first_imgThe Irish Wildlife Trust has announced that their smooth newt survey will be running again in 2012 and are calling on people across Donegal to once again get out and search their local pond for newts!The smooth newt is one of our few native amphibian species and this survey aims to increase our knowledge of the distribution of the species.We also hope to make Irish people more familiar with this little ‘water dragon’, so that they will value it as part of our natural heritage. This year the group will be focussing our efforts in counties where we currently have few or no records, including county Donegal. A training day will be taking place on April 07th at Glenveagh National Park.If you would like to attend the training day, you must register with us. Members of the Irish Wildlife Trust and unwaged can attend the workshop for free. Places are limited so book early to avoid disappointment.To register as a surveyor or for more information contact Dr Daniel Buckley at newts@iwt.ie or on 0863691982 or check out our website www.iwt.ieThis project is funded by Dublin zoo and Fota Wildlife Park. Donegal training day location: Glenveagh National ParkDate: 07h AprilTime: 11:00am NOW SOME GOOD NEWTS! DONEGAL TO HOLD NEW WILDLIFE SURVEY was last modified: March 21st, 2012 by StephenShare this:Click to share on Facebook (Opens in new window)Click to share on Twitter (Opens in new window)Click to share on LinkedIn (Opens in new window)Click to share on Reddit (Opens in new window)Click to share on Pocket (Opens in new window)Click to share on Telegram (Opens in new window)Click to share on WhatsApp (Opens in new window)Click to share on Skype (Opens in new window)Click to print (Opens in new window) Tags:Irish Wildlife Surveynewtssurveylast_img read more

DEAL SNUBBED! Prem duo keeping tabs on Roma defender’s contract situation

first_imgKostas Manolas has put Arsenal and Chelsea on red alert by snubbing Roma’s latest contract offer.The defender was linked with a move away from the Italian capital in the summer after impressing last season.The Premier League duo were both keen on the Greece international, but they were priced out of a move in the end.Roma are now trying to tie the 25-year-old down to a new deal but, according to Calciomercato, he has rejected their latest offer.The Serie A side have offered a contract worth around £42,000-a-week, but he is holding out for a bigger increase on his current £34,000-a-week deal, which expires in the summer of 2019. Kostas Manolas: The 25-year-old could be set to leave the Italian capital 1last_img

10 Katyusha rockets explode in southern Lebanon

first_imgJERUSALEM Israel’s military said Hezbollah guerrillas fired at least 10 Katyusha rockets into southern Lebanon early Tuesday. None hit inside Israel and no injuries were reported. The rocket explosions reported by Israel came hours after the start of a U.N. cease-fire in Lebanon. The military said it has not responded to the rockets, which were fired over a two-hour period. Hezbollah, which frequently used the Katyusha rockets in its battle against Israel, has said it will attack Israeli forces in southern Lebanon despite the truce. The army would not comment on whether the rockets landed near Israeli forces there. The Katyushas has a range of just over 12 miles. AD Quality Auto 360p 720p 1080p Top articles1/5READ MOREWhy these photogenic dumplings are popping up in Los Angeles Israeli forces had launched an 11th-hour offensive just days before the cease-fire took place, partly to push Hezbollah behind the Litani River, some 18 miles from the Israeli border, and get Israeli towns out of the rockets’ range. Monday saw a tense calm emerge in Israel and Lebanon as Israel halted its offensive and airstrikes and Hezbollah stopped firing rockets into Israel However, Israeli forces killed six Hezbollah fighters in four separate skirmishes that illustrated the fragility of the truce that ended 34 days of fighting. 160Want local news?Sign up for the Localist and stay informed Something went wrong. Please try again.subscribeCongratulations! You’re all set!last_img read more

