Flashing night time-lighting fixtures may additionally help reduce jet lag, circadian issues

Exposing snoozing human beings to a chain of quick flashing lighting fixtures at night may assist them alter extra quickly to time area changes, in keeping with a new U.S. study.

In experiments, the method – that is based totally on the way non-visual components of the mind reply to light – changed into much more effective than sustained vibrant mild just like that from devices from time to time used to fight sleep disorders or seasonal depression.

“Jet lag itself is surely a nuisance syndrome as it's miles self-resolving,” stated senior author Jamie Zeitzer, assistant professor of psychiatry and behavioral sciences at the Stanford college faculty of drugs in California.

Zeitzer became at the committee that eliminated jet lag as a "disease" from the Diagnostic and Statistical manual of intellectual issues, 5th edition (DSM-five), the manual that psychiatrists use to diagnose mental ailments.

“however, the remedies which might be advanced for jet lag may be used for less customary, though far more good sized societal problems which includes not on time sleep in teens (in whom we've an ongoing medical trial the use of the flash method) and shift workers who try to flip among a night time time table for work and a day time schedule for entertainment,” he advised Reuters fitness by e-mail.

The study covered 39 people, 31 of whom were uncovered to a sequence of two-millisecond light flashes with changing periods whilst slumbering, and eight of whom have been uncovered to 60 mins of continuous bright light.

a series of flashes just like a digicam flash brought each 10 seconds over a 60-minute duration not on time sleepiness through two hours, compared to a 36-minute delay for the ones uncovered to non-stop mild for an hour, in line with the effects published inside the journal of scientific research.

“In essence, the usage of the night before you traveled from California to N.Y. could circulate your circadian system two-thirds of the manner there before you even left,” Zeitzer stated.

Arriving in the big apple, you will be synced to the local time after sooner or later, he said.

“The circadian clock is the relevant conductor of the numerous clocks which are located in nearly all tissues of your body,” Zeitzer said. “This clock remains synchronized with the external day through everyday publicity to light.” nighttime flashes alternate the timing of the circadian clock, he stated.

“For transferring your device to a later time, consisting of might be essential when traveling East-to-West, mild throughout the first few hours of the night time is right,” he said. “For shifting your machine to an earlier time, together with might be essential while journeying West-to-East, mild all through the previous few hours of the night is right.”

The night flashes require special generation and equipment, beyond only a phone, which can be still in development, Zeitzer stated.

In a previous examine, the quick flashes of light at night time did not interrupt sleep or lessen its exceptional, he added. 

“this is one of the actual benefits of this system - you could change circadian timing at the same time as you sleep, without interfering with sleep,” he said.

Mistiming mild remedy can make jet lag worse, recommended Anna Wirz-Justice, professor emeritus at the middle for Chronobiology at the university of Basel in Switzerland, who became not part of the brand new examine.

WHO seeks $25 million for six-month combat in opposition to Zika

the sector health business enterprise will are looking for $25 million for a six-month programme to combat the Zika virus linked to beginning defects, consisting of research on whether or not it's miles unfold by using intercourse or through blood transfusion, a senior WHO authentic advised Reuters on Friday.

two instances of Zika being transmitted thru blood transfusions have been reported in Brazil on Thursday, adding to worries over the virus that has been linked to microcephaly, a circumstance that can purpose excessive delivery defects.

Dr. Sylvie Briand, director of who is branch of pandemic and epidemic illnesses, said pregnant women in affected countries have to have get entry to to counseling and generation to make informed selections, along with whether or not to abort foetuses with microcephaly.

Briand, asked about several suspected instances of Zika spread by way of sex or through blood transfusion, stated mosquitoes remained the "main path".

"There is probably different modes of transmission, but for which we need to gather proof and to broaden specific studies to check that this is a real mode of transmission," she stated in a telephone interview.

"It (mosquitoes) seems the most probable way of transmission. due to the fact while you observe the facts on the humans that have been inflamed by means of Zika, it's all age agencies...(together with) babies and elderly."

but studies is missing on Zika, in spite of it emerging in Uganda in the Forties. Briand said it took West Africa's Ebola epidemic to recognise that deadly haemorrhagic fever virus can stay in semen for months and be transmitted.

"So we ignored virtually a few cases of (sexual) transmission because of that. however now with Ebola we have discovered that it is within the semen as well and might continue to be for pretty a long time."

The WHO, which declared Zika an international emergency on Monday, is working with the 31 affected international locations and territories to standardise techniques of gathering data to gather similar proof, Briand stated.

"we will use locations wherein we're going to follow-up being pregnant and pregnant women and paediatric devices to look for the microcephaly. after which of course all round being pregnant is likewise birth manage and all those form of centers which might be typically connected to pregnancy," she stated.

"nations have to just be aware that in the event that they have had a Zika outbreak the range of pregnant girls having a hazard of microcephaly might also boom although we have no longer yet installed completely the casual courting but this is a possibility."

in advance, Zeid Ra'ad Al Hussein, the top U.N. human rights reliable, referred to as for nations with the Zika virus to make to be had sexual and reproductive health counselling to ladies and uphold their right to terminate pregnancies.

"it is very critical for governments to install place the proper approach in order that women are protected and that they may be knowledgeable about the chance however also be accompanied up and feature access to sonography, and many others," Briand stated.

Florida extends fitness emergency over Zika amid growing U.S. issue

Florida Governor Rick Scott improved a public fitness emergency over the Zika virus on Thursday, including a 5th county to the list of areas in the kingdom with tour-associated instances.

His motion got here as the mosquito-borne virus generates increasing problem inside the america. Zika is spreading unexpectedly within the Americas, and has been connected to a spike in birth defects in thousands of infants in Brazil.

Florida's warm weather and nearly year-round mosquito season makes it specifically at risk of spreading, although to date all of the kingdom's cases have been received abroad, officials said.

Scott has directed kingdom officials to pay unique attention to mosquito manipulate inside the affected counties. they are Broward and Miami-Dade in south Florida, Hillsborough inside the Tampa vicinity, Lee County in southwest Florida and Santa Rosa County within the Florida Panhandle.

"much like a typhoon, we must ensure Florida is secure," Scott said on Thursday, calling it prudent to prepare for the worst and desire for the nice.

