Target e*Informed Consent (Target e*ICF™)
The Clinical Trials Transformation Initiative (CTTI) is very active supporting the modernization of the informed consent process. Part of this effort is utilizing an electronic informed consent integrated with electronic signatures. Some solutions include the use of stand-alone dedicated tablets and others are web-based. As we live in a modern world where electronic devices are somewhat ubiquitous, there is a push to BYOD (bring your own device). As a result, we created a web-based solution fully integrated with Target e*CRF®.
A global clinical trial will begin in January with 3 languages. Study participants will first be registered in Target e*CRF® by the clinical site. Subjects will then be able to read the informed consent page by page, ask questions on line, receive answers online, and then sign online once the subject confirms that all questions have been answered. Authorized user at the clinical site will then sign the electronic Informed Consent and only then can the clinical site enter data. For flexibility, the system is also designed to allow for confirmation of the signing of a paper informed consent.
Target e*ICF™ can be used as a stand-alone application or fully integrated with Target e*CRF®. The benefits are huge and introductory programs are available.
Autumn In NY – View Form the 24th Floor at Target Health’s Corporate Headquarters
ON TARGET is the newsletter of Target Health Inc., a NYC – based, full – service, contract research organization (eCRO), providing strategic planning, regulatory affairs, clinical research, data management, biostatistics, medical writing and software services to the pharmaceutical and device industries, including the paperless clinical trial.
For more information about Target Health contact Warren Pearlson (212 – 681 – 2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.
Joyce Hays, Founder and Editor in Chief of On Target
Jules Mitchel, Editor
Non-Surgical Method to Reverse Cataracts – HUGE !
Photo Credit: MedPageToday, PHANIE/ALAMY
As reported last week in Science, a naturally occurring steroid has dissolved cataracts in mice, a potentially game changing development in the search for a nonsurgical treatment of the eye disease, cataracts. A new study using steroid eye 1) ___ to reverse cataracts could offer an alternative to invasive surgical treatments. The steroid eye drops were shown to reverse cataracts in 2) ___.
More than half of Americans over the age of 70 have cataracts, caused by clumps of proteins collecting in the eye lens. At present, the only way to remove them is 3) ___, an unavailable or unaffordable option for many of the 20 million people worldwide who are blinded by the condition. Now, a new study in mice suggests eye drops made with a naturally occurring steroid could reverse cataracts by teasing apart the protein clumps. This is a game changer in the treatment of cataracts, says Roy Quinlan, a molecular biologist at Durham University in the United Kingdom who was not part of the study. It takes decades for the 4) ___ to get to that point, so if you can reverse that by a few drops in the eye over a couple of weeks, that’s amazing.
The proteins that make up the human lens are among the oldest in the body, forming at about 4 weeks after fertilization. The majority are crystallins, a family of proteins that allow the eye to focus and keep the lens 5) ___. Two of the most abundant crystallins, CRYAA and CRYAB, are produced in response to stress or injury. They act as chaperones, identifying and binding to damaged and misfolded proteins in the lens, preventing them from aggregating. But over the years, as damaged proteins accumulate in the lens, these chaperones become overwhelmed. The mutated proteins then clump together, blocking light and producing the tell-tale cloudiness of cataracts.
To treat cataracts without surgery – which is out of reach for many patients in developing nations – researchers have looked to 6) ___ treatments. Although boosting the function of CRYAA and CRYAB seems to be a good target, developing a therapeutic has been challenging. Most drugs that act on disease-related proteins work by changing how the protein functions, something scientists can measure by monitoring the protein’s enzymatic activity. CRYAA, CRYAB, and similar proteins are known as undruggable because their activity can’t be 7) ___, says Jason Gestwicki, a biochemist at the University of California (UC), San Francisco, and a senior author of the new study, published in Science. Gestwicki’s team decided to use a technology called differential scanning fluorimetry, which allows scientists to measure the temperature at which a target protein begins to melt. They analyzed CRYAA and CRYAB and discovered that in one type of hereditary cataract, CRYAB takes on a mutant form with a much higher melting temperature than its normal version. If they could find a molecule that would bind to the mutant CRYAB protein and lower its melting 8) ___ back to that of a healthy CRYAB, they speculated, CRYAB should function normally and prevent damaged proteins from clumping in the lens. They then turned to a bank of 2450 molecules that exhibited similar properties to CRYAA and CRYAB. They added molecules to the mutant CRYAB, looking for one that would stabilize their target. They settled on compound 29, a steroid found naturally in the bloodstream but not in the lens, which has no blood supply. To test the concept, mice with age-related and hereditary cataracts received drops in the right eye, whereas the left eye went untreated. After just a few weeks, the treated eye was visibly clearer. Cataract severity is measured on a scale of zero to four, with four being the worst case. On average, mice in the study had about a one-grade improvement in cataract severity after 4 weeks of treatment. This is the second study this year to find that eye drops made from a class of 9) ___ called sterols can successfully reverse cataracts. In July, researchers from UC San Diego reported that lanosterol, a steroid found in the human eye, reversed cataracts in dogs.
One key difference between the two studies is the way the different steroids were administered. The dog study administered the drug both by injection into the eye and eye drops. The new study used only eye drops. There’s still a lot to uncover before either study can move into clinical trials. The lens in the human eye is very different from those in mice or dogs, and neither study explains how the steroids work on cataracts. Figuring out how the treatment reverses cataracts is the team’s next task, a key step toward 10) ___ trials, which Gestwicki hopes to launch in the next year. ViewPoint Therapeutics, a biotech company he co-founded in San Francisco, California, holds the license to the technology and will launch more animal studies soon. Source: ScienceDaily.com
ANSWERS: 1) drops; 2) mice; 3) surgery; 4) cataracts; 5) clear; 6) drug; 7) measured; 8) temperature; 9) steroids; 10) clinical
The exact cause of cataracts is unknown. While the risk grows as you get older, other factors may also contribute like: diabetes, smoking, excess alcohol use, eye injury. Source: WebMD
Cataract surgery is easy today, but dissolving a cataract with steroid drops will be the easiest of all. Source: WebMD
Editor’s note: The reading done, for this week’s History of Medicine, was so interesting, that we’ve made this section a little longer than usual, in the hopes that our readers will be fascinated, as well. Ophthalmologists are really interesting people. Enjoy the longer read:
Couching is the earliest documented form of cataract surgery. As a cataract is a clouding in the lens of the eye, couching is a technique of dislodging the lens, thus removing the opacity. Although couching is nowadays routinely practiced merely in remote areas in third world countries, it was a precursor to modern cataract surgery and pars plana vitrectomy. Cataract surgery by couching (lens depression) was, without a doubt, one of the oldest surgical procedures. This technique involved using a sharp instrument to push the cloudy lens to the bottom of the eye. Perhaps this procedure is that which is mentioned in the articles of the Code of Hammurabi (ca. 1792-1750 BCE).