Leigh Griffiths: Celtic success hinges on Champions League qualification

first_img Leigh Griffiths Leigh Griffiths admits the success of Celtic’s entire campaign could hinge on Wednesday night’s “make or break” Champions League clash with Astana.After sweeping all domestic rivals aside last term, Brendan Rodgers’ outfit once again have aspirations of making their mark in Europe.They take on the Kazakhstan champions on Wednesday in the opening leg of their final qualifier, with a ticket for the group stages and a potential £30million windfall on the line.But Griffiths admits that, with the new season barely a month old, they are already facing a match that could define their year.He said: “It makes or breaks our season if we get to the Champions League.“Last year it set us up on a great platform. We knew it was a difficult group but having Champions League football back at Celtic Park after two disappointing years previously was massive for everybody involved.“If we can get back into the group it will put everyone on a real high. The fans will be shouting from the rooftops and it will make the start we’ve made to the season worthwhile.”Victory over Rosenborg in the previous round guaranteed that Rodgers’ treble winners would be playing in European fixtures until December at worst.All that remains to be settled against Astana is whether that is in the continent’s premier competition, or its poor relation the Europa League.But Griffiths was defiant when it was put to him by a Kazakh reporter that defeat to their opponents from Central Asia would be “catastrophic”.“I don’t think about losing,” he shot back. “We as a club don’t think about losing. I only think about the Champions League group stages. I don’t think about the Europa League.”Celtic head into the first leg boosted by having a packed dossier on Astana following their clash in the third qualifying round last year.But while Rodgers reckons the Kazakhs have not changed much, he says his side have developed a steelier edge in the 12 months since.“We played them last year and had two tough games which thankfully we got through,” said the Northern Irishman, who will still be without defenders Erik Sviatchenko, Dedryck Boyata and striker Moussa Dembele.“The style hasn’t changed so much. It’s the same coach, a lot of the same players and the game in which they play is quite direct.“They play up to the big striker who has good technique and has good mobility for a big striker. They then play off the wide player Patrick Twumasi who is very fast on the counter attack.“So that actual style of the game is pretty much the same.“But the European games we had last year helped us gain a resilience. It was interesting watching last season’s qualifiers back and in terms of how we played the game, what our idea of football was, it was nowhere near what it is now.“So what we have built up since then is that mental resilience.“We’re missing some key players but it’s not a computer game. It’s not Football Manager where if you lose one you can just pick one straight off the computer and put him straight in.“It’s much more difficult than that – but I have always put trust in the players I have.”Griffiths grabbed goals in both legs last year before Dembele’s late penalty saw the Hoops edge out Astana 3-2 on aggregate.With the Frenchman out injured, the responsibility for firing Celtic through now falls squarely on Griffiths’ shoulders.He has shaken off a calf injury to declare himself “fully fit and raring to go” but Rodgers has already admitted the uncertainty over his top two marksmen could see him bring in a third poacher.But the Scotland striker reckons there is enough firepower in the Parkhead dressing room to make that unnecessary.“You have got Moussa and me but when we’re both injured it’s obviously difficult at times,” he said. “But when we’re fully fit I wouldn’t have any other two strikes in the league to be honest.“I don’t think there’s any added pressure on me right now [being the only fit striker]. I showed last year even when Moussa was fit I was still the main man to go to and get the goals to fire us into the Champions League.“Yeah if Moussa was fit it would be a massive help to us but with the quality we have got in the dressing room we’re more than capable of getting through the two ties.” 1last_img read more

New billboard tells drivers to slow down

first_img For more on this story, pick up tomorrow’s Whittier Daily News. 165Let’s talk business.Catch up on the business news closest to you with our daily newsletter. Something went wrong. Please try again.subscribeCongratulations! You’re all set! PICO RIVERA – City officials Tuesday unveiled a new billboard that urges drivers to watch out for pedestrians. “You’re in the driver’s seat,” the massive sign at Smith Park tells motorists. It includes a photo of James Picha, a 15-year-old El Rancho High School student who was killed in 1956 while walking to school along Rosemead Boulevard. The billboard highlights Pedestrian Safety Awareness Month, officials said. “I hope people pay attention to this,” said Pico Rivera Mayor Pete Ramirez. “I think it’ll make them aware that they’re driving a 4,000-pound vehicle, compared to a 75-pound person crossing the street.” last_img read more

Get Live Help with CSS-Tricks Office Hours

first_imgImagine you’ve been struggling with a frustrating CSS issue on a web page. No matter what you’ve tried in the past couple hours, the page isn’t displaying as you designed. You get online in a Google Hangout, share your screen, and ask web designer and author Chris Coyier if he can help you fix the problem. Chris looks at your screen, takes a look at your stylesheet, and suggests some changes to styles. And your frustrating CSS issue is resolved in less than five minutes.Sound like a dream? Not any longer. With today’s announcement from CSS-Tricks about their new Office Hours, you can get live help from expert web designers and developers. Held three times a week in August, the free two-hour help sessions feature expert web designers and developers including:Chris CoyierMarie MosleyLara SchenckGeoff GrahamRobin RendleThe sessions will be held on Google Hangout so you can talk face-to-face and share screens. Live chat will be available via a private Slack channel.If it gets busy and people are waiting, Office Hours staff will work in five-minute chunks of time.If you ask me, Office Hours is pretty amazing. Kudos to all the staff for offering their expertise and knowledge.Check out the Office Hours schedule for days and times. Share this:Click to share on Twitter (Opens in new window)Click to share on Facebook (Opens in new window)Click to print (Opens in new window)Like this:Like Loading…RelatedDeborah’s Weekly Web Resources Roundup: July 8, 2012This week’s resources include an interview with web designer Chris Coyier, a short video from Microsoft on Windows 8 tablet accessibility, an excellent guide for user experience benchmarking, and more. Hope you find the resources helpful in your projects. CSS New Pure CSS3 Progress Bars: Using the tutorial from Chris…In “Web design & development links”Weekly Roundup of Web Design and Development Resources: August 14, 2015In this week’s roundup of web design and development resources, you’ll discover a great design methods resource, find out how a software developer found his way back to loving his work, learn about an online tool to test your responsive web design by breakpoints, and more. If you’re new to…In “Web design & development links”Weekly Roundup of Web Design and Development Resources: July 17, 2015In this week’s roundup of web design and development resources, you’ll learn why plain language is vital for website usability, discover strategies for ensuring accessibility is built in from the beginning of a project, find out about a 24-hour free livestreamed Genesis event, and more. If you’re new to my…In “Web design & development links”last_img read more

