You Are Selling for Competitive Advantage

first_imgYou aren’t just trying to compete for your dream client’s business; you’re trying to win their business. Everything you do, every sales interaction, needs to be designed to create a competitive advantage. You want a complete and total mismatch when your dream client evaluates you against your competitors (and against you most dangerous nemesis, the status quo).Trust and RelationshipYou want the competitive advantage of having the strongest relationship. Trust is the foundation of that relationship. Caring is, in part, the foundation of trust. As much talk is there is today about insights and ideas, you still want the competitive advantage of being known, liked, and trusted.All things being equal, relationships win. All things being unequal, relationships still probably win. You seek to make all things unequal by developing the relationships you need to stack the deck in your favor.Perception of ValueYour relationships allow you to spend time with your dream clients. That access gives you the ability to uncover and understand your dream client’s perception of value. If you have really strong relationships, you have the ability to help shape that perception of value.Creating the greatest–and highest levels–of value is a massive wedge of a competitive advantage. You sell to create that value.Ability to ExecuteOne of the ways you create a competitive mismatch is by selling in a way that proves you have the ability to execute. More than ever, your dream clients need to know that when they make the necessary investments that they’ll get the results that they paid for. They’re afraid of risk. They’re afraid of failing. They’re afraid of change.You create a competitive advantage by providing proof and evidence of your ability to execute, be it through references, site visits, or implementation meetings. Execution isn’t just something you do after you sell; it’s part of what you sell to create a stacked deck.Tilt the Playing FieldYou are selling so that you can tilt the playing field in your direction. You want an absolute advantage over your competitors. You sell to make it easy for your dream client to say “yes” to you and “no” to your competitors. How well you sell determines whether or not you create a competitive advantage.QuestionsHow does how you sell create a competitive advantage?How much does relationships and trust count towards a real competitive advantage?Do heavily does your dream client’s perception of value create a competitive advantage?When is it right to focus on execution?last_img read more

Eliminate Distractions And Do Good Work

first_imgYou don’t really need to be interrupted every time someone calls you. You worry about not picking up the phone because you are afraid you will miss something. If what you are doing is really important, it is better that you give it your full, undivided attention. If you can’t miss a call, set up a voice mail message indicating who your caller should contact in your absence, or tell them to call back immediately if what they need is urgent.You don’t need to know that you have received a text message the minute you receive it. Many of the text messages you receive don’t rise to level of requiring your immediate attention. By responding in real-time, you are giving everyone you know permission to interrupt you at any time. This means everything and everyone is more important than what you were doing.You are allowed to close your email. You can close it for hours at a time. No lives will be lost. Nowhere on your job description is their even a hint that you primary duties require that you respond to email in real-time. Email isn’t your job; it’s a tool. Two hours from now, all of the emails that have come into your inbox will be there for you.Can you imagine being surrounded by people, each of them tapping you on the shoulder to gain your attention one after another? How productive can you be when you are interrupted every few minutes? How can you do quality work when you won’t give yourself permission to turn off all distractions long enough to give yourself over to your work?There is some work you do where it will be okay to allow yourself to be distracted. To do the best work your capable of, you must eliminate distractions. Essential Reading! Get my 3rd book: Eat Their Lunch “The first ever playbook for B2B salespeople on how to win clients and customers who are already being serviced by your competition.” Buy Nowlast_img read more

