Autumn Souffle


A delicious medley of flavors, just in time for Halloween or Thanksgiving dinner.  The item in the background is a piece of cauliflower cake with black sesame seeds that I’m experimenting with and will share when ready.  ©Joyce Hays, Target Health Inc.



Just out of the oven and onto the table.  Smells wonderful! ©Joyce Hays, Target Health Inc.




1 pound carrots, scrubbed but not peeled

1 sweet potato, scrubbed

1 butternut squash

1 teaspoon turmeric

1 teaspoon cumin

1 teaspoon coriander

1/2 teaspoon ginger, freshly grated

2 Tablespoons canola oil

3 Tablespoons Tofutti

3 Tablespoons sour cream

3 eggs

1 Tablespoon honey

2 Tablespoons agave

1/2 can water chestnuts, removed from can and drained on paper towel

3 Tablespoons almond flour

1 teaspoon baking powder

1 teaspoon vanilla

pinch salt (optional)

1 onion, chopped

3 garlic cloves, sliced not squeezed

1 cup golden raisins

1 Tablespoon Marsala wine

1 cup almond slivers, toasted and set aside (save ? cup for garnish)

Pinch chili flakes

Pinch black pepper




Make sure you have everything, by putting all ingredients in one spot. ©Joyce Hays, Target Health Inc.




Preheat oven to 350 degrees

Scrub then peel the carrots, sweet potato and butternut squash first. Next cut into large pieces and roast in oven until soft. Remove and let them cool down.





Roasting the veggies. ©Joyce Hays, Target Health Inc.



It was easier for me to get this aluminum container out, than dig for the baking sheet, so am toasting the almond slivers, here. No oil here. Using an oven mitt, I will take this out in 4-5 minutes and just shake it, to move the almonds around for a more even toasting. ©Joyce Hays, Target Health Inc.



Toast the almond slivers on a flat baking sheet, while roasting the veggies. After 4 minutes, stir them around just to get them evenly toasted. But keep your eye on the almonds. They will be done in about 6 to 10 minutes. You don’t want to burn them, or you’ll have to do another batch of almonds.




Chopping the onion & garlic. ©Joyce Hays, Target Health Inc.



Cooking the onion & garlic. ©Joyce Hays, Target Health Inc.


While veggies are roasting, add 1 Tablespoon of the canola oil to a pan and on a low flame, cook the onion and garlic until they get a little soft and transparent. Remove pan from heat.




About to start up the food processor. ©Joyce Hays, Target Health Inc.



So far, so good. ©Joyce Hays, Target Health Inc.



In food processor, slowly blend: first the eggs, canola oil, Tofutti, sour cream, honey, agave, almond flour, baking powder, and vanilla.




Here, we’re pulsing the orange veggies and some water chestnuts. ©Joyce Hays, Target Health Inc.



As your food processor fills up, scrape the processed ingredients, out into a large bowl




Container on top has the water chestnuts, draining, and about to be added to the food processor. The water chestnuts add a nice crunch to a recipe. As for the golden raisins and almond slivers, (which have just been toasted in the oven). Don’t add them to the food processor yet, And don’t pulse them, whatever you do. Stir them in by hand, after everything has been “pulsed.“ ©Joyce Hays, Target Health Inc.



Next, add to the food processor, the water chestnuts, Marsala, onions and garlic, the carrots, sweet potato, butternut squash and all of the spices and the ginger, while you slowly pulse the food processor. Keep pulsing until the 3 orange veggies are not quite a puree (you want to have some texture in the souffle). Before you remove the mixture, add the golden raisins and 1/2 of the toasted almond slivers and stir in, by hand. Don’t pulse these last ingredients.




This is everything scraped out of the food processor. Now, the toasted almonds and golden raisins are being stirred in, by hand. ©Joyce Hays



Re-set oven temperature down to 300 degrees.


Brush some canola oil onto a baking dish and then with a spatula, scrape all of the contents of the blender, into the baking dish.




Here, the contents of the bowl have been scraped into this oiled baking dish. About to go into the oven. ©Joyce Hays, Target Health Inc.



Just out of the oven and about to sprinkle toasted almonds on top. ©Joyce Hays, Target Health Inc.



Here’s an earlier experiment with toasted pistachios on top (also good). ©Joyce Hays, Target Health Inc.



Bake at 300 degrees for 45 minutes, or until just firm. When you insert something sharp, (long skewer) and it comes out clean, the dish is done. It’s nice to have baking dishes that can go from the oven, to table, to fridge.

Time the baking so you can serve the orange veggie souffle, when it comes, right out of the oven.

When you remove from oven, sprinkle the remaining 1/2 cup of toasted almond slivers over the top of the dish and serve.




Hall is a very well-known vineyard in Napa Valley. We like their reds much better than the whites but, hey, we drank this whole bottle, with no effort. J


He wanted red and I wanted white. His Chateauneuf du Pape was v-err-y robust with a long warm finish. But I felt like my favorite sauvignon blanc, Aveta, from Stag’s Leap Wine Cellars, floral nose, strong statement on palate and soothing finish.


We had a wonderful weekend. So much fun at a play called, Ripcord, with a talkback afterwards.