Piracy decline gives Somalis hope

first_imgSuspected pirates keep their hands in the air as directed by the guided-missile cruiser USS Vella Gulf as the visit, board, search and seizure team prepares to apprehend them. Vella Gulf is the flagship for Combined Task Force 151, a multi-national task force conducting counterpiracy operations to detect and deter piracy in and around the Gulf of Aden, Arabian Gulf, Indian Ocean and Red Sea.(Image: Jason R Zalasky, US Navy) MEDIA CONTACTS • Obinna Anyadike  Editor-in-Chief, Irin  +254 20 7622 1343 RELATED ARTICLES • Co-operating to cut down piracy • Maritime piracy under the spotlight • Eye in the sky benefits society • SA women marine pilots make history • SA Agulhas in historic polar tripSource: Irin NewsRusting hulks of capsized boats decorate the waters around Berbera, a port city in the self-declared republic of Somaliland. Further down Somalia’s coast, pirates raid freighters in the Gulf of Aden. But efforts are under way to help Somalis make better use of their 3 300km coastline – the longest on the African continent – by increasing fishing and seafood exports to lucrative markets in the Middle East and Europe.In 2013, the EU will spend US$6.5-million (R57-million) to help Somaliland pursue its long-term goal of netting 120 000 tons of seafood each year, the sale of which could generate $1.2 billion (R10.5-billion) in foreign currency.“In Somalia, people have lived for a long time with their backs to the sea,” says Isabel Faria de Almedia, the EU development chief for Somalia. “It’s a country of agro-pastoralists with a strong nomadic tradition. We think there is a huge potential for the consumption and export of fish.”Until the second half of the 20th century, few Somalis outside fishing communities consumed fish and the sector was entirely artisanal in nature. This began to change in the 1970s with the development of better cold-storage facilities and the creation, with Soviet help, of an industrial fleet.But for want of spare parts and maintenance, these vessels quickly fell into disuse. See here for a detailed, if slightly dated, overview of the Somali fishing industry. Luring pirates away from piracyIn the middle of the last decade, Somali fishermen complained they were being forced into piracy by foreign trawlers operating illegally in waters claimed by Somalia.Coastal Somalis recount as a “eureka” moment the time self-appointed coastguards impounded a foreign trawler and levied a fine on its owners; they quickly realized seizing vessels was more lucrative than competing with commercial vessels for dwindling fish stocks.Amina Farah Arshe, who employs 40 fishermen aboard 11 vessels from Berbera, the main port of Somaliland, says fishing revenues could provide an alternative to raiding freighters far into the Indian Ocean.“We can stop it by empowering the people. We can stop it by giving jobs to the youth. People would make money, the government would collect tax revenues, and piracy would diminish,” she said. “But we need support. We need training, boats, fishing gear and cold storage.”For years, the UN has said that tackling Somali piracy should involve creating work for the jobless young Somalis who board skiffs, armed with assault rifles and rocket-propelled grenades, to hunt vessels on the high seas.But only now has the security situation made this a realistic possibility. Somalia has recently selected its most viable president and government in years. Somali and AU forces have driven Al-Shabab insurgents from major cities.Out at sea, foreign warships and on-deck private security guards deter piracy. Only 70 raids took place in the first nine months of 2012, compared to 199 in the same period last year, according to the International Maritime Bureau. Logistical challengeSomalia’s new president, Hassan Sheikh Mohamud, says he wants to “increase local food production to end poverty forever”. Some 2.1-million people in the country are faced with hunger, particularly in the turbulent south.The future of large-scale fishing in Somali waters is tied up in a legal dispute over how far these waters extend from the country’s coastline.While the UN Convention on the Law of the Sea, which Somalia ratified in 1989, establishes 12 nautical miles from shore as an international norm for states’ territorial waters, Somalia has asserted sovereignty over seas up to 200 nautical miles from the coast. Mogadishu has resisted international pressure to declare these outer waters an exclusive economic zone, a designation that confers numerous rights to the country but falls short of full sovereignty.Alan Cole, who runs anti-piracy operations for the UN Office on Drugs and Crime, says Somaliland’s Berbera and Puntland’s Bosaso have real potential. But exporting fresh fish from the remote central coast – site of many pirate bases – offers a “logistical challenge”, he said.The UN agency spends $40-million (R351-million) each year tackling piracy, helping prosecute sea-borne raiders, training and equipping coastguards, creating jobs, and providing refrigerated trucks and storerooms to the fishing industry.“We need to get the fishing fleets of Somalia back to sea,” Cole said. “One of the challenges for fisherman is that the pirates will steal your fish. So you come back to the same issue of needing wider maritime security for Somalia so that the fishermen can safely make their living at sea.”last_img read more

