Astronomers To Peer Into A Black Hole For The First Time With New Event Horizon Telescope.


Ever since first mentioned by Jon Michell in a letter to the Royal Society in 1783, black holes have captured the imagination of scientists, writers, filmmakers and other artists. Perhaps part of the allure is that these enigmatic objects have never actually been “seen”. But this could now be about to change as an international team of astronomers is connecting a number of telescopes on Earth in the hope of making the first ever image of a black hole. The Conversation

Black holes are regions of space inside which the pull of gravity is so strong that nothing – not even light – can escape. Their existence was predicted mathematically by Karl Schwarzchild in 1915, as a solution to equations posed in Albert Einstein’s theory of general relativity.

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We don’t know what the black hole at the centre of the Milky Way will look like.

Astronomers have had circumstantial evidence for many decades that supermassive black holes – a million to a billion times more massive than our sun – lie at the hearts of massive galaxies. That’s because they can see the gravitational pull they have on stars orbiting around the galactic centre. When overfed with material from the surrounding galactic environment, they also eject detectable plumes or jets of plasma to speeds close to that of light. Last year, the LIGO experiment provided even more proof by famously detecting ripples in space-timecaused by two medium-mass black holes that merged millions of years ago.

But while we now know that black holes exist, questions regarding their origin, evolution and influence in the universe remain at the forefront of modern astronomy.

Catching a tiny spot on the sky

On April 5-14 2017, the team behind the Event Horizon Telescope hopes to test the fundamental theories of black-hole physics by attempting to take the first ever image of a black hole’s event horizon (the point at which theory predicts nothing can escape). By connecting a global array of radio telescopes together to form the equivalent of a giant Earth-sized telescope – using a technique known as Very Long Baseline Interferometry and Earth-aperture synthesis – scientists will peer into the heart of our Milky Way galaxy where a black hole that is 4m times more massive than our sun – Sagittarius A* – lurks.

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Sagittarius A*. This image was taken with NASA’s Chandra X-Ray Observatory. Ellipses indicate light echoes.
Astronomers know there is a disk of dust and gas orbiting around the black hole. The path the light from this material takes will be distorted in the gravitational field of the black hole. Its brightness and colour are also expected to be altered in predictable ways. The tell-tale signature astronomers hope to see with the Event Horizon Telescope is a bright crescent shape rather than a disk. And they may even see the shadow of the black hole’s event horizon against the backdrop of this brightly shining swirling material.

The array connects nine stations spanning the globe – some individual telescopes, others collections of telescopes – in Antarctica, Chile, Hawaii, Spain, Mexico and Arizona. The “virtual telescope” has been in development for many years and the technology has been tested. However, these tests initially revealed a limited sensitivity and an angular resolution that was insufficient to probe down to the scales needed to reach the black hole. But the addition of sensitive new arrays of telescopes – including the Atacama Large Millimeter Array in Chile and the South Pole Telescope – will give the network a much-needed boost in power. It’s rather like putting on spectacles and suddenly being able to see both headlights from an oncoming car rather than a single blur of light.

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The Atacama Large Millimeter submillimeter Array ALMA by night under the Magellanic Clouds.

The black hole is a compact source on the sky – its view at optical wavelengths (light that we can see) is completely blocked by large quantities of dust and gas. However, telescopes with sufficient resolution and operating at longer, radio millimetre wavelengths can peer through this cosmic fog.

The resolution of any kind of telescope – the finest detail that can be discerned and measured – is usually quoted as a small angle corresponding to the ratio of an object’s size to its distance. The angular size of the moon as seen from the Earth is about half a degree, or 1800 arc seconds. For any telescope, the bigger its aperture, the smaller the detail that can be resolved.

The resolution of a single radio telescope (typically with an aperture of 100 metres) is roughly about 60 arc seconds. This is comparable to the resolution of the unaided human eye and about a sixtieth of the apparent diameter of the full moon. But by connecting many telescopes, the Event Horizon Telescope will be about to achieve a resolution of 15-20 microarcsecond (0,000015 arcseconds), corresponding to being able to spy a grape at the distance of the moon.

What’s at stake?

Although the practice of connecting many telescopes in this way is well known, particular challenges lie ahead for the Event Horizon Telescope. The data recorded at each station in the network will be shipped to a central processing facility where a supercomputer will carefully combine all the data. Different weather, atmospheric and telescope conditions at each site will require meticulous calibration of the data so that scientists can be sure any features they find in the final images are not artefacts.

If it works, imaging the material inside the black hole region with angular resolutions comparable to that of its event horizon will open a new era of black hole studies and solve a number of big questions: do event horizons even exist? Does Einstein’s theory work in this region of extreme strong gravity or do we need a new theory to describe gravity this close to a black hole? Also, how are black holes fed and how is material ejected?

It may even even be possible to image the black holes at the centre of nearby galaxies, such as the giant elliptical galaxy that lies at the heart of our local cluster of galaxies.

Ultimately, the combination of mathematical theory and deep physical insight, global international scientific collaborations and remarkable, tenacious long-term advances in cutting edge experimental physics and engineering look set to make revealing the nature of spacetime a defining feature of early 21st century science.

Source:http://www.huffingtonpost.co.uk/

Dr. Paul LaViolette — Will a Superwave Arrive in in 2017?


An earlier posting (http://etheric.com/the-date-revealed-at-garabandal-for-the-coming-world-miracle/), discussed the revelation of Garabandal and attempted to infer the date of the miracle that the four young girls were told would affect the whole earth.  I had narrowed the possibilities down to two years: 2017 and 2020.  Based on hints left by one of the surviving girls, I had inferred that the “miracle” is to occur between April 8th through the 16th, hence during easter holy week.  Of the two years, I had chosen 2020 as a more likely possibility, based on the recurring miracle at St. Nicholas Russian Orthodox church in Milano.

A number of people who have responded to the posting, however, believe that the true date will instead be in 2017.  One person has suggested it will occur in May of 2017.  The 2017 date coincides with the prediction of Jake Simpson, a black project whistleblower who claims that a wave of energy will impact the solar system in that year causing a major global catastrophe.  In our Project Camelot interview, Kerry Cassidy suggested to me that the event Simpson was referring to might be a galactic superwave, whose arrival I had long been saying is much overdue.  See interview excerpt here:

Dr. Paul LaVioletter — The Galactic Superwave Will Hit by 2017

For the entire interview click here: https://www.youtube.com/watch?v=oURVtGKW420 

Also Bob Dean another black project whistleblower who was interviewed by Project Camelot  also points to 2017 as a significant date, although he speaks of Earth encountering a planet (e.g., Planet X).

So, it is up to you to decide how much faith to place in these various predictions.  But it may be a good idea for one to be prepared in 2017, just in case.  If a superwave were to strike this coming year, the Starburst Foundation will go into high gear to help out in any way possible to inform people about the situation.  But since there could be an internet outage associated with this, it could be difficult to get the word out.  At this point I can offer the following advice.  The first indication of the super wave’s arrival would be the impact of a gravity wave which would affect the whole planet, triggering earthquakes.  Immediately afterward the high energy cosmic rays would begin arriving and a bluish white star will begin to appear in the sky at the location of the Galactic center.  One should not delay to seek shelter at once in a cave or underground tunnel to escape the radiation hazard.  It would help to be prepared with a bag full of clothes and supplies that you could grab on a moment’s notice. Remember to meditate or pray and to stay calm as there could be unusual psychological effects associated with the passage of the superwave.  The solar system will be bathed in negatively charged particles which will produce a negative mass gravitational potential (gravity potential hill), whereas normally we have been used to being surrounded by a positive mass gravity potential  (gravity potential well) produced by the Galactic core and Sun.  This G potential flip could produce noticeable psychological/mental effects.

The first three days will be the worst since the barrage will be most intense during that period.  After that one might venture outside if the radiation intensity is sufficiently low.  A geiger counter would come in very handy.  Hopefully by that time there will be people around who will have some information on the degree of the radiation hazard.  It would also help if you have access to a solar powered home that is off the grid.  Be aware that the Sun could become aggravated during the event and could produce excessive flares which could have more lethal effects than the superwave.

For more about superwaves read the postings on the sidebar of this webpage or read books available here such as Earth Under Fire  or  Galactic Superwaves.

About Dr. Paul LaViolette

Paul A. LaViolette, PH.D, is author of Secrets of Antigravity PropulsionSubquantum Kinetics, Earth Under Fire,Genesis of the Cosmos, Decoding the Message of the PulsarsGalactic Superwaves and their Impact on the Earth, and is editor of A Systems View of Man. He has also published many original papers in physics, astronomy, climatology, systems theory, and psychology.

He received his BA in physics from Johns Hopkins, his MBA from the University of Chicago, and PhD from Portland State University. He is currently president and director of the Starburst Foundation.

He has served as a solar energy consultant for the Greek government and also has consulted a Fortune 500 company on ways of stimulating innovation. Research he conducted at Harvard School of Public Health led him to invent an improved pulsation dampener for air sampling pumps. Related work led him to develop an improved life-support rebreather apparatus for protection against hazardous environments and for which he received two patents.

Dr. LaViolette is the first to predict that high intensity volleys of cosmic ray particles travel directly to our planet from distant sources in our Galaxy, a phenomenon now confirmed by scientific data. He is also the first to discover high concentrations of cosmic dust in Ice Age polar ice, indicating the occurrence of a global cosmic catastrophe in ancient times.  Based on this work, he made predictions about the entry of interstellar dust into the solar system ten years before its confirmation in 1993 by data from the Ulysses spacecraft and by radar observations from New Zealand.

