Is this Galaxy S10 price drop normal

first_imgThe most major cut seems to be through the site idealo.de – also in Germany. I won’t link to the site directly because I don’t want you to rush out and buy a phone that’s not necessarily compatible with your network here in the USA – but the price is a significant cut. Right now the price of the Samsung Galaxy S10 Plus is approximately €70 lower than initial launch. Let’s assume for a moment that we’re dealing with basic 1:1 monetary units here to make figuring out this situation simple. If the standard price drop for a Galaxy S phone is 140 (from S9 to S10) one year after launch (more than that, but we’re being general), what should the price of the Galaxy S10 be now?Right now we’re at around one year after the reveal/launch of the Galaxy S10. If we split our year into 12 parts for 12 months, we get 1/12 or 0.083. Approximately $999 times 0.083 equals 82.92. So actually, if we’re still being very general about this whole thing, a regular price drop each month on its way to 140 one year later would mean the Galaxy S10 Plus SHOULD have a discount at around 83 right this minute. So we’re right on track! Story TimelineThese clever Galaxy S10 wallpapers embrace the hole-punch cameraGalaxy S10 ultrasonic fingerprint scanner to get software fixesSamsung Galaxy S10 5G has a release date, and its price is bananas Right this minute you can purchase a Samsung Galaxy S9 Plus from Samsung online for $700 USD. You can get a refurbished version of the same phone for around $470. The Samsung Galaxy S9 Plus was initially launched for approximately $840. So the price isn’t exactly massively lowered from initial launch – for that, you’ll want to head back even further. But pay heed – you might want to consider the drawbacks of buying an older-model phone if that’s your plan. Samsung has the Galaxy S10 Plus up on their site right now for $999 USD. That’s the same price as the device was at launch. These are US-based prices for the phone aimed at the US market. If we look at the price chart of this device in its “Duos” edition over at a site like Geizhals (in Germany) you’ll see the price fluctuate a bit, starting in on discounted sales a little less than a month after initial launch. The average price cut here seems to be around €50, give or take a few tenners.On the UK-based version of the price comparison network, Skinflint (that is QUITE the interesting brand name, I must say), they also show sales of discounted versions of the S10 Plus starting in at less than a month after initial launch. That’s for the duos version as well. On average, it would seem that the Galaxy S10 Plus Duos version is selling for around £50 lower than its initial asking price.center_img There’s a certain price drop in effect right now for the Galaxy S10 – and some of our readers have suggested it’s pretty significant. But let’s take a look at price drops around the world real quick and see. Is this really a significant movement in cost, or is this just the way things go with Samsung’s phones every year, and it’s only now that we’ve suddenly started paying attention?last_img read more

Read More
Garmin DriveSmart 65 navigator makes Alexa your car copilot

first_imgOf course, the navigator is fitted with the usual features of a Garmin product. Those include turn-by-turn directions, built-in Wi-Fi, and a set of maps for North American roads and national parks.The Garmin DriveSmart 65 with Amazon Alexa retails for $299.99. In addition to built-in Wi-Fi, it includes a traffic cable and an extra USB port for charging devices. Additional preloaded content includes TripAdivsor traveler ratings, Foursquare POIs, and HERE maps. Voice-controlled actions are becoming popular in homes thanks to smart speakers but, on the road, they’re more than just a convenience. When you need your hands to be on the wheel and your eyes up ahead, voice is pretty much the only form of communication you can have with your phone or your car.With the DriveSmart 65, you can do that not just for the navigation that has made Garmin a household name in that market. You can ask Alexa anything from the weather to playing your music from Amazon Music, Pandora or iHeartRadio, to taking notes for your grocery list. The communication also happens both ways, with you getting notifications from the device as well. When Amazon first announced the Amazon Echo smart speaker and its Alexa assistant, there were some jokes about putting it inside cars somehow. With the Echo Dot and third-party batteries, that almost became possible. Now they won’t have to resort to hacks and workarounds thanks to the new Garmin DriveSmart 65 that not only gets drivers and their passengers to their destination, they can also make their shopping list on the go, all hands-free.last_img read more

Read More
Health Exchanges Set To Launch Oct 1 Amid High Stakes And Political

first_imgPolitico predicts that Tuesday will be a split-screen day — tracking developments related to the government shutdown and launch day of the health law’s online marketplaces. Those who are watching the insurance exchanges note that it may be months after opening day, even years, before it’s possible to assess how well they are working. Politico: As Government Shutdown Looms, Obamacare Exchanges Still Set For Launch It’s looking more and more like Tuesday will be a split-screen day: The government will shut down, and Obamacare will open for business. That’s going to annoy a lot of Republicans — because the ones who are pushing the shutdown are doing so precisely because they want to halt Obamacare (Cunningham and Nather, 9/29).Los Angeles Times: As Key Parts Of Obamacare Kick in, Stakes Are High For Both PartiesThe debate over President Obama’s signature health care law enters a crucial phase this week as the real effect on consumers starts to come into focus after more than 3 1/2 years of partisan claims and counter-claims. For both sides in the protracted battle over what has come to be called Obamacare, it is a moment of political peril (Levey, 9/29).Bloomberg: Obamacare’s Latino Push May Give Democrats Political EdgeThe battle over Obamacare is taking on political importance as Democrats hope a successful roll-out among Hispanics will further bind those voters to the Democratic Party and undermine Republican efforts to build more support before the 2016 presidential election. In California, where Hispanics will outnumber whites within a year, backers of the Affordable Care Act are ramping up outreach in places like Richmond, a San Francisco Bay Area city whose population is almost 40 percent Hispanic and where about 18 percent of residents live below the poverty line (Vekshin, 9/30).The New York Times: U.S. Plans To Unveil New Insurance OptionsThe Obama administration plans on Monday to announce scores of new health insurance options to be offered to consumers around the country by the Blue Cross and Blue Shield Association and the United States Office of Personnel Management, the agency that arranges health benefits for federal employees, according to administration officials. The options are part of a multistate insurance program that Congress authorized in 2010 to increase options for consumers shopping in the online insurance markets scheduled to open on Tuesday (Pear, 2/29).The New York Times: On The Threshold Of Obamacare, WarilyThe insurance marketplaces that form the centerpiece of President Obama’s health care law are scheduled to open on Tuesday, a watershed moment for the Obama administration, but also a crucial turning point for millions of Americans who will finally get the chance to square the law’s lofty ambitions with their own personal needs. While some people desperate for coverage will need no persuading to sign up, for others the decision will amount to a series of complicated calculations that would challenge an accounting whiz, let alone an ordinary human (Thomas and Abelson, 9/28).Kaiser Health News: Three Critical Measures Of Marketplaces’ Impact Could Take Several Years To AssessRev your engines: On Oct. 1 people can start shopping for insurance on the new on-line marketplaces created by the health law. The first weeks and months will be closely watched, but many policy experts say don’t speed to judgment on how well they are working. While people can enroll for insurance until the end of March, real assessments of these marketplaces will take months if not years (Rau, 9/29).NPR: One Key Thing No One Knows About ObamacareTuesday is a big day for Obamacare. The online marketplaces where people can shop for health insurance are supposed to open for business. No one really knows who is going to sign up — not the Obama administration, not the insurance industry, not the president’s critics. Yet the success of the law hangs on this question: Will the right mix of people sign up? In particular, will healthy people buy health insurance? (Kestenbaum, 9/30). Health Exchanges Set To Launch Oct. 1 Amid High Stakes And Political Pressure This is part of the KHN Morning Briefing, a summary of health policy coverage from major news organizations. Sign up for an email subscription.last_img read more