Prospects You Should Avoid

first_imgAs you sell, there are certain types of prospects you will encounter that should be avoided. These prospects will waste your time, and winning their business would cost you far more than your time. Your time is better spent with your dream clients. One key to your success will be identifying these prospects quickly and moving on.These are the prospects you should avoid: Essential Reading! Get my first book: The Only Sale Guide You’ll Ever Need “The USA Today bestseller by the star sales speaker and author of The Sales Blog that reveals how all salespeople can attain huge sales success through strategies backed by extensive research and experience.” Buy Now Price Shoppers: Avoid any prospective customer who reveals their current price with your competitor and suggests that they will meet with you if you can do better. If the only motivation for change is a lower price, then there is no real value you can create as there is no outcome that is worth paying more to obtain. Besides, your bottom-feeding competitor’s will undercut you by another penny to win the business.Unsolicited RFP Requesters: Avoid prospects who invite you to respond to their Request for Proposal without ever having met you. There is no value in being column fodder for an RFP that you have 0.0% chance of winning. If you can’t get beyond arms-length, your time and effort is better spent with prospects who will meet with you face-to-face, or virtually face to virtual face.Responsibility Avoiders: Avoid any prospect who confesses your competitor’s sins and failings when you recognize that their challenges have nothing to do with your competitor and are really your prospect’s unwillingness to change. You’ve no doubt experienced this, and if you haven’t, you will. Once you know that your prospect’s real problems are not your competitor’s fault, you also know that your prospect is unwilling to change.Dominators: Avoid any prospect who reveals a belief that you are a vendor and, as such, should be subservient. You sell from the position of a peer. You work as a trusted advisor. You are consultative. If you allow them to dominate you, you are cannot be a value creator.Freeloaders: Avoid prospects who are going to require a massive amount of work without the willingness or ability to pay for what they need. Anyone can have anything they want, as long as they are willing to pay for it. But wanting things and not being willing to pay for those things is a poor combination and not one you want to deal with. Invest your time with those who are going to make the necessary investments for the results they want.Unqualified: Avoid every prospect who does not perceive value in what you do and how you do it. Even if they want to buy, neither of you will ever be happy working together. Your time is better spent identifying, pursuing, and working with people who value you.last_img read more

The Problem with Modeling Your Best Sales Reps

first_img Get the Free eBook! Learn how to sell without a sales manager. Download my free eBook! You need to make sales. You need help now. We’ve got you covered. This eBook will help you Seize Your Sales Destiny, with or without a manager. Download Now I once had a friend who asked a company to come in and observe their sales force to understand what their highest achieving sales reps were doing so they could uncover what would need to change for the rest of the sales force to improve their results. As it turned out, the only thing the lower performers would have had to do to improve their performance was to wait until their peers left the company and inherit their clients.There is a lot you can learn from high performing salespeople. But there are also problems with trying to model your top performers directly.High performing salespeople’s effectiveness allows them to win more deals with less activity than their peers.One of the primary challenges you have when you use them as a model is that it is difficult for most reps to model their effectiveness. Some top 20% salespeople produce greater results with less activity. In many cases, poor performing salespeople find themselves in this category because they aren’t doing enough of the work necessary to create new opportunities (i.e. prospecting). Coupling low activity with a low effectiveness, using something like win rate as a measurement, only worsens their performance.Producing better results means pulling the Gaussian curve to the right, moving every rep towards the best performance possible. More activity provides more opportunities to learn, to make distinctions about what works and what doesn’t, and more coaching to improve their effectiveness over time.Many high performing salespeople have very strong intangibles, many of which are difficult to replicate.Here we run dead into the old question about whether salespeople are born or made. The answer is that salespeople can be made. But many are born with a set of intangibles that make selling easier for them.Some people are charismatic, possessing the intangible that causes people to be attracted to them very quickly and with no effort on their part. Others have very fast rapport skills, allowing them to connect with people, causing them to engage with these reps without needing time to develop the relationship. Other salespeople have the type of business experience and demeanor that looks like executive presence and allows them to have their advice heard, received, and taken.None of this is to say that one must have all these intangibles to succeed, and there as many different types of clients with different preferences when it comes to what the right partner looks like to them.But the intangibles that make success easier for some than others are difficult to replicate in others, meaning that you may not be able to model some of what make them successful.High performing salespeople win larger deals and their success gives them more time and space to focus on larger deals.One thing you’ll notice about the top of any stack ranking of salespeople is that they didn’t get there by winning a lot of small deals. I would like to write that it is rare that you see a rep at the top of the stack with small deals, but because I have never seen that myself, I am not sure it has ever happened.The best performing reps tend win large deals—and with higher success rates than their peers. It takes time for salespeople to learn to sell larger, more complex deals-especially those that require consensus from a large group of stakeholders. Learning requires an investment in development and coaching. One of the reasons successful reps do well is because they win large deals, and winning these deals provides them with the time and space to pursue other large deals, a luxury other reps cannot afford.There is much to learn from people who produce a result you want. But not everything is easy to replicate, and not many are achieved without great effort—and time.last_img read more