He also originated the glacier wave flood theory that not only provides a reasonable scientific explanation for widespread continental floods, but also presents a credible explanation for the sudden freezing of the arctic mammoths and demise of the Pleistocene mammals. Also he developed a novel theory that links geomagnetic flips to the past occurrence of immense solar flare storm outbursts.

He is the developer of subquantum kinetics, a novel approach to microphysics that not only accounts for electric, magnetic, gravitational, and nuclear forces in a unified manner, but also resolves many long-standing problems in physics such as the field singularity problem, the wave-particle dualism, and the field source problem, to mention a few.

Moreover based on the predictions of this theory, he developed an alternative cosmology that effectively replaces the big bang theory. In fact, in 1986, he was the first to cast doubt on the big bang theory by showing that it makes a far poorer fit to existing astronomical data when compared to this new non-expanding universe cosmology.

The subquantum kinetics cosmology also led him to make successful predictions about galaxy evolution that were later verified with the Hubble Space Telescope.

Dr. LaViolette is credited with the discovery of the planetary-stellar mass-luminosity relation which demonstrates that the Sun, planets, stars, and supernova explosions are powered by spontaneous energy creation through photon blueshifting. With this relation, he successfully predicted the mass-luminosity ratio of the first brown dwarf to be discovered.  More recently, his maser signal blueshifting prediction has found confirmation following publication of the discovery of a blueshift in the Pioneer 10 spacecraft tracking data.

In addition, Paul LaViolette has developed a new theory of gravity that replaces the deeply flawed theory of general relativity.  Predicted from subquantum kinetics, it accounts for the electrogravitic coupling phenomenon discovered by Townsend Brown and may explain the advanced aerospace propulsion technology utilized in the B-2 bomber.

He is the first to discover that certain ancient creation myths and esoteric lores metaphorically encode an advanced science of cosmogenesis.  His contributions to the field of Egyptology and mythology may be compared to the breaking of the Rosetta Stone hieroglyphic code.   For a partial listing of these discoveries click here:  Mythology Insights.

He is also the co-developer of the Gray-LaViolette feeling tone theory which explains how the brain/mind forms creative thoughts.  This has led to a new understanding of how the brain functions and to a novel approach in education.

Paul LaViolette also briefly worked as a patent examiner in the U. S. Patent Office.  The Patent Office Society “Unofficial Gazette” ran an article about his being newly hired.  During this period he was responsible for expanding civil rights law to cover cases where an employer has terminated an employee on the basis of his scientific beliefs.

Source: The Sphinx Stargate

Gravitational Wave Kicks Monster Black Hole Out Of Galactic Core


Gravitational Wave Kicks Monster Black Hole Out Of Galactic Core

Gravitational Wave Kicks Monster Black Hole Out Of Galactic Core
Runaway black hole is the most massive ever detected far from its central home
Normally, hefty black holes anchor the centers of galaxies. So researchers were surprised to discover a supermassive black hole speeding through the galactic suburbs. Black holes cannot be observed directly, but they are the energy source at the heart of quasars — intense, compact gushers of radiation that can outshine an entire galaxy. NASA’s Hubble Space Telescope made the discovery by finding a bright quasar located far from the center of the host galaxy.Researchers estimate that it took the equivalent energy of 100 million supernovas exploding simultaneously to jettison the black hole. What could pry this giant monster from its central home? The most plausible explanation for this propulsive energy is that the monster object was given a kick by gravitational waves unleashed by the merger of two black holes as a result of a collision between two galaxies. First predicted by Albert Einstein, gravitational waves are ripples in the fabric of space that are created when two massive objects collide.

Astronomers have uncovered a supermassive black hole that has been propelled out of the center of a distant galaxy by what could be the awesome power of gravitational waves.

Though there have been several other suspected, similarly booted black holes elsewhere, none has been confirmed so far. Astronomers think this object, detected by NASA’s Hubble Space Telescope, is a very strong case. Weighing more than 1 billion suns, the rogue black hole is the most massive black hole ever detected to have been kicked out of its central home.

Researchers estimate that it took the equivalent energy of 100 million supernovas exploding simultaneously to jettison the black hole. The most plausible explanation for this propulsive energy is that the monster object was given a kick by gravitational waves unleashed by the merger of two hefty black holes at the center of the host galaxy.

First predicted by Albert Einstein, gravitational waves are ripples in space that are created when two massive objects collide. The ripples are similar to the concentric circles produced when a hefty rock is thrown into a pond. Last year, the Laser Interferometer Gravitational-Wave Observatory (LIGO) helped astronomers prove that gravitational waves exist by detecting them emanating from the union of two stellar-mass black holes, which are several times more massive than the sun.

Hubble’s observations of the wayward black hole surprised the research team. “When I first saw this, I thought we were seeing something very peculiar,” said team leader Marco Chiaberge of the Space Telescope Science Institute (STScI) and Johns Hopkins University, in Baltimore, Maryland. “When we combined observations from Hubble, the Chandra X-ray Observatory, and the Sloan Digital Sky Survey, it all pointed towards the same scenario. The amount of data we collected, from X-rays to ultraviolet to near-infrared light, is definitely larger than for any of the other candidate rogue black holes.”

Chiaberge’s paper will appear in the March 30 issue of Astronomy & Astrophysics.

Hubble images taken in visible and near-infrared light provided the first clue that the galaxy was unusual. The images revealed a bright quasar, the energetic signature of a black hole, residing far from the galactic core. Black holes cannot be observed directly, but they are the energy source at the heart of quasars – intense, compact gushers of radiation that can outshine an entire galaxy. The quasar, named 3C 186, and its host galaxy reside 8 billion light-years away in a galaxy cluster. The team discovered the galaxy’s peculiar features while conducting a Hubble survey of distant galaxies unleashing powerful blasts of radiation in the throes of galaxy mergers.

“I was anticipating seeing a lot of merging galaxies, and I was expecting to see messy host galaxies around the quasars, but I wasn’t really expecting to see a quasar that was clearly offset from the core of a regularly shaped galaxy,” Chiaberge recalled. “Black holes reside in the center of galaxies, so it’s unusual to see a quasar not in the center.”

The team calculated the black hole’s distance from the core by comparing the distribution of starlight in the host galaxy with that of a normal elliptical galaxy from a computer model. The black hole had traveled more than 35,000 light-years from the center, which is more than the distance between the sun and the center of the Milky Way.

Based on spectroscopic observations taken by Hubble and the Sloan survey, the researchers estimated the black hole’s mass and measured the speed of gas trapped near the behemoth object. Spectroscopy divides light into its component colors, which can be used to measure velocities in space. “To our surprise, we discovered that the gas around the black hole was flying away from the galaxy’s center at 4.7 million miles an hour,” said team member Justin Ely of STScI. This measurement is also a gauge of the black hole’s velocity, because the gas is gravitationally locked to the monster object.

The astronomers calculated that the black hole is moving so fast it would travel from Earth to the moon in three minutes. That’s fast enough for the black hole to escape the galaxy in 20 million years and roam through the universe forever.

The Hubble image revealed an interesting clue that helped explain the black hole’s wayward location. The host galaxy has faint arc-shaped features called tidal tails, produced by a gravitational tug between two colliding galaxies. This evidence suggests a possible union between the 3C 186 system and another galaxy, each with central, massive black holes that may have eventually merged.

Based on this visible evidence, along with theoretical work, the researchers developed a scenario to describe how the behemoth black hole could be expelled from its central home. According to their theory, two galaxies merge, and their black holes settle into the center of the newly formed elliptical galaxy. As the black holes whirl around each other, gravity waves are flung out like water from a lawn sprinkler. The hefty objects move closer to each other over time as they radiate away gravitational energy. If the two black holes do not have the same mass and rotation rate, they emit gravitational waves more strongly along one direction. When the two black holes collide, they stop producing gravitational waves. The newly merged black hole then recoils in the opposite direction of the strongest gravitational waves and shoots off like a rocket.

The researchers are lucky to have caught this unique event because not every black-hole merger produces imbalanced gravitational waves that propel a black hole in the opposite direction. “This asymmetry depends on properties such as the mass and the relative orientation of the back holes’ rotation axes before the merger,” said team member Colin Norman of STScI and Johns Hopkins University. “That’s why these objects are so rare.”

An alternative explanation for the offset quasar, although unlikely, proposes that the bright object does not reside within the galaxy. Instead, the quasar is located behind the galaxy, but the Hubble image gives the illusion that it is at the same distance as the galaxy. If this were the case, the researchers should have detected a galaxy in the background hosting the quasar.

If the researchers’ interpretation is correct, the observations may provide strong evidence that supermassive black holes can actually merge. Astronomers have evidence of black-hole collisions for stellar-mass black holes, but the process regulating supermassive black holes is more complex and not completely understood.

The team hopes to use Hubble again, in combination with the Atacama Large Millimeter/submillimeter Array (ALMA) and other facilities, to more accurately measure the speed of the black hole and its gas disk, which may yield more insight into the nature of this bizarre object.