Read More
State Highlights New Va GovernorElect Pledges To Expand Medicaid

first_imgState Highlights: New Va. Governor-Elect Pledges To Expand Medicaid This is part of the KHN Morning Briefing, a summary of health policy coverage from major news organizations. Sign up for an email subscription. A selection of health policy stories from Virginia, Wisconsin, Florida, California and Colorado.The Associated Press/Washington Post: McAuliffe Elected Governor, Defeats Cuccinelli After Pledging To Expand State’s Medicaid RollsIn his emotional concession speech, Cuccinelli also noted the lopsided spending and vowed he would not give up on his fight against Democrats’ national health care law. … From the outset, the campaign shaped up as a barometer of voters’ moods and a test of whether a swing-voting state like Virginia would elect a tea party-style governor. Republicans bet a deeply conservative candidate would be their best shot at holding onto the governor’s office, passing over a lieutenant governor for Cuccinelli, a crusader against the federal health care law (11/6).The Milwaukee Journal Sentinel: Health Plan Cost Increases Below 7% For Large Area EmployersEmployers and employees in the Milwaukee area overall saw larger increases in the cost of health benefits this year than in 2012, with the smallest employers seeing the sharpest increases, according to an annual survey done by HCTrends. The online survey, in which more than 200 employers participated, found that health plan costs increased on average by 8 percent to 10 percent this year compared with an average increases of 5 percent to 7 percent last year (Boulton, 11/5). Miami Herald: Miami-Dade Voters Approve $830 Million For Jackson Health SystemFour months of campaign messages about the long-deferred needs of Jackson Health System and the urgency for the aging public hospital system to more effectively compete against South Florida’s private and not-for-profit hospitals paid off Tuesday (Chang,11/5).The California Health Report: Doctors To Check For Domestic Abuse During Regular ExamsStudies show that the majority of Californians — as many as two-thirds — don’t know where to turn for help if they, or someone they care about, is a victim of domestic violence. Meanwhile, research shows that 44 percent of adult women suffer domestic abuse at some point in their lives, according to figures from Kaiser Permanente. But a new provision of the Affordable Care Act could change those estimates, and soon. As of Jan. 1, health care providers will begin screening all women during regular checkups for signs of domestic abuse (Bookwalter, 11/6).California Healthline: New Map Shows Health Technology ReachCalifornia Health eQuality yesterday released a map of health information organizations across the state. It shows a marked increase from last year’s tally of counties that have some kind of health information exchange network. “It shows progress,” said Rayna Caplan, senior program officer at the UC-Davis Institute for Population and Health Improvement, which oversees the CHeQ program. … The map highlights 35 counties which either have operational or emerging community HIO initiatives. That’s well over half of California’s 58 counties, and it’s a big difference from last year’s progress, Caplan said (Gorn, 11/5).Health Policy Solutions (a Colo. news service): Tepid Recovery Leaves One In Seven UninsuredThe number of uninsured people declined slightly in Colorado over the last two years as the economy began to rebound. But more than 741,000 people — or one in seven Coloradans — has remained uninsured while another 720,000 are underinsured, meaning that their out-of-pocket health costs exceed 10 percent of their income. Nearly half of the uninsured said they’ve gone without health coverage for more than five years and one in 10 have never had it (Kerwin McCrimmon, 11/5).last_img read more

Read More
CMS Pushes Alaska To Become First State To Apply For Waiver To

first_imgCMS Pushes Alaska To Become First State To Apply For Waiver To Change Medicaid Program Into Block Grant System A block grant would transform Medicaid from an open-ended entitlement program into one with capped benefits. The concept, however, is a controversial one that most certainly would create legal battles for the state. Medicaid news comes out of Tennessee, as well. NPR’s Audie Cornish speaks with Nashville Tennessean reporter Brett Kelman about why Tennessee’s health insurance programs dropped more than 100,000 low-income children from the rolls over two years. (Cornish, 4/4) The Trump administration has been urging Alaska’s governor to apply to be the first state to change its Medicaid program funding to a block grant. “Your Medicaid administrator, Seema Verma, has urged us to be the first state to receive Medicaid dollars as a block grant,” Gov. Mike Dunleavy (R) wrote in a letter to President Trump. “We are eager to do this, but your support of her on this ‘first’ will keep the proper focus and speed on this application.” (Weixel, 4/4) The Hill: Trump Administration Urging Alaska To Be First To Apply For Medicaid Block Grant  center_img WBUR: How 128,000 Low-Income Kids Lost Health Care In Tennessee Over 2 Years This is part of the KHN Morning Briefing, a summary of health policy coverage from major news organizations. Sign up for an email subscription.last_img read more

Read More
Bank of Canada could resume hikes if data proves slowdown temporary Poloz

first_img Reuters Reddit The Bank of Canada could start hiking rates again “sometime down the road,” although such a move will depend on whether upcoming economic data backs up its assessment that a current slowdown is only a temporary detour, the central bank’s head said on Thursday.The Bank of Canada has raised interest rates five times since July 2017, although it has stayed on the sidelines in recent decisions as global trade concerns, the slumping oil sector and a weaker housing sector have weighed on the Canadian economy.The bank again held rates steady on Wednesday but took a more dovish stance than in recent releases, removing wording around the need for “future hikes,” while lowering its growth forecasts for 2019.But in a televised interview with Maclean’s magazine on Thursday, Governor Stephen Poloz said the central bank believed the slowdown would be temporary, lasting “a couple of quarters,” and implied the worst was already over. Brent could hit $100 before year-end, but it won’t end well for global economy, analyst says Bank of Canada holds rate, drops bias for future hikes as economy stalls William Watson: Trumpians consider mucking with monetary policy just when it’s working beautifully “What we have to do then is wait and see if the data proves to us that we were right about that,” he said. “Assuming we are, then sometime down the road we’ll be able to say: ‘OK, now it’s time to start normalizing again,’ but that remains to be seen.”Related Stories:Bank of Canada expected to part ways with central bankers around the world todayBank of Canada content to leave rates unchanged, frets about trade war damageHigh-flying loonie could give Bank of Canada pause in this week’s interest rate decisionHe repeated that any move would be data-dependent.The Bank of Canada estimates its neutral range is between 2.25 and 3.25 per cent. The overnight interest rate is currently at 1.75 per cent.Poloz also said there was nothing to signal that Canada was on the verge of recession, but when asked if U.S. President Donald Trump’s protectionist trade policies could provoke a new global recession, he said: “Certainly.”“When you think about the gains in income and living standards that have been created by trade liberalization in a postwar period, to erase even a portion of those would be to risk causing a recession globally,” Poloz said.© Thomson Reuters 2019 Sponsored By: Stephen Poloz, Governor of the Bank of Canada.THE CANADIAN PRESS/Sean Kilpatrick Bank of Canada could resume hikes if data proves slowdown temporary: Poloz The Governor warns that U.S. President Donald Trump’s protectionist trade policies could provoke a new global recession What you need to know about passing the family cottage to the next generation Featured Stories Facebook advertisement Share this storyBank of Canada could resume hikes if data proves slowdown temporary: Poloz Tumblr Pinterest Google+ LinkedIn center_img Recommended For YouEssilorLuxottica looks to buy Dutch eyewear retailer Grandvision – BloombergWall St slips as railroads slide after CSX signals trade impactOne direction: Brexit-hit pound facing gravity of parityGSMA Signs £38 Million Funding Partnership With the Department of International DevelopmentFifth Wall raises $503 mln from property owners seeking tech edge Comment April 26, 20197:55 AM EDT Filed under News Economy Join the conversation → 3 Comments More Email Twitter ← Previous Next →last_img read more

Read More
Tesla is launching a new retail offensive with a focus on malls

first_imgTesla is significantly expanding its retail presence this week with 11 new stores in the US and it’s focusing on locations inside malls with foot traffic. more…The post Tesla is launching a new retail offensive with a focus on malls appeared first on Electrek. Source: Charge Forwardlast_img

Read More
New Jersey launches partnership to develop EV infrastructure

first_img Author Liberty Access TechnologiesPosted on June 25, 2019Categories Electric Vehicle News Source: Electric Vehicles Magazine New Jersey Governor Phil Murphy has launched the New Jersey Partnership to Plug-In, which aims to develop EV infrastructure throughout the state and register 330,000 zero-emission vehicles by 2025.The partnership will be led by the state’s Board of Public Utilities, Department of Environmental Protection and Economic Development Authority. Each participating agency will oversee its own set of tasks, including:Mapping existing and planned charging assetsInstalling EV charging infrastructureWorking with lawmakers to create an EV rebate and inventive programCreating an attractive corporate environmentThe Department of Transportation, Motor Vehicle Commission and Department of Community Affairs will also participate by performing tasks such as installing signage and tracking vehicle registrations.The New Jersey Partnership to Plug-In will also dedicate $7 million of the money it received from Volkswagen settlement funds for fast-charging infrastructure technology.Governor Murphy said, “The New Jersey Partnership to Plug-In ensures that we are working collaboratively across state agencies and with our private sector partners, to not only meet, but exceed our goal of registering 330,000 electric vehicles in New Jersey by 2025. This new initiative is part of our broader effort to make renewable energy solutions work for everyone in New Jersey.”Joseph L. Fiordaliso, New Jersey Board of Public Utilities (NJBPU) President, said, “With the transportation sector contributing more than 40 percent of New Jersey’s greenhouse gas emissions, it is critical that we electrify this industry as part of Governor Murphy’s commitment to 100 percent clean energy by 2050. The NJBPU is eager to partner with our sister agencies in supporting the growth of zero-emission vehicles.” Source: State of New Jerseylast_img read more