Cong. for CBI probe into Mehsana custodial death

first_imgThe opposition Congress in Gujarat on Sunday demanded a CBI probe into the custodial death of Patidar youth Ketan Patel in Mehsana. The party has joined the Patidar community and family of the deceased in demanding a probe by the Central agency, alleging that Ketan died of police beating in custody.On Sunday, a Congress delegation led by party in-charge Ashok Gehlot met Governor O.P. Kohli to submit a memorandum demanding a CBI probe. State Congress president Bharatsinh Solanki and Leader of the Opposition Shankarsinh Vaghela were also part of the delegation.“We have demanded a CBI probe because the person has died in Gujarat police custody,” Mr. Gehlot told media persons in Gandhinagar.Subsequently, Mr. Vaghela met the family members of Ketan in the Mehsana civil hospital. Following the death of Ketan, who was earlier arrested in a petty theft case, tempers in north Gujarat town soared as the Patidar community alleged that the police had killed Ketan in custody, a charge the local police have rejected.Two autopsies The family of the deceased refused to accept the body even after two autopsies were conducted by a panel of doctors in the Mehsana civil hospital.According to sources, the post-mortem reports have revealed that Ketan died of multiple injuries due to excessive beating by the police. However, the State authorities have not revealed the contents of the autopsy reports.After the death, there were a few incidents of violence, as Patidars torched two buses and a portion of the Mehsaha civic body’s office.last_img read more

Maharashtra enacts law against discrimination by caste panchayats

first_imgMaharashtra has become the first State in the country to enact a law against social boycott from caste panchayats. President Pranab Mukherjee has given his nod to implement the Prohibition of Social Boycott Bill in the State.The bill had been cleared in last year’s Budget Session with Chief Minister Devendra Fadnavis claiming that it would deal with the scourge of social boycott with an ‘iron hand’. As per the procedure, the bill was forwarded by the Central government to the President for his assent.A senior officer from the State Home Department said Maharashtra has received approval from the Centre to implement the Act all over the State. Despite repeated reminders from the State to the Centre, the clearance of the Bill was inordinately delayed. An officer said, “The bill involved four ministries including the Ministry of Tribal Affairs. We answered all queries satisfactorily and have now we have received the go-ahead.”The State answered questions raised by the Scheduled Tribes development department regarding overlapping of certain conditions in the bill with existing laws. With growing instances of boycotts of individuals or families by caste panchayats, the need to enact a special law was echoed in the State in 2010. The bill makes provision for punishment of up to three years in jail and/or a fine up to ₹1 lakh. The case has to be fast tracked within six months from the date of filing the charge sheet. The fine charged from accused will be partially or fully handed over to the victim.The Maharashtra Andhashraddha Nirmulan Samiti (MANS), which led the movement demanding the law, expressed satisfaction over the enactment of the bill. Krushna Chandgude, an activist with MANS, said, “Years of struggle have finally been paid off. We campaigned for the Act and were successful in convincing the political class that the issue of social boycott by caste panchayats was not only a matter of law and order but also social justice.” Mr. Chandgude slain rationalist Dr. Narendra Dabholkar has also campaigned against social boycott by caste panchayats in Maharashtra and the bill turning in to an Act was a tribute to the fighting spirit of Dr. Dabholkar.Avinash Patil, executive president, MANS, said, “Now that the Act has been cleared by the President, MANS will run a special campaign for the implementation of it at the district level.”last_img read more

Where is Darjeeling MP, asks Gorkha outfit

first_imgPolitical parties united in carrying the over month-long agitation in the Darjeeling hills demanding the separate State of Gorkhaland appear divided over the role of Bharatiya Janata Party (BJP) MP of Darjeeling, S.S. Ahulwalia.Representatives of the Gorkha National Liberation Front (GNLF) marched to the Darjeeling Sadar Police Station and lodged a missing person complaint for S.S. Ahluwalia. The complaint was registered by G.M. Subba, chief convenor of the GNLF’s Darjeeling unit. “The people of Darjeeling are not aware how our MP, whom we had elected in 2014, is doing. How is he? Where is he? We do not know. Therefore, in the interests of the people, we have lodged a missing person complaint,” Mr. Subba said. Apart from the complaint, posters of Mr. Ahluwalia seeking details about his whereabouts in Nepali were put up at some places in Darjeeling. Prakash Gurung, president of the youth wing of the Gorkha Janmukti Morcha (GJM), however, came to the defence of the MP.“If a missing person complaint has to be registered, it must be against Bhaichung Bhutia, whom the GNLF supported in the 2014 polls. Our MP is in Delhi and is working for the cause of Gorkhaland,” Mr. Gurung said. Discontent has been brewing in certain political circles over the absence of the MP since the unrest in the hills began on June 8. Mr. Ahluwalia won the 2014 Lok Sabha polls from Darjeeling with the support of the GJMlast_img read more