Manhattan Theatre Club, (where Target Health Inc. is a corporate patron), presents its sixth collaboration with playwright David Lindsay-Abaire, in 2015.Ripcord, the Pulitzer Prize winner’s latest work is a comedy revolving around a viscous battle of wits between two elderly women in a care home. In the lead roles of Abby and Marilyn are Emmy winner Holland Taylor (The Practice, Two and a Half Men) and Drama Desk Award winner Marylouise Burke (Fuddy Meers), while Frasier alumni David Hyde Pierce directs.


The playwright, David Lindsay-Abaire is a writer who excels in a dizzying variety of genres and forms, Lindsay-Abaire first came to the world’s attention with his 2007 play Rabbit Hole. An honest and surprisingly comic tale of grieving parents, it won its author the Pulitzer Prize for Drama. Since then, he’s produced numerous comedic and dramatic works as well as the book for Shrek The Musical. This range also stretches to his work in Hollywood, having adapted Rabbit Hole for the screen with Nicole Kidman in the lead role, but also written the screenplay for the children’s animated feature Rise of the Guardians.

Especially suited for people 49 and over, Ripcord will amuse you, startle you and even make you cry. The acting is first rate and so are the sets, sound and lighting design, not to mention fine directing. Go if you can! It’s about 2 and ? hours long.


Sunday we stuck to our exercise routine (sometimes it takes discipline) and I beat Jules in Scrabble which always makes me feel good. (He won last weekend, however.)


Hope your weekend was a good one!


From Our Table to Yours!


Bon Appetit!


October 22, 2015

University of Tsukuba

REM sleep — the phase of night-time mammalian sleep physiology where dreams occur — has long fascinated scientists, clinicians, philosophers, and artists alike, but the identity of the neurons that control REM sleep, and its function in sleep have been controversial due to a lack of precise genetic methods to study the sleeping brain. Now, in a remarkable demonstration of a recent brain technology, neuroscientists provide the first answers to both questions, identifying a neural circuit in the brain that regulates REM sleep, and showing that REM sleep controls the physiology of the other major sleep phase, called non-REM (NREM) sleep.



REM sleep — the phase of night-time mammalian sleep physiology where dreams occur — has long fascinated scientists, clinicians, philosophers, and artists alike, but the identity of the neurons that control REM sleep, and its function in sleep have been controversial due to a lack of precise genetic methods to study the sleeping brain. (stock image)
Credit: © asife / Fotolia



REM sleep — the phase of night-time mammalian sleep physiology where dreams occur — has long fascinated scientists, clinicians, philosophers, and artists alike, but the identity of the neurons that control REM sleep, and its function in sleep have been controversial due to a lack of precise genetic methods to study the sleeping brain. Now, in a remarkable demonstration of a recent brain technology, neuroscientists provide the first answers to both questions, identifying a neural circuit in the brain that regulates REM sleep, and showing that REM sleep controls the physiology of the other major sleep phase, called non-REM (NREM) sleep.

The Japanese research team, led by Yu Hayashi of the University of Tsukuba’s International Institute for Integrative Sleep Medicine (WPI-IIIS) and Shigeyoshi Itohara of RIKEN Brain Science Institute, published the study in Science this week. The study began when the team noticed that many cells in the brain area called the pons, where REM sleep control was suspected, were actually visitors from a distant brain area, called the rhombic lip, during early embryonic development. Like neural detectives, the team reasoned that if they could mark rhombic lip cells, they could track their migration to the pons and artificially reactivate them during sleep. However, no such method existed, until recently.

Enter a method called DREADD, standing for “Designer Receptors Exclusively Activated by Designer Drugs.” The genetic technique involved transgenic mice that express a DREADD receptor in rhombic lip cells that express Atoh1 during the developmental stage, and which then migrate to the pons. The researchers applied a drug that binds to the receptor called CNO to activate the cells in the pons during sleep measured by observing brain activity from electrodes placed on the head. The data showed that activating Atoh1 cells that are excitatory could suppress REM sleep, leading to an increase of NREM sleep. A second pool of REM inhibitory cells was also identified that are downstream from Atoh1 cells.

After identifying the cells responsible for inhibiting REM sleep, the researchers moved on to examine the role of the REM phase in general sleep physiology. They took recordings from the brains of mice during NREM sleep that is characterized by large slow waves of activity that sweep through the brain, in contrast to the relatively quiet, desynchronized activity in REM sleep. Using the DREADD system they shortened or elongated REM sleep and were surprised to find that the amplitude of slow waves during the following NREM sleep became correspondingly smaller or larger. The results demonstrate for the first time that sleep phases interact in a hierarchy, with NREM sleep under the control of REM sleep.

The findings have implications for how and why sleep in mammals evolved to its current two-phase structure. It is known that novel experiences during wakefulness are stored in the brain during subsequent NREM sleep, and that slow waves play an important role in this process. Based on the current study, REM sleep also contributes to this process, because the generation of slow waves during NREM sleep relies on REM sleep. The authors plan to continue using DREADD and other brain research technologies being developed by neuroscientists to try to determine the actual evolutionary role of REM sleep in mammals and find the answers to other mysteries. Among these, they caution that laboratory mice do not have measurable dreams, although they can replay sequences of activity from the prior waking day in NREM. The relationship between REM sleep and the replay of experience in NREM is a future area of interest.