Studies that intentionally infect people with disease-causing bugs are on the rise

first_imgVibrio cholerae, a comma-shaped bacterium that contaminates water and food, can kill fast. Acids in the stomach can wipe out billions of the bacteria, but if a person swallows as few as 1000 with food, some may survive the swim to the small intestine. There, the invaders will release enzymes to penetrate a thick mucous layer that lines the epithelium. Once through, the bacteria will attach to epithelial cells and begin dividing, establishing microcolonies that secrete toxins. Then the death clock begins ticking.Irritated by the main cholera toxin, the intestine will gush fluid, and a person will develop cramping, vomiting, and, most notoriously, diarrhea that rapidly becomes a staggering volume of “rice-water” stool: a watery liquid filled with mucous flakes and epithelial cells. In severe cases, people lose a liter of rice-water stool per hour and, without rehydration to replace lost body water and electrolytes, can die within half a day.In 1976, at the behest of a U.S. government panel, Myron “Mike” Levine of the University of Maryland School of Medicine in Baltimore began intentionally giving humans V. cholerae. He is still doing so today. The cholera studies led to the scuttling of a leading vaccine candidate, a finer understanding of effective immune responses, and, ultimately, compelling evidence that a different cholera vaccine worked. In June, the U.S. Food and Drug Administration (FDA) will consider licensing a cholera vaccine for travelers based largely on Levine’s work. This is the most influential role the human challenge model has ever played in the FDA approval process.Modern volunteersOver the next decade, Levine’s group expanded to challenges with Salmonella typhi, E. coli, and rotavirus. The only other substantial human challenge operation was the Common Cold Unit established by the Medical Research Council in Salisbury, U.K. Then in 1985, a team led by Ripley Ballou began human challenges with malaria at the Walter Reed Army Institute of Research (WRAIR) in Silver Spring, Maryland. That program pioneered advances that have lowered the risks of human malaria challenges and increased the benefits, opening the way to the trials flourishing today in several places.Ballou, who now heads vaccine R&D in the United States at GlaxoSmithKline (GSK), and his team bred mosquitoes in an insectary, and then fed them on human blood infected with the malaria parasite Plasmodium falciparum. He and five other Army colleagues each took a candidate malaria vaccine and then let five infected mosquitoes—which their group had determined was the number needed to reliably transmit the parasite—lunch on their arms. “I got a full-blown case of malaria and was never so sick in my life,” Ballou says, even though he was promptly treated. “It made a huge impression on me and I was committed to finding a way to stop this disease.”In WRAIR’s first vaccine trial, all the participants were “my friends in the laboratory or from down the hall,” says Ballou, and they went home after being infected. Now, WRAIR recruits civilians—special policies govern participation of people serving in the military—who for up to 10 days stay in a hotel together, where they receive regular checkups. Technology has also made the experiment safer than when Ballou infected himself: The polymerase chain reaction test can detect minute amounts of parasite DNA and identify an infection 2 days earlier than traditional microscopy, and if volunteers receive immediate treatment, they rarely suffer any symptoms. Paul Fetters Intentionally infecting a human—let alone a child—with a disfiguring and even deadly disease would never pass ethical muster today. But as recently as the early 20th century, intentional infection was seen as cutting-edge: Austrian psychiatrist Julius Wagner-Jauregg won the 1927 Nobel Prize in Physiology or Medicine for injecting blood from people with malaria into patients with neurosyphilis, which putatively cured them of insanity and paralysis. As journalist Lawrence Altman documented in his book Who Goes First?, many investigators have challenged themselves with pathogens to prove the worth of their own experimental medicines or theories. Some died.In the 1940s, the University of Chicago in Illinois and the U.S. Army collaborated on challenge experiments that tested malaria drugs in 400 Illinois prisoners. Nazi doctors, who horrified the world with their own medical experiments, including malaria tests that killed several hundred people, cited the U.S. studies in their defense when they were put on trial in Nuremberg, Germany, in 1947. This led to the Nuremberg Code, which spells out what are now the standard research principles of informed consent, voluntary participation, and the freedom to quit a study.Yet U.S. experiments on prisoners continued, leading to investigative journalist Jessica Mitford’s 1973 exposé in The Atlantic Monthly, “Experiments Behind Bars.” Levine, who was just starting his career, was then challenging humans with shigella and typhoid at the Maryland House of Correction in Jessup—experiments he insists were conducted ethically. “The studies done at Jessup were 2 decades ahead of their time in terms of the methods of informed consent,” he says. But in 1976, the U.S. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research—the country’s first bioethics policy effort—issued a report that effectively brought human challenge experiments in prisons to a halt.The first question I ask is, ‘Would I want my kids … to participate?’Myron “Mike” Levine, University of Maryland School of MedicineOutside of prisons, however, research continued. In 1974 the U.S. National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland, awarded the University of Maryland a half-million dollars to create a new vaccine testing center, headed by Levine, that would recruit volunteers from colleges and church groups. The center began with influenza challenges, which were conducted in refurbished rooms at the University of Maryland Hospital that had bunk beds for 22 people and an isolated air system. The researchers had little trouble recruiting volunteers, who received the same fee as jurors ($20 a day), which the researchers deemed fair but not coercive. Volunteers had to take a written test to prove that they understood the risks.Two years later, at the request of NIAID’s Cholera Panel, Levine’s group added challenges with V. cholerae to test cholera vaccines. “One of the really big questions was, ‘Would anyone be willing to participate?’” Levine recalls. “It’s one thing doing flu, which most people experience every other year or so, and it’s another thing to take this exotic tropical infection and set that up.”Maryland required that the hospital fly a yellow flag to warn of a cholera quarantine area. Again, finding volunteers presented few obstacles. “These were the same young people who would go down the hairiest parts of rivers on rafts,” Levine says. In a 1970s University of Maryland cholera study, this man needed 26 liters of intravenous electrolytes to replace lost fluids. Ripley Ballou led malaria challenge trials to test vaccines at the Walter Reed Army Institute of Research starting in 1985. Volunteers—including Ballou—willingly exposed their arms to malarial mosquitoes. Myron “Mike” Levine University of Michigan Health System, Gift of Pfizer Inc. UMHS.23 Courtesy of Myron M. Levine Forty years ago Levine was one of a tiny cadre of researchers doing so-called human challenge studies—intentionally infecting people with V. cholerae and other pathogens to test drugs and vaccines. But in the past few decades, this practice, which has a long and checkered past, “has become much more mainstream,” Levine says. Stricter safety procedures and new ways to weaken pathogens to reduce their risks are leading investigators in industry, universities, and government to take a new look at human challenge trials, which offer a powerful tool for studying diseases and potential therapies. There’s even a commercial company, hVIVO in London, that specializes in human challenges. Today, people are being deliberately infected with malaria, influenza, shigella, dengue, norovirus, tuberculosis, rhinovirus, Escherichia coli, typhoid, giardia, and campylobacter.Sign up for our daily newsletterGet more great content like this delivered right to you!Country *AfghanistanAland IslandsAlbaniaAlgeriaAndorraAngolaAnguillaAntarcticaAntigua and BarbudaArgentinaArmeniaArubaAustraliaAustriaAzerbaijanBahamasBahrainBangladeshBarbadosBelarusBelgiumBelizeBeninBermudaBhutanBolivia, Plurinational State ofBonaire, Sint Eustatius and SabaBosnia and HerzegovinaBotswanaBouvet IslandBrazilBritish Indian Ocean TerritoryBrunei DarussalamBulgariaBurkina FasoBurundiCambodiaCameroonCanadaCape VerdeCayman IslandsCentral African RepublicChadChileChinaChristmas IslandCocos (Keeling) IslandsColombiaComorosCongoCongo, The Democratic Republic of theCook IslandsCosta RicaCote D’IvoireCroatiaCubaCuraçaoCyprusCzech RepublicDenmarkDjiboutiDominicaDominican RepublicEcuadorEgyptEl SalvadorEquatorial GuineaEritreaEstoniaEthiopiaFalkland Islands (Malvinas)Faroe IslandsFijiFinlandFranceFrench GuianaFrench PolynesiaFrench Southern TerritoriesGabonGambiaGeorgiaGermanyGhanaGibraltarGreeceGreenlandGrenadaGuadeloupeGuatemalaGuernseyGuineaGuinea-BissauGuyanaHaitiHeard Island and Mcdonald IslandsHoly See (Vatican City State)HondurasHong KongHungaryIcelandIndiaIndonesiaIran, Islamic Republic ofIraqIrelandIsle of ManIsraelItalyJamaicaJapanJerseyJordanKazakhstanKenyaKiribatiKorea, Democratic People’s Republic ofKorea, Republic ofKuwaitKyrgyzstanLao People’s Democratic RepublicLatviaLebanonLesothoLiberiaLibyan Arab JamahiriyaLiechtensteinLithuaniaLuxembourgMacaoMacedonia, The Former Yugoslav Republic ofMadagascarMalawiMalaysiaMaldivesMaliMaltaMartiniqueMauritaniaMauritiusMayotteMexicoMoldova, Republic ofMonacoMongoliaMontenegroMontserratMoroccoMozambiqueMyanmarNamibiaNauruNepalNetherlandsNew CaledoniaNew ZealandNicaraguaNigerNigeriaNiueNorfolk IslandNorwayOmanPakistanPalestinianPanamaPapua New GuineaParaguayPeruPhilippinesPitcairnPolandPortugalQatarReunionRomaniaRussian FederationRWANDASaint Barthélemy Saint Helena, Ascension and Tristan da CunhaSaint Kitts and NevisSaint LuciaSaint Martin (French part)Saint Pierre and MiquelonSaint