He additionally referred to as for federal fitness officers to offer the country with at the least 1,000 Zika antibody exams so the nation can take a look at pregnant girls who've traveled to affected international locations and experienced signs and symptoms of the virus. The kingdom is also boosting its inventory of trying out kits for energetic instances, Scott said.

meanwhile, the big apple Governor Andrew Cuomo increased his country's loose Zika checking out to encompass all pregnant ladies who've traveled to nations wherein human beings are being inflamed.

authorities in Texas said on Tuesday someone in Dallas had grow to be infected with Zika after having intercourse with another person who had traveled in Venezuela, in which the virus is circulating.

neighborhood fitness officials stated on Thursday both the ones human beings have fully recovered from the virus.

United kingdom to spray insecticide inside planes from Zika-affected areas: mother or father

Planes landing within the united kingdom from international locations stricken by the Zika virus must be sprayed internal with insecticide, the United Kingdom government announced on Friday, in step with the mother or father newspaper.

it's miles a precautionary measure to fight the mosquito-borne Zika virus connected to heaps of birth defects in Brazil, the mum or dad said. (bit.ly/20d0Q8K)

health officers stated Zika outbreaks were mentioned in as a minimum 26 countries within the Americas. Brazil has been the kingdom hardest hit however outbreaks were pronounced in Mexico, the Caribbean, significant the usa and South the us.

in the united kingdom, the general public of aircraft from the ones areas are already sprayed inside as a precaution against malaria, another ailment transmitted by way of mosquitoes, the newspaper stated.

the world fitness company on Monday declared the rapidly spreading Zika virus to be a global emergency.

Mosquito repellant income growth in Brazil amid Zika scare

worry of the mosquito-borne Zika virus has Brazilians speeding to shop for repellant, growing a shortage of some manufacturers on pharmacy shelves and boosting income for the industry - a fashion some manufacturers are making ready for somewhere else as the outbreak spreads.

Following the detection of Zika in April, income of repellant in Brazil rose by way of one-third final year, consistent with client studies company Nielsen, doubling sales for the sector to $55.7 million. shopping for became additionally spurred with the aid of an boom in cases of dengue, some other virus spread through the Aedes aegypti mosquito.

sales have risen even more sharply in view that Brazilian government in November flagged a ability hyperlink among Zika and suspected instances of microcephaly, a circumstance marked with the aid of abnormally small head size in newborns that may bring about developmental problems.

Raia Drogasil, Brazil's biggest chain of pharmacies, stated repellant income in December jumped seven-fold from a 12 months earlier.

Brazil's biggest retailer, the Pao de Acucar organization, said grocery store income of repellant had been up a hundred and twenty percent within the first weeks of 2016, in comparison to the identical length a year in advance. The upward push become sharpest inside the Northeast place at the center of the outbreak, in which income rose fourfold, and in the Brazil's 2nd metropolis of Rio de Janeiro, where they tripled.

In Rio, safety towards Zika is a pinnacle precedence for the metropolis's 6.five million inhabitants and hundreds of hundreds of vacationers because the usa's largest Carnival birthday party kicks off on Friday. Rio may also host the Olympic games in August.

Even at small neighborhood pharmacies in Rio, waiting lists for the maximum sought-after repellant, Exposis, stretch to loads of names, with expectant moms and their families speeding from shop to store in search of the product.

Exposis, advanced by way of France's Osler, has received media interest in Brazil because it's miles the best brand on the market with the energetic ingredient Icaridin. Many Brazilians recollect it the only repellant against the Aedes mosquito, although studies suggest its efficacy is similar to brands using DEET.

Cristiane Padrao, a 36-year-antique bodily schooling instructor in her 6th month of being pregnant, said she could not locate Exposis everywhere regardless of scouring the net and enlisting the help of own family in other parts of Brazil.

"i'm on my 0.33 tube of it," she said. "i bought one in Rio. My sister turned into able to shop for one in Belo Horizonte and my mother bought two for me" in Minas Gerais state north of Rio.

components FLOWN IN via JET

Osler has hiked production of Exposis at its Brazilian facilities 28-fold within the beyond two months, however it can't hold up with call for, stated Paulo Guerra Vieira, the employer's head in Brazil. He expects if you want to meet demand by using give up-February.

in place of uploading the energetic factor in Exposis from Germany by ship - because it did earlier than the Zika scare Osler now flies it in through aircraft.

Vieira stated the enterprise plans to go into 9 different nations this month - which include america, Colombia and Mexico - as difficulty over Zika spreads.

because it became detected in Brazil in April, the virus has unfold to 26 international locations in the Americas. the sector health employer declared Zika an worldwide health emergency this week, mentioning a "strongly suspected" courting between the virus in being pregnant and microcephaly.

Brazil's government is investigating the potential hyperlink among Zika and extra than 4,000 suspected cases of microcephaly. Researchers have identified evidence of Zika in 17 of those cases however have not confirmed the virus can cause the circumstance.

Brazil has stated a few shape of repellant need to be used to defend against Zika but has not encouraged any product.

family-owned U.S. company SC Johnson said in a statement that it turned into increasing its production of its OFF! repellent in Brazil and turned into working with the authorities to ensure good enough components.

Reckitt Benckiser said it became elevating output of Repelex to meet call for, especially in northeastern Brazil and within the maximum populous kingdom, Sao Paulo.

in the u.s.a., industry insiders are preparing for a rise in sales as soon as the mosquito season starts offevolved inside the south in March or April, then rolls northwards as temperatures rise.

"An growth in call for for offerings this summer time could now not marvel us as information of Zika virus escalates," stated Ron Harrison, entomologist at extermination company Orkin, owned by Rollins Inc.

Rollins shares have jumped five percentage throughout this year's stock marketplace selloff due to the fact buyers anticipate Zika fears to lead to accelerated sales.

Eric Kenney, who leads the advertising for the home & garden enterprise of Spectrum brands, which incorporates the repellants Cutter and Repel, said the employer had already seen a spike in demand inside the u.s., mainly in current weeks.

"Given the growing issues concerning the Zika virus, we do count on that demand will step by step increase inside the coming weeks, and feature organized as a result," he stated.

Tropical Tonga declares Zika outbreak after five instances confirmed

The tiny South Pacific island nation of Tonga has declared a scourge of the Zika virus after 5 cases of the mosquito-borne contamination have been showed and every other 259 suspected, the us of a's leader clinical officer stated on Friday.

chief scientific Officer Dr. Reynold Ofanoa said that officials became suspicious after a sharp upward thrust inside the quantity of patients suffering acute fever and rashes due to the fact that the beginning of the yr.