Maharshi Sushruta, an ancient Indian surgeon, first described the procedure in Sushruta Samhita, Uttar Tantra, an Indian medical treatise from 800 BCE. Since that time the procedure seems to have been wide spread throughout the world. Evidence shows that couching was widely practiced in China, Europe, and Africa. After the 19th century, with the development of modern cataract surgery (Intra ocular extraction of lens (1748), couching fell out of fashion, though it is still used in parts of Asia and Africa. Couching continues to be popular in some developing countries where modern surgery may be difficult to access or where the population may prefer to rely on traditional treatments. It is commonly practiced in Sub-Saharan Africa. In Mali it remains more popular than modern cataract surgery, despite the fact that the cost of both methods is similar, but with much poorer outcome with couching. In Burkina Faso, a majority of patients were unaware of the causes of cataracts and believed it to be due to fate. It is not performed by ophthalmologists, but rather by local healers or witch doctors. A sharp instrument, such as a thorn or needle, was used to pierce the eye either at the edge of the cornea or the sclera, near the limbus. The opaque lens was pushed downwards, in the eye, out of the way of vision, allowing light to enter the eye. The cataract phlegm was then blown out of the nose. The eye would later be soaked with warm clarified butter and then bandaged. Once the patients saw shapes or movement, the procedure was stopped. The patient was left without a lens (aphakic), therefore, later in history, this couching procedure included a powerful lens to compensate for the lost one.
Couching, still done in the 21st Century, is a largely unsuccessful technique with abysmal outcomes. A minority of patients may regain the ability to sense light and some movement, but over 70% are left totally blind. A Nigerian study showed other complications include secondary glaucoma, hyphaema, and optic atrophy. Couching does not compare favorably to modern cataract surgery.
Here is translation from the original Sanskrit written around 800 BCE:
vv.55-56: Now procedure of surgical operation of slai?mika lidganasa (cataract) will be described. It should be taken up (for treatment) if the diseased portion in the pupillary region is not shaped like half-moon, sweat drop or pearl: not fixed, uneven and thin in the center, streaked or variegated and is not found painful or reddish.
vv. 57-61ab: In moderate season, after unction and sudation, the patient should be positioned and held firmly while gazing at his nose steadily. Now the wise surgeon leaving two parts of white circle from the black one towards the outer canthus should open his eyes properly free from vascular network and then with a barley-tipped rod-like instrument held firmly in hand with middle, index and thumb fingers should puncture the natural hole-like point with effort and confidence not below, above or in sides. The left eye should be punctured with right hand and vice-versa. When punctured properly a drop of fluid comes out and also there is some typical sound.
vv. 61bc-64ab: Just after puncturing, the expert should irrigate the eye with breast-milk and foment it from outside with vata-[wind-]alleviating tender leaves, irrespective of dosa [defect] being stable or mobile, holding the instrument properly in position. Then the pupillary circle should be scraped with the tip of the instrument while the patient, closing the nostril of the side opposite to the punctured eye, should blow so that kapha [phlegm] located in the region be eliminated.
vv. 64cd-67: When pupillary region becomes clear like cloudless sun and is painless, it should be considered as scraped properly.
(If do?a [defect] can’t be eliminated or it reappears, puncturing is repeated after unction and sudation.)
When the sights are seen properly the salaka [probe] should be removed slowly, eye anointed with ghee (similar to butter) and bandaged. Then the patient should lie down in supine position in a peaceful chamber.
He should avoid belching, coughing, sneezing, spitting and shaking during the operation and thereafter should observe the restrictions, as after intake of sneha [oil].
v.68: Eye should be washed with vata-[wind-]alleviating decoctions after every three days and to eliminate fear of (aggravation of ) vayu [wind], it should also be fomented as mentioned before (from outside and mildly).
v.69: After observing restrictions for ten days in this way, post-operative measures to normalize vision should be employed along with light diet in proper quantity.
The removal of cataract by surgery was also introduced into China from India, and flourished in the Sui (AD 581-618) and Tang dynasties (CE 618-907). The first references to cataract and its treatment in the West are found in 29 CE in De Medicinae, the work of the Latin philosopher and encyclopedist Aulus Cornelius Celsus, which also describes a couching operation.
Artifacts show, that the lens of the human eye can also be removed by suction through a hollow instrument. Bronze oral suction instruments have been unearthed that seem to have been used for this method of cataract extraction during the 2nd century CE. Such a procedure was described by the 10th-century Persian physician Muhammad ibn Zakariya al-Razi, who attributed it to Antyllus, a 2nd-century Greek physician. The procedure required a large incision in the eye, a hollow needle, and an assistant with an extraordinary lung capacity. This suction procedure was also described by the Iraqi ophthalmologist Ammar ibn Ali of Mosul, in his Choice of Eye Diseases, also written in the 10th century. He presented case histories of its use, claiming to have had success with it on a number of patients.
Extracting the lens has the benefit of removing the possibility of the lens migrating back into the field of vision. A later variant of the cataract needle in 14th-century Egypt, reported by the oculist Al-Shadhili, used a screw to produce suction.
Couching continued to be used throughout the Middle Ages and is still used in some parts of Africa and in Yemen. However, couching is an ineffective and dangerous method of cataract therapy, and often results in patients remaining blind or with only partially restored vision. For the most part, it has now been replaced by extracapsular cataract surgery and, especially, phacoemulsification. In 1748, Jacques Daviel was the first modern European physician to successfully extract cataracts from the eye. Jacques Daviel (11 August 1696 – 30 September 1762) was a French ophthalmologist credited with originating the first significant advance in cataract surgery since couching was invented. Daviel performed the first extracapsular cataract extraction on April 8, 1747. Daviel earned his medical degree from the Medical School of Rouen, practiced in Marseille where he was affiliated with the medical school there, then restricted his practice to ophthalmology in 1728. He was on the staff of Hospital d’Invalides and became oculist to Louis XV. In March 1756 he was elected a Fellow of the Royal Society. In 1759, He was elected a foreign member of the Royal Swedish Academy of Sciences. Daviel died of apoplexy in 1762 while on a trip to Geneva, Switzerland.