Read More
Why Is It So Difficult For Rep Jackie Speier A Lawyer To
first_img Order Your Copy Strategies For Minimizing Risk Under The FCPA A compliance guide with issue-spotting scenarios, skills exercises and model answers. “This book is a prime example of why corporate compliance professionals and practitioners alike continue to listen to Professor Koehler.” Politicians of any party are entitled to whatever opinions they have regarding public policy issues or other politicians.However, they are not entitled to opinions about the basics of a law and what it captures.Representative Jackie Speier (D-CA) is a lawyer and received a J.D. from UC Hastings College of the Law.  As such presumably she knows how to read a statute and determine its essential elements.Yet time and time again, as it relates to Representative Speier’s views on President Donald Trump, she has displayed a shocking misunderstanding of what the Foreign Corrupt Practices Act covers.As highlighted in this 2017 post, Representative Speier stated on MSNBC’s Hardball:“[I]f you do business in any country where you believe that there is money that`s being used that is being laundered, you`re subject to the Foreign Corrupt Practices Act.”As highlighted in this February 2019 post, Representative Speier went on CNN and proclaimed the following about the FCPA:“It is a requirement that anyone doing business with a foreign entity make sure that none of the money that comes into a project has been laundered.”Most recently, Representative Speier went on CNN and continued to make false and misleading statements about the FCPA. She stated:“[W]e see that [President Trump] is willing to engage in criminal conduct, whether it’s in the White House or before he even became president. When he was willing to accept money from anyone and not comply with the Foreign Corrupt Practices Act, which would require him to determine whether the money was laundered. And he accepted a lot of cash for many of his real properties. So you have criminality there.”Dear Representative Speier:Here is a copy of the FCPA statute. If you have any questions about the statute and what it covers, I’d be happy to answer questions. In fact, you can reach me at fcpaprofessor@gmail.com. Should you have any further questions, I invite you to my two-day FCPA Institute to elevate your FCPA knowledge.Regardless, please stop spreading false and misleading information about the FCPA. As a lawyer, you should really know better.To the media who continue to provide Representative Speier a platform to spread false and misleading information about a law – why?last_img
Read More
Locke Lord Busy Boosting Energy Practice

first_img Lost your password? Password Remember me Usernamecenter_img The firm has announced two lateral moves to its energy practice over the past few weeks . . .You must be a subscriber to The Texas Lawbook to access this content. Not a subscriber? Sign up for The Texas Lawbook.last_img

Read More
Wenatchee celebrates Multicultural Community and MLK Junior DayWeather Prompts After School CancellationsBreakfast

first_imgOver two dozen groups from North Central Washington will display art, food, crafts, and more of their cultural heritage at the City of Wenatchee’s Multicultural and Martin Luther King Jr. Festival on Saturday at the Wenatchee Valley Museum.For the first time this year, the museum has created an exhibit about the life of Martin Luther King Jr.  The event starts at 10am with the City of Wenatchee presentation of Civil Rights and Social Justice Awards  set for approximately 10:30am.The festival features hands-on cultural experiences for kids.  Each child will receive a sticker for their passport when they visit booths and learn about a different culture. Live musicians will perform Celtic, Mariachi, American Folk, Chinese and Native American Flute music throughout the event.  The festival runs from 10am to 4pm at the museum, 127 S. Mission St. and is free to attend. A free lunch will be provided while supplies last starting at 11am by Paradise Restaurant.  Sponsors include Chelan PUD, Coordinated Care and Real Solutions  and HealthCarelast_img read more

Read More
Driver Flees Deputy Crashes On Odabashian BridgeMonday Night Shooting Under InvestigationUPDATE Grant

first_imgA man who failed to pull over for a traffic stop tried to flee a Chelan County Sheriff’s Deputy and crashed his pickup into another vehicle at the east end of Odabashian Bridge near Sunset Highway.Chelan County Sheriff Brian Burnett said his deputy tried to stop a vehicle at the west end of the bridge but stopped the pursuit when the suspect began to reach 100 mph in heavy traffic.  The suspect continued eastbound over the bridge and lost control, colliding with a pickup.  The suspect and the driver of he vehicle that was rear ended were both transported to Central Washington Hospital but Sheriff Burnett did not know the extent of their injuries.The suspect, a 26 year old Wenatchee man was booked into the Chelan County Regional Jail and was  facing several charges including felony eluding.last_img read more

Read More
Richard Taylors Last Newsletter

first_imgby, Kavan Peterson, Editor, ChangingAging.orgTweet7Share26Share4Email37 Shares Dr. Richard TaylorSubscriber’s to the late Richard Taylor’s e-newsletter Alzheimer’s From the Inside Out had the bittersweet privilege of receiving his last email yesterday with a forward from his brother Jason:To  All:I could never thank all of you enough for all the kind words you have sent to our family about Richard. Many of you have sent the most amazing stories about how you met Richard, projects you worked on, and even how he touched your lives in his own unique way. That was the Richard I grew up knowing. As promised I am sending out the last newsletter Richard started. I am going to send it out exactly as he left it and hope this will still provide everyone some helpful information. So apologies in advance for the lack of editing. In the near future I will have to close down Richard’s E-mail account. I know some of you still have a few projects working with Richard which I am doing everything I can to jump in and help see completed. So I ask that any of you who need my direct contact information to please reply and I will be sure to get it to you.The first question I am continually asked is who will take Richard’s place in this fight? My personal wish is not for any one person to replace him. I would wish to see hundreds if not thousands that take his place and all STANDUP AND SPEAK OUT!-JasonChangingAging usually republishes Richard’s newsletters in full but to view his final email we’d like to direct readers to Ken Clasper’s blog Living Well with Lewy Body Dementia, where it has been published. As Jason argues, we need hundreds and thousands of people living with dementia to stand up and speak out on behalf of themselves.On August 19, the Dementia Alliance International will host an online tribute for Richard, who was a founding member:The members of DAI send their deepest sympathy to his family and close friends, and we hope they know how much he was loved and will continue to positively influence the dementia community.This Tribute to Richard is your opportunity to remember Richard amongst others who also loved him.There will be a number of speakers, including Dr Al Power paying their respects to Richard, followed by the opportunity for you to express in your own words (max 2  minutes), the influence Richard had on your life.Click here to register.Related PostsFor Richard Taylor The Battle Gets TougherIn this week’s edition of Dr. Richard Taylor’s influential newsletter Alzheimer’s from the Inside Out, Richard shared the difficult news that in addition to being a leading advocate for and person living with dementia he is now also a person living with a rare and dangerous form of cancer.Hello, Richard“Hello. My name is Richard, and I have dementia, probably of the Alzheimer’s type.” These are the words Dr. Richard Taylor used to open each of his presentations, as he enlightened the world about the lived experience of changing cognitive ability. Richard passed away at his home on July 25th,…Latest Alzheimer’s From The Inside Out NewsletterThe latest edition of Richard Taylor’s newsletter Alzheimer’s From the Inside Out was published today. If you want a deeper understanding of dementia, and the people who live with it, I highly recommend you become a subscriber by clicking here. Here’s what Richard has to say about the latest research…Tweet7Share26Share4Email37 SharesTags: Alzheimers Dementia Richard Taylorlast_img read more

Read More
Fights with spouse may worsen symptoms for people with chronic conditions