The Hubble Space Telescope is a project of international cooperation between NASA and ESA (European Space Agency). NASA’s Goddard Space Flight Center in Greenbelt, Maryland, manages the telescope. The Space Telescope Science Institute in Baltimore conducts Hubble science operations. STScI is operated for NASA by the Association of Universities for Research in Astronomy, Inc., in Washington, D.C.

Source:http://hubblesite.org

Virology: Fighting for a cause.


When Judy Mikovits found links between chronic fatigue syndrome and a virus, the world took notice. Now, she’s caught between the patients who believe her work and the researchers who don’t.

On a sunny January afternoon in Santa Rosa, California, a small crowd waits patiently for Judy Mikovits to arrive. She is scheduled to deliver a talk on a mysterious virus called XMRV, which she believes underlies chronic fatigue syndrome. Although she’s two hours late — held up by fog at San Francisco International Airport — not a single person has left. And when she arrives, they burst into applause.

To a rapt audience, she gives a chaotic and wide-ranging talk that explores viral sequences, cell-culture techniques and some of the criticisms that have been thrown at her since she published evidence1 of a link between XMRV and chronic fatigue in 2009. Afterwards, Mikovits is swarmed by attendees. A middle-aged woman who spent most of the talk in a motorized scooter stands up to snap pictures of her with a digital camera. Ann Cavanagh, who has chronic fatigue and has tested positive for XMRV, says that she came in part for information and in part to show her support for Mikovits. “I just wish there were a hundred of her,” Cavanagh says.

The event was “surreal”, says Mikovits, a viral immunologist at the Whittemore Peterson Institute for Neuro-Immune Disease (WPI) in Reno, Nevada. She is discomfited by the attention from patients, which at times borders on adulation. But her reception among scientists has been markedly cooler. Numerous follow-up studies have found no link between the virus and the disease; no group has published a replication of her findings; and some scientists argue that XMRV is an artefact of laboratory contamination. Now, even some of Mikovits’s former collaborators are having second thoughts.

Mikovits has dug in, however, attacking her critics’ methods and motives. She says that their distrust of her science stems from doubts about the legitimacy of chronic fatigue syndrome itself. Chronic fatigue, also known as myalgic encephalomyelitis, affects an estimated 17 million people worldwide, but it is extremely difficult to diagnose. Many with the disorder are told that their symptoms — which include exhaustion, joint and muscle pain, cognitive issues, and heart and respiratory problems — are psychosomatic. “I had no idea there was that much bias against this disease,” Mikovits says.

The stakes are high and many are taking the risks seriously. Several countries have barred people with chronic fatigue from donating blood in case the virus spreads (see ‘Something in the blood’). And the US government has launched a US$1.3-million study to investigate the link. Patients are already being tested for XMRV, and some are taking antiviral drugs on the assumption that the virus causes chronic fatigue by attacking their immune defences. Many say that such action is premature, but Mikovits is steadfast. “We’re not changing our course,” she says.

First findings

In October 2007, Mikovits attended a prostate-cancer meeting near Lake Tahoe, Nevada, where she met Robert Silverman, a virologist at the Cleveland Clinic in Ohio. Silverman co-discovered XMRV, which stands for xenotropic murine leukaemia virus-related virus2. While examining human prostate tumours, he and his collaborators found genetic sequences that resemble retroviruses found in the mouse genome. Like all retroviruses, XMRV rewrites its RNA genome into DNA on infection, then slips the DNA into the genomes of host cells. Ancient remnants of such viruses litter animal genomes. But the only active retroviruses conclusively linked to human disease are HTLV-1, which causes leukaemia, and HIV.

At the meeting, Silverman was presenting research linking XMRV to deficiencies in a virus-defence pathway. Mikovits recalled that the same pathway was weakened in some patients with chronic fatigue. She wondered whether the prostate-tumour virus could also be behind chronic fatigue. After the meeting, Silverman sent Mikovits reagents to test for XMRV.

The idea excited Mikovits, but she had other priorities. After stints in industry and at the US National Cancer Institute (NCI) in Maryland, she had recently joined the WPI to lead its research programme. The WPI was founded in 2006 by physician Daniel Peterson, an expert on chronic fatigue, and by Annette Whittemore, the wife of a well-connected Nevada businessman, whose daughter Andrea has had chronic fatigue for more than 20 years. The Whittemores spent $5 million establishing the WPI, and several million more to support Mikovits’s research, which has attracted few other grants.

At the WPI, Mikovits established a sample collection from Peterson’s patients and began screening it for signs of an infection. A litany of pathogens has been linked to chronic fatigue over the years, including Epstein-Barr virus, Borna disease virus, human herpes virus 6 and HTLV-2. None panned out. Still, the disorder bears some hallmarks of an infection. Many patients report acute illness before chronic symptoms appear, and their bodies often show signs of an immune system at war. The disease can also crop up in apparent outbreaks, including one characterized by Peterson near Lake Tahoe in the 1980s.

Just before Christmas 2008, Mikovits turned her attention to Silverman’s reagents. She and her postdoc, Vincent Lombardi, known as Vinny, asked a graduate student to test for XMRV DNA in white blood cells from some of the most seriously ill people being studied at the WPI.

The first try turned up just two positives out of 20. But by tweaking the conditions of the test, Mikovits says her team found XMRV in all 20. “Vinny and I looked at each other and said, ‘Well, that’s interesting’,” she says. They spent the next few weeks convincing themselves that they were onto something, and soon conscripted Silverman and Mikovits’s former mentor at the NCI, Frank Ruscetti, to help prove that XMRV infection was behind chronic fatigue.

“We really retooled our entire programme and did nothing but focus on that,” she says. They kept the effort under wraps, dubbing it ‘Project X’. Even Peterson and the Whittemores weren’t clued in. Mikovits says that the secrecy was necessary because her team also found XMRV in the blood of some healthy people, raising concerns about blood products. She hoped to build an airtight case because she worried that sceptical public-health officials would undermine her work.

In May 2009, the team submitted a paper to Science reporting the identification of XMRV genetic material in two-thirds of the 101 patients with chronic fatigue they had tested and in 3.7% of 218 healthy people. They also included data suggesting that infected white blood cells could pass the virus on to uninfected cells.

“They call me every single day. I spend so much time trying to understand the patients, to understand this disease.”

Reviewers wanted more evidence: a clear electron micrograph of virus-infected cells, proof that patients mounted an immune response to the virus, an evolutionary tree showing XMRV’s relationship to other viruses and the locations where viral DNA was integrating into patient genomes. Mikovits’s team went to work. “None of us took any time off, not even a weekend,” she says. They resubmitted the paper in early July with everything the reviewers had asked for, except the DNA integration sites, which many scientists consider a gold standard in proving a retroviral infection.

Later that month, NCI officials who had learned about the work invited Mikovits to give a talk at a closed-door meeting with other XMRV researchers and government scientists. “When I finished speaking you could’ve heard a pin drop,” she says. Mikovits says she thinks at least one of her manuscript’s reviewers was at the meeting, because soon after, she got a call from a Science editor. Their paper had been accepted.

Jonathan Stoye, a retrovirologist at the MRC National Institute for Medical Research in London, wrote a commentary about the paper for Science3. He had never heard of Mikovits, but Frank Ruscetti’s name on the paper gave him confidence, he says, and “if it were true, it was clearly very important”. Stoye’s co-author John Coffin, a retrovirologist at Tufts University in Boston, Massachusetts, says he was satisfied with the data and thought it was time to “let the field and public chew on them”.

The BBC, US National Public Radio, The New York Times, The Wall Street Journal and dozens of other news outlets covered the research. “Prostate cancer pathogen may be behind the disease once dubbed ‘yuppie flu’,” Nature announced on its news website the day the paper came out. Phoenix Rising, a forum for patients with chronic fatigue that has become a hub for all things XMRV, called the work a “game changer”, and patients flocked to learn more about a virus that they hoped would explain their condition. But others, including Britain’s leading chronic fatigue patient group, urged caution until more research buttressed the link.

The first negative findings started to arrive in January 2010 — failing to find XMRV in 186 people with chronic fatigue from the United Kingdom4. A month later, a team including Stoye published a paper5showing no evidence of XMRV in more than 500 blood samples from patients with chronic fatigue and healthy people. One day later, theBritish Medical Journal accepted a paper reporting more negative results in Dutch patients6. Studies began piling up so fast that Coffin made a scorecard to show at talks. “I’ve lost count now,” he says.

Mikovits says that the discrepancies can be explained by differences in the geographical distribution of XMRV or in the methods used.

Judy Mikovits says that she will not abandon the hypothesis that XMRV and related viruses cause chronic fatigue syndrome, despite a growing chorus of critics.

The most common way to detect XMRV is PCR, or polymerase chain reaction, which amplifies viral DNA sequences to a level at which they can be identified. Mikovits and her team used this method to detect XMRV in some of their patients, but she contends that the most sensitive way to detect the virus is to culture patients’ blood cells with a cell line in which the virus replicates more quickly. This should create more copies of the virus, making it easier to detect with PCR and other techniques. She says that none of the negative studies applied this method exactly, a fact that annoys her. “Nobody’s tried to rep-li-cate it,” she says, sounding out each syllable for emphasis.

In summer 2010, some evidence emerged in Mikovits’s corner. Harvey Alter, a hepatitis expert at the NIH’s Clinical Center, and his team identified viruses similar to XMRV in 32 of 37 people with chronic fatigue and in 3 of 44 healthy people. They were preparing to publish their results in the Proceedings of the National Academy of Sciences. But scientists at the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, were about to publish a negative report. The authors delayed publication of both papers7,8for several weeks to assess discrepancies. The move agitated Mikovits as well as the chronic-fatigue community, who suspected that important data were being suppressed.