In the 1940s Harold Ridley introduced the concept of implantation of the intraocular lens which permitted more efficient and comfortable visual rehabilitation possible after cataract surgery. The implantation of a foldable intraocular lens is the procedure considered the state-of-the-art. Sir Nicholas Harold Lloyd Ridley (10 July 1906 – 25 May 2001) was an English ophthalmologist who invented the intraocular lens and pioneered intraocular lens surgery for cataract patients. Nicholas Harold Lloyd Ridley was the son of Nicholas Charles Ridley and his wife Margaret, n?e Parker; he had a younger brother, Olden. Harold had a stammer which he largely managed to cure. As a child he met and sat on the lap of Florence Nightingale, a close friend of his mother. He was educated at Charterhouse School before studying at Pembroke College, Cambridge from 1924-1927, and completed his medical training in 1930 at St Thomas’ Hospital. Subsequently he worked as a surgeon at both St Thomas’ Hospital and Moorfields Eye Hospital in London, specializing in ophthalmology. In 1938 Ridley was appointed full surgeon and consultant at Moorfields Hospital and later appointed consultant surgeon in 1946. During World War II, Ridley saw Royal Air Force casualties with eye injuries and noticed that when splinters of acrylic plastic from aircraft cockpit canopies became lodged in the eyes of wounded pilots, they did not trigger rejection as glass splinters did, leading him to propose the use of artificial lenses in the eye to correct cases of cataracts. He had a lens manufactured using the same material – brand name Perspex made by ICI – and on 29 November 1949 at St Thomas’ Hospital, Harold Ridley achieved the first implant of an intraocular lens, although it was not until 8 February 1950 that he left an artificial lens permanently in place in an eye. The first lens was manufactured by the Rayner Company of Brighton & Hove, East Sussex, a company which continues to manufacture and market modern, small-incision intraocular lenses today. The first IOL implant in the United States was performed in 1952, a Ridley-Rayner lens implanted at the Wills Eye Hospital in Philadelphia. Ridley pioneered this treatment in the face of prolonged strong opposition from the medical community. He worked hard to overcome complications, and had refined his technique by the late 1960s. With his pupil Peter Choyce he eventually achieved worldwide support for the technique. The intraocular lens was finally approved as safe and effective and approved for use in the US by the Food and Drug Administration in 1981. The first US Food and Drug Administration (FDA) approved lenses, (Choyce Mark VIII and Choyce Mark IX Anterior Chamber lenses) were manufactured by Rayner. Cataract extraction surgery with intraocular lens implantation is now the most common type of eye surgery. Ridley retired from NHS hospital service in 1971. In the 1990s he underwent successful bilateral intraocular lens implantation at St Thomas’s Hospital by surgeon Mr. Michael Falcon. Thus Harold Ridley benefitted from his own invention and the operational procedure he had pioneered but what was most pleasing to him was that he had it done in the same hospital where he performed the first operation. Sir Harold Ridley resided in Stapleford near Salisbury, Wiltshire until his death on 25 May 2001.
The Medical Maverick, Grandfather of Small Incision Surgeries Charlie Kelman MD (1930-2004)
In 1967, American ophthalmologist, and a pioneer in cataract surgery, Charles D. Kelman, (1930-2004) introduced phacoemulsification, a technique that uses ultrasonic waves to emulsify the nucleus of the crystalline lens in order to remove the cataracts without a large incision. This new method of surgery decreased the need for an extended hospital stay and made the surgery ambulatory. Patients who undergo cataract surgery hardly complain of pain or even discomfort during the procedure. However patients who have topical anesthesia, rather than peribulbar block anesthesia, may experience some discomfort.
According to surveys of members of the American Society of Cataract and Refractive Surgery, approximately 2.85 million cataract procedures were performed in the United States during 2004 and 2.79 million in 2005, using Kelman’s procedure.
Kelman was born in Brooklyn, New York, on May 23, 1930, to Eva and David Kelman. After graduating from Forest Hills High School and Tufts University, he completed medical studies at the University of Geneva, Switzerland, an internship at Kings County Hospital, Brooklyn, and residency in ophthalmology at the Wills Eye Hospital, Philadelphia. He started a private practice in New York City in 1960. In 1962, Dr. Kelman devised the cryoprobe, a freezing instrument for the extraction of cataracts within their capsules. This became the most widely used method for cataract removal in the world until about 1978, when it was supplanted by extracapsular cataract extraction with irrigation and aspiration, also introduced by Dr. Kelman and still the technique used by a majority of cataract surgeons today. In 1963, Dr. Kelman pioneered the use of freezing for the repair of retinal detachments. Retinal cryopexy remains a frequent adjunct in retinal surgery to this day. Kelman phacoemulsification, introduced in 1967, reduced recovery from cataract surgery from a 10-day hospital stay to today’s outpatient cataract surgery, allowing the patient immediate return to activity. The procedure employs a small ultrasonic tip whose vibrations break up the mass of the cataractous lens within its capsule and suction it out through a small needle. An estimated 100 million such procedures have been performed worldwide. In 1975, Dr. Kelman began designing lens implants for use in conjunction with cataract surgery. Numerous companies including Allergan Medical Optics, IOLAB, Alcon Surgical, Domilens, and Storz Ophthalmics sought his services. Dr. Kelman became the world’s most successful intraocular lens designer. Neurosurgeons have adapted the Kelman phacoemulsification machine for use in the dissection of tumors from the delicate brain and spinal cord tissue in children. In this way, the device has saved hundreds of young lives. Phacoemulsification was the stimulus for small incision surgery.
Later in life, Kelman worked on several projects, including artificial blood vessels, artificial corneas, and a magnetic cataract extraction procedure which retains the patient’s normal ability to focus on near and distant objects. Other applications of the magnetic technique can be used to remove plaque from arteries and growths from the digestive tract, prostate, bladder, and other areas without invasive surgery.