"We had been suspecting a likely outbreak of both Zika, dengue or chikungunya," he advised Reuters, regarding  other mosquito-borne viruses. "So we despatched the blood specimens for testing overseas and while we acquired the effects it showed that we have got showed high quality blood exams for Zika."

The tropical archipelago had in no way previously had any confirmed cases of the Zika virus, Ofanoa stated, so it became in all likelihood delivered into the country via an infected character after which spread by mosquitoes.

"I suppose this is the primary time it took place in Tonga, so without a doubt the disease came from distant places."

There had been no immediate plans to introduce journey restrictions in or out of the country, he stated.

because it changed into detected in Brazil in April, the virus has unfold to 26 nations within the Americas. the world fitness employer declared Zika an international fitness emergency this week, citing a "strongly suspected" dating between the virus in being pregnant and microcephaly, a condition in which infants are born with abnormally small heads and might suffer developmental issues.

Brazil's authorities is investigating the capacity link between Zika and more than 4,000 suspected cases of microcephaly. Researchers have identified proof of Zika in 17 of these cases however have now not showed the virus can reason the situation.

Xarelto trial outcomes reaffirmed regardless of defective device

Europe's drug regulator stated on Friday the defective blood clotting take a look at tool utilized in a key trial for the approval of Bayer's pinnacle-promoting anti-clotting drug Xarelto did now not distort the observe's foremost findings.

"Xarelto can stay used as earlier than, in step with the present day prescribing facts," the ecu medicines employer (EMA) said on its website.

The take a look at called ROCKET as compared Xarelto with older drug warfarin for stopping strokes in patients with a sort of irregular heartbeat common many of the aged.

that is by means of some distance the most important market for the drug, which Bayer at the same time evolved with

Johnson & Johnson, and which competes with Bristol Myers-Squibb and Pfizer's Eliquis.

A so-called INR tool by using Alere, which measures how quickly blood starts offevolved clotting and which was used within the trial, become recalled in December 2014 after giving falsely low test outcomes.

"A disorder with the worldwide normalized ratio (INR) device used within the ROCKET examine does not exchange its conclusions on the overall safety or gain-threat stability of Xarelto," EMA said within the statement. Bayer stated at the quit of October that Xarelto has a 34 percent marketplace share globally. Bayer chalked up 1.sixty eight billion euros ($1.eight billion) in revenue from Xarelto in 2014 and 1.60 billion within the first nine months of 2015, up 38 percent from a year earlier, making it Bayer's exceptional-selling drug.

Smoking bans result in higher countrywide health

humans residing in international locations with public smoking bans have lower publicity to secondhand smoke and better health, in line with a sparkling have a look at beyond studies from 21 international locations.

Smoking bans had been tied to a lower in fitness problems and deaths - particularly the ones related to heart ailment, researchers report in the journal Cochrane Library, on-line February 4.

"I assume the bans benefit everyone through a discount of secondhand smoke exposure," said senior creator Cecily

Kelleher, of university college Dublin in eire.

imposing those bans across the globe, especially in developing countries with rising continual fitness problems, may want to have a massive effect at the population's health, she informed Reuters health.

Tobacco is currently chargeable for the death of approximately one in every 10 adults around the sector, the researchers write. They did their analysis for the Cochrane Collaboration, which is understood for reviewing scientific proof and determining its pleasant.

A previous Cochrane overview determined that smoking bans reduced people's exposure to secondhand smoke, but back then the reviewers were not in a position to expose that reduced smoke publicity caused better health.

"We undertook the authentic assessment in 2010, and the proof base was nothing just like the evidence now," said Kelleher.

This time, the researchers in particular included research that seemed past secondhand smoke publicity. as an instance, they seemed in medical databases for studies inspecting hyperlinks among smoking bans and costs of coronary heart assaults, strokes, respiratory issues, toddler health and deaths.

in the long run, they protected 77 studies from 21 nations. most of the research used facts from hospitals, country wide fitness registries and workplaces.

forty-3 studies especially tested coronary heart attacks and acute coronary syndrome. Thirty-three of the papers discovered a link among introducing smoking bans and a lower in the ones occasions.

Of the six studies that examined the hyperlink among strokes and smoking bans, five observed benefits.

as an example, a study from eire mentioned a 26% fall in deaths from coronary heart disorder and a 32% decrease in stroke deaths.

The reviewers additionally determined evidence that the smoking bans were useful to respiration and newborn health.

The first-rate of evidence at the back of those findings have been very low, however.

"these are persuasive that these bans are useful," Kelleher said of the outcomes.

She delivered, however, that higher and extra uniform studies is wanted to reinforce the evidence in the back of those benefits.

"in case you study a number of the authors' conclusions, that is very compelling evidence of the consequences of any policy that impacts secondhand smoke exposure," said Liz Klein, of the center of Excellence in Regulatory Tobacco technological know-how on the Ohio nation college in Columbus.

preceding pointers that smoking bans help save you heart attacks have been met with skepticism, stated Klein, who changed into no longer concerned in the new overview.

"in this evaluate, that proof is so always robust that it indicates while you ban smoking in those public areas, you spot much less heart assaults on the community degree," she told Reuters health.

Klein said no longer each city or country has these policies in vicinity, however in which they do exist, they protect the general public's fitness.

Kelleher said, "The message for policy makers is that bans are an effective method."

Puerto Rico broadcasts public health emergency over Zika virus

Puerto Rico Governor Alejandro Garcia Padilla on Friday declared a public health emergency because of the mosquito-borne Zika virus, a government assertion said.

Puerto Rican fitness officials have confirmed 22 cases, which includes a pregnant girl and a person with Zika who developed Guillain-Barre syndrome, a separate authorities statement said. Guillain-Barre is a rare ailment in which the frame's immune machine attacks the nerves.

health authorities would tune the Zika instances and file consequences weekly, the government stated.

The virus is having an impact on tourism, with a few traveller agencies canceling reservations, in particular weddings in resorts at the Caribbean island. There have been no reviews of conventions being canceled, the assertion said.

Puerto Rico pronounced its first case of Zika in December, the virus having emerged at a hard time for the U.S. territory because it tries to clear up an monetary and financial disaster. The island, suffering to restructure its debt, will run out of financial emergency measures by way of June, the authorities improvement bank president stated on Friday.

