autoantibodies in women with normal thyroid function could be associated with a subtle deficiency in the availability of thyroid hormones (a fall in circulating free thyroid hormones within the reference range) or a lower capacity of the thyroid gland to adequately rise to the demand for augmented synthesis of thyroid hormones required in pregnancy.14 Given that minor perturbations in thyroxine concentrations within the normal range can lead to an association between thyroid autoantibodies and adverse pregnancy outcomes, trials have been conducted to evaluate the effects of supplementation with levothyroxine on pregnancy outcomes in women with normal thyroid function who tested positive for thyroid autoantibodies. Secondly, thyroid autoantibodies might be an indicator of an underlying enhanced global autoimmune state. This itself can have a direct adverse effect on placental or fetal development.14Given the importance of the potential association between thyroid autoantibodies and adverse pregnancy outcomes, we systematically reviewed and meta analysed the association between thyroid autoantibodies and miscarriage and preterm birth. Given the possible role of levothyroxine in improving pregnancy outcomes, we also reviewed the available randomised evidence on the effect of treatment with levothyroxine on pregnancy outcomes.MethodsThis systematic review was conducted with a prospective protocol with widely recommended methods.15Identification of studiesWe searched Medline (1951 2011), Embase (1974 2011), the Cochrane Library (2011), and SCISEARCH (1974 2011) for relevant citations and examined the reference lists of all known primary and review articles to identify cited articles not captured by the electronic searches. Language restrictions were not applied. We used a combination of MeSH and text words to generate two subsets of citations, one indexing thyroid autoantibodies ("thyroid autoimmune antibodies", exp thyroid/ AND exp antibodies, thyroid AND autoimmune AND antibodies) and the other indexing outcomes ("miscarriage", "abortion", "pregnancy loss",
replica van cleef and arpels sweet alhambra necklace, "preterm", "premature", "early labo(u)r", "pret$"). These subsets were combined with "AND" to generate a subset of citations relevant to our research question.Study selection and data extraction proceduresThe electronic searches were scrutinised and two independent reviewers (ST and EK) obtained full manuscripts of all citations that were likely to meet the predefined selection criteria. Studies were selected if they included women with normal thyroid function who tested positive for thyroid autoantibodies, and the outcomes included adverse maternal and fetal outcomes. We excluded articles in which women were known to have overt biochemical hypothyroidism or hyperthyroidism. When disagreements occurred, they were resolved by consensus and discussion with a third reviewer (AC). In cases of duplicate publication, we selected the most recent and complete versions.Information was extracted from each selected article on study characteristics, quality, and test results. Data were used to construct 22 tables of thyroid autoantibody results (test positive if concentrations were above a threshold as defined in the primary study, and test negative if these were below the threshold) and pregnancy outcomes (miscarriage and preterm delivery). We also extracted data on mean age and serum concentrations of thyroid stimulating hormone and free thyroxine. For the randomised trials, we extracted data on study population, quality of the methods, details of the interventions, and outcomes.Assessment of quality of methodsWe used the Newcastle Ottawa scale16 to assess methodological quality of the selected studies, with the components of study design that are related to internal validity. Information on adequacy of definition of cases or cohorts, representativeness of the sample, selection and evaluation of controls, comparability, ascertainment of exposure, and outcome were evaluated for cohort and case control studies.16 The study was considered to have low risk of bias if it scored a maximum of 4 for selection, 2 for comparability, and 3 for assessment of outcome or ascertainment of exposure. Any study that scored 1 or zero for selection or zero for comparability or for outcome assessment was categorised as having a high risk of bias. Studies that scored in between were rated as having medium risk of bias.We assessed quality of randomised trials evaluating the effectiveness of levothyroxine according to appropriate randomisation, concealment of allocation, blinding, analysis by intention to treat, and follow up rates. A quality score for the randomised trials was given on Jadad's scale.17Data synthesisOdds ratios from individual studies were pooled separately for the cohort and case control studies with the random effects model. Heterogeneity of treatment effects was evaluated graphically with forest plots and statistically with 2 and I2 tests. We generated the pooled mean difference in age and weighted mean difference in serum thyroid stimulating hormone between groups with positive and negative results for thyroid autoantibodies. All analyses were performed with Stata 10.0 and Revman 5 statistical software.18 19ResultsFigure 1 summarises the processes of literature identification and selection of studies evaluating the relation between thyroid autoantibodies and adverse pregnancy outcomes. From the 389 citations identified from electronic and hand searches, we included 30 primary articles with 36 studies (31 for miscarriage and five for preterm birth) in the systematic review.Fig 1 Flow chart of study selection in review of association between thyroid