The latter often triggers a partisan split within Congress, including those with the F159S mutation.K. says company scientists were rightfully included in the papers they helped produce The Bahia results helped Oxitec win approval from Brazil’s National Technical Commission for Biosecurity to release mosquitoes commercially They also impressed Pedro Mello Piracicaba’s health secretary Mello’s office on the eighth floor of a municipal building overlooks a prosperous downtown area of red tile roofs and a new Oxitec billboard: "The friendly mosquitoes are arriving in the central Piracicaba district" As he explains the project Mello scribbles figures on printer paper and punctuates his points with underlines then hastily crumples the sheets This is no academic collaboration; Mello’s department is investing in a potential solution to the city’s mosquito problem Because Oxitec doesn’t have market clearance from Brazil’s National Health Surveillance Agency yet the city’s payments are classified as a "contribution" to the project Releases began in CECAP last year and are now expanding to 10 downtown neighborhoods encompassing 12 km2 with nearly 60000 residents To make that possible Oxitec is setting up a new facility just outside town where it hopes to produce about 30 million mosquitoes a week by this fall then scale up to 60 million—30 times the current production at its Campinas site That’s far beyond what Oxitec needs for Piracicaba says Glen Slade director of the company’s Brazilian subsidiary in Campinas Slade says he is in "advanced discussions" with other municipalities The goal here is not to kill mosquitoes It’s to prevent people from getting infected and sick and dying Thomas Scott epidemiologist and insect ecologist University of California Davis If Oxitec’s mosquitoes are on a suicide mission Eliminate Dengue’s are missionaries designed not to wipe out wild mosquito populations but to transform them On a drizzly morning in the Niterói favela of Jurujuba the research team spreads out across hillsides of crumbling concrete to restock egg release containers which about 130 households here have agreed to host The white plastic tubs are hidden like oversized Easter eggs—under stairwells beside doorsteps in an alcove behind a pile of plywood and old bicycle parts The adults that escape from the tubs carry Wolbachia a parasite thought to occur naturally in about 60% of all insect species It wasn’t until 2005 that researchers coaxed the bacterium to take up residence in A aegypti Then the co-founder of Eliminate Dengue medical entomologist Scott O’Neill at Monash University in Melbourne Australia discovered that Wolbachia-infected mosquitoes fed blood spiked with dengue or chikungunya were much less likely to test positive for the virus (and to transmit it) than controls Earlier this year researchers from the Oswaldo Cruz Foundation (Fiocruz) the national public health institute that collaborates with Eliminate Dengue in Brazil reported similar results with Zika Researchers suspect that the parasite competes with the virus for limited resources inside mosquito cells; Wolbachia may also activate its host’s immune system helping it fight subsequent infections Because Wolbachia is only passed to offspring through eggs spreading it requires the release of females which can bite But because of the bacterium the females pose no transmission risk O’Neill says Eliminate Dengue has released mosquitoes in more than 40 areas in Australia Vietnam Indonesia Colombia and Brazil funded largely by grants from the Bill & Melinda Gates Foundation Studies showed that the parasite can spread to the point of "fixation" over the course of 10 to 20 weeks and remain in the population for at least 5 years Eliminate Dengue aims to make a permanent change to a mosquito population and move on—a key difference from Oxitec’s solution which would have to be applied year after year lest the population rebound But both approaches have only local effects; Wolbachia does not spread much beyond the area where it’s unleashed Brazil is one of several countries where Eliminate Dengue is testing a scale-up of releases in urban areas It has presented unexpected challenges A few weeks after the first release Fiocruz’s Luciano Moreira saw a drop in the percentage of Wolbachia-infected mosquitoes It turned out that the lab strain which had never been exposed to insecticides was so much less resistant to them than wild mosquitoes that it couldn’t compete in the heavily sprayed release area The team spent 3 months crossing lab mosquitoes with wild ones—actually driving up their resistance—until they matched the hearty natives Another complication: Certain neighborhoods that might host future releases are dominated by the drug trade Visiting one of them in Niterói felt "like something out of a science fiction movie" O’Neill says "We had to wind our windows down so that people could see us in the car as we drove in There was a horse with a big gash down its side that was being used for transport and bullet holes in all of the walls at ground level" he says "If we are able to successfully deploy [the project] there I think we can deploy it just about anywhere in the world" Technicians separate male from female mosquito larvae in Oxitec’s Brazilian production facility Paulo Freidman The looming question for both projects is simple: Do these disease-fighting mosquitoes actually reduce disease "The goal here is not to kill mosquitoes It’s to prevent people from getting infected and sick and dying" says Thomas Scott an epidemiologist and insect ecologist at the University of California Davis So far there’s no proof that either approach does that It may seem intuitive that fewer infectious mosquitoes mean fewer infections but just a few A aegypti may be enough to transmit disease through a susceptible