When Alter’s work came out in late August7, Mikovits was ecstatic, and the WPI released a YouTube video of her touting it. For other researchers, however, the new paper had shortcomings. The viral sequences from Alter’s paper differed from XMRV, says Greg Towers, a retrovirologist at University College London. “He doesn’t get variation, he gets a totally different virus.” Towers says that mouse DNA, which is chock-full of virus sequences like those Alter’s team found, probably contaminated their samples, which were collected in the 1990s. But Alter says that his team found no contamination from mouse DNA and recovered the same viral sequences from the same patients sampled a decade later.

Contamination became a dirty word for Mikovits. Just before Christmas 2010, Retrovirology published four papers9,10,11,12 that highlighted laboratory contamination as a possible explanation for her findings. One showed, for example, that mouse DNA contaminates an enzyme from a commercial kit commonly used for PCR. Coffin, an author on two of the Retrovirology papers, urges caution against over-extrapolating. These papers do not say that contamination explains Mikovits’s results, he says, just that extreme care is required to avoid it.

Towers and his colleague Paul Kellam, a virologist at the Wellcome Trust Sanger Institute near Cambridge, UK, are less charitable, however. Their study12 showed that the XMRV sequences that Mikovits and Silverman had extracted from patients lacked the diversity expected of a retrovirus that accumulates mutations as it passes between patients. “This doesn’t look like an onwardly transmittable infectious virus,” says Kellam. A press release for the paper issued by the Sanger Institute put it more bluntly: “Chronic fatigue syndrome is not caused by XMRV.”

Mikovits is riled when the topic turns to Towers’s paper over dinner one night in Reno — “Christmas garbage”, she calls it. Contamination cannot explain why her team can reproduce its results both in her lab in Reno and at Ruscetti’s at the NCI, she says. Her team checks for contamination in reagents and in the cells it grows the patients’ samples with. She says that her team has also collected viral sequences that will address Towers’s and Kellam’s criticism but that it hasn’t yet been able to publish them. Meanwhile, an unpublished study of patients in Britain with chronic fatigue bears out the link to XMRV, she says. “I haven’t for one second seen a piece of data that convinced me they’re not infected.”

Jay Levy, a virologist at the Univer­sity of California, San Francisco, has a window in his closet-sized office that looks out into the laboratory where, in the 1980s, he became one of the first scientists to isolate HIV. After his discovery was scooped by other researchers, Levy turned his attention to chronic fatigue and started a long but fruitless search for an infectious cause.

Now, Levy is putting the finishing touches on what could be the most thorough response yet to Mikovits’s Science paper, adopting the same cell-culture techniques to detect the virus and using samples from the same patients. He’s done this with the help of Daniel Peterson, who left the WPI in 2010 for what Peterson says are “personal reasons”. Peterson has questioned the institute’s singular pursuit of XMRV, a research direction that was pursued without his consultation.

Mikovits says that she kept the XMRV work secret from Peterson over fears he would tell his patients, and left his name off the original Science manuscript until a reviewer questioned the omission. When asked whether that episode contributed to his departure, he says, “I was surprised at the secrecy and lack of collaboration.” As for his motivation to team up with Levy: “I’m just trying to get to the truth. It’s my only motive, because this is such a deserving group of patients who need to know what’s going on.”

Others, too, are rallying for a definitive answer. Ian Lipkin, a microbial epidemiologist at Columbia University in New York, has a reputation for getting to the bottom of mysterious disease–pathogen links. His team debunked the association between Borna disease virus and chronic fatigue, for example. Now he is spearheading the $1.3-million effort funded by the US government. He is leaving the testing to three labs: Mikovits’s at the WPI, Alter’s at the NIH and the CDC. Each will receive coded samples of white blood cells and plasma from 150 patients with chronic fatigue and from 150 healthy controls. The labs will test for XMRV using their method of choice. Lipkin will crunch the data and unblind the samples.

But even if a study confirms the link to chronic fatigue, it won’t be able to determine whether the virus is the cause. XMRV could, for example, be an opportunistic infection affecting those whose immune systems are already dampened by chronic fatigue. Even Mikovits can only hypothesize as to how it might cause disease.

The virus might not even exist as a natural infection. At a retrovirus conference this month in Boston, Massachusetts, Coffin and his colleague Vinay Pathak at the NCI in Frederick, Maryland, presented data showing that XMRV emerged in the 1990s, during the development of a prostate-tumour cell line called 22Rv1. Developing the line involved implanting a prostate-tumour sample into mice, retrieving cells that might divide indefinitely and repeating the process. But looking back at DNA samples taken throughout the cell-line’s development showed that human cells became infected only after passing through several different mice. Importantly, XMRV’s sequence seems to have come from two different mouse strains. “They just sort of snapped together like two puzzle pieces,” says Coffin, an event extremely unlikely to have happened twice.

Bumper stickers are just one of the supportive gifts given to the WPI.D. 

XMRV sequences retrieved from patients with prostate cancer and chronic fatigue — including some who have had chronic fatigue since the mid-1980s — are nearly identical to the virus from 22Rv1 cells. The implication, says Coffin, is that this virus, born in a laboratory, has probably been infecting samples for more than a decade, but not people. “Although people on the blogs aren’t going to believe me, I’m afraid this is by far the most reasonable explanation for how XMRV came to be,” says Coffin, who hoped that the association with chronic fatigue would pan out and still thinks some pathogen other than XMRV could explain the disease.

Silverman, who no longer works with Mikovits, says that he wasn’t using 22Rv1 cells when XMRV was discovered. Nonetheless, the work has rattled his confidence in XMRV’s link to both prostate cancer and chronic fatigue.

Mikovits, however, is undeterred. The WPI owns a company that charges patients up to $549 to be tested for XMRV, and Mikovits believes that patients who test positive should consult their doctors about getting antiretroviral drugs normally prescribed to those with HIV. Levy and others worry that she is overreaching. “That’s scary for me. These antiretroviral drugs are not just like taking an aspirin,” he says. Mikovits argues that they might be some patients’ only hope. “The people who we know they’re infected should have a right to get therapy,” she says, “They have nothing. They have no other choice.”

Context and debate

Back in her Reno laboratory two days after the talk in Santa Rosa, Mikovits examines a stack of small plastic flasks under a microscope. Some contain patient cells that she hopes will turn into cell lines and churn out XMRV. “On Wednesdays I get to take care of my cells, and that’s where I’m the happiest,” she says.

She has just come off the phone from a sobbing patient infected with XMRV whose symptoms had worsened. “They call me every single day,” Mikovits says. “I don’t do science any more. I spend so much time trying to understand the patients, to understand this disease. People have moved to Reno to be here,” she says. They’ve left gifts: stuffed animals, and stacks of bumper stickers that say “Today’s Discoveries, Tomorrow’s Cures” and, more boldly, “It’s the virus XMRV”.

Mikovits clearly shares in the frustration of those with chronic fatigue who have been marginalized over the years and told that their disease is not real. She says that this disbelief in the disorder drives the criticism of her work. Kellam and the others say that this isn’t true. They don’t deny the existence of the syndrome or even the possibility of an infectious origin. “What we’re trying to understand is the aetiology,” Kellam says. “It’s a scientific debate.”

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Mikovits says that she’s analysed all the papers critical of her work and found flaws in each of them. Nevertheless, she’s quick to endorse findings that support her work. She claims that Coffin and Pathak’s study, for example, “says nothing about human infection”. Yet new work presented at a different meeting that found XMRV using next-generation DNA sequencing offers “no doubt it’s not contamination — that the whole story’s real”, she says.

Despite the growing choir of sceptics, Mikovits says that she has simply seen too many data implicating XMRV and other related viruses in chronic fatigue to change her mind. For her supporters, that steadfastness offers legitimacy and hope. “The scientists are moving forward,” she announced at her talk in Santa Rosa, “and I think the politics will go away shortly.” The crowd responded with vigorous applause. 

Ewen Callaway writes for Nature from London.

  • References

    1. Lombardi, V. C. et al. Science 326, 585-589 (2009). | Article | PubMed | ISI | ChemPort |
    2. Urisman, A. et al. PLoS Pathog. 2, e25 (2006). | Article | PubMed | ChemPort |
    3. Coffin, J. M. & Stoye, J. P. Science 326, 530-531 (2009). | Article | PubMed | ChemPort |
    4. Erlwein, O. et al. PLoS ONE 5, e8519 (2010). | Article | PubMed | ChemPort |
    5. Groom, H. C. et al. Retrovirology 7, 10 (2010). | Article | PubMed | ChemPort |
    6. Van Kuppeveld, F. J. et al. Br. Med. J. 340, c1018 (2010).
    7. Lo, S. C. et al. Proc. Natl Acad. Sci. USA 107, 15874-15879 (2010).
    8. Switzer, W. M. et al. Retrovirology 7, 57 (2010).
    9. Robinson, M. J. et al. Retrovirology 7, 108 (2010).
    10. Oakes, B. et al. Retrovirology 7, 109 (2010).
    11. Sato, E. , Furuta, R. A. & Miyazawa, T. Retrovirology 7, 110 (2010).
    12. Hué, S. et al. Retrovirology 7, 111 (2010).