Story Source:

The above post is reprinted from materials provided byUniversity of Tsukuba. Note: Materials may be edited for content and length.

Journal Reference:

  1. Yu Hayashi, Mitsuaki Kashiwagi, Kosuke Yasuda, Reiko Ando, Mika Kanuka, Kazuya Sakai, and Shigeyoshi Itohara.Cells of a common developmental origin regulate REM/non-REM sleep and wakefulness in mice. Science, 22 October 2015 DOI: 10.1126/science.aad1023


Source: University of Tsukuba. “New insights into REM sleep crack an enduring mystery.” ScienceDaily. ScienceDaily, 22 October 2015. <>.

October 21, 2015

Princeton University

Scientists have predicted a new phase of superionic ice, a special form of ice that could exist on Uranus and Neptune, in a theoretical study performed by a team of researchers.



Neptune. Unlike Earth, which has two magnetic poles (north and south), ice giants can have many local magnetic poles, which leading theories suggest may be due to superionic ice and ionic water in the mantle of these planets.
Credit: NASA



Scientists have predicted a new phase of superionic ice, a special form of ice that could exist on Uranus and Neptune, in a theoretical study performed by a team of researchers at Princeton University.

“Superionic ice is this in-between state of matter that we can’t really relate to anything we know of — that’s why it’s interesting,” Salvatore Torquato, a Professor of Chemistry who jointly led the work with Roberto Car, the Ralph W. ’31 Dornte Professor in Chemistry. Unlike water or regular ice, in superionic ice the water molecules dissociate into charged atoms called ions, with the oxygen ions locked in a solid lattice, while the hydrogen ions move like the molecules in a liquid.

Published on Aug. 28 in Nature Communications, the research revealed an entirely new type of superionic ice that they call the P21/c-SI phase, which occurs at pressures even higher than in the interior of giant ice planets of our solar system. Two other phases of superionic ice thought to exist on the planets are body centered cubic superionic ice (BCC-SI) and, close-packed superionic ice (CP-SI).

Each phase has a unique arrangement of oxygen ions that gives rise to distinct properties. For example, each of the phases allows hydrogen ions to flow in a characteristic way. The effects of this ionic conductivity could be observed by planetary scientists in search of superionic ice. “These unique properties could essentially be used as signatures of superionic ice,” said Torquato, “so now that you know what to look for, you have a better chance of finding it.”

Unlike Earth, which has two magnetic poles (north and south), ice giants can have many local magnetic poles, which leading theories suggest may be due to superionic ice and ionic water in the mantle of these planets. In ionic water both oxygen and hydrogen ions show liquid-like behavior. Scientists have proposed that heat emanating outward from the planet’s core may pass through an inner layer of superionic ice, and through convection, create vortices on the outer layer of ionic water that give rise to local magnetic fields.

By using theoretical simulations, the researchers were able to model states of superionic ice that would be difficult to study experimentally. They simulated pressures that were beyond the highest possible pressures attainable in the laboratory with instruments called diamond anvil cells. Extreme pressure can be achieved through shockwave experiments but these rely on creating an explosion and are difficult to interpret, Professor Car explained.

The researchers calculated the ionic conductivity of each phase of superionic ice and found unusual behavior at the transition where the low temperature crystal, in which both oxygen and hydrogen ions are locked together, transforms into superionic ice. In known superionic materials, generally the conductivity can change either abruptly (type I) or gradually (type II), but the type of change will be specific to the material. However, superionic ice breaks from convention, as the conductivity changes abruptly with temperature across the crystal to close-packed superionic transition and continuously at the crystal to P21/c-SI transition.

As a foundational study, the research team investigated superionic ice treating the ions as if they were classical particles, but in future studies they plan to take quantum effects into account to further understand the properties of the material.

This work was supported by the National Science Foundation (DMS-1065894) and the US Department of Energy (DE-SC0008626 and DE-SC0005180).

Story Source:

The above post is reprinted from materials provided byPrinceton University. Note: Materials may be edited for content and length.

Journal Reference:

  1. Jiming Sun, Bryan K. Clark, Salvatore Torquato, Roberto Car. The phase diagram of high-pressure superionic ice.Nature Communications, 2015; 6: 8156 DOI:10.1038/ncomms9156


Source: Princeton University. “Scientists predict cool new phase of superionic ice.” ScienceDaily. ScienceDaily, 21 October 2015. <>.

October 20, 2015

Radiological Society of North America

The main pumping chamber of the heart ages differently in men and women, according to a MRI study. Researchers said the findings may support different treatment approaches for men and women with heart disease.



Magnetic resonance imaging. The main pumping chamber of the heart ages differently in men and women, according to a new magnetic resonance imaging (MRI) study. (stock image)
Credit: © / Fotolia



The main pumping chamber of the heart ages differently in men and women, according to a new magnetic resonance imaging (MRI) study published online in the journal Radiology. Researchers said the findings may support different treatment approaches for men and women with heart disease.

The mass of the left ventricle–the chamber of the heart that pumps blood throughout the body–is a predictor of cardiovascular events. The ventricle walls may thicken from having to work harder to pump blood in the presence of high blood pressure or other conditions.