Farooq hits out at BJP-ruled States

first_imgNational Conference president Farooq Abdullah on Wednesday said changing the names of cities was an attempt to change the pluralistic visage of India and a premeditated attempt to deviate the attention of people from the developmental deficit across the country.“India is a mosaic of cultures and the contribution of Muslims cannot be belittled. Their contribution to the cultural pool of India is discernible in linguistics, crafts, food and other art forms,” he said in a statement.“Such attempts reveal the antipathy of the BJP-led State governments, including the incumbent Uttar Pradesh government, for academics and historical facts,” he alleged. India had historically been a point of convergence of different cultures and the names of various cities reflected its pluralistic culture, he said.last_img read more

Massive snow clearance operation underway to restore Jammu-Srinagar NH

first_imgA massive snow-clearance operation is underway to restore the 270-km Jammu-Srinagar National Highway which remained closed for vehicular traffic for the third consecutive day Wednesday, officials said. The snow clearance operation on both sides of the Jawahar Tunnel — the gateway to Kashmir — was started and the snow-clearance operation is going on in full swing, Deputy Superintendent of Police, Traffic National Highway, Pardeep Singh Sen told PTI. An avalanche had also struck the Jawahar Tunnel area on Tuesday, blocking both tubes on Qazigund side. The Border Roads Organisation (BRO), which maintains the Jawahar tunnel stretch of the highway, pressed its men and machines to clear the road of the accumulated snow yesterday, Mr. Sen said. We are expecting the highway to be open for traffic by late afternoon. However, only the stranded vehicles will be allowed to move on the highway once we get the green signal, he added. Hundreds of vehicles, mostly trucks, are stranded at various places along the highway, the only all weather road linking Kashmir with rest of the country, officials said. They said the road from Banihal, which recorded over two and a half feet of snow, to Jawahar tunnel was also being cleared, while the Banihal-Ramban stretch is almost clear after agencies concerned removed minor landslides and stones which came down at different places due to incessant rains. Jammu woke up to a sunny morning, providing relief to the denizens of the city who were reeling under intense cold after the mercury nose-dived due to inclement weather over the past four days. The day temperature is expected to rise after plummeting to 10.4 degrees Celsius yesterday — 8.4 degrees below normal during this part of the season, a spokesman of the MET department said. The night temperature also marked a slight dip and settled at 8.3 degrees Celsius against the previous night’s 8.7 degrees Celsius, the spokesman said adding the night temperature continues to remain over one degree above normal owing to cloud cover. He said Katra, the base camp for the pilgrims visiting Vaishno Devi shrine, recorded a minimum of 6 degrees Celsius, while the snow-bound areas of highway including Banihal and Batote townships along with Badherwah in Doda district were reeling under sub-zero temperature. Batote was the coldest recorded place in Jammu division with a low of minus 2.4 degrees Celsius, while Banihal and Bhaderwah recorded a minimum of minus 0.3 degrees Celsius.last_img read more

‘KALIA unique model for agri growth’

first_imgOdisha Governor Ganeshi Lal hoisted the national flag at the State-level Republic Day celebrations here on Saturday, while Chief Minister Naveen Patnaik gave an address from the historic Barabati Stadium in Cuttack.The State-level celebrations saw a parade by police personnel and students of various schools and colleges. Tableaux showcasing implementation of various welfare schemes and achievements of industrial units rolled their way down Mahatma Gandhi Marg. As many as 54 contingents and cultural troupes participated in the parade. Security personnel had been put on high alert in the city since Friday.“Make in Odisha has given a boost to investors’ confidence. Six lakh new jobs have been generated following grounding of investment to the tune of ₹4,20,000 crore. Successful organisation of 18 Men’s World Cup has helped increase respect of the State in the world arena,” said Mr. Patnaik.“The newly launched KALIA, a farm development incentive scheme, has proved to be a unique model for agriculture development in the country. This is not my word, agriculture experts have recognised it. As many as 12 lakh farmers have got assistance under the scheme till Friday,” he said.last_img read more