autoantibodies and adverse pregnancy outcomeThyroid autoantibodies and miscarriageThirty one studies (12126 women)6 7 8 9 10 11 12 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 evaluated the association between thyroid autoantibodies and miscarriage. Nineteen studies were cohort studies, and 12 were case control studies. Thirteen studies (three cohort, 10 case control) evaluated the association in women with recurrent miscarriage, nine studies (seven cohort, two case control) in women with subfertility and nine cohort studies in unselected or other populations. The studies were judged to have low risk of bias for assessment of outcome (19/19 cohort studies) and ascertainment of exposure (12/12 case control studies) on the Newcastle Ottawa scale.16 Nearly half the cohort studies (9/19) had low selection bias and the others (10/19) had medium selection bias. All the case control studies had medium selection bias. Eight of the 19 (42%) cohort studies had established good comparability of the groups compared with 16% (2/12) of the case control studies. All studies tested for thyroid peroxidase antibodies. Studies varied in the frequency and timing of the autoantibody testing, ranging from testing before pregnancy, in early pregnancy, and after delivery or miscarriage. The commonest threshold concentration of thyroid peroxidase for a diagnosis of positive thyroid autoantibodies was >100 U/ml.Twenty eight of the 31 (19/19 cohort and 9/12 case control) studies showed a positive association between thyroid autoantibodies and spontaneous miscarriage. Meta analysis of the cohort studies found more than tripling in the odds of miscarriage in the presence of thyroid autoantibodies (odds ratio 3.90, 95% confidence interval 2.48 to 6.12; P). The odds of miscarriage with thyroid autoantibodies was increased for women with recurrent miscarriages (4.22, 0.97 to 18.44; P=0.06), women with subfertility (3.15, 2.23 to 4.44; P2=75%) and the unselected population (I2=89%). There was no evidence of heterogeneity for studies in women with subfertility (I2=0%) (fig 2).To explore the hypothesis that women who are positive for thyroid autoantibodies have relative hypothyroidism, we meta analysed the serum thyroid stimulating hormone concentrations in six studies. The weighted mean difference for thyroid stimulating hormone was significantly higher in the thyroid autoantibody positive group compared with the negative group by 0.51 mIU/L (95% confidence interval 0.14 to 0.88; P=0.007),
replica sweet alhambra necklace, giving credibility to this hypothesis (fig 5). There were insufficient data on serum free thyroxine (fT4) and free triiodothyronine (T3) concentrations for meta analysis.Thyroid autoantibodies and preterm birthFive studies28 29 30 43 44 including a total of 12566 women evaluated the association between thyroid autoantibodies and preterm birth. All were cohort studies and had low risk of bias for selection and outcome assessment on the Newcastle Ottawa scale.16 Three studies were judged to have medium risk of bias and two as high risk of bias for comparability of cohorts. All showed a positive association between the presence of thyroid autoantibodies and preterm births. Meta analysis showed an increase in the odds of preterm birth in the presence of thyroid autoantibodies (2.07, 1.17 to 3.68; P=0.01) (fig 6).Effect of levothyroxine treatment on pregnancy outcomesTwo randomised studies, including a total of 187 women, evaluated the effect of levothyroxine treatment on pregnancy outcomes.23 44 Both studies were in women with normal thyroid function with thyroid autoantibodies. One study was in unselected women44 and the other in women scheduled to have in vitro fertilisation treatment.23 One used levothyroxine at a dose of 1 g/kg/day,
vca necklace replica,23 and the other used a titrated dose, with a mean levothyroxine dose of 49.7 g/day (SD 14 g) in the treatment group.44 The Jadad score17 for quality of the studies was 5/5 and 3/5. Both studies showed a reduction in miscarriage rates (36% and 75% relative reductions), and when the results were pooled, there was a significant 52% relative risk reduction in miscarriages with levothyroxine (0.48, 0.25 to 0.92; P=0.03) (fig 7). One of the two studies reported on preterm birth44; this study (n=115) found a 69% relative risk reduction in preterm births with levothyroxine (0.31, 0.11 to 0.90).DiscussionAssociation of thyroid autoantibodies with adverse pregnancy outcomesOur systematic review and meta analysis of the published literature showed that in women with normal thyroid function, there is a strong association between the presence of thyroid autoantibodies and poor obstetric outcomes, for both miscarriage and preterm birth. The odds of miscarriage more than tripled and that of preterm birth doubled in women with thyroid autoantibodies.Given the high prevalence of thyroid autoantibodies in women of reproductive age group, these increases in miscarriage and preterm birth are clinically highly relevant at the individual and population level. We showed that the increase in miscarriage rates in women positive for thyroid autoantibodies could not be accounted for by confounding factors such as a difference in age. Our review of the effectiveness of treatment with levothyroxine has provided preliminary evidence on its efficacy in reducing the rates of miscarriages and preterm births.Five reviews have examined the association between thyroid autoantibodies and miscarriage,4 5 14 45 46 and one has examined the association with preterm birth.47 Several new studies have emerged since these reviews were completed, however, and the existing reviews have used limited meta analytical methods, necessitating our review.