Studies have shown both increases and decreases in left ventricular mass with age. Many of these studies have been cross-sectional, or focused on one point in time, and based on comparisons between the young and old, which doesn’t account for different lifestyles and other historical factors. But for the new study, researchers were able to assess long-term changes in the same people by acquiring a baseline cardiac MRI and then comparing it with another taken at a later date.

“We had the opportunity to re-examine the same people after 10 years so that we could see what happened to their hearts after a decade,” said John Eng, M.D., from Johns Hopkins University School of Medicine in Baltimore. “This is a more reliable way to assess left ventricular changes over time.”

Dr. Eng and colleagues used cardiac MRI to study the left ventricles of 2,935 participants in the Multi-Ethnic Study of Atherosclerosis, a large observational study focused on cardiovascular disease. Participants were free of clinical cardiovascular disease at baseline and ranged in age from 54 to 94 years old at follow-up. Median time between baseline and follow-up cardiac MRI was 9.4 years.

Comparing the two genders, the researchers found something surprising: while both men and women had decreases in left ventricular volume, left ventricular mass increased in men and decreased slightly in women.

“The shape of the heart changes over time in both men and women, but the patterns of change are different,” Dr. Eng said. “Men’s hearts tend to get heavier and the amount of blood they hold is less, while women’s hearts don’t get heavier.”

The reasons for the differences between left ventricular mass in men and women will require more research, Dr. Eng said. However, the findings suggest that optimum treatment for heart failure might not be the same for women and men.

“We’ve been talking a lot lately about personalized medicine, and here’s an example where perhaps men and women might have to be treated differently,” Dr. Eng said.

The study appeared to confirm the importance of blood pressure and diet to cardiac health. Increased left ventricular mass was associated with higher blood pressure and body mass index and negatively associated with treated hypertension and high-density lipoprotein cholesterol, the so-called “good” cholesterol that helps reduce the risk of heart disease.

The study also highlighted the advantages of cardiac MRI over other imaging modalities in measuring left ventricular mass.

“Most heart imaging is done by echocardiography, but the measurements require a few assumptions and may not be as precise as you would like,” Dr. Eng said. “MRI gives you clearer pictures of the heart, allowing more precise computerized measurements.”

Story Source:

The above post is reprinted from materials provided by Radiological Society of North America. Note: Materials may be edited for content and length.

Journal Reference:

  1. John Eng, Robyn L. McClelland, Antoinette S. Gomes, W. Gregory Hundley, Susan Cheng, Colin O. Wu, J. Jeffrey Carr, Steven Shea, David A. Bluemke, Joao A. C. Lima. Adverse Left Ventricular Remodeling and Age Assessed with Cardiac MR Imaging: The Multi-Ethnic Study of Atherosclerosis. Radiology, 2015; 150982 DOI:10.1148/radiol.2015150982


Source: Radiological Society of North America. “MRI shows heart ages differently in women than in men.” ScienceDaily. ScienceDaily, 20 October 2015. <>.

October 18, 2015

University of New South Wales

A jump in global average temperatures of 1.5°C to 2°C will see the collapse of Antarctic ice shelves and lead to hundreds and even thousands of years of sea level rise, according to new research.



Paradise Bay, Antarctica (stock image).
Credit: © mrallen / Fotolia



A jump in global average temperatures of 1.5°C-2°C will see the collapse of Antarctic ice shelves and lead to hundreds and even thousands of years of sea level rise, according to new research published in Nature.

The research highlights the moral significance of decisions made now about mitigating climate change.

An international team led by Dr Nicholas Golledge, a senior research fellow at New Zealand’s Victoria University’s Antarctic Research Centre, published the study ‘The multi-millennial Antarctic commitment to future sea-level rise’, which predicts how the Antarctic ice-sheet will respond to future atmospheric warming.

Using state-of-the-art computer modelling, Dr Golledge and his colleagues including researchers from UNSW simulated the ice-sheet’s response to a warming climate under a range of greenhouse gas emission scenarios. They found in all but one scenario (that of significantly reduced emissions beyond 2020) large parts of the Antarctic ice-sheet were lost, resulting in a substantial rise in global sea-level.

“The long reaction time of the Antarctic ice-sheet — which can take thousands of years to fully manifest its response to changes in environmental conditions — coupled with the fact that CO₂ lingers in the atmosphere for a very long time means that the warming we generate now will affect the ice sheet in ways that will be incredibly hard to undo,” Dr Golledge said.

The 2013 Intergovernmental Panel on Climate Change (IPCC) report predicted that the Antarctic ice sheet would contribute only five centimetres to global sea-level rise by the end of this century even for its warmest emissions scenario.

But Professor Tim Naish, who worked with Dr Golledge on the study and was also a lead IPCC author, said that when the report was written there was insufficient scientific knowledge about how the Antarctic ice sheet might respond to future warming. Those sea-level projections could have been too modest.

“Our new models include processes that take place when ice sheets come into contact with the ocean, he said.

“Around 93% of the heat from anthropogenic global warming has gone into the ocean, and these warming ocean waters are now coming into contact with the floating margins of the Antarctic ice sheet, known as ice shelves. If we lose these ice shelves, the Antarctic contribution to sea-level rise by 2100 will be nearer 40 centimetres.”