Brazil reveals Zika in saliva, urine; professional warns against kissing

Scientists identified the Zika virus inside the saliva and urine of  infected patients, a pinnacle Brazilian biomedical research organization said on Friday, prompting its president to urge pregnant ladies not to kiss strangers just as local carnival celebrations start.

the invention added to the growing challenge over Zika, which is spreading unexpectedly in the people and has been linked to thousands of severe beginning defects in Brazil.

They said they used genetic testing to pick out the virus in saliva and urine samples from two patients who had symptoms due to Zika infection, and decided that the virus changed into active, which means it had the capacity to purpose infection, scientists at the public Oswaldo Cruz foundation said.

They stated greater studies changed into had to decide whether or not Zika might be transmitted by way of either fluid.

This marked the first time the mosquito-borne infection that has triggered a worldwide health scare has been detected in saliva and urine, the scientists informed newshounds in Rio de Janeiro, host of the 2016 summer Olympic games in August.

The considerable majority of Zika infections were caused by mosquito bites, but word surfaced this week of infections because of sexual transmission and blood transfusions.

those traits come simply as Rio kicks off its annual carnival celebrations, a raucous 5-day bacchanalia known for avenue events and masses of alcohol and kissing. a few revelers even maintain music of the wide variety of entire strangers they kiss.

due to the fact Zika has been connected to the delivery disorder microcephaly, a situation wherein infants are born with abnormally small heads and can suffer developmental troubles, the Oswaldo Cruz foundation scientists advocated that pregnant women take special precautions and avoid crowds in the course of carnival.

"In mild of the possibility of being in touch with someone who's inflamed, do no longer kiss, obviously," Dr. Paulo Gadelha, the muse's president, instructed journalists.

"We can't say nowadays that there may be no possibility of transmission," Gadelha brought.

Fiocruz, as the muse is informally regarded, said it made the discovery after wearing out a partial genome sequencing of the virus located within the samples from the 2 sufferers.

"imagine the social and economic impact of having a mega carrying event with hundreds of thousands of attendees with a brutal infection in the usa ... particularly at a time we are going thru an financial disaster," stated Dr. Leonardo Vedolin, a neuroradiologist in Porto Alegre.

there is no treatment or vaccine for Zika. maximum infections motive either no symptoms or signs which include a mild fever, pores and skin rash and conjunctivitis that normally final for two to seven days, in step with the sector fitness agency.

Its affiliation with microcephaly and Guillain-Barré syndrome, a situation wherein the frame's immune machine assaults a part of the anxious device, has expanded alarm over Zika. Researchers are working to affirm that the virus reasons those conditions.

Brazil's government may additionally determine to revise a law subsequent week that restricts the united states's capacity to send scientific samples overseas, and does now not actually define protocol when a public fitness emergency, like Zika, is involved.

two authorities sources said the choice would be made at a meeting next Wednesday between the fitness, technological know-how and era ministries as well as President Dilma Rousseff's leader of personnel.

Brazil's fitness ministry said it have been collaborating with the U.S. centers for ailment manage and Prevention to attempt to nail down whether Zika reasons Guillain-Barré. Of medical samples amassed in Salvador, in northeast Brazil, one 1/3 will stay in Brazil and the relaxation will visit the united states for studies, the ministry said.

Athletes weigh gold lust towards Zika fitness fears

As international health chiefs attempt to convey a Zika virus epidemic below manipulate, aspiring Olympic athletes are weighing their lust for gold in opposition to health fears surrounding the mosquito-borne virus in Brazil.

Alarm has grown because the international health organisation (WHO) on Monday declared Zika an international health emergency that would infect as many as four million humans within the Americas.

Zika is carried with the aid of mosquitoes, which transmit the virus to human beings, at the same time as two cases inside the u.s.a. advise it could also be transmitted sexually.

The signs and symptoms, which can encompass fever and skin rash, are normally moderate. but health officers are maximum concerned via its ability hyperlink to microcephaly, a birth illness wherein infants are born with abnormally small heads and underdeveloped brains.

although the hyperlink hasn't been proven yet, some athletes are rethinking their plans for the Rio Olympics, which get underway on Aug.five. Many others say they will take precautions however might not allow a low risk of contamination blur their attention.

"The way I see it, it is better to die for an Olympic gold than be scared and sit down at home," Indian taking pictures train Ronak Pandit advised Reuters in a cellphone call from his Mumbai domestic.

Pandit, a former shooter, now coaches his dentist spouse Heena Sidhu, who closing month earned her Rio location in air pistol taking pictures.

"The concept would be not to get bitten with the aid of mosquitoes," she stated. "Use mosquito repellent or nets, exit simplest in complete-sleeve garments, that sort of issue. i'm not changing my preparation. i am no longer genuinely thinking about it."

Danish sailor Anne Marie Rindom is likewise unperturbed. "i will just buy a few in reality strong insect repellent," she stated. "it is how plenty I’ve concept approximately it. I’m no longer concerned about it."

plenty are worried, although.

"From what i've seen and heard, in case you are a pregnant woman it's miles very dangerous," U.S. sprinter Justin Gatlin instructed Reuters.

Gatlin, an Olympic and world Champion sprinter, stated

he would probable keep away from Brazil beforehand of the games but the lure of the Olympics themselves might probably show too sturdy.

"At this point in time, if I had to take the risk approximately the virus, i am going to take it," he stated. "i am seeking to seize my victory and my glory on the Olympics. optimistically the Zika virus can be extra contained with the aid of August."

danger DEBATE

Pre-Olympic trials are scheduled in Rio in advance of the August video games and the IOC says the games will take area throughout the iciness months whilst a drier, cooler weather reduces the presence of mosquitoes and chance of contamination.

Scientists say that growing a vaccine for Zika may want to take years and, at the same time as the IOC says there have been no discussions about cancelling or suspending the video games, a few health workers say this is exactly what have to occur.

"The Rio games ought to be deferred," Arthur Caplan, Director of the medical Ethics software on the new york university scientific middle, advised Reuters.

"The video games are important, however they may be games and that’s now not as critical as a first-rate fitness trouble," said Caplan, who has worked with WHO on ebola and pandemic flu ethics committees.