Source: Nature.com

WHO issues ethics guidance to protect rights of TB patients


New tuberculosis (TB) ethics guidance, launched today by the World Health Organization (WHO), aims to help ensure that countries implementing the End TB Strategy adhere to sound ethical standards to protect the rights of all those affected.

TB, the world’s top infectious disease killer, claims 5 000 lives each day. The heaviest burden is carried by communities which already face socio-economic challenges: migrants, refugees, prisoners, ethnic minorities, miners and others working and living in risk-prone settings, and marginalized women, children and older people.

“TB strikes some of the world’s poorest people hardest,” said Dr Margaret Chan, WHO Director-General. “WHO is determined to overcome the stigma, discrimination, and other barriers that prevent so many of these people from obtaining the services they so badly need.”

Poverty, malnutrition, poor housing and sanitation, compounded by other risk factors such as HIV, tobacco, alcohol use and diabetes, can put people at heightened risk of TB and make it harder for them to access care. More than a third (4.3 million) of people with TB go undiagnosed or unreported, some receive no care at all and others access care of questionable quality.

The new WHO ethics guidance addresses contentious issues such as, the isolation of contagious patients, the rights of TB patients in prison, discriminatory policies against migrants affected by TB, among others. It emphasizes five key ethical obligations for governments, health workers, care providers, nongovernmental organizations, researchers and other stakeholders to:

  • provide patients with the social support they need to fulfil their responsibilities
  • refrain from isolating TB patients before exhausting all options to enable treatment adherence and only under very specific conditions
  • enable “key populations” to access same standard of care offered to other citizens
  • ensure all health workers operate in a safe environment
  • rapidly share evidence from research to inform national and global TB policy updates.

From guidance to action

Protecting human rights, ethics and equity are principles which underpin WHO’s End TB Strategy. But it is not easy to apply these principles on the ground. Patients, communities, health workers, policy makers and other stakeholders frequently face conflicts and ethical dilemmas. The current multidrug-resistant TB (MDR-TB) crisis and the health security threat it poses accentuate the situation even further.

“Only when evidence-based, effective interventions are informed by a sound ethical framework, and respect for human rights, will we be successful in reaching our ambitious goals of ending the TB epidemic and achieving universal health coverage. The SDG aspiration of leaving no one behind is centred on this,” said Dr Mario Raviglione, Director, WHO Global TB Programme.

“The guidance we have released today aims to identify the ethical predicaments faced in TB care delivery, and highlights key actions that can be taken to address them,” he added.

World TB Day is an opportunity to mobilize political and social commitment for further progress in efforts to end TB. This year, World TB Day signals new momentum at the highest levels with the announcement of the first ever Global Ministerial Conference on Ending TB, which will be held in Moscow in November 2017.

“The Global Ministerial Conference will highlight the need for an accelerated multisectoral response to TB in the context of the Sustainable Development Goals,” said Dr Ren Minghui, Assistant Director-General HIV/AIDS, Tuberculosis, Malaria and Neglected Tropical Diseases. “It will emphasize that global action against antimicrobial resistance must include optimized care, surveillance and research to address MDR-TB urgently”.

The Conference will inform the UN General Assembly high-level meeting on TB which will be held in 2018.

Source:WHO

Surprising new role for lungs—making blood


lung
Lung tissue. 

Using video microscopy in the living mouse lung, UC San Francisco scientists have revealed that the lungs play a previously unrecognized role in blood production. As reported online March 22, 2017 in Nature, the researchers found that the lungs produced more than half of the platelets—blood components required for the clotting that stanches bleeding—in the mouse circulation. In another surprise finding, the scientists also identified a previously unknown pool of blood stem cells capable of restoring blood production when the stem cells of the bone marrow, previously thought to be the principal site of blood production, are depleted.

 “This finding definitely suggests a more sophisticated view of the lungs—that they’re not just for respiration but also a key partner in formation of crucial aspects of the ,” said pulmonologist Mark R. Looney, MD, a professor of medicine and of laboratory medicine at UCSF and the new paper’s senior author. “What we’ve observed here in mice strongly suggests the may play a key role in blood formation in humans as well.”

The findings could have major implications for understanding human diseases in which patients suffer from low platelet counts, or thrombocytopenia, which afflicts millions of people and increases the risk of dangerous uncontrolled bleeding. The findings also raise questions about how residing in the lungs may affect the recipients of lung transplants.

Mouse lungs produce more than 10 million platelets per hour, live imaging studies show

The new study was made possible by a refinement of a technique known as two-photon intravital imaging recently developed by Looney and co-author Matthew F. Krummel, PhD, a UCSF professor of pathology. This imaging approach allowed the researchers to perform the extremely delicate task of visualizing the behavior of individual cells within the tiny blood vessels of a living mouse lung.

Looney and his team were using this technique to examine interactions between the immune system and circulating platelets in the lungs, using a mouse strain engineered so that platelets emit bright green fluorescence, when they noticed a surprisingly large population of platelet-producing cells called megakaryocytes in the lung vasculature (see video S1, video S2). Though megakaryocytes had been observed in the lung before, they were generally thought to live and produce platelets primarily in the bone marrow.

“When we discovered this massive population of megakaryocytes that appeared to be living in the lung, we realized we had to follow this up,” said Emma Lefrançais, PhD, a postdoctoral researcher in Looney’s lab and co-first author on the new paper.

 More detailed imaging sessions soon revealed megakaryocytes in the act of producing more than 10 million platelets per hour within the lung vasculature (see video S5), suggesting that more than half of a mouse’s total platelet production occurs in the lung, not the bone marrow, as researchers had long presumed. Video microscopy experiments also revealed a wide variety of previously overlooked megakaryocyte progenitor cells and blood stem cells sitting quietly outside the lung vasculature—estimated at 1 million per mouse lung.

Newly discovered blood stem cells in the lung can restore damaged bone marrow

The discovery of megakaryocytes and blood stem cells in the lung raised questions about how these cells move back and forth between the lung and bone marrow. To address these questions, the researchers conducted a clever set of lung transplant studies:

First, the team transplanted lungs from normal donor mice into recipient mice with fluorescent megakaryocytes, and found that fluorescent megakaryocytes from the recipient mice soon began turning up in the lung vasculature. This suggested that the platelet-producing megakaryocytes in the lung originate in the bone marrow.

“It’s fascinating that megakaryocytes travel all the way from the bone marrow to the lungs to produce platelets,” said Guadalupe Ortiz-Muñoz, PhD, also a postdoctoral researcher in the Looney lab and the paper’s other co-first author. “It’s possible that the lung is an ideal bioreactor for platelet production because of the mechanical force of the blood, or perhaps because of some molecular signaling we don’t yet know about.”

In another experiment, the researchers transplanted lungs with fluorescent megakaryocyte progenitor cells into mutant mice with low platelet counts. The transplants produced a large burst of fluorescent platelets that quickly restored normal levels, an effect that persisted over several months of observation—much longer than the lifespan of individual megakaryocytes or platelets. To the researchers, this indicated that resident megakaryocyte progenitor cells in the transplanted lungs had become activated by the recipient mouse’s low platelet counts and had produced healthy new megakaryocyte cells to restore proper platelet production.

Finally, the researchers transplanted healthy lungs in which all cells were fluorescently tagged into mutant mice whose bone marrow lacked normal blood stem cells. Analysis of the bone marrow of recipient mice showed that fluorescent cells originating from the transplanted lungs soon traveled to the damaged bone marrow and contributed to the production not just of platelets, but of a wide variety of blood cells, including immune cells such as neutrophils, B cells and T cells. These experiments suggest that the lungs play host to a wide variety of blood progenitor cells and stem cells capable of restocking damaged bone marrow and restoring production of many components of the blood.

“To our knowledge this is the first description of blood progenitors resident in the lung, and it raises a lot of questions with clinical relevance for the millions of people who suffer from thrombocytopenia,” said Looney, who is also an attending physician on UCSF’s pulmonary consult service and intensive care units.

In particular, the study suggests that researchers who have proposed treating platelet diseases with platelets produced from engineered megakaryocytes should look to the lungs as a resource for platelet production, Looney said. The study also presents new avenues of research for stem cell biologists to explore how the bone marrow and lung collaborate to produce a healthy blood system through the mutual exchange of stem cells.

“These observations alter existing paradigms regarding blood cell formation, lung biology and disease, and transplantation,” said pulmonologist Guy A. Zimmerman, MD, who is associate chair of the Department of Internal Medicine at the University of Utah School of Medicine and was an independent reviewer of the new study for Nature. “The findings have direct clinical relevance and provide a rich group of questions for future studies of platelet genesis and megakaryocyte function in lung inflammation and other inflammatory conditions, bleeding and thrombotic disorders, and transplantation.”

The observation that blood stem cells and progenitors seem to travel back and forth freely between the lung and lends support to a growing sense among researchers that stem cells may be much more active than previously appreciated, Looney said. “We’re seeing more and more that the stem that produce the blood don’t just live in one place but travel around through the blood stream. Perhaps ‘studying abroad’ in different organs is a normal part of stem cell education.”

“It has been known for decades that the lung can be a site of , but this study amplifies this idea by demonstrating that the murine lung is a major participant in the process,” said Traci Mondoro, PhD, project officer at the Translational Blood Science and Resources Branch of the NHLBI. “Dr. Looney and his team have disrupted some traditional ideas about the pulmonary role in -related hematopoiesis, paving the way for further scientific exploration of this integrated biology.”