May 15 2018A fight with a spouse may end in hurt feelings, but for those with chronic conditions like arthritis or diabetes, those arguments may have physical repercussions as well, according to researchers.They found that in two groups of older individuals — one group with arthritis and one with diabetes — the patients who felt more tension with their spouse also reported worse symptoms on those days.”It was exciting that we were able to see this association in two different data sets — two groups of people with two different diseases,” said Lynn Martire, professor of human development and family studies, Penn State Center for Healthy Aging. “The findings gave us insight into how marriage might affect health, which is important for people dealing with chronic conditions like arthritis or diabetes.”Martire said it’s important to learn more about how and why symptoms of chronic disease worsen. People with osteoarthritis in their knees who experience greater pain become disabled quicker, and people with diabetes that isn’t controlled have a greater risk for developing complications.The researchers said that while previous research has shown a connection between satisfying marriages and better health, both physically and psychologically, there’s been a lack of research into how day-to-day experiences impact those with chronic illness.”We study chronic illnesses, which usually involve daily symptoms or fluctuations in symptoms,” Martire said. “Other studies have looked at the quality of someone’s marriage right now. But we wanted to drill down and examine how positive or negative interactions with your spouse affect your health from day to day.”Data from two groups of participants were used for the study. One group was comprised of 145 patients with osteoarthritis in the knee and their spouses. The other included 129 patients with type 2 diabetes and their spouses.Related StoriesHow a simple MRI scan can help patients with anginaSleep quality and fatigue among women with premature ovarian insufficiencyOpioid overdose deaths on the decline says CDC but the real picture may still be grimParticipants in both groups kept daily diaries about their mood, how severe their symptoms were, and whether their interactions with their spouse were positive or negative. The participants in the arthritis and diabetes groups kept their diaries for 22 and 24 days, respectively.The researchers found that within both groups of participants, patients were in a worse mood on days when they felt more tension than usual with their spouse, which in turn led to greater pain or severity of symptoms.Additionally, the researchers found that within the group with arthritis, the severity of the patient’s pain also had an effect on tensions with their spouse the following day. When they had greater pain, they were in a worse mood and had greater tension with their partner the next day.”This almost starts to suggest a cycle where your marital interactions are more tense, you feel like your symptoms are more severe, and the next day you have more marital tension again,” Martire said. “We didn’t find this effect in the participants with diabetes, which may just be due to differences in the two diseases.”Martire said the results — recently published in the journal Annals of Behavioral Medicine — could potentially help create interventions targeted at helping couples with chronic diseases.”We usually focus on illness-specific communications, but looking at tension in a marriage isn’t tied to the disease, it’s not a symptom of the disease itself,” Martire said. “It’s a measure you can get from any couple. It suggests to me that looking beyond the illness, to improve the overall quality of the relationship might have some impact on health.”Source: http://news.psu.edu/story/520727/2018/05/15/research/love-hurts-spats-spouse-may-worsen-chronic-pain-other-symptoms read more

Read More
Researchers identify novel mutation in amyloid diseases

first_imgJun 26 2018Researchers have identified a one-of-a kind mutation in the DNA of a patient who died of transthyretin (TTR) amyloidosis, a progressive condition characterized by the buildup of abnormal deposits of a misfolded protein called amyloid in the body’s organs and tissues.The findings, published in the journal Proceedings of the National Academy of Sciences, may help identify much-needed new targets for treatment of this debilitating disease which can lead to organ failure and even death.Protein misfolding (when a protein structure does not assume its functional state) underlies a number of diseases including cystic fibrosis, Alzheimer’s disease, dementia and Parkinson’s disease among others. Amyloid formation by a misfolded protein causes some of these and other diseases, including TTR amyloidosis, a common form of systemic amyloid disease worldwide.According to John Berk, MD, associate clinical director of the Amyloid Treatment and Research Program at Boston University School of Medicine (BUSM) who treated the patient, the strategy of stabilizing the structure of a mutated protein to prevent its misfolding works for many patients with familial TTR amyloidosis. “Studying those that do not respond to treatment provides critical insights into the molecular basis of the disease and offers new strategies for better treatments.” The patient with this new TTR mutation did not respond to treatment. The researchers wanted to understand why the drug was ineffective.In order to determine how this new mutation in TTR affects the structural stability and misfolding of the protein and its interactions with the drug used to treat the disease, lead author Elena Klimtchuk, PhD, research scientist at BUSM, generated recombinant proteins that mimic normal transthyretin and its disease-causing variants. These proteins were then analyzed by Klimtchuk and colleagues using a battery of biophysical, biochemical and bioinformatics methods. The results showed that the mutation greatly destabilized the protein and enhanced amyloid formation, and that the drug failed to block this deleterious process.Related StoriesNew gene-editing protocol allows perfect mutation-effect matchingSchwann cells capable of generating protective myelin over nerves finds researchGene-editing could shorten life instead of prolonging, suggests new study”We were surprised to find that the mutation had little, if any, effect on the drug binding to its target protein, TTR. We suspect that a higher dose of this drug is unlikely to help patients with this gene mutation,” explained corresponding author Olga Gursky, PhD, professor of Physiology and Biophysics at BUSM.The researchers believe this study helps explain why the drug that is currently used to treat TTR amyloidosis has limited effect and does not work for all patients. “Our findings indicate that new drugs must target different sites on the protein to stabilize TTR and inhibit its deposition as amyloid,” added Gursky.This study impacts the treatment of TTR amyloidosis, a debilitating and deadly disease that affects approximately 40,000 worldwide, and has broader implications for understanding the molecular basis of other amyloid diseases caused by various proteins. “Increasing our understanding of the protein misfolding processes and how drugs intended to stabilize the particular protein succeed and fail provides insights into the design of more effective drugs.” Source:https://www.bmc.orglast_img read more

Read More
From crib to court Trump administration summons immigrant infants

first_imgChristina Jewett: ChristinaJ@kff.org, @by_cjewettShefali Luthra: ShefaliL@kff.org, @Shefalil This article was reprinted from khn.org with permission from the Henry J. Kaiser Family Foundation. Kaiser Health News, an editorially independent news service, is a program of the Kaiser Family Foundation, a nonpartisan health care policy research organization unaffiliated with Kaiser Permanente. Jul 19 2018The Trump administration has summoned at least 70 infants to immigration court for their own deportation proceedings since Oct. 1, according to Justice Department data provided to Kaiser Health News.These are children who need frequent touching and bonding with a parent and naps every few hours, and some were of breastfeeding age, medical experts say. They’re unable to speak and still learning when it’s day versus night.”For babies, the basics are really important. It’s the holding, the proper feeding, proper nurturing,” said Shadi Houshyar, who directs early childhood and child welfare initiatives at advocacy group Families USA.The number of infants under age 1 involved has been rising — up threefold from 24 infants in the fiscal year that ended last Sept. 30, and 46 infants the year before.The Justice Department data show that a total of 1,500 “unaccompanied” children, from newborns to age 3, have been called in to immigration court since Oct. 1, 2015.Roughly three-fourths of the children involved are represented by a lawyer and they have to make their case that they should stay in the United States.Officials who review such deportation cases say most children under 1 cross the border with a parent and their deportation cases proceed together.But some of the infants were deemed “unaccompanied” only after law enforcement separated them from their parents during the Trump administration’s “zero-tolerance” immigration policy. The children were sent to facilities across the U.S. under the supervision of the Department of Health and Human Services.”This is to some extent a … crisis of the creation of the government,” said Robert Carey, who previously headed the Office of Refugee Resettlement, which takes custody of unaccompanied minors. “It’s a tragic and ironic turn of events.”Younger children are also considered unaccompanied if they enter the U.S. with an older family member who is not yet 18. The data do not clarify which children arrived that way or which were separated from their parents.The Justice Department did not respond to a request for further data about where the children are housed. They could be in a foster care home, at a group home, with a relative or sponsor or reunited with a parent. HHS, which operates the refugee resettlement office, did not provide comment by publication  time.In previous statements, the government has argued that separation — and its consequences — are unfortunate but unavoidable under the law.”There is a surefire way to avoid separation from your children. Present yourself legally … or stay back at your home country, and go through the process others do,” HHS Secretary Alex Azar said on a media call earlier this month. “None of us want children separated from their parents. I want no children in our care and custody.”The number of unaccompanied children called in to court since Oct. 1, 2015, swells to 2,900 if kids up to 5 are included. The total will rise between now and Sept. 30, when the fiscal year ends, noted Susan Long, a statistician at Syracuse University and director of TRAC, a repository of immigration and federal court data. There’s also an ongoing backlog in entering the data.In June, a district judge in San Diego ordered the government to reunify families within a month, specifically directing them to unite children younger than 5 with parents by July 10.HHS reunited about half of those children by July 12 — 57 out of 103. Others, the government said, could not be placed with a parent, citing in some cases “serious criminal history” or parents currently being in jail.In 12 cases, those children’s parents had already been deported. In another, the government had failed to figure out where the child’s parent was located, and in another, the parent had a “communicable disease,” HHS said.The Department of Homeland Security, which issues the court orders, also did not respond to a request for comment.In the removal cases, children have no right to an appointed lawyer, but rather to a list of legal aid attorneys that the child’s current caregiver can contact.And young children rarely know the details of why they fled their home country, especially without a parent present, noted Eileen Blessinger, a Virginia-based immigration lawyer who has been aiding parents.Related StoriesNew curriculum to improve soft skills in schools boosts children’s health and behaviorResearch questions whether tongue-tie surgery to improve breastfeeding is neededNew network for children and youth with special health care needs seeks to improve systems of care”Think about it as a parent. You’re not going to tell your child they might be killed, right?” she said. “A lot of the kids don’t know.”Immigration court, which is an administrative unit of the Department of Justice, is different from typical courts. It handles “respondents” who may be too young to speak, but has no social workers or legal remedies focused on the best interest of a child, said Lenni Benson, a New York Law School professor and founder of the Safe Passage  Project, which provides legal services to migrant youth.”An immigration judge has no discretion,” Benson said. “There’s no ‘I’m hearing the mom wants the kid, I’m going to decide what’s best,'” she said. Instead, “it’s ‘the government has charged you with being removable from the U.S. Do you have evidence to show you have a right to be here?'”Benson recounted being in immigration court in 2014 when a judge asked for a crying baby to be removed from the courtroom. She said she paused to inform the judge that the baby was the next respondent on the docket — and asked that the child’s grandmother stand in.The stakes for the babies, and any migrant fleeing violence, are high, said Paul Wickham Schmidt, a former immigration judge who retired in 2016 after 13 years on the bench in Arlington, Va.”Final orders of deportation have consequences,” he said. “For something that has a very serious result, this system has been described as death penalty cases in traffic court.”Ashley Tabaddor, president of the National Association of Immigration Judges and a judge specializing in juvenile cases in Los Angeles, acknowledged that the administration narrowed a directive on how much judges can assist juveniles in court. Still, she said, judges do their best to ensure that young children get a fair hearing.Justice Department data show that asylum denials are at a nearly 10-year high at 42 percent, and the Associated Press reported that the administration has raised the bar for making a successful case.At the same time, children can be strapped for resources, Blessinger said.She described one client whose 7-year-old daughter received legal support from a New York-based charity. Even in that case, she said, the organization acted simply as a “friend of the court” — rather than a full-fledged attorney — requesting delays in proceedings until the child and mother could be reunited. That finally happened Tuesday night, she said.”It’s the saddest experience. These people are not going to be recovering anytime soon,” she said. “The parents are crying even after they’re reunited.”KHN’s coverage of children’s health care issues is supported in part by the Heising-Simons Foundation. last_img read more