Brazil expects as many as 380,000 travelers to go to Rio in August and Caplan stated there was a risk a few should spread the virus to new regions when they return to domestic.

but Chris Barker, a expert in mosquito-borne ailments, told Reuters it changed into too early to make any decision to cancel the video games. professionals could not appropriately expect the Zika scenario in six months' time even as the seasonal factors and Rio's dedication to intensive mosquito manage meant tourists' risk of contracting Zika was "possibly very low."

though, he stated 'at risk categories' must be prudent: "If I were a women who became pregnant or may end up pregnant i might no longer tour to the games," Barker said.

medical evidence

Brazil is investigating Zika's viable links to extra than 4,000 suspected instances of microcephaly amongst newborns.

Researchers have diagnosed proof of Zika infection in at the least 17 of those cases, either inside the child or inside the mom, however have not showed a causal link to Zika.

Researchers in northeastern Pernambuco kingdom said on Wednesday that they found Zika antibodies in 12 babies with microcephaly. Barker stated that advised that further research become more likely to verify the Zika hyperlink to microcephaly.

a few sports federations say their athletes are but to specific any fears and they agree with the organizers.

"We had our check event in Rio days ago and everybody got here lower back safe and alive," United global Wrestling president Nenad Lalovic instructed Reuters.

"there's large difficulty... however I do no longer suppose it's miles as serious as it's miles supplied. we will be there within the wintry weather and that gives us an advantage. in the past we had such a lot of threats of epidemics, hen flu, chook flu and not anything took place."

global swimming federation FINA government Director Cornel Marculescu told Reuters no concerns have been voiced through countrywide swimming federations.

British rower Andrew Triggs Hodge is taking action, however.

A gold medalist in Beijing in 2008 and London 4 years later, the 36-yr-old goes for a hat-trick of golds in Rio, but he might be alone after he and his wife Eeke determined she might stay at home.

"For anybody who wishes a circle of relatives, Zika is a totally real and horrifying risk," he informed Britain's times newspaper. He said a few research recommended girls inflamed with Zika ought to wait two years before attempting for children.

"it is now not a fee well worth paying," he stated. "i've been asking approximately mosquito nets, but if you're there for seven days you're going to get bitten."

CDC widens Zika virus guidelines for pregnant ladies

The U.S. facilities for ailment control and Prevention on Friday revised its hints for pregnant girls to encompass a advice that even the ones without signs of the Zika virus ought to be tested after returning from affected areas.

The updated suggestions recommend pregnant girls be offered testing  to 12 weeks after returning from places where the virus has inflamed human beings. earlier, the enterprise suggested exams for the ones already experiencing signs and symptoms.

Obstetricians have stated that in view that eighty percent of these inflamed by means of the virus display no signs and symptoms, it leaves many pregnant ladies no manner of knowing early enough to make an knowledgeable choice approximately their unborn child.

although sexual transmission of Zika virus is viable, mosquito bites remain the primary manner it's miles transmitted, the CDC said. It recommended that pregnant women and their male partners must talk any capability exposure with the aid of the male to Zika, or a history of Zika-like contamination, with their doctor.

men with a pregnant associate who stay in or have traveled to an area of active Zika transmission and their companion have to continually and correctly use condoms for the duration of intercourse or abstain at some stage in the pregnancy, the CDC stated. If the person lives in or has traveled to an active Zika place the couple might also remember the usage of condoms or abstaining from intercourse.

"The technological know-how isn't always clear on how lengthy the threat have to be prevented," the CDC said. "studies is now underway to answer this question as soon as feasible."

there's no vaccine or remedy for Zika, which has prompted outbreaks in at least 26 international locations in the Americas.

Brazil is investigating more than four,000 suspected cases of microcephaly, a situation marked by means of abnormally small head size that could reason everlasting mind damage in newborns, that can be connected to Zika.

The suspected hyperlink appears "stronger and stronger" as researchers look at whether there may be a causal connection, the director of the CDC stated on Friday.

It additionally issued new guidelines for each pregnant ladies and girls of reproductive age who stay in affected regions. Pregnant ladies experiencing signs must be straight away tested, and people not, are advocated to once they start prenatal care.

Dallas County suggested on Tuesday that the first acknowledged case of Zika contracted inside the usa become someone inflamed after having sex with someone who had again from Venezuela.

FDA rejects elevated use of Vertex's cystic fibrosis drug

The U.S. food and Drug management has denied the elevated use of Vertex Pharmaceutical Inc's bestseller, Kalydeco, in sure cystic fibrosis sufferers, the agency stated on Friday.

The regulator rejected the employer's utility for the usage of the drug in cystic fibrosis sufferers aged 2 or older, who have one in all 23 residual characteristic mutations.

The enterprise's shares fell 7.7 pct to $nine.60 in premarket buying and selling.

Cystic fibrosis is caused by a faulty gene that disrupts the function of the lungs and digestive device, generating a build-up of thick, sticky mucus leading to inflammation and recurrent bacterial infections. half of the humans with cystic fibrosis live longer than 28 years, consistent with the world health agency.

Emotional misery tied to weapon use for teens

despite the fact that a extensive variety of social and monetary factors might also influence whether or not teens get involved with guns, two matters appear to growth the chances for white, black and Hispanic teenagers alike – emotional misery and substance abuse – a current U.S. examine shows.

earlier involvement with guns is also tied to better future odds of sporting or using a gun or knife for teens in all three agencies, the take a look at found.

amongst teenagers that carried weapons, 17 percent had shot or stabbed someone in the past yr, the analysis of survey records additionally discovered.

“primarily based on information from our study, most of the people of teenagers who bring weapons had no longer shot or stabbed everybody,” said lead creator Dr. Rashmi Shetgiri of the la Biomedical research Institute at Harbor-UCLA medical center.

“Weapon sporting and weapon use are correlated with each other, so it is not surprising that a proportion of youngsters who carried guns also had used weapons,” Shetgiri brought with the aid of e-mail.

At a time whilst almost thirteen percentage of U.S. high school students record being victimized by weapons, Shetgiri and colleagues took a observe data from the Nineties whilst this wasn’t so common and searched for clues that could give an explanation for what elements ought to motivate youngsters to these days to reach for weapons and knives.

Researchers analyzed responses from national surveys of 20,745 students in grades 7 via 12 and 17,670 in their mother and father executed in 1994 and 1995, as well as observe-up surveys with 14,738 of the youngster members completed in 1996. The teenager interviews had been approximately three hundred and sixty five days apart.

roughly 13 percentage of black, 10 percent of Hispanic and seven percentage of white excessive faculty students said they were concerned with guns.

compared to youth who didn’t use guns on the begin of the have a look at, white teenagers that did have been 5 times more likely to additionally accomplish that at the time of the second one interview, the survey located. Black teens had more than four instances the chances of the usage of weapons on the quit in the event that they did so on the begin, at the same time as for Hispanic young people the probabilities had been more than six times higher.