Imphal court releases student activist on bail

first_imgFour days after Manipur student activist Veemon Thokchom was arrested from his residence in Delhi for a Facebook post over the Citizenship (Amendment) Bill, an Imphal court on Tuesday released him on bail noting that the post was not seditious. Chief Judicial Magistrate Ningthoujam Lanleima remarked that the content of Mr. Thokchom’s Facebook post “cannot be stated to bring into hatred or contempt, or excite or attempt to excite disaffection towards the government”. “At the most, the accused mention the incident of burning of Assembly with approval, but I don’t find any attempt or incitement to commit violence,” the judge said. As a condition for his release on bail, the judge has directed him not to commit an offence similar to the one he is accused of. Following the court’s order, Mr. Thokchom was released during the day and reached his home in Manipur around 4 p.m. Mr. Thokchom, 24, was arrested by a joint team of Manipur and Delhi Police on February 15 from his rented residence in Saket, Delhi. Second such case Mr. Thokchom is the second case in recent months where the Manipur government has booked individuals for sedition, an offence which entails a maximum punishment of life imprisonment. In December last year, Manipur journalist Kishorechandra Wangkhemcha, who had posted an alleged offensive Facebook post on Chief Minister N. Biren Singh, was booked for sedition and later detained for 12 months under the National Security Act.last_img read more

Video: Sailfish Star in Slasher Film

first_imgIf sardines produced a horror film, the vicious serial killer would be a sailfish. Sailfish (Istiophorus platypterus), named for their sail-like dorsal fins, brandish elongated knifelike bills and swim at speeds up to 110 kilometers per hour—12 times faster than Michael Phelps. The function of the pointy bill eluded scientists, though some argued sailfish wield the appendages as a weapon when hunting schooling fish. To test this idea, a team of researchers plunged into the open ocean and recorded over 4 hours of sailfish stalking and preying on schools of round sardines (Sardinella aurita). Analyzing their footage frame by frame, the team compiled the first direct evidence of sailfish using their bills to attack prey. In the above video, a sailfish corrals the sardines into position before slashing through the school with its sharp bill, gashing several fish and creating a cloud of torn scales. The slicing attack employs one of the highest accelerations ever recorded in an aquatic vertebra and is nearly impossible for the sardines to dodge, the team reports online today in the Proceedings of the Royal Society B. The team also spotted sailfish stealthily spearing individual sardines without alarming the rest of the school. By injuring their prey first, the team found that sailfish increase their odds of a successful hunt more than threefold and earn their place as the ocean’s slasher stars.last_img read more