Vincent and the GrenadinesSamoaSan MarinoSao Tome and PrincipeSaudi ArabiaSenegalSerbiaSeychellesSierra LeoneSingaporeSint Maarten (Dutch part)SlovakiaSloveniaSolomon IslandsSomaliaSouth AfricaSouth Georgia and the South Sandwich IslandsSouth SudanSpainSri LankaSudanSurinameSvalbard and Jan MayenSwazilandSwedenSwitzerlandSyrian Arab RepublicTaiwanTajikistanTanzania, United Republic ofThailandTimor-LesteTogoTokelauTongaTrinidad and TobagoTunisiaTurkeyTurkmenistanTurks and Caicos IslandsTuvaluUgandaUkraineUnited Arab EmiratesUnited KingdomUnited StatesUruguayUzbekistanVanuatuVenezuela, Bolivarian Republic ofVietnamVirgin Islands, BritishWallis and FutunaWestern SaharaYemenZambiaZimbabweI also wish to receive emails from AAAS/Science and Science advertisers, including information on products, services and special offers which may include but are not limited to news, careers information & upcoming events.Required fields are included by an asterisk(*)The risks are obvious: Otherwise healthy people can suffer harm and, if the disease is contagious, potentially sicken others. But if done right, the benefits are compelling, a growing number of researchers say. The standard pharmaceutical development path for products that target pathogens moves slowly from studying safety, dosing, and biological responses in hundreds of people to an expensive efficacy trial with thousands of participants at high risk of becoming naturally infected. Human challenge studies, which only involve a few dozen volunteers, speed the process of deciding whether to scrap or pursue a promising lead, saving time and money. And tests that intentionally infect people can quickly and efficiently flag potential side effects, advocates say. “You certainly can’t do a $100 million study for every candidate vaccine that appears safe and immunogenic,” says Mark Mulligan, a molecular virologist who heads the vaccine center at Emory University in Atlanta and does human challenges with norovirus and tuberculosis.Insights from human challenges reach far beyond drugs and vaccine development. Christine Moe, another Emory University researcher, has shown that norovirus more readily transmits via vomit than diarrhea, and that this “Ferrari of viruses,” famous for the speed at which it races through vacationers on cruise ships, is impervious to alcohol-based hand sanitizers and to power-washing the oysters that carry it. She notes that “sometimes human challenge studies are the only way to answer critical questions.”Checkered pastHuman challenges date back to the 18th century and the first vaccine, when English physician Edward Jenner attempted to persuade the world that infecting a person with harmless cowpox could prevent disease from its dreaded cousin, smallpox. Jenner scraped “matter” taken from a cowpox sore on a dairymaid’s hand into the skin of 8-year-old James Phipps, the son of his occasional gardener, and then repeatedly tried to infect him with smallpox. “Poor Phipps,” as Jenner later referred to the boy, never came down with smallpox. Jenner reported that some 6000 other people were vaccinated and then the “far greater part of them” were challenged with smallpox. Two centuries later, the vaccine Jenner pioneered eradicated the virus from the human population. Vaccine pioneer Edward Jenner put cowpox fluid into James Phipps’s arm in 1796, then challenged him with smallpox. Walter Reed Army Institute of Research The Army’s malaria challenge studies have yielded impressive dividends. “We trashed a whole bunch of vaccines,” Ballou says. They also contributed to the development of GSK’s RTS,S, the only malaria vaccine that has so far demonstrated efficacy, albeit modest, in a large-scale field trial.The resurgenceTrials launched more recently face greater regulatory scrutiny than Levine’s and Ballou’s did. Since the mid-1990s, FDA has deemed that organisms used in challenge studies are experimental medicines, and the agency has required researchers to submit Investigational New Drug applications before conducting trials. Institutional reviews have intensified, too.Human challenge studies with influenza provide a glimpse of the new landscape. In the 1980s and 1990s, for example, Frederick Hayden of the University of Virginia School of Medicine in Charlottesville conducted challenge studies with influenza that helped speed the development of Tamiflu and Relenza, drugs that have become the mainstays of treatment. But the work ground to a halt in 2000 after a volunteer in one of Hayden’s studies experienced what FDA calls an “adverse event.” A 21-year-old man testing a flu drug developed heart abnormalities after being challenged with the virus. “I still don’t know what caused that episode,” Hayden says. “There were a lot of sleepless nights.” No long-term harm occurred, but the incident has led to a thorough review of cardiac events in other influenza challenge studies.So there was considerable concern when NIAID’s Matthew Memoli proposed new human challenge studies with influenza in 2011, which ultimately aimed to test novel treatments and vaccines. Some of his colleagues were so wary that the ethics department at the National Institutes of Health (NIH), NIAID’s