To avoid the loss of the Antarctic ice shelves, and a long-term commitment to many metres of sea-level rise, atmospheric warming needs to be kept below 2°C above present levels.

“Missing the 2°C target will result in an Antarctic contribution to sea-level rise that could be up to 10 metres higher than today,” Dr Golledge said.

“The stakes are obviously very high — 10 percent of the world’s population lives within 10 metres of present sea level.”

What makes the report particularly compelling is the way the results were reached.

“The striking thing about these findings is that we have taken the most conservative estimates possible,” said co-author of the paper, Dr Chris Fogwill from UNSW Australia’s Climate Change Research Centre.

“In all IPCC global warming scenarios, only one (RCP2.6) saw Antarctic ice shelves avoid ongoing collapse. In every other case we saw significant collapse and rising sea levels continue for hundreds to thousands of years.

“The results suggest Antarctic ice shelf stability has a tipping point dependent on a critical temperature threshold that can lead to substantial sea level rise even if we reduce emissions after that threshold has been reached.”

The findings raise an ethical decision for us all, according to Dr Golledge.

“Without significant reduction in greenhouse gas emissions over the next couple of decades, we will commit the Antarctic ice sheet to ongoing and widespread melting for the next few thousand years. Is that something for which we really want to be responsible?”

Dr Golledge said the time has come for some serious questions to be answered.

“It becomes an issue of whether we choose to mitigate now for the benefit of future generations or adapt to a world in which shorelines are significantly re-drawn.

“In all likelihood we’re going to have to do both, because we are already committed to 25 centimetres by 2050, and at least 50 centimetres of sea-level rise by 2100.”

According to Dr Golledge the last time CO₂ concentrations in the atmosphere were similar to present levels was about three million years ago.

“At that time average global temperatures were two or three degrees warmer, large parts of the Antarctic ice-sheet had melted, and sea-levels were a staggering 20 metres higher than they are now.”

“We’re currently on track for a global temperature rise of a couple of degrees which will take us into that ballpark, so there may well be a few scary surprises in store for us, possibly within just a few hundred years.”

Story Source:

The above post is reprinted from materials provided by University of New South Wales. The original item was written by Alvin Stone. Note: Materials may be edited for content and length.

Journal References:

  1. N. R. Golledge, D. E. Kowalewski, T. R. Naish, R. H. Levy, C. J. Fogwill, E. G. W. Gasson. The multi-millennial Antarctic commitment to future sea-level rise. Nature, 2015; 526 (7573): 421 DOI: 10.1038/nature15706
  2. Alexander Robel. Climate science: The long future of Antarctic melting. Nature, 2015; 526 (7573): 327 DOI: 10.1038/526327a


Source: University of New South Wales. “Two degree Celsius warming locks in sea level rise for thousands of years.” ScienceDaily. ScienceDaily, 18 October 2015. <>.

Drug Development at Target Health – All About Action


At Target Health, in addition to its state-of-the-art software supporting the paperless clinical trial, not only do we provide drug and device development strategic planning and individual CRO services such as clinical monitoring, data management, biostatistics, medical writing and regulatory affairs, we can also provide a full turnkey operation and be a full development partner to get products to the market. We just landed a full-service program in multiple sclerosis and Huntington’s disease, together with an international program in dermatology. Other ongoing programs include urology, with the NDA due Q4 2015, and a de novo 510(k) to prevent hairloss in women undergoing breast cancer chemotherapy which is currently under FDA review.


Two major FDA approvals where Target Health provided full turnkey CRO services include 1) a biologic to treat Gaucher disease for Protalix BioTherapeutics sold toPfizer and 2) a drug to treat headlice for Summers Laboratories, which is now being marketed by Concordia Pharmaceuticals. This week Protalix announced that it sold its share in the collaboration agreement for ELELYSOTM to Pfizer Inc. Under the initial collaboration agreement, Pfizer and Protalix shared revenues and expenses for the development and commercialization of ELELYSO, excluding Israel and Brazil. As amended, Pfizer is responsible for 100% of expenses, and entitled to all of the revenues, globally for ELELYSO, excluding Brazil, where Protalix will be responsible for all expenses and retain all revenues.


Mabry Mill – Misty Autumn Morning


From James Farley to the readers of On Target:


While it was still dark, on Saturday morning, I drove to Meadows of Dan, VA to photograph the Mabry Mill in the Autumn leaves. I was the first to the pond! The real trick was to get the shot with the flowing water over the wheel! It was not obvious at first! Glad to have figured that one out!


This was shot with my Canon 5D Mark III, 17mm Tilt-Shift lens with the 2x Extender, effectively at 34mm focal length and with an aperture of f16 as a 3 second exposure. Lee Filters Landscape Circular Polarizer used, as well as a 0.6 Grad ND.




Mabry Mill – Misty Autumn Morning


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



Filed Under News | Leave a Comment

Artemisia annua From the Daisy Family – (fill in the blanks)


Artemisia has been shown to be effective in the treatment of 1) ___.