 

Source:medicalxpress.com

Evaluation of Biomarkers for HER3-targeted Therapies in Cancer


Integration of biomarkers into the majority of drug development programs has led to a need for robust measurements and assay validation techniques for analyses of biological samples. The importance of solid methodologies for biomarker assessment is heightened by the fact that new drugs frequently only offer modest benefit and that many potential biomarkers are continuous variables, the application of which relies on data interpretation, with the risk of subjectivity bias, to establish thresholds. Patritumab is a fully human anti-human epidermal growth factor receptor 3 (HER3) antibody that inhibits HER3 from binding to HRG (Mendell et al., 2015). In the HERALD phase II trial, before data unblinding but after subject enrollment, heregulin (HRG) was prospectively declared to be the predictive biomarker for patritumab efficacy. Advanced non-small cell lung cancer (NSCLC) patients previously treated with at least one chemotherapy regimen were randomized to erlotinib plus patritumab (high- or low-dose) or erlotinib plus placebo (Mendell et al., 2015). Testing a single primary predictive biomarker hypothesis to identify those patients most likely to benefit from patritumab was a secondary objective of the trial and HRG was identified as a continuous biomarker to predict outcome.

Members of the HER family of receptor tyrosine kinases (RTK) and their respective ligands constitute a robust biologic system that plays a key role in the regulation of cell-proliferative growth, survival, and differentiation (Ma et al., 2014). HER3 transactivation via dimerization with other RTKs is frequently observed in various malignancies, including NSCLC. Binding of the alpha and beta forms of neuregulin 1, collectively known as HRG, exposes a dimerization arm in the extracellular domain of HER3 and promotes receptor–receptor interactions (Ma et al., 2014, Carraway et al., 1994). HER3 contains six phosphotyrosine binding sites for the p85 subunit of PI3K, the greatest number of all HER family members, and is a major cause of treatment failure in cancer therapy (Ma et al., 2014, Fedi et al., 1994). Recently, the role of HER3 in primary and acquired resistance to EGFR-targeted or other targeted therapies in NSCLC patients has attracted considerable attention (Ma et al., 2014, Torka et al., 2014). Since HER3 lacks or has weak intrinsic kinase activity, targeting it with blocking antibodies that inhibit HRG binding is one strategy currently being investigated in order to overcome therapeutic resistance (Ma et al., 2014).

In the study by Mendell et al., although no progression-free survival (PFS) benefit was observed overall with the addition of patritumab to erlotinib, when patients were stratified according to HRG mRNA levels HRG-high patients treated with patritumab and erlotinib had significantly improved PFS compared with patients treated with erlotinib alone in both the high- and low-dose arms (Hazard Ratio (HR), 0.37 [95%CI, 0.16–0.85] and 0.29 [95%CI, 0.13–0.66]) (Mendell et al., 2015). No PFS benefit was observed in HRG-low patients. An exploratory analysis suggested that high HRG expression might also be a negative prognostic factor in patients treated with single-agent erlotinib (Mendell et al., 2015).

The role of HRG expression as a marker of HER3 activity has been previously reported. Constitutive activation of HER3 signaling can occur in the absence of direct genetic activation of HER3 or HRG while HER3 activation does not occur as a result of mutation or amplification of the HER3 co-receptors EGFR or HER2. Chronic HER3 signaling is driven by high level and potentially autocrine expression of HRG (Holmes et al., 1992). When HRG and HER3 expressions were profiled in more than 750 patients with head and neck squamous cell carcinoma, high-level expression of HRG was associated with constitutive activation of HER3, defining an actionable biomarker for interventions targeting HER3 (Shames et al., 2013).

Since the arrival of erlotinib and gefitinib, metastatic EGFR positive lung cancer patients can be offered therapeutic alternatives with proven superiority over standard platinum-based chemotherapy (Rosell et al., 2013). Testing for EGFR mutations to guide patient selection for EGFR inhibitors, in all patients with advanced-stage adenocarcinoma, regardless of sex, race, smoking history, or other clinical risk factors, is highly recommended (Lindeman et al., 2013). As commented by Mendell et al., the use of a prospective–retrospective approach applied to a single predictive biomarker hypothesis has the advantage of avoiding a high false-positive rate due to multiple comparisons when multiple biomarker hypotheses are evaluated on an equal footing in an exploratory fashion (Mendell et al., 2015). But are statistical simulations able to dismiss the confounding interactions that EGFR-sensitizing mutations could have on the HRs observed in the study? Some readers may also wonder why, in a study of primarily erlotinib treatment where samples were obtained from most patients, EGFR mutations were not assessed? Clinical trials with EGFR inhibitors designed without using EGFR mutation status, as an enrolment criterion should not be an acceptable practice anymore. Finally, having lost >50% of samples for analyzing HRG mRNA, can we safely conclude that high HRG mRNA and not HER3 expression levels are correlated with patritumab efficacy?

Although technological improvements in terms of specimen acquisition and processing have been made, much work remains to be done to ensure the quality of biospecimens and harmonization of tissue collection, processing and storage procedures, attributable largely to the long-standing success of formalin-fixed paraffin-embedded tissue analysis as the standard in diagnostic pathology. There is an ongoing trend to improve standardization of procedures for biomarker development in oncology that involves academia, professional organizations, and industry. Identification and widespread use of biomarkers will ensure that patients receive the best possible therapeutic strategies, thereby avoiding unnecessary treatments and associated toxicities, and reducing total health costs. Increased awareness of HER3 function in cancer progression and tumor recurrence following drug resistance has several implications for future lines of investigation. High expression of HRG seems to accurately define a population of tumors that may have an oncogenic dependency on ligand-activated signaling via HER3 (Mendell et al., 2015). Based on the results of the Mendell et al. study, a two-part phase III study (NCT02134015) has been initiated to examine patritumab plus erlotinib treatment in EGFR wild-type patients with advanced NSCLC. Part A will enroll subjects with any HRG value to further refine the HRG cutoff level while evaluating the efficacy of patritumab plus erlotinib versus erlotinib in the HRG-high group. Part B will enroll only HRG-high (as per revised criteria) patients to evaluate efficacy and safety of patritumab plus erlotinib versus erlotinib.

Source:http://www.ebiomedicine.com

A Natural Solution to Water Security


New report analyzes 4,000 cities to demonstrate the health, climate and biodiversity benefits of source water protection.

When you turn on the tap in Quito, Ecuador, the water that emerges does so after a long journey. It starts high in the Andes, in springs and streams that merge into rivers, and flows downhill.

There, the water filters through cloud forests and grasslands, picking up more spring water and snowmelt from glaciers, continuing its downstream journey until it eventually reaches Quito’s municipal water system.

The quality of the water entering Quito, and many other cities around the world, is directly dependent on the landscapes through which the water flows. Good land management can promote water filtration, produce more reliable downstream flows, and reduce the amount of sediments and nutrients that can make their way into the rivers, springs and aquifers that feed urban water supplies. The city of Quito and upstream landholders have invested in taking care of their water sources for many years.

 Unfortunately, many of our lands around the world are not always managed well, which leads to impaired downstream water quality and flows. Deforestation, poor agricultural practices and other land uses have led to moderate to high degradation in 40 percent of the world’s urban source watersheds. Water quality and quantity challenges have typically been met with the addition of more gray infrastructure—including aqueducts, reservoirs and treatment plants—to move and treat water for human and industrial purposes.

But the path to water security doesn’t have to be lined exclusively in concrete. Improving the health of the lands around our water sources—a strategy called source water protection—can improve water quality, restore reliable water flows and bring added benefits to local ecosystems and communities.

As cities around the world use nature-based solutions to improve water quality, they are learning that those solutions provide so much more. Photo © Kevin Arnold
As cities around the world use nature-based solutions to improve water quality, they are learning that those solutions provide so much more.
In Bloomington, Illinois, agricultural runoff caused nitrate levels in the water supply to surpass federal standards. But a combination of wetland restoration and improved farming practices has shown to effectively remove inflowing nitrates at a cost-competitive rate. Photo © Cristina Rutter/The Nature Conservancy
In Bloomington, Illinois, agricultural runoff caused nitrate levels in the water supply to surpass federal standards. But a combination of wetland restoration and improved farming practices has shown to effectively remove inflowing nitrates at a cost-competitive rate.
Monterrey, Mexico has experienced flooding and drought during recent years. The city is investing in reforestation and many other activities designed to improve the lands within the watershed. Through this work, the watershed’s capacity to absorb available water could increase by 20 percent. Photo © Alejandro Lopez-Serrano/TNC
Monterrey, Mexico has experienced flooding and drought during recent years. The city is investing in reforestation and many other activities designed to improve the lands within the watershed. Through this work, the watershed’s capacity to absorb available water could increase by 20 percent.
Drought and sedimentation of reservoirs is causing water stress in São Paulo, Brazil. To decrease erosion in the watershed, about 13,000 hectares of land were identified for reforestation. Reforestation can help the city meet carbon storage goals—each hectare can store around 102 metric tonnes of carbon. Photo © Scott Warren
Drought and sedimentation of reservoirs is causing water stress in São Paulo, Brazil. To decrease erosion in the watershed, about 13,000 hectares of land were identified for reforestation. Reforestation can help the city meet carbon storage goals—each hectare can store around 102 metric tonnes of carbon.
Cattle feces contaminated the drinking water source in Pucará, Bolivia. A water fund now rewards ranchers and farmers who protect lands and streams in the watershed with payments, beehives or irrigation system materials. The program improves water quality and local lives. Photo © Nigel Asquith/Natura Bolivia
Cattle feces contaminated the drinking water source in Pucará, Bolivia. A water fund now rewards ranchers and farmers who protect lands and streams in the watershed with payments, beehives or irrigation system materials. The program improves water quality and local lives.
Runoff from bamboo farms polluted Longwu Reservoir, which provides water to 3,000 people in China. A water fund now pays farmers to transition to organic bamboo farming methods. Nutrient pollution has been reduced, and it is hoped that the water fund can be financially supported by the business venture. Photo © Haijiang Zhang/TNC
Runoff from bamboo farms polluted Longwu Reservoir, which provides water to 3,000 people in China. A water fund now pays farmers to transition to organic bamboo farming methods. Nutrient pollution has been reduced, and it is hoped that the water fund can be financially supported by the business venture.
Farming, quarrying and road construction in Nairobi, Kenya’s watershed led to increased sediment in the Tana River. A water fund improves agricultural practices that reduce sedimentation and could deliver a 2-to-1 return on investment. These actions also create pollinator habitat and carbon storage. Photo © Nick Hall
Farming, quarrying and road construction in Nairobi, Kenya’s watershed led to increased sediment in the Tana River. A water fund improves agricultural practices that reduce sedimentation and could deliver a 2-to-1 return on investment. These actions also create pollinator habitat and carbon storage. Photo © Nick Hall