Clinical Professor of Ophthalmology at New York Medical College, Dr. Kelman held the position of attending surgeon at the New York Eye and Ear Infirmary and Manhattan Eye, Ear and Throat Hospital. He was also a consultant surgeon at many hospitals throughout the world, and he received some of the highest honors in science and technological innovation. A past president of the American Society of Cataract and Refractive Surgeons, Dr. Kelman has written hundreds of articles, papers, and scientific books, as well as a lay book on cataracts and an autobiography entitled Through My Eyes.
Known as Charlie to his friends, Dr. Kelman found time to learn to pilot his own helicopter and avidly followed his hobbies of golf, music, and performing. He entertained on The Tonight Show, The David Letterman Show, The Oprah Winfrey Show, and numerous others. Charlie appeared in concert with Lionel Hampton and Dizzy Gillespie, and performed in concert at Carnegie Hall, Las Vegas, and Atlantic City with Regis Philbin, and others. Columbia Records also released an instrumental recording of Moonlight Serenade in which all the reed parts were played by Charlie.
Dr. Kelman continued to teach his surgical techniques to doctors around the world, while devoting his spare time to writing lyrics and music for several musicals, The Marrano and most passionately, The Right Pair of Shoes, until his death in 2004 from lung cancer. Posthumously, Dr. Kelman was honored with the Lasker Award, the nation’s highest award for medical science, among other accolades. Undoubtedly, Dr. Kelman’s impact is as unique as his personality and practices. Charlie Kelman’s phacoemulsification surgery has proven to be the rare technology with longevity – it is still the most common method used worldwide for the procedure. The program cites unheard of statistics for a 30-year-old innovation: nearly 100% of the almost 3 million cataract surgeries performed each year in the United States are done with phacoemulsification, and nearly 10 million each year worldwide. The procedure saves millions in healthcare costs both in the way the procedure is done and by the outcome of preventing blindness, thus allowing people to continue to contribute to society. Kelman spawned an empire that thrives to this day. Additionally, as his colleague Dr. Jack Dodick, chairman, department of ophthalmology, New York University Langone Medical Center and attending in ophthalmology at the Manhattan Eye, Ear, and Throat Institute, notes in the program, When Charlie was first able to remove an unwanted tissue inside the human body through a small hole, he basically became the grandfather of all small incision surgery in the whole body.
Dr. Kelman received some of the highest honors in science and technological innovation including the National Medal of Technology and Innovation (formerly known as the National Medal of Technology), the highest honor for technological achievement bestowed by the President of the United States on America’s leading innovators; and the American Academy of Ophthalmology’s prestigious Laureate Award, awarded six months before he died of cancer. Posthumously, Kelman was honored with the Lasker Award, the nation’s highest award for medical science, among other accolades. In 2013, a biographical profile of Dr. Kelman was included in a bestselling book called Saving Sight: An eye surgeon’s look at life behind the mask and the heroes who changed the way we see, by Andrew Lam (author), M.D. Dr. Kelman’s accomplishments and his gift for showmanship brought him unusual fame for an ophthalmologist, including many television appearances. But success was not immediate. In his memoir, ”Through My Eyes: The Story of a Surgeon Who Dared to Take On the Medical World” (Crown, 1985), Dr. Kelman described a low point in his research when, having spent $250,000 in grant money, he failed to find a solution. Among other approaches, he had tried small drills on lab animals; while they removed the cataract, they also destroyed the eye.
Then he went to a dentist have his teeth cleaned. ”I sat in his chair, as he reached over, took a long silver instrument out of its cradle and turned it on,” Dr. Kelman wrote. ”A fine mist came off the tip but the tip didn’t seem to be moving. He applied the tip to my teeth, and I felt an exquisite vibration and heard a high-pitched sound.” Dr. Kelman asked, ”What is that thing?” An ultrasonic probe, came the reply. ”I knew this was the moment,” Dr. Kelman wrote. In 1967, the phacoemulsification procedure was introduced. Instead of making a large incision in the eye and removing the lens, doctors could make a tiny one. Then they inserted an ultrasonic tip which, vibrating thousands of times a second, broke up the cataracts without damaging the surrounding tissue. The remains of the cataract were suctioned out. The procedure, which Dr. Kelman taught to thousands of doctors around the world, is now performed more than a million times a year in the United States alone. Artificial lenses that he developed in the 1970’s are now routinely implanted in patients’ eyes, making unnecessary the ultra-thick glasses that once were common after surgery. And his ultrasonic approach has been adopted in other fields of medicine, including neurosurgery. ”It was not evolutionary, it was revolutionary,” said Dr. Elliot Finkelstein, a past president of the American Academy of Ophthalmology. The discovery brought recognition to a man who had long wanted it, if not necessarily by this path.
Kelman dreamed of being a musician when he was a child, and, in fact, became a well-regarded amateur jazz saxophonist and clarinetist. He also did an occasional stand-up routine in nightclubs and helped produce several Broadway shows. The combination of his medical achievements, performing skills and robust self-confidence made him a natural for television. Dr. Kelman made numerous appearances with hosts like Johnny Carson, Merv Griffin, Barbara Walters, Oprah Winfrey and David Letterman. He also played with jazz stars like Lionel Hampton and Dizzy Gillespie, some of whom, like Hampton, were his patients. He rented Carnegie Hall to give a performance. And in his 40’s, he learned to fly a helicopter, landing it on the roof of a hospital in Long Island where he was working. Some of the more conservative members of his field were put off by the flamboyance of the man who sometimes referred to himself as ”the world’s No. 1 ophthalmologist.” Even his supporters agreed that bashfulness was not in his nature. ”Charlie was the ultimate extrovert,” Dr. Finkelstein said. ”But he was a guy who really produced.”
Even before adapting ultrasound for cataract surgery, Dr. Kelman devised a groundbreaking cataract-removal technique that became widely used. It involved an instrument called a cryoprobe, which he invented in 1962 and which made it easier to remove the lens and cataracts by freezing them first — a technique still used in retina surgery.
In a 1992 interview, Dr. Kelman recalled that when he was 17, his father asked him to take his saxophone to the basement. After the young man played a Jimmy Dorsey tune, his father asked if he had played it as well as Dorsey could. Charlie conceded that he had not. Mr. Kelman replied, ”You’ll be a doctor.” From the day his high school principal told him he wasn’t college material and ought to go to trade school, Charles Kelman upset conventional wisdom-with stunning success. Kelman was a pioneering ophthalmologist who bucked the medical establishment in his search for a less risky, less intrusive and more effective method of cataract removal. Thanks to his persistence and intelligence, millions of people can see again.