Read More
Study Greening vacant urban land reduces feelings of depression for surrounding residents

first_imgJul 20 2018Greening vacant urban land significantly reduces feelings of depression and improves overall mental health for the surrounding residents, researchers from the Perelman School of Medicine and the School of Arts & Sciences at the University of Pennsylvania and other institutions show in a new randomized, controlled study published in JAMA Network Open. The findings have implications for cities across the United States, where 15 percent of land is deemed “vacant” and often blighted or filled with trash and overgrown vegetation.For the first time, the research team measured the mental health of Philadelphia residents before and after nearby vacant lots had been converted into green spaces, as well as residents living near untreated abandoned lots, and those that just received trash clean-up. They found that people living within a quarter of a mile radius of greened lots had a 41.5 percent decrease in feelings of depression compared to those who lived near the lots that had not been cleaned. Those living near green lots also experienced a nearly 63 percent decrease in self-reported poor mental health compared to those living near lots that received no intervention.The findings add to the growing body of evidence showing how revitalized spaces in blighted urban areas can help improve safety and health, such as reducing crime, violence, and stress levels. The most recent study from the same team in February found up to a 29 percent decrease in gun violence near treated lots. This latest work is believed to be the first experimental study to test changes in the mental health of residents after nearby vacant lots were greened.”Dilapidated and vacant spaces are factors that put residents at an increased risk of depression and stress, and may explain why socioeconomic disparities in mental illness persist,” said lead author Eugenia C. South, MD, MSHP, an assistant professor of Emergency Medicine and a member of the Center for Emergency Care and Policy Research at Penn. “What these new data show us is that making structural changes, like greening lots, has a positive impact on the health of those living in these neighborhoods. And that it can be achieved in a cost-effective and scalable way – not only in Philadelphia but in other cities with the same harmful environmental surroundings.”For the trial, 541 vacant lots throughout Philadelphia were randomly assigned to one of three study arms: greening intervention, a trash clean-up intervention, or a control group with no intervention. The greening intervention involved removing trash, grading the land, planting new grass and a small number of trees, installing a low wooden perimeter fence, and regular monthly maintenance. The trash clean-up involved removing trash, limited grass mowing where possible, and regular monthly maintenance. The Pennsylvania Horticultural Society LandCare program performed the greening, trash clean-up, and maintenance.Related StoriesScientists describe microbiome composition in patients suffering from IBD and PSCTeens who can describe negative emotions are better protected against depressionPerinatal depression screenings may overlook women having suicidal ideationTwo sets of pre-intervention and post-intervention mental health surveys were performed among 342 people, 18 months before revitalization and 18 months after. Researchers used the Kessler Psychological Distress Scale (K6), a widely used community screening tool, to evaluate the prevalence of serious mental illness in the community. Participants were asked to indicate how often they felt nervous, hopeless, restless, depressed, that everything was an effort, and worthless.Results were most pronounced when looking only at neighborhoods below the poverty line, with feelings of depression among residents who lived near green lots decreasing significantly–by more than 68 percent.Analyses of the trash clean-up intervention compared to no intervention showed no significant changes in self-reported mental health.”The lack of change in these groups is likely because the trash clean-up lots had no additional green space created,” said co-author John MacDonald, PhD, a professor of criminology and sociology at Penn. “The findings support that exposure to more natural environments can be part of restoring mental health, particularly for people living in stressful and chaotic urban environments.”The study shows transforming blighted neighborhood environments into green space can improve the trajectory of the residents’ mental health, the authors said. Adding green space to neighborhoods should be considered alongside individual treatments to address mental health problems in low resource communities. Additionally, greening is an affordable approach, costing about $1,600 per vacant lot and $180 per year to maintain. For these reasons, the authors said, vacant lot greening may be an extremely attractive intervention for policy makers seeking to address urban blight and promote health.”Greening vacant land is a highly inexpensive and scalable way to improve cities and enhance people’s health while encouraging them to remain in their home neighborhoods,” said senior author Charles C. Branas, PhD, chair of Epidemiology at Columbia University and an adjunct professor in the department of Biostatistics and Epidemiology at Penn’s Perelman School of Medicine. “While mental health therapies will always be a vital aspect of treatment, revitalizing the places where people live, work, and play, may have broad, population-level impact on mental health outcomes.”Source: https://www.pennmedicine.org/news/news-releases/2018/july/greening-vacant-lots-reduces-feelings-of-depression-in-city-dwellers-penn-study-findslast_img read more

Read More
New system accelerates discovery of chemical compounds that inhibit enzyme implicated in

first_img Source:http://www.asbmb.org/ Reviewed by James Ives, M.Psych. (Editor)Sep 6 2018Researchers at the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health, have developed a system to accelerate the discovery of chemical compounds that inhibit an enzyme implicated in a number of cancers. The set of tools and methods, which the researchers used to test more than 16,000 compounds, is described in a new paper published in the Journal of Biological Chemistry.The enzyme, NSD2, is overactive in cancers such as acute lymphoblastic leukemia and certain types of multiple myeloma, so inhibiting NSD2 activity seems like a promising strategy for treating those conditions. But, so far, researchers have not been able to find any chemicals that reliably block NSD2 even in a test tube in the laboratory, much less to test as drug candidates in living models.”There’s a total lack of available chemical probes, druglike molecules, to help study (NSD2) function,” said Matthew Hall, the NCATS scientist who oversaw the new work.Part of the reason it’s been difficult to discover chemical inhibitors of NSD2 is that the enzyme is difficult to work with in the laboratory. NSD2 modifies histones, the proteins around which DNA is wound. For technical reasons, scientists ordinarily would study this kind of activity using a fragment of the enzyme and a fragment of histone protein. But NSD2 works on only whole nucleosomes: units of histone protein in combination with DNA.”(NSD2 and similar proteins) are very picky, because they prefer to only act on whole nucleosomes,” Hall said. “They’re snobby when it comes to what they’re willing to interact with.”Related StoriesInhibition of p38 protein boosts formation of blood vessels in colon cancerResearch sheds light on sun-induced DNA damage and repairMother calls for protein shake regulation after daughter diesCollaborating with the biotechnology company Reaction Biology, Hall’s team, including lead author Nathan Coussens, developed laboratory tests involving whole nucleosomes that could be used to see whether NSD2 was able to modify histone proteins in the presence of various compounds. The compounds the team tested came from NCATS’s massive library of bioactive chemicals.But finding a compound that appears to block NSD2 activity is only the beginning. To confirm that the chemicals identified in the initial massive screen were indeed bona fide inhibitors that would reliably and reproducibly perform this function in future researchers’ studies, the NCATS team needed to use multiple types of biochemical methods to confirm the activity of each compound.”We screened 16,000 molecules, and we got 174 hits, but that doesn’t mean they all really work,” Hall said. “When we whittle away through the (additional screening methods), we get down to 44 molecules. You triage candidates out of your screen after you rigorously ask your molecule to prove itself to you.”With several molecules now having proved themselves in this round of screening, Hall’s team hopes to continue the search for reliable NSD2 inhibitors that can be used as research tools and then, further down the road, possibly as medicines.”We are in the process of planning to screen hundreds of thousands of molecules in order to find molecules that can be optimized for inhibition of NSD2 and disseminate these to the research community,” Hall said.last_img read more