10 Gt/yr

Source water protection could reduce CO2 emissions by 10 gigatonnes annually.


There are many effective source water protection activities, including forest protection, reforestation and improvement of agricultural practices on lands near water sources.

To implement these strategies, The Nature Conservancy is working with cities and water users around the world to create water funds, which enable water users to collectively invest in source water protection activities for the purpose of securing better water quality and improving the health and well-being of local communities. The Conservancy and its partners already have 29 water funds in operation and another 30 in development. The first of these was created more than 15 years ago—in Quito.

“Communities downstream are going to benefit if their water comes when they want it and how they want it,” said Andrea Erickson, managing director for water security at The Nature Conservancy. “Source water protection can provide that connection between downstream users and upstream individuals—the farmers, ranchers and other community members that are a critical part of the solution.”

At a time when there is growing demand for limited water supplies—and when climate change is making availability of water even more uncertain—source water protection is a powerful strategy to not only secure clean water but also mitigate and adapt to climate change, protect biodiversity, and support human health and well-being across watersheds.

Healthy Lands, Healthy Waters

 


What Are the Benefits of Source Water Protection?

Source water protection is first and foremost a strategy for securing clean, reliable natural water sources. The benefits of this approach are documented in “Beyond the Source: the environmental, economic and community benefits of source water protection,” a new report developed by The Nature Conservancy in partnership with the Natural Capital Project, Forest Trends, the Inter-American Development Bank and the Latin American Water Funds Partnership.

This global analysis demonstrates that four out of five of the more than 4,000 cities studied could meaningfully reduce sediment and nutrient pollution in the water they use through three source water protection activities—reforestation of pastureland, forest protection and the planting of cover crops.

In many cases, source water protection can pay for itself through water treatment savings. The Conservancy found that one in six of the cities studied could see a positive return on investment in source water protection through reduced annual treatment costs alone. But even cities that don’t break even on utility costs may realize great value through the other benefits that source water protection offers for people living in and around upstream watersheds and for the natural ecosystems that these watersheds support.

 MITIGATES CARBON EMISSIONS

Restoring and protecting forests, which filter water and help to control runoff, are two of the most effective strategies for ensuring clean water for downstream users. But these practices also have the added benefit of capturing and avoiding the release of carbon into the atmosphere, helping to mitigate climate change. With 64 percent of the total carbon in tropical above-ground biomass located in source watersheds, preserving these ecosystems is a vital part of a comprehensive mitigation strategy.

“Since I have about six hectares of reforestation, when the forest is grown I’ll trap about 600 tons of carbon." - Carlos Alberto Marques. Photo © Devan King/The Nature Conservancy
“Since I have about six hectares of reforestation, when the forest is grown I’ll trap about 600 tons of carbon.”

This is happening in the Guandu watershed in Brazil, which supplies drinking water for 8 million people in Rio de Janeiro. Deforestation in the watershed, driven by farming and ranching, had contributed to a steep decline in water quality. The Guandu Water Producer Project, launched in November 2008, collects fees from downstream users, which are used to compensate farmers and ranchers for reforesting their lands and leaving existing riparian forests standing. The result is both cleaner water in Rio and less carbon released into the atmosphere.

“Since I have about six hectares of reforestation, when the forest is grown I’ll trap about 600 tons of carbon,” says Carlos Alberto Marques, a retired farmer participating in the project. “And I am very small. Now, imagine if all the large landowners in this country did a little bit of what I’m doing here with my partners.”

 ENHANCES CLIMATE RESILIENCE

In addition to mitigating climate change, many source water protection measures can also help communities adapt to climate change impacts today and in the future. Changes in the hydrological cycle driven by climate change have resulted in increased incidences of both drought and flooding. Models predict increased soil erosion in 83 percent of source watersheds by mid-century and increased fire frequency in 24 percent.

It’s a scenario already evident in northern New Mexico, which is experiencing hotter, drier and longer fire seasons. These conditions are particularly dangerous in forests that are overgrown from fire suppression, where a wildfire can all but eviscerate the landscape.

“When these overgrown forests burn, they burn way too hot and destroy the headwater forests that are so critical for downstream users,” says Laura McCarthy, senior policy advisor for forest and fire restoration at The Nature Conservancy.

“When these overgrown forests burn, they burn way too hot and destroy the headwater forests that are so critical for downstream users." - Laura McCarthy. Photo © Alan W. Eckert Photography
“When these overgrown forests burn, they burn way too hot and destroy the headwater forests that are so critical for downstream users.” – Laura McCarthy.

When rains do come, water can more easily rush over the scorched land, which can result in flash floods that inundate the Rio Grande River with sediment, debris and ash—affecting water quality downstream.

In response to this heightened threat, a coalition of land owners, government agencies, nonprofits and private companies have come together to invest in stream restoration, flood control, tree thinning and other wildfire management techniques.

These measures are proving much less expensive than treating water after it’s been polluted, and the fire control measures are reducing risk for nearby communities.

IMPROVES HUMAN HEALTH AND WELL-BEING

A clean water supply is a crucial part of any healthy community, but source water protection also contributes to human well-being in other ways. Some source water protection activities can reduce the transmission of water-borne diseases. They can also protect natural habitat for bees and other pollinating insects, which are crucial for the production of fruit and vegetable crops that deliver essential micronutrients to millions of people around the world.

“They educated us on how the trees aided preservation of water. Avocado trees have been good for the soil, and also to feed ourselves, to sell and to support my family.” - Maria Esmeralda Marcillo. Photo © TNC
“They educated us on how the trees aided preservation of water. Avocado trees have been good for the soil, and also to feed ourselves, to sell and to support my family.” – Maria Esmeralda Marcillo.

More than 28 million farming households around the world could see potential improvements in crop production and increased longevity of their farms if source water protection activities were implemented throughout watersheds.

In Colombia’s Cauca Valley, small landowners are learning to use agroforestry and silvopasture practices, which involve growing crops and grazing livestock in areas interspersed with trees and other vegetation.

The strategy reduces sediment runoff, preserves natural habitat and improves long-term soil health, while also bolstering food security and incomes through increased agricultural output for many families.

Maria Esmeralda Marcillo, a farmer in the Cauca valley, describes her experience: “They educated us on how the trees aided preservation of water. Avocado trees have been good for the soil, and also to feed ourselves, to sell and to support my family.”

SUPPORTS BIODIVERSITY

Source water protection has important benefits for nature, too. More than three-fourths of urban source watersheds are within regions of high species diversity combined with high concentrations of species unique to those regions. But deforestation and other changes in land use are major threats to these ecosystems. In fact, according to WWF, tracked animal species populations in freshwater systems have declined by a staggering 81 percent over the last 40 years. Source water protection can play an important role in protecting habitat for both terrestrial and aquatic plant and animal species.

“Through reforestation, native trees are being planted, which are sources of food for these animals, and they are returning.” - Carlos Marques. Photo © Devan King/The Nature Conservancy
“Through reforestation, native trees are being planted, which are sources of food for these animals, and they are returning.” – Carlos Marques.

The same reforestation projects and changes in farming practices that are improving water quality and storing carbon in Brazil’s Guandu watershed, for example, are also contributing to the conservation of native plant and animal species populations. Both rare and representative species have been found in surveys of areas where habitats are being restored and protected.

Marques describes what he’s seen in the Guandu watershed: “Through reforestation, native trees are being planted, which are sources of food for these animals, and they are returning.”


Water Funds: A Mechanism for Realizing Source Water Protection

A key question, of course, is how to fund source water protection. The Conservancy estimates that an increase in annual global spending on ecosystem service programs between US$42 billion and US$48 billion would be required to achieve a 10 percent reduction in sediment and nutrient pollution in source watersheds worldwide. This level of spending could improve water security for at least 1.4 billion people. However, the question of who should bear that cost remains.