parent, was asked to conduct a formal review of the protocol. “We went through a lot of steps,” Memoli says. The ethicists were particularly concerned about the proposed “high levels of payment”—up to $4000—but deemed this was not an “undue influence” because no one had an obligation to accept the offer.Volunteers were “meticulously” screened, Memoli says: They had to be under 45 and undergo a battery of tests, including electrocardiograms. Memoli and colleagues also worked with FDA to grow a strain of the virus that met the agency’s good manufacturing practices, and they precisely calculated the minimum dose needed to cause disease in most volunteers.In ongoing studies, the researchers spray influenza virus into the noses of volunteers via a mist, created by an atomizer that only produces particles larger than 10 microns. These relatively fat particles can cause infections in the upper respiratory pathway but do not reach the lungs, where influenza virus can cause life-threatening pneumonia. To avoid infecting others, participants remain in hospital isolation rooms for 9 days. “I’ve challenged nearly 200 people and have had no serious complications,” Memoli says. “The worst thing that happened is a guy slipped in a shower.”Memoli stresses that intentionally infecting people is an odd pursuit for a doctor. “We’re purposefully making people sick,” Memoli says. “It’s a different idea than what you originally go to medical school for. But over the course of the next few years I think we’re going to get information that’s going to be tremendously helpful.” In a study published online in mBio on 19 April, Memoli and his co-workers reported that their challenge studies indicated that a widely ignored antibody response to influenza vaccines might be a better predictor of effectiveness than the antibody routinely analyzed today.Five years ago, the small community that studies dengue began discussing challenge trials, which made some people nervous, says Anna Durbin of Johns Hopkins Bloomberg School of Public Health in Baltimore. The mosquito-borne infection can trigger a high fever, serious joint pain, and intense rashes; in rare cases, it can lead to hemorrhaging and death. No drugs specifically target dengue virus. “We heard, ‘You can’t treat dengue so you can’t do a human challenge model,’” Durbin says. Human challenges with dengue date back a century, but the last intentional infections of volunteers took place at WRAIR in 2001, and a few of the participants developed dengue fever.In 2011, WRAIR and NIH sponsored a workshop to discuss “reintroducing” the human challenge model for dengue. Several attendees, including Durbin, argued that the trials could be done safely and would speed development of a badly needed vaccine for this disease.With the blessing of FDA, Durbin in June 2013 began challenging volunteers who had received a dengue vaccine made by NIAID. Instead of using wild-type dengue virus, Durbin and her Hopkins team infected people with a naturally weak isolate of the virus that had been further attenuated in the lab. “I don’t think you need to make people sick” to see whether they develop an infection, Durbin says.As she and her group reported online on 16 March in Science Translational Medicine, none of the 21 people who received the vaccine became infected after the challenge, but all 20 controls had the virus in their blood, and 16 developed a rash. Based in part on these results, the Butantan Institute in São Paulo, Brazil, this year launched an efficacy trial of the vaccine that plans to enroll 17,000 people. Regulations of human challenge studies differ from place to place. In the United Kingdom, for example, challenge agents are not considered drugs, and experiments with them thus don’t require regulatory approval. A group at the University of Oxford led by pediatrician Andrew Pollard has conducted a challenge study of experimental vaccines against typhoid and paratyphoid. Although both diseases are contagious, the researchers allow volunteers to go home instead of staying in isolation. “They’re potentially shedding organisms that are going into a flush toilet,” says Levine, who collaborates with the Oxford group. “That’s something that’s not amenable to being carried out in the USA.”The United Kingdom is “much more permissive,” agrees Pollard, but he says the trials go through extensive ethical reviews, and the risk of transmission is “near zero” if people have good hygiene.The human challenge model has its limits, Levine stresses, noting that his group declined to participate in an experiment done elsewhere that put Neisseria gonorrhoeae in a penile catheter to study gonorrhea transmission. “The first question I ask is, ‘Would I want my kids, siblings, or spouse to participate?’” Levine says. “If the answer is ‘no,’ we don’t do it.” And he worries that even though researchers today address risks more carefully than ever before, someone could push too far and undo the gains the field has made. “This should not be a Wild West show,” he says. “Some newcomers may not be totally aware of the burden the pioneers went through. It has taken a lot of time to get buy-in from everyone imaginable.”last_img read more