Slideshow: PETA’s crusade against animal research

first_img Dustin Quasar/Flickr anyaivanova/iStock 1996: PETA convinces Gillette to adopt a moratorium on animal testing by holding stock shares and proposing shareholder resolutions at the company’s annual meetings. PETA 2013: PETA launches its International Science Consortium, which promotes and funds animal alternatives in biomedical research. PETA 1981: Pacheco goes undercover at a Silver Spring, Maryland, monkey laboratory, exposing injured animals being kept in filthy conditions. The lead scientist is charged with animal cruelty, the first such conviction for a U.S. researcher. ( 1989: PETA supporters don rabbit suits to persuade several major companies to stop testing on animals. 1992: PETA targets factory farms, launching an undercover investigation into foie gras production that leads to a police raid. 1980: PETA is founded by Ingrid Newkirk and Alex Pacheco. It organizes its first protest against animal research: “World Day for Laboratory Animals.” 2014: PETA protests maternal deprivation experiments at a National Institutes of Health monkey lab with hundreds of ads and disruptions at scientific conferences. Campaign spurs four federal lawmakers to http://news.sciencemag.or Since its founding in 1980, People for the Ethical Treatment of Animals (PETA) has sought to end animal research. Its tactics have changed over the years, as have its targets, which have broadened to include fast food, factory farms, and the cosmetics industry. As PETA shifts gears yet again—launching a new campaign to target animal research by publishing in peer-reviewed scientific literature—Science looks back at its 4-decade crusade.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(*) PETA PETA 2010: After a PETA undercover investigation, Utah legislators prohibit forced selling of shelter cats and dogs for biomedical research. 2000 to 2001: PETA targets fast food companies, convincing McDonald’s, Burger King, and Wendy’s to improve the welfare of the animals used in their food. PETA David Shankbone/Flickr PETA PETA 1986: A Maryland laboratory stops putting chimpanzees in isolation chambers after PETA protests. 2010: PETA activists strip down to protest wearing fur, taking to the streets with signs reading “Love in, fur out.” 1980: PETA is founded by Ingrid Newkirk and Alex Pacheco. It organizes its first protest against animal research: “World Day for Laboratory Animals.” center_img 2009: PETA targets the University of Wisconsin, Madison, labs for using cats in sound localization experiments. The campaign involves bus ads and protests. 2014: After international protests by PETA, China Southern Airlines announces that it will “stop transporting live primates for laboratory experiments on all flights.” Mark Lennihan/AP Images 1994: PETA targets the fur industry, with supporters occupying the office of designer Calvin Klein in New York. 2010: Justin Goodman becomes an associate director of research at PETA. He soon begins publishing in peer-reviewed scientific journals and presenting at meetings. PETA 2012: PETA donates simulators to Egypt so the country will stop using animals in medical trauma training. Steve Rhodes/Flickr PETA 2008: PETA announces a $1 million prize for lab-grown meat, but abandons the prize in 2014, citing lack of interest. PETA ‹› PETA PETA PETA PETA 2011: PETA files a lawsuit in federal court claiming that SeaWorld orcas are “slaves” under the U.S. Constitution’s 13th Amendment. PETA Slideshow: PETA’s crusade against animal research By David GrimmJan. 22, 2015 , 2:00 PM 2014: PETA protests maternal deprivation experiments at a National Institutes of Health monkey lab with hundreds of ads and disruptions at scientific conferences. Campaign spurs four federal lawmakers to http://news.sciencemag.or last_img read more