Read More
This ball of gas is racing around the black hole at our

first_imgFollowing up on the serendipitous discovery, the astronomers saw the three flares move in small 45-minute orbits, and the polarization of their light rotated full circle in the same period. The scientists calculated that this must be material circulating around the black hole, just outside the closest orbit in which objects can move without being sucked in. The finding, the team says, is another firm piece of evidence that Sagittarius A* is the galaxy’s fathomless dark heart. Email By Daniel CleryOct. 31, 2018 , 5:00 AM Earlier this year, astronomers were looking for signs that S2, the star with the closest known orbit to the supermassive black hole thought to be at the center of the Milky Way, might—as predicted by Albert Einstein—deviate from the orbital path prescribed by Newtonian gravity.But while they were watching, they spied something else: three bright infrared flares unrelated to the star (visualization above). Those flares, the researchers reveal today, are the signs of superheated gas racing almost as close to the black hole as possible without getting sucked in—at 30% the speed of light.Observing the action so close to the galactic center, known as Sagittarius A*, is extremely challenging because it is distant, small, and shrouded in gas and dust. The team used the world’s largest optical instrument, the European Southern Observatory’s Very Large Telescope in Chile, and combined the light of its four 8.2-meter mirrors to get the resolution of a 130-meter virtual telescope using a new instrument called GRAVITY. This ball of gas is racing around the black hole at our galaxy’s heart Click to view the privacy policy. Required fields are indicated by an asterisk (*) ESO/Gravity Consortium/L. Calçada Sign up for our daily newsletter Get more great content like this delivered right to you! Country Country * Afghanistan Aland Islands Albania Algeria Andorra Angola Anguilla Antarctica Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia, Plurinational State of Bonaire, Sint Eustatius and Saba Bosnia and Herzegovina Botswana Bouvet Island Brazil British Indian Ocean Territory Brunei Darussalam Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Cayman Islands Central African Republic Chad Chile China Christmas Island Cocos (Keeling) Islands Colombia Comoros Congo Congo, the Democratic Republic of the Cook Islands Costa Rica Cote d’Ivoire Croatia Cuba Curaçao Cyprus Czech Republic Denmark Djibouti Dominica Dominican Republic Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Falkland Islands (Malvinas) Faroe Islands Fiji Finland France French Guiana French Polynesia French Southern Territories Gabon Gambia Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guatemala Guernsey Guinea Guinea-Bissau Guyana Haiti Heard Island and McDonald Islands Holy See (Vatican City State) Honduras Hungary Iceland India Indonesia Iran, Islamic Republic of Iraq Ireland Isle of Man Israel Italy Jamaica Japan Jersey Jordan Kazakhstan Kenya Kiribati Korea, Democratic People’s Republic of Korea, Republic of Kuwait Kyrgyzstan Lao People’s Democratic Republic Latvia Lebanon Lesotho Liberia Libyan Arab Jamahiriya Liechtenstein Lithuania Luxembourg Macao Macedonia, the former Yugoslav Republic of Madagascar Malawi Malaysia Maldives Mali Malta Martinique Mauritania Mauritius Mayotte Mexico Moldova, Republic of Monaco Mongolia Montenegro Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands New Caledonia New Zealand Nicaragua Niger Nigeria Niue Norfolk Island Norway Oman Pakistan Palestine Panama Papua New Guinea Paraguay Peru Philippines Pitcairn Poland Portugal Qatar Reunion Romania Russian Federation Rwanda Saint Barthélemy Saint Helena, Ascension and Tristan da Cunha Saint Kitts and Nevis Saint Lucia Saint Martin (French part) Saint Pierre and Miquelon Saint Vincent and the Grenadines Samoa San Marino Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Singapore Sint Maarten (Dutch part) Slovakia Slovenia Solomon Islands Somalia South Africa South Georgia and the South Sandwich Islands South Sudan Spain Sri Lanka Sudan Suriname Svalbard and Jan Mayen Swaziland Sweden Switzerland Syrian Arab Republic Taiwan Tajikistan Tanzania, United Republic of Thailand Timor-Leste Togo Tokelau Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Turks and Caicos Islands Tuvalu Uganda Ukraine United Arab Emirates United Kingdom United States Uruguay Uzbekistan Vanuatu Venezuela, Bolivarian Republic of Vietnam Virgin Islands, British Wallis and Futuna Western Sahara Yemen Zambia Zimbabwelast_img read more

Read More
How long do vaccines last The surprising answers may help protect people