Violence exposure, alcohol use and peer delinquency have been risk elements for white and black teens using guns. It’s feasible that among young adults uncovered to violence, weapon carrying may be in self-protection or a reaction to fear of violence, the authors word.

Gun availability in the domestic turned into a issue related most effective with weapons involvement for black young adults, the examine additionally located.

high academic aspirations, but, have been associated with a decreased hazard of weapons involvement for each black and Hispanic teens, and more potent family connections turned into additionally a deterrent for Hispanic teens.

One dilemma of the take a look at is that data dates again  many years, the authors note in the magazine of Pediatrics. additionally they lacked records on children who were no longer attending college or who had been incarcerated, which would possibly downplay weapons use.

on the other hand, the findings propose that techniques to reduce teenager weapon violence may cognizance on some common elements including intellectual fitness and substance abuse, in addition to sure individuals which can range with the aid of race or ethnicity, the authors advocate. 

“understanding which businesses are victimized or who have sure high threat behaviors can assist healthcare providers and public health systems assume social assist and schooling desires,” Dr. Denise Dowd, a researcher at kids’s Mercy health facility in Kansas metropolis who wasn’t worried in the examine said through electronic mail.

The high-quality method also depends on what issue is maximum urgent to clear up, mentioned Kimberly Mitchell, a researcher at the Crimes in opposition to kids research middle at the university of new Hampshire who wasn’t concerned within the examine.

“If the instantaneous and main concern is carrying the weapon, steps like metallic detectors and police presence may be the approach,” Mitchell stated by means of electronic mail.

“considering the fact that sporting and using a weapon hardly ever takes place in isolation … we regularly recommend a broader approach to prevention which includes socio-emotional learning programs which intention to help humans recognize and manage emotions, set and obtain high-quality dreams, fell and show empathy for others, establish and maintain wonderful relationships, and make responsible decisions,” Mitchell delivered.

Eating soy might also defend against reproductive results of BPA

eating soy ingredients can also assist guard in opposition to reproductive results of bisphenol A (BPA), a chemical in many plastic purchaser products and lining the interior of some canned foods, in step with a have a look at of women undergoing fertility remedies.

“The effects have been virtually precisely what we have been looking ahead to to locate,” said lead creator Dr. Jorge E. Chavarro of the Harvard school of Public fitness-nutrients in Boston.

BPA is thought to imitate estrogen inside the body, and consequently it’s believed to disrupt idea and implantation of a fertilized egg inside the womb, the researchers write in the journal of clinical Endocrinology and Metabolism.

Experiments in rodents propose that soy, which additionally interacts with estrogen receptors, may want to offset or mitigate those outcomes of BPA, they upload.

“We wanted to comply with-up on the consequences of  experimental models in rodents where two impartial groups had found that a few negative reproductive outcomes of BPA may be averted with the aid of setting the mice on a soy based totally eating regimen,” Chavarro advised Reuters health by using email. “We desired to see whether or not a comparable interplay happened in human beings.”

The researchers studied 239 girls who underwent in vitro fertilization cycles between 2007 and 2012. The women finished nutritional questionnaires and furnished urine samples earlier than egg retrieval for every fertility cycle.

The questionnaire included assessment of the girls’s consumption of 15 soy-based meals, inclusive of tofu, soy burgers, miso soup, soy protein and soy bars. intake of these gadgets ranged from never or less than once per month to twice daily.

nearly 3 quarters of the ladies said they ate up as a minimum some soy ingredients.

maximum women underwent one IVF cycle, 18 percentage underwent  cycles and 11 percentage underwent 3 cycles.

As urinary BPA degrees multiplied, the girls who did now not consume soy ingredients had lower quotes of implantation, clinical pregnancy and stay birth. but for ladies who did consume soy, growing BPA degrees have been no longer tied to fertility effects.

“We still want to evaluate whether or not the equal is likewise true for couples looking to get pregnant without clinical help or whether or not risks expand to the health of kids,” Chavarro said.

In one of the preceding mice research, BPA became capable of activate and rancid certain genes and soy averted BPA from doing so, Chavarro stated.

“We can not be positive whether this is the same mechanism operating in our case or whether different mechanisms but to be diagnosed may also be at play,” he said.

BPA is secure inside the modern-day ranges occurring in foods, in keeping with the U.S. food and Drug administration.

“based totally on nationally representative surveys we understand that more than ninety percent of american citizens are uncovered at varying stages,” but publicity to BPA may be minimized by switching from ingesting canned ingredients to their sparkling or frozen opposite numbers, replacing tough polycarbonate plastic food packing containers with glass or metal containers, and no longer handling thermal receipts together with the ones utilized in supermarkets, ATMs and gasoline stations, Chavarro stated.

it's miles crucial to affirm those findings, since that is the primary time that an interaction among BPA and weight loss plan has been stated in human beings, he stated.

however soy on its personal, regardless of whether or not or now not it interacts with weight loss program, appears to be useful to women who're looking to grow to be pregnant, he stated.

Condom makers step as much as help with Zika effort

Condom makers including Ansell Ltd are presenting to assist Zika-affected countries after the primary case of the virus being sexually transmitted introduced to growing concerns over the spread of the disease.

The virus, that is spreading quickly across the Americas, is generally transmitted by way of mosquitoes. but, the first recognised case reduced in size within the u.s.a. was someone infected after having intercourse with a person who had returned from Venezuela.

international fitness agency (WHO) spokesman Gregory Hartl careworn that "almost a one hundred percentage of the cases" are transmitted via the bite of a mosquito.

however, the possibility of Zika being sexually transmitted adds a brand new size to the hazard the sickness poses.

"Ansell might be approaching local associations in Brazil and different countries to offer its assistance and know-how in assuaging this principal public fitness issue," Jeyan Heper, president and general supervisor of the Australian enterprise's sexual well being international commercial enterprise unit told Reuters in an electronic mail.

Ansell, which makes Skyn and existence condoms in addition to commercial and surgical gloves, stated it supplied almost 1 million surgical gloves to combat the Ebola outbreak in West Africa in 2014.

lady fitness Co, which makes condoms for girls, stated it has been in touch with numerous health companies, consisting of the U.S. facilities for sickness manipulate and Prevention and the WHO, and has visible a growing number of enquiries.