When he died, a Memorial Tribute to Charles D. Kelman, M.D. was held on September 13, 2004 at the St. James Theatre on Broadway and was a celebration of Dr. Kelman’s life. This very special Tribute was hosted by Dr. Frank Field and featured colleagues, family and friends, as well as video presentations and photo montages of Dr. Kelman as surgeon, performer, helicopter pilot and more. Broadway entertainers performed many of the songs that Dr. Kelman wrote.
Sources: The New York Times; Wikipedia; drcharlesandannkelmanfamilyfoundation.org
NIH Will No Longer Support Biomedical Research on Chimpanzees
The following is From Francis S. Collins, M.D., Ph.D., Director, National Institutes of Health
Research with non-human primates has and continues to be vital to helping us understand and improve human health in a multitude of ways, including the development of treatments and interventions. However, use of non-human primates needs to be supported by the science. It has been two and half years sinceNIH announced its decision in June 2013 to significantly reduce the use of chimpanzees in agency-supported biomedical research and retain only a small population of chimpanzees for future biomedical research. As part of this decision, NIH indicated it would identify 50 chimpanzees that would be retained based on the characteristics necessary to support the research of the projects submitted, and periodically review this decision based on scientific needs. To be considered, projects would have to meet a strict set of principles and criteria, set forth by the Institute of Medicine and accepted by the NIH, after having cleared scientific review. Since June 2013, based on recommendations from the Council of Councils, NIH has phased out all previously active biomedical research protocols using chimpanzees that did not meet the IOM principles and criteria, and no new biomedical research projects have been approved.
Another major development occurred last summer. On June 16, 2015, the U.S. Fish and Wildlife Service announced that it has designated captive chimpanzees as endangered. Among other things, this designation requires that researchers apply for and obtain a permit to use captive chimpanzees in research if it could harm the animal. Up to this point, we are not aware of any permits that have been sought for this purpose. As a result of these numerous changes over the last few years and the significantly reduced demand for chimpanzees in NIH-supported biomedical research, it is clear that we’ve reached a tipping point. In accordance with NIH’s commitment in June 2013, I have reassessed the need to maintain chimpanzees for biomedical research and decided that effective immediately, NIH will no longer maintain a colony of 50 chimpanzees for future research. All NIH-owned chimpanzees that reside outside of the Federal Sanctuary System operated by Chimp Haven, Keithville, Louisiana, are now eligible for retirement. Relocation of the chimpanzees to the Federal Sanctuary System will be conducted as space is available and on a timescale that will allow for optimal transition of each individual chimpanzee with careful consideration of their welfare, including their health and social grouping.
These decisions are specific to chimpanzees. Research with other non-human primates will continue to be valued, supported, and conducted by the NIH.
Batten Disease May Benefit From Gene Therapy
Target health is very active in 2 lysosomal storage disease programs. One is in Gaucher disease and the other is in Fabray disease. The Gaucher disease drug product was developed by Protalix Biotherapeutics (Israel) and is marketed by Pfizer.
Batten disease is a rare and fatal lysosomal storage disorder, a group of diseases that causes problems with a cell’s ability to breakdown specific molecules. Early symptoms may include vision loss, subtle changes in personality and behavior, slow learning, clumsiness, or stumbling. Eventually, the children become blind, bedridden and demented, and typically die within the first decade of their lives. Currently there are no effective treatments.
According to a study published online in Science Translational Medicine, (11 November 2015), it was shown that a new way to deliver replacement genes may be effective at slowing the development of childhood Batten disease. The key may be to inject viruses that carry the codes for the gene products into the ventricles, which are fluid-filled compartments in the center of the brain that serve as a plumbing system.
The study focused on the late infantile form of the disease that starts in children 2 to 4 years of age and is most often caused by mutations in the gene for the soluble lysosomal enzyme tripeptidyl peptidase 1 (TPP1), an enzyme which degrades proteins. The authors showed that if they treated dogs that have a similar disorder by injecting a safe virus containing the TPP1 gene code into the cerebrospinal fluid that fills ventricles, the dogs lived about twice as long as untreated dogs. Symptoms including problems with movement, pupil dilation and making decisions were delayed or, in some cases, did not occur. The treatment, however, did not fully improve the dogs’ vision suggesting that delivery to the eye itself may be necessary as well. When the authors inspected the dogs’ brains, they found that the treatment reduced the damage normally caused by the disease. In comparison with untreated dogs, the treated dogs had less reactive glial cells and stored lipofuscins, fatty deposits that are hallmarks of Batten disease and similar disorders, called neuronal ceroid lipofuscinoses.
Further inspections of the dogs’ brains confirmed the hypothesis about how the therapy worked. The results suggested that parenchymal cells that line the ventricles and surface of the brain took up the injected genes from the cerebrospinal fluid and made more TPP1 protein. These cells then secreted the protein that, in turn, spread throughout the brain. Initial experiments showed the importance treating the dogs with the immunosuppressant, mycophenolate mofetil, before injecting the TPP1 gene. The immunosuppressant prevented the production of antibodies that accelerated TPP1 clearance from the cerebrospinal fluid.
FDA Approves Easy-to-Use Nasal Spray to Treat Opioid Overdose
Opioids are a class of drugs that include prescription medications such as oxycodone, hydrocodone, and morphine, as well as the illegal drug heroin. Drug overdose deaths, driven largely by prescription drug overdoses, are now the leading cause of injury death in the United States – surpassing motor vehicle crashes. In 2013, the Centers for Disease Control and Prevention reported the number of drug overdose deaths had steadily increased for more than a decade. When someone overdoses on an opioid, it can be difficult to awaken the person, and breathing may become shallow or stop – leading to death if there is no medical intervention. If naloxone is administered quickly, it can counter the overdose effects, usually within two minutes.
The FDA has approved Narcan nasal spray, the first FDA-approved nasal spray version of naloxone hydrochloride, a life-saving medication that can stop or reverse the effects of an opioid overdose. Until this approval, naloxone was only approved in injectable forms, most commonly delivered by syringe or auto-injector. Many first responders and primary caregivers, however, feel a nasal spray formulation of naloxone is easier to deliver, and eliminates the risk of a contaminated needle stick. As a result, there has been widespread use of unapproved naloxone kits that combine an injectable formulation of naloxone with an atomizer that can deliver naloxone nasally. Now, people have access to an FDA-approved product for which the drug and its delivery device have met the FDA’s high standards for safety, efficacy and quality.