Ultrasound therapies target brain cancers and Alzheimer’s disease

first_imgFrom imaging babies to blasting apart kidney stones, ultrasound has proved to be a versatile tool for physicians. Now, several research teams aim to unleash the technology on some of the most feared brain diseases.The blood-brain barrier, a tightly packed layer of cells that lines the brain’s blood vessels, protects it from infections, toxins, and other threats but makes the organ frustratingly hard to treat. A strategy that combines ultrasound with microscopic blood-borne bubbles can briefly open the barrier, in theory giving drugs or the immune system access to the brain. In the clinic and the lab, that promise is being evaluated.This month, in one of the first clinical tests, Todd Mainprize, a neurosurgeon at the University of Toronto in Canada, hopes to use ultrasound to deliver a dose of chemotherapy to a malignant brain tumor. And in some of the most dramatic evidence of the technique’s potential, a research team reports this week in Science Translational Medicine that they used it to rid mice of abnormal brain clumps similar to those in Alzheimer’s disease, restoring lost memory and cognitive functions. If such findings can be translated from mice to humans, “it will revolutionize the way we treat brain disease,” says biophysicist Kullervo Hynynen of the Sunnybrook Research Institute in Toronto, who originated the ultrasound method.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(*)Some scientists stress that rodent findings can be hard to translate to humans and caution that there are safety concerns about zapping the brain with even the low-intensity ultrasound used in the new study, which is similar to that used in diagnostic scans. Opening up the blood-brain barrier just enough to get a beneficial effect without scorching tissue, triggering an excessive immune reaction, or causing hemorrhage is the “crux,” says Brian Bacskai, a neurologist at Massachusetts General Hospital in Boston who studies Alzheimer’s disease and used to work with Hynynen.Safely and temporarily opening the blood-brain barrier is a long-sought goal in medicine. About a decade ago, Hynynen began exploring a strategy combining ultrasound and microbubbles. The premise is that ultrasound causes such bubbles to expand and contract, jostling the cells forming the blood-brain barrier and making it slightly leaky. That could help cancer physicians such as Mainprize deliver chemotherapy drugs into the brain. Hynynen also hypothesized that the brief leakage would rev up the brain’s inflammatory response against β amyloid—the toxic protein that clumps outside neurons in Alzheimer’s and may be responsible for killing them. Disposing of such debris is normally the role of the microglia, a type of brain cell. But previous studies have shown that when β amyloid forms clumps in the brain, it “seems to overwhelm microglia,” Bacskai says. Exposing the cells to anti bodies that leak in when the blood-brain barrier is breached could spur them to “wake up and do their jobs,” he says. Some antibodies in blood may also bind directly to the β-amyloid protein and flag the clumps for destruction.Hynynen and others have recently tested the ultrasound strategy in a mouse model of Alzheimer’s. In December 2014, for example, he and colleagues reported in Radiology that the method reduces amyloid plaques in a strain of mice engineered to develop the deposits, leading to improvements in cognition and spatial learning. Microglia consumed more β amyloid after the treatment, suggesting the cells do play a role in the effect, says neuroscientist Isabelle Aubert, who collaborates with Hynynen at Sunnybrook.This week, neuroscientist Jürgen Götz of the Queensland Brain Institute in St. Lucia, Australia, and his Ph.D. student Gerhard Leinenga report that they have built on Hynynen and Aubert’s protocol, using a different mouse model of Alzheimer’s. After injecting these animals with a solution of microscopic bubbles, they scanned an ultrasound beam in a zigzag pattern across each animal’s entire skull, rather than focusing on discrete areas as others have done. After six to eight weekly treatments, the team tested the rodents on three different memory tasks. Alzheimer’s mice in the control group, which received microbubble injections but no stimulation, showed no improvement. Mice whose blood-brain barriers had been made permeable, in contrast, saw “full restoration of memory in all three tasks,” Götz says.The team also found a two- to fivefold reduction in different types of β-amyloid plaques in the brain tissue of the treated group. The attempt to stoke microglia’s appetite appeared to work; Götz and Leinenga found much more β-amyloid protein within the trash-eating cells of treated animals. Yet rousing microglia may not be the only mechanism responsible for the rodents’ memory boost, Aubert notes. She and Hynynen recently reported in Brain Stimulation that ultrasound also boosts the birth and growth of new neurons in mice.Götz and Leinenga next plan to test the whole-brain ultrasound scan method in larger animals with β-amyloid deposits, such as sheep. The approach, which could in theory be used for other brain diseases involving abnormal protein clumps, “is exciting,” says Gerald Grant, a neurosurgeon at the Stanford University School of Medicine in Palo Alto, California. “We’ve been thinking of opening up the blood-brain barrier as a way to get things into the brain, but this pays attention to getting things out.”It’s far from settled that eliminating β-amyloid deposits outside of neurons is the key to treating or stopping Alzheimer’s disease, however. And Bacskai is skeptical that the mouse results say much about the technique’s potential in humans. The range between a mouse that can learn and one that cannot learn “is pretty small,” so big gains in behavioral tests in mice may mean nothing in humans, he says. He adds that nonstandardized ultrasound equipment makes it hard to answer basic safety questions: “How long is the blood-brain barrier open? How big are the pores? What’s the damage?”Hynynen, who is working with a medical imaging company to commercialize the technique, notes that ultrasound application to the brains of animals including rabbits and monkeys has produced no negative side effects. And Mainprize’s clinical trial may provide more safety data. He hopes to open the blood-barrier to increase chemotherapy delivery to a brain cancer patient just before he operates to remove the tumor. Using Hynynen’s technology, he and colleagues will apply ultrasound and microbubbles to tissue in and around the tumor, as well as to several unaffected brain areas. Then they’ll examine excised tissue for hemorrhages and to see if the treatment boosted the concentration of the drug. A similar trial is now recruiting participants in France.If these phase I trials establish safety, “it opens the door for phase II trials looking to see if there’s any benefit” to opening the blood-brain barrier, including for conditions beyond cancer, Mainprize says. Despite his doubts, Bacskai can’t fully resist the dream driving this fledging field. “Imagine if your grandmother went to the clinic once per year, and it cleared amyloid β and that was all it took—no surgery, no drugs. It would be amazing.” EMMANUEL THÉVENOT/LAB OF ISABELLE AUBERT; COURTESY OF SUNNYBROOK RESEARCH INSTITUTE last_img read more

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