first_img Tetanus 34.75% Long-lived plasma cells (top) may be a key to more durable vaccines. Viruslike particles (bottom), made of virus surface proteins, can trigger a lasting antibody response from the cells. (GRAPHIC) N. DESAI/SCIENCE; (DATA) J. FERDINANDS ET AL., CLINICAL INFECTIOUS DISEASES, VOL. 64, 544, 2017 Flu protection plummets Seasonal flu vaccines protect against several influenza strains, including H3N2, the one that vaccines typically have the most trouble stopping. These U.S. data from 2011–2015 analyzed the effectiveness of vaccines against H3N2. Researchers are ramping up efforts to figure out why some vaccines protect for mere weeks but others work for life. “We simply don’t know what the rules are to inducing long-lasting immunity,” says Plotkin, who began to research vaccines in 1957. “For years, we were making vaccines without a really deep knowledge of immunology. Everything of course depends on immunologic memory, and we have not systematically measured it.”Bali Pulendran, an immunologist at Stanford University in Palo Alto, California, has reached the same frustrating conclusion about vaccine durability. “I keep saying, ‘It’s not well understood, it’s not well understood.’ This is one of the major issues in vaccines.” Deepening the confusion, two essential vaccines, against diphtheria and tetanus, appear to have better durability than widely presumed.Yet some clues are surfacing from unusually successful vaccines that drive the immune system to mount effective responses for decades, if not an entire human life. One comes from the vaccine against the cancer-causing, sexually transmitted human papillomavirus (HPV), which has proved remarkably durable since it debuted about a decade ago, spotlighting a novel mechanism of long-lasting protection. New insights about durability are also leading researchers to more intensively scrutinize the vaccine booster recommendations by ACIP and similar oversight bodies.Still, Wayne Koff, an immunologist who heads the nonprofit Human Vaccines Project in New York City, says vaccine durability deserves far more attention than it has received. “If you could understand this,” Koff says, “you could make all vaccines better.”Mimicking natural immunityMore than 150 years ago, a natural experiment on a rocky, volcanic archipelago between Scandinavia and Iceland proved that an infection can trigger lifelong immunologic memory. Measles raced through residents of the Faroe Islands in 1781. The disease did not reappear on the isolated island group for 65 years, when a visitor brought it back. A thorough study found that no one alive during the first outbreak became ill again. Their elderly immune systems remembered and fought off the virus.Vaccinemakers aim to duplicate such spectacular feats of immune memory. They create harmless mimics of disease-causing viruses or bacteria, or their toxins, designed to teach immune systems to recognize the real thing and quickly mount robust immune responses. Immunologists believe that for many infectious diseases, long-lived memory B cells are key to that response. When confronted by known enemies, those cells quickly expand and produce hordes of antibodies that latch onto the invaders, preventing infections. Vaccines also can train “killer” T cells, which mop up when antibodies fail, eliminating infected cells.”For a lot of the things we have vaccines against, antibodies are probably the protective mechanism,” says Mark Slifka, an immunologist who specializes in vaccine studies at the Oregon National Primate Research Center in Beaverton. “For the hard ones to vaccinate against—TB [tuberculosis], malaria, HIV—antibodies play some role, but you need T cells.”Vaccine designers debate the best way to trigger those responses. Some designers hold fast to the idea that a live but weakened pathogen—or genes from it stitched into a harmless virus that acts as a Trojan horse—induces the longest-lasting, most robust responses. Just such a weakened virus is the basis of the measles vaccine, for example, which protects for life. But Pulendran calls this notion simpleminded. He and others argue that a killed pathogen or a genetically engineered variant of it can work equally well.For the flu, both killed (also known as inactivated) and live virus vaccines exist—and neither offers sturdy protection. Even when they closely match the circulating strains of influenza viruses, both types protect only about 60% of vaccinated people. And those modest immune responses rapidly wane. Country * Afghanistan Aland Islands Albania Algeria Andorra Angola Anguilla Antarctica Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia, Plurinational State of Bonaire, Sint Eustatius and Saba Bosnia and Herzegovina Botswana Bouvet Island Brazil British Indian Ocean Territory Brunei Darussalam Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Cayman Islands Central African Republic Chad Chile China Christmas Island Cocos (Keeling) Islands Colombia Comoros Congo Congo, the Democratic Republic of the Cook Islands Costa Rica Cote d’Ivoire Croatia Cuba Curaçao Cyprus Czech Republic Denmark Djibouti Dominica Dominican Republic Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Falkland Islands (Malvinas) Faroe Islands Fiji Finland France French Guiana French Polynesia French Southern Territories Gabon Gambia Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guatemala Guernsey Guinea Guinea-Bissau Guyana Haiti Heard Island and McDonald Islands Holy See (Vatican City State) Honduras Hungary Iceland India Indonesia Iran, Islamic Republic of Iraq Ireland Isle of Man Israel Italy Jamaica Japan Jersey Jordan Kazakhstan Kenya Kiribati Korea, Democratic People’s Republic of Korea, Republic of Kuwait Kyrgyzstan Lao People’s Democratic Republic Latvia Lebanon Lesotho Liberia Libyan Arab Jamahiriya Liechtenstein Lithuania Luxembourg Macao Macedonia, the former Yugoslav Republic of Madagascar Malawi Malaysia Maldives Mali Malta Martinique Mauritania Mauritius Mayotte Mexico Moldova, Republic of Monaco Mongolia Montenegro Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands New Caledonia New Zealand Nicaragua Niger Nigeria Niue Norfolk Island Norway Oman Pakistan Palestine Panama Papua New Guinea Paraguay Peru Philippines Pitcairn Poland Portugal Qatar Reunion Romania Russian Federation Rwanda Saint Barthélemy Saint Helena, Ascension and Tristan da Cunha Saint Kitts and Nevis Saint Lucia Saint Martin (French part) Saint Pierre and Miquelon Saint Vincent and the Grenadines Samoa San Marino Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Singapore Sint Maarten (Dutch part) Slovakia Slovenia Solomon Islands Somalia South Africa South Georgia and the South Sandwich Islands South Sudan Spain Sri Lanka Sudan Suriname Svalbard and Jan Mayen Swaziland Sweden Switzerland Syrian Arab Republic Taiwan Tajikistan Tanzania, United Republic of Thailand Timor-Leste Togo Tokelau Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Turks and Caicos Islands Tuvalu Uganda Ukraine United Arab Emirates United Kingdom United States Uruguay Uzbekistan Vanuatu Venezuela, Bolivarian Republic of Vietnam Virgin Islands, British Wallis and Futuna Western Sahara Yemen Zambia Zimbabwe It’s not just flu. Recent studies show vaccines for mumps, pertussis, meningococcal disease, and yellow fever also lose their effectiveness faster than official immunization recommendations suggest. Vaccines have been a crucial public health tool for decades, so it may seem strange that their durability isn’t well understood. But vaccines are approved and come to market years before it’s clear how long protection lasts. Later, fading protection can go unnoticed because a vaccine in wide use has largely eliminated transmission of the microbes it protects against, making “breakthrough” infections rare. Even if viruses or bacteria are still in circulation, people vaccinated against them will sometimes receive natural boosting of their immunity. And declining vaccine immunity is not an all-or-nothing phenomenon: A breakthrough infection often leads to much less severe symptoms of the disease. 100% Just why one vaccine in the trio fades while the others work for almost a lifetime underscores the broader mystery of how to make vaccines more durable. But clues are coming from an unusual vaccine against HPV.Concerned that an attenuated or an inactivated HPV vaccine might still contain viral components that can cause cancer, researchers genetically engineered another virus to manufacture copies of a harmless HPV surface protein that self-assembles into what’s called a viruslike particle (VLP). Trials have shown that nearly everyone vaccinated with that noninfectious VLP develops high levels of HPV-neutralizing antibodies. Those levels decline moderately after 2 years but then remain stable for at least a decade. “Until we did the human studies with the vaccine, we really weren’t aware we were going to get such consistent and durable antibody responses,” says John Schiller, an oncologist at the National Cancer Institute in Bethesda, Maryland, who in the 1990s pioneered development of the vaccine, which protects against genital cancers and warts.VLPs challenge the widely held notion that durability depends primarily on memory B cells waking and expanding when an infection occurs. Schiller notes that the HPV vaccine leads to consistent blood levels of neutralizing antibodies for years on end. “If it were memory B cells, you should see spikes, blips up and down,” he says.Schiller and others contend that VLPs trigger production of a different set of B cells called long-lived plasma cells (LLPCs), which reside in the bone marrow and continually produce antibodies specific to different foreign antigens. “Viruslike particles are clearly the best way to make LLPCs,” Schiller says.In the wake of the HPV vaccine’s success, VLPs have become a trendy vaccine strategy. A hepatitis E vaccine on the market in China uses VLPs, and experimental influenza, norovirus, chikungunya, encephalitis, malaria, and dengue VLP vaccines are in development.Yet no one knows precisely how VLPs prod the immune system to make LLPCs. Schiller points to the work of Nobel Prize winner Rolf Zinkernagel of the University of Zurich in Switzerland and his then–graduate student Martin Bachmann. They reported 25 years ago that dense, highly repetitive proteins on the surfaces of viruses trigger the strongest antibody responses. A VLP is just such a structure. In theory, that allows the viral antigens to “cross-link” to many receptors on the surface of B cells. That, in turn, triggers a cascade of signals in immune cells that lead to strong, durable antibodies. How? “That’s the million-dollar question,” Slifka says.Such unknowns frustrate him, he says. He also laments what he sees as a disconnect between epidemiologists who investigate vaccine breakthrough infections during outbreaks and the type of laboratory studies he and other researchers conduct about immune mechanisms of protection and their durability. “How do we sort out this mess?” he asks. “We need to have the epidemiologists and the immunologists discuss their findings. Both sides could learn so much.”The flu season in North America is ending. CDC estimates that the virus sickened nearly 40 million people, hospitalized half a million, and killed up to 50,000. Neither Stanley Plotkin nor his wife developed the disease. Like millions of people in the United States last year, Stanley Plotkin and his wife got vaccinated against influenza at the start of the Northern Hemisphere’s flu season, in early October. Plotkin, a physician and emeritus professor at the University of Pennsylvania, knew well the value of the shot: He is one of the world’s most renowned vaccinologists, having had a hand in several vaccines on the market, including the one for rubella. He’s even the co-author of the standard medical textbook, Vaccines.In January, just 3 months later, the couple got a second flu shot.That was an unusual choice, one not recommended by the U.S. Advisory Committee on Immunization Practices (ACIP), which guides the country’s vaccine usage. But a growing body of evidence that the protective immune responses triggered by flu vaccines wane in a matter of weeks persuaded Plotkin to return to the clinic. “The time and cost was trivial compared to the importance of influenza at my age,” says Plotkin, 86. “With flu, we’re not talking about getting a case of the sniffles.” Email 25 75 How long do vaccines last? The surprising answers may help protect people longer 20 Most vaccine durability estimates are based on tested antibody levels. The HPV estimate is based on a model of the Cervarix vaccine. Waning pertussis immunity is estimated from outbreak cases per year following a fifth dose of vaccine and before a subsequent booster. Smallpox estimate draws on data from six outbreaks a century ago and assesses protection from disease, not infection. Sign up for our daily newsletter Get more great content like this delivered right to you! Country By Jon CohenApr. 