population Scott says In July Oxitec published numbers showing that dengue cases in CECAP dropped 91% over the previous year—from 133 to 12 The rest of the municipality saw only a 52% reduction But Scott notes that dengue outbreaks are episodic: "You can have an epidemic in one town and no transmission in the one next door and the next year it can be flipped" The last word on efficacy would come from trials that monitor disease in residents of neighborhoods randomized to receive mosquitoes or act as controls These two groups are inherently leaky because people are mobile; that means such studies have to be large—and costly—to be meaningful In March a World Health Organization working group chaired by Scott deemed both Oxitec’s and Eliminate Dengue’s strategies worthy of "carefully planned pilot development" but called for large epidemiological studies Eliminate Dengue already has an efficacy study underway in Yogyakarta Indonesia which will track disease rates in 24 areas of about 14500 people each half of which will receive Wolbachia mosquitoes A network of clinics across the city is testing continuously for dengue over 2 years An even larger study is being planned in Vietnam Oxitec meanwhile is enlisting independent experts to design a trial tentatively slated for 2018 Over the long term both kinds of modified mosquito could lose their edge because evolutionary pressure could select for resistance to either Oxitec’s lethal gene or Wolbachia’s virus-fighting powers Everything you do in the public sector has risks But I still think the biggest risk is to let people die without giving them any kind of alternatives Pedro Mello Piracicaba’s health secretary Even if either type of mosquito—or both—proves a success there’s still the issue of the cost Not every community in Brazil will likely be able to afford mosquitoes which raises new questions says Fred Gould an insect geneticist at North Carolina State University in Raleigh "There’s a whole issue of justice: Who gets these mosquitoes and who doesn’t Who gets Zika and who doesn’t" The Fiocruz facility makes about 40000 Wolbachia-infected mosquitoes a week to supply roughly 300 release containers but a new facility will have a capacity of about 12 million a week Eliminate Dengue was not able to provide an estimate of current costs in Brazil but aims to bring them down to $1 per person or less Oxitec’s mosquitoes are currently more expensive The Piracicaba expansion will cost the city roughly $11 million over 2 years—some $10 per person in the treated area—about half of which will come out of the existing mosquito control budget Oxitec itself is paying even more than that says Slade but it’s too early to tell how much the mosquitoes will cost if they are reared on a much larger scale "It’s only when you roll up your sleeves and build a factory that you know what your costs are" Oxitec’s plan to sell the mosquitoes before the epidemiological evidence is in troubles some scientists "They’re good salesmen—that’s the bottom line" says population geneticist Jeffrey Powell of Yale University "They go out and they talk to the people in various countries saying ‘We’ve got this magic bullet’" And the need for continuous mosquito releases is a serious economic downside adds molecular entomologist Marcelo Jacobs-Lorena of Johns Hopkins University in Baltimore Maryland "It is a forever proposal" he says "That may be good for the company but maybe not so good for the overall control efforts" For Slade the dramatic population reductions already show that Oxitec’s approach works far better than pesticides which are also a "forever proposal" "I personally don’t accept that without [an epidemiology study] we don’t have the evidence that this is the best tool" he says Community members observe Wolbachia-infected mosquitoes in Eliminate Dengue’s Brazilian laboratory Peter Ilicciev/Fiocruz Eventually other alternatives will hatch In Margareth Capurro’s So Paulo lab larvae from new transgenic strains line the shelves She like a handful of other researchers is betting on so-called gene drives which bias the inheritance of a particular gene to quickly and irreversibly spread it through the population Capurro is working on a gene allowing mosquito cells to recognize an enzyme produced by the dengue virus and release a self-destruct signal Such strategies may be more difficult to get approved because they would make an entire wild population transgenic Oxitec’s transgenic males and their offspring die within days which has gone a long way to appease GM-wary regulators says entomologist Zach Adelman of Texas A&M University College Station In the long run Adelman and Capurro envision a time when public health departments can shop for a strain of disease-fighting mosquito that makes the most sense for them Some may want an inexpensive option that doesn’t require indefinite releases for instance whereas residents in some areas may be uncomfortable with biting females Some may want to combine approaches—knocking the population down before introducing a new gene "You’ll have a market rather than one game in town" Adelman says Piracicaba does not want to wait for that market—or even for more definitive evidence that Oxitec’s mosquitoes work Being the first city in Brazil to pay for an experimental disease-fighting mosquito was a calculated risk Mello says "Everything you do in the public sector has risks" he says "But I still think the biggest risk is to let people die without giving them any kind of alternatives" Bice says the finding demonstrates the need to consider river systems, who headed Google’s China operations before the company left in 2010. The brain stimulation treatments were originally designed to treat depression by boosting feelings of happiness and engagement.

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