Narcan nasal spray does not require assembly and delivers a consistent, measured dose when used as directed. This prescription product can be used on adults or children and is easily administered by anyone, even those without medical training. The drug is sprayed into one nostril while the patient is lying on his or her back, and can be repeated if necessary. However, it is important to note that it is not a substitute for immediate medical care, and the person administering Narcan nasal spray should seek further immediate medical attention on the patient’s behalf.
The FDA granted fast-track designation and priority review for Narcan nasal spray. Fast track is a process designed to facilitate development and expedite review of drugs intended to treat serious conditions and that demonstrate the potential to address an unmet medical need. The agency’s priority review program provides for an expedited review of drugs that offer a significant improvement in the safety or effectiveness of the treatment, prevention, or diagnosis of a serious condition. Narcan nasal spray was approved in less than four months, significantly ahead of the product’s prescription drug user fee goal date of January 20, 2016.
In clinical trials conducted to support the approval of Narcan nasal spray, administering the drug in one nostril delivered approximately the same levels or higher of naloxone as a single dose of an FDA-approved naloxone intramuscular injection, and achieved these levels in approximately the same time frame.
The National Institute on Drug Abuse played a critical role in the development of Narcan nasal spray as well, forming a public-private partnership by designing and conducting the clinical trials required to determine that the intranasal formulation delivered naloxone as quickly and as effectively as an injection. NIDA then worked with its private sector partners to obtain FDA approval. Increasing access to and the use of naloxone is part of the targeted strategy that Health and Human Services Secretary Sylvia M. Burwell put forward in March to address the opioid epidemic and save lives. In July, addiction and advocacy groups called for expanded availability of naloxone during an FDA-sponsored public workshop exploring the uptake and use of the drug.
The use of Narcan nasal spray in patients who are opioid dependent may result in severe opioid withdrawal characterized by body aches, diarrhea, increased heart rate (tachycardia), fever, runny nose, sneezing, goose bumps (piloerection), sweating, yawning, nausea or vomiting, nervousness, restlessness or irritability, shivering or trembling, abdominal cramps, weakness, and increased blood pressure.
Narcan nasal spray is distributed by Adapt Pharma, Inc., of Radnor, Pennsylvania.
Thanksgiving Sweet Potato Rounds with Sticky Pecan Topping
This is a de-lish dish and easy to make. Jules loves these sweet potato-pecan rounds and gives them a top score (1 to 5) of 5+++++. He can’t stop eating them. Just one or two of these, per person, lights up the whole table. They are perfect for any holiday. ©Joyce Hays, Target Health Inc.
6 Tablespoons unsalted butter (important, no salt)
1 cup packed dark brown sugar (not light brown)
3/4 cup golden syrup (this is NOT corn syrup, got it on Amazon)
1 tiny pinch sea salt, and no more (optional)
2 cups pecan halves
1 teaspoon apple cider vinegar
2 Tablespoons bourbon
2 teaspoons vanilla extract
3 large eggs
Just a few ingredients, for a successful Thanksgiving or holiday dish. ©Joyce Hays, Target Health Inc.
Preheat oven to 350 degrees.
Toast the pecans first, on an oiled baking sheet (or pan), then set aside. This will only take a few minutes. You can toast them when you bake the sweet potatoes. After toasting the pecans, chop them a little . . . not a lot. You want to have recognizable pieces of these nuts.
Toasting the pecans, on the stove or in the oven. ©Joyce Hays, Target Health Inc.
After toasting, chop the pecans, but not too much. ©Joyce Hays, Target Health Inc.
Bake the sweet potatoes. ©Joyce Hays, Target Health Inc.
Bake the sweet potatoes, in 350 degree, pre-heated oven for 20 to 30 minutes. Use foil to cut the baking time a little. Each oven is different, so test the potatoes after baking for 20 minutes. Put back, if needed, etc.
Next, with skins on, cut them into rounds about 1 to 1.5 inches thick. Into a bowl, scoop out a small amount of potato from the top of each round. Be careful, not to damage the skins. You need the intact skins to hold everything together. Put each round onto a well-oiled baking dish and set aside. Save the scooped out potato, to be used a little later.
In a medium saucepan, combine butter, brown sugar, golden syrup and very tiny pinch of salt (or no salt). Bring to a simmer over medium heat and cook for 2 minutes, stirring, the whole time. Remove from heat and stir in pecans, (that have been toasted), cider vinegar, vanilla and bourbon. After 2 minutes, with a spatula, scrape all of this mixture out of the hot pan and into a bowl and set the mixture aside to cool for about 10 minutes.
Here, over a medium flame, the butter, brown sugar, syrup, pinch salt, are being stirred. ©Joyce Hays, Target Health Inc.
Flame is off and chopped pecans were added. Next, vanilla, cider vinegar and bourbon will be added and mixture moved, to cool down. After cooling, eggs will be added. ©Joyce Hays, Target Health Inc.
When the mixture has cooled down, into the bowl, whisk the eggs in, but one at a time. Stir to combine all the ingredients well. Add the scooped out potato to this mixture and stir it in.
Onto each potato round, add a heaping spoonful of mixture. Don’t worry if some of the mixture drips down, it will taste even better.
Bake these potato rounds, for about 40 minutes, until the topping gets crispy and crunchy and serve nice and warm. Let the potatoes cool down just a bit and then serve.
Here the sweet potato rounds are going into the oven. The kitchen smells so good! ©Joyce Hays, Target Health Inc.
Just coming out of the oven. See how the brown sugar has caramelized a little. Oh-h the aroma! ©Joyce Hays, Target Health Inc.
There will be nothing left-over, of these warm and crunchy pecan/potato rounds. ©Joyce Hays, Target Health Inc.
For people coming to the Big Apple for Thanksgiving, and looking for interesting theater, there is plenty of it.
This past weekend, we saw one of the world’s worst plays, Night is a Room, and encourage you to avoid it.
Of the theater we’ve seen recently, what stands out is, Fool For Love by Sam Shepard. If you like theater of the absurd, Shepard’s work represents for me, the latest in a long continuum, beginning with Albert Camus, Samuel Beckett, Harold Pinter, David Mamet and Sam Shepard.