Artemisia annua is an herb traditionally used in Chinese medicine to treat fever, inflammation, and malaria. A compound in artemisia was shown to be effective in treating malaria in a clinical trial. Another case study showed that artemisia was effective in treating chronic bladder infection. Artemisia prevented cancer cells from dividing in laboratory studies but clinical trials have not been conducted to support this.


Commonly known as wormwood or sweet sagewort, Artemisia annua has been used in traditional 2) ___ medicine for reducing fevers, inflammation, headaches, bleeding and for treating malaria. In vitro studies indicate that artemisinin, the active principle of A. annua, may be an effective treatment for protozoal infections including leishmaniasis, Chagas’ disease, and African sleeping 3) ___. Systematic reviews of artemisinin show that it is as effective as 4) ___ in treating both uncomplicated and severe malaria. However, increased risk of relapse may limit its uses. It is also unclear whether A. annua is effective against strains of malaria that are resistant to quinine.


A study done in a rat model suggests that A. annua may also have contraceptive effects. A. annua has been investigated for its anticancer properties. Terpenoids and flavonoids isolated from the herb exert cytotoxic effects in several human tumor 5) ___ lines. Two of the components, artemisinin and artesunate, have been studied as anticancer treatments.


Artemisinin, the active constituent of A. annua, exerts anti-malarial effects: free radicals formed via cleavage of the endoperoxide bond in its structure, are responsible for eradicating Plasmodium species. In addition to antimalarial effects, artemisinin also effectively induces apoptosis and cell cycle arrest of Leishmani donovani promastigotes. Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, 65demonstrates anti-6) ___ activity by attenuating COX-2 production via down-regulation of serine/threonine kinase (AKT) and mitogen activated protein kinase (MAPK) pathway. Artemisinin also has antiproliferative effects on medullary thyroid carcinoma cells, and induces apoptosis in a lung cancer cell line by modulating p38 and calcium signaling. In another study, it significantly inhibited cell growth and proliferation, and caused cell cycle arrest in the G1 phase in neuroblastoma cell lines. Recent findings suggest that dihydroartemisinin-triggered apoptosis, in colorectal cells, occurs through the reactive oxygen species (ROS)-mediated mitochondria-dependent pathway.


Side effects and warnings:


Patients with ulcers or gastrointestinal disorders should not take Artemisia.


Other possible side effects:


1. A case of hepatitis was reported following consumption of a herbal supplement containing artemisinin.

2. Topical use of 7) ___ may cause dermatitis.

3. Antiseizure medications: Artemisia can induce seizures resulting in decreased efficacy of antiseizure medications.

4. Cytochrome P450 (CYP450) substrates: Extracts from Artemisia induce CYP2B6 and CYP3A4 and may affect the serum concentration of drugs metabolized by these enzymes.


Artemisia is the plant involved in this year’s 8) ___ prize in medicine, won by Youyou Tu from China.




Tarragon (Artemisia dracunculus) is a species of perennial herb in the sunflower family. It is widespread in the wild across much of Eurasia and North America, and is cultivated for culinary and medicinal purposes in many lands.


Click on the link for further reading on Chinese medicine


Sources: Memorial Sloan Kettering Cancer Center; Wikipedia; The New York Times


ANSWERS: 1) malaria; 2) Chinese; 3) sickness; 4) quinine; 5) cell; 6) inflammatory; 7) Artemisia; 8) Nobel


Dr. Youyou Tu, 2015 Nobel Prize Winner


Youyou Tu (Literal meaning: (the sound of) deer bleating


Youyou Tu (Chinese; born 30 December 1930) is a Chinese medical scientist, pharmaceutical chemist, pharmacist, and educator. She is best known for discovering artemisinin (also known as qinghaosu) and dihydroartemisinin, used to treat malaria, which has saved millions of lives. Her discovery of artemisinin and its treatment of malaria is regarded as a significant breakthrough of tropical medicine in the 20th century and health improvement for people of tropical developing countries in South Asia, Africa, and South America. For her work, Tu received the 2011 Lasker Award in clinical medicine and the 2015 Nobel Prize in Physiology or Medicine jointly with William C. Campbell and Satoshi Omura. Tu is the first Chinese Nobel laureate in physiology or medicine and the first citizen of the People’s Republic of China to receive the Nobel Prize in natural sciences, as well as the first Chinese person to receive the Lasker Award. She was born and educated and carried out research exclusively in China.


Tu carried on her work in the 1960s and 70s during China’s Cultural Revolution, when scientists were denigrated as one of the nine black categories in society according to Maoist theory (or possibly that of the Gang of Four). In 1967, during the Vietnam War, Ho Chi Minh, the leader of North Vietnam, which was at war against South Vietnam and the United States, asked Chinese Premier Zhou Enlai for help in developing a malaria treatment for his soldiers trooping down the Ho Chi Minh trail, where a majority came down with a form of malaria which is resistant to chloroquine. Because malaria was also a major cause of death in China’s southern provinces including Hainan, Yunnan, Guangxi, and Guangdong, Zhou Enlai convinced Mao Zedong to set up a secret drug discovery project, named Project 523 after its starting date, 23 May 1967. Upon joining the project unit, Tu was initially sent to Hainan where she studied patients who had been infected with the disease. During the time she spent there, her husband was banished to the countryside, meaning that her daughter had to be entrusted to a nursery in Beijing.