‘Australian cricket rewards merit, loves a gamble and reflects vigour of a young nation’

first_imgIRON OZ: The victorious world champs at the Wanderers, JohannesburgThe Australians were far and away the least sentimental, most spirited and most professional team in the World Cup. As with the cases solved by Sherlock Holmes, the little things told the story. Asked to absolve his famous leg-spinner in a,IRON OZ: The victorious world champs at the Wanderers, JohannesburgThe Australians were far and away the least sentimental, most spirited and most professional team in the World Cup. As with the cases solved by Sherlock Holmes, the little things told the story.Asked to absolve his famous leg-spinner in a manner nowadays more available to Australian captains than to humble citizens such as Popes, Ricky Ponting refused to do so. Ranks did not close around Shane Warne. The facts were faced, the truth was told, and the show moved on. A slightly demented young man from West Australia took over the spinning duties and promptly proved harder to read than Dostoevsky. Warne was harshly treated by a sceptical Australian public, most of whom viewed his punishment as mild. Meanwhile South Africans were trying to convince themselves that Hansie Cronje was not so bad after all, a notion that has survived the revelation that he had 71 bank accounts, more than some villages manage.Nor was there any shilly-shallying among the Australians about Jason Gillespie. As soon as it was discovered that he could not bowl again, he was put on a plane and flown home. Meanwhile Jonty Rhodes was desperately trying to persuade his selectors to allow him to stay with the party as a talisman. Strong teams do not rely upon emblems and symbols, let alone the superstitions with which half of India tried to convince itself that the Australians must fall at the final fence, a fate that once befell a horse belonging to the Queen but was never likely to affect a bunch of rough Antipodeans.Captain Ricky Ponting has inherited a strong ethos from Steve Waugh and maintained it in his own uncomplicated way. His team did not look back with regret or sideways with concern. Instead it simply marched towards the next match, confident of victory. The Australians were far more aware of their strengths than their weaknesses. TOp Of The PopsThey were not trying to defend a title that had been won by a previous team under a captain who had suffered the fate of all Australian cricketers, the phone call that comes a year earlier than it is the case in countries where sentiment rules. Instead they were trying to put their own mark on the game as a vibrant team led by a man with a chequered past and strong convictions.Ponting’s team regarded this World Cup as a wonderful opportunity to prove itself. Significantly Warne and Gillespie were hardly mentioned from the first day till the last. If the Australians wanted to prepare the ground in case of defeat they could have reminded all and sundry that the squad had been wounded. No such timidity was tolerated; Ponting & Co were not interested in hard luck stories. They wanted to win the Cup.The Australians are a tough lot. On the way up they must survive a rigorous system that weeds out weeds and eradicates soft thinking. Andrew Symonds did mention Warne once, saying he had been so angry with him that he produced the innings of his life when his team was in trouble against Pakistan.To understand the Australians properly it is necessary to put the clock back a couple of years. In those days Matthew Hayden was too stentorian to score runs against top-class bowling. Symonds was an overrated cricketer with a poor record. Andrew Bichel was a willing worker who could not quite cut it in the highest company. Adam Gilchrist had moved to Perth to get a game and was booed on his first appearance for his country. Steve Waugh was a great captain and competitor. Brett Lee was on the comeback trail and seemed as likely to succeed as Bob Dole. Brad Hogg was hanging on to his place with his state side and could not land his wrist-spinners. Ponting was a headstrong fellow inclined towards drinking and fighting. Oh yes, and the coach was a gook. None of them seemed like supermen. Somehow Australian cricket managed to detect and extract their strengths. No one bothered much about their supposed weak points.Service is important in Australian cricket. The prevailing philosophy is that the team is greater than the individual and the country is more important than either. When Mark Waugh’s time is up he is thanked and dumped. The minute Steve Waugh starts looking old he is dropped from the 50-over side, and there is no going back. People argue in Australian cricket because it is the national game and it matters. No one has an agenda. Whereas past players from India and England secretly and sometimes blatantly seek power, their Antipodean counterparts serve in whatever capacity is decreed. For years Allan Border was happy to assist the youth team. Dennis Lillee has helped the fast bowlers, and Rod Marsh coached at the academy. Not that positions in Australian cricket are reserved for the great men of yesterday. On the contrary, the current senior and academy coaches owe their appointments not to any achievements on the field but to their accomplishments in the relevant area. Unlike other countries, Australian cricket is not a closed shop, the preserve of famous men convinced that they alone have the key to the cabinet. Rather, men are regarded and decisions made upon their merits. The same applies further down the scale.All five age-group teams at local clubs practise together. Men bat in the order of their arrival. Regular absentees are not considered for selection. If a man scores runs, he goes up whilst repeated failures herald demotion. Players of exceptional ability are, however, spotted early and pushed along because Australians like sport and want to see it played well. After wintering in the Northern Hemisphere when I returned Down Under, I rang up a former Australian player to ask if there was “anything or anyone about”. He replied that there was a young bloke from Launceston called Ricky Ponting they reckoned could play a bit and someone said he could straight drive off the back foot. The point is that he had heard of this 16-year-old from an obscure island and was excited by him. My newspaper printed the resulting article in a prominent position. Australians are not scared to take a punt. They are direct and intolerant of procrastination.The willingness to take risks and to give youth a chance reflects the vigour of a young nation that finds in sport an opportunity to forge an identity and to put into constructive form the drive and physicality of a people suspicious of sophistication and still trying to survive the challenges of a harsh land. Australian cricket has a unity and purpose missing in any rival, characteristics that turn a small nation into a mighty force on the cricket field. Australian cricketers can be ruthless and abrasive but they are seldom dull or cynical because they realise they represent something more than themselves, namely a tradition symbolised by the decrepit cap Steve Waugh made such a point of wearing. Australian cricket tries and often succeeds in combining the best of its past, present and future. Now it is up to the rest to catch up.Sydney-based Peter Roebuck is former captain of Somerset and one of the world’s foremost cricket writers.advertisementadvertisementlast_img read more