The term, Theater of the Absurd, is derived from an essay by the French philosopher Albert Camus, who defined the human situation as meaningless and absurd, where human existence is out of step with the rest of the universe. This existential philosophy/thinking was strongly influenced by the horrors of the Second World War, which highlighted the precariousness of human life and its fundamental meaninglessness and arbitrariness. WW2 cruelty and uncertainty was followed by the trauma of living after1945 under threat of nuclear annihilation, referred to as the cold war. Is it any wonder that in a world so filled with barbarism, (including the banality of evil) the arts would mirror back, theater of the absurd, and pop art?
As I wrote, a few weeks ago, Fool For Love, is superbly acted and directed, with excellent sets, sound and lighting design. It has now been hailed by the critics and has been extended for a few more weeks.
A toast for a Happy Thanksgiving to all of our friends and colleagues!
From Our Table to Yours!
November 19, 2015
University of Queensland
A new form of secret light communication used by marine animals has been discovered by scientists. The findings may have applications in satellite remote sensing, biomedical imaging, cancer detection, and computer data storage.
Researchers from the Queensland Brain Institute at The University of Queensland have uncovered a new form of secret light communication used by marine animals.
The findings may have applications in satellite remote sensing, biomedical imaging, cancer detection, and computer data storage.
Dr Yakir Gagnon, Professor Justin Marshall and colleagues previously showed that mantis shrimp (Gonodactylaceus falcatus) can reflect and detect circular polarising light, an ability extremely rare in nature. Until now, no-one has known what they use it for.
The new study shows the shrimp use circular polarisation as a means to covertly advertise their presence to aggressive competitors.
“In birds, colour is what we’re familiar with; in the ocean, reef fish display with colour. This is a form of communication we understand. What we’re now discovering is there’s a completely new language of communication,” said Professor Marshall.
Linear polarised light is seen only in one plane, whereas circular polarised light travels in a spiral — clockwise or anti-clockwise — direction.
The team determined that mantis shrimp display circular polarised patterns on the body, particularly on the legs, head and heavily armoured tail; these are the regions most visible when when they curl up during conflict.
“These shrimp live in holes in the reef,” said Professor Marshall. “They like to hide away; they’re secretive and don’t like to be in the open.”
Researchers dropped a mantis shrimp into a tank with two burrows to hide in: one reflecting unpolarised light and the other, circular polarised light. The shrimp chose the unpolarised burrow 68% of the time — suggesting the circular polarised burrow was perceived as being occupied by another mantis shrimp.
“If you essentially label holes with circular polarising light, by shining circular polarising light out of them, shrimps won’t go near it,” said Professor Marshall. “They know — or they think they know — there’s another shrimp there.
The findings may help doctors to better detect cancer. “Cancerous cells do not reflect polarised light, in particular circular polarising light, in the same way as healthy cells,” said Professor Marshall. So cameras equipped with circular polarising sensors may detect cancel cells long before the human eye can see them.
Another study involving Professor Marshall, published in the same edition ofCurrent Biology, showed that linear polarised light is used as a form of communication by fiddler crabs.
Fiddler crabs (Uca stenodactylus) live on mudflats, a very reflective environment, and they behave differently depending on the amount of polarisation reflected by objects, the researchers found.
“It appears that fiddler crabs have evolved inbuilt sunglasses, in the same way as we use polarising sunglasses to reduce glare,” Professor Marshall said.
The crabs were able to detect and identify ground-base objects base on how much polarised light was reflected. They either moved forward in a mating stance, or retreated back into their holes, at varying speeds.
“These animals are dealing in a currency of polarisation that is completely invisible to humans,” Professor Marshall said. “It’s all part of this new story on the language of polarisation.”
Both studies will be published in the print edition of Current Biology in December 2015.
- Yakir Luc Gagnon, Rachel Marie Templin, Martin John How, N. Justin Marshall. Circularly Polarized Light as a Communication Signal in Mantis Shrimps. Current Biology, 2015; DOI: 10.1016/j.cub.2015.10.047
- Martin J. How, John H. Christy, Shelby E. Temple, Jan M. Hemmi, N. Justin Marshall, Nicholas W. Roberts. Target Detection Is Enhanced by Polarization Vision in a Fiddler Crab. Current Biology, 2015; DOI:10.1016/j.cub.2015.09.073
Source: University of Queensland. “Marine animals use new form of secret light communication.” ScienceDaily. ScienceDaily, 19 November 2015. <www.sciencedaily.com/releases/2015/11/151119113510.htm>.
Gamma interferon given 24 hours before and up to 24 hours after exposure completely protects mice from death from Ebola
November 18, 2015
University of Iowa Health Care
A new study suggests that gamma interferon, which is an FDA-approved drug, may have potential as an antiviral therapy to prevent Ebola infection when given either before or after exposure to the virus. The study found that gamma interferon, given up to 24 hours after exposure, can inhibit Ebola infection in mice and completely protect the animals from death.
The recent Ebola outbreak in West Africa has claimed more than 11,300 lives and starkly revealed the lack of effective options for treating or preventing the disease. Progress has been made on developing vaccines, but there is still a need for antiviral therapies to protect health care workers and local populations in the event of future outbreaks.
A new study led by University of Iowa virologist Wendy Maury, PhD, suggests that gamma interferon, which is an FDA-approved drug, may have potential as an antiviral therapy to prevent Ebola infection when given either before or after exposure to the virus.
The study, published in the journal PLOS Pathogens, found that gamma interferon, given up to 24 hours after exposure, can inhibit Ebola infection in mice and completely protect the animals from death.
Ebola infection appears to be a stepwise process. First, the virus targets and infects macrophages or dendritic cells, two types of immune system cells found in the liver, spleen, and lymph nodes. Ebola then replicates in those cells. Following this initial infection, which happens at day 3 or 4 in non-human primates, Ebola virus is released into the blood and infects a plethora of other different cell populations.
“It goes from an early stage with a very targeted infection of only these few cell types, to everything being infected,” explains Maury, who is a professor of microbiology in the UI Carver College of Medicine. “We think what’s happening with gamma interferon is that it’s targeting macrophages and blocking the infection of those initial cell targets so you don’t get the second round of infection.”
The UI does not have a specializing BioSafety Level 4 (BSL4) lab that is required for experiment using Ebola virus, so Maury and her UI colleagues made their initial findings using a surrogate virus, which targets and infects the same cells as Ebola, but does not cause the disease. This Ebola lookalike — a sheep in wolf’s clothing — consists of a less dangerous vesicular stomatitis virus (VSV) that expresses Ebola glycoproteins on its surface.