Scientists worldwide had screened over 240,000 compounds without success. In 1969, Tu, then 39 years old, had an idea of screening Chinese herbs. She first investigated the Chinese medical classics in history, visiting practitioners of traditional Chinese medicine all over the country on her own. She gathered her findings in a notebook called A Collection of Single Practical Prescriptions for Anti-Malaria. Her notebook summarized 640 prescriptions. Her team also screened over 2,000 traditional Chinese recipes and made 380 herbal extracts, which were tested on mice. One compound was effective, sweet wormwood (Artemisia annua), which was used for “intermittent fevers,“ a hallmark of malaria. As Tu also presented at the project seminar, its preparation was described in a 1,600-year-old text, in a recipe titled, “Emergency Prescriptions Kept Up One’s Sleeve“. At first, it didn’t work, because they extracted it with traditional boiling water. Youyou Tu discovered that a low-temperature extraction process could be used to isolate an effective antimalarial substance from the plant; Tu says she was influenced by a traditional Chinese herbal medicine source, The Handbook of Prescriptions for Emergency Treatments, written in 340 by Ge Hong, which states that this herb should be steeped in cold water. This book contained the useful reference to the herb: “A handful of qinghao immersed with two liters of water, wring out the juice and drink it all.“ After rereading the recipe, Tu realized the hot water had already damaged the active ingredient in the plant; therefore she proposed a method using low-temperature ether to extract the effective compound instead. The animal tests showed it was completely effective in mice and monkeys. Furthermore, Tu volunteered to be the first human subject. “As head of this research group, I had the responsibility“ she said. It was safe, so she conducted successful clinical trials with human patients. Her work was published anonymously in 1977. In 1981, she presented the findings relating to artemisinin at a meeting with the World Health Organization.


Tu was born in Ningbo, Zhejiang, China on 30 December 1930. She attended Xiaoshi Middle School for junior high school and the first year of high school, before transferring to Ningbo Middle School in 1948. From 1951 to 1955, she attended Peking University Medical School / Beijing Medical College. Tu studied at the Department of Pharmaceutical Sciences, and graduated in 1955. Later Tu was trained for two and a half years in traditional Chinese medicine. After graduation, Tu worked at the Academy of Chinese Medicine (now the China Academy of Chinese Medical Sciences) in Beijing. She was promoted to a Researcher (the highest researcher rank in mainland China, equivalent to the academic rank of a full professor) in 1980 shortly after the Chinese economic reform began in 1978. In 2001 she was promoted to academic advisor for doctoral candidates. Currently she is the Chief Scientist in the Academy.


As of 2007, her office is in an old apartment building in Dongcheng District, Beijing. Before 2011, Tu had been obscure for decades, and is described as “almost completely forgotten by people.“


Tu is regarded as the Professor of Three Noes – no postgraduate degree (there was no postgraduate education then in China), no study or research experience abroad, and not a member of any Chinese national academies, i.e. Chinese Academy of Sciences and Chinese Academy of Engineering. Up until 1979, there were no postgraduate degree programs in China, and China was largely isolated from the rest of the world. Tu is now regarded as a representative figure of the first generation of Chinese medical workers since the establishment of the People’s Republic of China in 1949. Tu and her husband, Li Tingzhao, a metallurgy engineer, live in Beijing. Li Tingzhao was Tu’s classmate in Xiaoshi Middle School. Her younger daughter also lives in Beijing. Her older daughter is working in Cambridge University.


Her first name, Youyou, was given by my father, who adapted it from the sentence translated as ?Deer bleat “youyou“ while they are eating the wild Hao’ in the Chinese Book of Odes. How this links my whole life with qinghao will probably remain an interesting coincidence forever.


During her early years, Tu studied Lobelia chinensis, a traditional Chinese medicine, for curing schistosomiasis, caused by parasitic worms which infect the urinary tract or the intestines, which was widespread in the first half of the 20th century in South China. Tu started her malaria research in China when the Cultural Revolution was in progress. In early 1969, Tu was appointed head of the project, named Project 523 research group at her institute. She collected 2000 candidate recipes, ancient texts, and folk remedies for possible leads for her research. By 1971, her team had made 380 extracts from 200 herbs, and discovered the extracts from qinghao (Artemisia annua, sweet wormwood) looked particularly promising in dramatically inhibiting Plasmodium growth in animals. Tu found the way to extract it and her innovations boosted potency and slashed toxicity of this extract. In 1972, she and her colleagues obtained the pure substance and named it qinghaosu, or artemisinin as it is commonly called in the west, which has saved millions of lives, especially in the developing world. Tu also studied the chemical structure and pharmacology of artemisinin. Tu’s group first determined the chemical structure of artemisinin. In 1973, Tu wanted to confirm the carbonyl group in the artemisinin molecule, therefore she accidentally synthesized dihydroartemisinin. For her work, she was awarded the Nobel Prize in Medicine on 5 October 2015.




Dr. Youyou Tu at home in Beijing Credit: Giles Sabrie for the New York Times

Treating Low Blood Sugar in the Newborn


Glucose levels that are too low — or too high — may lead to brain injury in newborns and possibly result in severe intellectual and developmental disabilities. The threshold for blood sugar had only been an estimate, never having been verified by a research study in people.