"we are running with the nearby health ministers at those countries to assist offer the product that they may either be dispensing or recommending to the general public," Michele Greco, chief monetary officer of the U.S.-based organisation instructed Reuters.

Trojan condom maker Church & Dwight Co Inc stated it has been in contact with various public fitness agencies for regular fame updates and that it might maintain to screen the situation intently to determine suitable subsequent steps.

The WHO stated as a minimum 26 international locations in the Americas have a Zika outbreak, and countries which includes ireland, Australia and Canada have mentioned instances of vacationers testing nice for the virus after visiting an inflamed area.

agencies ranging from vaccine builders to mosquito repellant makers have come below the highlight after the outbreak, as they work with government companies to fight the growing hazard.

Supernus beats Allergan over epilepsy drug patents

A federal decide on Friday stated Allergan %'s deliberate time-honored model of a drug supposed to deal with epilepsy infringed patents belonging to Supernus pharmaceuticals Inc.

stocks of Supernus soared as tons as forty four percent after the selection was issued. They closed up $2.00, or 19.7 percent, at $12.13 on the Nasdaq.

Supernus sells Oxtellar XR, a as soon as-a-day tablet used to deal with partial epilepsy seizures in adults and youngsters over the age of six, and sued the previous Actavis Inc to stop it from selling a time-honored version.

Actavis, now called Allergan, had filed with U.S. regulators to promote its established in March 2013, much less than  months after Oxtellar XR become released. It maintained at the time that Supernus' patents had been invalid, court papers show.

however in a 136-page selection, U.S. District decide Renée Marie Bumb in Camden, New Jersey stated Allergan's proposed typical infringed  of the 3 Supernus patents in query. She also said all the patents have been legitimate.

The choose ruled after a seven-day non-jury trial that resulted in early December.

A U.S.-based spokesman for Allergan did now not without delay reply to requests for remark. The agency is based in Dublin, ireland.

Oxtellar XR is one among two epilepsy merchandise that Supernus sells, and which together account for most of the Rockville, Maryland-based business enterprise's sales, regulatory filings display.

Epilepsy can not be cured but can be managed with treatment.

Accidents at work may additionally increase danger of losing one’s task

even though employee protections are speculated to save you it, a brand new U.S. examine of nursing home employees unearths that within six months of an injury, employees are more likely to lose their jobs.

in comparison to colleagues reporting no injuries, employees who had been hurt were greater than twice as in all likelihood to be fired in the next six months.

“The outcomes demonstrate better risk of being fired but we do not have information to mention why exactly workers are being fired. we are able to only say that their dangers are higher,” said lead writer Cassandra Okechukwu of the Harvard T. H. Chan college of Public fitness in Boston.

people who had been injured multiple times were also two times as probable to stop their jobs in the next six months as colleagues and not using a accidents, the examine discovered.

In popular, employees are most probable to be injured for the duration of the first few months in a brand new work environment, the have a look at crew notes in Occupational and Environmental medicine. So this activity turnover increases the possibilities an injured employee could be injured again in a brand new administrative center.

The effects also indicate that federal and kingdom-level rules, which can be imagined to defend workers from being fired after accidents and to present people reimbursement and enough time to get over an harm, may not always be observed.

The researchers used facts from a look at accomplished with the aid of the paintings, family and health community concerning direct care employees from 30 nursing houses throughout New England. Its unique aim was to take a look at workplace regulations intended to improve people’ health, safety, and wellness, Okechukwu cited in an email.

For the harm examine, Okechukwu’s team analyzed information on 1,331 nursing domestic employees who finished 4 interviews - at the begin of the look at, after six months, at 365 days and finally after 18 months had handed.

At each interview, contributors suggested whether or not they had been injured at work within the beyond six months and how typically. nine in 10 of the contributors have been girls and extra than two thirds have been certified nursing assistants.

The examine group extensively utilized administrative information from the nursing houses to decide which employees lost their jobs and whether they have been fired or chose to depart.

After twelve months, 30 percentage of employees had been injured at work and about a quarter were no longer hired at that activity after 18 months.

compared with those who had been now not injured, injured employees had been 30 percentage much more likely to now not be in their jobs within six months of the damage, whether voluntarily or involuntarily.

people who had been injured extra than once have been more likely to choose to go away their jobs than human beings with out a injuries, even as humans injured only as soon as were much more likely to be fired.

Peter Smith, a researcher at the Institute for paintings and fitness at the college of Toronto said it's far enormous that the look at looked at ordinarily women employees.

“The previous research does advise that the impact of a work harm on activity loss is probably more mentioned for girls than it is for guys,” said Smith, adding that it is also crucial to look at why ladies are much more likely to lose their jobs.

employees can be fired due to the fact their employers sense they can now not perform the process responsibilities, or due to issues that they may be injured once more, said Smith, who wasn’t worried within the have a look at.

He stated that people may additionally pick out to depart their jobs for worry of being injured. “In some situations an company won't have installed region protections to lessen an harm occurring again, together with removing the dangers that result in the harm,” he said with the aid of e mail.

“whilst these situations should no longer be going on in the modern people’ compensation legislation, we do understand that they sometimes do occur, notwithstanding the legislation in area,” Smith said.

“paintings isn't always supposed to result in injury,” Smith said, and employers have to provide workers sources to defend their health and income. “Measures need to be put in place to make sure that employers do no longer hearth or area people because they have got had a piece-related harm,” he stated.

Kansas confirms one norovirus case associated with Buffalo Wild Wings

One superb case of norovirus associated with an research at eating place chain operator Buffalo Wild Wings Inc has been confirmed, the Kansas fitness department's Johnson County workplace stated on Friday.

Buffalo Wild Wings' shares fell as much as 13 percentage to a 15-month low on Friday, earlier than easing returned to shut down 8 percentage at $142.08.

The research is associated with a gastrointestinal contamination that affected as a minimum 10 those who ate at a Buffalo Wild Wings' eating place in Overland Park in suburban Kansas town.

"these kinds of infection are common this time of yr," Johnson County department of health and environment Director Lougene Marsh stated in a announcement. (bit.ly/1PZUvOv)

Norovirus is the most commonplace purpose of meals-borne disorder outbreaks inside the usa and infections usually happens in locations inclusive of hospitals, cruise ships and universities, where humans eat and stay in near quarters.