This is where the water fund enters the equation. Water funds provide a mechanism for downstream users to directly or indirectly compensate upstream users for activities that deliver water benefits to the payer.

Public and private water users, including businesses, utilities and local governments, invest collectively in conservation of the watersheds from which they source their water.

In fact, for half of the cities that the Conservancy studied, such a mechanism could fund source water protection activities at a cost of just US$2 or less per person per year.

Nairobi, Kenya, offers a good example. The conversion of forests and wetlands to agricultural uses in the Upper Tana River watershed, which supplies Nairobi’s water, has led to heavy sedimentation in the river—reducing the capacity of reservoirs, impacting the delivery of water to Nairobi water users and limiting hydropower generation during low-flow periods.

Nairobi Water Fund: A First for Africa

A number of water users and conservation groups, including the Nairobi City Water and Sewerage Company, The Nature Conservancy and the Kenya Electricity Generating Company, came together to establish the Upper Tana-Nairobi Water Fund, which is currently working with over 15,000 farmers in the watershed, providing funding and training to help farmers improve their land management practices. By planting cover crops and digging trenches that trap soil runoff, farmers are able to improve their crop yields while also reducing sedimentation in the Tana and other rivers.

“We always realized green infrastructure would be a part and parcel of our operation,” says Philip Gichukki, managing director of the Nairobi City Water and Sewer Company. “When the idea of the water fund came about, we were excited because we found it was possible for us to engage with everybody involved in water catchment conservation, and it was possible to pool together the resources of people whose businesses relied on water along with those of us who manage the water.”

An image of an aracari (Pteroglossus) from Brazil. Photo © Shutterstock/Cuson
An image of an aracari (Pteroglossus) from Brazil.

Could see reduced risk of extinction through watershed reforestation.

Bringing Communities and Partners Together for Shared Benefit

Successful source water protection strategies require the cooperation of parties both upstream and downstream, including landowners, governments, corporations, NGOs and many others with seemingly disparate interests. But these strategies are effective precisely because they can generate benefits for all these stakeholders.

“The most important component for a successful water fund is understanding the value of the engagement it provides for people,” Erickson says. “Everyone will come to the table when they understand that they really have something to gain.”

Brooklyn Bridge Park looking towards Manhattan. Photo © Kevin Arnold
Brooklyn Bridge Park looking towards Manhattan.

McCarthy agrees. Source water protection is effective, she says, because “people are ready for big scale solutions that unite everyone in working on a problem together.”

Source water protection shows that even economic development and nature preservation can be achieved together. The Rio Grande Water Fund in New Mexico, which has 53 signatory organizations, has created 70 new jobs in its first year of operation and project managers estimate that 300 to 600 seasonal forest worker jobs will be created annually in the future.

Reforestation work in Brazil’s Guandu watershed has created more than 300 new formal jobs and another 350 informal jobs. Many of the jobs in Guandu are being filled by people who were previously working in illegal logging—a win for the community and for nature.

Achieving these win-win situations is crucial for the next generation, says Debora Dos Santos Leite, principal at the Rio das Pedras Municipal School in Brazil. “Nature is everything to people. It is life. It is the future of the generation that we have here, the very little ones. Everyone is grateful for the work we are doing because, in addition to bringing benefits to the families and to the community, the greatest benefit is to the children.”

Source:global.nature.org

More than 200 migrants feared drowned in Mediterranean


More than 200 migrants are feared dead after five bodies were discovered off the Libyan coast, a Spanish aid organisation says.

Proactiva said the bodies were found floating near two capsized boats which could each hold more than 100 people.

The group’s Laura Lanuza said the five they pulled from the Mediterranean were young men who appeared to have drowned.

A body is lifted on to Proactiva Open Arm's ship Golfo Azzurro on 23 March 2017

A spokesman for Italy’s coast guard, which co-ordinates rescues, confirmed the five deaths.

The spokesman told the BBC that the coast guard could not confirm whether any boats had sunk, and said no distress calls had been received.

Ms Lanuza said at least 240 migrants may have died as the boats were often overloaded by smugglers.

“We brought on board five corpses recovered from the sea, but no lives,” the group wrote on its Facebook page.

“It is a harsh reality check of the suffering here that is invisible in Europe.”

Numbers of migrants trying to reach Europe from Libya via Italy have risen dramatically this year since the route between Turkey and Greece was effectively shut down.

The Italian coast guard said they had co-ordinated more than 40 rescue operations in the last few days.

The International Organization for Migration (IOM) says more than 20,000 migrants have arrived in Italy so far this year – and some 559 people are estimated to have died or gone missing en route.

This compares with fewer than 19,000 arrivals in Italy and about 350 deaths in the first three months of 2016.

“We have yet to complete March, and we are already racing at a pace of arrivals that has exceeded anything we’ve seen before in the Mediterranean,” IOM spokesman Joel Millman said earlier this week.

“This is typical of spring, getting very busy, but it’s not typical to have the numbers be so high this early and the corresponding deaths that go with it.”

source: BBC

SCIENCE An Atomic Bomb went off on Earth 12000 years ago?


Ancient civilizations and pagan religions have left many marks in history with scripts, monuments and numerous objects that make us reevaluate what we know so far regarding our past and where we are going as a civilization.

One of the most important questions most of us have tried to never ask, is if we were visited in the distant past by other civilizations beyond earth. There are hundreds and hundreds of unanswered questions, but there are texts that shed much light, if not almost entirely, illuminating the path of a truly untold story.

The Mahabharata and the Ramayana offer many answers to numerous questions regarding our past, present and future.

The Mahabharata is one of the two major Sanskrit epics of ancient India, the other being the Ramayana. It consists of 100,000 verses divided into 18 parts or books that are equivalent to eight times the Iliad and Odyssey combined. these ancient texts are more than a historical narration. It is a combination of facts, legends stories and myths. A vast collection of didactic discourses written that were written in a beautiful language, nurturing all Hindu mythology and creating one of the major world religions: Hinduism.

Among those historical texts, we see a story of a devastation that occurred in the past, one that cannot be compared to anything else in the past, a devastation much similar to what we know today is destruction caused by nuclear weapons. Historian Kisari Mohan Ganguli, argues that the Mahabharata and the Ramayana are full of descriptions of large nuclear holocausts that are apparently of incredibly higher proportions than those at Hiroshima and Nagasaki.

When a student asked Dr. Oppenheimer if the first nuclear device that went off was the one at Alamogordo. during the Manhattan Project, he responded… Well … yes. In modern times, yes, of course.

The ancient Hindu text the Mahabharata:

“Gurkha, flying a swift and powerful vimana,
hurled a single projectile
charged with the power of the Universe.

An incandescent column of smoke and flame,
as bright as ten thousand suns,
rose with all its splendor.

It was an unknown weapon,
an iron thunderbolt,
a gigantic messenger of death,
which reduced to ashes
the entire race of the Vrishnis and the Andhakas.

The corpses were so burned
as to be unrecognizable.

Hair and nails fell out;
Pottery broke without apparent cause,
and the birds turned white.

…After a few hours
all foodstuffs were infected…
…to escape from this fire
the soldiers threw themselves in streams
to wash themselves and their equipment.”

A second passage.

“Dense arrows of flame,
like a great shower,
issued forth upon creation,
encompassing the enemy.
A thick gloom swiftly settled upon the Pandava hosts.
All points of the compass were lost in darkness.
Fierce wind began to blow
Clouds roared upward,
showering dust and gravel.

Birds croaked madly…
the very elements seemed disturbed.
The sun seemed to waver in the heavens
The earth shook,
scorched by the terrible violent heat of this weapon.

Elephants burst into flame
and ran to and fro in a frenzy…
over a vast area,
other animals crumpled to the ground and died.
From all points of the compass
the arrows of flame rained continuously and fiercely.” — The Mahabharata


 

There are many other references in the Ramayana which seem to be very similar to those described in the above texts. It is very clear that these texts allude to a great holocaust that killed thousands of lives. One that can be easily traced to nuclear weapons we use today.

But is there evidence, other than the texts supporting the theory that a nuclear device went off on Earth thousands of years ago? In 1992 researchers discovered in Rajasthan a layer of radioactive ash, covering an area of about eight square kilometers, 16 kilometers west of Jodhpur. The radiation is so intense that it still contaminates the area today. Researchers excavated at Harappa and Mohenjo-Daro, discovering skeletons scattered throughout the area as if a sudden event occurred that devastated entire cities.

 “(It was a weapon) so powerful
that it could destroy the earth in an instant–
A great soaring sound in smoke and flames–
And on it sits death…” . — The Ramayana

The site where researchers have found skeletons and remains of radioactivity is very similar to Hiroshima and Nagasaki, but with one striking difference: the radiation levels found at Harappa and Mohenjo-Daro were 50 times higher than the remains of the nuclear holocaust of Hiroshima and Nagasaki.

WHAT REALLY HAPPENED?

What really happened? Are the Mahabharata and the Ramayana really describing a nuclear device exploding on Earth tens of thousands of years ago? If so where id it come from? Ancient astronaut theorists are talking about a nuclear holocaust which happened around 12,000 years ago. An explosion that according to theories, created a crater with 2154 meters in diameter, located 400 kilometers from Mumbai.
The dating ranges from 12,000 to 50,000 years ago so researchers have a gigantic time frame to work with.

Source:https://spiritegg.com