Newborns have blood glucose levels far lower than would be tolerable for adults and older children, yet most do not experience any ill effects. For example, in older children and adults, a blood glucose level below 60 mg per dL (deciliter) is considered low. But at birth, it’s common for a newborn to have a blood glucose level as low as 30 mg per dl, which will gradually increase to 54 to 72 mg per dl. According to guidelines from the American Academy of Pediatrics, the generally accepted blood glucose level for treating newborn hypoglycemia is 47 mg per dL.


Now, according to an article published in the New England Journal of Medicine (15 October 2015), it was shown that treating hypoglycemia, or low blood glucose, in newborns according to current recommendations is safe and appears to prevent brain damage. According to the latest study, infants treated for hypoglycemia at the recommended threshold level were no more likely to experience neurological problems by two years of age than those in a comparable group who did not need treatment. According to the authors, hypoglycemia may affect 15% of newborns, but the exact level at which to treat the condition is unknown.


The current study enrolled a total of 404 newborns at the Waikato Hospital in Hamilton, New Zealand. All study participants were born at risk of hypoglycemia, and were tested for blood glucose periodically for up to 48 hours. Results showed that of these infants, 216 had blood glucose levels below 47 mg per dL. These infants were treated with additional feedings of oral or intravenous glucose until their blood sugar was above this threshold. Hospital staff caring for the infants took blood samples to check the infants’ glucose levels. In addition, infants were fitted with a device that monitored their blood glucose level continuously, charting their levels every 5 minutes. To care for the infants, hospital staff relied solely on the blood samples; they were unable to see the readings on the continuous monitor during the study. When all the children reached two years of age, they were tested to measure their developmental progress, cognitive and language skills, vision, hearing, physical coordination and executive functioning (ability to concentrate and carry out tasks appropriate for their age.) Results showed no deficits in any of these areas (referred to collectively as “neurosensory impairments“) between the two groups (children who needed treatment and children who did not). When the authors checked the readings from the glucose monitor, they found that many children in both groups had temporary episodes of hypoglycemia that were not apparent from the blood samples taken by hospital staff. These children were no more likely to have a neurosensory impairment than were the children who did not have low blood glucose levels.


Of the infants who were treated, the authors found that those who later developed high blood glucose levels were more likely to have a neurosensory impairment at age 2 than were other infants in the study. In addition, infants whose glucose levels fluctuated widely during the first 48 hours of birth also were more likely to be impaired. In general, the more time an infant’s blood glucose levels were fluctuating– very high or very low– the more likely the infant was to experience neurosensory impairment. According to the authors, additional studies are needed to confirm the potential links between high or fluctuating glucose levels and neurosensory impairment.


Dormant Viral Genes May Awaken to Cause ALS


Currently, there is no effective treatment for the more than 12,000 Americans who live with amyotrophic lateral sclerosis (ALS). This fatal disorder destroys neurons that control movements, including speaking, walking, breathing and swallowing. On rare occasions, HIV-infected, AIDS patients develop ALS-like symptoms. In many of these patients, the symptoms can be reversed by treatment with antiretroviral drugs. Previous studies found reverse transcriptase, a protein encoded by retroviral genes, in the blood of some ALS patients but its role in the disorder is unknown.


According to an article published in Science Translational Medicine (30 September 2015), it has been observed that reactivation of ancient viral genes embedded in the human genome may cause the destruction of neurons in some forms of ALS. The results suggest a link between human endogenous retroviral genes (HERVs) and ALS. The findings also raise the question of whether antiretroviral drugs, similar to those used for suppressing HIV, may help some ALS patients. For generations, humans have been passing on genetic remnants of HERV infections that may have happened millions of years ago. Although nearly 8% of the normal human genome is made up of these genes, very little is known about their role in health and disease.


Initially, the authors showed that brain samples from ALS patients had higher than normal levels of messenger RNA (mRNA) encoded by genes of the human endogenous retrovirus K (HERV-K). A protein encoded by a critical HERV-K gene, called env, was found in brain samples from ALS patients but not from healthy individuals or patients with Alzheimer’s disease. They also showed that activation of HERV-K genes killed healthy human neurons grown in-vitro. To test the role of HERVs in ALS, the authors genetically modified mice so that their neurons activated the HERV-K env gene. The mice died earlier than normal and had problems with balance and walking that progressively worsened with age. When the authors inspected the brains, spinal cords and muscles of these mice they found that only motor neurons were damaged. These are the cells that control movements in ALS and which eventually die as the disease progresses. Cells in other parts of the nervous system remained healthy. Finally the authors showed that activation of HERV-K genes may be controlled by TDP-43, a gene-regulating protein that has been strongly linked to ALS and known to control HIV production. Genetically enhancing TDP-43 in human neurons increased the cells’ production of HERV-K mRNA and proteins whereas genetically blocking TDP-43 in other cells reduced HERV-K reverse transcriptase activity. The authors are now collaborating with the ALS center at Johns Hopkins University to study whether antiretroviral treatments are effective at controlling HERV-K replication in a subset of patients with ALS.


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