However, all of the results Maury’s team found using the surrogate virus, were repeated using mouse-adapted Ebola virus in the BSL4 lab of Maury’s long-time collaborator Robert Davey at Texas Biomedical Institute in San Antonio, Texas.
The team showed that gamma interferon inhibits the virus’s ability to infect human and mouse macrophages, in part by blocking virus replication in the cells. The researchers then showed that pretreating mice with interferon gamma 24 hours before exposure protects the animals from infection and death. To their surprise, the researchers found that treatment up to 24 hours after what would have been a lethal exposure also completely protected the animals from death, and the scientists could no longer detect any Ebola virus in the mouse cells. These findings suggest that interferon gamma may be useful both as a prophylaxis and post-exposure treatment against Ebola.
The team still has to determine how late gamma interferon can be given to the mice and still prevent infection. However, the results suggest a window of time after exposure when gamma interferon may be an effective antiviral therapy
“My guess is that if you delay the gamma interferon too much, you miss this window of opportunity to block the infection in macrophage cells and the gamma interferon can no longer provide protection,” Maury says.
Working with Martha Monick, PhD, now a UI professor emeritus in internal medicine, Maury and lead study author Bethany Rhein, PhD, investigated how gamma interferon might be helping the cells fight off Ebola virus. They identified that expression of more than 160 genes in human macrophages are stimulated by gamma interferon. Introduction of some of these genes into cells was sufficient to prevent Ebola infection.
“This mechanistic information might suggest more precise drug targets rather than the broad effects, including adverse side-effects, that are produced by gamma-interferon,” Maury says.
Gamma interferon is approved by the FDA to treat Chronic Granulomatous Disease (an immune disease) and Severe Malignant Osteopetrosis.
In addition to moving the studies into larger animal models, Maury now plans to study the ability of gamma interferon to inhibit Ebola infection in conjunction with other developing antivirals.
“Right now there are no FDA-approved antiviral therapies for Ebola, but there are some being developed that target virus entry,” she says. “We know that gamma interferon blocks replication but not entry into cells. So combining an entry inhibitor with gamma interferon may allow us to reduce amount of gamma interferon needed and target two different steps in the virus’s life cycle, which has been shown in HIV to be critically important for controlling virus.”
In addition to Maury, Monick, Rhein, and Davey, the research team included Linda Powers, Kai Rogers Manu Anantpadma, Brajesh Singh, Yasuteru Sakurai, Thomas Bair, Catherine Miller-Hunt, and Patrick Sinn.
- Bethany A. Rhein, Linda S. Powers, Kai Rogers, Manu Anantpadma, Brajesh K. Singh, Yasuteru Sakurai, Thomas Bair, Catherine Miller-Hunt, Patrick Sinn, Robert A. Davey, Martha M. Monick, Wendy Maury. Interferon-γ Inhibits Ebola Virus Infection. PLOS Pathogens, 2015; 11 (11): e1005263 DOI: 10.1371/journal.ppat.1005263
Source: University of Iowa Health Care. “FDA-approved drug protects mice from Ebola: Gamma interferon given 24 hours before and up to 24 hours after exposure completely protects mice from death from Ebola.” ScienceDaily. ScienceDaily, 18 November 2015. <www.sciencedaily.com/releases/2015/11/151118131734.htm>.
November 17, 2015
Florida State University
A high-performance computing researcher has predicted a physical effect that would help physicists and astronomers provide fresh evidence of the correctness of Einstein’s general theory of relativity.
A Florida State University high-performance computing researcher has predicted a physical effect that would help physicists and astronomers provide fresh evidence of the correctness of Einstein’s general theory of relativity.
Bin Chen, who works at the university’s Research Computing Center, describes the yet-to-be-observed effect in the paper “Probing the Gravitational Faraday Rotation Using Quasar X-ray Microlensing,” published today in the journal Scientific Reports.
“To be able to test general relativity is of crucial importance to physicists and astronomers,” Chen said.
This testing is especially so in regions close to a black hole, according to Chen, because the current evidence for Einstein’s general relativity — light bending by the sun, for example — mainly comes from regions where the gravitational field is very weak, or regions far away from a black hole.
Electromagnetism demonstrates that light is composed of oscillating electric and magnetic fields. Linearly polarized light is an electromagnetic wave whose electric and magnetic fields oscillate along fixed directions when the light travels through space.
The gravitational Faraday effect, first predicted in the 1950s, theorizes that when linearly polarized light travels close to a spinning black hole, the orientation of its polarization rotates according to Einstein’s theory of general relativity. Currently, there is no practical way to detect gravitational Faraday rotation.
In the paper, Chen predicts a new effect that can be used to detect the gravitational Faraday effect. His proposed observation requires monitoring the X-ray emissions from gravitationally lensed quasars.
“This means that light from a cosmologically distant quasar will be deflected, or gravitationally lensed, by the intervening galaxy along the line of sight before arriving at an observer on the Earth,” said Chen of the phenomenon of gravitational lensing, which was predicted by Einstein in 1936. More than 100 gravitational lenses have been discovered so far.
“Astronomers have recently found strong evidence showing that quasar X-ray emissions originate from regions very close to supermassive black holes, which are believed to reside at the center of many galaxies,” Chen said. “Gravitational Faraday rotation should leave its fingerprints on such compact regions close to a black hole.
“Specifically, the observed X-ray polarization of a gravitationally microlensed quasar should vary rapidly with time if the gravitational Faraday effect indeed exists,” he said. “Therefore, monitoring the X-ray polarization of a gravitationally lensed quasar over time could verify the time dependence and the existence of the gravitational Faraday effect.”
If detected, Chen’s effect — a derivative of the gravitational Faraday effect — would provide strong evidence of the correctness of Einstein’s general relativity theory in the “strong-field regime,” or an environment in close proximity to a black hole.
Chen generated a simulation for the paper on the FSU Research Computing Center’s High-Performance Computing cluster — the second-largest computer cluster in Florida.
- Bin Chen. Probing the gravitational Faraday rotation using quasar X-ray microlensing. Scientific Reports, 2015; 5: 16860 DOI:10.1038/srep16860
Source: Florida State University. “More proof of Einstein’s general theory of relativity.” ScienceDaily. ScienceDaily, 17 November 2015. <www.sciencedaily.com/releases/2015/11/151117145055.htm>.