There had been no in addition reviews of illnesses and extra results on the prevailing cases are pending lab affirmation, the branch stated.

Buffalo Wild Wings, whose retailers are acknowledged for his or her fowl wings, stated no matter the only advantageous take a look at, there has been no affirmation that its Overland Park eating place become the source.

The company voluntarily closed the eating place for cleansing after it learnt of the illnesses and reopened it tomorrow after consulting the health branch, a enterprise spokesman said in an e mail.

"we are monitoring the situation and will hold to paintings closely with the fitness branch till their investigation is whole," the spokesman said.

closing year, two norovirus outbreaks had been suggested on the Massachusetts and California outlets of popular burrito chain operator Chipotle Mexican Grill Inc.

about 19 million to 21 million norovirus cases, with 570 to 800 related deaths are mentioned within the u.s. every 12 months, in line with the U.S. centers for ailment manage and Prevention.

Hyperlink among Zika, microcephaly appears "more potent and more potent"

The suspected hyperlink between the Zika virus and a delivery disorder referred to as microcephaly seems "more potent and more potent" as researchers study whether there is a causal connection, the top of the U.S. facilities for disease manipulate and Prevention stated on Friday.

Scientists are looking to set up whether or not contamination with the Zika virus during pregnancy causes microcephaly, in which toddlers are born with abnormally small heads and an underdeveloped mind. Dr. Tom Frieden, director of the CDC, said the business enterprise is likewise running with researchers in Brazil to study a potential hyperlink among Zika and a much wider array of developmental disorders in babies.

FDA body of workers backs biosimilar to Remicade

U.S. meals and Drug management group of workers contributors on Friday stated Celltrion Inc's biosimilar shape of Johnson & Johnson's Remicade arthritis drug appeared "tremendously comparable" to the extensively used branded product.

The information despatched stocks of J&J, whose annual Remicade income of $6.5 billion are on the whole in the america, down almost 4 percent. It also hit AbbVie Inc and Amgen Inc, whose arthritis remedies paintings the same way.

AbbVie, whose Humira is the world's top-selling drug, fell almost 6 percentage, and Amgen, maker of Enbrel, became down 3 percent. Pfizer Inc, which has teamed up with South Korea's Celltrion in marketing the biosimilar, rose nearly 1 percentage.

FDA scientists launched their favorable document ahead of a meeting Tuesday of an impartial clinical advisory panel to the enterprise. The panel will determine whether or not to suggest approval of Remsima to treat rheumatoid arthritis and inflammatory bowel conditions like Crohn's disorder.

Celltrion and Pfizer want to sell Remsima within the u.s. as a cut-charge copy of Remicade, or infliximab. some analysts anticipate it to sell for a 25 percentage cut price.

"The facts submitted via Celltrion display that (Remsima) is especially similar to U.S.-certified Remicade" in treating rheumatoid arthritis and a related situation referred to as ankylosing spondylitis, the FDA briefing paper stated. It referred to only "minor differences in clinically inactive additives."

Celltrion supplied the FDA with medical records on using Remsima against rheumatoid arthritis and ankylosing spondylitis, but the FDA's team of workers stated it's miles likely additionally secure and effective for other situations Remicade treats, inclusive of Crohn's and ulcerative colitis.

Raymond James analyst Chris Raymond stated that large interpretation of Remsima's likely effectiveness should signal its approval as a remedy for all illnesses for which Remicade can now be marketed.

"As such, we continue to be cautious on Amgen shares," Raymond stated.

Morningstar analyst Damien Conover said Remsima and another Remicade biosimilar can be brought inside the usa in 2018. The branded J&J drug could lose half of its sales through 2020, he added.

"the largest capacity harm could be to J&J, which has U.S. rights to Remicade," said Conover. He anticipated Pfizer would seize approximately $500 million in annual Remsima sales.

The FDA record did not harm stocks of Merck & Co, which sells Remicade remote places. however the inventory slumped Wednesday after the enterprise stated biosimilar opposition in Europe helped drive its fourth-sector sales of Remicade down nearly 30 percent to $396 million.

Celltrion already sells Remsima in dozens of other countries.

Remicade, Humira and Enbrel paintings with the aid of blocking an infection-inflicting protein referred to as Tumor Necrosis element (TNF). Raymond said greater than 60 different anti-TNF biosimilars are in improvement and will commoditize the drug elegance a great deal sooner than thought.

Remsima might become the second one accredited biosimilar in the united states of america, following Novartis AG's September introduction of Zarzio. That drug is a model of Amgen's Neulasta, which reinforces infection-combating white blood cells in patients who've gone through chemotherapy.

Obama budget to regulate insurance 'Cadillac tax': consultant

President Barack Obama can propose trade the arguable "Cadillac tax" on high-priced non-public insurance set ups to replicate regional variations once he releases his 2017 budget plan next week, a senior White House consultant aforementioned in a piece free on Wed.

Obama's proposal would scale back the bite of the less-traveled tax by raising the edge wherever it takes impact in areas wherever tending is especially high-priced, in keeping with the article within the geographic region Journal of drugs co-written by Jason Furman, chairman of the White House Council of Economic Advisers. (bit.ly/1QdGlDG)

The tax on high-cost employer-based tending plans, passed as a part of the president's 2010 reasonable Care Act and set to require impact in 2018, has generated growing opposition partially as a result of labor unions say it may encourage employers to chop back on insurance plans for staff.

The tax was expected to boost some $87 billion a year to assist get hold of the reform typically referred to as Obamacare.

U.S. Navy examining rise in health problems among F/A-18 pilots

The U.S. Navy is investigation an increase in health problems reportable since 2009 by pilots of Boeing Co F/A-18 and EA-18G fighter jets, that will be associated with scant gas or different factors, a key U.S. leader aforementioned Thursday.

Representative Michael Turner, chairman of the House Armed Services committee on plan of action Air and Land Forces, aforementioned pilots had to report any episodes within which they old "a loss in performance associated with scant gas, depressurization or different factors gift throughout flight."

Turner aforementioned the Navy had created a special team to analyze the incidents and confirm the foundation cause, however it might be a fancy method since symptoms associated with depressurization, tissue drive and contamination intoxication usually overlapped.

"We perceive that decisive the foundation cause or causes of physiological episodes in F/A-18 craft could be a add progress," Turner aforementioned at the beginning of a hearing on military service strike fighters.