18, 2019 , 2:00 PM 150 HPV 0% In a 2018 review of 11 recent studies on the durability of influenza vaccines, researchers concluded that effectiveness can vanish as soon as 90 days after vaccination. The article, published in Clinical Infectious Diseases, further noted that 20% of Americans received their flu vaccines for a given season by the end of September—which means the vaccine may do nothing come peak flu spread in January and February. “The further away you get from your vaccine, the higher the risk that you’ll contract influenza,” says study co-author Kunal Rambhia, a drug delivery specialist working on a Ph.D. at the University of Michigan in Ann Arbor. “This has huge implications.”Rambhia says ACIP has good reason to urge people to get vaccinated early, given the challenge of immunizing more than 100 million Americans each year. “They’re making the best decision they can,” he says. “They acknowledge that the vaccine might be less effective toward the end of the flu season.”He and others also note that a vaccine can offer a benefit even if it “fails.” In people who receive the flu vaccine but become ill, the disease often is markedly less severe. Such partial protection was first recognized more than a century ago with the smallpox vaccine, which fully prevents disease for only a few decades, but powerfully shields people from severe illness and death for life.Resurgence of mumpsBefore the mumps vaccine came to market in 1967, more than 90% of U.S. children suffered from the viral disease, which swells the salivary glands and causes a puffy face and fever. By the 2000s, the country had only a few hundred cases per year. But then in 2006, mumps surged on college campuses in the Midwest, with 6500 cases tallied before the year’s end. Nearly 85% of the college-age people who became ill had received the recommended two doses of the mumps vaccine. Despite wide use of the vaccine, mumps outbreaks continue in the United States on college campuses and in tightly knit religious communities.Some researchers speculate that the vaccine fails because mutations in the virus allow it to evade the immunity generated by the vaccine. But epidemiologist Joseph Lewnard of the University of California, Berkeley, and immunologist Yonatan Grad of the Harvard T.H. Chan School of Public Health in Boston recently analyzed data on the outbreaks—which have also occurred in Europe, Asia, and Canada. They reported last year in Science Translational Medicine that the disease disproportionately strikes people between 18 and 29. That pattern, Lewnard and Grad conclude, implies the vaccine itself loses effectiveness, because a new mumps strain that has genetically “escaped” should strike other age groups just as often. In a dozen other studies of mumps outbreaks around the world, researchers have also found signs of waning protection.Lewnard and Grad’s modeling indicates that adding a third dose of mumps vaccine around age 18 and then booster shots every 10 years could dramatically decrease the likelihood of outbreaks. The researchers note that since 1991 the U.S. military has given all its recruits a mumps vaccine booster and not had a single outbreak, even though troops live in close quarters. 125 Days after vaccination If you could understand [durability], you could make all vaccines better.center_img Sorting out waning immunity from other factors that influence a vaccine’s success isn’t straightforward, as a mumps outbreak that began in Arkansas in August 2016 shows. More than half the cases were in school-aged children, 92% of whom had been fully vaccinated. “At first, I thought the data had to be wrong because they didn’t fit our model,” Grad says.The outbreak, which continued until September 2017 and afflicted nearly 3000 people, was concentrated in people from the Marshall Islands. According to a February report in The Lancet Infectious Diseases, they have a large community in rural Arkansas that attends the same churches and lives in jam-packed houses. Intense exposure to mumps in the close-knit community apparently overwhelmed what should have been robust protection. “Protection from a vaccine is not all or nothing,” Grad says. “The more exposed you are, the likelier you are to get infected.”Last year, ACIP recommended a third dose of the mumps vaccine—but only for people who are “part of a group or population at increased risk” because of an outbreak.Needing a boost?The growing understanding of the speed at which vaccine-trained immune systems can lose their muscle has raised concerns about some recent public health decisions. In 2016, the World Health Organization (WHO) in Geneva, Switzerland, changed its legally binding regulations about use of the yellow fever vaccine, an attenuated form of the virus, which went into wide use in the 1940s and has spared untold millions from disease and death. Three years earlier, an expert committee had found a mere 12 cases of yellow fever among the more than 540 million people worldwide vaccinated against the disease over nearly 70 years. So WHO shifted from requiring booster shots every 10 years to a single, lifetime shot.That was a mistake, says Slifka, who, along with his work at the primate lab, is president of Najít Technologies, a Beaverton-based company making a new yellow fever vaccine. In the December 2016 issue of the Expert Review of Vaccines, he and his Najít colleague Ian Amanna argue that what looked like near-perfect protection to the expert committee reflects the fact that many vaccinated people are never exposed to yellow fever. The authors also point to a Brazilian study that came out after the expert committee’s analysis, which reported 459 cases of the disease in vaccinated people in that country alone over 35 years. In 52% of those cases, 10 years or more had passed since the person’s vaccination. “The yellow fever vaccine–induced immunity is long-lived, but only in 80% of people,” Slifka says.Antibody data back that argument. Slifka and Amanna point to a Centers for Disease Control and Prevention (CDC) review of nine studies that analyzed blood levels of yellow fever antibodies that can “neutralize” the virus, a test tube measure of potency that is key to a vaccine’s effectiveness. Four of the studies were done in people from areas where yellow fever virus circulates, finding that 97.6% of them had detectable neutralizing antibodies 10 years after vaccination. But in the other five studies, from areas with little or no yellow fever, only 83.7% of vaccinated people had those signs of immunity. To Slifka, that finding indicates that without periodic exposure to the pathogen, people gradually lose protection. “We need at least one booster,” he says.Plotkin says he strongly agrees that WHO should reconsider its recommendation to drop booster shots. “There’s no doubt there’s a problem,” he says.A WHO spokesperson for the expert committee that evaluates vaccines says it continues to review new data on breakthrough cases of yellow fever, closely monitoring the duration of immunity in people who received a single dose. “The evidence provided does not support the need for [a] booster dose,” the spokesperson says, noting that WHO cautions against “overinterpretation” of antibody data.Combo confusionSome vaccinologists are also questioning a 1991 switch to a putatively safer vaccine against pertussis, which causes whooping cough. For decades, the United States and other countries enjoyed great success with a vaccine made from killed Bordetella pertussis, the bacterium that causes the disease. But that “whole cell” vaccine became the centerpiece of an antivaccine movement some 40 years ago because of a much-debated claim that in rare cases it caused serious neurological damage. So an acellular vaccine, containing an inactivated version of the pertussis toxin that causes the disease as well as pieces of B. pertussis, replaced it.The vaccine is given with two others, against diphtheria and tetanus. ACIP calls for six doses of the triple-combo vaccine between infancy and age 12. It then recommends tetanus and diphtheria boosters every 10 years for adults. Despite the rigorous vaccination schedule, in 2010–11 and 2014–15 California experienced about 20,000 pertussis cases in two massive outbreaks.To find out whether waning protection was to blame, Kaiser Permanente in Northern California, a health care system that has detailed medical records for its millions of long-term patients, examined more than 4000 children from 2006 to 2015. The team concluded that protection waned 27% per year after children’s fifth dose of the acellular vaccine, which is given between ages 4 and 6. “We will be increasingly vulnerable to pertussis outbreaks until vaccines which provide more enduring protection are developed,” the researchers concluded in their analysis in the 8 June 2017 issue of Vaccine.Slifka says the replacement of the whole cellular vaccine with the acellular one was unnecessary and a mistake. “Acellular starts with 80% to 90% protection but crashes over the next few years,” he says, which leaves many children dangerously susceptible between their fifth dose and sixth given at 11 or 12 years of age. (B. pertussis causes relatively mild symptoms, if any, in teens and adults but can be deadly in younger children.)Ironically, the two other components of the triple vaccine have surprising staying power. The primate center where Slifka works draws blood from its employees to monitor potential infections to and from monkeys and other nonhuman primates. Slifka, Amanna, and colleagues obtained blood samples collected over a 26-year period and assessed how quickly antibodies to the tetanus and diphtheria bacteria decayed after vaccination. It would take more than 40 years for people to begin to lose protective immunity against those two pathogens, they reported last year in PLOS Biology. “We have a much higher level of immunity than previously realized,” Slifka says.WHO, Slifka notes, already does not recommend tetanus and diphtheria boosters for adults who have received their complete childhood shots. He says ACIP, a rotating group of vaccine experts that meets three times a year and regularly revises recommendations, should also consider withdrawing its recommendation for boosters. He estimates eliminating those shots would save the United States about $1 billion per year.Durability clues (GRAPHIC) N. DESAI/SCIENCE; (DATA) JOSEPH LEWNARD/UC BERKELEY; HIROSHI NISHIURA/HOKKAIDO UNIVERSITY; T. F. SCHWARZ ET AL., CANCER MED, 11, 2723, 2017; N. KLEIN ET AL., VACCINE, 35, 3395 2017 Durability difference Vaccine-induced immunity fades over time and the loss of protection differs with each disease. Mathematical models, based on cases from outbreaks as well as antibody levels and their decay, project how long immunity lasts in people who have received a full vaccine regimen. Click to view the privacy policy. Required fields are indicated by an asterisk (*) 50 Wayne Koff, Human Vaccines Project Measles 25 70 Diphtheria 100 Most vaccine durability estimates are based on tested antibody levels. The HPV estimate is based on a model of the Cervarix vaccine. Waning pertussis immunity is estimated from outbreak cases per year following a fifth dose of vaccine and before a subsequent booster. The smallpox estimate draws on data from six outbreaks a century ago and assesses protection from disease, not infection. Smallpox 50 0 Years 0 Mumps *No estimates available after 30 years Influenza vaccine effectiveness 0 Years Pertussis Rubella 40% (TOP TO BOTTOM) F. EUN-HYUNG LEE/EMORY UNIVERSITY; YORGO MODIS/UNIVERSITY OF CAMBRIDGE last_img read more

Read More